scholarly journals AutoBend: An automated approach for estimating intervertebral joint function from bone-only digital models

2021 ◽  
Author(s):  
K E Jones ◽  
R J Brocklehurst ◽  
S E Pierce
Keyword(s):  
Soft Tissues ◽  
Ex Vivo ◽  
Critical Role ◽  
Axial Skeleton ◽  
Functional Evolution ◽  
Joint Function ◽  
Joint Spacing ◽  
Center Of Rotation ◽  
Extinct Species ◽  
The Impact

Abstract Deciphering the biological function of rare or extinct species is key to understanding evolutionary patterns across the tree of life. While soft tissues are vital determinants of joint function, they are rarely available for study. Therefore, extracting functional signals from skeletons, which are more widely available via museum collections, has become a priority for the field of comparative biomechanics. While most work has focused on the limb skeleton, the axial skeleton plays a critical role in body support, respiration, and locomotion, and is therefore of central importance for understanding broad-scale functional evolution. Here, we describe and experimentally validate AutoBend, an automated approach to estimating intervertebral joint function from bony vertebral columns. AutoBend calculates osteological range of motion (oROM) by automatically manipulating digitally articulated vertebrae while incorporating multiple constraints on motion, including both bony intersection and the role of soft tissues by restricting excessive strain in both centrum and zygapophyseal articulations. Using AutoBend and biomechanical data from cadaveric experiments on cats and tegus, we validate important modeling parameters required for oROM estimation, including the degree of zygapophyseal disarticulation, and the location of the center of rotation. Based on our validation, we apply a model with the center of rotation located within the vertebral disc, no joint translation, around 50% strain permitted in both zygapophyses and discs, and a small amount of vertebral intersection permitted. Our approach successfully reconstructs magnitudes and craniocaudal patterns of motion obtained from ex vivo experiments, supporting its potential utility. It also performs better than more typical methods that rely solely on bony intersection, emphasizing the importance of accounting for soft tissues. We estimated the sensitivity of the analyses to vertebral model reconstruction by varying joint spacing, degree of overlap, and the impact of landmark placement. The effect of these factors was small relative to biological variation craniocaudally and between bending directions. Within, we also present a new approach for estimating joint stiffness directly from oROM and morphometric measurements that can successfully reconstruct the craniocaudal patterns, but not magnitudes, derived from experimental data. Together, this work represents a significant step forward for understanding vertebral function in difficult-to-study (e.g., rare or extinct) species, paving the way for a broader understanding of patterns of functional evolution in the axial skeleton.

scholarly journals Mechanical Response Changes in Porcine Tricuspid Valve Anterior Leaflet Under Osmotic-Induced Swelling

2019 ◽  
Vol 6 (3) ◽  
pp. 70 ◽  
Author(s):  
Samuel D. Salinas ◽  
Margaret M. Clark ◽  
Rouzbeh Amini
Keyword(s):  
Tricuspid Valve ◽  
Soft Tissues ◽  
Mechanical Response ◽  
Ex Vivo ◽  
Control Group ◽  
Anterior Leaflet ◽  
Buffer Solution ◽  
Tissue Samples ◽  
The Impact

Since many soft tissues function in an isotonic in-vivo environment, it is expected that physiological osmolarity will be maintained when conducting experiments on these tissues ex-vivo. In this study, we aimed to examine how not adhering to such a practice may alter the mechanical response of the tricuspid valve (TV) anterior leaflet. Tissue specimens were immersed in deionized (DI) water prior to quantification of the stress–strain responses using an in-plane biaxial mechanical testing device. Following a two-hour immersion in DI water, the tissue thickness increased an average of 107.3% in the DI water group compared to only 6.8% in the control group, in which the tissue samples were submerged in an isotonic phosphate buffered saline solution for the same period of time. Tissue strains evaluated at 85 kPa revealed a significant reduction in the radial direction, from 34.8% to 20%, following immersion in DI water. However, no significant change was observed in the control group. Our study demonstrated the impact of a hypo-osmotic environment on the mechanical response of TV anterior leaflet. The imbalance in ions leads to water absorption in the valvular tissue that can alter its mechanical response. As such, in ex-vivo experiments for which the native mechanical response of the valves is important, using an isotonic buffer solution is essential.

scholarly journals The gammaherpesvirus 68 viral cyclin facilitates expression of LANA

2021 ◽  
Vol 17 (11) ◽  
pp. e1010019
Author(s):  
Brian F. Niemeyer ◽  
Bridget Sanford ◽  
Joy E. Gibson ◽  
Jennifer N. Berger ◽  
Lauren M. Oko ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Critical Role ◽  
Productive Infection ◽  
Latent Reservoir ◽  
Cellular Distribution ◽  
Viral Cyclin ◽  
Latently Infected ◽  
Infected Cells ◽  
Gammaherpesvirus 68 ◽  
The Impact

Gammaherpesviruses establish life-long infections within their host and have been shown to be the causative agents of devastating malignancies. Chronic infection within the host is mediated through cycles of transcriptionally quiescent stages of latency with periods of reactivation into detectable lytic and productive infection. The mechanisms that regulate reactivation from latency remain poorly understood. Previously, we defined a critical role for the viral cyclin in promoting reactivation from latency. Disruption of the viral cyclin had no impact on the frequency of cells containing viral genome during latency, yet it remains unclear whether the viral cyclin influences latently infected cells in a qualitative manner. To define the impact of the viral cyclin on properties of latent infection, we utilized a viral cyclin deficient variant expressing a LANA-beta-lactamase fusion protein (LANA::βla), to enumerate both the cellular distribution and frequency of LANA gene expression. Disruption of the viral cyclin did not affect the cellular distribution of latently infected cells, but did result in a significant decrease in the frequency of cells that expressed LANA::βla across multiple tissues and in both immunocompetent and immunodeficient hosts. Strikingly, whereas the cyclin-deficient virus had a reactivation defect in bulk culture, sort purified cyclin-deficient LANA::βla expressing cells were fully capable of reactivation. These data emphasize that the γHV68 latent reservoir is comprised of at least two distinct stages of infection characterized by differential LANA expression, and that a primary function of the viral cyclin is to promote LANA expression during latency, a state associated with ex vivo reactivation competence.

Elevated level of circulatory sTLT1 induces inflammation through SYK/MEK/ERK signalling in coronary artery disease

2019 ◽  
Vol 133 (22) ◽  
pp. 2283-2299
Author(s):  
Apabrita Ayan Das ◽  
Devasmita Chakravarty ◽  
Debmalya Bhunia ◽  
Surajit Ghosh ◽  
Prakash C. Mandal ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Chronic Inflammation ◽  
Ex Vivo ◽  
Human Subjects ◽  
Critical Role ◽  
Atherosclerotic Cardiovascular Disease ◽  
Tnf Α ◽  
Artery Disease

Abstract The role of inflammation in all phases of atherosclerotic process is well established and soluble TREM-like transcript 1 (sTLT1) is reported to be associated with chronic inflammation. Yet, no information is available about the involvement of sTLT1 in atherosclerotic cardiovascular disease. Present study was undertaken to determine the pathophysiological significance of sTLT1 in atherosclerosis by employing an observational study on human subjects (n=117) followed by experiments in human macrophages and atherosclerotic apolipoprotein E (apoE)−/− mice. Plasma level of sTLT1 was found to be significantly (P<0.05) higher in clinical (2342 ± 184 pg/ml) and subclinical cases (1773 ± 118 pg/ml) than healthy controls (461 ± 57 pg/ml). Moreover, statistical analyses further indicated that sTLT1 was not only associated with common risk factors for Coronary Artery Disease (CAD) in both clinical and subclinical groups but also strongly correlated with disease severity. Ex vivo studies on macrophages showed that sTLT1 interacts with Fcɣ receptor I (FcɣRI) to activate spleen tyrosine kinase (SYK)-mediated downstream MAP kinase signalling cascade to activate nuclear factor-κ B (NF-kB). Activation of NF-kB induces secretion of tumour necrosis factor-α (TNF-α) from macrophage cells that plays pivotal role in governing the persistence of chronic inflammation. Atherosclerotic apoE−/− mice also showed high levels of sTLT1 and TNF-α in nearly occluded aortic stage indicating the contribution of sTLT1 in inflammation. Our results clearly demonstrate that sTLT1 is clinically related to the risk factors of CAD. We also showed that binding of sTLT1 with macrophage membrane receptor, FcɣR1 initiates inflammatory signals in macrophages suggesting its critical role in thrombus development and atherosclerosis.

The Laryngeal Epithelium in Reflux

2011 ◽  
Vol 21 (3) ◽  
pp. 112-117 ◽  
Author(s):  
Elizabeth Erickson-Levendoski ◽  
Mahalakshmi Sivasankar
Keyword(s):  
Laryngopharyngeal Reflux ◽  
Critical Role ◽  
Structure And Function ◽  
Laryngeal Disease ◽  
Health And Disease ◽  
And Function ◽  
The Impact

The epithelium plays a critical role in the maintenance of laryngeal health. This is evident in that laryngeal disease may result when the integrity of the epithelium is compromised by insults such as laryngopharyngeal reflux. In this article, we will review the structure and function of the laryngeal epithelium and summarize the impact of laryngopharyngeal reflux on the epithelium. Research investigating the ramifications of reflux on the epithelium has improved our understanding of laryngeal disease associated with laryngopharyngeal reflux. It further highlights the need for continued research on the laryngeal epithelium in health and disease.

The effect of surgery in tenosynovial giant cell tumours as measured by patient-reported outcomes on quality of life and joint function

2019 ◽  
Vol 101-B (3) ◽  
pp. 272-280 ◽  
Author(s):  
F. G. M. Verspoor ◽  
M. J. L. Mastboom ◽  
G. Hannink ◽  
W. T. A. van der Graaf ◽  
M. A. J. van de Sande ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Giant Cell ◽  
Diffuse Type ◽  
Joint Function ◽  
Population Means ◽  
Sf 36 ◽  
Patient Reported ◽  
The Impact

Aims The aim of this study was to evaluate health-related quality of life (HRQoL) and joint function in tenosynovial giant cell tumour (TGCT) patients before and after surgical treatment. Patients and Methods This prospective cohort study run in two Dutch referral centres assessed patient-reported outcome measures (PROMs; 36-Item Short-Form Health Survey (SF-36), visual analogue scale (VAS) for pain, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)) in 359 consecutive patients with localized- and diffuse-type TGCT of large joints. Patients with recurrent disease (n = 121) and a wait-and-see policy (n = 32) were excluded. Collected data were analyzed at specified time intervals preoperatively (baseline) and/or postoperatively up to five years. Results A total of 206 TGCT patients, 108 localized- and 98 diffuse-type, were analyzed. Median age at diagnosis of localized- and diffuse-type was 41 years (interquartile range (IQR) 29 to 49) and 37 years (IQR 27 to 47), respectively. SF-36 analyses showed statistically significant and clinically relevant deteriorated preoperative and immediate postoperative scores compared with general Dutch population means, depending on subscale and TGCT subtype. After three to six months of follow-up, these scores improved to general population means and continued to be fairly stable over the following years. VAS scores, for both subtypes, showed no statistically significant or clinically relevant differences pre- or postoperatively. In diffuse-type patients, the improvement in median WOMAC score was statistically significant and clinically relevant preoperatively versus six to 24 months postoperatively, and remained up to five years’ follow-up. Conclusion Patients with TGCT report a better HRQoL and joint function after surgery. Pain scores, which vary hugely between patients and in patients over time, did not improve. A disease-specific PROM would help to decipher the impact of TGCT on patients’ daily life and functioning in more detail. Cite this article: Bone Joint J 2019;101-B:272–280.

scholarly journals The lung–gut axis during viral respiratory infections: the impact of gut dysbiosis on secondary disease outcomes

2021 ◽  
Author(s):  
Valentin Sencio ◽  
Marina Gomes Machado ◽  
François Trottein
Keyword(s):  
Gut Microbiota ◽  
Bacterial Infections ◽  
Respiratory Infections ◽  
Critical Role ◽  
Good Health ◽  
Disease Outcomes ◽  
And Function ◽  
Viral Respiratory Infections ◽  
The Impact ◽  
Viral Respiratory

AbstractBacteria that colonize the human gastrointestinal tract are essential for good health. The gut microbiota has a critical role in pulmonary immunity and host’s defense against viral respiratory infections. The gut microbiota’s composition and function can be profoundly affected in many disease settings, including acute infections, and these changes can aggravate the severity of the disease. Here, we discuss mechanisms by which the gut microbiota arms the lung to control viral respiratory infections. We summarize the impact of viral respiratory infections on the gut microbiota and discuss the potential mechanisms leading to alterations of gut microbiota’s composition and functions. We also discuss the effects of gut microbial imbalance on disease outcomes, including gastrointestinal disorders and secondary bacterial infections. Lastly, we discuss the potential role of the lung–gut axis in coronavirus disease 2019.

scholarly journals Methionine Diet Evoked Hyperhomocysteinemia Causes Hippocampal Alterations, Metabolomics Plasma Changes and Behavioral Pattern in Wild Type Rats

2021 ◽  
Vol 22 (9) ◽  
pp. 4961
Author(s):  
Maria Kovalska ◽  
Eva Baranovicova ◽  
Dagmar Kalenska ◽  
Anna Tomascova ◽  
Marian Adamkov ◽  
...  
Keyword(s):  
Morphological Changes ◽  
Brain Area ◽  
Critical Role ◽  
Cerebrovascular Diseases ◽  
Behavioral Pattern ◽  
Cell Physiology ◽  
Male Wistar Rats ◽  
High Level ◽  
Hippocampal Alterations ◽  
The Impact

L-methionine, an essential amino acid, plays a critical role in cell physiology. High intake and/or dysregulation in methionine (Met) metabolism results in accumulation of its intermediate(s) or breakdown products in plasma, including homocysteine (Hcy). High level of Hcy in plasma, hyperhomocysteinemia (hHcy), is considered to be an independent risk factor for cerebrovascular diseases, stroke and dementias. To evoke a mild hHcy in adult male Wistar rats we used an enriched Met diet at a dose of 2 g/kg of animal weight/day in duration of 4 weeks. The study contributes to the exploration of the impact of Met enriched diet inducing mild hHcy on nervous tissue by detecting the histo-morphological, metabolomic and behavioural alterations. We found an altered plasma metabolomic profile, modified spatial and learning memory acquisition as well as remarkable histo-morphological changes such as a decrease in neurons’ vitality, alterations in the morphology of neurons in the selective vulnerable hippocampal CA 1 area of animals treated with Met enriched diet. Results of these approaches suggest that the mild hHcy alters plasma metabolome and behavioural and histo-morphological patterns in rats, likely due to the potential Met induced changes in “methylation index” of hippocampal brain area, which eventually aggravates the noxious effect of high methionine intake.

scholarly journals NLRP7 Promotes Choriocarcinoma Growth and Progression through the Establishment of an Immunosuppressive Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2999
Author(s):  
Deborah Reynaud ◽  
Roland Abi Nahed ◽  
Nicolas Lemaitre ◽  
Pierre-Adrien Bolze ◽  
Wael Traboulsi ◽  
...  
Keyword(s):  
Immune Response ◽  
Tumor Cells ◽  
Major Gene ◽  
Critical Role ◽  
Orthotopic Model ◽  
Independent Manner ◽  
Maternal Immune Response ◽  
The Impact

The inflammatory gene NLRP7 is the major gene responsible for recurrent complete hydatidiform moles (CHM), an abnormal pregnancy that can develop into gestational choriocarcinoma (CC). However, the role of NLRP7 in the development and immune tolerance of CC has not been investigated. Three approaches were employed to define the role of NLRP7 in CC development: (i) a clinical study that analyzed human placenta and sera collected from women with normal pregnancies, CHM or CC; (ii) an in vitro study that investigated the impact of NLRP7 knockdown on tumor growth and organization; and (iii) an in vivo study that used two CC mouse models, including an orthotopic model. NLRP7 and circulating inflammatory cytokines were upregulated in tumor cells and in CHM and CC. In tumor cells, NLRP7 functions in an inflammasome-independent manner and promoted their proliferation and 3D organization. Gravid mice placentas injected with CC cells invalidated for NLRP7, exhibited higher maternal immune response, developed smaller tumors, and displayed less metastases. Our data characterized the critical role of NLRP7 in CC and provided evidence of its contribution to the development of an immunosuppressive maternal microenvironment that not only downregulates the maternal immune response but also fosters the growth and progression of CC.

scholarly journals Training may enhance early childhood educators’ self-efficacy to lead physical activity in childcare

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Brianne A. Bruijns ◽  
Andrew M. Johnson ◽  
Jennifer D. Irwin ◽  
Shauna M. Burke ◽  
Molly Driediger ◽  
...  
Keyword(s):  
Physical Activity ◽  
Early Childhood ◽  
Self Efficacy ◽  
Critical Role ◽  
Early Childhood Educators ◽  
Outdoor Play ◽  
Future Research ◽  
Intervention Component ◽  
Space Extension ◽  
The Impact

Abstract Background Early childhood educators (ECEs) play a critical role in promoting physical activity (PA) among preschoolers in childcare; thus, PA-related training for ECEs is essential. The Supporting PA in the Childcare Environment (SPACE) intervention incorporated: 1. shorter, more frequent outdoor play sessions; 2. provision of portable play equipment; and, PA training for ECEs. An extension of the SPACE intervention (the SPACE-Extension) incorporated only the shorter, more frequent outdoor play periods component of the original SPACE intervention. The purpose of this study was to explore the individual impact of these interventions on ECEs’ PA-related self-efficacy and knowledge. Methods ECEs from the SPACE (n = 83) and SPACE-Extension (n = 31) were administered surveys at all intervention time-points to assess: self-efficacy to engage preschoolers in PA (n = 6 items; scale 0 to 100); self-efficacy to implement the intervention (n = 6 items); and, knowledge of preschooler-specific PA and screen-viewing guidelines (n = 2 items). A linear mixed effects model was used to analyze the impact of each intervention on ECEs’ self-efficacy and knowledge and controlled for multiple comparison bias. Results The SPACE intervention significantly impacted ECEs’ self-efficacy to engage preschoolers in PA for 180 min/day (main effect), and when outdoor playtime was not an option (interaction effect). Further, the interaction model for ECEs’ knowledge of the total PA guideline for preschoolers approached significance when compared to the main effects model. Participants within the SPACE-Extension did not demonstrate any significant changes in self-efficacy or knowledge variables. Conclusions Findings from this study highlight the benefit of ECE training in PA with regard to fostering their PA-related self-efficacy and knowledge. Future research should explore the impact of PA training for ECEs uniquely in order to determine if this intervention component, alone, can produce meaningful changes in children’s PA behaviours at childcare.

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