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Myocardial ischaemia reperfusion injury (IRI) occurring from acute coronary artery disease or cardiac surgical interventions such as bypass surgery can result in myocardial dysfunction, presenting as, myocardial "stunning", arrhythmias, infarction, and adverse cardiac remodelling, and may lead to both a systemic and a localised inflammatory response. This localised cardiac inflammatory response is regulated through the nucleotide-binding oligomerisation domain (NACHT), leucine-rich repeat (LRR)-containing protein family pyrin domain (PYD)-3 (NLRP3) inflammasome, a multimeric structure whose components are present within both cardiomyocytes and in cardiac fibroblasts. The NLRP3 inflammasome is activated via numerous danger signals produced by IRI and is central to the resultant innate immune response. Inhibition of this inherent inflammatory response has been shown to protect the myocardium and stop the occurrence of the systemic inflammatory response syndrome following the re-establishment of cardiac circulation. Therapies to prevent NLRP3 inflammasome formation in the clinic are currently lacking, and therefore, new pharmacotherapies are required. This review will highlight the role of the NLRP3 inflammasome within the myocardium during IRI and will examine the therapeutic value of inflammasome inhibition with particular attention to carbon monoxide, nitric oxide, and hydrogen sulphide as potential pharmacological inhibitors of NLRP3 inflammasome activation. [ABSTRACT FROM AUTHOR]

Patients undergoing cardiopulmonary bypass procedures require inotropic support to improve hemodynamic function and cardiac output. Current inotropes such as dobutamine, can promote arrhythmias, prompting a demand for improved inotropes with little effect on intracellular Ca2+ flux. Low‐dose carbon monoxide (CO) induces inotropic effects in perfused hearts. Using the CO‐releasing pro‐drug, oCOm‐21, we investigated if this inotropic effect results from an increase in myofilament Ca2+ sensitivity. Male Sprague Dawley rat left ventricular cardiomyocytes were permeabilized, and myofilament force was measured as a function of ‐log [Ca2+] (pCa) in the range of 9.0–4.5 under five conditions: vehicle, oCOm‐21, the oCOm‐21 control BP‐21, and levosimendan, (9 cells/group). Ca2+ sensitivity was assessed by the Ca2+ concentration at which 50% of maximal force is produced (pCa50). oCOm‐21, but not BP‐21 significantly increased pCa50 compared to vehicle, respectively (pCa50 5.52 vs. 5.47 vs. 5.44; p < 0.05). No change in myofilament phosphorylation was seen after oCOm‐21 treatment. Pretreatment of cardiomyocytes with the heme scavenger hemopexin, abolished the Ca2+ sensitizing effect of oCOm‐21. These results support the hypothesis that oCOm‐21‐derived CO increases myofilament Ca2+ sensitivity through a heme‐dependent mechanism but not by phosphorylation. Further analyses will confirm if this Ca2+ sensitizing effect occurs in an intact heart. [ABSTRACT FROM AUTHOR]

Summary In the UK, half a million people care for people with severe mental illnesses (Princess Royal Trust for Carers 2002). This article reviews the findings of a study of [...]

Abstract Background Ghrelin is an orexigenic hormone principally produced by the stomach, but also by numerous peripheral tissues including the placenta. Ghrelin acts via growth hormone secretagogue receptors (GHSR-1a) to alter food intake, fat utilization, and cellular proliferation, and has been suggested to play a role in the developmental growth of the fetoplacental unit. The placental expression of ghrelin and its role in ruminant species is not known. We tested the hypotheses that ghrelin and its functional receptor, GHSR-1a, are present in tissues of the ovine placenta, and that their expression is linked to the stage of development. Methods Antibodies raised against ghrelin and GHSR-1a were used in standard immunohistochemical protocols on placental tissues collected from pregnant ewes (n = 6 per gestational time point) at days 50, 80, 100, 128 and 135 of gestation (term ≈ day 145). Immunostaining for ghrelin and GHSR-1a was quantified using computer-aided image analysis. Image analysis data were subjected to one-way ANOVA, with differences in immunostaining between time-points determined by Fisher's least significant difference. Results Positive immunostaining for ghrelin was detected in ovine placentae at all gestational time points, with staining localized to the maternal epithelium, caruncle and trophectoderm. There was a significant effect of gestational age (p < 0.001) on the placental expression of ghrelin, with maximal levels at gestational day 80. GHSR-1a immunostaining was detected in the fetal trophectoderm at all time points. In contrast to the gestational pattern of ghrelin expression, there was no effect of gestational age on placental GHSR-1a immunoexpression. Conclusion Ghrelin and GHSR-1a are both present in the ovine placenta, and ghrelin displays a developmentally-related pattern of expression. Therefore, these data strongly suggest that the ghrelin system may have a role in feto-placental development in sheep.

British guidelines recommend epidemiological treatment for all chlamydia contacts during the look back period. Some UK sexual health clinics follow a test and wait process for chlamydia contacts presenting after 14 days of exposure. The aim of this retrospective service evaluation was to determine the potential impact of implementing such a process for chlamydia contacts at our clinic. We reviewed the patient records of 548 chlamydia contacts over a 1-year period, and 588 patients with chlamydia over a 5-month period. Demographic and clinical characteristics data were collected. Chlamydia prevalence was 46% (254/548) in contacts, with prevalence varying by age (p=.008) and sexual risk (p=.04), but not by time since exposure (p=.29). For patients with chlamydia, there was a mean of 1.9 days between results notification and attending for treatment; a mean of 2.2 attempts were required to contact patients to return for treatment. Chlamydia prevalence in contacts is high. Not giving empirical treatment to contacts presenting after 14 days of exposure would result in 13.1% of the cohort needing to return for treatment. Patients found to have chlamydia returned promptly once informed of positive results. [ABSTRACT FROM AUTHOR]

Background: Pulmonary exacerbations in cystic fibrosis are characterized by airway inflammation and may cause irreversible lung damage. Early identification of such exacerbations may facilitate early initiation of treatment, thereby potentially reducing long-term morbidity.Research Question: Is it possible to predict pulmonary exacerbations in children with cystic fibrosis, using inflammatory markers obtained from BAL fluid?Study Design and Methods: A longitudinal analysis was conducted of children aged 0 to 7 years included in the Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF) study between 2005 and 2015. The association between inflammatory markers from annual BAL fluid and time to pulmonary exacerbation requiring hospital admission in the 6-month period post-BAL was analyzed using Kaplan-Meier curves and Weibull regression, adjusting for annually repeated measurements. Admissions for Pseudomonas eradication were excluded in the main analysis, because of the standard policy in participating centers to treat Pseudomonas in-hospital.Results: Nine hundred seventy-six BAL samples from 308 children were analyzed. After exclusion of admissions for Pseudomonas eradication (n = 43), there were 145 pulmonary exacerbations recorded within 6 months of BAL; median time to exacerbation was 31 days (interquartile range, 9-100). In univariate analyses, high IL-8 (hazard ratio [HR], 2.25 for 75th vs 25th percentile; 95% CI, 1.87-2.72), neutrophil elastase (HR, 3.00; 95% CI, 2.03-4.42), and high neutrophil percentage (HR, 1.80 for 75th vs 25th percentile; 95% CI, 1.56-2.04) were all significantly associated with risk for a pulmonary exacerbation (P < .001). The inflammatory markers remained significant predictors after adjustment for clinical predictive variables.Interpretation: Inflammatory markers in BAL fluid are significant predictors of pulmonary exacerbations in young children with cystic fibrosis. The development of noninvasive measures of lung inflammation may facilitate routine surveillance of cystic fibrosis. [ABSTRACT FROM AUTHOR]

The optimisation of the aqueous solubility of organic carbon monoxide releasing molecules based on a norborn‐2‐en‐7‐one scaffold is reported. This culminated in the synthesis of oCOm‐54 and oCOm‐56 which contain water solubilising polyethylene oxide groups. Both compounds are highly water soluble and release CO at pH 7.4 with half‐lives of 180 and 320 minutes respectively, to produce a reversible vasodilatory response in isolated, preconstricted tissue. Preliminary analysis indicates these oCOms are capable of forming micellar particles. Both oCOms exhibit significantly less cellular toxicity in AC16 human cardiomyocytes than earlier amine‐containing oCOms. [ABSTRACT FROM AUTHOR]

Abstract Background The gut hormone, ghrelin, is involved in the neuroendocrine and metabolic responses to hunger. In monogastric species, circulating ghrelin levels show clear meal-related and body weight-related changes. The pattern of secretion and its role in ruminant species is less clear. Ghrelin acts via growth hormone secretagogue receptors (GHSR-1a) to alter food intake, fat utilization, and cellular proliferation. There is also evidence that ghrelin is involved in reproductive function. In the present study we used immunohistochemistry to investigate the presence of ghrelin and GHSR-1a in sheep reproductive tissues. In addition, we examined whether ghrelin and GHSR-1a protein expression is developmentally regulated in the adult and fetal ovine testis, and whether there is an association with markers of cellular proliferation, i.e. stem cell factor (SCF) and proliferating cell nuclear antigen (PCNA). Methods Antibodies raised against ghrelin and its functional receptor, GHSR-type 1a, were used in standard immunohistochemical protocols on various reproductive tissues collected from adult and fetal sheep. GHSR-1a mRNA presence was also confirmed by in situ hybridisation. SCF and PCNA immunoexpression was investigated in fetal testicular samples. Adult and fetal testicular immunostaining for ghrelin, GHSR-1a, SCF and PCNA was analysed using computer-aided image analysis. Image analysis data were subjected to one-way ANOVA, with differences in immunostaining between time-points determined by Fisher's least significant difference. Results In adult sheep tissue, ghrelin and GHSR-1a immunostaining was detected in the stomach (abomasum), anterior pituitary gland, testis, ovary, and hypothalamic and hindbrain regions of the brain. In the adult testis, there was a significant effect of season (photoperiod) on the level of immunostaining for ghrelin (p < 0.01) and GHSR-1a (p < 0.05). In the fetal sheep testis, there was a significant effect of gestational age on the level of immunostaining for ghrelin (p < 0.001), GHSR-1a (p < 0.05), SCF (p < 0.05) and PCNA (p < 0.01). Conclusion Evidence is presented for the presence of ghrelin and its receptor in various reproductive tissues of the adult and fetal sheep. In addition, the data indicate that testicular expression of ghrelin and its receptor is physiologically regulated in the adult and developmentally regulated in the fetus. Therefore, the ghrelin ligand/receptor system may have a role (endocrine and/or paracrine) in the development (cellular proliferation) and function of the reproductive axis of the sheep.

Rationale: Historical studies suggest that airway infection in cystic fibrosis initiates with Staphylococcus aureus and Haemophilus influenzae, with later emergence of Pseudomonas aeruginosa. Aspergillus species are regarded as relatively infrequent, late-occurring infections.Objectives: To assess the prevalence and change in prevalence of early lower airway infections in a modern cohort of children with cystic fibrosis.Methods: All infants diagnosed with cystic fibrosis after newborn screening participating in the Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF) cohort study between 2000 and 2018 were included. Participants prospectively underwent BAL at 3-6 months, 1 year, and annually up to 6 years of age. Lower airway infection prevalence was described. Changes in prevalence patterns were assessed longitudinally using generalized estimating equations controlling for age and repeated visits.Measurements and Main Results: A total of 380 infants underwent 1,759 BALs. The overall prevalence and median age of first acquisition of the most common infections were as follows: S. aureus, 11%, 2.5 years; P. aeruginosa, 8%, 2.4 years; Aspergillus species, 11%, 3.2 years; and H. influenzae, 9%, 3.1 years. During the study, a significant decrease in prevalence of P. aeruginosa (P < 0.001) and S. aureus (P < 0.001) was observed with a significant change toward more aggressive treatment. Prevalence of Aspergillus infections did not significantly change (P = 0.669).Conclusions:Aspergillus species and P. aeruginosa are commonly present in the lower airways from infancy. The decrease in prevalence of P. aeruginosa and S. aureus since 2000, coinciding with a more aggressive therapeutic approach, has resulted in Aspergillus becoming the most commonly isolated pathogen in young children. Further research is warranted to understand the implication of these findings. [ABSTRACT FROM AUTHOR]

This research examines the significance of the Victorian and Edwardian back-to-back houses in Leeds and whether the built heritage (plan-form typology, urban character, style, traditional materials and construction) might be at risk. The methodology is based on a historic area assessment of the Harehills district. The development of the area is traced from historic maps and archival documents, and is supplemented with a survey of the houses. The plan-form typologies and decorative designs are identified, and mapped to show groups of like houses, which cross-references to a gazetteer detailing the main identifying features of each group. A second level of analysis is concerned with the houses as they stand today, focusing particularly on the extant decorative features and construction materials, the modifications that have compromised the architectural composition of the houses, and the uniformity of the urban setting. The research concludes that the back-to-back houses do have heritage significance, but a review of national and local policy reveals that this has never been recognised. The lack of protection has resulted in diminished significance and presents an ongoing risk. Suggestions are made for future research and protection strategies. [ABSTRACT FROM AUTHOR]

The treatment of Mycobacterium abscessus complex (MABSC) pulmonary infections is an emerging challenge in patients with cystic fibrosis (CF). Multidrug therapy for prolonged durations is required and carries the significant burden of drug-related toxicity, cost and selective pressure for multiresistant bacteria. International guidelines acknowledge that clinical and in vitro data to support treatment regimens are limited, particularly in children. As part of a collaboration between the infectious diseases and respiratory units at our institution, we have developed a modified treatment guideline that aims to balance the aims of MABSC eradication and slowing disease progression with minimising drug toxicity and resistance. The outcomes of this treatment approach will be monitored and reported. In this manuscript, we discuss the available evidence for treatment choices and present our treatment guideline for paediatric patients with CF and MABSC infection. [ABSTRACT FROM AUTHOR]

Summary: Objective: Altered autonomic activity has been implicated in the development of cardiac dysfunction during seizures. This study investigates whether intervening in seizure progression with diazepam will reduce seizure‐induced cardiomyopathy. Second, this study examines the hypothesis that combining atenolol with diazepam, as an intervention after seizure onset, will combat cardiac injury during status epilepticus. Methods: Male Sprague‐Dawley rats were implanted with electroencephalographic/electrocardiographic electrodes to allow simultaneous recordings during seizures induced by intrahippocampal (2 nmol, 1 μL) kainic acid (KA). Subcutaneous saline, atenolol (5 mg·kg−1), diazepam (5 mg·kg−1), or atenolol and diazepam (n = 12/group) were administered at 60 minutes post‐KA and daily for 7 days, at which point echocardiography, susceptibility to aconitine‐induced arrhythmias, and histology were evaluated. Results: Seizure activity was associated with immediately increased heart rate, QTc interval, and blood pressure (BP; 10%‐30% across indices). Seven days postseizure, saline‐treated animals were found to have reduced left ventricular function, increased fibrotic scarring, and an elevated risk of aconitine‐induced arrhythmias. Diazepam treatment significantly reduced cumulative seizure behaviors by 79% compared to saline‐treated animals but offered no cardiac protection. Diazepam significantly raised BP (35%) and increased the risk of bigeminal arrhythmias (36%) compared to saline‐treated animals. Atenolol administration, either alone or with diazepam, reduced heart rate, QTc interval, and BP back to control levels. Atenolol also preserved cardiac morphology and reduced arrhythmia risk. Significance: Attenuation of seizure with diazepam offered no cardiac protection; however, coadministration of atenolol with diazepam prevented the development of seizure‐induced cardiac dysfunction. This study demonstrates that atenolol intervention should be strongly considered as an adjunct clinical treatment to reduce cardiomyopathy during seizures. [ABSTRACT FROM AUTHOR]

This paper traces the development of back-to-back house building in Leeds. It first outlines the origin of the house type, before examining the urban layout, building form and social aspects of back-to-back courts in the first half of the 19th century, and the role of speculative developers, building societies and sanitary reformers. The focus then turns to the bills, acts and by-laws of the later 19th and early 20th century, and the determination of the people of Leeds to retain their preferred house type. Together, these brought improvements to the design and facilities, culminating in a house type that was far superior to that which was condemned by the back-to-back critics, and arguably had overcome all of the criticisms by the time construction of back-to-backs was prohibited in 1909. [ABSTRACT FROM PUBLISHER]

Distributed feedback fiber laser (DFB FL) sensors have been the subject of considerable research interest over the past decade, due primarily to their remarkable inherent strain sensitivity. Recent research has led to significant advances in both fundamental understanding of DFB FL devices and in practical performance outcomes in demanding real-world applications. Here, we provide an overview of the basic operating principles of wavelength division multiplexed DFB FL sensor systems and review the underlying theory of DFB FL. [ABSTRACT FROM PUBLISHER]

Background: Childhood interstitial lung disease (chILD) represents a rare heterogeneous group of respiratory disorders. In the absence of randomized controlled clinical trials, global collaborations have utilized case series with an aim to standardising approaches to diagnosis and management. Australasian data are lacking. The aim of this study was to calculate prevalence and report the experience of chILD in Australasia over a decade.Methods: Paediatric pulmonologists in Australia and New Zealand involved in the care of patients aged 0-18 years with chILD completed a questionnaire on demographics, clinical features and outcomes, over a 10 year period. These data, together with data from the 2 reference genetics laboratories, were used to calculate prevalence.Results: One hundred fifteen cases were identified equating to a period prevalence (range) of 1.5 (0.8-2.1) cases/million for children aged 0-18years. Clinical data were provided on 106 patients: the <2 year group comprised 66 children, median age (range) 0.50 years (0.01-1.92); the ≥2 year group comprised 40 children, median age 8.2 years (2.0-18.0). Management approach was heterogeneous. Overall, 79% of patients had a good clinical outcome. Mortality rate was 7% in the study population.Conclusion: chILD is rare in Australasia. This study demonstrates variation in the investigations and management of chILD cases across Australasia, however the general outcome is favorable. Further international collaboration will help finesse the understanding of these disorders. [ABSTRACT FROM AUTHOR]

We evaluated the implementation of a cystic fibrosis annual review process in a tertiary paediatric hospital. After implementation, there was demonstrated improvement in an important outcome measure-the use of inhaled mucolytic agents. [ABSTRACT FROM AUTHOR]

Seizures are associated with altered autonomic activity, which has been implicated in the development of cardiac dysfunction and structural damage. This study aimed to investigate the involvement of the autonomic nervous system in seizure-induced cardiomyopathy. Male Sprague-Dawley rats (320-350 g) were implanted with EEG/ECG electrodes to allow simultaneous telemetric recordings during seizures induced by intrahippocampal (2 nmol, 1 μl/min) kainic acid and monitored for 7 days. Seizure activity occurred in conjunction with increased heart rate (20%), blood pressure (25%), and QTc prolongation (15%). This increased sympathetic activity was confirmed by the presence of raised plasma noradrenaline levels at 3 h post-seizure induction. By 48 h post-seizure induction, sympathovagal balance was shifted in favor of sympathetic dominance, as indicated by both heart rate variability (LF/HF ratio of 3.5 ± 1.0) and pharmacological autonomic blockade. Functional cardiac deficits were evident at 7 and 28 days, as demonstrated by echocardiography showing a decreased ejection fraction (14% compared with control, P < 0.05) and dilated cardiomyopathy present at 28 days following seizure induction. Histological changes, including cardiomyocyte vacuolization, cardiac fibrosis, and inflammatory cell infiltration, were evident within 48 h of seizure induction and remained present for up to 28 days. These structural changes most probably contributed to an increased susceptibility to aconitine-induced arrhythmias. This study confirms that prolonged seizure activity results in acute and chronic alterations in cardiovascular control, leading to a deterioration in cardiac structure and function. This study further supports the need for modulation of sympathetic activity as a promising therapeutic approach in seizure-induced cardiomyopathy. [ABSTRACT FROM AUTHOR]