Κυριακή, 14 Φεβρουαρίου 2016

Time Decay for Nonlinear Dissipative Schrödinger Equations in Optical Fields

We consider the initial value problem for the nonlinear dissipative Schrödinger equations with a gauge invariant nonlinearity of order for arbitrarily large initial data, where the lower bound is a positive root of for and for Our purpose is to extend the previous results for higher space dimensions concerning -time decay and to improve the lower bound of under the same dissipative condition on : and as in the previous works.

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The PMIPv6-Based Group Binding Update for IoT Devices

Internet of Things (IoT) has been booming with rapid increase of the various wearable devices, vehicle embedded devices, and so on, and providing the effective mobility management for these IoT devices becomes a challenge due to the different application scenarios as well as the limited energy and bandwidth. Recently, lots of researchers have focused on this topic and proposed several solutions based on the combination of IoT features and traditional mobility management protocols, in which most of these schemes take the IoT devices as mobile networks and adopt the NEtwork MObility (NEMO) and its variants to provide the mobility support. However, these solutions are in face of the heavy signaling cost problem. Since IoT devices are generally combined to realize the complex functions, these devices may have similar movement behaviors. Clearly analyzing these characters and using them in the mobility management will reduce the signaling cost and improve the scalability. Motivated by this, we propose a PMIPv6-based group binding update method. In particular, we describe its group creation procedure, analyze its impact on the mobility management, and derive its reduction ratio in terms of signaling cost. The final results show that the introduction of group binding update can remarkably reduce the signaling cost.

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Segmental Testicular Infarction, an Underdiagnosed Entity: Case Report with Histopathologic Correlation and Review of the Diagnostic Features

A 30-year-old male presented with a 1-day history of left scrotal pain and a tender left testicle and epididymis on physical exam. Scrotal ultrasound showed an avascular, heterogeneous, hypoechoic lesion in the superior left testis suggestive of infarction or neoplasm. The patient was managed conservatively; however, his pain continued and follow-up ultrasound 6 days later showed interval increase in the size of the mass. Left radical orchiectomy was done and pathology result showed segmental infarction of the left testis.

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Evaluating the Effects of Tetrachloro-1,4-benzoquinone, an Active Metabolite of Pentachlorophenol, on the Growth of Human Breast Cancer Cells

Tetrachloro-1,4-benzoquinone (TCBQ), an active metabolite of pentachlorophenol (PCP), is genotoxic and potentially carcinogenic. As an electrophilic and oxidative molecule, TCBQ can conjugate with deoxyguanosine in DNA molecules and/or impose oxidative stress in cells. In the current study, we investigated the effects of TCBQ on intracellular ROS production, apoptosis, and cytotoxicity against three different subtypes of human breast cancer cells. Luminal A subtype MCF7 (ER+, PR+, HER2−) cells maintained the highest intracellular ROS level and were subjected to TCBQ-induced ROS reduction, apoptosis, and cytotoxicity. HER2 subtype Sk-Br-3 (ER−, PR−, HER2+) cells possessed the lowest intracellular ROS level. TCBQ promoted ROS production, inhibited apoptosis, and elevated cytotoxicity (due to necrosis) against Sk-Br-3 cells. Triple-negative/basal-like subtype MDA-MB-231 cells were less sensitive towards TCBQ treatment. Therefore, the effect of prolonged exposure to PCP and its active metabolites on cancer growth is highly cancer-cell-type specific.

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Plant Responses to High Frequency Electromagnetic Fields

High frequency nonionizing electromagnetic fields (HF-EMF) that are increasingly present in the environment constitute a genuine environmental stimulus able to evoke specific responses in plants that share many similarities with those observed after a stressful treatment. Plants constitute an outstanding model to study such interactions since their architecture (high surface area to volume ratio) optimizes their interaction with the environment. In the present review, after identifying the main exposure devices (transverse and gigahertz electromagnetic cells, wave guide, and mode stirred reverberating chamber) and general physics laws that govern EMF interactions with plants, we illustrate some of the observed responses after exposure to HF-EMF at the cellular, molecular, and whole plant scale. Indeed, numerous metabolic activities (reactive oxygen species metabolism, α- and β-amylase, Krebs cycle, pentose phosphate pathway, chlorophyll content, terpene emission, etc.) are modified, gene expression altered (calmodulin, calcium-dependent protein kinase, and proteinase inhibitor), and growth reduced (stem elongation and dry weight) after low power (i.e., nonthermal) HF-EMF exposure. These changes occur not only in the tissues directly exposed but also systemically in distant tissues. While the long-term impact of these metabolic changes remains largely unknown, we propose to consider nonionizing HF-EMF radiation as a noninjurious, genuine environmental factor that readily evokes changes in plant metabolism.

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A Method to Construct Generalized Fibonacci Sequences

The main purpose of this paper is to study the convergence properties of Generalized Fibonacci Sequences and the series of partial sums associated with them. When the proper values of an real matrix are real and different, we give a necessary and sufficient condition for the convergence of the matrix sequence to a matrix .

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The SELFNET Approach for Autonomic Management in an NFV/SDN Networking Paradigm

To meet the challenging key performance indicators of the fifth generation (5G) system, the network infrastructure becomes more heterogeneous and complex. This will bring a high pressure on the reduction of OPEX and the improvement of the user experience. Hence, shifting today’s manual and semi-automatic network management into an autonomic and intelligent framework will play a vital role in the upcoming 5G system. Based on the cutting-edge technologies, such as Software-Defined Networking and Network Function Virtualization, a novel management framework upon the software-defined and Virtualized Network is proposed by EU H2020 SELFNET project. In the paper, the reference architecture of SELFNET, which is divided into Infrastructure Layer, Virtualized Network Layer, SON Control Layer, SON Autonomic Layer, NFV Orchestration and Management Layer, and Access Layer, will be presented.

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New Claims for Wild Carrot (Daucus carota subsp. carota) Essential Oil

The essential oil of Daucus carota subsp. carota from Portugal, with high amounts of geranyl acetate (29.0%), α-pinene (27.2%), and 11αH-himachal-4-en-1β-ol (9.2%), was assessed for its biological potential. The antimicrobial activity was evaluated against several Gram-positive and Gram-negative bacteria, yeasts, dermatophytes, and Aspergillus strains. The minimal inhibitory concentration (MIC) and minimal lethal concentration (MLC) were evaluated showing a significant activity towards Gram-positive bacteria (MIC = 0.32–0.64 μL/mL), Cryptococcus neoformans (0.16 μL/mL), and dermatophytes (0.32–0.64 μL/mL). The inhibition of the germ tube formation and the effect of the oil on Candida albicans biofilms were also unveiled. The oil inhibited more than 50% of filamentation at concentrations as low as 0.04 μL/mL (MIC/128) and decreased both biofilm mass and cell viability. The antioxidant capacity of the oil, as assessed by two in chemico methods, was not relevant. Still, it seems to exhibit some anti-inflammatory potential by decreasing nitric oxide production around 20% in LPS-stimulated macrophages, without decreasing macrophages viability. Moreover, the oils safety profile was assessed on keratinocytes, alveolar epithelial cells, macrophages, and hepatocytes. Overall, the oil demonstrated a safety profile at concentrations below 0.64 μL/mL. The present work highlights the bioactive potential of D. carota subsp. carota suggesting its industrial exploitation.

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Epigenetic Studies Point to DNA Replication/Repair Genes as a Basis for the Heritable Nature of Long Term Complications in Diabetes

Metabolic memory (MM) is defined as the persistence of diabetic (DM) complications even after glycemic control is pharmacologically achieved. Using a zebrafish diabetic model that induces a MM state, we previously reported that, in this model, tissue dysfunction was of a heritable nature based on cell proliferation studies in limb tissue and this correlated with epigenetic DNA methylation changes that paralleled alterations in gene expression. In the current study, control, DM, and MM excised fin tissues were further analyzed by MeDIP sequencing and microarray techniques. Bioinformatics analysis of the data found that genes of the DNA replication/DNA metabolism process group (with upregulation of the apex1, mcm2, mcm4, orc3, lig1, and dnmt1 genes) were altered in the DM state and these molecular changes continued into MM. Interestingly, DNA methylation changes could be found as far as 6–13 kb upstream of the transcription start site for these genes suggesting potential higher levels of epigenetic control. In conclusion, DNA methylation changes in members of the DNA replication/repair process group best explain the heritable nature of cell proliferation impairment found in the zebrafish DM/MM model. These results are consistent with human diabetic epigenetic studies and provide one explanation for the persistence of long term tissue complications as seen in diabetes.

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Study on Time-Dependent Behavior of Granite and the Creep Model Based on Fractional Derivative Approach Considering Temperature

Based on mineral components and the creep experimental studies of Three Gorges granite and Beishan granite from different regions of China at various temperatures, the strength and creep property of two types of granites are compared and analyzed. Considering the damage evolution process, a new creep constitutive model is proposed to describe the creep property of granite at different temperatures based on fractional derivative. The parameters of the new creep model are determined on the basis of the experimental results of the two granites. In addition, a sensitivity study is carried out, showing effects of stress level, fractional derivative order, and the exponent . The results indicate that the proposed creep model can describe the three creep stages of granite at different temperatures and contribute to further research on the creep property of granite.

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Exact Boundary Derivative Formulation for Numerical Conformal Mapping Method

Conformal mapping is a useful technique for handling irregular geometries when applying the finite difference method to solve partial differential equations. When the mapping is from a hyperrectangular region onto a rectangular region, a specific length-to-width ratio of the rectangular region that fitted the Cauchy-Riemann equations must be satisfied. In this research, a numerical integral method is proposed to find the specific length-to-width ratio. It is conventional to employ the boundary integral method (BIEM) to perform the conformal mapping. However, due to the singularity produced by the BIEM in seeking the derivatives on the boundaries, the transformation Jacobian determinants on the boundaries have to be evaluated at inner points instead of directly on the boundaries. This approximation is a source of numerical error. In this study, the transformed rectangular property and the Cauchy-Riemann equations are successfully applied to derive reduced formulations of the derivatives on the boundaries for the BIEM. With these boundary derivative formulations, the Jacobian determinants can be evaluated directly on the boundaries. Furthermore, the results obtained are more accurate than those of the earlier mapping method.

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Stochastic Geometry Analysis and Additional Small Cell Deployment for HetNets Affected by Hot Spots

Hot spots (HSs) of mobile users that were not expected in the original network planning may occur after a heterogeneous network (HetNet) has been deployed and affect the network performance. In this case, deploying additional small cells on top of the existing HetNet without changing the existing network infrastructure is considered as a solution. In this paper, we first provide a stochastic geometry analysis for a HetNet affected by a large HS and for the additional small cells that need to be deployed based on the spatial bivariate Poisson point process. The optimal numbers of additional small cells required in the HS and non-HS areas are obtained by minimizing the difference between the numbers of macrocell users after and before the HS occurs based on the analytical results. We then propose an algorithm to maximize the average user throughput by jointly optimizing the locations of additional small cells and user associations of all cells. Simulation results show that the proposed algorithm can maintain the average user throughput above a threshold with excellent fairness among all users even for a very high density of HS users.

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Genotyping of Cryptosporidium Species and Their Clinical Manifestations in Patients with Renal Transplantation and Human Immunodeficiency Virus Infection

In the present study we aimed to determine (i) frequency of Cryptosporidium species among patients with renal transplantation (RT) and human immunodeficiency virus (HIV) infection and (ii) relationship of the nature, severity, and duration of symptoms with different species and load of Cryptosporidium. Stool samples from 70 (42 RT and 28 HIV) and 140 immunocompromised patients with and without cryptosporidiosis by modified Kinyoun’s staining were subjected to qPCR-melting curve analysis for identification of parasite species. qPCR detected one microscopically negative sample to be positive for cryptosporidiosis. C. hominis, C. parvum, and mixed infection were detected in 50/71 (70.4%), 19/71 (26.8%), and 2/71 (2.8%) patients, respectively. Patients with cryptosporidiosis had higher stool frequency (median, IQR: 4, 3–6/d versus 3, 2–4/d; ) and watery stool (52/71 [73%] versus 64/139 [46%]; ). Parasite load (median, IQR: Log10 6.37 (5.65–7.12), Log10 5.81 (4.26–6.65); ) and nausea/vomiting (29/50 [58%] versus 5/19 [26%]; ) were more frequent with C. hominis than with C. parvum infection. Thus, Cryptosporidium spp. (mainly C. hominis) is a common cause of diarrhoea in RT and HIV patients.

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The New TLC Method for Separation and Determination of Multicomponent Mixtures of Plant Extracts

The new mode of two-dimensional gradient thin layer chromatography (MGD-2D TLC) has been presented. Short distance development of sample in the first dimension leads to formation of the preconcentrated narrow zones. They are consecutively separated in the second dimension with the mobile phase gradient in several steps of development until the eluent reaches the further end of the chromatographic plate. The use of the above-mentioned technique allows isolating and then identifying the compounds of various polarity from the multicomponent mixture. The practical application of two-dimensional gradient thin layer chromatography has been performed for isolation of the two plant (Juniperus and Thymus) oils components as the examples of test mixtures. The experiments have been carried out with the use of silica gel plates as well as a normal phase condition. The results of solute separation with isocratic one-dimensional thin layer chromatography system have been compared with those of two-dimensional gradient system. It has been observed that application of the latter mode leads to almost triplicated number of zones in comparison with the former one. It is purposeful to apply the proposed mode to control the purity of the dominant component or components of the mixture.

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The Brief Introduction of Different Laser Diagnostics Methods Used in Aeroengine Combustion Research

Combustion test diagnosis has always been one of the most important technologies for the development of aerospace engineering. The traditional methods of measurement have been unable to meet the requirements of accurate capture of the flow field in the development process of the aeroengine combustor. Therefore, the development of high-precision measurement and diagnostic techniques to meet the needs of the aeroengine combustor design is imperative. Laser diagnostics techniques developed quickly in the past several years. They are used to measure the parameters of the combustion flow field such as velocity, temperature, and components concentration with high space and time resolution and brought no disturbance. Planar laser-induced fluorescence, coherent anti-Stokes Raman scattering, tunable diode laser absorption spectroscopy, and Raman scattering were introduced systemically in this paper. After analysis of their own advantages and disadvantages, the authors considered validated Raman scattering system and Tunable Diode Laser Absorption Tomography are more suitable for research activities on aeroengine combustion systems.

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Trends in Extreme Precipitation Indices in Iran: 1951–2007

We investigate trends in extreme precipitation in Iran for 1951–2007 using the recently released APHRODITE daily rainfall time series. We find that seven different indices of extreme precipitation all show an upward trend through the study period. The seven different precipitation indices include annual precipitation total, number of days above a certain threshold, maximum precipitation received over a certain period of time, maximum one-day precipitation, and number of days with precipitation above the 90th percentile. A principal components analysis reveals one eigenvector explaining much of the variance in the seven indices and reveals that this component exhibits a strong upward trend for the whole of Iran. On a regional level, we find that the upward trend in extreme precipitation has a strong southwest-to-northeast gradient across the country for all the indices. We repeated all the analyses for 42 stations across the country to compare with the results from the gridded data; trends in extreme rainfall generated from the station data compare favorably with the results from the APHRODITE daily rainfall time series thereby reinforcing the robustness of our conclusions.

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Twelve-Year Trends of PM10 and Visibility in the Hefei Metropolitan Area of China

China has been experiencing severe air pollution and previous studies have mostly focused on megacities and a few hot spot regions. Hefei, the provincial capital city of Anhui province, has a population of near 5 million in its metropolitan area, but its air quality has not been reported in literature. In this study, daily PM10 and visibility data in 2001–2012 were analyzed to investigate the air quality status as well as the twelve-year pollution trends in Hefei. The results reveal that Hefei has been suffering high PM10 pollution and low visibility during the study period. The annual average PM10 concentrations are 2~3 times of the Chinese Ambient Air Quality Standard. PM10 shows fluctuating variation in 2001–2007 and has a slightly decreasing trend after 2008. The annual average visibility range is generally lower than 7 km and shows a worsening trend from 2001 to 2006 followed by an improving trend from 2007 to 2012. Wind speed, precipitation, and relative humidity have negative effects on PM10 concentrations in Hefei, while temperature could positively or negatively affect PM10. The results provide a general understanding of the status and long-term trends of PM10 pollution and visibility in a typical second-tier city in China.

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Synthesis, In Vivo Anti-Inflammatory Activity, and Molecular Docking Studies of New Isatin Derivatives

A novel synthesis of 2-hydroxy-N′-(2-oxoindolin-3-ylidene) benzohydrazide derivatives was synthesized by the condensation of 2-hydroxybenzohydrazide with substituted isatins. The synthesized compounds were characterized by FT-IR, 1H-NMR, and mass spectral data. Further, the compounds were screened for in vivo anti-inflammatory activity by carrageenan induced paw edema method. The tested compounds have shown mild-to-moderate anti-inflammatory activity. The compounds VIIc and VIId exhibited 65% and 63% of paw edema reduction, respectively. The molecular docking studies were also carried out into the active site of COX-1 and COX-2 enzymes (PDB ID: 3N8Y, 3LN1, resp.) using VLife MDS 4.3. The compounds VIIc, VIId, and VIIf exhibited good docking scores of −57.27, −62.02, and −58.18 onto the active site of COX-2 and least dock scores of −8.03, −9.17, and −8.94 on COX-1 enzymes and were comparable with standard COX-2 inhibitor celecoxib. A significant correlation was observed between the in silico and the in vivo studies. The anti-inflammatory and docking results highlight the fact that the synthesized compounds VIIc, VIId, and VIIf could be considered as possible hit as therapeutic agents.

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Boolean Modeling of Cellular and Molecular Pathways Involved in Influenza Infection

Systems virology integrates host-directed approaches with molecular profiling to understand viral pathogenesis. Self-contained statistical approaches that combine expression profiles of genes with the available databases defining the genes involved in the pathways (gene-sets) have allowed characterization of predictive gene-signatures associated with outcome of the influenza virus (IV) infection. However, such enrichment techniques do not take into account interactions among pathways that are responsible for the IV infection pathogenesis. We investigate dendritic cell response to seasonal H1N1 influenza A/New Caledonia/20/1999 (NC) infection and infer the Boolean logic rules underlying the interaction network of ligand induced signaling pathways and transcription factors. The model reveals several novel regulatory modes and provides insights into mechanism of cross talk between NFκB and IRF mediated signaling. Additionally, the logic rule underlying the regulation of IL2 pathway that was predicted by the Boolean model was experimentally validated. Thus, the model developed in this paper integrates pathway analysis tools with the dynamic modeling approaches to reveal the regulation between signaling pathways and transcription factors using genome-wide transcriptional profiles measured upon influenza infection.

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quality of care; +32 new citations

32 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

quality of care

These pubmed results were generated on 2016/02/14

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.



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An insight on the alkaloid content of Capparis spinosa L. root by HPLC-DAD-MS, MS/MS and (1)H qNMR.

An insight on the alkaloid content of Capparis spinosa L. root by HPLC-DAD-MS, MS/MS and (1)H qNMR.

J Pharm Biomed Anal. 2016 Feb 2;123:53-62

Authors: Khatib M, Pieraccini G, Innocenti M, Melani F, Mulinacci N

Abstract
The Capparis spinosa L. has a wide distribution in the Old World from South Europe, North and East Africa, Madagascar, Southwest and Central Asia to Australia and Oceania. The consolidated traditional use of C. spinosa root as remedy against different pains in human is well known since the antiquity. Various secondary metabolites have been found in caper plant, nevertheless, few studies have been focused to the analysis of root constituents. To date, several free and glycosilated spermidine alkaloids and a more polar alkaloid, the stachydrine, have been isolated from the root of C. spinosa. Aim of this work was to improve the knowledge on the alkaloid content of the root of a Syrian sample of C. spinosa by HPLC-DAD-MS(n) and to propose methods to quantify these molecules in different raw extracts. A decoction, an hydroalcoholic extraction and a fractionation process to selectively recover the spermidine alkaloids were applied. To our knowledge, this is the first HPLC-DAD-MS(n) profile that pointed out the co-presence of stachydrine, several isobaric forms of capparispine and/or capparisine in free and glycosylated forms and some isobars of isocodonocarpine or codonocarpine as monoglycosides in extracts of C. spinosa root. The determination by HPLC/DAD for the spermidine alkaloids expressed as p-OH-coumaric acid gave values up to 3.5mg/g dried root and the stachydrine evaluated by (1)H NMR was close to 12.5mg/g dried root. Overall, the total alkaloids were almost doubled in hydroalcoholic extract with respect to the decoction, and the stachydrine in the cortex was almost double than in the whole root.

PMID: 26874255 [PubMed - as supplied by publisher]



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Laryngeal squamous cell carcinoma progression is associated with the NFκB signaling pathway regulated by IκB kinase β

OBJECTIVE: We aimed to analyze the association of NFκB signaling pathway with the carcinogenesis of laryngeal squamous cell carcinoma (LSCC).

PATIENTS AND METHODS: Protein array was used to identify the differentially expressed proteins involved in NFκB signaling pathway between LSCC cells and normal throat mucosa. Correlation analysis between significantly expressed proteins and clinical characteristics (differentiation, clinical stage, and node metastasis) was performed. The expression of IκB kinase-β (IKK-β) in Hep-2 cells transfected with IKK-β-siRNA or pcDNA3.1-IKK-β was detected both by real-time polymerase chain reaction and western blot. Besides, a tetrazolium-based colorimetric assay (MTT), flow cytometer, and transwell assay were used to examine the proliferation, apoptosis, and migration rate of Hep-2 cells, respectively.

RESULTS: Three differentially expressed proteins were identified. Among them, tumor necrosis factor receptor 1 (TNFR1) and IKK-β were significantly up-regulated (p < 0.01) and Fas-associated via death domain (FADD) was significantly down-regulated (p < 0.01). The correlation analysis showed that IKK-β expression had a significant association with differentiation, clinical stage, and node metastasis (p < 0.05). Besides, high expressed IKK-β resulted in significantly increased proliferation and migration rate (p < 0.05). Reversely, Hep-2 cells transfected with IKK-β-siRNA showed significantly lower proliferation and migration rate (p < 0.05) and significantly higher apoptosis rate (p < 0.05) than normal cells.

CONCLUSIONS: The NFκB signaling pathway involved TNFR1, IKK-β, and FADD is significantly associated with the development of LSCC. Over-expressed IKK-β efficiently inhibits cell apoptosis and has positive effects on cell proliferation and migration.

L'articolo Laryngeal squamous cell carcinoma progression is associated with the NFκB signaling pathway regulated by IκB kinase β sembra essere il primo su European Review.



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Cerebrospinal fluid IgG against TB-SA for diagnosis of tuberculous meningitis

OBJECTIVE: A commercial enzyme linked immunosorbent assay (ELISA) detecting cerebrospinal fluid (CSF) IgG against TB-SA (CYPCO TB (IgG) ELISA assay) for diagnosing tuberculous meningitis (TBM) was evaluated retrospectively. Meanwhile, Pandy test was introduced to grade patients, improving its role in the detection of TBM.

PATIENTS AND METHODS: 187 consecutive cases with determined diagnosis were enrolled and divided into TBM group and Non-TBM group. CSFs were collected and sent for Pandy test, cytology, routine biochemistry tests, acid-fast smear and mycobacterial culture. The diagnostic parameters of the ELISA assay were evaluated. Differences in sensitivity between groups were estimated using a McNemar’s test.

RESULTS: The overall sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio of the ELISA assay were 31.6% (95% CI: 21.0-44.5%), 97.7% (95% CI: 93.4-99.2%), 85.8, 76.5, 13.7 and 0.7, respectively. McNemar’s test showed the sensitivity of CYPCO TB (IgG) ELISA assay significantly positively correlated with the results of Pandy test (p < 0.05). The ten Pandy test “3+” patients were all TBM. Therefore, patients with “3+” Pandy test are highly suspected of TBM.

CONCLUSIONS: The commercial CYPCO TB (IgG) ELISA assay is able to rapidly confirm a diagnosis of TBM. The sensitivity of the ELISA assay is significantly positively correlated with the results of Pandy test. Patients with “3+” Pandy test are highly suspected of TBM.

L'articolo Cerebrospinal fluid IgG against TB-SA for diagnosis of tuberculous meningitis sembra essere il primo su European Review.



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Renal circulation and microcirculation during intra-abdominal hypertension in a porcine model

OBJECTIVE: The purpose of the study is to further investigate the effects of increased intra-abdominal pressure (IAP) on renal hemodynamics and renal perfusion, and to evaluate the renal cortical and sublingual microcirculation by sidestream dark field (SDF) imaging, both with a porcine model.

MATERIALS AND METHODS: IAP was increased stepwise to 10, 15, 20, 25 mmHg, during which hemodynamic parameters, urinary output, renal contrast-enhanced ultrasound (CEUS), sublingual and renal SDF videos were all recorded from 12 pigs.

RESULTS: Wash in time (WT) and time to peak (TTP) prolonged significantly (p<0.05), while peak intensity (PI) wash in slope (WS) and AUC (area under curve) in CEUS declined significantly (p<0.05) compared with baseline when IAP elevated to 25 mm Hg. With an increase of abdominal pressure, sublingual microvascular flow index (MFI) drop significantly, especially upon IAP was over 20 mmHg. But other parameters such as the total vascular density (TVD), De Backer Score, proportion of perfused vessels (PPV), perfused vessel density (PVD), and heterogeneity index (HI) of tongue were not significantly changed. With increasing IAP, renal vascular resistance increased and MFI decreased about 30%. RFG, instead of RFG showed a moderate correlation with AUC (R=0.47, p<0.05) and MFI (R=0.49, p<0.05).

CONCLUSIONS: CEUS is a safe, real-time dynamic, noninvasive and simple technique to evaluate renal microvascular perfusion in intra-abdominal hypertension. Descending slope, PI and AUC can be used for the diagnosis of the renal microvascular damage in a porcine model of IAP-induced renal impairment. Also, SDF on the surface of the kidney is a useful tool to evaluate the microcirculation of kidney but sublingual SDF imaging was barely useful.

L'articolo Renal circulation and microcirculation during intra-abdominal hypertension in a porcine model sembra essere il primo su European Review.



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Occult urinary incontinence in elderly women and its association with geriatric condition

OBJECTIVE: Many older women are hesitated to initiate discussions about urinary symptoms and their incontinence. The aim of this study is to determine the prevalence of occult urinary incontinence in outpatient older women and to evaluate its association with other geriatric conditions.

PATIENTS AND METHODS: 100 female patients 65 years and older were assessed at the geriatric outpatient clinic. The validated form of the Turkish version of the International Consultation on Incontinence Questionnaire-Short Form was used to evaluate urinary incontinence and quality of life. Comprehensive geriatric assessment including activities of daily living, instrumental activities of daily living, mini mental state examination and geriatrics depression scale was performed. The number of falls, comorbid conditions and number of medications were noted. The association between urinary incontinence and geriatric domains were evaluated with logistic regression analysis.

RESULTS: A total of 100 patients were evaluated, 64 of them included in the study. The median age of patients was 72.5. The rate of urinary incontinence was found 40.6%. The association between urinary incontinence and quality of life, performance status and comorbidity was found statistically significant with logistic regression (p = 0.033, p = 0.005, p = 0.031 respectively). Half of the patients with UI believe that it is part of normal aging and no definite treatment is available.

CONCLUSIONS: Occult urinary incontinence is a significant problem in older women that inversely affecting the quality of life. The study suggests that awareness and education regarding incontinence should be increased among elderly patients and screening of urinary incontinence is an important part of the geriatric assessment. The evaluation and management of functional status and comorbid conditions should be the initial step during incontinence management in elderly patients.

L'articolo Occult urinary incontinence in elderly women and its association with geriatric condition sembra essere il primo su European Review.



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Suppression of collagen-induced arthritis by lipopolysaccharide in DBA/1 mice

OBJECTIVE: Injection of lipopolysaccharide (LPS) has both promotion and inhibition effects on the autoimmune disease. Given the variable roles of LPS in autoimmune diseases, the role of LPS played in collagen-induced arthritis (CIA, autoimmune disease) model remains to be further determined.

MATERIALS AND METHODS: CIA was induced by intradermal injection of collagen type II (CII) in DBA/1 mice (day 0) followed by a booster injection on day 21. Mice of CIA with LPS injection group (CIA+ LPS group) were intraperitoneally injected with 50 µg LPS on day 42. Tissues such as carpal joints and fingers were stained with hematoxylin and eosin (H&E) for histopathology analysis. Inflammation, pannus formation and bone resorption were monitored by a macroscopic scoring system. Serum level of IgG2a antibody was determined by enzyme-linked immunosorbent assay (ELISA).

RESULTS: The incidence of arthritis in CIA group was much higher than that in CIA+ LPS group (100%: 46.5%, p < 0.05), as same as the arthritis score (5.38:1.37, p = 8.16 × 10-6). Besides, the histopathologic score was also higher in CIA group than that in CIA+ LPS group (15.0:5.36). Compared with CIA group, mild synovial hyperplasia and no articular cartilage damage were observed in CIA+ LPS group. Besides, mice of CIA group produced a significantly higher level of IgG2a than CIA+ LPS group (3922 ng/ml: 2084 ng/ml, p = 0.0333) when arthritis developed.

CONCLUSIONS: Our findings showed that LPS might suppress CIA progression under special conditions, opening up a new understanding of the roles of LPS in arthritis and new possibilities for a clinical therapy of CIA.

L'articolo Suppression of collagen-induced arthritis by lipopolysaccharide in DBA/1 mice sembra essere il primo su European Review.



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Expression profile analysis of new candidate genes for the therapy of primary osteoporosis

OBJECTIVE: Primary osteoporosis is a progressive bone disease that is characterized by a decrease in bone mass and density which can lead to an increased risk of fracture. Most of present treatments are effective for osteoporosis, but have limitations and side-effects. With the aging of the world population is increasing, the incidence of osteoporosis is rising. Therefore, the purpose of this study was to identify new candidate genes used as the therapeutic targets of primary osteoporosis.

MATERIALS AND METHODS: In this study, microarray data GSE35958 were downloaded from Gene Expression Omnibus, then the differentially expressed genes (DEGs) were identified by limma package. Gene Ontology (GO) and KEGG pathway enrichment analyses were performed for both up- and down-regulated DEGs using DAVID. In addition, the transcription factor analysis was conducted for DEGs. The protein-protein interaction (PPI) network was constructed by STRING and Cytoscape. Finally, CFinder was used to analyze the PPI sub-network.

RESULTS: Totally, 327 up-regulated DEGs and 396 down-regulated DEGs were identified. The DEGs such as EGFR and AKT1 were mainly enriched in the pathway of focal adhesion. EGFR was also involved in cell adhesion based on GO enrichment analysis. Functional analysis of DEGs indicated that 26 transcription factors were screened. Moreover, EGFR, AKT1 and transcription factor CTNNB1 were the key nodes with high degrees according to PPI network and sub-network.

CONCLUSIONS: The literature suggested that AKT1, EGFR and CTNNB1 were closely related to osteoblastic differentiation and osteoclastogenesis. Some crucial DEGs such as EGFR, AKT1 and CTNNB1 might be connected with primary osteoporosis and could be used as therapeutic targets of osteoporosis.

L'articolo Expression profile analysis of new candidate genes for the therapy of primary osteoporosis sembra essere il primo su European Review.



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Novel approach of treating Gorham-Stout disease in the humerus – Case report and review of literature

Gorham-Stout disease or the so-called vanishing bone syndrome is a rare disorder characterized by intra-osseous proliferation of vascular channels resulting in destruction and resorption of the osseous matrix. The exact pathology of this disease showed no evidence of malignant, neuropathic, or infectious components involved in the causation of this disorder except for the culprit of lympho-vascular malformations in the bone. The mechanism of bone resorption is yet to be clarified. The clinical presentation of Gorham’s disease varies according to the organ of involvement. Patients diagnosed with Gorham’s disease in the bone may initially present with insidious onset of dull aching pain, progressive weakness, or pathologic fractures as the initial presentation. Gorham’s disease is progressive in most patients; yet it can be self-limiting in a few reported cases. The axes of treating this disease as reported in the literature include the use of medical treatment, surgical intervention, radiotherapy and/or the combination of any them. However, there is no consensus about the most effective approach for treating this rare disease. The challenge in this disease lies in both: how to diagnose and how to treat. Our novel approach combined surgical intervention, medication and radiotherapy as a treatment of Graham-Stout disease in the humerus, and showed no progression of the disease our case.

L'articolo Novel approach of treating Gorham-Stout disease in the humerus – Case report and review of literature sembra essere il primo su European Review.



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Pears and renal stones: possible weapon for prevention? A comprehensive narrative review

Urinary stones have been recognized as a human disease since dawn of history and treatment of this condition is reported by Egyptian medical writings. Also, pears have a very long history, being one of the earliest cultivated fruit trees and also known for medicinal use. Urinary tract stone formation represents a common condition and also a significant burden for health care service, due also to possible frequent relapses. Furthermore, urinary stones have been reported to have relationship with different metabolic derangements, and appropriate diet could contribute to avoid or reduce urinary stone formation. Citrate is an inhibitor of crystal growth in the urinary system, and hypocitraturia represents a main therapeutical target in stone formers. Pears contain a significant amount of malic acid, a precursor of citrate, and have antioxidant activity as well. A diet supplemented with pears, and associated with low consumption of meat and salt could impact positively cardiometabolic risk and urinary tract stone formation. However, very few studies evaluated the impact of pears utilization on health, and none on urinary tract stone formation in particular. High content in malate could warrant protection against stone formation, avoiding patients at high risk to be compelled to assume a considerable and expensive amount of pills.

L'articolo Pears and renal stones: possible weapon for prevention? A comprehensive narrative review sembra essere il primo su European Review.



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Evaluation of SCUBE-1 and sCD40L biomarkers in patients with hypothyroidism due to Hashimoto’s thyroiditis: a single-blind, controlled clinical study

OBJECTIVE: This study was performed to investigate the levels of platelet activation marker SCUBE-1 and sCD40L which plays some role in the progression of atherosclerosis, in patients with hypothyroidism due to Hashimoto’s thyroiditis.

PATIENTS AND METHODS: The cohort of this study includes 90 patients and 35 healthy volunteers, who admitted to the internal medicine out-patient. Simultaneously in the same samples; SCUBE-1 and sCD40L measurements were accomplished by enzyme-linked immunosorbent assay (ELISA). The data obtained were analyzed statistically.

RESULTS: Hypothyroidism due to Hashimoto’s thyroiditis in comparison to the control group that includes healthy volunteers; SCUBE-1 and sCD40L, were increased. And these results were statistically significant (p < 0.05).

CONCLUSIONS: SCUBE-1 and sCD40L levels were increased in Hashimoto’s hypothyroidism patients. This may indicate an increased endothelial dysfunction, platelet activation and cardiovascular risk in hypothyroidism. SCUBE-1 and sCD40L may be helpful in cardiovascular risk assessment of hypothyroid patients.

L'articolo Evaluation of SCUBE-1 and sCD40L biomarkers in patients with hypothyroidism due to Hashimoto’s thyroiditis: a single-blind, controlled clinical study sembra essere il primo su European Review.



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Hypoxia responsive miR-210 promotes cell survival and autophagy of endometriotic cells in hypoxia

OBJECTIVE: Hypoxia may play a role in the survival of ectopic endometrial cells. This study aimed to explore how hypoxia responsive miR-210 is involved in cell survival and autophagic response of endometriotic cells.

MATERIALS AND METHODS: The expression of hypoxia-inducible factor 1-alpha (HIF-1α) and miR-210 in eutopic and ectopic endometrial tissues were measured. The expression changes of HIF-1α and miR-210 in ovarian endometriotic cell line CRL-7566 after hypoxic culture were further explored. The influence of miR-210 on cell viability and apoptosis was quantified using CCK-8 assay and flow cytometry analysis. The effect of miR-210 on Bcl-2 expression and the effect of miR-210/Bcl-2 axis on autophagy in the cells were measured by Western blot analysis.

RESULTS: Ectopic lesion had stronger HIF-1α positive signals, as well as more HIF-1α positive cells per visual field than the eutopic endometrium. MiR-210 expression was also elevated in the ectopic lesions. In in-vitro models, CRL-7566 cells had significantly higher expression of HIF-1α and miR-210 after hypoxic treatment. MiR-210 overexpression partly preserved cell viability in hypoxia, while miR-210 knockdown facilitated the loss of cell viability. In addition, miR-210 significantly attenuated hypoxia-induced apoptosis in CRL-7566 cells. Enforced miR-210 overexpression significantly promoted autophagy in hypoxia. Knockdown of endogenous Bcl-2 significantly enhanced autophagy, the effect of which was similar to that of miR-210.

CONCLUSIONS: The hypoxia-induced higher miR-210 expression may contribute to pathological development of endometriosis at least through enhancing cell survival and promoting autophagy via Bcl2/Beclin-1 axis.

L'articolo Hypoxia responsive miR-210 promotes cell survival and autophagy of endometriotic cells in hypoxia sembra essere il primo su European Review.



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Bacteria Foraging Algorithm in Antenna Design

A simple design procedure to realize an optimum antenna using bacteria foraging algorithm (BFA) is proposed in this paper. The first antenna considered is imaginary. This antenna is optimized using the BFA along with a suitable fitness function formulated by considering some performance parameters and their best values. To justify the optimum design approach, one 12-element Yagi-Uda antenna is considered for an experiment. The optimized result of this antenna obtained using the optimization algorithm is compared with nonoptimized (conventional) result of the same antenna to appreciate the importance of optimization.

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Cancer Related Fatigue and Quality of Life in Patients with Advanced Prostate Cancer Undergoing Chemotherapy

Cancer related fatigue (CRF) is a common and debilitating symptom that can influence quality of life (QoL) in cancer patients. The increase in survival times stresses for a better understanding of how CRF affects patients’ QoL. This was a cross-sectional descriptive study with 148 randomly recruited prostate cancer patients aiming to explore CRF and its impact on QoL. Assessments included the Cancer Fatigue Scale, EORTC QLQ-C30, and EORTC QLQ-PR25. Additionally, 15 in-depth structured interviews were performed. Quantitative data were analyzed with simple and multiple regression analysis and independent samples -test. Qualitative data were analyzed with the use of thematic content analysis. The 66.9% of the patients experienced CRF with higher levels being recorded for the affective subscale. Statistically significant differences were found between the patients reporting CRF and lower levels of QoL (mean = 49.1) and those that did not report fatigue and had higher levels of QoL (mean = 72.1). The interviews emphasized CRF’s profound impact on the patients’ lives that was reflected on the following themes: “dependency on others,” “loss of power over decision making,” and “daily living disruption.” Cancer related fatigue is a significant problem for patients with advanced prostate cancer and one that affects their QoL in various ways.

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Rotigotine Objectively Improves Sleep in Parkinson’s Disease: An Open-Label Pilot Study with Actigraphic Recording

Sleep disturbances represent important predictors of poor quality of life (QoL) in Parkinson’s disease (PD). This open-label pilot study aimed to objectively assess, by means of actigraphic recording, effect of rotigotine on sleep in PD patients with self-reported sleep complaints. 15 PD patients underwent one-week actigraphic recording before (T0) and during (T1) rotigotine treatment, which was titrated to the dose subjectively improving motor symptoms (4–8 mg/24 h). Sleep disturbances, daytime sleepiness, cognitive performance, QoL, and depression were also evaluated with questionnaires. Actigraphic recordings showed a significant reduction in nocturnal motor activity and mean duration of wake episodes after sleep onset during rotigotine treatment compared to baseline. In 10 patients presenting objective evidence of poor sleep quality at T0 (sleep efficiency ≤ 85%), rotigotine also significantly improved other sleep parameters and further reduced nocturnal motor activity and mean duration of wake episodes. A significant decrease in number and duration of daytime sleep episodes was also observed at T1. Finally we confirmed that rotigotine significantly improves perceived sleep quality and QoL. Our study showed for the first time that rotigotine is associated with an objective improvement of nocturnal and diurnal sleep disturbances in PD patients with self-reported sleep complaints. This study is registered with AIFA-observational study registry number 12021.

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Efficient Alternative for Construction of the Linear System Stemming from Numerical Solution of Heat Transfer Problems via FEM

This paper proposes an efficient alternative to construction of the linear system coming from a solution via the Finite Element Method that is able to significantly decrease the time of construction of this system. From the presentation of the methodology used and a numerical application it will be clear that the purpose of this work is to be able to decrease 6-7 times (on average) the linear system building time.

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Recent Advances and Perspective of Studies on Phlegm Syndrome in Chinese Medicine

This review paper summarized the current situation of studies on the essence of phlegm syndrome and relation between phlegm syndrome, diseases, and therapeutics based on published English articles. In studies on the essence of phlegm syndrome, omic technologies were used to explore the molecular basis of phlegm syndrome; in studies on relation between phlegm syndrome and diseases, discovery of markers of phlegm syndrome in diseases becomes a hotspot; the distribution of phlegm syndromes in some common chronic diseases was found; in the therapy of phlegm syndrome, two therapeutic models, treatment with CM formula and treatment with a combination of CM formula and Western medicine, were used most frequently. It is certainly that using one omic technology is not able to deal with the complexity of phlegm syndrome and that the use of a combination of multiple omic methods will be a trend in future studies. Meanwhile, for rapidly increasing clinical research quality of phlegm syndrome, a series of agreed criteria, such as syndrome diagnostic criteria and efficacy criteria clinical studies of phlegm syndrome, needed to be established urgently, and there was an urgent need of standardizing syndrome names in English.

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Inhibition of Mycobacterium-RmlA by Molecular Modeling, Dynamics Simulation, and Docking

The increasing resistance to anti-tb drugs has enforced strategies for finding new drug targets against Mycobacterium tuberculosis (Mtb). In recent years enzymes associated with the rhamnose pathway in Mtb have attracted attention as drug targets. The present work is on α-D-glucose-1-phosphate thymidylyltransferase (RmlA), the first enzyme involved in the biosynthesis of L-rhamnose, of Mtb cell wall. This study aims to derive a 3D structure of RmlA by using a comparative modeling approach. Structural refinement and energy minimization of the built model have been done with molecular dynamics. The reliability assessment of the built model was carried out with various protein checking tools such as Procheck, Whatif, ProsA, Errat, and Verify 3D. The obtained model investigates the relation between the structure and function. Molecular docking interactions of Mtb-RmlA with modified EMB (ethambutol) ligands and natural substrate have revealed specific key residues Arg13, Lys23, Asn109, and Thr223 which play an important role in ligand binding and selection. Compared to all EMB ligands, EMB-1 has shown better interaction with Mtb-RmlA model. The information thus discussed above will be useful for the rational design of safe and effective inhibitors specific to RmlA enzyme pertaining to the treatment of tuberculosis.

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The Efficacy of Shen Shuaining Capsule on Chronic Kidney Disease: A Systematic Review and Meta-Analysis

Objective. To evaluate the efficacy of Shen shuaining capsule on treating chronic kidney disease (CKD). Methods. All randomized controlled trials (RCTs) of Shen shuaining capsule in treating CKD were collected from CBM, CNKI, VIP, Wanfang, EMBASE, MEDLINE, PubMed, and Cochrane library clinical controlled trials database. Two reviewers independently performed analysis of the included trials according to the inclusion and exclusion criteria. The risk of bias tool was from the Cochrane Handbook version 5.1.0. The Review Manager 5.2 software was employed for data analysis. Funnel plot and Egger’s test were applied to evaluate publication bias. Results. 20 studies including 1606 participants met the inclusion criteria, most of which were of low quality. Meta-analysis indicated that Shen shuaining capsule was effective for CKD in terms of SCR, BUN, Hb, and response rate and with less adverse effects, of which SCR and BUN decreased significantly (MD = −84.72, 95% CI: −107.36, −62.07, ) (MD = −4.30, 95% CI: −5.71, −2.89, ); Hb and response rate increased significantly (MD = 9.94, 95% CI: 9.24, 10.64, ) (OR = 4.25, 95% CI (3.32, 5.42), ). Conclusion. Shen shuaining capsule significantly reduced SCR and BUN, increased HB, and improved total efficiency of the symptoms and signs in patients with CKD. Subgroup analysis found that Shen shuaining capsule group was better than control group. Due to low quality of the methodology of included studies, further high-quality researches were needed to study its efficacy and safety.

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The Oncogenic Functions of Nicotinic Acetylcholine Receptors

Nicotinic acetylcholine receptors (nAChRs) are ion channels that are expressed in the cell membrane of all mammalian cells, including cancer cells. Recent findings suggest that nAChRs not only mediate nicotine addiction in the brain but also contribute to the development and progression of cancers directly induced by nicotine and its derived carcinogenic nitrosamines whereas deregulation of the nAChRs is observed in many cancers, and genome-wide association studies (GWAS) indicate that SNPs nAChRs associate with risks of lung cancers and nicotine addiction. Emerging evidences suggest nAChRs are posited at the central regulatory loops of numerous cell growth and prosurvival signal pathways and also mediate the synthesis and release of stimulatory and inhibitory neurotransmitters induced by their agonists. Thus nAChRs mediated cell signaling plays an important role in stimulating the growth and angiogenic and neurogenic factors and mediating oncogenic signal transduction during cancer development in a cell type specific manner. In this review, we provide an integrated view of nAChRs signaling in cancer, heightening on the oncogenic properties of nAChRs that may be targeted for cancer treatment.

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Competitive binding of anticancer drugs 5-fluorouracil and cyclophosphamide with serum albumin: Calorimetric insights

Publication date: Available online 6 February 2016
Source:Biochimica et Biophysica Acta (BBA) - General Subjects
Author(s): Anu A. Thoppil, Sinjan Choudhary, Nand Kishore
BackgroundIsothermal titration calorimetry (ITC) has emerged as an excellent method to characterize drug–protein interactions. 5-Fluorouracil and cyclophosphamide have been used in combination for the treatment of breast carcinoma, though individually these drugs have also been useful in treating other types of cancer. A quantitative understanding of binding of these drugs with the transport protein under different conditions is essential for optimizing recognition by the protein and delivery at the target.MethodsThe values of binding constant, enthalpy, and entropy of binding have been determined by using ITC. Fluorescence and circular dichroism spectroscopies have been used to obtain further support to calorimetric observations, monitor conformational changes in the protein and establishing stoichiometry of association.ResultsThe thermodynamic parameters have enabled a quantitative understanding of the affinity of 5-fluorouracil and cyclophosphamide with bovine serum albumin. The nature of binding has been unraveled based on effect of ionic strength, tetrabutyl-ammonium bromide, and sucrose which interfere in ionic, hydrophobic, and hydrogen bonding interactions. The binding site has been identified by using site marker warfarin in combination with 5-fluorouracil and cyclophosphamide. Further, the experiments have been done to establish whether both the drugs share the same binding site, and the effect of antibiotic drug carbenecillin and anti-inflammatory drug naproxen on their association.General significanceTuning optimum association of drugs with the transport vehicles for effective drug delivery requires identification of the nature of interacting groups in terms of energetics of interactions. Such studies employing ITC have direct significance in rational drug design. This article is part of a Special Issue entitled Microcalorimetry in the BioSciences — Principles and Applications, edited by Fadi Bou-Abdallah.

Graphical abstract

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Is there too much stress on stress? - The Guardian


The Guardian

Is there too much stress on stress?
The Guardian
Most had fever (sometimes with mental confusion), an enlarged spleen or liver, inflamed tonsils, a skin rash and so forth…”. Moreover .... Cooper wrote a book examining the links between such emotional stress and cancer (links that are debatable ...



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Team limber up for Cancer Centre Campaign - Gazette


Gazette

Team limber up for Cancer Centre Campaign
Gazette
"Through all the hardship, chemotherapy, radiotherapy, having to be feed through a tube and many, many hospital appointments, he came out at the end having kicked cancer. "We want to raise as much money as we can for the cancer centre at Colchester ...



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Vil sette legers verdier i spill

Som leder for Skottlands allmennleger vil Miles Mack sikre tjenestene via bevisstgjort indre motivasjon snarere enn gamle, ytre reguleringer.

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Protective effects of retinoid x receptors on retina pigment epithelium cells

Publication date: Available online 13 February 2016
Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
Author(s): VictoriaBelén Ayala-Peña, Fiorella Pilotti, Yanel Volonté, Nora P. Rotstein, Luis E. Politi, Olga Lorena German
Age-related macular degeneration (AMD) is among the main pathologies leading to blindness in adults and has currently no cure or effective treatment. Selective apoptosis of retina pigment epithelial (RPE) cells results in the progressive loss of photoreceptor neurons, with the consequent gradual vision loss. Oxidative stress plays an important role in this process. We have previously determined that activation of RXRs protects rat photoreceptor neurons from oxidative stress- induced apoptosis. In this study we investigated whether RXR ligands prevented apoptosis in an RPE cell line, D407 cells, exposed to hydrogen peroxide (H2O2). H2O2 induced apoptosis of D407 cells, promoting p65NFκB nuclear translocation, increasing Bax mRNA expression, activating caspase-3 and altering cell morphology. We show, for the first time, that HX630, a RXR pan-agonist, protected D407 cells from H2O2-induced apoptosis, preventing p65NFκB nuclear translocation, increasing Bclxl and PPARγ mRNA levels and simultaneously decreasing Bax mRNA levels and caspase-3 activation. Pretreatment with a RXR antagonist blocked HX630 protection. LG100754, which binds RXRs but only activates heterodimers and is an antagonist of RXR homodimers, also had a protective effect. In addition, only agonists known to bind to RXR/PPARγ were protective. As a whole, our results suggest that RXR activation protects RPE cells from oxidative stress-induced apoptosis and this protection might involve signaling through a heterodimeric receptor, such as RXR/PPARγ. These data also imply that RXR agonists might provide potential pharmacological tools for treating retina degenerative diseases.



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IJMS, Vol. 17, Pages 36: Drosophotoxicology: An Emerging Research Area for Assessing Nanoparticles Interaction with Living Organisms

The rapid development of nanotechnology allowed the fabrication of a wide range of different nanomaterials, raising many questions about their safety and potential risks for the human health and environment. Most of the current nanotoxicology research is not standardized, hampering any comparison or reproducibility of the obtained results. Drosophotoxicology encompasses the plethora of methodological approaches addressing the use of Drosophila melanogaster as a choice organism in toxicology studies. Drosophila melanogaster model offers several important advantages, such as a relatively simple genome structure, short lifespan, low maintenance cost, readiness of experimental manipulation comparative to vertebrate models from both ethical and technical points of view, relevant gene homology with higher organisms, and ease of obtaining mutant phenotypes. The molecular pathways, as well as multiple behavioral and developmental parameters, can be evaluated using this model in lower, medium or high throughput type assays, allowing a systematic classification of the toxicity levels of different nanomaterials. The purpose of this paper is to review the current research on the applications of Drosophila melanogaster model for the in vivo assessment of nanoparticles toxicity and to reveal the huge potential of this model system to provide results that could enable a proper selection of different nanostructures for a certain biomedical application.

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Cholesteatoma growth patterns: are there audiometric differences between posterior epitympanic and posterior mesotympanic cholesteatoma?

Abstract

The objective of this is to verify whether the hearing impairment caused by posterior epitympanic differed from that caused by posterior mesotympanic cholesteatomas by a cross-sectional study. We evaluated 264 ears of patients with cholesteatoma, who had not been subjected to ear surgery. Otoendoscopy and pure-tone audiometry were performed. Analyzed route involved in cholesteatoma formation: posterior epitympanic or posterior mesotympanic, air–bone gaps at 512–4000 Hz and pure-tone averages. The mean age of the patients enrolled in this study was 33.8 years, and 51.8 % of them was male. Posterior epitympanic cholesteatoma was found in 50.4 % of the study population. When the air–bone gaps were compared, the mesotympanic group had greater thresholds at 500, 2000 Hz, and a greater pure-tone average (P = 0.003, P = 0.03, and P = 0.02, respectively). Posterior mesotympanic cholesteatoma showed greater air–bone gaps thresholds at the speech frequencies than posterior epitympanic cholesteatoma did. Moreover, the two growth patterns were very similar with regard to all other audiometric parameters analyzed in this study.



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Autophagy protects podocytes from sublytic complement induced injury

Publication date: Available online 13 February 2016
Source:Experimental Cell Research
Author(s): Qianying Lv, Fengjie Yang, Kun Chen, Yu Zhang
Podocyte injury induced by sublytic complement attack is the main feature of membranous nephropathy (MN). This study aimed at investigating the impact of sublytic complement attack-related autophagy on podocyte injury in vitro. Here, we show that sublytic complement attack enhances MPC5 podocyte autophagy in vitro. Inhibition of autophagy by treatment with 3-methyladenine (3-MA) significantly increased sublytic complement attack-induced changes in the injury-related morphology, stress fibre, and podocyte apoptosis, but decreased the survival and adhesion of MPC5 podocytes. In contrast, promotion of autophagy by treatment with rapamycin mitigated sublytic complement attack-induced changes in the injury-related morphology, stress fibre, and podocyte apoptosis, but increased the survival and adhesion of MPC5 podocytes. These data suggest that autophagy may protect podocytes from sublytic complement attack-induced injury in vitro.



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Real Gems for Valentine's Day

Love-of-the-Sea-courtesy-of-Nomadic.jpg

Let's explore some shiny and huggable geology!

-- Read more on ScientificAmerican.com
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Pathogens, Vol. 5, Pages 19: Why Serological Responses during Cystitis are Limited

The high frequency of urinary tract infections (UTIs), some of which appear to be endogenous relapses rather than reinfections by new isolates, point to defects in the host’s memory immune response. It has been known for many decades that, whereas kidney infections evoked an antibody response to the infecting bacteria, infections limited to the bladder failed to do so. We have identified the existence of a broadly immunosuppressive transcriptional program associated with the bladder, but not the kidneys, during infection of the urinary tract that is dependent on bladder mast cells. This involves the localized secretion of IL-10 and results in the suppression of humoral immune responses in the bladder. Mast cell-mediated immune suppression could suggest a role for these cells in critically balancing the needs to clear infections with the imperative to prevent harmful immune reactions in the host.

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Pathogens, Vol. 5, Pages 20: Histone Deacetylase 6 Regulates Bladder Architecture and Host Susceptibility to Uropathogenic Escherichia coli

Histone deacetylase 6 (HDAC6) is a non-canonical, mostly cytosolic histone deacetylase that has a variety of interacting partners and substrates. Previous work using cell-culture based assays coupled with pharmacological inhibitors and gene-silencing approaches indicated that HDAC6 promotes the actin- and microtubule-dependent invasion of host cells by uropathogenic Escherichia coli (UPEC). These facultative intracellular pathogens are the major cause of urinary tract infections. Here, we examined the involvement of HDAC6 in bladder colonization by UPEC using HDAC6 knockout mice. Though UPEC was unable to invade HDAC6−/− cells in culture, the bacteria had an enhanced ability to colonize the bladders of mice that lacked HDAC6. This effect was transient, and by six hours post-inoculation bacterial titers in the HDAC6−/− mice were reduced to levels seen in wild type control animals. Subsequent analyses revealed that the mutant mice had greater bladder volume capacity and fluid retention, along with much higher levels of acetylated -tubulin. In addition, infiltrating neutrophils recovered from the HDAC6−/− bladder harbored significantly more viable bacteria than their wild type counterparts. Cumulatively, these changes may negate any inhibitory effects that the lack of HDAC6 has on UPEC entry into individual host cells, and suggest roles for HDAC6 in other urological disorders such as urinary retention.

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