Docetaxel and bortezomib downregulate <Emphasis Type="Italic">Bcl-2</Emphasis> and sensitize PC-3-<Emphasis Type="Italic">Bcl-2</Emphasis> expressing prostate cancer cells to irradiation

Background  Currently, docetaxel is used to treat hormone-refractory metastatic prostate cancer. Docetaxel not only inhibits microtubule formation but can also downregulate expression of Bcl-2, a known antiapoptotic oncogene. Furthermore, the 26S proteasome inhibitor bortezomib can downregulate Bcl-2 expression. Previously, we demonstrated that overexpression of Bcl-2 renders cells resistant to radiation therapy. In this study, we investigated whether treating human prostate cancer cells with docetaxel, bortezomib, or both could modulate Bcl-2 expression and whether such modulation could render Bcl-2-overexpressing cells more susceptible to radiation. Methods  PC-3-Bcl-2 and PC-3-Neo human prostate cancer cells treated with docetaxel and/or bortezomib in addition to irradiation were analyzed in vitro for proliferation, clonogenic survival, cell cycle phase distribution, and expression of Bcl-2 and Bcl-xL proteins. Results  Docetaxel and bortezomib alone had significant cytotoxic effects. In addition, docetaxel, bortezomib, or radiation resulted in a G2M phase arrest in PC-3-Bcl-2, whereas only docetaxel or radiation did so in PC-3-Neo cells. Both cell lines were more sensitized to radiation’s killing effects when treated with the combination of docetaxel and bortezomib than when treated with either agent alone. Furthermore, docetaxel and bortezomib-treated cells exhibited marked changes in the expression of Bcl-2 and Bcl-xL. Conclusions  This is the first study to demonstrate that docetaxel and bortezomib in combination can effectively sensitize Bcl-2-overexpressing human prostate cancer cells to radiation effects by modulating the expression of key members of the Bcl-2 family. Together, these findings warrant further evaluation of the combination of docetaxel and bortezomib in prostate cancer.     

Frequency of Occurrence of the Zygomandibularis Muscle: A Recently Described Structure

Many anatomical variations of the infratemporal area exist: muscle fusion, muscle belly separation, distinctly different origins, and both separate and aponeurotic insertions. This study is an attempt to find the frequency of occurrence of the zygomandibularis muscle, a recently described human structure. The zygomandibularis muscle may occur unilaterally, bilaterally, or may be absent. In this study, 23 female Caucasian cadavers and 27 male Caucasian cadavers were evaluated; the zygomandibularis muscle was found in 42% of the population of 50 cadavers.     

Health Literacy among Medically Underserved: The Role of Demographic Factors,Social Influence,and Religious Beliefs

The current study examined the sociodemographic and psychosocial variables that predicted being at risk for low health literacy among a population of racially and ethnically diverse patients accessing primary care services at community-based clinics. Participants (N = 416) were aged 50–75 years, currently not up-to-date with colorectal cancer (CRC) screening, at average CRC risk, and enrolled in a randomized controlled trial (RCT) aimed at promoting CRC screening. Participants completed a baseline interview that assessed health literacy as measured by Rapid Estimate of Adult Literacy in Medicine-Revised, sociodemographic factors, and psychosocial variables (e.g., health beliefs) prior to randomization and receipt of an intervention. Thirty-six percent of the participants were found to be at risk for low health literacy. Sociodemographic and psychosocial variables were assessed as predictors of being at risk for low health literacy using logistic regression. In the final model, predictors were male gender, being from a racial/ethnic minority group, being unable to work, having higher social influence scores, and having higher religious belief scores. These findings suggest several patient characteristics that may be associated with low health literacy, and highlight the importance of supporting all patients through simplified and clear communications and information to improve understanding of CRC screening information.     

Innate Immunity to Aspergillus Species

Summary: All humans are continuously exposed to inhaled Aspergillus conidia, yet healthy hosts clear the organism without developing disease and without the development of antibody- or cell-mediated acquired immunity to this organism. This suggests that for most healthy humans, innate immunity is sufficient to clear the organism. A failure of these defenses results in a uniquely diverse set of illnesses caused by Aspergillus species, which includes diseases caused by the colonization of the respiratory tract, invasive infection, and hypersensitivity. A key concept in immune responses to Aspergillus species is that the susceptibilities of the host determine the morphological form, antigenic structure, and physical location of the fungus. In this review, we summarize the current literature on the multiple layers of innate defenses against Aspergillus species that dictate the outcome of this host-microbe interaction.     

Selection of Deep Brain Stimulation Candidates in Private Neurology Practices: Referral May Be Simpler than a Computerized Triage System

Objective: The objective of this study is to compare a computerized deep brain stimulation (DBS) screening module (Comparing Private Practice vs. Academic Centers in Selection of DBS Candidates [COMPRESS], NeuroTrax Corp., Bellaire, TX, USA) with traditional triage by a movement disorders specialized neurologist as the gold standard. Methods: The COMPRESS consists of a combination of the Florida Surgical Questionnaire for Parkinson disease (FLASQ‐PD), a cognitive assessment battery provided by MindStreams® (NeuroTrax Corp.), and the Geriatric Depression Scale and the Zung Anxiety Self‐Assessment Scale. COMPRESS resulted in the classification of patients into three categories: “optimal candidate,”“probable candidate,” and “not a good candidate.” Similar categorical ratings made by a referring private practice neurologist and by a trained movement disorders specialist were compared with the ratings generated by COMPRESS. Results: A total of 19 subjects with Parkinson's disease were enrolled from five private neurological practices. The clinical impressions of the private practice neurologist vs. those of the movement disorders specialist were in agreement approximately half the time (10/19 cases). The movement disorders specialist and COMPRESS agreed on 15/19 cases. A further comparison between outcomes from the entire COMPRESS module and the FLASQ‐PD questionnaire by itself resulted in high agreement (18/19 cases in agreement). Conclusions: The COMPRESS agreed with an in‐person evaluation by a movement disorders neurologist approximately 80% of the time. The computerized COMPRESS did not provide any screening advantage over the short FLASQ‐PD paper questionnaire. Larger studies will be needed to assess the utility and cost effectiveness of this computerized triage method for DBS.