Caffeine intake interacts with Asian gene variants in Parkinson's disease: a study in 4488 subjects.

Background: Caffeine intake reduces risk of Parkinson's disease (PD), but the interaction with genes is unclear. The interaction of caffeine with genetic variants in those at high PD risk has healthcare importance. We investigate interactions of caffeine intake with risk variants found in Asians, and determine PD risk estimates in caffeine-drinkers carrying these variants. Methods: PD patients and controls without neurological disorders were included. Caffeine intake was assessed using a validated evaluation tool. Leucine rich repeat kinase 2 (LRRK2) risk variants were genotyped. Statistical analysis was conducted with logistic regression models. Gene-caffeine interactions were quantified using attributable proportion (AP) due to interaction (positive interaction defined as AP >0). Findings: 5100 subjects were screened and 4488 subjects (1790 PD, 2698 controls) with genetic data of at least one LRRK2 variant were included. Risk-variant-carriers who were non-caffeine-drinkers had increased PD odds compared to wildtype carriers who were caffeine-drinkers for G2385R [OR 8.6 (2.6-28.1) p < 0.001; AP = 0.71], R1628P [OR 4.6 (1.6-12.8) p = 0.004; AP = 0.50] and S1647T [OR 4.0 (2.0-8.1) p < 0.001; AP = 0.55] variants. Interpretation: Caffeine intake interacts with LRRK2 risk variants across three different groups of gene carriers. Asymptomatic risk-variant-carriers who are non-caffeine-drinkers have four to eight times greater PD risk compared to wildtype-caffeine-drinkers. Lifestyle modifications to mitigate PD risk in asymptomatic healthy risk variant carriers have potential roles in our Asian cohort. Funding: This study was supported by the National Medical Research Council (STaR and PD OF LCG 000207 grants) and Duke-NUS Medical School.

Multiple System Atrophy (MSA) and smoking: a meta-analysis and mechanistic insights.

BACKGROUND: The association between cigarette smoking and multiple system atrophy (MSA) has been debated. We conducted a systematic review and a meta-analysis to investigate this link. RESULTS: We identified 161 articles from database searching and bibliographic review. Five case-control studies satisfied the inclusion and exclusion criteria, and 435 and 352 healthy controls and MSA patients were examined. The prevalence of MSA amongst ever smokers was lower compared to never smokers (aOR=0.57; 95% CI, 0.29-1.14), although this result did not reach statistical significance. This was also observed for current and former smokers, with a stronger association for current smokers (aOR=0.63 vs aOR=0.96). CONCLUSIONS: There is a suggestion that smoking protects against MSA. Prospective studies in larger patient cohorts are required to further evaluate the cause-effect relationship and functional studies in cellular and animal models will provide mechanistic insights on their potential etiologic links. METHODS: PubMed and Cochrane Library were searched from inception to July 7, 2019 to identify case-control studies that analyzed smoking as an environmental risk or protective factor for MSA. Two authors independently extracted data and performed risk-of-bias and quality assessment. The random-effects model was assumed to account for between-study variance when pooling the crude and adjusted odds ratios.

Etiologic links between environmental and lifestyle factors and Essential tremor.

Essential tremor (ET) is one of the most common adult movement disorders, characterized by clinical tremor and other nonmotor symptoms. It is a progressive disease that shares features with other neurodegenerative diseases. ET is a complex disease with both genetic and environmental underpinnings. While genetic forms of ET are well recognized, the role of environmental and lifestyle factors in ET has been debated. Studies suggest that exposure to neurotoxic compounds such as ß-carboline alkaloids and ethanol are potential risk factors for ET, while antioxidant intake may be protective. In addition, smoking acts as a protective factor in ET, parallel to its effects in other neurological diseases. New evidence points to pesticide and lead exposure as potential risk factors. There is growing evidence to suggest that environmental and lifestyle factors play a role in ET but additional research is needed in order to completely understand their cause and effect association. There is also a need for larger case-control and prospective cohort studies across different populations to further evaluate the etiological importance of these factors in ET.

Transapical cardioscopic mitral annuloplasty: a short-term survival study in a porcine model.

OBJECTIVES: The transapical approach provides concurrent surgical access to the mitral and the aortic valves, the root of the aorta and the left atrium. We previously showed the feasibility of transapical cardioscopic (TAC) surgery in a non-survival porcine model. However, reproducibility and feasibility of ring implantation using TAC have not been reported. Therefore, in this study, we hypothesized that implantation of a mitral annuloplasty ring can be feasibly and safely carried out endoscopically via the apex of the heart. METHODS: Using a porcine model in a short-term survival study, TAC mitral annuloplasty was performed in 6 pigs via an incision over the xyphoid, under cardiopulmonary bypass and cardiac arrest. A mitral annuloplasty ring was implanted via the apex to a normal mitral annulus, using a customized set of instruments and techniques. Haemodynamics, echocardiography, cardiac computed tomography, ventriculography, electrocardiography and histopathology studies were used to evaluate the function of the mitral valve and the left ventricle, coronary system and conduction system in the perioperative period and 4 weeks later. RESULTS: All 6 animals survived and recovered from the TAC annuloplasty procedure. Postimplantation examination showed that the mitral valve was competent, left ventricular ejection fraction was 63 ± 4%, left ventricular length was 6.2 ± 0.5 cm and left ventricular end-diastolic volume was 80 ± 10 ml, which were comparable to preoperative values. Apart from a dense scar at the apex, no significant injury was noticed on the ventricle, the chordae and the mitral leaflets. The bypass, cross-clamp and implantation times were 181 ± 55 min, 130 ± 37 min and 47 ± 6 min, respectively. CONCLUSIONS: Despite long surgical times due to the initial learning curve, successful execution of mitral ring annuloplasty could be safely achieved using the TAC approach, via a small incision without the involvement of sternum or the right pleural cavity, thereby potentially expanding the indication to patients with high-risk full sternotomy or right thoracotomy.

Video-assisted thoracoscopic surgery atrial clipping for atrial fibrillation.

The majority of thrombi that arise due to atrial fibrillation occur in the left atrial appendage. Eliminating this cul-de-sac within the left atrium reduces the risk of stroke in these patients. We present a unique case of left atrial appendage occlusion performed via video-assisted thoracoscopic surgery, using an Atriclip to occlude the left atrial appendage in a patient with atrial fibrillation in whom anticoagulation was contraindicated due to a history of recurrent upper gastrointestinal bleeding.

Long-chain polyunsaturated fatty acid status during pregnancy and maternal mental health in pregnancy and the postpartum period: results from the GUSTO study.

OBJECTIVE: Studies have demonstrated a relationship between lower omega-3 long-chain polyunsaturated fatty acid (LC-PUFA) status and anxiety and depression. It is uncertain whether similar associations occur in pregnant women, when anxiety and depression could have long-term effects on the offspring. We examined the associations between plasma LC-PUFA status during pregnancy and perinatal mental health. METHOD: At 26-28 weeks' gestation, plasma LC-PUFAs were measured in mothers of the Growing Up in Singapore Toward healthy Outcomes (GUSTO) mother-offspring cohort study, who were recruited between June 2009 and September 2010. Maternal symptoms of anxiety and depression were assessed with the State-Trait Anxiety Inventory (STAI) and Edinburgh Postnatal Depression Scale (EPDS) during the same period and at 3 months' postpartum. The STAI-state subscale was used as a continuous measure of current anxiety, while EPDS scores ≥ 15 during pregnancy or ≥ 13 postpartum were indicative of symptoms of probable depression. RESULTS: In adjusted regression analyses (n = 698), lower plasma total omega-3 PUFA concentrations (ß = -6.49 STAI-state subscale scores/unit increase of omega-3 fatty acid; 95% CI, -11.90 to -1.08) and higher plasma omega-6:omega-3 PUFA ratios (ß = 6.58 scores/unit increase of fatty acid ratio; 95% CI, 1.19 to 12.66), specifically higher arachidonic acid (AA):docosahexaenoic acid, AA:eicosapentaenoic acid, and AA:docosapentaenoic acid ratios, were associated with increased antenatal anxiety (P < .05 for all), but not postpartum anxiety. There was no association between plasma PUFAs and perinatal probable depression. CONCLUSIONS: No association was found with probable depression in pregnancy or postpartum. Lower plasma omega-3 fatty acids and higher omega-6:omega-3 fatty acid ratios were associated with higher antenatal anxiety, but not postpartum anxiety. Replication in other studies is needed to confirm the findings and determine the direction of causality. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01174875.