Serotonin as a biomarker of toxin-induced Parkinsonism.

BACKGROUND: Loss of dopaminergic neurons underlies the motor symptoms of Parkinson's disease (PD). However stereotypical PD symptoms only manifest after approximately 80% of dopamine neurons have died making dopamine-related motor phenotypes unreliable markers of the earlier stages of the disease. There are other non-motor symptoms, such as depression, that may present decades before motor symptoms. METHODS: Because serotonin is implicated in depression, here we use niche, fast electrochemistry paired with mathematical modelling and machine learning to, for the first time, robustly evaluate serotonin neurochemistry in vivo in real time in a toxicological model of Parkinsonism, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). RESULTS: Mice treated with acute MPTP had lower concentrations of in vivo, evoked and ambient serotonin in the hippocampus, consistent with the clinical comorbidity of depression with PD. These mice did not chemically respond to SSRI, as strongly as control animals did, following the clinical literature showing that antidepressant success during PD is highly variable. Following L-DOPA administration, using a novel machine learning analysis tool, we observed a dynamic shift from evoked serotonin release in the hippocampus to dopamine release. We hypothesize that this finding shows, in real time, that serotonergic neurons uptake L-DOPA and produce dopamine at the expense of serotonin, supporting the significant clinical correlation between L-DOPA and depression. Finally, we found that this post L-DOPA dopamine release was less regulated, staying in the synapse for longer. This finding is perhaps due to lack of autoreceptor control and may provide a ground from which to study L-DOPA induced dyskinesia. CONCLUSIONS: These results validate key prior hypotheses about the roles of serotonin during PD and open an avenue to study to potentially improve therapeutics for levodopa-induced dyskinesia and depression.

Public knowledge and attitudes towards bystander cardiopulmonary resuscitation (CPR) in Ghana, West Africa.

BACKGROUND AND OBJECTIVES: Early bystander cardiopulmonary resuscitation (CPR) is one of the most important predictors of out-of-hospital cardiac arrests (OHCA) survival. There is a dearth of literature on CPR engagement in countries such as Ghana, where cardiovascular events are increasingly prevalent. In this study, we sought to evaluate Ghanaians' knowledge of and attitudes towards bystander CPR, in the context of the country's nascent emergency medicine network. METHODS: Capitalizing on the growing ubiquity and use of social media across the country, we used a novel social media sampling strategy for this study. We created, pre-tested, and distributed an online survey, using the two most utilized social media platforms in Ghana: WhatsApp and Facebook. An airtime data incentive of 5 US dollars, worth between 5 and 10 GB of cellular data based on mobile phone carrier, was provided as incentive. Inclusion criteria were (1) ≥ 18 years of age, (2) living in Ghana. Survey participants were encouraged to distribute the survey within their own networks to expand its reach. We stratified participants' responses by healthcare affiliation, and further grouped healthcare workers into ambulance and non-ambulance personnel. We used chi-square (χ2)/Fisher's Exact tests to compare differences in responses between the groups. Based on the question "have you ever heard of CPR?", an alpha of 0.05 and a 95% confidence interval, we expected to have 80% power to detect a 15% difference in responses between lay and healthcare providers with an estimated sample size of 246 study participants. RESULTS: The survey was launched on 8 July 2019 and closed approximately 51 h post-launch. With a 64% completion rate and 479 unique survey completions, the study was overpowered at 96% power, to detect differences in responses between the groups. There was geographic representation across all 10 historic regions of Ghana. Over half (57.8%, n = 277) of the respondents were non-medically affiliated, and 71.9% were women. Healthcare workers were more aware of CPR than lay respondents (96.5% vs 68.1%; p < 0.001). Eighty-five percent of respondents were aware that CPR involves chest compressions, and almost 70% indicated that "mouth to mouth" is a necessary component of CPR. Fewer than 10% were unwilling to administer CPR. Lack of skills (44.9%) and fear of causing harm (25.5%) were barriers noted by respondents for not administering CPR. Notably, a quarter of ambulance workers reported never having received CPR training. If they were to witness a collapse, 62.0% would call an ambulance, and 32.6% would hail a taxi. CONCLUSION: The majority of participants are willing to perform CPR. Contextualized training that emphasizes hands-only CPR and builds participants' confidence may increase bystander willingness and engagement.