Medicine and Health Sciences Commons^™

Dual Engagement Of The Nlrp3 And Aim2 Inflammasomes By Plasmodium-Derived Hemozoin And Dna During Malaria, Parisa Kalantari, Rosane B. Deoliveira, Jennie Chan, Yolanda Corbett, Vijay A. K. Rathinam, Andrea Stutz, Eicke Latz, Ricardo T. Gazzinelli, Douglas T. Golenbock, Katherine A. Fitzgerald

Katherine A. Fitzgerald

Hemozoin (Hz) is the crystalline detoxification product of hemoglobin in Plasmodium-infected erythrocytes. We previously proposed that Hz can carry plasmodial DNA into a subcellular compartment that is accessible to Toll-like receptor 9 (TLR9), inducing an inflammatory signal. Hz also activates the NLRP3 inflammasome in primed cells. We found that Hz appears to colocalize with DNA in infected erythrocytes, even before RBC rupture or phagolysosomal digestion. Using synthetic Hz coated in vitro with plasmodial genomic DNA (gDNA) or CpG oligodeoxynucleotides, we observed that DNA-complexed Hz induced TLR9 translocation, providing a priming and an activation signal for inflammasomes. After phagocytosis, Hz and …

Attitudes Of Women In Their Forties Toward The 2009 Uspstf Mammogram Guidelines: A Randomized Trial On The Effects Of Media Exposure, Autumn Davidson, Xun Liao, B. Magee

B. Dale Magee

OBJECTIVE: The objective of the study was to assess women's attitudes toward 2009 US Preventive Services Task Force mammography screening guideline changes and evaluate the role of media in shaping opinions. STUDY DESIGN: Two hundred forty-nine women, aged 39-49 years, presenting for annual examinations randomized to read 1 of 2 articles, and survey completion comprised the design of the study. RESULTS: Eighty-eight percent overestimated the lifetime breast cancer (BrCa) risk. Eighty-nine percent want yearly mammograms in their 40s. Eighty-six percent felt the changes were unsafe, and even if the changes were doctor recommended, 84% would not delay screening until age …

Role Of Multiple Births In Very Low Birth Weight And Infant Mortality, B. Magee

B. Dale Magee

OBJECTIVE: To determine the percentage of very-low-birth-weight (VLBW) infants (g) and infant deaths attributable to multiple births in the general population and in women aged 35+. STUDY DESIGN: The year 2000 Massachusetts birth certificate database with linked births-deaths was examined. Etiologic fractions (EF) for VLBW and infant mortality attributable to multiples were calculated for the general population and the 35+ age group. The percentages of multiples occurring in the 35+ age group were calculated. Infant deaths due to congenital anomalies and "perinatal conditions" were calculated. RESULTS: There were 81,582 resident births in Massachusetts in 2000. Of them 4.3% were multiples. …

Xk Aprosencephaly And Anencephaly In Sibs, Phillip Townes, Karen Reuter, E. Rosquete, B. Magee

B. Dale Magee

Recent studies have suggested a causal and pathogenetic relationship between holoprosencephaly and anencephaly. In support of the proposed relationship we report a sibship that includes anencephalic male twins and a female infant with a severe form of alobar holoprosencephaly, radial aplasia, and oligodactyly. The upper limb and brain malformations are considered to represent aprosencephaly syndrome. The coexistence of anencephaly and aprosencephaly within a sibship suggests that XK aprosencephaly syndrome may be an autosomal recessive disorder.

Doing The Best With What We Have: We Need Better: Informing Obstetric Policy With Administrative Data, Tiffany Moore Simas, B. Magee, Ellen Delpapa

B. Dale Magee

In this issue of Medical Care, Backes Kozhimannil and colleagues present data from the National Inpatient Sample on differences between rural and urban obstetric care. We applaud their efforts in examining this issue and agree that all women should be afforded safe deliveries, and ideally each woman’s experience would not be different. That being said, there are some practical considerations that must be applied to their analyses and recommendations. We would like to take this opportunity to capitalize on their efforts and speak to 2 other highly related implications for policy and practice.

Role Of Smoking In Low Birth Weight, B. Magee, Dale Hattis, Nancy Kivel

B. Dale Magee

OBJECTIVE: To assess the role of smoking on low birth weight (LBW). STUDY DESIGN: From Massachusetts for 1998, 79,904 birth certificates were reviewed. Birth weight, gestational age, plurality and maternal race were analyzed in relation to the mother's smoking status during the pregnancy. The etiologic fraction (EF) was calculated for smoking and LBW for the group as a whole as well as for various subgroups. RESULTS: A total of 11.7% of women acknowledged smoking during pregnancy. The overall LBW rate was 6.83%. The relative risk (RR) of LBW among smokers was 1.58. For all births the EF for smoking was …

Imp3 Expression Is Associated With Poor Outcome And Epigenetic Deregulation In Intrahepatic Cholangiocarcinoma, Yuanyuan Gao, Michelle Yang, Zhong Jiang, Bruce A. Woda, Arthur M. Mercurio, Jianjie Qin, Xinli Huang, Feng Zhang

Arthur M. Mercurio

IMP3 is a fetal protein not expressed in normal adult tissues. IMP3 is an oncoprotein and a useful biomarker for a variety of malignancies and is associated with reduced overall survival of a number of them. IMP3 expression and its prognostic value for patients with intrahepatic cholangiocarcinoma (ICC) have not been well investigated. The molecular mechanism underlying IMP3 expression in human cancer cells remains to be elucidated. Here we investigated IMP3 expression in ICC and adjacent nonneoplastic liver in 72 unifocal primary ICCs from a single institute by immunohistochemistry, immunoblotting, and real-time polymerase chain reaction. IMP3 was specifically expressed in …

Hippocampal Functional Connectivity Patterns During Spatial Working Memory Differ In Right Versus Left Temporal Lobe Epilepsy., Gaelle Eve Doucet, Karol Osipowicz, Ashwini Sharan Md, Michael R Sperling, Joseph I Tracy

Gaelle Eve Doucet

Temporal lobe epilepsy (TLE), affecting the medial temporal lobe, is a disorder that affects not just episodic memory but also working memory (WM). However, the exact nature of hippocampal-related network activity in visuospatial WM remains unclear. To clarify this, we utilized a functional connectivity (FC) methodology to investigate hippocampal network involvement during the encoding phase of a functional magnetic resonance imaging (fMRI) visuospatial WM task in right and left TLE patients. Specifically, we assessed the relation between FC within right and left hippocampus-seeded networks, and patient performance (rate of correct responses) during the encoding phase of a block span WM …

30-Year Trends In Patient Characteristics, Treatment Practices, And Long-Term Outcomes Of Adults Aged 35 To 54 Years Hospitalized With Acute Myocardial Infarction, Mayra Tisminetzky, David Mcmanus, Joel Gore, Jorge Yarzebski, Andrew Coles, Darleen Lessard, Robert Goldberg

Jorge L. Yarzebski

Much of our knowledge about the characteristics, clinical management, and postdischarge outcomes of acute myocardial infarction (AMI) is derived from clinical studies in middle-aged and older subjects with little contemporary information available about the descriptive epidemiology of AMI in relatively young men and women. The objectives of our population-based study were to describe >3-decade-long trends in the clinical features, treatment practices, and long-term outcomes of young adults aged 35 to 54 years discharged from the hospital after AMI. The study population consisted of 2,142 residents of the Worcester (Massachusetts) metropolitan area who were hospitalized with AMI at all central Massachusetts …

Systematic Review Of The Use Of Online Questionnaires Of Older Adults, Meegan Remillard, Kathleen Mazor, Sarah Cutrona, Jerry Gurwitz, Jennifer Tjia

Jennifer Tjia

OBJECTIVES: To describe methodological approaches to population targeting and sampling and to summarize limitations of Internet-based questionnaires in older adults.

DESIGN: Systematic literature review.

SETTING: Studies using online questionnaires in older adult populations.

PARTICIPANTS: English-language articles using search terms for geriatric, age 65 and over, Internet survey, online survey, Internet questionnaire, and online questionnaire in PubMed and EBSCO host between 1984 and July 2012. Inclusion criteria were study population mean age 65 and older and use of an online questionnaire for research. Review of 336 abstracts yielded 14 articles for full review by two investigators; 11 articles met inclusion criteria. …

Antipsychotic Use In Nursing Homes Varies By Psychiatric Consultant, Jennifer Tjia, Terry Field, Celeste Lemay, Kathleen Mazor, Michelle Pandolfi, Ann Spenard, Shih-Yieh Ho, Abir Kanaan, Jennifer Donovan, Jerry Gurwitz, Becky Briesacher

Jennifer Tjia

BACKGROUND: The relationship between psychiatric consultation and antipsychotic prescribing in nursing homes (NH) is unknown. OBJECTIVE: To identify the association between psychiatric consultant groups and NH-level antipsychotic prescribing after adjustment for resident case-mix and facility characteristics. RESEARCH DESIGN AND SUBJECTS: Nested cross-sectional study of 60 NHs in a cluster randomized trial. We linked facility leadership surveys to October 2009-September 2010 Minimum Data Set, Nursing Home Compare, the US Census, and pharmacy dispensing data. MEASURES: The main exposure is the psychiatric consultant group and the main outcome is NH-level prevalence of atypical antipsychotic use. We calculated annual means and interquartile ranges …

Use Of Mechanical Ventilation By Patients With And Without Dementia, 2001 Through 2011, Tara Lagu, Marya Zilberberg, Jennifer Tjia, Penelope Pekow, Peter Lindenauer

Jennifer Tjia

Increasing demand for US critical care resources, including beds, intensivists, and invasive mechanical ventilation (IMV),has placed substantial strain on the critical care system. Since 2000, elderly patients treated in the intensive care unit have received higher intensity care (and have experienced lower mortality rates) than historical cohorts. Yet certain populations of elderly patients exposed to intensive care experience substantial long-term adverse effects, including functional decline and excess mortality. Patients with dementia receiving IMV, for example, are at high risk for delirium, which confers a 3.2-fold increased risk of 6-month mortality. The increasing use of aggressive therapies suggests that demand for …

Novel Ubiquitin Neuropathology In Frontotemporal Dementia With Valosin-Containing Protein Gene Mutations, Mark Forman, Ian Mackenzie, Nigel Cairns, Eric Swanson, Philip Boyer, David Drachman, Bharati Jhaveri, Jason Karlawish, Alan Pestronk, Thomas Smith, Pang-Hsien Tu, Giles Watts, William Markesbery, Charles Smith, Virginia Kimonis

Jason Karlawish

Frontotemporal dementia (FTD) with inclusion body myopathy and Paget disease of bone (IBMPFD) is a rare, autosomal-dominant disorder caused by mutations in the valosin-containing protein (VCP) gene, a member of the AAA-ATPase gene superfamily. The neuropathology associated with sporadic FTD is heterogeneous and includes tauopathies and frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). However, there is limited information on the neuropathology in IBMPFD. We performed a detailed, systematic analysis of the neuropathologic changes in 8 patients with VCP mutations. A novel pattern of ubiquitin pathology was identified in IBMPFD that was distinct from sporadic and familial FTLD-U without VCP gene …

Managed Mental Health Care's Effects On Arrest And Forensic Commitment, William Fisher, Sharon-Lise Normand, Barbara Dickey, Ira Packer, Albert Grudzinskas, Hocine Azeni

Ira K Packer

No abstract provided.

Self-Reported Lifetime Psychiatric Hospitalization Histories Of Jail Detainees With Mental Disorders: Comparison With A Non-Incarcerated National Sample, William Fisher, Ira Packer, Steven Banks, David Smith, Lorna Simon, Kristen Roy-Bujnowski

Ira K Packer

Lack of access to hospitalization is an often-cited risk factor for incarceration among persons with severe mental illness. This proposition is examined by comparing self-reports of lifetime psychiatric hospitalization histories of mentally ill jail inmates with data from a national sample of non-incarcerated mentally ill. Roughly 52% of mentally ill jail detainees reported at least one psychiatric hospitalization, a rate nearly three times that of the comparison group. The data call into question the notion that mentally ill jail inmates have reduced access to psychiatric inpatient treatment, without addressing the adequacy of the treatment received. Longitudinal studies are needed to …

Community Mental Health Services And The Prevalence Of Severe Mental Illness In Local Jails: Are They Related, William Fisher, Ira Packer, Lorna Simon, David Smith

Ira K Packer

The excessive prevalence of severe mental illness noted in correctional settings has sometimes been attributed to the inadequacy of community based mental health services. This study examines the prevalence of severe mental illness in two jails situated within catchment areas featuring markedly different levels of community mental health services. We use these settings to test the hypothesis that greater levels of services in a community are associated with lower prevalence of severe mental illness in the community's jail. An epidemiologic approach, using standardized field instruments, was used to estimate the prevalence of major mental illness in detainees arriving at the …

Relationship Between Race And Ethnicity And Forensic Clinical Triage Dispositions, Debra Pinals, Ira Packer, William Fisher, Kristen Roy-Bujnowski

Ira K Packer

OBJECTIVE: Racial and ethnic disparities in the criminal justice system have been widely reported, as have racial and ethnic disparities in diagnoses and certain aspects of clinical management. This study examined the association between race and ethnicity and dispositions for pretrial defendants who were referred for forensic mental health evaluations. METHODS: Available data were reviewed for all defendants in Massachusetts who were referred to a Massachusetts court clinic from 1994 to 2001 for a screening evaluation of their competence to stand trial, their criminal responsibility, or both. Logistic regression models were developed to assess the relationship between defendants' race and …

From Case Management To Court Clinic: Examining Forensic System Involvement Of Persons With Severe Mental Illness, William Fisher, Ira Packer, Thomas Grisso, Melissa Mcdermeit, Julie-Marie Brown

Ira K Packer

The study examined the flow of a state mental health agency's case-managed clients into its forensic mental health court clinic systems for evaluation of competency to stand trial (CST) for a criminal offense. An analysis of merged encounter data from the case management and court clinic systems revealed that roughly 2% of the case-managed population were referred to court clinics for evaluation of CST during a 1-year period, but that these 2% represented roughly one eighth of that year's court clinic evaluees. The likelihood of this involvement was higher for males, African-Americans, and Latinos, and for persons with a history …

An Electronic Health Record-Based Intervention To Increase Follow-Up Office Visits And Decrease Rehospitalization In Older Adults, Jerry Gurwitz, Terry Field, Jessica Ogarek, Jennifer Tjia, Sarah Cutrona, Leslie Harrold, Shawn Gagne, Peggy Preusse, Jennifer Donovan, Abir Kanaan, George Reed, Lawrence Garber

Jennifer Tjia

OBJECTIVES: To assess the effect of an electronic health record-based transitional care intervention involving automated alerts to primary care providers and staff when older adults were discharged from the hospital.

DESIGN: Randomized controlled trial.

SETTING: Large multispecialty group practice.

PARTICIPANTS: Individuals aged 65 and older discharged from hospital to home.

INTERVENTION: In addition to notifying primary care providers about the individual's recent discharge, the system provided information about new drugs added during the inpatient stay, warnings about drug-drug interactions, recommendations for dose changes and laboratory monitoring of high-risk medications, and alerts to the primary care provider's support staff to schedule …

Striving For Cultural Competence In An Hiv Program: The Transformative Impact Of A Microsystem In A Larger Health Network, Judith N Sabino, Timothy Friel, Lynn Deitrick, Debbie Salas-Lopez

Debbie Salas-Lopez MD, MPH

No abstract provided.

Barriers And Facilitators For Colorectal Cancer Screening Practices In The Latino Community: Perspectives From Community Leaders, Ana Natale-Pereira, Jonnie Marks, Marielos Vega, Dawne Mouzon, Shawna Hudson, Debbie Salas-Lopez

Debbie Salas-Lopez MD, MPH

BACKGROUND: Colorectal cancer (CRC) is the second-leading cause of cancer-related death in the United States and the third most commonly diagnosed cancer among Latinos. While Latinos represent one of the fastest-growing ethnic groups in the United States, their participation in cancer prevention and treatment trials is low. METHODS: Thirty-six Latino community leaders participated in five focus groups that examined factors affecting CRC screening practices among Latinos. RESULTS: The top four barriers identified were low knowledge and awareness of CRC, language barriers, lack of insurance, and undocumented legal status. Additional barriers included seeking health care only when sick, fatalism, fear, denial …

Perspectives On Cancer Screening Among Latino Community Members And Internal Medicine Residents, Debbie Salas-Lopez, Dawne Mouzon, Jonnie Marks, Neil Kothari, Ana Natale-Pereira

Debbie Salas-Lopez MD, MPH

BACKGROUND: Latinos have lower rates of cancer screening, partially because of cultural beliefs that conflict with those of health care professionals. Moreover, established programs for training physicians in cultural competency often fail to incorporate input from the community.

METHODS: To explore beliefs about cancer and cancer screening among Latino community members and internal medicine residents. Three focus groups of Latino community members (n = 31) and one focus group of internal medicine residents (n = 9) were conducted to compare ideas regarding cancer and cancer screening.

RESULTS: We identified clear disconnects between residents and Latino community members regarding their understandings …

Binge Ethanol And Liver: New Molecular Developments, Shivendra Shukla, Stephen Pruett, Gyongyi Szabo, Gavin Arteel

Gyongyi Szabo

Binge consumption of alcohol is an alarming global health problem. Binge (acute) ethanol (EtOH) is implicated in the pathophysiology of alcoholic liver disease (ALD). New studies from experimental animals and from humans indicate that binge EtOH has profound effects on immunological, signaling, and epigenetic parameters of the liver. This is in addition to the known metabolic effects of acute EtOH. Binge EtOH alters the levels of several cellular components and dramatically amplifies liver injury in chronically EtOH exposed liver. These studies highlight the importance of molecular investigations into binge effects of EtOH for a better understanding of ALD and also …

Another Armed Cd4(+) T Cell Ready To Battle Hepatocellular Carcinoma, Roniel Cabrera, Gyongyi Szabo

Gyongyi Szabo

No abstract provided.

Human Ezrin-Moesin-Radixin Proteins Modulate Hepatitis C Virus Infection, Terence Bukong, Karen Kodys, Gyongyi Szabo

Gyongyi Szabo

Host cytoskeletal proteins of the ezrin-moesin-radixin (EMR) family have been shown to modulate single-stranded RNA virus infection through regulating stable microtubule formation. Antibody engagement of CD81, a key receptor for hepatitis C virus (HCV) entry, induces ezrin phosphorylation. Here we tested the role of EMR proteins in regulating HCV infection and explored potential therapeutic targets. We show that HCV E2 protein induces rapid ezrin phosphorylation and its cellular redistribution with F-actin by way of spleen tyrosine kinase (SYK). Therapeutically blocking the functional roles of SYK or F-actin reorganization significantly reduced Huh7.5 cell susceptibility to HCV J6/JFH-1 infection. Using gene regulation, …

Differences In Innate Immune Signaling Between Alcoholic And Non-Alcoholic Steatohepatitis, Jan Petrasek, Timea Csak, Michal Ganz, Gyongyi Szabo

Gyongyi Szabo

The similar histopathological characteristics of alcoholic steatohepatitis (ASH) and non-alcoholic steatohepatitis (NASH), and the crucial role of the innate immune response in both conditions may lead to the assumption that ASH and NASH represent the same pathophysiological entities caused by different risk factors. In this review paper, we elaborate on the pathophysiological differences between these two entities and highlight the disease-specific involvement of signaling molecules downstream of the Toll-like receptor 4, and the differential mechanism by which the inflammasome contributes to ASH versus NASH. Our findings emphasize that ASH and NASH have disease-specific mechanisms and therefore represent distinct biological entities. …

Human Type 2 Myeloid Dendritic Cells Produce Interferon-Lambda And Amplify Interferon-Alpha In Response To Hepatitis C Virus Infection, Shuye Zhang, Karen Kodys, Kui Li, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND and AIMS: The type III interferons (IFN-lambdas: interleukin [IL]-28a, IL-28b, and IL-29) have important roles in hepatitis C virus (HCV) infection, but little is understood about what cells produce these cytokines or how production is activated. We investigated whether human immune cells recognize HCV-infected cells and respond by producing IFN-lambda. METHODS: We cultured healthy human peripheral blood mononuclear cells (PBMCs) with different populations of immune cells and Japanese fulminant hepatitis-1 (JFH-1) HCV-infected Huh7.5 (cell culture-derived HCV particles [HCVcc]/Huh7.5) cells. RESULTS: Human PBMCs recognized HCVcc/Huh7.5 cells and responded by producing IFN-alpha, IFN-gamma, and IFN-lambda. A rare subset of myeloid dendritic …

Toll-Like Receptors In Liver Disease, Jan Petrasek, Timea Csak, Gyongyi Szabo

Gyongyi Szabo

Activation of inflammatory signaling pathways is of central importance in the pathogenesis of alcoholic liver disease (ALD) and nonalcoholic steatohepatitis (NASH). Recent studies demonstrated that Toll-like receptors, the sensors of microbial and endogenous danger signals, are expressed and activated in innate immune cells as well as in parenchymal cells in the liver and thereby contribute to ALD and NASH. In this review, we emphasize the importance of gut-derived endotoxin and its recognition by TLR4 in the liver. The significance of TLR-induced intracellular signaling pathways and cytokine production as well as the contribution of individual cell types to the inflammation is …

National Trauma Institute Prospective Evaluation Of The Ventilator Bundle In Trauma Patients: Does It Really Work?, Martin A. Croce Md, Karen J. Brasel Md, Mph, Raul Coimbra Md, Phd, Charles A. Adams Jr, Md, Preston R. Miller Md, Michael D. Pasquale Md, Facs, Fccm, Chanchai S. Mcdonald Phd, Somchan Vuthipadadon Phd, Timothy C. Fabian Md, Elizabeth A. Tolley Phd

Michael D Pasquale MD, FACS, FCCM

BACKGROUND: Since its introduction by the Institute for Healthcare Improvement, the ventilator bundle (VB) has been credited with a reduction in ventilator-associated pneumonia (VAP). The VB consists of stress ulcer prophylaxis, deep venous thrombosis prophylaxis, head-of-bed elevation, and daily sedation vacation with weaning assessment. While there is little compelling evidence that the VB is effective, it has been widely accepted. The Centers for Medical and Medicaid Services has suggested that VAP should be a "never event" and may reduce payment to providers. To provide evidence of its efficacy, the National Trauma Institute organized a prospective multi-institutional trial to evaluate the …

Evaluation Of Short And Tall Stature In Children, Benjamin Nwosu, Mary Lee

Mary M. Lee

Children and adolescents whose heights and growth velocities deviate from the normal percentiles on standard growth charts present a special challenge to physicians. Height that is less than the 3rd percentile or greater than the 97th percentile is deemed short or tall stature, respectively. A growth velocity outside the 25th to 75th percentile range may be considered abnormal. Serial height measurements over time documented on a growth chart are key in identifying abnormal growth. Short or tall stature is usually caused by variants of a normal growth pattern, although some patients may have serious underlying pathologies. A comprehensive history and …