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A randomized controlled trial of mindfulness-based stress reduction for women with early-stage breast cancer receiving radiotherapy

Tue, 05/12/2015 - 10:32pm

PURPOSE: To testthe relative effectiveness of a mindfulness-based stress reduction program (MBSR) compared with a nutrition education intervention (NEP) and usual care (UC) in women with newly diagnosed early-stage breast cancer (BrCA)undergoing radiotherapy.

METHODS: Datawere available from a randomized controlled trialof 172 women, 20 to 65 years old, with stage I or II BrCA. Data from women completing the 8-week MBSR program plus 3 additional sessions focuses on special needs associated with BrCA were compared to women receiving attention control NEP and UC. Follow-up was performed at 3 post-intervention points: 4 months, and 1 and 2 years. Standardized, validated self-administered questionnaires were used to assess psychosocial variables. Descriptive analyses compared women by randomization assignment. Regression analyses, incorporating both intention-to-treat and post hoc multivariable approaches, were used to control for potential confounding variables.

RESULTS: A subset of 120 women underwent radiotherapy; 77 completed treatment prior to the study, and 40 had radiotherapy during the MBSR intervention. Women who actively received radiotherapy (art) while participating in the MBSR intervention (MBSR-art) experienced a significant (P < .05) improvement in 16 psychosocial variables compared with the NEP-art, UC-art, or both at 4 months. These included health-related, BrCA-specific quality of life and psychosocial coping, which were the primary outcomes, and secondary measures, including meaningfulness, helplessness, cognitive avoidance, depression, paranoid ideation, hostility, anxiety, global severity, anxious preoccupation, and emotional control.

CONCLUSIONS: MBSR appears to facilitate psychosocial adjustment in BrCA patients receiving radiotherapy, suggesting applicability for MBSR as adjunctive therapy in oncological practice.

Sonic hedgehog mediates the proliferation and recruitment of transformed mesenchymal stem cells to the stomach

Tue, 05/12/2015 - 10:32pm

Studies using Helicobacter-infected mice show that bone marrow-derived mesenchymal stem cells (MSCs) can repopulate the gastric epithelium and promote gastric cancer progression. Within the tumor microenvironment of the stomach, pro-inflammatory cytokine interferon-gamma (IFNgamma) and Sonic hedgehog (Shh) are elevated. IFNgamma is implicated in tumor proliferation via activation of the Shh signaling pathway in various tissues but whether a similar mechanism exists in the stomach is unknown. We tested the hypothesis that IFNgamma drives MSC proliferation and recruitment, a response mediated by Shh signaling. The current study uses transplantation of an in vitro transformed mesenchymal stem cell line (stMSC(vect)), that over-expresses hedgehog signaling, in comparison to non-transformed wild-type MSCs (wtMSCs), wtMSCs transfected to over-express Shh (wtMSC(Shh)), and stMSCs transduced with lentiviral constructs containing shRNA targeting the Shh gene (stMSC(ShhKO)). The effect of IFNgamma on MSC proliferation was assessed by cell cycle analysis in vitro using cells treated with recombinant IFNgamma (rmIFNgamma) alone, or in combination with anti-Shh 5E1 antibody, and in vivo using mice transplanted with MSCs treated with PBS or rmIFNgamma. In vitro, IFNgamma significantly increased MSC proliferation, a response mediated by Shh that was blocked by 5E1 antibody. The MSC population collected from bone marrow of PBS- or IFNgamma-treated mice showed that IFNgamma significantly increased the percentage of all MSC cell lines in S phase, with the exception of the stMSCs(ShhKO) cells. While the MSC cell lines with intact Shh expression were recruited to the gastric mucosa in response to IFNgamma, stMSCs(ShhKO) were not. Hedgehog signaling is required for MSC proliferation and recruitment to the stomach in response to IFNgamma.

Quantification of nanosized extracellular membrane vesicles with scanning ion occlusion sensing

Tue, 05/12/2015 - 10:32pm

BACKGROUND: Cells secrete different types of membrane vesicles (MVs), which may act as important entities in normal human physiology and in various pathological processes. The established methods for quantification of MVs require purification or preanalytical handling of samples with labeling moieties. AIM: The authors' aim was to develop a method for high-throughput, labeling-free quantification of nonpurified MVs.

MATERIALS and METHODS: Scanning ion occlusion sensing technology, which relies on the detection of particles upon their movement through a nanopore, was investigated for the ability to quantify nanosized MVs ( < 400 nm) in bodily fluids and cell culture supernatants.

RESULTS: Scanning ion occlusion sensing allowed for rapid and easy measurement of the concentration of MVs in all biological fluids tested.

CONCLUSION: Scanning ion occlusion sensing technology enables the quantification of MVs in biological samples without the requirement of MV isolation and/or labeling. This offers a highly valuable addition to the currently used repertoire of MV quantification methods.

Optimal selection of patients for elective abdominal aortic aneurysm repair based on life expectancy

Tue, 05/12/2015 - 10:32pm

OBJECTIVE: Elective abdominal aortic aneurysm (AAA) repair is beneficial when rupture is likely during a patient's expected lifetime. The purpose of this study was to identify predictors of long-term mortality after elective AAA repair for moderately sized AAAs ( < 6.5-cm diameter) to identify patients unlikely to benefit from surgery.

METHODS: We analyzed 2367 elective infrarenal AAA ( < 6.5 cm) repairs across 21 centers in New England from 2003 to 2011. Our main outcome measure was 5-year life-table survival. Cox proportional hazards analysis was used to describe associations between patient characteristics and 5-year survival.

RESULTS: During the study period, 1653 endovascular AAA repairs and 714 open AAA repairs were performed. Overall, 5-year survival rates were similar by procedure type (75% endovascular repair, 80% open repair; P = .14). Advanced age greater than or equal to 75 years (hazard ratio [HR], 2.0; P < .01) and age > 80 years (HR, 2.6; P < .01), coronary artery disease (HR, 1.4; P < .04), unstable angina or recent myocardial infarction (HR, 4.6; P < .01), oxygen-dependent chronic obstructive pulmonary disease (HR, 2.7; P < .01), and estimated glomerular filtration rate < 30 mL/min/1.73 m(2) (HR, 2.8; P < .01) were associated with poor survival. Aspirin (HR, 0.8; P < .03) and statin (HR, 0.7; P < .01) use were associated with improved survival. We used these risk factors to develop risk strata for low-risk, medium-risk, and high-risk groups with survival, respectively, of 85%, 69%, and 43% at 5 years (P < .001).

CONCLUSIONS: More than 75% of patients with moderately sized AAAs who underwent elective repair in our region survived 5 years, but 4% were at high risk for 5-year mortality. Patients with multiple risk factors, especially age > 80 years, unstable angina, oxygen-dependent chronic obstructive pulmonary disease, and estimated glomerular filtration rate < 30 mL/min/1.73 m(2), are unlikely to achieve sufficient long-term survival to benefit from surgery, unless their AAA rupture risk is very high.

Expectant management of cystotomy at the time of midurethral sling placement: a retrospective case series

Tue, 05/12/2015 - 10:32pm

INTRODUCTION AND HYPOTHESIS: Cystotomy is one of the most common complications of retropubic midurethral sling placement. Some centers manage cystotomy with prolonged catheter drainage, and there are few published studies evaluating this practice. The purpose of this study is to review postoperative outcomes of patients who experienced cystotomy at the time of sling placement and did not undergo prolonged catheter drainage.

METHODS: This is a retrospective review of all patients undergoing midurethral sling placement complicated by a cystotomy at the University of Rochester between 2004 and 2009. Outpatient and inpatient records were reviewed and data collected include demographics, intraoperative details, voiding trial results, postoperative complications, and voiding function. Descriptive statistics were performed.

RESULTS: Between 2004 and 2009, 30 subjects experienced a cystotomy of the 374 subjects that had a midurethral sling placed, all by a suprapubic approach. There were 25 patients who underwent a voiding trial on the day of surgery and 20 (80 %) were discharged home without prolonged drainage. Five subjects (20 %) had urinary retention and were discharged with an indwelling catheter. All five successfully voided within 4 days of discharge. No subject required subsequent catheterization for any reason and at the 6-week postoperative evaluation all subjects denied voiding dysfunction or irritative bladder symptoms. No subject required additional intervention and postoperative complications were rare.

CONCLUSIONS: In this study, the majority of subjects experiencing a cystotomy during midurethral sling placement were successfully discharged home the day of surgery without catheter drainage. The results suggest that prolonged catheter drainage after a cystotomy during midurethral sling placement may be unnecessary.

Regional infant brain development: an MRI-based morphometric analysis in 3 to 13 month olds

Tue, 05/12/2015 - 10:32pm

Elucidation of infant brain development is a critically important goal given the enduring impact of these early processes on various domains including later cognition and language. Although infants' whole-brain growth rates have long been available, regional growth rates have not been reported systematically. Accordingly, relatively less is known about the dynamics and organization of typically developing infant brains. Here we report global and regional volumetric growth of cerebrum, cerebellum, and brainstem with gender dimorphism, in 33 cross-sectional scans, over 3 to 13 months, using T1-weighted 3-dimensional spoiled gradient echo images and detailed semi-automated brain segmentation. Except for the midbrain and lateral ventricles, all absolute volumes of brain regions showed significant growth, with 6 different patterns of volumetric change. When normalized to the whole brain, the regional increase was characterized by 5 differential patterns. The putamen, cerebellar hemispheres, and total cerebellum were the only regions that showed positive growth in the normalized brain. Our results show region-specific patterns of volumetric change and contribute to the systematic understanding of infant brain development. This study greatly expands our knowledge of normal development and in future may provide a basis for identifying early deviation above and beyond normative variation that might signal higher risk for neurological disorders.

Temporal induction of immunoregulatory processes coincides with age-dependent resistance to viral-induced type 1 diabetes

Tue, 05/12/2015 - 10:32pm

The dilute plasma cytokine milieu associated with type 1 diabetes (T1D), while difficult to measure directly, is sufficient to drive transcription in a bioassay that uses healthy leukocytes as reporters. Previously, we reported disease-associated, partially IL-1 dependent, transcriptional signatures in both T1D patients and the BioBreeding (BB) rat model. Here, we examine temporal signatures in congenic BBDR.lyp/lyp rats that develop spontaneous T1D, and BBDR rats where T1D progresses only after immunological perturbation in young animals. After weaning, the BBDR temporal signature showed early coincident induction of transcription related to innate inflammation as well as IL-10- and TGF-beta-mediated regulation. BBDR plasma cytokine levels mirrored the signatures showing early inflammation, followed by induction of a regulated state that correlated with failure of virus to induce T1D in older rats. In contrast, the BBDR.lyp/lyp temporal signature exhibited asynchronous dynamics, with delayed induction of inflammatory transcription and later, weaker induction of regulatory transcription, consistent with their deficiency in regulatory T cells. Through longitudinal analyses of plasma-induced signatures in BB rats and a human T1D progressor, we have identified changes in immunoregulatory processes that attenuate a preexisting innate inflammatory state in BBDR rats, suggesting a mechanism underlying the decline in T1D susceptibility with age.