RESUMEN
People with a disorder of intellectual development (German draft of the ICD-11, which came into force on 1 January 2022) suffer more frequently from mental illnesses. According to the international treatment guidelines multimodal approaches should include not only psychopharmacological treatment, but also disorder-specific psychotherapeutic methods. These psychotherapeutic interventions have to be adapted to the communicative and cognitive abilities (performance diagnostics with IQ tests) as well as the emotional developmental stage (developmental diagnostics, e.g., with the scale of emotional development, short version, SED-S 2; [1]). To ensure this, the rules of simple language should be observed and when appropriate relatives or caregivers should be involved in the therapeutic process. The effectiveness of cognitive behavioral therapy has received most scientific attention, especially for affective disorders. Posttraumatic stress disorders can be validly treated with eye movement desensitization and reprocessing (EMDR). There is also good evidence for exposure therapy with reinforcement in the treatment of anxiety disorders.
Asunto(s)
Terapia Cognitivo-Conductual , Desensibilización y Reprocesamiento del Movimiento Ocular , Trastornos por Estrés Postraumático , Humanos , Psicoterapia/métodos , Trastornos por Estrés Postraumático/diagnóstico , Trastornos por Estrés Postraumático/terapia , Trastornos por Estrés Postraumático/psicología , Terapia Cognitivo-Conductual/métodos , Trastornos de Ansiedad , Desensibilización y Reprocesamiento del Movimiento Ocular/métodos , Resultado del TratamientoRESUMEN
Anti-cancer small molecule ONC201 upregulates the integrated stress response (ISR) and acts as a dual inactivator of Akt/ERK, leading to TRAIL gene activation. ONC201 is under investigation in multiple clinical trials to treat patients with cancer. Given the unique imipridone core chemical structure of ONC201, we synthesized a series of analogs to identify additional compounds with distinct therapeutic properties. Several imipridones with a broad range of in vitro potencies were identified in an exploration of chemical derivatives. Based on in vitro potency in human cancer cell lines and lack of toxicity to normal human fibroblasts, imipridones ONC206 and ONC212 were prioritized for further study. Both analogs inhibited colony formation, and induced apoptosis and downstream signaling that involves the integrated stress response and Akt/ERK, similar to ONC201. Compared to ONC201, ONC206 demonstrated improved inhibition of cell migration while ONC212 exhibited rapid kinetics of activity. ONC212 was further tested in >1000 human cancer cell lines in vitro and evaluated for safety and anti-tumor efficacy in vivo. ONC212 exhibited broad-spectrum efficacy at nanomolar concentrations across solid tumors and hematological malignancies. Skin cancer emerged as a tumor type with improved efficacy relative to ONC201. Orally administered ONC212 displayed potent anti-tumor effects in vivo, a broad therapeutic window and a favorable PK profile. ONC212 was efficacious in vivo in BRAF V600E melanoma models that are less sensitive to ONC201. Based on these findings, ONC212 warrants further development as a drug candidate. It is clear that therapeutic utility extends beyond ONC201 to include additional imipridones.
Asunto(s)
Antineoplásicos/farmacología , Regulación Neoplásica de la Expresión Génica , Compuestos Heterocíclicos de 4 o más Anillos/farmacología , Melanoma/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Animales , Antineoplásicos/síntesis química , Antineoplásicos/farmacocinética , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Compuestos Heterocíclicos de 4 o más Anillos/síntesis química , Compuestos Heterocíclicos de 4 o más Anillos/farmacocinética , Humanos , Imidazoles , Melanoma/genética , Melanoma/metabolismo , Melanoma/patología , Ratones , Proteína Quinasa 1 Activada por Mitógenos/antagonistas & inhibidores , Proteína Quinasa 1 Activada por Mitógenos/genética , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/antagonistas & inhibidores , Proteína Quinasa 3 Activada por Mitógenos/genética , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Especificidad de Órganos , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas B-raf/metabolismo , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Piridinas , Pirimidinas , Transducción de Señal , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología , Relación Estructura-Actividad , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVE: Lack of sleep among college students negatively impacts health and academic outcomes. Building on research that implied motion imagery increases brain activity, this project tested visual design strategies to increase viewers' engagement with a health communication campaign promoting napping to improve sleep habits. PARTICIPANTS: PARTICIPANTS (N = 194) were recruited from a large southwestern university in October 2012. METHODS: Utilizing an experimental design, participants were assigned to 1 of 3 conditions: an implied motion superhero spokes-character, a static superhero spokes-character, and a control group. RESULTS: The use of implied motion did not achieve the hypothesized effect on message elaboration, but superheroes are a promising persuasive tool for health promotion campaigns for college audiences. CONCLUSIONS: Implications for sleep health promotion campaigns and the role of implied motion in message design strategies are discussed, as well as future directions for research on the depiction of implied motion as it relates to theoretical development.
Asunto(s)
Publicidad/métodos , Servicios de Salud Escolar/estadística & datos numéricos , Sueño , Estudiantes/psicología , Universidades , Adolescente , Adulto , Femenino , Humanos , Masculino , Estudiantes/estadística & datos numéricos , Encuestas y CuestionariosRESUMEN
INTRODUCTION: The needs and issues of rural women regarding pharmacologic information and therapy are rarely explored. We sought to explore the needs and issues of rural women in Canada regarding drug-related information and prescription and nonprescription pharmaceuticals. METHODS: We used the qualitative methodology of interpretive description. In-depth semistructured face-to-face interviews were conducted with 20 women aged 17-88 years who lived in rural southwestern Ontario. RESULTS: Although rural women accessed prescription medications, complementary and alternative medicine (CAM) was highly favoured, and alcohol and illicit drugs such as marijuana, crystal meth and cocaine were prevalent in rural communities. Factors that affected rural women's decisions about which medications to use included access to health care practitioners, costs of medications, experiences of family members and friends with prescribed and alternative medications, attitudes and approaches of health care providers and health store employees, and the women's own expectations and desires. Factors that affected the use of illicit drugs included availability, boredom, peer pressure and cultural norms. Rural factors that influenced access to drug information and use included presence or lack of confidential care, distance to resources, and presence, accessibility and acceptability of rural resources. CONCLUSION: Rural women use a variety of drug therapies and sources of information, and experience unique socioeconomic and environmental issues that affect access to appropriate drug-related information and therapies. Further research is needed to clarify and articulate pharmacologic needs, issues and solutions for women in diverse rural settings.