Publication Type
December Total
Articles
127
Editorial Material
9
Biographical Item
1
Reviews
15
Total Publications Fiscal Year to Date:
Total
152
775
Publications in Top Quartile Journals 112 out of 152 (73.7%)
All rights reserved. Contents are the property of the authors and/or journals cited. Cover Image from “Characterization of Endothelial Cilia Distribution During Cerebral-Vascular Development in Zebrafish (Danio rerio)�
Ramani Ramchandran, PhD Professor Department of Pediatrics Developmental Vascular Biology Program & Zebrafish Drug Screening Core Patrick J. & Margaret G. McMahon Professor & Vice Chair for Research Department of Obstetrics and Gynecology Medical College of Wisconsin
The Developmental Vascular Biology program in the Children’s Research Institute, Children’s Hospital of Wisconsin is directed by Professor in Pediatrics Ramani Ramchandran, Patrick J. and Margaret G. McMahon Endowed Professor in Obstetrics and Gynecology. The goal of this research program is to investigate the molecular mechanisms underlying vascular patterning in vertebrates. We are interested in understanding how endothelial cells (ECs) in the brain communicate with other cells in the microenvironment to pattern the brain vasculature during development. We use zebrafish, a genetically tractable vertebrate model, and mouse mammalian model to investigate this question. Knowing the basic underlying mechanisms of this EC-driven cross talk with other cell types in the brain is likely to provide opportunities for targeting in diseases influenced by aberrant brain vascular network namely, pediatric cerebral arteriovenous malformations (AVMs) and intracerebral hemorrhage (ICH).
“Characterization of Endothelial Cilia Distribution During Cerebral-Vascular Development in Zebrafish (Danio rerio)” Eisa-Beygi S, Benslimane FM, El-Rass S, et al. Arteriosclerosis, Thrombosis and Vascular Biology. 2018;38:2806-2818. We have identified a microtubule-based structure, cilia in brain ECs of the developing zebrafish. Using highresolution imaging of the transgenic fish line where endothelial cells (marked in red), and cilia (marked in green), cilia were found in ECs prior to flow, which was not described before. This observation suggested that cilia plays a role beyond its traditional mechano-sensor role in the vasculature. Loss of ciliary proteins lead to brain ICH, which was rescued by endothelial-specific expression of the ciliary protein. This work was performed by the Kelleigh Gustafson Research Fellow Dr. Shahram Eisa-Beygi, first author on this work, and is supported by Kelleigh’s Foundation, an organization dedicated to AVM research. Dr. Patricia Burrows who treats Kelleigh was also an integral member of this research team. Figure 1.
Top Panel: Images depicted of cilia in green and endothelial cells in red from a 24 hours post fertilization (hpf) zebrafish embryo shown in the panel. Black box indicates the region of the head vasculature marked by primordial midbrain channel (PMBC). A drawing of the actual data is provided adjacent to the data image. Bottom Panel: Images depicted of cilia in green and endothelial cells in red from a 33 hours post fertilization (hpf) zebrafish embryo shown in the panel. Black box indicates the region of the head vasculature marked by primordial hindbrain channel (PHBC), and emerging central arteries (CtAs). Drawings depicts the series of data from 33 hpf to 55 hpf observed in imaging. A single central artery data image is shown at the far right of the panel.
Figure 2.
Left Panel: Cilium in green emerging into the lumen from a red endothelial cell is shown. Note the tilt of cilium in the middle panel. These images were captured from the transgenic line described in the manuscript. Right Panel: Cilium structure and all the components associated with the structure are labeled.
Danny A. Riley, PhD
I am currently Professor Emeritus of Cell Biology, Neurobiology & Anatomy. Previously, I was Professor and Director of Research in the Department of Physical Medicine & Rehabilitation. While I was President of the American Society for Gravitational and Space Biology, I received their highest honor, the Founders Award.
Professor Department of Cell Biology, Neurobiology & Anatomy Medical College of Wisconsin
“Soleus Muscle Stability in Wild Hibernating Black Bears” Riley DA, Van Dyke JM, Vogel V, et al. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 2018;315(2):R369-R379. As principal investigator, I directed NASA-funded space research on humans and rats to understand the causes of skeletal muscle atrophy during spaceflight aboard the Space Shuttle, Russian biosatellites and the International Space Station. Because astronauts and bed rested patients lose muscle, countermeasures are needed. This spurred my 14 year research study to determine whether hibernating bears resist atrophy during 6 months of winter denning. I led a team of researchers from MCW, Marquette University, Ball State University, and the Wisconsin Dept. of Natural Resources, and engaged over one hundred Wisconsin communityparticipating members to examine hibernating black bears. This field research published 2018 in the American Journal of Physiology reports minimal muscle atrophy and encourages research to determine mechanism. Figure 1. Scatter plots of muscle fiber size to body mass for soleus muscles of summer (n = 16), fall (n = 11), and winter (n = 12) bears. Each symbol represents one individual. For summer bears, the linear regression line (solid line) illustrates a significant (P = 0.0289) correlation (Pearson’s r = 0.6848) of muscle fiber area (µm2) to body mass (kg). Data points of the fall and winter bears all lie within the 95% prediction interval (between the dotted lines) for the summer population.
Suneeta Gollapudy, MD Associate Professor Department of Anesthesiology Director Division of Neuroanesthesiology Medical College of Wisconsin
I am an Associate Professor in the Department of Anesthesiology and Director for the Division of Neuroanesthesiology. My clinical research interests lie in neurosurgical and ENT surgeries. I also have interest in perioperative pharmacological interactions, sideeffects, and off-label usage of drugs. There is always a debate on the choice of anesthesia for endoscopic sinus surgery and claims that total intravenous anesthesia is superior to inhalational anesthetic. This retrospective study was designed to give us some answers and alleviate any misconceptions about the anesthetic choices.
“Total Intravenous Versus Inhaled Anesthesia in Transsphenoidal Tumor Surgery” Gollapudy S, Poetker DM, Sidhu J, Riess ML. American Journal of Otolaryngology. 2018;39(5):567-569.
Endoscopic transsphenoidal surgery is challenging due to a constricted nasal passage and highly vascular tissue. Maintenance of hemostasis is essential for adequate surgical visualization and working space, and in turn reduces complications. We conducted a retrospective chart review and data analysis of patients who underwent endoscopic transsphenoidal resection of pituitary tumors under general anesthesia and sought to determine if total intravenous anesthesia with propofol and remifentanil leads to decreased bleeding, surgical duration, time to extubation and/or length of stay in the recovery room compared to inhaled anesthesia with sevoflurane or desflurane. The results of our study suggest that TIVA is not superior to inhaled anesthesia and that the increased costs associated with TIVA do not benefit the patient in respect with EBL, extubation time or recovery room length of stay. Table 2. Primary and secondary outcomes InhA (n = 50)
TIVA (n = 54)
P-value
Total EBL (ml)
87 ± 12
77 ± 9
0.50
EBL rate (ml/min)
0.65 ± 0.07
0.58 ± 0.06
0.45
Duration of surgery (min)
126 ± 7
133 ± 6
0.41
Time to extubation (min)
14 ± 1
15 ± 1
0.46
Recovery room LOS (min)
61 ± 2
63 ± 4
0.62
All data are mean ± standard error. InhA = inhaled anesthesia; TIVA = total intravenous anesthesia; EBL = estimated blood loss; LOS = length of stay.
Raquel Farias-Moeller, MD Assistant Professor Departments of Neurology and Pediatrics Medical College of Wisconsin
I am a pediatric ICU neurologist with a subspecialty in epilepsy. My research has been focused on super refractory status epilepticus (SRSE) and in ICU EEG. A specific entity that combines SRSE and ICU EEG is febrile infection related epilepsy syndrome (FIRES). FIRES is a devastating epileptic encephalopathy that affects school age children. Patients typically present with explosive onset SRSE that is extremely difficult to control. The etiology of this condition remains elusive. Outcomes for FIRES are usually poor. I collaborate nationally and internationally with FIRES research. I have published manuscripts on early electroencephalographic features as well as on hypotheses of etiological factors contributing to seizure refractoriness in FIRES.
“Fueling the FIRES: Hemophagocytic Lymphohistiocytosis in Febrile Infection-Related Epilepsy Syndrome� Farias-Moeller R, LaFrance-Corey R, Bartolini L, et al. Epilepsia. 2018;59(9):1753-1763. Although the etiology for FIRES is unknown it is postulated that innate immune system dysregulation plays a role. Another condition associated with exaggerated inflammatory responses is hemophagocytic lymphohistiocytosis (HLH). This publication aims to establish common pathophysiologic inflammatory changes in a subset of FIRES patients who developed secondary HLH in efforts to establish a common inflammatory phenotype. We identified five patients with FIRES with clinical deterioration and multi-organ dysfunction prompting HLH screening 3 weeks after admission. CNS and serum inflammatory markers were assessed at various time-points with cytokine/chemokine analyses as well as CSF neopterin. Three patients met clinical criteria for secondary HLH. Primary HLH was ruled out in all patients. Elevation of specific cytokines/chemokines was variable. CSF neopterin, HMGB1 and CXCL-8 were significantly elevated in all patients. FIRES patients had significantly higher CSF neopterin than published values for other neuroinflammatory conditions. We summarize our hypothesized mechanisms for the association of FIRES and secondary HLH in the below figure. Figure 4. Proposed mechanism of FIRES and HLH inflammatory interplay.
Abhay Singh Chauhan, PhD, MPharm, Bpharm Assistant Professor Department of Biopharmaceutical Sciences School of Pharmacy Medical College of Wisconsin
I work in the area of nanotechnology-based drug delivery systems. My main research focus is on dendrimer nanotechnology. Dendrimers are widely recognized as members of the fourth major architectural class of polymers after linear, cross-linked and branched architectural types. I have carried out detailed pioneering work on establishing dendrimers for enhancement of aqueous solubility, stability, dissolution; dendrimer based transdermal nano-formulations, multiple drug delivery, reduction of drug toxicity, nose to brain delivery, and multifunctional dendrimer for drug targeting. I have successfully developed dendrimer formulations for pharmaceutical, in-vitro diagnostics, personal care, and agriculture applications. I am involved in creating nanotechnology awareness globally and currently working on understanding critical nanoscale design parameters (CNDPs) in PAMAM dendrimer nanoparticles for drug delivery applications.
“Engineering of ‘Critical Nanoscale Design Parameters’ (CNDPs) in PAMAM Dendrimer Nanoparticles for Drug Delivery Applications” Chauhan AS, Kaul M. Journal of Nanoparticle Research. 2018;20:226. Dendrimers have become a desirable polymer category for drug delivery applications based on the ability to readily structure control their 6 “critical nanoscale design parameters“ (CNDPs). These CNDPs include; (1) size, (2) shape, (3) surface chemistry, (4) flexibility/rigidity, (5) architecture and (6) elemental composition. Drugs can either be physically entrapped or chemically conjugated onto dendrimers. PAMAM dendrimers are available with a variety of surface groups, cores and generations (i.e., sizes), however, drug associations with dendrimers are most dramatically influenced by the dendrimer’s interior composition, generations (i.e., sizes) and surface chemistries. The physical drug-dendrimer associations are often defined by the periodic dendrimer property patterns which are manifested as a function of dendrimer architecture and generations. Engineering the “critical nanoscale design parameters” of dendrimers provides a systematic strategy for optimizing dendrimer (host) and drug (guest) relationships. Figure 1. Schematic representation of muco-adhesiveness of thiolated dendrimers.
I. Disulfide bond formation with glycoproteins of mucus membrane. II. Inter cross linking of thiolated dendrimers to form polymeric network.
Cynthia Kay, MD, MS Assistant Professor Division of General Internal Medicine Department of Medicine Medical College of Wisconsin Zablocki VA Medical Center
I am an Assistant Professor of General Internal Medicine at the Zablocki VA Medical Center and MCW. I practice as a primary care provider at the VA and also do inpatient wards with the medicine teams. I did my undergraduate and medical school training at the University of Illinois at Chicago. Subsequently, I completed my internal medicine residency and Academic Fellowship in Primary Care Research at MCW. My research interests include chronic pain, chronic opioid use, resident education and chronic disease management.
“Health Care Utilization by Veterans Prescribed Chronic Opioids” Kay C, Wozniak E, Ching A, Bernstein J. Journal of Pain Research. 2018;11:1779-1787. This retrospective chart review examined instances of health care utilization (emergency department [ED] visits, hospitalizations, clinic visits, telephone triage calls, telephone calls/secure messages/nurse visits) of 617 patients on chronic opioid therapy (COT) at a VA’s primary care clinics. Patients were likely to have more telephone calls, secure messages, or nurse visits if prescribed a schedule II opioid or if they were on more than one opioid. Model-based results found patients on COT were more likely to have ED visits, telephone triage calls, and clinic contact compared to patients who were not on COT. These results are despite having a Patient Aligned Care Team, which is the VA’s patient-centered medical home. This suggests that reducing health care utilization for patients on COT may not be possible with just primary care involvement.
Table 1. Model-adjusted odds of health care utilization for pain versus non-pain patients Adjusted ORa
95% CI
P-value
ED visitsb
1.9
1.4-2.4
<0.001
Hospitalizationsc
1.3
0.9-1.9
0.11
Clinic visitsd
1.2
0.9-1.6
0.15
Telephone triagec
1.4
1.0-1.9
0.03
Messagese
1.6
1.2-2.0
<0.001
Notes: aModels were adjusted by applying a stepwise model selection process to the following patient characteristics: age; race; provider (advanced practioner vs physician); psychiatric diagnosis; depression; diabetes; hypertension; cardiac, renal, and pulmonary disease; neuropathy; obesity; tobacco use or substance use disorder; arthritis; service connection; and nonsteroidal anti-inflammatory, antiepileptic, or benzodiazepine prescriptions. bAdjusted common odds ratio for the ordinal outcome of 0, 1, or 2+ visits. cAdjusted odds ratio given any vs none as binary outcome. dAdjusted common odds ratio for the ordinal outcome of 1, 2-3, 4+ visits. eAdjusted common odds ratio for the ordinal outcome of 0-2, 3-5, or 6+ telephone calls, secure message contacts, or nurse visits. Abbreviation: ED, emergency department.
George Noid, PhD Medical Physicist Instructor Department of Radiation Oncology Medical College of Wisconsin
I am a medical physicist in the department of Radiation Oncology. My research is focused on enhancing CT image quality for both improved radiation therapy planning and treatment response assessment. More specifically I’ve been working on the application of derived images from Dual Energy CT to both CT sim acquisitions (for planning) and daily IGRT CT (for treatment assessment).
“Technical Note: Enhancing Soft Tissue Contrast and Radiation-Induced Image Changes with Dual-Energy CT for Radiation Therapy” Noid G, Tai A, Schott D, et al. Medical Physics. 2018;45(9):4238-4245. Our publication was an investigation into the use of mono-energetic images (MEI) derived from sequential DECT for enhanced soft tissue contrast. We found that the lowest available MEI offered the largest enhancement in soft tissue contrast. We then demonstrated that this effect improved the contrast between the pancreas and duodenum for pancreatic cancer patients. Furthermore we found that over the course of fractionated radiation therapy, the change in both mean CTN and histogram features in the target was amplified in the low energy MEI relative to the conventional CT images. Figure 3. A. Change in mean CTN between first and last week of treatment for the 10 pancreas patients in the study as measured at 120 kVp and 40 keV. B. Mean CTN change (HU) in target and aorta along with target location for each patient.
Figure 4. Changes in selected histogram features (mean CTN and normalized entropy) for two patients during treatment for both 120 kVp PEI and 40 keV MEI.
“Free Dialysis in Nepal: Logistical Challenges Explored” McGee J, Pandey B, Maskey A, Frazer T, Mackinney T. Hemodialysis International. 2018;22(3):283-289. We summarize renal replacement therapy (RRT) statistics in Nepal in 2016, when the country established free hemodialysis (HD). Since 2010, when the last data was published, there was a 223% increase in HD centers, and 303% increase in HD patients. HD cost is US$2300 per patient annually. If all ESRD patients were treated, 2.1% of the annual health budget would be allocated to 0.01% of the population. The capital, Kathmandu, contains 50% of HD centers and only 14.5% of Nepal’s population. 48% live in zones without HD, therefore infrastructure challenges exist in providing sustainable and equitable access to free dialysis.
John “Jack” McGee, BS MD Candidate, 2019 Department of Medicine
Philip Lange PhD Candidate Tarakanova Lab Department of Microbiology & Immunology
“Liver X Receptors Suppress Activity of Cholesterol and Fatty Acid Synthesis Pathways To Oppose Gammaherpesvirus Replication” Lange PT, Schorl C, Sahoo D, Tarakanova VL. mBio. 2018;9(4):e01115-18. Gammaherpesviruses are oncogenic pathogens that persist in ~95% of the adult population. Cellular metabolic pathways have emerged as important regulators of many viral infections, including gammaherpesviruses. Liver X receptors (LXRs) are transcription factors that regulate lipid homeostasis. Here we describe an antiviral role for LXRs in the context of gammaherpesvirus infection of primary macrophages. We show that type I interferon increased LXR expression following infection. Surprisingly, there was not a corresponding induction of LXR target genes. Rather, LXRs suppressed the expression of target genes, leading to decreased fatty acid and cholesterol synthesis, two metabolic pathways that support gammaherpesvirus replication.