Additive antibacterial activity of naringenin and antibiotic combinations against multidrug resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus has been causing numerous problems in the health care sector. This is mainly due to its ability to develop resistance to a number of antibiotics used to treat staphylococcal infections. Medicinal plants have been used to treat various ailments over the years and are generating a lot of interest as alternative treatment options. Naringenin is a plant derived flavonoid that possesses antibacterial properties, among others. This study assessed the effect of combinations of naringenin and four antibiotics against two Staphylococcus aureus strains. The minimum inhibitory concentrations were determined using the disk diffusion and broth microdilution assays. In the disk diffusion assay, naringenin did not inhibit bacterial growth, nor did it enhance the antibacterial activity of the antibiotics in the combination study. This was attributed to its slow rate of diffusion out of the disks. On the contrary, in the broth microdilution assay, naringenin exhibited additive effects when combined with the antibiotics (at sub-inhibitory concentrations). These results show the potential of naringenin as an antibacterial agent. Furthermore, the additive effects observed at low naringenin concentrations showed that it can potentially be used in combination with antibiotics against multidrug resistant bacteria

Calibration of stochastic computer simulators using likelihood emulation

We calibrate a stochastic computer simulation model of ‘moderate’ computational expense. The simulator is an imperfect representation of reality, and we recognise this discrepancy to ensure a reliable calibration. The calibration model combines a Gaussian process emulator of the likelihood surface with importance sampling. Changing the discrepancy specification changes only the importance weights, which lets us investigate sensitivity to different discrepancy specifications at little computational cost. We present a case study of a natural history model that has been used to characterise UK bowel cancer incidence. Data sets and computer code are provided as supplementary material

A cholinergic neuroskeletal interface promotes bone formation during postnatal growth and exercise.

The autonomic nervous system is a master regulator of homeostatic processes and stress responses. Sympathetic noradrenergic nerve fibers decrease bone mass, but the role of cholinergic signaling in bone has remained largely unknown. Here, we describe that early postnatally, a subset of sympathetic nerve fibers undergoes an interleukin-6 (IL-6)-induced cholinergic switch upon contacting the bone. A neurotrophic dependency mediated through GDNF-family receptor-α2 (GFRα2) and its ligand, neurturin (NRTN), is established between sympathetic cholinergic fibers and bone-embedded osteocytes, which require cholinergic innervation for their survival and connectivity. Bone-lining osteoprogenitors amplify and propagate cholinergic signals in the bone marrow (BM). Moderate exercise augments trabecular bone partly through an IL-6-dependent expansion of sympathetic cholinergic nerve fibers. Consequently, loss of cholinergic skeletal innervation reduces osteocyte survival and function, causing osteopenia and impaired skeletal adaptation to moderate exercise. These results uncover a cholinergic neuro-osteocyte interface that regulates skeletogenesis and skeletal turnover through bone-anabolic effects

ShORRT (Short, all-Oral Regimens for Rifampicin-resistant Tuberculosis) Research Package

TDR in close collaboration with the Global TB Programme at WHO and technical partners the WHO Global TB Programme is leading the development of ShORRT (Short, all-Oral Regimens For Rifampicin-resistant Tuberculosis), an operational research package to assess the effectiveness, safety, feasibility, acceptability, cost and impact (including on health-related quality of life) of the use of all-oral shorter drug regimens for adults and children with MDR/RR-TB

The clinical effectiveness of a physiotherapy delivered physical and psychological group intervention for older adults with neurogenic claudication: the BOOST randomised controlled trial.

This is the final version. Available from Oxford University Press via the DOI in this record. BACKGROUND: Neurogenic claudication (NC) is a debilitating spinal condition affecting older adults' mobility and quality of life. METHODS: A randomised controlled trial of 438 participants evaluated the effectiveness of a physical and psychological group intervention (BOOST programme) compared to physiotherapy assessment and tailored advice (best practice advice [BPA]) for older adults with NC. Participants were identified from spinal clinics (community and secondary care) and general practice records and randomised 2:1 to the BOOST programme or BPA. The primary outcome was the Oswestry Disability Index (ODI) at 12 months. Data was also collected at 6 months. Other outcomes included ODI walking item, 6-minute walk test (6MWT) and falls. The primary analysis was intention-to-treat. RESULTS: The average age of participants was 74.9 years (SD 6.0) and 57% (246/435) were female. There was no significant difference in ODI scores between treatment groups at 12 months (adjusted mean difference (MD): -1.4 [95% Confidence Intervals (CI) -4.03, 1.17]), but, at 6 months, ODI scores favoured the BOOST programme (adjusted MD: -3.7 [95% CI -6.27, -1.06]). At 12 months, the BOOST programme resulted in greater improvements in walking capacity (6MWT MD 21.7m [95% CI 5.96, 37.38]) and ODI walking item (MD -0.2 [95% CI -0.45, -0.01]) and reduced falls risk (odds ratio 0.6 [95% CI 0.40, 0.98]) compared to BPA. No serious adverse events were related to either treatment. CONCLUSIONS: The BOOST programme substantially improved mobility for older adults with NC. Future iterations of the programme will consider ways to improve long-term pain related disability.National Institute for Health Research (NIHR

The Clinical Effectiveness of a Physiotherapy Delivered Physical and Psychological Group Intervention for Older Adults With Neurogenic Claudication: The BOOST Randomized Controlled Trial

Background Neurogenic claudication (NC) is a debilitating spinal condition affecting older adults’ mobility and quality of life. Methods A randomized controlled trial of 438 participants evaluated the effectiveness of a physical and psychological group intervention (BOOST program) compared to physiotherapy assessment and tailored advice (best practice advice [BPA]) for older adults with NC. Participants were identified from spinal clinics (community and secondary care) and general practice records and randomized 2:1 to the BOOST program or BPA. The primary outcome was the Oswestry Disability Index (ODI) at 12 months. Data were also collected at 6 months. Other outcomes included ODI walking item, 6-minute walk test (6MWT), and falls. The primary analysis was intention-to-treat. Results The average age of participants was 74.9 years (standard deviation [SD] 6.0) and 57% (246/435) were female. There was no significant difference in ODI scores between treatment groups at 12 months (adjusted mean difference [MD]: −1.4 [95% confidence intervals (CI) −4.03, 1.17]), but, at 6 months, ODI scores favored the BOOST program (adjusted MD: −3.7 [95% CI −6.27, −1.06]). At 12 months, the BOOST program resulted in greater improvements in walking capacity (6MWT MD: 21.7m [95% CI 5.96, 37.38]) and ODI walking item (MD: −0.2 [95% CI −0.45, −0.01]) and reduced falls risk (odds ratio: 0.6 [95% CI 0.40, 0.98]) compared to BPA. No serious adverse events were related to either treatment. Conclusions The BOOST program substantially improved mobility for older adults with NC. Future iterations of the program will consider ways to improve long-term pain-related disability. Clinical Trials Registration Number: ISRCTN1269867

BrAPI-an application programming interface for plant breeding applications

Motivation: Modern genomic breeding methods rely heavily on very large amounts of phenotyping and genotyping data, presenting new challenges in effective data management and integration. Recently, the size and complexity of datasets have increased significantly, with the result that data are often stored on multiple systems. As analyses of interest increasingly require aggregation of datasets from diverse sources, data exchange between disparate systems becomes a challenge. Results: To facilitate interoperability among breeding applications, we present the public plant Breeding Application Programming Interface (BrAPI). BrAPI is a standardized web service API specification. The development of BrAPI is a collaborative, community-based initiative involving a growing global community of over a hundred participants representing several dozen institutions and companies. Development of such a standard is recognized as critical to a number of important large breeding system initiatives as a foundational technology. The focus of the first version of the API is on providing services for connecting systems and retrieving basic breeding data including germplasm, study, observation, and marker data. A number of BrAPI-enabled applications, termed BrAPPs, have been written, that take advantage of the emerging support of BrAPI by many databases

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

An assessment of Emotional Intelligence in M.Pharm. undergraduates

Background: Emotional Intelligence (EI) is the ability to perceive, understand and manage emotions. Higher EI is associated with effective leadership and improved patient outcomes (Sfantou et al., 2017). EI may be developed through training, however the majority of UK pharmacy schools do not explicitly teach leadership. An assessment of M.Pharm. students’ EI may determine whether current teaching supports EI development. Aims: To measure M.Pharm. students’ EI and explore any variation between and within year groups. Method: All M.Pharm. students at one UK university were invited to complete the short form trait EI questionnaire (TEIQue-SF) online (Petrides, 2009). TEIQue-SF measures an overall global trait EI score and produces separate scores in four domains: well-being, self-control, emotionality and sociability. Participants rated their agreement with 30 statement items on a 7- point Likert scale (1 = strongly disagree, 7 = strongly agree). A mean score was calculated for each measure with higher scores indicating greater EI. An open question was included to capture leadership experience. Descriptive and inferential statistics were used to characterise participant responses and explore the relationship with leadership experience. Results: Eighty-two (22%) students participated and the mean ± SD EI score was 5.02 ± 0.7. There was no correlation between EI and year of study. Mean EI score was higher in students with self-identified leadership experience (5.10 ± 0.61) than those without (4.61 ± 0.13, ISTT, p<0.001). Figure 1 illustrates the distribution of domain scores across the different cohorts. Statistical analysis of EI scores across the four domains was prohibited due to the distribution of response. Figure 1: Distribution of EI domain scores by cohort Conclusion: Possible explanations for the higher EI scores in those with leadership experience include that those with higher EI are more likely to seek leadership positions or that leadership experience supports the development of higher EI. Further investigation is required to explore how the M.Pharm. degree can support EI development

Testing of Eight Medicinal Plant Extracts in Combination with Kresoxim-Methyl for Integrated Control of Botrytis cinerea in Apples

Botrytis cinerea is a fungus that causes gray mold on many fruit crops. Despite the availability of a large number of botryticides, the chemical control of gray mold has been hindered by the emergence of resistant strains. In this paper, tests were done to determine the botryticidal efficacy of selected plant extracts alone or combined with kresoxim-methyl. In total, eight South African medicinal plants viz Artemisia afra, Elyptropappus rhinocerotis, Galenia africana, Hypoxis hemerocallidea, Siphonochilus aetheopicus, Sutherlandia frutescens, Tulbaghia violacea and Tulbaghia alliacea were screened. Allium sativum, a plant species known to have antifungal activity, was included in the in vivo studies. For the in vitro studies, synergistic interactions between the plant extracts and the kresoxim-methyl fungicide were tested with radial growth assays. Data indicated synergistic inhibitory effects between the fungicide and the plant extracts. Next, different doses of plant extracts combined with kresoxim-methyl were used for decay inhibition studies on Granny Smith apples. Synergistic and additive effects were observed for many of the combinations. Even though this study was done using only one strain of B. cinerea, results showed that the tested indigenous South African plant species possess natural compounds that potentiate the activity of kresoxim-methyl