Physiological Characterization Of Protoplasts Of Zea Mays L And Hyoscyamus Muticus L

Protoplasts isolated from the economically important grasses do not readily divide in culture. This is especially true of Zea mays L. from which only one cell line, B73, has been established from a primary protoplast culture. The cell line is not morphogenetic and has cytogenetic abnormalities. The early physiological events of cell wall regeneration and DNA synthesis in protoplast cultures of Zea mays L. (cultivar Seneca 60), the B73 maize cell line and Hyoscyamus muticus L. were studied to compare the non-regenerating primary protoplast culture of Zea mays with two regenerating protoplast populations, B73 and H. muticus.;Cell wall regeneration and DNA synthesis in the cultured protoplasts were analyzed with fluorescent dyes on a fluorescence activated cell sorter, the FACS II. Cell walls were stained with Calcofluor White. DNA content was measured by the binding of Hoechst 33258, a quantitative fluorochrome for DNA.;The fluorescence activated cell sorter (FACS II) operates by passing stained cells in a flow stream past an argon-krypton laser beam and measuring the relative size of each cell given by the low angle, forward light scatter and the amount of fluorescence of each cell. Approximately 2.5 x 10(\u274) cells per second can be analyzed, and the data from 10(\u275) cells were collected.;Survival studies on the three cultures showed protoplast death in the early days of culture. Analysis of DNA showed that all three cultures had protoplasts in G1 and G2 of the cell cycle and that the loss of protoplasts preferentially occurred among G2 protoplasts. All cultures, after day 3 showed an increase of G2 protoplasts indicating that DNA synthesis was occurring in all populations. Se60 protoplasts showed a third peak of DNA content that occurred at less than the G1 peak and, presumably, represented degenerating cells. Hyoscyamus and B73 protoplasts did not show this peak.;Hyoscyamus and B73 protoplasts both showed cell wall fluorescence and both had subpopulations having varying rates of cell wall synthesis. Se60 showed a very small peak of increased synthesis on day 4 of culture but this population was lost by day 6

What factors influence adherence and non-adherence to multi-drug therapy for the treatment of leprosy within the World Health Organisation South East Asia region? A systematic review

Introduction Leprosy is an infection caused by Mycobacterium leprae. Despite curative treatment being available, leprosy is still prevalent worldwide, with little change in annual cases observed in the past decade. The WHO South East Asia region is the worst affected, accounting for over 70% of new cases. One reason leprosy transmission still occurs is non-adherence to multi-drug therapy. This project aims to determine the factors that influence adherence. Methods A systematic review was performed using 6 databases. This returned 402 unique results. Screening of the title and abstract resulted in 362 of these being excluded. From the remaining 40, full-text analysis identified 17 studies that met the inclusion criteria and formed the review. Both qualitative and quantitative methods of collecting and analyzing data were used to form a non-quantitative synthesis of the findings. Results Four factors influenced adherence: medication-related, healthcare-related, patient-related and society-related. From these, lack of knowledge about leprosy and multi-drug therapy was a predominant barrier to adherence, which related to all of these factors. Stigma and being female were also seen as important barriers to adherence - these manifested in numerous ways. Conclusion The review identified diverse barriers to adherence to MDT and no simple intervention will overcome these. Rather, wider issues such as continuous access to healthcare (particularly for women), stigma reduction and patient education need to be addressed. Improving these will increase patient confidence in, and access to, MDT, which will ultimately result in improved adherence to therapy

Indigenous Voice Closing the Gap and Putting Communication for Social Change into Practice

Australian journalism schools are full of students who have never met an Aboriginal or Torres Strait Islander and who do not know their history. Journalism educators are illequipped to redress this imbalance as the large majority are themselves non-Indigenous and many have had little or no experience with the coverage of Indigenous issues. Such a situation calls for educational approaches that can overcome these disadvantages and empower journalism graduates to move beyond the stereotypes that characterise the representation of Indigenous people in the mainstream media. This paper will explore three different courses in three Australian Tertiary Journalism Education Institutions who use Work Integrated Learning approaches to instil the cultural competencies necessary to encourage a more informed reporting of Indigenous issues. The findings from the three projects illustrate the importance of adopting a collaborative approach between the industry, the Indigenous community and educators to ensure a significant impact on the students’ commitment to quality journalism practices when covering Indigenous issues

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Acceptance and Commitment Therapy plus usual care for improving quality of life in people with motor neuron disease (COMMEND) : a multicentre, parallel, randomised controlled trial in the UK

Background Motor neuron disease is a progressive, fatal neurodegenerative disease for which there is no cure. Acceptance and Commitment Therapy (ACT) is a psychological therapy incorporating acceptance, mindfulness, and behaviour change techniques. We aimed to evaluate the effectiveness of ACT plus usual care, compared with usual care alone, for improving quality of life in people with motor neuron disease. Methods We conducted a parallel, multicentre, two-arm randomised controlled trial in 16 UK motor neuron disease care centres or clinics. Eligible participants were aged 18 years or older with a diagnosis of definite or laboratory-supported probable, clinically probable, or possible familial or sporadic amyotrophic lateral sclerosis; progressive muscular atrophy; or primary lateral sclerosis; which met the World Federation of Neurology's El Escorial diagnostic criteria. Participants were randomly assigned (1:1) to receive up to eight sessions of ACT adapted for people with motor neuron disease plus usual care or usual care alone by a web-based system, stratified by site. Participants were followed up at 6 months and 9 months post-randomisation. Outcome assessors and trial statisticians were masked to treatment allocation. The primary outcome was quality of life using the McGill Quality of Life Questionnaire-Revised (MQOL-R) at 6 months post-randomisation. Primary analyses were multi-level modelling and modified intention to treat among participants with available data. This trial was pre-registered with the ISRCTN Registry (ISRCTN12655391). Findings Between Sept 18, 2019, and Aug 31, 2022, 435 people with motor neuron disease were approached for the study, of whom 206 (47%) were assessed for eligibility, and 191 were recruited. 97 (51%) participants were randomly assigned to ACT plus usual care and 94 (49%) were assigned to usual care alone. 80 (42%) of 191 participants were female and 111 (58%) were male, and the mean age was 63·1 years (SD 11·0). 155 (81%) participants had primary outcome data at 6 months post-randomisation. After controlling for baseline scores, age, sex, and therapist clustering, ACT plus usual care was superior to usual care alone for quality of life at 6 months (adjusted mean difference on the MQOL-R of 0·66 [95% CI 0·22–1·10]; d=0·46 [0·16–0·77]; p=0·0031). Moderate effect sizes were clinically meaningful. 75 adverse events were reported, 38 of which were serious, but no adverse events were deemed to be associated with the intervention. Interpretation ACT plus usual care is clinically effective for maintaining or improving quality of life in people with motor neuron disease. As further evidence emerges confirming these findings, health-care providers should consider how access to ACT, adapted for the specific needs of people with motor neuron disease, could be provided within motor neuron disease clinical services

Efficacy and safety of baricitinib or ravulizumab in adult patients with severe COVID-19 (TACTIC-R): a randomised, parallel-arm, open-label, phase 4 trial

Background From early in the COVID-19 pandemic, evidence suggested a role for cytokine dysregulation and complement activation in severe disease. In the TACTIC-R trial, we evaluated the efficacy and safety of baricitinib, an inhibitor of Janus kinase 1 (JAK1) and JAK2, and ravulizumab, a monoclonal inhibitor of complement C5 activation, as an adjunct to standard of care for the treatment of adult patients hospitalised with COVID-19. Methods TACTIC-R was a phase 4, randomised, parallel-arm, open-label platform trial that was undertaken in the UK with urgent public health designation to assess the potential of repurposing immunosuppressants for the treatment of severe COVID-19, stratified by a risk score. Adult participants (aged ≥18 years) were enrolled from 22 hospitals across the UK. Patients with a risk score indicating a 40% risk of admission to an intensive care unit or death were randomly assigned 1:1:1 to standard of care alone, standard of care with baricitinib, or standard of care with ravulizumab. The composite primary outcome was the time from randomisation to incidence (up to and including day 14) of the first event of death, invasive mechanical ventilation, extracorporeal membrane oxygenation, cardiovascular organ support, or renal failure. The primary interim analysis was triggered when 125 patient datasets were available up to day 14 in each study group and we included in the analysis all participants who were randomly assigned. The trial was registered on ClinicalTrials.gov (NCT04390464). Findings Between May 8, 2020, and May 7, 2021, 417 participants were recruited and randomly assigned to standard of care alone (145 patients), baricitinib (137 patients), or ravulizumab (135 patients). Only 54 (39%) of 137 patients in the baricitinib group received the maximum 14-day course, whereas 132 (98%) of 135 patients in the ravulizumab group received the intended dose. The trial was stopped after the primary interim analysis on grounds of futility. The estimated hazard ratio (HR) for reaching the composite primary endpoint was 1·11 (95% CI 0·62–1·99) for patients on baricitinib compared with standard of care alone, and 1·53 (0·88–2·67) for ravulizumab compared with standard of care alone. 45 serious adverse events (21 deaths) were reported in the standard-of-care group, 57 (24 deaths) in the baricitinib group, and 60 (18 deaths) in the ravulizumab group. Interpretation Neither baricitinib nor ravulizumab, as administered in this study, was effective in reducing disease severity in patients selected for severe COVID-19. Safety was similar between treatments and standard of care. The short period of dosing with baricitinib might explain the discrepancy between our findings and those of other trials. The therapeutic potential of targeting complement C5 activation product C5a, rather than the cleavage of C5, warrants further evaluation