RESUMEN
We previously reported that enhanced corticotropin-releasing factor (CRF) signaling in the bed nucleus of the stria terminalis (BNST) caused the aversive responses during acute pain and suppressed the brain reward system during chronic pain. However, it remains to be examined whether chronic pain alters the excitability of CRF neurons in the BNST. In this study we investigated the chronic pain-induced changes in excitability of CRF-expressing neurons in the oval part of the BNST (ovBNSTCRF neurons) by whole-cell patch-clamp electrophysiology. CRF-Cre; Ai14 mice were used to visualize CRF neurons by tdTomato. Electrophysiological recordings from brain slices prepared from a mouse model of neuropathic pain revealed that rheobase and firing threshold were significantly decreased in the chronic pain group compared with the sham-operated control group. Firing rate of the chronic pain group was higher than that of the control group. These data indicate that chronic pain elevated neuronal excitability of ovBNSTCRF neurons.
Asunto(s)
Dolor Crónico , Hormona Liberadora de Corticotropina , Neuronas , Núcleos Septales , Animales , Núcleos Septales/metabolismo , Hormona Liberadora de Corticotropina/metabolismo , Neuronas/metabolismo , Dolor Crónico/fisiopatología , Dolor Crónico/metabolismo , Masculino , Potenciales de Acción/fisiología , Ratones Endogámicos C57BL , RatonesRESUMEN
Hypertension is a significant contributor to premature mortality, and the regular monitoring of blood pressure (BP) enables the early detection of hypertension and cardiovascular disease. There is an urgent need for the development of highly accurate cuffless BP devices. We examined BP measurements based on a target spectral camera's recordings and evaluated their accuracy. Images of 215 adults' palms and faces were recorded, and BP was measured. The camera captured RGB wavelength data at 640 × 480 pixels and 150 frames per second (fps). These recordings were analyzed to extract pulse transit time (PTT) values between the face and palm, a key parameter for estimating BP. Continuous BP measurements were taken using a CNAPmonitor500 for validation. Three frequency wavelengths were measured from video images. A machine learning model was constructed to determine hypertension, defined as a systolic BP of 130 mmHg or higher or a diastolic BP of 80 mmHg or higher, using the visualized data. The discrimination between hypertension and normal BP was 95.0% accurate within 30 s and 90.3% within 5 s, based on the captured images. The results of heartbeat-by-heartbeat analyses can be used to determine hypertension based on only one second of camera footage or one heartbeat. The data extracted from a video recorded by a target spectral camera enabled accurate hypertension diagnoses, suggesting the potential for simplified BP monitoring.
Asunto(s)
Determinación de la Presión Sanguínea , Hipertensión , Humanos , Hipertensión/diagnóstico , Hipertensión/fisiopatología , Masculino , Femenino , Persona de Mediana Edad , Adulto , Estudios Prospectivos , Determinación de la Presión Sanguínea/métodos , Determinación de la Presión Sanguínea/instrumentación , Presión Sanguínea , Anciano , Análisis de la Onda del Pulso/métodos , Aprendizaje Automático , Frecuencia Cardíaca , Adulto JovenRESUMEN
Patients with heart failure (HF) often experience repeated acute decompensation and develop comorbidities such as chronic kidney disease and frailty syndrome. Although this suggests pathological interaction among comorbidities, the mechanisms linking them are poorly understood. Here, we identified alterations in hematopoietic stem cells (HSCs) as a critical driver of recurrent HF and associated comorbidities. Bone marrow transplantation from HF-experienced mice resulted in spontaneous cardiac dysfunction and fibrosis in recipient mice, as well as increased vulnerability to kidney and skeletal muscle insults. HF enhanced the capacity of HSCs to generate proinflammatory macrophages. In HF mice, global chromatin accessibility analysis and single-cell RNA-seq showed that transforming growth factor-ß (TGF-ß) signaling was suppressed in HSCs, which corresponded with repressed sympathetic nervous activity in bone marrow. Transplantation of bone marrow from mice in which TGF-ß signaling was inhibited similarly exacerbated cardiac dysfunction. Collectively, these results suggest that cardiac stress modulates the epigenome of HSCs, which in turn alters their capacity to generate cardiac macrophage subpopulations. This change in HSCs may be a common driver of repeated HF events and comorbidity by serving as a key carrier of "stress memory."
Asunto(s)
Insuficiencia Cardíaca , Inmunidad Innata , Memoria Inmunológica , Ratones Endogámicos C57BL , Animales , Insuficiencia Cardíaca/inmunología , Ratones , Masculino , Multimorbilidad , Factor de Crecimiento Transformador beta/metabolismo , Células Madre Hematopoyéticas/inmunología , Transducción de Señal/inmunología , Macrófagos/inmunología , Inmunidad EntrenadaRESUMEN
Understanding the desires and motivations of children with ADHD is important in helping them thrive. Their inner worlds, however, have not been well captured. The Three Wishes task provides minimal cues and structure to elicit their desires and hopes in an unbiased manner. The wishes of 299 school-aged children with ADHD (193 boys, aged 6-12) were elicited during a research diagnostic assessment. We developed a coding scheme to characterize different aspects of their wishes, including beneficiary, valence, and immediacy. Maslow's hierarchy of needs, adapted to take account of the participants' ages, was used to identify the motivations underlying the children's wishes. As expected, many of the wishes reported were for immediate fulfillment, with many reflecting material desires. Affiliative wishes, highlighting the children's desire for positive interpersonal relationships, were also common. There was some evidence for self-actualization/self-betterment goals and a small number of altruistic wishes. A word cloud presents the content of the children's wishes grouped according to this hierarchy. This study highlights the diversity and typicality of the self-reported needs, desires and hopes of children with ADHD. It also serves as a timely reminder of the value of seeking such information directly from children themselves.