mRNA vaccination boosts S-specific T cell memory and promotes expansion of CD45RAint TEMRA-like CD8+ T cells in COVID-19 recovered individuals.

SARS-CoV-2 infection and mRNA vaccination both elicit spike (S)-specific T cell responses. To analyze how T cell memory from prior infection influences T cell responses to vaccination, we evaluated functional T cell responses in naive and previously infected vaccine recipients. Pre-vaccine S-specific responses are predictive of subsequent CD8+ T cell vaccine-response magnitudes. Comparing baseline with post-vaccination TCRß repertoires, we observed large clonotypic expansions correlated with the frequency of spike-specific T cells. Epitope mapping the largest CD8+ T cell responses confirms that an HLA-A∗03:01 epitope was highly immunodominant. Peptide-MHC tetramer staining together with mass cytometry and single-cell sequencing permit detailed phenotyping and clonotypic tracking of these S-specific CD8+ T cells. Our results demonstrate that infection-induced S-specific CD8+ T cell memory plays a significant role in shaping the magnitude and clonal composition of the circulating T cell repertoire after vaccination, with mRNA vaccination promoting CD8+ memory T cells to a TEMRA-like phenotype.

Lithotripsy-Assisted Transcatheter Mitral Valve Replacement for Severe Mitral Annular and Valve Calcification.

Background: Transcatheter mitral valve replacement (TMVR) is evolving; however, limitations include severe calcification of the mitral valve leaflets and mitral annular calcification (MAC), which may be associated with incomplete valve expansion. Shockwave intravascular lithotripsy (IVL)-assisted percutaneous mitral valvuloplasty to treat calcific mitral stenosis has been reported. We describe the first human use of IVL-assisted transseptal TMVR with the Intrepid valve to treat a severely calcified mitral valve in a patient with severe stenosis and regurgitation. Methods: An 83-year-old man with rheumatic heart disease and severe MAC (MAC score, 10; calcium volume score, 7756 cm3) presented with combined mitral stenosis and regurgitation (valve area, 1.5 cm2; 3+ mitral regurgitation [MR]) and medically refractory heart failure symptoms and was enrolled into the APOLLO (Transcatheter Mitral Valve Replacement With the Medtronic Intrepid TMVR System in Patients With Severe Symptomatic Mitral Regurgitation) trial of Intrepid valve TMVR. Transseptal implantation of a 48-mm Intrepid valve was facilitated by Shockwave IVL delivered via two 8.0 × 60-mm M5+ balloons placed across the mitral annulus before implantation. Cerebral embolic protection during IVL and valve implant was provided by a Sentinel device and left subclavian balloon occlusion. Results: Despite initial postimplant valve frame deformation and moderate central MR, postdilation achieved valve frame expansion and reduced MR. Echocardiography and computed tomography performed before hospital discharge and at 30 days show progressive valve frame expansion in the anteroposterior dimension, increased valve area, and resolution of MR. Conclusions: Intravascular lithotripsy of severe MAC before self-expanding TMVR may enhance annular compliance, mitigate fibroelastic recoil, and minimize TMVR valve frame deformation. Although promising, further study is required before IVL is considered a routine adjunct for TMVR in severe MAC.

Supporter-focused early intervention for recent sexual assault survivors: Study protocol for a pilot randomized clinical trial.

INTRODUCTION: Sexual assault is a common form of trauma that is associated with elevated risk for negative psychosocial outcomes. Although survivors' social relationships could serve as a major protective factor against negative outcomes, survivors' supporters often lack knowledge regarding effective responses and may inadvertently respond in ways that are detrimental to healing. Communication and Recovery Enhancement (CARE) is a 2-session early intervention for survivors of a past-10-week sexual assault and their supporters that aims to improve supporters' ability to respond effectively. OBJECTIVE: In this paper, we present a study protocol for a pilot randomized clinical trial of CARE (NCT05345405). The goal of this pilot trial is to understand the feasibility, acceptability, and preliminary efficacy of two versions of CARE: a version in which survivors and supporters attend sessions together (dyadic version) and a version in which supporters attend sessions alone (supporter-only version). METHODS: Survivors aged 14+ with elevated posttraumatic stress will enroll with a supporter of their choosing. Dyads will be randomized to dyadic CARE, supporter-only CARE, or waitlist control, and will complete self-report assessments at baseline, post-session-1, and follow-ups (1, 2, and 3 months post-baseline). We will use descriptive statistics, effect sizes, and exploratory statistical tests to characterize the acceptability of both CARE versions, impact on knowledge change from baseline to 1 month, impact on disclosure experiences at 1 month, and impact on functional outcomes at 3 months. DISCUSSION: Results will be used to inform future changes to CARE and determine whether a fully-powered randomized controlled trial is warranted.

Development of a COVID-19 alternate care site from ground zero: A nursing perspective.

The novel coronavirus disease SARS-CoV-2 (COVID-19) outbreak rapidly generated an unprecedented global, national, and state public health crisis with the need to rapidly develop alternate care sites (ACS) to care for COVID-19 patients within an overburdened health care system. A hospital care model ACS to increase the health care capacity, provide care for mild to moderately symptomatic patients, and offer local self-sustainment for a surge of patients was developed in Memphis, Tennessee located in Shelby County. We completed a temporary conversion of a large unused newspaper publication building to a health care facility for COVID-19 patients. Developing an ACS from ground zero was met with many challenges, and throughout the process important lessons were learned. With the goal to complete the building conversion within a 28-day timeframe, collaboration among the numerous governmental, health care, and private agencies was critical and nursing leadership was key to this process. The purpose of this paper is to describe the development of a COVID-19 ACS in Memphis, TN, which has a large at-risk population with limited access to health care. Specifically, we will discuss the strong leadership role of nursing faculty, key challenges, and lessons learned, as well as provide checklists and models for others in similar circumstances.

Factors Associated With Follow-Up Attendance Among Rape Victims Seen in Acute Medical Care.

OBJECTIVE: Rape is associated with posttraumatic stress disorder (PTSD) and related comorbidities. Most victims do not obtain treatment for these conditions. Acute care medical settings are well positioned to link patients to services; however, difficulty engaging victims and low attendance at provided follow-up appointments is well documented. Identifying factors associated with follow-up can inform engagement and linkage strategies. METHOD: Administrative, patient self-report, and provider observational data from Harborview Medical Center were combined for the analysis. Using logistic regression, we examined factors associated with follow-up health service utilization after seeking services for rape in the emergency department. RESULTS: Of the 521 diverse female (n = 476) and male (n = 45) rape victims, 28% attended the recommended medical/counseling follow-up appointment. In the final (adjusted) logistic regression model, having a developmental or other disability (OR = 0.40, 95% CI = 0.21-0.77), having a current mental illness (OR = 0.25, 95% CI = 0.13-0.49), and being assaulted in public (OR = 0.50, 95% CI = 0.28-0.87) were uniquely associated with reduced odds of attending the follow-up. Having a prior mental health condition (OR = 3.02, 95% CI = 1.86-4.91), a completed Sexual Assault Nurse Examiner's (SANE) examination (OR = 2.97, 95% CI = 1.84-4.81), and social support available to help cope with the assault (OR = 3.54, 95% CI = 1.76-7.11) were associated with an increased odds of attending the follow-up. CONCLUSIONS: Findings point to relevant characteristics ascertained at the acute care medical visit for rape that may be used to identify victims less likely to obtain posttraumatic medical and mental health services. Efforts to improve service linkage for these patients is warranted and may require alternative service delivery models that engage rape survivors and support posttraumatic recovery.

Optimization and qualification of a memory B-cell ELISpot for the detection of vaccine-induced memory responses in HIV vaccine trials.

Various aspects of the human immune system can be analyzed to determine the efficacy of a vaccine. We have developed a B-cell ELISpot to measure HIV-specific antibody-secreting B cells in the peripheral blood as a result of vaccination or natural infection. Our method includes stimulating peripheral blood mononuclear cells with interleukin-2 and a polyclonal activator, R848, to induce memory B cells to differentiate into antibody-secreting cells. Total immunoglobulin-secreting as well as antigen-specific B cells are then quantified. We have tested several HIV Env gp120 and gp140 proteins from different HIV subtypes, as well as a sensitive consensus group M Env gp140. Our findings indicate that the B-cell ELISpot provides a sensitive and specific tool to detect antigen-specific memory B-cell responses, and it is equally suited to detect antibody-secreting plasmablasts present in the circulation shortly after infection or vaccination.

Pore-scale investigation of biomass plug development and propagation in porous media.

Biomass plugging of porous media finds application in enhanced oil recovery and bioremediation. An understanding of biomass plugging of porous media was sought by using a porous glass micromodel through which biomass and nutrient were passed. This study describes the pore-scale physics of biomass plug propagation of Leuconostoc mesenteroides under nutrient-rich conditions. It was found that, as the nutrient flowed through the micromodel, the initial biomass plug occurred at the nutrient-inoculum interface due to growth in the larger pore throats. As growth proceeded, biomass filled and closed these larger pore throats, until only isolated groupings of pore throats with smaller radii remained empty. As nutrient flow continued, a maximum pressure drop was reached. At the maximum pressure drop, the biomass yielded in a manner similar to a Bingham plastic to form a breakthrough channel consisting of a path of interconnected pore throats. The channel incorporated the isolated groupings of empty pore throats that had been present before breakthrough. As the nutrient flow continued, subsequent plugs developed as breakthrough channels refilled with biomass and in situ growth was stimulated in the region just downstream of the previous plug. The downstream plugs had a higher fraction of isolated groupings of empty pore throats, which can be attributed to depletion of nutrient downstream. When the next breakthrough channel formed, it incorporated these isolated groupings, causing the breakthrough channels to be branched. It was observed that the newly formed plug could be less stable with this higher fraction of empty pore throats and that the location of breakthrough channels changed in subsequent plugs. This change in breakthrough channel location could be attributed to the redistribution of nutrient flow and the changes in flowrate in the pore throats.