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Beginning in the early stages of Alzheimer's disease (AD), the hippocampus reduces its functional connections to other cortical regions due to synaptic depletion. However, little is known regarding connectivity abnormalities within the hippocampus. Here, we describe rostral-caudal hippocampal convergence (rcHC), a metric of the overlap between the rostral and caudal hippocampal functional networks, across the clinical spectrum of AD. We predicted a decline in rostral-caudal hippocampal convergence in the early stages of the disease. Using fMRI, we generated resting-state hippocampal functional networks across 56 controls, 48 early MCI (EMCI), 35 late MCI (LMCI), and 31 AD patients from the Alzheimer's Disease Neuroimaging Initiative cohort. For each diagnostic group, we performed a conjunction analysis and compared the rostral and caudal hippocampal network changes using a mixed effects linear model to estimate the convergence and differences between these networks, respectively. The conjunction analysis showed a reduction of rostral-caudal hippocampal convergence strength from early MCI to AD, independent of hippocampal atrophy. Our results demonstrate a parallel between the functional convergence within the hippocampus and disease stage, which is independent of brain atrophy. These findings support the concept that network convergence might contribute as a biomarker for connectivity dysfunction in early stages of AD. [ABSTRACT FROM AUTHOR]

We present the Canadian Open Neuroscience Platform (CONP) portal to answer the research community's need for flexible data sharing resources and provide advanced tools for search and processing infrastructure capacity. This portal differs from previous data sharing projects as it integrates datasets originating from a number of already existing platforms or databases through DataLad, a file level data integrity and access layer. The portal is also an entry point for searching and accessing a large number of standardized and containerized software and links to a computing infrastructure. It leverages community standards to help document and facilitate reuse of both datasets and tools, and already shows a growing community adoption giving access to more than 60 neuroscience datasets and over 70 tools. The CONP portal demonstrates the feasibility and offers a model of a distributed data and tool management system across 17 institutions throughout Canada., (© 2023. The Author(s).)

Objectives: To identify, critically appraise and summarise evidence on the impact of employing primary healthcare professionals (PHCPs: family physicians/general practitioners (GPs), nurse practitioners (NP) and nurses with increased authority) in the emergency department (ED) triage, on patient flow outcomes., Methods: We searched Medline (Ovid), EMBASE (Ovid), Cochrane Library (Wiley) and CINAHL (EBSCO) (inception to January 2020). Our primary outcome was the time to provider initial assessment (PIA). Secondary outcomes included time to triage, proportion of patients leaving without being seen (LWBS), length of stay (ED LOS), proportion of patients leaving against medical advice (LAMA), number of repeat ED visits and patient satisfaction. Two independent reviewers selected studies, extracted data and assessed study quality using the National Institute for Health and Care Excellence quality assessment tool., Results: From 23 973 records, 40 comparative studies including 10 randomised controlled trials (RCTs) and 13 pre-post studies were included. PHCP interventions were led by NP (n=14), GP (n=3) or nurses with increased authority (n=23) at triage. In all studies, PHCP-led intervention effectiveness was compared with the traditional nurse-led triage model. Median duration of the interventions was 6 months. Study quality was generally low (confounding bias); 7 RCTs were classified as moderate quality. Most studies reported that PHCP-led triage interventions decreased the PIA (13/14), ED LOS (29/30), proportion of patients LWBS (8/10), time to triage (3/3) and repeat ED visits (5/6), and increased the patient satisfaction (8/10). The proportion of patients LAMA did not differ between groups (3/3). Evidence from RCTs (n=8) as well as other study designs showed a significant decrease in ED LOS favouring the PHCP-led interventions., Conclusions: Overall, PHCP-led triage interventions improved ED patient flow metrics. There was a significant decrease in ED LOS irrespective of the study design, favouring the PHCP-led interventions. Evidence from well-designed high-quality RCTs is required prior to widespread implementation., Prospero Registration Number: CRD42020148053., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Objectives: To conduct a scoping review to identify and summarise the existing literature on interventions involving primary healthcare professionals to manage emergency department (ED) overcrowding., Design: A scoping review., Data Sources: A comprehensive database search of Medline (Ovid), EMBASE (Ovid), Cochrane Library (Wiley) and CINAHL (EBSCO) databases was conducted (inception until January 2020) using peer-reviewed search strategies, complemented by a search of grey literature sources., Eligibility Criteria: Interventions and strategies involving primary healthcare professionals (PHCPs: general practitioners (GPs), nurse practitioners (NPs) or nurses with expanded role) to manage ED overcrowding., Methods: We engaged and collaborated, with 13 patient partners during the design and conduct stages of this review. We conducted this review using the JBI guidelines. Two reviewers independently selected studies and extracted data. We conducted descriptive analysis of the included studies (frequencies and percentages)., Results: From 23 947 records identified, we included 268 studies published between 1981 and 2020. The majority (58%) of studies were conducted in North America and were predominantly cohort studies (42%). The reported interventions were either 'within ED' (48%) interventions (eg, PHCP-led ED triage or fast track) or 'outside ED' interventions (52%) (eg, after-hours GP clinic and GP cooperatives). PHCPs involved in the interventions were: GP (32%), NP (26%), nurses with expanded role (16%) and combinations of the PHCPs (42%). The 'within ED' and 'outside ED' interventions reported outcomes on patient flow and ED utilisation, respectively., Conclusions: We identified many interventions involving PHCPs that predominantly reported a positive impact on ED utilisation/patient flow metrics. Future research needs to focus on conducting well-designed randomized controlled trials (RCTs) and systematic reviews to evaluate the effectiveness of specific interventions involving PHCPs to critically appraise and summarise evidence on this topic., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Identifying individuals destined to develop Alzheimer's dementia within time frames acceptable for clinical trials constitutes an important challenge to design studies to test emerging disease-modifying therapies. Although amyloid-β protein is the core pathologic feature of Alzheimer's disease, biomarkers of neuronal degeneration are the only ones believed to provide satisfactory predictions of clinical progression within short time frames. Here, we propose a machine learning-based probabilistic method designed to assess the progression to dementia within 24 months, based on the regional information from a single amyloid positron emission tomography scan. Importantly, the proposed method was designed to overcome the inherent adverse imbalance proportions between stable and progressive mild cognitive impairment individuals within a short observation period. The novel algorithm obtained an accuracy of 84% and an under-receiver operating characteristic curve of 0.91, outperforming the existing algorithms using the same biomarker measures and previous studies using multiple biomarker modalities. With its high accuracy, this algorithm has immediate applications for population enrichment in clinical trials designed to test disease-modifying therapies aiming to mitigate the progression to Alzheimer's disease dementia., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Recent literature proposes that amyloid β (Aβ) and phosphorylated tau (p-tau) synergism accelerates biomarker abnormalities in controls. Yet, it remains to be answered whether this synergism is the driving force behind Alzheimer disease (AD) dementia., Methods: We stratified 314 mild cognitive impairment individuals using [ 18 F]florbetapir positron emission tomography Aβ imaging and cerebrospinal fluid p-tau. Regression and voxel-based logistic regression models with interaction terms evaluated 2-year changes in cognition and clinical status as a function of baseline biomarkers., Results: We found that the synergism between [ 18 F]florbetapir and p-tau, rather than their additive effects, was associated with the cognitive decline and progression to AD. Furthermore, voxel-based analysis revealed that temporal and inferior parietal were the regions where the synergism determined an increased likelihood of developing AD., Discussion: Together, the present results support that progression to AD dementia is driven by the synergistic rather than a mere additive effect between Aβ and p-tau proteins., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Our knowledge with respect to psychological, endocrine, and neural correlates of attentional bias in individuals with high vulnerability to developing depression - the subclinically depressed, still remains limited., Design: The study used a 2 × 2 mixed design., Methods: Attentional bias toward happy and sad faces in healthy (N = 26) and subclinically depressed individuals (N = 22) was assessed via a neuroimaging dot-probe attention task. Participants also completed trait and state psychological measures and provided saliva samples for cortisol analysis., Results: The subclinical group showed attentional bias toward happy faces; past use of problem-focused coping strategies when dealing with a personally relevant stressor as well as state levels of anxiety, together, contributed to this bias. In the control group, the happy attentional bias was positively correlated with activity in the right caudate. In the subclinical group, the bias was negatively associated with the left fusiform gyrus and positively with the left inferior parietal lobule and bilateral putamen. We observed group differences in association between cortisol levels during the task and neural activity during happy attentional bias processing within the key regions involved in attention., Conclusions: The attentional bias toward happy faces may reflect an active coping attempt by the subclinical participants.

In healthy individuals, behavioral outcomes are highly associated with the variability on brain regional structure or neurochemical phenotypes. Similarly, in the context of neurodegenerative conditions, neuroimaging reveals that cognitive decline is linked to the magnitude of atrophy, neurochemical declines, or concentrations of abnormal protein aggregates across brain regions. However, modeling the effects of multiple regional abnormalities as determinants of cognitive decline at the voxel level remains largely unexplored by multimodal imaging research, given the high computational cost of estimating regression models for every single voxel from various imaging modalities. VoxelStats is a voxel-wise computational framework to overcome these computational limitations and to perform statistical operations on multiple scalar variables and imaging modalities at the voxel level. VoxelStats package has been developed in Matlab(®) and supports imaging formats such as Nifti-1, ANALYZE, and MINC v2. Prebuilt functions in VoxelStats enable the user to perform voxel-wise general and generalized linear models and mixed effect models with multiple volumetric covariates. Importantly, VoxelStats can recognize scalar values or image volumes as response variables and can accommodate volumetric statistical covariates as well as their interaction effects with other variables. Furthermore, this package includes built-in functionality to perform voxel-wise receiver operating characteristic analysis and paired and unpaired group contrast analysis. Validation of VoxelStats was conducted by comparing the linear regression functionality with existing toolboxes such as glim_image and RMINC. The validation results were identical to existing methods and the additional functionality was demonstrated by generating feature case assessments (t-statistics, odds ratio, and true positive rate maps). In summary, VoxelStats expands the current methods for multimodal imaging analysis by allowing the estimation of advanced regional association metrics at the voxel level.

Background: Several lines of evidence suggest the involvement of neuroinflammatory changes in Alzheimer's disease (AD) pathophysiology such as amyloidosis and neurodegeneration. In fact, genome-wide association studies (GWAS) have shown a link between genes involved in neuroinflammation and AD. In order to further investigate whether interactions between candidate genetic variances coding for neuroinflammatory molecules are associated with brain amyloid β (Aβ) fibrillary accumulation, we conducted an epistasis analysis on a pool of genes associated with molecular mediators of inflammation., Methods: [(18)F]Florbetapir positron emission tomography (PET) imaging was employed to assess brain Aβ levels in 417 participants from ADNI-GO/2 and posteriorly 174 from ADNI-1. IL-1β, IL4, IL6, IL6r, IL10, IL12, IL18, C5, and C9 genes were chosen based on previous studies conducted in AD patients. Using the [(18)F]florbetapir standardized uptake value ratio (SUVR) as a quantitative measure of fibrillary Aβ, epistasis analyses were performed between two sets of markers of immune-related genes using gender, diagnosis, and apolipoprotein E (APOE) as covariates. Voxel-based analyses were also conducted. The results were corrected for multiple comparison tests. Cerebrospinal fluid (CSF) Aβ1-42/phosphorylated tau (p-tau) ratio concentrations were used to confirm such associations., Results: Epistasis analysis unveiled two significant single nucleotide polymorphism (SNP)-SNP interactions (false discovery rate (FDR) threshold 0.1), both interactions between C9 gene (rs261752) and IL6r gene (rs4240872, rs7514452). In a combined sample, the interactions were confirmed (p ≤ 10-5) and associated with amyloid accumulation within cognitively normal and AD spectrum groups. Voxel-based analysis corroborated initial findings. CSF biomarker (Aβ1-42/p-tau) confirmed the genetic interaction. Additionally, rs4240872 and rs7514452 SNPs were shown to be associated with CSF and plasma concentrations of IL6r protein., Conclusions: Certain allele combinations involving IL6r and C9 genes are associated with Aβ burden in the brain. Hypothesis-driven search for epistasis is a valuable strategy for investigating imaging endophenotypes in complex neurodegenerative diseases.

Eating disorder (ED) variants characterized by "binge-eating/purging" symptoms differ from "restricting-only" variants along diverse clinical dimensions, but few studies have compared people with these different eating-disorder phenotypes on measures of neurocognitive function and brain activation. We tested the performances of 19 women with "restricting-only" eating syndromes and 27 with "binge-eating/purging" variants on a modified n-back task, and used functional magnetic resonance imaging (fMRI) to examine task-induced brain activations in frontal regions of interest. When compared with "binge-eating/purging" participants, "restricting-only" participants showed superior performance. Furthermore, in an intermediate-demand condition, "binge-eating/purging" participants showed significantly less event-related activation than did "restricting-only" participants in a right posterior prefrontal region spanning Brodmann areas 6-8-a region that has been linked to planning of motor responses, working memory for sequential information, and management of uncertainty. Our findings suggest that working memory is poorer in eating-disordered individuals with binge-eating/purging behaviors than in those who solely restrict food intake, and that observed performance differences coincide with interpretable group-based activation differences in a frontal region thought to subserve planning and decision making., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

This study aimed to identify vulnerability patterns in psychological, physiological and neural responses to mild psychosocial challenge in a population that is at a direct risk of developing depression, but who has not as yet succumbed to the full clinical syndrome. A group of healthy and a group of subclinically depressed participants underwent a modified Montreal Imaging Stress task (MIST), a mild neuroimaging psychosocial task and completed state self-esteem and mood measures. Cortisol levels were assessed throughout the session. All participants showed a decrease in performance self-esteem levels following the MIST. Yet, the decline in performance self-esteem levels was associated with increased levels of anxiety and confusion in the healthy group, but increased levels of depression in the subclinical group, following the MIST. The subclinical group showed overall lower cortisol levels compared with the healthy group. The degree of change in activity in the subgenual anterior cingulate cortex in response to negative evaluation was associated with increased levels of depression in the whole sample. Findings suggest that even in response to a mild psychosocial challenge, those individuals vulnerable to depression already show important maladaptive response patterns at psychological and neural levels. The findings point to important targets for future interventions., (© The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.)

Objective: The hyperglycemic response to surgery may be a risk factor for cognitive dysfunction. We hypothesize that strict maintenance of normoglycemia during cardiac surgery preserves postoperative cognitive function., Methods: As part of a larger randomized, single-blind, interventional efficacy study on the effects of hyperinsulinemic glucose control in cardiac surgery (NCT00524472), consenting patients were randomly assigned to receive combined administration of insulin and glucose, titrated to preserve normoglycemia (3.5-6.1 mmol L(-1); experimental group), or standard metabolic care (blood glucose 3.5-10 mmol L(-1); control group), during open heart surgery. The patients' cognitive function was assessed during three home visits, approximately two weeks before the operation, and two months and seven months after surgery. The following tests were performed: Rey Auditory Verbal Learning Task (RAVLT for verbal learning and memory), Digit Span Task (working memory), Trail Making A & B (visuomotor tracking and attention), and the Word Pair Task (implicit memory). Questionnaires measuring specific traits known to affect cognitive performance, such as self-esteem, depression, chronic stress and social support, were also administered. The primary outcome was to assess the effect of hyperinsulinemic-normoglycemic clamp therapy versus standard therapy on specific cognitive parameters in patients receiving normoglycemic clamp, or standard metabolic care., Results: Twenty-six patients completed the study with 14 patients in the normoglycemia and 12 patients in the control group. Multiple analysis of covariance (MANCOVA) for the RAVLT showed a significant effect for the interaction of group by visit (F = 4.07, p = 0.035), and group by visit by recall (F = 2.21, p = 0.04). The differences occurred at the second and third visit. MANCOVA for the digit span task, trail making and word pair association test showed no significant effect., Conclusions: Preserving intraoperative normoglycemia by intravenous insulin and glucose may prevent the impairment of memory function, both short and long-term, after cardiac surgery.

Background: The retrieval of consolidated memories may result in their destabilization, requiring a restabilization process called reconsolidation. During reconsolidation, memories become sensitive to psychological and pharmacological modifications again, thus providing an opportunity to alter unwanted memories. Although such reconsolidation manipulations might open the door to novel treatment approaches for psychiatric disorders such as posttraumatic stress disorder, the brain mechanisms underlying reconsolidation processes in humans are completely unknown. Here, we asked whether a β-adrenergic receptor antagonist might interfere with the reconsolidation of emotional episodic memories and what brain mechanisms are involved in these effects., Methods: Healthy participants were administered the β-adrenergic receptor antagonist propranolol or a placebo before they reactivated previously learned neutral and emotional material. Recognition memory was tested 24 hours later. Functional magnetic resonance images were collected during reactivation and recognition testing., Results: Propranolol during reactivation specifically reduced the subsequent memory for emotional pictures; memory for neutral pictures remained unaffected. This emotional memory impairment was associated with significantly increased activity in the amygdala and the hippocampus for correctly recognized pictures at test. Most interestingly, the same structures were active (but not modulated by propranolol) during memory reactivation. Memory reactivation alone or propranolol without reactivation had no effect on subsequent memory., Conclusions: Our results demonstrate how the consequences of memory reconsolidation processes are represented in the human brain, suggesting that the brain areas that are recruited during reactivation undergo changes in activity that are associated with subsequent memory recall., (Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Major depressive disorder is associated with dysregulated basal cortisol levels and small hippocampal (HC) volume. However, it is still debated whether these phenomena are a consequence of the illness or whether they may represent a vulnerability marker existing before the illness onset. Here, we aimed to examine this notion of vulnerability by assessing whether abnormalities in basal cortisol secretion and HC volumes are already present in a sample of healthy young adults who showed varying levels of depressive tendencies, but at subclinical levels., Methods: We recruited healthy young men and women from the local university. On the basis of depression scores derived from standard questionnaires, three groups were formed: a control group (n = 27), a subclinical group (n = 23), and a high-risk subclinical group (n = 9). The participants underwent a magnetic resonance imaging scan and collected saliva samples for the assessment of diurnal cortisol levels., Results: Both the subclinical and the high-risk subclinical group failed to show a significant increase in cortisol levels after awakening. The high-risk subclinical group also showed a lower area-under-the-curve increase of cortisol levels after awakening compared with control subjects. In addition, this group also had smaller total HC volume compared with control subjects., Conclusions: The findings from this subclinical sample suggest that dysregulated cortisol awakening response and small HC volume may constitute vulnerability factors for major depressive disorder. Further investigations are needed to discern the mechanisms that may underlie these phenomena., (Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Recent neuroimaging studies investigating neural correlates of psychological stress employ cognitive paradigms that induce a significant hormonal stress response in the scanner. The Montreal Imaging Stress Task (MIST) is one such task that combines challenging mental arithmetic with negative social evaluative feedback. Due to the block design nature of the MIST, it has not been possible thus far to investigate which brain areas respond specifically to the key components of the MIST (mental arithmetic, failure, negative social evaluation). In the current study, we developed an event-related MIST (eventMIST) in order to investigate which neural activation patterns are associated with performing mental arithmetic vs. processing of social evaluative threat. Data was available from twenty healthy university students. The eventMIST induced a significant stress response in a subsample of subjects, called the responders (n=7). Direct comparison between brain activity changes in responders vs. non-responders, in response to challenging math, revealed increased activity bilaterally in dorsomedial prefrontal cortex (PFC), left temporal pole, and right dorsolateral PFC. In response to negative social evaluation, responders showed reduction of brain activity in limbic system regions (medial orbitofrontal cortex and hippocampus), which was largely lacking in non-responders. Direct comparison between the groups for this contrast did not reveal any significant difference, probably due to small number of events available. This is the first study to use an event-related paradigm to investigate brain activity patterns in relation to challenging math and social evaluative threat separately.

Results presented in this paper describe the ability of Bacillus subtilis strain M4 to reduce disease incidence caused by Colletotrichum lagenarium and Pythium aphanidermatum on cucumber and tomato, respectively. Disease protection in both pathosystems was most probably due to induction of resistance in the host plant since experiments were designed in order to avoid any direct contact between the biocontrol agent and the pathogen. Pre-inoculation with strain M4 thus sensitised both plants to react more efficiently to subsequent pathogen infection. In cucumber, the use of endospores provided a disease control level similar to that obtained with vegetative cells. In contrast, a mixture of lipopeptides from the surfactin, iturin and fengycin families showed no resistance-inducing potential. Interestingly, treatment with strain M4 was also associated with significant changes in gene transcription in the host plant as revealed by cDNA-AFLP analyses. Several AFLP fragments corresponded to genes not expressed in control plants and specifically induced by the Bacillus treatment. In support to the macroscopic protective effect, this differential accumulation of mRNA also illustrates the plant reaction following perception of strain M4, and constitutes one of the very first examples of defence-associated modifications at the transcriptional level elicited by a non-pathogenic bacterium in a host plant.

Fire blight, caused by the bacterium Erwinia amylovora (Burill Winslow et al.), is the most important bacterial disease in European pear growing. It can cause a lot of damage in some countries on apple and on pear trees in orchards and also in the fruit tree nurseries. In Belgium, the disease is present since 1972. Control of fire blight in Belgian fruit orchards is made on a broad basis of measurements in and around the fruit trees. The use of an antibiotic is allowed for application only during the primary blossom period under strict controlled regulations. The use of antobiotics in agriculture is strongly discussed on the European level today and will probably disappear in the near future. Therefore, the research on fire blight control concentrates on the possibilities of biological control with antagonistic bacteria such as Pantoea agglomerans (Erwinia herbicola), Bacillus subtilis or Pseudomonas syringae strain A 506. The use of Serratine-P, a phage tail-like bacteriocin, produced by Serratia plymiticum, shows an interesting antibacterial activity against Erwinia amylovora. Its mode of action consists in the perforation of the cytoplasmic membrane of the target cell, inducing perturbations in cellular exchanges and a final lysis of the bacterial cell. In this paper some trials are discussed on the use of Serratine-P at different doses and on different infection types on pear trees. The results indicate interesting protection possibilities on blossom- and fruit infections.

Skeletal muscle sarcolemma preparations, predominantly in the form of inside-out vesicles, were obtained from porcine muscle by a LiBr-extraction procedure. In the presence of ATP, these preparations were able to accumulate 94 nmol Ca/mg protein after 20 min at 37 degrees C. Sarcolemmal calcium uptake was completely blocked by the calcium ionophore, A23187, but was unaffected by monovalent cation ionophores. Calcium uptake was markedly inhibited by vanadate, with an approximate Ki of 0.5 microM. Oxalate (5 mM) had little effect on the initial phase of calcium uptake, while inorganic phosphate, at concentrations up to 50 mM, had a significant stimulatory effect on sarcolemmal calcium uptake. In contrast to ATP, acetylphosphate had minimal ability and p-nitrophenylphosphate had no ability to support calcium uptake. The maximal initial velocity of skeletal muscle sarcolemmal calcium uptake was 10.0 nmol Ca mg-1 min-1 at 37 degrees C, with a K 1/2 for Ca2+ of 0.88 microM. Addition of either 1 microM calmodulin, or 5 microM cAMP and 0.1 mg/ml cAMP-dependent protein kinase, increased the Vmax to 12.5 and 12.8 nmol Ca mg-1 min-1, respectively, and decreased the K 1/2 for Ca2+ to 0.67 and 0.70 microM, respectively; simultaneous addition of calmodulin and cAMP-dependent protein kinase increased the Vmax to 15.2 nmol Ca mg-1 min-1 and further lowered the K 1/2 to 0.51 microM. When concentrations of NaCl from 10 to 60 mM were added to vesicles that had been loaded with calcium in the presence of ATP, an immediate release of calcium occurred. This process had an approximate K 1/2 for sodium of 10-20 mM and an approximate maximal rate of 50 nmol Ca mg-1 min-1. We conclude that skeletal muscle sarcolemma contains a cAMP-dependent protein kinase- and calmodulin-stimulatable ATP-dependent calcium transport, as well as a sodium: calcium exchange activity.

The content and distribution of acetylcholinesterase (AChE) activity in the skeletal muscle disorder malignant hyperthermia (MH) was examined. The AChE activity of sarcolemma membranes isolated from MH-susceptible (MHS) swine was increased twofold when compared with normal sarcolemma. The total AChE activity of muscle extracts was also doubled in MHS tissue; however, the relative distribution between low-salt extractable (globular forms) and high-salt extractable (asymmetric forms) AChE activities were similar in MHS and normal muscle. Our results suggest that, for as yet unexplained reasons, both the sarcolemmal and total AChE activity of skeletal muscle is increased in porcine MH.