Postural effects on spontaneous retinal venous pulsations in healthy individuals

© 2019 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd Purpose: To assess amplitudes of spontaneous retinal venous pulsations (SVP) in three various postures (sitting, supine and lateral decubitus) in healthy individuals. Methods: Thirty participants (28 ± 8 years, 25 females) were included in the study. Intraocular pressure (IOP), blood pressure (BP) and SVP's were measured at three different postures using a calibrated Tono-Pen applanation tonometer, a digital sphygmomanometer, and a custom-built handheld video ophthalmoscope, respectively. Retinal venous pulsations (SVP) amplitudes were extracted from the retinal videos using a custom written MATLAB algorithm. Mean arterial pressure (MAP = (systolic + 2diastolic)/3) and mean ocular perfusion pressure (MOPP = (2/3 MAP)-IOP) were also calculated at each posture. A one-way ANOVA was applied to each parameter to determine any significant difference for the various postural changes. Results: Mean IOP increased (p < 0.0001) and mean SVP decreased (p < 0.0001) from sitting to supine. The mean IOP (mmHg) and SVP (MU; measuring units) in sitting, supine and lateral decubitus were 16.2 ± 2, 19.4 ± 4, 19.8 ± 2 mmHg and 5.8 ± 2, 4.5 ± 2, and 4.7 ± 2 MU, respectively. Mean arterial pressure (MAP) and MOPP also decreased significantly from sitting to supine (p < 0.001, p < 0.001) and sitting to lateral decubitus (p < 0.05, p < 0.01). There were no significant differences between IOP, SVP, MAP or MOPP during a postural modification from supine to lateral decubitus. Conclusions: In this study, we showed a significant reduction in SVP amplitudes and a significant increase in IOP from sitting to supine position in a healthy young cohort. This supports the rationale to further study such phenomenon in ocular conditions such as glaucoma to determine whether relative SVP change, for a similar postural change, can reveal early signs of vascular dysfunction

Double-Change Circular Covering Designs: Constructions And Applications

A double-change circular covering design (dcccd) is an ordered set of blocks with block size k is an ordered collection of b block, B={B1,...,Bb}, each an unordered subset of k distinct elements from [v], which obey: (1) each block differs from the previous block by two elements, as does the last from the first, and, (2) every unordered pair of [v] appears in at least one block. The first object is to minimize b for a fixed v when k=3 and arrange them in a circular manner. And the second object is to determine whether the covering designs are economical or tight

Congenital Toxoplasmosis with Aplastic Anemia: A Rare Association

Congenital toxoplasmosis is caused by transmission of an intracellular obligate coccidian protozoan (Toxoplasma gondii) via vertical transmission during pregnancy. The clinical manifestations are wide ranging from asymptomatic to intracranial calcifications, seizures, developmental delay, chorioretinal lesions and even fetal death. Aplastic anemia is one of the rare presentations of congenital toxoplasmosis. Hence, we are reporting a case of a 23-year-old male who presented to us with aplastic anemia due to congenital toxoplasmosis. Thus, congenital toxoplasmosis should always be considered as a cause when evaluating a case of aplastic anemia

Role of slip and twinning on the forming behaviour of AZ31 magnesium sheet in bending and roll forming

This study answered how magnesium sheet alloy behave during bending and roll forming process. It highlighted the springback and slip and twinning behavior. The finding pointed to support roll formability of magnesium alloys in the automotive industry.<br /

Extracellular vesicles secreted by Saccharomyces cerevisiae are involved in cell wall remodelling

Extracellular vesicles (EVs) are membranous vesicles that are released by cells. In this study, the role of the Endosomal Sorting Complex Required for Transport (ESCRT) machinery in the biogenesis of yeast EVs was examined. Knockout of components of the ESCRT machinery altered the morphology and size of EVs as well as decreased the abundance of EVs. In contrast, strains with deletions in cell wall biosynthesis genes, produced more EVs than wildtype. Proteomic analysis highlighted the depletion of ESCRT components and enrichment of cell wall remodelling enzymes, glucan synthase subunit Fks1 and chitin synthase Chs3, in yeast EVs. Interestingly, EVs containing Fks1 and Chs3 rescued the yeast cells from antifungal molecules. However, EVs from fks1∆ or chs3∆ or the vps23∆chs3∆ double knockout strain were unable to rescue the yeast cells as compared to vps23∆ EVs. Overall, we have identified a potential role for yeast EVs in cell wall remodelling.Kening Zhao, Mark Bleackley, David Chisanga, Lahiru Gangoda, Pamali Fonseka, Michael Liem, Hina Kalra, Haidar Al Saffar, Shivakumar Keerthikumar, Ching-Seng Ang, Christopher G. Adda, Lanzhou Jiang, Kuok Yap, Ivan K. Poon, Peter Lock, Vincent Bulone, Marilyn Anderson, Suresh Mathivana

Hypertension and increased endothelial mechanical stretch promote monocyte differentiation and activation: roles of STAT3, interleukin 6 and hydrogen peroxide

Aims: Monocytes play an important role in hypertension. Circulating monocytes in humans exist as classical, intermediate and non-classical forms. Monocyte differentiation can be influenced by the endothelium, which in turn is activated in hypertension by mechanical stretch. We sought to examine the role of increased endothelial stretch and hypertension on monocyte phenotype and function. Methods and Results: Human monocytes were cultured with confluent human aortic endothelial cells undergoing either 5% or 10% cyclical stretch. We also characterized circulating monocytes in normotensive and hypertensive humans. In addition, we quantified accumulation of activated monocytes and monocyte-derived cells in aortas and kidneys of mice with Angiotensin II-induced hypertension. Increased endothelial stretch enhanced monocyte conversion to CD14++CD16+ intermediate monocytes and monocytes bearing the CD209 marker and markedly stimulated monocyte mRNA expression of interleukin (IL)-6, IL-1β, IL-23, chemokine (C-C motif) ligand 4 and tumor necrosis factor α. STAT3 in monocytes was activated by increased endothelial stretch. Inhibition of STAT3, neutralization of IL-6 and scavenging of hydrogen peroxide prevented formation of intermediate monocytes in response to increased endothelial stretch. We also found evidence that nitric oxide inhibits formation of intermediate monocytes and STAT3 activation. In vivo studies demonstrated that humans with hypertension have increased intermediate and non-classical monocytes and that intermediate monocytes demonstrate evidence of STAT3 activation. Mice with experimental hypertension exhibit increased aortic and renal infiltration of monocytes, dendritic cells and macrophages with activated STAT3. Conclusions: These findings provide insight into how monocytes are activated by the vascular endothelium during hypertension. This is likely in part due to a loss of nitric oxide signaling and increased release of IL-6 and hydrogen peroxide by the dysfunctional endothelium and a parallel increase in STAT activation in adjacent monocytes. Interventions to enhance bioavailable nitric oxide, reduce IL-6 or hydrogen peroxide production or to inhibit STAT3 may have anti-inflammatory roles in hypertension and related conditions

Oral administration of bovine milk-derived extracellular vesicles induces senescence in the primary tumor but accelerates cancer metastasis

The concept that extracellular vesicles (EVs) from the diet can be absorbed by the intestinal tract of the consuming organism, be bioavailable in various organs, and in-turn exert phenotypic changes is highly debatable. Here, we isolate EVs from both raw and commercial bovine milk and characterize them by electron microscopy, nanoparticle tracking analysis, western blotting, quantitative proteomics and small RNA sequencing analysis. Orally administered bovine milk-derived EVs survive the harsh degrading conditions of the gut, in mice, and is subsequently detected in multiple organs. Milk-derived EVs orally administered to mice implanted with colorectal and breast cancer cells reduce the primary tumor burden. Intriguingly, despite the reduction in primary tumor growth, milk-derived EVs accelerate metastasis in breast and pancreatic cancer mouse models. Proteomic and biochemical analysis reveal the induction of senescence and epithelial-to-mesenchymal transition in cancer cells upon treatment with milk-derived EVs. Timing of EV administration is critical as oral administration after resection of the primary tumor reverses the pro-metastatic effects of milk-derived EVs in breast cancer models. Taken together, our study provides context-based and opposing roles of milk-derived EVs as metastasis inducers and suppressors

High blood pressure and cyclic stretch after cerebral amyloid deposition and endothelial function

Theoretical thesis.Bibliography: leaves 50-61.1. Introduction -- 2. Material and methods -- 3. Results -- 4. Discussion -- 5. Summary and conclusions.Background: Amyloid β (Aβ) deposition is a hallmark of Alzheimer’s disease (AD). Increased pulsatility, endothelial dysfunction (ED) and inflammation, indicators of vascular stiffness, are associated with AD. Additionally, vascular stiffness is linked to hypertension, a risk factor for AD. Aim: This study aimed to determine effects of high blood pressure (BP) on cerebral Aβ deposition in rodent models, spontaneously hypertensive (SHR) and normotensive Wistar Kyoto rats (WKY) and investigate effects of cyclic stretch (CS) on expression of amyloid precursor protein (APP), endothelial nitric oxide synthase (eNOS) and intercellular cell adhesion molecule-1 (ICAM-1) in human cerebral microvascular endothelial cells (hCMEC). Methods: Hippocampal (HC) and frontal cortex (FC) regions of SHR and WKY rats were analysed using western blotting to determine effect of BP on cerebral Aβ deposition. hCMEC were subjected to 5%, 10% or 20 % CS compared to control (0% CS) to evaluate pulsatility, ED and inflammation using western blotting and/or RTqPCR. Results: Aβ oligomerisation increased in SHR compared to WKY in HC (P<0.01) and FC (P<0.001). APP mRNA expression increased at 5%, decreased at 20% CS; eNOS decreased at both (P<0.0001). APP and ICAM-1 protein expression dose-dependently increased at 5% and 10% CS (P<0.01) and decreased at 20% CS. eNOS protein levels decreased at all CS (P<0.0001). Conclusions: Results suggest that high BP and CS respectively alter the processing and expression of cerebral APP. Prolonged CS may induce ED by increasing ICAM-1, thereby mitigating eNOS expression. Findings mechanistically support the association of elevated pulsatility and arterial stiffness with AD.Mode of access: World wide web1 online resource (xi, 61 leaves illustrations (some colour

AI digitalization and automation of the apparel industry and the human workforce skills

Cobb, KellyArtificial Intelligence (AI) digitalization and automation are transforming industries such as automotive, pharmaceutical and electronics at a blurring speed. As the technological pace of change in the apparel industry gains momentum, organizations across the apparel industry are facing a rapidly changing context for skills training and the development of the workforce. ☐ The purpose of this research was to explore the impacts of AI digitalization and automation in regards to apparel industry processes, through objectives seeking to better understand how the transition to AI is affecting skill competencies required for the human workforce. As well, this research aimed to vision how to train the workforce and with what methods to train the workforce, in an effort to best prepare (both workers and businesses) for Industrial shift to AI and automation. The study adopted a qualitative approach, conducting semi-structured interviews with 21 participants from 5 different countries (USA, Sri Lanka, China, India, Hong Kong). ☐ The study explored six research questions. While the results of this study were very comprehensive, the findings related to future apparel job functions will be highlighted. It was found that intellectual, innovative, and creative jobs will have a significant demand in the future of AI and automation. Results also showed that hard-skills (technical and digital skills) priority in skill-training of apparel employees, requiring a shift of focus from soft-skill training (management and behavioral skills). Findings from this study reveal significant collaborative opportunities between industry and academia, identifying and forecasting future skills requirements of the apparel workforce, and developing learning platforms to train employees on future skill needs. As well, findings suggest that sustainable and ethical practices are critical within the emerging technology space, implementation of ethics regarding technology and sustainability as well as policies of accountability will be critical for the future of the apparel industry.University of Delaware, Department of Fashion and Apparel StudiesM.S

Cyclic stretch of brain microvascular endothelial cells and regulation of amyloid processing and expression: evidence for contribution of vascular pulsatility in Alzheimer's disease

Thesis by publication.Bibliography: pages 222-238.1. Introduction -- 2. Literature review -- 3. Optimisation of mechanical stretch of endothelial cells for protein and RNA quantification -- 4. Cyclic stretch as a novel modulator of APP and associated inflammatory markers in human cerebral endothelial cells -- 5. Signalling pathways that mediate cerebral endothelial responses to cyclic stretch -- 6. Effect of endothelial cell passaging and cyclic stretch on APP expression, amyloid secretion, and NO signalling -- 7. Effect of cyclic stretch in cerebral endothelial cells pre-exposed to Aβ -- 8. Efflect of cyclic stretch and glycosphingolipid inhibition on cerebral endothelial cells -- 9. A preliminary study of the effect of a high salt diet on APP processing, eNOS signalling and aortic stiffness -- 10. Conclusions, limitations and future directions -- Appendices.Alzheimer's disease (AD) is characterised by amyloid-β (Aβ) plaques arising from amyloid precursor protein (APP) processed by β secretase-1 (BACE-1). Increasing evidence suggests a role of vascular factors in AD, namely hypertension, elevated pulse pressure and arterial stiffness, all associated with increased vascular pulsatility imposing mechanical stretch on the endothelium. This thesis addresses the role of cyclic stretch on human cerebral microvascular endothelial cells (HCMECs) in expression and processing of APP. It also investigates effect of high salt diet on APP processing in rat brains, given associations of high salt diet and cognitive impairment. In vitro studies involved cultured HCMECs subjected to 0%, 5%, 10% or 15% stretch (18 hours, 1 Hz) and analysis of protein and RNA expression, nitric oxide and Aβ levels. In vivo study included treatment of rats with high (8% NaCl, HS) or a low (0.26% NaCl, control) for 10-13 weeks and examination of brain tissue. Established for the first time was that APP expression and Aβ secretion are altered in response to HCMECs stretch, and that this response is differentially mediated in early and late passage HCMECs. In late passage HCMECs, APP and BACE-1 expression increased 2-3-fold with 10 and 15% stretch compared to 0%, with proportional increases in Aβ42/Aβ40 with % stretch (R2=0.21). In early passage HCMECs stretched at 15%, APP expression, BACE-1, Aβ42 levels were decreased 2-3-fold compared to late passage HCMECs. Glycosphingolipid inhibition prior to cyclic stretching at 15% increased APP expression and Aβ42 secretion 1-fold. In vivo findings provide preliminary evidence of altered APP processing in HS rats compared to controls parallel with increases in markers of arterial stiffness. Overall results suggest a role of arterial stiffness and vascular pulsatility strengthening the evidence of vascular contributions to AD. Future studies identifying associated molecular mechanisms will provide novel therapeutic targets for AD.1 online resource (xx, 238 pages : illustrations