A BCG kill switch strain protects against Mycobacterium tuberculosis in mice and non-human primates with improved safety and immunogenicity.

Improved vaccination strategies for tuberculosis are needed. Intravenous (i.v.

Engineered Mycobacterium tuberculosis triple-kill-switch strain provides controlled tuberculosis infection in animal models.

Human challenge experiments could accelerate tuberculosis vaccine development. This requires a safe Mycobacterium tuberculosis (Mtb) strain that can both replicate in the host and be reliably cleared. Here we genetically engineered Mtb strains encoding up to three kill switches: two mycobacteriophage lysin operons negatively regulated by tetracycline and a degron domain-NadE fusion, which induces ClpC1-dependent degradation of the essential enzyme NadE, negatively regulated by trimethoprim.

How macrophage heterogeneity affects tuberculosis disease and therapy.

Macrophages are the primary host cell type for infection by Mycobacterium tuberculosis in vivo. Macrophages are also key immune effector cells that mediate the control of bacterial growth. However, the specific macrophage phenotypes that are required for optimal immune control of M.

High-dose intravenous BCG vaccination induces enhanced immune signaling in the airways.

Intradermal Bacillus Calmette-Guérin (BCG) is the most widely administered vaccine, but it does not sufficiently protect adults against pulmonary tuberculosis. Recent studies in nonhuman primates show that intravenous BCG administration offers superior protection against (). We used single-cell analysis of bronchoalveolar lavage cells from rhesus macaques vaccinated via different routes and doses of BCG to identify alterations in the immune ecosystem in the airway following vaccination.

Xylazine-Associated Necrotic Upper-Extremity Wounds: A Single Hospital System's Experience with 82 Patients and 125 Wounds.

Background: The rise in xylazine-adulterated heroin and fentanyl poses novel challenges to hand surgeons and a rising epidemic of necrotic upper-extremity wounds. While prior case studies have focused on particularly severe and complex xylazine-associated necrotic (XAN) wounds, the aim of this consecutive case series was to characterize the variability of presentations (ranging from mild to severe) at a single institution at the epicenter of the xylazine epidemic.

Methods: Patients presenting to a tertiary referral center for XAN upper-extremity wounds were retrospectively identified from emergency department visits and hospital admissions between January 2021 and December 2023.

Humoral correlates of protection against following intravenous BCG vaccination in rhesus macaques.

Altering Bacille Calmette-Guérin (BCG) immunization from low-dose intradermal (i.d.) to high-dose intravenous (i.

Predictors and implications of renal injury after CD19 chimeric antigen receptor T-cell therapy.

Chimeric Antigen Receptor (CAR) T cells targeting CD19 induce durable remissions in patients with relapsed or refractory non-Hodgkin lymphoma (NHL), but many patients experience treatmentrelated toxicity. Cytokine release syndrome and immune effector cell-associated neurologic syndrome are extensively characterized. However, limited data exist on the burden, predictors, and implications of acute kidney injury (AKI) after CAR T cell therapy.

Dominant negative mutations in yeast Hsp90 indicate triage decision mechanism targeting client proteins for degradation.

Dominant negative (DN) mutations provide valuable tools for investigating protein mechanisms but can be difficult to isolate because of their toxic effects. We used a mutational scanning approach to identify DN mutations in yeast Hsp90. In a previous mutational scan of the ATPase domain of Hsp90, we noticed that many mutations were at very low frequency after outgrowth in cells coexpressing wildtype Hsp90.

Markov Field network model of multi-modal data predicts effects of immune system perturbations on intravenous BCG vaccination in macaques.

Analysis of multi-modal datasets can identify multi-scale interactions underlying biological systems, but can be beset by spurious connections due to indirect impacts propagating through an unmapped biological network. For example, studies in macaques have shown that BCG vaccination by an intravenous route protects against tuberculosis, correlating with changes across various immune data modes. To eliminate spurious correlations and identify critical immune interactions in a public multi-modal dataset (systems serology, cytokines, cytometry) of vaccinated macaques, we applied Markov Fields (MF), a data-driven approach that explains vaccine efficacy and immune correlations via multivariate network paths, without requiring large numbers of samples (i.

Dysphagia in an 80-Year-Old Woman: A Rare Case of Metastatic Melanoma Presenting in the Small Bowel.

This report discusses the case of an 80-year-old female presenting with non-specific gastrointestinal symptoms and who was ultimately diagnosed as having metastatic melanoma of the jejunum. Notably, on admission, the patient had failed to report a past medical history of melanoma on her back a few years prior, and this significantly impacted the diagnostic process. This case highlights the challenges in diagnosing metastatic melanoma.

Markov field network model of multi-modal data predicts effects of immune system perturbations on intravenous BCG vaccination in macaques.

Analysis of multi-modal datasets can identify multi-scale interactions underlying biological systems but can be beset by spurious connections due to indirect impacts propagating through an unmapped biological network. For example, studies in macaques have shown that Bacillus Calmette-Guerin (BCG) vaccination by an intravenous route protects against tuberculosis, correlating with changes across various immune data modes. To eliminate spurious correlations and identify critical immune interactions in a public multi-modal dataset (systems serology, cytokines, and cytometry) of vaccinated macaques, we applied Markov fields (MFs), a data-driven approach that explains vaccine efficacy and immune correlations via multivariate network paths, without requiring large numbers of samples (i.

Uncommon occipital ganglioglioma in a child: The critical role of MRI in diagnosis and management.

Epilepsy is a prevalent neurological disorder in children, with 30-35% of cases developing into intractable epilepsy despite appropriate anti-seizure medications (ASMs). Advanced imaging is crucial for early diagnosis, especially in detecting structural causes like gangliogliomas, which are associated with drug-resistant focal epilepsy. We report a 5-year-old boy with recurrent seizures, initially undetected by EEG.

The Performance of a Customized Generative Pre-trained Transformer on the American Society for Surgery of the Hand Self-Assessment Examination.

Introduction:  Multimodal large language models (MLLMs), such as OpenAI's ChatGPT (San Francisco, CA), have the potential to improve medical care delivery and education, although important shortcomings in accuracy and image interpretation have been noted. The aim of this study was to assess the multimodal performance of a ChatGPT model customized with hand surgery-specific knowledge.

Methods: A customized generative pre-trained transformer (GPT) was trained using peer-reviewed literature recommended by the American Society for Surgery of the Hand (ASSH).

Skull evolution and lineage diversification in endemic Malagasy carnivorans.

Madagascar is one of the world's foremost biodiversity hotspots with more than 90% of its species endemic to the island. Malagasy carnivorans are one of only four extant terrestrial mammalian clades endemic to Madagascar. Although there are only eight extant species, these carnivorans exhibit remarkable phenotypic and ecological diversity that is often hypothesized to have diversified through an adaptive radiation.

Comparing Current Practice Habits for Treatment of Subcondylar Fracture Among Craniomaxillofacial Surgeons.

Study Design: Survey.

Objective: Subcondylar fractures stand out as a particular challenge when treating maxillofacial trauma. The fracture site is often difficult to access and adjacent to critical structures like the facial nerve.

The Impact of Using Intraoperative Computed Tomography on the Number of Surgical Approaches Used for Zygomaticomaxillary Complex Repair.

Zygomaticomaxillary complex (ZMC) fractures are repaired using a variety of surgical approaches. Utilization of intraoperative computed tomography (CT) may reduce the number of surgical approaches. To compare the use of intraoperative CT for the operative repair of ZMC fractures, as measured by the number of surgical approaches.

Do teams of strangers create health care dangers? The effect of OR team consistency on operative times in adolescent idiopathic scoliosis.

Purpose: Teamwork and communication are important components of any surgical team. This study uses a simple, reproducible, and quantitative "team consistency score" and a nodal-based model for examining prior interactions amongst team members to represent and quantify the regularity of an OR team for a specific surgical case.

Methods: The electronic medical record (EMR) at our institution was queried for pediatric patients undergoing spinal surgery from January 2021 through December 2023.

Intravenous Bacillus Calmette-Guérin (BCG) Induces a More Potent Airway and Lung Immune Response than Intradermal BCG in Simian Immunodeficiency Virus-infected Macaques.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is one of the leading causes of death due to an infectious agent. Coinfection with HIV exacerbates M. tuberculosis infection outcomes in people living with HIV.