Publications

UNLABELLED

Study purposes were to determine the prevalence of persistent pain in the breast; characterize distinct persistent pain classes using growth mixture modeling; and evaluate for differences among these pain classes in demographic, preoperative, intraoperative, and postoperative characteristics. In addition, differences in the severity of common symptoms and quality of life outcomes measured prior to surgery, among the pain classes, were evaluated. Patients (n = 398) were recruited prior to surgery and followed for 6 months. Using growth mixture modeling, patients were classified into no (31.7%), mild (43.4%), moderate (13.3%), and severe (11.6%) pain groups based on ratings of worst breast pain. Differences in a number of demographic, preoperative, intraoperative, and postoperative characteristics differentiated among the pain classes. In addition, patients in the moderate and severe pain classes reported higher preoperative levels of depression, anxiety, and sleep disturbance than the no pain class. Findings suggest that approximately 25% of women experience significant and persistent levels of breast pain in the first 6 months following breast cancer surgery.

PERSPECTIVE

Persistent pain is a significant problem for 25% of women following surgery for breast cancer. Severe breast pain is associated with clinically meaningful decrements in functional status and quality of life.

BACKGROUND

As the population ages, an increasing number of elderly persons will undergo surgery for rectal cancer. The use of sphincter-sparing surgery in frail older adults is controversial.

OBJECTIVE

The aim of this study was to examine mortality and bowel function after proctectomy in nursing home residents.

DESIGN

This is a retrospective cohort study.

SETTING

This investigation was conducted in nursing homes in the United States contracted with the Center for Medicare and Medicaid Services.

PATIENTS

Nursing home residents age 65 and older undergoing proctectomy for rectal cancer (2000-2005) were included.

MAIN OUTCOME MEASURES

The primary outcomes measured were fecal incontinence and the 1-year mortality rate.

RESULTS

Operative mortality was 18% after proctectomy with permanent colostomy and 13% after sphincter-sparing proctectomy (adjusted relative risk, 1.25 (95% CI 0.90-1.73), p = 0.188). One-year mortality was high: 40% after sphincter-sparing proctectomy and 51% after proctectomy with permanent colostomy (adjusted hazard ratio 1.32 (95% CI 1.09-1.60), p = 0.004). After sphincter-sparing proctectomy, 37% of residents were incontinent of feces. Residents with the poorest functional status (Minimum Data Set-Activities of Daily Living quartile 4) were significantly more likely to be incontinent of feces than residents with the best functional status (Minimum Data Set-Activities of Daily Living quartile 1) (76% vs 13%, adjusted relative risk 3.28 (95% CI 1.74- 6.18), p= 0.0002). Fecal incontinence was also associated with dementia (adjusted relative risk 1.55 (95% CI 1.15-2.09), p = 0.004) and renal failure (adjusted relative risk 1.93 (95% CI 1.10-3.38), p = 0.022).

LIMITATIONS

Measures of fecal incontinence in nursing home registries are not as well studied as those commonly used in clinical practice.

CONCLUSIONS

Sphincter-sparing proctectomy in nursing home residents is frequently associated with postoperative fecal incontinence and should be considered only for continent patients with good functional status.

INTRODUCTION

Prostate cancer is the second leading cause of cancer death in men in the United States. The disease is driven by androgen receptor (AR) signaling, and the majority of patients initially respond to androgen deprivation therapies. The lethal form of this disease occurs when metastatic lesions progress in the setting of low testosterone levels, in what is conventionally referred to as castration-resistant prostate cancer (CRPC). Recent insights suggest that CRPC continues to rely on an active AR pathway for cell survival and growth.

AREAS COVERED

This review summarizes the rationale, mechanism of action and relevant clinical data of abiraterone acetate , an oral androgen biosynthesis inhibitor, in the management of CRPC.

EXPERT OPINION

Abiraterone acetate is an oral, well-tolerated drug that targets a newly elucidated paradigm of continued AR activation in CRPC. Abiraterone acetate is approved in CRPC patients who have received docetaxel, and recent data suggest that the drug will also be effective and utilized in the pre-chemotherapy setting. Significant areas of scientific investigation remain in the optimization and further understanding of the therapy.

The accessory Sec system of Streptococcus gordonii is comprised of SecY2, SecA2, and five proteins (Asp1 through -5) that are required for the export of a serine-rich glycoprotein, GspB. We have previously shown that a number of the Asps interact with GspB, SecA2, or each other. To further define the roles of these Asps in export, we examined their subcellular localization in S. gordonii and in Escherichia coli expressing the streptococcal accessory Sec system. In particular, we assessed how the locations of these accessory Sec proteins were altered by the presence of other components. Using fluorescence microscopy, we found in E. coli that SecA2 localized within multiple foci at the cell membrane, regardless of whether other accessory Sec proteins were expressed. Asp2 alone localized to the cell poles but formed a similar punctate pattern at the membrane when SecA2 was present. Asp1 and Asp3 localized diffusely in the cytosol when expressed alone or with SecA2. However, these proteins redistributed to the membrane in a punctate arrangement when all of the accessory Sec components were present. Cell fractionation studies with S. gordonii further corroborated these microscopy results. Collectively, these findings indicate that Asp1 to -3 are not integral membrane proteins that form structural parts of the translocation channel. Instead, SecA2 serves as a docking site for Asp2, which in turn attracts a complex of Asp1 and Asp3 to the membrane. These protein interactions may be important for the trafficking of GspB to the cell membrane and its subsequent translocation.

Profiling miRNA expression in cells that directly contribute to human disease pathogenesis is likely to aid the discovery of novel drug targets and biomarkers. However, tissue heterogeneity and the limited amount of human diseased tissue available for research purposes present fundamental difficulties that often constrain the scope and potential of such studies. We established a flow cytometry-based method for isolating pure populations of pathogenic T cells from bronchial biopsy samples of asthma patients, and optimized a high-throughput nano-scale qRT-PCR method capable of accurately measuring 96 miRNAs in as little as 100 cells. Comparison of circulating and airway T cells from healthy and asthmatic subjects revealed asthma-associated and tissue-specific miRNA expression patterns. These results establish the feasibility and utility of investigating miRNA expression in small populations of cells involved in asthma pathogenesis, and set a precedent for application of our nano-scale approach in other human diseases. The microarray data from this study (Figure 7) has been submitted to the NCBI Gene Expression Omnibus (GEO; http://ncbi.nlm.nih.gov/geo) under accession no. GSE31030.

We previously showed that reduced infectivity of HIV with incompletely processed capsid-spacer protein 1 (CA-SP1) is rescued by cellular activation or increased expression of HSP90AB1, a member of the cytosolic heat shock protein 90 family. Here we show that HSP90AB1 is present in HIV virions and that HSP90AB1, but not nonfunctional mutated HSP90AB1(E42A+D88A), restores infectivity to HIV with mutations in CA that alter core stability. Further, the CA mutants were hypersensitive to pharmacological inhibition of HSP90AB1. In agreement with Roesch et al. (2012), we found that culturing HIV at 39.5°C enhanced viral infectivity up to 30-fold in human peripheral blood mononuclear cells (p=0.002) and rescued CA-mutant infectivity in nonactivated cells, concurrent with elevated expression of HSP90AB1 during hyperthermia. In sum, the transdominant effect of HSP90AB1 on CA-mutant HIV infectivity suggests a potential role for this class of cellular chaperones in HIV core stability and uncoating.