Micronutrients, Frailty, and Cognitive Impairment: Design and Preliminary Results from the CogLife 2.0 Study

Background: Among preventive strategies against dementia, nutrition is considered a powerful one and the recently established “nutritional cognitive neuroscience of aging” is a highly active research field. Objective: The present study was designed to deeply characterize older adults across the continuum from cognitive integrity to mild cognitive impairment (MCI) and better elucidate the prognostic role of lipophilic micronutrients within their lipidomic signature. Methods: 123 participants older than 65 years across the continuum from cognitive integrity to MCI were included [49 with subjective cognitive impairment, 29 women, 72.5±5.4 years, 26 MCI, 9 women, 74.5±5.8 years and 50 without cognitive impairment, 21 women, 70.8±4.3 years]. All participants underwent neuropsychological and nutritional examination as well as comprehensive geriatric assessment with calculation of the Multidimensional Prognostic Index (MPI) as a proxy of frailty and biological age and blood withdrawal for the analyses of lipophilic micronutrients, metabolomics and oxylipidomics. One year after the evaluation, same tests are ongoing. Results: After adjustment for age, sex, daily fruit and vegetable intake and cholesterol, we found a significant positive correlation between lutein and the number of correct words in category fluency (p = 0.016). Conclusions: This result supports the importance of carotenoids as robust biomarkers of cognitive performance independent of the nutritional status and frailty of the participants, as the entire present study collective was robust (MPI 0–0.33). The complete analyses of the metabolome and the oxylipidome will hopefully shed light on the metabolic and prognostic signature of cognitive decline in the rapidly growing population at risk of frailty

Management and outcomes of sellar, suprasellar and parasellar masses in low- and middle-income countries: a scoping review protocol

Sellar, suprasellar or parasellar masses refer to space-occupying lesions that arise from the area surrounding the pituitary gland and many other vital structures, which can impact quality of life if damaged. Therefore, optimal management by a multidisciplinary team, which includes neurosurgeons, would be required to ensure that patients receive timely intervention to prevent long-term co-morbidities. The landscape of management of these masses in high-income countries are well described in the literature, however, there is a lack of clarity in the counterpart low- and middle-income countries, thus necessitating an evaluation of the literature. This protocol outlines how we will conduct our scoping review on the topic of interest. MEDLINE, Embase, Global Index Medicus and African Journals Online will be searched from year 2000 to date in order to identify the relevant studies. Patients with a sellar, suprasellar or parasellar masses managed in an LMIC will be included. Surgical, medical and conservative management of the relevant masses will be considered. Articles in English and French will be included. Primary outcome will describe the management of sellar, suprasellar, or parasellar masses in LMICs. Secondary outcomes will include describing the epidemiology, presentation and outcomes of patients with sellar, suprasellar or parasellar masses. This scoping review will be the first to evaluate the current landscape of the management and outcomes of sellar, suprasellar and parasellar masses in LMICs, highlighting important themes that may be used to guide further research as well as health system strengthening efforts by policymakers, governments and stakeholders

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

Hydrogen sulphide (H 2S) 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 H 2S 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 H 2S 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 H 2S 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 H 2S delivery whereas gels without PG have potential for therapy requiring sustained H 2S delivery

OTHR-17 MANAGEMENT AND OUTCOMES OF SELLAR, SUPRASELLAR, AND PARASELLAR MASSES IN LOW- AND MIDDLE-INCOME COUNTRIES: A SCOPING REVIEW AND PROPORTIONAL META-ANALYSIS OF 6584 MASSES

OBJECTIVE: To aggregate data on treatment modalities, management approaches, and clinical outcomes of sellar, suprasellar, and parasellar masses in LMICs. METHODS: We conducted a scoping review as per the Arksey and O’Malley framework. MEDLINE, Embase, Global Index Medicus, and African Journals Online were searched and included articles between 2000 and 2021 screened against predefined eligibility criteria. Pooled statistics were calculated using measures of central tendency and spread. A proportional meta-analysis was conducted to pool the mortality rates. RESULTS: Of the 3526 articles generated by the search strategy, 173 articles were included. The mean age was 35.5 ± 15 years, and most were females (56.47%). Sellar masses predominated (85%; 95% CI = 93.16–118.58), and the most commonly used neuroimaging modality to diagnose these masses was an MRI (65.31%). Surgical resection was mostly utilised with endoscopic surgery (78%; 95% CI = 17.29–154.96) predominating over microsurgery (22%; 95% CI = 11.51–47.73). The transsphenoidal approach was mostly used for both endoscopic surgery and microsurgery (92.13% vs 93.21%), and the extent of resection was gross total resection in most cases (n = 3611). Non-surgical management included hormonal therapies (n = 2080), chemotherapy (n = 96 patients), and radiosurgery (n = 357). New onset diabetes insipidus (34.27%), followed by postoperative infection (27.95%), were the most commonly reported postoperative complications. The pooled overall mortality rate was 8.1% (95% CI: 0.031–0.146). CONCLUSION: Although MRIs are considered to be the gold standard means of diagnosis for these masses, their use in LMICs is less reported. Despite new minimally invasive treatment options, endoscopic surgery is commonly used in LMICs. These translates to the fact that more effort is required in the effective care of patients with these masses in LMICs