18440 N 68Th St Apt 2003
Phoenix AZ 85054
Medical School: Other - Unknown
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Dynamic control and quantification of bacterial population dynamics in droplets. - Biomaterials
Culturing and measuring bacterial population dynamics are critical to develop insights into gene regulation or bacterial physiology. Traditional methods, based on bulk culture to obtain such quantification, have the limitations of higher cost/volume of reagents, non-amendable to small size of population and more laborious manipulation. To this end, droplet-based microfluidics represents a promising alternative that is cost-effective and high-throughput. However, difficulties in manipulating the droplet environment and monitoring encapsulated bacterial population for long-term experiments limit its utilization. To overcome these limitations, we used an electrode-free injection technology to modulate the chemical environment in droplets. This ability is critical for precise control of bacterial dynamics in droplets. Moreover, we developed a trapping device for long-term monitoring of population dynamics in individual droplets for at least 240Â h. We demonstrated the utility of this new microfluidic system by quantifying population dynamics of natural and engineered bacteria. Our approach can further improve the analysis for systems and synthetic biology in terms of manipulability and high temporal resolution.Copyright Â© 2015 Elsevier Ltd. All rights reserved.
Association of childhood trauma with fatigue, depression, stress, and inflammation in breast cancer patients undergoing radiotherapy. - Psycho-oncology
This pilot study examined whether breast cancer patients with childhood trauma exhibit increased fatigue, depression, and stress in association with inflammation as a result of whole breast radiotherapy (RT).Twenty breast cancer patients were enrolled in a prospective, longitudinal study of fatigue, depression, and perceived stress prior to RT, week 6 of RT, and 6 weeks post-RT. Six weeks after RT, subjects completed the childhood trauma questionnaire (CTQ). Patients were also administered the multidimensional fatigue inventory, inventory of depressive symptomatology-self-reported, and perceived stress scale at all three time-points and underwent blood sampling prior to RT for gene expression and inflammatory markers previously associated with childhood trauma and behavioral symptoms in breast cancer patients.Eight subjects (40%) had past childhood trauma (CTQ+). Compared to CTQ- patients, CTQ+ patients had significantly higher fatigue, depression, and stress scores before, during, and after RT (pâ€‰<â€‰0.05); however, RT did not increase these symptoms in either group. CTQ+ patients also exhibited increased baseline expression of gene transcripts related to inflammatory signaling, and baseline inflammatory markers including c-reactive protein, interleukin (IL)-6, and IL-1 receptor antagonist were positively correlated with depression, fatigue, and stress scores in CTQ+ but not CTQ- patients.Childhood trauma was prevalent and was associated with increased symptoms of fatigue, depression, and stress irrespective of RT. Increased symptoms in CTQ+ patients were also associated with baseline inflammatory markers. Treatments targeting childhood trauma and related inflammation may improve symptoms in breast cancer patients. Copyright Â© 2015 John Wiley & Sons, Ltd.Copyright Â© 2015 John Wiley & Sons, Ltd.
Validation of the ASSIST for Detecting Unhealthy Alcohol Use and Alcohol Use Disorders in Urgent Care Patients. - Alcoholism, clinical and experimental research
Screening and brief intervention (SBI) is effective in reducing alcohol use, particularly among moderate risk patients. Results of SBI are inconsistent among patients with alcohol use disorders (AUDs). The Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) is used as a screening tool in many existing SBI programs. ASSIST validation studies have identified risk level cutoff scores using criteria for AUD and have not included a criterion measure for at-risk drinking (ARD), the group for whom SBI is most effective. This study examines the ability of the ASSIST to identify unhealthy alcohol use (ARD or AUD) and AUD in patients presenting to urgent care.Data were obtained from interviews with 442 adult drinkers presenting to 1 of 3 urgent care clinics. Subjects completed the ASSIST, a 90-day timeline follow-back interview to detect ARD, and a modified Diagnostic Interview Schedule to identify AUD. Validity measures compared the specificity and sensitivity of cutoff scores for the ASSIST in detecting unhealthy alcohol use and AUDs.The optimal ASSIST score for detecting unhealthy alcohol use is 6+ for males (sensitivity and specificity 68 and 66%, respectively) and 5+ for females (62%/70%). Sensitivity, specificity, and receiver operating characteristic values were lower than those previously reported for the Alcohol Use Disorders Identification Test (AUDIT). For AUD, the optimal ASSIST cutoff scores are 10+ for males (63%/85%) and 9+ for females (63%/85%). While higher scores provided increased specificity, thereby reducing the percentage of false positives, sensitivity dropped sharply as scores increased.Optimal ASSIST cutoff scores for unhealthy alcohol use are lower than those commonly used in many SBI programs. Use of lower ASSIST cutoff scores may increase detection of unhealthy alcohol use and increase the numbers served by SBI programs.Copyright Â© 2015 by the Research Society on Alcoholism.
Gemcitabine plus vinorelbine as the second-line treatment and beyond in elderly patients with platinum-pretreated advanced non-small cell lung cancer. - Chemotherapy
The efficacy and tolerance of a gemcitabine and vinorelbine (GV) combination as salvage therapy have not been reported in elderly patients with advanced non-small cell lung cancer (NSCLC).We reviewed elderly patients with advanced NSCLC who had disease progression after one or more chemotherapy regimens, at least one including platinum, and then who were treated with GV as the salvage therapy.In total 40 patients were analyzed. GV was at least the third-line chemotherapy in 24 patients (60.0%). Only 2 patients (5.0%) experienced grade 3 febrile neutropenia. Nonhematologic toxicities were generally mild and there was no treatment-related mortality. Among 29 patients evaluable for treatment response, 10 (34.5%) and 9 (31.0%) achieved a partial response and stable disease, respectively. The median overall survival was 10.3 months and the median progression-free survival was 3.1 months.GV in combination is an effective and tolerable salvage regimen in elderly and heavily pretreated patients with advanced NSCLC. Â© 2015 S. Karger AG, Basel.
A power-law dependence of bacterial invasion on mammalian host receptors. - PLoS computational biology
Pathogenic bacteria such as Listeria and Yersinia gain initial entry by binding to host target cells and stimulating their internalization. Bacterial uptake entails successive, increasingly strong associations between receptors on the surface of bacteria and hosts. Even with genetically identical cells grown in the same environment, there are vast differences in the number of bacteria entering any given cell. To gain insight into this variability, we examined uptake dynamics of Escherichia coli engineered to express the invasin surface receptor from Yersinia, which enables uptake via mammalian host Î²1-integrins. Surprisingly, we found that the uptake probability of a single bacterium follows a simple power-law dependence on the concentration of integrins. Furthermore, the value of a power-law parameter depends on the particular host-bacterium pair but not on bacterial concentration. This power-law captures the complex, variable processes underlying bacterial invasion while also enabling differentiation of cell lines.
Altered esophageal histamine receptor expression in Eosinophilic Esophagitis (EoE): implications on disease pathogenesis. - PloS one
Eosinophilic Esophagitis (EoE) is a chronic allergic disorder, whose pathobiology is incompletely understood. Histamine-producing cells including mast cells and basophils have been implicated in EoE. However, very little is currently known about the role of histamine and histamine receptor (HR) expression and signaling in the esophageal epithelium. Herein, we characterized HR (H1R, H2R, H3R, and H4R) expression in human esophageal biopsies and investigate the role of histamine signaling in inducible cytokine expression in human esophageal epithelial cells in vitro. HR expression was quantified in esophageal biopsies from non-EoE control (N = 23), inactive EoE (<15 eos/hpf, N = 26) and active EoE (>15 eos/hpf, N = 22) subjects using qRT-PCR and immunofluorescent localization. HR expression and histamine-mediated cytokine secretion were evaluated in human primary and telomerase-immortalized esophageal epithelial cells. H1R, H2R, and H4R expression were increased in active EoE biopsies compared to inactive EoE and controls. H2R was the most abundantly expressed receptor, and H3R expression was negligible in all 3 cohorts. Infiltrating eosinophils expressed H1R, H2R, and H4R, which contributed to the observed increase in HR in active subjects. H1R and H2R, but not H3R or H4R, were constitutively expressed by primary and immortalized cells, and epithelial histamine stimulation induced GM-CSF, TNFÎ±, and IL-8, but not TSLP or eotaxin-3 secretion. Epithelial priming with the TLR3 ligand poly (I:C) induced H1R and H2R expression, and enhanced histamine-induced GM-CSF, TNFÎ±, and IL-8 secretion. These effects were primarily suppressed by H1R antagonists, but unaffected by H2R antagonism. Histamine directly activates esophageal epithelial cytokine secretion in vitro in an H1R dependent fashion. However, H1R, H2R and H4R are induced in active inflammation in EoE in vivo. While systemic antihistamine (anti-H1R) therapy may not induce clinical remission in EoE, our study suggests that further study of histamine receptor signaling in EoE is warranted and that targeting of additional histamine receptors may lead to novel treatment strategies for this important disease.
Irinotecan and capecitabine combination chemotherapy in a patient with triple-negative breast cancer relapsed after adjuvant chemotherapy with anthracycline and taxane. - Tumori
The most effective regimen for taxane- and anthracycline-refractory triple-negative breast cancer (TNBC) has not yet been established. Capecitabine was approved by the US Food and Drug Administration for the treatment of advanced breast cancer and has shown efficacy in advanced breast cancer refractory to anthracyclines and taxanes. Irinotecan has synergism with 5-fluorouracil and shows efficacy in advanced breast cancer. Here we report on a patient with TNBC who relapsed with widespread bone and lung metastases shortly after adjuvant anthracycline followed by taxane chemotherapy. She achieved a metabolic complete response with irinotecan and capecitabine combination therapy and had 10 months' progression-free survival and 22 months' overall survival. She relapsed with and died of brain metastasis without any definite signs of progression of the lung and bone lesions she had had before the irinotecan and capecitabine combination therapy. To validate this favorable result, larger clinical trials are warranted in patients with metastatic or relapsed TNBC.
Collective antibiotic tolerance: mechanisms, dynamics and intervention. - Nature chemical biology
Bacteria have developed resistance against every antibiotic at a rate that is alarming considering the timescale at which new antibiotics are developed. Thus, there is a critical need to use antibiotics more effectively, extend the shelf life of existing antibiotics and minimize their side effects. This requires understanding the mechanisms underlying bacterial drug responses. Past studies have focused on survival in the presence of antibiotics by individual cells, as genetic mutants or persisters. Also important, however, is the fact that a population of bacterial cells can collectively survive antibiotic treatments lethal to individual cells. This tolerance can arise by diverse mechanisms, including resistance-conferring enzyme production, titration-mediated bistable growth inhibition, swarming and interpopulation interactions. These strategies can enable rapid population recovery after antibiotic treatment and provide a time window during which otherwise susceptible bacteria can acquire inheritable genetic resistance. Here, we emphasize the potential for targeting collective antibiotic tolerance behaviors as an antibacterial treatment strategy.
Fatal congenital hypertrophic cardiomyopathy and a pancreatic nodule morphologically identical to focal lesion of congenital hyperinsulinism in an infant with costello syndrome: case report and review of the literature. - Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society
Costello syndrome is characterized by constitutional mutations in the proto-oncogene HRAS, causing dysmorphic features, multiple cardiac problems, intellectual disability, and an increased risk of neoplasia. We report a male infant with dysmorphic features, born prematurely at 32 weeks, who, during his 3-month life span, had an unusually severe and ultimately fatal manifestation of hypertrophic cardiomyopathy and hyperinsulinemic hypoglycemia. Molecular studies in this patient demonstrated the uncommon Q22K mutation in the HRAS gene, diagnostic of Costello syndrome. The major autopsy findings revealed hypertrophic cardiomyopathy, congenital myopathy, and a 1.4-cm pancreatic nodule that was positive for insulin expression and morphologically identical to a focal lesion of congenital hyperinsulinism. Sequencing of KCNJ11 and ABCC8, the 2 most commonly mutated genes in focal lesion of congenital hyperinsulinism, revealed no mutations. While hyperinsulinism is a recognized feature of RASopathies, a focal proliferation of endocrine cells similar to a focal lesion of hyperinsulinism is a novel pathologic finding in Costello syndrome.
Genes required for survival in microgravity revealed by genome-wide yeast deletion collections cultured during spaceflight. - BioMed research international
Spaceflight is a unique environment with profound effects on biological systems including tissue redistribution and musculoskeletal stresses. However, the more subtle biological effects of spaceflight on cells and organisms are difficult to measure in a systematic, unbiased manner. Here we test the utility of the molecularly barcoded yeast deletion collection to provide a quantitative assessment of the effects of microgravity on a model organism. We developed robust hardware to screen, in parallel, the complete collection of ~4800 homozygous and ~5900 heterozygous (including ~1100 single-copy deletions of essential genes) yeast deletion strains, each carrying unique DNA that acts as strain identifiers. We compared strain fitness for the homozygous and heterozygous yeast deletion collections grown in spaceflight and ground, as well as plus and minus hyperosmolar sodium chloride, providing a second additive stressor. The genome-wide sensitivity profiles obtained from these treatments were then queried for their similarity to a compendium of drugs whose effects on the yeast collection have been previously reported. We found that the effects of spaceflight have high concordance with the effects of DNA-damaging agents and changes in redox state, suggesting mechanisms by which spaceflight may negatively affect cell fitness.
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18440 N 68Th St Apt 2003 Phoenix, AZ 85054
6950 E Chauncey Ln Suite 150