Investigating a Multimodal Approach to Clinical Diagnosis of Mild Cognitive Impairment and Alzheimer’s Disease

An estimated 5.8 million Americans suffer from dementia due to Alzheimer’s disease (AD), with that number projected to grow to 13.8 million by mid-century (Alzheimer’s Association, 2019). Mild cognitive impairment (MCI) describes the stage between normal cognitive decline that comes with aging and a dementia diagnosis (Peterson, 1999). Due to a lack of a cure or particularly effective treatment, a major goal of treatment is to focus on improving quality of life (Budson & Solomon, 2016). An early and accurate diagnosis can address this goal in a variety of ways. Despite the high prevalence and immense amount of research in MCI and AD, there is still no individual assessment measure that can definitively diagnose either. A multimodal approach must be implemented by clinicians and investigated by researchers to ensure early and accurate diagnosis. This study used multivariate logistic regression to analyze how two neuropsychological screening tests, two brain structures’ volumes, and an eye-tracking outcome all contributed to the diagnostic process. The two screening tests were the only unique contributors to the predictive model, and there was only slight evidence to suggest that the multimodal approach using these measures improved accuracy of diagnosis

Transmission of Yellow Fever Vaccine Virus Through Blood Transfusion and Organ Transplantation in the USA in 2021: Report of an Investigation

BACKGROUND: In 2021, four patients who had received solid organ transplants in the USA developed encephalitis beginning 2-6 weeks after transplantation from a common organ donor. We describe an investigation into the cause of encephalitis in these patients. METHODS: From Nov 7, 2021, to Feb 24, 2022, we conducted a public health investigation involving 15 agencies and medical centres in the USA. We tested various specimens (blood, cerebrospinal fluid, intraocular fluid, serum, and tissues) from the organ donor and recipients by serology, RT-PCR, immunohistochemistry, metagenomic next-generation sequencing, and host gene expression, and conducted a traceback of blood transfusions received by the organ donor. FINDINGS: We identified one read from yellow fever virus in cerebrospinal fluid from the recipient of a kidney using metagenomic next-generation sequencing. Recent infection with yellow fever virus was confirmed in all four organ recipients by identification of yellow fever virus RNA consistent with the 17D vaccine strain in brain tissue from one recipient and seroconversion after transplantation in three recipients. Two patients recovered and two patients had no neurological recovery and died. 3 days before organ procurement, the organ donor received a blood transfusion from a donor who had received a yellow fever vaccine 6 days before blood donation. INTERPRETATION: This investigation substantiates the use of metagenomic next-generation sequencing for the broad-based detection of rare or unexpected pathogens. Health-care workers providing vaccinations should inform patients of the need to defer blood donation for at least 2 weeks after receiving a yellow fever vaccine. Despite mitigation strategies and safety interventions, a low risk of transfusion-transmitted infections remains. FUNDING: US Centers for Disease Control and Prevention (CDC), the Biomedical Advanced Research and Development Authority, and the CDC Epidemiology and Laboratory Capacity Cooperative Agreement for Infectious Diseases

Children’s conversations reveal in-depth learning at the zoo

Learning in the zoo is a complex process with many influences affecting outcomes, which traditional methods of evaluation may not consider. This study used conversational content analysis, an innovative and under-used technique, to investigate children’s learning in the zoo setting during an educational experience. The children’s conversations were observed at Fota Wildlife Park and Dingle Aquarium in Ireland at three different animal exhibits (1) free-ranging ring-tailed lemurs (Lemur catta) (2) Gentoo penguins (Pygoscelis papua) and (3) Humboldt penguins (Spheniscus humboldti). Some groups of children (the treatment group) participated in a purposefully designed educational intervention, while others (the control group) experienced the standard curriculum only. Descriptive statistics indicated that all children engaged in diverse topics of conversation indicative of learning as they viewed animals. However, further analysis using a general linear model showed that participation in the treatment or control group (p < 0.001) and species viewed (p < 0.001) affected the proportion of positive comments made by children. Groups that viewed free-ranging ring-tailed lemurs and Gentoo penguins made more types of positive comments than those that viewed Humboldt penguins, and children who experienced the educational intervention made more types of positive comments than children in the control group. Conversely, children in the control group made more types of negative comments (p < 0.001) than those in the treatment group. The results indicate that children do learn in the zoo setting; however, this was enhanced based on the type of educational activity the children experienced and the species they viewed. Overheard conversation offers a unique insight into the visitors’ experience at the zoo, but further research is required to establish if conversation can reveal a propensity for pro-conservation behavior

Plasmodium falciparum Liver Stage Infection and Transition to Stable Blood Stage Infection in Liver-Humanized and Blood-Humanized FRGN KO Mice Enables Testing of Blood Stage Inhibitory Antibodies (Reticulocyte-Binding Protein Homolog 5) In Vivo

The invention of liver-humanized mouse models has made it possible to directly study the preerythrocytic stages of Plasmodium falciparum. In contrast, the current models to directly study blood stage infection in vivo are extremely limited. Humanization of the mouse blood stream is achievable by frequent injections of human red blood cells (hRBCs) and is currently the only system with which to study human malaria blood stage infections in a small animal model. Infections have been primarily achieved by direct injection of P. falciparum-infected RBCs but as such, this modality of infection does not model the natural route of infection by mosquito bite and lacks the transition of parasites from liver stage infection to blood stage infection. Including these life cycle transition points in a small animal model is of relevance for testing therapeutic interventions. To this end, we used FRGN KO mice that were engrafted with human hepatocytes and performed a blood exchange under immune modulation to engraft the animals with more than 50% hRBCs. These mice were infected by mosquito bite with sporozoite stages of a luciferase-expressing P. falciparum parasite, resulting in noninvasively measurable liver stage burden by in vivo bioluminescent imaging (IVIS) at days 5–7 postinfection. Transition to blood stage infection was observed by IVIS from day 8 onward and then blood stage parasitemia increased with a kinetic similar to that observed in controlled human malaria infection. To assess the utility of this model, we tested whether a monoclonal antibody targeting the erythrocyte invasion ligand reticulocyte-binding protein homolog 5 (with known growth inhibitory activity in vitro) was capable of blocking blood stage infection in vivo when parasites emerge from the liver and found it highly effective. Together, these results show that a combined liver-humanized and blood-humanized FRGN mouse model infected with luciferase-expressing P. falciparum will be a useful tool to study P. falciparum preerythrocytic and erythrocytic stages and enables the testing of interventions that target either one or both stages of parasite infection