Anatomy Commons^™

Treatment Of Gravitational Pulling Sensation In Patients With Mal De Debarquement Syndrome (Mdds): A Model-Based Approach, Sergei B. Yakushin, Theodore Raphan, Catherine Cho

Publications and Research

Perception of the spatial vertical is important for maintaining and stabilizing vertical posture during body motion. The velocity storage pathway of vestibulo-ocular reflex (VOR), which integrates vestibular, optokinetic, and proprioception in the vestibular nuclei vestibular-only (VO) neurons, has spatio-temporal properties that are defined by eigenvalues and eigenvectors of its system matrix. The yaw, pitch and roll eigenvectors are normally aligned with the spatial vertical and corresponding head axes. Misalignment of the roll eigenvector with the head axes was hypothesized to be an important contributor to the oscillating vertigo during MdDS. Based on this, a treatment protocol was developed using simultaneous …

Stimulating The Facial Nerve To Treat Ischemic Stroke: A Systematic Review, Turner S. Baker, Justin Robeny, Danna Cruz, Alexis Bruhat, Alfred-Marc Iloreta, Anthony Costa, Thomas James Oxley

Publications and Research

Acute ischemic stroke (AIS) is a common devastating disease that has increased yearly in absolute number of cases since 1990. While mechanical thrombectomy and tissue plasminogen activator (tPA) have proven to be effective treatments, their window-of-efficacy time is very short, leaving many patients with no viable treatment option. Over recent years there has been a growing interest in stimulating the facial nerves or ganglions to treat AIS. Pre-clinical studies have consistently demonstrated an increase in collateral blood flow (CBF) following ganglion stimulation, with positive indications in infarct size and neurological scores. Extensive human trials have focused on trans-oral electrical stimulation …

A Systematic Review And Meta-Analysis On The Efficacy Of Stem Cell Therapy On Bone Brittleness In Mouse Models Of Osteogenesis Imperfecta, Lauren Battle, Shoshana Yakar, Alessandra Carriero

Publications and Research

There is no cure for osteogenesis imperfecta (OI), and current treatments can only partially correct the bone phenotype. Stem cell therapy holds potential to improve bone quality and quantity in OI. Here, we conduct a systematic review and meta-analysis of published studies to investigate the efficacy of stem cell therapy to rescue bone brittleness in mouse models of OI. Identified studies included bone marrow, mesenchymal stem cells, and human fetal stem cells. Effect size of fracture incidence, maximum load, stiffness, cortical thickness, bone volume fraction, and raw engraftment rates were pooled in a random-effects meta-analysis. Cell type, cell number, injection …

Notch Signaling Represses Cone Photoreceptor Formation Through The Regulation Of Retinal Progenitor Cell States, Xueqing Chen, Mark M. Emerson

Publications and Research

Notch signaling is required to repress the formation of vertebrate cone photoreceptors and to maintain the proliferative potential of multipotent retinal progenitor cells. However, the mechanism by which Notch signaling controls these processes is unknown. Recently, restricted retinal progenitor cells with limited proliferation capacity and that preferentially generate cone photoreceptors have been identified. Thus, there are several potential steps during cone genesis that Notch signaling could act. Here we use cell type specific cis-regulatory elements to localize the primary role of Notch signaling in cone genesis to the formation of restricted retinal progenitor cells from multipotent retinal progenitor cells. Localized …

A Bisphosphonate With A Low Hydroxyapatite Binding Affinity Prevents Bone Loss In Mice After Ovariectomy And Reverses Rapidly With Treatment Cessation, Abigail A. Coffman, Jelena Basta-Pljakic, Rosa M. Guerra, Frank H. Ebetino, Mark W. Lundy, Robert J. Majeska, Mitchell B. Schaffler

Publications and Research

Bisphosphonates (BPs) are a mainstay of osteoporosis treatment; however, concerns about bone health based on oversuppression of remodeling remain. Long-term bone remodeling suppression adversely affects bone material properties with microdamage accumulation and reduced fracture toughness in animals and increases in matrix mineralization and atypical femur fractures in patients. Although a “drug holiday” from BPs to restore remodeling and improve bone quality seems reasonable, clinical BPs have long functional half-lives because of their high hydroxyapatite (HAP) binding affinities. This places a practical limit on the reversibility and effectiveness of a drug holiday. BPs with low HAP affinity and strong osteoclast inhibition …

Age And Sex Differences In Load-Induced Tibial Cortical Bone Surface Strain Maps, Alessandra Carriero, Behzad Javaheri, Neda Bassir Kazeruni, Andrew A. Pitsillides, Sandra J. Shefelbine

Publications and Research

Bone adapts its architecture to the applied load; however, it is still unclear how bone mechano-adaptation is coordinated and why potential for adaptation adjusts during the life course. Previous animal models have suggested strain as the mechanical stimulus for bone adaptation, but yet it is unknown how mouse cortical bone load-related strains vary with age and sex. In this study, full-field strain maps (at 1 N increments up to 12 N) on the bone surface were measured in young, adult, and old (aged 10, 22 weeks, and 20 months, respectively), male and female C57BL/6J mice with load applied using a …

Endothelial Iqgap1 Regulates Leukocyte Transmigration By Directing The Lbrc To The Site Of Diapedesis, David P. Sullivan, Prarthana J. Dalal, Fanny Jaulin, David B. Sacks, Geri Kreitzer, William A. Muller

Publications and Research

Transendothelial migration (TEM) of leukocytes across the endothelium is critical for inflammation. In the endothelium, TEM requires the coordination of membrane movements and cytoskeletal interactions, including, prominently, recruitment of the lateral border recycling compartment (LBRC). The scaffold protein IQGAP1 was recently identified in a screen for LBRC-interacting proteins. Knockdown of endothelial IQGAP1 disrupted the directed movement of the LBRC and substantially reduced leukocyte TEM. Expression of truncated IQGAP1 constructs demonstrated that the calponin homology domain is required for IQGAP1 localization to endothelial borders and that the IQ domain, on the same IQGAP1 polypeptide, is required for its function in TEM. …

Extreme Events Reveal An Alimentary Limit On Sustained Maximal Human Energy Expenditure, Caitlin Thurber, Lara R. Dugas, Cara Ocobock, Bryce Carlson, John R. Speakman, Herman Pontzer

Publications and Research

The limits on maximum sustained energy expenditure are unclear but are of interest because they constrain reproduction, thermoregulation, and physical activity. Here, we show that sustained expenditure in humans, measured as maximum sustained metabolic scope (SusMS), is a function of event duration. We compiled measurements of total energy expenditure (TEE) and basal metabolic rate (BMR) from human endurance events and added new data from adults running ~250 km/week for 20 weeks in a transcontinental race. For events lasting 0.5 to 250+ days, SusMS decreases curvilinearly with event duration, plateauing below 3× BMR. This relationship differs from that of shorter events …

Case Presentation On Congestive Heart Failure And Pulmonary Edema, Tetiana Soloviova, Denise Aris

Publications and Research

No abstract provided.

Equalization Of Four Cardiovascular Risk Algorithms After Systematic Recalibration: Individual-Participant Meta-Analysis Of 86 Prospective Studies, Lisa Pennells, Stephen Kaptoge, Angela Wood, Mike Sweeting, Xiaohui Zhao, Ian White, Stephen Burgess, Peter Willeit, Thomas Bolton, Karel G. M. Moons, Yvonne T. Van Der Schouw, Randi Selmer, Kay-Tee Khaw, Vilmundur Gudnason, Gerd Assman, Philippe Amouyel, Veikko Salomaa, Mika Kivimaki, Borge G. Nordestgaard, Michael J. Blaha, Lewis H. Kuller, Hermann Brenner, Richard F. Gillum, Christa Meisinger, Ian Ford, Matthew W. Knuiman, Annika Rosengren, Debbie A. Lawlor, Henry Volzke, Cyrus Cooper, Alejandro Marin Ibañez, Edoardo Casiglia, Jussi Kauhanen, Jackie A. Cooper, Beatriz Rodriguez, Johan Sundstrom, Elizabeth Barrett-Connor, Rachel Dankner, Paul J. Nietert, Karina W. Davidson, Robert B. Wallace, Dan G. Blazer, Cecilia Bjorkelund, Chiara Donfrancesco, Harlan M. Krumholz, Aulikki Nissinen, Barry R. Davis, Sean Coady, Peter H. Whincup, Torben Jorgensen, Pierre Ducimetiere, Maurizo Trevisan, Gunnar Engstrom, Carlos J. Crespo, Tom W. Meade, Marjolein Visser, Daan Kromhout, Stefan Kiechl, Makoto Daimon, Jackie F. Price, Agustin Gomez De La Camara, J. Wouter Jukema, Benoit Lamarche, Altan Onat, Leon A. Simons, Maryam Kavousi, Yoav Ben-Shlomo, John Gallacher, Jacqueline M. Dekker, Hisatomi Arima, Nawar Shara, Robert W. Tipping, Ronan Roussel, Eric J. Brunner, Wolfgang Koenig, Masaru Sakurai, Jelena Pavlovic, Ron T. Gansevoort, Dorothea Nagel, Uri Goldbourt, Elizabeth L. M. Barr, Luigi Palmieri, Inger Njolstad, Shinichi Sato, W. M. Monique Verschuren, Cherian V. Varghese, Ian Graham, Oyere Onuma, Philip Greenland, Mark Woodward, Majid Ezzati, Bruce M. Psaty, Naveed Sattar, Rod Jackson, Paul M. Ridker, Nancy R. Cook, Ralph B. D'Agostino Sr., Simone G. Thompson, John Danesh, Emanuele Di Angelantonio

Publications and Research

Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after ‘recalibration’, a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied.

Methods & Results: Using individual-participant data on 360737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and …

Hominoid Intraspecific Cranial Variation Mirrors Neutral Genetic Diversity, Julia M. Zichello, Karen L. Baab, Kieran P. Mcnulty, Christopher J. Raxworthy, Michael E. Steiper

Publications and Research

Natural selection, developmental constraint, and plasticity have all been invoked as explanations for intraspecific cranial variation in humans and apes. However, global patterns of human cranial variation are congruent with patterns of genetic variation, demonstrating that population history has influenced cranial variation in humans. Here we show that this finding is not unique to Homo sapiens but is also broadly evident across extant ape species. Specifically, taxa that exhibit greater intraspecific cranial shape variation also exhibit greater genetic diversity at neutral autosomal loci. Thus, cranial shape variation within hominoid taxa reflects the population history of each species. Our results suggest …

Measuring The Energy Of Ventilation And Circulation During Human Walking Using Induced Hypoxia, Masahiro Horiuchi, Yoshiyuki Fukuoka, Yoko Handa, Daijiro Abe, Herman Pontzer

Publications and Research

Energy expenditure (EE) during walking includes energy costs to move and support the body and for respiration and circulation. We measured EE during walking under three different oxygen concentrations. Eleven healthy, young, male lowlanders walked on a treadmill at seven gait speeds (0.67–1.83 m s−1) on a level gradient under normobaric normoxia (room air, 21% O2), moderate hypoxia (15% O2), and severe hypoxia (11% O2). By comparing the hypoxia-induced elevation in heart rate (HR [bpm]), ventilation (VE [L min−1]) with the change in energy expenditure (EE [W]) at each speed, we were able to determine circulatory and respiratory costs. In …

The Effect Of Object-Centered Instructions In Cartesian And Polar Coordinates On Saccade Vector, Jay A. Edelman, Alexa M. Mieses, Kira Konnova, David Shiu

Publications and Research

Express saccades (ES) are the most reflexive saccadic eye movements, with very short reaction times of 70– 110 ms. It is likely that ES have the shortest saccade reaction times (SRTs) possible given the known physiological and anatomical delays present in sensory and motor systems. Nevertheless, it has been demonstrated that a vector displacement of ES to spatially extended stimuli can be influenced by spatial cognition. Edelman, Kristjansson, and Nakayama (2007) found that when two horizontally separated visual stimuli appear at a random location, the spatial vector, but not the reaction time, of human ES is strongly influenced by an …

Gait Changes In A Line Of Mice Artificially Selected For Longer Limbs, Leah M. Sparrow, Emily Pellattt, Sabrina S. Yu, David A. Raichlen, Herman Pontzer, Campbell Rolian

Publications and Research

In legged terrestrial locomotion, the duration of stance phase, i.e., when limbs are in contact with the substrate, is positively correlated with limb length, and negatively correlated with the metabolic cost of transport. These relationships are well documented at the interspecific level, across a broad range of body sizes and travel speeds. However, such relationships are harder to evaluate within species (i.e., where natural selection operates), largely for practical reasons, including low population variance in limb length, and the presence of confounding factors such as body mass, or training. Here, we compared spatiotemporal kinematics of gait in Longshanks, a long-legged …

Liver Enzymes And Risk Of Ischemic Heart Disease And Type 2 Diabetes Mellitus: A Mendelian Randomization Study, Junxi Liu, Shiu Lun Au Yeung, Gabriel M. Leung, C. Mary Schooling

Publications and Research

We used Mendelian randomization to estimate the causal effects of the liver enzymes, alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma glutamyltransferase (GGT), on diabetes and cardiovascular disease, using genetic variants predicting these liver enzymes at genome wide significance applied to extensively genotyped case-control studies of diabetes (DIAGRAM) and coronary artery disease (CAD)/myocardial infarction (MI) (CARDIoGRAMplusC4D 1000 Genomes). Genetically higher ALT was associated with higher risk of diabetes, odds ratio (OR) 2.99 per 100% change in concentration (95% confidence interval (CI) 1.62 to 5.52) but ALP OR 0.92 (95% CI 0.71 to 1.19) and GGT OR 0.88 (95% CI 0.75 …

Ethics Pertaining To The Legalities Of Male Routine Infant Circumcision And Surrogate Consent To Non-Therapeutic Surgery, Jason A. Domashevskiy, Artem V. Domashevskiy

Publications and Research

Circumcision is the most contentious surgery performed in the world today. Approximately 38% of the world male population has been circumcised, mostly during the neonatal and prepubescent periods. Circumcision in regularly practiced ubiquitously throughout the Islamic countries, Israel, and the United States; the US is only country who regularly circumcises its boys for a non-religious reason. No world health body advocates circumcision prior to adulthood. Routine Infant Circumcision (RIC) violates the United Nations Policy on Genital Integrity, the Hippocratic Oath taken by doctors, and the rules for surrogate consent to surgery. Studies have shown no benefits to circumcision during the …

Combining Body Mass And Shape Indices In Clinical Practice, Jesse C. Krakauer, Nir Y. Krakauer

Publications and Research

We present preliminary clinical experience with combined consideration of the commonly used BMI (body mass index) and the newly developed ABSI (a body shape index) using a point of care anthropometric calculator for comparisons of index values and associated relative risks to population normals. In a series of 282 patients, BMI and ABSI were close to being independently distributed, supporting the value of considering both indices. Three selected cases illustrate scenarios where assessment of ABSI together with BMI could inform patient care and counseling. These data suggest that combined assessment of BMI and ABSI may prove useful in clinical practice.

Atypical Multisensory Integration In Niemann-Pick Type C Disease – Towards Potential Biomarkers, Gizely N. Andrade, Sophie Molholm, John S. Butler, Alice Brown Brandwein, Steven U. Walkley, John J. Foxe

Publications and Research

Background: Niemann-Pick type C (NPC) is an autosomal recessive disease in which cholesterol and glycosphingolipids accumulate in lysosomes due to aberrant cell-transport mechanisms. It is characterized by progressive and ultimately terminal neurological disease, but both pre-clinical studies and direct human trials are underway to test the safety and efficacy of cholesterol clearing compounds, with good success already observed in animal models. Key to assessing the effectiveness of interventions in patients, however, is the development of objective neurobiological outcome measures. Multisensory integration mechanisms present as an excellent candidate since they necessarily rely on the fidelity of long-range neural connections between the …

Osteoarthritis And Articular Cartilage: Biomechanics And Novel Treatment Paradigms, Ray Marks

Publications and Research

Background: Osteoarthritis is a widespread highly painful disabling age-related disease with no known cure. Although novel strategies for ameliorating osteoarthritic damage abound, it is likely that none will be successful over time if the entire spectrum of the disease and the effects of joint biomechanics on joint tissues are not carefully considered.

Objectives: 1) To detail the structure of healthy articular cartilage, the key tissue affected by osteoarthritis. 2) To detail what aspects of cartilage damage best characterize osteoarthritis. 3) To consider the role of biomechanical factors in developing solutions to treat osteoarthritic joint damage. Methods: Literature sources from 1980 …

Centrosomal Kinase Nek2 Cooperates With Oncogenic Pathways To Promote Metastasis, T K. Das, Dibyendu Dana, Suneeta S. Paroly, S. K. Perumal, S. Singh, H. Jhun, J. Pendse, R. L. Cagan, T. T. Talele, Sanjai Kumar

Publications and Research

Centrosomal kinase Nek2 is overexpressed in different cancers, yet how it contributes toward tumorigenesis remains poorly understood. dNek2 overexpression in a Drosophila melanogaster model led to upregulation of Drosophila Wnt ortholog wingless (Wg), and alteration of cell migration markers—Rho1, Rac1 and E-cadherin (Ecad)—resulting in changes in cell shape and tissue morphogenesis. dNek2 overexpression cooperated with receptor tyrosine kinase and mitogen-activated protein kinase signaling to upregulate activated Akt, Diap1, Mmp1 and Wg protein to promote local invasion, distant seeding and metastasis. In tumor cell injection assays, dNek2 cooperated with Ras and Src signaling to promote aggressive colonization of tumors into different …

Infective Endocarditis In The U.S., 1998–2009: A Nationwide Study, David H. Bor, Steffie Woolhandler, Rachel Nardin, David Brusch, David U. Himmelstein

Publications and Research

Background
Previous studies based on local case series estimated the annual incidence of endocarditis in the U.S. at about 4 per 100,000 population. Small-scale studies elsewhere have reported similar incidence rates. However, no nationally-representative population-based studies have verified these estimates.

Methods and Findings
Using the 1998–2009 Nationwide Inpatient Sample, which provides diagnoses from about 8 million U.S. hospitalizations annually, we examined endocarditis hospitalizations, bacteriology, co-morbidities, outcomes and costs. Hospital admissions for endocarditis rose from 25,511 in 1998 to 38, 976 in 2009 (12.7 per 100,000 population in 2009). The age-adjusted endocarditis admission rate increased 2.4% annually. The proportion of patients …

Composition Of The Adult Digestive Tract Bacterial Microbiome Based On Seven Mouth Surfaces, Tonsils, Throat And Stool Samples, Nicola Segata, Susan Kinder Haake, Peter Mannon, Katherine P. Lemon, Levi Waldron, Dirk Gevers, Curtis Huttenhower, Jacques Izard

Publications and Research

Background: To understand the relationship between our bacterial microbiome and health, it is essential to define the microbiome in the absence of disease. The digestive tract includes diverse habitats and hosts the human body’s greatest bacterial density. We describe the bacterial community composition of ten digestive tract sites from more than 200 normal adults enrolled in the Human Microbiome Project, and metagenomically determined metabolic potentials of four representative sites.

Results: The microbiota of these diverse habitats formed four groups based on similar community compositions: buccal mucosa, keratinized gingiva, hard palate; saliva, tongue, tonsils, throat; sub- and supra-gingival plaques; and stool. …

Estimated Birth Weight And Adult Cardiovascular Risk Factors In A Developing Southern Chinese Population: A Cross Sectional Study, C. Mary Schooling, C. Q. Jiang, T. H. Lam, B. J. Cowling, S. L. Yeung, W. S. Zhang, K. K. Cheng, G. M. Leung

Publications and Research

Background: Birth weight is negatively associated with cardiovascular diseases and diabetes, but the associations are less well-established in developing populations where birth weight is often unavailable. We studied the association of birth weight and cardiovascular risk, using birth rank as an instrumental variable, in Southern China.

Methods: We used published data on birth weight by birth rank from an appropriate population and baseline data from the Guangzhou Biobank Cohort Study phases 2 & 3 (2005-8) to examine the adjusted associations, using instrumental variable analysis, of birth weight with clinically measured cardiovascular risk factors and the metabolic syndrome in older …

Myelin-Associated Glycoprotein Interacts With Neurons Via A Sialic Acid Binding Site At Arg118 And A Distinct Neurite Inhibition Site, Song Tang, Ying Jing Shen, Maria Elena Debellard, Gitali Mukhopadhyay, James L. Salzer, Paul R. Crocker, Marie T. Filbin

Publications and Research

Inhibitory components in myelin are largely responsible for the lack of regeneration in the mammalian CNS. Myelin-associated glycoprotein (MAG), a sialic acid binding protein and a component of myelin, is a potent inhibitor of neurite outgrowth from a variety of neurons both in vitro and in vivo. Here, we show that MAG’s sialic acid binding site is distinct from its neurite inhibitory activity. Alone, sialic acid–dependent binding of MAG to neurons is insufficient to effect inhibition of axonal growth. Thus, while soluble MAG-Fc (MAG extracellular domain fused to Fc), a truncated form of MAG-Fc missing Ig-domains 4 and 5, MAG(d1-3)-Fc, …