Comparison of Multi-Drug Resistant Organisms Causing Early Ventilator-Associated Pneumonia in Three Geographically Distinct Trauma Intensive Care Units.

It is unclear why differences in patient location change organisms causing ventilator-associated pneumonia (VAP). We investigated VAP organisms in three geographically separate trauma intensive care units (TICUs). A retrospective review of organisms causing VAP (bronchoalveolar lavage [BAL] performed ≤7 d after admission and growing ≥10 cfu/mL) in three geographically separate TICUs was conducted.

Rib and Sternum Nonunions: Diagnosis and Treatment and Awareness of Other Potential Posttraumatic Pathology.

As the operative management of acute, chest wall, skeletal injury escalates throughout the world, it has become commonplace for patients with posttraumatic conditions to present with clinical reconstructive challenges as well. In addition, it is becoming clear that rib nonunions are not rare, likely more than 5% of rib fractures. No subspecialty is better equipped to address such painful conditions than orthopaedic surgery.

A Small-Molecule Inhibitor of Gut Bacterial Urease Protects the Host from Liver Injury.

Hyperammonemia is characterized by the accumulation of ammonia within the bloodstream upon liver injury. Left untreated, hyperammonemia contributes to conditions such as hepatic encephalopathy that have high rates of patient morbidity and mortality. Previous studies have identified gut bacterial urease, an enzyme that converts urea into ammonia, as a major contributor to systemic ammonia levels.

Deaminase-mediated chromatin accessibility profiling with single-allele resolution.

Binding of transcription factors (TFs) at gene regulatory elements controls cellular epigenetic state and gene expression. Current genome-wide chromatin profiling approaches have inherently limited resolution, complicating assessment of TF occupancy and co-occupancy, especially at individual alleles. In this work, we introduce Accessible Chromatin by Cytosine Editing Site Sequencing with ATAC-seq (ACCESS-ATAC), which harnesses a double-stranded DNA cytosine deaminase (Ddd) enzyme to stencil TF binding locations within accessible chromatin regions.

The CoREST complex inhibitor, corin, leads to decreased tumor growth, increased cellular differentiation and extended lifespan in atypical teratoid rhabdoid tumor xenograft models.

Background: Atypical teratoid rhabdoid tumor (ATRT) is the most common malignant brain tumor in infants, and more than 60% of children with ATRT die from their tumor. ATRT is associated with mutational inactivation/deletion of , a member of the SWI/SNF chromatin remodeling complex, suggesting that epigenetic events play a critical role in tumor development and progression. Moreover, disruption of SWI/SNF allows unopposed activity of epigenetic repressors, which contribute to tumorigenicity.

Transplant-Free Approach in Relapsed Hodgkin Lymphoma in Children, Adolescents, and Young Adults: A Nonrandomized Clinical Trial.

Importance: Retrieval strategies for children, adolescents, and young adults with relapsed classic Hodgkin lymphoma (cHL) aim to maintain efficacy while minimizing long-term toxic effects. Children, adolescents, and young adults with low-risk, relapsed cHL may benefit from replacing high-dose chemotherapy and autologous stem cell transplant with less intensive involved-site radiotherapy (ISRT).

Objective: To evaluate a risk-stratified, response-adapted, transplant-free approach for treatment of children, adolescents, and young adults with low-risk relapsed cHL with nivolumab plus brentuximab vedotin (BV) followed by BV plus bendamustine for patients with suboptimal response and ISRT (30.

CoREST Complex Inhibition Alters RNA Splicing to Promote Neoantigen Expression and Enhance Tumor Immunity.

Unlabelled: Epigenetic complexes tightly regulate gene expression and colocalize with RNA splicing machinery; however, the consequences of these interactions are uncertain. Here, we identify unique interactions of the CoREST repressor complex with RNA splicing factors and their functional consequences in tumorigenesis. Using mass spectrometry, in vivo binding assays, and cryo-EM we find that CoREST complex-splicing factor interactions are direct and perturbed by the CoREST complex inhibitor, corin, leading to extensive changes in RNA splicing in melanoma and other malignancies.

Feasibility of Utilizing a Brief Neurocognitive Battery in 3-Year-Old Patients During Treatment for Acute Lymphoblastic Leukemia.

Treatment of acute lymphoblastic leukemia (ALL) is associated with neurocognitive deficits in young children. While computerized measures have been utilized in pediatric oncology research, they exclude patients below the age of 4 years. Patients enrolled on "Treatment of Newly Diagnosed Acute Lymphoblastic Leukemia in Children and Adolescents" were offered participation in an optional neurocognitive study.

Nuclear GTPSCS functions as a lactyl-CoA synthetase to promote histone lactylation and gliomagenesis.

Histone lysine lactylation is a physiologically and pathologically relevant epigenetic pathway that can be stimulated by the Warburg effect-associated L-lactate. Nevertheless, the mechanism by which cells use L-lactate to generate lactyl-coenzyme A (CoA) and how this process is regulated remains unknown. Here, we report the identification of guanosine triphosphate (GTP)-specific SCS (GTPSCS) as a lactyl-CoA synthetase in the nucleus.

Circular Engineered Sortase for Interrogating Histone H3 in Chromatin.

Reversible modification of the histone H3 N-terminal tail is critical in regulating the chromatin structure, gene expression, and cell states, while its dysregulation contributes to disease pathogenesis. Understanding the crosstalk between H3 tail modifications in nucleosomes constitutes a central challenge in epigenetics. Here, we describe an engineered sortase transpeptidase, cW11, that displays highly favorable properties for introducing scarless H3 tails onto nucleosomes.

Targeting lysine acetylation readers and writers.

Lysine acetylation is a major post-translational modification in histones and other proteins that is catalysed by the 'writer' lysine acetyltransferases (KATs) and mediates interactions with bromodomains (BrDs) and other 'reader' proteins. KATs and BrDs play key roles in regulating gene expression, cell growth, chromatin structure, and epigenetics and are often dysregulated in disease states, including cancer. There have been accelerating efforts to identify potent and selective small molecules that can target individual KATs and BrDs with the goal of developing new therapeutics, and some of these agents are in clinical trials.

Opinion on the Importance of Sharing Toxicologic Pathology Data for Educational and/or Scientific Purposes.

Sharing pathology data is critical for educational and scientific purposes. Since most pharmaceutical or (agro)chemical companies outsource nonclinical safety assessment studies to contract research organizations (CROs), the pathology data of those studies are not owned by the investigator but is the legal property of the respective company sponsoring the work. Although some companies have installed policies that govern sharing of pathology data, many companies generally do not allow the external use of data by either the CRO-based study pathologist or the sponsor pathologist.

[Cannabis and medicine students : who, how and why ?].

Introduction: Cannabis is the third most commonly used substance by students. The aim of this study is to describe cannabis use among medical students and understand their motivations. It seeks to establish the link between cannabis and higher education, especially in medicine.

Pulsed lighting for adults with Dyslexia: very limited impact, confined to individuals with severe reading deficits.

The goal of this study is to evaluate the impact of pulsed lighting on the reading performance of young adults with dyslexia. A total of 42 participants were recruited, including individuals diagnosed with developmental dyslexia and adults without reported reading difficulties. The severity of each participant's reading deficit was assessed on a continuous scale using a reading impairment score, derived from four reading tests: an isolated-word reading test, a pseudoword reading test, and two reading fluency tests.

AANAT kinetics of CoASH-targeted electrophiles of tryptamine and related analogs.

Arylalkylamine N-acetyltransferase (AANAT) catalyzes the rate-limiting step in melatonin synthesis and is a potential target for disorders involving melatonin overproduction, such as seasonal affective disorder. Previously described AANAT inhibitor bromoacetyltryptamine (BAT) and benzothiophenes analogs were reported to react with CoASH to form potent bisubstrate inhibitors through AANAT's alkyltransferase function, which is secondary to its role as an acetyltransferase. We replaced the bromoacetyl group in BAT with various Michael acceptors to mitigate possible off-target activity of its bromoacetyl group.

Comparative transcriptomics of broad-spectrum and synthetic cannabidiol treated C2C12 skeletal myotubes.

Cannabidiol (CBD) is widely used in sports for recovery, pain management, and sleep improvement, yet its effects on muscle are not well understood. This study aimed to determine the transcriptional response of murine skeletal muscle myotubes to broad-spectrum CBD and synthetic CBD (sCBD). Differentiated C2C12 myotubes were treated with 10 μM CBD, sCBD, or vehicle control (DMSO) for 24 h before RNA extraction.

The National Cancer Institute Clinical Trials Planning Meeting to Address Gaps in Observational and Intervention Trials for Cancer-Related Cognitive Impairment.

Cancer-related cognitive impairment (CRCI) is a broad term encompassing subtle cognitive problems to more severe impairment. CRCI severity is influenced by host, disease, and treatment factors and affects patients prior to, during, and following cancer treatment. The National Cancer Institute (NCI) Symptom Management and Health-Related Quality of Life Steering Committee (SxQoL SC) convened a Clinical Trial Planning Meeting (CTPM) to review the state of the science on CRCI and to develop both Phase II/III intervention trials aimed at improving cognitive function in cancer survivors with non-central nervous system (CNS) disease and longitudinal studies to understand the trajectory of cognitive impairment and contributing factors.

The CoREST complex is a therapeutic vulnerability in malignant peripheral nerve sheath tumors.

Malignant peripheral nerve sheath tumor (MPNST) is a highly aggressive sarcoma that may be seen in patients with neurofibromatosis type 1 (NF1) or occur sporadically. While surgery is the primary treatment for localized MPNST with a 61.9% overall survival rate, metastatic disease is often fatal due to resistance to systemic therapies which underscores the urgent need for effective treatments.

Multifaceted regulation of sirtuin 2 (Sirt2) deacetylase activity.

Sirtuin 2 (Sirt2) is a member of the sirtuin family of NAD-dependent lysine deacylases and plays important roles in regulation of the cell cycle and gene expression. As a nucleocytoplasmic deacetylase, Sirt2 has been shown to target both histone and nonhistone acetylated protein substrates. The central catalytic domain of Sirt2 is flanked by flexible N and C termini, which vary in length and composition with alternative splicing.