Incarceration history and opioid use among adults living with HIV and chronic pain: a secondary analysis of a prospective cohort study.

Background: Adults living with HIV have disproportionately high chronic pain, prescription opioid use, history of substance use, and incarceration. While incarceration can have long-lasting health impacts, prior studies have not examined whether distant (>1 year prior) incarceration is associated with opioid use for chronic pain, or with opioid misuse or opioid use disorder among people living with HIV and chronic pain.

Methods: We conducted a secondary analysis of a prospective cohort study of adults living with HIV and chronic pain.

Trajectories of Opioid Misuse and Opioid Use Disorder Among Adults With Chronic Pain and HIV: An Observational Study.

Objectives: In a longitudinal cohort of patients with HIV and chronic pain, we sought to (1) identify trajectories of opioid misuse and opioid use disorder (OUD) symptoms, and to (2) determine whether prescription opioid dose was associated with symptom trajectories.

Methods: We leveraged an existing 12-month longitudinal observational study, Project PIMENTO, of persons living with HIV and chronic pain who received care at a hospital system in the Bronx, New York. A quota sampling strategy was used to ensure variability of prescribed opioid use in the recruited sample.

Predictors of Colonoscopy Use Among Asian Indians in New York City, 2003 to 2016.

Background: Asian Americans have the lowest colorectal cancer screening uptake of any racial and ethnic group in the United States. Asian Indians are among the most under-screened Asian American subgroups, but there is limited data for this population. We sought to characterize predictors of colonoscopy use among Asian Indians in New York City.

Up-to-Date Colonoscopy Use in Asian and Hispanic Subgroups in New York City, 2003-2016.

Background: Colorectal cancer screening uptake in the United States overall has increased, but racial/ethnic disparities persist and data on colonoscopy uptake by racial/ethnic subgroups are lacking. We sought to better characterize these trends and to identify predictors of colonoscopy uptake, particularly among Asian and Hispanic subgroups.

Study: We used data from the New York City Community Health Survey to generate estimates of up-to-date colonoscopy use in Asian and Hispanic subgroups across 6 time periods spanning 2003-2016.

Factors Associated with Up-to-Date Colonoscopy Use Among Puerto Ricans in New York City, 2003-2016.

Background: Colorectal cancer is the second leading cause of cancer death among Hispanic Americans. Puerto Ricans are the second largest Hispanic subgroup in the USA and the largest in New York City, but little is known about predictors of colorectal cancer screening uptake in this population.

Aims: We used the New York City Community Health Survey, a population-based telephone survey, to investigate predictors of up-to-date colonoscopy use over time among Puerto Ricans aged ≥ 50 years in NYC.

Observations on the Early Stages of Corrosion on AA2099-T83.

An Al–Cu–Li aerospace alloy has been investigated to determine the order in which corrosion at different types of sites occurs in AA2099-T83. Specifically, the sequence of galvanic attack on intermetallic (IM) particles and other sites of AA2099-T83 was determined as a function of time, in 0.1 M NaCl, through the use of scanning electron microscopy and electron backscatter diffraction characterization techniques.

Investigation of the Internal Structure of a Modern Seafloor Hydrothermal Chimney With a Combination of EBSD, EPMA, and XRD.

Samples from the sphalerite-dominated zone of a seafloor massive sulfide chimney, the Satanic Mills Chimney of the PACMANUS hydrothermal field, have been investigated to determine the internal macrostructure and microstructure of this zone, the phases present, and the distribution of metals. A combination of electron probe microanalysis, electron backscattered diffraction, and x-ray diffraction has been used. At the macroscale, this zone of the chimney wall is heavily porous and is comprised primarily of sphalerite, enclosing minor chalcopyrite, pyrite, and wurtzite.

Soft X-Ray and Cathodoluminescence Examination of a Tanzanian Graphite Deposit.

Hyperspectral soft X-ray emission (SXE) and cathodoluminescence (CL) spectrometry have been used to investigate a carbonaceous-rich geological deposit to understand the crystallinity and morphology of the carbon and the associated quartz. Panchromatic CL maps show both the growth of the quartz and the evidence of recrystallization. A fitted CL map reveals the distribution of Ti4+ within the grains and shows subtle growth zoning, together with radiation halos from 238U decay.

Characteristics of methadone maintenance treatment patients prescribed opioid analgesics.

Background: Opioid analgesic use and disorders have dramatically increased among the general American population and those receiving methadone maintenance treatment (MMT). Most research among MMT patients focuses on opioid analgesics misuse or disorders; few studies focus on MMT patients prescribed opioid analgesics. We describe demographic, clinical, and substance use characteristics of MMT patients prescribed opioid analgesics and compare them with MMT patients not prescribed opioid analgesics.

Structure-based design and synthesis of potent, ethylenediamine-based, mammalian farnesyltransferase inhibitors as anticancer agents.

A potent class of anticancer, human farnesyltransferase (hFTase) inhibitors has been identified by "piggy-backing" on potent, antimalarial inhibitors of Plasmodium falciparum farnesyltransferase (PfFTase). On the basis of a 4-fold substituted ethylenediamine scaffold, the inhibitors are structurally simple and readily derivatized, facilitating the extensive structure-activity relationship (SAR) study reported herein. Our most potent inhibitor is compound 1f, which exhibited an in vitro hFTase IC(50) value of 25 nM and a whole cell H-Ras processing IC(50) value of 90 nM.

Electron-beam-induced carbon contamination on silicon: characterization using Raman spectroscopy and atomic force microscopy.

Electron-beam-induced carbon film deposition has long been recognized as a side effect of scanning electron microscopy. To characterize the nature of this type of contamination, silicon wafers were subjected to prolonged exposure to 15 kV electron beam energy with a probe current of 300 pA. Using Raman spectroscopy, the deposited coating was identified as an amorphous carbon film with an estimated crystallite size of 125 A.

Non-peptidic substrate-mimetic inhibitors of Akt as potential anti-cancer agents.

Akt has emerged as a critical target for the development of anti-cancer therapies. It has been found to be amplified, overexpressed, or constitutively activated in numerous human malignancies with oncogenesis derived from the simultaneous promotion of cell survival and suppression of apoptosis. A valuable alternative to the more common ATP-mimetic based chemotherapies is a substrate-mimetic approach, which has the potential advantage of inherent specificity of the substrate-binding pocket.

An oxazole-based small-molecule Stat3 inhibitor modulates Stat3 stability and processing and induces antitumor cell effects.

Stat3 is hyperactivated in many human tumors and represents a valid target for anticancer drug design. We present a novel small-molecule Stat3 inhibitor, S3I-M2001, and describe the dynamics of intracellular processing of activated Stat3 within the context of the biochemical and biological effects of the Stat3 inhibitor. S3I-M2001 is an oxazole-based peptidomimetic of the Stat3 Src homology (SH) 2 domain-binding phosphotyrosine peptide that selectively disrupts active Stat3:Stat3 dimers.

Isoform selective inhibition of STAT1 or STAT3 homo-dimerization via peptidomimetic probes: structural recognition of STAT SH2 domains.

The identification of constitutively activated STAT (Signal Transducers and Activators of Transcription) proteins in aberrant cell signaling pathways has led to investigations targeting the selective disruption of specific STAT isoforms directly associated with oncogenisis. We have identified, through the design of a library of peptidomimetic inhibitors, agents that selectively disrupt STAT1 or STAT3 homo-dimerization at low micromolar concentrations. ISS840 has 20-fold higher inhibition of STAT1 homo-dimerization (IC(50) value of 31 microM) relative to STAT3 (IC(50) value of 560 microM).

Modifications of the GSK3beta substrate sequence to produce substrate-mimetic inhibitors of Akt as potential anti-cancer therapeutics.

Amplification, overexpression, and elevated activation of Akt have been detected in many human malignancies making it an important target for cancer therapy. The Akt substrate-binding site offers a large number of potential interactions to an appropriately designed small molecule and can form the basis for the development of selective inhibitors. Here, we report the progression of GSK3beta substrate-mimetic inhibitors towards the development of a potent, small molecule substrate-mimetic inhibitor of Akt.

Design, synthesis, potency, and cytoselectivity of anticancer agents derived by parallel synthesis from alpha-aminosuberic acid.

Chemotherapy in the last century was characterized by cytotoxic drugs that did not discriminate between cancerous and normal cell types and were consequently accompanied by toxic side effects that were often dose limiting. The ability of differentiating agents to selectively kill cancer cells or transform them to a nonproliferating or normal phenotype could lead to cell- and tissue-specific drugs without the side effects of current cancer chemotherapeutics. This may be possible for a new generation of histone deacetylase inhibitors derived from amino acids.

Structurally simple, potent, Plasmodium selective farnesyltransferase inhibitors that arrest the growth of malaria parasites.

Third world nations require immediate access to inexpensive therapeutics to counter the high mortality inflicted by malaria. Here, we report a new class of antimalarial protein farnesyltransferase (PFT) inhibitors, designed with specific emphasis on simple molecular architecture, to facilitate easy access to therapies based on this recently validated antimalarial target. This novel series of compounds represents the first Plasmodium falciparum selective PFT inhibitors reported (up to 145-fold selectivity), with lead inhibitors displaying excellent in vitro activity (IC(50) < 1 nM) and toxicity to cultured parasites at low concentrations (ED(50) < 100 nM).

Differential effects of Stat3 inhibition in sparse vs confluent normal and breast cancer cells.

The signal transducer and activator of transcription-3 (Stat3) is persistently activated in many cancers such as cancer of the breast and is required for transformation by a number of oncogenes. Signaling through Stat3 is determined by a key phosphorylation at tyr-705. We previously demonstrated that cell-to-cell adhesion brought about through cell aggregation or confluence of cultured cells causes a dramatic increase in Stat3 tyr705 phosphorylation and consequently Stat3 activity in both normal and tumor cells.

Antiproliferative and phenotype-transforming antitumor agents derived from cysteine.

Selective destruction of malignant tumor cells without damaging normal cells is an important goal for cancer chemotherapy in the 21st century. Differentiating agents that transform cancer cells to either a nonproliferating or normal phenotype could potentially be tissue-specific and avoid side effects of current drugs. However, most compounds that are presently known to differentiate cancer cells are histone deacetylase inhibitors that are of low potency or suffer from low bioavailability, rapid metabolism, reversible differentiation, and nonselectivity for cancer cells over normal cells.

Novel peptidomimetic inhibitors of signal transducer and activator of transcription 3 dimerization and biological activity.

The critical role of signal transducer and activator of transcription 3 (Stat3) in the growth and survival of human tumor cells identifies it as a promising target for cancer drug discovery. We previously identified a Stat3 SH2 domain-binding phosphopeptide, PY*LKTK, and its tripeptide derivatives, PY*L and AY*L (where Y* represents phosphotyrosine), which inhibit Stat3 biochemical activity and biological function. Here, we report novel peptidomimetic compounds based on PY*L (or AY*L) with substitution of the Y-1 residue by benzyl, pyridyl, or pyrazinyl derivatives that are selective and greater than 5-fold more potent in disrupting Stat3 activity in vitro than lead tripeptides.

Conformationally homogeneous cyclic tetrapeptides: useful new three-dimensional scaffolds.

The most commonly recognized motifs in protein-protein interactions are gamma and beta turns, which are defined by three to four contiguous amino acids in a peptide sequence. Cyclic tetrapeptides thus represent minimalist turn mimetics, but their usefulness is compromised by strain in their 12-membered rings, making them difficult to cyclize, unstable to hydrolysis/metabolism, and conformationally heterogeneous in polar solvents. Appropriate placement of a beta amino acid in a tetrapeptide creates a 13-membered ring that is shown to be easier to cyclize, hydrolytically more stable, and conformationally homogeneous in polar solvents such as DMSO and water.