Empirical determination of an ECG compression ratio for mobile telecardiology applications.

It is important to consider electrocardiogram (ECG) data compression that does not sacrifice diagnostic quality significantly before applying ECG data compression to mobile telecardiology applications. In this paper, we assessed the reconstructed ECG quality after compression with a wavelet-based low-delay algorithm, using both subjective and objective indices. We included diverse ECG databases including both normal and abnormal ECG data, and evaluated the relationship between the subjective and objective indices, paying close attention to specific cases in which there was a large discrepancy between the objective and subjective quality. Based on our observations, an empirically determined compression ratio can be applied to compress continuous ECG signals in limited-bandwidth mobile telecardiology applications.

Wavelet-based low-delay ECG compression algorithm for continuous ECG transmission.

The delay performance of compression algorithms is particularly important when time-critical data transmission is required. In this paper, we propose a wavelet-based electrocardiogram (ECG) compression algorithm with a low delay property for instantaneous, continuous ECG transmission suitable for telecardiology applications over a wireless network. The proposed algorithm reduces the frame size as much as possible to achieve a low delay, while maintaining reconstructed signal quality. To attain both low delay and high quality, it employs waveform partitioning, adaptive frame size adjustment, wavelet compression, flexible bit allocation, and header compression. The performances of the proposed algorithm in terms of reconstructed signal quality, processing delay, and error resilience were evaluated using the Massachusetts Institute of Technology University and Beth Israel Hospital (MIT-BIH) and Creighton University Ventricular Tachyarrhythmia (CU) databases and a code division multiple access-based simulation model with mobile channel noise.

Kaiser Permanente's Convergent Medical Terminology.

This paper describes Kaiser Permanente's (KP) enterprise-wide medical terminology solution, referred to as our Convergent Medical Terminology (CMT). Initially developed to serve the needs of a regional electronic health record, CMT has evolved into a core KP asset, serving as the common terminology across all applications. CMT serves as the definitive source of concept definitions for the organization, provides a consistent structure and access method to all codes used by the organization, and is KP's language of interoperability, with cross-mappings to regional ancillary systems and administrative billing codes. The core of CMT is comprised of SNOMED CT, laboratory LOINC, and First DataBank drug terminology. These are integrated into a single poly-hierarchically structured knowledge base. Cross map sets provide bi-directional translations between CMT and ancillary applications and administrative billing codes. Context sets provide subsets of CMT for use in specific contexts. Our experience with CMT has lead us to conclude that a successful terminology solution requires that: (1) usability considerations are an organizational priority; (2) "interface" terminology is differentiated from "reference" terminology; (3) it be easy for clinicians to find the concepts they need; (4) the immediate value of coded data be apparent to clinician user; (5) there be a well defined approach to terminology extensions. Over the past several years, there has been substantial progress made in the domain coverage and standardization of medical terminology. KP has learned to exploit that terminology in ways that are clinician-acceptable and that provide powerful options for data analysis and reporting.

A non-transgenic mouse model (icv-STZ mouse) of Alzheimer's disease: similarities to and differences from the transgenic model (3xTg-AD mouse).

Alzheimer's disease (AD) can be divided into sporadic AD (SAD) and familial AD (FAD). Most AD cases are sporadic and result from multiple etiologic factors, including environmental, genetic, and metabolic factors, whereas FAD is caused by mutations in the presenilins or amyloid-ß (Aß) precursor protein (APP) genes. A commonly used animal model for AD is the 3xTg-AD transgenic mouse model, which harbors mutated presenilin 1, APP, and tau genes and thus represents a model of FAD. There is an unmet need in the field to characterize animal models representing different AD mechanisms, so that potential drugs for SAD can be evaluated preclinically in these animal models. A mouse model generated by intracerebroventricular (icv) administration of streptozocin (STZ), the icv-STZ mouse, shows many aspects of SAD. In this study, we compared the non-cognitive and cognitive behaviors as well as biochemical and immunohistochemical alterations between the icv-STZ mouse and the 3xTg-AD mouse. We found that both mouse models showed increased exploratory activity as well as impaired learning and spatial memory. Both models also demonstrated neuroinflammation, altered synaptic proteins and insulin/IGF-1 (insulin-like growth factor-1) signaling, and increased hyperphosphorylated tau in the brain. The most prominent brain abnormality in the icv-STZ mouse was neuroinflammation, and in the 3xTg-AD mouse it was elevation of hyperphosphorylated tau. These observations demonstrate the behavioral and neuropathological similarities and differences between the icv-STZ mouse and the 3xTg-AD mouse models and will help guide future studies using these two mouse models for the development of AD drugs.

Brain gene expression of a sporadic (icv-STZ Mouse) and a familial mouse model (3xTg-AD mouse) of Alzheimer's disease.

Alzheimer's disease (AD) can be divided into sporadic AD (SAD) and familial AD (FAD). Most AD cases are sporadic and may result from multiple etiologic factors, including environmental, genetic and metabolic factors, whereas FAD is caused by mutations of presenilins or amyloid-ß (Aß) precursor protein (APP). A commonly used mouse model for AD is 3xTg-AD mouse, which is generated by over-expression of mutated presenilin 1, APP and tau in the brain and thus represents a mouse model of FAD. A mouse model generated by intracerebroventricular (icv) administration of streptozocin (STZ), icv-STZ mouse, shows many aspects of SAD. Despite the wide use of these two models for AD research, differences in gene expression between them are not known. Here, we compared the expression of 84 AD-related genes in the hippocampus and the cerebral cortex between icv-STZ mice and 3xTg-AD mice using a custom-designed qPCR array. These genes are involved in APP processing, tau/cytoskeleton, synapse function, apoptosis and autophagy, AD-related protein kinases, glucose metabolism, insulin signaling, and mTOR pathway. We found altered expression of around 20 genes in both mouse models, which affected each of above categories. Many of these gene alterations were consistent with what was observed in AD brain previously. The expression of most of these altered genes was decreased or tended to be decreased in the hippocampus of both mouse models. Significant diversity in gene expression was found in the cerebral cortex between these two AD mouse models. More genes related to synaptic function were dysregulated in the 3xTg-AD mice, whereas more genes related to insulin signaling and glucose metabolism were down-regulated in the icv-STZ mice. The present study provides important fundamental knowledge of these two AD mouse models and will help guide future studies using these two mouse models for the development of AD drugs.

Differential effects of an O-GlcNAcase inhibitor on tau phosphorylation.

Abnormal hyperphosphorylation of microtubule-associated protein tau plays a crucial role in neurodegeneration in Alzheimer's disease (AD). The aggregation of hyperphosphorylated tau into neurofibrillary tangles is also a hallmark brain lesion of AD. Tau phosphorylation is regulated by tau kinases, tau phosphatases, and O-GlcNAcylation, a posttranslational modification of proteins on the serine or threonine residues with ß-N-acetylglucosamine (GlcNAc). O-GlcNAcylation is dynamically regulated by O-GlcNAc transferase, the enzyme catalyzing the transfer of GlcNAc to proteins, and N-acetylglucosaminidase (OGA), the enzyme catalyzing the removal of GlcNAc from proteins. Thiamet-G is a recently synthesized potent OGA inhibitor, and initial studies suggest it can influence O-GlcNAc levels in the brain, allowing OGA inhibition to be a potential route to altering disease progression in AD. In this study, we injected thiamet-G into the lateral ventricle of mice to increase O-GlcNAcylation of proteins and investigated the resulting effects on site-specific tau phosphorylation. We found that acute thiamet-G treatment led to a decrease in tau phosphorylation at Thr181, Thr212, Ser214, Ser262/Ser356, Ser404 and Ser409, and an increase in tau phosphorylation at Ser199, Ser202, Ser396 and Ser422 in the mouse brain. Investigation of the major tau kinases showed that acute delivery of a high dose of thiamet-G into the brain also led to a marked activation of glycogen synthase kinase-3ß (GSK-3ß), possibly as a consequence of down-regulation of its upstream regulating kinase, AKT. However, the elevation of tau phosphorylation at the sites above was not observed and GSK-3ß was not activated in cultured adult hippocampal progenitor cells or in PC12 cells after thiamet-G treatment. These results suggest that acute high-dose thiamet-G injection can not only directly antagonize tau phosphorylation, but also stimulate GSK-3ß activity, with the downstream consequence being site-specific, bi-directional regulation of tau phosphorylation in the mammalian brain.

Subungual squamous cell carcinoma of the toe: working toward a standardized therapeutic approach.

Subungual squamous cell carcinoma (SCC) is a rare malignancy with very few reported cases that occur on the toe. The etiology of these lesions is not known, and although this location is generally considered low risk for metastasis, cases of inguinal lymph node metastasis after toe amputation have been reported. Patients with subungual disease may meet criteria other than location that increase their risk for metastasis. Currently, no standardized approach to therapy for these patients has been established. In this article, we describe a patient with SCC of the right fourth toe with no clinical evidence of lymph-node metastasis. This patient underwent toe amputation and has done well for 2.5 years with no evidence of recurrence. We discuss this case of subungual SCC of the toe along with others in the literature to propose an optimal standardized approach for therapy and follow-up. In so doing, we aim to advance medical knowledge of subungual SCC and to improve patient care.

The dentate gyrus neurogenesis: a therapeutic target for Alzheimer's disease.

Neurogenesis persists in the aged human dentate gyrus but its role and regulation in pathological conditions such as Alzheimer's disease (AD), where the neurotrophic environment is changed, are poorly understood. In this study we investigated the effect of changes in the neurotrophic environment on neurogenesis in cultured rat hippocampal progenitors and in normal adult rats as models. In hippocampal progenitor cells from adult rats, fibroblast growth factor-2 (FGF-2) dose-dependently decreased microtubule-associated protein 2 and increased tau levels, indicating an FGF-2-induced dendrite to axon polarity shift. Cerebrolysin, a neurotrophic drug which has been shown to improve cognition and mood of AD patients, was found to increase neuron-like differentiated adult rat hippocampal progenitors in culture both by reducing apoptosis and by counteracting the FGF-2-induced polarity shift. Intraperitoneal administration of Cerebrolysin enhanced dentate gyrus neurogenesis and maze performance of 8- to 12-month-old female rats. These studies suggest that AD pathogenesis might involve an abnormally elevated FGF-2-associated dysregulation of dentate gyrus neurogenesis, especially neuronal polarity and that the neurogenesis pathology is a promising therapeutic target for this disease.