Purpose Impaired consciousness in epileptic seizures has a major negative impact on patient quality of life. Prior work on epileptic unconsciousness has mainly used retrospective and nonstandardized methods. Our goal was to validate and to obtain initial data using a standardized prospective testing battery. Methods The responsiveness in epilepsy scale (RES) was used on 52 patients during continuous video/EEG monitoring. RES begins with higher-level questions and commands, and switches adaptively to more basic sensorimotor responses depending on patient performance. RES continues after seizures and includes postictal memory testing. Scoring was conducted based on video review. Key Findings Testing on standardized seizure simulations yielded good intra-rater and inter-rater reliability. We captured 59 seizures from 18 patients (35% of participants) during 1420 hours of RES monitoring. RES impairment was greatest during and after tonic-clonic seizures, less in partial seizures, and minimal in auras and subclinical seizures. In partial seizures, ictal RES impairment was significantly greater if EEG changes were present. Maximum RES impairment (lowest ictal score) was also significantly correlated with long postictal recovery time, and poor postictal memory. Significance We found that prospective testing of responsiveness during seizures is feasible and reliable. RES impairment was related to EEG changes during seizures, as well as to postictal memory deficits and recovery time. With a larger patient sample it is hoped that this approach can identify brain networks underlying specific components of impaired consciousness in seizures. This may allow the development of improved treatments targeted at preventing dysfunction in these networks.
Highlights d Assessed HIV Env-reactive peripheral blood plasmablast response post-vaccination d Boosting with AIDSVAX B/E protein induced robust plasmablast responses d Env-specific repertoire was dominated by VH1 gene usage and V3-region targeting Abs d Plasmablast-derived lineages persisted in bone marrow CD138 + long-lived plasma cells
People with disabilities constitute a marginalized population who experience significant health care disparities resulting from structural, socioeconomic, and attitudinal barriers to accessing health care. It has been reported that education on the care of marginalized groups helps to improve awareness, patient-provider rapport, and patient satisfaction. Yet, emergency medicine (EM) residency education on care for people with disabilities may be lacking. The goal of this paper is to review the current state of health care for patients with disabilities, review the current state of undergraduate and graduate medical education on the care of patients with disabilities, and provide suggestions for an improved EM residency curriculum that includes education on the care for patients with disabilities.
Induction of long-lived plasma cells producing protective HIV-1 Envelope (Env)-specific antibody (Ab) is a primary goal of HIV vaccine strategies. However, vaccine-induced Env-specific human plasma cells have not yet been identified. In an effort to do so, samples were obtained from HVTN 105, a phase I trial in which participants were immunized with the same bivalent gp120 protein, AIDSVAX B/E, as used in RV144, although combined with a DNA immunogen (instead of ALVAC-HIV) in various prime/boost strategies. Participants who received a boosting regimen that included AIDSVAX B/E had robust peripheral blood plasmablast responses as measured by Env-specific ELISpot (n=21) and flow cytometry (n=20). The Env-specific immunoglobulin repertoire of the plasmablasts, assessed by monoclonal Ab generation (>110 mAbs total from 15 participants), was dominated by VH1 gene usage (~60%, VH1-2>VH1-46>VH1-24), and had modest mutation from germline (~5%). Ongoing epitope mapping has indicated V3 is a dominant target; however other regions including V1/V2 and C1/C5 were also targeted. The majority of the mAbs are high avidity, and a subset can mediate Ab-dependent cellular phagocytosis; additional functional analysis is ongoing. Bone marrow was evaluated ~7 months after immunization (n=3), and although ELISpot of CD138+ plasma cells could readily detect influenza specific IgG Ab secreting cells (ASCs), Env-specific IgG ASCs were not convincingly detected by ELISpot. However, when using VH deep sequencing of the bone marrow (n=4), multiple members of plasmablast-derived mAb clonal lineages were detected. Our results indicate that HIV-1 Env-specific B cells are present in human bone marrow after vaccination, but may persist at very low frequency.
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