The optimization of harm reduction services in Massachusetts through the use of GIS: Location-allocation analyses, 2019-2021.

Background: Fatal opioid-related overdoses (OOD) continue to be a leading cause of preventable death across the US. Opioid Overdose Education and Naloxone Distribution programs (OENDs) play a vital role in addressing morbidity and mortality associated with opioid use, but access to such services is often inequitable. We utilized a geographic information system (GIS) and spatial analytical methods to inform prioritized placement of OEND services in Massachusetts.

Trends in Fatal Opioid-Related Overdose in American Indian and Alaska Native Communities, 1999-2021.

Introduction: Opioid-related overdose mortality rates have increased sharply in the U.S. over the past two decades, and inequities across racial and ethnic groups have been documented.

Spatial access to buprenorphine-waivered prescribers in the HEALing communities study: Enhanced 2-step floating catchment area analyses in Massachusetts, Ohio, and Kentucky.

Introduction: The opioid overdose epidemic continues to impact a large swath of the population in the US. Medications for opioid use disorders (MOUD) are an effective resource to combat the epidemic; however, there is limited research on MOUD treatment access that accounts for both supply of and demand for services. We aimed to examine access to buprenorphine prescribers in the HEALing Communities Study (HCS) Wave 2 communities in Massachusetts, Ohio, and Kentucky during 2021, and the association between buprenorphine access and opioid-related incidents, specifically fatal overdoses and opioid-related responses by emergency medical services (EMS).

Methods for jurisdictional vulnerability assessment of opioid-related outcomes.

In 2020, an estimated 2.7 million people in the US had opioid use disorder, increasing their risk of opioid-related morbidity and mortality. While jurisdictional vulnerability assessments (JVA) of opioid-related outcomes have been conducted previously in the US, there has been no unifying methodological framework.

Opioid-related mortality: Dynamic temporal and spatial trends by drug type and demographic subpopulations, Massachusetts, 2005-2021.

Background: Fatal opioid-related overdoses (OOD) present significant public health challenges. Intuitive and replicable analytical approaches are needed to inform targeted public health responses.

Methods: We obtained fatal OOD data for 2005-2021 from the Massachusetts Registry of Vital Records and Statistics.

Disruption of Core Planar Cell Polarity Signaling Regulates Renal Tubule Morphogenesis but Is Not Cystogenic.

Oriented cell division (OCD) and convergent extension (CE) shape developing renal tubules, and their disruption has been associated with polycystic kidney disease (PKD) genes, the majority of which encode proteins that localize to primary cilia. Core planar cell polarity (PCP) signaling controls OCD and CE in other contexts, leading to the hypothesis that disruption of PCP signaling interferes with CE and/or OCD to produce PKD. Nonetheless, the contribution of PCP to tubulogenesis and cystogenesis is uncertain, and two major questions remain unanswered.

Microtubules enable the planar cell polarity of airway cilia.

Background: Airway cilia must be physically oriented along the longitudinal tissue axis for concerted, directional motility that is essential for proper mucociliary clearance.

Results: We show that planar cell polarity (PCP) signaling specifies directionality and orients respiratory cilia. Within all airway epithelial cells, a conserved set of PCP proteins shows interdependent, asymmetric junctional localization; nonautonomous signaling coordinates polarization between cells; and a polarized microtubule (MT) network is likely required for asymmetric PCP protein localization.

A novel role for FOXA2 and SHH in organizing midbrain signaling centers.

The floor plate (FP) is a midline signaling center, known to direct ventral cell fates and axon guidance in the neural tube. The recent identification of midbrain FP as a source of dopaminergic neurons has renewed interest in its specification and organization, which remain poorly understood. In this study, we have examined the chick midbrain and spinal FP and show that both can be partitioned into medial (MFP) and lateral (LFP) subdivisions.

E2A proteins enhance the histone acetyltransferase activity of the transcriptional co-activators CBP and p300.

The E2A gene encodes the E-protein transcription factors E12 and E47 that play critical roles in B-lymphopoiesis. A somatic chromosomal translocation detectable in 5% of cases of acute lymphoblastic leukemia (ALL) involves E2A and results in expression of the oncogenic transcription factor E2A-PBX1. CREB binding protein (CBP) and its close paralog p300 are transcriptional co-activators with intrinsic histone acetyltransferase (HAT) activity.

Mapping acetylation sites in E2A identifies a conserved lysine residue in activation domain 1 that promotes CBP/p300 recruitment and transcriptional activation.

E-proteins are basic helix-loop-helix transcription factors that function in cell type specification. The gene E2A encodes two E-proteins, E12 and E47, which are required in B-lymphopoiesis. E2A proteins can interact directly with the transcriptional co-activators and lysine acetyltranferases (KATs) CBP, p300 and PCAF to induce target gene transcription.

Pointing in the right direction: new developments in the field of planar cell polarity.

Planar cell polarity (PCP) is observed in an array of developmental processes that involve collective cell movement and tissue organization, and its disruption can lead to severe developmental defects. Recent studies in flies and vertebrates have identified new functions for PCP as well as new signalling components, and have proposed new mechanistic models. However, despite this progress, the search to simplify principles of understanding continues and important mechanistic uncertainties still pose formidable challenges.

Lifestyle factors, hormonal contraception, and premenstrual symptoms: the United Kingdom Southampton Women's Survey.

Objective: To estimate the prevalence of premenstrual symptoms in women from the general population in Southampton, U.K., and examine their association with lifestyle factors and contraceptive use.

Diversification of the expression patterns and developmental functions of the dishevelled gene family during chordate evolution.

Dishevelled (Dvl) proteins are key transducers of Wnt signaling encoded by members of a multi-gene family in vertebrates. We report here the divergent, tissue-specific expression patterns for all three Dvl genes in Xenopus embryos, which contrast dramatically with their expression patterns in mice. Moreover, we find that the expression patterns of Dvl genes in the chick diverge significantly from those of Xenopus.

Regulation of ventral midbrain patterning by Hedgehog signaling.

In the developing ventral midbrain, the signaling molecule sonic hedgehog (SHH) is sufficient to specify a striped pattern of cell fates (midbrain arcs). Here, we asked whether and precisely how hedgehog (HH) signaling might be necessary for ventral midbrain patterning. By blocking HH signaling by in ovo misexpression of Ptc1(Delta)(loop2), we show that HH signaling is necessary and can act directly at a distance to specify midbrain cell fates.

Ecology of the microbial community removing phosphate from wastewater under continuously aerobic conditions in a sequencing batch reactor.

All activated sludge systems for removing phosphate microbiologically are configured so the biomass is cycled continuously through alternating anaerobic and aerobic zones. This paper describes a novel aerobic process capable of decreasing the amount of phosphate from 10 to 12 mg P liter(-1) to less than 0.1 mg P liter(-1) (when expressed as phosphorus) over an extended period from two wastewaters with low chemical oxygen demand.

Critical role for a single leucine residue in leukemia induction by E2A-PBX1.

In roughly 5% of cases of acute lymphoblastic leukemia, a chromosomal translocation leads to expression of the oncogenic protein E2A-PBX1. The N-terminal portion of E2A-PBX1, encoded by the E2A gene, is identical in sequence to the corresponding portion of the E proteins E12/E47 and includes transcriptional activation domains. The C terminus consists of most of the HOX interacting transcription factor PBX1, including its DNA-binding homeodomain.

E2A-PBX1 interacts directly with the KIX domain of CBP/p300 in the induction of proliferation in primary hematopoietic cells.

The E2A gene encodes DNA-binding transcription factors, called E12 and E47, involved in cell specification and maturation. E2A is also involved in a chromosomal translocation that leads to the expression of an oncogenic transcription factor called E2A-PBX1 in cases of acute leukemia. In the work described here, we elucidate the interaction between E2A-PBX1 and transcriptional co-activators.

Role for homodimerization in growth deregulation by E2a fusion proteins.

The oncogenic transcription factor E2a-Pbx1 is expressed in some cases of acute lymphoblastic leukemia as a result of chromosomal translocation 1;19. The early observation that E2a-Pbx1 incorporates transcriptional activation domains from E2a and a DNA-binding homeodomain from Pbx1 inspired a model in which E2a-Pbx1 promotes leukemogenic transformation of lymphoid progenitor cells through transcriptional induction of target genes defined by the Pbx1 portion of the molecule. However, the subsequent demonstration that the only known DNA-binding module on the molecule, the Pbx1 homeodomain, is dispensable for the induction of lymphoblastic lymphoma in transgenic mice called into question the contribution made by the Pbx1 portion.

Use of flexible intermediate and intensive care to reduce multiple transfers of patients.

Objective: To test an alternative flexible approach to traditional fixed intermediate and intensive care to minimize transfers of patients.

Methods: Patients admitted to a 28-bed nursing unit with intermediate care potential and a 12-bed intensive care unit at a 300-bed teaching community hospital were studied. The group included 524 patients with a discharge diagnosis code for mechanical ventilation.

Incidence of deep venous thrombosis associated with femoral venous catheterization.

Objective: To determine in adult medical patients the incidence of deep venous thrombosis (DVT) resulting from femoral venous catheterization (FVC).

Methods: A prospective, observational study was performed at a 420-bed community teaching hospital. Heparin-coated 7-FR cm femoral venous catheters were inserted unilaterally into a femoral vein.

Identification of a 13-kDa protein associated with the polyhydroxyalkanoic acid granules from Acinetobacter spp.

Proteins associated with poly-beta-hydroxybutyrate (PHB) granules were purified from four Acinetobacter strains isolated from modified activated sludge treatment plants. Four predominant proteins of 64 kDa, 41 kDa, 38 kDa and 13 kDa were identified. N-terminal amino acid sequencing of the 64-kDa and 13-kDa proteins from Acinetobacter RA3849 identified these proteins as the products of the phaCAc and phaPAc (formerly designated ORF1) genes, respectively.

Phosphate concentration regulates transcription of the Acinetobacter polyhydroxyalkanoic acid biosynthetic genes.

The polyhydroxyalkanoic acid (PHA) biosynthetic gene locus was cloned and characterized from an Acinetobacter sp. isolated from activated sludge. Nucleotide sequence analysis identified three clustered genes, phaAAc (encoding a beta-ketothiolase), phaBAc (encoding an acetoacetyl coenzyme A reductase), and phaCAc (encoding a PHA synthase).

Clinical features and natural history of Beckwith-Wiedemann syndrome: presentation of 74 new cases.

Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth syndrome with variable expression. To define the range and frequency of complications in BWS, we have studied a cohort of 76 affected patients (two previously reported). The most frequent complications were macroglossia (97%), abdominal wall defect (80%) and birth weight or postnatal growth > 90th centile (88%).

Cloning and analysis of the polyhydroxyalkanoic acid synthase gene from an Acinetobacter sp.: evidence that the gene is both plasmid and chromosomally located.

The polyhydroxyalkanoic acid (PHA) synthase gene (phaCAc) of a species of Acinetobacter isolated from an activated sludge treatment plant was cloned by heterologous complementation in a poly-beta-hydroxybutyrate (PHB) negative mutant of Alcaligenes eutrophus. Nucleotide sequence analysis of phaCAc revealed an open reading frame of 1770 bp with potential to encode a 67.7 kDa protein.

Differentiation of polyphosphate and poly-beta-hydroxybutyrate granules in an Acinetobacter sp. isolated from activated sludge.

Cells containing polyphosphate 71 micrograms P (mg protein)-1 and no poly-beta-hydroxybutyrate showed metachromatic granules but no lipid granules; cells containing poly-beta-hydroxybutyrate (15% of dry weight) showed fluorescence lipid granules but no metachromatic granules; whereas cells containing both polyphosphate and poly-beta-hydroxybutyrate showed both types of granules. These observations, together with a critical review of the literature, show a clear distinction between metachromatic (or volutin) granules and lipid granules.