Short-term immobilization influences use-dependent cortical plasticity and fine motor performance

Short-term immobilization that reduces muscle use for 8-10h is known to influence cortical excitability and motor performance. However, the mechanisms through which this is achieved, and whether these changes can be used to modify cortical plasticity and motor skill learning, are not known. The purpose of this study was to investigate the influence of short-term immobilization on use-dependent cortical plasticity, motor learning and retention. Twenty-one adults were divided into control and immobilized groups, both of which underwent two experimental sessions on consecutive days. Within each session, transcranial magnetic stimulation (TMS) was used to assess motor-evoked potential (MEP) amplitudes, short- (SICI) and long-interval intracortical inhibition (LICI), and intracortical facilitation (ICF) before and after a grooved pegboard task. Prior to the second training session, the immobilized group underwent 8h of left hand immobilization targeting the index finger, while control subjects were allowed normal limb use. Immobilization produced a reduction in MEP amplitudes, but no change in SICI, LICI or ICF. While motor performance improved for both groups in each session, the level of performance was greater 24-h later in control, but not immobilized subjects. Furthermore, training-related MEP facilitation was greater after, compared with before, immobilization. These results indicate that immobilization can modulate use-dependent plasticity and the retention of motor skills. They also suggest that changes in intracortical excitability are unlikely to contribute to the immobilization-induced modification of cortical excitability.George M. Opie, Alexandra Evans, Michael C. Ridding and John G. Semmle

Novel coronavirus mitigation measures implemented by radiotherapy centres in low and middle-income countries: a systematic review.

Background: The aim of the study was to identify strategies adopted by radiotherapy centres in low- and middle-income countries (LMICs) to mitigate the effects of COVID-19. Studies summarising COVID-19 mitigation strategies designed and implemented by radiotherapy centres in LMICs to avoid delays, deferrments and interruptions of radiotherapy services are lacking. Materials and methods: A systematic review was conducted and reported in accordance with the preferred reporting items for systematic review and meta-analysis guideline. Ovid Embase, Ovid MEDLINE and CINAHL were searched for peer-reviewed articles that reported measures adopted by radiotherapy centres in LMICs to reduce the risk of COVID-19. Information on different strategies were extracted from the included studies and textual narrative synthesis was conducted. Results: Of 60 articles retrieved, eleven were included. Majority of the studies were conducted in China. Ten of the included studies employed a qualitative design. Four themes were identified: preparing and equipping staff; reinforcing infection prevention and control policies; strengthening coordination and communication; and maintaining physical distancing. Studies reported that radiotherapy centres had: formed COVID-19 response multidisciplinary team; maximised the use of telehealth; adjusted the layout of waiting areas; divided staff into teams; dedicated a room for isolating suspected cases; and adopted triage systems. Conclusions: Local adaptation of established global strategies coupled with timely development of guidelines, flexibility and innovation have allowed radiotherapy leaders to continue to deliver radiotherapy services to cancer patients in LMICs during the COVID-19 crisis. Robust data collection must be encouraged in LMICs to provide an evidence-based knowledge for use in the event of another pandemic

Establishing local reference intervals for full blood count and white blood cell differential counts in Cape Town, South Africa

Background. Accurate laboratory reference intervals (RIs) are essential to differentiate between health and disease. There are variations in haematological indices within populations relating to gender, age, ethnicity and environment. Iron deficiency is common, has a wide range of clinical morbidities and affects red cell indices. Locally derived RIs for full blood count (FBC) parameters are needed for the Western Cape region of South Africa, after the exclusion of iron deficiency. In addition, information regarding the prevalence of iron deficiency in first-time blood donors would inform blood transfusion services regarding policies to screen for and treat iron deficiency.Objectives. To establish locally derived RIs for FBC and white blood cell (WBC) differential count parameters in healthy adults in the Cape Town area, by including first-time blood donors and excluding those with iron deficiency and thalassaemic indices. These new locally established RIs could update those in use by the local National Health Laboratory Service. A secondary objective was to establish the prevalence of iron deficiency in first-time blood donors. This would inform blood donation policies regarding screening and appropriate iron supplementation in high-risk groups prior to blood donation.Methods. This was a prospective, descriptive study with direct convenience sampling. Participants were prospective voluntary blood donors aged between 18 and 60 years, presenting for first-time blood donation. Ethnicity was self-identified. Participants who tested positive for HIV or hepatitis B and/or C viruses were excluded. Prospective participants with iron deficiency, defined by serum ferritin levels below the RI, and those with red cell indices suggestive of an underlying thalassaemia trait were excluded. FBC samples were analysed using a Sysmex XN-1000 cell counter. Statistical non-parametric methods were used to calculate the RIs, according to international guidelines.Results. Of the 774 participants screened, 82 (11%) had iron deficiency and were excluded. Six hundred and sixty-two patients were included for analysis, 409 (62%) female and 253 (38%) male. The majority of the participants, 348 (53%), were between 20 and 29 years of age, with a mean age of 29 years for females and 28 years for males. Participants comprised a mix of the various ethnic groups residing in Western Cape Province. The mean haemoglobin concentration for females was lower than that for males (p<0.0001). There were significant gender differences for total WBC count, absolute neutrophil count and platelet count, with females having higher counts than males.Conclusions. Locally established, population-specific RIs are essential for the accurate interpretation of haematological indices. This study established locally derived gender-specific RIs for the Cape Town region, after exclusion of iron deficiency. These new RIs have implications for the accurate diagnoses of cytopenias, cytoses and other blood count abnormalities. Iron deficiency is common in first-time blood donors, and screening for iron deficiency using point-of-care testing should be considered

Conditions for proton temperature anisotropy to drive instabilities in the solar wind

Using high-resolution data from Solar Orbiter, we investigate the plasma conditions necessary for the proton temperature anisotropy driven mirror-mode and oblique firehose instabilities to occur in the solar wind. We find that the unstable plasma exhibits dependencies on the angle between the direction of the magnetic field and the bulk solar wind velocity which cannot be explained by the double-adiabatic expansion of the solar wind alone. The angle dependencies suggest that perpendicular heating in Alfv\'enic wind may be responsible. We quantify the occurrence rate of the two instabilities as a function of the length of unstable intervals as they are convected over the spacecraft. This analysis indicates that mirror-mode and oblique firehose instabilities require a spatial interval of length greater than 2 to 3 unstable wavelengths in order to relax the plasma into a marginally stable state and thus closer to thermodynamic equilibrium in the solar wind. Our analysis suggests that the conditions for these instabilities to act effectively vary locally on scales much shorter than the correlation length of solar wind turbulence.Comment: 16 pages, 8 figures. Accepted for publication in Ap

Requirements for a Dashboard to Support Quality Improvement Teams in Pain Management

Pain management is often considered lower priority than many other aspects of health management in hospitals. However, there is potential for Quality Improvement (QI) teams to improve pain management by visualising and exploring pain data sets. Although dashboards are already used by QI teams in hospitals, there is limited evidence of teams accessing visualisations to support their decision making. This study aims to identify the needs of the QI team in a UK Critical Care Unit (CCU) and develop dashboards that visualise longitudinal data on the efficacy of patient pain management to assist the team in making informed decisions to improve pain management within the CCU. This research is based on an analysis of transcripts of interviews with healthcare professionals with a variety of roles in the CCU and their evaluation of probes. We identified two key uses of pain data: direct patient care (focusing on individual patient data) and QI (aggregating data across the CCU and over time); in this paper, we focus on the QI role. We have identified how CCU staff currently interpret information and determine what supplementary information can better inform their decision making and support sensemaking. From these, a set of data visualisations has been proposed, for integration with the hospital electronic health record. These visualisations are being iteratively refined in collaboration with CCU staff and technical staff responsible for maintaining the electronic health record. The paper presents user requirements for QI in pain management and a set of visualisations, including the design rationale behind the various methods proposed for visualising and exploring pain data using dashboards

Application of an equine composite pain scale and its association with plasma adrenocorticotropic hormone concentrations and serum cortisol concentrations in horses with colic

This study assessed the application of a modified equine composite pain scale (CPS) and identified the inter‐observer reliability. Associations between CPS scores and the measured concentrations of serum cortisol ([cortisol]) and plasma adrenocorticotrophic hormone ([ACTH]) in horses presenting with colic were determined. The study design was prospective, uni‐centred and observational. The inter‐observer reliability of the adapted CPS was determined for 59 horses hospitalised for a variety of conditions. The associations between CPS, ACTH and cortisol were assessed in a further 49 horses admitted for medical or surgical colic. During hospitalisation, blood samples were obtained each morning and analysed for serum [cortisol] and plasma [ACTH]. Horses were pain scored using the adapted CPS score. Data from the most painful time point (n = 48 horses; n = 48 [cortisol]; n = 44 [ACTH]) and all data time points (n = 49 horses and n = 133 time points) were used for analysis of association between [cortisol], [ACTH] and CPS score. The CPS score inter‐observer reliability was excellent (n = 59 horses; n = 102 pain scores; weighted kappa 0.863). CPS score and [cortisol] were positively associated at the most painful time point (P < 0.001) and at all data time points (P < 0.001). No significant association was found between CPS score and [ACTH]. [ACTH] was associated with [cortisol] (P = 0.034) when all time points were analysed but not when only the most painful point was analysed. The significant correlation identified between CPS score and [cortisol] in medical and surgical colic cases provides physiological validation of pain scores as a marker of underlying stress in horses with colic

The PGE2-Stat3 interaction in doxorubicin-induced myocardial apoptosis

Aims Both cyclooxygenase-2 (COX-2) and the transcription factor signal transducer and activator of transcription 3 (Stat3) are involved in adaptive growth and survival of cardiomyocytes. In ventricular cardiomyocytes, prostaglandin E2 (PGE2), a major COX-2 product, leads to adaptive growth via Stat3 activation, but whether this transcription factor acts as a signalling molecule in PGE2-induced cell survival is unknown. Therefore, the purpose of this study was to determine whether PGE2 counteracts cardiac apoptosis induced by doxorubicin (DOX), and if so, whether Stat3 plays a critical role in this cardioprotective effect. Methods and results Neonatal rat ventricular cardiomyocytes were incubated with DOX (0.5 µM) and/or PGE2 (1 µM). Apoptosis was assessed by determining caspase3 activation and apoptotic DNA fragmentation. The role of Stat3 was evaluated in vitro and in vivo by transfecting cardiomyocytes with siRNA targeting rat Stat3 and by using cardiomyocyte-restricted Stat3 knockout (Stat3 KO) mice, respectively. Incubation of ventricular cardiomyocytes with PGE2 led to a time-dependent decrease in the DOX-induced caspase3 activation, reaching a maximal inhibition of 70 ± 5% after 4 h. Similarly, PGE2 inhibited DOX-induced DNA fragmentation by 58 ± 5% after 24 h. This antiapoptotic action of PGE2 was strongly reduced by the ERK1/2 inhibitor, U0126, whereas the p38 MAP kinase inhibitor, SB203580, had no effect. Depleting Stat3 expression by 50-60% in isolated ventricular cardiomyocytes markedly reduced the protective effect of PGE2 on DOX-induced caspase3 activation and DNA fragmentation. Likewise, the stable PGE2 analogue, 16,16-dimethyl-PGE2, was unable to counteract cardiac apoptosis induced by DOX in Stat3 KO mice. Conclusion Our results demonstrate that PGE2 prevents myocardial apoptosis induced by DOX. This protection requires the activation of the prosurvival pathways of Stat3 and ERK1/

Preventing mental health problems in offspring by targeting dietary intake of pregnant women

The concept of \u27early life programming\u27 considers the importance of very early environmental exposures throughout the gestational period on the subsequent health outcomes of offspring. The role of maternal dietary intake, specifically, has been highlighted after recent studies have shown maternal diet quality to predict mental health problems in offspring. Even in the pre-conception period, maternal nutrition can have permanent and sustained phenotypic consequences for offspring

Screening for primary aldosteronism- normal ranges for aldosterone and renin in three South African population groups

Objective. To establish normal ranges for plasma aldosterone, renin and aldosterone / renin (A/ R) ratio in South African normotensives under typical ou tpatient conditions, and to estimate the prevalence of primary aldosteronism (PA) among hypertensives in primary care settings.Design and methods. One hundred and thirty-six normotensive subjects and 154 sex- and age-matched hypertensives at three primary care clinics had measurements of blood pressure, plasma creatinine, K+, aldosterone, plasma renin activity, and spot urine for urinary Na+/ creatinine ratio. Medication was not withdrawn before testing.Results. Mean plasma renin activity in black normotensive subjects (0.95 ± 1.25 ng/ ml/ h, mean± standard deviation (SD)) was significantly lower than in white (2.09 ± 1.12 ng/ ml/ h; P &lt; 0.0001) and coloured (1.81 ± 1.86 ng/ ml/ h, P = 0.013) normotensives. Mean plasma aldosterone in black normotensives (306 ± 147 pmol/ 1) was also significantly lower than in white (506 ± 324 pmol/1, P = 0.0002) and coloured (418 ± 304 pmol/1, P = 0.0148) normotensives. In hypertensives, there were no significant differences in renin or aldosterone levels between the three population groups. Urinary Na+ /creatinine ratios, an index of Na+ intake, were not significantly different in the three population groups. None of the normotensives had an A/R ratio ≥ 1 000 plus aldosterone ≥ 750, while 7.1% of hypertensives exceeded these levels, suggesting that they are appropriate criteria for screening for PA.Conclusions. A large fraction of black normotensive subjects had low renin and aldosterone levels compared with whites, suggesting a salt-retaining tendency in black subjects. These results have important implications for the interpretation of plasma renin and aldosterone levels in hypertensive patients. In primary care settings, 7.1% of hypertensives had biochemical results indicating the need for investigation of PA