Exploring the properties and potential of the neural extracellular matrix for next-generation regenerative therapies.

The extracellular matrix (ECM) is a dynamic and complex network of proteins and molecules that surrounds cells and tissues in the nervous system and orchestrates a myriad of biological functions. This review carefully examines the diverse interactions between cells and the ECM, as well as the transformative chemical and physical changes that the ECM undergoes during neural development, aging, and disease. These transformations play a pivotal role in shaping tissue morphogenesis and neural activity, thereby influencing the functionality of the central nervous system (CNS).

Age-Related Differences in the Presentation, Management, and Clinical Outcomes of 100,000 Patients With Venous Thromboembolism in the RIETE Registry.

Introduction: Although older adults represent a significant proportion of patients with venous thromboembolism (VTE), the data on the impact of age-related differences in the clinical presentation, management, and outcomes of VTE are scarce.

Methods: We analyzed data from the RIETE registry database, an ongoing global observational registry of patients with objectively confirmed VTE, to compare patient characteristics, clinical presentation, treatments, and outcomes between elderly (≥70 years) vs. non-elderly (<70 years) patients.

Enhanced Neuron Growth and Electrical Activity by a Supramolecular Netrin-1 Mimetic Nanofiber.

Neurotrophic factors are essential not only for guiding the organization of the developing nervous system but also for supporting the survival and growth of neurons after traumatic injury. In the central nervous system (CNS), inhibitory factors and the formation of a glial scar after injury hinder the functional recovery of neurons, requiring exogenous therapies to promote regeneration. Netrin-1, a neurotrophic factor, can initiate axon guidance, outgrowth, and branching, as well as synaptogenesis, through activation of deleted in colorectal cancer (DCC) receptors.

The highs and the lows: Recreational marijuana laws and mental health treatment.

Recreational marijuana laws (RMLs) continue to grow in popularity, but the effects on mental health treatment are unclear. This paper uses an event-study within a difference-in-differences framework to study the short-run impact of state RMLs on admissions into mental health treatment facilities. The results indicate that shortly after a state adopts an RML, they experience a decrease in the average number of mental health treatment admissions.

Artificial extracellular matrix scaffolds of mobile molecules enhance maturation of human stem cell-derived neurons.

Human induced pluripotent stem cell (hiPSC) technologies offer a unique resource for modeling neurological diseases. However, iPSC models are fraught with technical limitations including abnormal aggregation and inefficient maturation of differentiated neurons. These problems are in part due to the absence of synergistic cues of the native extracellular matrix (ECM).

Medicaid Expansion and mental health treatment: Evidence from the Affordable Care Act.

This study uses a difference-in-differences design within an event-study framework to examine how state decisions to expand Medicaid following the passage of the Affordable Care Act (ACA) affected mental health treatment. The findings suggest that expansion states experienced increased admissions to mental health treatment facilities and Medicaid-reimbursed prescriptions for medications used to treat common forms of mental illness. The results also indicate an increase in admissions with trauma, anxiety, conduct, and depression disorders.

Racial and Ethnic Disparities: Essential Workers, Mental Health, and the Coronavirus Pandemic.

Evidence is emerging of the pandemic disproportionately impacting communities of color. This study investigates mental health distress among essential workers during the coronavirus pandemic across race and ethnicity. We evaluate individual responses to the patient health questionnaire and general anxiety disorder questionnaire using a unique, nationally representative data set.

Institution of Higher Education Substance Use Amnesty Policies and Sexual Violence Reporting.

Sexual violence (SV) is common among college students, but the vast majority of these experiences are not formally reported to institutions of higher education (IHEs). While it is well known that alcohol and drug use is highly associated with SV, little is known about whether policies and procedures regarding substance use (SU) at IHEs may contribute to low rates of reporting. This study describes the association between SU violations and SV reporting at IHE campuses in the US and examines whether SU amnesty policies are associated with more SV reporting.

Comprehensive Characterization of the LSD1 Small Molecule Inhibitor Class in Oncology.

Lysine-specific demethylase 1 (LSD1 or KDM1A) is a chromatin modifying enzyme playing a key role in the cell cycle and cell differentiation and proliferation through the demethylation of histones and nonhistone substrates. In addition to its enzymatic activity, LSD1 plays a fundamental scaffolding role as part of transcription silencing complexes such as rest co-repressor (CoREST) and nucleosome remodeling and deacetylase (NuRD). A host of classical amine oxidase inhibitors such as tranylcypromine, pargyline, and phenelzine together with LSD1 tool compounds such as SP-2509 and GSK-LSD1 have been extensively utilized in LSD1 mechanistic cancer studies.

Flipping the script: The effects of opioid prescription monitoring on specialty-specific provider behavior.

Mandatory access Prescription Drug Monitoring Programs (MA-PDMPs) aim to curb the epidemic at a common point of initiation of use, the prescription. However, there is recent concern about whether opioid policies have been too restrictive and reduced appropriate access to patients with the most need for opioid pharmaceuticals. We assess MA-PDMP's effect on specialty-specific opioid prescribing behavior of Medicare providers.

Impact of Perioperative Blood Transfusion in Anemic Patients Undergoing Infra Inguinal Bypass.

Objective: Patients who present with lower extremity ischemia are frequently anemic and the optimal transfusion threshold for this cohort remains controversial. We sought to evaluate the impact of blood transfusion on postoperative major adverse cardiac events (MACE), including myocardial infarction, dysrhythmia, stroke, congestive heart failure, and 30-day mortality for these patients.

Methods: All consecutive patients who underwent infra-inguinal bypass at our institution from 2011 to 2020 were included.

Substance use disorders among older populations: What role do race and ethnicity play in treatment and completion?

Research that explores the role of substance use treatment among older individuals is scarce. This paper offers a historical investigation of admissions and discharges for treatment episodes over the past two decades across race, ethnicity, gender, and age. Our results suggest that although older individuals are not typically associated with risky behavior, they are increasingly seeking treatment for substance use disorders.

STRA6 Polymorphisms Are Associated With EGFR Mutations in Locally-Advanced and Metastatic Non-Small Cell Lung Cancer Patients.

Retinol plays a significant role in several physiological processes through their nuclear receptors, whose expression depends on retinol cytoplasmic concentration. Loss of expression of nuclear receptors and low retinol levels have been correlated with lung cancer development. Stimulated by retinoic acid 6 (STRA6) is the only described cell membrane receptor for retinol uptake.

Modulation of KDM1A with vafidemstat rescues memory deficit and behavioral alterations.

Transcription disequilibria are characteristic of many neurodegenerative diseases. The activity-evoked transcription of immediate early genes (IEGs), important for neuronal plasticity, memory and behavior, is altered in CNS diseases and governed by epigenetic modulation. KDM1A, a histone 3 lysine 4 demethylase that forms part of transcription regulation complexes, has been implicated in the control of IEG transcription.

Sequence Changes Modulate Peptoid Self-Association in Water.

Peptoids, -substituted glycine oligomers, are a class of diverse and sequence-specific peptidomimetics with wide-ranging applications. Advancing the functional repertoire of peptoids to emulate native peptide and protein functions requires engineering peptoids that adopt regular secondary and tertiary structures. An understanding of how changes to peptoid sequence change structural features, particularly in water-soluble systems, is underdeveloped.

Chemoprobe-based assays of histone lysine demethylase 1A target occupation enable pharmacokinetics and pharmacodynamics studies of KDM1A inhibitors.

Screening of cellular activity for inhibitors of histone lysine modifiers is most frequently performed indirectly by analyzing changes in the total levels of histone marks targeted by lysine methylases/demethylases. However, inhibition of histone lysine modifiers often leads to local rather than total changes in histone marks. Also, because histone modifications can be modulated by more than one cellular enzyme, it is not always clear whether changes in histone marks are a direct or indirect consequence of the inhibitor treatment applied.

Solution effects on the self-association of a water-soluble peptoid.

A desire to replicate the structural and functional complexity of proteins with structured, sequence-specific oligomers motivates study of the structural features of water-soluble peptoids (N-substituted glycine oligomers). Understanding the molecular-level details of peptoid self-assembly in water is essential to advance peptoids' application as novel materials. Peptoid 1, an amphiphilic, putatively helical peptoid previously studied in our laboratory, shows evidence of self-association in aqueous solution.

Botulinum Toxin Conditioning Enhances Motor Axon Regeneration in Mouse and Human Preclinical Models.

Background: Peripheral axon regeneration is improved when the nerve lesion under consideration has recently been preceded by another nerve injury. This is known as the conditioning lesion effect (CLE). While the CLE is one of the most robust and well characterized means to enhance motor axon regeneration in experimental models, it is not considered a clinically feasible strategy.

All-Optical Electrophysiology for High-Throughput Functional Characterization of a Human iPSC-Derived Motor Neuron Model of ALS.

Human induced pluripotent stem cell (iPSC)-derived neurons are an attractive substrate for modeling disease, yet the heterogeneity of these cultures presents a challenge for functional characterization by manual patch-clamp electrophysiology. Here, we describe an optimized all-optical electrophysiology, "Optopatch," pipeline for high-throughput functional characterization of human iPSC-derived neuronal cultures. We demonstrate the method in a human iPSC-derived motor neuron (iPSC-MN) model of amyotrophic lateral sclerosis (ALS).

ORY-1001, a Potent and Selective Covalent KDM1A Inhibitor, for the Treatment of Acute Leukemia.

The lysine-specific demethylase KDM1A is a key regulator of stem cell potential in acute myeloid leukemia (AML). ORY-1001 is a highly potent and selective KDM1A inhibitor that induces H3K4me2 accumulation on KDM1A target genes, blast differentiation, and reduction of leukemic stem cell capacity in AML. ORY-1001 exhibits potent synergy with standard-of-care drugs and selective epigenetic inhibitors, reduces growth of an AML xenograft model, and extends survival in a mouse PDX (patient-derived xenograft) model of T cell acute leukemia.

The Subventricular Zone: A Key Player in Human Neocortical Development.

One of the main characteristics of the developing brain is that all neurons and the majority of macroglia originate first in the ventricular zone (VZ), next to the lumen of the cerebral ventricles, and later on in a secondary germinal area above the VZ, the subventricular zone (SVZ). The SVZ is a transient compartment mitotically active in humans for several gestational months. It serves as a major source of cortical projection neurons as well as an additional source of glial cells and potentially some interneuron subpopulations.

Oxygen Levels Regulate the Development of Human Cortical Radial Glia Cells.

The oxygen (O2) concentration is a vital parameter for controlling the survival, proliferation, and differentiation of neural stem cells. A prenatal reduction of O2 levels (hypoxia) often leads to cognitive and behavioral defects, attributable to altered neural development. In this study, we analyzed the effects of O2 levels on human cortical progenitors, the radial glia cells (RGCs), during active neurogenesis, corresponding to the second trimester of gestation.

KDM1 histone lysine demethylases as targets for treatments of oncological and neurodegenerative disease.

Histone methylation and demethylation are important processes associated with the regulation of gene transcription, and alterations in histone methylation status have been linked to a large number of human diseases. Initially thought to be an irreversible process, histone methylation is now known to be reversed by two families of proteins containing over 30 members that act to remove methyl groups from specific lysine residues present in the tails of histone H3 and histone H4. A rapidly growing number of reports have implicated the FAD-dependent lysine specific demethylase (KDM1) family in cancer, and several small-molecule inhibitors are in development for the treatment of cancer.

Advances in the development of histone lysine demethylase inhibitors.

The covalent modification of histones is closely associated with regulation of gene transcription. Chromatin modifications have been suggested to represent an epigenetic code that is dynamically 'written' and 'erased' by specialized proteins, and 'read', or interpreted, by proteins that translate the code into gene expression changes. Initially thought to be an irreversible process, histone methylation is now known to be reversed by demethylases, FAD dependent amineoxidases and by iron(II)-alpha-ketoglutarate dependent deoxygenases of the Jumonji family.