Cutting Edge: T Cell Responses to B.1.1.529 (Omicron) SARS-CoV-2 Variant Induced by COVID-19 Infection and/or mRNA Vaccination Are Largely Preserved.

Several studies have demonstrated that the SARS-CoV-2 variant-of-concern B.1.1.

Early age-related atrophy of cutaneous lymph nodes precipitates an early functional decline in skin immunity in mice with aging.

Secondary lymphoid organs (SLOs) (including the spleen and lymph nodes [LNs]) are critical both for the maintenance of naive T (TN) lymphocytes and for the initiation and coordination of immune responses. How they age, including the exact timing, extent, physiological relevance, and the nature of age-related changes, remains incompletely understood. We used “time stamping” to indelibly mark newly generated naive T cells (also known as recent thymic emigrants) (RTEs) in mice, and followed their presence, phenotype, and retention in SLOs.

Stakeholder engagement and participation in the design, delivery, and dissemination of the ostomy self-management telehealth (OSMT) program.

Purpose: Stakeholder engagement is increasingly integrated into clinical research processes. We conducted a mixed methods analysis to describe stakeholders' (peer ostomates, ostomy nurses, telehealth engineers) perceptions of their engagement and participation in a multisite, randomized trial of a telehealth-delivered curriculum for cancer survivors with ostomies.

Methods: Stakeholder notes were analyzed using narrative analysis.

Smartphone-based sensitive detection of SARS-CoV-2 from saline gargle samples via flow profile analysis on a paper microfluidic chip.

Respiratory viruses, especially coronaviruses, have resulted in worldwide pandemics in the past couple of decades. Saliva-based paper microfluidic assays represent an opportunity for noninvasive and rapid screening, yet both the sample matrix and test method come with unique challenges. In this work, we demonstrated the rapid and sensitive detection of SARS-CoV-2 from saliva samples, which could be simpler and more comfortable for patients than existing methods.

Frailty assessment using a novel approach based on combined motor and cardiac functions: a pilot study.

Background: Previous research showed association between frailty and an impaired autonomic nervous system; however, the direct effect of frailty on heart rate (HR) behavior during physical activity is unclear. The purpose of the current study was to determine the association between HR increase and decrease with frailty during a localized upper-extremity function (UEF) task to establish a multimodal frailty test.

Methods: Older adults aged 65 or older were recruited and performed the UEF task of rapid elbow flexion for 20 s with the right arm.

Opioid-induced microglia reactivity modulates opioid reward, analgesia, and behavior.

Opioid-induced microglia reactivity affects opioid reward and analgesic processes in ways that may contribute to the neurocognitive impairment observed in opioid addicted individuals. Opioids elicit microglia reactivity through the actions of opioid metabolites at TLR4 receptors, that are located primarily on microglia but are also present on astrocytes. Specifically, the M3G metabolite, which has no affinity for opioid receptors, exerts off-target effects on TLR4 receptors that can trigger downstream immunologic consequences.

Splenocyte transfer from hypertensive donors eliminates premenopausal female protection from ANG II-induced hypertension.

Premenopausal females are protected from angiotensin II (ANG II)-induced hypertension following the adoptive transfer of T cells from normotensive donors. For the present study, we hypothesized that the transfer of hypertensive T cells (HT) or splenocytes (HS) from hypertensive donors would eliminate premenopausal protection from hypertension. Premenopausal recombination-activating gene-1 (Rag-1) females received either normotensive (NT) or hypertensive cells 3 wk before ANG II infusion (14 days, 490 ng/kg/min).

Direct capture and smartphone quantification of airborne SARS-CoV-2 on a paper microfluidic chip.

SARS, a new type of respiratory disease caused by SARS-CoV, was identified in 2003 with significant levels of morbidity and mortality. The recent pandemic of COVID-19, caused by SARS-CoV-2, has generated even greater extents of morbidity and mortality across the entire world. Both SARS-CoV and SARS-CoV-2 spreads through the air in the form of droplets and potentially smaller droplets (aerosols) via exhaling, coughing, and sneezing.

Post-Stroke Administration of the p75 Neurotrophin Receptor Modulator, LM11A-31, Attenuates Chronic Changes in Brain Metabolism, Increases Neurotransmitter Levels, and Improves Recovery.

The aim of this study was to test whether poststroke oral administration of a small molecule p75 neurotrophin receptor (p75) modulator (LM11A-31) can augment neuronal survival and improve recovery in a mouse model of stroke. Mice were administered LM11A-31 for up to 12 weeks, beginning 1 week after stroke. Metabolomic analysis revealed that after 2 weeks of daily treatment, mice that received LM11A-31 were distinct from vehicle-treated mice by principal component analysis and had higher levels of serotonin, acetylcholine, and dopamine in their ipsilateral hemisphere.

Research and resource needs for understanding host immune responses to SARS-CoV-2 and COVID-19 vaccines during aging.

On 16 and 17 March 2021, the National Institute of Allergy and Infectious Diseases and the National Institute of Aging convened a virtual workshop to discuss developments in SARS-CoV-2 research pertaining to immune responses in older adults, COVID-19 vaccines in both aged animals and older individuals, and to gain some perspective on the critical knowledge gaps that need addressing to establish scientific priorities for future research studies.

Repeated Administration of 2-Hydroxypropyl-β-Cyclodextrin (HPβCD) Attenuates the Chronic Inflammatory Response to Experimental Stroke.

Globally, more than 67 million people are living with the effects of ischemic stroke. Importantly, many stroke survivors develop a chronic inflammatory response that may contribute to cognitive impairment, a common and debilitating sequela of stroke that is insufficiently studied and currently untreatable. 2-Hydroxypropyl-β-cyclodextrin (HPβCD) is an FDA-approved cyclic oligosaccharide that can solubilize and entrap lipophilic substances.

Age-Related Differences in T-Cell Subsets in a Nationally Representative Sample of People Older Than Age 55: Findings From the Health and Retirement Study.

Though T-cell immunosenescence is a major risk factor for age-related diseases, susceptibility to infections, and responses to vaccines, differences in T-cell subset counts and representation by age and sex have not been determined for a large sample representative of the national population of the United States. We evaluated the counts of T-cell subsets including total, CD4+, and CD8+ T cells and their naïve (Tn), effector memory (Tem), and effector subsets, in the context of age, sex, and exposure to cytomegalovirus (CMV) infection among 8 848 Health and Retirement Study participants, a nationally representative study of adults older than 55 years. Total T cells (CD3+) and CD4+ cells declined markedly with age; CD8+ T cells declined somewhat less.

Immune responses to two and three doses of the BNT162b2 mRNA vaccine in adults with solid tumors.

Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have shown high efficacy, but immunocompromised participants were excluded from controlled clinical trials. In this study, we compared immune responses to the BNT162b2 mRNA Coronavirus Disease 2019 vaccine in patients with solid tumors (n = 53) who were on active cytotoxic anti-cancer therapy to a control cohort of participants without cancer (n = 50). Neutralizing antibodies were detected in 67% of patients with cancer after the first immunization, followed by a threefold increase in median titers after the second dose.

Antihypertensive drug treatment and susceptibility to SARS-CoV-2 infection in human PSC-derived cardiomyocytes and primary endothelial cells.

The pathogenicity of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been attributed to its ability to enter through the membrane-bound angiotensin-converting enzyme 2 (ACE2) receptor. Therefore, it has been heavily speculated that angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) therapy may modulate SARS-CoV-2 infection. In this study, exposure of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) and human endothelial cells (hECs) to SARS-CoV-2 identified significant differences in protein coding genes involved in immunity, viral response, and cardiomyocyte/endothelial structure.

Infection-induced type I interferons critically modulate the homeostasis and function of CD8 naïve T cells.

Naïve T (Tn) cells require two homeostatic signals for long-term survival: tonic T cell receptor:self-peptide-MHC contact and IL-7 stimulation. However, how microbial exposure impacts Tn homeostasis is still unclear. Here we show that infections can lead to the expansion of a subpopulation of long-lived, Ly6C CD8 Tn cells with accelerated effector function.

Physical and Cognitive Function Assessment to Predict Postoperative Outcomes of Abdominal Surgery.

Background: Current evaluation methods to assess physical and cognitive function are limited and often not feasible in emergency settings. The upper-extremity function (UEF) test to assess physical and cognitive performance using wearable sensors. The purpose of this study was to examine the (1) relationship between preoperative UEF scores with in-hospital outcomes; and (2) association between postoperative UEF scores with 30-d adverse outcomes among adults undergoing emergent abdominal surgery.

Immune response to COVID-19 in older adults.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the third highly pathogenic coronavirus to emerge in the human population in last two decades. SARS-CoV-2 spread from Wuhan, China, across the globe, causing an unprecedented public healthcare crisis. The virus showed remarkable age dependent pathology, with symptoms resembling common cold in most adults and children while causing more severe respiratory distress and significant mortality in older and frail humans.

Nonlinear analysis of the movement variability structure can detect aging-related differences among cognitively healthy individuals.

Studying the dynamics of nonlinear systems can provide additional information about the variability structure of the system. Within the current study, we examined the application of regularity and local stability measures to capture motor function alterations due to dual-tasking using a previously validated upper-extremity function (UEF). We targeted young (ages 18 and 30 years) and older adults (65 years or older) with normal cognition based on clinical screening.

Immune Responses to COVID-19 mRNA Vaccines in Patients with Solid Tumors on Active, Immunosuppressive Cancer Therapy.

Vaccines against SARS-CoV-2 have shown high efficacy, but immunocompromised participants were excluded from controlled clinical trials. We compared immune responses to the Pfizer/BioNTech mRNA vaccine in solid tumor patients (n=53) on active cytotoxic anti-cancer therapy to a control cohort (n=50) as an observational study. Using live SARS-CoV-2 assays, neutralizing antibodies were detected in 67% and 80% of cancer patients after the first and second immunizations, respectively, with a 3-fold increase in median titers after the booster.

Dual-task performance is associated with brain MRI Morphometry in individuals with mild cognitive impairment.

Background And Purpose: Cognitive impairment is a critical health problem in the elderly population. Research has shown that patients with mild cognitive impairment (MCI) may develop dementia in later years. Therefore, early identification of MCI could allow for interventions to help delay the progression of this devastating disease.

IL-6 can singlehandedly drive many features of frailty in mice.

Frailty is a geriatric syndrome characterized by age-related declines in function and reserve resulting in increased vulnerability to stressors. The most consistent laboratory finding in frail subjects is elevation of serum IL-6, but it is unclear whether IL-6 is a causal driver of frailty. Here, we characterize a new mouse model of inducible IL-6 expression (IL-6 mice) following administration of doxycycline (Dox) in food.

Transcranial magnetic stimulation reveals diminished homoeostatic metaplasticity in cognitively impaired adults.

Homoeostatic metaplasticity is a neuroprotective physiological feature that counterbalances Hebbian forms of plasticity to prevent network destabilization and hyperexcitability. Recent animal models highlight dysfunctional homoeostatic metaplasticity in the pathogenesis of Alzheimer's disease. However, the association between homoeostatic metaplasticity and cognitive status has not been systematically characterized in either demented or non-demented human populations, and the potential value of homoeostatic metaplasticity as an early biomarker of cognitive impairment has not been explored in humans.