Medicine and Health Sciences Commons^™

Orientia Tsutsugamushi Ankyrin Repeat-Containing Protein Family Members Are Type 1 Secretion System Substrates That Traffic To The Host Cell Endoplasmic Reticulum, Lauren Viebrock, Sean M. Evans, Andrea R. Beyer, Charles L. Larson, Paul A. Beare, Hong Ge, Smita Singh, Kyle G. Rodino, Robert A. Heinzen, Allen L. Richards, Jason A. Carlyon

Microbiology and Immunology Publications

Scrub typhus is an understudied, potentially fatal infection that threatens one billion persons in the Asia-Pacific region. How the causative obligate intracellular bacterium, Orientia tsutsugamushi, facilitates its intracellular survival and pathogenesis is poorly understood. Many intracellular bacterial pathogens utilize the Type 1 (T1SS) or Type 4 secretion system (T4SS) to translocate ankyrin repeat-containing proteins (Anks) that traffic to distinct subcellular locations and modulate host cell processes. The O. tsutsugamushi genome encodes one of the largest known bacterial Ank repertoires plus T1SS and T4SS components. Whether these potential virulence factors are expressed during infection, how the Anks are potentially secreted, and …

Increased B Cell Adam10 In Allergic Patients And Th2 Prone Mice, Lauren Folgosa Cooley, Rebecca K. Martin, Hannah B. Zellner, Anne-Marie Irani, Cora Uram-Tuculescu, Mohey Eldin El Shikh, Daniel H. Conrad

Microbiology and Immunology Publications

ADAM10, as the sheddase of the low affinity IgE receptor (CD23), promotes IgE production and thus is a unique target for attenuating allergic disease. Herein, we describe that B cell levels of ADAM10, specifically, are increased in allergic patients and Th2 prone WT mouse strains (Balb/c and A/J). While T cell help augments ADAM10 expression, Balb WT B cells exhibit increased ADAM10 in the naïve state and even more dramatically increased ADAM10 after anti-CD40/IL4 stimulation compared C57 (Th1 prone) WT B cells. Furthermore, ADAM17 and TNF are reduced in allergic patients and Th2 prone mouse strains (Balb/c and A/J) compared …

Essential Domains Of Anaplasma Phagocytophilum Invasins Utilized To Infect Mammalian Host Cells, David Seidman, Kathryn S. Hebert, Hilary K. Truchan, Daniel P. Miller, Brittney K. Tegels, Richard T. Marconi, Jason A. Carlyon

Microbiology and Immunology Publications

Anaplasma phagocytophilum causes granulocytic anaplasmosis, an emerging disease of humans and domestic animals. The obligate intracellular bacterium uses its invasins OmpA, Asp14, and AipA to infect myeloid and non-phagocytic cells. Identifying the domains of these proteins that mediate binding and entry, and determining the molecular basis of their interactions with host cell receptors would significantly advance understanding of A. phagocytophilum infection. Here, we identified the OmpA binding domain as residues 59 to 74. Polyclonal antibody generated against a peptide spanning OmpA residues 59 to 74 inhibited A. phagocytophilum infection of host cells and binding to its receptor, sialyl Lewis x …

Phylogenetic And Syntenic Data Support A Single Horizontal Transference To Atrypanosoma Ancestor Of A Prokaryotic Proline Racemase Implicated In Parasite Evasion From Host Defences, Zuleima C. Caballero, Andre G. Costa-Martins, Robson C. Ferreira, João M P Alves, Myrna G. Serrano, Erney P. Camargo, Gregory A. Buck, Paola Minoprio, Marata M G Teixeira

Microbiology and Immunology Publications

Background

Proline racemase (PRAC) enzymes of Trypanosoma cruzi (TcPRAC), the agent of Chagas disease, and Trypanosoma vivax (TvPRAC), the agent of livestock trypanosomosis, have been implicated in the B-cells polyclonal activation contributing to immunosuppression and the evasion of host defences. The similarity to prokaryotic PRAC and the absence in Trypanosoma brucei andTrypanosoma congolense have raised many questions about the origin, evolution, and functions of trypanosome PRAC (TryPRAC) enzymes.

Findings

We identified TryPRAC homologs as single copy genes per haploid genome in 12 of 15Trypanosoma species, including T. cruzi and T. cruzi …

Hiv Protease Inhibitors Sensitize Human Head And Neck Squamous Carcinoma Cells To Radiation By Activating Endoplasmic Reticulum Stress, Runping Liu, Luyong Zhang, Jing Yang, Xiaoxuan Zhang, Ross Mikkelsen, Shiyu Song, Huiping Zhou

Microbiology and Immunology Publications

Background

Human head and neck squamous cell carcinoma (HNSCC) is the sixth most malignant cancer worldwide. Despite significant advances in the delivery of treatment and surgical reconstruction, there is no significant improvement of mortality rates for this disease in the past decades. Radiotherapy is the core component of the clinical combinational therapies for HNSCC. However, the tumor cells have a tendency to develop radiation resistance, which is a major barrier to effective treatment. HIV protease inhibitors (HIV PIs) have been reported with radiosensitizing activities in HNSCC cells, but the underlying cellular/molecular mechanisms remain unclear. Our previous study has shown that …

Mri Evaluation Of Lumbar Disc Degenerative Disease, Pokhraj Suthar, Rupal Patel, Chetan Mehta, Narrotam Patel

Orthopaedic Surgery Publications

Introduction:

Lower back pain secondary to degenerative disc disease is a condition that affects young to middle-aged persons with peak incidence at approximately 40 y. MRI is the standard imaging modality for detecting disc pathology due to its advantage of lack of radiation, multiplanar imaging capability, excellent spinal soft-tissue contrast and precise localization of intervertebral discs changes.

Aims and Objective:

To evaluate the characterization, extent, and changes associated with the degenerative lumbar disc disease by Magnetic Resonance Imaging.

Study Design:

Cross-sectional and observational study.

Materials and Methods:

A total 109 patients of the lumbar disc degeneration with age group between …

Role Of Nitric Oxide In The Radiation-Induced Bystander Effect, Vasily A. Yakovlev

Radiation Oncology Publications

Cells that are not irradiated but are affected by “stress signal factors” released from irradiated cells are called bystander cells. These cells, as well as directly irradiated ones, express DNA damage-related proteins and display excess DNA damage, chromosome aberrations, mutations, and malignant transformation. This phenomenon has been studied widely in the past 20 years, since its first description by Nagasawa and Little in 1992, and is known as the radiation-induced bystander effect (RIBE). Several factors have been identified as playing a role in the bystander response. This review will focus on one of them, nitric oxide (NO), and its role …

Prehospital Use Of Plasma In Traumatic Hemorrhage (The Pupth Trial): Study Protocol For A Randomised Controlled Trial, Penny S. Reynolds, Mary Jane Michael, Emily D. Cochran, Jacob A. Wegelin, Bruce D. Spiess

Anesthesiology Publications

Background

Severe traumatic injury and haemorrhagic shock are frequently associated with disruptions of coagulation function (such as trauma-induced coagulopathy TIC) and activation of inflammatory cascades. These pathologies may be exacerbated by current standard of care resuscitation protocols. Observational studies suggest early administration of plasma to severely-injured haemorrhaging patients may correct TIC, minimise inflammation, and improve survival. The proposed randomised clinical trial will evaluate the clinical effectiveness of pre-hospital plasma administration compared with standard- of-care crystalloid resuscitation in severely-injured patients with major traumatic haemorrhage.

Methods/design

This is a prospective, randomized, open-label, non-blinded trial to determine the effect of pre-hospital administration of …

Burr Hole Washout Versus Craniotomy For Chronic Subdural Hematoma: Patient Outcome And Cost Analysis, Jacqueline M. Regan, Emmagene Worley, Christopher Shelburne, Ranjit Pullarkat, Joseph C. Watson

Neurosurgery Publications

Chronic subdural hematomas (CSDH), which are frequently encountered in neurosurgical practice, are, in the majority of cases, ideally treated with surgical drainage. Despite this common practice, there is still controversy surrounding the best surgical procedure. With lack of clear evidence of a superior technique, surgeons are free to base the decision on other factors that are not related to patient care. A retrospective chart review of 119 patients requiring surgical drainage of CSDH was conducted at a large tertiary care center over a three-year period. Of the cases reviewed, 58 patients underwent craniotomy, while 61 patients underwent burr hole washout. …

A Simple Method For Discovering Druggable, Specific Glycosaminoglycan-Protein Systems. Elucidation Of Key Principles From Heparin/Heparan Sulfate-Binding Proteins, Aurijit Sarkar, Umesh R. Desai

Psychology Publications

Glycosaminoglycans (GAGs) affect human physiology and pathology by modulating more than 500 proteins. GAG-protein interactions are generally assumed to be ionic and nonspecific, but specific interactions do exist. Here, we present a simple method to identify the GAG-binding site (GBS) on proteins that in turn helps predict high specific GAG–protein systems. Contrary to contemporary thinking, we found that the electrostatic potential at basic arginine and lysine residues neither identifies the GBS consistently, nor its specificity. GBSs are better identified by considering the potential at neutral hydrogen bond donors such as asparagine or glutamine sidechains. Our studies also reveal that an …

The Glucagon-Like Peptide-1 Receptor As A Potential Treatment Target In Alcohol Use Disorder: Evidence From Human Genetic Association Studies And A Mouse Model Of Alcohol Dependence, P. Suchankova, J. Yan, M. L. Schwandt, B. L. Stangl, E. C. Caparelli, R. Momenan, E. Jerlhag, J. A. Engel, C. A. Hodgkinson, M. Egli, M. F. Lopez, H. C. Becker, D. Goldman, M. Heilig, V. A. Ramchandani, L. Leggio

Psychiatry Publications

The hormone glucagon-like peptide-1 (GLP-1) regulates appetite and food intake. GLP-1 receptor (GLP-1R) activation also attenuates the reinforcing properties of alcohol in rodents. The present translational study is based on four human genetic association studies and one preclinical study providing data that support the hypothesis that GLP-1R may have a role in the pathophysiology of alcohol use disorder (AUD). Case–control analysis (N=908) was performed on a sample of individuals enrolled in the National Institute on Alcohol Abuse and Alcoholism (NIAAA) intramural research program. The Study of Addiction: Genetics and Environment (SAGE) sample (N=3803) was used for …

Qtc Prolongation In Veterans With Heroin Dependence On Methadone Maintenance Treatment, Sameer Hassamal, Antony Fernandez, Hossein Moradi Rekabdarkolaee, Ananda Pandurangi

Psychiatry Publications

Background:

QTc prolongation and Torsade de Ppointes have been reported in patients on methadone maintenance.

Objectives:

In this study, QTc was compared before and after the veteran (n = 49) was on a stable dosage of methadone for 8.72 ± 4.50 years to treat heroin dependence. Risk factors were correlated with the QTc once the veteran was on a stable dose of methadone. Differences in the clinical risk factors in subgroups of veterans with below and above mean QTc change was compared.

Patients and Methods:

ECG data was obtained from a 12-lead electrocardiogram (pre-methadone and on methadone) on 49 veterans. …

Molecular Signatures Of Major Depression, Na Cai, Simon Chang, Yihan Li, Qiban Li, Jingchu Hu, Jieqin Liang, Li Song, Warren Kretzschmar, Xiangchao Gan, Jerome Nicod, Margarita Rivera, Hong Deng, Bo Du, Keqing Li, Wenhu Sang, Jingfang Gao, Shugui Gao, Baowei Ha, Hung-Yao Ho, Chunmei Hu, Jian Hu, Zhenfei Hu, Guoping Huang, Guoqing Jiang, Tao Jiang, Wei Jin, Gongying Li, Kan Li, Yi Li, Yingrui Li, Youhui Li, Yu-Ting Lin, Lanfen Liu, Tiebang Liu, Ying Liu, Yuan Liu, Yao Lu, Luxian Lv, Huaqing Meng, Puyi Qian, Hong Sang, Jianhua Shen, Jianguo Shi, Jing Sun, Ming Tao, Gang Wang, Guangbiao Wang, Jian Wang, Linmao Wang, Xueyi Wang, Xumei Wang, Huanming Yang, Lijun Yang, Ye Yin, Jinbei Zhang, Kerang Zhang, Ning Sun, Wei Zhang, Xiuqing Zhang, Zhen Zhang, Hui Zhong, Gerome Breen, Jun Wang, Jonathan Marchini, Yiping Chen, Qi Xu, Xun Xu, Richard Mott, Guo-Jen Huang, Kenneth S. Kendler, Jonathan Flint

Psychiatry Publications

Adversity, particularly in early life, can cause illness. Clues to the responsible mechanisms may lie with the discovery of molecular signatures of stress, some of which include alterations to an individual’s somatic genome. Here, using genome sequences from 11,670 women, we observed a highly significant association between a stress-related disease, major depression, and the amount of mtDNA (p = 9.00 × 10−42, odds ratio 1.33 [95% confidence interval [CI] = 1.29–1.37]) and telomere length (p = 2.84 × 10−14, odds ratio 0.85 [95% CI = 0.81–0.89]). While both telomere length and mtDNA amount were associated with adverse life events, conditional …

Generalised Anxiety Disorder – A Twin Study Of Genetic Architecture, Genome-Wide Association And Differential Gene Expression, Matthew N. Davies, Serena Verdi, Andrea Burri, Maciej Trzaskowski, Minyoung Lee, John M. Hettema, Rick Jansen, Dorret I. Boomsma, Tim D. Spector

Psychiatry Publications

Generalised Anxiety Disorder (GAD) is a common anxiety-related diagnosis, affecting approximately 5% of the adult population. One characteristic of GAD is a high degree of anxiety sensitivity (AS), a personality trait which describes the fear of arousal-related sensations. Here we present a genome-wide association study of AS using a cohort of 730 MZ and DZ female twins. The GWAS showed a significant association for a variant within the RBFOX1 gene. A heritability analysis of the same cohort also confirmed a significant genetic component with h2 of 0.42. Additionally, a subset of the cohort (25 MZ twins discordant for AS) was …

Integrating Basic Research With Prevention/Intervention To Reduce Risky Substance Use Among College Students, Danielle Dick, Linda C. Hancock

Psychiatry Publications

Too often basic research on etiological processes that contribute to substance use outcomes is disconnected from efforts to develop prevention and intervention programming. Substance use on college campuses is an area of concern where translational efforts that bring together basic scientists and prevention/intervention practitioners have potential for high impact. We describe an effort at a large, public, urban university in the United States to bring together researchers across the campus with expertise in college behavioral health with university administration and health/wellness practitioners to address college student substance use and mental health. The project “Spit for Science” examines how genetic and …

A Brief Analysis Of Suicide Methods And Trends In Virginia From 2003 To 2012, Sameer Hassamal, Lori Keyser-Marcus, Ericka Crouse Breden, Kathrin Hobron, Atit Bhattachan, Ananda Pandurangi

Psychiatry Publications

Background. The objective is to analyze and compare Virginia suicide data from 2003 to 2012 to US suicide data. Methods. Suicide trends by method, age, gender, and race were obtained from Virginia’s Office of the Chief Medical Examiner’s annual reports. Results. Similar to US suicide rates, suicide rates in Virginia increased between 2003 and 2012 from 10.9/100,000 people to 12.9/100,000 people. The most common methods were firearm, asphyxia, and intentional drug overdose, respectively. The increase in asphyxia (𝑟 = 0.77, 𝑃 ≤ 0.01) and decrease in CO poisoning (𝑟 = −0.89, 𝑃 ≤ 0.01) were significant. Unlike national trends, intentional …

Dpy-17 And Mua-3 Interact For Connective Tissue-Like Tissue Integrity In Caenorhabditis Elegans: A Model For Marfan Syndrome, Pauline Fotopoulos, Jeongho Kim, Moonjung Hyun, Waiss Qamari, Inhwan Lee, Young-Jai You

Biochemistry and Molecular Biology Publications

mua-3 is a Caenorhabditis elegans homolog of the mammalian fibrillin1, a monogenic cause of Marfan syndrome. We identified a new mutation of mua-3that carries an in-frame deletion of 131 amino acids in the extracellular domain, which allows the mutants to survive in a temperature-dependent manner; at the permissive temperature, the mutants grow normally without obvious phenotypes, but at the nonpermissive temperature, more than 90% die during the L4 molt due to internal organ detachment. Using the temperature-sensitive lethality, we performed unbiased genetic screens to isolate suppressors to find genetic interactors of MUA-3. From two independent screens, we isolated …

The Phosphorylated Prodrug Fty720 Is A Histone Deacetylase Inhibitor That Reactivates Erα Expression And Enhances Hormonal Therapy For Breast Cancer, Nitai C. Hait, Dorit Avni, Akimitsu Yamada, Masayuki Nagahashi, Tomoyoshi Aoyagi, Hiroaki Aoki, Catherine I. Dumur, Z Zelenko, E J. Gallagher, D Leroith, Sheldon Milstien, Kazuaki Takabe, Sarah Spiegel

Biochemistry and Molecular Biology Publications

Estrogen receptor-α (ERα)-negative breast cancer is clinically aggressive and does not respond to conventional hormonal therapies. Strategies that lead to re-expression of ERα could sensitize ERα-negative breast cancers to selective ER modulators. FTY720 (fingolimod, Gilenya), a sphingosine analog, is the Food and Drug Administration (FDA)-approved prodrug for treatment of multiple sclerosis that also has anticancer actions that are not yet well understood. We found that FTY720 is phosphorylated in breast cancer cells by nuclear sphingosine kinase 2 and accumulates there. Nuclear FTY720-P is a potent inhibitor of class I histone deacetylases (HDACs) that enhances histone acetylations and regulates expression of …

Dual Action Of Mir-125b As A Tumor Suppressor And Oncomir-22 Promotes Prostate Cancer Tumorigenesis, William Budd, Sarah J. Seashols-Williams, Gene C. Clark, Danielle Weaver, Valerie Calvert, Emanuel Petricoin, Ema A. Dragoescu, Katherine O’Hanlon, Zendra E. Zehner

Biochemistry and Molecular Biology Publications

MicroRNAs (miRs) are a novel class of small RNA molecules, the dysregulation of which can contribute to cancer. A combinatorial approach was used to identify miRs that promote prostate cancer progression in a unique set of prostate cancer cell lines, which originate from the parental p69 cell line and extend to a highly tumorigenic/metastatic M12 subline. Together, these cell lines are thought to mimic prostate cancer progression in vivo. Previous network analysis and miR arrays suggested that the loss of hsa-miR-125b together with the overexpression of hsa-miR-22 could contribute to prostate tumorigenesis. The dysregulation of these two miRs was …

Evaluation Of Methyl-Binding Domain Based Enrichment Approaches Revisited, Karolina A. Aberg, Linying Xie, Robin F. Chan, Min Zhao, Ashutosh K. Pandey, Gaurav Kumar, Shaunna L. Clark, Edwin J. C. G. Van Den Oord

Biomarker Research and Personalized Medicine Publications

Methyl-binding domain (MBD) enrichment followed by deep sequencing (MBD-seq), is a robust and cost efficient approach for methylome-wide association studies (MWAS). MBD-seq has been demonstrated to be capable of identifying differentially methylated regions, detecting previously reported robust associations and producing findings that replicate with other technologies such as targeted pyrosequencing of bisulfite converted DNA. There are several kits commercially available that can be used for MBD enrichment. Our previous work has involved MethylMiner (Life Technologies, Foster City, CA, USA) that we chose after careful investigation of its properties. However, in a recent evaluation of five commercially available MBD-enrichment kits the …

Screening And Brief Intervention For Alcohol Misuse In Older Adults: Training Outcomes Among Physicians And Other Healthcare Practitioners In Community-Based Settings, Constance L. Coogle, Myra G. Owens

Forensic Science Publications

Screening and brief intervention (SBI) is increasingly available to older adults who engage in at-risk drinking. This study examined the extent to which SBI training influenced the willingness of healthcare providers in a community-based hospital and other clinical settings to promote the implementation of SBI. Ninety-three healthcare practitioners (primarily physicians, nurses, and social workers) who attended SBI training were asked about their intentions to apply the information in their professional practice, as well as their enthusiasm about recommending the training to others in their profession. Although there were no differences among the professions in terms of commitment to apply the …

Procalcitonin Identifies Cell Injury, Not Bacterial Infection, In Acute Liver Failure, Jody A. Rule, Linda S. Hynan, Nahid Attar, Corron Sanders, William J. Korzun, William M. Lee, Acute Liver Failure Study Group

Health Administration Publications

Background

Because acute liver failure (ALF) patients share many clinical features with severe sepsis and septic shock, identifying bacterial infection clinically in ALF patients is challenging. Procalcitonin (PCT) has proven to be a useful marker in detecting bacterial infection. We sought to determine whether PCT discriminated between presence and absence of infection in patients with ALF.

Method

Retrospective analysis of data and samples of 115 ALF patients from the United States Acute Liver Failure Study Group randomly selected from 1863 patients were classified for disease severity and ALF etiology. Twenty uninfected chronic liver disease (CLD) subjects served as controls.

Results …

High Fat High Cholesterol Diet (Western Diet) Aggravates Atherosclerosis, Hyperglycemia And Renal Failure In Nephrectomized Ldl Receptor Knockout Mice: Role Of Intestine Derived Lipopolysaccharide, Siddhartha S. Ghosh, Samuel Righi, Richard Krieg, Le Kang, Daniel Carl, Jing Wang, H. Davis Massey, Domenic A. Sica, Todd W. B. Gehr, Shobha Ghosh

Anatomy and Neurobiology Publications

A high fat meal, frequently known as western diet (WD), exacerbates atherosclerosis and diabetes. Both these diseases are frequently associated with renal failure. Recent studies have shown that lipopolysaccharide (LPS) leaks into the circulation from the intestine in the setting of renal failure and after WD. However, it is not clear how renal function and associated disorders are affected by LPS. This study demonstrates that circulatory LPS exacerbates renal insufficiency, atherosclerosis and glucose intolerance. Renal insufficiency was induced by 2/3 nephrectomy in LDL receptor knockout mice. Nx animals were given normal diet (Nx) or WD (Nx+WD). The controls were sham …

Elucidating The Role Of Injury-Induced Electric Fields (Efs) In Regulating The Astrocytic Response To Injury In The Mammalian Central Nervous System, Matthew L. Baer, Scott C. Henderson, Raymond J. Colello

Anatomy and Neurobiology Publications

Injury to the vertebrate central nervous system (CNS) induces astrocytes to change their morphology, to increase their rate of proliferation, and to display directional migration to the injury site, all to facilitate repair. These astrocytic responses to injury occur in a clear temporal sequence and, by their intensity and duration, can have both beneficial and detrimental effects on the repair of damaged CNS tissue. Studies on highly regenerative tissues in non-mammalian vertebrates have demonstrated that the intensity of direct-current extracellular electric fields (EFs) at the injury site, which are 50–100 fold greater than in uninjured tissue, represent a potent signal …

Adiposity And Spinal Cord Injury, Ashraf S. Gorgey, Kathryn M. Wells, Timothy L. Austin

Physical Medicine and Rehabilitation Publications

The drastic changes in body composition following spinal cord injury (SCI) have been shown to play a significant role in cardiovascular and metabolic health. The pattern of storage and distribution of different types of adipose tissue may impact metabolic health variables similar to carbohydrate, lipid and bone metabolism. The use of magnetic resonance imaging provides insights on the interplay among different regional adipose tissue compartments and their role in developing chronic diseases. Regional adipose tissue can be either distributed centrally or peripherally into subcutaneous and ectopic sites. The primary ectopic adipose tissue sites are visceral, intramuscular and bone marrow. Dysfunction …

Ultrasound-Guided Glenohumeral Joint Injection Using The Posterior Approach, Carl P. C. Chen, Henry L. Lew, Chih-Chin Hsu

Physical Medicine and Rehabilitation Publications

Injection treatment to the glenohumeral joint is often needed to treat shoulder problems such as adhesive capsulitis. This can be done through blind palpation technique and fluoroscopic or musculoskeletal ultrasound guidance. In recent years, ultrasound has been proven to increase the accuracy of needle placement into the glenohumeral joint. Ultrasound is radiation free and offers real-time images in performing needle-guided injection procedures.

Glenohumeral joint injection can be done using the anterior rotator interval approach or the posterior approach technique. Both techniques are generally well tolerated by the patients. However, it was shown that the posterior injection technique offers an easier …

Structural Studies Of Aav2 Rep68 Reveal A Partially Structured Linker And Compact Domain Conformation, Faik N. Musayev, Francisco Zarate-Perez, Martino Bardelli, Clayton Bishop, Emil F. Saniev, R. Michael Linden, Els Henckaerts, Carlos R. Escalante

Medicinal Chemistry Publications

Adeno-associated virus (AAV) nonstructural proteins Rep78 and Rep68 carry out all DNA transactions that regulate the AAV life cycle. They share two multifunctional domains: an N-terminal origin binding/nicking domain (OBD) from the HUH superfamily and a SF3 helicase domain. A short linker of ~20 amino acids that is critical for oligomerization and function connects the two domains. Although X-ray structures of the AAV5 OBD and AAV2 helicase domains have been determined, information about the full-length protein and linker conformation is not known. This article presents the solution structure of AAV2 Rep68 using small-angle X-ray scattering (SAXS). We first determined the …

Plasmin Regulation Through Allosteric, Sulfated, Small Molecules, Rami A. Al-Horani, Rajesh Karuturi, Domonique T. White, Umesh R. Desai

Medicinal Chemistry Publications

Plasmin, a key serine protease, plays a major role in clot lysis and extracellular matrix remodeling. Heparin, a natural polydisperse sulfated glycosaminoglycan, is known to allosterically modulate plasmin activity. No small allosteric inhibitor of plasmin has been discovered to date. We screened an in-house library of 55 sulfated, small glycosaminoglycan mimetics based on nine distinct scaffolds and varying number and positions of sulfate groups to discover several promising hits. Of these, a pentasulfated flavonoid-quinazolinone dimer 32 was found to be the most potent sulfated small inhibitor of plasmin (IC50 = 45 μM, efficacy = 100%). Michaelis-Menten kinetic studies revealed …

Prevalence And Factors Predictive Of Intraocular Fungal Infection In Patients With Fungemia At An Academic Urban Tertiary Care Center, Elena Geraymovych, Joseph H. Conduff, Puneet S. Braich, Christopher T. Leffler, Vikram S. Brar

Ophthalmology Publications

Objective: To report the prevalence and to identify factors predictive of intraocular infection in patients with fungemia receiving prophylactic antifungal therapy.
Methods: A retrospective review of patients who received prophylactic antifungal therapy and a dilated fundus examination at an academic urban tertiary care center from 2000 to 2007. Basic demographic information, fungal species grown, antifungal agent(s) used, number of positive blood culture specimens, visual acuity, visual symptoms, and known risks of disseminated candidiasis were noted. Logistic regression analysis was used to determine the factors significantly associated with intraocular fungal infection.
Results: A total of 132 patients with positive fungemia culture …

A Fatal Twist: Volvulus Of The Small Intestine In A 46-Year-Old Woman, Jared Klein, Kathryn Baxstrom, Stephen Donnelly, Patrick Feasel, Paul Koles

Pediatrics Publications

A 46-year-old woman presented to two emergency departments within 12 hours because of acute abdominal pain. Physical exam demonstrated tenderness and epigastric guarding. An ultrasound was interpreted as negative; she was discharged home. Later that evening, she was found dead. Postmortem exam revealed acute hemorrhagic necrosis of a segment of jejunum secondary to volvulus. Clinical clues suggesting presentations of small bowel volvulus are usually nonspecific; the diagnosis is typically confirmed at surgery. Her unremitting abdominal pain, persistent vomiting, and absolute neutrophilia were consistent with an acute process. The etiology of this volvulus was caused by an elastic fibrous band at …