Efficacy of the Getting Ready Intervention and the Role of Parental Depression.

This study reports the results of a randomized trial of a parent engagement intervention (the Getting Ready Project) on directly observed learning-related social behaviors of children from families of low-income in the context of parent-child interactions. The study explored the moderating effect of parental depression on intervention outcomes. Participants were 204 children and their parents, and 29 Head Start teachers. Semi-structured parent-child interaction tasks were videotaped two times annually over the course of two academic years. Observational codes of child behaviors included agency, persistence, activity level, positive affect, distractibility, and verbalizations. Controlling for gender and disability concerns, relative to children in the control group, those in the treatment condition experienced a significant decline in activity level. Furthermore, compared to children of non-depressed mothers and to control children, those in the experimental condition whose parent reported elevated levels of depression showed greater gains in positive affect and in verbalizations.

A food store-based environmental intervention is associated with reduced BMI and improved psychosocial factors and food-related behaviors on the Navajo nation.

The prevalence of obesity is significantly higher among American Indians (AIs) and is associated with increased rates of diabetes, hypertension, and cardiovascular disease. We implemented a 14-mo intervention trial (Navajo Healthy Stores) on the Navajo Nation that sought to increase availability of healthier foods in local food stores and to promote these foods at the point of purchase and through community media. We divided the Navajo Nation into 10 store regions, half of which were randomized to intervention and half to comparison. We evaluated the program by using a pre-post sample of systematically sampled adult Navajo consumers (baseline, n = 276; postintervention, n = 145). Intervention impact was examined by analyzing pre-post differences by intervention group and by intervention exposure level. When intervention and comparison groups were compared, only body mass index (BMI) showed a trend toward impact of the intervention (P = 0.06). However, greater exposure to the intervention was associated with significantly reduced BMI (P ≤ 0.05) and improved healthy food intentions (P ≤ 0.01), healthy cooking methods (P ≤ 0.05), and healthy food getting (P ≤ 0.01). With increasing exposure, the odds of improving overweight or obese status was 5.02 (95% CI: 1.48, 16.99; P ≤ 0.01) times the odds of maintaining or worsening overweight or obese status. In summary, a food store intervention was associated with reduced overweight/obesity and improved obesity-related psychosocial and behavioral factors among those persons most exposed to the intervention on an AI reservation.

Dasatinib is synergistic with cetuximab and cisplatin in triple-negative breast cancer cells.

BACKGROUND: Patients presenting with triple-negative breast cancers (TNBCs) have a poorer prognosis compared with those with other subtypes of breast cancer. The majority of TNBCs overexpress epidermal growth factor receptor (EGFR). However, EGFR inhibition as a monotherapy, as with the monoclonal antibody cetuximab, is ineffective. Src family tyrosine kinases play a critical role in signal transduction downstream of growth factor receptors and are involved in the development of EGFR inhibitor resistance. We hypothesize that dasatinib, an Src family tyrosine kinase inhibitor, may help overcome EGFR resistance to cetuximab, and in combination with cisplatin may enhance growth inhibition and apoptosis and reduce metastatic potential. METHODS: Growth inhibition, apoptosis, cell migration and invasion, and effects on EGFR, Akt, and mitogen-activated protein kinase phosphorylation were examined in a panel of breast cancer cell lines, including seven TNBC cell lines. RESULTS: Six out of seven TNBC cell lines demonstrated a synergistic interaction using the triple-drug combination, compared with only two TNBC cell lines with the cisplatin and cetuximab combination. An induction of apoptosis and decrease in EGFR and mitogen-activated protein kinase phosphorylation, and thus resensitization to EGFR inhibition, was observed using the three-drug treatment regimen. A significant reduction (P < 0.001) in tumor cell migration and invasion was also found following dasatinib treatment alone or in combination. CONCLUSIONS: These findings may have important clinical implications in treating TNBC patients whose tumors co-overexpress both EGFR and c-Src. Identification of this subset of patients may be beneficial in the design of a clinical trial using this treatment regimen.

The role of chemoprevention in modifying the risk of breast cancer in women with atypical breast lesions.

Women with atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), lobular carcinoma in situ (LCIS), and severe ADH are at increased risk of breast cancer, but a systematic quantification of this risk and the efficacy of chemoprevention in the clinical setting is still lacking. The objective of this study is to evaluate a woman's risk of breast cancer based on atypia type and to determine the effect of chemoprevention in decreasing this risk. Review of 76,333 breast pathology reports from three institutions within Partners Healthcare System, Boston, from 1987 to 2010 using natural language processing was carried out. This approach identified 2,938 women diagnosed with atypical breast lesions. The main outcome of this study is breast cancer occurrence. Of the 2,938 patients with atypical breast lesions, 1,658 were documented to have received no chemoprevention, and 184/1,658 (11.1 %) developed breast cancer at a mean follow-up of 68 months. Estimated 10-year cancer risks were 17.3 % with ADH, 20.7 % with ALH, 23.7 % with LCIS, and 26.0 % with severe ADH. In a subset of patients treated from 1999 on (the chemoprevention era), those who received no chemoprevention had an estimated 10-year breast cancer risk of 21.3 %, whereas those treated with chemoprevention had a 10-year risk of 7.5 % (p < 0.001). Chemoprevention use significantly reduced breast cancer risk for all atypia types (p < 0.05). The risk of breast cancer with atypical breast lesions is substantial. Physicians should counsel patients with ADH, ALH, LCIS, and severe ADH about the benefit of chemoprevention in decreasing their breast cancer risk.

A novel technique for lower extremity limb salvage: the vastus lateralis muscle flap with concurrent use of the vacuum-assisted closure device.

Free tissue transfer is an essential component of lower extremity limb reconstruction and has dramatically improved salvage attempts. In this report, we examine the use of the underutilized free vastus lateralis muscle flap and describe our treatment protocol that involves a novel application for the vacuum-assisted closure device in an effort to reduce edema and congestion in lower extremity limb salvage. Thirteen patients underwent reconstruction with 14 vastus lateralis flaps with closure occurring on average 35.2 days after injury and an average case duration of 4:34 days. We report one flap failure, one superficial abscess, and one donor site hematoma. All patients were ambulatory at 6 months. Our early experience using this underutilized flap and novel protocol demonstrate successful lower extremity reconstruction with few complications, and good function and contour. Given its advantages, this versatile flap should be included as an option in lower extremity limb salvage operations.

Power of the pinch: pinch lower lid blepharoplasty.

Lower lid blepharoplasty is performed with great variation in technique. Conventional lower lid blepharoplasty with anterior fat removal via the orbital septum has a potential lower lid malposition rate of 15% to 20%. Lower lid malposition and the stigma of obvious lower lid surgery have led plastic surgeons to continue to change their approach to lower lid rejuvenation. In recent years, some surgeons have come to rely on alternative procedures like laser resurfacing alone or in conjunction with transconjunctival fat removal and canthopexy in an effort to avoid such complications. The pinch blepharoplasty technique removes redundant skin without undermining. This allows for more controlled wound healing, predictable recovery, and potential for simultaneous laser resurfacing. The combination of pinch blepharoplasty with transconjunctival fat removal leaves the middle lamella intact and reduces the chance of scleral show or ectropion. The purpose of this series is to demonstrate that pinch excision of redundant lower eyelid skin can be safely performed and that it can be used with laser resurfacing and/or transconjunctival fat removal for optimal treatment of the aging eye. A retrospective review of 46 consecutive patients who underwent pinch blepharoplasty, either in isolation or with other periorbital procedures was performed. Follow-up was at least 4 months (range of 4-24 months). In addition, we performed a prospective study of 25 consecutive patients to quantify the amount of skin removed and evaluate results and complications. An average of 8 mm of skin was resected (range of 4-12 mm) with the pinch blepharoplasty technique. Of these patients, 5.6% also underwent transconjunctival blepharoplasty, laser resurfacing, and/or fat grafting of the nasojugal groove. Despite the addition of simultaneous laser resurfacing, we did not see an increase in lower lid malposition. Three of the 71 patients had temporary scleral show that resolved with lower lid massage. In total, only 4 patients had isolated pinch lower lid blepharoplasty. Twelve patients had orbicularis suspension and 15 had either canthopexy or canthoplasty. Five patients who had orbicularis suspension, canthopexy, or canthoplasty had periorbital edema. Two also had pronounced chemosis. Four patients had mild rounding of the lower lid. Pinch blepharoplasty is a versatile technique that produces consistent results. This study confirms that more skin from the lower lid can be resected than classically described. Pinch blepharoplasty can be performed safely in combination with other procedures to enhance lower lid appearance. The absence of skin undermining allows for safe simultaneous laser resurfacing. Preserving the middle lamella and supporting it when necessary allows one to resect significant amounts of lower lid skin without significant risk of scleral show, lower lid rounding, and ectropion. Patients with poor lid tone or laxity may benefit from supportive procedures such as the canthopexy or canthoplasty.

Viral gene transfer of the antiapoptotic factor Bcl-2 protects against chronic postischemic heart failure.

BACKGROUND: Apoptosis secondary to acute ischemia and chronic remodeling is implicated as a mediator of heart failure. This study was designed to assess the effect of in vivo viral gene transfer of the anti-apoptotic factor Bcl-2 to block apoptosis and preserve ventricular geometry and function. METHODS AND RESULTS: In a rabbit model of regional ischemia followed by reperfusion, an experimental group treated with adeno-Bcl-2 was compared with a control group receiving empty vector adeno-null. Function was assessed by echocardiography, and sonomicrometry of the border zone was compared with the normal left ventricle (LV). Animals were killed at 6 weeks, and an additional group was killed after 3 days to see whether virus administration conferred an immediate effect. Animals that were administered Bcl-2 maintained higher ejection fractions at 2, 4, and 6 weeks compared with controls. Sonomicrocrystals demonstrated greater protection of border zone fractional shortening at 6 weeks. The Bcl-2 group had superior preservation of LV geometry with less ventricular dilatation and wall thinning. There was also reduced apoptosis compared with the controls. Finally, in the animals killed at 3 days, no functional difference was observed between the Bcl-2 and control groups. CONCLUSIONS: Gene transfer of Bcl-2 preserves LV function after ischemia despite the absence of an observed acute protective effect. The benefit at 6 weeks is postulated to result from a Bcl-2-mediated reduction in apoptosis and ventricular remodeling. Adeno-Bcl-2 administration offers a potential strategy to protect the heart from late postischemic heart failure.

Prenatal drug exposure and peer victimization in early adolescence: testing childhood anxiety/depression and aggression as possible mediators.

OBJECTIVE: Children who are prenatally exposed to drugs may be at risk for emotion dysregulation, including childhood anxiety/depression and aggression, potentially increasing their risk for peer victimization. The objectives of this study were to investigate how prenatal drug exposure relates to adolescent peer victimization and the mediating effects of childhood anxiety/depression and aggression. METHODS: Seventy-six prenatally drug exposed (PDE) and 38 nonexposed (NE) adolescent-caregiver dyads followed since birth and middle childhood, respectively, participated in an evaluation during adolescence. In middle childhood, caregivers reported on their child's anxiety/depression and aggression, and children reported on violence exposure. In adolescence, caregivers and adolescents responded to a parallel single-item measure of peer victimization. Analyses were conducted using multivariate linear and logistic regression models, adjusting for covariates, including violence exposure. RESULTS: One-third (33.3%, n = 35) of the sample endorsed peer victimization: 40.8% PDE and 17.6% NE, p = .01. In middle childhood, PDE youth had more aggressive behaviors (11.92 vs 7.45, p < .01) and anxiety/depression symptoms (3.43 vs 1.76, p < .01) than NE youth. Anxious/depressed behavior during childhood mediated the association between prenatal drug exposure and adolescent peer victimization. Aggression was not a significant mediator. CONCLUSIONS: The consequences of prenatal drug exposure extend into adolescence. Prenatal drug exposure may interfere with emotion regulation, resulting in anxious/depressed behavior during childhood and significantly increasing the risk for peer victimization during adolescence, even in the presence of violence exposure. Strategies to reduce anxious/depressed behavior among children with a history of prenatal drug exposure may reduce adolescent peer victimization.

Late venous thrombosis in free flap breast reconstruction: strategies for salvage after this real entity.

BACKGROUND: Microvascular free-tissue transfer is a reliable pillar of reconstructive surgery, yet pedicle thrombosis remains a challenge. The authors examined the phenomenon of late venous thrombosis (after postoperative day 3) and detail a method of flap salvage that can be utilized following this microvascular insult. METHODS: A retrospective review was performed of all free flap breast reconstructions performed by the senior author (J.M.S.) from 1991 to 2008, utilizing a prospectively maintained database. All cases of postoperative thromboses were evaluated. Late venous thrombosis was defined as a thrombosis occurring after postoperative day 3. RESULTS: A total of 1277 free flap breast reconstructions were performed over the 17-year period. Nineteen flaps had venous thromboses (1.5 percent), and 10 of these occurred after postoperative day 3 (average, 5.67 days; range, 4 to 12 days). Operative exploration was employed in seven of 10 cases, with the remaining patients presenting too late or too advanced for operative intervention. Sixty percent of flaps were fully salvaged, and two were partially saved, with some subsequent volume loss. Earlier late venous thrombosis presentation led to better outcomes overall. CONCLUSIONS: Late venous thrombosis is a rare phenomenon that, although occurring late in the postoperative course, is an acute event. Early recognition and urgent treatment are key to flap salvage, with clinical judgment dictating the treatment choice. In the absence of extenuating circumstances, the authors prefer urgent exploration in the operating room, as flap survival following late venous thrombosis is a race against time but with a high probability of salvage if the proper steps are taken. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

The feasibility of using natural language processing to extract clinical information from breast pathology reports.

OBJECTIVE: The opportunity to integrate clinical decision support systems into clinical practice is limited due to the lack of structured, machine readable data in the current format of the electronic health record. Natural language processing has been designed to convert free text into machine readable data. The aim of the current study was to ascertain the feasibility of using natural language processing to extract clinical information from >76,000 breast pathology reports. APPROACH AND PROCEDURE: Breast pathology reports from three institutions were analyzed using natural language processing software (Clearforest, Waltham, MA) to extract information on a variety of pathologic diagnoses of interest. Data tables were created from the extracted information according to date of surgery, side of surgery, and medical record number. The variety of ways in which each diagnosis could be represented was recorded, as a means of demonstrating the complexity of machine interpretation of free text. RESULTS: There was widespread variation in how pathologists reported common pathologic diagnoses. We report, for example, 124 ways of saying invasive ductal carcinoma and 95 ways of saying invasive lobular carcinoma. There were >4000 ways of saying invasive ductal carcinoma was not present. Natural language processor sensitivity and specificity were 99.1% and 96.5% when compared to expert human coders. CONCLUSION: We have demonstrated how a large body of free text medical information such as seen in breast pathology reports, can be converted to a machine readable format using natural language processing, and described the inherent complexities of the task.

A specific vascular endothelial growth factor receptor tyrosine kinase inhibitor enhances the antiproliferative effect of trastuzumab in human epidermal growth factor receptor 2 overexpressing breast cancer cell lines.

BACKGROUND: Trastuzumab has been found to have potent antiproliferative effects in human epidermal growth factor receptor 2 (HER-2)-overexpressing human breast tumors. Inhibition of vascular endothelial growth factor receptor (VEGFR), a protein often overexpressed in breast carcinoma, has been shown to induce apoptosis. METHODS: Breast carcinoma cell lines were cultured with increasing doses of trastuzumab and/or a VEGFR tyrosine kinase inhibitor (TKI). Growth inhibition and apoptosis were assessed after 5 days and 48 hours of treatment, respectively. Combination index values were calculated to determine the effectiveness of this drug combination. RESULTS: A dose-dependent growth inhibition was shown in all cell lines tested with the VEGFR TKI, whereas trastuzumab was effective only in the HER-2-positive cells. A synergistic interaction was shown in the HER-2-overexpressing cell lines, accompanied by an increase in apoptosis. CONCLUSIONS: The combination of trastuzumab and a VEGFR TKI may be of therapeutic value in select breast cancer patients.

The use of polyacrylamide gel in soft-tissue augmentation: an experimental assessment.

BACKGROUND: An increasing number of soft-tissue filler substances that lack experimental and clinical data have been introduced into plastic surgery practice outside the United States. One of these substances is polyacrylamide gel. It contains 2.5% polyacrylamide and 97.5% water. It is homogenous and stable, and has optimum viscosity and elasticity. METHODS: One milliliter of polyacrylamide gel was injected into the subcutaneous layer of the right ear in 28 rabbits. The rabbits were divided into two groups, according to when the material was harvested and evaluated. Material was harvested at 4 months in 15 rabbits and 7 months in 13 rabbits. Each group underwent volumetric ultrasound evaluation, magnetic resonance imaging, and histological evaluation with hematoxylin and eosin and CD68 staining. RESULTS: Results were easily observed because of the superficial position of the injected material. There were no systemic or local complications. The samples harvested showed a clear and jelly-like consistency similar to that of the initially injected material. The volume was constant after 6 weeks, after an initial period of acute stretching. Ultrasound volumetric analysis was also constant in all groups. At 7 months, a stable volume of 1.0 +/- 0.2 ml was observed. Magnetic resonance imaging scanning showed that the material was stable and that there was no inflammatory reaction. Histological analysis revealed a minimal foreign-body reaction, and the injected material was occasionally surrounded by a thin collagen membrane. The material remained in place. CONCLUSIONS: Polyacrylamide gel has a long-lasting effect, with minimal volume variation. It remains soft to the touch and in place.