ABSTRACTBackground: In the context of a randomized controlled trial evaluating the efficacy of augmenting fluoxetine treatment in young adults with major depressive disorder (MDD) using a modified repeated partial sleep deprivation protocol contrasting 2 weeks of restricted time in bed (i.e., 6 h TIB) to no time in bed restriction (i.e., 8 h TIB) the study examines whether sleep duration and the timing of repeated partial sleep deprivation predicts patient-reported affect ratings. Participants: Participants included 58 young adults with DSM-IV-diagnosed MDD. Methods: Daily ratings of affect and sleep were collected during the first 2 weeks of initiating fluoxetine treatment, yielding 630 person-days. Actigraphy monitoring was employed to assess compliance with time in bed condition. Results: Negative affect ratings and positivity ratios in the morning were more improved among participants assigned to the 6 h TIB condition compared to the 8 h TIB group. Participants whose bedtime was delayed by 2-h nightly demonstrated the most significant improvement in negative affect and positivity ratio during the first 2 weeks of fluoxetine therapy. Moreover, the trajectory of morning negative affect ratings in the first 2 weeks was predictive of remission after 4 weeks of fluoxetine therapy. Conclusions: These findings suggest that monitoring changes in daily affect may be a valuable marker of early treatment response in young adults with MDD. 相似文献
Pituitary - Growth hormone-producing pituitary adenomas are divided into two clinically relevant histologic subtypes, densely (DG-A) and sparsely (SG-A) granulated. Histologic subtype was evaluated... 相似文献
Background: Cystic fibrosis (CF) is challenged with pathophysiological barriers for effective airway drug-delivery. Hence, we standardized the therapeutic efficacy of the novel dendrimer-based autophagy-inducing anti-oxidant drug, cysteamine.
Research design and methods: Human primary-CF epithelial-cells, CFBE41o-cells were used to standardize the efficacy of the dendrimer-cystamine in correcting impaired-autophagy, rescuing ΔF508-CFTR and Pseudomonas-aeruginosa (Pa) infection.
Results: We first designed a novel cystamine-core dendrimer formulation (G4-CYS) that significantly increases membrane-ΔF508CFTR expression in CFBE41o-cells (p < 0.05) by forming its reduced-form cysteamine, in vivo. Additionally, G4-CYS treatment corrects ΔF508-CFTR-mediated impaired-autophagy as observed by a significant decrease (p < 0.05) in Ub-LC3-positive aggresome-bodies. Next, we verified that in non-permeabilized CFBE41o-cells, G4-CYS significantly (p < 0.05) induces ΔF508-CFTR’s forward-trafficking to the plasma membrane. Furthermore, cysteamine’s known antibacterial and anti-biofilm properties against Pa were enhanced as our findings demonstrate that both G4-CYS and its control DAB-core dendrimer, G4-DAB, exhibited significant (p < 0.05) bactericidal-activity against Pa. We also found that both G4-CYS and G4-DAB exhibit marked mucolytic-activity against porcine-mucus (p < 0.05). Finally, we demonstrate that G4-CYS not only corrects the autophagy-impairment by rescuing ΔF508-CFTR in CFBE41o-cells but also corrects the intrinsic phagocytosis defect (p < 0.05).
Conclusions: Overall, our data demonstrates the efficacy of novel cystamine-dendrimer formulation in rescuing ΔF508-CFTR to the plasma membrane and inhibiting Pa bacterial-infection by augmenting autophagy. 相似文献
To quantify eating disorder (ED) stability and diagnostic transition among a community-based sample of adolescents and young adult females in the United States.
Methods
Using 11 prospective assessments from 9,031 U.S. females ages 9–15 years at baseline of the Growing Up Today Study, we classified cases of the following EDs involving bingeing and purging: bulimia nervosa (BN), binge ED, purging disorder (PD), and subthreshold variants defined by less frequent (monthly vs. weekly) bingeing and purging behaviors. We measured number of years symptomatic and probability of maintaining symptoms, crossing to another diagnosis, or resolving symptoms across consecutive surveys.
Results
Study lifetime disorder prevalence was 2.1% for BN and roughly 6% each for binge ED and PD. Most cases reported symptoms during only one survey year. Twenty-six percent of cases crossed between diagnoses during follow-up. Among participants meeting full threshold diagnostic criteria, transition from BN was most prevalent, crossing most frequently from BN to PD (12.9% of BN cases). Within each disorder phenotype, 20%–40% of cases moved between subthreshold and full threshold criteria across consecutive surveys.
Conclusions
Diagnostic crossover is not rare among adolescent and young adult females with an ED. Transition patterns from BN to PD add support for considering these classifications in the same diagnostic category of disorders that involve purging. The prevalence of crossover between monthly and weekly symptom frequency suggests that a continuum or staging approach may increase utility of ED classification for prognostic and therapeutic intervention. 相似文献
The genetic hallmark of epithelioid hemangioendothelioma (EHE) is a recurrent WWTR1‐CAMTA1 fusion, which is present in most cases bearing a conventional histology. A subset of cases is characterized by a distinct morphology and harbors instead of YAP1‐TFE3 fusion. Nevertheless, isolated cases lack these canonical fusions and remain difficult to classify. Triggered by an index case of a left atrial mass in a 76‐year‐old female with morphologic features typical of EHE, but which showed a WWTR1‐MAML2 fusion by targeted RNA sequencing, we searched our files for similar cases displaying alternative WWTR1 fusions. A total of 6 EHE cases were identified with variant WWTR1 fusions, four of them presenting within the heart. There were three females and three males, with a wide age range at diagnosis (21‐76 years, mean 62, median 69). The four cardiac cases occurred in older adults (mean age of 72, equal gender distribution); three involved the left atrium and one the right ventricle. One case presented in the vertebral bone and one in pelvic soft tissue. Microscopically, all tumors had morphologic features within the spectrum of classic EHE; two of the cases appeared overtly malignant. All cases were tested by FISH and four were investigated by targeted RNA sequencing. Two tumors harbored WWTR1‐MAML2 fusions, one WWTR1‐ACTL6A, and in three cases, no WWTR1 partner was identified. Of the four patients with follow‐up, two died of disease, one was alive with lung metastases, and the only patient free of disease was s/p resection of a T11 vertebral mass. Our findings report on additional genetic variants involving WWTR1 rearrangements, with WWTR1‐MAML2 being a recurrent event, in a small subset of EHE, which appears to have predilection for the heart. 相似文献