9961 Sierra Ave
Fontana CA 92335
Medical School: University Of California, Irvine, California College Of Medicine - 1994
Accepts Medicare: Yes
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License #: A60101
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The Effect of Transcranial Direct Current Stimulation (tDCS) Electrode Size and Current Intensity on Motor Cortical Excitability:Â Evidence From Single and Repeated Sessions. - Brain stimulation
Current density is considered an important factor in determining the outcomes of tDCS, and is determined by the current intensity and electrode size. Previous studies examining the effect of these parameters on motor cortical excitability with small sample sizes reported mixed results.This study examined the effect of current intensity (1Â mA, 2Â mA) and electrode size (16Â cm(2), 35Â cm(2)) on motor cortical excitability over single and repeated tDCS sessions.Data from seven studies in 89 healthy participants were pooled for analysis. Single-session data were analyzed using mixed effects models and repeated-session data were analyzed using mixed design analyses of variance. Computational modeling was used to examine the electric field generated.The magnitude of increases in excitability after anodal tDCS was modest. For single-session tDCS, the 35Â cm(2) electrodes produced greater increases in cortical excitability compared to the 16Â cm(2) electrodes. There were no differences in the magnitude of cortical excitation produced by 1Â mA and 2Â mA tDCS. The repeated-sessions data also showed that there were greater increases in excitability with the 35Â cm(2) electrodes. Further, repeated sessions of tDCS with the 35Â cm(2) electrodes resulted in a cumulative increase in cortical excitability. Computational modeling predicted higher electric field at the motor hotspot for the 35Â cm(2) electrodes.2Â mA tDCS does not necessarily produce larger effects than 1Â mA tDCS in healthy participants. Careful consideration should be given to the exact positioning, size and orientation of tDCS electrodes relative to cortical regions.Copyright Â© 2015 Elsevier Inc. All rights reserved.
Quantitative power Doppler ultrasound measures of peripheral joint synovitis in poor prognosis early rheumatoid arthritis predict radiographic progression. - Rheumatology (Oxford, England)
To assess the value of quantitative vascular imaging by power Doppler US (PDUS) as a tool that can be used to stratify patient risk of joint damage in early seropositive RA while still biologic naive but on synthetic DMARD treatment.Eighty-five patients with seropositive RA of <3 years duration had clinical, laboratory and imaging assessments at 0 and 12 months. Imaging assessments consisted of radiographs of the hands and feet, two-dimensional (2D) high-frequency and PDUS imaging of 10 MCP joints that were scored for erosions and vascularity and three-dimensional (3D) PDUS of MCP joints and wrists that were scored for vascularity.Severe deterioration on radiographs and ultrasonography was seen in 45 and 28% of patients, respectively. The 3D power Doppler volume and 2D vascularity scores were the most useful US predictors of deterioration. These variables were modelled in two equations that estimate structural damage over 12 months. The equations had a sensitivity of 63.2% and specificity of 80.9% for predicting radiographic structural damage and a sensitivity of 54.2% and specificity of 96.7% for predicting structural damage on ultrasonography.In seropositive early RA, quantitative vascular imaging by PDUS has clinical utility in predicting which patients will derive benefit from early use of biologic therapy.Â© The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: firstname.lastname@example.org.
Exercise preconditioning improves traumatic brain injury outcomes. - Brain research
To determine whether 6 weeks of exercise performed prior to traumatic brain injury (TBI) could improve post-TBI behavioral outcomes in mice, and if exercise increases neuroprotective molecules (vascular endothelial growth factor-A [VEGF-A], erythropoietin [EPO], and heme oxygenase-1 [HO-1]) in brain regions responsible for movement (sensorimotor cortex) and memory (hippocampus).120 mice were randomly assigned to one of four groups: (1) no exercise+no TBI (NOEX-NOTBI [n=30]), (2) no exercise+TBI (NOEX-TBI [n=30]), (3) exercise+no TBI (EX-NOTBI [n=30]), and (4) exercise+TBI (EX-TBI [n=30]). The gridwalk task and radial arm water maze were used to evaluate sensorimotor and cognitive function, respectively. Quantitative real time polymerase chain reaction and immunostaining were performed to investigate VEGF-A, EPO, and HO-1 mRNA and protein expression in the right cerebral cortex and ipsilateral hippocampus.EX-TBI mice displayed reduced post-TBI sensorimotor and cognitive deficits when compared to NOEX-TBI mice. EX-NOTBI and EX-TBI mice showed elevated VEGF-A and EPO mRNA in the cortex and hippocampus, and increased VEGF-A and EPO staining of sensorimotor cortex neurons 1 day post-TBI and/or post-exercise. EX-TBI mice also exhibited increased VEGF-A staining of hippocampal neurons 1 day post-TBI/post-exercise. NOEX-TBI mice demonstrated increased HO-1 mRNA in the cortex (3 days post-TBI) and hippocampus (3 and 7 days post-TBI), but HO-1 was not increased in mice that exercised.Improved TBI outcomes following exercise preconditioning are associated with increased expression of specific neuroprotective genes and proteins (VEGF-A and EPO, but not HO-1) in the brain.Copyright Â© 2015 Elsevier B.V. All rights reserved.
Viral and atypical bacterial aetiologies of infection in hospitalised patients admitted with clinical suspicion of influenza in Thailand, Vietnam and Indonesia. - Influenza and other respiratory viruses
Influenza constitutes a leading cause of morbidity and mortality worldwide. There is limited information about the etiology of infection presenting clinically as influenza in hospitalized adults and children in Southeast Asia. Such data are important for future management of respiratory infections.To describe the etiology of infection presenting clinically as influenza in those hospitalized in Southeast Asia METHODS: Respiratory specimens archived from July 2008 to June 2009 from patients hospitalised with suspected influenza from (Indonesia, Thailand and Vietnam were tested for respiratory viruses and atypical bacteria by polymerase chain reaction.A total of 1222 patients' samples were tested. 776/1222 (63.5%) patients were under the age of 5. Viruses detected included rhinoviruses in 229/1222 patients (18.7%), bocaviruses in 200/1222 (16.4%), respiratory syncytial viruses in 144 (11.8%), parainfluenzaviruses in 140 (11.5%; PIV1: 32; PIV2: 12; PIV3: 71;PIV4: 25), adenovirus in 102 (8.4%), influenza viruses in 93 (7.6%; influenza A: 77; influenza B: 16), coronaviruses in 23 (1.8%; OC43: 14; E229: 9). Bacterial pathogens were: Mycoplasma pneumoniae (n=33, 2.7%), Chlamydophila psittaci (n=2), C. pneumoniae (n=1), Bordetella pertussis (n=1), and Legionella pneumophila (n=2). Overall in-hospital case fatality rate was 29/1222 (2.4%).Respiratory viruses were the most commonly detected pathogens in patients hospitalized with a clinical suspicion of influenza. Rhinovirus was the most frequently detected virus, and M. pneumoniae the most common atypical bacterium. The low number of detected influenza viruses demonstrate a low benefit for empirical oseltamivir therapy, unless during an influenza outbreak. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.
Characterization of Zinc Influx Transporters (ZIPs) in Pancreatic Î² Cells: ROLES IN REGULATING CYTOSOLIC ZINC HOMEOSTASIS AND INSULIN SECRETION. - The Journal of biological chemistry
Zinc plays an essential role in the regulation of pancreatic Î² cell function, affecting important processes including insulin biosynthesis, glucose-stimulated insulin secretion, and cell viability. Mutations in the zinc efflux transport protein ZnT8 have been linked with both type 1 and type 2 diabetes, further supporting an important role for zinc in glucose homeostasis. However, very little is known about how cytosolic zinc is controlled by zinc influx transporters (ZIPs). In this study, we examined the Î² cell and islet ZIP transcriptome and show consistent high expression of ZIP6 (Slc39a6) and ZIP7 (Slc39a7) genes across human and mouse islets and MIN6 Î² cells. Modulation of ZIP6 and ZIP7 expression significantly altered cytosolic zinc influx in pancreatic Î² cells, indicating an important role for ZIP6 and ZIP7 in regulating cellular zinc homeostasis. Functionally, this dysregulated cytosolic zinc homeostasis led to impaired insulin secretion. In parallel studies, we identified both ZIP6 and ZIP7 as potential interacting proteins with GLP-1R by a membrane yeast two-hybrid assay. Knock-down of ZIP6 but not ZIP7 in MIN6 Î² cells impaired the protective effects of GLP-1 on fatty acid-induced cell apoptosis, possibly via reduced activation of the p-ERK pathway. Therefore, our data suggest that ZIP6 and ZIP7 function as two important zinc influx transporters to regulate cytosolic zinc concentrations and insulin secretion in Î² cells. In particular, ZIP6 is also capable of directly interacting with GLP-1R to facilitate the protective effect of GLP-1 on Î² cell survival.Â© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
Dengue in adults admitted to a referral hospital in Hanoi, Vietnam. - The American journal of tropical medicine and hygiene
Knowledge of adult dengue virus (DENV) infection from Hanoi, Vietnam, is limited. In 2008, we prospectively studied 143 (77 male) confirmed (nonstructural 1 antigen enzyme-linked immunosorbent assay [ELISA], DENV polymerase chain reaction, paired serology) adult dengue patients of median age 23.5 (range 16-72) years. They were admitted to the National Hospital for Tropical Diseases, Hanoi, on median illness day (D) 5 (range 1-8). By D8, 141 (98.6%) were afebrile. Platelet counts and hematocrit (median, interquartile range [IQR]) nadired and peaked on D5 and D4, respectively: 40,000/Î¼L (10,000-109,000/Î¼L), 43.4% (34.9-49.7%). Four (2.8%) patients had severe dengue: 1) D10 shock (N = 1) and 2) aspartate aminotransferase (AST) â‰¥ 1,000 IU/L (N = 3, D5 and D7). Of 143 patients, 118 (82.5%) had â‰¥ 1 warning sign (World Health Organization [WHO] 2009 criteria): mucosal bleeding 66/143 (46.1%), soft tissue edema 54/143 (37.7%), and ultrasound detected plasma leakage (pleural effusions/ascites) 30/129 (23.25%). 138 (96.5%) patients received intravenous (IV) fluids: 3 L (IQR: 0.5-8.5 L). Most patients had non-severe dengue with warning signs. High rates of edema and plasma leakage may be explained partly by liberal use of IV fluids. Studies are needed on optimizing fluid management in non-severe adult dengue.Â© The American Society of Tropical Medicine and Hygiene.
Molecular subgroups of atypical teratoid rhabdoid tumours in children: an integrated genomic and clinicopathological analysis. - The Lancet. Oncology
Rhabdoid brain tumours, also called atypical teratoid rhabdoid tumours, are lethal childhood cancers with characteristic genetic alterations of SMARCB1/hSNF5. Lack of biological understanding of the substantial clinical heterogeneity of these tumours restricts therapeutic advances. We integrated genomic and clinicopathological analyses of a cohort of patients with atypical teratoid rhabdoid tumours to find out the molecular basis for clinical heterogeneity in these tumours.We obtained 259 rhabdoid tumours from 37 international institutions and assessed transcriptional profiles in 43 primary tumours and copy number profiles in 38 primary tumours to discover molecular subgroups of atypical teratoid rhabdoid tumours. We used gene and pathway enrichment analyses to discover group-specific molecular markers and did immunohistochemical analyses on 125 primary tumours to evaluate clinicopathological significance of molecular subgroup and ASCL1-NOTCH signalling.Transcriptional analyses identified two atypical teratoid rhabdoid tumour subgroups with differential enrichment of genetic pathways, and distinct clinicopathological and survival features. Expression of ASCL1, a regulator of NOTCH signalling, correlated with supratentorial location (p=0Â·004) and superior 5-year overall survival (35%, 95% CI 13-57, and 20%, 6-34, for ASCL1-positive and ASCL1-negative tumours, respectively; p=0Â·033) in 70 patients who received multimodal treatment. ASCL1 expression also correlated with superior 5-year overall survival (34%, 7-61, and 9%, 0-21, for ASCL1-positive and ASCL1-negative tumours, respectively; p=0Â·001) in 39 patients who received only chemotherapy without radiation. Cox hazard ratios for overall survival in patients with differential ASCL1 enrichment treated with chemotherapy with or without radiation were 2Â·02 (95% CI 1Â·04-3Â·85; p=0Â·038) and 3Â·98 (1Â·71-9Â·26; p=0Â·001). Integrated analyses of molecular subgroupings with clinical prognostic factors showed three distinct clinical risk groups of tumours with different therapeutic outcomes.An integration of clinical risk factors and tumour molecular groups can be used to identify patients who are likely to have improved long-term radiation-free survival and might help therapeutic stratification of patients with atypical teratoid rhabdoid tumours.C17 Research Network, Genome Canada, b.r.a.i.n.child, Mitchell Duckman, Tal Doron and Suri Boon foundations.Copyright Â© 2015 Elsevier Ltd. All rights reserved.
Factors associated with participation in research conducted in a pediatric emergency department. - Pediatric emergency care
To examine the association of demographic and study characteristics in eligible subjects who agree to participate compared with those who did not participate in clinical research studies in a pediatric emergency department (PED).Information for all families approached for participation in PED-based clinical research studies during a 6-year period was recorded in an electronic database. This included demographic factors, decision to participate, primary reason for not participating, and study characteristics. Forty studies were included in this analysis. Differences in participation rate among demographic and study characteristics were examined. Multivariable logistic regression was used to predict the likelihood of participation.Participation rates were similar with respect to sex (50.1% in male vs 49.9% in female), whereas families with younger children were more likely to participate (mean age, 8.5 years vs 10.2 years among nonparticipants P < 0.001). White patients were more likely to participate than African American patients (54.7% vs 45.6% in African Americans, P < 0.001). The presence of compensation, brief time requirement, and older children was negatively associated with participation for moderate to very invasive studies. However, for noninvasive and mildly invasive studies, the presence of compensation and the time required were not associated with participation.Study characteristics including invasiveness, time required of patients, and whether compensation is offered, along with demographic factors, influence participation in clinical studies conducted in the PED. When designing a research study in the PED, these, along with novel approaches to including all races and ethnicities in PED research, should be considered.
A PROGNOSTIC SCORE FOR ACUTE GRAFT-VERSUS-HOST DISEASE BASED ON BIOMARKERS: A MULTICENTER STUDY. - The Lancet. Haematology
Graft-versus-host disease (GVHD) is the major cause of non-relapse mortality (NRM) after allogeneic hematopoietic stem-cell transplantation (HCT). The severity of symptoms at the onset of GVHD does not accurately define risk, and thus most patients are treated alike with high dose systemic corticosteroids. We aimed to define clinically meaningful risk strata for patients with newly diagnosed acute GVHD using plasma biomarkers.We prospectively collected plasma from 492 HCT patients with newly diagnosed acute GVHD and randomly divided them into training (n=328) and test (n=164) sets. We used the concentrations of three recently validated biomarkers (TNFR1, ST2, and REG3Î±) to create an algorithm that computed the probability of NRM six months after GVHD onset for individual patients in the training set alone. We rank ordered the probabilities and identified thresholds that created three distinct NRM scores. We evaluated the algorithm in the testset, and again in an independent validation set of 300 additional HCT patients enrolled on multicenter clinical trials of primary therapy for acute GVHD.In all three datasets, the cumulative incidence of twelve month NRM significantly increased as the GVHD score increased (8% [95% confidence interval (CI); 3%, 16%], 27% [95% CI; 20%%, 34%], and 46% [95% CI; 33%, 58%], for scores 1, 2 and 3 respectively in the multicenter validation set, p<0 Â· 0001). Conversely, the response rates to primary GVHD treatment decreased as the GVHD score increased (86%, 67%, and 46%, for scores 1, 2 and 3 respectively in the multicenter validation set, p<0 Â· 0001).Biomarker-based scores can be used to guide risk-adapted therapy at the onset of acute GVHD.
Preexisting human antibodies neutralize recently emerged H7N9 influenza strains. - The Journal of clinical investigation
The emergence and seasonal persistence of pathogenic H7N9 influenza viruses in China have raised concerns about the pandemic potential of this strain, which, if realized, would have a substantial effect on global health and economies. H7N9 viruses are able to bind to human sialic acid receptors and are also able to develop resistance to neuraminidase inhibitors without a loss in fitness. It is not clear whether prior exposure to circulating human influenza viruses or influenza vaccination confers immunity to H7N9 strains. Here, we demonstrate that 3 of 83 H3 HA-reactive monoclonal antibodies generated by individuals that had previously undergone influenza A virus vaccination were able to neutralize H7N9 viruses and protect mice against homologous challenge. The H7N9-neutralizing antibodies bound to the HA stalk domain but exhibited a difference in their breadth of reactivity to different H7 influenza subtypes. Mapping viral escape mutations suggested that these antibodies bind at least two different epitopes on the stalk region. Together, these results indicate that these broadly neutralizing antibodies may contribute to the development of therapies against H7N9 strains and may also be effective against pathogenic H7 strains that emerge in the future.
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