Phosphoproteomic approach for agonist-specific signaling in mouse brains: mTOR pathway is involved in κ opioid aversion.

Kappa opioid receptor (KOR) agonists produce analgesic and anti-pruritic effects, but their clinical application was limited by dysphoria and hallucinations. Nalfurafine, a clinically used KOR agonist, does not cause dysphoria or hallucinations at therapeutic doses in humans. We found that in CD-1 mice nalfurafine produced analgesic and anti-scratch effects dose-dependently, like the prototypic KOR agonist U50,488H.

The Nutritional Status of HIV-Infected US Adults.

Nutrition is critical to HIV mortality and morbidity. Improved treatment modalities have increased life expectancy of HIV-infected individuals. More than 1 million US adults are living with HIV, but little is known about their nutritional status.

Conformational switching of the pseudokinase domain promotes human MLKL tetramerization and cell death by necroptosis.

Necroptotic cell death is mediated by the most terminal known effector of the pathway, MLKL. Precisely how phosphorylation of the MLKL pseudokinase domain activation loop by the upstream kinase, RIPK3, induces unmasking of the N-terminal executioner four-helix bundle (4HB) domain of MLKL, higher-order assemblies, and permeabilization of plasma membranes remains poorly understood. Here, we reveal the existence of a basal monomeric MLKL conformer present in human cells prior to exposure to a necroptotic stimulus.

Global Burden of Multiple Myeloma: A Systematic Analysis for the Global Burden of Disease Study 2016.

Introduction: Multiple myeloma (MM) is a plasma cell neoplasm with substantial morbidity and mortality. A comprehensive description of the global burden of MM is needed to help direct health policy, resource allocation, research, and patient care.

Objective: To describe the burden of MM and the availability of effective therapies for 21 world regions and 195 countries and territories from 1990 to 2016.

Embryogenesis and Adult Life in the Absence of Intrinsic Apoptosis Effectors BAX, BAK, and BOK.

Intrinsic apoptosis, reliant on BAX and BAK, has been postulated to be fundamental for morphogenesis, but its precise contribution to this process has not been fully explored in mammals. Our structural analysis of BOK suggests close resemblance to BAX and BAK structures. Notably, BokBaxBak animals exhibited more severe defects and died earlier than BaxBak mice, implying that BOK has overlapping roles with BAX and BAK during developmental cell death.

Autoregulation of the Streptococcus mutans SloR Metalloregulator Is Constitutive and Driven by an Independent Promoter.

, one of ∼600 bacterial species in the human oral cavity, is among the most acidogenic constituents of the plaque biofilm. Considered to be the primary causative agent of dental caries, harbors a 25-kDa SloR metalloregulatory protein which controls metal ion transport across the bacterial cell membrane to maintain essential metal ion homeostasis. The expression of SloR derives in part from transcriptional readthrough of the operon, which encodes a Mn/Fe ABC transport system.

ZnSe quantum dots modified with a Ni(cyclam) catalyst for efficient visible-light driven CO reduction in water.

A precious metal and Cd-free photocatalyst system for efficient CO reduction in water is reported. The hybrid assembly consists of ligand-free ZnSe quantum dots (QDs) as a visible-light photosensitiser combined with a phosphonic acid-functionalised Ni(cyclam) catalyst, NiCycP. This precious metal-free photocatalyst system shows a high activity for aqueous CO reduction to CO (Ni-based TON > 120), whereas an anchor-free catalyst, Ni(cyclam)Cl, produced three times less CO.

More to gain: dietary energy density is related to smoking status in US adults.

Background: Given the current prevalence of both cigarette use and obesity in the United States, identification of dietary patterns that reduce mortality risk are important public health priorities. The objective of the present study was to evaluate the correlation between cigarette use and dietary energy density, a marker for diet quality, in a population of current smokers, former smokers, and never smokers.

Methods: Data from a nationally representative sample of 5293 adults who participated in the 2013-2014 National Health and Nutrition Examination Surveys (NHANES) were analyzed.

Phoenixin: a novel brain-gut-skin peptide with multiple bioactivity.

In this brief review we summarize the current fndings relative to the discovery of a small peptide ligand, phoenixin (PNX). Using a bioinformatic approach, two novel peptides PNX-14 and PNX-20 containing 14 and 20 amino acids, respectively, were isolated from diverse tissues including the brain, heart, lung and stomach. Mass spectrometry analysis identified a major and minor peak corresponding to PNX-14 and PNX-20, in rat or mouse spinal cord extracts.

Plasma cell diseases and organ transplant: A comprehensive review.

Plasma cell diseases are a class of hematologic diseases that are sometimes present as preexisting diagnoses prior to organ transplantation, causative factors leading to a need for organ transplantation, or may occur posttransplant as part of the spectrum of posttransplant lymphoproliferative disorders. Herein, we review the most common plasma cell diseases, both as coexisting with other causes of organ failure, but also as a primary underlying cause for organ failure. In many cases, treatment of the underlying clonal disease may be indicated before proceeding with organ transplant.

Public Health Opportunities to Improve Late-Adolescent Immunization.

Seven state/local immunization program managers were convened to discuss how public health immunization programs could enhance their efforts to promote adolescent vaccination, with an emphasis on late adolescence (ages 16-18 years). The Centers for Disease Control and Prevention's revised childhood immunization schedule for 2017 and a recently proposed preventive care platform at 16 years of age provide a unique opportunity to focus on increasing adolescent immunization rates in this population. Public health officials discussed challenges to immunizing this population and suggested key strategies for supporting late-adolescent immunization, including partnerships between public health and immunization providers; nationally supported public information campaigns; and using immunization data specific to this population to track progress.

Circulating Plasma Cells at the Time of Collection of Autologous PBSC for Transplant in Multiple Myeloma Patients is a Negative Prognostic Factor Even in the Age of Post-Transplant Maintenance Therapy.

Circulating plasma cells (CPCs) have been detected in patients with multiple myeloma (MM) at various stages of disease and associated with worse outcomes. Little data exist regarding the impact of CPCs at the time of autologous peripheral blood stem cell (PBSC) collection on outcomes, and the impact of maintenance therapy after autologous stem cell transplantation (ASCT) on prognosis in patients with CPC-containing collections. All patients with MM who underwent first ASCT at Fred Hutchinson Cancer Research Center from 2012 to 2015 and had evaluation for CPCs at the time of PBSC collection were included in our analysis.

Directing the mechanism of CO reduction by a Mn catalyst through surface immobilization.

Immobilization of a Mn polypyridyl CO reduction electrocatalyst on nanocrystalline TiO electrodes yields an active heterogeneous system and also significantly triggers a change in voltammetric and catalytic behaviour, relative to in solution. A combination of spectroelectrochemical techniques are presented here to elucidate the mechanism of the immobilized catalyst in situ.

The Small Intestine Converts Dietary Fructose into Glucose and Organic Acids.

Excessive consumption of sweets is a risk factor for metabolic syndrome. A major chemical feature of sweets is fructose. Despite strong ties between fructose and disease, the metabolic fate of fructose in mammals remains incompletely understood.

ATR-Chk1 activation mitigates replication stress caused by mismatch repair-dependent processing of DNA damage.

The mismatch repair pathway (MMR) is essential for removing DNA polymerase errors, thereby maintaining genomic stability. Loss of MMR function increases mutation frequency and is associated with tumorigenesis. However, how MMR is executed at active DNA replication forks is unclear.

Alcohol and older people: A systematic review of barriers, facilitators and context of drinking in older people and implications for intervention design.

Background: Harmful alcohol consumption in older people has increased and effective approaches to understanding and addressing this societal concern are needed.

Methods: Systematic review of qualitative studies in older populations (55+ years) to identify barriers, facilitators or context of drinking in older people. Multiple databases (MEDLINE, EMBASE, PsycINFO, CINAHL, CENTRAL, Social Sciences Citation Index, York Centre for Reviews and Dissemination, Cochrane database and grey literature) were searched from 2000 to February 2017 for studies in English, from OECD countries using MeSH terms and text words relating to alcohol combined with older age terms.

Sources of Added Sugars in Young Children, Adolescents, and Adults with Low and High Intakes of Added Sugars.

High intake of added sugars is associated with excess energy intake and poorer diet quality. The objective of this cross-sectional study ( = 16,806) was to estimate usual intakes and the primary food sources of added sugars across the range of intakes (i.e.

Detection and Identification of Psilocybe cubensis DNA Using a Real-Time Polymerase Chain Reaction High Resolution Melt Assay.

Psilocybe cubensis, or "magic mushroom," is the most common species of fungus with psychedelic characteristics. Two primer sets were designed to target Psilocybe DNA using web-based software and NBCI gene sequences. DNA was extracted from eighteen samples, including twelve mushroom species, using the Qiagen DNeasy Plant Mini Kit.

A Randomised Controlled Trial of a Universal Bonding Agent at Three Years: Self Etch vs Total Etch.

General dental practice is increasingly being recognised as the ideal situation for the conduct of clinical trials into the longevity of restorations. The aim of this study was to investigate the survival of 64 nanofilled resin composite (Filtek Supreme XTE) restorations placed principally in loadbearing cavities using a Universal dentine bonding agent (Scotchbond Universal), in five UK dental practices by members of the UK-based practice-based research group, the PREP Panel. A split mouth design was used, comprising patients who required two restorations, with one of the restorations receiving a total etch approach using phosphoric acid and the other being placed using a self-etch approach.

Extracellular polymeric substance production in high rate algal oxidation ponds.

Integrated algal pond systems (IAPSs) combine anaerobic and aerobic bioprocesses to affect sewage treatment. The present work describes the isolation and partial characterisation of soluble extracellular polymeric substances (EPSs) associated with microalgal bacterial flocs (MaB-flocs) generated in high rate algal oxidation ponds (HRAOPs) of an IAPS treating domestic sewage. Productivity and change in MaB-flocs concentration, measured as mixed liquor suspended solids (MLSS) between morning (MLSS) and evening (MLSS) were monitored and the substructure of the MaB-flocs matrix examined by biochemical analysis and Fourier transform infrared spectroscopy (FT-IR).

Total Body Irradiation Is Safe and Similarly Effective as Chemotherapy-Only Conditioning in Autologous Stem Cell Transplantation for Mantle Cell Lymphoma.

Autologous stem cell transplant (ASCT) consolidation has become a standard approach for patients with mantle cell lymphoma (MCL), yet there is little consensus on the role of total body irradiation (TBI) as part of high-dose transplantation conditioning. We analyzed 75 consecutive patients with MCL who underwent ASCT at our institution between 2001 and 2011 with either TBI-based (n = 43) or carmustine, etoposide, cytarabine, melphalan (BEAM; n = 32) high-dose conditioning. Most patients (97%) had chemosensitive disease and underwent transplantation in first remission (89%).

Interventions to prevent and reduce excessive alcohol consumption in older people: a systematic review and meta-analysis.

Background: harmful alcohol consumption is reported to be increasing in older people. To intervene and reduce associated risks, evidence currently available needs to be identified.

Methods: two systematic reviews in older populations (55+ years): (1) Interventions to prevent or reduce excessive alcohol consumption; (2) Interventions as (1) also reporting cognitive and dementia outcomes.

The Role of Electrode-Catalyst Interactions in Enabling Efficient CO Reduction with Mo(bpy)(CO) As Revealed by Vibrational Sum-Frequency Generation Spectroscopy.

Group 6 metal carbonyl complexes ([M(bpy)(CO)], M = Cr, Mo, W) are potentially promising CO reduction electrocatalysts. However, catalytic activity onsets at prohibitively negative potentials and is highly dependent on the nature of the working electrode. Here we report in situ vibrational SFG (VSFG) measurements of the electrocatalyst [Mo(bpy)(CO)] at platinum and gold electrodes.

Pegylated GCSF Can Be Used With First-Line da-EPOCH-R Without Compromising Dose Intensity, Safety, or Efficacy.

Introduction: Infusional da-EPOCH-R (dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine, prednisone, and rituximab) is a dose-intensified regimen with a potential role in treating high-risk subtypes of aggressive B-cell non-Hodgkin lymphoma (B-NHL). Studies of da-EPOCH-R use daily injections of granulocyte colony-stimulating factor (GCSF) to tailor chemotherapy dosing, and whether 1-time administration of pegylated GCSF (peg-GCSF) is as efficacious has not been addressed.

Patients And Methods: We reviewed aggressive B-NHL patients treated at our center with first-line da-EPOCH-R for clinician choice of growth factor, and analyzed dose level achieved, rate of unplanned hospitalizations, and patient outcomes.