Expression of human beta-defensins 1 and 2 in kidneys with chronic bacterial infection

BACKGROUND: Constitutive expression and localization of antimicrobial human β-defensin-1 (HBD-1) in human kidneys as a potential mechanism of antimicrobial defense has been previously reported. Inducible expression of human β-defensin-2 (HBD-2) has been described in various epithelial organs but not for the urogenital tract. METHODS: We investigated the gene- and protein expression of HBD-1 and HBD-2 by reverse transcriptase-polymerase chain reaction, and immunohistochemistry in 15 normal human kidney samples and 15 renal tissues with chronic bacterial infection. Additionally, cell culture experiments were performed to study HBD gene expression by real-time RT-PCR in response to inflammatory cytokines TNFα and IL-1β as well as lipopolysaccharide from Gram-negative bacteria. RESULTS: Constitutive HBD-1 gene- and protein expression was detected in normal renal tissue and kidneys with chronic infection. As a novel finding, inducible HBD-2 gene- and protein expression was demonstrated in tubulus epithelia with chronic infection but not in normal renal tissue. In pyelonephritic kidneys HBD-1 and HBD-2 expression showed a similar pattern of localizaton in distal tubules, loops of Henle and in collecting ducts of the kidney. Furthermore, real-time RT-PCR of kidney derived cell lines stimulated with inflammatory agents TNF-α, IL-1β and LPS revealed a strong increase in relative HBD-2 transcription level and also a slight increase in relative HBD-1 transcription level. CONCLUSIONS: Upregulated HBD-2 expression in renal tubulus epithelium indicates a role of a wider range of human defensins for antimicrobial host defense in the urogenital tract than previously recognized

The cost-effectiveness of domiciliary non-invasive ventilation in patients with end-stage chronic obstructive pulmonary disease:a systematic review and economic evaluation

Background: Chronic obstructive pulmonary disease (COPD) is a chronic progressive lung disease characterised by non-reversible airflow obstruction. Exacerbations are a key cause of morbidity and mortality and place a considerable burden on health-care systems. While there is evidence that patients benefit from non-invasive ventilation (NIV) in hospital during an acute exacerbation, evidence supporting home use for more stable COPD patients is limited. In the UK, domiciliary NIV is considered on health economic grounds in patients after three hospital admissions for acute hypercapnic respiratory failure. Objective: To assess the clinical effectiveness and cost-effectiveness of domiciliary NIV by systematic review and economic evaluation. Data sources: Bibliographic databases, conference proceedings and ongoing trial registries up to September 2014. Methods: Standard systematic review methods were used for identifying relevant clinical effectiveness and cost-effectiveness studies assessing NIV compared with usual care or comparing different types of NIV. Risk of bias was assessed using Cochrane guidelines and relevant economic checklists. Results for primary effectiveness outcomes (mortality, hospitalisations, exacerbations and quality of life) were presented, where possible, in forest plots. A speculative Markov decision model was developed to compare the cost-effectiveness of domiciliary NIV with usual care from a UK perspective for post-hospital and more stable populations separately. Results: Thirty-one controlled effectiveness studies were identified, which report a variety of outcomes. For stable patients, a modest volume of evidence found no benefit from domiciliary NIV for survival and some non-significant beneficial trends for hospitalisations and quality of life. For post-hospital patients, no benefit from NIV could be shown in terms of survival (from randomised controlled trials) and findings for hospital admissions were inconsistent and based on limited evidence. No conclusions could be drawn regarding potential benefit from different types of NIV. No cost-effectiveness studies of domiciliary NIV were identified. Economic modelling suggested that NIV may be cost-effective in a stable population at a threshold of £30,000 per quality-adjusted life-year (QALY) gained (incremental cost-effectiveness ratio £28,162), but this is associated with uncertainty. In the case of the post-hospital population, results for three separate base cases ranged from usual care dominating to NIV being cost-effective, with an incremental cost-effectiveness ratio of less than £10,000 per QALY gained. All estimates were sensitive to effectiveness estimates, length of benefit from NIV (currently unknown) and some costs. Modelling suggested that reductions in the rate of hospital admissions per patient per year of 24% and 15% in the stable and post-hospital populations, respectively, are required for NIV to be cost-effective. Limitations: Evidence on key clinical outcomes remains limited, particularly quality-of-life and long-term (> 2 years) effects. Economic modelling should be viewed as speculative because of uncertainty around effect estimates, baseline risks, length of benefit of NIV and limited quality-of-life/utility data. Conclusions: The cost-effectiveness of domiciliary NIV remains uncertain and the findings in this report are sensitive to emergent data. Further evidence is required to identify patients most likely to benefit from domiciliary NIV and to establish optimum time points for starting NIV and equipment settings. Future work recommendations: The results from this report will need to be re-examined in the light of any new trial results, particularly in terms of reducing the uncertainty in the economic model. Any new randomised controlled trials should consider including a sham non-invasive ventilation arm and/or a higher- and lower-pressure arm. Individual participant data analyses may help to determine whether or not there are any patient characteristics or equipment settings that are predictive of a benefit of NIV and to establish optimum time points for starting (and potentially discounting) NIV. Study registration: This study is registered as PROSPERO CRD42012003286. Funding: The National Institute for Health Research Health Technology Assessment programme

Growth and Survival of Nearshore Fishes in Lake Michigan

F-138-R-2 issued October 1, 2000Report issued on: October 1, 2000INHS Technical Report prepared for Division of Fisheries, Illinois Department of Natural Resource

Cyclones Affect Vocalization and the Marine Soundscape Within a Blue Hole

Tropical cyclones are a major disturbance on nearshore marine and reef communities, which are highly valuable for their biodiversity and for commercial and recreational purposes. The increasing study of soundscape ecology and the usefulness of sound in the marine environment has led to growing awareness of factors altering the marine soundscape and how changes in the soundscape impact fish behavior, usually negatively. Studies have noted the input of sound from cyclones alter the marine soundscape, though these studies are mainly limited to offshore and deep-water environments. Sound has rarely been used to quantify cyclone effects on coral reefs. Here we use a long time-series of acoustic recordings to examine and quantify the effects of four tropical cyclones (hurricanes Matthew, Irma, Jose, and Maria), on the coral reef soundscape and fish vocalizations at Dean’s Blue Hole (DBH), The Bahamas. We used both root mean square and spectral analyses from the audio recorded on a 12.9s per 5 minute duty cycle, sampled at 20 kHz. We found that the hurricanes increased the sound pressure and spectrum levels on the DBH soundscape on the order of 2-6 days and across all frequencies examined (0-10 kHz). During this period, the hurricanes that were close enough to directly input high winds also showed an elevated effect on frequency range of 200 – 2000 Hz, associated with fish hearing and sound production. Vocalization behavior, identified and counted from the same recordings, significantly decreased in response to the soundscape changes in the study site across three of the four cyclones examined. This is the first record of decreased fish vocalization behavior as a direct response of the passage of close and relatively distant cyclones, as well as the first quantitative assessment of the effect of these cyclones on coral reef soundscapes. The study shows that tropical cyclones continue to impact reef soundscapes after their ephemeral passage and may further exacerbate other associated stressors on reef communities