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Many older LGBT+ people have experienced a lifetime of discrimination, which can exacerbate mental and physical health issues. [ABSTRACT FROM AUTHOR]

Our work at the intersection of language and the arts has led us to fundamental critiques of both language and understanding, which we outline here as possible starting points for the future development of this domain of research. In Bradley & Atkinson's arts-based research with linguistic landscapes ([11]), "language", as encountered visually in public spaces, is decentred, as participants explore their own sensory engagements in these everyday spaces through the arts. IV Conclusions We have considered the two domains of language education and the arts, the possibilities and impossibilities in research and practice at the margins, or I entre mundos i ([29], p. xxi), and the value of decentring (see also [40]). Keywords: creativity; engagement; intercultural communication; language education; the arts EN creativity engagement intercultural communication language education the arts 359 367 9 03/02/23 20230301 NES 230301 I Opening comments We thank the editors for inviting us to make this final comment on the special issue, which represents an important opening-up of the language education field to consider, and make more prominent, the links between language and intercultural education, the arts and social engagement. [Extracted from the article]

Ever-increasing stresses placed on emergency departments (EDs) can make it hard for nurses to dedicate the time and attention to each patient that they might want – especially when winter pressures kick in. [ABSTRACT FROM AUTHOR]

Many inpatients in mental health settings will have a period during their admission. However, experts say there is a lack of training, understanding and recognition about the importance of upholding period dignity for these patients. [ABSTRACT FROM AUTHOR]

When communicating information to patients, the words you choose can be as important as the message itself. A nurse's choices of language can affect how patients view their health. [ABSTRACT FROM AUTHOR]

This article reports on part of an ethnographic research project undertaken over a period of 20 months in Leeds, UK, with a youth spoken word (YSW) poetry organisation. The research focused on the fluid practices in which the youth engage that span spoken, written, visual, gestural, digital, musical and spatial modes, and across times and places. Given its inherent fluidities, YSW is a particularly interesting practice for studying semiosis. Among other aspects, the research focused on the trajectories of poems written and performed by youth and the semiotic transformations they undergo across time and space. The article explores how resemiotisation sheds light on the complexities of the transformations that one particular poem undergoes as it travels. It focuses on a poem titled 'To Him', written and performed by a 17-year old poet. The main arguments put forward are that: (1) translanguaging is a more comprehensive term than others for describing how the poet engages her communicative repertoire; (2) resemiotisation is both a lens for conceptualising translanguaging, and an indispensable analytical process in the case of the data studied for understanding the complexities of the poet's meaning-making practices. Looking beyond our own discipline and making use of musical annotation, we contend that focusing solely on spoken and written language would be insufficient to gauge the complexity of the meaning-making process undertaken by the young poet. [ABSTRACT FROM AUTHOR]

Cardiac fibroblasts are critical mediators of fibrotic remodeling in the failing heart and transform into myofibroblasts in the presence of profibrotic factors such as transforming growth factor-β. Myocardial fibrosis worsens cardiac function, accelerating the progression to decompensated heart failure (HF). We investigated the effects of a novel inhibitor (NM922; NovoMedix, San Diego, CA) of the conversion of normal fibroblasts to the myofibroblast phenotype in the setting of pressure overload-induced HF. NM922 inhibited fibroblast-to-myofi- broblast transformation in vitro via a reduction of activation of the focal adhesion kinase-Akt-p70S6 kinase and STAT3/4E-binding protein 1 pathways as well as via induction of cyclooxygenase-2. NM922 preserved left ventricular ejection fraction (P < 0.05 vs. vehicle) and significantly attenuated transverse aortic constriction-induced LV dilation and hypertrophy (P < 0.05 compared with vehicle). NM922 significantly (P < 0.05) inhibited fibroblast activation, as evidenced by reduced myofibroblast counts per square millimeter of tissue area. Picrosirius red staining demonstrated that NM922 reduced (P < 0.05) interstitial fibrosis compared with mice that received vehicle. Similarly, NM922 hearts had lower mRNA levels (P < 0.05) of collagen types I and III, lysyl oxidase, and TNF-α at 16 wk after transverse aortic constriction. Treatment with NM922 after the onset of cardiac hypertrophy and HF resulted in attenuated myocardial collagen formation and adverse remodeling with preservation of left ventricular ejection fraction. Future studies are aimed at further elucidation of the molecular and cellular mechanisms by which this novel antifibrotic agent protects the failing heart. [ABSTRACT FROM AUTHOR]

Oxidative stress results in mtDNA damage and contributes to myocardial cell death. mtDNA repair enzymes are crucial for mtDNA repair and cell survival. We investigated a novel, mitochondria-targeted fusion protein (Exscien1- III) containing endonuclease III in myocardial ischemia-reperfusion injury and transverse aortic constriction (TAC)-induced heart failure. Male C57/BL6J mice (10-12 wk) were subjected to 45 min of myocardial ischemia and either 24 h or 4 wk of reperfusion. Exscien1- III (4 mg/kg ip) or vehicle was administered at the time of reperfusion. Male C57/BL6J mice were subjected to TAC, and Exscien1-III (4 mg/kg i.p) or vehicle was administered daily starting at 3 wk post- TAC and continued for 12 wk. Echocardiography was performed to assess left ventricular (LV) structure and function. Exscien1-III reduced myocardial infarct size (P < 0.01) at 24 h of reperfusion and preserved LV ejection fraction at 4 wk postmyocardial ischemia. Exscien1-III attenuated TAC-induced LV dilation and dysfunction at 6-12 wk post-TAC (P < 0.05). Exscien1-III reduced (P < 0.05) cardiac hypertrophy and maladaptive remodeling after TAC. Assessment of cardiac mitochondria showed that Exscien1-III localized to mitochondria and increased mitochondrial antioxidant and reduced apoptotic markers. In conclusion, our results indicate that administration of Exscien1-III provides significant protection against myocardial ischemia and preserves myocardial structure and LV performance in the setting of heart failure. [ABSTRACT FROM AUTHOR]

For centuries, garlic has been shown to exert substantial medicinal effects and is considered to be one of the best disease-preventative foods. Diet is important in the maintenance of health and prevention of many diseases including cardiovascular disease (CVD). Preclinical and clinical evidence has shown that garlic reduces risks associated with CVD by lowering cholesterol, inhibiting platelet aggregation, and lowering blood pressure. In recent years, emerging evidence has shown that hydrogen sulfide (H2S) has cardioprotective and cytoprotective properties. The active metabolite in garlic, allicin, is readily degraded into organic diallyl polysulfides that are potent H2S donors in the presence of thiols. Preclinical studies have shown that enhancement of endogenous H2S has an impact on vascular reactivity. In CVD models, the administration of H2S prevents myocardial injury and dysfunction. It is hypothesized that these beneficial effects of garlic may be mediated by H2S-dependent mechanisms. This review evaluates the current knowledge concerning the cardioprotective effects of garlic-derived diallyl polysulfides. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) reduces endothelial nitric oxide (NO) bioavailability and exacerbates vascular dysfunction in patients with preexisting vascular diseases. Nitrite, a storage form of NO, can mediate vascular function during pathological conditions when endogenous NO is reduced. The aims of the present study were to characterize the effects of severe MetS and obesity on dyslipidemia, myocardial oxidative stress, and endothelial NO synthase (eNOS) regulation in the obese Ossabaw swine (OS) model and to examine the effects of a novel, sustained-release formulation of sodium nitrite (SR-nitrite) on coronary vascular reactivity and myocardial redox status in obese OS subjected to critical limb ischemia (CLI). After 6 mo of an atherogenic diet, obese OS displayed a MetS phenotype. Obese OS had decreased eNOS functionality and NO bioavailability. In addition, obese OS exhibited increased oxidative stress and a significant reduction in antioxidant enzymes. The efficacy of SR-nitrite therapy was examined in obese OS subjected to CLI. After 3 wk of treatment, SR-nitrite (80 mg·kg-1·day-1 bid po) increased myocardial nitrite levels and eNOS function. Treatment with SR-nitrite reduced myocardial oxidative stress while increasing myocardial antioxidant capacity. Ex vivo assessment of vascular reactivity of left anterior descending coronary artery segments demonstrated marked improvement in vasoreactivity to sodium nitroprusside but not to substance P and bradykinin in SR-nitrite-treated animals compared with placebo-treated animals. In conclusion, in a clinically relevant, large-animal model of MetS and CLI, treatment with SR-nitrite enhanced myocardial NO bioavailability, attenuated oxidative stress, and improved ex vivo coronary artery vasorelaxation. [ABSTRACT FROM AUTHOR]

Nitrite is a storage reservoir of nitric oxide that is readily reduced to nitric oxide under pathological conditions. Previous studies have demonstrated that nitrite levels are significantly reduced in cardiovascular disease states, including peripheral vascular disease. We investigated the cytoprotective and proangiogenic actions of a novel, sustained-release formulation of nitrite (SR-nitrite) in a clinically relevant in vivo swine model of critical limb ischemia (CLI) involving central obesity and metabolic syndrome. CLI was induced in obese Ossabaw swine (n = 18) by unilateral external iliac artery deployment of a full crosssectional vessel occlusion device positioned within an endovascular expanded polytetrafluoroethylene-lined nitinol stent-graft. At post- CLI day 14, pigs were randomized to placebo (n = 9) or SR-nitrite (80 mg, n= 9) twice daily by mouth for 21 days. SR-nitrite therapy increased nitrite, nitrate, and S-nitrosothiol in plasma and ischemic skeletal muscle. Oxidative stress was reduced in ischemic limb tissue of SR-nitrite- compared with placebo-treated pigs. Ischemic limb tissue levels of proangiogenic growth factors were increased following SR-nitrite therapy compared with placebo. Despite the increases in cytoprotective and angiogenic signals with SR-nitrite therapy, new arterial vessel formation and enhancement of blood flow to the ischemic limb were not different from placebo. Our data clearly demonstrate cytoprotective and proangiogenic signaling in ischemic tissues following SR-nitrite therapy in a very severe model of CLI. Further studies evaluating longer-duration nitrite therapy and/or additional nitrite dosing strategies are warranted to more fully evaluate the therapeutic potential of nitrite therapy in peripheral vascular disease. [ABSTRACT FROM AUTHOR]

In today's society, numerous situations arise in which sleep deprivation is a common occurrence. Subjective perceptions are a vital component to understanding the effects of sustained performance during sleep deprivation, as they may be the first indication of the effects of sustained performance or sleep deprivation on the individual. Using the theoretical framework of the Controlled Attention Model, this study examined the effects of 16 h of sustained performance under 28 h of acute sleep deprivation on perceived effort, motivation, and stress of 24 participants while completing a complex cognitive and a simple vigilance task. Perceived effort increased for both tasks, with higher effort reported on the cognitive than the vigilance task at the beginning of the experimental period, but with higher effort reported on the vigilance than the cognitive task at the end. Subjective motivation decreased for both tasks, with significantly higher levels of motivation on the cognitive than the vigilance task. Perceived stress did not change for either task. Results suggest that functioning under sustained performance and sleep-deprivation conditions affects subjective perceptions differently for cognitive versus vigilance tasks. The controlled attention model offers one means of understanding how different tasks could affect a person's subjective perceptions and ability to perform, in that different levels of controlled attention are required for the two tasks. (Author correspondence: ) [ABSTRACT FROM AUTHOR]

It was a keynote presentation by Professor Keri Facer at the United Kingdom Literacy Association (UKLA) international conference and subsequent article in Literacy that sparked the discussions which inspired the focus of this special issue. In July 2021, with a mix of end of term exhaustion and intellectual exhilaration, we gathered online to interview Keri and do that important activity we rarely manage to achieve in our performative academic culture, that is, to talk and think together. We wanted to share this process with you, and so we present our questions and Keri's responses with minimal editing and with the 'epistemic hope'1 we felt in that moment and want to share. [ABSTRACT FROM AUTHOR]

The article offers information regarding submission of contributions from researchers on themes such as literacy.

Mitoxantrone (MXT) is an androstenedione that is used to treat cancers and progressive forms of multiple sclerosis; however, its use is limited by its cardiotoxicity. Pituitary adenylate cyclase activating polypeptide (PACAP) is a member of the secretin/growth hormone-releasing hormone/vasoactive intestinal peptide family and has many functions, including cytoprotection and immunosuppression. We tested the hypothesis that PACAP can protect against MXT-induced cardiotoxicity in mice. Female BALB/c mice were treated once weekly for 4 weeks with saline (n = 14) or MXT (3 mg/kg, i.p.; n = 14). Half of the mice in each group received PACAP (10 μg, i.p.) 1 h before and 24 and 48 h after MXT, while the remaining mice received injections of saline on the same schedule. Echocardiography was used to assess cardiac structure and function. In mice treated with MXT and saline, body weight was significantly reduced after the third dose of MXT. PACAP significantly attenuated the reduction in body weight; however, the weights did not return to control level. Compared to controls, MXT-treated mice had significantly increased left ventricular (LV) diameter and LV volume and decreased LV posterior wall thickness. Fractional shortening (FS) and ejection fraction (EF) were also significantly decreased. Treatment with PACAP prevented MXT-induced LV dilation and significantly attenuated the reductions in FS and EF, although FS and EF did not return to control level. PACAP38 did not prevent MXT-induced decreases in LV posterior wall thickness. MXT dose-dependently decreased the viability of cultured U937 (human leukemia) cells; PACAP did not protect cultured U937 cells from MXT-mediated cell death. In conclusion, PACAP can attenuate MXT-mediated LV dilation and dysfunction in mice. [ABSTRACT FROM AUTHOR]

A key feature of heart failure is adverse extracellular matrix (ECM) remodeling, which is associated with increases in the collagen cross-linking enzyme, lysyl oxidase (LOX). In this study, we assess the progression of cardiovascular remodeling from the compensatory to decompensatory phase, with a focus on the change in LOX expression and activity as it relates to alterations in ECM composition and changes in cardiac function. Adult male Sprague-Dawley rats were studied after 4, 14, or 21 weeks of aortocaval fistula-induced volume overload (VO). Progressive increases in the left and right ventricular mass indicated biventricular hypertrophy. Echocardiography revealed significant increases in the posterior wall thickness and internal diameter of the left ventricle as early as 3 weeks, which persisted until the 21 week endpoint. There were also significant decreases in eccentric index and fractional shortening in VO animals. Hemodynamic measurements showed progressive decreases in contractility, indicative of systolic dysfunction. There were progressive VO-induced increases in LOX expression and activity, collagen, and collagen cross-linking during the course of these experiments. We observed a negative correlation between LOX activity and cardiac function. Additional rats were treated with an inhibitor of LOX activity starting at 2 weeks post-surgery and continued to 14 weeks. LOX inhibition prevented the cardiac dysfunction and collagen accumulation caused by VO. Overall these data suggest a detrimental role for the chronic increase of cardiac LOX expression and activity in the transition from compensated remodeling to decompensated failure. [ABSTRACT FROM AUTHOR]

An editorial is presented on exploring the role of literacy educators in helping children making sense of the turbulent, anxious, and changing times. Topics include children creating and sharing the multimodal, multilingual stories, and developing new digital literacy practices; foregrounded in critical engagement with voice in research with children and young people; and engaging in and with storytelling in addition to activism.

Previous studies have demonstrated that hydrogen sulfide (H2S) protects against multiple cardiovascular disease states in a similar manner as nitric oxide (NO). H2S therapy also has been shown to augment NO bioavailability and signaling. The purpose of this study was to investigate the impact of H2S deficiency on endothelial NO synthase (eNOS) function, NO production, and ischemia/reperfusion (I/R) injury. We found that mice lacking the H2S-producing enzyme cystathionine γ-lyase (CSE) exhibit elevated oxidative stress, dysfunctional eNOS, diminished NO levels, and exacerbated myocardial and hepatic I/R injury. In CSE KO mice, acute H2S therapy restored eNOS function and NO bioavailability and attenuated I/R injury. In addition, we found that H2S therapy fails to protect against I/R in eNOS phosphomutant mice (S1179A). Our results suggest that H2S-mediated cytoprotective signaling in the setting of I/R injury is dependent in large part on eNOS activation and NO generation. [ABSTRACT FROM AUTHOR]

We have previously reported gender differences in ventricular remodeling and development of heart failure using the aortocaval fistula model of chronic volume overload in rats. In contrast to males, female rats exhibited no adverse ventricular remodeling and less mortality in response to volume overload. This gender-specific cardioprotection was lost following ovariectomy and was partially restored using estrogen replacement. However, it is not known if estrogen treatment would be as effective in males. The purpose of this study was to evaluate the structural and functional effects of estrogen in male rats subjected to chronic volume overload. Four groups of male rats were studied at 3 days and 8 wk postsurgery as follows: fistula and sham-operated controls, with and without estrogen treatment. Biochemical and histological studies were performed at 3 days postsurgery, with chronic structural and functional effects studied at 8 wk. Measurement of systolic and diastolic pressure-volume relationships was obtained using a blood-perfused isolated heart preparation. Both fistula groups developed significant ventricular hypertrophy after 8 wk of volume overload. Untreated rats with fistula exhibited extensive ventricular dilatation, which was coupled with a loss of systolic function. Estrogen attenuated left ventricular dilatation and maintained function in treated rats. Estrogen treatment was also associated with a reduction in oxidative stress and circulating endothelin-1 levels, as well as prevention of matrix metalloproteinase-2 and -9 activation and breakdown of ventricular collagen in the early stage of remodeling. These data demonstrate that estrogen attenuates ventricular remodeling and disease progression in male rats subjected to chronic volume overload. [ABSTRACT FROM AUTHOR]

The objective of this prospective study was to assess patient exposure to the psychiatric use of unscheduled medications at all nine Pennsylvania state hospitals and to unify practice guidelines in this regard. In August 2004, a decision was made to discontinue the use of p.r.n. orders for psychiatric indications. All unscheduled medications, (p.r.n. and STAT physician’s order) administered for psychiatric indications were entered into a uniform database. A total of 46,913 unscheduled medications were administered to people served in the hospital system throughout this 15 month study. During March 2004, 87.7 unscheduled medications per 1,000 days-of-care were administered in the hospital system. During the last month of this study, May 2005, this rate had decreased to 17 per 1,000 days-of-care. Many hospital safety measures significantly improved as a result of this change. Cessation of p.r.n. medication use for psychiatric indications has significantly decreased patient exposure to unnecessary psychotropic medications and has resulted in a safer hospital system. [ABSTRACT FROM AUTHOR]

Zucker rats, lean and obese, treated with low dose intraperitoneal injections of streptozocin become hyperglycemic within 24 h. Insulin levels fall, although the obese animal remains hyperinsulinemic. Associated with these changes in glucose and insulin there are transient decreases in caloric intake. Macronutrient selection studies show that protein consumption decreases. There is a trend for fat intake to decrease. The levels of hypothalamic neurotransmitters in the lean animals are not altered by streptozocin. The levels of 5-hydroxyindoleacetic acid increases in the streptozocin-treated obese animal in the paraventricular region, ventromedial region and the raphe. Serotonin is also significantly increased in the paraventricular region of the obese rat. These results suggest that acutely, treatment with streptozocin injures pancreatic islets, causing, in turn, decreases in insulin levels so that hyperglycemia ensues in both phenotypes. Associated with these perturbations are decreases in caloric intake. The magnitude of change in insulin levels is much greater in the obese rat. It is hypothesized that in the obese Zucker rat decrements in food intake are mediated by increase in serotonin turnover in the hypothalamus and these changes are related to changes of insulin levels. These data support the concept that circulating insulin affects hypothalamic neurotransmitters. [ABSTRACT FROM AUTHOR]

Introduction: Consensus has formed that hydrogen sulfide (H2S) has robust cytoprotective actions in multiple organ systems. The pro-survival actions and biological profiles of H2S are remarkably similar to those of nitric oxide (NO). Although there is recent evidence of cross-talk between H2S and NO, these molecules are thought to modulate independent signaling pathways. Methods/Results: Mice devoid of the key H2S producing enzyme, cystathionine gamma-lyase (CSE KO), exhibited impaired endothelial nitric oxide synthase (eNOS) function and diminished circulating nitrite (0.41 uM vs 0.73μM, p <0.05) nitrosylated protein (3.37nM vs 15.03nM, p <0.05), and cyclic GMP (9.3 vs 28.05pmol/ml, p <0.01) levels compared to wild-type (WT) mice. Further studies revealed that H2S therapy in CSE KO mice restored eNOS function and NO levels. eNOS KO mice and mice with phospho-dead eNOS (S1179A) were subjected to 45min of ischemia, followed by 24h of reperfusion. The H2S donor, Na2S (100μg/kg), or vehicle (0.9% NaCl) was administered 5min before reperfusion. There was no significant change in myocardial infarction in the H2S-treated group compared to the vehicle-treated group. Conclusion: These findings reveal that H2S modulates eNOS activity and nitric oxide signaling. Moreover, the inability of H2S therapy to protect eNOS dysfunctional mice against myocardial ischemia/reperfusion injury indicates that the cardioprotective actions of H2S are dependent on eNOS function and NO signaling. [Copyright &y& Elsevier]

Introduction: CBS, CSE and 3-MST are the enzymatic source of endogenous hydrogen sulfide (H2S), a gaseous signaling molecule implicated in a wide range of physiological processes. We investigated the status of CBS, CSE, and 3-MST as well as the extent of oxidative stress in skeletal muscle tissue obtained from patients suffering from critical limb ischemia (CLI) ± diabetes mellitus (Db). Methods/Results: We found that both mRNA and protein levels of CSE, CBS, and 3-MST were significantly decreased in skeletal muscle of CLI (>2 fold, p <0.05) and CLI +Db (2 fold, p <0.05) patients as judged by RT-qPCR and immunoblot, respectively. We also observed reduced expression of nuclear factor-erythriod 2-related factor (Nrf2), a factor responsible for the expression of antioxidant response element-regulated genes (2 fold, p <0.05) and Cu, Zn-super oxide dismutase, an antioxidant enzyme (2 fold, P <0.05) in skeletal muscle of both patients. Biomarkers of oxidative stress, such as malondialdehyde and protein carbonyl formation were significantly increased (2 fold) in skeletal muscle of CLI and CLI +Db patients as compared with age-matched controls. Conclusion: The present study suggests that the induction of oxidative stress in skeletal muscle of both CLI and CLI +Db patients may directly down-regulate the expression of the endogenous H2S-generating enzymes: CSE, CBS, and 3-MST. Increased oxidative stress and reductions in H2S bioavailability may contribute to the pathogenesis of CLI. [Copyright &y& Elsevier]

Introduction: Hydrogen sulfide (H2S) is the endogenous signaling gasotransmitter, offering protective effects on oxidative stress including ischemia–reperfusion and hypertrophy/heart failure (HF). CSE is believed to be the major H2S-generating enzyme in the heart. Our previous study investigated that CSE KO mice are more susceptible to oxidative stress. NF-kappaB is a marker of cellular oxidative stress and its activation has been found to increase in ischemia–reperfusion and hypertrophy/HF. The purpose of the present study was to investigate the role of NF-kappaB in response to CSE. Methods/results: We found that both mRNA and protein levels of NF-kappaB-p65 were significantly increased in the heart tissues of CSE KO mice compared with control as they were judged by RT-qPCR and immunoblot, respectively. Interestingly, phosphorylation of p65 was increased (1.4 fold, p <0.05) in CSE KO mice. By utilizing electrophoretic mobility shift assay, we found increased NF-kappaB DNA binding activity in CSE KO mice compared to control. In addition, biomarkers of oxidative stress such as malondialdehyde (1.3 fold, p <0.05) and protein carbonyl (2 fold, p <0.01) formation were increased in heart tissues of CSE KO mice compared to wild type. Conclusion: Since we observed that the activation of NF-kappaB occurred in the heart tissues of CSE KO mice, our findings suggest that CSE may protect the heart from oxidative injury, such as that which occurs during ischemia–reperfusion, hypertrophy/HF. [Copyright &y& Elsevier]