Extreme eutrophication and salinisation in the Coorong estuarine-lagoon ecosystem of Australia's largest river basin (Murray-Darling).

Estuaries in rainfall poor regions are highly susceptible to climatic and hydrological changes. The Coorong, a Ramsar-listed estuarine-coastal lagoon at the end of the Murray-Darling Basin (Australia), has experienced declining ecological health over recent decades. Twenty years of environmental data were analysed to assess patterns and drivers of water quality changes. Large areas of the Coorong are now persistently hyper-saline (salinity >80 psu) and hypereutrophic (total nitrogen, TN > 4 mg L-1, total phosphorus, TP > 0.2 mg L-1, chlorophyll a > 50 µg L-1) which coincided with reduced flushing due to diminished freshwater inflows and increasing evapo-concentration. Sediment quality also was related to flushing, with higher concentrations of organic carbon, TN, TP and sulfides as salinity increased. While total nutrient levels are very high, dissolved inorganic nutrients are generally low. Increased lagoonal flushing would be beneficial to reduce the hypersalinisation and hypereutrophication and improve ecosystem health.

Left ventricular dysfunction and intra-ventricular dyssynchrony in idiopathic pulmonary arterial hypertension.

BACKGROUND: Left ventricular (LV) filling pressures are normal in idiopathic pulmonary arterial hypertension (IPAH). However, direct and indirect interactions between the RV and LV can affect LV performance. We explored LV strain and LV intra-ventricular dyssynchrony in IPAH using feature tracking CMR (CMR-FT). METHODS: Seventy IPAH patients and 40 healthy volunteers were included. Patients underwent CMR and right heart catheterisation. The 4-chamber cine was used to calculate LV longitudinal strain (EllLV). LV circumferential (EccLV) and radial strain (ErrLV) were derived from a short axis cine. LV longitudinal, circumferential and radial intra-ventricular dyssynchrony indices were calculated. RESULTS: There were no differences between the IPAH and healthy volunteer group in LV ejection fraction (66.1% vs 64.2% p = 0.6672). EccLV (-29.1 vs -32.1 p = 0.0323) and EllLV (-16.6 vs -23.7 p < 0.0001) were lower in IPAH. In patients with more severe disease, there was greater impairment of ErrLV compared to mild disease (50.9 vs 87.5 P < 0.0001). LV synchrony was impaired in all directions in IPAH. ErrLV was associated with RV ejection fraction (r = 0.66), RV end-systolic volume index (r = -0.59), pulmonary vascular resistance (PVR)(r = 0.51) and stroke volume index (SVI)(r = 0.44). In a multivariate model with age, SVI and PVR, ErrLV (HR 0.970 p = 002) and radial dyssynchrony (HR 3.759 p < 0.0001) independently predicted survival. CONCLUSION: In IPAH, LV is dyssynchronous with impaired function. Measures of LV strain and intraventricular synchrony were associated with known markers of disease severity. These LV variables which are likely to be related to ventricular interaction, may add incremental value to known prognostic variables in IPAH.

Neighborhood Alcohol Environment: Differential Effects on Hazardous Drinking and Mental Health by Sex in Persons Living with HIV (PLWH).

Despite greater mental health co-morbidities and heavier alcohol use among PLWH, few studies have examined the role of the neighborhood alcohol environment on either alcohol consumption or mental health. Utilizing cross-sectional data from a cohort study in a southern U.S. metropolitan area, we examine the association between neighborhood alcohol environments on hazardous drinking and mental health among 358 in-care PLWH (84% African American, 31% female). Multilevel models were utilized to quantify associations between neighborhood alcohol exposure on hazardous drinking and effect modification by sex. Neighborhood alcohol density was associated with hazardous drinking among men but not women. Women living in alcohol dense neighborhoods were nearly two-fold likely to report depression compared to those in less dense neighborhoods, with no association between neighborhood alcohol density and depression among men. Neighborhood alcohol environments may be an important contextual factor to consider in reducing heavy alcohol consumption and improving mental health among PLWH.

Prevalence of non-tuberculous mycobacteria in HIV-infected patients admitted to hospital with pneumonia.

People living with the human immunodeficiency virus (PLWH) may be particularly vulnerable to the consequences of non-tuberculous mycobacteria (NTM) given their defective T cell-mediated immunity and high rates of structural lung disease. To determine the prevalence of NTM in PLWH hospitalized with pneumonia and to assess the potential predictors of NTM isolation. Secondary data analysis of a prospective cohort study (2007-2011) of early bronchoscopy in PLWH presenting with suspected pneumonia was undertaken. Subjects with any species of NTM, henceforth described as 'NTM of undetermined significance' (NTM-US), isolated from sputum or bronchoalveolar lavage fluid (BALF), were included in the analysis. Potential predictors were chosen a priori. Among 196 HIV-infected subjects hospitalized with pneumonia, 96 had respiratory samples positive for NTM-US, with 91% of all NTM-US isolated from sputum compared with BALF. The overall prevalence of NTM-US was 49% (96/196). More NTM subjects were smokers (P = 0.08), with a history of chronic obstructive pulmonary disease (P = 0.08). Among those with pathogenic NTM, 39% (34/88) would have met American Thoracic Society microbiologic criteria for NTM pulmonary disease (17% of total cohort). Respiratory cultures, predominantly sputum samples, were positive for NTM-US in 45% of HIV-infected subjects admitted to hospital for pneumonia. Further research is needed to characterize the prevalence of NTM in PLWH and help establish specific diagnostic criteria in this population. .

Increasing temperature decreases the predatory effect of the intertidal shanny Lipophrys pholis on an amphipod prey.

Interactions between Lipophrys pholis and its amphipod prey Echinogammarus marinus were used to investigate the effect of changing water temperatures, comparing current and predicted mean summer temperatures. Contrary to expectations, predator attack rates significantly decreased with increasing temperature. Handling times were significantly longer at 19° C than at 17 and 15° C and the maximum feeding estimate was significantly lower at 19° C than at 17° C. Functional-response type changed from a destabilizing type II to the more stabilizing type III with a temperature increase to 19° C. This suggests that a temperature increase can mediate refuge for prey at low densities. Predatory pressure by teleosts may be dampened by a large increase in temperature (here from 15 to 19° C), but a short-term and smaller temperature increase (to 17° C) may increase destabilizing resource consumption due to high maximum feeding rates; this has implications for the stability of important intertidal ecosystems during warming events.

Influence of sex and habitat on the size and shape of anal and dorsal fins of the blackstripe topminnow Fundulus notatus.

The size and shape of the anal and dorsal fin in the blackstripe topminnow Fundulus notatus from lake and stream habitats across multiple ages and sexes were examined. Differences in the size and shape of anal and dorsal fins were sex-specific and not related to habitat differences. Males have longer and more pointed anal fins and longer, larger and more pointed dorsal fins than females. These sex differences occur predominantly in the older age class. The angle (i.e. pointedness) of the dorsal and anal fins is tightly correlated suggesting that fins follow a similar growth trajectory as individuals become sexually mature.

Serum and bal beta-D-glucan for the diagnosis of Pneumocystis pneumonia in HIV positive patients.

BACKGROUND/PURPOSE: The diagnosis of patients with pulmonary infiltrates and human immunodeficiency virus (HIV) infection remains a challenge. In current clinical practice the gold standard for Pneumocystis jirovecii pneumonia (PCP) diagnosis remains the identification of the organism in bronco alveolar lavage (BAL) using microscopy (e.g., silver stain). (1->3)-ß -d-glucan (BG) is a polysaccharide that is present within the cell wall of Pneumocystis and other fungi. METHODS: We analyzed serum and BAL lavage fluid from a cohort of 119 patients that did have HIV, a diagnosis of pneumonia and underwent bronchoscopy (FOB) for diagnosis of PCP. RESULTS: The discriminative power of serum BG for the diagnosis of PCP in this group of patients was very high. Using a cutoff of 300 pg/mL, the sensitivity, specificity, positive predictive value(PPV) and negative predictive value (NPV) were 91%, 92%, 89% and 93% respectively. A model for ROC with just serum BG (N = 108) had an AUC of 0.95. Serum procalcitonin (PCT) and BAL BG were not as accurate for the diagnosis of PCP. For BAL BG using a cutoff of 783 pg/mL, the sensitivity,specificity, positive predictive value (PPV) and negative predictive value (NPV) were 72%, 79%,72% and 79% respectively. The differences between the medians for serum PCT between the group with a without PCP did not reach statistical significance (p = 0.6137). CONCLUSION: The measurement of serum BG should be incorporated in the diagnostic work up of HIV positive patients with dyspnea and infiltrates on chest X X-ray. Our study confirms the diagnostic value of serum BG previously reported by others but we add a cutoff value that we believe is more accurate for patients with AIDS and suspicion of PCP.

Genetic and clinical factors predict lithium's effects on PER2 gene expression rhythms in cells from bipolar disorder patients.

Bipolar disorder (BD) is associated with abnormal circadian rhythms. In treatment responsive BD patients, lithium (Li) stabilizes mood and reduces suicide risk. Li also affects circadian rhythms and expression of 'clock genes' that control them. However, the extent to which BD, Li and the circadian clock share common biological mechanisms is unknown, and there have been few direct measurements of clock gene function in samples from BD patients. Hence, the role of clock genes in BD and Li treatment remains unclear. Skin fibroblasts from BD patients (N=19) or healthy controls (N=19) were transduced with Per2::luc, a rhythmically expressed, bioluminescent circadian clock reporter gene, and rhythms were measured for 5 consecutive days. Rhythm amplitude and period were compared between BD cases and controls with and without Li. Baseline period was longer in BD cases than in controls. Li 1 mM increased amplitude in controls by 36%, but failed to do so in BD cases. Li 10 mM lengthened period in both BD cases and controls. Analysis of clock gene variants revealed that PER3 and RORA genotype predicted period lengthening by Li, whereas GSK3ß genotype predicted rhythm effects of Li, specifically among BD cases. Analysis of BD cases by clinical history revealed that cells from past suicide attempters were more likely to show period lengthening with Li 1 mM. Finally, Li enhanced the resynchronization of damped rhythms, suggesting a mechanism by which Li could act therapeutically in BD. Our work suggests that the circadian clock's response to Li may be relevant to molecular pathology of BD.

Functional genetic variation in the Rev-Erbα pathway and lithium response in the treatment of bipolar disorder.

Bipolar disorder (BD) is characterized by disruptions in circadian rhythms such as sleep and daily activity that often normalize after lithium treatment in responsive patients. As lithium is known to interact with the circadian clock, we hypothesized that variation in circadian 'clock genes' would be associated with lithium response in BD. We determined genotype for 16 variants in seven circadian clock genes and conducted a candidate gene association study of these in 282 Caucasian patients with BD who were previously treated with lithium. We found that a variant in the promoter of NR1D1 encoding Rev-Erbα (rs2071427) and a second variant in CRY1 (rs8192440) were nominally associated with good treatment response. Previous studies have shown that lithium regulates Rev-Erbα protein stability by inhibiting glycogen synthase kinase 3ß (GSK3ß). We found that GSK3ß genotype was also suggestive of a lithium response association, but not statistically significant. However, when GSK3ß and NR1D1 genotypes were considered together, they predicted lithium response robustly and additively in proportion to the number of response-associated alleles. Using lymphoblastoid cell lines from patients with BD, we found that both the NR1D1 and GSK3ß variants are associated with functional differences in gene expression. Our findings support a role for Rev-Erbα in the therapeutic mechanism of lithium and suggest that the interaction between Rev-Erbα and GSK3ß may warrant further study.

Pneumocystis colonisation is common among hospitalised HIV infected patients with non-Pneumocystis pneumonia.

BACKGROUND: When Pneumocystis DNA is recovered from respiratory specimens of patients without Pneumocystis pneumonia (PCP), patients are said to be colonised with Pneumocystis, although the significance of this state is unknown. Understanding risk factors for and outcomes of colonisation may provide insights into the life cycle and transmission dynamics of Pneumocystis jirovecii. METHODS: We performed a cross sectional study of the prevalence and clinical predictors of Pneumocystis colonisation in 172 HIV infected, PCP negative inpatients undergoing diagnostic evaluation of 183 episodes of pneumonia at either the Medical Center of Louisiana at New Orleans between 2003 and 2005 or San Francisco General Hospital between 2000 and 2005. DNA was extracted from sputum and bronchoalveolar lavage specimens and amplified using a nested PCR assay at the mitochondrial large subunit (18S) ribosomal RNA locus. Colonisation was deemed present if Pneumocystis DNA was identified by both gel electrophoresis and direct DNA sequencing. RESULTS: 68% (117/172) of all patients were colonised with Pneumocystis. No strong associations with colonisation were identified for any demographic factors. Among clinical factors, having a CD4+ T cell count

The effects of hypoxia on the cells of the pulmonary vasculature.

Pulmonary hypertension is associated with remodelling of pulmonary vessels. Chronic hypoxia is a common cause of pulmonary hypertension and pulmonary vascular remodelling. Vascular remodelling is characterised largely by fibroblast, smooth muscle and endothelial cell proliferation, which results in lumen obliteration. Chronic hypoxia elicits expression of mitogens, growth factors and cytokines by fibroblasts and endothelial cells, and also the suppression of endothelial nitric oxide synthase. Although hypoxic pulmonary vascular remodelling is associated with medial hypertrophy, many in vitro studies have found that hypoxia does not lead to a direct increase in smooth muscle cell proliferation. This paradox is not well understood and this review aims to examine the various reasons why this might be so. The present authors reviewed data from in vitro studies and also considered whether hypoxia could act on adjacent cells such as fibroblasts and endothelial cells to trigger smooth muscle cell proliferation. It is possible that hypoxia is sensed by fibroblasts, endothelial cells, or both, and relayed to adjacent pulmonary artery smooth muscle cells by intercellular signalling, causing proliferation. The present article reviews the data from in vitro studies of hypoxia on the three cellular components of the pulmonary vascular wall, namely endothelial cells, smooth muscle cells and fibroblasts.

Exploring spatiotemporal organization of SCN circuits.

Suprachiasmatic nucleus (SCN) neuroanatomy has been a subject of intense interest since the discovery of the SCN's function as a brain clock and subsequent studies revealing substantial heterogeneity of its component neurons. Understanding the network organization of the SCN has become increasingly relevant in the context of studies showing that its functional circuitry, evident in the spatial and temporal expression of clock genes, can be reorganized by inputs from the internal and external environment. Although multiple mechanisms have been proposed for coupling among SCN neurons, relatively little is known of the precise pattern of SCN circuitry. To explore SCN networks, we examine responses of the SCN to various photic conditions, using in vivo and in vitro studies with associated mathematical modeling to study spatiotemporal changes in SCN activity. We find an orderly and reproducible spatiotemporal pattern of oscillatory gene expression in the SCN, which requires the presence of the ventrolateral core region. Without the SCN core region, behavioral rhythmicity is abolished in vivo, whereas low-amplitude rhythmicity can be detected in SCN slices in vitro, but with loss of normal topographic organization. These studies reveal SCN circuit properties required to signal daily time.

Differential temperature acclimatization responses in the membrane phospholipids of Posthodiplostomum minimum and its second intermediate host, Lepomis macrochirus.

The effects of temperature change on phospholipid content in metacercariae of Posthodiplostomum minimum and their second intermediate hosts, Lepomis macrochirus, were examined to gauge similarities in the homeoviscous adaptation of host and parasite membranes to environmental thermal change. Heart, liver, and muscle tissues from individual L. macrochirus responded to environmental temperature declines with a decrease in the ratio of phosphatidylethanolamine (PE) to phosphatidylcholine (PC). Increases in membrane PE concentration increase membrane fluidity, maintaining fish membrane function as environmental temperature declines. However, the metacercariae of P. minimum exhibit changes in cholesterol levels, total lipid levels, and lipid composition (PE/PC) that contrast the normal changes for homeoviscous membrane adaptation exhibited by their fish intermediate hosts. The parasites seem to rely on their hosts for homeoviscous adaptation within normal developmental temperature ranges, pooling both cholesterol and PE as energetic stores for development and ontological transitions signaled by elevated temperatures.

TRPC3 mediates pyrimidine receptor-induced depolarization of cerebral arteries.

We tested the hypothesis that TRPC3, a member of the canonical transient receptor potential (TRP) family of channels, mediates agonist-induced depolarization of arterial smooth muscle cells (SMCs). In support of this hypothesis, we observed that suppression of arterial SMC TRPC3 expression with antisense oligodeoxynucleotides significantly decreased the depolarization and constriction of intact cerebral arteries in response to UTP. In contrast, depolarization and contraction of SMCs induced by increased intravascular pressure, i.e., myogenic responses, were not altered by TRPC3 suppression. Interestingly, UTP-evoked responses were not affected by suppression of a related TRP channel, TRPC6, which was previously found to be involved in myogenic depolarization and vasoconstriction. In patch-clamp experiments, UTP activated a whole cell current that was greatly reduced or absent in TRPC3 antisense-treated SMCs. These results indicate that TRPC3 mediates UTP-induced depolarization of arterial SMCs and that TRPC3 and TRPC6 may be differentially regulated by receptor activation and mechanical stimulation, respectively.

A retrospective review comparing the use of Gonal-F and Metrodin-HP for in-vitro fertilisation (IVF).

All cycles of IVF with pituitary down-regulation (n = 57) done at the Damansara Fertility Centre in the year 2000 were studied. All the 57 patients had controlled ovarian hyperstimulation, either using Metrodin HP (n = 27) or Gonal-F (n = 30). Of these, 53 patients reached oocyte pick-up, 26 patients in Metrodin HP group and 27 patients in Gonal-F group. Gonal-F resulted in a higher clinical pregnancy rate of 66.6% compared to Metrodin HP 38.5% (p < 0.05). The live birth rate tends to be higher in Gonal-F group (40.7%) compared to Metrodin HP (30.8%), (p > 0.05).

Ambulatory pulmonary artery pressure monitoring during sleep and exercise in normal individuals and patients with COPD.

BACKGROUND: Pulmonary hypertension is a common complication of chronic obstructive airways disease (COPD) and its presence implies a poor prognosis. However, it is difficult to measure and its specific contribution to symptoms is difficult to quantify. A micromanometer tipped pulmonary artery catheter was used to measure pulmonary artery pressure (PAP) during sleep and on exercise. METHODS: Ten patients (five with COPD receiving long term oxygen therapy and five normal individuals) were studied. Pulmonary artery pressure was recorded continuously during two periods of sleep (breathing oxygen followed by air for the COPD group) and during exercise. RESULTS: In the COPD group PAP during sleep on oxygen was significantly lower than PAP during sleep breathing air (mean (SD) difference 9.6 (5.3) mm Hg, 95% CI 4.9 to 14.3, p= 0.016). PAP during exercise was not significantly different from PAP during sleep breathing air (mean (SD) difference 0.8 (8.9) mm Hg, 95% CI -7.0 to 8.6, p= 0.851). In normal individuals the group mean (SD) PAP was 15 (5.9) mm Hg for the first nocturnal period and 15 (5.7) mm Hg for the second nocturnal period. PAP during exercise was not significantly different from PAP during sleep breathing air (mean (SD) difference 3.3 (2.2) mm Hg, 95% CI 1.1 to 5.5, p= 0.061). CONCLUSION: In patients with COPD, PAP rose significantly during sleep to levels similar to those measured during exercise, but this could be reversed with oxygen.

A sleep diary and questionnaire study of naturally short sleepers.

Whereas most people require more than 6 h of sleep to feel well rested, there appears to be a group of people who can function well on between 3 and 6 h of sleep. The aims of the present study were to compare 12 naturally short (3-6 h) sleepers (9 males 3 females, mean age 39.6 years, SD age 10.1 years) recruited by a media publicity campaign with age, gender and chronotype matched medium length (7-8.5 h) sleepers on various measures. Measurement instruments included diaries and questionnaires to assess sleep duration and timing, as well as questionnaire assessments of sleep pathology, morningness-eveningness, extroversion, neuroticism, pathological daytime sleepiness, subclinical hypomania, optimism, depressive symptoms, exercise, and work habits. Few measures showed reliable differences between naturally short sleepers and controls except the obvious ones related to sleep duration. There was, however, some evidence for subclinical hypomanic symptoms in naturally short sleepers.

Host defense in respiratory infections.

Respiratory defenses against infection involve a diverse and complex system. Mechanical barriers limit exposure of the respiratory tract to potential pathogenic organisms, whereas the mucociliary apparatus and cough reflexes work to expel any microbes that may bypass the initial defenses. When microorganisms have gained entry to the lower respiratory tract, the alveolar macrophage and recruited phagocytes may eliminate the culprits before active infection can be established. Only after the failure of the innate immune defenses is a specific immune response mounted. Examination of clinical defects in host defense allows one to understand the importance of the multitude of components of the lung's immune defense system.

Preserved contractile function despite atrophic remodeling in unloaded rat hearts.

The present study was designed to determine whether myocardial atrophy is necessarily associated with changes in cardiac contractility. Myocardial unloading of normal hearts was produced via heterotopic transplantation in rats. Contractions of isolated myocytes (1.2 mM Ca2+; 37 degrees C) were assessed during field stimulation (0.5, 1.0, and 2.0 Hz), and papillary muscle contractions were assessed during direct stimulation (2.0 mM Ca2+; 37 degrees C; 0.5 Hz). Hemodynamic unloading was associated with a 41% decrease in median myocyte volume and proportional decreases in myocyte length and width. Nevertheless, atrophic myocytes had normal fractional shortening, time to peak contraction, and relaxation times. Despite decreases in absolute maximal force generation (F(max)), there were no differences in F(max)/ area in papillary muscles isolated from unloaded transplanted hearts. Therefore, atrophic remodeling after unloading is associated with intact contractile function in isolated myocytes and papillary muscles when contractile indexes are normalized to account for reductions in cell length and cross-sectional area, respectively. Nevertheless, in the absence of compensatory increases in contractile function, reductions in myocardial mass will lead to impaired overall work capacity.