RESUMO
Increasingly, individuals with anxiety disorders are seeking mind-body interventions (e.g., yoga), but their effectiveness is unclear. This report summarizes seven additional, secondary outcomes measuring anxiety and depression symptoms from a study of 226 adults with generalized anxiety disorder who were randomized to 12-week Kundalini Yoga, Cognitive-Behavior Therapy (CBT) or stress education (control). At post-treatment, participants receiving CBT displayed significantly lower symptom severity, compared to those in the control group, on 6 of the 7 measures. Participants who received Yoga (vs. those in the control group) displayed lower symptom severity on 3 of the 7 measures. No significant differences were detected between participants receiving CBT vs those receiving Yoga. At the 6-month follow-up, participants from the CBT continued to display lower symptoms than the control group.
Assuntos
Terapia Cognitivo-Comportamental , Yoga , Adulto , Humanos , Depressão/terapia , Transtornos de Ansiedade/terapia , Ansiedade/terapiaRESUMO
We recently described X-linked acrogigantism (X-LAG), a condition of early childhood-onset pituitary gigantism associated with microduplications of the GPR101 receptor. The expression of GPR101 in hyperplastic pituitary regions and tumors in X-LAG patients, and GPR101's normally transient pituitary expression during fetal development, suggest a role in the regulation of growth. Nevertheless, little is still known about GPR101's physiological functions, especially during development. By using zebrafish models, we investigated the role of gpr101 during embryonic development and somatic growth. Transient ectopic gpr101 expression perturbed the embryonic body plan but did not affect growth. Loss of gpr101 led to a significant reduction in body size that was even more pronounced in the absence of maternal transcripts, as well as subfertility. These changes were accompanied by gastrulation and hypothalamic defects. In conclusion, both gpr101 loss- and gain-of-function affect, in different ways, fertility, embryonic patterning, growth and brain development.
Assuntos
Acromegalia/genética , Desenvolvimento Embrionário/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Gigantismo/genética , Receptores Acoplados a Proteínas G/genética , Proteínas de Peixe-Zebra/genética , Peixe-Zebra/crescimento & desenvolvimento , Peixe-Zebra/genética , Acromegalia/complicações , Animais , Feminino , Fertilização/genética , Gastrulação/genética , Regulação da Expressão Gênica no Desenvolvimento , Gigantismo/complicações , Hipotálamo/patologia , Mutação/genética , Óvulo/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais/genética , Temperatura , Transcriptoma/genética , Regulação para Cima/genética , Proteínas de Peixe-Zebra/metabolismo , Zigoto/metabolismoRESUMO
Niemann-Pick disease type C1 (NPC1) is a rare autosomal recessive lysosomal storage disease primarily caused by mutations in NPC1 NPC1 is characterized by abnormal accumulation of unesterified cholesterol and glycolipids in late endosomes and lysosomes. Common signs include neonatal jaundice, hepatosplenomegaly, cerebellar ataxia, seizures and cognitive decline. Both mouse and feline models of NPC1 mimic the disease progression in humans and have been used in preclinical studies of 2-hydroxypropyl-ß-cyclodextrin (2HPßCD; VTS-270), a drug that appeared to slow neurological progression in a Phase 1/2 clinical trial. However, there remains a need to identify additional therapeutic agents. High-throughput drug screens have been useful in identifying potential therapeutic compounds; however, current preclinical testing is time and labor intensive. Thus, development of a high-capacity in vivo platform suitable for screening candidate drugs/compounds would be valuable for compound optimization and prioritizing subsequent in vivo testing. Here, we generated and characterize two zebrafish npc1-null mutants using CRISPR/Cas9-mediated gene targeting. The npc1 mutants model both the early liver and later neurological disease phenotypes of NPC1. LysoTracker staining of npc1 mutant larvae was notable for intense staining of lateral line neuromasts, thus providing a robust in vivo screen for lysosomal storage. As a proof of principle, we were able to show that treatment of the npc1 mutant larvae with 2HPßCD significantly reduced neuromast LysoTracker staining. These data demonstrate the potential value of using this zebrafish NPC1 model for efficient and rapid in vivo optimization and screening of potential therapeutic compounds.This article has an associated First Person interview with the first author of the paper.