Citations

PurposeCorticomuscular electroencephalographic-electromyographic (EEG-EMG) coherence elicited by speech and nonspeech oromotor tasks in healthy participants and those with Parkinson’s disease (PD) was examined. Hypotheses were the following: (a) corticomuscular coherence is demonstrable between orbicularis oris (OO) muscles' EMG and scalp EEG recording; (b) the presence, location, and magnitude of coherence is task specific; (c) differences in corticomuscular coherence patterns exist between healthy and PD participants; and (d) differences will manifest as either increased or decreased coherence values in certain frequency bands, with EEG localization at primary sensorimotor cortex and/or supplementary motor area (SMA).MethodSimultaneous EEG, EMG (OO), and speech samples were recorded on 20 healthy and 20 PD participants during speech and nonspeech tasks. Fast Fourier transform and coherence analysis was performed with Neuroscan software on 1,000 randomly generated epochs per task per group. Corticomuscular coherence was analyzed between each EEG electrode and right and left superior and inferior OO muscles up to 200 Hz. Significant coherence peaks exceeded 95% confidence limits (.003).ResultsCorticomuscular coherence existed for both groups and for all tasks, but to varying degrees in primary sensorimotor cortex and SMA.ConclusionsResults support task specificity for both groups and, in PD, a diminished modulation flexibility linked to the sensorimotor area and reduced corticomuscular coherence at the SMA.

AbstractImmune-related deficiencies are well-known complications of chronic lymphocytic leukemia (CLL). Although recent data indicate that almost all CLL patients are preceded by a monoclonal B-cell lymphocytosis precursor state, patterns of immune defects preceding CLL diagnosis are unclear. We identified 109 persons who developed CLL from the prospective and nationwide Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial with 77 469 participants, with serially collected prediagnostic serum samples. We assayed monoclonal (M)–proteins, κ/λ free light chains (FLCs) in prediagnostic obtained up to 9.8 years before CLL diagnosis. The prevalence of an abnormal FLC ratio, M-protein, and hypogamma-globulinemia before CLL diagnosis was 38% (95% confidence interval, 29%-47%), 13% (7%-21%), and 3% (1%-8%), respectively. M-proteins and abnormal FLC ratios were detected up to 9.8 years before CLL diagnosis in a total of 48 persons (44%). Hypogammaglobulinemia was not present until 3 years before the diagnosis of CLL. Among 37 patients with information on tumor cell immunophenotype, an association between immunophenotype and involved FLC (P = .024, Fisher exact test) was observed. Among 61 persons with a normal FLC ratio and without an M-protein, 17 had elevated κ and/or λ FLC levels, indicating polyclonal B-cell activation in 17 of 109 (16%) patients. These findings support a role for chronic immune stimulation in CLL genesis.

AbstractBackgroundThe burden of disease, disability, and mortality that could be averted by surgery is growing. However, few low and middle income countries (LMICs) have the infrastructure or capacity to provide surgical services to meet this growing need. Equally, few of these countries have been assessed for key infrastructural capacity including surgical and anesthesia providers, equipment, and supplies. These assessments are critical to revealing magnitude of the evolving surgical and anesthesia workforce crisis, related morbidity and mortality, and necessary steps to mitigate the impact of the crisis.MethodsA pilot Internet‐based survey was conducted to estimate per‐capita anesthesia providers in LMICs. Information was obtained from e‐mail respondents at national health care addresses, and from individuals working in‐country on anesthesia‐related projects.ResultsWorkers from 6 of 98 countries responded to direct e‐mail inquiries, and an additional five responses came from individuals who were working or had worked in‐country at the time of the survey. The data collected revealed that the per‐capita anesthesia provider ratio in the countries surveyed was often 100 times lower than in developed countries.ConclusionsThis pilot study revealed that the number of anesthesia providers available per capita of population is markedly reduced in low and lower middle income countries compared to developed countries. As anesthesia providers are an integral part of the delivery of safe and effective surgical care, it is essential that more data is collected to fully understand the deficiencies in workforce and capacity in low and middle income countries.

We previously identified a SNF1/AMPK-related protein kinase, Hunk, from a mammary tumor arising in an MMTV-neu transgenic mouse. The function of this kinase is unknown. Using targeted deletion in mice, we now demonstrate that Hunk is required for the metastasis of c-myc-induced mammary tumors, but is dispensable for normal development. Reconstitution experiments revealed that Hunk is sufficient to restore the metastatic potential of Hunk-deficient tumor cells, as well as defects in migration and invasion, and does so in a manner that requires its kinase activity. Consistent with a role for this kinase in the progression of human cancers, the human homologue of Hunk is overexpressed in aggressive subsets of carcinomas of the ovary, colon, and breast. In addition, a murine gene expression signature that distinguishes Hunk-wild type from Hunk-deficient mammary tumors predicts clinical outcome in women with breast cancer in a manner consistent with the pro-metastatic function of Hunk in mice. These findings identify a direct role for Hunk kinase activity in metastasis and establish an in vivo function for this kinase.

Abstract Eosinophil granule proteins are deposited in cutaneous lesions in many human diseases, but how these proteins contribute to pathophysiology is obscure. We injected eosinophil cationic protein (ECP or RNase 3), eosinophil-derived neurotoxin (EDN or RNase 2), eosinophil peroxidase (EPO), and major basic protein-1 (MBP1) intradermally into guinea pig and rabbit skin. ECP and EDN each induced distinct skin lesions at ≥2.5 μM that began at 2 days, peaking at ∼7 days and persisting up to 6 wk. These lesions were ulcerated (ECP) or crusted (EDN) with marked cellular infiltration. EPO and MBP1 (10 μM) each produced perceptible induration and erythema with moderate cellular infiltration resolving within 2 wk. ECP and EDN localized to dermal cells within 2 days, whereas EPO and MBP1 remained extracellular. Overall, cellular localization and RNase activity of ECP and EDN were critical for lesion formation; differential glycosylation, net cationic charge, or RNase activity alone did not account for lesion formation. Ulcerated lesions from patients with the hypereosinophilic syndrome showed ECP and EDN deposition comparable to that in guinea pig skin. In conclusion, ECP and EDN disrupt skin integrity and cause inflammation. Their presence in ulcerative skin lesions may explain certain findings in human eosinophil-associated diseases.

OBJECTIVE Transgenic expression of diacylglycerol acyltransferase-1 (DGAT1) in skeletal muscle leads to protection against fat-induced insulin resistance despite accumulation of intramuscular triglyceride, a phenomenon similar to what is known as the “athlete paradox.” The primary objective of this study is to determine how DGAT1 affects muscle fatty acid oxidation in relation to whole-body energy metabolism and insulin sensitivity. RESEARCH DESIGN AND METHODS We first quantified insulin sensitivity and the relative tissue contributions to the improved whole-body insulin sensitivity in muscle creatine kisase (MCK)-DGAT1 transgenic mice by hyperinsulinemic-euglycemic clamps. Metabolic consequences of DGAT1 overexpression in skeletal muscles were determined by quantifying triglyceride synthesis/storage (anabolic) and fatty acid oxidation (catabolic), in conjunction with gene expression levels of representative marker genes in fatty acid metabolism. Whole-body energy metabolism including food consumption, body weights, oxygen consumption, locomotor activity, and respiration exchange ratios were determined at steady states. RESULTS MCK-DGAT1 mice were protected against muscle lipoptoxicity, although they remain susceptible to hepatic lipotoxicity. While augmenting triglyceride synthesis, DGAT1 overexpression also led to increased muscle mitochondrial fatty acid oxidation efficiency, as compared with wild-type muscles. On a high-fat diet, MCK-DGAT1 mice displayed higher basal metabolic rates and 5–10% lower body weights compared with wild-type littermates, whereas food consumption was not different. CONCLUSIONS DGAT1 overexpression in skeletal muscle led to parallel increases in triglyceride synthesis and fatty acid oxidation. Seemingly paradoxical, this phenomenon is characteristic of insulin-sensitive myofibers and suggests that DGAT1 plays an active role in metabolic “remodeling” of skeletal muscle coupled with insulin sensitization.

Background The authors determined associated cardiac arrest and death rates in cases from Canada and the United States as reported to The North American Malignant Hyperthermia (MH) Registry and analyzed factors associated with a higher risk of poor outcomes. Methods The authors searched the database for AMRA (adverse metabolic/musculoskeletal reaction to anesthesia) reports with inclusion criteria as follows: event date between January 1, 1987, and December 31, 2006; "very likely" or "almost certain" MH as ranked by MH Clinical Grading Scale; location in Canada or the United States; and one or more anesthetic agents given. The exclusion criterion was a pathologic condition other than MH independently judged by the authors. Severe MH outcomes were analyzed as regards clinical history and presentation, using Wilcoxon rank sum tests for continuous variables and Pearson exact chi-square tests for categorical variables. A Bonferroni correction adjusted for multiple comparisons. Results Of 291 events, 8 (2.7%) resulted in cardiac arrests and 4 (1.4%) resulted in death. The median age in cases of cardiac arrest/death was 20 yr (range, 2-31 yr). Associated factors were muscular build (odds ratio, 18.7; P = 0.0016) and disseminated intravascular coagulation (odds ratio, 49.7; P < 0.0001). Increased risk of cardiac arrest/death was related to a longer time period between anesthetic induction and maximum end-tidal carbon dioxide (216 vs. 87 min; P = 0.003). Unrelated factors included patient or family history, anesthetic management, and the MH episode. Conclusions Modern US anesthetic practice did not prevent MH-associated cardiac arrest and death in predominantly young, healthy patients undergoing low- to intermediate-risk surgical procedures.