Future trends of nursing homes

Introduction: Nursing homes are a major part of the long term care sector and have provided services to elders and the disabled population for years. Regulation change and new demands from the market have forced nursing homes to adapt. The purpose of this literature review was to analyze current regulation in place in the nursing home sector and determine how nursing homes will adapt and continue to provide quality care to patients in the future. Methodology: The methodology of this research was a literature review. Overall, there were 4 databases used to gather research and 35 sources were used throughout the entirety of the paper. Results: Within our findings, there were several sources to support our claims. The research that was gathered was analyzed to determine the future use and demand of nursing homes. The results supported the original hypothesis that nursing homes will undergo changes in the inner culture and policy, but they will remain a staple in the long term care sector. Discussion/Conclusion: Nursing homes have been around for years and research has shown that adjustments are constantly being made in regulation and the individual culture or attractiveness of every nursing home. Through these changes, nursing homes will remain to attract large demand from the elderly population that is rapidly growing. Thus, nursing homes will continue to provide services to those in need

Formation of the oxide fume and aerosol dispersal from the oxidation of uranium metal at temperatures less than 1000 °C

Master of ScienceDepartment of Chemical EngineeringLarry E. EricksonThe reaction chemistry of uranium metal has been well documented for use in the development of nuclear fuels. The oxidation of uranium from the thermal stress of nearby combustion is different than that of a reactor environment due to the selectivity of the various competing reactions. This work extracts available information in literature and various experiments over the last 60 years to provide a critical look at the response of uranium metal to thermal stress. The oxide fume formed and the equilibrium phase shifts during the dispersal of the airborne particulate are of principal interest when determining potential consequences to the health and safety of the workers, members of the public, and the environment. The transport phenomena and reaction kinetics of the oxide fume are also discussed at various distances from the source material. Uranium is a versatile element that can form numerous compounds, of which the oxides are the forms that are most readily generated under thermal stress and also pose the largest health risk to human beings, primarily through inhalation. A general summary of uranium and the dry compounds (oxides and carbides) is provided discussing the different structures of each state. The reaction kinetics and selectivity as the oxidation progresses is discussed for typical uranium metal forms at temperatures above and below the ignition point. Characteristics of potential fires are qualified for determining thermal stress. The creation of the oxide fume is outlined followed by dispersal characteristics of the aerosol. These molecular processes are related to the release fractions of uranium under fire scenarios which are compared with available experimental data from the regulatory handbooks. A critical look at the conclusions of the handbook with recommendations for revising the existing guidelines and additional testing are made in the interest of ensuring that derived controls are appropriate to reduce the risk of accidents involving the oxidation of uranium metal

Integral Field Spectroscopy of Compact Elliptical Galaxies.

The rare compact elliptical galaxies (cEs) are thought to have been formed through atidal stripping process of a once much larger progenitor, as they do not adhere to themass-size, mass-metalicity and black hole-bulge mass scaling relations like their moremassive early-type cousins. By using observations taken with the FLAMES/GI-RAFFE integral field spectrographs of the European Southern Observatory’s (ESO)8.2m Very Large Telescope (VLT), we searched for evidence for the presence ofoverly massive SMBHs in our sample of cEs. The raw reduction was performed bythe workflow environment EsoReflex, Voronoi binned spectra from 4 target cEs wereobtained using the VorBin method. We performed a full spectrum fit of cE spectrausing the Penalized Pixel Fitting (pPXF) method, to extract resolved kinematics i.ethe Line Of Sight Velocity Distribution (LOSVD). Dynamical mass estimates of or-der 109Mwere obtained. Dynamical to stellar mass ratios for 3 cEs (NGC5846cE,NGC3268cE1 and AHcE0) reveal the likely presence of an overly massive SMBH,favoring the tidal stripping scenario for cE formatio

An unexpected twist to the activation of IKKβ:TAK1 primes IKKβ for activation by autophosphorylation

IKKβ {IκB [inhibitor of NF-κB (nuclear factor κB)] kinase β} is required to activate the transcription factor NF-κB, but how IKKβ itself is activated in vivo is still unclear. It was found to require phosphorylation by one or more ‘upstream’ protein kinases in some reports, but by autophosphorylation in others. In the present study, we resolve this contro-versy by demonstrating that the activation of IKKβ induced by IL-1 (interleukin-1) or TNF (tumour necrosis factor) in embryonic fibroblasts, or by ligands that activate Toll-like receptors in macrophages, requires two distinct phosphorylation events: first, the TAK1 [TGFβ (transforming growth factor β)-activated kinase-1]-catalysed phosphorylation of Ser(177) and, secondly, the IKKβ-catalysed autophosphorylation of Ser(181). The phosphorylation of Ser(177) by TAK1 is a priming event required for the subsequent autophosphorylation of Ser(181), which enables IKKβ to phosphorylate exogenous substrates. We also provide genetic evidence which indicates that the IL-1-stimulated, LUBAC (linear ubiquitin chain assembly complex)-catalysed formation of linear ubiquitin chains and their interaction with the NEMO (NF-κB essential modulator) component of the canonical IKK complex permits the TAK1-catalysed priming phosphorylation of IKKβ at Ser(177) and IKKα at Ser(176). These findings may be of general significance for the activation of other protein kinases

The NEDD8 E3 ligase DCNL5 is phosphorylated by IKK alpha during Toll-like receptor activation

The activity of Cullin-RING ubiquitin E3 ligases (CRL) is regulated by NEDD8 modification. DCN-like proteins promote Cullin neddylation as scaffold-like E3s. One DCNL, DCNL5, is highly expressed in immune tissue. Here, we provide evidence that DCNL5 may be involved in innate immunity, as it is a direct substrate of the kinase IKKα during immune signalling. We find that upon activation of Toll-like receptors, DCNL5 gets rapidly and transiently phosphorylated on a specific N-terminal serine residue (S41). This phosphorylation event is specifically mediated by IKKα and not IKKβ. Our data for the first time provides evidence that DCNL proteins are post-translationally modified in an inducible manner. Our findings also provide the first example of a DCNL member as a kinase substrate in a signalling pathway, indicating that the activity of at least some DCNLs may be regulated

DNA Damage Response and Repair: Insights into Strategies for Radiation Sensitization

The incorporation of radiotherapy into multimodality treatment plans has led to significant improvements in glioma patient survival. However, local recurrence from glioma resistance to ionizing radiation remains a therapeutic challenge. The tumoricidal effect of radiation therapy is largely attributed to the induction of dsDNA breaks (DSBs). In the past decade, there have been tremendous strides in understanding the molecular mechanisms underlying DSB repair. The identification of gene products required for DSB repair has provided novel therapeutic targets. Recent studies revealed that many US FDA-approved cancer agents inhibit DSB repair by interacting with repair proteins. This article will aim to provide discussion of DSB repair mechanisms to provide molecular targets for radiation sensitization of gliomas and a discussion of FDA-approved cancer therapies that modulate DSB repair to highlight opportunities for combination therapy with radiotherapy for glioma therapy

Massive autophosphorylation of the Ser/Thr-rich domain controls protein kinase activity of TRPM6 and TRPM7.

TRPM6 and TRPM7 are bifunctional proteins expressing a TRP channel fused to an atypical alpha-kinase domain. While the gating properties of TRPM6 and TRPM7 channels have been studied in detail, little is known about the mechanisms regulating kinase activity. Recently, we found that TRPM7 associates with its substrate myosin II via a kinase-dependent mechanism suggesting a role for autophosphorylation in substrate recognition. Here, we demonstrate that the cytosolic C-terminus of TRPM7 undergoes massive autophosphorylation (32+/-4 mol/mol), which strongly increases the rate of substrate phosphorylation. Phosphomapping by mass spectrometry indicates that the majority of autophosphorylation sites (37 out of 46) map to a Ser/Thr-rich region immediately N-terminal of the catalytic domain. Deletion of this region prevents substrate phosphorylation without affecting intrinsic catalytic activity suggesting that the Ser/Thr-rich domain contributes to substrate recognition. Surprisingly, the TRPM6-kinase is regulated by an analogous mechanism despite a lack of sequence conservation with the TRPM7 Ser/Thr-rich domain. In conclusion, our findings support a model where massive autophosphorylation outside the catalytic domain of TRPM6 and TRPM7 may facilitate kinase-substrate interactions leading to enhanced phosphorylation of those substrates

WNK1-OSR1 kinase-mediated phospho-activation of Na+-K+-2Cl- cotransporter facilitates glioma migration

Background: The bumetanide (BMT)-sensitive Na+-K+-2Cl- cotransporter isoform 1 (NKCC1) maintains cell volume homeostasis by increasing intracellular K+ and Cl- content via regulatory volume increase (RVI). Expression levels of NKCC1 positively correlate with the histological grade and severity of gliomas, the most common primary adult brain tumors, and up-regulated NKCC1 activity facilitates glioma cell migration and apoptotic resistance to the chemotherapeutic drug temozolomide (TMZ). However, the cellular mechanisms underlying NKCC1 functional up-regulation in glioma and in response to TMZ administration remain unknown. Methods: Expression of NKCC1 and its upstream kinases With-No-K (Lysine) kinase 1 (WNK1) and oxidative stress-responsive kinase-1 (OSR1) in different human glioma cell lines and glioma specimens were detected by western blotting and immunostaining. Live cell imaging and microchemotaxis assay were applied to record glioma cell movements under different treatment conditions. Fluorescence indicators were utilized to measure cell volume, intracellular K+ and Cl- content to reflect the activity of NKCC1 on ion transportation. Small interfering RNA (siRNA)-mediated knockdown of WNK1 or OSR1 was used to explore their roles in regulation of NKCC1 activity in glioma cells. Results of different treatment groups were compared by one-way ANOVA using the Bonferroni post-hoc test in the case of multiple comparisons. Results: We show that compared to human neural stem cells and astrocytes, human glioma cells exhibit robust increases in the activation and phosphorylation of NKCC1 and its two upstream regulatory kinases, WNK1 and OSR1. siRNA-mediated knockdown of WNK1 or OSR1 reduces intracellular K+ and Cl- content and RVI in glioma cells by abolishing NKCC1 regulatory phospho-activation. Unexpectedly, TMZ activates the WNK1/OSR1/NKCC1 signaling pathway and enhances glioma migration. Pharmacological inhibition of NKCC1 with its potent inhibitor BMT or siRNA knockdown of WNK1 or OSR1 significantly decreases glioma cell migration after TMZ treatment. Conclusion: Together, our data show a novel role for the WNK1/OSR1/NKCC1 pathway in basal and TMZ-induced glioma migration, and suggest that glioma treatment with TMZ might be improved by drugs that inhibit elements of the WNK1/OSR1/NKCC1 signaling pathway

Inhibition of SIK2 and SIK3 during differentiation enhances the anti-inflammatory phenotype of macrophages

The salt-inducible kinases (SIKs) control a novel molecular switch regulating macrophage polarization. Pharmacological inhibition of the SIKs induces a macrophage phenotype characterized by the secretion of high levels of anti-inflammatory cytokines, including interleukin (IL)-10, and the secretion of very low levels of pro-inflammatory cytokines, such as tumour necrosis factor α. The SIKs, therefore, represent attractive new drug targets for the treatment of macrophage-driven diseases, but which of the three isoforms, SIK1, SIK2 or SIK3, would be appropriate to target remains unknown. To address this question, we developed knock-in (KI) mice for SIK1, SIK2 and SIK3, in which we introduced a mutation that renders the enzymes catalytically inactive. Characterization of primary macrophages from the single and double KI mice established that all three SIK isoforms, and in particular SIK2 and SIK3, contribute to macrophage polarization. Moreover, we discovered that inhibition of SIK2 and SIK3 during macrophage differentiation greatly enhanced the production of IL-10 compared with their inhibition in mature macrophages. Interestingly, macrophages differentiated in the presence of SIK inhibitors, MRT199665 and HG-9-91-01, still produced very large amounts of IL-10, but very low levels of pro-inflammatory cytokines, even after the SIKs had been reactivated by removal of the drugs. Our data highlight an integral role for SIK2 and SIK3 in innate immunity by preventing the differentiation of macrophages into a potent and stable anti-inflammatory phenotype