Untangling the Role of TREM2 in Conjugation with Microglia in Neuronal Dysfunction: A Hypothesis on a Novel Pathway in the Pathophysiology of Alzheimer's Disease.

Alzheimer's disease (AD) is a complex neurodegenerative disorder involving heterogenous pathophysiological characteristics, which has become a challenge to therapeutics. The major pathophysiology of AD comprises amyloid-ß (Aß), tau, oxidative stress, and apoptosis. Recent studies indicate the significance of Triggering receptor expressed on myeloid cells 2 (TREM2) and its mutant variants in AD. TREM2 are the transmembrane receptors of microglial cells that performs a broad range of physiological cell processes. Phagocytosis of Aß is one of the physiological roles of TREM2, which plays a pivotal role in AD progression. R47H, a mutant variant of TREM2, increases the risk of AD by impairing TREM2-Aß binding. Inconclusive evidence regarding the TREM2 signaling cascade mechanism of Aß phagocytosis motivates the current review to propose a new hypothesis. The review systematically assesses the cross talk between TREM2 and other AD pathological domains and the influence of TREM2 on amyloid and tau seeding. Disease associated microglia (DAM), a novel state of microglia with unique transcriptional and functional signatures reported in neurodegenerative conditions, also depend on the TREM2 pathway for its differentiation. DAM is suggested to have a neuroprotective role. We hypothesize that TREM2, along with its signaling adaptors and endogenous proteins, play a key role in ameliorating Aß clearance. We indicate that TREM2 has the potential to ameliorate the Aß burden, though with differential clearance ability and may act as a potential therapeutic target.

Dynamics of Mask Use as a Prevention Strategy against SARS-CoV-2 in Panama.

Early in the SARS-CoV-2 pandemic, many national public health authorities implemented non-pharmaceutical interventions to mitigate disease outbreaks. Panamá established mandatory mask use two months after its first documented case. Initial compliance was high, but diverse masks were used in public areas. We studied behavioral dynamics of mask use through the first two COVID-19 waves in Panama, to improve the implementation of effective, low-cost public health containment measures when populations are exposed to novel air-borne pathogens. Mask use behavior was recorded from pedestrians in four Panamanian populations (August to December 2020). We recorded facial coverings and if used, the type of mask, and gender and estimated age of the wearer. Our results showed that people were highly compliant (>95%) with mask mandates and demonstrated important population-level behaviors: (1) decreasing use of cloth masks over time, and increasing use of surgical masks; (2) mask use was 3-fold lower in suburban neighborhoods than other public areas and (3) young people were least likely to wear masks. Results help focus on highly effective, low-cost, public health interventions for managing and controlling a pandemic. Considerations of behavioral preferences for different masks, relative to pricing and availability, are essential for optimizing public health policies. Policies to increase the availability of effective masks, and behavioral nudges to increase acceptance, and to facilitate mask usage, during the ongoing SARS-CoV-2 pandemic, and for future pandemics of respiratory pathogens, are key tools, especially for nations lagging in access to expensive vaccines and pharmacological approaches.

'The dual pandemic' of suicide and COVID-19: A biopsychosocial narrative of risks and prevention.

The Coronavirus disease 2019 (COVID-19) has emerged as a new global health threat. By increasing the risk of isolation, fear, stigma, abuse and economic fallout, COVID-19 has led to increase in risk of psychiatric disorders, chronic trauma and stress, which eventually increase suicidality and suicidal behavior. There is limited data on association of pandemics and suicides. Cases of suicides have been rising since COVID-19 first emerged in China. The association between suicides and pandemics can possibly be explained through various models like Durkheim's theory, Joiner's interpersonal theory, social stress theory, biological theories, etc. The frontline workers, elderly, migrants, homeless, socio-economically impoverished classes as well as those with pre-existing mental disorders, substance abuse and family history of suicides are at higher risk. Suicides are preventable and need early detection, awareness and socio-culturally tailored interventions. This narrative review draws global perspectives on the association of suicidality and pandemics, the theories and risk factors related to same based on the available evidence. It also hypothesizes neuroimmunity and immune based risk factors as possible links between the psychosocial vulnerabilities and suicide during outbreaks like COVID-19. Proposed strategies of suicide-prevention, as an integral part of public health response to the pandemic are subsequently discussed.