A Delphi consensus to identify the key screening tests/questions for a digital neurological examination for epidemiological research.

BACKGROUND: Most neurological diseases have no curative treatment; therefore, focusing on prevention is key. Continuous research to uncover the protective and risk factors associated with different neurological diseases is crucial to successfully inform prevention strategies. eHealth has been showing promising advantages in healthcare and public health and may therefore be relevant to facilitate epidemiological studies. OBJECTIVE: In this study, we performed a Delphi consensus exercise to identify the key screening tests to inform the development of a digital neurological examination tool for epidemiological research. METHODS: Twelve panellists (six experts in neurological examination, five experts in data collection-two were also experts in the neurological examination, and three experts in participant experience) of different nationalities joined the Delphi exercise. Experts in the neurological examination provided a selection of items that allow ruling out neurological impairment and can be performed by trained health workers. The items were then rated by them and other experts in terms of their feasibility and acceptability. RESULTS: Ten tests and seven anamnestic questions were included in the final set of screening items for the digital neurological examination. Three tests and five anamnestic questions were excluded from the final selection due to their low ratings on feasibility. CONCLUSION: This work identifies the key feasible and acceptable screening tests and anamnestic questions to build an electronic tool for performing the neurological examination, in the absence of a neurologist.

Transdermal delivery of mitochondrial-targeted hydrogen sulphide donor, AP39 protects against 6-hydroxydopamine-induced mitochondrial dysfunction.

Hydrogen sulphide (H2S) is an important gaseous signalling molecule with emerging roles as a neuroprotectant. The objective of this study was to investigate the feasibility of transdermal delivery of mitochondrial-targeted H2S donor, AP39 whilst investigating the ability of permeated AP39 on abrogating 6-hydroxydopamine (6-OH-dop)-induced mitochondrial dysfunction, as a model of Parkinson's disease, established in human neuroblastoma cells, SHSY-5Y. Aqueous hypromellose gels (5% w/v) were prepared with up to 10% v/v propylene glycol (PG) with 0.002% w/w AP39. AP39 permeation from formulations across excised murine skin into PBS was quantified over 24 h using HPLC-UV detection. Media was collected and applied to a microvasculature blood-brain-barrier (BBB) model to evidence AP39 permeability. Following, the permeate was applied to neuroblastoma cells SHSY-5Y to evidence its therapeutic potential in modulating the mitochondrial bioenergetics and antioxidant in response to 6-OH-dop-induced mitochondrial dysfunction. The presence of PG in gel formulations significantly increased the cumulative amount of AP39 permeated across murine skin over 24 h from 24.40 ± 2.39 % to 48.59 ± 2.93 %. Conditioned media applied to a microvasculature BBB model observed AP39 permeation across the barrier and H2S release. Finally, permeated AP39 enhanced parameters of mitochondrial bioenergetics in SHSY-5Y exposed to 6-OH-dop. Moreover, permeated AP39 abrogated mitochondrial-specific reactive oxygen species generation induced by 6-OH-dop. These findings demonstrate transdermal delivery of AP39 may provide a promising alternative to deliver this mitochondrial-targeted H2S donor and this approach allows the potential to cross the BBB reaching CNS organs in the treatment of neurodegenerative conditions such as Parkinson's disease. Moreover, our observations show that gels prepared with 10% v/v PG have the potential for use in conditions requiring rapid H2S delivery whereas gels without PG have potential for therapy requiring sustained H2S delivery.

Effect of passive smoke exposure on general anesthesia for pediatric dental patients.

The purpose of this study was to test the null hypothesis that children with environmental tobacco smoke (ETS) exposure (also known as passive smoke exposure) do not demonstrate an increased likelihood of adverse respiratory events during or while recovering from general anesthesia administered for treatment of early childhood caries. Parents of children (ages 19 months-12 years) preparing to receive general anesthesia for the purpose of dental restorative procedures were interviewed regarding the child's risk for ETS. Children were observed during and after the procedure by a standardized dentist anesthesiologist and postanesthesia care unit nurse who independently recorded severity of 6 types of adverse respiratory events-coughing, laryngospasm, bronchospasm, breath holding, hypersecretion, and airway obstruction. Data from 99 children were analyzed. The children for whom ETS was reported were significantly older than their ETS-free counterparts (P = .03). If the primary caregiver smoked, there was a significantly higher incidence of smoking by other members of the family (P < .0001) as well as smoking in the house (P < .0005). There were no significant differences between the adverse respiratory outcomes of the ETS (+) and ETS (-) groups. The ETS (+) children did have significantly longer recovery times (P < .0001) despite not having significantly more dental caries (P = .38) or longer procedure times. ETS is a poor indicator of post-general anesthesia respiratory morbidity in children being treated for early childhood caries.