Acetylcholine modulates the temporal dynamics of human theta oscillations during memory.

The cholinergic system is essential for memory. While degradation of cholinergic pathways characterizes memory-related disorders such as Alzheimer's disease, the neurophysiological mechanisms linking the cholinergic system to human memory remain unknown. Here, combining intracranial brain recordings with pharmacological manipulation, we describe the neurophysiological effects of a cholinergic blocker, scopolamine, on the human hippocampal formation during episodic memory. We found that the memory impairment caused by scopolamine was coupled to disruptions of both the amplitude and phase alignment of theta oscillations (2-10 Hz) during encoding. Across individuals, the severity of theta phase disruption correlated with the magnitude of memory impairment. Further, cholinergic blockade disrupted connectivity within the hippocampal formation. Our results indicate that cholinergic circuits support memory by coordinating the temporal dynamics of theta oscillations across the hippocampal formation. These findings expand our mechanistic understanding of the neurophysiology of human memory and offer insights into potential treatments for memory-related disorders.

Riding brain "waves" to identify human memory genes.

While there is extensive research on memory-related oscillations and brain gene expression, the relationship between oscillations and gene expression has rarely been studied. Recently, progress has been made to identify specific genes associated with oscillations that are correlated with episodic memory. Neocortical regions, in particular the temporal pole, have been examined in this line of research due to their accessibility during neurosurgical procedures. By harnessing this accessibility, a unique and powerful study design has allowed gene expression and intracranial oscillatory data to be sourced from the same human patients. These studies have identified a plethora of understudied gene targets that should be further characterized with respect to human brain function. Future work should extend to other brain regions to increase our understanding of the genetic signatures of oscillations and, ultimately, human cognition.

Biopsychosocial Experiences of Elite Athletes Retiring From Sport for Career-Ending Injuries: A Critically Appraised Topic.

CLINICAL SCENARIO: Injuries cause individuals varying amounts of time loss from participation, which may depend on injury and sport-specific factors such as level of participation. Athletes who never return to sport either choose or are forced to retire due to numerous factors. At elite levels of play, when an athlete chooses retirement, they have the opportunity to create and execute a retirement plan; however, if unexpected (eg, due to career-ending injury), athletes may struggle to transition out of sport effectively, impacting physical, mental, and social health. The biopsychosocial model looks at the relationship between biology, psychology, and socio-environmental factors. Therefore, the purpose of this study was to better understand the biopsychosocial experiences elite athletes face after a career-ending injury so that sport stakeholders can develop and implement strategies to support a healthy transition. CLINICAL QUESTION: How does suffering a career-ending injury affect elite athletes' biopsychosocial experiences during retirement from sport? SUMMARY OF KEY FINDINGS: All studies found that a career-ending injury negatively impacted athlete's biopsychosocial health during the transition period. In addition, social support was identified as a positive coping mechanism and research highlighted the role of education in promoting successful transitions. Sport stakeholders should educate athletes regarding the importance of creating secondary plans. By creating a culture of athletic and nonathletic identity, athletes can feel empowered to navigate different phases of their life despite transition being forced upon them due to injury. CLINICAL BOTTOM LINE: Career-ending injuries negatively impact the biopsychosocial experiences of elite athletes as they transition out of sport. Athletes may face many transitional challenges including a loss of identity, a lack of external support, and/or mental health decline; those more closely identifying with their role as an athlete tend to have a harder transition. Therefore, it is important for all athletes to be adequately prepared for sport retirement, especially given the uncertainty about when and how retirement may occur. STRENGTH OF RECOMMENDATION: Collectively, the body of evidence included to answer the clinical question aligns with the strength of recommendation of C.

Sex Differences in Nicotine Enhancement of Conditioned Place Avoidance Driven by Footshock in Male and Female Rats.

INTRODUCTION: Tobacco use is driven by nicotine, which can enhance the ability of non-nicotine stimuli, including aversive stimuli, to alter behavior. Sex differences exist in the reinforcement enhancement properties of nicotine, but the degree to which this extends to nicotine's ability to enhance behavior driven by aversive stimuli is unclear. AIMS AND METHODS: The current study used adult male and female Sprague-Dawley rats to explore sex differences in nicotine enhancement of footshock (FS)-conditioned place avoidance. FS-conditioned and control rats were tested for conditioned avoidance of FS- or control-paired chambers after injections of saline or nicotine (0.3 mg/kg, subcutaneously). RESULTS: FS supported place avoidance in both male and female rats, and nicotine enhanced avoidance. Females showed more avoidance after nicotine than males, even in nonconditioned control rats. CONCLUSIONS: These results support the idea that sex differences do exist in nicotine enhancement of aversive stimuli, and suggest the mechanisms through which nicotine supports tobacco dependence in males and females may differ. IMPLICATIONS: Nicotine enhancement of nondrug stimuli is thought to play a role in tobacco dependence. Yet previous research of enhancement has overwhelmingly used male subjects and appetitive stimuli. Our findings confirm that nicotine also enhances behavior driven by aversive stimuli, and suggests that females may be more susceptible to nicotine enhancement. Such sex differences suggest sex may be an important factor to consider in treating dependence.

Fatty Acid Uptake in T Cell Subsets Using a Quantum Dot Fatty Acid Conjugate.

Fatty acid (FA) metabolism directly influences the functional capabilities of T cells in tumor microenvironments. Thus, developing tools to interrogate FA-uptake by T cell subsets is important for understanding tumor immunosuppression. Herein, we have generated a novel FA-Qdot 605 dye conjugate with superior sensitivity and flexibility to any of the previously commercially available alternatives. For the first time, we demonstrate that this nanoparticle can be used as a specific measure of fatty acid uptake by T cells both in-vitro and in-vivo. Flow cytometric analysis shows that both the location and activation status of T cells determines their FA uptake. Additionally, CD4+ Foxp3+ regulatory T cells (Tregs) uptake FA at a higher rate than effector T cell subsets, supporting the role of FA metabolism for Treg function. Furthermore, we are able to simultaneously detect glucose and fatty acid uptake directly within the tumor microenvironment. Cumulatively, our results suggest that this novel fluorescent probe is a powerful tool to understand FA utilization within the tumor, thereby providing an unprecedented opportunity to study T cell FA metabolism in-vivo.

Critical Success Factors and Engagement Methodology for Successful Project Delivery.

TELUS Health will share its critical success factors and engagement methodology to successfully deliver a project on time, while meeting the client's vision.

Fast left prefrontal rTMS reduces post-gastric bypass surgery pain: findings from a large-scale, double-blind, sham-controlled clinical trial.

BACKGROUND: A single session of left prefrontal rTMS has been shown to have analgesic effects, and to reduce post-operative morphine use. We sought to test these findings in a larger sample, and try and see if multiple sessions had additive analgesic benefit. METHODS: 108 patients undergoing laparoscopic gastric bypass surgery received two sessions of 10 Hz rTMS (110% of motor threshold) over the left dorsolateral prefrontal cortex (one immediately following surgery and one 4 h later). Participants were randomly assigned to receive 2 sessions of real rTMS, 2 sessions of sham, 1 real then 1 sham, or 1 sham then 1 real rTMS treatments. Patients and study staff were blind to rTMS conditions. RESULTS: Unlike previous rTMS trials for post-operative pain, no differences emerged between groups with respect to total patient-controlled analgesia usage (IV hydromorphone). However, despite no difference in IV analgesic usage, subjects that received 2 real rTMS sessions rated both the affective and sensory dimensions of their pain significantly lower than those in the sham­sham group at several time points during the post-surgical/post-rTMS period. CONCLUSIONS: This study suggests that left prefrontal rTMS may produce significant analgesic effects in the perioperative setting. However, further work is needed to understand this effect and attempt to make it clinically useful in light of the lack of effect on PCA hydromorphone use.

The effect of adherence to ACLS protocols on survival of event in the setting of in-hospital cardiac arrest.

AIM: Advanced Cardiac Life Support (ACLS) algorithms are the default standard of care for in-hospital cardiac arrest (IHCA) management. However, adherence to published guidelines is relatively poor. The records of 149 patients who experienced IHCA were examined to begin to understand the association between overall adherence to ACLS protocols and successful return of spontaneous circulation (ROSC). METHODS: A retrospective chart review of medical records and code team worksheets was conducted for 75 patients who had ROSC after an IHCA event (SE group) and 74 who did not survive an IHCA event (DNS group). Protocol adherence was assessed using a detailed checklist based on the 2005 ACLS Update protocols. Several additional patient characteristics and circumstances were also examined as potential predictors of ROSC. RESULTS: In unadjusted analyses, the percentage of correct steps performed was positively correlated with ROSC from an IHCA (p<0.01), and the number of errors of commission and omission were both negatively correlated with ROSC from an IHCA (p<0.01). In multivariable models, the percentage of correct steps performed and the number of errors of commission and omission remained significantly predictive of ROSC (p<0.01 and p<0.0001, respectively) even after accounting for confounders such as the difference in age and location of the IHCAs. CONCLUSIONS: Our results show that adherence to ACLS protocols throughout an event is correlated with increased ROSC in the setting of cardiac arrest. Furthermore, the results suggest that, in addition to correct actions, both wrong actions and omissions of indicated actions lead to decreased ROSC after IHCA.

Observational study and estimate of cost savings from use of a health information exchange in an academic emergency department.

BACKGROUND: Federal initiatives to improve health care information sharing have led to the development of a new type of regional electronic medical record known as a health information exchange (HIE). OBJECTIVE: Our aim was to investigate the ability of an HIE to decrease health services use for emergency department (ED) patients. METHODS: We performed an observational, prospective study using a voluntary, anonymous survey among clinicians at an urban academic ED. All ED clinicians were eligible to participate. Survey items addressed clinician perception of whether information from the HIE avoided the use of hospital resources, improved quality of care, and reduced length of stay (LOS). Cost savings were estimated by multiplying the number of services the clinicians completing our survey reported they avoided through use of the HIE by the costs of those services at our facility. The study was approved by the Institutional Review Board at the study site. RESULTS: The study was conducted between August and December of 2011. There were 18,529 patient encounters during the study period and 60 clinicians at the study site who were eligible to participate. The clinicians consulted the HIE for 5.39% of these encounters (998 patients). Surveys were completed by the clinicians caring for 13.8% (n = 138) of these patients. Of the completed surveys, 76% (105 surveys) referenced patients for whom the HIE was found to contain information on the patient under care by the clinician participant. These 105 patients formed the sample on which our analysis was based. Within this sample of patients, the following studies were reported to have been avoided by the clinicians participating in our survey: values are percent of patients for whom a study was reported to have been avoided (actual number of studies avoided): laboratory/microbiology: 30.5% (32 studies); radiologic studies: 47.6% (50 studies); consultations: 19% (20 consultations); and admissions: 11.4% (12 admissions). Calculated cost savings based on these estimates were as follows: laboratory/microbiology: $462.85; radiologic studies: $160,893.00; consultations: $3,990.00; and admissions: $118,131.84. Total savings: $283,477. Clinicians participating in the study reported improved quality of care for 86.7% of their patients, as well as a mean time savings of 120.8 minutes. CONCLUSIONS: According to clinician estimates, use of an HIE in this urban academic ED resulted in reduced use of hospital resources, noteworthy cost savings, decreased LOS, and improved quality of care. Limitations included the observational nature of the study, selection bias, the Hawthorne effect, and cost estimates being from a single institution. Allowance was not made for additional services used because of information obtained from the HIE.

Sex differences in fatigue resistance are muscle group dependent.

PURPOSE: Women are often reported to be generally more resistant to fatigue than men for relative-intensity tasks. This has been observed repeatedly for elbow flexors, whereas at the ankle, sex differences appear less robust, suggesting localized rather than systemic influences. Thus, the purpose of this study was to examine sex differences in fatigue resistance at muscle groups in a single cohort and which factors, if any, predict endurance time. METHODS: Thirty-two young adults (age = 19-44 yr, 16 women) performed sustained isometric contractions at 50% maximum voluntary isometric contraction to failure for elbow flexion and ankle dorsiflexion. Pain, exertion, and muscle EMG were assessed throughout. Self-reported baseline activity was measured using the International Physical Activity Questionnaire. RESULTS: Women were significantly more resistant to fatigue than men at the elbow (112.3 ± 6.2 vs 80.3 ± 5.8 s, P = 0.001) but not at the ankle (140.6 ± 10.7 vs 129.2 ± 10.5 s, P = 0.45). Peak torque was greater in men than that in women (P < 0.0001) at the ankle (45.0 ± 1.7 vs 30.1 ± 1.0 N·m) and at the elbow (75.7 ± 3.1 vs 34.4 ± 2.2 N·m). Peak torque was significantly related to endurance time at the elbow (R2= 0.30) but not at the ankle (R2 = 0.03). Peak pain, rate of pain increase, peak exertion, EMG, and baseline physical activity did not differ between sexes. CONCLUSIONS: Sex differences in fatigue resistance are muscle group specific. Women were more fatigue resistant at the elbow but not at the ankle during a sustained isometric contraction. Further, factors that may contribute to fatigue resistance for one muscle group (e.g., sex, peak torque) may not be critical at another.