Ethnic Inequalities in Psychological Distress : A Population Data Linkage Study on the Pacific Island of Guåhån/Guam

Psychological distress and mental illness has been found to be elevated in migrant groups living in sovereign countries, as well as for indigenous people living under colonial or administrative rule. The north Pacific island of Guam is unusual in its ethnic composition as it has no majority ethnic group, has a large indigenous population and remains a territory of the U.S. This study aimed to identify ethnic differences in self-reported psychological distress between the main ethnic groups on Guam. The study uses a cross sectional design with data linkage methodology, drawing on the Guam Census and the Behavioral Risk Factor Surveillance System health survey for Guam. The results showed that the native Chamorro population had worse self-reported psychological distress (defined as a ‘mental health condition or emotional problem’) than White/Caucasians (OR 2.09, 95% CI 1.52–2.87), particularly for severe distress (OR 3.61, 95% CI 1.33–2.77). This relationship persisted even after adjusting for a wide range of socio-demographic and economic factors (OR 2.58, 95% CI 1.15–5.76). Other Pacific Islanders also had higher psychological distress compared to White/Caucasians, but this association was largely explained by the adjusted factors. The findings are discussed in terms of social and economic disadvantage for Pacific Island peoples on Guam, as well as the impact of colonial administration, disaffection, and lack of autonomy for the Chamorro of Guam. Recommendations are made to improve psychiatric treatment for these groups by considering wider socio-political factors in assessment and treatment, as well as broader implications for the national dialogue on self-determination.Peer reviewe

Therapeutic advantage of pro-electrophilic drugs to activate the Nrf2/ARE pathway in Alzheimer’s disease models

Alzheimer's disease (AD) is characterized by synaptic and neuronal loss, which occurs at least partially through oxidative stress induced by oligomeric amyloid-β (Aβ)-peptide. Carnosic acid (CA), a chemical found in rosemary and sage, is a pro-electrophilic compound that is converted to its active form by oxidative stress. The active form stimulates the Keap1/Nrf2 transcriptional pathway and thus production of phase 2 antioxidant enzymes. We used both in vitro and in vivo models. For in vitro studies, we evaluated protective effects of CA on primary neurons exposed to oligomeric Aβ. For in vivo studies, we used two transgenic mouse models of AD, human amyloid precursor protein (hAPP)-J20 mice and triple transgenic (3xTg AD) mice. We treated these mice trans-nasally with CA twice weekly for 3 months. Subsequently, we performed neurobehavioral tests and quantitative immunohistochemistry to assess effects on AD-related phenotypes, including learning and memory, and synaptic damage. In vitro, CA reduced dendritic spine loss in rat neurons exposed to oligomeric Aβ. In vivo, CA treatment of hAPP-J20 mice improved learning and memory in the Morris water maze test. Histologically, CA increased dendritic and synaptic markers, and decreased astrogliosis, Aβ plaque number, and phospho-tau staining in the hippocampus. We conclude that CA exhibits therapeutic benefits in rodent AD models and since the FDA has placed CA on the ‘generally regarded as safe' (GRAS) list, thus obviating the need for safety studies, human clinical trials will be greatly expedited

Ocular Drug Delivery

Ocular drug delivery has been a major challenge to pharmacologists and drug delivery scientists due to its unique anatomy and physiology. Static barriers (different layers of cornea, sclera, and retina including blood aqueous and blood–retinal barriers), dynamic barriers (choroidal and conjunctival blood flow, lymphatic clearance, and tear dilution), and efflux pumps in conjunction pose a significant challenge for delivery of a drug alone or in a dosage form, especially to the posterior segment. Identification of influx transporters on various ocular tissues and designing a transporter-targeted delivery of a parent drug has gathered momentum in recent years. Parallelly, colloidal dosage forms such as nanoparticles, nanomicelles, liposomes, and microemulsions have been widely explored to overcome various static and dynamic barriers. Novel drug delivery strategies such as bioadhesive gels and fibrin sealant-based approaches were developed to sustain drug levels at the target site. Designing noninvasive sustained drug delivery systems and exploring the feasibility of topical application to deliver drugs to the posterior segment may drastically improve drug delivery in the years to come. Current developments in the field of ophthalmic drug delivery promise a significant improvement in overcoming the challenges posed by various anterior and posterior segment diseases