Miracle-dz/UniFAR-FTUs huggingface dataset:
Time‐dependent expression of Endothelin‐1 in lungs and the effects of TNF‐ƒÑ blocking peptide on acute lung injury in an endotoxemic rat model

Endothelin (ET)‐1 is a potent vasoconstrictor that has been implicated in the pathogenesis of a number of diseases, and some studies suggest that circulating ET‐1 is elevated in sepsis. The present study investigated whether ET plays a role in sepsis‐mediated acute lung injury and whether its expression (ET) could be down regulated by blockade of TNF‐α in septic lung. Male Wistar rats at 8 weeks of age were administered with either saline or lipopolysaccharide (LPS) at different time points (1, 3, 6 and 10 hours), after which various tests were then performed. The features of acute lung injury were observed at 1h after LPS administration, which gradually became severe with time. Systolic and diastolic pressures were reduced just about an hour after LPS administration, where as pulmonary TNF‐α levels were significantly increased at various time points after LPS administration. LPS induced a time‐dependent expression of ET‐1 and ETA receptor in the lungs compared to control, peaking and increasing by 3 fold at 6 h after induction of endotoxemia, whereas levels of ETB receptor, which has vasodilating effects, were remarkably down regulated time‐dependently. We conclude that the time‐dependent increase of ET‐1 and ETA receptor with the down regulation of ETB receptor may play a role in the pathogenesis of acute lung injury in endotoxemia. Finally, treatment of LPS‐administered rats with TNF‐α blocking peptide for three hours significantly suppressed levels of pulmonary ET‐1. These data taken together, led us to conclude that differential alteration in ET expression and its receptors may be mediated by TNFα and may, in part, account for the pathogenesis of acute lung injury in endotoxemia.
A pilot study of the tolerability and efficacy of antiviral therapy in hepatitis C virus–infected patients awaiting liver transplantation

Decompensated liver disease associated with chronic hepatitis C virus (HCV) infection is the most common indication for liver transplantation. It was shown previously that greater pretransplantation HCV titers are associated with relatively poor patient and graft survival. The tolerability and efficacy of antiviral therapy in patients with decompensated liver disease are not known. We conducted a pilot study to determine the likely tolerability and efficacy of pretransplantation antiviral therapy with interferon alfa‐2b, with or without ribavirin. HCV RNA–positive patients at or near the top of their respective waiting lists were randomly assigned to one of three treatment regimens until the time of liver transplantation: (1) group A, interferon alfa‐2b, 1 × 106 U/d; (2) group B, interferon alfa‐2b, 3 × 106 U three times weekly; or (3) group C, interferon alfa‐2b, 1 × 106 U/d, plus ribavirin, 400 mg twice daily. Less than half the patients screened met entry criteria, with thrombocytopenia and leukopenia the most common reasons for exclusion. Fifteen patients were administered antiviral therapy; three patients in group A and six patients each in groups B and C. Loss of detectable HCV RNA was seen in 33% of patients, whereas 55% had a decrease in viral titers on therapy. Twenty‐three adverse events occurred, including 20 serious adverse events. Thrombocytopenia was the most common adverse event. Two infectious complications occurred; one of these had a fatal outcome. We conclude that although pretransplantation antiviral therapy may reduce HCV titers in a minority of patients who meet treatment initiation criteria, adverse events associated with therapy are frequent and often severe in patients with Child's class B and C cirrhosis.
The paraodx of homelessness in rural and regional Queensland mining communities

Homelessness in Australian rural and regional mining communities is both a product of the decade long mining boom from 2002 to 2012 and a result of the mining downturn. The mining cycle is a structural driver of homelessness in these communities, compounding the social and economic dynamics that influence homelessness across any community or region. Despite some extraordinary mining cycle factors that placed more people in those communities at risk of homelessness, homelessness has not been recognised as a major social issue in rural and regional mining communities. This raises the question of how does the nation prepare for the inevitable future periods of mining boom and downturns? This qualitative research project involved in-depth interviews and focus groups with 43 participants, including 12 participants from the communities of Mackay, Moranbah and Dysart who were either experiencing homelessness at the time of the study or had experienced homelessness within the last eight years. The research also included participants from specialist homelessness services, generic community and government services and other community representatives from the three communities of interest to this study. Mining companies declined the offer to participate in this study. The key findings from this research include identifying contextual factors that influenced homelessness in these mining communities in the mining boom and downturn periods. Eight specific contextual themes were identified regarding the impact of the phases of the mining cycle on homelessness in these three mining communities. The research further identifies three pathways to homelessness in mining communities throughout the mining cycle. The three pathways are: (1) relationship and family breakdown and domestic and family violence, (2) unemployment and housing affordability, and (3) high vulnerability and lack of access to housing and support services. These pathways build on previous literature about pathways to homelessness and in some instances indicate how people can end their experiences of homelessness in mining communities. The research explores how mining communities could prevent and reduce homelessness irrespective of the stage of the mining cycle through mandating the ‘Social License to Operate’, longer term social planning and policy processes, and improving access to appropriate and affordable housing. Finally, the research concludes with a list of planning, policy and practice recommendations aimed at preventing and reducing homelessness in rural and regional mining communities. These recommendations emphasise prevention and early approaches to homelessness throughout the mining cycle and more crisis accommodation options during the mining boom.
Arabidopsis Plastid AMOS1/EGY1 Integrates Abscisic Acid Signaling to Regulate Global Gene Expression Response to Ammonium Stress1[W][OA]

Ammonium (NH4+) is a ubiquitous intermediate of nitrogen metabolism but is notorious for its toxic effects on most organisms. Extensive studies of the underlying mechanisms of NH4+ toxicity have been reported in plants, but it is poorly understood how plants acclimate to high levels of NH4+. Here, we identified an Arabidopsis (Arabidopsis thaliana) mutant, ammonium overly sensitive1 (amos1), that displays severe chlorosis under NH4+ stress. Map-based cloning shows amos1 to carry a mutation in EGY1 (for ethylene-dependent, gravitropism-deficient, and yellow-green-like protein1), which encodes a plastid metalloprotease. Transcriptomic analysis reveals that among the genes activated in response to NH4+, 90% are regulated dependent on AMOS1/EGY1. Furthermore, 63% of AMOS1/EGY1-dependent NH4+-activated genes contain an ACGTG motif in their promoter region, a core motif of abscisic acid (ABA)-responsive elements. Consistent with this, our physiological, pharmacological, transcriptomic, and genetic data show that ABA signaling is a critical, but not the sole, downstream component of the AMOS1/EGY1-dependent pathway that regulates the expression of NH4+-responsive genes and maintains chloroplast functionality under NH4+ stress. Importantly, abi4 mutants defective in ABA-dependent and retrograde signaling, but not ABA-deficient mutants, mimic leaf NH4+ hypersensitivity of amos1. In summary, our findings suggest that an NH4+-responsive plastid retrograde pathway, which depends on AMOS1/EGY1 function and integrates with ABA signaling, is required for the regulation of expression of NH4+-responsive genes that maintain chloroplast integrity in the presence of high NH4+ levels.
Connecting, learning, leaving: supporting young parents in the community.

Providing support and parenting education through home visiting is a key early intervention strategy with young parents. Less is known about what home visitors do that makes a difference. The purpose of this paper is to describe the role and experiences of professional staff working with young parents participating in a multicomponent parent support programme (home visiting and supported parenting groups) provided by a non-government organisation in a socially disadvantaged area of Sydney, Australia. This was a qualitative descriptive study. Data were collected through three focus groups conducted with the same six staff over an 18-month period. Participant descriptions of their role and experiences working with young mothers were analysed thematically. Additional data from 20 anonymised client records were analysed through content analysis. Analysis of the focus group data revealed two themes, 'Connecting' and 'Facilitating Learning'. The theme 'Connecting' reflected the development of a relationship with the young mother commencing with 'how do we engage them? ', 'building trust' through to formation of a relationship described as 'they know we're not friends, they know we're workers'. The second theme, 'Facilitating Learning' was informed by the analysis of both group and client record data and comprised a number of themes around what and how mothers learnt, through to 'ending the relationship' as the mothers left the programme. The quality of a mothers' learning was dependent on the quality of the connection between herself and the staff, similarly their capacity and, or confidence to leave the programme was dependent on the relationship, 'connecting' and the learning undertaken. Role modelling through interactions with children as well as with each other was seen as the most effective way to facilitate social and parenting skill development, while formal education sessions were evaluated by the workers to be less successful than informal ones.
Increased Circulating miR-625-3p: A Potential Biomarker for Patients With Malignant Pleural Mesothelioma

Introduction: We investigated the ability of cell-free microRNAs (miRNAs) in plasma and serum to serve as a biomarker for malignant mesothelioma (MM). Methods: Using miRNA microarrays, we profiled plasma samples from MM patients and healthy controls. miRNAs with significantly different abundance between cases and controls were validated in a larger series of MM patients and in an independent series of MM patients using quantitative real-time polymerase chain reaction. Levels of candidate miRNAs were also quantified in MM tumor samples. Results: We compared cell-free miRNA profiles in plasma from MM patients with healthy controls. Reviewing 90 miRNAs previously reported to be associated with MM, we found that the levels of two miRNAs, miR-29c* and miR-92a, were elevated in plasma samples from MM patients. In addition, we identified 15 novel miRNAs present at significantly higher levels in the plasma of MM patients. Further analysis of candidate miRNAs by real time-quantitative polymerase chain reaction confirmed that one of them, miR-625-3p, was present in significantly higher concentration in plasma/serum from MM patients and was able to discriminate between cases and controls, in both the original and the independent series of patients. MiR-625-3p was also found to be up-regulated in tumor specimens from a group of 18 MM patients, who underwent extrapleural pneumonectomy. Conclusion: Our data confirm the potential of miR-29c* and miR-92a as candidate tumor markers and reveal that miR-625-3p is a promising novel diagnostic marker for MM.
Shift from depolarizing to hyperpolarizing glycine action in rat auditory neurones is due to age‐dependent Cl− regulation

1 The inhibitory neurotransmitter glycine can elicit depolarizing responses in immature neurones. We investigated the changes in glycine responses and their ionic mechanism in developing neurones of the rat lateral superior olive (LSO), an auditory brainstem nucleus involved in sound localization. 2 Whole‐cell and gramicidin perforated‐patch recordings were performed from visually identified LSO neurones in brain slices and glycine was pressure applied for 3–100 ms to the soma. Glycine‐evoked currents were reversibly blocked by strychnine. They were mostly monophasic, but biphasic responses occurred in ∼30% of P8‐11 neurones in perforated‐patch recordings. 3 In whole‐cell recordings from P2‐11 neurones, the reversal potential of glycine‐evoked currents (EGly) was determined by the transmembranous Cl− gradient and corresponded closely to the Nernst potential for Cl−, regardless of age. This indicates that Cl− is the principle ion permeating glycine receptors, but is also consistent with a low relative (10–20%) permeability for HCO3−. The Cl− gradient also determined the polarity and amplitude of glycine‐evoked membrane potential changes. 4 Leaving the native intracellular [Cl−] undisturbed with gramicidin perforated‐patch recordings, we found a highly significant, age‐dependent change of EGly from −46.8 ± 1.8 mV (P1‐4, n= 28) to −67.6 ± 3.3 mV (P5‐8, n= 10) to −82.2 ± 4.1 mV (P9–11, n= 18). The majority of P1–4 neurones were depolarized by glycine (∼80%) and spikes were evoked in ∼30%. In contrast, P9–11 neurones were hyperpolarized. 5 In perforated‐patch recordings, EGly was influenced by the voltage protocol and the glycine application interval; it could be shifted in the positive and negative direction. For a given application interval, these shifts were always larger in P1–4 than in P8–11 neurones, pointing to less effective Cl− regulation mechanisms in younger neurones. 6 Furosemide (frusemide), a blocker of cation‐Cl− cotransporters, reversibly shifted EGly in the negative direction in P2–4 neurones, yet in the positive direction in P8–10 neurones, suggesting the blockade of net inward and net outward Cl− transporters, respectively. 7 Taken together, age‐dependent changes in active Cl− regulation are likely to cause the developmental shift from depolarizing to hyperpolarizing glycine responses. A high intracellular [Cl−] is generated in neonatal LSO neurones which decreases during maturation.
The laminar distribution and ultrastructure of fibers projecting from three thalamic nuclei to the somatic sensory‐motor cortex of the opossum

The projections of the ventrobasal complex (VB), the ventrolateral complex (VL), and the central intralaminar nucleus (CIN) to the somatic sensory‐motor (SSM) cortex of the Virginia opossum were studied with light and electron microscopic autoradiographic methods. VB, VL, and CIN have overlapping projections to SSM cortex and each one also projects to an additional cortical area. Unit responses to somatic sensory stimulation and the areal and laminar distribution of axons in cortex is different for VB, VL, and CIN, but the axons from each form similar round asymmetrical synapses, predominantly with dendritic spines.
Circulating inflammatory biomarkers can predict and characterize tuberculosis-associated immune reconstitution inflammatory syndrome

Objective:To identify inflammatory biomarker profiles during paradoxical and unmasking tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS), and determine whether differences in biomarkers prior to antiretroviral therapy (ART) predict subsequent development of TB-IRIS. Design:Case–control study within a cohort of patients initiating ART in South Africa (n = 498). Methods:Participants were followed up for 24 weeks for development of TB-IRIS. Plasma samples were collected at baseline and presentation with symptoms. Groups of cases and controls were as follows: pre-ART TB and developed paradoxical TB-IRIS (n = 9); pre-ART TB but no IRIS (n = 12); no pre-ART TB but developed unmasking TB-IRIS (n = 13); no pre-ART TB and no TB or IRIS during treatment (n = 12). Concentrations of 18 cytokines and chemokines, and C-reactive protein (CRP), were measured and compared. Results:Event samples were drawn a median of 28 days after ART initiation [interquartile range (IQR) 14–56 days]. During paradoxical TB-IRIS events, there were lower median concentrations of interleukin-10 [IL-10; 22.1 (IQR 15.3–34.9) vs. 82.2 (29.4–128.4) pg/ml, P = 0.047] and monocyte chemotactic protein-1 [MCP-1; 27.6 (20.0–29.7) vs. 71.4 (40.6–77.8) pg/ml, P = 0.005], and higher CRP: IL-10 ratio [2.2 × 103 (1.8–3.4) vs. 0.3 × 103 (0.2–0.5), P = 0.003] than in controls. Patients who developed unmasking TB-IRIS had higher median pre-ART levels of CRP [25 (8–47) vs. 6 (lower limit of detection, LLD–12) mg/l, P = 0.046] and interferon gamma (IFN-γ) [9.1 (4.4–24.7) vs. 0.9 (LLD–8.7) pg/ml, P = 0.032] than controls. Conclusion:Patients with unmasking TB-IRIS had higher pre-ART levels of plasma IFN-γ and CRP, consistent with preexisting subclinical TB. Paradoxical TB-IRIS was associated with lower levels of biomarkers of monocyte and regulatory T-cell activity, and higher CRP.
Endothelial function is more impaired in hemodialysis patients than renal transplant recipients

Abstract: Background: Endothelial dysfunction (ED) is a common precursor and denominator of cardiovascular events including development of atherosclerosis. In this cross‐sectional, controlled study, we aimed to investigate ED measured by ischemia‐induced forearm vasodilatation in chronic hemodialysis (HD) patients and renal transplant recipients (rTX).
Role of CD14 Promoter Polymorphisms in Helicobacter pylori Infection–Related Gastric Carcinoma

Purpose: Genetic variation in CD14 may affect CD14 expression and susceptibility to Helicobacter pylori infection–related cancers. This study examined functional single nucleotide polymorphisms (SNP) in the CD14 promoter and their associations with risk of developing gastric carcinoma in relation to H. pylori infection. Experimental Design: Thirty individual DNAs were sequenced to identify variants, and the function of the variants was examined by reporter gene assays. Genotypes and haplotypes were analyzed in 470 patients and 470 controls, and odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by logistic regression. Serologic H. pylori antibody and soluble CD14 (sCD14) levels were measured by ELISA. Results: Two SNPs (−651C>T and −260C>T) were identified, of which the −260CT and −260TT genotypes were associated with elevated risk of gastric carcinoma (OR, 1.77; 95% CI, 1.09-2.85 and OR, 1.95; 95% CI, 1.20-3.16, respectively). Haplotype analysis suggested a synergistic effect of the two SNPs (OR for the T−651-T−260 haplotype, 3.39 versus OR for the C−651-T−260 haplotype, 1.45; P = 0.02), which is consistent with reporter gene assays. A multiplicative joint effect between H. pylori infection and −260C>T polymorphism was observed (OR for the presence of both −260TT genotype and H. pylori infection, 4.03; 95% CI, 1.80-9.04). Patients had significantly higher sCD14 than controls (1,866 ± 2,535 ng/mL versus 1,343 ± 2,119 ng/mL; P < 0.001), and this difference was associated with the CD14 −260 polymorphism and H. pylori infection. Conclusions: Functional polymorphism in CD14 is associated with greater risk of H. pylori–related gastric carcinoma, which might be mediated by elevated sCD14.
Effects of serotonin transporter inhibition on gastrointestinal motility and colonic sensitivity in the mouse

Abstract Serotonin‐selective reuptake transporter (SERT) expression is decreased in animal models of intestinal inflammation and in individuals with inflammatory bowel disease (IBD) or irritable bowel syndrome (IBS), and it is possible that resultant changes in intestinal serotonin signalling contribute to the manifestation of clinical features associated with these disorders. The objective of this investigation was to determine whether inhibition of SERT function leads to changes in gut motility and sensitivity. Mice underwent a 14‐day treatment with the SERT inhibitor, paroxetine (20 mg kg−1), or vehicle (saline/propylene glycol). Gastrointestinal (GI) transit following charcoal gavage, colonic motility, stool frequency and visceromotor responses to colorectal distension were evaluated. In mice treated with paroxetine, stool output was decreased, upper GI transit was delayed, and colonic sensitivity to a nociceptive stimulus was attenuated. These results demonstrate that reduced SERT function (via pharmacological blockade) significantly alters GI motility and sensitivity in mice, and support the concept that altered SERT expression and function could contribute to symptoms associated with IBS and IBD.
Pharmacological interventions other than botulinum toxin for spasticity after stroke.

BACKGROUND The long-term risk of stroke increases with age, and stroke is a common cause of disability in the community. Spasticity is considered a significantly disabling impairment that develops in people who have had a stroke. The burden of care is higher in stroke survivors who have spasticity when compared with stroke survivors without spasticity with regard to treatment costs, quality of life, and caregiver burden. OBJECTIVES To assess if pharmacological interventions for spasticity are more effective than no intervention, normal practice, or control at improving function following stroke. SEARCH METHODS We searched the Cochrane Stroke Group Trials Register (May 2016), the Cochrane Central Register of Controlled Trials (CENTRAL, 2016, Issue 5), MEDLINE (1946 to May 2016), Embase (2008 to May 2016), CINAHL (1982 to May 2016), AMED (1985 to May 2016), and eight further databases and trial registers. In an effort to identify further studies, we undertook handsearches of reference lists and contacted study authors and commercial companies. SELECTION CRITERIA We included randomised controlled trials (RCTs) that compared any systemically acting or locally acting drug versus placebo, control, or comparative drug with the aim of treating spasticity. DATA COLLECTION AND ANALYSIS Two review authors independently assessed the studies for inclusion and extracted the data. We assessed the included studies for both quality and risk of bias. We contacted study authors to request further information when necessary. MAIN RESULTS We included seven RCTs with a total 403 participants. We found a high risk of bias in all but one RCT. Two of the seven RCTs assessed a systemic drug versus placebo. We pooled data on an indirect measure of spasticity (160 participants) from these two studies but found no significant effect (odds ratio (OR) 1.66, 95% confidence interval (CI) 0.21 to 13.07; I2 = 85%). We identified a significant risk of adverse events per participant occurring in the treatment group versus placebo group (risk ratio (RR) 1.65, 95% CI 1.12 to 2.42; 160 participants; I2 = 0%). Only one of these studies used a functional outcome measure, and we found no significant difference between groups.Of the other five studies, two assessed a systemic drug versus another systemic drug, one assessed a systemic drug versus local drug, and the final two assessed a local drug versus another local drug. AUTHORS' CONCLUSIONS The lack of high-quality RCTs limited our ability to make specific conclusions. Evidence is insufficient to determine if systemic antispasmodics are effective at improving function following stroke.