Generation, expansion, gene delivery, and single-cell profiling in rhesus macaque plasma B cells.

A key step in developing engineered B cells for therapeutic purposes is evaluation in immunocompetent, large-animal models. Therefore, we developed methods to purify, expand, and differentiate non-human primate (NHP; rhesus macaque) B cells. After 7 days in culture, B cells expanded 10-fold, differentiated into a plasma cell phenotype (CD38, CD138), and secreted immunoglobulin G.

Bioethics at the bedside: considering the adolescent voice in withdrawal of life-sustaining therapy.

Durable mechanical circulatory devices are commonly used to support children and adolescents in end-stage heart failure. However, these patients remain at high risk of acute medical complications, which may lead to significant impairment in functional capacity, altered quality of life, or death. We explore the incorporation of adolescent directives into medical decision-making in this scenario through a clinical case vignette.

Reduction of the acquisition time needed to obtain somatosensory evoked potentials by estimation of the required averaging sweep count by an algorithm.

Somatosensory evoked potentials are frequently acquired by stimulation of the median or tibial nerves (mSEPs and tSEPs) for intraoperative monitoring of sensory pathways. Due to their low amplitudes it is common practice to average 200 or more sweeps to discern the evoked potentials from the background EEG. The aim of this study was to investigate if an algorithm designed to determine the lowest sweep count needed to obtain reproducible evoked potentials in each patient significantly reduces the median necessary sweep count to under 200.

Healthcare Provider Experiences With Unvaccinated COVID-19 Patients: A Qualitative Study.

Importance: In the setting of an active pandemic the impact of public vaccine hesitancy on healthcare workers has not yet been explored. There is currently a paucity of literature that examines how patient resistance to disease prevention in general impacts practitioners.

Objectives: The COVID-19 pandemic created unprecedented healthcare challenges with impacts on healthcare workers' wellbeing.

Head movement dynamics in dystonia: a multi-centre retrospective study using visual perceptive deep learning.

Dystonia is a neurological movement disorder characterised by abnormal involuntary movements and postures, particularly affecting the head and neck. However, current clinical assessment methods for dystonia rely on simplified rating scales which lack the ability to capture the intricate spatiotemporal features of dystonic phenomena, hindering clinical management and limiting understanding of the underlying neurobiology. To address this, we developed a visual perceptive deep learning framework that utilizes standard clinical videos to comprehensively evaluate and quantify disease states and the impact of therapeutic interventions, specifically deep brain stimulation.

Invasive Group A Streptococcal Infections in Pediatric Critical Care: A Retrospective Cohort Study.

Background And Objective: The reported rising global rates of invasive group A Streptococcus (iGAS) infection raise concern for disease related increase in critical illness and fatalities. An enhanced understanding of various presentations to health care and clinical course could improve early recognition and therapy in children with iGAS. The objective of this study was to describe the epidemiology of iGAS infections among children admitted to critical care.

Effect of Thalamic versus Pallidal Deep Brain Stimulation on Head Tremor in Dystonic and Essential Tremor Patients-A Retrospective Video-Blinded Study.

Background: Head tremor is common in dystonia syndromes and difficult to treat. Deep brain stimulation (DBS) is a therapeutic option in medically-refractory cases. In most DBS-centers, the globus pallidus internus (GPi) is targeted in patients with predominant dystonia and the ventrointermediate nucleus of the thalamus (Vim) in predominant tremor.

Through the looking glass: qualitative study of critical care clinicians engaging in humanities.

Purpose: Critical care medicine is facing an epidemic of burnout and consequent attrition. Interventions are needed to re-establish the medical field as a place of professional growth, resilience, and personal well-being. Humanities facilitate creation, reflection, and meaning-making, holding the promise of personal and community transformation.

The role of the motor thalamus in deep brain stimulation for essential tremor.

The advent of next-generation technology has significantly advanced the implementation and delivery of Deep Brain Stimulation (DBS) for Essential Tremor (ET), yet controversies persist regarding optimal targets and networks responsible for tremor genesis and suppression. This review consolidates key insights from anatomy, neurology, electrophysiology, and radiology to summarize the current state-of-the-art in DBS for ET. We explore the role of the thalamus in motor function and describe how differences in parcellations and nomenclature have shaped our understanding of the neuroanatomical substrates associated with optimal outcomes.

The Challenge of Choosing the Right Stimulation Target for Dystonic Tremor-A Series of Instructive Cases.

Background: Thalamic deep brain stimulation (DBS) is established for medically refractory tremor syndromes and globus pallidus stimulation (GPi-DBS) for medically refractory dystonia syndromes. For combined tremor and dystonia syndromes, the best target is unclear.

Objectives: We present four patients with two different profiles whose clinical course demonstrates that our current analysis of clinical symptomatology is not a sufficient predictor of surgical success.

The Role of Levodopa Challenge in Predicting the Outcome of Subthalamic Deep Brain Stimulation.

Background: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective and evidence-based treatment for idiopathic Parkinson's disease (iPD). A minority of patients does not sufficiently benefit from STN-DBS.

Objective: The predictive validity of the levodopa challenge for individual patients is analyzed.

The care of critically ill adults with COVID-19 in Ontario pediatric intensive care units.

Purpose: To describe and review the experience of two pediatric intensive care units (PICUs) in Ontario, Canada, adapting and providing care to critically ill adults during the COVID-19 pandemic.

Clinical Features: At a time of extreme pressure to adult intensive care unit (ICU) capacity, two PICUs provided care to critically ill adults with COVID-19 pneumonia. Substantial yet rapid planning was required to facilitate safe delivery of critical care to adult patients while maintaining PICU services, including thoughtful development of care pathways and patient selection.

Intravenous thrombolysis and mechanical recanalization for acute ischemic stroke in deep brain stimulation patients: a case series.

Background: Intravenous thrombolysis (IVT) and endovascular mechanical thrombectomy therapy (MT) are well established in the treatment of acute ischemic stroke. It is currently unclear whether these treatments can be applied in patients with previous deep brain stimulation (DBS) surgery and how long the interval to the DBS operation should be.

Methods: Four patients with ischemic stroke and IVT or MT were included in this retrospective case series.

Long-term efficacy with deep brain stimulation of the globus pallidus internus in cervical dystonia: a retrospective monocentric study.

Background: Cervical dystonia (CD) is characterized by involuntary contractions of the cervical muscles. Data on long-term effectiveness of deep brain stimulation (DBS) are rare. The aim of this study was to evaluate the longitudinal ten years treatment efficacy of DBS in the globus pallidus internus (GPI).

Measurement of ATP utilization in RNA unwinding and RNA chaperone activities by DEAD-box helicase proteins.

RNA helicase proteins perform coupled reactions in which cycles of ATP binding and hydrolysis are used to drive local unwinding of double-stranded RNA (dsRNA). For some helicases in the ubiquitous DEAD-box family, these local unwinding events are integral to folding transitions in structured RNAs, and thus these helicases function as RNA chaperones. An important measure of the efficiency of the helicase-catalyzed reaction is the ATP utilization value, which represents the average number of ATP molecules hydrolyzed during RNA unwinding or a chaperone-assisted RNA structural rearrangement.

The Contribution of Subthalamic Nucleus Deep Brain Stimulation to the Improvement in Motor Functions and Quality of Life.

Background: Subthalamic nucleus deep brain stimulation (STN-DBS) effectively treats motor symptoms and quality of life (QoL) of advanced and fluctuating early Parkinson's disease. Little is known about the relation between electrode position and changes in symptom control and ultimately QoL.

Objectives: The relation between the stimulated part of the STN and clinical outcomes, including the motor score of the Unified Parkinson's Disease Rating Scale (UPDRS) and the quality-of-life questionnaire, was assessed in a subcohort of the EARLYSTIM study.

MaDoPO: Magnetic Detection of Positions and Orientations of Segmented Deep Brain Stimulation Electrodes: A Radiation-Free Method Based on Magnetoencephalography.

Background: Current approaches to detect the positions and orientations of directional deep brain stimulation (DBS) electrodes rely on radiative imaging data. In this study, we aim to present an improved version of a radiation-free method for magnetic detection of the position and the orientation (MaDoPO) of directional electrodes based on a series of magnetoencephalography (MEG) measurements and a possible future solution for optimized results using emerging on-scalp MEG systems.

Methods: A directional DBS system was positioned into a realistic head-torso phantom and placed in the MEG scanner.

Who am I? Narratives as a window to transformative moments in critical care.

Critical care clinicians practice a liminal medicine at the border between life and death, witnessing suffering and tragedy which cannot fail to impact the clinicians themselves. Clinicians' professional identity is predicated upon their iterative efforts to articulate and contextualize these experiences, while a failure to do so may lead to burnout. This journey of self-discovery is illuminated by clinician narratives which capture key moments in building their professional identity.

The Treatment of Neglected Clubfoot.

The adolescent neglected clubfoot is mostly treated in humanitarian programs by those with a great deal of surgical experience. This deformity needs a major correction, which can compromise the blood circulation and wound healing. A bony correction is preferable over an isolated soft tissue release.