Initial Validation and Measurement Invariance of the Active Inhibition Scale Among Traumatized and Grieving Youth

The Active Inhibition Scale (AIS; Ayers, Sandler, & Twohey, 1998) is an 11-item, self-report measure of emotional suppression among children and adolescents. Previous research with the AIS has linked emotional suppression to several clinically significant outcomes, such as posttraumatic stress symptoms (PTSS) and suicide, among trauma-exposed and bereaved youth; however, there are no published evaluations of its psychometric properties. We examined the factor structure and criterion validity of the AIS in two samples. Sample 1 included youth (M = 12.22 years, SD = 2.96, range: 6–18 years; 55.4% female) referred to an outpatient psychology clinic specializing in childhood trauma and grief. Sample 2 included youth (M = 13.18 years, SD = 2.58, range: 8–18 years; 61.8% female) referred to a community grief counseling center. Confirmatory factor analytic results supported a one-factor solution, Cronbach's α = .94. Additionally, AIS scores correlated positively with PTSS, depression, and maladaptive grief, rs = .43–.64. Evidence of factorial invariance was found across gender, race/ethnicity, and age group. Emotional suppression scores were higher among girls compared to boys, Black and Hispanic youth compared to White youth, and older compared to younger age groups. The magnitude of correlations between AIS and symptom measure scores was comparable across groups. These results support the reliability and criterion validity of the AIS with diverse youth populations and underscore the role that emotional suppression may play in explaining group differences in mental health symptoms.     

Osteoclasts are dispensable for hematopoietic stem cell maintenance and mobilization

Hematopoietic stem cells (HSCs) are maintained in a specific bone marrow (BM) niche in cavities formed by osteoclasts. Osteoclast-deficient mice are osteopetrotic and exhibit closed BM cavities. Osteoclast activity is inversely correlated with hematopoietic activity; however, how osteoclasts and the BM cavity potentially regulate hematopoiesis is not well understood. To investigate this question, we evaluated hematopoietic activity in three osteopetrotic mouse models: op/op, c-Fos-deficient, and RANKL (receptor activator of nuclear factor kappa B ligand)-deficient mice. We show that, although osteoclasts and, by consequence, BM cavities are absent in these animals, hematopoietic stem and progenitor cell (HSPC) mobilization after granulocyte colony-stimulating factor injection was comparable or even higher in all three lines compared with wild-type mice. In contrast, osteoprotegerin-deficient mice, which have increased numbers of osteoclasts, showed reduced HSPC mobilization. BM-deficient patients and mice reportedly maintain hematopoiesis in extramedullary spaces, such as spleen; however, splenectomized op/op mice did not show reduced HSPC mobilization. Interestingly, we detected an HSC population in osteopetrotic bone of op/op mice, and pharmacological ablation of osteoclasts in wild-type mice did not inhibit, and even increased, HSPC mobilization. These results suggest that osteoclasts are dispensable for HSC mobilization and may function as negative regulators in the hematopoietic system.     

Management of Pain and Nausea in Outpatient Surgery

The cost associated with surgical procedures has been dramatically decreased by the ability to perform these procedures on an outpatient basis. Pain and nausea, two common symptoms after anesthesia and surgical procedures, are among the greatest concerns for patients and their family members. As a result of the distress and sequelae associated with these symptoms, clinicians have attempted to determine the optimal intraoperative and postoperative symptom management for patients. The purpose of this quality improvement project was to describe the incidence of these symptoms and their management in patients who underwent planned outpatient surgical procedures in a cancer center. A sample of 39 patients were accrued at a comprehensive cancer center over a 3-month period. Data were collected at three specific time points (i.e., preoperatively, at 24 hours and at 7 days postoperatively). Postoperative pain and nausea were generally well managed, but improvement was needed in preoperative patient teaching, including the topics of drug and nondrug interventions. The methods used in this project have potential application for the measurement of other clinical outcomes after outpatient surgical procedures.     

Twenty Years of Active Bacterial Core Surveillance

Active Bacterial Core surveillance (ABCs) was established in 1995 as part of the Centers for Disease Control and Prevention Emerging Infections Program (EIP) network to assess the extent of invasive bacterial infections of public health importance. ABCs is distinctive among surveillance systems because of its large, population-based, geographically diverse catchment area; active laboratory-based identification of cases to ensure complete case capture; detailed collection of epidemiologic information paired with laboratory isolates; infrastructure that allows for more in-depth investigations; and sustained commitment of public health, academic, and clinical partners to maintain the system. ABCs has directly affected public health policies and practices through the development and evaluation of vaccines and other prevention strategies, the monitoring of antimicrobial drug resistance, and the response to public health emergencies and other emerging infections.     

(R)-2-Phenylpyrrolidine Substituted Imidazopyridazines: A New Class of Potent and Selective Pan-TRK Inhibitors

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Pharmacokinetics of Gefitinib in a Patient with Non-Small Cell Lung Cancer Undergoing Continuous Ambulatory Peritoneal Dialysis

A 72-year-old man undergoing continuous ambulatory peritoneal dialysis (CAPD) for chronic renal failure and who had undergone right upper lobectomy for lung adenocarcinoma (pT2aN0M0) 2 years ago was admitted for recurrence of lung cancer presenting as multiple brain metastases. An epidermal growth factor receptor mutation analysis of his lung cancer revealed a deletion of 15 nucleotides (E746-A750) in exon 19. After whole-brain radiotherapy, we started daily administration of 250 mg gefitinib under the continuation of CAPD and performed a pharmacokinetic analysis. We speculated that the plasma concentration of gefitinib reached the steady state at least by day 16 after the start of gefitinib (626.6 ng/ml at trough level). On day 46, the plasma concentration was 538.4 ng/ml at trough level and the concentration in the peritoneal dialysis fluid was 34.6 ng/ml, suggesting that CAPD appeared to have little effect on the pharmacokinetics of gefitinib. During gefitinib therapy, there were no significant adverse events except for grade 2 diarrhea. Gefitinib could be safely administered to a patient undergoing CAPD.Key Words: Gefitinib, Continuous ambulatory peritoneal dialysis, Chronic renal failure, Epidermal growth factor receptor, Non-small cell lung cancer     

In Vitro and In Vivo Antiviral Activity and Resistance Profile of the Hepatitis C Virus NS3/4A Protease Inhibitor ABT-450

The development of direct-acting antiviral agents is a promising therapeutic advance in the treatment of hepatitis C virus (HCV) infection. However, rapid emergence of drug resistance can limit efficacy and lead to cross-resistance among members of the same drug class. ABT-450 is an efficacious inhibitor of HCV NS3/4A protease, with 50% effective concentration values of 1.0, 0.21, 5.3, 19, 0.09, and 0.69 nM against stable HCV replicons with NS3 protease from genotypes 1a, 1b, 2a, 3a, 4a, and 6a, respectively. In vitro, the most common amino acid variants selected by ABT-450 in genotype 1 were located in NS3 at positions 155, 156, and 168, with the D168Y variant conferring the highest level of resistance to ABT-450 in both genotype 1a and 1b replicons (219- and 337-fold, respectively). In a 3-day monotherapy study with HCV genotype 1-infected patients, ABT-450 was coadministered with ritonavir, a cytochrome P450 3A4 inhibitor shown previously to markedly increase peak, trough, and overall drug exposures of ABT-450. A mean maximum HCV RNA decline of 4.02 log₁₀ was observed at the end of the 3-day dosing period across all doses. The most common variants selected in these patients were R155K and D168V in genotype 1a and D168V in genotype 1b. However, selection of resistant variants was significantly reduced at the highest ABT-450 dose compared to lower doses. These findings were informative for the subsequent evaluation of ABT-450 in combination with additional drug classes in clinical trials in HCV-infected patients. (Study M11-602 is registered at ClinicalTrials.gov under registration no. {"type":"clinical-trial","attrs":{"text":"NCT01074008","term_id":"NCT01074008"}}NCT01074008.)