Medicine and Health Sciences Commons^™

Hla Class I Supertype Associations With Clinical Outcome Of Secondary Dengue Virus Infections In Ethnic Thais, Sasijit Vejbaesya, Rungrot Thongpradit, Siripen Kalayanarooj, Komon Luangtrakool, Panpimon Luangtrakool, Robert V. Gibbons, Duangporn Srinak, Somporn Ngammthaworn, Kusuma Apisawes, In-Kyu Yoon, Stephen J. Thomas, Richard G. Jarman, Anon Srikiatkhachorn, Sharone Green, Dasnayanee Chandanayingyong, Sangshin Park, Jennifer Friedman, Alan L. Rothman, Henry A.F. Stephens

Sharone Green

BACKGROUND: Human leukocyte antigen (HLA) supertypes are groups of functionally related alleles that present structurally similar antigens to the immune system.

OBJECTIVES: To analyze HLA class I supertype associations with clinical outcome in hospitalized Thai children with acute dengue illness.

METHODS: Seven hundred sixty-two patients and population-matched controls recruited predominantly in Bangkok were HLA-A and -B typed. HLA supertype frequencies were compared and tested for significant dengue disease associations using logistic regression analyses. Multivariable models were built by conducting forward stepwise selection procedures.

RESULTS: In the final logistic regression model, the HLA-B44 supertype was protective against dengue hemorrhagic fever (DHF) …

Manic Symptoms And Behavioral Dysregulation In Youth With Velocardiofacial Syndrome (22q11.2 Deletion Syndrome)., Alka Aneja, Wanda Fremont, Kevin Antshel, Stephen Faraone, Nuria Abdulsabur, Anne Marie Higgins, Robert Shprintzen, Wendy Kates

Robert J. Shprintzen

Mania and bipolar disorder have been reported in adolescents and adults with velocardiofacial syndrome (VCFS; also known as 22q11.2 deletion syndrome). Children with VCFS have a high prevalence of attention-deficit/hyperactivity disorder (ADHD), which may constitute a risk factor for the eventual development of bipolar disorder in this population. Therefore, we sought to determine whether children with VCFS exhibit more manic symptoms than community controls that also may have learning disorders and ADHD. The study population consisted of 86 children with VCFS and 36 community controls from ages 9 to 15 years, using measures of Young Mania Rating Scale-Parent Version, Schedule …

22q11.2ds Deletion Syndrome: Developmental Milestones In Infants And Toddlers, Nancy Roizen, Kevin Antshel, Wanda Fremont, Nuria Abdulsabur, Anne Marie Higgins, Robert Shprintzen, Wendy Kates

Robert J. Shprintzen

The majority of children with 22q11.2DS deletion syndrome (22q11.2DS) have learning disabilities, and a substantial number have mental retardation. Although cognitive data have been reported on several samples of children with 22q11.2DS, data on their early developmental milestones are limited. Methods: The present study used a retrospective design and asked parents to recall developmental milestones. The participants were 88 children with 22q11.2DS, 47 community controls, and 29 sibling controls. Results: Although very early gross motor and expressive language milestones did not differ significantly from comparison groups, subsequent gross motor and expressive language milestones did, suggesting that children with 22q11.2DS may …

Overt Cleft Palate Phenotype And Tbx1 Genotype Correlations In Velo-Cardio-Facial/Digeorge/22q11.2 Deletion Syndrome Patients, Sean Herman, Tingwei Guo, Donna Mcdonald Mcginn, Anna Blonska, Alan Shanske, Anne Bassett, Eva Chow, Mark Bowser, Molly Sheridan, Frits Beemer, Koen Devriendt, Ann Swillen, Jeroen Breckpot, Maria Digilio, Bruno Marino, Bruno Dallapiccola, Courtney Carpenter, Xin Zheng, Jacob Johnson, Jonathan Chung, Anne Marie Higgins, Nicole Philip, Tony Simon, Karlene Coleman, Damian Heine Suñer, Jordi Rosell, Wendy Kates, Marcella Devoto, Elaine Zackai, Tao Wang, Robert Shprintzen, Beverly Emanuel, Bernice Morrow, International Chromosome 22q11.2 Consortium

Robert J. Shprintzen

Velo-cardio-facial syndrome/DiGeorge syndrome, also known as 22q11.2 deletion syndrome (22q11DS) is the most common microdeletion syndrome, with an estimated incidence of 1/2,000 – 1/4,000 live births. Approximately 9–11% of patients with this disorder have an overt cleft palate (CP), but the genetic factors responsible for CP in the 22q11DS subset are unknown. The TBX1 gene, a member of the T-box transcription factor gene family, lies within the 22q11.2 region that is hemizygous in patients with 22q11DS. Inactivation of one allele of Tbx1 in the mouse does not result in CP, but inactivation of both alleles does. Based on these data, …

Catatonia In An Adolescent With Velo-Cardio-Facial Syndrome, Gianni Faedda, Lee Wachtel, Anne Marie Higgins, Robert Shprintzen

Robert J. Shprintzen

Velo-cardio-facial syndrome (VCFS) is the most common microdeletion syndrome in humans and is probably the most frequent genetic cause of psychosis currently known. Many psychiatric disorders have been reported to occur in people with VCFS including, but not limited to schizophrenia, unipolar and bipolar mood disorders (with or without psychotic features), schizoaffective disorder, psychosis NOS, social phobia, generalized and separation anxiety, obsessive-compulsive disorder, autism spectrum disorder, cognitive impairment, and ADHD. This report describes the psychiatric onset and development of catatonia in an adolescent female with VCFS that was undiagnosed until 15 years of age. Catatonia may be a relatively common …

Associations Between Performance On The Rey-Osterrieth Complex Figure And Regional Brain Volumes In Children With And Without Velocardiofacial Syndrome, Kevin Antshel, Jena Peebles, Nuria Abdulsabur, Anne Marie Higgins, Nancy Roizen, Robert Shprintzen, Wanda Fremont, Robert Natasi, Wendy Kates

Robert J. Shprintzen

Ninety-two children with velocardiofacial syndrome (VCFS), a genetic disorder caused by a microdeletion of chromosome 22q11.2 and an age, race, and gender-ratio comparable sample of 59 control participants were included in the project. Participants received an MRI as well as a comprehensive neuropsychological battery; the primary outcome measure in the current report is the Rey-Osterrieth Complex Figure (ROCF). Children with VCFS performed less well on the ROCF and have lower whole brain volume compared to controls. After controlling for whole brain volume differences, children with VCFS have bilaterally less parietal lobe gray and white matter yet more frontal lobe white …

Measurement Invariance Of The Kidney Disease And Quality Of Life Instrument (Kdqol-Sf) Across Veterans And Non-Veterans, Karen Saban, Fred Bryant, Dominic Reda, Kevin Stroupe, Denise Hynes

Fred B. Bryant

Background Studies have demonstrated that perceived health-related quality of life (HRQOL) of patients receiving hemodialysis is significantly impaired. Since HRQOL outcome data are often used to compare groups to determine health care effectiveness it is imperative that measures of HRQOL are valid. However, valid HRQOL comparisons between groups can only be made if instrument invariance is demonstrated. The Kidney Disease Quality of Life-Short Form (KDQOL-SF) is a widely used HRQOL measure for patients with chronic kidney disease (CKD) however, it has not been validated in the Veteran population. Therefore, the purpose of this study was to examine the measurement invariance …

Anterior Cervical Foraminotomy: Short Term Outcomes In Patients With Isolated Cervical Radiculopathy, Howard Eisenbrock, Mark Rivkin, Amir Dehdashti

Mark Rivkin

Intro: Anterior cervical foraminotomy (ACF) is a novel approach involving direct decompression of nerve from an offending agent without fusion. Historically, several anterior and posterior approaches were utilized to treat cervical radiculopathy. Anterior cervical discectomy necessitates fusion and is subject to adjacent segment disease as well as loss of ROM. Posterior laminoforaminotomy seldom allows for removal of disc fragment and is associated with higher postoperative pain. Methods: Between May 2010 and March 2013, 16 patients with one or two level cervical spondylosis with radiculopathy without myelopathy who failed conservative therapies such as anti-inflammatory medications, physical therapy or injections underwent anterior …

Kyphotic Progression After Thoracolumbar Burst Fractures Treated Conservatively, With Mis, Or Via Open Approach, Mark Rivkin, Howard Eisenbrock

Mark Rivkin

Management of thoracolumbar burst fractures (AO A3) without neurological deficit is subject to debate in the literature. While TLICS provides guidance for injuries necessitating intervention, it makes little mention of best surgical approaches. Furthermore, intact patients with suspected posterior ligamentous complex injury (TLICS 4) compose an additional level of management uncertainty. Present study examined outcomes for TL burst fractures in neurologically intact patients with suspected disruption of the PLC treated with bracing, MIS, or open fixation and fusion.

The Mind-Body Connection: The Association Between Adolescent Locus Of Control And Indicators Of Physical Health, C. Brahler, James Cropper

C. Jayne Brahler

Locus of control (LOC) describes an individual’s generalized beliefs or expectancies that their reinforcements are under internal versus external control (1). An individual exhibits either an internal or external LOC. This study examines the link between LOC and selected health risk factors in adolescents. A convenience sample of 167 high school physical education students completed a 13-item LOC questionnaire based on Rotter’s 1966 instrument. Various anthropometric measurements, blood pressure, body mass index (BMI), and body fat were recorded on all subjects. A subsample of 61 female students received blood chemistry analysis that included a lipid profile, hemoglobin A1c (HbA1c), Apo …

News From Cart, Patricia Fanning, Amos Nwosu

Patricia J. Fanning

No abstract provided.

Gating Of The Polycystin Ion Channel Signaling Complex In Neurons And Kidney Cells, Patrick Delmas, Surya Nauli, Xiaogang Li, Bertrand Coste, Nancy Osorio, Marcel Crest, David Brown, Jing Zhou

David C. Brown

Mutations in either polycystin-2 (PC2) or polycystin-1 (PC1) proteins cause severe, potentially lethal, kidney disorders and multiple extrarenal (including brain) disease phenotypes. PC2, a member of the transient receptor potential channel superfamily, and PC1, an orphan membrane receptor of largely unknown function, are thought to be part of a common signaling pathway. Here, we show that in rat sympathetic neurons and kidney cells, coassembly of full-length PC1 with PC2 forms a plasmalemmal ion channel signaling complex in which PC1 stimulation simultaneously activates PC2 ion channels and G(i/o)-proteins. PC2 activation occurs through a structural rearrangement of PC1, independent of G-protein activation. …

Detection Of Diabetic Foot Ulcers Using Svm Based Classification, Lei Wang, Peder Pedersen, Diane Strong, Bengisu Tulu, Emmanuel Agu, Qian He, Ronald Ignotz, Raymond Dunn, David Harlan, Sherry Pagoto

Emmanuel O. Agu

Diabetic foot ulcers represent a significant health issue, for both patients’ quality of life and healthcare system costs. Currently, wound care is mainly based on visual assessment of wound size, which suffers from lack of accuracy and consistency. Hence, a more quantitative and computer-based method is needed. Supervised machine learning based object recognition is an attractive option, using training sample images with boundaries labeled by experienced clinicians. We use forty sample images collected from the UMASS Wound Clinic by tracking 8 subjects over 6 months with a smartphone camera. To maintain a consistent imaging environment and facilitate the capture process …

Disease Will Limit Future Food Supply From The Global Crustacean Fishery And Aquaculture Sectors, G. Stentiford, D. Neil, E. Peeler, J. Shields, H. Small, T. Flegel, J. Vlak, B. Jones, F. Morado, S. Moss, J. Lotz, Lyric Bartholomay, D. Behringer, C. Hauton, D. Lightner

Lyric Bartholomay

Seafood is a highly traded food commodity. Farmed and captured crustaceans contribute a significant proportion with annual production exceeding 10 M metric tonnes with first sale value of $40bn. The sector is dominated by farmed tropical marine shrimp, the fastest growing sector of the global aquaculture industry. It is significant in supporting rural livelihoods and alleviating poverty in producing nations within Asia and Latin America while forming an increasing contribution to aquatic food supply in more developed countries. Nations with marine borders often also support important marine fisheries for crustaceans that are regionally traded as live animals and commodity products. …

Perceiving One's Heart Condition To Be Cured Following Hospitalization For Acute Coronary Syndromes: Implications For Patient-Provider Communication, Molly Waring, David Mcmanus, Stephenie Lemon, Joel Gore, Milena Anatchkova, Richard Mcmanus, Arlene Ash, Robert Goldberg, Catarina Kiefe, Jane Saczynski

Richard H. McManus

OBJECTIVE: We examined the proportion of patients perceiving their heart condition to be cured following hospitalization for ACS and identified characteristics associated with these perceptions.

METHODS: We conducted a prospective cohort study of adults hospitalized with ACS (N=396). Patient interviews during hospitalization and one week post-discharge provided demographic and psychosocial characteristics. Medical records provided clinical characteristics. At one week, patients who rated "My heart condition is cured" as "definitely true" or "mostly true" were considered to perceive their heart condition cured.

RESULTS: Participants were aged 60.7 (SD:11.0) years, 26.5% female, and 89.0% non-Hispanic white; 16.7% had unstable angina, 59.6% NSTEMI, …

Targeting Dusps In Glioblastomas–Wielding A Double‐Edged Sword, Sheila Abraham, Swapna Asuthkar, William Lee, Srinivasulu Chigurupat, Andrew Tsung, Kiran Kiran

Sheila Prabhakar Abraham

Several dual-specificity phosphatases (DUSPs) that play key roles in the direct or indirect inactivation of different MAP kinases (MAPKs) have been implicated in human cancers over the past decade. This has led to a growing interest in identifying DUSPs and their specific inhibitors for further testing and validation as therapeutic targets in human cancers. However, the lack of understanding of the complex regulatory mechanisms and cross-talks between MAPK signaling pathways, combined with the fact that DUSPs can act as a double-edged sword in cancer progression, calls for a more careful and thorough investigation. Among the various types of brain cancer, …

Prescribing Patterns Of Metformin In High-Risk Patients With Prediabetes, Daniel Stirling, Ifeanyi Onor, Daniel Sarpong, Kristi Isaac Rapp, Lori Crawford

Ifeanyi Onor, PharmD, BCPS

Working Therapeutically With Deaf People Recovering From Trauma And Addiction, Melissa Anderson, Neil Glickman, Lisa Mistler, Marco Gonzalez

Melissa L. Anderson

OBJECTIVE: This article reviews what is known about behavioral health treatment of deaf persons with comorbid trauma and addiction.

METHOD: We discuss how to work therapeutically with deaf people with comorbid trauma and addiction, both through a review of the literature and through clinical observations of the authors. The article also includes the personal stories of two people-a Deaf peer specialist and a hearing psychiatrist-who share their humbling stories about the recovery process for deaf people and the challenges of learning to become an effective Deaf mental health care provider.

FINDINGS: Deaf people report higher rates of mental health problems …

Circulating Micrornas In Cardiovascular Disease, David Mcmanus, Victor Ambros

Victor R. Ambros

Comment on: Transcoronary concentration gradients of circulating microRNAs. [Circulation. 2011]

Mifepristone Utilization In Cushing’S From Large Bilateral Adrenal Adenoma Prior To Surgery, Vasudev Magaji, Sarah Park, Katie Mastoris, Maura Bucciarelli, Scott Beman

Vasudev G Magaji MD, MS

Utilization of mifepristone was described to mitigate hypercortisolism from bilateral adrenal Cushing’s syndrome. A 47-year-old female on abdominal pain evaluation with CT was found to have a 5.4 × 1.7 × 4.9 cm right adrenal nodule and a 4.3 × 2.9 × 3.3 cm left adrenal nodule with calcification on CT scan with each having density of -3 Housefield units. She had hypercortisolism with testing revealing high urine free cortisol, unsuppressed cortisol on 1 mg and 8 mg overnight dexamethasone suppression testing, high 11 pm salivary cortisol × 2 along with elevated random cortisol and undetectable ACTH. Her DHEA-S, plasma …

Characteristics Of Contemporary Patients Discharged From The Hospital After An Acute Coronary Syndrome, Robert Goldberg, Jane Saczynski, David Mcmanus, Molly Waring, Richard Mcmanus, Jeroan Allison, David Parish, Darleen Lessard, Sharina Person, Joel Gore, Catarina Kiefe

Richard H. McManus

BACKGROUND: Limited contemporary data compare the clinical and psychosocial characteristics and acute management of patients hospitalized with an initial vs a recurrent episode of acute coronary disease. We describe these factors in a cohort of patients recruited from 6 hospitals in Massachusetts and Georgia after an acute coronary syndrome. MATERIALS AND METHODS: We performed structured baseline in-person interviews and medical record abstractions for 2174 eligible and consenting patients surviving hospitalization for an acute coronary syndrome between April 2011 and May 2013. RESULTS: The average patient age was 61 years, 64% were men, and 47% had a high school education or …

Characteristics, Treatment Practices, And In-Hospital Outcomes Of Older Adults Hospitalized With Acute Myocardial Infarction, Han-Yang Chen, David Mcmanus, Jane Saczynski, Jerry Gurwitz, Joel Gore, Jorge Yarzebski, Robert Goldberg

Jorge L. Yarzebski

OBJECTIVES: To examine overall and decade-long trends (1999-2009), characteristics, treatment practices, and hospital outcomes in individuals aged 65 and older hospitalized for acute myocardial infarction (AMI) and to describe how these factors varied in the youngest, middle, and oldest-old individuals.

DESIGN: Retrospective cohort study.

SETTING: Population-based Worcester Heart Attack Study.

MEASUREMENTS: Analyses were conducted to examine the sociodemographic and clinical characteristics, cardiac treatments, and hospital outcomes of older adults in three age strata (65-74, 75-84, > /=85).

PARTICIPANTS: The study sample consisted of 3,851 individuals aged 65 and older hospitalized with AMI every other year between 1999 and 2009; 32% were …

Classification Of Dengue Illness Based On Readily Available Laboratory Data, James Potts, Stephen Thomas, Anon Srikiatkhachorn, Pra-On Supradish, Wenjun Li, Ananda Nisalak, Suchitra Nimmannitya, Timothy Endy, Daniel Libraty, Robert Gibbons, Sharone Green, Alan Rothman, Siripen Kalayanarooj

Sharone Green

The aim of this study was to examine retrospective dengue-illness classification using only clinical laboratory data, without relying on X-ray, ultrasound, or percent hemoconcentration. We analyzed data from a study of children who presented with acute febrile illness to two hospitals in Thailand. Multivariable logistic regression models were used to distinguish: (1) dengue hemorrhagic fever (DHF) versus dengue fever (DF), (2) DHF versus DF + other febrile illness (OFI), (3) dengue versus OFI, and (4) severe dengue versus non-severe dengue + OFI. Data from the second hospital served as a validation set. There were 1,227 patients in the analysis. The …

Health Action Process Approach: Application To Medication Adherence In Cardiac Rehabilitation Patients, Anna Greer, Kerry Milner, Richard Marcello, Katie Mazin

Anna E. Greer

The purpose of this study was to examine the relationship between Health Action Process Approach (HAPA) post-intentional constructs (maintenance self-efficacy, recovery self-efficacy, action planning, coping planning) and medication adherence among phase II cardiac rehabilitation (CR) patients. Research Method: Purposive sampling was used to recruit 91 phase II CR patients age 50 years and over. All respondents completed paper and pencil questionnaire examining HAPA post-intentional constructs (action planning, coping planning, maintenance self-efficacy, recovery self-efficacy), medication adherence, and demographic characteristics. Validity and reliability were confirmed for all scales included in the questionnaire. Descriptive statistics were used to describe respondents’ characteristics. Bivariate statistics …

Alcohol And Hcv: Implications For Liver Cancer, Gyongyi Szabo, Banishree Saha, Terence Bukong

Gyongyi Szabo

Liver cancers are one of the deadliest known malignancies which are increasingly becoming a major public health problem in both developed and developing countries. Overwhelming evidence suggests a strong role of infection with hepatitis B and C virus (HBV and HCV), alcohol abuse, as well as metabolic diseases such as obesity and diabetes either individually or synergistically to cause or exacerbate the development of liver cancers. Although numerous etiologic mechanisms for liver cancer development have been advanced and well characterized, the lack of definite curative treatments means that gaps in knowledge still exist in identifying key molecular mechanisms and pathways …

A Novel Human Radixin Peptide Inhibits Hepatitis C Virus Infection At The Level Of Cell Entry, Terence Bukong, Karen Kodys, Gyongyi Szabo

Gyongyi Szabo

Hepatitis C virus infection of hepatocytes is a multistep process involving the interaction between viral and host cell molecules. Recently, we identified ezrin-moesin-radixin proteins and spleen tyrosine kinase (SYK) as important host therapeutic targets for HCV treatment development. Previously, an ezrin hinge region peptide (Hep1) has been shown to exert anti-HCV properties in vivo, though its mechanism of action remains limited. In search of potential novel inhibitors of HCV infection and their functional mechanism we analyzed the anti-HCV properties of different human derived radixin peptides. Sixteen different radixin peptides were derived, synthesized and tested. Real-time quantitative PCR, cell toxicity assay, …

The Genetics Of Hepatitis C Virus Underlie Its Ability To Escape Humoral Immunity, Jay Kolls, Gyongyi Szabo

Gyongyi Szabo

Hepatitis C virus (HCV) is a leading cause of chronic liver disease, and efforts to develop therapeutic vaccine strategies have been limited by immune escape due to HCV variants that are resistant to current vaccines or HCV variants that rapidly acquire new resistance-conferring mutations. Recently, the crystal structure of the viral envelope protein E2 region was resolved as well as how E2 docks to the host CD81 protein; therefore, antibodies that block this interaction should prevent viral entry into host cells. In this issue of the JCI, Bailey and colleagues show that immune escape of HCV can occur by naturally …

Gut-Liver Axis In Alcoholic Liver Disease, Gyongyi Szabo

Gyongyi Szabo

Alcoholic liver disease (ALD) has been among the leading causes of cirrhosis and liver-related death worldwide for decades. Early discoveries in alcoholic liver disease identified increased levels of bacterial endotoxin in the portal circulation, suggesting a role for gut-derived toxins in ALD. Indeed, alcohol consumption can disrupt the intestinal epithelial barrier and result in increased gut permeability that increasingly is recognized as a major factor in ALD. Bacterial endotoxin, lipopolysaccharide, is a prototypic microbe-derived inflammatory signal that contributes to inflammation in ALD through activation of the Toll-like receptor 4. Recent studies also have shown that alcohol consumption is associated with …

Elevated Serum Glucose Levels And Survival After Acute Heart Failure: A Population-Based Perspective, Benjamin Helfand, Nicholas Maselli, Darleen Lessard, Jorge Yarzebski, Joel Gore, David Mcmanus, Jane Saczynski, Robert Goldberg

Jorge L. Yarzebski

BACKGROUND: Limited data are available about the characteristics, treatment and survival in patients without diabetes mellitus (DM), previously diagnosed DM and patients with hyperglycaemia who present with acute decompensated heart failure (ADHF). Our objectives were to examine differences in these endpoints in patients hospitalized with ADHF. METHODS: Patients hospitalized with ADHF during 1995, 2000, 2002 and 2004 comprised the study population. RESULTS: A total of 5428 non-diabetic patients were hospitalized with ADHF, 3807 with diagnosed DM and 513 with admission hyperglycaemia. Patients with admission hyperglycaemia experienced the highest in-hospital death rates (9.9%) compared to those with diagnosed DM (6.5%) and …

Prepubertal Organochlorine Pesticide Concentrations And Age Of Pubertal Onset Among Russian Boys, Thuy Lam, Paige Williams, Mary Lee, Susan Korrick, Linda Birnbaum, Jane Burns, Oleg Sergeyev, Boris Revich, Larisa Altshul, Donald Patterson, Wayman Turner, Russ Hauser

Mary M. Lee

BACKGROUND: In animal studies, organochlorine pesticide (OCP) exposure alters pubertal development; however, epidemiological data are limited and inconsistent. OBJECTIVE: To evaluate the associations of serum OCP concentrations [hexachlorobenzene (HCB), beta-hexachlorocyclohexane (beta-HCH), and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE)] with male pubertal onset. METHODS: In Chapaevsk, Russia, a town environmentally contaminated with OCPs, 350 8-9 year old boys with measured OCPs were enrolled during 2003-2005 and were followed annually for eight years. We evaluated three measures of pubertal onset: testicular volume (TV) > 3 mL in either testis, or stage 2 or greater for genitalia (G2+), or pubic hair (P2+). We used multivariable interval-censored models to …