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1.
J Marital Fam Ther ; 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38602713

RESUMEN

The proliferation of technology has accelerated exponentially over the past 50 years. Contemporarily, researchers have explored the influences technology use is having on individuals and relationships. Theoretical frameworks such as the couple, family, and technology (CFT) Framework have been applied to individuals and couples in committed relationships to better understand the implications of technology adoption and use within this relational subsystem. Research examining technology's impact on couple relationships recognizes the potential for technology use to be either helpful or unhelpful to the relationship but fails to fully examine the helpful aspects of technology use. This study addresses this gap with the creation of a theory grounded in data from N = 45 couples (n = 90 individuals) in committed relationships. Results indicate couples' technology use can augment emotional connection and unity within the relationship as couples manage the influence of technology in a way that is relationally helpful.

2.
PRiMER ; 8: 14, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38406235
3.
Transl Behav Med ; 13(8): 612-623, 2023 08 11.
Artículo en Inglés | MEDLINE | ID: mdl-37086443

RESUMEN

Despite effective treatment options, people who experience mental health conditions often do not receive needed care. E-mental health, for instance the use of mobile apps, is emerging as a way to increase access to and extend care. However, little formal training is available to increase the digital literacy level among behavioral healthcare providers (BHPs), seeking to employ such technology. The purpose of this study was to explore the acceptability and usability of an adapted in-person Digital Navigation Training (DNT) curriculum into e-Learning modules focused on the integrated environment for BHPs. BHP confidence to serve as digital navigators was also explored. E-Learning modules were adapted from an existing in-person DNT. A purposeful sampling strategy was used to recruit BHPs (n = 8) to complete the modules. Acceptability, usability, and confidence were assessed via survey and semi-structured interviews. Descriptive statistics were calculated for survey data and qualitative data were analyzed using a directed content analysis approach. BHPs who completed the training (n = 8) felt the modules were usable, enjoyed the structure, and felt the amount of time to complete the modules was acceptable. All participants thought the structure of the training worked well and enjoyed learning new information. While participants' confidence in their digital navigation skills increased, they desired more information and/or experience with screening apps prior to increasing their use of apps within their care. E-Learning modules were an acceptable method of educating BHPs with digital navigation skills. Future research is needed to explore incentives needed for training along with if participating in these modules can increase use of quality mobile apps to augment care within BHP treatment plans.


Supporting the use of technology in the integrated primary care environment, where patients often seek care for mental health conditions requires training. Behavioral Health Providers (BHPs) are members of the integrated team. BHPs are prime candidates to promote engagement of mobile apps within this model of care. Understanding how providing training in an online format to BHPs which supports their ability to incorporate apps into this unique environment is needed. The purpose of this article is to explore the acceptability and usability, and subsequent confidence to serve as a digital navigator, of an adapted in-person Digital Navigation Training consisting of E-Learning modules. E-Learning module content includes education pertaining to digital skills, shared-decision making and mobile app evaluation to facilitate knowledge among BHPs as well as their confidence in digital navigation. Our findings suggest that the online training is acceptable and usable by those who completed the training and improves their confidence to serve as a digital navigator. BHPs suggested quality improvement changes to the training which are being undertaken to include creating a checklist and adding to the mobile app evaluation content. The training can be accessed at https://www.unmc.edu/bhecn/education/m-health-digital-navigation-training-for-integrated-behavioral-health/index.html.


Asunto(s)
Aplicaciones Móviles , Humanos , Salud Mental , Encuestas y Cuestionarios
4.
Mhealth ; 8: 33, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36338314

RESUMEN

Background: Recent surveys have revealed many adults have basic or below basic health literacy, which is linked to medical errors, increased illness, and compromised public health. Health literacy as a concept is multi-faceted extending beyond the individual to include social structures and the context in which health information is being accessed. Delivering health information via mobile devices (mHealth) expands the amount of information available while presenting challenges to ensuring these materials are suitable for a variety of literacy needs. The aims of this study are to discover how health literacy is addressed and evaluated in mHealth app development. Methods: A scoping review of 5 peer-reviewed databases was conducted. Eligible articles were written in English, addressed general literacy or mHealth/digital/eHealth literacy, and collected literacy information in order to incorporate literacy into the design and/or modification of an app or collected literacy information to describe the population being studied. The "Health Literacy Online" (HLO) United States (U.S.) government guide was used as a framework. Results: Thirty-two articles were reviewed. Articles included health literacy recommendations for all HLO categories and some recommendations not aligned with these categories. Most articles addressed health literacy using specific HLO categories though none incorporated every HLO category. The most common categories addressed engagement and testing of mHealth content. Though several studies addressed health literacy through a formal assessment tool, most did not. Evaluation of health literacy in mHealth was end-user focused and did not extensively evaluate content for fit to a variety of individuals with limited health literacy. Conclusions: The recommendations seen consistently in our results in conjunction with formal HLO categories can act as beginning steps towards development of a health literacy evaluation tool for mHealth apps themselves. It is clear efforts are being made to reduce barriers to using mHealth for those with literacy deficits, however, it was also clear that this space has room to be more pragmatic in evaluation of mHealth tools for literacy. End user engagement in design and testing is necessary in future mHealth literacy tool development.

5.
Transl Behav Med ; 11(9): 1708-1716, 2021 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-34231855

RESUMEN

The use of mobile applications or "apps" is beginning to be identified as a potential cost-effective tool for treating depression. While the use of mobile apps for health management appears promising, little is known on how to incorporate these tools into integrated primary care settings-especially from the viewpoints of patients and the clinic personnel. The purpose of this study was to explore patient- and clinic-level perceptions of the use of depression self-management apps within an integrated primary care setting. Patients (n = 17), healthcare providers, and staff (n = 15) completed focus groups or semi-structured interviews in-person or via Zoom between January and July 2020. Participants were asked about barriers and facilitators to app use, how to best integrate it into care, and reviewed pre-selected mental health apps. Data were analyzed using a directed content analysis approach. From a patient perspective, features within the app such as notifications, the provision of information, easy navigation, and a chat/support function as well as an ability to share data with their doctor were desirable. Providers and staff identified integration of app data into electronic health records to be able to share data with patients and the healthcare team as well as clear evidence of effectiveness as factors that could facilitate implementation. All participants who reviewed apps identified at least one of them they would be interested in continuing to use. Overall, patients, healthcare providers, and staff believed depression apps could be beneficial for both patients and the clinic.


Asunto(s)
Aplicaciones Móviles , Automanejo , Depresión/terapia , Estudios de Factibilidad , Humanos , Atención Primaria de Salud
6.
J Pers Soc Psychol ; 120(3): 672-693, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32658522

RESUMEN

Stereotypes linking Black Americans with guns can have life-altering outcomes, making it important to identify factors that shape such weapon identification biases and how they do so. We report 6 experiments that provide a mechanistic account of how category salience affects weapon identification bias elicited by male faces varying in race (Black, White) and age (men, boys). Behavioral analyses of error rates and response latencies revealed that, when race was salient, faces of Black versus White males (regardless of age) facilitated the classification of objects as guns versus tools. When a category other than race was salient, racial bias in behavior was reduced, though not eliminated. In Experiments 1-4, racial bias was weaker when participants attended to a social category besides race (i.e., age). In Experiments 5 and 6, racial bias was weaker when participants attended to an applicable, yet nonsubstantive category (i.e., the color of a dot on the face). Across experiments, process analyses using diffusion models revealed that, when race was salient, seeing Black versus White male faces led to an initial bias to favor the "gun" response. When a category besides race (i.e., age, dot color) was salient, racial bias in the relative start point was reduced, though not eliminated. These results suggest that the magnitude of racial bias in weapon identification may differ depending on what social category is salient. The collective findings also highlight the utility of diffusion modeling for elucidating how category salience shapes processes underlying racial biases in behavior. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Asunto(s)
Negro o Afroamericano/psicología , Racismo , Percepción Social/psicología , Estereotipo , Armas , Población Blanca/psicología , Adolescente , Factores de Edad , Técnicas de Apoyo para la Decisión , Reconocimiento Facial , Femenino , Armas de Fuego , Humanos , Masculino , Tiempo de Reacción , Adulto Joven
7.
Psychol Bull ; 146(5): 451-479, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31944796

RESUMEN

To what extent are research results influenced by subjective decisions that scientists make as they design studies? Fifteen research teams independently designed studies to answer five original research questions related to moral judgments, negotiations, and implicit cognition. Participants from 2 separate large samples (total N > 15,000) were then randomly assigned to complete 1 version of each study. Effect sizes varied dramatically across different sets of materials designed to test the same hypothesis: Materials from different teams rendered statistically significant effects in opposite directions for 4 of 5 hypotheses, with the narrowest range in estimates being d = -0.37 to + 0.26. Meta-analysis and a Bayesian perspective on the results revealed overall support for 2 hypotheses and a lack of support for 3 hypotheses. Overall, practically none of the variability in effect sizes was attributable to the skill of the research team in designing materials, whereas considerable variability was attributable to the hypothesis being tested. In a forecasting survey, predictions of other scientists were significantly correlated with study results, both across and within hypotheses. Crowdsourced testing of research hypotheses helps reveal the true consistency of empirical support for a scientific claim. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Asunto(s)
Colaboración de las Masas , Psicología/métodos , Proyectos de Investigación , Adulto , Humanos , Distribución Aleatoria
9.
J Marital Fam Ther ; 46(2): 186-200, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31820834

RESUMEN

The mental health field is increasingly integrating and growing a teletherapy presence, and couple and family therapists are uniquely situated to offer these services based on our history of innovative approaches to therapeutic services. To do so successfully, careful consideration of training and education must occur. To evaluate current teletherapy training and education opportunities of COAMFTE accredited couple, marriage, and family therapy programs, an inductive qualitative content analysis was conducted on the responses of 95 faculty at COAMFTE accredited programs. Findings indicate that more than two thirds of the participants were in favor of teletherapy integration in training programs; however, most programs currently do not offer such opportunities. Barriers that prevent such integration were highlighted as well as existing concerns to training graduate students in teletherapy. Implications for training programs, policies, and regulations are discussed.


Asunto(s)
Terapia de Parejas/educación , Curriculum , Brecha Digital , Terapia Familiar/educación , Telemedicina , Humanos , Investigación Cualitativa
10.
Proc Natl Acad Sci U S A ; 116(32): 15877-15882, 2019 08 06.
Artículo en Inglés | MEDLINE | ID: mdl-31332014

RESUMEN

Despite extensive attention to racial disparities in police shootings, two problems have hindered progress on this issue. First, databases of fatal officer-involved shootings (FOIS) lack details about officers, making it difficult to test whether racial disparities vary by officer characteristics. Second, there are conflicting views on which benchmark should be used to determine racial disparities when the outcome is the rate at which members from racial groups are fatally shot. We address these issues by creating a database of FOIS that includes detailed officer information. We test racial disparities using an approach that sidesteps the benchmark debate by directly predicting the race of civilians fatally shot rather than comparing the rate at which racial groups are shot to some benchmark. We report three main findings: 1) As the proportion of Black or Hispanic officers in a FOIS increases, a person shot is more likely to be Black or Hispanic than White, a disparity explained by county demographics; 2) race-specific county-level violent crime strongly predicts the race of the civilian shot; and 3) although we find no overall evidence of anti-Black or anti-Hispanic disparities in fatal shootings, when focusing on different subtypes of shootings (e.g., unarmed shootings or "suicide by cop"), data are too uncertain to draw firm conclusions. We highlight the need to enforce federal policies that record both officer and civilian information in FOIS.


Asunto(s)
Policia , Grupos Raciales , Femenino , Humanos , Masculino , Oportunidad Relativa
11.
Psychol Sci ; 30(4): 553-562, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30789793

RESUMEN

Recent research has shown that race can influence perceptions of men's size and strength. Across two studies (Study 1: N = 1,032, Study 2: N = 303) examining men and women from multiple racial groups (Asian, Black, and White adults), we found that although race does impact judgments of size and strength, raters' judgments primarily track targets' objective physical features. In some cases, racial stereotypes actually improved group-level accuracy, as these stereotypes aligned with racial-group differences in size and strength according to nationally representative data. We conclude that individuals primarily rely on individuating information when making physical judgments but do not completely discount racial stereotypes, which reflect a combination of real group-level differences and culturally transmitted beliefs.


Asunto(s)
Tamaño Corporal , Juicio , Racismo , Estereotipo , Adolescente , Femenino , Humanos , Masculino , Fuerza Muscular , Percepción Social , Adulto Joven
12.
J Pers Soc Psychol ; 115(4): 601-623, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30221956

RESUMEN

Social psychologists have relied on computerized shooting tasks to test whether race influences decisions to shoot. These studies reveal that under some conditions untrained individuals shoot unarmed Black men more than unarmed White men. We modeled the decision to shoot as a sequential sampling process in which people start out with prior biases and accumulate evidence over time until a threshold is reached, prompting a decision. We used this approach to test how prior information (a proxy for police dispatch information) and police experience influence racial bias in shooting decisions. When no prior information was given, target race biased the rate at which untrained civilians accumulated evidence, leading to a greater rate of shooting Black targets. For sworn police officers, the race of the target impacted prior bias, but not evidence accumulation. Moreover, officers showed no race bias in the observed decision to shoot. For both untrained civilians and sworn police officers, prior information about a target's race was sufficient to eliminate racial bias in shooting decisions both at the process and behavioral level. These studies reveal that factors present in real-world shooting decisions (dispatch information and police experience) can moderate the role that race plays both in the underlying cognitive processes and ultimately on the observed decision. We discuss the benefits of using a dynamic cognitive model to understand the decision to shoot and the implications of these results for laboratory analogues of real-world decisions. (PsycINFO Database Record


Asunto(s)
Toma de Decisiones , Armas de Fuego , Policia/psicología , Competencia Profesional , Racismo/psicología , Violencia/psicología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estados Unidos
13.
J Vasc Surg ; 68(5): 1482-1490, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-29803681

RESUMEN

OBJECTIVE: The decision to perform a one- or two-stage basilic vein transposition (BVT) arteriovenous fistula often depends on factors such as the vessel's diameter, the patient's disposition, and the surgeon's preference. This study's aim was to analyze patency by BVT staging technique and to identify patient-specific characteristics associated with outcomes. METHODS: A retrospective review of all patients who underwent one- or two-stage BVT at our institution between 2008 and 2013 was performed. Comparisons of age, sex, race, and associated comorbidities were made. Clinical course was followed for 2 years after fistula construction, comparing maturation rate, thrombosis, stenosis, steal, and catheter infections. Continuous variables were expressed as means or medians and compared across stage and maturation groups by t-test; differences between categorical variables were assessed using Fisher exact test. A Kaplan-Meier survival analysis was performed to calculate patency rates and compared by log-rank test. RESULTS: There were 49 one-stage and 169 two-stage BVTs examined. The mean age of the patients at time of construction was 58 years and 61 years for one-stage and two-stage patients, respectively. There was no difference in mean proximal, mid, or distal basilic vein diameters between the groups. Fistula maturation was similar between stage groups, with primary failure affecting 26.5% of one-stage and 24.3% of two-stage BVTs (P = .78). Across one- and two-stage BVTs, 2-year primary patency rates were 51% and 52%, respectively (P = .68); primary assisted patency, 66% and 85% (P = .05); and secondary patency, 64% and 78% (P = .26). Multivariate logistic regression showed a trend toward diabetics at higher risk for primary failure (odds ratio, 1.60; 95% confidence interval, 0.95-2.55; P = .07). For two-stage BVT, the median interstage period between operations lasted 105.00 (interquartile range, 77.00-174.50) days and was associated with a large proportion of the overall primary failures (19/41 [46%]) and catheter-related infections (12/20 [60%]). CONCLUSIONS: This study demonstrates similar maturation, primary patency, primary assisted patency, secondary patency, and complication rates in a large series of BVTs constructed using a one- or two-stage transposition technique regardless of vein diameter. Diabetes was associated with primary failure by either technique. High proportions of overall primary failures and catheter-related infections observed in two-stage BVT occurred during the interstage, suggesting that a one-stage technique should be considered over a two-stage approach to minimize the risk of catheter infection and to decrease time to maturity.


Asunto(s)
Derivación Arteriovenosa Quirúrgica/métodos , Diálisis Renal , Extremidad Superior/irrigación sanguínea , Venas/cirugía , Adulto , Anciano , Derivación Arteriovenosa Quirúrgica/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Grado de Desobstrucción Vascular , Venas/diagnóstico por imagen , Venas/fisiopatología
14.
Wounds ; 30(7): 182-185, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29718811

RESUMEN

INTRODUCTION: Foot offloading is the mainstay treatment for plantar diabetic foot ulcers (DFUs). OBJECTIVE: This multicenter, single-blinded, randomized controlled trial evaluates the efficacy of a total offloading foot brace for healing plantar DFUs. MATERIALS AND METHODS: Seventeen patients were randomized to standard therapy (ie, reducing stress and pressure via mechanical offloading) or offloading foot brace. Comparison of plantar pressures was performed using digital pressure sensing films. The ulcers were assessed by physical inspection and digital planimetry of photographs. RESULTS: Reductions in peak plantar pressures ranged from 67.3% to 89.4% (P = .09). Healing at weeks 12 to 15 had minimal differences (brace vs. control: 71.7% vs. 80.3%, respectively). Although not significant, earlier periods of the brace versus the control demonstrated faster wound healing in weeks 2 to 5 (36.0% vs. 6.8%, respectively) and weeks 6 to 9 (50.7% vs. 17.0%, respectively). CONCLUSIONS: The total offloading foot brace minimizes plantar pressure, allowing for early healing of DFUs, and optimizations in brace design may enhance healing of plantar DFUs.


Asunto(s)
Pie Diabético/fisiopatología , Ortesis del Pié , Pie/irrigación sanguínea , Soporte de Peso/fisiología , Cicatrización de Heridas/fisiología , Pie Diabético/rehabilitación , Medicina Basada en la Evidencia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Presión , Factores de Tiempo , Resultado del Tratamiento
15.
Front Psychol ; 9: 67, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29449823

RESUMEN

Is 50 considered "old"? When do we stop being considered "young"? If individuals could choose to be any age, what would it be? In a sample of 502,548 internet respondents ranging in age from 10 to 89, we examined age differences in aging perceptions (e.g., how old do you feel?) and estimates of the timing of developmental transitions (e.g., when does someone become an older adult?). We found that older adults reported older perceptions of aging (e.g., choosing to be older, feeling older, being perceived as older), but that these perceptions were increasingly younger than their current age. The age to which individuals hope to live dramatically increased after age 40. We also found that older adults placed the age at which developmental transitions occurred later in the life course. This latter effect was stronger for transitions involving middle-age and older adulthood compared to transitions involving young adulthood. The current study constitutes the largest study to date of age differences in age perceptions and developmental timing estimates and yielded novel insights into how the aging process may affect judgments about the self and others.

16.
Psychon Bull Rev ; 25(4): 1301-1330, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-28983838

RESUMEN

The biasing role of stereotypes is a central theme in social cognition research. For example, to understand the role of race in police officers' decisions to shoot, participants have been shown images of Black and White males and instructed to shoot only if the target is holding a gun. Findings show that Black targets are shot more frequently and more quickly than Whites. The decision to shoot has typically been modeled and understood as a signal detection process in which a sample of information is compared against a criterion, with the criterion set for Black targets being lower. We take a different approach, modeling the decision to shoot as a dynamic process in which evidence is accumulated over time until a threshold is reached. The model accounts for both the choice and response time data for both correct and incorrect decisions using a single set of parameters. Across four studies, this dynamic perspective revealed that the target's race did not create an initial bias to shoot Black targets. Instead, race impacted the rate of evidence accumulation with evidence accumulating faster to shoot for Black targets. Some participants also tended to be more cautious with Black targets, setting higher decision thresholds. Besides providing a more cohesive and richer account of the decision to shoot or not, the dynamic model suggests interventions that may address the use of race information in decisions to shoot and a means to measure their effectiveness.


Asunto(s)
Toma de Decisiones/fisiología , Armas de Fuego , Violencia con Armas/psicología , Grupos Raciales/psicología , Racismo/psicología , Tiempo de Reacción/fisiología , Detección de Señal Psicológica/fisiología , Adulto , Humanos
17.
J Vasc Surg ; 66(5): 1445-1449, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28625670

RESUMEN

OBJECTIVE: Asymptomatic internal carotid artery occlusion (CO) presents a clinical dilemma, and presently, the natural history, stroke risk, and optimal management remain ill defined. This study compared outcomes, including neurovascular events (NVEs) and health care costs, between patients with CO and patients with asymptomatic carotid artery stenosis (CS). METHODS: A prospectively maintained database was queried to identify patients with CO and CS with at least >50% carotid stenosis by duplex. We identified and reviewed 622 consecutive patients with asymptomatic carotid artery disease at one academic medical center between 2011 and 2013. Patients with CO (n = 97) were identified and propensity matched by age and gender in a 1:2 ratio with CS patients (n = 194) for further analyses. Univariate and multivariate models were used to analyze baseline characteristics, clinical variables, and 1-year follow-up data from the date of diagnosis. Multivariate analysis was performed by multiple linear regression modeling. Institutional Review Board approval was obtained. RESULTS: Follow-up data were available for 99% of matched patients. CO patients were younger (72 vs 75 years; P < .01) and more likely male (67% vs 53%; P = .01) compared with CS patients. After propensity matching, baseline characteristics were similar between groups, with a trend toward higher use of statin therapy among patients with CO. Antiplatelet therapy was used in 79% of patients with CS and in 74% of patients with CO (P = .45). The rate of NVE among CO patients was higher than among CS patients at 1 year of follow-up (14% vs 7%; P = .03). Among those with NVE, neither antiplatelet therapy (64% vs 77%; P = .49) nor statin therapy (86% vs 77%; P = .58) appeared to have a significant effect. Health care costs ($14,361 vs $12,142; P = .44) and hospital admission rate (63% vs 71%; P = .18) were similar between groups. Not surprisingly, the rate of vascular procedures was higher in the CS group (55% vs 27%; P = .04). CONCLUSIONS: Patients with asymptomatic CO experience more NVEs compared with similar patients with moderately severe CS. Further study of preventative strategies, including intensity of medical therapy, is warranted.


Asunto(s)
Arteria Carótida Interna , Estenosis Carotídea/complicaciones , Accidente Cerebrovascular/etiología , Centros Médicos Académicos , Anciano , Anciano de 80 o más Años , Enfermedades Asintomáticas , Arteria Carótida Interna/diagnóstico por imagen , Arteria Carótida Interna/fisiopatología , Estenosis Carotídea/economía , Estenosis Carotídea/fisiopatología , Estenosis Carotídea/terapia , Bases de Datos Factuales , Femenino , Costos de la Atención en Salud , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Ohio , Pronóstico , Puntaje de Propensión , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/economía , Accidente Cerebrovascular/prevención & control , Grado de Desobstrucción Vascular
18.
Mol Microbiol ; 97(2): 381-95, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25898991

RESUMEN

The widespread use of chloroquine to treat Plasmodium falciparum infections has resulted in the selection and dissemination of variant haplotypes of the primary resistance determinant PfCRT. These haplotypes have encountered drug pressure and within-host competition with wild-type drug-sensitive parasites. To examine these selective forces in vitro, we genetically engineered P. falciparum to express geographically diverse PfCRT haplotypes. Variant alleles from the Philippines (PH1 and PH2, which differ solely by the C72S mutation) both conferred a moderate gain of chloroquine resistance and a reduction in growth rates in vitro. Of the two, PH2 showed higher IC50 values, contrasting with reduced growth. Furthermore, a highly mutated pfcrt allele from Cambodia (Cam734) conferred moderate chloroquine resistance and enhanced growth rates, when tested against wild-type pfcrt in co-culture competition assays. These three alleles mediated cross-resistance to amodiaquine, an antimalarial drug widely used in Africa. Each allele, along with the globally prevalent Dd2 and 7G8 alleles, rendered parasites more susceptible to lumefantrine, the partner drug used in the leading first-line artemisinin-based combination therapy. These data reveal ongoing region-specific evolution of PfCRT that impacts drug susceptibility and relative fitness in settings of mixed infections, and raise important considerations about optimal agents to treat chloroquine-resistant malaria.


Asunto(s)
Proteínas de Transporte de Membrana/genética , Plasmodium falciparum/efectos de los fármacos , Plasmodium falciparum/genética , Proteínas Protozoarias/genética , Cloroquina , Resistencia a Medicamentos , Eritrocitos/parasitología , Frecuencia de los Genes , Haplotipos , Humanos , Malaria Falciparum/parasitología , Proteínas de Transporte de Membrana/metabolismo , Mutación , Plasmodium falciparum/metabolismo , Proteínas Protozoarias/metabolismo
19.
J Biol Chem ; 287(13): 9731-9741, 2012 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-22282497

RESUMEN

Atovaquone is an anti-malarial drug used in combination with proguanil (e.g. Malarone(TM)) for the curative and prophylactic treatment of malaria. Atovaquone, a 2-hydroxynaphthoquinone, is a competitive inhibitor of the quinol oxidation (Q(o)) site of the mitochondrial cytochrome bc(1) complex. Inhibition of this enzyme results in the collapse of the mitochondrial membrane potential, disruption of pyrimidine biosynthesis, and subsequent parasite death. Resistance to atovaquone in the field is associated with point mutations in the Q(o) pocket of cytochrome b, most notably near the conserved Pro(260)-Glu(261)-Trp(262)-Tyr(263) (PEWY) region in the ef loop). The effect of this mutation has been extensively studied in model organisms but hitherto not in the parasite itself. Here, we have performed a molecular and biochemical characterization of an atovaquone-resistant field isolate, TM902CB. Molecular analysis of this strain reveals the presence of the Y268S mutation in cytochrome b. The Y268S mutation is shown to confer a 270-fold shift of the inhibitory constant (K(i)) for atovaquone with a concomitant reduction in the V(max) of the bc(1) complex of ∼40% and a 3-fold increase in the observed K(m) for decylubiquinol. Western blotting analyses reveal a reduced iron-sulfur protein content in Y268S bc(1) suggestive of a weakened interaction between this subunit and cytochrome b. Gene expression analysis of the TM902CB strain reveals higher levels of expression, compared with the 3D7 (atovaquone-sensitive) control strain in bc(1) and cytochrome c oxidase genes. It is hypothesized that the observed differential expression of these and other key genes offsets the fitness cost resulting from reduced bc(1) activity.


Asunto(s)
Antimaláricos/farmacología , Atovacuona/farmacología , Citocromos b/biosíntesis , Resistencia a Medicamentos , Regulación Enzimológica de la Expresión Génica , Mutación Missense , Plasmodium falciparum/enzimología , Proteínas Protozoarias/biosíntesis , Sustitución de Aminoácidos , Citocromos b/genética , Complejo III de Transporte de Electrones/genética , Complejo III de Transporte de Electrones/metabolismo , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Plasmodium falciparum/genética , Proguanil/farmacología , Proteínas Protozoarias/genética
20.
Mol Biochem Parasitol ; 165(2): 122-31, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19428659

RESUMEN

Quinine (QN) continues to be an important treatment option for severe malaria, however resistance to this drug has emerged in field isolates of the etiologic agent Plasmodium falciparum. Quantitative trait loci investigations of QN resistance have mapped three loci of this complex trait. Two coincide with pfcrt and pfmdr1, involved in resistance to chloroquine (CQ) and other quinoline-based antimalarials. A third locus on chromosome 13 contains the sodium-proton exchanger (pfnhe) gene. Previous studies have associated pfnhe polymorphisms with reduced QN sensitivity in culture-adapted field isolates. Here, we provide direct evidence supporting the hypothesis that pfnhe contributes to QN resistance. Using allelic exchange, we reduced pfnhe expression by introducing a truncated 3' untranslated region (UTR) from pfcrt into the endogenous pfnhe 3'UTR. Transfections were performed with 1BB5 and 3BA6 (both CQ- and QN-resistant) as well as GC03 (CQ- and QN-sensitive), all progenies of the HB3xDd2 genetic cross. RNA and protein analyses of the ensuing recombinant clones demonstrated a approximately 50% decrease in pfnhe expression levels. A statistically significant 30% decrease in QN IC(50) values was associated with these decreased expression levels in 1BB5 and 3BA6 but not in GC03. CQ, mefloquine and lumefantrine IC(50) values were unaltered. Cytosolic pH values were similar in all parental lines and recombinant clones. Our observations support a role for pfnhe in QN resistance in a strain-dependent manner, which might be contingent on pre-existing resistance to CQ and/or QN. These data bolster observations that QN resistance is a complex trait requiring the contribution of multiple transporter proteins.


Asunto(s)
Antimaláricos/farmacología , Resistencia a Medicamentos/genética , Plasmodium falciparum/efectos de los fármacos , Plasmodium falciparum/genética , Quinina/farmacología , Intercambiadores de Sodio-Hidrógeno/genética , Animales , Citosol/química , Regulación de la Expresión Génica , Técnicas de Silenciamiento del Gen , Concentración de Iones de Hidrógeno , Plasmodium falciparum/metabolismo , Proteínas Recombinantes/metabolismo , Intercambiadores de Sodio-Hidrógeno/metabolismo , Especificidad de la Especie , Factores de Tiempo
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