The Effect of Diesel Exhaust Particles on Adipose Tissue Mitochondrial Function and Inflammatory Status.

Air pollution poses a significant global health risk, with fine particulate matter (PM2.5) such as diesel exhaust particles (DEPs) being of particular concern due to their potential to drive systemic toxicities through bloodstream infiltration. The association between PM2.5 exposure and an increased prevalence of metabolic disorders, including obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM), is evident against a backdrop of rising global obesity and poor metabolic health. This paper examines the role of adipose tissue in mediating the effects of PM2.5 on metabolic health. Adipose tissue, beyond its energy storage function, is responsive to inhaled noxious stimuli, thus disrupting metabolic homeostasis and responding to particulate exposure with pro-inflammatory cytokine release, contributing to systemic inflammation. The purpose of this study was to characterize the metabolic response of adipose tissue in mice exposed to either DEPs or room air (RA), exploring both the adipokine profile and mitochondrial bioenergetics. In addition to a slight change in fat mass and a robust shift in adipocyte hypertrophy in the DEP-exposed animals, we found significant changes in adipose mitochondrial bioenergetics. Furthermore, the DEP-exposed animals had a significantly higher expression of adipose inflammatory markers compared with the adipose from RA-exposed mice. Despite the nearly exclusive focus on dietary factors in an effort to better understand metabolic health, these results highlight the novel role of environmental factors that may contribute to the growing global burden of poor metabolic health.

Differential Impact of Smoking on Methylome and Transcriptome in Crohn's Disease and Ulcerative Colitis.

BACKGROUND: Smoking is an environmental factor that differentially impacts Crohn's disease (CD) and ulcerative colitis (UC). The mechanism of impact of smoking on disease risk and clinical outcomes remains to be established. METHODS: This study used a prospective cohort of patients with CD or UC. Self-reported smoking status was validated using serum cotinine measurement. We profiled methylation changes in peripheral blood using the Illumina Methylation BeadChip. Transcriptomic profiling was performed on ileal and colonic tissue using an Illumina TruSeq platform. We compared the methylation and transcriptional changes in current, former, and never smokers stratified by disease type. RESULTS: Our cohort included 200 patients with CD or UC with methylation profiles and 160 with transcriptomic data. The mean serum cotinine level was higher in current compared with former or never smokers. Epigenetic changes common to both CD and UC included hypomethylation at AHRR. Smoking-associated MGAT3 hypomethylation was associated with severe disease course only in UC, while IER3 hypomethylation was associated with worse course only in CD. Smoking downregulated several inflammatory pathways in UC. Current smoking in CD but not in UC was associated with upregulation of several genes mediating Paneth cell function. Genes with opposite direction of effects in CD and UC include HSD3B2 and GSTA1. CONCLUSIONS: Our findings suggest both common and differential effects of cigarette smoking on CD and UC. Paneth cell dysfunction may mediate adverse impact of smoking on CD. Bile acid and oxidative stress pathways may be relevant for the differential effect of smoking on CD and UC.

Smoking is a key environmental risk factor for the development of inflammatory bowel disease. Smoking induces changes differential epigenetic changes in the peripheral blood in Crohn's disease and ulcerative colitis. Smoking also induces down regulation of expression of various proinflammatory genes in the colon in ulcerative colitis.

Investigating the experiences of medical students quarantined due to COVID-19 exposure.

Background: The COVID-19 pandemic profoundly impacted medical education systems worldwide. Between March 2020 and December 2021, 111 MD students at the University of Toronto completed two-week quarantines due to hospital or community exposures and experienced disrupted clinical instruction. We explored the experiences, barriers, and supports of these quarantined medical students to identify program development opportunities and improve student supports. Methods: We used a qualitative descriptive approach to explore experiences of clerkship students quarantined due to COVID-19 exposure. Methods included an online survey with open-ended questions and an audio-recorded interview. We analysed the demographic survey responses using descriptive statistics. Subsequently, we conducted descriptive thematic analysis of the narrative survey responses and transcribed interview recordings. Results: Concerns reported in surveys (n = 23, response rate 20.7%) and interviews (n = 5) included themes of illness uncertainty, racial tensions, confidentiality of COVID-19 status, unclear academic expectations, and financial burden. Supports included friends, family, and MD program administration. Recommendations related to communication, administration, equity considerations, supports, confidentiality/privacy, and academics. Conclusion: Supporting student wellbeing and learning is at the core of medical training. Enhanced understanding of health profession trainee needs during COVID can improve institutional supportive responses to students routinely and during times of crisis.

Contexte: La pandémie de la COVID-19 a eu des répercussions importantes sur les systèmes d'éducation médicale dans le monde entier. Entre mars 2020 et décembre 2021, 111 étudiants en médecine de l'Université de Toronto ont été contraints à l'auto-isolement pour une période de deux semaines après une exposition au virus à l'hôpital ou dans la collectivité, voyant du même coup leur apprentissage clinique perturbé. Nous avons exploré les expériences, les obstacles et les types de soutien que ces étudiants ont eus alors qu'ils étaient en quarantaine pour en tirer des leçons afin d'améliorer notre programme et de mieux soutenir nos étudiants. Méthodes: Nous avons utilisé une approche qualitative descriptive pour explorer le vécu des étudiants à l'externat mis en quarantaine en raison d'une exposition à la COVID-19. Les méthodes comprenaient une enquête en ligne avec des questions ouvertes et une interview enregistrée. Nous avons analysé les données démographiques à l'aide de méthodes statistiques descriptives. Par la suite, nous avons effectué une analyse thématique descriptive des réponses narratives à l'enquête en ligne et des transcriptions des entretiens. Résultats: Les préoccupations signalées dans les réponses à l'enquête en ligne (n=23, taux de réponse de 20,7 %) et les entretiens (n=5) touchaient à l'incertitude face à la maladie, aux tensions raciales, à la confidentialité du fait d'avoir été infecté , au manque de clarté quant aux attentes académiques, et au fardeau financier. Les sources de soutien citées comprenaient les amis, la famille et l'administration du programme d'études. Les recommandations concernaient la communication, l'administration, les considérations d'équité, le soutien, la confidentialité et les études. Conclusion: Le soutien au bien-être et à l'apprentissage des étudiants est au cœur de la formation médicale. Une meilleure compréhension des besoins des stagiaires des professions de la santé à l'occasion d'une infection par la COVID-19 peut améliorer le soutien institutionnel qui leur est offert en temps normal et en temps de crise.

Predictors of 1-year mortality after adult lung transplantation: Systematic review and meta-analyses.

BACKGROUND: Prognostic factors in lung transplantation are those variables that are associated with transplant outcomes. Knowledge of donor and recipient prognostic variables can aid in the optimal allocation of donor lungs to transplant recipients and can also inform post-operative discussions with patients about prognosis. Current research findings related to prognostic factors in lung transplantation are inconsistent and the relative importance of various factors is unclear. This review aims to provide the best possible estimates of the association between putative prognostic variables and 1-year all-cause mortality in adult lung transplant recipients. METHODS: We searched 5 bibliographic databases for studies assessing the associations between putative predictors (related to lung donors, recipients, or the transplant procedure) and 1-year recipient mortality. We pooled data across studies when justified and utilized GRADE methodology to assess the certainty in the evidence. RESULTS: From 72 eligible studies (2002-2020), there were 34 recipient variables, 4 donor variables, 10 procedural variables, and 7 post-transplant complication variables that were amenable to a meta-analysis. With a high degree of certainty in the evidence only post-transplant need for extra-corporeal membrane oxygenation (ECMO) (HR 1.91, 95% CI 1.79-2.04) predicted 1-year mortality. No donor variables appeared to predict transplant outcome with high or even moderate certainty. CONCLUSION: Across the range of contemporary donors and recipients that clinicians accept for lung transplantation, this review, with high certainty, found 1 prognostic factor that predicted 1-year mortality, and 37 additional factors with a moderate degree of certainty. The lack of prognostic significance for some widely accepted factors (e.g., donor smoking, age) likely relates to existing limits in the range of these variables at the time of donor and recipient selection.

Feasibility and Acceptability of a Physical Activity Tracker and Text Messages to Promote Physical Activity During Chemotherapy for Colorectal Cancer: Pilot Randomized Controlled Trial (Smart Pace II).

BACKGROUND: We conducted a pilot 2-arm randomized controlled trial to assess the feasibility of a digital health intervention to increase moderate-to-vigorous physical activity in patients with colorectal cancer (CRC) during chemotherapy. OBJECTIVE: This study aimed to determine whether a digital health physical activity intervention is feasible and acceptable during chemotherapy for CRC. METHODS: Potentially eligible patients with CRC expected to receive at least 12 weeks of chemotherapy were identified in person at the University of California, San Francisco, and on the web through advertising. Eligible patients were randomized 1:1 to a 12-week intervention (Fitbit Flex, automated SMS text messages) versus usual care. At 0 and 12 weeks, patients wore an Actigraph GT3X+ accelerometer for 7 days and completed surveys, body size measurements, and an optional 6-minute walk test. Participants could not be masked to their intervention arm, but people assessing the body size and 6-minute walk test outcomes were masked. The primary outcomes were adherence (eg, Fitbit wear and text response rate) and self-assessed acceptability of the intervention. The intervention would be considered feasible if we observed at least 80% complete follow-up and 70% adherence and satisfaction, a priori. RESULTS: From 2018 to 2020, we screened 240 patients; 53.3% (128/240) of patients were ineligible and 26.7% (64/240) declined to participate. A total of 44 patients (44/240, 18%) were randomized to the intervention (n=22) or control (n=22) groups. Of these, 57% (25/44) were women; 68% (30/44) identified as White and 25% (11/44) identified as Asian American or Pacific Islander; and 77% (34/44) had a 4-year college degree. The median age at enrollment was 54 years (IQR 45-62 years). Follow-up at 12 weeks was 91% (40/44) complete. In the intervention arm, patients wore Fitbit devices on a median of 67 out of 84 (80%) study days and responded to a median of 17 out of 27 (63%) questions sent via SMS text message. Among 19 out of 22 (86%) intervention patients who completed the feedback survey, 89% (17/19) were satisfied with the Fitbit device; 63% (12/19) were satisfied with the SMS text messages; 68% (13/19) said the SMS text messages motivated them to exercise; 74% (14/19) said the frequency of SMS text messages (1-3 days) was ideal; and 79% (15/19) said that receiving SMS text messages in the morning and evening was ideal. CONCLUSIONS: This pilot study demonstrated that many people receiving chemotherapy for CRC are interested in participating in digital health physical activity interventions. Fitbit adherence was high; however, participants indicated a desire for more tailored SMS text message content. Studies with more socioeconomically diverse patients with CRC are required. TRIAL REGISTRATION: ClinicalTrials.gov NCT03524716; https://clinicaltrials.gov/ct2/show/NCT03524716.

Non-Motor Features of Parkinson's Disease in Women.

BACKGROUND: Non-motor symptoms are common in Parkinson's disease (PD) and some, including hyposmia, constipation, and REM sleep behavior disorder, often precede the clinical diagnosis. OBJECTIVE: To assess the relation between combinations of non-motor features and presence of PD among women. METHODS: A nested case-control study was conducted among women in the Nurses' Health Study. Women were eligible if they responded to screening questions for constipation and probable REM sleep behavior disorder (pRBD) on a 2012 questionnaire and were under age 85 on January 1, 2012. 87 women with confirmed PD and 14,170 women without PD agreed to participate and completed in 2015 the Brief Smell Identification Test to assess hyposmia, as well as a questionnaire to assess parkinsonism and other non-motor PD features, including depressive symptoms, excessive daytime sleepiness, impaired color vision, and body pain. RESULTS: In age-adjusted logistic models, each non-motor feature was significantly associated with PD, and the odds of PD increased exponentially with the number of features. Women with constipation, pRBD, and hyposmia had an age-adjusted OR for PD of 211 (95% CI 84.2-529) compared to women with none of these features. The odds of having PD rose further with the presence of additional non-motor signs. Comparing women with at least 6 of the 7 features assessed in this study to women with one or none, the age-adjusted OR for PD was 356 (95% CI 113-1126). CONCLUSION: Results suggest that these non-motor features could be useful in discriminating PD patients from controls in women, and since they often appear during the prodromal period of PD, their combinations may prove useful for identifying populations at high risk of developing PD.

Alcohol intake and Parkinson's disease risk in the million women study.

BACKGROUND: Alcohol intake may be associated with a lower risk of Parkinson's disease (PD), but findings from previous studies have been inconclusive. OBJECTIVE: To determine the association between alcohol intake and PD risk in the Million Women Study, a large, prospective study of women in the UK. METHODS: Between 1996 and 2001, approximately 1.3 million women in the UK, mean age 56 (standard deviation, 5) years, were recruited into the Million Women Study. Information on alcohol intake, lifestyle factors, and medical history was collected at recruitment by questionnaire. Information on incident cases of PD was ascertained by record linkage to national hospital admission records and death registrations. We estimated multivariable-adjusted relative risks and corresponding 95% confidence intervals using Cox proportional hazards models according to categories of alcohol intake. RESULTS: During an average of 17.9 years of follow-up, 11,009 women had a new record of PD among 1,309,267 women. In drinkers, the multivariable-adjusted relative risk comparing women who drank more than 14 drinks of alcohol per week with women who drank 1 to 2 drinks of alcohol per week was 0.99 (95% confidence interval: 0.90, 1.10). Results did not materially change after excluding the first 10 years of follow-up (relative riskadjusted = 1.01; 95% confidence interval: 0.90, 1.13). There were no significant trends in alcohol-related PD risk among never smokers. Additionally, examining this association by type of alcohol intake also yielded null findings. CONCLUSION: These results do not support an association between alcohol intake and PD risk in women. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Interaction between apolipoprotein E genotype and hypertension on cognitive function in older women in the Nurses' Health Study.

OBJECTIVE: To examine the interaction between APOE genotypes and both treated and untreated hypertension on cognitive function in an updated analysis of Nurses' Health Study (NHS) data. DESIGN: At baseline (1995-2001) and 3 biennial follow-up assessments over ~6 years, cognitive function was assessed. SETTING AND PARTICIPANTS: 8300 NHS participants aged 70+ years underwent a cognitive battery, which comprised 6 tests including the Telephone Interview for Cognitive Status (TICS) and tests of verbal memory, category fluency, and working memory. MEASURES: We estimated the mean differences in average cognitive scores across up to 4 assessments using multiple linear regression. We also tested for interaction between APOE e4 allele carrier status and hypertension overall, as well as for apparently untreated and treated hypertension. RESULTS: We confirmed that, compared with those with APOE e3/3 genotype, APOE e4 allele carriers scored lower by 0.55 units on the average TICS score (95%CI:-0.67,-0.43). We also observed a significantly worse average TICS score among women with untreated hypertension compared with women without hypertension (difference = -0.23, 95%CI:-0.37,-0.09), while no significant difference was observed for women with treated hypertension. Significant interaction was detected between the APOE e4 allele and untreated hypertension (p-int = 0.02 for the TICS; p-int = 0.045 for global score), but not with treated hypertension. Specifically, compared with normotensive women with the APOE e3/3 genotype, APOE e4 allele carriers with treated hypertension scored lower by 0.50 units (95%CI:-0.69,-0.31); however, the APOE e4 allele carriers with untreated hypertension scored lower by 1.02 units on the TICS score (95%CI:-1.29, -0.76). This interaction of APOE e4 and untreated hypertension was also consistently observed for the global score. CONCLUSIONS: Women with hypertension and at least one APOE e4 allele had worse average cognitive function compared with women without hypertension with the e3/3 genotype; this difference was amplified among APOE e4 allele carriers with untreated hypertension.

Vitamin D Status and Mortality: A Systematic Review of Observational Studies.

Epidemiological evidence suggests that vitamin D deficiency is associated with increased mortality, but it is unclear whether this is explained by reverse causation, and if there are specific causes of death for which vitamin D might be important. We conducted a systematic review of observational studies investigating associations between circulating 25-hydroxyvitamin D (25(OH)D) concentration and all-cause or cause-specific mortality in generally healthy populations. Relevant studies were identified using PubMed and EMBASE searches. After screening 722 unique records and removing those that were ineligible, 84 articles were included in this review. The vast majority of studies reported inverse associations between 25(OH)D concentration and all-cause mortality. This association appeared to be non-linear, with progressively lower mortality with increasing 25(OH)D up to a point, beyond which there was no further decrease. There is moderate evidence that vitamin D status is inversely associated with cancer mortality and death due to respiratory diseases, while for cardiovascular mortality, there is weak evidence of an association in observational studies, which is not supported by the data from intervention or Mendelian randomization studies. The relationship between vitamin D status and other causes of death remains uncertain due to limited data. Larger long-term studies are required to clarify these associations.

Non-motor features of Parkinson's disease in a nested case-control study of US men.

BACKGROUND: Several non-motor features may individually contribute to identify prodromal Parkinson's disease (PD), but little is known on how they interact. METHODS: We conducted a case-control study nested within the Health Professionals Follow-up Study in a large cohort of men age 40-75 at recruitment in 1986. Cases (n=120) had confirmed PD, were<85 in January 2012, returned a 2012 questionnaire with questions on probable rapid eye movement sleep behaviour disorder (RBD) and constipation sent to all cohort participants and completed in 2014 the Brief Smell Identification Test and a questionnaire assessing parkinsonism and other non-motor PD features (including depressive symptoms, excessive daytime sleepiness, impaired colour vision and body pain). Controls (n=6479) met the same criteria as cases, except for the PD diagnosis. RESULTS: Concurrent constipation, probable RBD and hyposmia were present in 29.3% of cases and 1.1% of controls, yielding an age-adjusted OR of 160(95%CI 72.8to353) for three features versus none. The odds of PD increased exponentially with additional non-motor features (OR for 6-7 features versus none: 1325; 95%CI333to5279). Among men without PD, the number of non-motor features was associated with odds of parkinsonism (OR for 6-7 features versus none: 89; 95%CI21.2to375). We estimated that in a population with a prodromal PD prevalence of 2%, concurrent constipation, probable RBD and hyposmia would have a maximum sensitivity of 29% and a positive predictive value (PPV) of 35%. The PPV could increase up to 70% by including additional features, but with sharply decreased sensitivity. CONCLUSIONS: Concurrent constipation, probable RBD and hyposmia are strongly associated with PD. Because these features often precede motor symptoms and their co-occurrence could provide an efficient method for early PD identification.

Embryoid body test with morphological and molecular endpoints implicates potential developmental toxicity of trans-resveratrol.

Developmental toxicity of compounds, which women of reproductive age are exposed to, should be assessed to minimize the incidence of miscarriage and birth defects. The present study examined the potential developmental toxicity of resveratrol, a dietary supplement widely marketed with various health claims, using the P19C5 embryoid body (EB) morphogenesis assay, which evaluates adverse effects of chemical exposures on tissue growth and axial elongation. Resveratrol (trans isoform) impaired morphogenesis at 4 µM and higher, creating smaller and rounder EBs, whereas cis isoform, and glucuronated and sulfonated metabolites did not. Trans-resveratrol also altered expression levels of developmental regulator genes involved in embryonic patterning, such as Wnt3a, Tbx6, and Cyp26a1. To investigate the mechanisms of trans-resveratrol action, the roles of estrogen receptor, sirtuin 1 (SIRT1), and DNA replication in EB morphogenesis were examined. Neither activators of estrogen receptors (diethylstilbestrol [18 µM] and raloxifene [8 µM]) nor activator of SIRT1 (SRT1720 [2.4-3.2 µM]) caused morphological and molecular alterations that are comparable to trans-resveratrol (10 µM). By contrast, a reduction in the DNA replication rate with aphidicolin (0.4 µM) or hydroxyurea (40 µM) created smaller and rounder EBs and altered the expression levels of Wnt3a, Tbx6, and Cyp26a1 in a manner similar to trans-resveratrol. Consistently, trans-resveratrol significantly reduced the rate of EdU incorporation in P19C5 cells. These results suggest that a reduction in the DNA replication rate is one of the mechanisms by which trans-resveratrol impacts EB development. This study provides mechanistic insight for further investigations on the developmental toxicity of trans-resveratrol.

Genetic variants related to urate and risk of Parkinson's disease.

INTRODUCTION: Higher urate concentrations have been associated with a lower risk of developing Parkinson's disease (PD) and with slower rates of clinical decline in PD patients. Whether these associations reflect a neuroprotective effect of urate is unclear. Our objective was to assess whether genetic variants that modify circulating urate levels are also associated with altered PD risk. METHODS: Participants were from three large ongoing cohort studies: the Nurses' Health Study (NHS), the Health Professionals Follow-up Study (HPFS), and the Cancer Prevention Study II Nutrition Cohort (CPS-IIN). We examined associations between single nucleotide polymorphisms (SNPs) in SLC2A9 and other genes involved in urate transport and PD risk using conditional logistic regression among 1451 cases and 3135 matched controls. We assessed associations between SNPs and plasma urate levels in a subset of 1174 control participants with linear regression models. RESULTS: We found the expected associations between SNPs in SLC2A9 and plasma urate levels among men and women; however, SNPs in other genes tended not to be associated with urate. Each SNP in SLC2A9 explained less than 7% of the variance in plasma urate. We did not find significant associations between the SNPs in SLC2A9 and PD risk among men or women. CONCLUSION: Our results do not support an association between genetic variants associated with circulating urate levels and risk of PD, but larger investigations are needed to determine whether the modest genetic effects on blood urate contribute to predict PD risk.

Integration of risk factors for Parkinson disease in 2 large longitudinal cohorts.

OBJECTIVE: To prospectively examine how selected lifestyle factors and family history of Parkinson disease (PD) combine to determine overall PD risk. METHODS: We derived risk scores among 69,968 women in the Nurses' Health Study (NHS) (1984-2012) and 45,830 men in the Health Professionals Follow-up Study (HPFS) (1986-2012). Risk scores were computed for each individual based on the following factors previously associated with PD risk: total caffeine intake, smoking, physical activity, and family history of PD for the NHS, and additionally total flavonoid intake and dietary urate index for the HPFS. Hazard ratios were estimated using Cox proportional hazards models. In addition, we performed tests of interactions on both the multiplicative and additive scale between pairs of risk factors. RESULTS: We documented 1,117 incident PD cases during follow-up. The adjusted hazard ratios comparing individuals in the highest category of the reduced risk score to those in the lowest category were 0.33 (95% confidence interval: 0.21, 0.49; ptrend < 0.0001) in the NHS and 0.18 (95% confidence interval: 0.10, 0.32; ptrend < 0.0001) in the HPFS. Results were similar when applying the risk scores computed by summing the predictors weighted by the log of their individual effect sizes on PD risk in these cohorts. Additive interaction was present between no family history of PD and caffeine in men and between caffeine and physical activity in women. CONCLUSIONS: Our results suggest that known protective factors for PD tend to have additive or superadditive effects, so that PD risk is very low in individuals with multiple protective risk factors.

Interaction between caffeine and polymorphisms of glutamate ionotropic receptor NMDA type subunit 2A (GRIN2A) and cytochrome P450 1A2 (CYP1A2) on Parkinson's disease risk.

BACKGROUND: Caffeine intake has been inversely associated with Parkinson's disease (PD) risk. This relationship may be modified by polymorphisms of glutamate ionotropic receptor NMDA type subunit 2A (GRIN2A) and cytochrome P450 1A2 (CYP1A2), but the results of previous studies have been inconsistent. METHOD: We examined the interaction of caffeine intake with GRIN2A-rs4998386 and CYP1A2-rs762551 polymorphisms in influencing PD risk among 829 incident cases of PD and 2,754 matched controls selected among participants in the following 3 large prospective ongoing cohorts: the Nurses' Health Study, the Health Professionals' Follow-up Study, and the Cancer Prevention Study II Nutrition Cohort. Matching factors included cohort, birth year, source of DNA, date of DNA collection, and race. Relative risks and 95% confidence intervals were estimated using conditional logistic models. Interactions were tested both on the multiplicative scale and on the additive scale. RESULTS: Overall, caffeine intake was associated with a lower PD risk (adjusted relative risk for highest versus lowest tertile = 0.70; 95% confidence interval, 0.57-0.86; p < .001). In analyses stratified by the GRIN2A-rs4998386 genotype, the multivariable-adjusted relative risk of PD comparing the highest to the lowest tertile of caffeine was 0.69 (95% confidence interval, 0.55-0.88; p < .01) among individuals homozygous for the C allele, and 0.85 (95% confidence interval, 0.55-1.32; p = .47; pRERI = .43) among carriers for the T allele. Interactions between caffeine and GRIN2A were not significant in either the multiplicative or additive scales. We also did not observe significant interactions for CYP1A2-rs762551 and incident PD risk. CONCLUSION: Our findings do not support the hypothesis of an interaction between the GRIN2A-rs4998386 or CYP1A2-rs762551 polymorphism and caffeine intake in determining PD risk. © 2018 International Parkinson and Movement Disorder Society.

Differences in Parkinson's Disease Risk with Caffeine Intake and Postmenopausal Hormone Use.

BACKGROUND: Caffeine intake has been associated with a lower risk of Parkinson's disease (PD). This association is robust in men, but inconsistent in women due to a possible interaction with post-menopausal hormone (PMH) use. OBJECTIVE: To (1) evaluate the association between caffeine intake and PD risk and (2) assess potential effect modification of the association by PMH use among women. METHODS: We examined associations between caffeine intake and incident PD risk in the Nurses' Health Study (NHS) (N = 121,701 women) and the Health Professionals Follow-up Study (HPFS) (N = 51,529 men). Dietary data on coffee and caffeine from other sources were collected every four years using a validated semi-quantitative food frequency questionnaire for both cohorts. Information on lifestyle and incident PD diagnosis was updated biennially and PD diagnoses were confirmed by medical record review. We estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazards models. RESULTS: We documented a total of 1,219 PD cases over the follow-up period. The multivariable-adjusted HR comparing the highest to lowest quintile of caffeine intake was 0.50 (95% CI: 0.37, 0.68; Ptrend<0.0001) in the HPFS. Among women, there was a suggestion of an interaction between coffee intake and PMH use (P = 0.08). In the pooled analyses combining men and women who have never used PMH, the risk of PD was lower as coffee intake increased (Ptrend<0.001). CONCLUSIONS: Our results support previous findings that increased caffeine intake may be associated with a decreased PD risk in men and women who have never used PMH.

Intake of dairy foods and risk of Parkinson disease.

OBJECTIVE: To prospectively examine the association between commonly consumed dairy products and the risk of Parkinson disease (PD) in women and men. METHODS: Analyses were based on data from 2 large prospective cohort studies, the Nurses' Health Study (n = 80,736) and the Health Professionals Follow-up Study (n = 48,610), with a total of 26 and 24 years of follow-up, respectively. Both US-based studies were conducted via mailed biennial questionnaires. Dietary intake was assessed with food frequency questionnaires administered repeatedly over the follow-up period. Incident cases of PD (n = 1,036) were identified via questionnaires and subsequently confirmed by reviewing medical records. We also conducted a meta-analysis to combine our study with 3 previously published prospective studies on total milk intake and PD risk and 1 study on total dairy intake and PD risk. RESULTS: While total dairy intake was not significantly associated with PD risk in our cohorts, intake of low-fat dairy foods was associated with PD risk. The pooled, multivariable-adjusted hazard ratio (HR) comparing people who consumed at least 3 servings of low-fat dairy per day to those who consumed none was 1.34 (95% confidence interval [CI] 1.01-1.79, p trend = 0.04). This association appeared to be driven by an increased risk of PD associated with skim and low-fat milk (HR 1.39, 95% CI 1.12-1.73, p trend <0.01). Results were similar in women and men (p for heterogeneity >0.05). In the meta-analysis, the pooled relative risk comparing extreme categories of total milk intake was 1.56 (95% CI 1.30-1.88), and the association between total dairy and PD became significant (HR 1.27, 95% CI 1.04-1.55). CONCLUSIONS: Frequent consumption of dairy products appears to be associated with a modest increased risk of PD in women and men.

The Effect of Preoperative Occlusion Therapy on Long-term Outcome after Surgery for Early-onset Exotropia.

PURPOSE: To investigate the effect of preoperative part-time occlusion therapy on long-term surgical success in early-onset exotropia. METHODS: The medical records of patients who underwent surgery for exotropia with onset before the first year of age and who were followed for ≥3 years were reviewed. Patients were divided into two groups according to the degree of compliance with part-time occlusion therapy: the good compliance group (>50% adherence rate) and the poor compliance group (≤50% adherence rate). Surgical success was defined as orthophoria to exodeviation less than 10 prism diopters both at distance and near. The level of postoperative stereopsis was compared between the two study groups among total enrolled patients and among those with constant exotropia. RESULTS: Of the 51 patients, 26 were assigned to the good compliance group and the remaining 25 patients to the poor compliance group. The surgical success rate was significantly higher in the good compliance group than in the poor compliance group (80.8% vs. 52.0%, p = 0.040). Among 24 constant exotropia patients (12 patients for each group), the success rate was insignificantly higher in the good compliance group than in the poor compliance group (75.0% vs. 58.3%, p = 0.448). The good compliance group had a better level of stereopsis than the poor compliance group (p = 0.045 for all 44 patients, p = 0.020 for 19 patients with constant exotropia). CONCLUSIONS: Preoperative part-time occlusion therapy was useful for improving the surgical outcome of early-onset exotropia and postoperative stereopsis.