MicroRNA-214 targets PTK6 to inhibit tumorigenic potential and increase drug sensitivity of prostate cancer cells.

Prostate cancer is the most commonly diagnosed cancer in men with African American men disproportionally suffering from the burden of this disease. Biomarkers that could discriminate indolent from aggressive and drug resistance disease are lacking. MicroRNAs are small non-coding RNAs that affect numerous physiological and pathological processes, including cancer development and have been suggested as biomarkers and therapeutic targets. In the present study, we investigated the role of miR-214 on prostate cancer cell survival/migration/invasion, cell cycle regulation, and apoptosis. miR-214 was differentially expressed between Caucasian and African American prostate cancer cells. Importantly, miR-214 overexpression in prostate cancer cells induced apoptosis, inhibiting cell proliferation and colony forming ability. miR-214 expression in prostate cancer cells also inhibited cell migration and 3D spheroid invasion. Mechanistically, miR-214 inhibited prostate cancer cell proliferation by targeting protein tyrosine kinase 6 (PTK6). Restoration of PTK6 expression attenuated the inhibitory effect of miR-214 on cell proliferation. Moreover, simultaneous inhibition of PTK6 by ibrutinib and miR-214 significantly reduced cell proliferation/survival. Our data indicates that miR-214 could act as a tumor suppressor in prostate cancer and could potentially be utilized as a biomarker and therapeutic target

A Sweeping Jet Application on a High Reynolds Number Semispan Supercritical Wing Configuration

The FAST-MAC circulation control model was modified to test an array of unsteady sweeping-jet actuators at realistic flight Reynolds numbers in the National Transonic Facility at the NASA Langley Research Center. Two types of sweeping jet actuators were fabricated using rapid prototype techniques, and directed over a 15% chord simple-hinged flap. The model was configured for low-speed high-lift testing with flap deflections of 30 and 60, and a transonic cruise configuration with a 0 flap deflection. For the 30 flap high-lift configuration, the sweeping jets achieved comparable lift performance in the separation control regime, while reducing the mass flow by 54% as compared to steady blowing. However, the sweeping jets were not effective for the 60 flap. For the transonic cruise configuration, the sweeping jets reduced the drag by 3.3% at an off design condition. The drag reduction for the design lift coefficient for the sweeping jets provided only half the drag reduction shown for the steady blowing case (6.5%), but accomplished this with a 74% reduction in mass flow

Quality Measures for Hospice and Palliative Care: Piloting the PEACE Measures

Background: The Carolinas Center for Medical Excellence launched the PEACE project in 2006, under contract with the Centers for Medicare & Medicaid Services (CMS), to identify, develop, and pilot test quality measures for hospice and palliative care programs

Micro-Ethical Decision Making Among Baccalaureate Nursing Students: A Qualitative Investigation

Nursing students frequently encounter micro-ethical nursing practice problems during their clinical experience. The purpose of this study was to understand the lived experiences of senior-level baccalaureate students faced with making micro-ethical clinical decisions in practice settings. A descriptive qualitative design was used, and five central themes emerged. A dominant finding was the experience of unapplied and forgotten ethics education revealing a mismatch between what faculty perceived was taught and students’ experiences of that education. When faced with micro-ethical decisions, participants trusted and deferred to staff nurse recommendations, even if the advice contradicted best-practice standards. Contextual naivete was brought out of concealment, contributing to the experience of moral disequilibrium (i.e., students felt conflicted about what they learned in school as best practice and what they observed being role modeled in the clinical environment). This study resulted in theory-guided implications for nursing education and recommendations for future study

Use of Electronic Documentation for Quality Improvement in Hospice

Little evidence exists on the use of electronic documentation in hospice and its relationship to quality improvement practices. The purposes of this study were to: (1) estimate the prevalence of electronic documentation use in hospice; (2) identify organizational characteristics associated with use of electronic documentation; and (3) determine whether quality measurement practices differed based on documentation format (electronic vs. nonelectronic). Surveys concerning the use of electronic documentation for quality improvement practices and the monitoring of quality-related care and outcomes were collected from 653 hospices. Users of electronic documentation were able to monitor a wider range of quality-related data than users of nonelectronic documentation. Quality components such as advanced care planning, cultural needs, experience during care of the actively dying, and the number/types of care being delivered were more likely to be documented by users of electronic documentation. Use of electronic documentation may help hospices to monitor quality and compliance

Differences in Assisted Living Staff Perceptions, Experiences, and Attitudes

Research within residential care/assisted living (RC/AL) settings has shown that the attitudes of personal care (PC) staff towards their organization, and its residents and families, can affect the quality of resident care. This paper describes the perceptions, experiences, and attitudes of PC staff and their supervisors and considers these data in the context of non-hierarchical staffing patterns – a philosophically expected, yet unproven tenet of RC/AL. Using data collected from 18 RC/AL communities, these analyses compared the characteristics, perceptions, experiences, and attitudes of PC staff (N=250) and supervisors (N=30). Compared to supervisors, PC staff reported greater burden, frustration, depersonalization, hassles, and feeling significantly more controlling of, and less in partnership with, families (p<0.05). Because the PC staff experience is crucial for their and resident outcomes, more work is needed to create a work environment where PC staff are less burdened and have better attitudes towards work and families

Dementia in Relation to Family Caregiver Involvement and Burden in Long-Term Care

To better understand the process and outcomes of family involvement for long-term care residents with varying stages of dementia, we analyzed family and staff data for 467 residents of 24 residential care/assisted living and nursing home settings. Adjusted analyses found that although the amount of family visitation did not significantly vary by resident cognitive status (15 versus 20 visits/month to persons with and without dementia, respectively), the nature of the visit did. Families of cognitively intact residents spent more time in activities related to social and community engagement, such as taking residents on trips and calling and writing letters (p<0.001), while families of more impaired residents spent more time on care-related activities, including tasks related to nutrition (p<0.027), mobility (p=0.001), and discussing care with staff (p=0.007), the latter of which was associated with greater burden (p<0.001). Staff identified similar patterns, but perceived less family involvement

In vitro assessment of antibiotic-resistance reversal of a methanol extract from Rosa canina L.

The crude methanol extract of Rosa canina (RC) fruit was tested against multidrug-resistant (MDR) bacterial strains, including methicillin-resistant Staphylococcus aureus SA1199B, EMRSA16 and XU212 harbouring NorA, PBP2a and TetK resistance mechanisms, respectively, as well as S. aureus ATCC25923, a standard antimicrobial susceptible laboratory strain. The inhibition of the conjugal transfer of plasmid PKM101 and TP114 by the RC extract was also evaluated. The RC extract demonstrated a mild to poor antibacterial activity against the panel of bacteria having MIC values ranging from 256 to >512 μg/mL but strongly potentiated tetracycline activity (64-fold) against XU212, a tetracycline-effluxing and resistant strain. Furthermore, the extract showed moderate capacity to inhibit the conjugal transfer of TP114 and PKM101; transfer frequencies were between 40% and 45%. Cytotoxicity analysis of the RC extract against HepG2 cells line showed the IC50 > 500 mg/L and, thus, was considered non-toxic towards human cells. Phytochemical characterisation of the extracts was performed by the assessment of total phenolic content (RC: 60.86 mg TAE/g) and HPLC fingerprints with five main peaks at 360 nm. The results from this study provide new mechanistic evidence justifying, at least in part, the traditional use of this extract. However, the inhibition of bacterial plasmid conjugation opens the possibility of combination therapies to overcome antibiotic resistance

PET Imaging of Soluble Yttrium-86-Labeled Carbon Nanotubes in Mice

The potential medical applications of nanomaterials are shaping the landscape of the nanobiotechnology field and driving it forward. A key factor in determining the suitability of these nanomaterials must be how they interface with biological systems. Single walled carbon nanotubes (CNT) are being investigated as platforms for the delivery of biological, radiological, and chemical payloads to target tissues. CNT are mechanically robust graphene cylinders comprised of sp(2)-bonded carbon atoms and possessing highly regular structures with defined periodicity. CNT exhibit unique mechanochemical properties that can be exploited for the development of novel drug delivery platforms. In order to evaluate the potential usefulness of this CNT scaffold, we undertook an imaging study to determine the tissue biodistribution and pharmacokinetics of prototypical DOTA-functionalized CNT labeled with yttrium-86 and indium-111 ((86)Y-CNT and (111)In-CNT, respectively) in a mouse model.The (86)Y-CNT construct was synthesized from amine-functionalized, water-soluble CNT by covalently attaching multiple copies of DOTA chelates and then radiolabeling with the positron-emitting metal-ion, yttrium-86. A gamma-emitting (111)In-CNT construct was similarly prepared and purified. The constructs were characterized spectroscopically, microscopically, and chromatographically. The whole-body distribution and clearance of yttrium-86 was characterized at 3 and 24 hours post-injection using positron emission tomography (PET). The yttrium-86 cleared the blood within 3 hours and distributed predominantly to the kidneys, liver, spleen and bone. Although the activity that accumulated in the kidney cleared with time, the whole-body clearance was slow. Differential uptake in these target tissues was observed following intravenous or intraperitoneal injection.The whole-body PET images indicated that the major sites of accumulation of activity resulting from the administration of (86)Y-CNT were the kidney, liver, spleen, and to a much less extent the bone. Blood clearance was rapid and could be beneficial in the use of short-lived radionuclides in diagnostic applications

FoxQ1 Overexpression Influences Poor Prognosis in Non-Small Cell Lung Cancer, Associates with the Phenomenon of EMT

BACKGROUND: We determined the expression of forkhead box Q1 (FoxQ1), E-cadherin (E-cad), Mucin 1 (MUC1), vimentin (VIM) and S100 calcium binding protein A4 (S100A4), all epithelial-mesenchymal transition (EMT) indicator proteins in non-small cell lung cancer (NSCLC) tissue samples. We also investigated the relationship between these five proteins expression and other clinicopathologic factors in NSCLC. Finally, we assessed the potential value of these markers as prognostic indicators of survival in NSCLC's patients. METHODS: Quantitative real-time PCR and immunohistochemistry were used to characterize the expression of the FoxQ1 mRNA and protein in NSCLC. Expression of transcripts and translated products for the other four EMT indicator proteins was assessed by immunohistochemistry in the same clinical NSCLC samples. RESULTS: FoxQ1 mRNA and protein were up-regulated in NSCLC compared with normal tissues (P = 0.015 and P<0.001, respectively). Expression of FoxQ1 in adenocarcinoma was higher than in squamous cell carcinoma (P = 0.005), and high expression of FoxQ1 correlated with loss of E-cad expression (P = 0.012), and anomalous positivity of VIM (P = 0.024) and S100A4 (P = 0.004). Additional survival analysis showed that high expression of FoxQ1 (P = 0.047) and E-cad (P = 0.021) were independent prognostic factors. CONCLUSION: FoxQ1 maybe plays a specific role in the EMT of NSCLC, and could be used as a prognostic factor for NSCLC