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1.
Cancer ; 129(21): 3490-3497, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37395291

RESUMEN

BACKGROUND: The purpose of this study was to understand the experiences of Black patients with cancer in health care by comparing drivers of high and low ratings. METHODS: Semistructured in-depth interviews were conducted with 18 Black patients with cancer recruited from cancer survivorship support groups and Facebook between May 2019 and March 2020. Interviews were coded across all transcripts by using a thematic analysis approach before comparing low- and high-rating groups. RESULTS: There were three major themes that influenced whether patients rated their care as low or high, which included the patient-provider relationship, health care staff interactions, and cancer care coordination. For example, the high-rating group described good communication with the health care team as physicians listening to their needs, being responsive to their concerns, and providing recommendations on how to address side effects. In contrast, the low-rating group described poor communication with their health care team as their needs being dismissed and being excluded from decision-making processes. Additionally, there were two distinct themes that influenced patients' low ratings: insurance and financial toxicity issues and experiences of health care discrimination. CONCLUSIONS: In an effort to promote equitable cancer care experiences for Black patients, it is important that health systems work to prioritize patient interactions with health care providers and staff, comprehensive care management for patients with cancer, and reductions in the financial burden of caring for cancer.

2.
J Card Fail ; 29(8): 1175-1183, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-36948269

RESUMEN

OBJECTIVE: Newer therapies have increased heart failure (HF) survival rates, but these therapies are rarely curative. The consequence of increased longevity is the likelihood that patients with HF will experience higher symptom burdens over time. Exercise such as cardiac rehabilitation programs can palliate symptom burdens, but numerous barriers prevent exercise participation and adherence. Small pilot studies indicate short-term beneficial effects of gentle forms of exercise such as yoga to address symptom burdens and accommodate comorbidities. Long-term symptom benefit and adherence to yoga are currently unknown. Therefore, a novel a home-based, gentle-stretching intervention that addresses issues of exercise access and adherence is described in this article. PURPOSE: The purpose of this article is to describe the background, design and study methodology of the Getting Into Light Exercise for HF (GENTLE-HF) randomized controlled trial. Gentle-HF will test a gentle stretching and education intervention compared to an education control group concerning symptom burden (dyspnea, exercise, activity adherence, depression, and anxiety) and quality of life. As an exploratory aim, we also will determine whether rurality moderates the relationships between exercise participation and symptom burden as a measure of health equity. METHODS: We designed a randomized controlled trial study (n = 234) with 2 arms: a gentle stretching intervention arm with HF education and an HF education-only control. Participants will be recruited from U.S. cardiology clinics in the mid-Atlantic and the San Francisco Bay areas. This recruitment strategy will include individuals from urban, suburban and rural areas and individuals that have diverse racial and ethnic backgrounds. All participants will be provided with an iPad set up to access HF educational topics, and the intervention arm will have both educational and gentle-stretching class links. Both arms will access the HF health education icons on their iPads weekly; they correspond to the 6 months (26 weeks) of study participation. Symptom burden (dyspnea, fatigue, exercise intolerance, depression, anxiety) and quality of life will be measured at the study's start and completion. Study adherence will be measured by using attendance rates and number of class minutes attended. RESULTS: The GENTLE-HF study is a randomized study that will test the effect of a home-based, video-conference-delivered gentle stretching and HF education intervention designed for patients with HF. The findings will inform whether gentle stretching can decrease symptom burden and potentially provide access to symptom palliation for a diverse population of patients with HF.


Asunto(s)
Ejercicio Físico , Yoga , Humanos , Insuficiencia Cardíaca , Calidad de Vida
3.
Matern Child Nutr ; 19(1): e13451, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36349962

RESUMEN

Evidence suggests children HIV-exposed and uninfected (CHEU) experience poor growth. We analysed child anthropometrics and explored factors associated with stunting among Malawian CHEU. Mothers with HIV and their infants HIV-exposed were enroled in a nationally representative prospective cohort within the National Evaluation of Malawi's Prevention of Mother-to-Child HIV Transmission Programme after Option B+ implementation (2014-2018). Anthropometry was measured at enrolment (age 1-6 months), visit 1 (approximately 12 months), and visit 2 (approximately 24 months). Weight-for-age (WAZ) and length-for-age (LAZ) z-scores were calculated using World Health Organization Growth Standards; underweight and stunting were defined as WAZ and LAZ more than 2 standard deviations below the reference median. Multivariable logistic regression restricted to CHEU aged 24 months (±3 months) was used to identify factors associated with stunting. Among 1211 CHEU, 562/1211 attended visit 2, of which 529 were aged 24 months (±3 months) and were included. At age 24 months, 40.4% of CHEU were stunted and/or underweight, respectively. In multi-variable analysis, adjusting for child age and sex, the odds of stunting were higher among CHEU with infectious disease diagnosis compared to those with no diagnosis (adjusted odds ratio = 3.35 [95% confidence interval: 1.82-6.17]), which was modified by co-trimoxazole prophylaxis (p = 0.028). Infant low birthweight was associated with an increased odds of stunting; optimal feeding and maternal employment were correlated with reduced odds. This is one of the first studies examining CHEU growth since Option B+. Interventions to improve linear growth among CHEU should address their multi-faceted health risks, alongside maternal ART prescription, and follow-up of mother-child pairs.


Asunto(s)
Infecciones por VIH , Transmisión Vertical de Enfermedad Infecciosa , Lactante , Femenino , Humanos , Preescolar , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , VIH , Delgadez/epidemiología , Estudios Prospectivos , Malaui/epidemiología , Infecciones por VIH/tratamiento farmacológico , Trastornos del Crecimiento/epidemiología , Factores de Riesgo
4.
Med Care ; 59(4): 295-303, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33528232

RESUMEN

BACKGROUND: Racial/ethnic minorities are more likely to be diagnosed at a later stage of colorectal cancer (CRC). Therefore, our objective was to identify whether racial/ethnic differences in patient experiences (PE) with health care are associated with stage at CRC diagnosis. METHODS: The authors used the National Cancer Institute Surveillance, Epidemiology and End Results registry data linked with the Consumer Assessment of Healthcare Providers and Systems to conduct a retrospective cohort analysis. They examined composite measures from surveys to assess 3 domains: patient-centeredness, timeliness, and realized access. Multivariable logistic regression was used to determine the association between PE with care and earlier stage at diagnosis. RESULTS: Of the 9211 patients, 31.1% non-Hispanic White, 27.2% non-Hispanic Black (NHB), 32.3% Hispanic, and 36.4% Asian were diagnosed with early stage cancer. Compared with non-Hispanic White patients, for the timeliness domain, Hispanic [ß=-2.82; 95% confidence interval (CI), -5.42 to -0.39] and Asian (ß=-6.65; 95% CI, -9.44 to -3.87) patients had significant lower adjusted mean score for getting care quickly. For the realized access domain, Asian (ß=-5.78; 95% CI, -8.51 to -3.05) and NHB patients (ß=-3.18; 95% CI, -5.50 to -0.87) had significantly lower adjusted mean score for getting needed prescription drugs compared with non-Hispanic White patients. Among NHB patients, a 5-Unit increase in getting needed care quickly was associated with higher odds of earlier CRC stage at diagnosis (odds ratio, 1.06; 95% CI, 1.01-1.10). CONCLUSION: There are racial/ethnic disparities in PE with timeliness and realized access to care preceding a CRC diagnosis. Among NHB patients, poor experiences with timeliness and realized access of care may be associated with later stage at diagnosis.


Asunto(s)
Neoplasias Colorrectales/etnología , Neoplasias Colorrectales/terapia , Disparidades en Atención de Salud/etnología , Grupos Minoritarios/estadística & datos numéricos , Tiempo de Tratamiento/estadística & datos numéricos , Negro o Afroamericano/estadística & datos numéricos , Factores de Edad , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/patología , Etnicidad/estadística & datos numéricos , Femenino , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Hispánicos o Latinos/estadística & datos numéricos , Humanos , Modelos Logísticos , Masculino , Atención Dirigida al Paciente/estadística & datos numéricos , Grupos Raciales/estadística & datos numéricos , Estudios Retrospectivos , Programa de VERF , Factores Socioeconómicos , Estados Unidos , Población Blanca/estadística & datos numéricos
5.
Anticancer Drugs ; 32(2): 111-116, 2021 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-33395068

RESUMEN

Sodium dichloroacetate (DCA) is a metabolic regulator used to treat diabetes. Since DCA inhibits pyruvate dehydrogenase kinase, decreasing lactic acid formation, it can reverse the Warburg effect in cancer cells, promoting apoptosis. Therefore, this study aimed to investigate the potential of DCA as a drug repurposing candidate for the treatment of melanoma. For the in-vitro assay, murine B16-F10 melanoma cells were treated with 0.5, 1, 5, 10, 20 or 50 mM DCA for 3 days, analyzed with the crystal violet method. The in-vivo effect of DCA was evaluated in B16-F10 tumor-bearing C57BL/6 mice treated with different doses of DCA (0, 25, 75 or 150 mg/kg) by gavage for 10 days, followed by measurement of tumor volume. Upon necropsy, representative slices of lung, liver, kidney, spleen and intestine were collected, processed and submitted for histopathological examination. The DCA concentrations of 10, 20 and 50 mM reduced B16-F10 cell viability after 48 and 72 h of treatment, whereas 20 and 50 mM were effective after 24 h of treatment. A significant reduction in tumor growth was observed in B16-F10 melanoma bearing mice at all doses, with no change in body weight or histology. DCA attenuates the growth of B16-F10 melanoma in vitro and in vivo, without systemic toxic effects. Therefore, DCA is a candidate for drug repurposing against melanomas.


Asunto(s)
Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Ácido Dicloroacético/farmacología , Ácido Dicloroacético/uso terapéutico , Melanoma Experimental/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Animales , Antineoplásicos/administración & dosificación , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ácido Dicloroacético/administración & dosificación , Relación Dosis-Respuesta a Droga , Masculino , Ratones , Ratones Endogámicos C57BL , Carga Tumoral/efectos de los fármacos
6.
Support Care Cancer ; 29(6): 3017-3024, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33034750

RESUMEN

PURPOSE: Distress from being diagnosed with breast cancer can impact a woman's decision to continue taking adjuvant endocrine therapy (AET). The purpose of this study is to explore how religion and/or spirituality influence women's psychosocial adjustment to breast cancer and subsequent symptom management among women on active AET. METHODS: Semi-structured in-depth interviews were conducted with breast cancer survivors (n = 19) from California and Texas. Interview questions prompted discussion about AET and how women adjusted to a breast cancer diagnosis and treatment with AET. Interview transcripts were analyzed with a deductive grounded theory approach, and an inductive constant comparison approach was used to identify the sources of religion and spirituality. RESULTS: Religion supported women in their psychosocial adjustment to breast cancer by offering them a sense of purpose and meaning in life. It helped women make sense of their AET treatment as they persisted with it despite experiencing adverse side-effects. Spirituality played a prominent role in women's mental and physical wellbeing by facilitating positive and calm attitudes, which lessened women's fear during their cancer diagnosis and treatment. CONCLUSION: We identified that religion and/or spirituality helps women with their adjustment to breast cancer and influences their continued use and management of side-effects from AET. IMPLICATIONS FOR BREAST CANCER SURVIVORS: This study illustrates the importance of developing meaning-centered interventions that harness religion and spirituality to help women cope with AET. Our findings support the development of interventions that work to enhance AET persistence among breast cancer survivors.


Asunto(s)
Neoplasias de la Mama/psicología , Terapia Neoadyuvante/métodos , Religión , Espiritualidad , Anciano , Supervivientes de Cáncer/psicología , Femenino , Humanos , Persona de Mediana Edad
7.
Dev Med Child Neurol ; 63(10): 1161-1170, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-33987826

RESUMEN

Widespread use of antiretroviral drugs for pregnant/breastfeeding females with human immunodeficiency virus (HIV) has led to declining vertical transmission. Despite being HIV-uninfected, the increasing number of children who are HIV-exposed and uninfected (CHEU) often present with developmental alterations. We review seminal and recent evidence on the neurological development of CHEU and associations with early life HIV/antiretroviral exposure. Our conceptual model highlights the numerous exposures and universal risk factors for CHEU developmental disorders. Early studies suggest a significant association between HIV exposure and neurological abnormalities, varying according to the burden of HIV-specific exposures and other risk factors. More recent observations from the modern era are inconsistent, although some studies suggest specific antiretrovirals may adversely affect neurological development of CHEU. As the CHEU population continues to grow, alongside simultaneous increases in types and combinations of antiretrovirals used in pregnancy, long-term monitoring of CHEU is necessary for understanding the effects of HIV/antiretroviral exposure on CHEU developmental outcomes. What this paper adds Evidence on the neurological development of children who are human immunodeficiency virus (HIV)-exposed and uninfected (CHEU) is synthesized. Comparisons are made to children who are HIV-unexposed, across treatment eras and settings, and by antiretroviral drug regimens and drug classes. CHEU exposures are complex and include HIV-specific and universal risk factors which may affect development during the early years of life.


Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Trastornos del Neurodesarrollo/epidemiología , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Efectos Tardíos de la Exposición Prenatal/epidemiología , Lactancia Materna/estadística & datos numéricos , Preescolar , Femenino , Infecciones por VIH/epidemiología , Inhibidores de Integrasa VIH/uso terapéutico , Inhibidores de la Proteasa del VIH/uso terapéutico , Humanos , Lactante , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Desnutrición/epidemiología , Pobreza/estadística & datos numéricos , Embarazo , Complicaciones del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/epidemiología , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Factores de Riesgo
8.
Health Promot Pract ; 22(3): 423-432, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-32111139

RESUMEN

Purpose. Peer crowd-targeted campaigns are a novel approach to engage high-risk young adults in tobacco use prevention and cessation. We elicited the perspectives of young adult key informants to understand how and why two social branding interventions were effective: (1) "COMMUNE," designed for "Hipsters" as a movement of artists and musicians against Big Tobacco, and (2) "HAVOC," designed for "Partiers" as an exclusive, smoke-free clubbing experience. Design. Qualitative study (27 semistructured qualitative phone interviews). Setting. Intervention events held in bars in multiple U.S. cities. Participants: Twenty-seven key informants involved in COMMUNE or HAVOC as organizers (e.g., musicians, event coordinators) or event attendees. Measures. We conducted semistructured, in-depth interviews. Participants described intervention events and features that worked or did not work well. Analysis. We used an inductive-deductive approach to thematically code interview transcripts, integrating concepts from intervention design literature and emergent themes. Results: Participants emphasized the importance of fun, interactive, social environments that encouraged a sense of belonging. Anti-tobacco messaging was subtle and nonjudgmental and resonated with their interests, values, and aesthetics. Young adults who represented the intervention were admired and influential among peers, and intervention promotional materials encouraged brand recognition and social status. Conclusion. Anti-tobacco interventions for high-risk young adults should encourage fun experiences; resonate with their interests, values, and aesthetics; and use subtle, nonjudgmental messaging.


Asunto(s)
Productos de Tabaco , Cese del Uso de Tabaco , Humanos , Grupo Paritario , Nicotiana , Uso de Tabaco , Adulto Joven
9.
Cancer Causes Control ; 31(1): 13-23, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31797123

RESUMEN

BACKGROUND: Black women are more likely to be diagnosed with later stage breast cancer compared to white women due to biological or access to care factors. Therefore, our objective was to identify whether racial/ethnic differences in patient experiences with healthcare are associated with stage at diagnosis. METHODS: We used the SEER registry data linked with patient surveys from the Consumer Assessment of Healthcare Providers and Systems (CAHPS) completed prior to the diagnosis date. We examined responses about various aspects of their care such as the ability to get needed care, and to get care quickly. We used multivariable linear regression to examine racial/ethnic differences in patient experiences, and a multivariable ordinal logistic regression to determine the association between patient experiences and earlier stage at diagnosis. RESULTS: Of the 10,144 patients, 80.7% were non-Hispanic white, 7.6% black, 7.1% Hispanic, and 4.6% Asian. After controlling for potential confounders, black patients had significantly lower mean scores for getting care quickly (ß = - 2.78), getting needed care (ß = - 2.26), getting needed prescription drugs (ß = - 3.83), and lower ratings of their health care (ß = - 2.33) compared to white patients. More importantly, we found that black patients who reported a 1-unit increase in rating of their experiences with customer service (OR 1.04, 95% CI 1.01-1.06) and the ability to get care quickly (OR 1.03, 1.01-1.05) had higher odds of earlier stage breast cancer. CONCLUSION: Racial/ethnic minorities reported poorer patient experiences with care preceding a diagnosis of breast cancer. Better ratings among black patients were associated with earlier stage at diagnosis.


Asunto(s)
Neoplasias de la Mama/etnología , Neoplasias de la Mama/terapia , Satisfacción del Paciente , Adulto , Negro o Afroamericano , Anciano , Neoplasias de la Mama/diagnóstico , Etnicidad , Femenino , Hispánicos o Latinos , Humanos , Modelos Logísticos , Persona de Mediana Edad , Grupos Minoritarios , Análisis Multivariante , Atención Dirigida al Paciente , Sistema de Registros , Estudios Retrospectivos , Programa de VERF , Estados Unidos , Población Blanca
10.
Support Care Cancer ; 28(1): 271-278, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31037379

RESUMEN

BACKGROUND: Adjuvant endocrine therapy (AET) significantly reduces recurrence and mortality in women with estrogen receptor-positive breast cancer. Adherence to AET is about 50-60% for 5 years, and while numerous studies have identified barriers to AET adherence, few have identified the role of social support as a facilitator. Therefore, the objective of this study is to explore the role of social support during the ongoing management of AET. METHODS: We conducted semi-structured in-depth interviews with breast cancer survivors (n = 22) who filled a prescription for AET in the previous 12 months. Women were recruited from Los Angeles, California, and Houston, Texas, between 2014 and 2015. Interview questions prompted discussion about AET and how social support affects AET adherence. We analyzed interview transcripts with a grounded theory approach and grouped social support into four categories (emotional, informational, instrumental, and appraisal), then used a thematic content analysis to identify the sources and delivery of support. RESULTS: Women described that informational support was provided by medical providers who explained the purpose, benefits, and management of AET. Emotional support in the form of reassurance, communication, and empathy was provided by family, survivorship groups, medical providers, and spirituality/religiosity. Women identified several organizations and exercises that provided them with instrumental and appraisal support in the form of physical and emotional benefits, which was also provided by family, friends, and medical providers. CONCLUSION: We identified that social support delivered to breast cancer survivors provided women with educational, physical, and emotional benefits that may play an important role in their continuation of AET.


Asunto(s)
Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Supervivientes de Cáncer/psicología , Cumplimiento de la Medicación , Recurrencia Local de Neoplasia/prevención & control , Apoyo Social , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/patología , Neoplasias de la Mama/psicología , Quimioterapia Adyuvante , Terapia Combinada , Emociones/fisiología , Ejercicio Físico/fisiología , Femenino , Humanos , Entrevistas como Asunto , Los Angeles/epidemiología , Cumplimiento de la Medicación/psicología , Cumplimiento de la Medicación/estadística & datos numéricos , Persona de Mediana Edad , Encuestas y Cuestionarios , Texas/epidemiología
11.
Educ Psychol Meas ; 83(5): 861-884, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37663536

RESUMEN

Even though the impact of the position of response options on answers to multiple-choice items has been investigated for decades, it remains debated. Research on this topic is inconclusive, perhaps because too few studies have obtained experimental data from large-sized samples in a real-world context and have manipulated the position of both correct response and distractors. Since multiple-choice tests' outcomes can be strikingly consequential and option position effects constitute a potential source of measurement error, these effects should be clarified. In this study, two experiments in which the position of correct response and distractors was carefully manipulated were performed within a Chilean national high-stakes standardized test, responded by 195,715 examinees. Results show small but clear and systematic effects of options position on examinees' responses in both experiments. They consistently indicate that a five-option item is slightly easier when the correct response is in A rather than E and when the most attractive distractor is after and far away from the correct response. They clarify and extend previous findings, showing that the appeal of all options is influenced by position. The existence and nature of a potential interference phenomenon between the options' processing are discussed, and implications for test development are considered.

12.
Arq Gastroenterol ; 60(4): 463-469, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38018551

RESUMEN

BACKGROUND: Colorectal cancer (CRC) has high mortality rates worldwide. In Brazil, it is the second most common cancer in both sexes. Delay in detecting premalignant lesions contributes to increased morbidity and mortality. In this scenario, the Piranhas project was created to track CRC in a low-income population in the hinterland of Alagoas. OBJECTIVE: The study aimed to establish the main strategies and verify the feasibility of implementing a CRC tracking program and demonstrate the results obtained in the CRC Prevention Campaign in Piranhas/AL. METHODS: The program took place in Piranhas, Alagoas, Brazil, through public-private partnerships. Individuals aged between 50 and 70 years of age were included for screening with a fecal occult blood test (FOBT) and colonoscopy in positive cases. Patient data were collected on standard forms. RESULTS: A total of 2152 patients, aged between 50 and 70 years, were screened, 130 of which underwent colonoscopy. Several preneoplastic lesions were detected in 58 patients. The adenoma detection rate (ADR) was 33.85%. CONCLUSION: The study proved to be effective and viable since 44.6% of the program participants, who underwent screening with FOBT, followed by colonoscopy in positive cases, had some type of preneoplastic lesion. In addition, the program generated a significant social impact on the population of Piranhas due to the opportunity to diagnose and treat CRC precursor lesions.


Asunto(s)
Neoplasias Colorrectales , Detección Precoz del Cáncer , Masculino , Femenino , Humanos , Persona de Mediana Edad , Anciano , Detección Precoz del Cáncer/métodos , Neoplasias Colorrectales/patología , Colonoscopía , Tamizaje Masivo/métodos , Sangre Oculta
13.
Front Vet Sci ; 10: 1186650, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37520008

RESUMEN

Oral mucosal melanoma (OMM) is a common neoplasm in canines, although it is rare in humans. Cancer cells present alterations in energetic metabolism, and the Warburg effect states that most cancer cells undergo aerobic glycolysis. This can be reversed by certain drugs, resulting in decreased cell viability and cell death. We sought to evaluate the effects of sodium dichloroacetate (DCA) and omeprazole (OMP) alone or in combination on canine OMM and human melanoma cells. CMGD5 and SK-MEL-28 cell lines were treated with DCA and OMP alone or in combination, and cell viability was assessed using the crystal violet assay. Cell death (apoptosis and necrosis) was assessed by Annexin V and propidium iodide (PI) staining assays using flow cytometry. In addition, the oxygen consumption rate (OCR) was evaluated using a SeaHorse XF assay. Treatment with DCA or OMP alone resulted in a significant, but not dose-dependent, reduction in cell viability in both cell lines; however, the combination of DCA and OMP resulted in a significant and dose-dependent decrease in viability in both cell lines. DCA and OMP, alone or in combination, did not alter OCR at the concentrations tested in either cell line. Since the combination of DCA and OMP potentialized the inhibition of viability and increased cell death in a synergistic manner in melanoma cells, this approach may represent a new repurposing strategy to treat cancer.

14.
Biochemistry ; 51(23): 4685-92, 2012 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-22594498

RESUMEN

Using molecular phylogeny has accelerated the discovery of peptidic ligands targeted to ion channels and receptors. One clade of venomous cone snails, Asprella, appears to be significantly enriched in conantokins, antagonists of N-methyl d-aspartate receptors (NMDARs). Here, we describe the characterization of two novel conantokins from Conus rolani, including conantokin conRl-B that has shown an unprecedented selectivity for blocking NMDARs that contain NR2B subunits. ConRl-B shares only some sequence similarity with the most studied NR2B selective conantokin, conG. The divergence between conRl-B and conG in the second inter-Gla loop was used to design analogues for structure-activity studies; the presence of Pro10 was found to be key to the high potency of conRl-B for NR2B, whereas the ε-amino group of Lys8 contributed to discrimination in blocking NR2B- and NR2A-containing NMDARs. In contrast to previous findings for Tyr5 substitutions in other conantokins, conRl-B[L5Y] showed potencies on the four NR2 NMDA receptor subtypes that were similar to those of the native conRl-B. When delivered into the brain, conRl-B was active in suppressing seizures in the model of epilepsy in mice, consistent with NR2B-containing NMDA receptors being potential targets for antiepileptic drugs. Circular dichroism experiments confirmed that the helical conformation of conRl-B is stabilized by divalent metal ions. Given the clinical applications of NMDA antagonists, conRl-B provides a potentially important pharmacological tool for understanding the differential roles of NMDA receptor subtypes in the nervous system. This work shows the effectiveness of coupling molecular phylogeny, chemical synthesis, and pharmacology for discovering new bioactive natural products.


Asunto(s)
Conotoxinas/metabolismo , Caracol Conus/metabolismo , Péptidos/metabolismo , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Secuencia de Aminoácidos , Animales , Anticonvulsivantes/química , Anticonvulsivantes/metabolismo , Anticonvulsivantes/farmacología , Clonación Molecular , ADN/genética , Epilepsia/tratamiento farmacológico , Regulación de la Expresión Génica , Genoma , Ratones , Conformación Proteica
15.
Front Pediatr ; 10: 882468, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35795331

RESUMEN

Background: With the implementation of lifelong antiretroviral therapy (ART) for HIV treatment and prevention, the proportion of children exposed to ART in utero from conception is increasing. We estimated the effect of timing of ART exposure on growth of children HIV-exposed and uninfected (CHEU) up to Up to 24 months of age in Malawi. Methods: Data were collected from a prospective cohort of infants HIV-exposed aged 1-6 months (enrollment) and their mothers with HIV enrolled in the National Evaluation of Malawi's Prevention of Mother-to-Child Transmission of HIV Programme (2014-2018). Anthropometry was measured at enrollment, visit 1 (approximately 12 months), and visit 2 (approximately 24 months). Weight-for-age (WAZ) and length-for-age (LAZ) were calculated using the WHO Growth Standards. Multivariable mixed-effects models with linear splines for age were used to examine differences in growth by timing of ART exposure (from conception, first/second trimester, or third trimester/postpartum). Models were adjusted for confounders selected a priori guided by a conceptual framework. Hypothesized interactions and potential mediators were explored, and interactions with splines were included in final models if P < 0.1. Results: A total of 1,206 singleton CHEU and their mothers were enrolled and 563 completed the follow-up through 24 months of age. Moreover, 48% of CHEU were exposed to ART from conception, 40% from first/second trimester, and 12% from third trimester/postpartum. At enrollment, 12% of infants had low birthweight (LBW), 98% had been breastfed in past 7 days, and 57% were enrolled in an HIV care clinic. CHEU growth trajectories demonstrated cohort-wide growth faltering after the age of 12 months. Of 788 and 780 CHEU contributing to WAZ and LAZ multivariable models, respectively, there was no evidence of differences in mean WAZ or LAZ among those exposed from conception or first/second trimester vs. third trimester/postpartum and no evidence of a difference in WAZ or LAZ rate of change by timing of ART exposure (all interactions P > 1.0). Conclusion: Reassuringly, ART exposure from conception was not associated with decreased WAZ or LAZ in CHEU Up 24 months of age. Overall growth trajectories suggest CHEU experience growth faltering after 12 months of age and may need support through and beyond the first 2 years of life.

17.
JCO Oncol Pract ; 17(5): e645-e653, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33974829

RESUMEN

PURPOSE: Black patients with cancer report worse experiences with health care compared with White patients; however, little is known about what influences these ratings. The objective of this study is to explore the multilevel factors that influence global ratings of care for Black cancer survivors. METHODS: We conducted semistructured in-depth interviews with 18 Black cancer survivors. We assessed the global ratings of their personal doctor, specialist, health plan, prescription drug plan, and overall health care, and asked patients to elaborate on their rating. We analyzed the interviews with a deductive grounded theory approach using the socioecologic model to identify the individual, interpersonal, organizational, and environmental influences on Black cancer patient experiences with global ratings of care. We used an inductive constant comparison approach to identify additional themes that emerged. Two coauthors separately coded a set of transcripts and met to refine the codebook. RESULTS: On average, participants reported the highest mean rating for their specialist (9.39/10) and the lowest mean rating for their personal doctor (7.33/10). Emerging themes that influenced patient ratings were perceptions about their interaction with medical providers, physician communication, the doctor's expertise, and aspects of the physical facilities. Global ratings of care measures were widely influenced by patient interactions with their providers that were empathetic, nondiscriminatory, and where the doctors addressed all concerns. CONCLUSION: This grounded theory study identifies multiple aspects of health care that intervention researchers, health care administrators, and providers may target to improve Black cancer patient experiences with care.


Asunto(s)
Negro o Afroamericano , Neoplasias , Comunicación , Humanos , Neoplasias/terapia , Evaluación del Resultado de la Atención al Paciente , Población Blanca
18.
Rev Assoc Med Bras (1992) ; 67(2): 195-199, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34231766

RESUMEN

OBJECTIVE: Free intra-abdominal fluid describes an accumulation of free fluid in the peritoneal cavity. It has different etiologies, but it frequently constitutes a meaningful clinical sign. In this study, the authors interrogate whether abdominal ultrasound augments the medical students' ability to identify free intra-abdominal fluid. METHODS: Thirty-one medical students without any previous formal ultrasound training were subjected to cognitive assessment before and after four and a half-hour of theoretical lecture and hands-on course about the diagnosis of free intra-abdominal fluid by physical examination and abdominal ultrasound. The hands-on sessions were done in healthy volunteers with a simulated peritoneal catheter and in patients treated with peritoneal dialysis with different amounts of dialysate in their cavity. RESULTS: The cognitive assessment before and after the course increased from 6.7±2.3 to 11.6±1.1 points (p<0.0001). The sensitivity, specificity, and accuracy in the diagnosis of free intra-abdominal fluid were higher when students used abdominal ultrasound. The students agree with the inclusion of abdominal ultrasound in the diagnose of free intra-abdominal fluid in the undergraduate curriculum. CONCLUSIONS: This study demonstrates that incorporating abdominal ultrasound is feasible and improves medical students' short-time competency in performing and interpreting the findings diagnostic of free intra-abdominal fluid.


Asunto(s)
Educación de Pregrado en Medicina , Estudiantes de Medicina , Competencia Clínica , Curriculum , Humanos , Ultrasonografía
19.
Front Vet Sci ; 8: 670451, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34179163

RESUMEN

Oral mucosal melanomas (OMM) are aggressive cancers in dogs, and are good models for human OMM. Gap junctions are composed of connexin units, which may have altered expression patterns and/or subcellular localization in cancer cells. Cell-to-cell communication by gap junctions is often impaired in cancer cells, including in melanomas. Meanwhile, the upregulated expression of the gap junction protein connexin 43 (Cx43) inhibits melanoma progression. The α-connexin carboxyl-terminal (aCT1) peptide reportedly maintains Cx43 expression and cell-cell communication in human mammary cells and increases the communication activity through gap junctions in functional assays, therefore causing decreased cell proliferation. The Bowman-Birk protease inhibitor (BBI), a component of soybeans, induces Cx43 expression in several tumor cells as a trypsin-chymotrypsin inhibition function, with antineoplastic effects. This study investigated the effect of aCT1 peptide and BBI treatment, alone or in combination, on TLM1 canine melanoma cell viability. Cell viability after treatment with aCT1, the reverse sequence peptide (R-pep), and/or BBI for 5 days was analyzed by PrestoBlue assay. Immunofluorescence was used to observe Cx43 localization and expression. aCT1 (200 µM) alone did not significantly decrease cell viability in TLM1 cells, whereas BBI (400 µg/ml) alone significantly decreased the TLM1 viability. Combined treatment with both aCT1 (200 µM) and BBI (400 µg/ml) significantly decreased cell viability in TLM1 cells. Cx43 expression, as identified by immunostainings in TLM1 cells, was increased in the cell membrane after the combination treatment with BBI and aCT1. This dual treatment can be combined to achieve the anticancer activity, possibly by increasing Cx 43 expression and affecting Cx43 migration to the cell membrane. In conclusion, a treatment strategy targeting Cx43 with BBI and aCT1 may possibly lead to new effective therapies for canine OMM.

20.
J Pediatr (Rio J) ; 97(6): 651-657, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33713629

RESUMEN

OBJECTIVES: The authors aim to evaluate the "point-of-care" transfontanellar ultrasound (TU) as an extension to pediatric physical examination and suggest a TU teaching protocol. METHODS: The students were randomly divided into two groups, group A (12 participants) and group B (15 participants). The first group only received theoretical training, while the second group received theoretical and practical training. A third group, group C, included 15 pediatricians and interns who also received theoretical and practical training. All the participants underwent multiple-choice testing before and after a four-hour short course on TU. Six months later, another evaluation was performed to analyze the retained knowledge. Furthermore, a questionnaire based on the Likert scale was administered to evaluate satisfaction. RESULTS: The cognitive evaluation (maximum score=10 points) before and after training increased in group A from 4,0±1,04 to 7,5±1,2 (p<0.001) and, 6 months later, to 6,5±1,16 (p<0.003); in group B from 3,8±1,24 to 8,8±1,01 (p<0.001) and, 6 months later, to 8,46±0,91 (p<0.001); and in group C from 6,0±0,75 to 9,0±0,75 (p<0.001) and, 6 months later, to 8,8±0,77 (p<0.001). The average satisfaction estimated by the Likert scale was over 80% for all questions. CONCLUSION: Cognitive assessment before and after classes and training reveals progress in learning, with knowledge retention in 6 months. Theoretical-practical courses are well accepted.


Asunto(s)
Educación de Pregrado en Medicina , Estudiantes de Medicina , Niño , Curriculum , Evaluación Educacional , Humanos , Pediatras , Sistemas de Atención de Punto
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