It's a spiral staircase, not just two steps: An iterative approach to assessing patient capacity for medical decision-making.

The assessment of medical decision-making capacity as part of the process of clinical informed consent has been considered a bioethical housekeeping matter for decades. Yet in practice, the reality bears little resemblance to what is described in the medical literature and professed in medical education. Most literature on informed consent refers to medical decision-making capacity as a precondition to the consent process.

Heterogeneity in lung macrophage control of Mycobacterium tuberculosis is modulated by T cells.

Following Mycobacterium tuberculosis infection, alveolar macrophages are initially infected but ineffectively restrict bacterial replication. The distribution of M. tuberculosis among different cell types in the lung changes with the onset of T cell immunity when the dominant infected cellular niche shifts from alveolar to monocyte-derived macrophages (MDM).

Gamified Crowdsourcing as a Novel Approach to Lung Ultrasound Data Set Labeling: Prospective Analysis.

Background: Machine learning (ML) models can yield faster and more accurate medical diagnoses; however, developing ML models is limited by a lack of high-quality labeled training data. Crowdsourced labeling is a potential solution but can be constrained by concerns about label quality.

Objective: This study aims to examine whether a gamified crowdsourcing platform with continuous performance assessment, user feedback, and performance-based incentives could produce expert-quality labels on medical imaging data.

Visual Outcomes and Risk of Endophthalmitis in Open Globe Injuries without Intraocular Foreign Bodies with Delayed Repair.

Purpose: To assess and compare the rate of endophthalmitis and visual outcomes in cases of open globe injuries (OGIs) without intraocular foreign bodies repaired within and greater than 24 hours from the time of injury.

Design: A retrospective review of 2002 cases of OGIs presenting to a single institution.

Participants: Patients with OGIs were admitted and managed according to a standardized protocol.

Performance of Single-Lead Handheld Electrocardiograms for Atrial Fibrillation Screening in Primary Care: The VITAL-AF Trial.

Background: Handheld single-lead electrocardiographic (1L ECG) devices are increasingly used for atrial fibrillation (AF) screening, but their real-world performance is not well understood.

Objectives: The purpose of this study was to quantify the diagnostic test characteristics of 1L ECG automated interpretations for prospective AF screening.

Methods: We calculated the diagnostic test characteristics of the AliveCor KardiaMobile 1L ECG (AliveCor, US) algorithm using unblinded cardiologist overread as the gold standard using single 30s tracings administered by medical assistants among individuals aged ≥65 years participating in the VITAL-AF trial (NCT03515057) of population-based AF screening embedded within routine primary care.

Arrestin-3-assisted activation of JNK3 mediates dopaminergic behavioral sensitization.

In rodents with unilateral ablation of neurons supplying dopamine to the striatum, chronic treatment with the dopamine precursor L-DOPA induces a progressive increase of behavioral responses, a process known as behavioral sensitization. This sensitization is blunted in arrestin-3 knockout mice. Using virus-mediated gene delivery to the dopamine-depleted striatum of these mice, we find that the restoration of arrestin-3 fully rescues behavioral sensitization, whereas its mutant defective in c-Jun N-terminal kinase (JNK) activation does not.

Development of a predictive algorithm for patient survival after traumatic injury using a five analyte blood panel.

Severe trauma can induce systemic inflammation but also immunosuppression, which makes understanding the immune response of trauma patients critical for therapeutic development and treatment approaches. By evaluating the levels of 59 proteins in the plasma of 50 healthy volunteers and 1000 trauma patients across five trauma centers in the United States, we identified 6 novel changes in immune proteins after traumatic injury and further new variations by sex, age, trauma type, comorbidities, and developed a new equation for prediction of patient survival. Blood was collected at the time of arrival at Level 1 trauma centers and patients were stratified based on trauma level, tissues injured, and injury types.

Rodents Used for the Propagation of Hookworms and .

Helminthiasis due to hookworm infestations in humans and in sheep cause untold levels of disease and economic losses worldwide. Drug resistance is an ever-growing problem with pathogenic helminths. Thus, there is a critical need for new treatment strategies for hookworms and that depends on animal models.

KRAS Promotes GLI2-Dependent Transcription during Pancreatic Carcinogenesis.

Aberrant activation of GLI transcription factors has been implicated in the pathogenesis of different tumor types including pancreatic ductal adenocarcinoma. However, the mechanistic link with established drivers of this disease remains in part elusive. In this study, using a new genetically engineered mouse model overexpressing constitutively active mouse form of GLI2 and a combination of genome-wide assays, we provide evidence of a novel mechanism underlying the interplay between KRAS, a major driver of pancreatic ductal adenocarcinoma development, and GLI2 to control oncogenic gene expression.

Adeno-associated viral delivery of Env-specific antibodies prevents SIV rebound after discontinuing antiretroviral therapy.

An alternative to lifelong antiretroviral therapy (ART) is needed to achieve durable control of HIV-1. Here we show that adeno-associated virus (AAV)-delivery of two rhesus macaque antibodies to the SIV envelope glycoprotein (Env) with potent neutralization and antibody-dependent cellular cytotoxicity can prevent viral rebound in macaques infected with barcoded SIV239M after discontinuing suppressive ART. Following AAV administration, sustained antibody expression with minimal anti-drug antibody responses was achieved in all but one animal.

Unveiling Melanoma: A Deep Dive into Disparities at a Latin-American Cancer Institute.

Introduction: The worldwide incidence of melanoma has increased in the last 40 years. Our aim was to describe the clinic-pathological characteristics and outcomes of three cohorts of patients diagnosed with melanoma in a Latin-American cancer institute during the last 20 years.

Methods: We evaluated three retrospective patient cohorts diagnosed with melanoma at Instituto Nacional de Enfermedades Neoplasicas (INEN), a public hospital in Lima, Peru, for the years 2005-2006, 2010-2011, and 2017-2018.

GENETIC ABLATION OF THE C-TYPE LECTIN RECEPTOR CLEC2D INCREASES PERITONITIS MORTALITY, INFLAMMATION, AND PHYSIOLOGY WITHOUT DIMINISHING ORGAN INJURY.

Background: Sepsis accounts for substantial morbidity and mortality motivating investigators to continue the search for pathways and molecules driving the pathogenesis of the disease. The current study examined if the novel C-type lectin receptor (CLR), Clec2d, plays a significant role in the pathogenesis of sepsis. Methods: Clec2d knockout (KO) mice were fully backcrossed onto the C57/BL6 background.

Trends in Initial Anticoagulation Among US Patients Hospitalized With Acute Pulmonary Embolism 2011-2020.

Study Objective: Guidelines recommend low-molecular-weight heparin (LMWH) and direct oral anticoagulants (DOACs) rather than unfractionated heparin (UFH) for treatment of acute pulmonary embolism (PE) given their efficacy and reduced risk of bleeding. Using data from a large consortium of US hospitals, we examined trends in initial anticoagulation among hospitalized patients diagnosed with acute PE.

Methods: We conducted a retrospective study of inpatient and observation cases between January 1, 2011, and December 31, 2020, among individuals aged more than or equal to 18 years treated at acute care hospitals contributing data to the Premier Healthcare Database.

Distinct TB-antigen stimulated cytokine profiles as predictive biomarkers for unfavorable treatment outcomes in pulmonary tuberculosis.

Introduction: The assessment of tuberculosis (TB) treatment outcomes predominantly relies on sputum culture conversion status. To enhance treatment management, it is crucial to identify non-sputum-based biomarkers that can predict unfavorable outcomes. Cytokines are widely studied as diagnostic biomarkers for active TB.

Probing the neurocardiac circuit in trauma and posttraumatic stress.

The neurocardiac circuit is integral to physiological regulation of threat and trauma-related responses. However, few direct investigations of brain-behavior associations with replicable physiological markers of PTSD have been conducted. The current study probed the neurocardiac circuit by examining associations among its core regions in the brain (e.

Once-daily upadacitinib versus placebo in adults with extensive non-segmental vitiligo: a phase 2, multicentre, randomised, double-blind, placebo-controlled, dose-ranging study.

Background: Janus kinase (JAK) inhibition is a promising approach for treating vitiligo. We aimed to assess the efficacy and safety of upadacitinib, an oral selective JAK inhibitor, in adults with non-segmental vitiligo.

Methods: This was a phase 2, multicentre, randomised, double-blind, placebo-controlled, dose-ranging study completed at 33 clinical centres in the United States, Canada, France, and Japan.