eEF2K regulates pain through translational control of BDNF.

mRNA translation is integral to pain, yet the key regulatory factors and their target mRNAs are unclear. Here, we uncover a mechanism that bridges noxious insults to multiple phases of translational control in murine sensory neurons. We find that a painful cue triggers repression of peptide chain elongation through activation of elongation factor 2 kinase (eEF2K).

Advancements in Immunity and Dementia Research: Highlights from the 2023 AAIC Advancements: Immunity Conference.

The immune system is a key player in the onset and progression of neurodegenerative disorders. While brain resident immune cell-mediated neuroinflammation and peripheral immune cell (eg, T cell) infiltration into the brain have been shown to significantly contribute to Alzheimer's disease (AD) pathology, the nature and extent of immune responses in the brain in the context of AD and related dementias (ADRD) remain unclear. Furthermore, the roles of the peripheral immune system in driving ADRD pathology remain incompletely elucidated.

Shiftwork and leisure-time physical inactivity (LTPI) among U.S. workers.

Physical inactivity may exacerbate the adverse health effects associated with shift work. We investigated the association of shift work with leisure-time physical inactivity (LTPI). A cross-sectional analysis included 33 983 adults from National Health Interview Survey who self-reported their work schedule and leisure-time physical activity.

Chemical engineering of CRISPR-Cas systems for therapeutic application.

Clustered regularly interspaced short palindromic repeats (CRISPR) technology has transformed molecular biology and the future of gene-targeted therapeutics. CRISPR systems comprise a CRISPR-associated (Cas) endonuclease and a guide RNA (gRNA) that can be programmed to guide sequence-specific binding, cleavage, or modification of complementary DNA or RNA. However, the application of CRISPR-based therapeutics is challenged by factors such as molecular size, prokaryotic or phage origins, and an essential gRNA cofactor requirement, which impact efficacy, delivery and safety.

CPX-351 plus gemtuzumab ozogamicin for relapsed/refractory acute myelogenous leukemia: a University of California Hematologic Malignancies Consortium trial.

In this multicenter phase Ib trial, we investigated the combination of CPX-351 and gemtuzumab ozogamicin (GO) in relapsed/refractory acute myeloid leukemia (AML). Cohort A received CPX-351 plus a single dose of GO, while cohort B received two doses of GO. Thirteen participants received investigational treatment.

Anemia in Myelofibrosis: A Focus on Proactive Management and the Role of Momelotinib.

Anemia is a common and progressive clinical manifestation of myelofibrosis that may occur as part of the disease pathogenesis as well as due to the myelosuppressive effects of some treatments, with a substantial impact on quality of life, prognosis, and healthcare resource utilization. Despite these burdens, anemia management has traditionally been a secondary priority to spleen and symptom control, due in part to the limitations of available therapeutic approaches. With the initial regulatory approvals of momelotinib, a Janus kinase 1 (JAK1), JAK2, and activin A receptor type 1 inhibitor that provides anemia-related benefits in addition to addressing splenomegaly and symptoms, re-evaluation of anemia as an early and prominent treatment consideration is warranted.

Impact of prenatal exposure to delta 9-tetrahydrocannabinol and cannabidiol on birth size and postnatal growth trajectories.

Background: Prenatal exposure to cannabis (or more specifically, delta 9-tetrahydrocannabinol [Δ9-THC]) has been consistently linked to low birthweight. Animal models further show that Δ9-THC is associated with rapid postnatal growth. Whether this association is modified by breastfeeding is unknown.

Non-pharmaceutical treatments for irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a chronic disorder of gut-brain interaction that impacts a significant portion of the population and is associated with substantial morbidity, reduced quality of life, and economic impact globally. The pathophysiology of IBS is complex and incompletely understood, and the heterogeneity of IBS is reflected in the variety of pharmaceutical and non-pharmaceutical therapies utilized for the management of IBS. Given limitations with pharmaceutical treatments, many patients with IBS seek non-pharmaceutical options.

Indoor Tanning Addiction: Biological Mechanisms and Association with Other Disorders.

Although many people who use tanning beds are aware of the negative consequences, they continue to indoor tan, possibly due to addictive properties. The purpose of this paper is to review the existing literature on tanning addiction, its potential biological mechanisms, and its association with psychological disorders. A PubMed search was conducted using the terms "Tanning Addiction," "UVR AND B-endorphin," and "tanning dependence AND gene.

Arterial effects of anthracycline: structural & inflammatory assessments in non-human primates and lymphoma patients.

Anthracyclines, such as doxorubicin, are important anti-cancer therapies but are associated with arterial injury. Histopathological insights have been limited to small animal models and the role of inflammation in the arterial toxic effects of anthracycline is unclear in humans. Our aims were: 1) To evaluate aortic media fibrosis and injury in non-human primates treated with anthracyclines; 2) To assess the effect of anthracycline on aortic inflammation in patients treated for lymphoma.

Ancestral Genomic Functional Differences in Oligodendroglia: Implications for Alzheimer's Disease.

Background: This study aims to elucidate ancestry-specific changes to the genomic regulatory architecture in induced pluripotent stem cell (iPSC)-derived oligodendroglia, focusing on their implications for Alzheimer's disease (AD). This work addresses the lack of diversity in previous iPSC studies by including ancestries that contribute to African American (European/African) and Hispanic/Latino populations (Amerindian/African/European).

Methods: We generated 12 iPSC lines-four African, four Amerindian, and four European- from both AD patients and non-cognitively impaired individuals, with varying genotypes ( and ).

Perception and Identification of Behavioral and Psychological Symptoms of Dementia (BPSD) in China Medical Community.

Background: Behavioral and psychological symptoms of dementia (BPSD), as neuropsychiatric manifestations within dementia, constitute core features of dementia. However, there remains a gap in understanding the recognition of BPSD in China. Our current study was to explore the clinical awareness and treatment approaches for BPSD in China, focusing especially on the perspectives of neurologists and psychiatrists.

COPD and Immune Checkpoint Inhibitors for Cancer: A Literature Review.

Purpose: Immune checkpoint inhibitors are a standard treatment option for many patients with cancer and are most frequently used to treat lung cancer. Chronic obstructive pulmonary disease (COPD) is the most common comorbidity of patients with lung cancer. As the cancer-specific survival of patients with lung cancer continues to increase with modern treatments, it is critical to optimize comorbidities to improve overall survival.

Supporting Patient Involvement in U.S. Medical Education Through Changes in Accreditation.

For over half of a century, there have been calls for greater patient and community involvement in U.S. medical education.

Identification of TUBB3 as an immunotherapy target in lung cancer by genome wide in vivo CRISPR screening.

Recent development of immune checkpoint inhibitors has revolutionized cancer immunotherapy. Although these drugs show dramatic effects on a subset of cancer patients, many other tumors are non-responsive and the pathological mechanism of the resistance is largely unknown. To identify genes underlying anti-PD-1 immunotherapy resistance using a systematic approach, we performed an in vivo genome wide CRISPR screening in lung cancer cells.

Multilevel factors influence the use of a cardiovascular disease assessment tool embedded in the electronic health record in oncology care.

Digital health tools are positive for delivering evidence-based care. However, few studies have applied rigorous frameworks to understand their use in community settings. This study aimed to identify implementation determinants of the Automated Heart-Health Assessment (AH-HA) tool within outpatient oncology settings as part of a hybrid effectiveness-implementation trial.

Associations of nonoccupational sedentary behaviors with cardiometabolic outcomes: coronary artery risk development in young adults (CARDIA).

Background: The association between sedentary behavior (SB) and cardiometabolic risk may differ by SB domain and context. Nonoccupational SB is particularly important because it is discretionary and more amenable to change. This study estimated associations of nonoccupational SB contexts with hypertension (HTN) and diabetes mellitus (DM).

Accountability Frameworks in Medical Weight Loss Programs: A Comprehensive Literature Review.

Limited adherence to weight loss regimens is a major contributor to the unsuccessful treatment of obesity in patients. Accountability approaches have been used to enhance weight loss program adherence. The purpose of our review is to characterize techniques used to improve patient accountability during weight loss programs.

A Randomized Controlled Trial of Medial Prefrontal Cortex Theta Burst Stimulation for Cocaine Use Disorder: A Three-Month Feasibility and Brain Target-Engagement Study.

Background: Cue-induced craving precipitates relapse in drug and alcohol use disorders. Theta burst stimulation (TBS) to the left frontal pole of the medial prefrontal cortex (MPFC) has previously been shown to reduce drinking and brain reactivity to alcohol cues. This randomized, double-blind, sham-controlled target-engagement study aimed to assess whether TBS has similar effects in individuals with cocaine use disorder (CUD).

Comprehensive landscape analysis for usable real-world wound care data.

Background: The Wound Care Collaborative Community (WCCC) aims to assess current usable real-world data (RWD) sources to determine which real-world databases (DBs) are suitable and usable for studying the natural history of chronic wounds. Randomized controlled trials (RCTs) do not fully reflect the complexity of patients with chronic wounds. Using RWD, establishment of a scientifically grounded "road map" for RCTs is needed to better navigate the real-world complexity of the patients with chronic wounds.