420 research outputs found

    Diel turbidity cycles in a headwater stream: evidence of nocturnal bioturbation?

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    Purpose: A small number of recent studies have linked daily cycles in stream turbidity to nocturnal bioturbation by aquatic fauna, principally crayfish, and demonstrated this process can significantly impact upon water quality under baseflow conditions. Adding to this limited body of research, we use high-resolution water quality monitoring data to investigate evidence of diel turbidity cycles in a lowland, headwater stream with a known signal crayfish (Pacifastacus leniusculus) population and explore a range of potential causal mechanisms. Materials and methods: Automatic bankside monitoring stations measured turbidity and other water quality parameters at 30-min resolution at three locations on the River Blackwater, Norfolk, UK during 2013. Specifically, we focused on two 20-day periods of baseflow conditions during January and April 2013 which displayed turbidity trends typical of winter and spring seasons, respectively. The turbidity time-series, which were smoothed with 6.5 hour Savitzky-Golay filters to highlight diel trends, were correlated against temperature, stage, dissolved oxygen and pH to assess the importance of abiotic influences on turbidity. Turbidity was also calibrated against suspended particulate matter (SPM) over a wide range of values via linear regression. Results and discussion: Pronounced diel turbidity cycles were found at two of the three sites under baseflow conditions during April. Spring night-time turbidity values consistently peaked between 21:00 and 04:00 with values increasing by ~10 nephelometric turbidity units (NTU) compared with the lowest recorded daytime values which occurred between 10:00 and 14:00. This translated into statistically significant increases in median midnight SPM concentration of up to 76% compared with midday, with night-time (18:00 – 05:30) SPM loads also up to 30% higher than that recorded during the daytime (06:00 – 17:30). Relating turbidity to other water quality parameters exhibiting diel cycles revealed there to be neither any correlation that might indicate a causal link, nor any obvious mechanistic connections to explain the temporal turbidity trends. Diel turbidity cycles were less prominent at all sites during the winter. Conclusions: Considering the seasonality and timing of elevated turbidity, visual observations of crayfish activity, and an absence of mechanistic connections with other water quality parameters, the results presented here are consistent with the hypothesis that nocturnal bioturbation is responsible for generating diel turbidity cycles under baseflow conditions in headwater streams. However, further research in a variety of fluvial environments is required to better assess the spatial extent, importance and causal mechanisms of this phenomenon

    Homologous and heterologous desensitization of guanylyl cyclase-B signaling in GH3 somatolactotropes

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    The guanylyl cyclases, GC-A and GC-B, are selective receptors for atrial and C-type natriuretic peptides (ANP and CNP, respectively). In the anterior pituitary, CNP and GC-B are major regulators of cGMP production in gonadotropes and yet mouse models of disrupted CNP and GC-B indicate a potential role in growth hormone secretion. In the current study, we investigate the molecular and pharmacological properties of the CNP/GC-B system in somatotrope lineage cells. Primary rat pituitary and GH3 somatolactotropes expressed functional GC-A and GC-B receptors that had similar EC50 properties in terms of cGMP production. Interestingly, GC-B signaling underwent rapid homologous desensitization in a protein phosphatase 2A (PP2A)-dependent manner. Chronic exposure to either CNP or ANP caused a significant down-regulation of both GC-A- and GC-B-dependent cGMP accumulation in a ligand-specific manner. However, this down-regulation was not accompanied by alterations in the sub-cellular localization of these receptors. Heterologous desensitization of GC-B signaling occurred in GH3 cells following exposure to either sphingosine-1-phosphate or thyrotrophin-releasing hormone (TRH). This heterologous desensitization was protein kinase C (PKC)-dependent, as pre-treatment with GF109203X prevented the effect of TRH on CNP/GC-B signaling. Collectively, these data indicate common and distinct properties of particulate guanylyl cyclase receptors in somatotropes and reveal that independent mechanisms of homologous and heterologous desensitization occur involving either PP2A or PKC. Guanylyl cyclase receptors thus represent potential novel therapeutic targets for treating growth-hormone-associated disorders

    Environmental Factors in the Relapse and Recurrence of Inflammatory Bowel Disease:A Review of the Literature

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    The causes of relapse in patients with Crohn's disease (CD) and ulcerative colitis (UC) are largely unknown. This paper reviews the epidemiological and clinical data on how medications (non-steroidal anti-inflammatory drugs, estrogens and antibiotics), lifestyle factors (smoking, psychological stress, diet and air pollution) may precipitate clinical relapses and recurrence. Potential biological mechanisms include: increasing thrombotic tendency, imbalances in prostaglandin synthesis, alterations in the composition of gut microbiota, and mucosal damage causing increased permeability

    Gabapentin for the hemodynamic response to intubation: systematic review and meta-analysis

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    Purpose Endotracheal intubation is the gold standard for securing the airway before surgery. Nevertheless, this procedure can produce an activation of the sympathetic nervous system and result in a hemodynamic response which, in high-risk patients, may lead to cardiovascular instability and myocardial ischemia. The aim of this review was to evaluate whether gabapentin can attenuate this response and whether such an attenuation could translate into reduced myocardial ischemia and mortality. Source We searched MEDLINE®, EMBASE™, CINAHL, AMED, and unpublished clinical trial databases for randomized-controlled trials that compared gabapentin with control, fentanyl, clonidine, or beta blockers for attenuating the hemodynamic response to intubation. Primary outcomes were mortality, myocardial infarction, and myocardial ischemia. Secondary outcomes were hemodynamic changes following intubation. Principal findings We included 29 randomized trials with only two studies at low risk of bias. No data were provided for the primary outcomes and no studies included high-risk patients. The use of gabapentin resulted in attenuation in the rise in mean arterial blood pressure [mean difference (MD), −12 mmHg; 95% confidence interval (CI), −17 to −8] and heart rate (MD, −8 beats·min−1; 95% CI, −11 to −5) one minute after intubation. Gabapentin also reduced the risk of hypertension or tachycardia requiring treatment (risk ratio, 0.15; 95% CI, 0.05 to 0.48). Data were limited on adverse hemodynamic events such as bradycardia and hypotension. Conclusion It remains unknown whether gabapentin improves clinically relevant outcomes such as death and myocardial infarction since studies failed to report on these. Nevertheless, gabapentin attenuated increases in heart rate and blood pressure following intubation when compared with the control group. Even so, the studies included in this review were at potential risk of bias. Moreover, they did not include high-risk patients or report adverse hemodynamic outcomes. Future studies are required to address these limitations

    Mindful Aging: The Effects of Regular Brief Mindfulness Practice on Electrophysiological Markers of Cognitive and Affective Processing in Older Adults

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    There is growing interest in the potential benefits of mindfulness meditation practices in terms of counteracting some of the cognitive effects associated with aging. Pursuing this question, the aim of the present study was to investigate the influence of mindfulness training on executive control and emotion regulation in older adults, by means of studying behavioral and electrophysiological changes. Participants, 55 to 75 years of age, were randomly allocated to an 8-week mindful breath awareness training group or an active control group engaging in brain training exercises. Before and after the training period, participants completed an emotional-counting Stroop task, designed to measure attentional control and emotion regulation processes. Concurrently, their brain activity was measured by means of 64-channel electroencephalography. The results show that engaging in just over 10 min of mindfulness practice five times per week resulted in significant improvements in behavioral (response latency) and electrophysiological (N2 event-related potential) measures related to general task performance. Analyses of the underlying cortical sources (Variable Resolution Electromagnetic Tomography, VARETA) indicate that this N2-related effect is primarily associated with changes in the right angular gyrus and other areas of the dorsal attention network. However, the study did not find the expected specific improvements in executive control and emotion regulation, which may be due to the training instructions or the relative brevity of the intervention. Overall, the results indicate that engaging in mindfulness meditation training improves the maintenance of goal-directed visuospatial attention and may be a useful strategy for counteracting cognitive decline associated with aging

    Essential Domains of Anaplasma phagocytophilum Invasins Utilized to Infect Mammalian Host Cells

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    Anaplasma phagocytophilum causes granulocytic anaplasmosis, an emerging disease of humans and domestic animals. The obligate intracellular bacterium uses its invasins OmpA, Asp14, and AipA to infect myeloid and non-phagocytic cells. Identifying the domains of these proteins that mediate binding and entry, and determining the molecular basis of their interactions with host cell receptors would significantly advance understanding of A. phagocytophilum infection. Here, we identified the OmpA binding domain as residues 59 to 74. Polyclonal antibody generated against a peptide spanning OmpA residues 59 to 74 inhibited A. phagocytophilum infection of host cells and binding to its receptor, sialyl Lewis x (sLex-capped P-selectin glycoprotein ligand 1. Molecular docking analyses predicted that OmpA residues G61 and K64 interact with the two sLex sugars that are important for infection, α2,3-sialic acid and α1,3-fucose. Amino acid substitution analyses demonstrated that K64 was necessary, and G61 was contributory, for recombinant OmpA to bind to host cells and competitively inhibit A. phagocytophilum infection. Adherence of OmpA to RF/6A endothelial cells, which express little to no sLex but express the structurally similar glycan, 6-sulfo-sLex, required α2,3-sialic acid and α1,3-fucose and was antagonized by 6-sulfo-sLex antibody. Binding and uptake of OmpA-coated latex beads by myeloid cells was sensitive to sialidase, fucosidase, and sLex antibody. The Asp14 binding domain was also defined, as antibody specific for residues 113 to 124 inhibited infection. Because OmpA, Asp14, and AipA each contribute to the infection process, it was rationalized that the most effective blocking approach would target all three. An antibody cocktail targeting the OmpA, Asp14, and AipA binding domains neutralized A. phagocytophilumbinding and infection of host cells. This study dissects OmpA-receptor interactions and demonstrates the effectiveness of binding domain-specific antibodies for blocking A. phagocytophilum infection

    Characterization of a fluvial aquifer at a range of depths and scales: the Triassic St Bees Sandstone Formation, Cumbria, UK

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    Fluvial sedimentary successions represent porous media that host groundwater and geothermal resources. Additionally, they overlie crystalline rocks hosting nuclear waste repositories in rift settings. The permeability characteristics of an arenaceous fluvial succession, the Triassic St Bees Sandstone Formation in England (UK), are described, from core-plug to well-test scale up to ~1 km depth. Within such lithified successions, dissolution associated with the circulation of meteoric water results in increased permeability (K~10−1–100 m/day) to depths of at least 150 m below ground level (BGL) in aquifer systems that are subject to rapid groundwater circulation. Thus, contaminant transport is likely to occur at relatively high rates. In a deeper investigation (> 150 m depth), where the aquifer has not been subjected to rapid groundwater circulation, well-test-scale hydraulic conductivity is lower, decreasing from K~10−2 m/day at 150–400 m BGL to 10−3 m/day down-dip at ~1 km BGL, where the pore fluid is hypersaline. Here, pore-scale permeability becomes progressively dominant with increasing lithostatic load. Notably, this work investigates a sandstone aquifer of fluvial origin at investigation depths consistent with highly enthalpy geothermal reservoirs (~0.7–1.1 km). At such depths, intergranular flow dominates in unfaulted areas with only minor contribution by bedding plane fractures. However, extensional faults represent preferential flow pathways, due to presence of high connective open fractures. Therefore, such faults may (1) drive nuclear waste contaminants towards the highly permeable shallow (< 150 m BGL) zone of the aquifer, and (2) influence fluid recovery in geothermal fields

    Introducing ‘Ngaruroro’, a New Model for Understanding Māori Wellbeing

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    Indigenous peoples around the world are revitalising their ancestral beliefs, practices, and languages, including traditional understandings of health and wellbeing. In the Aotearoa (New Zealand) context, a number of ground-breaking Māori health- and wellbeing-related models have emerged, each with their own scope and applications. We sought in our qualitative studies to explore and identify several key sources of wellbeing for Māori individuals. Nine interviews were conducted with members of Māori communities to identify key themes of Māori wellbeing. We performed a Reflexive Thematic Analysis on these data and then conducted a further fifteen interviews to revise, refine, and reposition the previously generated themes. The Ngaruroro model describes wellbeing as the embodied and active process of being well in relation with one’s (1) here tāngata (social and familial ties), (2) te taiao (the environment), and (3) taonga tuku iho (cultural treasures) while doing what one can to make lifestyle choices that are conducive to the health of one’s (4) tinana (body) and (5) wairua (spirit) while cultivating a balanced (6) ngākau (inner-system), fulfilling (7) matea (core needs) and exercising your (8) mana (authority). These themes illustrate that Māori wellbeing is dynamic, interconnected, and holistic

    Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

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    BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

    The self-reported Montgomery-Åsberg depression rating scale is a useful evaluative tool in major depressive disorder

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    Abstract Background The use of Patient-reported Outcomes (PROs) as secondary endpoints in the development of new antidepressants has grown in recent years. The objective of this study was to assess the psychometric properties of the 9-item, patient-administered version of the Montgomery-Åsberg Depression Rating Scale (MADRS-S). Methods Data from a multicentre, double-blind, 8-week, randomised controlled trial of 278 outpatients diagnosed with Major Depressive Disorder were used to evaluate the validity, reliability and sensitivity to change of the MADRS-S using psychometric methods. A Receiver Operating Characteristic (ROC) curve was plotted to identify the most appropriate threshold to define perceived remission. Results No missing values were found at the item level, indicating good acceptability of the scale. The construct validity was satisfactory: all items contributed to a common underlying concept, as expected. The correlation between MADRS-S and physicians' MADRS was moderate (r = 0.54, p Conclusion Taking account of patient's perceptions of the severity of their own symptoms along with the psychometric properties of the MADRS-S enable its use for evaluative purposes in the development of new antidepressant drugs.</p
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