Opioid receptor antagonism and neural response to monetary rewards: Pilot studies in light and heavy alcohol users.

Alcohol use disorder (AUD) is a prevalent condition associated with high degree of comorbidity and mortality. Among the few approved pharmacotherapies for AUD, two involve opioid receptor antagonism. Naltrexone and nalmefene are thought to act via opioid receptor blockage to reduce neural response to alcohol and drug-associated cues and consumption, but there have been limited efforts to characterize these effects in humans.

Tell Us What You Really Think: A Think Aloud Protocol Analysis of the Verbal Cognitive Reflection Test.

The standard interpretation of cognitive reflection tests assumes that correct responses are reflective and lured responses are unreflective. However, prior process-tracing of reflection tests has cast doubt on this interpretation. In two studies (N = 201), we deployed a validated think-aloud protocol in-person and online to test how this assumption is satisfied by the new, validated, less familiar, and non-mathematical verbal Cognitive Reflection Test (vCRT).

Human cell-based estrogen receptor beta dimerization assay.

Estrogen is not only responsible for important functions in the human body, such as cell growth, reproduction, differentiation, and development, but it is also deeply related to pathological processes, such as cancer, metabolic and cardiovascular diseases, and neurodegeneration. Estrogens and other estrogenic compounds have transcriptional activities through binding with the estrogen receptor (ER) to induce ER dimerization. The two estrogen receptor subtypes, estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ), show structural differences and have different expression ratios in specific cells and tissues.

Influence of age and sex on alcohol pharmacokinetics and subjective pharmacodynamic responses following intravenous alcohol exposure in humans.

There are substantial inter-individual variations in alcohol metabolism and response that are likely due to sex and age; however, these are not well understood. We investigated age and sex influences on alcohol elimination rate (AER) and subjective responses following intravenous (IV) administration in non-dependent drinkers. Participants underwent a 2-session study where they received IV alcohol (target breath alcohol level: 0.

Testing for implicit bias: Values, psychometrics, and science communication.

Our understanding of implicit bias and how to measure it has yet to be settled. Various debates between cognitive scientists are unresolved. Moreover, the public's understanding of implicit bias tests continues to lag behind cognitive scientists'.

The Motivation for Alcohol Reward: Predictors of Progressive-Ratio Intravenous Alcohol Self-Administration in Humans.

The Progressive Ratio (PR) self-administration paradigm is a common pre-clinical method used to examine the motivation for a drug attributed to a craving, reward, or the relief of negative affect. The Computer-assisted Alcohol Infusion System (CAIS) enables intravenous alcohol self-administration behavior in humans. This system provides the investigator with control over the trajectory of each incremental breath alcohol concentration (BrAC) reward and the maximum BrAC allowed in a session.

An In vitro dimerization assay for the adverse outcome pathway approach in risk assessment of human estrogen receptor α-mediated endocrine-disrupting chemicals.

The adverse outcome pathway (AOP) has been recently proposed as an effective framework for chemical risk assessment. The AOP framework offers the advantage of effectively integrating individual in vitro studies and in silico prediction models. Thus, the development of an effective testing method to measure key events caused by chemicals is essential for chemical risk assessment through a fully developed AOP framework.

Glutathione sensitive vesicles prepared from supramolecular amphiphiles.

Glutathione (GSH) sensitive vesicles were prepared by the self-assembly of amphiphilic inclusion complexes. These novel chemically sensitive supramolecular amphiphiles are anticipated to have applications in drug delivery; the nanocarriers can protect the encapsulated cargo and release it triggered degradation in high concentrations of GSH. Additionally, the sensitivity of the vesicles to GSH indicates that the dynamic covalent disulfide bond at the vesicle surface can be used for post-modification of the nanocarrier a thiol-disulfide exchange, a strategy that can be exploited to introduce targeting moieties to increase treatment specificity.

Microbial Degradation of Citric Acid in Low Level Radioactive Waste Disposal: Impact on Biomineralization Reactions.

Organic complexants are present in some radioactive wastes and can challenge waste disposal as they may enhance subsurface mobility of radionuclides and contaminant species via chelation. The principal sources of organic complexing agents in low level radioactive wastes (LLW) originate from chemical decontamination activities. Polycarboxylic organic decontaminants such as citric and oxalic acid are of interest as currently there is a paucity of data on their biodegradation at high pH and under disposal conditions.

Your health vs. my liberty: Philosophical beliefs dominated reflection and identifiable victim effects when predicting public health recommendation compliance during the COVID-19 pandemic.

In response to crises, people sometimes prioritize fewer specific identifiable victims over many unspecified statistical victims. How other factors can explain this bias remains unclear. So two experiments investigated how complying with public health recommendations during the COVID19 pandemic depended on victim portrayal, reflection, and philosophical beliefs (Total N = 998).

Rediscovering empowerment with breastfeeding in an urban First Nation's population.

Background: An inner-city neighbourhood of Regina, Saskatchewan continues to have recurring issues of drug and alcohol use affecting parents' caregiving opportunity. In relation to this, many children, mostly of First Nations descent, are raised in out-of-home care away from their families. With the promotion of breastfeeding, in a neighbourhood prenatal/postnatal support program, breastfeeding rates have doubled and mothers' participation in their children's care has increased.

Not all who ponder count costs: Arithmetic reflection predicts utilitarian tendencies, but logical reflection predicts both deontological and utilitarian tendencies.

Conventional sacrificial moral dilemmas propose directly causing some harm to prevent greater harm. Theory suggests that accepting such actions (consistent with utilitarian philosophy) involves more reflective reasoning than rejecting such actions (consistent with deontological philosophy). However, past findings do not always replicate, confound different kinds of reflection, and employ conventional sacrificial dilemmas that treat utilitarian and deontological considerations as opposite.

A comparison of seasonal trends in asthma exacerbations among children from geographic regions with different climates.

Background: The fall peak in childhood asthma exacerbations is thought to be related to an increase in viral infections and allergen exposure when children return to school. Whether the seasonality of asthma attacks among children from different geographic regions follows similar trends is unclear.

Objective: To compare seasonal trends in asthma exacerbations among school-age children who lived in different geographic locations, with different climates, within the United States.

Patterns of care for renal surgery: Underutilization of nephron-sparing procedures.

Background: Nephron-sparing procedures are well-described, provide similar oncologic outcomes to nephrectomy, and potentially decrease morbidity as compared to nephrectomy.

Methods: We analyzed academic and community health system data from Virginia and Kentucky to evaluate the utilization and cost of nephron-sparing procedures. Primary International Classification of Disease (ICD-9) diagnosis and procedure codes were employed to target subjects of interest.

Promoting identities and mental health via cultural/community activities among racially/ethnically mixed urban American Indians.

This qualitative, focus group study explored the role of cultural/community activities in potentially promoting identities and mental health among urban American Indians who have mixed racial/ethnic heritages (e.g., African, Hispanic, and Caucasian) including those with mental illness in Philadelphia, Pennsylvania (n = 25).

A screen-printed, amperometric biosensor array incorporated into a novel automated system for the simultaneous determination of organophosphate pesticides.

Organophosphate pesticides present serious risks to human and environmental health. A rapid reliable, economical and portable analytical system will be of great benefit in the detection and prevention of contamination. A biosensor array based on six acetylcholinesterase enzymes for use in a novel automated instrument incorporating a neural network program is described.

Neoclerodane diterpenes as a novel scaffold for mu opioid receptor ligands.

Structural modification of salvinorin A, the active component of Salvia divinorum, has resulted in the synthesis of novel neoclerodane diterpenes with opioid receptor affinity and activity. We report in this study a nonnitrogenous neoclerodane diterpene with mu opioid receptor affinity (13) that is an agonist at mu opioid receptors. This represents the identification of a novel structural class of mu opioid receptor agonists.

Loss of Gbx2 results in neural crest cell patterning and pharyngeal arch artery defects in the mouse embryo.

Several syndromes characterized by defects in cardiovascular and craniofacial development are associated with a hemizygous deletion of chromosome 22q11 in humans and involve defects in pharyngeal arch and neural crest cell development. Recent efforts have focused on identifying 22q11 deletion syndrome modifying loci. In this study, we show that mouse embryos deficient for Gbx2 display aberrant neural crest cell patterning and defects in pharyngeal arch-derived structures.

Sonic hedgehog is required for cardiac outflow tract and neural crest cell development.

The Hedgehog signaling pathway is critical for a significant number of developmental patterning events. In this study, we focus on the defects in pharyngeal arch and cardiovascular patterning present in Sonic hedgehog (Shh) null mouse embryos. Our data indicate that, in the absence of Shh, there is general failure of the pharyngeal arch development leading to cardiac and craniofacial defects.

Hedgehog signaling in murine vasculogenesis and angiogenesis.

Vasculogenesis-the formation of blood vessels de novo from endothelial cells-and angiogenesis-the process of blood vessel remodeling-are regulated by a number of signal transduction pathways, some specific to the vascular system and others used more broadly during embryogenesis. Recent evidence in both zebrafish and mouse suggests a role for Hedgehog (Hh) signaling in both vasculogenesis and angiogenesis. Hh signaling can target endothelial cells directly or can stimulate blood vessel support cells to produce vascular growth factors.

Chorioallantoic fusion defects and embryonic lethality resulting from disruption of Zfp36L1, a gene encoding a CCCH tandem zinc finger protein of the Tristetraprolin family.

The mouse gene Zfp36L1 encodes zinc finger protein 36-like 1 (Zfp36L1), a member of the tristetraprolin (TTP) family of tandem CCCH finger proteins. TTP can bind to AU-rich elements within the 3'-untranslated regions of the mRNAs encoding tumor necrosis factor (TNF) and granulocyte-macrophage colony-stimulating factor (GM-CSF), leading to accelerated mRNA degradation. TTP knockout mice exhibit an inflammatory phenotype that is largely due to increased TNF secretion.

Hedgehog signaling is required for the differentiation of ES cells into neurectoderm.

Mouse embryonic stem cells can differentiate in vitro into cells of the nervous system, neurons and glia. This differentiation mimics stages observed in vivo, including the generation of primitive ectoderm and neurectoderm in embryoid body culture. We demonstrate here that embryonic stem cell lines mutant for components of the Hedgehog signaling cascade are deficient at generating neurectoderm-containing embryoid bodies.

Gradual evolution in bacteria: evidence from Bacillus systematics.

The bacterial genome projects have suggested a central role for horizontal transfer in bacterial adaptation, but it is difficult to rule out an adaptive role for ordinary genetic change in existing genes. The bacterial systematics literature can readily address the importance of gene acquisition in adaptive evolution, since phenotypic characterization typically assesses presence versus absence of metabolic capabilities, and metabolic gains and losses are most likely due to horizontal transfer and/or gene loss. Bacterial systematists have not geared their studies toward quantitative differences in metabolic capabilities, which are more likely to involve adjustments of existing genes.

From survival to success. It takes more than theory.

Health care does not always attract change agents. As a result, norms, values, and rules become ingrained. Attempting to change this is difficult.