Emergency department use by patients with end-stage renal disease in the United States.

BACKGROUND: We sought to describe the national characteristics of ED visits by patients with end-stage renal disease (ESRD) in the United States in order to improve the emergency treatment and screening of ESRD patients. METHODS: We analyzed data from 2014 to 2016 ED visits provided by the National Hospital Ambulatory Medical Care Survey. We sampled adult (age ≥ 18 years) ED patients with ESRD. By proportion or means of weighted sample variables, we quantified annual ED visits by patients with ESRD. We investigated demographics, ED resource utilization, clinical characteristics, and disposition of patients with ESRD and compared these to those of patients without ESRD. Logistic regression models were used to estimate the association between these characteristics and ESRD ED visits. RESULTS: Approximately 722,692 (7.78%) out of 92,899,685 annual ED visits represented ESRD patients. Males were more likely to be ESRD patients than females (aOR: 1.34; 95% CI: 1.09-1.66). Compare to whites, non-Hispanic Blacks were 2.55 times more likely to have ESRD (aOR: 2.55; 95% CI: 1.97-3.30), and Hispanics were 2.68 times more likely to have ESRD (95% CI: 1.95-3.69). ED patients with ESRD were more likely to be admitted to the hospital (aOR: 2.70; 95% CI: 2.13-3.41) and intensive care unit (ICU) (aOR: 2.21; 95% CI: 1.45-3.38) than patients without ESRD. ED patients with ESRD were more likely to receive blood tests and get radiology tests. CONCLUSION: We described the unique demographic, socioeconomic, and clinical characteristics of ED patients with ESRD, using the most comprehensive, nationally representative study to date. These patients' higher hospital and ICU admission rates indicate that patients with ESRD require a higher level of emergency care.

Earliest hydraulic enterprise in China, 5,100 years ago.

Here we present one of the world's oldest examples of large-scale and formalized water management, in the case of the Liangzhu culture of the Yangtze Delta, dated at 5,300-4,300 years cal B.P. The Liangzhu culture represented a peak of early cultural and social development predating the historically recorded Chinese dynasties; hence, this study reveals more about the ancient origins of hydraulic engineering as a core element of social, political, and economic developments. Archaeological surveys and excavations can now portray the impressive extent and structure of dams, levees, ditches, and other landscape-transforming features, supporting the ancient city of Liangzhu, with an estimated size of about 300 ha. The results indicate an enormous collective undertaking, with unprecedented evidence for understanding how the city, economy, and society of Liangzhu functioned and developed at such a large scale. Concurrent with the evidence of technological achievements and economic success, a unique relationship between ritual order and social power is seen in the renowned jade objects in Liangzhu elite burials, thus expanding our view beyond the practicalities of water management and rice farming.

Neural Interface: Frontiers and Applications : Cochlear Implants.

The theory and implementation of modern cochlear implant are presented in this chapter. Major signal processing strategies of cochlear implants are discussed in detail. Hardware implementation including wireless signal transmission circuit, integrated circuit design of implant circuit, and neural response measurement circuit are provided in the latter part of the chapter. Finally, new technologies that are likely to improve the performance of current cochlear implants are introduced.

Adsorption of Cu2+ and mechanism by natural biofilm.

The biofilm culturing device fixed on the slides was vertically placed in the commonly called small Li Lake of Jiangnan University. The adsorption experiment of Cu2+ was carried out by mature biofilm. Besides, scanning electron microscope (SEM), polymerase chain reaction and denaturing gradient gel electrophoresis (PCR-DGGE), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy-energy spectrum (SEM-EDX) were used to analysis the effect of Cu2+ on the morphological structure of biofilm. The result indicated that when the initial concentration of Cu2+ was 5 mg·L-1, the absorption capacity of Cu2+ by unit mass biofilm is the maximum. More extracellular polymeric substances (EPS) were released by biofilm due to the stimulation of Cu2+. EPS was beneficial to the adsorption of Cu2+ by biofilm. After the adsorption of Cu2+, the bacterial diversity index decreased, while there were no significant differences in microbial communities on biofilm. Moreover, the main groups combining Cu2+ were the hydroxyl groups and amide groups in S-EPS and B-EPS. Ion exchange is a mechanism of the adsorption of Cu2+ by EPS.

Hydrostatin-TL1, an Anti-Inflammatory Active Peptide from the Venom Gland of Hydrophis cyanocinctus in the South China Sea.

Tumor necrosis factor (TNF)-α is a pleiotropic cytokine with intense pro-inflammatory and immunomodulatory properties, and anti-TNF-α biologics are effective therapies for various inflammatory diseases such as inflammatory bowel disease (IBD) and sepsis. Snake venom, as a traditional Chinese medicine, has been used in the treatment of inflammatory diseases in China for centuries. In this research, we constructed a venom gland T7 phage display library of the sea snake Hydrophis cyanocinctus to screen bioactive compounds that antagonize TNF-α and identified a novel nine-amino-acid peptide, termed hydrostatin-TL1 (H-TL1). In enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR) analyses, H-TL1 inhibited the interaction between TNF-α and TNF receptor 1 (TNFR1). Further, H-TL1 attenuated the cytotoxicity of TNF-α in L929 cells as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. H-TL1 also decreased the mRNA expression of TNF-α/TNFR1 downstream targets and suppressed the phosphorylation of well-characterized proteins of downstream signal transduction pathways in HEK-293 cells. In vivo data demonstrated that H-TL1 protects animals against dextran sodium sulfate (DSS)-induced acute colitis and lipopolysaccharide (LPS)-induced acute shock. Given its significant anti-inflammatory activity in vitro and in vivo, H-TL1 is a potential peptide for the development of new agents to treat TNF-α-associated inflammatory diseases.

Spectral motion contrast as a speech context effect.

Spectral contrast effects may help "normalize" the incoming sound and produce perceptual constancy in the face of the variable acoustics produced by different rooms, talkers, and backgrounds. Recent studies have concentrated on the after-effects produced by the long-term average power spectrum. The present study examined contrast effects based on spectral motion, analogous to visual-motion after-effects. In experiment 1, the existence of spectral-motion after-effects with word-length inducers was established by demonstrating that the identification of the direction of a target spectral glide was influenced by the spectral motion of a preceding inducer glide. In experiment 2, the target glide was replaced with a synthetic sine-wave speech sound, including a formant transition. The speech category boundary was shifted by the presence and direction of the inducer glide. Finally, in experiment 3, stimuli based on synthetic sine-wave speech sounds were used as both context and target stimuli to show that the spectral-motion after-effects could occur even with inducers with relatively short speech-like durations and small frequency excursions. The results suggest that spectral motion may play a complementary role to the long-term average power spectrum in inducing speech context effects.

The TGF-ß/MMP9/RAGE axis induces sRAGE secretion by neutrophils and promotes oral carcinogenesis.

In the tumor microenvironment, transforming growth factor ß (TGF-ß) contributes to neutrophil development toward a pro-tumor phenotype; however, the molecular mechanism by which this occurs remains unclear. Therefore, we explored the role of TGF-ß in N2 neutrophil polarization and the subsequent effect on oral leukoplakia/oral squamous cell carcinoma (OL/OSCC) cells. The TGF-ß-stimulated N2 culture supernatant promoted the proliferation of OL/OSCC cells. Analysis of the N2 supernatant using a cytokine array revealed significantly upregulated expression of soluble forms of receptor for advanced glycation end products (RAGE). TGF-ß was found to induce the expression of RAGE and matrix metalloproteinase 9 (MMP9) in neutrophils. Additionally, MMP9 treatment could cleave RAGE and promote its secretion by neutrophils, thereby promoting cancer cell proliferation. In an established mouse model of oral cancer using 4NQO, RAGE were found to be highly expressed. Importantly, neutralizing antibodies against RAGE significantly inhibited oral cancer progression in mice. Analysis of clinical data from the TCGA database revealed that RAGE and MMP9 are highly expressed in head and neck squamous cell carcinoma (HNSCC) and that RAGE expression is significantly positively correlated with neutrophil infiltration. In conclusion, our results indicate that TGF-ß promotes N2 neutrophil polarization through upregulation of soluble RAGE (sRAGE) secretion, leading to OSCC cell proliferation. Our findings also suggest that the sRAGE formed during N2 polarization may be a potential therapeutic target in OL/OSCC.

A Multiplexed 32 × 32 2D Matrix Array Transducer for Flexible Sub-Aperture Volumetric Ultrasound Imaging.

A fully-sampled two-dimensional (2D) matrix array ultrasonic transducer is essential for fast and accurate three-dimensional (3D) volumetric ultrasound imaging. However, these arrays, usually consisting of thousands of elements, not only face challenges of poor performance and complex wiring due to high-density elements and small element sizes but also put high requirements for electronic systems. Current commercially available fully-sampled matrix arrays, dividing the aperture into four fixed sub-apertures to reduce system channels through multiplexing are widely used. However, the fixed sub-aperture configuration limits imaging flexibility and the gaps between sub-apertures lead to reduced imaging quality. In this study, we propose a high-performance multiplexed matrix array by the design of 1-3 piezocomposite and gapless sub-aperture configuration, as well as optimized matching layer materials. Furthermore, we introduce a sub-aperture volumetric imaging method based on the designed matrix array, enabling high-quality and flexible 3D ultrasound imaging with a low-cost 256-channel system. The influence of imaging parameters, including the number of sub-apertures and steering angle on imaging quality was investigated by simulation, in vitro and in vivo imaging experiments. The fabricated matrix array has a center frequency of 3.4 MHz and a -6 dB bandwidth of above 70%. The proposed sub-aperture volumetric imaging method demonstrated a 10% improvement in spatial resolution, a 19% increase in signal-to-noise ratio, and a 57.7% increase in contrast-to-noise ratio compared with the fixed sub-aperture array imaging method. This study provides a new strategy for high-quality volumetric ultrasound imaging with a low-cost system.

A transcranial multiple waves suppression method for plane wave imaging based on Radon transform.

Transcranial ultrasound imaging presents a significant challenge due to the intricate interplay between ultrasound waves and the heterogeneous human skull. The skull's presence induces distortion, refraction, multiple scattering, and reflection of ultrasound signals, thereby complicating the acquisition of high-quality images. Extracting reflections from the entire waveform is crucial yet exceedingly challenging, as intracranial reflections are often obscured by strong amplitude direct waves and multiple scattering. In this paper, a multiple wave suppression method for ultrasound plane wave imaging is proposed to mitigate the impact of skull interference. Drawing upon prior research, we developed an enhanced high-resolution linear Radon transform using the maximum entropy principle and Bayesian method, facilitating wavefield separation. We detailed the process of wave field separation in the Radon domain through simulation of a model with a high velocity layer. When plane waves emitted at any steering angles, both multiple waves and first arrival waves manifested as distinct energy points. In the brain simulation, we contrasted the characteristic differences between skull reflection and brain-internal signal in Radon domain, and demonstrated that multiples suppression method reduces side and grating lobe levels by approximately 30 dB. Finally, we executed in vitro experiments using a monkey skull to separate weak intracranial reflection signals from strong skull reflections, enhancing the contrast-to-noise ratio by 85 % compared to conventional method using full waveform. This study deeply explores the effect of multiples on effective signal separation, addresses the complexity of wavefield separation, and verifies its efficacy through imaging, thereby significantly advancing ultrasound transcranial imaging techniques.

A New Method of Plane-Wave Ultrasound Imaging Based on Reverse Time Migration.

Coherent plane-wave compounding technique enables rapid ultrasound imaging with comparable image quality to traditional B-mode imaging that relies on focused beam transmission. However, existing methods assume homogeneity in the imaged medium, neglecting the heterogeneity in sound velocities and densities present in real tissues, resulting in noise reverberation. This study introduces the Reverse Time Migration (RTM) method for ultrasound plane-wave imaging to overcome this limitation, which is combined with a method for estimating the speed of sound in layered media. Simulation results in a homogeneous background demonstrate that RTM reduces side lobes and grating lobes by approximately 30 dB, enhancing the contrast-to-noise ratio by 20% compared to conventional delay and sum (DAS) beamforming. Moreover, RTM achieves superior imaging outcomes with fewer compounding angles. The lateral resolution of the RTM with 5-9 angle compounding is able to achieve the effectiveness of the DAS method with 15-19 angle compounding, and the CNR of the RTM with 11-angle compounding is almost the same as that of the DAS with 21-angle compounding. In a heterogeneous background, experimental simulations and in vitro wire phantom experiments confirm RTM's capability to correct depth imaging, focusing reflected waves on point targets. In vitro porcine tissue experiments enable accurate imaging of layer interfaces by estimating the velocities of multiple layers containing muscle and fat. The proposed imaging procedure optimizes velocity estimation in complex media, compensates for the impact of velocity differences, provides more reliable imaging results.

A novel approach for quantitatively distinguishing between anthropogenic and natural effects on paleovegetation.

How to distinguish and quantify past human impacts on vegetation is a significant challenge in paleoecology. Here, we propose a novel method, the error inflection point-discriminant technique. It finds out the inflection points (IPs) of the regression errors of pollen-climate transfer functions using modern pollen spectra from vegetation with different values of the Human Influence Index (HII), which represent the HII threshold values of native/secondary and secondary/artificial vegetation systems. Our results show that the HII value at the native/secondary vegetation IPs is approximately 22 and globally uniform, whereas it varies regionally for the secondary/artificial vegetation IPs. In a case study of the Liangzhu archaeological site in the lower Yangtze River, discriminant functions for pollen spectra from three vegetation types and pollen-climate transfer functions of the native vegetation were established to reconstruct paleovegetation and paleoclimate over the past 6,600 years. Our study demonstrates this method's feasibility for quantitatively distinguishing human impacts on paleovegetation and assessing quantitative paleoclimate reconstructions using pollen data.

Time-to-Event Genome-Wide Association Study for Incident Cardiovascular Disease in People With Type 2 Diabetes.

OBJECTIVE: To identify genetic risk factors for incident cardiovascular disease (CVD) among people with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: We conducted a multiancestry time-to-event genome-wide association study for incident CVD among people with T2D. We also tested 204 known coronary artery disease (CAD) variants for association with incident CVD. RESULTS: Among 49,230 participants with T2D, 8,956 had incident CVD events (event rate 18.2%). We identified three novel genetic loci for incident CVD: rs147138607 (near CACNA1E/ZNF648, hazard ratio [HR] 1.23, P = 3.6 × 10-9), rs77142250 (near HS3ST1, HR 1.89, P = 9.9 × 10-9), and rs335407 (near TFB1M/NOX3, HR 1.25, P = 1.5 × 10-8). Among 204 known CAD loci, 5 were associated with incident CVD in T2D (multiple comparison-adjusted P < 0.00024, 0.05/204). A standardized polygenic score of these 204 variants was associated with incident CVD with HR 1.14 (P = 1.0 × 10-16). CONCLUSIONS: The data point to novel and known genomic regions associated with incident CVD among individuals with T2D.

Proteomics analysis indicates the involvement of immunity and inflammation in the onset stage of SOD1-G93A mouse model of ALS.

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron degenerative disease, and the pathogenic mechanism that underlies ALS is still unclear. We analyzed the differentially expressed proteins (DEPs) in the spinal cord between SOD1-G93A transgenic mice at the onset stage and non-transgenic (NTG) littermates based on 4D label-free quantitative proteomics (4D-LFQ) with liquid chromatography-tandem mass spectrometry (LC-MS/MS). In our study, 189 DEPs were screened, of which 166 were up-regulated and 23 down-regulated. Clusters of Orthologous Groups (COG)/ EuKaryotic Orthologous Groups (KOG) classification, subcellular localization annotation, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, clustering analysis and protein-protein interaction (PPI) network analyses were performed. Parallel reaction monitoring (PRM) analysis validated 48 proteins from immunity and inflammation-related pathways of KEGG. We described the function and distribution of DEPs, most of which were involved in the following pathways: complement and coagulation cascades, antigen processing and presentation, NF-kappa B signaling pathway, Retinoic acid-inducible gene I (RIG) -I-like receptor signaling pathway, the extracellular matrix-receptor (ECM-receptor) interaction, focal adhesion, phagosome and lysosome. PPI network analysis identified Fn1, Fga, Serpina1e and Serpina3n as potential biomarkers. Our discoveries broaden the view and expand our understanding of immunity and inflammation in ALS. SIGNIFICANCE: This study gives a comprehensive description of DEPs in the spinal cord proteomics of SOD1-G93A mice at the onset period. Compared with a previous study focusing on progressive stage, we showed that immunity and inflammation play an important role at the onset stage of ALS. Several pathways validated by PRM bring new insight to the pathological mechanisms of ALS. The participation of RIG-I-like signaling pathway in ALS and potential biomarkers Fga, Fn1, Serpina1e and Serpina3n are supplements to existing knowledge.

Heterogeneous effects on type 2 diabetes and cardiovascular outcomes of genetic variants and traits associated with fasting insulin.

Hyperinsulinemia is a complex and heterogeneous phenotype that characterizes molecular alterations that precede the development of type 2 diabetes (T2D). It results from a complex combination of molecular processes, including insulin secretion and insulin sensitivity, that differ between individuals. To better understand the physiology of hyperinsulinemia and ultimately T2D, we implemented a genetic approach grouping fasting insulin (FI)-associated genetic variants based on their molecular and phenotypic similarities. We identified seven distinctive genetic clusters representing different physiologic mechanisms leading to rising FI levels, ranging from clusters of variants with effects on increased FI, but without increased risk of T2D (non-diabetogenic hyperinsulinemia), to clusters of variants that increase FI and T2D risk with demonstrated strong effects on body fat distribution, liver, lipid, and inflammatory processes (diabetogenic hyperinsulinemia). We generated cluster-specific polygenic scores in 1,104,258 individuals from five multi-ancestry cohorts to show that the clusters differed in associations with cardiometabolic traits. Among clusters characterized by non-diabetogenic hyperinsulinemia, there was both increased and decreased risk of coronary artery disease despite the non-increased risk of T2D. Similarly, the clusters characterized by diabetogenic hyperinsulinemia were associated with an increased risk of T2D, yet had differing risks of cardiovascular conditions, including coronary artery disease, myocardial infarction, and stroke. The strongest cluster-T2D associations were observed with the same direction of effect in non-Hispanic Black, Hispanic, non-Hispanic White, and non-Hispanic East Asian populations. These genetic clusters provide important insights into granular metabolic processes underlying the physiology of hyperinsulinemia, notably highlighting specific processes that decouple increasing FI levels from T2D and cardiovascular risk. Our findings suggest that increasing FI levels are not invariably associated with adverse cardiometabolic outcomes.

Time-to-Event Genome-Wide Association Study for Incident Cardiovascular Disease in People with Type 2 Diabetes Mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2D) confers a two- to three-fold increased risk of cardiovascular disease (CVD). However, the mechanisms underlying increased CVD risk among people with T2D are only partially understood. We hypothesized that a genetic association study among people with T2D at risk for developing incident cardiovascular complications could provide insights into molecular genetic aspects underlying CVD. METHODS: From 16 studies of the Cohorts for Heart & Aging Research in Genomic Epidemiology (CHARGE) Consortium, we conducted a multi-ancestry time-to-event genome-wide association study (GWAS) for incident CVD among people with T2D using Cox proportional hazards models. Incident CVD was defined based on a composite of coronary artery disease (CAD), stroke, and cardiovascular death that occurred at least one year after the diagnosis of T2D. Cohort-level estimated effect sizes were combined using inverse variance weighted fixed effects meta-analysis. We also tested 204 known CAD variants for association with incident CVD among patients with T2D. RESULTS: A total of 49,230 participants with T2D were included in the analyses (31,118 European ancestries and 18,112 non-European ancestries) which consisted of 8,956 incident CVD cases over a range of mean follow-up duration between 3.2 and 33.7 years (event rate 18.2%). We identified three novel, distinct genetic loci for incident CVD among individuals with T2D that reached the threshold for genome-wide significance (P<5.0×10-8): rs147138607 (intergenic variant between CACNA1E and ZNF648) with a hazard ratio (HR) 1.23, 95% confidence interval (CI) 1.15 - 1.32, P=3.6×10-9, rs11444867 (intergenic variant near HS3ST1) with HR 1.89, 95% CI 1.52 - 2.35, P=9.9×10-9, and rs335407 (intergenic variant between TFB1M and NOX3) HR 1.25, 95% CI 1.16 - 1.35, P=1.5×10-8. Among 204 known CAD loci, 32 were associated with incident CVD in people with T2D with P<0.05, and 5 were significant after Bonferroni correction (P<0.00024, 0.05/204). A polygenic score of these 204 variants was significantly associated with incident CVD with HR 1.14 (95% CI 1.12 - 1.16) per 1 standard deviation increase (P=1.0×10-16). CONCLUSIONS: The data point to novel and known genomic regions associated with incident CVD among individuals with T2D.

Vowel enhancement effects in cochlear-implant users.

Auditory enhancement of certain frequencies can occur through prior stimulation of surrounding frequency regions. The underlying neural mechanisms are unknown, but may involve stimulus-driven changes in cochlear gain via the medial olivocochlear complex (MOC) efferents. Cochlear implants (CIs) bypass the cochlea and stimulate the auditory nerve directly. If the MOC plays a critical role in enhancement then CI users should not exhibit this effect. Results using vowel stimuli, with and without preceding sounds designed to enhance formants, provided evidence of auditory enhancement in both normal-hearing listeners and CI users, suggesting that vowel enhancement is not mediated solely by cochlear effects.

Emergency Department Visits by Patients with Substance Use Disorder in the United States.

INTRODUCTION: We aimed to characterize emergency department (ED) utilization and clinical characteristics of patients with substance use disorder (SUD) seeking emergency care for all reasons. METHODS: Using 2016-2017 ED data from the National Hospital Ambulatory Medical Care Survey, we investigated demographics, ED resource utilization, and clinical characteristics of patients with SUD vs those without SUD. RESULTS: Of all adult ED visits (N = 27,609) in the US in 2016-2017, 11.1% of patients had SUD. Among ED patients with SUD, they were mostly non-Hispanic White (62.5%) and were more likely to be male (adjusted odds ratio [aOR] 1.80 confidence interval [CI], 1.66-1.95). Emergency department patients with SUD were also more likely to return to the ED within 72 hours (aOR 1.32, CI, 1.09-1.61) and more likely to be admitted to the hospital (aOR 1.28, CI, 1.14-1.43) and intensive care unit (aOR 1.40, CI, 1.05-1.85). CONCLUSION: Patients with SUD have specific demographic, socioeconomic, and clinical characteristics associated with their ED visits. These findings highlight the importance of recognizing co-existing SUD as risk factors for increasing morbidity in acutely ill and injured patients, and the potential role of the ED as a site for interventions aimed at reducing harm from SUD.

A New Approach for Noise Suppression in Cochlear Implants: A Single-Channel Noise Reduction Algorithm.

The cochlea "translates" the in-air vibrational acoustic "language" into the spikes of neural "language" that are then transmitted to the brain for auditory understanding and/or perception. During this intracochlear "translation" process, high resolution in time-frequency-intensity domains guarantees the high quality of the input neural information for the brain, which is vital for our outstanding hearing abilities. However, cochlear implants (CIs) have coarse artificial coding and interfaces, and CI users experience more challenges in common acoustic environments than their normal-hearing (NH) peers. Noise from sound sources that a listener has no interest in may be neglected by NH listeners, but they may distract a CI user. We discuss the CI noise-suppression techniques and introduce noise management for a new implant system. The monaural signal-to-noise ratio estimation-based noise suppression algorithm "eVoice," which is incorporated in the processors of Nurotron® EnduroTM, was evaluated in two speech perception experiments. The results show that speech intelligibility in stationary speech-shaped noise can be significantly improved with eVoice. Similar results have been observed in other CI devices with single-channel noise reduction techniques. Specifically, the mean speech reception threshold decrease in the present study was 2.2 dB. The Nurotron society already has more than 10,000 users, and eVoice is a start for noise management in the new system. Future steps on non-stationary-noise suppression, spatial-source separation, bilateral hearing, microphone configuration, and environment specification are warranted. The existing evidence, including our research, suggests that noise-suppression techniques should be applied in CI systems. The artificial hearing of CI listeners requires more advanced signal processing techniques to reduce brain effort and increase intelligibility in noisy settings.

In vivo hepatocyte growth factor gene transfer reduces myocardial ischemia-reperfusion injury through its multiple actions.

BACKGROUND: Hepatocyte growth factor (HGF) is reported to protect the heart against ischemia-reperfusion injury. However, whether in vivo adenovirus-mediated HGF gene transfer before ischemia is protective against ischemia-reperfusion and its precise mechanisms are still unknown. METHODS AND RESULTS: By using a rabbit model of ischemia-reperfusion injury, we demonstrate that HGF gene transfer is cardioprotective through its multiple beneficial actions, such as angiogenesis, Bcl-2 overexpression, and decreasing hydroxyl radicals, deoxyuride-5'-triphosphate biotin nick end labeling (TUNEL)-positive myocytes, and fibrotic area. After HGF gene transfer, the rabbits underwent 30 minutes of coronary occlusion and 30 minutes, 4 hours, 48 hours, and 14 days of reperfusion. The infarct size at 48 hours of reperfusion was significantly reduced in the HGF group (13.4% +/- 2.3%) compared with that in the LacZ group (36.5% +/- 2.0%) and saline group (40.3% +/- 3.2%). At 14 days of reperfusion, HGF gene transfer improved left ventricular ejection fraction and fractional shortening, reduced the fibrotic area, and increased the capillary density in the risk area. At 4 hours of reperfusion, Bcl-2 protein was overexpressed and the incidence of TUNEL-positive myocytes was significantly decreased in the risk area in the HGF group compared with the LacZ and saline groups. The myocardial interstitial 2,5-dihydroxybenzoic acid level, an indicator of hydroxyl radical, increased during 30 minutes of ischemia and 30 minutes of reperfusion in the LacZ and saline groups, and was significantly inhibited in the HGF group. CONCLUSION: HGF gene therapy may be a novel therapeutic strategy against unstable angina pectoris or severe angina pectoris, which may progress to acute myocardial infarction.

Implementation and preliminary evaluation of 'C-tone': A novel algorithm to improve lexical tone recognition in Mandarin-speaking cochlear implant users.

OBJECTIVES: Because of limited spectral resolution, Mandarin-speaking cochlear implant (CI) users have difficulty perceiving fundamental frequency (F0) cues that are important to lexical tone recognition. To improve Mandarin tone recognition in CI users, we implemented and evaluated a novel real-time algorithm (C-tone) to enhance the amplitude contour, which is strongly correlated with the F0 contour. METHODS: The C-tone algorithm was implemented in clinical processors and evaluated in eight users of the Nurotron NSP-60 CI system. Subjects were given 2 weeks of experience with C-tone. Recognition of Chinese tones, monosyllables, and disyllables in quiet was measured with and without the C-tone algorithm. Subjective quality ratings were also obtained for C-tone. RESULTS: After 2 weeks of experience with C-tone, there were small but significant improvements in recognition of lexical tones, monosyllables, and disyllables (P < 0.05 in all cases). Among lexical tones, the largest improvements were observed for Tone 3 (falling-rising) and the smallest for Tone 4 (falling). Improvements with C-tone were greater for disyllables than for monosyllables. Subjective quality ratings showed no strong preference for or against C-tone, except for perception of own voice, where C-tone was preferred. DISCUSSION: The real-time C-tone algorithm provided small but significant improvements for speech performance in quiet with no change in sound quality. Pre-processing algorithms to reduce noise and better real-time F0 extraction would improve the benefits of C-tone in complex listening environments. CONCLUSIONS: Chinese CI users' speech recognition in quiet can be significantly improved by modifying the amplitude contour to better resemble the F0 contour.