Faculty Bibliography

Pediatric multiple sclerosis (MS) is an increasingly recognized rare subgroup of patients presenting with a unique set of diagnostic challenges. Understanding the early development of MS may offer a window into the pathogenesis of disease; however further research is needed, particularly within the field of genetics and to understand the complex environmental and biological interactions at work. Acute disseminated encephalomyelitis (ADEM) remains a hallmark presentation of early pediatric disease and can be a monophasic illness or end up being reclassified as a relapsing disorder. The clinical expression is shaped in part by the prepubertal or postpubertal state of the patient. Other syndromes can also present with ADEM, and a specific differential diagnosis exists for children presenting with any initial demyelinating event (IDE). New definitions and criteria have allowed early detection of MS. However applying adult criteria to very young children should be approached with caution. There is now a major effort in studying disease-modifying therapy (DMT) in children due to requirements from regulatory authorities. Pediatric patients respond well to therapy and often do best with an interdisciplinary approach focusing on social aspects, cognition, and fatigue which enhances the achievement of successful outcomes.
Copyright

One means of stimulating the mammalian innate immune system is via Toll-like receptor 9 (TLR9) being exposed to unmethylated cytosine-phosphate-guanine (CpG) DNA, also known as pathogen-associated molecular patterns (PAMPs) of microbial origin. Synthetic CpG oligodeoxynucleotides (ODNs) with defined CpG motifs possess broad immunostimulatory properties that make CpG ODNs suitable as therapeutic interventions in a variety of human disease conditions, including Alzheimer's disease (AD). Rodent models are often used to preclinically test the effectiveness of CpG ODN therapeutic agents for AD and other disorders. However, the translatability of findings in such models is limited due to the significant difference of the expression of TLR9 between primates and rodents. The squirrel monkey (SQM), a New World non-human primate (NHP), is known to be phylogenetically proximate to humans, and develops extensive age-dependent cerebral amyloid angiopathy (CAA), a key pathological feature of AD. Hence, this model is currently being used to test AD therapeutics. In the present study, we conducted the first examination of Class C CpG ODN's immunomodulatory role in elderly SQMs. We documented the effectiveness of CpG ODN to trigger an immune response in an aged cohort whose immune system is senescent. The specific immune response patterns detected here closely resembled CpG ODN-induced immunostimulatory patterns observed in prior human studies. Overall, our findings provide critical data regarding the immunomodulatory potential of CpG ODN in this NHP model, allowing for future translational studies of innate immunity stimulation via TLR9 agonists for diverse indications, including AD therapeutics.

COVID-19 is a severe infectious disease that has claimed >150,000 lives and infected millions in the United States thus far, especially the elderly population. Emerging evidence has shown the virus to cause hemorrhagic and immunologic responses, which impact all organs, including lungs, kidneys, and the brain, as well as extremities. SARS-CoV-2 also affects patients', families', and society's mental health at large. There is growing evidence of re-infection in some patients. The goal of this paper is to provide a comprehensive review of SARS-CoV-2-induced disease, its mechanism of infection, diagnostics, therapeutics, and treatment strategies, while also focusing on less attended aspects by previous studies, including nutritional support, psychological, and rehabilitation of the pandemic and its management. We performed a systematic review of >1,000 articles and included 425 references from online databases, including, PubMed, Google Scholar, and California Baptist University's library. COVID-19 patients go through acute respiratory distress syndrome, cytokine storm, acute hypercoagulable state, and autonomic dysfunction, which must be managed by a multidisciplinary team including nursing, nutrition, and rehabilitation. The elderly population and those who are suffering from Alzheimer's disease and dementia related illnesses seem to be at the higher risk. There are 28 vaccines under development, and new treatment strategies/protocols are being investigated. The future management for COVID-19 should include B-cell and T-cell immunotherapy in combination with emerging prophylaxis. The mental health and illness aspect of COVID-19 are among the most important side effects of this pandemic which requires a national plan for prevention, diagnosis and treatment.

BACKGROUND:Depression is associated with a broad range of cognitive deficits, including processing speed (PS) and executive functioning (EF). Cognitive symptoms commonly persist with the resolution of affective symptoms and increase risk of relapse and recurrence. The cognitive control network is comprised of brain areas implicated in EF and mood regulatory functions. Prior research has demonstrated the effectiveness of computerized cognitive training (CCT) focused on PS and EF in mitigating both cognitive and affective symptoms of depression. METHODS:Ninety participants aged 18-29 with a current diagnosis of major depressive disorder or persistent depressive disorder, or a Hamilton Depression Rating Scale score ≥12, will be randomized to either PS/EF CCT, verbal CCT, or waitlist control. Participants in the active groups will complete 15 min of training 5 days/week for 8 weeks. Clinical and neuropsychological assessments will be completed at baseline, week 4, week 8, and 3-month follow-up. Structural and functional magnetic resonance imaging (fMRI) will be completed at baseline and week 8. We will compare changes in mood, cognition, daily functioning, and fMRI data. We will explore cognitive control network functioning using resting-state and task-based fMRI. RESULTS:Recruitment began in October 2019; we expect to finish recruitment by April 2022 and subsequently begin data analysis. CONCLUSIONS:This study is innovative in that it will include both active and waitlist control conditions and will explore changes in neural activation. Identifying the neural networks associated with improvements following CCT will allow for the development of more precise and effective interventions. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov NCT03869463; https://clinicaltrials.gov/ct2/show/NCT03869463.