Corticotrophin releasing factor (CRF) induced reinstatement of cocaine seeking in male and female rats

Significant sex differences have been demonstrated in clinical and preclinical studies of cocaine addiction, with some of the most consistent differences noted in regard to the role of stress and craving. The current study examined stress-induced reinstatement of cocaine seeking in male and female rats in an animal model of relapse using corticotropin-releasing factor (CRF) administration. Both male and female rats demonstrated increased cocaine seeking in response to CRF. CRF-induced reinstatement was highly variable across both male and female rats, and further analysis revealed a subpopulation that was particularly sensitive to CRF (high responders). Female high responders displayed significantly increased responding to CRF compared to males. Individual differences in stress responsivity could thus contribute to the likelihood of relapse, with females showing greater heterogeneity to stress-induced relapse.     

Real-world effectiveness and safety of collagenase clostridium histolyticum-aaes injections for the treatment of thigh cellulite in women: An open-label study interim analysis

Background

Collagenase clostridium histolyticum-aaes (CCH-aaes) is approved in the United States for moderate-to-severe cellulite in the buttocks of adult women.

Aim

Interim analysis to evaluate efficacy/safety of CCH-aaes in the treatment of thigh cellulite.

Methods

Data were analyzed from a phase 3, open-label study (REAL). Women with mild-to-moderate cellulite on both thighs (Clinician Reported Photonumeric Cellulite Severity Scale score, 2 or 3) received ≤0.84 mg (volume, 18 ml) of CCH-aaes subcutaneously, in up to 12 dimples per posterolateral thigh, in up to 3 treatment sessions (Days 1, 22, and 43). Follow-up was on Day 90 (interim cutoff). A subset of women participated in the concurrent study (PIXELS), which included high-definition photography and 3D-image scanning of treatment areas.

Results

Twenty-two women (44 thighs) were included in the interim analysis (mean age, 42.3 years; thighs with mild cellulite, 68.2%). Investigators reported high percentages of responders (score of “improved” or better on Investigator Global Aesthetic Improvement Scale) at Day 90 for either thigh (86.4%; primary endpoint) or both thighs (72.7%). Patient-reported bother due to cellulite was reduced at Day 90; mean change was 15.3 points (85.5% reduction) in BODY-Q Appraisal of Cellulite Scale total score (possible range, 11–44). In PIXELS analysis, Day 90 3D-image scans showed improvement from baseline in skin roughness in some of the treated thigh areas. The most commonly reported adverse events were injection-site bruising and pain (95.5% and 50.0% of patients, respectively).

Conclusions

CCH-aaes treatment of mild-to-moderate thigh cellulite was effective and generally well tolerated, with markedly reduced cellulite-related bother.     

Diet Quality Is Inversely Associated with C-Reactive Protein Levels in Urban,Low-Income African-American and White Adults

BackgroundC-reactive protein (CRP), an inflammatory biomarker, is influenced by many factors, including socioeconomic position, genetics, and diet. The inverse association between diet and CRP is biologically feasible because micronutrients with antioxidative properties may enable the body to manage the balance between production and accumulation of reactive species that cause oxidative stress.ObjectiveTo determine the quality of the diet consumed by urban, low-income African-American and white adults aged 30 to 64 years, and association of diet quality with CRP.DesignData from a cross-sectional study were used to evaluate diet quality assessed by mean adequacy ratio (MAR). Two 24-hour recalls were collected by trained interviewers using the US Department of Agriculture automated multiple pass method.ParticipantsThe sample consisted of Healthy Aging in Neighborhoods of Diversity across the Life Span baseline study participants, 2004-2009, who completed both recalls (n=2,017).Main outcome measuresMAR equaled the average of the ratio of intakes to Recommended Dietary Allowance for 15 vitamins and minerals. CRP levels were assessed by the nephelometric method utilizing latex particles coated with CRP monoclonal antibodies.Statistical analysisLinear ordinary least square regression and generalized linear models were performed to determine the association of MAR (independent variable) with CRP (dependent variable) while adjusting for potential confounders.ResultsMAR scores ranged from 74.3 to 82.2. Intakes of magnesium and vitamins A, C, and E were the most inadequate compared with Estimated Average Requirements. CRP levels were significantly associated with MAR, dual-energy x-ray absorptiometry-measured body fat, and hypertension. A 10% increase in MAR was associated with a 4% decrease in CRP.ConclusionsThe MAR was independently and significantly inversely associated with CRP, suggesting diet is associated with the regulation of inflammation. Interventions to assist people make better food choices may not only improve diet quality but also their health, thereby possibly reducing risk for cardiovascular disease.     

Urelumab alone or in combination with rituximab in patients with relapsed or refractory B-cell lymphoma

Urelumab, a fully human, non-ligand binding, CD137 agonist IgG4 monoclonal antibody, enhances T-cell and natural killer-cell antitumor activity in preclinical models, and may enhance cytotoxic activity of rituximab. Here we report results in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and other B-cell lymphomas, in phase 1 studies evaluating urelumab alone (NCT01471210) or combined with rituximab (NCT01775631). Sixty patients received urelumab (0.3 mg/kg IV Q3W, 8 mg IV Q3W, or 8 mg IV Q6W); 46 received urelumab (0.1 mg/kg, 0.3 mg/kg, or 8 mg IV Q3W) plus rituximab 375 mg/m² IV QW. The maximum tolerated dose (MTD) of urelumab was determined to be 0.1 mg/kg or 8 mg Q3W after a single event of potential drug-induced liver injury occurred with urelumab 0.3 mg/kg. Treatment-related AEs were reported in 52% (urelumab: grade 3/4, 15%) and 72% (urelumab + rituximab: grade 3/4, 28%); three led to discontinuation (grade 3 increased AST, grade 4 acute hepatitis [urelumab]; one death from sepsis syndrome [urelumab plus rituximab]). Objective response rates/disease control rates were 6%/19% (DLBCL, n = 31), 12%/35% (FL, n = 17), and 17%/42% (other B-cell lymphomas, n = 12) with urelumab and 10%/24% (DLBCL, n = 29) and 35%/71% (FL, n = 17) with urelumab plus rituximab. Durable remissions in heavily pretreated patients were achieved; however, many were observed at doses exceeding the MTD. These data show that urelumab alone or in combination with rituximab demonstrated manageable safety in B-cell lymphoma, but the combination did not enhance clinical activity relative to rituximab alone or other current standard of care.     

Prevention of conversion to abnormal transcranial Doppler with hydroxyurea in sickle cell anemia: A Phase III international randomized clinical trial

Children with sickle cell anemia (SCA) and conditional transcranial Doppler (TCD) ultrasound velocities (170–199 cm/sec) may develop stroke. However, with limited available clinical data, the current standard of care for conditional TCD velocities is observation. The efficacy of hydroxyurea in preventing conversion from conditional to abnormal TCD (≥200 cm/sec), which confers a higher stroke risk, has not been studied prospectively in a randomized trial. Sparing Conversion to Abnormal TCD Elevation (SCATE #NCT01531387) was a National Heart, Lung, and Blood Institute‐funded Phase III multicenter international clinical trial comparing alternative therapy (hydroxyurea) to standard care (observation) to prevent conversion from conditional to abnormal TCD velocity in children with SCA. SCATE enrolled 38 children from the United States, Jamaica, and Brazil [HbSS (36), HbSβ⁰‐thalassemia (1), and HbSD (1), median age = 5.4 years (range, 2.7–9.8)]. Because of the slow patient accrual and administrative delays, SCATE was terminated early. In an intention‐to‐treat analysis, the cumulative incidence of abnormal conversion was 9% (95% CI = 0–35%) in the hydroxyurea arm and 47% (95% CI = 6–81%) in observation arm at 15 months (P = 0.16). In post hoc analysis according to treatment received, significantly fewer children on hydroxyurea converted to abnormal TCD velocities when compared with observation (0% vs. 50%, P = 0.02). After a mean of 10.1 months, a significant change in mean TCD velocity was observed with hydroxyurea treatment (?15.5 vs. +10.2 cm/sec, P = 0.02). No stroke events occurred in either arm. Hydroxyurea reduces TCD velocities in children with SCA and conditional velocities. Am. J. Hematol. 90:1099–1105, 2015. © 2015 Wiley Periodicals, Inc.     

The personal work of a first pregnancy: transforming identities, relationships, and women's work

The purpose of this qualitative research was to explore women's experiences and perceptions of work during a first pregnancy. In this article we present findings related to women's personal work, one aspect of pregnancy work identified in the larger study (1996-2002). Qualitative data were collected through semi-structured interviews with a purposeful, convenience sample of 29 women, ages 18-40 years, from diverse ethnic/racial, social, and economic backgrounds. Their personal work of pregnancy included growing a child, creating self as a mother, preparing for the baby, situating self vis-à-vis parental and societal models of motherhood, and personal relationship work. A first pregnancy transformed women's work as they added pregnancy to the mix and experienced significant shifts and transformations in personal and social identities and in the meanings, values, and priorities they attached to work. Findings were limited by the context and experiences of the participants in this convenience sample; however, they suggest the need for more attention to the complex personal work of pregnancy by clinicians and researchers and for continued expansion of conceptual frameworks of women's work during pregnancy.