Carrlewis7454

Purpose High demand for speech-language pathology services is reflected in long waiting lists. Waiting can be active or passive and has implications for stakeholders, including consumers, professionals, and organisations. The present study explored experiences and perspectives regarding waiting for speech-language pathology services through analysis of stakeholders' written submissions to an Australian Government Senate Inquiry.Method Written submissions (n = 337) were screened for terms related to waiting. Included submissions (n = 133) were written by organisations (36.8%), speech-language pathologists (29.3%), parents (27.8%), individuals with communication and/or swallowing difficulties (5.3%), and others.Result Inductive thematic analysis identified three themes. (1) Duration. Consistently described as long. (2) Consequences. Consumers' consequences included burden on physical health, finances, time, emotional wellbeing, and relationships, reduced continuity of care, and increased intervention needs. check details Professional consequences included stress and burnout impacting job satisfaction, and reduced effectiveness. Societal consequences included social and ethical burden, and a drain on health and legal systems. (3) Actions. Consumers advocated and sought alternatives (e.g. threats to harm their child, relocation to a capital city), professionals implemented service delivery and policy actions, and organisations lacked effective system-wide strategies.Conclusion Existing services did not appear to meet stakeholders' needs. Action is needed to improve speech-language pathology waiting lists and access to services, and minimise possible consequences for stakeholders.SIGNIFICANCE Hypoxic ischemic events due to intrapartum complications represent the second cause of neonatal mortality and initiates an acute brain disorder known as hypoxic ischemic encephalopathy (HIE). In HIE, the brain undergoes primary and secondary energy failure phases separated by a latent phase in which partial neuronal recovery is observed. A hypoxic ischemic event leads to oxygen restriction causing ATP depletion, neuronal oxidative stress and cell death. Mitochondrial dysfunction and enhanced oxidant formation in brain cells are characteristic phenomena associated with energy failure. Recent advances Mitochondrial sources of oxidants in neurons include complex I of the mitochondrial respiratory chain, as a key contributor to ONO) yields peroxynitrite, a mitochondrial and cellular toxin. Quantitation of the redox state of cytochrome c oxidase, through broadband near infrared spectroscopy, represents a promising monitoring approach to evaluate mitochondrial dysfunction in vivo in humans, in conjunction with the determination of cerebral oxygenation and their correlation with the severity of brain injury. CRITICAL ISSUES Being the energetic failure a key phenomenon in HIE connected with the severity of the encephalopathy, measurement of mitochondrial dysfunction in vivo provides an approach to assess evolution, prognosis and adequate therapies. Restoration of mitochondrial redox homeostasis constitutes a key therapeutic goal. FUTURE DIRECTIONS While hypothermia is the only current accepted therapy in clinical management to preserve mitochondrial function, other mitochondrial-targeted and/or redox-based treatments are likely to synergize to ensure further efficacy.Anucleate platelets, long viewed as merely cell fragments with a limited repertoire of rapid-acting hemostatic functions, are now recognized to have a complex and dynamic transcriptome mirroring that of many nucleated cells. The field of megakaryocyte and platelet transcriptomics has been rapidly growing, particularly with the advent of newer technologies such as next-generation RNA-sequencing. Studies interrogating the megakaryocyte and platelet transcriptome have led to a number of key insights into human health and disease. In this brief focused review, we will discuss some of the recent discoveries made through transcriptome analysis of megakaryocytes and platelets. We will also highlight the utility of integrating ribosome footprint analysis to augment discoveries. Both bulk and single-cell sequencing approaches will be reviewed, along with comparative studies between human and murine platelets under basal healthy settings and during acute systemic inflammatory diseases.OBJECTIVE The age at which arteriosclerosis begins to contribute to events is uncertain. We determined, across the adult lifespan, the extent to which arteriosclerosis-related changes in arterial function occur in those with precipitous arterial events (stroke and critical limb ischemia). Approaches and Results In 1082 black South Africans (356 with either critical limb ischemia [n=238] or stroke [n=118; 35.4% premature], and 726 age, sex, and ethnicity-matched randomly selected controls), arterial function was evaluated from applanation tonometry and velocity and diameter measurements in the outflow tract. Compared with age- and sex-matched controls, over 10-year increments in age from 20 to 60years, multivariate-adjusted (including steady-state pressures) aortic pulse wave velocity, characteristic impedance (Zc), forward wave pressures (Pf), and early systolic pulse pressure amplification were consistently altered in those with arterial events. Increases in Zc were accounted for by aortic stiffness (no differences in aortic diameter) and Pf by changes in Zc and not aortic flow or wave re-reflection. Multivariate-adjusted pulse wave velocity (7.48±0.30 versus 5.82±0.15 m/s, P less then 0.0001), Zc (P less then 0.0005), and Pf (P less then 0.0001) were higher and early systolic pulse pressure amplification lower (P less then 0.0001) in those with precipitous events than in controls. In comparison to age- and sex-matched controls, independent of risk factors, pulse wave velocity, and Zc (P less then 0.005 and less then 0.05) were more closely associated with premature events than events in older persons and Pf and early systolic pulse pressure amplification were at least as closely associated with premature events as events in older persons. CONCLUSIONS Arteriosclerosis-related changes in arterial function are consistently associated with arterial events beyond risk factors from as early as 20 years of age.OBJECTIVE Macrophages have been described in calcific aortic valve disease, but it is unclear if they promote or counteract calcification. We aimed to determine how macrophages are involved in calcification using the Notch1+/- model of calcific aortic valve disease. Approach and Results Macrophages in wild-type and Notch1+/- murine aortic valves were characterized by flow cytometry. Macrophages in Notch1+/- aortic valves had increased expression of MHCII (major histocompatibility complex II). We then used bone marrow transplants to test if differences in Notch1+/- macrophages drive disease. Notch1+/- mice had increased valve thickness, macrophage infiltration, and proinflammatory macrophage maturation regardless of transplanted bone marrow genotype. In vitro approaches confirm that Notch1+/- aortic valve cells promote macrophage invasion as quantified by migration index and proinflammatory phenotypes as quantified by Ly6C and CCR2 positivity independent of macrophage genotype. Finally, we found that macrophage interaction with aortic valve cells promotes osteogenic, but not dystrophic, calcification and decreases abundance of the STAT3β isoform. CONCLUSIONS This study reveals that Notch1+/- aortic valve disease involves increased macrophage recruitment and maturation driven by altered aortic valve cell secretion, and that increased macrophage recruitment promotes osteogenic calcification and alters STAT3 (signal transducer and activator of transcription 3) splicing. Further investigation of STAT3 and macrophage-driven inflammation as therapeutic targets in calcific aortic valve disease is warranted.OBJECTIVE Galectin-3 (formerly known as Mac-2), encoded by the LGALS3 gene, is proposed to regulate macrophage adhesion, chemotaxis, and apoptosis. We investigated the role of galectin-3 in determining the inflammatory profile of macrophages and composition of atherosclerotic plaques. Approach and Results We observed increased accumulation of galectin-3-negative macrophages within advanced human, rabbit, and mouse plaques compared with early lesions. Interestingly, statin treatment reduced galectin-3-negative macrophage accrual in advanced plaques within hypercholesterolemic (apolipoprotein E deficient) Apoe-/- mice. Accordingly, compared with Lgals3+/+Apoe-/- mice, Lgals3-/-Apoe-/- mice displayed altered plaque composition through increased macrophagesmooth muscle cell ratio, reduced collagen content, and increased necrotic core area, characteristics of advanced plaques in humans. Additionally, macrophages from Lgals3-/- mice exhibited increased invasive capacity in vitro and in vivo. Furthermore, loss of galectin-3 in vitro and in vivo was associated with increased expression of proinflammatory genes including MMP (matrix metalloproteinase)-12, CCL2 (chemokine [C-C motif] ligand 2), PTGS2 (prostaglandin-endoperoxide synthase 2), and IL (interleukin)-6, alongside reduced TGF (transforming growth factor)-β1 expression and consequent SMAD signaling. Moreover, we found that MMP12 cleaves macrophage cell-surface galectin-3 resulting in the appearance of a 22-kDa fragment, whereas plasma levels of galectin-3 were reduced in Mmp12-/-Apoe-/- mice, highlighting a novel mechanism where MMP12-dependent cleavage of galectin-3 promotes proinflammatory macrophage polarization. Moreover, galectin-3-positive macrophages were more abundant within plaques of Mmp12-/-Apoe-/- mice compared with Mmp12+/+Apoe-/- animals. CONCLUSIONS This study reveals a prominent protective role for galectin-3 in regulating macrophage polarization and invasive capacity and, therefore, delaying plaque progression.Prostanoids are a group of bioactive lipids that are synthesized de novo from membrane phospholipid-released arachidonic acid and have diverse functions in normal physiology and disease. NSAIDs, which are among the most commonly used medications, ameliorate pain, fever, and inflammation by inhibiting COX (cyclooxygenase), which is the rate-limiting enzyme in the biosynthetic cascade of prostanoids. The use of NSAIDs selective for COX-2 inhibition increases the risk of a thrombotic event (eg, myocardial infarction and stroke). All NSAIDs are associated with an increased risk of heart failure. Substantial variation in clinical responses to aspirin exists and is associated with cardiovascular risk. Limited clinical studies suggest the involvement of prostanoids in vascular restenosis in patients who received angioplasty intervention. mPGES (microsomal PG [prostaglandin] E2 synthase)-1, an alternative target downstream of COX, has the potential to be therapeutically targeted for inflammatory disease, with diminished thrombotic risk relative to selective COX-2 inhibitors. mPGES-1-derived PGE2 critically regulates microcirculation via its receptor EP (receptor for prostanoid E) 4. This review summarizes the actions and associated mechanisms for modulating the biosynthesis of prostanoids in thrombosis, vascular remodeling, and ischemic heart disease as well as their therapeutic relevance.