Mesowear Analysis of the Tapirus Pplkensis Population From the Gray Fossil Site, Tennessee, USA

Various methods exist for measuring and analyzing dental wear patterns in mam-mals, and these patterns have been extensively studied in ungulates. Mesowear has proven useful as a method to compare large numbers of individuals, particularly fossil individuals, observe trends through time or between groups, and estimate paleoenvi-ronmental conditions. Levels of attrition (tooth-on-tooth wear) and abrasion (tooth-on-food wear) can be readily compared by observing the shape of the cusp and relative crown height of the tooth. This study uses a modified method of mesowear analysis, examining actual cusp angles of the population of Tapirus polkensis from the Gray Fossil Site, a densely canopied, hickory and oak dominated forest located in Gray, Tennes-see. Crown height and cusp angle were measured for 38 specimens arranged into eruption series from young juveniles to old adults. Results found a strong correlation between eruption series and cusp angle with a steady increase in mean angle as the individuals increase in age. A strong correlation between cusp angle and crown height was also found. Overall, the population showed relatively low wear rates, as would be expected of a forest-dwelling browser. As a mesowear analysis across all age groups for a population has not been conducted before, this study could be useful for measuring relative wear rates at different life stages and could be applied across other com-munities

Are there gender differences in acute management and secondary prevention of acute coronary syndromes in Barbados? A cohort study.

OBJECTIVES: In Barbados, high case fatality rates have been reported after myocardial infarction (MI) with higher rates in women than men. To explore this inequality, we examined documented pharmacological interventions for ST-segment elevated myocardial infarction (STEMI), non-STEMI (NSTEMI) and unstable and chronic angina in women and men. DESIGN: Prospective cohort registry data for STEMI and NSTEMI and retrospective chart review for unstable and chronic angina. SETTING: Tertiary care (acute coronary syndromes) and primary care (chronic angina) centres in Barbados. PARTICIPANTS: For the years 2009-2016, a total of 1018 patients with STEMI or NSTEMI were identified via the prospective study. For unstable and chronic angina, 136 and 272 notes were reviewed respectively for the years 2010-2014. OUTCOME MEASURES: The proportions of patients prescribed recommended medication during the first 24 hours after an acute event, at discharge and for chronic care were calculated. Prescribed proportions were analysed by gender after adjustment for age. RESULTS: Between 2009 and 2016, for the acute management of patients with NSTEMI and STEMI, only two (aspirin and clopidogrel) of six drugs had documented prescription rates of 80% or more. Patients with STEMI (n=552) had higher prescription rates than NSTEMI (n=466), with gender differences being more pronounced in the former. Among patients with STEMI, after adjustment for age, diabetes, hypertension and smoking, men were more likely to receive fibrinolytics acutely, OR 2.28 (95% CI 1.24 to 4.21). Compared with men, a higher proportion of women were discharged on all recommended treatments; this was only statistically significant for beta-blockers: age-adjusted OR 1.87 (95% CI 1.16 to 3.00). There were no statistically significant differences in documented prescription of drugs for chronic angina. CONCLUSION: Following acute MI in Barbados, the proportion of patients with documented recommended treatment is relatively low. Although women were less likely to receive appropriate acute care than men, by discharge gender differences were reversed

Optic Nerve Sheath Mechanics in VIIP Syndrome

Visual Impairment and Intracranial Pressure (VIIP) syndrome results in a loss of visual function and occurs in astronauts following long-duration spaceflight. Understanding the mechanisms that lead to the ocular changes involved in VIIP is of critical importance for space medicine research. Although the exact mechanisms of VIIP are not yet known, it is hypothesized that microgravity-induced increases in intracranial pressures (ICP) drive the remodeling of the optic nerve sheath, leading to compression of the optic nerve which in turn may reduce visual acuity. Some astronauts present with a kink in the optic nerve after return to earth, suggesting that tissue remodeling in response to ICP increases may be taking place. The goal of this work is to characterize the mechanical properties of the optic nerve sheath (dura mater) to better understand its biomechanical response to increased ICP

Finite Element Modeling of the Posterior Eye in Microgravity

Microgravity experienced during spaceflight affects astronauts in various ways, including weakened muscles and loss of bone density. Recently, visual impairment and intracranial pressure (VIIP) syndrome has become a major concern for space missions lasting longer than 30 days. Astronauts suffering from VIIP syndrome have changes in ocular anatomical and visual impairment that persist after returning to earth. It is hypothesized that a cephalad fluid shift in microgravity may increase the intracranial pressure (ICP), which leads to an altered biomechanical environment of the posterior globe and optic nerve sheath (ONS).Currently, there is a lack of knowledge of how elevated ICP may lead to vision impairment and connective tissue changes in VIIP. Our goal was to develop a finite element model to simulate the acute effects of elevated ICP on the posterior eye and optic nerve sheath. We used a finite element (FE) analysis approach to understand the response of the lamina cribrosa and optic nerve to the elevations in ICP thought to occur in microgravity and to identify which tissue components have the greatest impact on strain experienced by optic nerve head tissues

Biomechanics of the Optic Nerve Sheath in VIIP Syndrome

Long-duration space flight carries the risk of developing Visual Impairment and Intracranial Pressure (VIIP) syndrome, a spectrum of ophthalmic changes including posterior globe flattening, choroidal folds, distension of the optic nerve sheath (ONS), optic nerve kinking and potentially permanent degradation of visual function. The slow onset of VIIP, its chronic nature, and certain clinical features strongly suggest that biomechanical factors acting on the ONS play a role in VIIP. Here we measure several relevant ONS properties needed to model VIIP biomechanics. The ONS (meninges) of fresh porcine eyes (n7) was reflected, the nerve proper was truncated near the sclera, and the meninges were repositioned to create a hollow cylinder of meningeal connective tissue attached to the posterior sclera. The distal end was cannulated, sealed, and pressure clamped (mimicking cerebrospinal fluid [CSF] pressure), while the eye was also cannulated for independent control of intraocular pressure (IOP). The meninges were inflated (CSF pressure cycling 7-50 mmHg) while ONS outer diameter was imaged. In another set of experiments (n4), fluid permeation rate across the meninges was recorded by observing the drainage of an elevated fluid reservoir (30 mmHg) connected to the meninges. The ONS showed behavior typical of soft tissues: viscoelasticity, with hysteresis in early preconditioning cycles and repeatable behavior after 4 cycles, and nonlinear stiffening, particularly at CSF pressures 15 mmHg (Figure). Tangent moduli measured from the loading curve were 372 101, 1199 358, and 2050 379 kPa (mean SEM) at CSF pressures of 7, 15 and 30 mmHg, respectively. Flow rate measurements through the intact meninges at 30mmHg gave a permeability of 1.34 0.46 lmincm2mmHg (mean SEM). The ONS is a tough, strain-stiffening connective tissue that is surprisingly permeable. The latter observation suggests that there could be significant CSF drainage through the ONS into the orbit, likely important for CSF transport in the optic nerve. These experimental measurements, extended to human eyes, are informing computational models of the pathophysiology and biomechanics of the ONS in VIIP syndrome

MicroRNA-135b promotes cancer progression by acting as a downstream effector of oncogenic pathways in colon cancer

MicroRNA deregulation is frequent in human colorectal cancers (CRCs), but little is known as to whether it represents a bystander event or actually drives tumor progression in vivo. We show that miR-135b overexpression is triggered in mice and humans by APC loss, PTEN/PI3K pathway deregulation, and SRC overexpression and promotes tumor transformation and progression. We show that miR-135b upregulation is common in sporadic and inflammatory bowel disease-associated human CRCs and correlates with tumor stage and poor clinical outcome. Inhibition of miR-135b in CRC mouse models reduces tumor growth by controlling genes involved in proliferation, invasion, and apoptosis. We identify miR-135b as a key downsteam effector of oncogenic pathways and a potential target for CRC treatment

VIIP: Central Nervous System (CNS) Modeling

Current long-duration missions to the International Space Station and future exploration-class missions beyond low-Earth orbit expose astronauts to increased risk of Visual Impairment and Intracranial Pressure (VIIP) syndrome. It has been hypothesized that the headward shift of cerebrospinal fluid (CSF) and blood in microgravity may cause significant elevation of intracranial pressure (ICP), which in turn may then induce VIIP syndrome through interaction with various biomechanical pathways. However, there is insufficient evidence to confirm this hypothesis. In this light, we are developing lumped-parameter models of fluid transport in the central nervous system (CNS) as a means to simulate the influence of microgravity on ICP. The CNS models will also be used in concert with the lumped parameter and finite element models of the eye described in the related IWS works submitted by Nelson et al., Feola et al. and Ethier et al

Müller glia provide essential tensile strength to the developing retina.

This is the final version of the article. It first appeared from the Rockefeller University Press via http://dx.doi.org/10.1083/jcb.201503115To investigate the cellular basis of tissue integrity in a vertebrate central nervous system (CNS) tissue, we eliminated Müller glial cells (MG) from the zebrafish retina. For well over a century, glial cells have been ascribed a mechanical role in the support of neural tissues, yet this idea has not been specifically tested in vivo. We report here that retinas devoid of MG rip apart, a defect known as retinoschisis. Using atomic force microscopy, we show that retinas without MG have decreased resistance to tensile stress and are softer than controls. Laser ablation of MG processes showed that these cells are under tension in the tissue. Thus, we propose that MG act like springs that hold the neural retina together, finally confirming an active mechanical role of glial cells in the CNS.This work was funded by a Herchel Smith Postdoctoral Fellowship to R.B.M., the Wellcome Trust programme in Developmental Biology to O.R. and J.O., NIH grants EY14358 (R.O.W.) and EY01730 (Vision Core), MRC Career Development Award and HFSP Young Investigator Grant to K.F., and a Wellcome Trust Investigator Award to W.A.H