Polypharmacy and Associated Health Outcomes in the PARI-HD Study.

Background: A growing body of evidence points to potential risks associated with polypharmacy (using ≥5 medications) in older adults, but most evidence is derived from studies where racial and ethnic minorities remain underrepresented among research participants. Objective: Investigate the association between polypharmacy and cognitive function, subjective health state, frailty, and falls in Hispanic older adults. Methods: Panama Aging Research Initiative-Health Disparities (PARI-HD) is a community-based cohort study of older adults free of dementia at baseline. Cognitive function was measured with a neuropsychological test battery. Frailty assessment was based on the Fried criteria. Subjective health state and falls were self-reported. Linear and multinomial logistic regression analyses were used to examine association. Results: Baseline evaluations of 468 individuals with a mean age of 69.9 years (SD = 6.8) were included. The median number of medications was 2 (IQR: 1-4); the rate of polypharmacy was 19.7% (95% confidence interval [CI] = 16.1-23.3). Polypharmacy was inversely associated with self-rated overall health (b =-5.89, p < 0.01). Polypharmacy users had 2.3 times higher odds of reporting two or more falls in the previous 12 months (odds ratio [OR] = 2.31, 95% CI = 1.06-5.04). Polypharmacy was independently associated with Fried's criteria for pre-frailty (OR = 2.90, 95% CI = 1.36-5.96) and frailty (OR = 5.14, 95% CI = 1.83-14.42). Polypharmacy was not associated with cognitive impairment. Conclusions: These findings illustrate the potential risks associated with polypharmacy among older adults in Panama and may inform interventions to improve health outcomes in this population.

Digital phenotyping: An equal opportunity approach to reducing disparities in Alzheimer's disease and related dementia research.

A rapidly aging world population is fueling a concomitant increase in Alzheimer's disease (AD) and related dementias (ADRD). Scientific inquiry, however, has largely focused on White populations in Australia, the European Union, and North America. As such, there is an incomplete understanding of AD in other populations. In this perspective, we describe research efforts and challenges of cohort studies from three regions of the world: Central America, East Africa, and East Asia. These cohorts are engaging with the Davos Alzheimer's Collaborative (DAC), a global partnership that brings together cohorts from around the world to advance understanding of AD. Each cohort is poised to leverage the widespread use of mobile devices to integrate digital phenotyping into current methodologies and mitigate the lack of representativeness in AD research of racial and ethnic minorities across the globe. In addition to methods that these three cohorts are already using, DAC has developed a digital phenotyping protocol that can collect ADRD-related data remotely via smartphone and/or in clinic via a tablet to generate a common data elements digital dataset that can be harmonized with additional clinical and molecular data being collected at each cohort site and when combined across cohorts and made accessible can provide a global data resource that is more racially/ethnically represented of the world population.

Development of in-house, indirect ELISAs for the detection of SARS-CoV-2 spike protein-associated serology in COVID-19 patients in Panama.

COVID-19 is the name of the acute respiratory disease caused by the new coronavirus SARS-CoV-2, a close relative of those that caused the severe outbreaks of SARS and MERS several years ago. Since first appearance on December of 2019, the COVID-19 pandemic has cause extremely high levels of mortality, morbidity, global economic breakdown, and the consequent human suffering. The main diagnostic test for the confirmation of symptomatic individuals is the detection of viral RNA by reverse transcriptase-quantitative real time PCR (RT-PCR). Additionally, serology techniques, such as ELISA are useful to measure the antibodies produced in humans after contact with the virus, as well as the direct presence of viral antigens. In this study we aim to assemble and evaluate four ELISA assays to measure the presence of IgG or IgM specific for the viral Spike protein in COVID-19 patients, using either the full recombinant SARS-CoV-2 Spike protein or the fragment corresponding to the receptor binding domain. As a control, we analyzed a group of pre-pandemic serum samples obtained before 2017. Strong reactivity was observed against both antigens. A few pre-pandemic samples displayed high OD values, suggesting the possibility of some cross reactivity. All four assays show very good repeatability, both intra- and inter-assay. Receiver operating characteristic analysis allowed the definition of cutoffs and evaluation of performance for each ELISA by estimation of the area under the curve. This performance parameter was high for all tests (AUC range: 0.98-0.99). Multiple comparisons between tests revealed no significant difference between each other (P values: 0.24-0.95). Our results show that both antigens are effective to detect both specific IgG and IgM antibodies, with high sensitivity (range 0.92-0.99), specificity (range 0.93-0.97) and congruence with the RT-PCR test (Cohen´s Kappa range 0.87-0.93). These assays will allow health authorities to have a new tool to estimate seroprevalence, in order to manage and improve the severe sanitary situation caused by this virus.

An Adenovirus Vector Expressing FMDV RNA Polymerase Combined with a Chimeric VLP Harboring a Neutralizing Epitope as a Prime Boost Strategy to Induce FMDV-Specific Humoral and Cellular Responses.

Foot and mouth disease is a highly contagious disease affecting cattle, sheep, and swine among other cloven-hoofed animals that imposes serious economic burden by its direct effects on farm productivity as well as on commerce of farmed produce. Vaccination using inactivated viral strains of the different serotypes is an effective protective measure, but has several drawbacks including a lack of cross protection and the perils associated with the large-scale growth of infectious virus. We have previously developed chimeric virus-like particles (VLPs) bearing an FMDV epitope which induced strong specific humoral responses in vaccinated pigs but conferred only partial protection against homologous challenge. While this and other FMD vaccines under development mostly rely on the induction of neutralizing responses, it is thought that induction of specific T-cell responses might improve both cross protective efficacy as well as duration of immunity. Therefore, we here describe the development of a recombinant adenovirus expressing the highly conserved nonstructural FMDV 3D protein as well as its capacity to induce specific T-cell responses in a murine model. We further describe the generation of an FMDV serotype C-specific chimeric VLP and analyze the immunogenicity of two different prime-boost strategies combining both elements in mice. This combination can effectively induce both humoral and cellular FMDV-specific responses eliciting high titers of ELISA and neutralizing antibodies anti-FMDV as well as a high frequency of IFNγ-secreting cells. These results provide the basis for further testing of this anti FMD vaccination strategy in cattle or pig, two of the most relevant natural host of this pathogen.

Chimeric RHDV Virus-Like Particles Displaying Foot-and-Mouth Disease Virus Epitopes Elicit Neutralizing Antibodies and Confer Partial Protection in Pigs.

Currently there is a clear trend towards the establishment of virus-like particles (VLPs) as a powerful tool for vaccine development. VLPs are tunable nanoparticles that can be engineered to be used as platforms for multimeric display of foreign antigens. We have previously reported that VLPs derived from rabbit hemorrhagic disease virus (RHDV) constitute an excellent vaccine vector, capable of inducing specific protective immune responses against inserted heterologous T-cytotoxic and B-cell epitopes. Here, we evaluate the ability of chimeric RHDV VLPs to elicit immune response and protection against Foot-and-Mouth disease virus (FMDV), one of the most devastating livestock diseases. For this purpose, we generated a set of chimeric VLPs containing two FMDV-derived epitopes: a neutralizing B-cell epitope (VP1 (140-158)) and a T-cell epitope [3A (21-35)]. The epitopes were inserted joined or individually at two different locations within the RHDV capsid protein. The immunogenicity and protection potential of the chimeric VLPs were analyzed in the mouse and pig models. Herein we show that the RHDV engineered VLPs displaying FMDV-derived epitopes elicit a robust neutralizing immune response in mice and pigs, affording partial clinical protection against an FMDV challenge in pigs.

Performance of a Point of Care Test for Detecting IgM and IgG Antibodies Against SARS-CoV-2 and Seroprevalence in Blood Donors and Health Care Workers in Panama.

Novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic, which has reached 28 million cases worldwide in 1 year. The serological detection of antibodies against the virus will play a pivotal role in complementing molecular tests to improve diagnostic accuracy, contact tracing, vaccine efficacy testing, and seroprevalence surveillance. Here, we aimed first to evaluate a lateral flow assay's ability to identify specific IgM and IgG antibodies against SARS-CoV-2 and second, to report the seroprevalence estimates of these antibodies among health care workers and healthy volunteer blood donors in Panama. We recruited study participants between April 30th and July 7th, 2020. For the test validation and performance evaluation, we analyzed serum samples from participants with clinical symptoms and confirmed positive RT-PCR for SARS-CoV-2, and a set of pre-pandemic serum samples. We used two by two table analysis to determine the test positive and negative percentage agreement as well as the Kappa agreement value with a 95% confidence interval. Then, we used the lateral flow assay to determine seroprevalence among serum samples from COVID-19 patients, potentially exposed health care workers, and healthy volunteer donors. Our results show this assay reached a positive percent agreement of 97.2% (95% CI 84.2-100.0%) for detecting both IgM and IgG. The assay showed a Kappa of 0.898 (95%CI 0.811-0.985) and 0.918 (95% CI 0.839-0.997) for IgM and IgG, respectively. The evaluation of serum samples from hospitalized COVID-19 patients indicates a correlation between test sensitivity and the number of days since symptom onset; the highest positive percent agreement [87% (95% CI 67.0-96.3%)] was observed at ≥15 days post-symptom onset (PSO). We found an overall antibody seroprevalence of 11.6% (95% CI 8.5-15.8%) among both health care workers and healthy blood donors. Our findings suggest this lateral flow assay could contribute significantly to implementing seroprevalence testing in locations with active community transmission of SARS-CoV-2.

Depression Mediates the Association Between Occupational Complexity and Late-Life Cognition in Hispanics.

There is a dearth of research in Latin America regarding risk and protective factors affecting older adults' cognition. This study aimed to investigate the factors mediating the association between occupational complexity and late-life cognition and daily function in a sample of Hispanic older adults. Participants (n = 588) aged 65 years and older underwent clinical, functional, and cognitive assessments. Mediation analyses revealed that depressive symptoms mediated the relationship between occupational complexity and cognitive as well as functional outcomes. Results provide evidence that depression may act as a risk factor for worse outcomes, even if older adults had a cognitively demanding occupation.