In vitro and in vivo effects of salbutamol on neutrophil function in acute lung injury

Background: Intravenous salbutamol (albuterol) reduces lung water in patients with the acute respiratory distress syndrome (ARDS). Experimental data show that it also reduces pulmonary neutrophil accumulation or activation and inflammation in ARDS. Aim: To investigate the effects of salbutamol on neutrophil function. Methods: The in vitro effects of salbutamol on neutrophil function were determined. Blood and bronchoalveolar lavage (BAL) fluid were collected from 35 patients with acute lung injury (ALI)/ARDS, 14 patients at risk from ARDS and 7 ventilated controls at baseline and after 4 days’ treatment with placebo or salbutamol (ALI/ARDS group). Alveolar–capillary permeability was measured in vivo by thermodilution (PiCCO). Neutrophil activation, adhesion molecule expression and inflammatory cytokines were measured. Results: In vitro, physiological concentrations of salbutamol had no effect on neutrophil chemotaxis, viability or apoptosis. Patients with ALI/ARDS showed increased neutrophil activation and adhesion molecule expression compared with at risk-patients and ventilated controls. There were associations between alveolar– capillary permeability and BAL myeloperoxidase (r = 0.4, p = 0.038) and BAL interleukin 8 (r = 0.38, p = 0.033). In patients with ALI/ARDS, salbutamol increased numbers of circulating neutrophils but had no effect on alveolar neutrophils. Conclusion: At the onset of ALI/ARDS, there is increased neutrophil recruitment and activation. Physiological concentrations of salbutamol did not alter neutrophil chemotaxis, viability or apoptosis in vitro. In vivo, salbutamol increased circulating neutrophils, but had no effect on alveolar neutrophils or on neutrophil activation. These data suggest that the beneficial effects of salbutamol in reducing lung water are unrelated to modulation of neutrophil-dependent inflammatory pathways

Different cell types in Neurospora crassa

Neurospora possesses more cell types than are commonly recognized. We have been able to identify 28 morphologically distinct types. Having the cell types clearly defined will be important for genome annotation, describing new mutant phenotypes, and determining sites of gene expression

Effects of mental health training on capacity, willingness and engagement in peer-to-peer support in rural New South Wales

ISSUE ADDRESSED: Rural Australians experience significant barriers in accessing mental health services, some of which may be overcome by increasing mental health literacy in rural communities. This paper evaluates Mental Health Support Skills (MHSS), short training courses developed by the Rural Adversity Mental Health Program (RAMHP). MHSS was designed to build the capacity of community members and gatekeepers to identify people with mental health concerns and link them to appropriate resources or services. METHODS: Program data from April 2017 to March 2020 were analysed to assess the reach and outcomes of MHSS training. Training feedback was collected through a post‐training survey, completed directly after courses, and a follow‐up survey two months after training. An app used by RAMHP coordinators (the trainers) recorded the geographic and demographic reach of courses. RESULTS: MHSS was provided to 10,208 residents across rural New South Wales. Survey participation was 49% (n = 4,985) for the post‐training survey and 6% (n = 571), for the follow‐up survey, two months post‐training. The training was well‐received and increased the mental health understanding and willingness to assist others of most respondents (91%‐95%). Follow‐up survey respondents applied learnings to assist others; 53% (n = 301) asked a total of 2,252 people about their mental health in the two months following training. Those in clinical roles asked a median of 6 people about their mental health, compared to 3 for those in nonclinical roles. Most follow‐up survey respondents (59%, n = 339) reported doing more to look after their own mental health in the two months after training. CONCLUSION: These results are encouraging as they suggest that short‐form mental health training can be an effective tool to address poorer mental health outcomes for rural residents by improving the ability of participants to help themselves and the people around them. SO WHAT? Serious consideration should be given to short mental health courses, such as MHSS, to increase literacy and connection to services, especially in rural areas

Hydrophilic and lipophilic radiopharmaceuticals as tracers in pharmaceutical development: In vitro – In vivo studies

BACKGROUND: Scintigraphic studies have been performed to assess the release, both in vitro and in vivo, of radiotracers from tablet formulations. Four different tracers with differing physicochemical characteristics have been evaluated to assess their suitability as models for drug delivery. METHODS: In-vitro disintegration and dissolution studies have been performed at pH 1, 4 and 7. In-vivo studies have been performed by scintigraphic imaging in healthy volunteers. Two hydrophilic tracers, ((99m)Tc-DTPA) and ((99m)Tc-MDP), and two lipophilic tracers, ((99m)Tc-ECD) and ((99m)Tc-MIBI), were used as drug models. RESULTS: Dissolution and disintegration profiles, differed depending on the drug model chosen. In vitro dissolution velocity constants indicated a probable retention of the radiotracer in the formulation. In vivo disintegration velocity constants showed important variability for each radiopharmaceutical. Pearson statistical test showed no correlation between in vitro drug release, and in vivo behaviour, for (99m)Tc-DTPA, (99m)Tc-ECD and (99m)Tc-MIBI. High correlation coefficients were found for (99m)Tc-MDP not only for in vitro dissolution and disintegration studies but also for in vivo scintigraphic studies. CONCLUSION: Scintigraphic studies have made a significant contribution to the development of drug delivery systems. It is essential, however, to choose the appropriate radiotracers as models of drug behaviour. This study has demonstrated significant differences in release patterns, depending on the model chosen. It is likely that each formulation would require the development of a specific model, rather than being able to use a generic drug model on the basis of its physicochemical characteristics

The No-Triangle Hypothesis for N=8 Supergravity

We study the perturbative expansion of N=8 supergravity in four dimensions from the viewpoint of the ``no-triangle'' hypothesis, which states that one-loop graviton amplitudes in N=8 supergravity only contain scalar box integral functions. Our computations constitute a direct proof at six-points and support the no-triangle conjecture for seven-point amplitudes and beyond.Comment: 43page

Nuclear medicine procedures and the evaluation of male sexual organs: a short review

Sexuality consists of three aspects that are interrelated and inseparable, biological, physiological and social. The biological aspect considers the individual's capability to give and to receive pleasure. In consequence, it covers the functionality of the sexual organs and the physiology of human sexual response cycle. Diagnostic imaging modalities, such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) have been used to evaluate clinical disorders of the male reproductive system. PET and SPECT procedures basically involve the administration of a radiopharmaceutical that has a higher uptake in a specific tumor or tissue. The aim of this brief review is to present some radiopharmaceuticals that have been used in the clinical evaluation of the male sexual organs (testes, prostate, seminal vesicles, penis) related with male sexuality. This information could be useful in better understanding the male sexual response cycle, as well as the sexual disorders, when considering the male sexual organs and the pelvic floor. Moreover, the findings obtained with PET and SPECT imaging could help to evaluate the efficacy of clinical results of therapeutic procedures. In conclusion, the knowledge from these images could aid in better understanding the physiology of the different organs related with sexuality. Furthermore, they could be important tools to evaluate the physiological integrity of the involved organs, to improve clinical strategies and to accompany the patients under treatment

Musicians’ perceptions and experiences of using simulation training to develop performance skills

Simulation has been applied as a tool for learning and training in sports, psychology and medicine for some time, but its current use and potential for training musicians is less well understood. The aim of this study was to explore musicians’ perceptions and experiences of using simulated performance environments. Nine conservatory students performed in two simulations, each with interactive virtual elements and vivid environmental cues: a recital with a virtual audience and an audition with virtual judges. Qualitative data were collected through a focus group interview and written reflective commentaries. Thematic analysis highlighted the musicians’ experiences in terms of (1) their anticipation of using the simulations, (2) the process of performing in the simulations, (3) the usefulness of simulation as a tool for developing performance skills and (4) ways of improving simulation training. The results show that while simulation was new to the musicians and individual levels of immersion differed, the musicians saw benefits in the approach for developing, experimenting with and enhancing their performance skills. Specifically, the musicians emphasised the importance of framing the simulation experience with plausible procedures leading to and following on from the performance, and they recognised the potential for combining simulation with complementary training techniques

Integrated multi-level quality control for proteomic profiling studies using mass spectrometry

BACKGROUND: Proteomic profiling using mass spectrometry (MS) is one of the most promising methods for the analysis of complex biological samples such as urine, serum and tissue for biomarker discovery. Such experiments are often conducted using MALDI-TOF (matrix-assisted laser desorption/ionisation time-of-flight) and SELDI-TOF (surface-enhanced laser desorption/ionisation time-of-flight) MS. Using such profiling methods it is possible to identify changes in protein expression that differentiate disease states and individual proteins or patterns that may be useful as potential biomarkers. However, the incorporation of quality control (QC) processes that allow the identification of low quality spectra reliably and hence allow the removal of such data before further analysis is often overlooked. In this paper we describe rigorous methods for the assessment of quality of spectral data. These procedures are presented in a user-friendly, web-based program. The data obtained post-QC is then examined using variance components analysis to quantify the amount of variance due to some of the factors in the experimental design. RESULTS: Using data from a SELDI profiling study of serum from patients with different levels of renal function, we show how the algorithms described in this paper may be used to detect systematic variability within and between sample replicates, pooled samples and SELDI chips and spots. Manual inspection of those spectral data that were identified as being of poor quality confirmed the efficacy of the algorithms. Variance components analysis demonstrated the relatively small amount of technical variance attributable to day of profile generation and experimental array. CONCLUSION: Using the techniques described in this paper it is possible to reliably detect poor quality data within proteomic profiling experiments undertaken by MS. The removal of these spectra at the initial stages of the analysis substantially improves the confidence of putative biomarker identification and allows inter-experimental comparisons to be carried out with greater confidence