Developing a national undergraduate medical education pain management and substance use disorder curriculum to address the opioid crisis: a program evaluation pilot study.

BACKGROUND: Pain and addiction are one of the most common reasons for adults to seek health care, yet educational programs focused on pain are often underrepresented in medical school curricula. In January 2021, the Association of Faculties of Medicine of Canada (AFMC) launched an online national, bilingual, competency-based curriculum for undergraduate medical (UGME) students in pain management and substance use in response to the opioid crisis and to bridge the content gaps in programs across Canada. The purpose of this study is to evaluate the pilot of this national curriculum. METHODS: UGME students, from across Canada, participated in the program evaluation by completing online pre- and post-program surveys that assessed the influence of the curriculum on participants' knowledge as well as the value, usability, and feasibility of this curriculum. RESULTS: Participants' perceived confidence in their new knowledge and in utilizing resources required to maintain their knowledge significantly increased (75% and 51% respectively). Their perceived knowledge that addressed the 72 learning objectives within the curriculum significantly increased from pre- to post-program. Over 90% of participants reported that the curriculum was valuable, feasible, and usable. The most frequently discussed program strengths were the clear and comprehensive content, interactive and well-organized design, and relevance of curriculum content for future clinical practice. The overall weakness of the curriculum included the length, repetition of content, the lack of clarity and relevance of the assessment questions, end-user technology issues, and French translation discrepancies. Participant's recommendations for improving the curriculum included streamlining content, addressing technology issues, and enhancing the clarity and relevance of assessment questions embedded within each of the modules. CONCLUSION: Participants agreed that an online pain management and substance use curriculum is a valuable, usable, and feasible learning opportunity. Given the severity of the opioid crisis in Canada, these online modules provide a curriculum that can be integrated into existing UGME programs or can provide self-directed learning.

Patient-reported health outcomes of SARS-CoV-2-tested patients presenting to emergency departments: a propensity score-matched prospective cohort study.

OBJECTIVE: This study aimed to compare the long-term physical and mental health outcomes of matched severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive and SARS-CoV-2-negative patients controlling for seasonal effects. STUDY DESIGN: This was a retrospective cohort study. METHODS: This study enrolled patients presenting to emergency departments participating in the Canadian COVID-19 Emergency Department Rapid Response Network. We enrolled consecutive eligible consenting patients who presented between March 1, 2020, and July 14, 2021, and were tested for SARS-CoV-2. Research assistants randomly selected four site and date-matched SARS-CoV-2-negative controls for every SARS-CoV-2-positive patient and interviewed them at least 30 days after discharge. We used propensity scores to match patients by baseline characteristics and used linear regression to compare Veterans RAND 12-item physical health component score (PCS) and mental health component scores (MCS), with higher scores indicating better self-reported health. RESULTS: We included 1170 SARS-CoV-2-positive patients and 3716 test-negative controls. The adjusted mean difference for PCS was 0.50 (95% confidence interval [CI]: -0.36, 1.36) and -1.01 (95% CI: -1.91, -0.11) for MCS. Severe disease was strongly associated with worse PCS (ß = -7.4; 95% CI: -9.8, -5.1), whereas prior mental health illness was strongly associated with worse MCS (ß = -5.4; 95% CI: -6.3, -4.5). CONCLUSION: Physical health, assessed by PCS, was similar between matched SARS-CoV-2-positive and SARS-CoV-2-negative patients, whereas mental health, assessed by MCS, was worse during a time when the public experienced barriers to care. These results may inform the development and prioritization of support programs for patients.

Trabecular bone score in people with cystic fibrosis.

People with cystic fibrosis (CF) are at increased risk of fractures. Our study found that low trabecular bone score (TBS) (a measure of bone strength) may help identify people with CF at risk of fractures especially when combined with bone density measured by DXA, age, hemoglobin A1c, and transplant status. INTRODUCTION: People with cystic fibrosis (CF) are at increased risk of fractures. This study aims to evaluate the association of trabecular bone score (TBS) with fractures in CF. METHODS: A cross-sectional study of adults with CF who completed bone density between 2009 and 2019. TBS was applied to lumbar spine studies. RESULTS: A total of 202 people with CF were included. A history of fracture was present in 36 (17.8%) subjects. Patients with history of fractures had higher hemoglobin A1c (A1C) (7.8 ± 2.7% vs. 6.7 ± 1.7%, p = 0.024), lower femoral neck (FN) Z/T-score (- 1.05 ± 1.08 vs. - 0.44 ± 1.08, p = 0.012), and lower TBS (1.36 ± 0.13 vs. 1.40 ± 0.11, p = 0.05) compared to those without. Lung transplant recipients had a higher prevalence of fractures (50% vs. 14.1%, p < 0.001). The odds ratio (95%CI) of having a fracture for subjects with TBS (≤ 1.2 vs. > 1.2) stratified by FN Z/T-score (≤ - 2.0 or > - 2.0) was 3.88 (0.92, 16.35), p = 0.07. ROC analysis showed TBS was significantly associated with fractures (p < 0.05); however, FN BMD was superior. A model combining FN BMD, age, A1c, transplant, and TBS improved ROC compared to FN BMD + age (0.837 vs. 0.779, p = 0.031). CONCLUSIONS: TBS ≤ 1.2 may identify people with CF at high risk of fractures. A model combining FN BMD, age, A1c, transplant, and TBS was significantly associated with fractures compared to FN BMD + age. Future studies are needed to evaluate the prediction of fractures in people with CF using clinical and bone parameters.

Infinite deflectometry enabling 2π-steradian measurement range.

We present a novel deflectometry implementation termed Infinite Deflectometry. The technique provides a full aperture surface reconstruction sag map of freeform surfaces, including previously challenging to measure optics such as highly convex surfaces. The method relies on the creation of a virtual source enclosure around the tested optic, which creates a virtual 2π-steradian measurement range. To demonstrate the performance, a fast f/1.26 convex optical surface was measured with a commercial interferometer and with the Infinite Deflectometry system. After removing Zernike terms 1 through 37, the metrology tests resulted in absolute RMS surface values of 18.48 nm and 16.26 nm, respectively. Additionally, a freeform Alvarez lens was measured with the new technique and measured 22.34 𝜇m of surface sag RMS after piston, tip/tilt, and defocus had been removed. The result deviated by 488 nm RMS from a profilometer measurement while standard interferometry failed to measure the Alvarez lens due to its non-nulled wavefront dynamic range limitation.

Making a move in exercise referral: co-development of a physical activity referral scheme.

Background: Translational research is required to ensure exercise referral schemes (ERSs) are evidence-based and reflect local needs. This article reports process data from the co-development phase of an ERS, providing an insight into (i) factors that must be considered when translating evidence to practice in an ERS setting, and (ii) challenges and facilitators of conducting participatory research involving multiple stakeholders. Methods: An ERS was iteratively co-developed by a multidisciplinary stakeholder group (commissioners, managers, practitioners, patients and academics) via five participatory meetings and an online survey. Audio data (e.g. group discussions) and visual data (e.g. whiteboard notes) were recorded and analysed using NVivo-10 electronic software. Results: Factors to consider when translating evidence to practice in an ERS setting included (i) current ERS culture; (ii) skills, safety and accountability; and (iii) resources and capacity. The co-development process was facilitated by needs-analysis, open questions, multidisciplinary debate and reflective practice. Challenges included contrasting views, irregular attendance and (mis)perceptions of evaluation. Conclusion: The multidisciplinary co-development process highlighted cultural and pragmatic issues related to exercise referral provision, resulting in an evidence-based intervention framework designed to be implemented within existing infrastructures. Further work is required to establish the feasibility and effectiveness of the co-developed intervention in practice.

Transient osteoporosis of the hip: review of the literature.

Transient osteoporosis of the hip (TOH) is a temporary clinical condition of unknown etiology which usually resolves with conservative therapy though may be complicated by fracture or progression to avascular necrosis (AVN). TOH may be slightly more prevalent in men but when it occurs in women, it is most often seen in the latter part of pregnancy. Though fracture is a rare complication of TOH when it occurs, it is most often associated with TOH occurring in pregnancy. Magnetic resonance imaging (MRI) is the best method to diagnosis TOH. Low signal intensity on T1-weighted images, high signal intensity on T2-weighted images, and homogenous pattern of edema (the femoral head and/or neck) with normal subchondral area are in favor of TOH. A shortened course to recovery is reported by use of bisphosphonates, calcitonin, or teriparatide. Based on reported cases, core decompression is not superior to medical therapy. Transient osteoporosis of the hip, which often has no known etiology, usually resolves with conservative therapy but may predispose the patient to fracture or avascular necrosis. Diagnostic method of choice is magnetic resonance imaging. Bisphosphonates, calcitonin, or teriparatide are reported as a useful approach to reduce duration of recovery.

Physical activity guidelines and cardiovascular risk in children: a cross sectional analysis to determine whether 60 minutes is enough.

BACKGROUND: Physical activity reduces cardiovascular mortality and morbidity. The World Health Organisation (WHO) recommends children engage in 60 min daily moderate-to-vigorous physical activity (MVPA). The effect of compliance with this recommendation on childhood cardiovascular risk has not been empirically tested. To evaluate whether achieving recommendations results in reduced composite-cardiovascular risk score (CCVR) in children, and to examine if vigorous PA (VPA) has independent risk-reduction effects. METHODS: PA was measured using accelerometry in 182 children (9-11 years). Subjects were grouped according to achievement of 60 min daily MVPA (active) or not (inactive). CCVR was calculated (sum of z-scores: DXA body fat %, blood pressure, VO2peak, flow mediated dilation, left ventricular diastolic function; CVR score ≥ 1SD indicated 'higher risk'). The cohort was further split into quintiles for VPA and odds ratios (OR) calculated for each quintile. RESULTS: Active children (92 (53 boys)) undertook more MVPA (38 ± 11 min, P < 0.001), had greater VO2peak (4.5 ± 0.8 ml/kg/min P < 0.001), and lower fat % (3.9 ± 1.1 %, P < 0.001) than inactive. No difference were observed between active and inactive for CCVR or OR (P > 0.05). CCVR in the lowest VPA quintile was significantly greater than the highest quintile (3.9 ± 0.6, P < 0.05), and the OR was 4.7 times higher. CONCLUSION: Achievement of current guidelines has positive effects on body composition and cardiorespiratory fitness, but not CCVR. Vigorous physical activity appears to have beneficial effects on CVD risk, independent of moderate PA, implying a more prescriptive approach may be needed for future VPA guidelines.

A critical hybrid realist-outcomes systematic review of relationships between medical education programmes and communities: BEME Guide No. 35.

BACKGROUND: The relationships between medical schools and communities have long inspired and troubled medical education programmes. Successive models of community-oriented, community-based and community-engaged medical education have promised much and delivered to varying degrees. A two-armed realist systematic review was undertaken to explore and synthesize the evidence on medical school-community relationships. METHOD: One arm used standard outcomes criteria (Kirkpatrick levels), the other a realist approach seeking out the underlying contexts, mechanisms and outcomes. 38 reviewers completed 489 realist reviews and 271 outcomes reviews; 334 articles were reviewed in the realist arm and 181 in the outcomes arm. Analyses were based on: descriptive statistics on both articles and reviews; the outcomes involved; the quality of the evidence presented; realist contexts, mechanisms, and outcomes; and an analysis of underlying discursive themes. FINDINGS: The literature on medical school-community relationships is heterogeneous and largely idiographic, with no common standards for what a community is, who represents communities, what a relationship is based on, or whose needs are or should be being addressed or considered. CONCLUSIONS: Community relationships can benefit medical education, even if it is not always clear why or how. There is much opportunity to improve the quality and precision of scholarship in this area.

Assessment of biochemical liver markers, physical activity, fitness and body mass index for a cardiometabolic risk model in childhood.

AIM: The aim of this study was to investigate clustered cardiometabolic risk scores in healthy 10- to 12-year-olds using anthropometric characteristics, measurements of cardiorespiratory fitness (CRF) and physical activity and blood markers of metabolic disease. We also evaluated how including markers of liver cell injury would affect the clustered cardiometabolic risk assessment model. METHODS: This cross-sectional study focused on 99 children aged 10-12 years. The main outcome included assessing participants with increased and low cardiometabolic risk factors using a clustered risk score model that incorporated markers implicated in metabolic syndrome pathogenesis. Two clustered risk scores were calculated, one incorporating markers of liver cell injury. RESULTS: Children classified as 'increased risk' exhibited significantly lower CRF and higher body mass index Z-scores than their 'low-risk' peers. No significant differences in physical activity were observed. This trend remained unchanged when markers of liver injury were included in the clustered risk assessment model. CONCLUSION: The clustered risk score model is a scientifically robust method of cardiometabolic risk assessment, which reiterates the importance of weight reduction and CRF promotion in childhood. Our study did not show a significant contribution of liver injury markers, and further research is needed to evaluate their effect on cardiometabolic risk stratification in childhood.

Genetic determinants for cadmium and arsenic resistance among Listeria monocytogenes serotype 4b isolates from sporadic human listeriosis patients.

In Listeria monocytogenes serotype 4b isolates from sporadic listeriosis, heavy metal resistance was primarily encountered in certain clonal groups (ECI, ECII, and ECIa). All arsenic-resistant isolates harbored the arsenic resistance cassette previously identified in pLI100; ECIa harbored additional arsenic resistance genes and a novel cadmium resistance determinant in a conserved chromosomal locus.

Pelvic fractures associated with long-term bisphosphonate therapy - case report.

Long term bisphosphonate use has been associated with "atypical" subtrochanteric and diaphyseal fractures of the femoral shaft. We are reporting a case of pelvic fractures in addition to atypical long bone fractures, in a patient with osteopenia treated with bisphosphonate for 8 years, and teriparatide for 2 years. After 5 years of bisphosphonate therapy the patient suffered an atraumatic fracture of the femoral shaft. With an additional 3 years of bisphosphonate use she fractured both the upper and lower pubic rami on the left side. Bone histomorphometry performed on a biopsy of right iliac crest was negative for malignancy and calcification defects. It showed normal to low/normal bone turnover which correlated well with a low NTX level. Post-surgical X-rays revealed cortical thickening of the femur and beaking at the femoral shaft fracture, the classic findings associated with alendronate-related fractures. The pelvic fractures also reveal beaking at the fracture sites. Spontaneous fracture of the pelvis with unusual characteristics, in a patient with an atypical fracture of the femur suggests that the pelvic fracture may be related to long term bisphosphonate therapy.

Lack of relationship between sedentary behaviour and vascular function in children.

Some evidence suggests that sedentary behaviour is independently associated with cardiovascular (CV) risk. Endothelial dysfunction is the earliest detectable manifestation of CVD and a strong independent predictor of CV events. No previous study has examined the relationship between sedentary behaviour and endothelial function. We assessed the basal association between conduit artery endothelial function and sedentary behaviour in children, along with the correlation between changes in sedentary behaviour and endothelial function. We studied 116 children (70♀: 10.7 ± 0.3; 46♂: 10.7 ± 0.3 years) on two occasions; in the summer (June) and late autumn (November). We assessed endothelial function via flow-mediated dilation (FMD) using high-resolution Doppler ultrasound. Sedentary behaviour (SB) was assessed using objective uni-axial accelerometry. At baseline, there were no significant differences between girls and boys for any measured variables with the exception of total physical activity time. FMD was not associated with sedentary behaviour in either group or in the cohort as a whole. Although FMD decreased (10.0 ± 4.3-7.9 ± 3.9%, P < 0.001) and SB increased (499.1 ± 103.5-559 ± 81.6 min/day, P < 0.001) between the seasons, no relationship existed between changes in these variables. Our data suggest that sedentary behaviour and changes in sedentary behaviour are not associated with endothelial function in children.

Impact of exercise training on endothelial function and body composition in young people: a study of mono- and di-zygotic twins.

Flow mediated dilation (FMD) is a surrogate marker of arterial function which can be improved by exercise training. To date, no study has assessed the magnitude of FMD changes in response to exercise training between groups of mono- (MZ) and di-zygotic (DZ) twins. The purpose of this study was therefore to compare FMD in MZ- and DZ twins before and after identical exercise training interventions. At baseline, FMD was assessed using high resolution Duplex ultrasound in 12 twin pairs (6 MZ pairs 13.5 ± 0.8 years, 6 DZ pairs 13.4 ± 0.8 years). Twins completed 8 weeks of exercise training (65-85% HR(max)), consisting of three 45-min sessions per week. Change (Δ) scores were entered into twin versus twin intraclass correlation analyses by group. Change in %body fat (r = 0.63, P = 0.05) was significantly correlated in the MZ, but not the DZ group (r = 0.31, P = 0.23). Change in FMD was also highly correlated in MZ (r = 0.74, P = 0.02) but not in the DZ group (r = 0.37, P = 0.18). Heritability of ΔFMD was estimated at 0.74. Exercise induced changes in FMD were similar within sets of monozygotic twins but not dizygotic twins. These data suggest that a significant portion of the arterial function response to exercise training may be genetically determined.

Knowledge, attitudes and behaviours associated with the provision of hepatitis C care by Canadian family physicians.

The role of primary care physicians in providing care for hepatitis C virus (HCV) infection is increasingly emphasized, but many gaps and challenges remain. This study explores family physicians' knowledge, attitudes and practices associated with providing care for HCV infection. Seven hundred and forty-nine members of the College of Family Physicians of Canada (CFPC) completed a self-administered survey examining knowledge, attitudes and behaviours regarding HCV infection screening and care. Multivariate analyses were performed using the outcome, HCV care provision, and variables based on a conceptual model of practice guideline adherence. Family physicians providing basic-advanced HCV care were more likely to be older, practice in a rural setting, have injection drug users (IDU) in their practice and have higher levels of knowledge about the initial assessment (OR = 1.77; 95% CI = 1.23-2.54) and treatment of HCV (OR = 1.74; 95% CI = 1.24-2.43). They were also less likely to believe that family physicians do not have a role in HCV care (OR = 0.41; 95% CI = 0.30-0.58). Educational programmes should target physicians less likely to provide HCV care, namely family physicians practicing in urban areas and those who do not care for any IDU patients. Training and continuing medical education programmes that aim to shift family physicians' attitudes about the provision of HCV care by promoting their roles as integral to HCV care could contribute to easing the burden on consultant physicians and lead to improved access to treatment for HCV infection.

RNA-Regulated TRA-1 nuclear export controls sexual fate.

TRA-1, a member of the GLI family of transcription factors, is required for C. elegans female development. We find that TRA-1 has a sex-specific distribution consistent with its role in female development: nuclear TRA-1 is higher in hermaphrodite intestines and in specific germline regions than in males. TRA-1 patterns rely on nuclear export since treatment with leptomycin B, a CRM1-dependent export inhibitor, increases nuclearTRA-1 in males. TRA-1 export requires TRA-1 binding to the tra-2 3' untranslated region (3' UTR), as disruption of binding increases nuclear TRA-1 and female development. Our data are consistent with coexport of a TRA-1/tra-2 mRNA complex reducing TRA-1 nuclear activity, and identify an interesting RNA-based mechanism for controlling transcriptional activity and cell fate determination.

Sphingosine-1-phosphate inhibits PDGF-induced chemotaxis of human arterial smooth muscle cells: spatial and temporal modulation of PDGF chemotactic signal transduction.

Activation of the PDGF receptor on human arterial smooth muscle cells (SMC) induces migration and proliferation via separable signal transduction pathways. Sphingosine-1-phosphate (Sph-1-P) can be formed following PDGF receptor activation and therefore may be implicated in PDGF-receptor signal transduction. Here we show that Sph-1-P does not significantly affect PDGF-induced DNA synthesis, proliferation, or activation of mitogenic signal transduction pathways, such as the mitogen-activated protein (MAP) kinase cascade and PI 3-kinase, in human arterial SMC. On the other hand, Sph-1-P strongly mimics PDGF receptor-induced chemotactic signal transduction favoring actin filament disassembly. Although Sph-1-P mimics PDGF, exogenously added Sph-1-P induces more prolonged and quantitatively greater PIP2 hydrolysis compared to PDGF-BB, a markedly stronger calcium mobilization and a subsequent increase in cyclic AMP levels and activation of cAMP-dependent protein kinase. This excessive and prolonged signaling favors actin filament disassembly by Sph-1-P, and results in inhibition of actin nucleation, actin filament assembly and formation of focal adhesion sites. Sph-1-P-induced interference with the dynamics of PDGF-stimulated actin filament disassembly and assembly results in a marked inhibition of cell spreading, of extension of the leading lamellae toward PDGF, and of chemotaxis toward PDGF. The results suggest that spatial and temporal changes in phosphatidylinositol turnover, calcium mobilization and actin filament disassembly may be critical to PDGF-induced chemotaxis and suggest a possible role for endogenous Sph-1-P in the regulation of PDGF receptor chemotactic signal transduction.

Incidence of lymphoma in a captive-bred colony of hamadryas baboons (Papio hamadryas).

OBJECTIVE: To assess the incidence of lymphoma and wasting-related deaths in the National Baboon Colony of Australia and relate it to the presence of simian T-cell lymphotrophic virus 1 (STLV-1) infection. DESIGN AND PROCEDURE: The records of all animals that had died since establishment of the National Baboon Colony in Australia were reviewed retrospectively. The clinical signs and histopathological findings were recorded and assessed to determine the involvement of lymphoma in the deaths. The presence of STLV-1 was recorded if known and correlated with the STLV-1 status of the colony. RESULTS: Of the deaths from disease or illness, 53% were diagnosed as or suspected to be lymphoma, occurring in mature animals with no sex predisposition. The most common presentation was rapidly occurring generalised lymphadenomegaly. CONCLUSIONS: This study has described a relatively high prevalence of lymphoma in a colony of captive-bred baboons, and it is evident that STLV-1 may play a role in the disease. Management practices in baboon colonies need to take into account the possible presence of STLV-1 and aim to reduce the transmission of the virus by preventing sexual contact between positive and negative animals. Lymphoma needs to be considered as one of the more common causes of wasting and death.

Systematic review of the methods used in economic evaluations of targeted physical activity and sedentary behaviour interventions.

The burden of noncommunicable diseases (NCD) on health systems worldwide is substantial. Physical inactivity and sedentary behaviour are major risk factors for NCD. Previous attempts to understand the value for money of preventative interventions targeting physically inactive individuals have proved to be challenging due to key methodological challenges associated with the conduct of economic evaluations in public health. A systematic review was carried out across six databases (Medline, SPORTSDiscus, EconLit, PsychINFO, NHS EED, HTA) along with supplementary searches. The review examines how economic evaluations published between 2009-March 2017 have addressed methodological challenges with the aim of bringing to light examples of good practice for future studies. Fifteen economic evaluations from four high-income countries were retrieved; there is a dearth of studies targeting sedentary behaviour as an independent risk factor from physical activity. Comparability of studies from the healthcare and societal perspectives were limited due to analysts' choice in cost categories, valuation technique and time horizon differing substantially. The scarcity of and inconsistencies across economic evaluations for these two behaviours have exposed a mismatch between calls for more preventative action to tackle NCD and the lack of information available on how resources may be optimally allocated in practice. Consequently, this paper offers a table of recommendations on how future studies can be improved.

Insulin-like growth factor-I and platelet-derived growth factor-BB induce directed migration of human arterial smooth muscle cells via signaling pathways that are distinct from those of proliferation.

Directed migration or chemotaxis of arterial smooth muscle cells (SMC) contributes to intimal SMC accumulation, a key event in the development of atherosclerotic lesions and in restenosis after angioplasty. The present study compares and contrasts insulin-like growth factor I (IGF-I) and platelet-derived growth factor (PDGF-BB) as chemoattractants and mitogens for human arterial SMC. Compared with PDGF-BB, IGF-I is a weaker SMC mitogen. Thus, PDGF-BB, but not IGF-I, evokes a strong and rapid activation of mitogen-activated protein (MAP) kinase kinase and MAP kinase. However, IGF-I is a potent stimulator of directed migration of human arterial SMC, as measured in a Boyden chamber assay. The half-maximal concentration for migration is similar to the Kd for IGF-I receptor interaction. An IGF-I receptor-blocking antibody blocks the effects of IGF-I, IGF-II, and insulin, indicating that the effects are indeed mediated through the IGF-I receptor. The maximal effect of IGF-I on directed migration ranges between 50% and 100% of the effect of PDGF-BB, the strongest known chemoattractant for SMC. The ability of IGF-I and PDGF-BB to induce chemotaxis coincides with their ability to stimulate phosphatidylinositol turnover, diacylglycerol formation, and intracellular Ca2+ flux and suggests that these signaling pathways, but not activation of the MAP kinase cascade, are required for chemotaxis of human arterial SMC.

Sleep and memory: a molecular perspective.

This review synthesizes data from behavioral studies examining the role of sleep in memory storage with what is known about the molecular mechanisms of memory consolidation. There are striking similarities in the effects on memory storage of post-training pharmacological manipulations and post-training manipulations of sleep. For example, inhibition of protein synthesis is most effective if it occurs at a time post-training when rapid eye movement (REM) sleep is required for memory consolidation. The neurochemical changes that occur across sleep/wake states, especially the cholinergic changes that occur in the hippocampus during REM sleep, might provide a mechanism by which sleep modulates specific cellular signaling pathways involved in hippocampus-dependent memory storage.