569 research outputs found
Glucocorticoid receptor mRNA ontogeny in the fetal and postnatal rat forebrain.
Glucocorticoid receptor (GR) ontogeny and distribution in postnatal rat brain have been demonstrated, but onset and distribution of GR gene expression during fetal life has not been reported. This study focuses on the distribution of GR-mRNA in the fetal and postnatal rat forebrain, with emphasis on hypothalamic and limbic structures. Time pregnant rats were decapitated at 8:30-9:30 AM on Gestational Days 14 (F14), F16, F17, F18, and F19. Postnatally, rats were sacrificed on Days 1, 4, 6, 10, and 16. Cryostat sections were subjected to in situ hybridization, using a cRNA probe directed to the GR-mRNA. GR-mRNA was detectible in the hippocamposeptal formation as early as F14. By F16, GR gene expression was evident in the hypothalamic paraventricular nucleus (PVN) as well. During late gestation (F17-F19), GR-mRNA was localized also in the thalamus, hippocampus, amygdala, and discrete cortical regions. Postnatally, GR-mRNA abundance was high in the PVN, CA1/CA2 hippocampal field, piriform cortex and dorsal endopiriform nucleus, specific amygdaloid nuclei, and the suprachiasmatic nucleus. In PVN, GR-mRNA was present prior to the onset of CRH gene expression (F17), which may suggest a role for GR in neuronal differentiation
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Effects of a specific glucocorticoid receptor antagonist on corticotropin releasing hormone gene expression in the paraventricular nucleus of the neonatal rat.
Mechanisms controlling the synthesis of corticotropin releasing hormone (CRH) in neonatal rats, and the ontogeny of glucocorticoid (GC) feedback control of hypothalamic CRH remain unknown. Specific issues are whether stress induces up-regulation of CRH gene expression during the first postnatal week, and the role of GC feedback, at the hypothalamic level, in the stress-hyporesponsive period. We studied the ontogeny of the negative feedback regulation of CRH gene expression by GC in the paraventricular nucleus (PVN). We implanted chronic cannulae containing a GC-receptor antagonist, RU 38486, in rats on postnatal days 3 to 13. Three days later, animals were sacrificed, and brains were analyzed for CRH-messenger RNA (CRH-mRNA), using semi-quantitative in situ hybridization. Animals implanted with cholesterol-containing cannulae served to evaluate the stressful effect of implantation on CRH-mRNA abundance. The presence of GC receptor messenger RNA (GR-mRNA) in the PVN of neonatal rats was also determined. RU 38486 did not increase CRH-mRNA abundance during the first postnatal week, despite the presence of GR-mRNA in the PVN. Chronic-implantation stress also failed to increase CRH synthesis. CRH gene expression in the PVN was enhanced in infant rats implanted with RU-38486 on postnatal day 9 or later. Cholesterol implantation on days 9, 10 (but not later), resulted in increased PVN-CRH-mRNA. Thus, CRH-mRNA is up-regulated by chronic blockade of GC receptors only subsequent to the eighth postnatal day. Furthermore, such blockade does not affect the response of CRH-mRNA to chronic stress in the neonatal rat
Gaze training enhances laparoscopic technical skill acquisition and multi-tasking performance: A randomized, controlled study
Background: The operating room environment is replete with stressors and distractions that increase the attention demands of what are already complex psychomotor procedures. Contemporary research in other fields (e.g., sport) has revealed that gaze training interventions may support the development of robust movement skills. This current study was designed to examine the utility of gaze training for technical laparoscopic skills and to test performance under multitasking conditions. Methods: Thirty medical trainees with no laparoscopic experience were divided randomly into one of three treatment groups: gaze trained (GAZE), movement trained (MOVE), and discovery learning/control (DISCOVERY). Participants were fitted with a Mobile Eye gaze registration system, which measures eye-line of gaze at 25 Hz. Training consisted of ten repetitions of the "eye-hand coordination" task from the LAP Mentor VR laparoscopic surgical simulator while receiving instruction and video feedback (specific to each treatment condition). After training, all participants completed a control test (designed to assess learning) and a multitasking transfer test, in which they completed the procedure while performing a concurrent tone counting task. Results: Not only did the GAZE group learn more quickly than the MOVE and DISCOVERY groups (faster completion times in the control test), but the performance difference was even more pronounced when multitasking. Differences in gaze control (target locking fixations), rather than tool movement measures (tool path length), underpinned this performance advantage for GAZE training. Conclusions: These results suggest that although the GAZE intervention focused on training gaze behavior only, there were indirect benefits for movement behaviors and performance efficiency. Additionally, focusing on a single external target when learning, rather than on complex movement patterns, may have freed-up attentional resources that could be applied to concurrent cognitive tasks. © 2011 The Author(s).published_or_final_versionSpringer Open Choice, 21 Feb 201
Multitask training promotes automaticity of a fundamental laparoscopic skill without compromising the rate of skill learning.
A defining characteristic of expertise is automated performance of skills, which frees attentional capacity to better cope with some common intraoperative stressors. There is a paucity of research on how best to foster automated performance by surgical trainees. This study examined the use of a multitask training approach to promote automated, robust laparoscopic skills.Eighty-one medical students completed training of a fundamental laparoscopic task in either a traditional single-task training condition or a novel multitask training condition. Following training, participants' laparoscopic performance was tested in a retention test, two stress transfer tests (distraction and time pressure) and a secondary task test, which was included to evaluate automaticity of performance. The laparoscopic task was also performed as part of a formal clinical examination (OSCE).The training groups did not differ in the number of trials required to reach task proficiency (p = .72), retention of skill (ps > .45), or performance in the clinical examination (p = .14); however, the groups did differ with respect to the secondary task (p = .016). The movement efficiency (number of hand movements) of single-task trainees, but not multitask trainees, was negatively affected during the secondary task test. The two stress transfer tests had no discernable impact on the performance of either training group.Multitask training was not detrimental to the rate of learning of a fundamental laparoscopic skill and added value by providing resilience in the face of a secondary task load, indicative of skill automaticity. Further work is needed to determine the extent of the clinical utility afforded by multitask training
Perceptual impairment and psychomotor control in virtual laparoscopic surgery
Background: It is recognised that one of the major difficulties in performing laparoscopic surgery is the translation of two-dimensional video image information to a three-dimensional working area. However, research has tended to ignore the gaze and eye-hand coordination strategies employed by laparoscopic surgeons as they attempt to overcome these perceptual constraints. This study sought to examine if measures related to tool movements, gaze strategy, and eye-hand coordination (the quiet eye) differentiate between experienced and novice operators performing a two-handed manoeuvres task on a virtual reality laparoscopic surgical simulator (LAP Mentor™). Methods: Twenty-five right-handed surgeons were categorised as being either experienced (having led more than 60 laparoscopic procedures) or novice (having performed fewer than 10 procedures) operators. The 10 experienced and 15 novice surgeons completed the "two-hand manoeuvres" task from the LAP Mentor basic skills learning environment while wearing a gaze registration system. Performance, movement, gaze, and eye-hand coordination parameters were recorded and compared between groups. Results: The experienced surgeons completed the task significantly more quickly than the novices, used significantly fewer movements, and displayed shorter tool paths. Gaze analyses revealed that experienced surgeons spent significantly more time fixating the target locations than novices, who split their time between focusing on the targets and tracking the tools. A more detailed analysis of a difficult subcomponent of the task revealed that experienced operators used a significantly longer aiming fixation (the quiet eye period) to guide precision grasping movements and hence needed fewer grasp attempts. Conclusion: The findings of the study provide further support for the utility of examining strategic gaze behaviour and eye-hand coordination measures to help further our understanding of how experienced surgeons attempt to overcome the perceptual difficulties inherent in the laparoscopic environment. © 2011 The Author(s).published_or_final_versionSpringer Open Choice, 21 Feb 201
Cytokine responses to two common respiratory pathogens in children are dependent on interleukin-1beta
Protracted bacterial bronchitis (PBB) in young children is a common cause of prolonged wet cough and may be a precursor to bronchiectasis in some children. Although PBB and bronchiectasis are both characterised by neutrophilic airway inflammation and a prominent interleukin (IL)-1β signature, the contribution of the IL-1β pathway to host defence is not clear.
This study aimed to compare systemic immune responses against common pathogens in children with PBB, bronchiectasis and control children and to determine the importance of the IL-1β pathway.
Non-typeable Haemophilus influenzae (NTHi) stimulation of peripheral blood mononuclear cells (PBMCs) from control subjects (n=20), those with recurrent PBB (n=20) and bronchiectasis (n=20) induced high concentrations of IL-1β, IL-6, interferon (IFN)-γ and IL-10. Blocking with an IL-1 receptor antagonist (IL-1Ra) modified the cellular response to pathogens, inhibiting cytokine synthesis by NTHi-stimulated PBMCs and rhinovirus-stimulated PBMCs (in a separate PBB cohort). Inhibition of IFN-γ production by IL-1Ra was observed across multiple cell types, including CD3+ T cells and CD56+ NK cells.
Our findings highlight the extent to which IL-1β regulates the cellular immune response against two common respiratory pathogens. While blocking the IL-1β pathway has the potential to reduce inflammation, this may come at the cost of protective immunity against NTHi and rhinovirus.Alice C-H. Chen, Yang Xi, Melanie Carroll, Helen L. Petsky, Samantha J. Gardiner, Susan J. Pizzutto, Stephanie T. Yerkovich, Katherine J. Baines, Peter G. Gibson, Sandra Hodge, Ian B. Masters, Helen M. Buntain, Anne B. Chang and John W. Upha
Polygenic resilience scores capture protective genetic effects for Alzheimer’s disease
Polygenic risk scores (PRSs) can boost risk prediction in late-onset Alzheimer’s disease (LOAD) beyond apolipoprotein E (APOE) but have not been leveraged to identify genetic resilience factors. Here, we sought to identify resilience-conferring common genetic variants in (1) unaffected individuals having high PRSs for LOAD, and (2) unaffected APOE-ε4 carriers also having high PRSs for LOAD. We used genome-wide association study (GWAS) to contrast “resilient” unaffected individuals at the highest genetic risk for LOAD with LOAD cases at comparable risk. From GWAS results, we constructed polygenic resilience scores to aggregate the addictive contributions of risk-orthogonal common variants that promote resilience to LOAD. Replication of resilience scores was undertaken in eight independent studies. We successfully replicated two polygenic resilience scores that reduce genetic risk penetrance for LOAD. We also showed that polygenic resilience scores positively correlate with polygenic risk scores in unaffected individuals, perhaps aiding in staving off disease. Our findings align with the hypothesis that a combination of risk-independent common variants mediates resilience to LOAD by moderating genetic disease risk
Methodological issues regarding power of classical test theory (CTT) and item response theory (IRT)-based approaches for the comparison of patient-reported outcomes in two groups of patients - a simulation study
<p>Abstract</p> <p>Background</p> <p>Patients-Reported Outcomes (PRO) are increasingly used in clinical and epidemiological research. Two main types of analytical strategies can be found for these data: classical test theory (CTT) based on the observed scores and models coming from Item Response Theory (IRT). However, whether IRT or CTT would be the most appropriate method to analyse PRO data remains unknown. The statistical properties of CTT and IRT, regarding power and corresponding effect sizes, were compared.</p> <p>Methods</p> <p>Two-group cross-sectional studies were simulated for the comparison of PRO data using IRT or CTT-based analysis. For IRT, different scenarios were investigated according to whether items or person parameters were assumed to be known, to a certain extent for item parameters, from good to poor precision, or unknown and therefore had to be estimated. The powers obtained with IRT or CTT were compared and parameters having the strongest impact on them were identified.</p> <p>Results</p> <p>When person parameters were assumed to be unknown and items parameters to be either known or not, the power achieved using IRT or CTT were similar and always lower than the expected power using the well-known sample size formula for normally distributed endpoints. The number of items had a substantial impact on power for both methods.</p> <p>Conclusion</p> <p>Without any missing data, IRT and CTT seem to provide comparable power. The classical sample size formula for CTT seems to be adequate under some conditions but is not appropriate for IRT. In IRT, it seems important to take account of the number of items to obtain an accurate formula.</p
Psychological determinants of whole-body endurance performance
Background: No literature reviews have systematically identified and evaluated research on the psychological determinants of endurance performance, and sport psychology performance-enhancement guidelines for endurance sports are not founded on a systematic appraisal of endurance-specific research.
Objective: A systematic literature review was conducted to identify practical psychological interventions that improve endurance performance and to identify additional psychological factors that affect endurance performance. Additional objectives were to evaluate the research practices of included studies, to suggest theoretical and applied implications, and to guide future research.
Methods: Electronic databases, forward-citation searches, and manual searches of reference lists were used to locate relevant studies. Peer-reviewed studies were included when they chose an experimental or quasi-experimental research design, a psychological manipulation, endurance performance as the dependent variable, and athletes or physically-active, healthy adults as participants.
Results: Consistent support was found for using imagery, self-talk, and goal setting to improve endurance performance, but it is unclear whether learning multiple psychological skills is more beneficial than learning one psychological skill. The results also demonstrated that mental fatigue undermines endurance performance, and verbal encouragement and head-to-head competition can have a beneficial effect. Interventions that influenced perception of effort consistently affected endurance performance.
Conclusions: Psychological skills training could benefit an endurance athlete. Researchers are encouraged to compare different practical psychological interventions, to examine the effects of these interventions for athletes in competition, and to include a placebo control condition or an alternative control treatment. Researchers are also encouraged to explore additional psychological factors that could have a negative effect on endurance performance. Future research should include psychological mediating variables and moderating variables. Implications for theoretical explanations of endurance performance and evidence-based practice are described
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