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1.
Artículo en Inglés | MEDLINE | ID: mdl-38446365

RESUMEN

Transgender youth are at an increased risk of suicide, substance use, experiencing violent assaults, and reporting major depressive episodes and greater psychological distress compared to their cisgender counterparts. This study examined mental health symptom severity in adolescents admitted to an inpatient psychiatric hospital who wished they were of a different gender compared to those who did not. A group of 180 adolescents admitted to an inpatient psychiatric hospital completed assessments to measure mental health symptom severity at admission. Gender diverse (n = 90) and cisgender (n = 90) groups were established. Analyses of variance (ANOVA) were used to examine between group (gender diverse vs. cisgender) difference on depression, anxiety, suicide risk, nighttime sleep quality, and emotion regulation problems. Results revealed significant differences in emotion regulation difficulties at admission, specifically in nonacceptance and awareness. There were no significant differences on measures of depression, anxiety, suicide risk, and nighttime sleep quality at admission. This study is one of the first to measure mental health symptom severity in gender diverse adolescents while admitted to an inpatient psychiatric setting. Adolescents in the gender diverse group had significantly higher level of difficulty with emotion regulation, which may indicate an increased risk of developing psychiatric symptoms such as depression and anxiety. This paper demonstrates the importance of using targeted interventions to address difficulties with emotion regulation in at-risk adolescents.

2.
J Neurooncol ; 153(3): 393-402, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34101093

RESUMEN

BACKGROUND: A randomized trial in glioblastoma patients with methylated-MGMT (m-MGMT) found an improvement in median survival of 16.7 months for combination therapy with temozolomide (TMZ) and lomustine, however the approach remains controversial and relatively under-utilized. Therefore, we sought to determine whether comprehensive genomic analysis can predict which patients would derive large, intermediate, or negligible benefits from the combination compared to single agent chemotherapy. METHODS: Comprehensive genomic information from 274 newly diagnosed patients with methylated-MGMT glioblastoma (GBM) was downloaded from TCGA. Mutation and copy number changes were input into a computational biologic model to create an avatar of disease behavior and the malignant phenotypes representing hallmark behavior of cancers. In silico responses to TMZ, lomustine, and combination treatment were biosimulated. Efficacy scores representing the effect of treatment for each treatment strategy were generated and compared to each other to ascertain the differential benefit in drug response. RESULTS: Differential benefits for each drug were identified, including strong, modest-intermediate, negligible, and deleterious (harmful) effects for subgroups of patients. Similarly, the benefits of combination therapy ranged from synergy, little or negligible benefit, and deleterious effects compared to single agent approaches. CONCLUSIONS: The benefit of combination chemotherapy is predicted to vary widely in the population. Biosimulation appears to be a useful tool to address the disease heterogeneity, drug response, and the relevance of particular clinical trials observations to individual patients. Biosimulation has potential to spare some patients the experience of over-treatment while identifying patients uniquely situated to benefit from combination treatment. Validation of this new artificial intelligence tool is needed.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Antineoplásicos Alquilantes/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Inteligencia Artificial , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Metilasas de Modificación del ADN/genética , Enzimas Reparadoras del ADN/genética , Quimioterapia Combinada , Glioblastoma/tratamiento farmacológico , Glioblastoma/genética , Humanos , Lomustina/uso terapéutico , Sobretratamiento , Preparaciones Farmacéuticas , Temozolomida/uso terapéutico , Proteínas Supresoras de Tumor/genética
3.
Pain Med ; 21(11): 2676-2683, 2020 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-32869092

RESUMEN

OBJECTIVE: The present study examined the effects of home-based remotely supervised transcranial direct current stimulation on quantitative sensory testing measurements in older adults with knee osteoarthritis. Participants were hypothesized to experience improved pain measurements over time. DESIGN: Open-label, single-arm trial. SETTING: Southeast Texas between March and November 2018 at a nursing school and participant homes. SUBJECTS: Older adults (aged 50-85 years) with self-reported unilateral or bilateral knee osteoarthritis pain who met eligibility criteria set by the American College of Rheumatology. METHODS: The intervention was applied with a constant current intensity for 20 minutes every weekday for two weeks (10 total sessions). Quantitative measures of pain were collected three times over 10 days (days 1, 5, and 10) and included heat threshold and tolerance, pressure pain threshold, punctate mechanical pain, pain, and conditioned pain modulation. Analyses used nonparametric tests to evaluate differences between day 1 and day 10. Generalized linear mixed models were then used to evaluate change across all three time points for each measure. Bayesian inference was used to provide the posterior probability of longitudinal effects. RESULTS: Nonparametric tests found improvements in seven measures, and longitudinal models supported improvements in 10 measures, with some nonlinear effects. CONCLUSIONS: The home-based, remotely supervised intervention improved quantitative measurements of pain in older adults with knee osteoarthritis. This study contributes to the growing body of literature supporting home-based noninvasive stimulation interventions.


Asunto(s)
Osteoartritis de la Rodilla , Estimulación Transcraneal de Corriente Directa , Anciano , Anciano de 80 o más Años , Teorema de Bayes , Humanos , Persona de Mediana Edad , Osteoartritis de la Rodilla/terapia , Dolor , Umbral del Dolor , Texas
4.
Pain Med ; 19(12): 2387-2397, 2018 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-29905879

RESUMEN

Background: Chronic pain is a serious health problem with high rates of health care utilization (HCU). Many patients become stymied in a perpetual cycle of unsuccessful attempts to find relief from suffering through frequent health care visits. Especially within low-income populations, the burdens of health care services are especially unpleasant due to significant financial costs, barriers to transportation, and high levels of stress. This study aimed to examine factors associated with HCU for chronic pain in low-income settings. Methods: As part of the Learning About My Pain (LAMP) trial, a randomized comparative effectiveness study of group-based psychosocial interventions (PCORI Contract #941, Beverly Thorn, PI; clinicaltrials.gov identifier NCT01967342) for patients receiving care for chronic pain at low-income clinics in Alabama, medical records one-year prior to randomization were retrospectively collected for data analysis. HCU was defined as the sum of health care visits for chronic pain over this one-year period. Sociodemographic traits (age, sex, race, poverty status, primary literacy, education level), pain related variables (pain severity, pain interference, disability, number of pain sites, number of pain types, opioid prescriptions), and psychological variables (depressive symptoms, pain catastrophizing) were entered into a hierarchical multiple regression model to predict HCU. Results: Results suggested that race/ethnicity, having received an opioid prescription in the year prior to treatment onset, and higher depressive symptoms were associated with increased HCU for chronic pain conditions. Conclusions: Depressive symptoms are an essential aspect of increased health care use. Study findings support the need for a biopsychosocial approach to chronic pain management.


Asunto(s)
Dolor Crónico/tratamiento farmacológico , Depresión/psicología , Trastorno Depresivo/tratamiento farmacológico , Aceptación de la Atención de Salud/psicología , Adulto , Anciano , Analgésicos Opioides/uso terapéutico , Catastrofización/psicología , Dolor Crónico/economía , Femenino , Humanos , Renta/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Dimensión del Dolor/métodos , Estudios Retrospectivos
5.
J Relig Health ; 57(3): 883-900, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28689270

RESUMEN

Religiousness and spirituality (R/S) exert important influences on individuals across a range of domains. Spiritual Openness is theoretically linked with the personality trait of Openness to Experience, suggesting promise for future research. Using responses from 366 undergraduates on the Spiritual Experience Index-Revised (SEI-R: subscales of Spiritual Openness and Spiritual Support), analyses evaluated and revised the SEI-R, deleting poor items and generating a 10-item measure. The new SEI-S exhibits better psychometric properties and reduced participant burden, and subscales displayed a curvilinear relationship in which increases in Spiritual Openness showed a trade-off in levels of Spiritual Support.


Asunto(s)
Psicometría/estadística & datos numéricos , Religión , Espiritualidad , Encuestas y Cuestionarios , Adolescente , Adulto , Femenino , Humanos , Estudiantes , Adulto Joven
6.
Pain Med ; 18(11): 2058-2069, 2017 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-28158514

RESUMEN

OBJECTIVE: Most studies done with Hispanics illustrate their preference for self-management practices; therefore, examining the factors driving patients to seek medical care for pain management will help elucidate what patients want and need from their doctors for pain management. The aim of the present study was to obtain patients' perspectives and enhance our understanding of the cultural beliefs influencing pain management decisions of foreign-born Spanish-speaking Hispanics with low acculturation. METHODS: Twenty-four individuals (17 females and 7 males) with self-reported chronic pain completed the study. Participants attended a focus group and shared about pain management practices and their experiences with medical care for pain management. Descriptive data on pain and mood variables were collected to examine how this population compares with the norms reported in the pain literature for Hispanics. RESULTS: Participants reported a preference for pain self-management and noninvasive medical treatments and expressed negative attitudes toward pain medications, although wanting the option of pain medications as a "last resort." Satisfaction with medical care for pain was highly influenced by the participants' expectations and preference for personal, warm, and friendly interactions. CONCLUSIONS: Our findings are consistent with previous reports on Hispanics' preference for self-care practices. Perhaps foreign-born Hispanics may rely on self-care practices and delay medical attention for pain management because of their unfamiliarity with the US health care system. Other potential explanations for a reliance on self-care for pain management involve patients having a limited understanding of or access to effective treatment options for chronic pain and negative experiences with US medical providers.


Asunto(s)
Aculturación , Dolor Crónico/terapia , Conocimientos, Actitudes y Práctica en Salud , Manejo del Dolor , Adulto , Femenino , Grupos Focales , Hispánicos o Latinos , Humanos , Masculino , Persona de Mediana Edad , Investigación Cualitativa , Autocuidado , Adulto Joven
7.
Arch Womens Ment Health ; 20(1): 129-138, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27778150

RESUMEN

Research has demonstrated that perceived stress and depression are risk factors for suicidal ideation in young adults, particularly women attending college. Female undergraduate students (N = 928) were administered measures assessing their levels of stress, depressive symptoms, suicidal thoughts, and mindfulness. A moderated-mediation analysis was conducted to examine the complex associations among these variables. Results indicated that mindfulness moderated the mediated effect of depressive symptoms on perceived stress and suicidal ideation. Specifically, the indirect effect was stronger in college women with lower levels of mindfulness as compared to those students who reported higher mindfulness. Thus, teaching mindfulness techniques on college campuses may be an important strategy for preventing suicide, especially among young adult women experiencing stress and depressive symptoms.


Asunto(s)
Depresión/diagnóstico , Atención Plena , Estrés Psicológico/psicología , Estudiantes/psicología , Ideación Suicida , Adolescente , Adulto , Estudios Transversales , Depresión/psicología , Femenino , Humanos , Universidades , Adulto Joven
8.
Pain Manag Nurs ; 18(2): 102-109, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-28259637

RESUMEN

This study examined the relationships of self-reported pain intensity with vital signs, pain catastrophizing, and state anxiety in patients presenting to the emergency department (ED) for acute pain, exacerbations of chronic pain, or acute pain with concurrent chronic (combined) pain, comparing the pattern of relationships among these three pain groups. One hundred fifty-eight patients presenting to the ED for pain were recruited. Vital signs and self-reported pain intensity were obtained at triage, then participants completed self-report measures of pain catastrophizing, state anxiety, and demographic information. No significant associations were found between vital signs and pain intensity at triage in any of the pain groups. Pain catastrophizing was significantly associated with self-reported pain intensity in the acute pain group (r = .34, p < .05) and combined pain group (r = .30, p < .05), and state anxiety was significantly associated with self-reported pain intensity in with the acute pain group (r = .27, p < .05). When pain catastrophizing and state anxiety were used in a stepwise multiple regression analysis to predict self-reported pain intensity in the acute pain group, only pain catastrophizing emerged as a unique predictor (ß = .405, p < .01). Consistent with previous research, vital signs were not associated with self-reported pain intensity in patients presenting to the ED for pain, including those with chronic pain. Given the significant association of pain catastrophizing and pain intensity among patients presenting to the ED for acute pain, brief measurement of pain catastrophizing may inform pain treatment in the ED.


Asunto(s)
Dolor Agudo/diagnóstico , Catastrofización/psicología , Umbral del Dolor/psicología , Signos Vitales , Adaptación Psicológica , Ansiedad/psicología , Servicio de Urgencia en Hospital , Femenino , Humanos , Masculino , Encuestas y Cuestionarios , Triaje/métodos
9.
Pain Med ; 17(6): 1069-78, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-26814269

RESUMEN

OBJECTIVE: Pain is one of the most common reasons for emergency department (ED) visits. Given the significant association of psychological variables and pain experience, it is critical to examine the relation of such factors with ED pain reports. This study sought to analyze the association of reported pain intensity in ED with pain catastrophizing and state anxiety. METHODS: One hundred participants presenting with a primary complaint of acute pain in an urban ED completed the study. The measures included a demographic survey with questions pertaining to pain intensity, type and duration of present pain, the Pain Catastrophizing Scale (PCS), and the State-Trait Anxiety Inventory-State Subscale (STAI-S). RESULTS: Pain intensity was significantly and positively associated with pain catastrophizing and state anxiety. Follow-up PROCESS mediation analysis revealed a significant indirect effect of pain catastrophizing on the relationship between state anxiety and pain intensity. CONCLUSIONS: The results suggest that it is important to assess the psychological distress due to anxiety and pain catastrophizing of patients presenting to EDs with acute pain. Setting-appropriate brief behavioral interventions in conjunction with pharmacological interventions could improve outcomes.


Asunto(s)
Dolor Agudo/psicología , Ansiedad/psicología , Catastrofización/psicología , Adulto , Servicio de Urgencia en Hospital , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor/métodos
10.
J Clin Psychol Med Settings ; 22(4): 199-212, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26628412

RESUMEN

Mounting evidence supports the value of integrated healthcare and the need for interprofessional practice within patient-centered medical homes (PCMH). Incorporating behavioral health services is key to fully implementing the PCMH concept. Unfortunately, psychologists have not been front and center in this integrative and interprofessional care movement nor have they typically received adequate training or experience to work effectively in these integrated care programs. This article builds the case for the value of PCMHs, particularly those that incorporate behavioral health services. Attention is paid to the diverse roles psychologists play in these settings, including as direct service providers, consultants, teachers/supervisors, scholars/program evaluators, and leaders. There is a discussion of the competencies psychologists must possess to play these roles effectively. Future directions are discussed, with a focus on ways psychologists can bolster the PCMH model by engaging in interprofessional partnerships related to education and training, practice, research, and leadership.


Asunto(s)
Atención Dirigida al Paciente , Rol Profesional , Psicología Clínica , Humanos , Atención Primaria de Salud
11.
Mol Carcinog ; 53(10): 793-806, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23765383

RESUMEN

Constitutive activation of STAT3 is frequently observed and closely linked with proliferation, survival, invasion, metastasis and angiogenesis in tumor cells. In the present study, we investigated whether ß-caryophyllene oxide (CPO), a sesquiterpene isolated primarily from the essential oils of medicinal plants such as guava (Psidium guajava), and oregano (Origanum vulgare L.), can mediate its effect through interference with the STAT3 activation pathway in cancer cells. The effect of CPO on STAT3 activation, associated protein kinases and phosphatase, STAT3-regulated gene products and apoptosis was investigated using both functional proteomics tumor pathway technology platform and different tumor cell lines. We found that CPO suppressed constitutive STAT3 activation in multiple myeloma (MM), breast and prostate cancer cell lines, with a significant dose- and time-dependent effects observed in MM cells. The suppression was mediated through the inhibition of activation of upstream kinases c-Src and JAK1/2. Also, vanadate treatment reversed CPO-induced down-regulation of STAT3, suggesting the involvement of a tyrosine phosphatase. Indeed, we found that CPO induced the expression of tyrosine phosphatase SHP-1 that correlated with the down-regulation of constitutive STAT3 activation. Interestingly, deletion of SHP-1 gene by siRNA abolished the ability of CPO to inhibit STAT3 activation. The inhibition of STAT3 activation by CPO inhibited proliferation, induced apoptosis and abrogated the invasive potential of tumor cells. Our results suggest for the first time that CPO is a novel blocker of STAT3 signaling cascade and thus has an enormous potential for the treatment of various cancers harboring constitutively activated STAT3.


Asunto(s)
Antineoplásicos/farmacología , Proteína Tirosina Fosfatasa no Receptora Tipo 6/metabolismo , Factor de Transcripción STAT3/metabolismo , Sesquiterpenos/farmacología , Transducción de Señal , Apoptosis , Proteínas Reguladoras de la Apoptosis/metabolismo , Línea Celular Tumoral , Núcleo Celular/metabolismo , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Inducción Enzimática/efectos de los fármacos , Expresión Génica/efectos de los fármacos , Humanos , Interleucina-6/fisiología , Janus Quinasa 2/metabolismo , Potencial de la Membrana Mitocondrial , Invasividad Neoplásica , Fosforilación , Sesquiterpenos Policíclicos , Unión Proteica , Procesamiento Proteico-Postraduccional , Proteína Tirosina Fosfatasa no Receptora Tipo 6/genética , Familia-src Quinasas/metabolismo
12.
J Transl Med ; 12: 128, 2014 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-24884660

RESUMEN

BACKGROUND: Glioblastoma (GBM) is an aggressive disease associated with poor survival. It is essential to account for the complexity of GBM biology to improve diagnostic and therapeutic strategies. This complexity is best represented by the increasing amounts of profiling ("omics") data available due to advances in biotechnology. The challenge of integrating these vast genomic and proteomic data can be addressed by a comprehensive systems modeling approach. METHODS: Here, we present an in silico model, where we simulate GBM tumor cells using genomic profiling data. We use this in silico tumor model to predict responses of cancer cells to targeted drugs. Initially, we probed the results from a recent hypothesis-independent, empirical study by Garnett and co-workers that analyzed the sensitivity of hundreds of profiled cancer cell lines to 130 different anticancer agents. We then used the tumor model to predict sensitivity of patient-derived GBM cell lines to different targeted therapeutic agents. RESULTS: Among the drug-mutation associations reported in the Garnett study, our in silico model accurately predicted ~85% of the associations. While testing the model in a prospective manner using simulations of patient-derived GBM cell lines, we compared our simulation predictions with experimental data using the same cells in vitro. This analysis yielded a ~75% agreement of in silico drug sensitivity with in vitro experimental findings. CONCLUSIONS: These results demonstrate a strong predictability of our simulation approach using the in silico tumor model presented here. Our ultimate goal is to use this model to stratify patients for clinical trials. By accurately predicting responses of cancer cells to targeted agents a priori, this in silico tumor model provides an innovative approach to personalizing therapy and promises to improve clinical management of cancer.


Asunto(s)
Ensayos de Selección de Medicamentos Antitumorales , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Simulación por Computador , Humanos , Estudios Retrospectivos
13.
Rural Remote Health ; 14(3): 2879, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25204693

RESUMEN

INTRODUCTION: Chronic pain is a major public health problem. Increased healthcare utilization by individuals with pain puts enormous burden on financial and health resources. There is extremely limited understanding of psychosocial factors that affect healthcare use and prescription of opioids in individuals who experience heightened healthcare disparities associated with being African-American, having low income, and with rural residency. Health disparities research indicates that rural residency and low socioeconomic status are associated with greater self-reported pain levels. It is logical to expect then that this would be associated with increased needs for health services. However, at the same time, these very variables function as barriers in accessing health care. This disparity between greater need and limited access in turn creates greater distress. Further complicating the picture is the rapidly emerging concern about the misuse of prescription opioids in rural areas. As a result, empirical inquiry has started focusing on the variables influencing the likelihood of receiving opioid prescriptions in rural areas. The understanding of psychosocial factors affecting healthcare use and prescription of opioids in individuals who experience heightened healthcare disparities associated with being African-American, low-income, and living in rural areas remains extremely limited. The primary aim of this study was to examine the demographic and psychosocial variables that affect health services use in a rural, low-income population with chronic pain. Secondarily, the influence of these same variables on receiving prescription for opioids was examined. METHODS: Healthcare use during a 3 month period, prescription analgesics, as well as medical comorbidities were obtained from the medical records of 64 patients with chronic pain. The participants were enrolling in an upcoming psychosocial intervention offered at two rural federally qualified health centers in a south-eastern state in the USA. For the present study, these participants consented to have their medical records reviewed for the 3 months prior to beginning the intervention protocol. Additionally, the pre-treatment (baseline) assessments were used in the present analyses. Demographic information, including age, sex, and education level, as well as measures of pain intensity, depressive symptoms, pain-related disability, and pain catastrophizing were collected. RESULTS: The participants were rural residents in medically underserved counties, primarily female (73.4%) and African-American (67.2%), and approximately 77% reported annual household income of less than $13,000. A majority had medical comorbidities, including diabetes mellitus (46.89%), cardiovascular disorders (29.7%), chronic renal disorder (14.1%), and asthma (6.3%). Approximately 30% had a diagnosis of depression. Demographic variables such as age, sex, and ethnicity did not influence the healthcare use or prescription of opioids. Depressive symptoms uniquely influenced health services use, with higher scores predicting greater health services utilization. In addition, those with a diagnosis of depression (per medical records) and those with a higher number of medical comorbidities were more likely to receive prescription opioids. CONCLUSIONS: This study adds to the current understanding of the factors affecting healthcare use and prescription of opioids in low-income individuals living in rural areas with chronic pain receiving treatment at federally qualified health centers. Since healthcare use was predicted by depressive symptoms and the prescription of opioids by a clinical diagnosis of depression, screening for depression is advised as part of the standard care of patients with pain, ideally with follow-up assessments and treatment of depression as necessary. Furthermore, making psychosocial interventions more available at rural healthcare centers may help in lowering psychological distress, which may have the ultimate effect of reducing opioid prescriptions for this subset of patients.


Asunto(s)
Analgésicos Opioides/uso terapéutico , Dolor Crónico/tratamiento farmacológico , Dolor Crónico/psicología , Servicios de Salud/estadística & datos numéricos , Población Rural/estadística & datos numéricos , Adulto , Negro o Afroamericano/estadística & datos numéricos , Factores de Edad , Analgésicos Opioides/administración & dosificación , Dolor Crónico/epidemiología , Comorbilidad , Depresión/epidemiología , Femenino , Accesibilidad a los Servicios de Salud , Humanos , Masculino , Área sin Atención Médica , Persona de Mediana Edad , Manejo del Dolor/métodos , Pobreza/estadística & datos numéricos , Proveedores de Redes de Seguridad/estadística & datos numéricos , Factores Sexuales , Factores Socioeconómicos
14.
J Health Psychol ; 29(7): 680-689, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38641873

RESUMEN

Prescribed opioids are a mainstay pain treatment after traumatic injury, but a subgroup of patients may be at risk for continued opioid use. We evaluated the predictive utility of a traditional screening tool, the Opioid Risk Tool (ORT), and two other measures: average in-hospital milligram morphine equivalents (MME) per day and an assessment of opioid demand in predicting pain outcomes. Assessments of pain-related outcomes (pain intensity, interference, injury-related stress, and need for additional pain treatment) were administered at 2 weeks and 12 months post-discharge in a sample of 34 patients hospitalized for traumatic injury. Bayesian linear models were used to evaluate changes in responses over time as a function of predictors. High-risk ORT, higher MME per day, and greater opioid demand predicted less change in outcomes over time. This report provides first evidence that malleable factors of opioid and opioid demand have utility in predicting pain outcomes following traumatic injury.


Asunto(s)
Analgésicos Opioides , Dolor , Heridas y Lesiones , Humanos , Masculino , Analgésicos Opioides/uso terapéutico , Analgésicos Opioides/efectos adversos , Femenino , Adulto , Heridas y Lesiones/complicaciones , Persona de Mediana Edad , Dolor/tratamiento farmacológico , Dolor/etiología , Dimensión del Dolor , Medición de Riesgo , Teorema de Bayes , Trastornos Relacionados con Opioides , Adulto Joven
15.
J Biol Chem ; 287(45): 38028-40, 2012 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-22992727

RESUMEN

Gastric cancer (GC) is a lethal malignancy and the second most common cause of cancer-related deaths. Although treatment options such as chemotherapy, radiotherapy, and surgery have led to a decline in the mortality rate due to GC, chemoresistance remains as one of the major causes for poor prognosis and high recurrence rate. In this study, we investigated the potential effects of isorhamnetin (IH), a 3'-O-methylated metabolite of quercetin on the peroxisome proliferator-activated receptor γ (PPAR-γ) signaling cascade using proteomics technology platform, GC cell lines, and xenograft mice model. We observed that IH exerted a strong antiproliferative effect and increased cytotoxicity in combination with chemotherapeutic drugs. IH also inhibited the migratory/invasive properties of GC cells, which could be reversed in the presence of PPAR-γ inhibitor. We found that IH increased PPAR-γ activity and modulated the expression of PPAR-γ regulated genes in GC cells. Also, the increase in PPAR-γ activity was reversed in the presence of PPAR-γ-specific inhibitor and a mutated PPAR-γ dominant negative plasmid, supporting our hypothesis that IH can act as a ligand of PPAR-γ. Using molecular docking analysis, we demonstrate that IH formed interactions with seven polar residues and six nonpolar residues within the ligand-binding pocket of PPAR-γ that are reported to be critical for its activity and could competitively bind to PPAR-γ. IH significantly increased the expression of PPAR-γ in tumor tissues obtained from xenograft model of GC. Overall, our findings clearly indicate that antitumor effects of IH may be mediated through modulation of the PPAR-γ activation pathway in GC.


Asunto(s)
Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , PPAR gamma/metabolismo , Quercetina/análogos & derivados , Transducción de Señal/efectos de los fármacos , Neoplasias Gástricas/tratamiento farmacológico , Anilidas/farmacología , Animales , Antineoplásicos/farmacología , Proteínas Reguladoras de la Apoptosis/metabolismo , Western Blotting , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Sinergismo Farmacológico , Femenino , Humanos , Ratones , Ratones Desnudos , Invasividad Neoplásica , PPAR gamma/antagonistas & inhibidores , Unión Proteica/efectos de los fármacos , Proteómica , Quercetina/metabolismo , Quercetina/farmacología , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Ensayos Antitumor por Modelo de Xenoinjerto
16.
J Cell Physiol ; 227(5): 2184-95, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-21792937

RESUMEN

The activation of signal transducers and activators of transcription 3 (STAT3) has been closely linked with the proliferation, survival, invasion, and angiogenesis of hepatocellular carcinoma (HCC) and represents an attractive target for therapy. In the present report, we investigated whether honokiol mediates its effect through interference with the STAT3 activation pathway. The effect of honokiol on STAT3 activation, associated protein kinases, and phosphatase, STAT3-regulated gene products and apoptosis was investigated using both functional proteomics tumor pathway technology platform and different HCC cell lines. We found that honokiol inhibited both constitutive and inducible STAT3 activation in a dose- and time-dependent manner in HCC cells. The suppression was mediated through the inhibition of activation of upstream kinases c-Src, Janus-activated kinase 1, and Janus-activated kinase 2. Vanadate treatment reversed honokiol-induced down-regulation of STAT3, suggesting the involvement of a tyrosine phosphatase. Indeed, we found that honokiol induced the expression of tyrosine phosphatase SHP-1 that correlated with the down-regulation of constitutive STAT3 activation. Moreover, deletion of SHP-1 gene by siRNA abolished the ability of honokiol to inhibit STAT3 activation. The inhibition of STAT3 activation by honokiol led to the suppression of various gene products involved in proliferation, survival, and angiogenesis. Finally, honokiol inhibited proliferation and significantly potentiated the apoptotic effects of paclitaxel and doxorubicin in HCC cells. Overall, the results suggest that honokiol is a novel blocker of STAT3 activation and may have a great potential for the treatment of HCC and other cancers.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Compuestos de Bifenilo/farmacología , Carcinoma Hepatocelular/fisiopatología , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Lignanos/farmacología , Neoplasias Hepáticas/fisiopatología , Proteína Tirosina Fosfatasa no Receptora Tipo 6/metabolismo , Factor de Transcripción STAT3/antagonistas & inhibidores , Antineoplásicos Fitogénicos/química , Compuestos de Bifenilo/química , Proteína Tirosina Quinasa CSK , Carcinoma Hepatocelular/patología , Caspasa 3/metabolismo , Línea Celular Tumoral , Fase G1/efectos de los fármacos , Genes Reporteros , Humanos , Interleucina-6/metabolismo , Janus Quinasa 1/metabolismo , Janus Quinasa 2/metabolismo , Lignanos/química , Neoplasias Hepáticas/patología , Modelos Biológicos , Poli(ADP-Ribosa) Polimerasas/metabolismo , Proteína Tirosina Fosfatasa no Receptora Tipo 6/genética , Proteínas Tirosina Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/efectos de los fármacos , Familia-src Quinasas
17.
Psychol Trauma ; 14(8): 1256-1262, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35084918

RESUMEN

OBJECTIVE: Bipolar disorder is associated with a history of childhood maltreatment, impulsive aggression, and lethal suicide attempts. Often, aggression and violence prevent the diagnosed individual from receiving timely access to mental health care, leading to adverse outcomes such as repeated psychiatric hospitalization or even incarceration. METHOD: In this study, we recruited a sample of 150 low-income patients with bipolar disorder from an outpatient behavioral health clinic affiliated with an urban public hospital in Southeastern United States. We explored whether different types of childhood maltreatment (physical, sexual, emotional) are associated with impulsive aggression among individuals with bipolar disorder. Additionally, we examined whether impulsive aggression is related to suicidality. Finally, we sought to test the potential mediated effect of impulsive aggression on the relationship between childhood maltreatment and suicidality. RESULTS: Findings suggest that all direct associations were significant and that impulsive aggression was a significant mediator in the relationship between childhood emotional and sexual abuse. However, when childhood physical abuse was included as an independent variable in the model, impulsive aggression did not mediate the association, even though impulsive aggression was related to suicidality. CONCLUSION: Results from this study suggest that impulsive aggression exerts a wide-ranging impact on suicidality in the context of childhood trauma in those with bipolar disorder. In the future, targeted interventions to address the underlying etiologies of aggression may translate into an improved quality of life, decreased rates of suicidality, and positive clinical outcomes among individuals with bipolar disorder. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Asunto(s)
Trastorno Bipolar , Maltrato a los Niños , Suicidio , Humanos , Niño , Calidad de Vida , Agresión/psicología , Maltrato a los Niños/psicología
18.
Exp Clin Psychopharmacol ; 30(1): 15-22, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32673047

RESUMEN

Opioid misuse and opioid-related death are a growing public health concern. One population of interest is recent trauma and/or surgery patients, who are at increased risk of developing an opioid use disorder (OUD). Although a variety of assessments have been developed to screen for risk of opioid misuse, each has limitations and prediction needs improvement. One promising measure is drug demand, a behavioral economic measure assessing drug consumption at different price points. In the current proposal, we assessed the utility of a brief assessment of opioid demand. Demand and various pain-related self-report measures among trauma-surgery patients (N = 103) were assessed at 4 weeks post-discharge. Opioid demand was significantly associated with self-report measures of pain and amount of morphine milligram equivalents (MME) received during the hospital stay. The current result support the utility of the opioid demand as an adjunctive and complementary measure to assess risk of opioid misuse. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Asunto(s)
Servicios Médicos de Urgencia , Trastornos Relacionados con Opioides , Cuidados Posteriores , Analgésicos Opioides/uso terapéutico , Humanos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Alta del Paciente
19.
J Opioid Manag ; 18(1): 17-25, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35238009

RESUMEN

OBJECTIVE: Prescription opioids are an effective pain treatment strategy but can lead to long-term opioid misuse. Identifying at risk patients during hospitalization can inform the development of prevention interventions post-discharge. Using the Opioid Risk Tool (ORT) as a screening measure, this study predicted factors associated with pain and opioid use at 2 weeks post-discharge in trauma patients. DESIGN: A quality improvement prospective study design was used. SETTING: Participant recruitment took place at an inpatient Level 1 trauma center in Houston, Texas. PARTICIPANTS: Participants (n = 103) were patients admitted to the adult trauma service. Patients completed the ORT in the hospital and a survey at 2 weeks post-discharge. MAIN OUTCOME MEASURE: The survey assessed pain intensity and interference, injury-related stress, medication use, and need for additional pain treatment. Wilcoxon-Mann-Whitney U test, the Spearman rank-order correlation, and chisquare test of independence tested the ORT as a predictor of follow-up outcomes. Post hoc analyses relied on logistic and quantile regression. RESULTS: The ORT identified 15.5 percent of patients at high risk for opioid-related aberrant behavior. Survey results indicated high percentages of patients reporting moderate to severe pain (79.6 percent), pain interference (77.9 percent), taking pain pills (59.6 percent), experiencing stress (76.9 percent), and needing pain treatment (52.4 percent). The ORT predicted injury-related stress with the high-risk category having higher stress levels than low risk (Z = 2.518, p = 0.012). CONCLUSION: Risk of opioid misuse assessed in hospitalized trauma patients was associated with injury-related stress reported post-discharge. This highlights the importance of including stress assessments in follow-up appointments.


Asunto(s)
Analgésicos Opioides , Trastornos Relacionados con Opioides , Adulto , Cuidados Posteriores , Analgésicos Opioides/efectos adversos , Humanos , Trastornos Relacionados con Opioides/diagnóstico , Dolor/tratamiento farmacológico , Alta del Paciente , Estudios Prospectivos
20.
Ann Transl Med ; 10(23): 1289, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36618786

RESUMEN

Background: Relapsed glioblastoma (GBM) is often an imminently fatal condition with limited therapeutic options. Computation biological modeling, i.e., biosimulation, of comprehensive genomic information affords the opportunity to create a disease avatar that can be interrogated in silico with various drug combinations to identify the most effective therapies. Case Description: We report the outcome of a GBM patient with chromosome 12q amplification who achieved substantial disease remission from a novel therapy using this approach. Following next generation sequencing (NGS) was performed on the tumor specimen. Mutation and copy number changes were input into a computational biologic model to create an avatar of disease behavior and the malignant phenotype. In silico responses to various drug combinations were biosimulated in the disease network. Efficacy scores representing the computational effect of treatment for each strategy were generated and compared to each other to ascertain the differential benefit in drug response from various regimens. Biosimulation identified CDK4/6 inhibitors, nelfinavir and leflunomide to be effective agents singly and in combination. Upon receiving this treatment, the patient achieved a prompt and clinically meaningful remission lasting 6 months. Conclusions: Biosimulation has utility to identify active treatment combinations, stratify treatment options and identify investigational agents relevant to patients' comprehensive genomic abnormalities. Additionally, the combination of abemaciclib and nelfinavir appear promising for GBM and potentially other cancers harboring chromosome 12q amplification.

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