Covalent Isothiocyanate Inhibitors of Macrophage Migration Inhibitory Factor as Potential Colorectal Cancer Treatments.

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that has roles in innate and adaptive human immune responses, as well as inflammation. MIF exerts its biological activity by binding to the cell surface receptor CD74 as well as intracellular signalling proteins. MIF also possesses keto-enol tautomerase activity.

Determinants of Hispanic and non-Hispanic Workers' Intent to Work Past Age 65: An Analysis From the Life Course Perspective.

The average retirement age in the United States (U.S.) has increased over the past few decades.

Plasminogen Receptors Promote Lipoprotein(a) Uptake by Enhancing Surface Binding and Facilitating Macropinocytosis.

Background: High levels of Lp(a) (lipoprotein(a)) are associated with multiple forms of cardiovascular disease. Lp(a) consists of an apoB-containing particle attached to the plasminogen homologue apo(a). The pathways for Lp(a) clearance are not well understood.

A Polynesianspecific missense CETP variant alters the lipid profile.

Identifying population-specific genetic variants associated with disease and disease-predisposing traits is important to provide insights into the genetic determinants of health and disease between populations, as well as furthering genomic justice. Various common pan-population polymorphisms at associate with serum lipid profiles and cardiovascular disease. Here, sequencing of identified a missense variant rs1597000001 (p.

Comparison of Clinical, Genetic, and Pathologic Features of Limbic and Diffuse Transactive Response DNA-Binding Protein 43 Pathology in Alzheimer's Disease Neuropathologic Spectrum.

Background: Increasing evidence suggests that TAR DNA-binding protein 43 (TDP-43) pathology in Alzheimer's disease (AD), or AD-TDP, can be diffuse or limbic-predominant. Understanding whether diffuse AD-TDP has genetic, clinical, and pathological features that differ from limbic AD-TDP could have clinical and research implications.

Objective: To better characterize the clinical and pathologic features of diffuse AD-TDP and differentiate it from limbic AD-TDP.

HIV Transmission Through Premastication.

Premastication is a potential route of transmission of HIV from caregiver to child. We report the case of a 13-month-old Alaska Native child from rural Alaska who presented with failure to thrive, recurrent pneumonias, severe dental decay, and dysphagia. The mother was HIV-uninfected.

Expression of stable and reliable preference and aversion phenotypes following place conditioning with psychostimulants.

Rationale And Objectives: Drug-seeking behavior occurs more readily in some individuals than others. This phenomenon is considered in studies of drug self-administration in which high drug-seeking/taking individuals can be identified. In contrast, studies of conditioned place preference (CPP) often involve a random sample of drug-naïve rodents that includes phenotypes not considered relevant to addiction.

Medical student confidence when training for a female genitourinary exam using models and standardized patients.

Aim: The purpose of this study is to investigate what factors make students feel confident and competent when performing a female genitourinary exam (FGUE) with normal, nonpathologic findings. We anticipated that students would increase their confidence and perceived competence from the first year to the second year of medical school, would prefer the use of specialized standardized patients (SSPs) over models, and that the results would vary by student demographics.

Methods: Student confidence and perceived competence were measured using voluntary survey methods pre- and postinterventions.

A Revised Measure of Acceptance of the Theory of Evolution: Introducing the MATE 2.0.

Hundreds of articles have explored the extent to which individuals accept evolution, and the Measure of Acceptance of the Theory of Evolution (MATE) is the most often used survey. However, research indicates the MATE has limitations, and it has not been updated since its creation more than 20 years ago. In this study, we revised the MATE using information from cognitive interviews with 62 students that revealed response process errors with the original instrument.

Examining Psychological and Knowledge Barriers to Colorectal Cancer Screening in Rural Appalachian Kentucky.

While recent rates of colorectal cancer (CRC) screening have improved in Appalachian Kentucky due to public health efforts, they remain lower compared to both KY as a whole, and the USA. Suboptimal screening rates represent a missed opportunity to engage in early detection and prevention. The purpose of this study is to determine the impact that lack of knowledge has on psychological barriers (e.

The mediating/moderating role of cultural context factors on self-care practices among those living with diabetes in rural Appalachia.

Background: The aim of this study was to examine whether cultural factors, such as religiosity and social support, mediate/moderate the relationship between personal/psychosocial factors and T2DM self-care in a rural Appalachian community.

Methods: Regression models were utilized to assess for mediation and moderation. Multilevel linear mixed effects models and GEE-type logistic regression models were fit for continuous (social support, self-care) and binary (religiosity) outcomes, respectively.

Rural Residents' Perspectives on an mHealth or Personalized Health Coaching Intervention: Qualitative Study With Focus Groups and Key Informant Interviews.

Background: Compared with national averages, rural Appalachians experience extremely elevated rates of premature morbidity and mortality. New opportunities, including approaches incorporating personal technology, may help improve lifestyles and overcome health inequities.

Objective: This study aims to gather perspectives on whether a healthy lifestyle intervention, specifically an app originally designed for urban users, may be feasible and acceptable to rural residents.

The effect of analyst training on fecal egg counting variability.

Fecal egg counts (FECs) are essential for veterinary parasite control programs. Recent advances led to the creation of an automated FEC system that performs with increased precision and reduces the need for training of analysts. However, the variability contributed by analysts has not been quantified for FEC methods, nor has the impact of training on analyst performance been quantified.

Expression of select mRNA in Thoroughbreds with catastrophic racing injuries.

Background: The ability to identify horses at risk for catastrophic injuries continues to be a pressing issue for the racing industry, especially given recent events in North America.

Objectives: Since most catastrophic injuries occur in areas of existing pathology and this pathology is likely to elicit an inflammatory response, it was hypothesised that analysis of messenger RNA (mRNA) expression would detect significant changes in select genes in horses at risk for a catastrophic injury.

Study Design: Prospective cohort study.

Diagnostic performance of McMaster, Wisconsin, and automated egg counting techniques for enumeration of equine strongyle eggs in fecal samples.

Fecal egg counts are the cornerstone of equine parasite control programs. Previous work led to the development of an automated, image-analysis-based parasite egg counting system. The system has been further developed to include an automated reagent dispenser unit and a custom camera (CC) unit that generates higher resolution images, as well as a particle shape analysis (PSA) algorithm and machine learning (ML) algorithm.

Evaluating the Feasibility and Acceptability of Internet-Based Cognitive Behavioral Therapy for Insomnia in Rural Women.

Insomnia, one of the most common sleep disorders among women in midlife, is associated with multiple negative health outcomes. Rural Appalachian women are disproportionately affected by insufficient sleep, but their barriers to care (, health care shortages, cultural norms) may prevent intervention. This study assessed the feasibility and acceptability of Sleep Healthy Using the Internet (SHUTi) an Internet-based version of cognitive behavioral therapy for insomnia in Appalachian women ages 45+ years.

Cyp2b-null male mice are susceptible to diet-induced obesity and perturbations in lipid homeostasis.

Obesity is an endemic problem in the United States and elsewhere, and data indicate that in addition to overconsumption, exposure to specific chemicals enhances obesity. CYP2B metabolizes multiple endo- and xenobiotics, and recent data suggests that repression of Cyp2b activity increases dyslipidemia and age-onset obesity, especially in males. To investigate the role played by Cyp2b in lipid homeostasis and obesity, we treated wildtype and Cyp2b-null mice with a normal (ND) or 60% high-fat diet (HFD) for 10 weeks and determined metabolic and molecular changes.

The evaluation of e-learning resources as an adjunct to otolaryngology teaching: a pilot study.

Background: The concept of e-Learning has been rapidly accepted as an important component of medical education and is especially adept at teaching clinical skills. However, their impact on learning, particularly in Otolaryngology Head and Neck Surgery (OHNS) medical school curriculum, has yet to be adequately explored. The aim of this pilot study is to develop interactive e-Learning resources and evaluate their impact in enhancing OHNS teaching in medical school.

Pancreatic mitochondrial complex I exhibits aberrant hyperactivity in diabetes.

It is well established that NADH/NAD redox balance is heavily perturbed in diabetes, and the NADH/NAD redox imbalance is a major source of oxidative stress in diabetic tissues. In mitochondria, complex I is the only site for NADH oxidation and NAD regeneration and is also a major site for production of mitochondrial reactive oxygen species (ROS). Yet how complex I responds to the NADH/NAD redox imbalance and any potential consequences of such response in diabetic pancreas have not been investigated.

Case Report: Immune-mediated Complete Response in a Patient With Recurrent Advanced Ewing Sarcoma (EWS) After Vigil Immunotherapy.

Ewing sarcoma is a highly resistant disease with a <10% chance of survival at 5 years after failure of frontline chemotherapy. This is a case report of an Ewing sarcoma patient with metastatic disease recurrence <2 years after standard chemotherapy/radiation who achieved a durable and sustained complete response after 2 series of treatments with Vigil (GMCSF/bi-shRNA furin DNA autologous tumor immunotherapy) serially manufactured from first and second recurrences with ELISPOT assay correlation. Results support justification of further testing of Vigil with ELISPOT assay as a biomarker to assess level of immune response and correlation with disease control.

Metformin Impairs Spatial Memory and Visual Acuity in Old Male Mice.

Metformin is an oral anti-diabetic used as first-line therapy for type 2 diabetes. Because benefits of metformin extend beyond diabetes to other age-related pathology, and because its effect on gene expression profiles resembles that of caloric restriction, metformin has a potential as an anti-aging intervention and may soon be assessed as an intervention to extend healthspan. However, beneficial actions of metformin in the central nervous system have not been clearly established.

Retrograde conditioning of place preference and motor activity with cocaine in mice.

Rationale: In order to improve understanding of the nature of drug-associated memory, the current studies addressed whether conditioned place preference (CPP) could develop under conditions in which there was a delay between presentation of context and drug exposure (i.e., retrograde or trace conditioning).

Bevacizumab and Temozolomide Plus Radiation Regimen for Glioblastoma Multiforme.

The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases. Questions or suggestions for topics should be addressed to Dominic A.

The yeast genome undergoes significant topological reorganization in quiescence.

We have examined the three-dimensional organization of the yeast genome during quiescence by a chromosome capture technique as a means of understanding how genome organization changes during development. For exponentially growing cells we observe high levels of inter-centromeric interaction but otherwise a predominance of intrachromosomal interactions over interchromosomal interactions, consistent with aggregation of centromeres at the spindle pole body and compartmentalization of individual chromosomes within the nucleoplasm. Three major changes occur in the organization of the quiescent cell genome.

Multiple binding modes of isothiocyanates that inhibit macrophage migration inhibitory factor.

Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that has roles in the innate immune response, and also contributes to inflammatory disease. While the biological properties of MIF are closely linked to protein-protein interactions, MIF also has tautomerase activity. Inhibition of this activity interferes with the interaction of MIF with protein partners e.