Medicine and Health Sciences Commons^™

Oral Supplementation With Non-Absorbable Antibiotics Or Curcumin Attenuates Western Diet-Induced Atherosclerosis And Glucose Intolerance In Ldlr−/− Mice – Role Of Intestinal Permeability And Macrophage Activation, Siddhartha S. Ghosh, Jinghua Bie, Jing Wang, Shobha Ghosh

Internal Medicine Publications

Association between circulating lipopolysaccharide (LPS) and metabolic diseases (such as Type 2 Diabetes and atherosclerosis) has shifted the focus from Western diet-induced changes in gut microbiota per se to release of gut bacteria-derived products into circulation as the possible mechanism for the chronic inflammatory state underlying the development of these diseases. Under physiological conditions, an intact intestinal barrier prevents this release of LPS underscoring the importance of examining and modulating the direct effects of Western diet on intestinal barrier function. In the present study we evaluated two strategies, namely selective gut decontamination and supplementation with oral curcumin, to modulate Western-diet …

Impact Of Appropriate Antimicrobial Therapy For Patients With Severe Sepsis And Septic Shock – A Quality Improvement Study, Paula K. O. Yokota, Alexandre R. Marra, Marines D. V. Martino, Elivane S. Victor, Marcelino S. Durão, Michael B. Edmond, Oscar F. P. Dos Santos

Internal Medicine Publications

Background

There is ample literature available on the association between both time to antibiotics and appropriateness of antibiotics and clinical outcomes from sepsis. In fact, the current state of debate surrounds the balance to be struck between prompt empirical therapy and care in the choice of appropriate antibiotics (both in terms of the susceptibility of infecting organism and minimizing resistance arising from use of broad-spectrum agents). The objective of this study is to determine sepsis bundle compliance and the appropriateness of antimicrobial therapy in patients with severe sepsis and septic shock and its impact on outcomes.

Material

This study was …

A Simple, Sensitive And Safe Method To Determine The Human Α/Β-Tryptase Genotype, Quang Trong Le, Sahar Lotfi-Emran, Hae-Ki Min, Lawrence B. Schwartz

Internal Medicine Publications

The human tryptase locus on chromosome 16 contains one gene encoding only β-tryptase and another encoding either β-tryptase or the homologous α-tryptase, providing α:β gene ratios of 0∶4, 1∶3 or 2∶2 in the diploid genome, these genotypes being of potential clinical relevance in severe atopy. Using an EcoRV restriction site in α- but not β- tryptase, PCR products, spanning intron 1 to exon 5, were used to determine α/β-tryptase gene ratios using non-radioactive labels, including ethidium bromide labeling of all PCR products, and either digoxigenin-primer or DY682-primer labeling of only the final PCR cycle products. Sensitivity increased ∼60-fold with each …

A Network Meta-Analysis On Randomized Trials Focusing On The Preventive Effect Of Statins On Contrast-Induced Nephropathy, Mariangela Peruzzi, Leonardo De Luca, Henrik S. Thomsen, Enrico Romagnoli, Fabrizio D’Ascenzo, Massimo Mancone, Gennaro Sardella, Luigi Lucisano, Antonio Abbate, Giacomo Frati, Giuseppe Giuseppe Biondi-Zoccai

Internal Medicine Publications

Contrast-induced nephropathy is a common complication of iodinated contrast administration. Statins may reduce the risk of contrast-induced nephropathy, but data remain inconclusive. We summarized the evidence based on statins for the prevention of contrast-induced nephropathy with a network meta-analysis. Randomized trials focusing on statins were searched and pooled with random-effect odds ratios. A total of 14 trials (6,160 patients) were included, focusing on atorvastatin (high/low dose), rosuvastatin (high dose), simvastatin (high/low dose), and placebo or no statin therapy before contrast administration. The risk of contrast-induced nephropathy was reduced by atorvastatin high dose and rosuvastatin high dose, with no difference between …

Perception And Barriers To Indoor Air Quality And Perceived Impact On Respiratory Health: An Assessment In Rural Honduras, Audrey Le, Gonzalo Bearman, Kakotan Sanogo, Michael P. Stevens

Internal Medicine Publications

Objective. The aim of this study was to identify household-specific factors associated with respiratory symptoms and to study the perceived impact of indoor air pollution (IAP) as a health issue. Methods. An IRB-approved, voluntary, anonymous 23-item survey was conducted in Spanish at a medical outreach clinic in June 2012 and at the homes of survey respondents (N = 79). Comparative analyses were performed to investigate relationships between specific house characteristics and respiratory complaints. Results. Seventy-nine surveys were completed. Respiratory symptoms were frequently reported by survey respondents: 42% stated that smoke in their household caused them to have …

Impact Of Appropriate Antimicrobial Therapy For Patients With Severe Sepsis And Septic Shock – A Quality Improvement Study, Paula K. O. Yokota, Alexandre R. Marra, Marines D. V. Martino, Elivane S. Victor, Marcelino S. Durão, Michael B. Edmond, Oscar F. P. Dos Santos

Internal Medicine Publications

Background

There is ample literature available on the association between both time to antibiotics and appropriateness of antibiotics and clinical outcomes from sepsis. In fact, the current state of debate surrounds the balance to be struck between prompt empirical therapy and care in the choice of appropriate antibiotics (both in terms of the susceptibility of infecting organism and minimizing resistance arising from use of broad-spectrum agents). The objective of this study is to determine sepsis bundle compliance and the appropriateness of antimicrobial therapy in patients with severe sepsis and septic shock and its impact on outcomes.

Material

This study was …

A Simple, Sensitive And Safe Method To Determine The Human Α/Β-Tryptase Genotype, Quang Trong Le, Sahar Lotfi-Emran, Hae-Ki Min, Lawrence B. Schwartz

Internal Medicine Publications

The human tryptase locus on chromosome 16 contains one gene encoding only β-tryptase and another encoding either β-tryptase or the homologous α-tryptase, providing α:β gene ratios of 0∶4, 1∶3 or 2∶2 in the diploid genome, these genotypes being of potential clinical relevance in severe atopy. Using an EcoRV restriction site in α- but not β- tryptase, PCR products, spanning intron 1 to exon 5, were used to determine α/β-tryptase gene ratios using non-radioactive labels, including ethidium bromide labeling of all PCR products, and either digoxigenin-primer or DY682-primer labeling of only the final PCR cycle products. Sensitivity increased ∼60-fold with each …

Inhibition Of The Mdm2 E3 Ligase Induces Apoptosis And Autophagy In Wild-Type And Mutant P53 Models Of Multiple Myeloma, And Acts Synergistically With Abt-737, Dongmin Gu, Shuhong Wang, Isere Kuiatse, Hua Wang, Jin He, Yun Dai, Richard J. Jones, Chad C. Bjorklund, Jing Yang, Steven Grant, Robert Z. Orlowski

Massey Comprehensive Cancer Center Publications

Intracellular proteolytic pathways have been validated as rational targets in multiple myeloma with the approval of two proteasome inhibitors in this disease, and with the finding that immunomodulatory agents work through an E3 ubiquitin ligase containing Cereblon. Another E3 ligase that could be a rational target is the murine double minute (MDM) 2 protein, which plays a role in p53 turnover. A novel inhibitor of this complex, MI-63, was found to induce apoptosis in p53 wild-type myeloma models in association with activation of a p53-mediated cell death program. MI-63 overcame adhesion-mediated drug resistance, showed anti-tumor activity in vivo, enhanced …

Live Cell Interferometry Quantifies Dynamics Of Biomass Partitioning During Cytokinesis, Thomas A. Zangle, Michael A. Teitell, Jason Reed

Massey Comprehensive Cancer Center Publications

The equal partitioning of cell mass between daughters is the usual and expected outcome of cytokinesis for self-renewing cells. However, most studies of partitioning during cell division have focused on daughter cell shape symmetry or segregation of chromosomes. Here, we use live cell interferometry (LCI) to quantify the partitioning of daughter cell mass during and following cytokinesis. We use adherent and non-adherent mouse fibroblast and mouse and human lymphocyte cell lines as models and show that, on average, mass asymmetries present at the time of cleavage furrow formation persist through cytokinesis. The addition of multiple cytoskeleton-disrupting agents leads to increased …

Circumvention Of Mcl-1-Dependent Drug Resistance By Simultaneous Chk1 And Mek1/2 Inhibition In Human Multiple Myeloma Cells, Xin-Yan Pei, Yun Dai, Jessica Felthousen, Shuang Shen, Yukie Takabatake, Liang Zhou, Leena E. Youssefian, Michael W. Sanderson, Wesley W. Bodie, Lora B. Kramer, Robert Z. Orlowski, Steven Grant

Massey Comprehensive Cancer Center Publications

The anti-apoptotic protein Mcl-1 plays a major role in multiple myeloma (MM) cell survival as well as bortezomib- and microenvironmental forms of drug resistance in this disease. Consequently, there is a critical need for strategies capable of targeting Mcl-1-dependent drug resistance in MM. The present results indicate that a regimen combining Chk1 with MEK1/2 inhibitors effectively kills cells displaying multiple forms of drug resistance stemming from Mcl-1 up-regulation in association with direct transcriptional Mcl-1 down-regulation and indirect disabling of Mcl-1 anti-apoptotic function through Bim up-regulation and increased Bim/Mcl-1 binding. These actions release Bak from Mcl-1, accompanied by Bak/Bax activation. Analogous …

Adjuvant Exemestane With Ovarian Suppression In Premenopausal Breast Cancer, Olivia Pagani, Meredith M. Regan, Barbara A. Walley, Gini F. Fleming, Marco Colleoni, István Láng, Henry L. Gomez, Carlo Tondini, Harold J. Burstein, Edith A. Perez, Eva Ciruelos, Vered Stearns, Hervé R. Bonnefoi, Silvana Martino, Charles E. Geyer Jr., Graziella Pinotti, Fabio Puglisi, Diana Crivellari, Thomas Ruhstaller, Eric P. Winer, Manuela Rabaglio-Poretti, Rudolf Maibach, Barbara Ruepp, Anita Giobbie-Hurder, Karen N. Price, Jürg Bernhard, Weixiu Luo, Karin Ribi, Giuseppe Viale, Alan S. Coates, Richard D. Gelber, Aron Goldhirsch, Prudence A. Francis

Massey Comprehensive Cancer Center Publications

BACKGROUND Adjuvant therapy with an aromatase inhibitor improves outcomes, as compared with tamoxifen, in postmenopausal women with hormone-receptor-positive breast cancer. METHODS In two phase 3 trials, we randomly assigned premenopausal women with hormone-receptor-positive early breast cancer to the aromatase inhibitor exemestane plus ovarian suppression or tamoxifen plus ovarian suppression for a period of 5 years. Suppression of ovarian estrogen production was achieved with the use of the gonadotropin-releasing-hormone agonist triptorelin, oophorectomy, or ovarian irradiation. The primary analysis combined data from 4690 patients in the two trials. RESULTS After a median follow-up of 68 months, disease-free survival at 5 years was …

Crystal Structures Of Influenza A Virus Matrix Protein M1: Variations On A Theme, Martin K. Safo, Faik N. Musayev, Philip D. Mosier, Qibing Zhou, Hang Xie, Umesh R. Desai

Medicinal Chemistry Publications

Matrix protein 1 (M1) of the influenza A virus plays multiple roles in virion assembly and infection. Interest in the pH dependence of M1's multiple functions led us to study the effect of subtle pH changes on M1 structure, resulting in the elucidation of a unique low-pH crystal structure of the N1-165-domain of A/WSN/33 (H1N1) M1 that has never been reported. Although the 2.2 Å crystal structure of M1 N-terminus shows a dimer with the two monomers interacting in a face-to-face fashion at low pH as observed earlier, a 44° rotation of the second monomer has led to a significantly …

Pediatric Emergency Medical Care In Yerevan, Armenia: A Knowledge And Attitudes Survey Of Out-Of-Hospital Emergency Physicians, Aline A. Baghdassarian, Ross I. Donaldson, Andrew D. Depiero, Nancy L. Chernett, Harsh Sule

Emergency Medicine Publications

Background

Out-of-hospital emergency care is at an early stage of development in Armenia, with the current emergency medical services (EMS) system having emergency physicians (EPs) work on ambulances along with nurses. While efforts are underway by the Ministry of Health and other organizations to reform the EMS system, little data exists on the status of pediatric emergency care (PEC) in the country. We designed this study to evaluate the knowledge and attitudes of out-of-hospital emergency physicians in pediatric rapid assessment and resuscitation, and identify areas for PEC improvement.

Methods

We distributed an anonymous, self-administered Knowledge and Attitudes survey to a …

Identification Of Novel Regulatory Cholesterol Metabolite, 5-Cholesten, 3Β,25-Diol, Disulfate, Shunlin Ren, Jin Koung Kim, Genta Kakiyama, Daniel Rodriguez-Agudo, William M. Pandak, Hae-Ki Min, Yanxia Ning

VCU Health Publications

Oxysterol sulfation plays an important role in regulation of lipid metabolism and inflammatory responses. In the present study, we report the discovery of a novel regulatory sulfated oxysterol in nuclei of primary rat hepatocytes after overexpression of the gene encoding mitochondrial cholesterol delivery protein (StarD1). Forty-eight hours after infection of the hepatocytes with recombinant StarD1 adenovirus, a water-soluble oxysterol product was isolated and purified by chemical extraction and reverse-phase HPLC. Tandem mass spectrometry analysis identified the oxysterol as 5-cholesten-3β, 25-diol, disulfate (25HCDS), and confirmed the structure by comparing with a chemically synthesized compound. Administration of 25HCDS to human THP-1-derived macrophages …

Clinical And Microbiologic Efficacy Of A Water Filter Program In A Rural Honduran Community, Jaclyn Arquiette, Michael P. Stevens, Jean M. Rabb, Kakotan Sanogo, Patrick Mason, Gonzalo Bearman

VCU Health Publications

Water purification in the rural Honduras is a focus of the nonprofit organization Honduras Outreach Medical Brigade Relief Effort (HOMBRE). We assessed water filter use and tested filter microbiologic and clinical efficacy. A 22-item questionnaire assessed water sources, obtainment/storage, purification, and incidence of gastrointestinal disease. Samples from home clay-based filters in La Hicaca were obtained and paired with surveys from the same home. We counted bacterial colonies of four bacterial classifications from each sample. Sixty-five surveys were completed. Forty-five (69%) individuals used a filter. Fifteen respondents reported diarrhea in their home in the last 30 days; this incidence was higher …

Abnormal Downward Gaze And Cold Caloric Examination Due To Propofol: A Case Study, Thuy-Anh Vu, Alia O'Meara, Jean Teasley

VCU Health Publications

Background: Adolescent patient with isolated abnormal downward gaze and oculovestibular (cold caloric) testing during propofol administration prompting concern of brainstem injury. PATIENT: An otherwise healthy 16 year old female presented after an intentional hanging. Brainstem reflexes were normal except that both eyes were in tonic downgaze on initial examination. Propofol was suspended for 30 minutes to evaluate level of responsiveness with eyes normalizing to midposition from tonic downgaze. With reinitiation of propofol, the eyes returned to the former position. C-collar stabilization prohibited oculocephalic (doll’s eyes) evaluation, and with cold caloric testing, eye movements were as follows: right sided cold water …

Targeting Tobacco In A Community-Based Addiction Recovery Cohort: Results From A Computerized, Brief, Randomized Intervention Trial, Alison Breland, Lauren Almond, Jennifer Kienzle, Steven J. Ondersma, Alton Hart, Michael Weaver, Pamela Dillon, Dace Svikis

Psychology Publications

Introduction. Nearly 80% of substance dependent individuals also use tobacco, and smoking cessation efforts during treatment for other substance use is associated with similar or even improved outcomes. However, smoking cessation is not routinely addressed during treatment for substance use disorders. The present study tested a computerized brief motivational intervention (C-BMI) for smoking cessation in an understudied population: a cohort recruited from a recovery community organization (RCO) center.

Methods. Following baseline assessment, participants were randomly assigned to either a 30-minute C-BMI plus access to free nicotine replacement therapy (NRT), or an information-only control group plus NRT access. Results. Reductions in …

Neuropathological Responses To Chronic Nmda In Rats Are Worsened By Dietary N-3 Pufa Deprivation But Are Not Ameliorated By Fish Oil Supplementation, Vasken L. Keleshian, Matthew Kellom, Hyung-Wook Kim, Ameer Y. Taha, Yewon Cheon, Miki Igarashi, Stanley I. Rapoport, Jagadeesh S. Rao

Anatomy and Neurobiology Publications

Background

Dietary long-chain n-3 polyunsaturated fatty acid (PUFA) supplementation may be beneficial for chronic brain illnesses, but the issue is not agreed on. We examined effects of dietary n-3 PUFA deprivation or supplementation, compared with an n-3 PUFA adequate diet (containing alpha-linolenic acid [18:3 n-3] but not docosahexaenoic acid [DHA, 22:6n-3]), on brain markers of lipid metabolism and excitotoxicity, in rats treated chronically with NMDA or saline.

Methods

Male rats after weaning were maintained on one of three diets for 15 weeks. After 12 weeks, each diet group was injected i.p. daily with saline (1 ml/kg) or a subconvulsive dose …

Facilitating Lewin's Change Model With Collaborative Evaluation In Promoting Evidence Based Practices Of Health Professionals, Julianne Manchester, Deanna L. Gray-Miceli, Judith A. Metcalf, Charlotte A. Paolini, Anne H. Napier, Constance L. Coogle, Myra G. Owens

Virginia Center on Aging Publications

Evidence based practices (EBPs) in clinical settings interact with and adapt to host organizational characteristics. The contextual factors themselves, surrounding health professions’ practices, also adapt as practices become sustained. The authors assert the need for better planning models toward these contextual factors, the influence of which undergird a well-documented science to practice gap in literature on EBPs. The mechanism for EBP planners to anticipate contextual effects as programs Unfreeze their host settings, create Movement, and become Refrozen (Lewin, 1951) is present in Lewin's 3-step change model. Planning for contextual change appears equally important as planning for the actual practice outcomes …

Older Prisoners, Edward F. Ansello

Director's Editorials from Age in Action

The impact of an aging prison population is causing concern among different stakeholders, including prison officials, legislative bodies, clergy, and some gerontologists. Prison officials are scrambling to accommodate the numbers and needs of older inmates, but they are confounded by constrained budgets, inappropriate prison architecture, lack of gerontologically and geriatrically trained staff members, indifferent legislative bodies, and a general lack of awareness among the public of these problems. Our states need not only retrofitted and newly designed physical facilities but also staffs and providers with gerontological and geriatric training, from corrections personnel to health care providers to clergy and mental …

The Healthy Brain Initiative, Edward F. Ansello

Director's Editorials from Age in Action

Cognitive health is being recognized increasingly as a vital part of overall health and central to aging well. The CDC and Alzheimer's Association have published a revised framework for translating science to practice in public health, with particular focus on the role that state and local public health agencies can play to improve cognitive health and to recognize and report cognitive impairment.

Calorie Labeling, Edward F. Ansello

Director's Editorials from Age in Action

As required by the Affordable Care Act, chain restaurants with 20 or more locations in the US will soon have to display calorie information on their menus. Does knowing this information translate to changing our eating behavior and improving our nutritional intake? Will this change affect older adults in a meaningful way? Menu labeling should be viewed as an early approach in governmental policy to address the obesity epidemic.

The Lifelong Learning Institute In Chesterfield: Ten Years Of Growing, Edward F. Ansello, Monica Hughes

Case Studies from Age in Action

Educational Objectives

1. To review changes in patterns of continuing learning and non-traditional education.

2. To profile membership and their interests in lifelong learning.

3. To highlight the development of the Lifelong Learning Institute of Chesterfield as a possible model for replication.

Protecting The Vulnerable: Free Ways To Prevent Financial Exploitation, Christopher Desimone

Case Studies from Age in Action

Educational Objectives

1. Relate recurring patterns of perpetrators who exploit older adults.

2. Describe no-cost actions to protect assets from financial exploitation.

3. Explain differences among types of power of attorney.

Remembering Through Music: Music Therapy And Dementia, Melissa Owens

Case Studies from Age in Action

Educational Objectives

1. Define music therapy and its benefits with older adults with dementia and related disorders/ diseases.

2. Describe active and passive music therapy interventions and strategies for older adult populations.

3. Identify the ways a non-musician can use music to engage older adults and mitigate some symptoms of dementia.

Correction: The Role Of Tumor-Associated Macrophages In Tumor Vascularization, Chunqing Guo, Annicole Buranych, Devanand Sarkar, Paul B. Fisher, Xiang-Yang Wang

Human and Molecular Genetics Publications

This is a correction to a previously published article.

Dietary Regimens Modify Early Onset Of Obesity In Mice Haploinsufficient For Rai1, Joseph T. Alaimo, Natalie H. Hahn, Sureni V. Mullegama, Sarah H. Elsea

Human and Molecular Genetics Publications

Smith-Magenis syndrome is a complex genomic disorder in which a majority of individuals are obese by adolescence. While an interstitial deletion of chromosome 17p11.2 is the leading cause, mutation or deletion of the RAI1 gene alone results in most features of the disorder. Previous studies have shown that heterozygous knockout of Rai1 results in an obese phenotype in mice and that Smith-Magenis syndrome mouse models have a significantly reduced fecundity and an altered transmission pattern of the mutant Rai1 allele, complicating large, extended studies in these models. In this study, we show that breeding C57Bl/6J Rai1+/−mice with FVB/NJ to …

A Placebo-Controlled, Double-Blind, Randomized, Multicenter Study To Assess The Effects Of Dronedarone 400 Mg Twice Daily For 12 Weeks On Atrial Fibrillation Burden In Subjects With Permanent Pacemakers, Michael D. Ezekowitz, Kenneth Ellenbogen , M.D., John P. Dimarco, Karoly Kaszala, Alexander Boddy, Gregory Geba P., Andrew Koren

Human and Molecular Genetics Publications

Purpose

Dronedarone is a benzofuran derivative with a pharmacological profile similar to amiodarone but has a more rapid onset of action and a much shorter half-life (13–19 h). Our goal was to evaluate the efficacy of dronedarone in atrial fibrillation (AF) patients using dual-chamber pacemakers capable of quantifying atrial fibrillation burden.

Methods

Pacemakers were adjusted to optimize AF detection. Patients with AF burden >1 % were randomized to dronedarone 400 mg twice daily (BID) or placebo. Pacemakers were interrogated after 4 and 12 weeks of treatment. The primary endpoint was the change in AF burden from baseline over the 12-week …

Electronic Health Record Functionality Needed To Better Support Primary Care, Alex H. Krist, John W . Beasley, Jesse C. Crosson, David C. Kibbe, Michael S. Klinkman, Christoph U. Lehmann, Chester H. Fox, Jason M. Mitchell, James W. Mold, Wilson D. Pace, Kevin A. Peterson, Robert L. Phillips, Robert Post, Jon Puro, Michael Raddock, Ray Simkus, Steven E. Waldren

Family Medicine and Population Health Publications

Electronic health records (EHRs) must support primary care clinicians and patients, yet many clinicians remain dissatisfied with their system. This manuscript presents a consensus statement about gaps in current EHR functionality and needed enhancements to support primary care. The Institute of Medicine primary care attributes were used to define needs and Meaningful Use (MU) objectives to define EHR functionality. Current objectives remain disease- rather than whole-person focused, ignoring factors like personal risks, behaviors, family structure, and occupational and environmental influences. Primary care needs EHRs to move beyond documentation to interpreting and tracking information over time as well as patient partnering …

Sjl Mice Infected With Acanthamoeba Castellanii Develop Central Nervous System Autoimmunity Through The Generation Of Cross-Reactive T Cells For Myelin Antigens, Chandirasegaran Massilamany, Francine Marciano-Cabral, Bruno Da Rocha-Azevedo, Melissa Jamerson, Arunakumar Gangaplara, David Steffen, Rana Zabad, Zsolt Illes, Raymond A. Sobel, Jay Reddy

Microbiology and Immunology Publications

We recently reported that Acanthamoeba castellanii (ACA), an opportunistic pathogen of the central nervous system (CNS) possesses mimicry epitopes for proteolipid protein (PLP) 139–151 and myelin basic protein 89–101, and that the epitopes induce experimental autoimmune encephalomyelitis (EAE) in SJL mice reminiscent of the diseases induced with their corresponding cognate peptides. We now demonstrate that mice infected with ACA also show the generation of cross-reactive T cells, predominantly for PLP 139–151, as evaluated by T cell proliferation and IAs/dextramer staining. We verified that PLP 139–151-sensitized lymphocytes generated in infected mice contained a high proportion of T helper 1 cytokine-producing cells, …