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1.
Breast Cancer Res Treat ; 199(2): 389-397, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37002487

RESUMEN

PURPOSE: Cancers deficient in homologous recombination DNA repair, such as those with BRCA1 or BRCA2 (BRCA1/2) mutations rely on a pathway mediated by the enzyme poly(adenosine diphosphate-ribose) polymerase (PARP). PARP inhibitors (PARPi's) have demonstrated efficacy in treating patients with germline (g)BRCA1/2, somatic (s)BRCA1/2, and gPALB2 mutations in clinical trials. However, patients with a poor performance status (PS) and those with severe organ impairment are often excluded from clinical trials and cancer-directed treatment. METHODS: We report the cases of two patients with metastatic breast cancer who had poor PS, significant visceral disease, and gPALB2 and sBRCA mutations, who derived significant clinical benefit from treatment with PARP inhibition. RESULTS: Patient A had germline testing demonstrating a heterozygous PALB2 pathogenic mutation (c.3323delA) and a BRCA2 variant of unknown significance (c.9353T>C), and tumor sequencing revealed PALB2 (c.228_229del and c.3323del) and ESR1 (c.1610A>C) mutations. Patient B was negative for pathologic BRCA mutations upon germline testing, but tumor sequencing demonstrated somatic BRCA2 copy number loss and a PIK3CA mutation (c.1633G>A). Treatment with PARPi's in these two patients with an initial PS of 3-4 and significant visceral disease resulted in prolonged clinical benefit. CONCLUSION: Patients with a poor PS, such as those described here, may still have meaningful clinical responses to cancer treatments targeting oncogenic drivers. More studies evaluating PARPi's beyond gBRCA1/2 mutations and in sub-optimal PS would help identify patients who may benefit from these therapies.


Asunto(s)
Neoplasias de la Mama , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Humanos , Femenino , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Proteína BRCA1/genética , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Proteína BRCA2/genética , Poli(ADP-Ribosa) Polimerasas/genética , Mutación de Línea Germinal
2.
J Perinat Med ; 50(8): 1030-1035, 2022 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-35570568

RESUMEN

OBJECTIVES: To determine the racial and ethnic compositions of the participants in obstetric randomized controlled trials (RCTs) and compare them to the US general population. METHODS: RCTs published in two premier US journals, American Journal of Obstetrics and Gynecology, Obstetrics and Gynecology from January 2010 to April 2020 were analyzed. The racial and ethnic distributions of the study participants were extracted and expressed as percentages for each article. Obstetrics articles were selected and then further divided into subcategories. Statistical analyses were performed on racial and ethnicity representation in each subcategory compared to a US population norm. RESULTS: Overall, a wide variation of racial and ethnic distribution was noted among studies. However, statistically significant overrepresentation of Non-Hispanic Black population and underrepresentation of White and Asian races were noted while Hispanic population's representation was comparable to the US general population. This observation was persistent across most of the subcategories. CONCLUSIONS: RCTs in the field of Obstetrics showed an overrepresentation of Black population. This observation was unique when we consider the previous reports in other fields of medicine. These findings should be taken into consideration when interpreting the results of RCTs conducted in US.


Asunto(s)
Etnicidad , Obstetricia , Femenino , Humanos , Embarazo , Grupos Raciales , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Retrospectivos , Estados Unidos
3.
Cell Physiol Biochem ; 46(5): 2017-2030, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29723871

RESUMEN

BACKGROUND/AIMS: Cyclic ADP-ribose (cADPR) is a Ca2+ -mobilization messenger that acts on ryanodine-sensitive Ca2+ channels in the sarcoplasmic reticulum (SR) Ca2+ stores. Moreover, it has been proposed that cADPR serves an additional role in activating the sarcoendoplasmic reticulum Ca2+ -ATPase (SERCA) pump. The aim of this study was to determine the exact mechanism by which cADPR regulates SR Ca2+ stores in physiologically relevant systems. METHODS: We analyzed Ca2+ signals as well as the production of Ca2+ mobilizing messengers in the skeletal muscle cells of mice subjected to intensive exercise or in the SR fractions from skeletal muscle cells after ß-adrenergic receptor (ß-AR) stimulation. RESULTS: We show that cADPR enhances SERCA activity in skeletal muscle cells in response to ß-AR agonists, increasing SR Ca2+ uptake. We demonstrate that cADPR is generated by CD38, a cADPR-synthesizing enzyme, increasing muscle Ca2+ signals and contractile force during exercise. CD38 is upregulated by the cAMP response element-binding protein (CREB) transcription factor upon ß-AR stimuli and exercise. CD38 knockout (KO) mice show defects in their exercise and cADPR synthesis capabilities, lacking a ß-AR agonist-induced muscle contraction when compared to wild-type mice. The skeletal muscle of CD38 KO mice exhibits delayed cytosolic Ca2+ clearance and reduced SERCA activity upon exercise. CONCLUSION: These findings provide insight into the physiological adaptive mechanism by which the CD38- cADPR-SERCA signaling axis plays an essential role in muscle contraction under exercise, and define cADPR as an endogenous activator of SERCA in enhancing the SR Ca2+ load.


Asunto(s)
ADP-Ribosil Ciclasa 1/metabolismo , Agonistas Adrenérgicos beta/farmacología , ADP-Ribosa Cíclica/metabolismo , Contracción Muscular/efectos de los fármacos , Músculo Esquelético/fisiología , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Línea Celular , Masculino , Ratones , Ratones Endogámicos C57BL , Receptores Adrenérgicos beta/metabolismo
4.
Reproduction ; 154(5): 595-605, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28780571

RESUMEN

CD31 has been shown to play a role in endothelial cell migration and angiogenesis, which are critical to the formation and function of the endometrium and myometrium in uterine development during early pregnancy. However, the role of CD31 in uterine receptivity during blastocyst implantation is poorly understood. The pregnancy rate in CD31-/- female mice mated with CD31+/+ male mice was higher than that observed in CD31+/+ female mice mated with CD31+/+ male mice. During the receptive phase of implantation, uterine glands were more developed in CD31-/- mice than in CD31+/+ mice, and the uterine weights of CD31-/- mice were increased. Leukemia inhibitory factor (LIF) was highly expressed in the CD31-/- mice during implantation and the expression of LIF was up-regulated by estradiol-17ß (E2 ) + progesterone (P4 ) in ovariectomized CD31-/- mice, compared with CD31+/+ mice at 8 h after hormone treatment. E2 -induced protein synthesis was inhibited by P4 in the CD31+/+ uterus, but not in the uterus of CD31-/- mice. Also, STAT3, HAND2, LIF, and mTOR signals were enhanced in CD31-/- mice. Stromal DNA replication was highly activated in the uterus of CD31-/- mice, manifested by upregulated cyclin series signaling and PCNA expression after E2 + P4 treatment. Collectively, CD31 inhibits E2 -mediated epithelial proliferation via recruitment and phosphorylation of SHP-2 upon receiving P4 signal in early pregnancy.


Asunto(s)
Molécula-1 de Adhesión Celular Endotelial de Plaqueta/fisiología , Progesterona/farmacología , Útero/metabolismo , Animales , Implantación del Embrión/efectos de los fármacos , Implantación del Embrión/genética , Endometrio/efectos de los fármacos , Endometrio/metabolismo , Estradiol/farmacología , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/genética , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Embarazo , Transducción de Señal/efectos de los fármacos , Útero/efectos de los fármacos
5.
Anal Chem ; 88(17): 8359-63, 2016 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-27490379

RESUMEN

Acute undifferentiated febrile illnesses (AFIs) represent a significant health burden worldwide. AFIs can be caused by infection with a number of different pathogens including dengue (DENV) and Chikungunya viruses (CHIKV), and their differential diagnosis is critical to the proper patient management. While rapid diagnostic tests (RDTs) for the detection of IgG/IgM against a single pathogen have played a significant role in enabling the rapid diagnosis in the point-of-care settings, the state-of-the-art assay scheme is incompatible with the multiplex detection of IgG/IgM to more than one pathogen. In this paper, we present a novel assay scheme that uses two-color latex labels for rapid multiplex detection of IgG/IgM. Adapting this assay scheme, we show that 4-plex detection of the IgG/IgM antibodies to DENV and CHIKV is possible in 10 min by using it to correctly identify 12 different diagnostic scenarios. We also show that blue, mixed, and red colorimetric signals corresponding to IgG, IgG/IgM, and IgM positive cases, respectively, can be associated with distinct ranges of hue intensities, which could be exploited by analyzer systems in the future for making accurate, automated diagnosis. This represents the first steps toward the development of a single RDT-based system for the differential diagnosis of numerous AFIs of interest.


Asunto(s)
Anticuerpos/análisis , Fiebre Chikungunya/diagnóstico , Colorimetría , Dengue/diagnóstico , Inmunoglobulina G/análisis , Inmunoglobulina M/análisis , Enfermedad Aguda , Virus Chikungunya/aislamiento & purificación , Virus del Dengue/aislamiento & purificación , Pruebas Diagnósticas de Rutina , Humanos , Sistemas de Atención de Punto
6.
J Clin Med ; 13(12)2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38929926

RESUMEN

Objectives: Risk assessment models for cardiac surgery do not distinguish between degrees of liver dysfunction. We have previously shown that preoperative liver stiffness is associated with hospital length of stay following cardiac surgery. The authors hypothesized that a liver stiffness measurement (LSM) ≥ 9.5 kPa would rule out a short hospital length of stay (LOS < 6 days) following isolated coronary artery bypass grafting (CABG) surgery. Methods: A prospective observational study of one hundred sixty-four adult patients undergoing non-emergent isolated CABG surgery at a single university hospital center. Preoperative liver stiffness measured by ultrasound elastography was obtained for each participant. Multivariate logistic regression models were used to assess the adjusted relationship between LSM and a short hospital stay. Results: We performed multivariate logistic regression models using short hospital LOS (<6 days) as the dependent variable. Independent variables included LSM (< 9.5 kPa, ≥ 9.5 kPa), age, sex, STS predicted morbidity and mortality, and baseline hemoglobin. After adjusting for included variables, LSM ≥ 9.5 kPa was associated with lower odds of early discharge as compared to LSM < 9.5 kPa (OR: 0.22, 95% CI: 0.06-0.84, p = 0.03). The ROC curve and resulting AUC of 0.76 (95% CI: 0.68-0.83) suggest the final multivariate model provides good discriminatory performance when predicting early discharge. Conclusions: A preoperative LSM ≥ 9.5 kPa ruled out a short length of stay in nearly 80% of patients when compared to patients with a LSM < 9.5 kPa. Preoperative liver stiffness may be a useful metric to incorporate into preoperative risk stratification.

7.
Front Plant Sci ; 12: 796956, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34992623

RESUMEN

Abiotic stresses, such as salt and heat stress, coexist in some regions of the world and can have a significant impact on agricultural plant biomass and production. Rice is a valuable crop that is susceptible to salt and high temperatures. Here, we studied the role of flavanol 3-hydroxylase in response to combined salt and heat stress with the aim of better understanding the defensive mechanism of rice. We found that, compared with wild-type plants, the growth and development of transgenic plants were improved due to higher biosynthesis of kaempferol and quercetin. Furthermore, we observed that oxidative stress was decreased in transgenic plants compared with that in wild-type plants due to the reactive oxygen species scavenging activity of kaempferol and quercetin as well as the modulation of glutathione peroxidase and lipid peroxidase activity. The expression of high-affinity potassium transporter (HKT) and salt overly sensitive (SOS) genes was significantly increased in transgenic plants compared with in control plants after 12 and 24 h, whereas sodium-hydrogen exchanger (NHX) gene expression was significantly reduced in transgenic plants compared with in control plants. The expression of heat stress transcription factors (HSFs) and heat shock proteins (HSPs) in the transgenic line increased significantly after 6 and 12 h, although our understanding of the mechanisms by which the F3H gene regulates HKT, SOS, NHX, HSF, and HSP genes is limited. In addition, transgenic plants showed higher levels of abscisic acid (ABA) and lower levels of salicylic acid (SA) than were found in control plants. However, antagonistic cross talk was identified between these hormones when the duration of stress increased; SA accumulation increased, whereas ABA levels decreased. Although transgenic lines showed significantly increased Na+ ion accumulation, K+ ion accumulation was similar in transgenic and control plants, suggesting that increased flavonoid accumulation is crucial for balancing Na+/K+ ions. Overall, this study suggests that flavonoid accumulation increases the tolerance of rice plants to combined salt and heat stress by regulating physiological, biochemical, and molecular mechanisms.

8.
Mol Neurobiol ; 56(5): 3819-3832, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30215158

RESUMEN

TRPM2 a cation channel is also known to work as an enzyme that hydrolyzes highly reactive, neurotoxic ADP-ribose (ADPR). Although ADPR is hydrolyzed by NUT9 pyrophosphatase in major organs, the enzyme is defective in the brain. The present study questions the role of TRPM2 in the catabolism of ADPR in the brain. Genetic ablation of Trpm2 results in the disruption of ADPR catabolism that leads to the accumulation of ADPR and reduction in AMP. Trpm2-/- mice elicit the reduction in autophagosome formation in the hippocampus. Trpm2-/- mice also show aggregations of proteins in the hippocampus, aberrant structural changes and neuronal connections in synapses, and neuronal degeneration. Trpm2-/- mice exhibit learning and memory impairment, enhanced neuronal intrinsic excitability, and imbalanced synaptic transmission. These results respond to long-unanswered questions regarding the potential role of the enzymatic function of TRPM2 in the brain, whose dysfunction evokes protein aggregation. In addition, the present finding answers to the conflicting reports such as neuroprotective or neurodegenerative phenotypes observed in Trpm2-/- mice.


Asunto(s)
Adenosina Difosfato Ribosa/metabolismo , Autofagia , Encéfalo/metabolismo , Eliminación de Gen , Agregado de Proteínas , Canales Catiónicos TRPM/deficiencia , Animales , Cognición , Hipocampo/metabolismo , Hidrólisis , Memoria , Ratones Endogámicos C57BL , Ratones Noqueados , Degeneración Nerviosa/metabolismo , Degeneración Nerviosa/patología , Plasticidad Neuronal , Neuronas/metabolismo , Transmisión Sináptica , Canales Catiónicos TRPM/metabolismo
9.
J Appl Physiol (1985) ; 124(2): 364-373, 2018 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-29146687

RESUMEN

The aim of the present study was to examine whether transient receptor potential melastatin 2 (TRPM2) plays a role in muscle fiber-type transition during exercise. Mice were trained at a speed of 12 m/min at a slope of 0° for 60 min for 5 consecutive days/wk for 4 wk. Exhaustion tests were performed on the treadmill (the speed was set at 6 m/min at a slope of 0° and increased at a rate of 1 m/min every 6 min). Isolated primary skeletal muscle cells from TRPM2-knockout (KO) mice showed lower amplitudes of electrical stimuli (ES)-induced Ca2+ signals when compared with wild-type (WT) mice due to a defect in Ca2+ influx. Moreover, TRPM2-KO mice had a higher proportion of fast-twitch skeletal muscle fibers and a lower proportion of slow-twitch muscle fibers before exercise than WT mice. After exercise, the expression of slow-twitch skeletal muscle fibers was increased only in WT mice but not in TRPM2-KO mice. ES-induced nuclear translocation of the Ca2+-dependent transcription factor NFATc1 was significantly lower in TRPM2-KO mice than in WT mice. TRPM2-KO mice also showed decreased mitochondrial Ca2+ and membrane potential. Lactate levels were higher in the skeletal muscle cells of TRPM2-KO mice before and after ES compared with WT mice. Collectively, these data indicate that TRPM2-mediated Ca2+ signaling plays a critical role in the regulation of fiber-type switching and mitochondrial function in skeletal muscle. NEW & NOTEWORTHY TRPM2 has been shown to play an important role in a variety of cellular functions. However, the role of TRPM2 in skeletal muscle remains poorly understood. Here, we provide evidence that TRPM2-mediated Ca2+ signaling is required for training-induced improvement in skeletal muscle mitochondrial function and fiber type transition.


Asunto(s)
Señalización del Calcio , Mitocondrias Musculares/metabolismo , Músculo Esquelético/fisiología , Condicionamiento Físico Animal/fisiología , Canales Catiónicos TRPM/metabolismo , Animales , Tolerancia al Ejercicio , Masculino , Ratones Noqueados , Piruvato Deshidrogenasa (Lipoamida)/metabolismo
10.
Biosens Bioelectron ; 99: 115-121, 2018 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-28750335

RESUMEN

Iron deficiency (ID) is an urgent public health problem that has devastating effects on maternal and child health. However, due to poor access and affordability, screening and diagnosis for ID is often limited to proxy hemoglobin measurements alone. Here, we report the development and validation of ironPhone, a mobile-device coupled portable diagnostics for quantification of serum ferritin concentrations, an iron status biomarker, within a few minutes, from a drop of fingerprick blood. The ironPhone diagnostic platform comprises of a smartphone accessory, an app, and a disposable lateral flow immunoassay test strip to quantify serum ferritin. For initial validation in the lab, we optimized and evaluated the performance of ironPhone with known ferritin concentrations in spiked buffer and serum samples. Following lab validation, we performed a human validation by collecting fingerprick whole blood samples from 20 participants to assess iron status using ironPhone and compared the results with the laboratory standard IMMULITE 2000 analyzer. Findings from the ironPhone for the buffer and spiked serum samples provided a calibration curve with R2 values of 0.97 (n=27) and 0.93 (n=12), respectively. On comparison with the laboratory standard IMMULITE analyzer in whole blood samples, a correlation of 0.92 (P<0.0001) was observed with a sensitivity of over 90% for predicting ID (ferritin<15.0µg/L) via the ironPhone, demonstrating its promise for iron status assessment at the point-of-care.


Asunto(s)
Técnicas Biosensibles , Ferritinas/sangre , Hierro/sangre , Teléfono Celular , Ferritinas/aislamiento & purificación , Humanos , Hierro/aislamiento & purificación
11.
JMIR Hum Factors ; 5(1): e9, 2018 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-29490894

RESUMEN

BACKGROUND: Technological advances in personal informatics allow people to track their own health in a variety of ways, representing a dramatic change in individuals' control of their own wellness. However, research regarding patient interpretation of traditional medical tests highlights the risks in making complex medical data available to a general audience. OBJECTIVE: This study aimed to explore how people interpret medical test results, examined in the context of a mobile blood testing system developed to enable self-care and health management. METHODS: In a preliminary investigation and main study, we presented 27 and 303 adults, respectively, with hypothetical results from several blood tests via one of the several mobile interface designs: a number representing the raw measurement of the tested biomarker, natural language text indicating whether the biomarker's level was low or high, or a one-dimensional chart illustrating this level along a low-healthy axis. We measured respondents' correctness in evaluating these results and their confidence in their interpretations. Participants also told us about any follow-up actions they would take based on the result and how they envisioned, generally, using our proposed personal health system. RESULTS: We find that a majority of participants (242/328, 73.8%) were accurate in their interpretations of their diagnostic results. However, 135 of 328 participants (41.1%) expressed uncertainty and confusion about their ability to correctly interpret these results. We also find that demographics and interface design can impact interpretation accuracy, including false confidence, which we define as a respondent having above average confidence despite interpreting a result inaccurately. Specifically, participants who saw a natural language design were the least likely (421.47 times, P=.02) to exhibit false confidence, and women who saw a graph design were less likely (8.67 times, P=.04) to have false confidence. On the other hand, false confidence was more likely among participants who self-identified as Asian (25.30 times, P=.02), white (13.99 times, P=.01), and Hispanic (6.19 times, P=.04). Finally, with the natural language design, participants who were more educated were, for each one-unit increase in education level, more likely (3.06 times, P=.02) to have false confidence. CONCLUSIONS: Our findings illustrate both promises and challenges of interpreting medical data outside of a clinical setting and suggest instances where personal informatics may be inappropriate. In surfacing these tensions, we outline concrete interface design strategies that are more sensitive to users' capabilities and conditions.

12.
Food Nutr Bull ; 38(2): 140-145, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28513261

RESUMEN

The need for improving methods of nutritional assessment and delivering primary health care globally cannot be overemphasized. While advances in medical technology typically create more disparities because of access being limited to resource-rich settings, a transition of health care to a mobile platform is increasingly leveling the field. Technological advances offer opportunities to scale laboratory procedures down to mobile devices, such as smartphones and tablets. Globalization also provides the required infrastructure and network capacity to support the use of mobile health devices in developing settings where nutritional deficiencies are most prevalent. Here, we discuss some of the applications and advantages provided by expanding markets of biomarker measurement coupled with primary health care and public health systems and how this is enhancing access and delivery of health services with significant global impact.


Asunto(s)
Distinciones y Premios , Dietética/métodos , Salud Global , Trastornos Nutricionales/diagnóstico , Pruebas en el Punto de Atención , Medicina de Precisión , Biomarcadores/metabolismo , Ahorro de Costo , Dietética/economía , Dietética/tendencias , Monitoreo Epidemiológico , Costos de la Atención en Salud , Humanos , Internacionalidad , Aplicaciones Móviles/economía , Aplicaciones Móviles/tendencias , Evaluación Nutricional , Trastornos Nutricionales/economía , Trastornos Nutricionales/metabolismo , Trastornos Nutricionales/terapia , Pruebas en el Punto de Atención/economía , Pruebas en el Punto de Atención/tendencias , Medicina de Precisión/economía , Medicina de Precisión/tendencias , Atención Primaria de Salud/economía , Atención Primaria de Salud/métodos , Atención Primaria de Salud/tendencias , Teléfono Inteligente/economía , Teléfono Inteligente/tendencias
13.
Curr Opin Biotechnol ; 44: 103-108, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-28043002

RESUMEN

Precision nutrition encompasses prevention and treatment strategies for optimizing health that consider individual variability in diet, lifestyle, environment and genes by accurately determining an individual's nutritional status. This is particularly important as malnutrition now affects a third of the global population, with most of those affected or their care providers having limited means of determining their nutritional status. Similarly, program implementers often have no way of determining the impact or success of their interventions, thus hindering their scale-up. Exciting new developments in the area of point-of-care diagnostics promise to provide improved access to nutritional status assessment, as a first step towards enabling precision nutrition and tailored interventions at both the individual and community levels. In this review, we focus on the current advances in developing portable diagnostics for assessment of nutritional status at point-of-care, along with the numerous design challenges in this process and potential solutions.


Asunto(s)
Evaluación Nutricional , Estado Nutricional , Sistemas de Atención de Punto , Humanos
14.
Biosens Bioelectron ; 90: 238-244, 2017 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-27914367

RESUMEN

Development of CNT-based CD4+ T cell imunosensors remains in its infancy due to the poor immobilization efficiency, lack of reproducibility, and difficulty in providing linear quantification. Here, we developed a fully-integrated single wall carbon nanotube (SWCNT)-based immunosensor capable of selective capture and linear quantification of CD4+ T cells with greater dynamic range. By employing repeated two-step oxygen (O2) plasma treatment processes with 35 days of recovery periods, we achieved the enhanced functionalization of the CNT surface and the removal of the byproduct of spray-coated SWCNTs that hinders charge transfer and stable CD4+ T cell sensing. As a result, a linear electrochemical signal was generated in direct proportion to the bound cells. The slope of a SWCNT electrode in a target concentration range (102~106cells/mL) was 4.55×10-2µA per concentration decade, with the lowest detection limit of 1×102cells/mL. Since the reduced number of CD4+ T cell counts in patients' peripheral blood corresponds to the progression of HIV disease, our CD4+ T cell-immunosensor provides a simple and low-cost platform which can fulfill the requirement for the development of point-of-care (POC) diagnostic technologies for human immunodeficiency virus (HIV) patients in resource-limited countries.


Asunto(s)
Anticuerpos Inmovilizados/química , Técnicas Biosensibles/instrumentación , Linfocitos T CD4-Positivos/citología , Técnicas Electroquímicas/instrumentación , Recuento de Linfocitos/instrumentación , Nanotubos de Carbono/química , Animales , Separación Celular/instrumentación , Electrodos , Humanos , Inmunoensayo/instrumentación , Ratones Endogámicos C57BL , Nanotubos de Carbono/ultraestructura , Oxígeno/química , Gases em Plasma/química , Sistemas de Atención de Punto
15.
Lab Chip ; 16(13): 2408-17, 2016 07 07.
Artículo en Inglés | MEDLINE | ID: mdl-27272753

RESUMEN

Micronutrient deficiency is widespread and negatively impacts morbidity, mortality, and quality of life globally. On-going advancements in nutritional biomarker discovery are enabling objective and accurate assessment of an individual's micronutrient and broader nutritional status. The vast majority of such assessment however still needs to be conducted in traditional centralized laboratory facilities which are not readily accessible in terms of cost and time in both the developed and developing countries. Lab-on-a-chip (LOC) technologies are enabling an increasing number of biochemical reactions at the point-of-need (PON) settings, and can significantly improve the current predicament in nutrition diagnostics by allowing rapid evaluation of one's nutritional status and providing an easy feedback mechanism for tracking changes in diet or supplementation. We believe that nutrition diagnostics represents a particularly appealing opportunity over other PON applications for two reasons: (1) healthy ranges for many micronutrients are well defined which allows for an unbiased diagnosis, and (2) many deficiencies can be reversed through changes in diet or supplementation before they become severe. In this paper, we provide background on nutritional biomarkers used in nutrition diagnostics and review the emerging technologies that exploit them at the point-of-need.


Asunto(s)
Dispositivos Laboratorio en un Chip , Técnicas de Diagnóstico Molecular/métodos , Estado Nutricional , Medicina de Precisión/instrumentación , Biomarcadores/análisis , Exposición Dietética/análisis , Técnicas Electroquímicas/instrumentación , Técnicas Electroquímicas/métodos , Humanos , Micronutrientes/deficiencia , Técnicas de Diagnóstico Molecular/instrumentación , Pruebas en el Punto de Atención , Medicina de Precisión/métodos , Teléfono Inteligente/instrumentación , Quiste del Uraco/metabolismo
16.
Sci Rep ; 6: 28237, 2016 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-27301282

RESUMEN

Vitamin B12 is necessary for formation of red blood cells, DNA synthesis, neural myelination, brain development, and growth. Vitamin B12 deficiency is often asymptomatic early in its course; however, once it manifests, particularly with neurological symptoms, reversal by dietary changes or supplementation becomes less effective. Access to easy, low cost, and personalized nutritional diagnostics could enable individuals to better understand their own deficiencies as well as track the effects of dietary changes. In this work, we present the NutriPhone, a mobile platform for the analysis of blood vitamin B12 levels in 15 minutes. The NutriPhone technology comprises of a smartphone accessory, an app, and a competitive-type lateral flow test strip that quantifies vitamin B12 levels. To achieve the detection of sub-nmol/L physiological levels of vitamin B12, our assay incorporates an innovative "spacer pad" for increasing the duration of the key competitive binding reaction and uses silver amplification of the initial signal. We demonstrate the efficacy of our NutriPhone system by quantifying physiologically relevant levels of vitamin B12 and performing human trials where it was used to accurately evaluate blood vitamin B12 status of 12 participants from just a drop (~40 µl) of finger prick blood.


Asunto(s)
Sistemas de Atención de Punto , Teléfono Inteligente , Vitamina B 12/sangre , Humanos , Sistemas de Atención de Punto/economía , Deficiencia de Vitamina B 12/diagnóstico
17.
PLoS One ; 10(4): e0123947, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25880904

RESUMEN

The metabolism of birds is finely tuned to their activities and environments, and thus research on avian systems can play an important role in understanding organismal responses to environmental changes. At present, however, the physiological monitoring of bird metabolism is limited by the inability to take real-time measurements of key metabolites during flight. In this study, we present an implantable biosensor system that can be used for continuous monitoring of uric acid levels of birds during various activities including flight. The system consists of a needle-type enzymatic biosensor for the amperometric detection of uric acid in interstitial fluids. A lightweight two-electrode potentiostat system drives the biosensor, reads the corresponding output current and wirelessly transfers the data or records to flash memory. We show how the device can be used to monitor, in real time, the effects of short-term flight and rest cycles on the uric acid levels of pigeons. In addition, we demonstrate that our device has the ability to measure uric acid level increase in homing pigeons while they fly freely. Successful application of the sensor in migratory birds could open up a new way of studying birds in flight which would lead to a better understanding of the ecology and biology of avian movements.


Asunto(s)
Técnicas Biosensibles/instrumentación , Técnicas Biosensibles/métodos , Columbidae/fisiología , Ácido Úrico/análisis , Animales , Diseño de Equipo , Vuelo Animal
18.
PLoS One ; 9(2): e89903, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24587112

RESUMEN

Hemorrhagic shock (HS) is the leading cause of death for people with traumatic injuries. The onset of HS is correlated with marked changes in the plasma vasopressin levels and some studies indicate that administrating vasopressin in the bloodstream can help stabilize the situation. This situation calls naturally for the use of implantable devices for both the monitoring and treatment of HS. In this work, we present a self-powered hemorrhagic-shock autonomous integrated device (hemoAID) that continuously monitors vasopressin levels and releases vasopressin automatically when levels drop below a certain threshold. We demonstrate that the device can operate at physiological concentrations of vasopressin, in sheep serum, thus paving the way towards the development of an autonomous implantable device for HS prevention.


Asunto(s)
Técnicas Biosensibles/instrumentación , Bombas de Infusión Implantables , Monitoreo Fisiológico/instrumentación , Choque Hemorrágico/prevención & control , Vasopresinas/administración & dosificación , Animales , Nanocables , Ovinos , Vasopresinas/sangre , Vasopresinas/uso terapéutico
19.
Lab Chip ; 14(8): 1437-42, 2014 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-24569647

RESUMEN

Vitamin D deficiency has been linked to a number of diseases and adverse outcomes including: osteoporosis, infections, diabetes, cardiovascular diseases, and even cancer. At present the vast majority of vitamin D testing is performed in large-scale laboratories at the request of a physician as part of an annual panel of blood tests. Here we present a system for rapid quantification of vitamin D levels on a smartphone. The system consists of a smartphone accessory, an app, and a test strip that allows the colorimetric detection of 25-hydroxyvitamin D using a novel gold nanoparticle-based immunoassay. We show that the system can be used to accurately measure physiological levels of 25-hydroxyvitamin D with accuracy better than 15 nM and a precision of 10 nM. We compare our system with well-established ELISA test kits for serum samples of unknown concentration and demonstrate equivalency of the results. We envision this as the first step towards the development of the NutriPhone, a comprehensive system for the analysis of multiple vitamins and micronutrients on a smartphone.


Asunto(s)
Teléfono Celular , Inmunoensayo/instrumentación , Vitamina D/análogos & derivados , Colorimetría , Ensayo de Inmunoadsorción Enzimática , Oro/química , Nanopartículas del Metal/química , Tiras Reactivas/química , Propiedades de Superficie , Vitamina D/análisis , Vitamina D/química
20.
Lab Chip ; 14(17): 3159-64, 2014 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-24700127

RESUMEN

The rapid expansion of mobile technology is transforming the biomedical landscape. By 2016 there will be 260 M active smartphones in the US and millions of health accessories and software "apps" running off them. In parallel with this have come major technical achievements in lab-on-a-chip technology leading to incredible new biochemical sensors and molecular diagnostic devices. Despite these advancements, the uptake of lab-on-a-chip technologies at the consumer level has been somewhat limited. We believe that the widespread availability of smartphone technology and the capabilities they offer in terms of computation, communication, social networking, and imaging will be transformative to the deployment of lab-on-a-chip type technology both in the developed and developing world. In this paper we outline why we believe this is the case, the new business models that may emerge, and detail some specific application areas in which this synergy will have long term impact, namely: nutrition monitoring and disease diagnostics in limited resource settings.


Asunto(s)
Teléfono Celular , Dispositivos Laboratorio en un Chip , Diagnóstico , Humanos , Monitoreo Fisiológico/instrumentación , Telemedicina
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