Concurrent Prescription Fills of Opioids and Benzodiazepines Among Postpartum Women During COVID-19.

Introduction: Concurrent prescribing of opioids and benzodiazepines is associated with increased risk of emergency department visits and overdose. Postpartum women commonly receive opioids for pain after delivery and are at risk for postpartum depression/anxiety. Although prior research finds increases in opioid prescribing and symptoms of depression/anxiety during COVID-19, concurrent prescribing among postpartum women has not been examined in the context of COVID-19.

Increases in benzodiazepine prescribing for postpartum anxiety during COVID-19.

Purpose: Postpartum mood disorders affect many women following childbirth. Prescribing medication for depression and anxiety is one strategy for the effective treatment of postpartum mood disorders. Left untreated, mothers experiencing these disorders and their infants face increased risks of adverse health outcomes.

HER2 and HLA-A*02 dual CAR-T cells utilize LOH in a NOT logic gate to address on-target off-tumor toxicity.

Background: One of the major challenges in chimeric antigen receptor (CAR)-T cell therapy for solid tumors is the potential for on-target off-tumor toxicity due to the expression of CAR tumor antigens in essential tissues and organs. Here, we describe a dual CAR NOT gate incorporating an inhibitory CAR (iCAR) recognizing HLA-A*02 ("A2") that enables effective treatment with a potent HER2 activating CAR (aCAR) in the context of A2 loss of heterozygosity (LOH).

Methods: A CAR-T cell screen was conducted to identify inhibitory domains derived from natural immune receptors (iDomains) to be used in a NOT gate, to kill A2 HER2 lung cancer cell lines but spare A2 HER2 lung cancer cell-lines with high specificity.

Medicaid Expansion and Availability of Opioid Medications in the Specialty Substance Use Disorder Treatment System.

Objective: Research has examined the effect of Medicaid expansion on access to physicians with buprenorphine waivers, but less attention has been paid to Medicaid's impact on opioid use disorder medication availability within the specialty substance use disorder treatment system. To address this gap in the literature, this study examined the impact of Medicaid expansion on availability of opioid medications in specialty programs.

Methods: This study used data from the National Survey of the Substance Abuse Treatment Services (2002-2017), containing all known substance use disorder treatment programs in the United States, to examine the effect of Medicaid expansion on the availability of opioid use disorder medications by treatment program ownership type (publicly owned, private for profit, and private nonprofit) among opioid treatment programs (OTPs) and non-OTPs.

Relationship of County Opioid Epidemic Severity to Changes in Access to Substance Use Disorder Treatment, 2009-2017.

Objective: The study measured the association between local opioid problem severity and changes in the availability of substance use disorder treatment programs, including the distance required for travel to treatment.

Methods: A two-part, multivariable regression estimated the number of treatment facilities in the county (per 100,000 residents) and the number of miles to the nearest program (for all treatment programs, programs offering opioid use disorder medication, and programs accepting Medicaid) using data from the 2009-2017 National Directory of Drug and Alcohol Abuse Treatment Facilities. The unit of analysis was the county-year (N=28,270).

County-level access to opioid use disorder medications in medicare Part D (2010-2015).

Objective: To identify geographic disparities in access to opioid use disorder (OUD) treatment medications and county demographic and economic characteristics associated with access to buprenorphine and oral naltrexone prescribers in Medicare Part D.

Data Sources/study Setting: We utilized data from the Medicare Part D Prescription Drug Event Standard Analytic File (2010-2015).

Study Design/data Collection: We used logistic regression to examine county-level access to OUD medication prescribers.

An empirical assessment of the relationship between Official Development Aid and child mortality, 2000-2015.

Objectives: To analyze the effect of Official Development Aid (ODA) dollars on child mortality over the course of the United Nation's Millennium Development Goals initiative.

Methods: The relationship between child mortality and Official Development Aid over the duration of the Millennium Development Goals (2000-2015) is examined here using a longitudinal panel of country-level data from the World Bank and the United Nations. An Ordinary Least Squares regression approach was used with country-level fixed effects.

Offsetting the Effects of Medical Expenses on Older Adults' Household Food Budgets: An Analysis of the Standard Medical Expense Deduction.

The Supplemental Nutrition Assistance Program (SNAP) provides critical nutrition assistance to over 40 million Americans each month. Low-income older adults (60 and older) and disabled participants experience additional budgetary constraints because of high out-of-pocket medical expenses. In recent years, some states have adopted a "Standard Medical Expense Deduction" (SMED) for senior and disabled beneficiaries, making it easier to report medical expenses in the SNAP application process.

Growth In SNAP Retailers Was Associated With Increased Client Enrollment In Georgia During The Great Recession.

Policies to improve food accessibility in underserved areas often use direct financial incentives to attract new food retailers. Our analysis of data on the Supplemental Nutrition Assistance Program (SNAP) in Georgia before and after the Great Recession suggests that increased program enrollment improves access to food for SNAP beneficiaries by acting as an indirect subsidy to retailers. We divided food stores into four categories: large, midsize, small, and specialty retailers.

An Empirical Analysis of the Association Between Cigarette Smoking and Participation in the Supplemental Nutrition Assistance Program.

Purpose: To examine the association between smoking and participation in Supplemental Nutrition Assistance Program (SNAP) among low-income families.

Design: A quasi-experimental design using pooled cross-sectional data from the Bureau of Labor Statistics' Consumer Expenditure Diary Survey.

Setting: A national, representative sample of US households from 2005 through 2012.

The Genetic Landscape of Hematopoietic Stem Cell Frequency in Mice.

Prior efforts to identify regulators of hematopoietic stem cell physiology have relied mainly on candidate gene approaches with genetically modified mice. Here we used a genome-wide association study (GWAS) strategy with the hybrid mouse diversity panel to identify the genetic determinants of hematopoietic stem/progenitor cell (HSPC) frequency. Among 108 strains, we observed ∼120- to 300-fold variation in three HSPC populations.

Prolonged fasting reduces IGF-1/PKA to promote hematopoietic-stem-cell-based regeneration and reverse immunosuppression.

Immune system defects are at the center of aging and a range of diseases. Here, we show that prolonged fasting reduces circulating IGF-1 levels and PKA activity in various cell populations, leading to signal transduction changes in long-term hematopoietic stem cells (LT-HSCs) and niche cells that promote stress resistance, self-renewal, and lineage-balanced regeneration. Multiple cycles of fasting abated the immunosuppression and mortality caused by chemotherapy and reversed age-dependent myeloid-bias in mice, in agreement with preliminary data on the protection of lymphocytes from chemotoxicity in fasting patients.

Adipocytic cells augment the support of primitive hematopoietic cells in vitro but have no effect in the bone marrow niche under homeostatic conditions.

Mesenchymal stem cells (MSCs), as well as osteoblastic cells derived from these MSCs, have been shown to be key components of the hematopoietic stem cell (HSC) niche. In this study, we wished to examine whether other cell types that are known to differentiate from MSCs similarly regulate the stem cell niche, namely cells of the adipocyte lineage. Recent studies have examined the role that adipocytes play in the biology of the HSCs in different bone locations and in transplantation settings; however, none have examined their role under homeostatic conditions.

Placental growth factor expression is required for bone marrow endothelial cell support of primitive murine hematopoietic cells.

Two distinct microenvironmental niches that regulate hematopoietic stem/progenitor cell physiology in the adult bone marrow have been proposed; the endosteal and the vascular niche. While extensive studies have been performed relating to molecular interactions in the endosteal niche, the mechanisms that regulate hematopoietic stem/progenitor cell interaction with bone marrow endothelial cells are less well defined. Here we demonstrate that endothelial cells derived from the bone marrow supported hematopoietic stem/progenitor cells to a higher degree than other endothelial or stromal cell populations.

Deficiency of GRP94 in the hematopoietic system alters proliferation regulators in hematopoietic stem cells.

We have previously reported that acute inducible knockout of the endoplasmic reticulum chaperone GRP94 led to an expansion of the hematopoietic stem and progenitor cell pool. Here, we investigated the effectors and mechanisms for this phenomenon. We observed an increase in AKT activation in freshly isolated GRP94-null HSC-enriched Lin(-) Sca-1(+) c-Kit(+) (LSK) cells, corresponding with higher production of PI(3,4,5)P3, indicative of PI3K activation.

Human osteosarcoma CD49f(-)CD133(+) cells: impaired in osteogenic fate while gain of tumorigenicity.

The biological relationships among self-renewal, tumorigenicity and lineage differentiation of human osteosarcoma-initiating cells (OSIC) remain elusive, making it difficult to identify and distinguish OSIC from osteosarcoma-forming cells (OSFC) for developing OSIC-targeted therapies. Using a new inverse-lineage tracking strategy coupled with serial human-to-mouse xenotransplantation, we identified a subpopulation of osteosarcoma cells with OSIC-like properties and sought to distinguish them from their progeny, OSFC. We found that serial transplantation of cells from different osteosarcoma cell lines and primary osteosarcoma tissues progressively increased the CD49f(+) subpopulation composing the bulk of the osteosarcoma mass.

The endoplasmic reticulum chaperone protein GRP94 is required for maintaining hematopoietic stem cell interactions with the adult bone marrow niche.

Hematopoietic stem cell (HSC) homeostasis in the adult bone marrow (BM) is regulated by both intrinsic gene expression products and interactions with extrinsic factors in the HSC niche. GRP94, an endoplasmic reticulum chaperone, has been reported to be essential for the expression of specific integrins and to selectively regulate early T and B lymphopoiesis. In GRP94 deficient BM chimeras, multipotent hematopoietic progenitors persisted and even increased, however, the mechanism is not well understood.

Blocking HIF1α activity eliminates hematological cancer stem cells.

Selective targeting of cancer stem cells (CSCs) has the potential to prevent cancer relapse. Wang et al. (2011) report that hypoxia-inducible factor 1α (HIF1α) represses Notch signaling to maintain CSC subsets from lymphoma, and that blocking HIF1α activity eliminates lymphoma and human acute myeloid leukemia (AML) CSCs.

Bone marrow fat is inversely related to cortical bone in young and old subjects.

Objective: Recent studies suggest a close local link between bone marrow adiposity and endosteal bone formation. Using magnetic resonance imaging, we examined whether the relation between the amount of marrow fat and cortical bone is present at multiple sites along the diaphyses of the long bones of young and old males and females.

Design: The relations between values for cortical bone area and percent marrow fat in each 5-mm section along the midthird of both femoral shafts were determined using magnetic resonance imaging in eight healthy young (aged <25 yr), and nine healthy old (aged >55 yr) men and women.

Pharmacologic modulation of the calcium-sensing receptor enhances hematopoietic stem cell lodgment in the adult bone marrow.

The ability of hematopoietic stem cells (HSCs) to undergo self-renewal is partly regulated by external signals originating from the stem cell niche. Our previous studies with HSCs obtained from fetal liver of mice deficient for the calcium-sensing receptor (CaR) have shown the crucial role of this receptor in HSC lodgment and engraftment in the bone marrow (BM) endosteal niche. Using a CaR agonist, Cinacalcet, we assessed the effects of stimulating the CaR on the function of murine HSCs.

Hematopoietic stem cell lodgment in the adult bone marrow stem cell niche.

Treatment of malignant blood disorders, such as leukemia, that can provide a better chance of long-term remission involves myeloablation followed by transplantation of matched donor hematopoietic stem cells (HSCs). For successful engraftment and re-establishment of hematopoiesis to occur in the recipient, the transplanted HSCs must first migrate from the blood circulation to the bone marrow (BM), a process known as homing, then localize and anchor in suitable microenvironments within the BM, a process known as lodgment. After lodgment, the specific fate of the transplanted HSCs is determined through complex, bidirectional interactions with various stromal cell components in the niche.

Retinoid-suppressed phosphorylation of RARalpha mediates the differentiation pathway of osteosarcoma cells.

Although retinoic acid (RA) is a potent agent that coordinates inhibition of proliferation with differentiation of many cell types, RA-mediated signaling pathways in osteosarcoma cell differentiation are uncharacterized. In this study, we show that in human U2OS osteosarcoma cells, decreased phosphorylation of RA receptor alpha (RARalpha) by RA treatment or overexpressing a phosphorylation-defective mutant RARalphaS77A results in the inhibition of proliferation and induction of differentiation, and that U2OS cells transduced with RARalphaS77A suppresses tumor formation in nude mice. Moreover, using different human primary osteosarcoma cells and human mesenchymal stem cells for gene expression analysis, we found that either RA or RARalphaS77A induces many of the same differentiation response pathways and signaling molecules involved in U2OS cell differentiation.

The influence of parathyroid hormone on the adult hematopoietic stem cell niche.

Adult hematopoietic stem cells (HSCs) reside in the bone marrow in stable microenvironments known as the stem cell niche. One key component of the stem cell niche is cells of the osteoblastic lineage. Factors that are known to affect osteoblast activity, such as parathyroid hormone (PTH), have also been shown to affect the HSCs.