Disruption of aromatase homeostasis as the cause of a multiplicity of ailments: A comprehensive review

Publication date: Available online 18 January 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Seema Patel
Human health is beset with a legion of ailments, which is exacerbated by the lifestyle errors. Out of the numerous enzymes in human body, aromatase, a cytochromes P450 enzyme is particularly very critical. Occurring at the crossroads of multiple signalling pathways, its homeostasis is vital. Unfortunately, medications, hormone therapy, chemical additives in food, and endocrine-disrupting personal care products are oscillating the aromatase concentration beyond the permissible level. As this enzyme converts androgens (C19) into estrogens (C18), its agitation has different outcomes in different genders and age groups. Some common pathologies associated with aromatase disruption include breast cancer, prostate cancer, polycystic ovary syndrome (PCOS), endometriosis, osteoporosis, ovarian cancer, gastric cancer, pituitary cancer, Alzheimer's disease, schizophrenia, male hypogonadism, and transgender issues. Several drugs, personal consumer products and pesticides act as the activators and suppressors of this vital enzyme. This carefully-compiled critical review is expected to increase public awareness regarding the threats resultant of the perturbations of this enzyme and to motivate researchers to further investigate this field.



http://ift.tt/2iM5I5S

p-Aminothiophenol-coated CdSe/ZnS quantum dots as a turn-on fluorescent probe for pH detection in aqueous media

Publication date: 1 May 2017
Source:Talanta, Volume 166
Author(s): Dong Li, Hu Xu, Dan Li, Yuhong Wang
Since controlling hydrogen ion concentration (i.e. pH) is fairly important in various fields, developing a facile pH detection method is highly desired. Owing to the superior optical properties, semiconductor quantum dots (QDs) have been developed as a promising alternative for organic fluorophores in fluorescence analysis. In this study, a hydrophilic p-aminothiophenol (pATP) capped CdSe/ZnS QDs (denoted as pATP-QDs) as a selective "turn-on" fluorescence probe for pH in aqueous media is reported. The pATP-QDs probe easily obtained via ligand exchange are characterized by various analytic techniques including ultraviolet-visible, fourier transform infrared, fluorescence, time-resolved fluorescence spectroscopies, and transmission electron microscope etc. pATP-QDs exhibits weak fluorescence since pATP acts as an effective hole trapper. As an organic base, pATP easily binds to proton and the formation of pATP-H⁺ complex alters the energetic position of HOMO for pATP, which enables pATP-QDs unfavorable for the effective hole transfer. Thus, the QDs photoluminescence (PL) was switched on. PL "off-on" mode, high PL quantum yield of QDs as well as extremely high stability of pATP-H⁺ complex (logKs =7.47) enables pATP-QDs to exhibit an excellent pH detection performance. Under optimal conditions, the present probe exhibits a good linear relationship between fluorescence response and pH values in pH range 3.2–6.0. Furthermore, the present probe exhibits a high selectivity for proton over other common cations and has been successfully used for pH detection in real water samples.

Graphical abstract

http://ift.tt/2jqoZfl

Clinical and biological effects of demethylating agents on solid tumours – a systematic review

Publication date: Available online 18 January 2017
Source:Cancer Treatment Reviews
Author(s): J.F. Linnekamp, R. Butter, R. Spijker, J.P. Medema, H.W.M. van Laarhoven
[Background]It is assumed that DNA methylation plays a key role in both tumour development and therapy resistance. Demethylating agents have been shown to be effective in the treatment of haematological malignancies. Based on encouraging preclinical results, demethylating agents may also be effective in solid tumours. This systematic review summarizes the evidence of the effect of demethylating agents on clinical response, methylation and the immune system in solid tumours.[Methods]We conducted a systematic literature search from 1949 to December 2016, according to the PRISMA guidelines. Studies which evaluated treatment with azacitidine, decitabine, guadecitabine, hydralazine, procaine, MG98 and/or zebularine in patients with solid tumours were included. Data on clinical response, effects on methylation and immune response were extracted.[Results]Fifty eight studies were included: in 13 studies complete responses (CR) were observed, 35 studies showed partial responses (PR), 47 studies stable disease (SD) and all studies except two showed progressive disease (PD). Effects on global methylation were observed in 11/15 studies and demethylation/re-expression of tumour specific genes was seen in 15/17 studies. No clear correlation between (de)methylation and clinical response was observed. In 14 studies immune-related responses were reported, such as re-expression of cancer-testis antigens and upregulation of interferon genes.[Conclusion]Demethylating agents are able to improve clinical outcome and alter methylation status in patients with solid tumours. Although beneficial effect has been shown in individual patients, overall response is limited. Further research on biomarker predicting therapy efficacy is indicated, particularly in earlier stage and highly methylated tumours.



http://ift.tt/2k2OwKv

Evaluation of remediation techniques in soils affected by residual contamination with heavy metals and arsenic

Publication date: 15 April 2017
Source:Journal of Environmental Management, Volume 191
Author(s): M. García-Carmona, A. Romero-Freire, M. Sierra Aragón, F.J. Martínez Garzón, F.J. Martín Peinado
Residual soil pollution from the Aznalcóllar mine spill is still a problem in some parts of the affected area, today converted in the Guadiamar Green Corridor. Dispersed spots of polluted soils, identified by the absence of vegetation, are characterized by soil acid pH and high concentrations of As, Pb, Cu and Zn. Ex situ remediation techniques were performed with unrecovered soil samples. Landfarming, Composting and Biopiles techniques were tested in order to immobilize pollutants, to improve soil properties and to promote vegetation recovery. The effectiveness of these techniques was assessed by toxicity bioassays: Lactuca sativa L. root elongation test, Vibrio fischeri bioluminescence reduction test, soil induced respiration test, and Eisenia andrei survival and metal bioaccumulation tests. Landfarming and Composting were not effective techniques, mainly due to the poor improvement of soil properties which maintained high soluble concentrations of Zn and Cu after treatments. Biopile technique, using adjacent recovered soils in the area, was the most effective action in the reduction of soil toxicity; the improvement of soil properties and the reduction in pollutants solubility were key to improve the response of the tested organisms. Therefore, the mixture of recovered soils with polluted soils in the areas affected by residual contamination is considered a more suitable technique to reduce the residual pollution and to promote the complete soil recovery in the Guadiamar Green Corridor.



http://ift.tt/2jqsPVv

Amplified using DNase I and aptamer/graphene oxide for sensing prostate specific antigen in human serum

Publication date: June 2017
Source:Sensors and Actuators B: Chemical, Volume 244
Author(s): Bi-Yun Fang, Chun-Yuan Wang, Cheng Li, Hai-Bo Wang, Yuan-Di Zhao
In this paper, we proposed an amplified assay using DNase I for sensitively sensing prostate specific antigen (PSA) based on CdSe/ZnS quantum dot labelled PSA aptamer/graphene oxide (QD-aptamer/GO). In this sensing system, GO could strongly bind QD conjugated aptamer and quench the fluorescence of QD, furthermore, GO could protect DNA from nuclease cleavage. When binding target PSA, aptamer probe released from the surface of GO nanosheet, then the free aptamer could be cleaved by nuclease, thus the QD and PSA were liberated, after that, the released PSA would bind another aptamer on GO nanosheet and start a new cycle, which resulted in amplification of restoring signal. The probe possessed steady fluorescence signal and high specificity due to the anti photobleaching of QD and the high affinity of aptamer to PSA. Under the optimum experimental conditions, fluorescence intensity increased linearly with the PSA concentration between 0.1fgmL⁻¹ and 3fgmL⁻¹ with the limit of quantification of 0.05fgmL⁻¹, which was three orders of magnitude lower than that without DNase I. Finally, the method was applied to quantification of PSA in human serum samples.



http://ift.tt/2jAak3K

Fatigue cracking characteristics of fiber Laser-VPTIG hybrid butt welded 7N01P-T4 aluminum alloy

Publication date: May 2017
Source:International Journal of Fatigue, Volume 98
Author(s): J.N. Qiao, J.X. Lu, S.K. Wu
In this paper, 4mm-thick AA7N01P-T4 was welded using fiber laser-variable polarity tungsten inert gas (VPTIG) hybrid welding with filler wire. After natural aging of 60days, microstructures and fatigue properties of hybrid welding joints were investigated by Optical Microscope (OM), Scanning Electron Microscope (SEM) equipped with Energy-Dispersive Spectroscopy (EDS), Transmission Electron Microscope (TEM), Electron Back Scattered Diffraction (EBSD) and high-cycle fatigue & fatigue cracking growth rate testing. The effect of reinforcement on the fatigue behavior was also investigated. The experimental results shown that natural aging induced the amount of precipitates enriched with Zn and Mg and the dislocation density in the joint to increase, and the precipitates distributing mainly along to the grain boundaries. Welding reinforcement has significant effect on the fatigue limit. The fatigue limit of joint with reinforcement is 115MPa and the fatigue crack is initiated along to the weld toe. Whereas, joints without reinforcement show the fatigue limit of 160MPa and the fatigue crack initiation and final fracture both in weld center. For the same aging weld without reinforcement, natural aging caused the fatigue crack growth rate to slow down compared to as-welded joint, which be equivalent to that of heat-affected zone (HAZ) and BM.

Graphical abstract

http://ift.tt/2jqu9rC

Fabrication of a novel NiFe2O4/Zn-Al layered double hydroxide intercalated with EDTA composite and its adsorption behavior for Cr(VI) from aqueous solution

Publication date: May 2017
Source:Journal of Physics and Chemistry of Solids, Volume 104
Author(s): Lin Deng, Zhou Shi, Li Wang, Shiqing Zhou
A novel magnetic NiFe2O4/Zn-Al layered double hydroxide intercalated with EDTA composite (NiFe2O4/ZnAl-EDTA LDH) was prepared through modified coprecipitation method and employed for adsorptive removal of Cr(VI) from aqueous solution. The adsorbents were characterized using Brunauer-Emmett-Teller (BET), scanning electron microscopy (SEM), transmission electron microscope (TEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), vibrating sample magnetometer (VSM), and X-ray photoelectron spectroscopy (XPS). Factors affecting the Cr(VI) adsorption, such as initial solution pH, adsorbent dosage, contact time, initial Cr(VI) concentration, temperature and coexisting ions, were studied systematically. Experiments results show that the magnetic NiFe2O4/ZnAl-EDTA LDH exhibits high adsorption efficiency within a wide pH range of 3.0–7.0 (R>80% at Cr(VI) concentration 50mgL⁻¹, contact time 360min, and adsorbent dosage 2g/L) and quick separation property. The adsorption process is fitted well with the Langmuir isotherm and pseudo-second-order kinetic model. The maximum theoretical adsorption capacity is found to be 77.22mgg⁻¹ at pH 6.0 and 318K. The positive ΔH value (2.907kJmol⁻¹) and negative ΔG value (−4.722kJmol⁻¹) at 298–318K reveals that the adsorption process is feasible, spontaneous and endothermic. Coexisting anions (PO4^3-, SO4²⁻, CO3²⁻, HCO3⁻, Cl⁻, and NO3⁻) have no significant effect on Cr(VI) removal. The mechanism study indicates that the adsorption of Cr(VI) onto NiFe2O4/ZnAl-EDTA LDH mainly involves electrostatic attraction and ion exchange interaction. It is interesting to note that a proportion of Cr(VI) adsorbed on the adsorbent surface are reduced to Cr(III) during the adsorption process. Results from this study demonstrate the potential utility of the magnetic NiFe2O4/ZnAl-EDTA LDH that could be developed into a viable technology for efficient removal of Cr(VI) from aqueous solution.



http://ift.tt/2jqxeIb

Sleep loss and structural plasticity

Publication date: June 2017
Source:Current Opinion in Neurobiology, Volume 44
Author(s): Cassandra C. Areal, Simon C. Warby, Valérie Mongrain
Wakefulness and sleep are dynamic states during which brain functioning is modified and shaped. Sleep loss is detrimental to many brain functions and results in structural changes localized at synapses in the nervous system. In this review, we present and discuss some of the latest observations of structural changes following sleep loss in some vertebrates and insects. We also emphasize that these changes are region-specific and cell type-specific and that, most importantly, these structural modifications have functional roles in sleep regulation and brain functions. Selected mechanisms driving structural modifications occurring with sleep loss are also discussed. Overall, recent research highlights that extending wakefulness impacts synapse number and shape, which in turn regulate sleep need and sleep-dependent learning/memory.



http://ift.tt/2k2VfUR

Patient with Rising Thyroglobulin : Hodgkin's Lymphoma,Thyroid Cancer

Patient with Rising Thyroglobulin : Hodgkin's Lymphoma,Thyroid Cancer

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Tumor Evolution: Linear, Branching, Neutral or Punctuated?

Publication date: Available online 19 January 2017
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Alexander Davis, Ruli Gao, Nicholas Navin
Intratumor heterogeneity has been widely reported in human cancers, but our knowledge of how this genetic diversity emerges over time remains limited. A central challenge in studying tumor evolution is the difficulty in collecting longitudinal samples from cancer patients. Consequently, most studies have inferred tumor evolution from single time-point samples, providing very indirect information. These data have led to several competing models of tumor evolution: linear, branching, neutral and punctuated. Each model makes different assumptions regarding the timing of mutations and selection of clones, and therefore has different implications for the diagnosis and therapeutic treatment of cancer patients. Furthermore, emerging evidence suggests that models may change during tumor progression or operate concurrently for different classes of mutations. Finally, we discuss data that supports the theory that most human tumors evolve from a single cell in the normal tissue. This article is part of a Special Issue entitled: Evolutionary principles - heterogeneity in cancer?, edited by Dr. Robert A. Gatenby.



http://ift.tt/2jbapr3

Cancer cell metabolism and mitochondria: nutrient plasticity for TCA cycle fueling

Publication date: Available online 18 January 2017
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Cyril Corbet, Olivier Feron
Warburg's hypothesis that cancer cells take up a lot of glucose in the presence of ambient oxygen but convert pyruvate into lactate due to impaired mitochondrial function led to the misconception that cancer cells rely on glycolysis as their major source of energy. Most recent ¹³C–based metabolomic studies, including in cancer patients, indicate that cancer cells may also fully oxidize glucose. In addition to glucose-derived pyruvate, lactate, fatty acids and amino acids supply substrates to the TCA cycle to sustain mitochondrial metabolism. Here, we discuss how the metabolic flexibility afforded by these multiple mitochondrial inputs allows cancer cells to adapt according to the availability of the different fuels and the microenvironmental conditions such as hypoxia and acidosis. In particular, we focused on the role of the TCA cycle in interconnecting numerous metabolic routes in order to highlight metabolic vulnerabilities that represent attractive targets for a new generation of anticancer drugs.



http://ift.tt/2k5WE18

The dangers of parathyroid biopsy

Thoracic outlet mass presenting with severe biochemical hyperparathyroidism and classic hypercalcemic symptoms of renal and bone involvement.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Masthead

Publication date: January–February 2017
Source:Brachytherapy, Volume 16, Issue 1





http://ift.tt/2iLII79

Table of Contents

Publication date: January–February 2017
Source:Brachytherapy, Volume 16, Issue 1





http://ift.tt/2iTTtb0

Editorial Board

Publication date: January–February 2017
Source:Brachytherapy, Volume 16, Issue 1





http://ift.tt/2iLPKbZ

American Brachytherapy Task Group Report: A pooled analysis of clinical outcomes for high-dose-rate brachytherapy for cervical cancer

Publication date: January–February 2017
Source:Brachytherapy, Volume 16, Issue 1
Author(s): Jyoti Mayadev, Akila Viswanathan, Yu Liu, Chin-Shang Li, Kevin Albuquerque, Antonio L. Damato, Sushil Beriwal, Beth Erickson
PurposeAdvanced imaging used in combination with brachytherapy (BT) has revolutionized the treatment of patients with cervical cancer. We present a comprehensive review of the literature for definitive radiation with high-dose-rate (HDR) BT. In addition, we investigate potential outcome improvement with image-based brachytherapy (IBBT) compared to studies using traditional Point A dosing. This review extensively investigates acute and late toxicities.Methods and MaterialsThis study reviews the literature from 2000 to 2015 with an emphasis on modern approaches including concurrent chemotherapy (chemoRT), radiation, and HDR BT and IBBT. Descriptive statistics and pelvic control (PC), disease-free survival (DFS), and overall survival (OS) outcomes were calculated using weighted means to report pooled analysis of outcomes.ResultsLiterature search yielded 16 prospective, 51 retrospective studies that reported survival outcomes, and 13 retrospective studies that focused on acute and late toxicity outcomes regardless of applicator type. There are 57 studies that report Point A dose specification with 33 having chemoRT, and 10 studies that use IBBT, 8 with chemoRT. Patients receiving radiation and chemoRT with HDR BT in the prospective studies, with >24 months followup, rates of PC were: for RT: 73%, SD: 11; CRT: 82%, SD: 8; DFS—RT: 55%, SD: 10; CRT: 65%, SD: 7; OS—RT: 66%, SD: 7; CRT: 70%, SD: 11. In the retrospective studies, the PC rates (weighted means) for the radiation and chemoradiation outcomes are 75% vs. 80%, and for DFS, the values were 55% vs. 63%, respectively. Comparing patients receiving chemoRT and IBBT to traditional Point A dose specification, there is a significant improvement in PC (p < 0.01) and DFS (p < 0.01) with IBBT. The range of genitourinary late toxicity reported for radiation was Grade 3: 1–6% and for chemoRT 2–20%. The range of late gastrointestinal toxicity for radiation was Grade 3: 4–11% and for chemoRT, 1–11%. For the late gynecologic toxicity, only 1 of the 16 prospective trials report a Grade 1–2 of 17% for radiation and 9% for chemoRT effects.ConclusionsWe present concise outcomes of PC, DFS, OS, and toxicity for cervical cancer patients treated with chemoradiation and HDR BT. Our data suggest an improvement in outcomes with the use of IBBT compared with traditional Point A dose prescriptions. In conclusion, HDR BT is a safe, effective modality when combined with IBBT.



http://ift.tt/2iU1ufM

The American College of Radiology and the American Brachytherapy Society practice parameter for transperineal permanent brachytherapy of prostate cancer

Publication date: January–February 2017
Source:Brachytherapy, Volume 16, Issue 1
Author(s): Nathan H.J. Bittner, Peter F. Orio, Gregory S. Merrick, Bradley R. Prestidge, Alan Charles Hartford, Seth A. Rosenthal
Transperineal permanent brachytherapy is a safe and effective treatment option for patients with organ-confined prostate cancer. Careful adherence to established brachytherapy standards has been shown to improve the likelihood of procedural success and reduce the incidence of treatment-related morbidity. A collaborative effort of the American College of Radiology (ACR) and the American Brachytherapy Society (ABS) has produced practice parameters for LDR prostate brachytherapy. These practice parameters define the qualifications and responsibilities of all the involved personnel, including the radiation oncologist, physicist and dosimetrist. Factors with respect to patient selection and appropriate use of supplemental treatment modalities such as external beam radiation and androgen suppression therapy are discussed. Logistics with respect to the brachytherapy implant procedure, the importance of dosimetric guidelines, and attention to radiation safety procedures and documentation are presented. Adherence to these parameters can be part of ensuring quality and safety in a successful prostate brachytherapy program.



http://ift.tt/2iLECfu

The American College of Radiology and the American Brachytherapy Society practice parameter for the performance of low-dose-rate brachytherapy

Publication date: January–February 2017
Source:Brachytherapy, Volume 16, Issue 1
Author(s): Akila N. Viswanathan, Beth A. Erickson, Geoffrey S. Ibbott, William Small, Patricia J. Eifel
Brachytherapy is the use of radionuclides to treat malignancies or benign conditions by means of a radiation source placed close to or into the tumor or treatment site. This practice parameter refers only to the use of radionuclide brachytherapy. Brachytherapy alone or combined with external beam therapy plays an important role in the management and treatment of patients with cancer. Low-dose-rate (LDR) brachytherapy has traditionally been used for treating prostate, head and neck, breast, cervical, and endometrial cancers as well as obstructive bile duct, esophageal, or bronchial lesions. It has been practiced for over a century with a variety of sources including radium-226, cesium-137, and, more recently, iridium- 192, iodine-125, and palladium-103. Low-dose-rate (LDR) brachytherapy can be given as interstitial, intracavitary, intraluminal, and/or plesiotherapy to a wide variety of treatment sites. This practice parameter addresses sealed sources as they are used for LDR brachytherapy. It is recognized that unsealed sources (e.g., yttrium-90) are also a form of LDR brachytherapy.



http://ift.tt/2iU5HQX

The American College of Radiology and the American Brachytherapy Society practice parameter for the performance of radionuclide-based high-dose-rate brachytherapy

Publication date: January–February 2017
Source:Brachytherapy, Volume 16, Issue 1
Author(s): Beth A. Erickson, Nathan H.J. Bittner, Manjeet Chadha, Firas Mourtada, D. Jeffrey Demanes
Brachytherapy is a radiation therapy method in which radionuclide sources are used to deliver a radiation dose at a distance of up to a few centimeters by surface, intracavitary, intraluminal, or interstitial application. This practice parameter refers only to the use of radionuclides for brachytherapy. Brachytherapy alone or combined with external beam therapy plays an important role in the management and treatment of patients with cancer. High-dose-rate (HDR) brachytherapy uses radionuclides such as iridium-192 at dose rates of 20 cGy per minute (12 Gy per hour) or more to a designated target point or volume. High-dose-rate (HDR) brachytherapy is indicated for treating malignant or benign tumors where the treatment volume or targeted points are defined and accessible.



http://ift.tt/2iLCVi1

Imaging of Intracranial and Orbital Complications of Sinusitis and Atypical Sinus Infection: What the Radiologist Needs to Know

Publication date: Available online 18 January 2017
Source:Current Problems in Diagnostic Radiology
Author(s): Vinodkumar Velayudhan, Zeshan A. Chaudhry, Wendy R.K. Smoker, Roman Shinder, Deborah Reede
Sinusitis is a common disease. Complications, however, are less common and can be life threatening. Major complications occur from extension of disease into the orbit and intracranial compartment and often require emergent treatment with intravenous antibiotics or operative intervention. Immunocompromised patients with acute sinusitis are susceptible to atypical infections, such as invasive fungal sinusitis, which is a surgical emergency. Therefore, it is important to accurately and promptly identify potentional complications of acute sinusitis to ensure appropriate treatment and minimize negative outcomes. This article reviews the imaging features of a spectrum of complications associated with acute sinusitis and atypical infections.



http://ift.tt/2iTIcqQ

Vasculature Characterization of a Multiterritory Perforator Flap: An Experimental Study

J reconstr Microsurg
DOI: 10.1055/s-0036-1598011

Background Tip necrosis in the perforator flap is a significant problem in clinical practice. This study aimed to characterize the vasculature of a multiterritory perforator flap using a rat model and to investigate the impact of the vasculature on flap survival. Methods In total, 105 Sprague Dawley rats were divided into seven groups, including the control, 3 hours postoperative (PO), 12 hours PO, 1 day PO, 3 days PO, 5 days PO, and 7 days PO. A perforator flap with three territories based on the deep iliac circumflex artery was performed. Flaps with only skin incisions and vessel exposure were performed in the control group. The first choke zone (FCZ) was located between the anatomical and dynamic territories, and the second choke zone (SCZ) was located between the dynamic and potential territories. Sodium fluorescein and lead oxide-gelatin angiography and histological examination were performed in each group. Results Sodium fluorescein angiography revealed delayed staining in the perforator flap PO, particularly in the FCZ and SCZ. The delay phenomenon disappeared after 12 hours PO in the FCZ and after 1 day PO in the SCZ. Nonfluorescein-stained areas were found distal to the potential territory. In the FCZ PO, the choke vessels were dilated, while the number of microvessels was increased in the SCZ without choke vessel dilation. Conclusions The remodeling of choke vessels and increase in microvessel number represent arteriogenesis and angiogenesis, respectively. This neovascularization was responsible for flap survival in the entire dynamic territory and part of the potential territory.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2iTF3Ys

Functional Outcome of CAD/CAM-Assisted versus Conventional Microvascular, Fibular Free Flap Reconstruction of the Mandible: A Retrospective Study of 30 Cases

J reconstr Microsurg
DOI: 10.1055/s-0036-1597823

Background Different advantages of virtually planned and guided mandibular reconstructions have been described. Functional analyses and comparisons with conventionally reconstructed patients. Methods We retrospectively analyzed 30 cases of mandibular reconstructions that involved virtually planned or conventional microvascular, fibular free flaps that occurred between April 2011 and December 2014 at a single center. The results were also compared with a healthy cohort of 30 participants. Axiographic measurements were performed postoperatively, and uni- and multivariate regressions analyses were performed to determine the association between possible predictor variables on functional outcome. Results Operation time, hospital stay, number of osteotomies, incidence of postoperative temporomandibular joint pain, noise, and tension did not differ significantly between the conventional and computer-aided design/computer-aided manufacturing (CAD/CAM) groups (each p > 0.05). Mouth opening and protrusion and laterotrusion also did not differ significantly (each p > 0.05) but were significantly reduced compared with the healthy group. Univariate analysis showed a significant influence of postoperative irradiation on mouth opening and laterotrusion in the conventional group (p = 0.047 and p = 0.028). In addition, multivariate analysis showed a significant influence of indication and number of osteotomies on laterotrusion (p = 0.005 and p = 0.043). Uni and multivariate analyses revealed a significant influence of indication, preoperative irradiation, and number of osteotomies on protrusion and mouth opening in the CAD/CAM group (p = 0.016, p = 0.044, and p = 0.028). Conclusion CAD/CAM-assisted reconstructions of the mandible give comparable functional results with those of the conventional technique, but no functional superiority has been established. Nevertheless, the integration of virtual planning and guided surgery is definitely of significant value but should be indicated individually case by case.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2iTGhD1

Cross-Lingual Neighborhood Effects in Generalized Lexical Decision and Natural Reading.

Author: Dirix, Nicolas; Cop, Uschi; Drieghe, Denis; Duyck, Wouter

DOI: 10.1037/xlm0000352

Publication Date: POST AUTHOR CORRECTIONS, 16 January 2017

http://ift.tt/2iTMRZV

Investigating Developmental Trajectories of Morphemes as Reading Units in German.

Author: Hasenacker, Jana; Schroter, Pauline; Schroeder, Sascha

DOI: 10.1037/xlm0000353

Publication Date: POST AUTHOR CORRECTIONS, 16 January 2017

http://ift.tt/2jpAhAh

Test Expectancy and Memory for Important Information.

Author: Middlebrooks, Catherine D.; Murayama, Kou; Castel, Alan D.

DOI: 10.1037/xlm0000360

Publication Date: POST AUTHOR CORRECTIONS, 16 January 2017

http://ift.tt/2iTB4Ld

How Our Own Speech Rate Influences Our Perception of Others.

Author: Bosker, Hans Rutger

DOI: 10.1037/xlm0000381

Publication Date: POST AUTHOR CORRECTIONS, 16 January 2017

http://ift.tt/2jpxqYf

Editorial Board

Publication date: February 2017
Source:Dental Materials, Volume 33, Issue 2





http://ift.tt/2iTyuoy

Editorial board

Publication date: 27 January 2017
Source:Polymer, Volume 109





http://ift.tt/2jaJGee

Graphical Contents list & Author index

Publication date: 27 January 2017
Source:Polymer, Volume 109





http://ift.tt/2jzlfdS

Can the Structure of Motor Variability Predict Learning Rate?.

Author: Barbado Murillo, David; Caballero Sanchez, Carla; Moreside, Janice; Vera-Garcia, Francisco J.; Moreno, Francisco J.

DOI: 10.1037/xhp0000303

Publication Date: POST AUTHOR CORRECTIONS, 16 January 2017

http://ift.tt/2iLiHFd

Identifying Stimuli That Cue Multiple Responses Triggers the Congruency Sequence Effect Independent of Response Conflict.

Author: Weissman, Daniel H.; Colter, Katelyn M.; Grant, Lauren D.; Bissett, Patrick G.

DOI: 10.1037/xhp0000350

Publication Date: POST AUTHOR CORRECTIONS, 16 January 2017

http://ift.tt/2iLdYDg

Diagnostic validity of ICDAS and DIAGNOdent combined: an in vitro study in pre-cavitated lesions

Abstract

In a continuous process such as caries, it is important to possess criteria or instruments that allow the lesions to be diagnosed at early stages so that preventive or interceptive treatments can be applied before cavitation takes place. The present study seeks to assess the diagnostic efficacy of the International Caries Detection and Assessment System (ICDAS II) criteria and the DIAGNOdent laser fluorescence (LF) pen in occlusal caries lesions, using histological sections as the gold standard. Sixty-four permanent teeth were examined by two researchers who previously performed and calibrated both the ICDAS II criteria and the use of DIAGNOdent pen. The teeth were then cut into sections and observed under an optical microscope. The sensitivity values were 0.82 (ICDAS II) and 0.85 (LF). The specificity values were 1.00 (ICDAS II) and 0.53 (LF). The intraexaminer reproducibility was 0.892 for ICDAS II and 0.912 for the DIAGNOdent, so it was high for both diagnostic methods. However, the DIAGNOdent pen showed greater sensitivity and the ICDAS criteria more specificity. It was concluded that both methods are efficacious individually but combining the two is recommended to improve the diagnosis.

http://ift.tt/2jaDPFP

Comments regarding: Radia S, Sherriff M, McDonald F, Naini FB. Relationship between maxillary central incisor proportions and facial proportions. J Prosthet Dent 2016;115:741-748

Publication date: Available online 18 January 2017
Source:The Journal of Prosthetic Dentistry
Author(s): Jeffrey L. Tarlow




http://ift.tt/2jzcRLz

Predicting brain metastases for non-small cell lung cancer based on magnetic resonance imaging

Abstract

In this study the relationship between brain structure and brain metastases (BM) occurrence was analyzed. A model for predicting the time of BM onset in patients with non-small cell lung cancer (NSCLC) was proposed. Twenty patients were used to develop the model, whereas the remaining 69 were used for independent validation and verification of the model. Magnetic resonance images were segmented into cerebrospinal fluid, gray matter (GM), and white matter using voxel-based morphometry. Automatic anatomic labeling template was used to extract 116 brain regions from the GM volume. The elapsed time between the MRI acquisitions and BM diagnosed was analyzed using the least absolute shrinkage and selection operator method. The model was validated using the leave-one-out cross validation (LOOCV) and permutation test. The GM volume of the extracted 11 regions of interest increased with the progression of BM from NSCLC. LOOCV test on the model indicated that the measured and predicted BM onset were highly correlated (r = 0.834, P = 0.0000). For the 69 independent validating patients, accuracy, sensitivity, and specificity of the model for predicting BM occurrence were 70, 75, and 66%, respectively, in 6 months and 74, 82, and 60%, respectively, in 1 year. The extracted brain GM volumes and interval times for BM occurrence were correlated. The established model based on MRI data may reliably predict BM in 6 months or 1 year. Further studies with larger sample size are needed to validate the findings in a clinical setting.

http://ift.tt/2iQZLrH

Seeing the unseen: uncover the bulk heterogeneous deformation processes in metallic glasses through surface temperature decoding

Publication date: Available online 18 January 2017
Source:Materials Today
Author(s): Yang Song, Xie Xie, Jiajia Luo, Peter K. Liaw, Hairong Qi, Yanfei Gao
Deformation processes in various materials are inhomogeneous in space and jerky in time, with the shear banding in bulk metallic glasses (BMGs) as a quintessential example, but there is a lack of in situ, nondestructive observations of such processes on the appropriate spatio-temporal scales. This work solves this long-lasting difficulty by the integration of in situ infrared (IR) measurements and innovative signal processing algorithms. A spatio-temporal unmixing method is developed to identify the discrete surface 'hot-spots' that are responsible for the initiation and propagation of macroscopic shear bands during the serrated flow. The use of a thermal-electric analogy further identifies depths of these hot-spots, whose magnitudes and locations evolve as the successive shearing process repeats on the major shear band. Seeing the previously 'unseen' localized heat sources and their 3D evolution patterns, both in situ and inside the bulk, reveals for the first time how the coupled structural/thermal softening mechanisms govern the heterogeneous deformation processes in BMGs.



http://ift.tt/2jz3MCu

Use of organic materials in dye-sensitized solar cells

Publication date: Available online 18 January 2017
Source:Materials Today
Author(s): Chuan-Pei Lee, Chun-Ting Li, Kuo-Chuan Ho
In the last two decades, dye-sensitized solar cells (DSSCs) have attracted more attention as an efficient alternative to economical photovoltaic devices, and the highest efficiency record has increased from ∼7% to ∼14%. To be more competitive in the solar cell markets, various organic materials are investigated and used in DSSCs to improve the cell efficiency, enhance the cell durability, and reduce the cost of production. In this review article, we provide a short review on the organic materials used for the preparation of photoanodes (including metal element-free organic dye sensitizers), quasi/all-solid-state electrolytes, and metal element-free electrocatalytic films in DSSCs with the cell efficiencies of >5%. Finally, the future perspectives for DSSCs are also briefly discussed.



http://ift.tt/2jppQga

Pseudoherpetic Transient Acantholytic Dermatosis (Grover disease): Case Series and Review of the Literature

Abstract

Three cases of pseudoherpetic transient acantholytic dermatosis (Grover disease) are presented, followed by a brief review of prior reports. All three patients were above the age of 60 and presented with a pruritic eruption composed of papules with or without vesicles distributed on the trunk. For all three patients, the clinical differential diagnosis included drug eruption but did not include Grover disease; in one patient, the clinical impression included herpesvirus infection. Similar histologic and immunohistochemical findings were demonstrated in all three cases. Intraepidermal vesicles with acantholysis, multinucleation, and and hypereosinophilic keratinocytes mimicking necrosis raised the possibility of herpesvirus infection. However, the focality of the process at scanning magnification, absence of true cytopathic effect despite multinucleation, and identification of dyskeratosis rather than true necrosis all permitted for morphologic distinction as pseudoherpetic change. Immunohistochemistry, negative for herpes simplex virus and varicella zoster virus antigens, also distinguished pseudoherpetic change in these patients from a true herpesvirus infection. This series highlights an uncommon histologic variant of a common disorder and describes morphologic and immunohistochemical findings to facilitate its distinction from true herpesvirus infection.

http://ift.tt/2jAK0WH

Interdisciplinary management of an adult patient with significant restorative treatment needs and a complex malocclusion

Abstract

Transverse maxillary deficiency may be associated with dental crowding, compromised aesthetics and impaired function. Non-surgical correction of maxillary transverse deficiency through rapid maxillary expansion is routinely performed for young patients, however, surgical intervention is generally required for adults. An interdisciplinary treatment approach is necessary to achieve the desired treatment objectives for challenging cases. This case report demonstrates a pleasing treatment outcome for a patient with a severe maxillary transverse deficiency, significant crowding and extensive active caries.

This article is protected by copyright. All rights reserved.

http://ift.tt/2jpnw8R

Whole pelvis radiotherapy for pathological node-positive prostate cancer

Abstract

Purpose

The goal of this work was to investigate the oncological outcome of whole pelvis radiotherapy (wpRT) in pathologic pelvic lymph node-positive (pN1) prostate cancer (PCa), evaluate the location of relapse, and identify potential prognostic factors.

Patients and methods

All patients undergoing pelvic lymph node dissection (PLND) since the year 2000 at a single tertiary care center were evaluated. A total of 154 patients with pN1 PCa were treated with wpRT (39 in an adjuvant setting) and 2–3 years of androgen deprivation therapy (ADT). Kaplan–Meier analysis was performed to estimate biochemical recurrence-free survival (bRFS), clinical progression-free survival (cPFS), and prostate cancer-specific survival (CSS). Uni- and multivariate regression analyses were performed to identify prognostic factors.

Results

Estimated bRFS was 67%, cPFS was 71%, and CSS was 96% at 5 years. Median follow-up was 55 months (interquartile range 25–87). Multivariate analysis identified having only 1 positive lymph node, a shorter time between diagnosis and PLND, and older age as independent favorable prognostic factors for biochemical and clinical recurrence. The number of positive lymph nodes was prognostic for CSS (hazard ratio [HR] 1.34, 95% confidence interval 1.17–1.54) and OS (HR 1.22, 95% confidence interval 1.10–1.36). Bone metastases were the most frequent location of PCa relapse (n = 32, 64%).

Conclusions

Patients with pN1 PCa treated with wpRT and 2–3 years ADT have an encouraging 5‑year CSS. Understaging of the disease extent may be the most important enemy in definitive pN1 PCa treatment.

http://ift.tt/2k5AADF

Turner syndrome and pituitary adenomas: a case report and review of literature

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


http://ift.tt/2jz4bod

Prevalence, risk factors and consequences of overweight and obesity among schoolchildren: a cross-sectional study in Kashmir, India

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


http://ift.tt/2iL5CeW

Epidermal growth factor receptor (EGFR) involvement in successful growth hormone (GH) signaling in GH transduction defect

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


http://ift.tt/2jzaCYr

Efficacy of long-term growth hormone therapy in short non-growth hormone-deficient children

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


http://ift.tt/2iLdOM5

Bone health assessment of food allergic children on restrictive diets: a practical guide

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


http://ift.tt/2jz4pvA

Association between screen time and snack consumption in children and adolescents: The CASPIAN-IV study

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


http://ift.tt/2iKZ6EW

The association between obesity, hypertension and left ventricular mass in adolescents

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


http://ift.tt/2jz7rQB

A standardized methanol extract of Eclipta prostrata (L.) L. (Asteraceae) reduces bronchial hyperresponsiveness and production of Th2 cytokines in a murine model of asthma

Publication date: 23 February 2017
Source:Journal of Ethnopharmacology, Volume 198
Author(s): Lucas Junqueira de Freitas Morel, Bruna Cestari de Azevedo, Fábio Carmona, Silvia Helena Taleb Contini, Aristônio Magalhães Teles, Fernando Silva Ramalho, Bianca Waléria Bertoni, Suzelei de Castro França, Marcos de Carvalho Borges, Ana Maria Soares Pereira
Ethnopharmacological relevanceEclipta prostrata (L.) L. (Asteraceae) has been used in Brazilian traditional medicine to treat asthma and other respiratory illnesses.Aims of the studyTo investigate the effects of different doses of a standardized extract of E. prostrata using a murine model of allergen induced asthma.Materials and methodsBalb/c mice were sensitized twice with ovalbumin (OVA) administered intraperitoneally and challenged over four alternate days with nasal instillations of OVA solution. The standardized methanol extract of E. prostrata was administered in doses of 100, 250 and 500mgkg⁻¹ concomitantly with nasal instillation over seven consecutive days. Control animals were treated with dexamethasone or saline solution. Bronchial hyperresponsiveness, production of Th1 and Th2 cytokines, allergen sensitization, airway and lung inflammation, mucous secretion and airway remodeling were assessed.ResultsThe concentrations of chemical markers in the standardized methanol extract were 0.02% oroboside, 1.69% demethylwedelolactone and 1.71% wedelolactone. Treatment with 250mgkg⁻¹ of extract, which provided 0.745, 4.22 and 4.30mgkg⁻¹day⁻¹ of oroboside, demethylwedelolactone and wedelolactone, respectively, significantly reduced (P<0.05) respiratory resistance and elastance. Such effects were comparable with those produced by dexamethasone. The total number of inflammatory cells and eosinophils in the bronchoalveolar lavage and the concentrations of interleukin (IL)-4, IL-5 and IL-13 in lung homogenate were significantly reduced (P<0.05) by the methanol extract of E. prostrata.ConclusionThe results presented herein demonstrate for the first time the anti-inflammatory activity of E. prostrata in a murine model of asthma, thereby supporting the ethnopharmacological uses of the plant.

Graphical abstract

http://ift.tt/2iTaYI8

LIPID OXIDATION PRODUCTS IN THE PATHOGENESIS OF NON-ALCOHOLIC STEATOHEPATITIS

Publication date: Available online 18 January 2017
Source:Free Radical Biology and Medicine
Author(s): Francesco Bellanti, Rosanna Villani, Antonio Facciorusso, Gianluigi Vendemiale, Gaetano Serviddio
Non-alcoholic fatty liver disease (NAFLD) is the major public health challenge for hepatologists in the twenty-first century. NAFLD comprises a histological spectrum ranging from simple steatosis or fatty liver, to steatohepatitis, fibrosis, and cirrhosis. It can be categorized into two principal phenotypes: (1) non-alcoholic fatty liver (NAFL), and (2) non-alcoholic steatohepatitis (NASH). The mechanisms of NAFLD progression consist of lipid homeostasis alterations, redox unbalance, insulin resistance, and inflammation in the liver. Even though several studies show an association between the levels of lipid oxidation products and disease state, experimental evidence suggests that compounds such as reactive aldehydes and cholesterol oxidation products, in addition to representing hallmarks of hepatic oxidative damage, may behave as active players in liver dysfunction and the development of NAFLD. This review summarizes the processes that contribute to the metabolic alterations occurring in fatty liver that produce fatty acid and cholesterol oxidation products in NAFLD, with a focus on inflammation, the control of insulin signalling, and the transcription factors involved in lipid metabolism.

Graphical abstract

http://ift.tt/2iKFZL3

Carbon monoxide reverses the metabolic adaptation of microglia cells to an inflammatory stimulus

Publication date: Available online 18 January 2017
Source:Free Radical Biology and Medicine
Author(s): Jayne Louise Wilson, Frédéric Bouillaud, Ana S. Almeida, Helena L. Vieira, Mohand Ouidir Ouidja, Jean-Luc Dubois-Randé, Roberta Foresti, Roberto Motterlini
Microglia fulfill important immunological functions in the brain by responding to pathological stresses and modulating their activities according to pro- or anti-inflammatory stimuli. Recent evidence indicates that changes in metabolism accompany the switch in microglia activation state, favoring glycolysis over oxidative phosphorylation when cells exhibit a pro-inflammatory phenotype. Carbon monoxide (CO), a byproduct of heme breakdown by heme oxygenase, exerts anti-inflammatory action and affects mitochondrial function in cells and tissues. In the present study, we analyzed the metabolic profile of BV2 and primary mouse microglia exposed to the CO-releasing molecules CORM-401 and CORM-A1 and investigated whether CO affects the metabolic adaptation of cells to the inflammatory stimulus lipopolysaccharide (LPS). Microglia respiration and glycolysis were measured using an Extracellular Flux Analyzer to provide a real-time bioenergetic assessment, and biochemical parameters were evaluated to define the metabolic status of the cells under normal or inflammatory conditions. We show that CO prevents LPS-induced depression of microglia respiration and reduction in ATP levels while altering the early expression of inflammatory markers, suggesting the metabolic changes induced by CO are associated with control of inflammation. CO alone affects microglia respiration depending on the concentration, as low levels increase oxygen consumption while higher amounts inhibit respiration. Increased oxygen consumption was attributed to an uncoupling activity observed in cells, at the molecular level (respiratory complex activities) and during challenge with LPS. Thus, application of CO is a potential countermeasure to reverse the metabolic changes that occur during microglia inflammation and in turn modulate their inflammatory profile.

Graphical abstract

http://ift.tt/2iKBArT

Redox regulation of electrophilic signaling by reactive persulfides in cardiac cells

Publication date: Available online 18 January 2017
Source:Free Radical Biology and Medicine
Author(s): Motohiro Nishida, Akiyuki Nishimura, Tetsuro Matsunaga, Hozumi Motohashi, Shingo Kasamatsu, Takaaki Akaike
Maintaining a redox balance by means of precisely controlled systems that regulate production, and elimination, and metabolism of electrophilic substances (electrophiles) is essential for normal cardiovascular function. Electrophilic signaling is mainly regulated by endogenous electrophiles that are generated from reactive oxygen species, nitric oxide, and the derivative reactive species of nitric oxide during stress responses, as well as by exogenous electrophiles including compounds in foods and environmental pollutants. Among electrophiles formed endogenously, 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP) has unique cell signaling functions, and pathways for its biosynthesis, signaling mechanism, and metabolism in cells have been clarified. Reactive persulfide species such as cysteine persulfides and polysulfides that are endogenously produced in cells are likely to be involved in 8-nitro-cGMP metabolism. These new aspects of redox biology may stimulate innovative and multidisciplinary research in cardiovascular physiology and pathophysiology. In our review, we focus on the redox-dependent regulation of electrophilic signaling via reduction and metabolism of electrophiles by reactive persulfides in cardiac cells, and we include suggestions for a new therapeutic strategy for cardiovascular disease.

Graphical abstract

http://ift.tt/2iKJbGD

Vascular remodeling: a redox-modulated mechanism of vessel caliber regulation

Publication date: Available online 18 January 2017
Source:Free Radical Biology and Medicine
Author(s): Leonardo Y. Tanaka, Francisco R.M. Laurindo
Vascular remodeling, i.e. whole-vessel structural reshaping, determines lumen caliber in (patho)physiology. Here we review mechanisms underlying vessel remodeling, with emphasis in redox regulation. First, we discuss confusing terminology and focus on strictu sensu remodeling. Second, we propose a mechanobiological remodeling paradigm based on the concept of tensional homeostasis as a setpoint regulator. We first focus on shear-mediated models as prototypes of remodeling closely dominated by highly redox-sensitive endothelial function. More detailed discussions focus on mechanosensors, integrins, extracellular matrix, cytoskeleton and inflammatory pathways as potential of mechanisms potentially coupling tensional homeostasis to redox regulation. Further discussion of remodeling associated with atherosclerosis and injury repair highlights important aspects of redox vascular responses. While neointima formation has not shown consistent responsiveness to antioxidants, vessel remodeling has been more clearly responsive, indicating that despite the multilevel redox signaling pathways, there is a coordinated response of the whole vessel. Among mechanisms that may orchestrate redox pathways, we discuss roles of superoxide dismutase activity and extracellular protein disulfide isomerase. We then discuss redox modulation of aneurysms, a special case of expansive remodeling. We propose that the redox modulation of vascular remodeling may reflect (1) remodeling pathophysiology is dominated by a particularly redox-sensitive cell type, e.g., endothelial cells (2) redox pathways are temporospatially coordinated at an organ level across distinct cellular and acellular structures or (3) the tensional homeostasis setpoint is closely connected to redox signaling. The mechanobiological / redox model discussed here can be a basis for improved understanding of remodeling and helps clarifying mechanisms underlying prevalent hard-to-treat diseases.



http://ift.tt/2iKJd1d

Redox regulation of cardiovascular inflammation – immunomodulatory function of mitochondrial and Nox-derived reactive oxygen and nitrogen species

Publication date: Available online 18 January 2017
Source:Free Radical Biology and Medicine
Author(s): Philip Wenzel, Sabine Kossmann, Thomas Münzel, Andreas Daiber
Oxidative stress is a major hallmark of cardiovascular diseases although a causal link was so far not proven by large clinical trials. However, there is a close association between oxidative stress and inflammation and increasing evidence for a causal role of (low-grade) inflammation for the onset and progression of cardiovascular diseases, which may serve as the missing link between oxidative stress and cardiovascular morbidity and mortality. With the present review we would like to highlight the multiple redox regulated pathways in inflammation, discuss the sources of reactive oxygen and nitrogen species that are of interest for these processes and finally discuss the importance of angiotensin II (AT-II) as a trigger of cardiovascular inflammation and the initiation and progression of cardiovascular diseases.



http://ift.tt/2iCX6n6

Hydrogen sulfide reduces RAGE toxicity through inhibition of its dimer formation

Publication date: Available online 18 January 2017
Source:Free Radical Biology and Medicine
Author(s): Hong Zhou, Lei Ding, Zhiyuan Wu, Xu Cao, Qichun Zhang, Li Lin, Jin-Song Bian
RAGE is important in the development of neurodegenerative diseases. The present study was designed to investigate the effect of hydrogen sulfide (H2S, an endogenous gaseous mediator) on the cytotoxicity caused by RAGE activation during the chronic oxidative stress. Aβ1–42 decreased cell viability and induced cell senescence in SH-SY5Y cells. Treatment with advanced glycation end products (AGEs) induced cell injury in HEK293 cells stably expressing RAGE (HEK293-RAGE) and stimulated inflammatory responses in SH-SY5Y cells. Pretreatment of SH-SY5Y cells with an H2S donor, NaHS, significantly attenuated the above harmful effects caused by Aβ1–42 or AGEs. Western blotting analysis shows that oxidative stress enhanced RAGE protein expression which was attenuated by either NaHS or over-expression of cystathionine β-synthase (CBS), a critical enzyme for producing H2S in brain cells. Both Western blots and split GFP complementation analysis demonstrate that NaHS reduced H2O2-enhanced RAGE dimerization. Immunofluorescence analysis shows that H2O2 up-regulated the membrane expression of wild-type RAGE. However, H2O2–enhanced expression of the RAGE harboring C259S/C310S double mutation (DM-RAGE) was observed in the endoplasmic reticulum. Treatment with NaHS attenuated the effects of H2O2 on the protein expression of WT-RAGE, but not that of DM-RAGE. Cycloheximide chase and ubiquitination assays show that NaHS reduced the half-life of WT-RAGE to a similar level of DM-RAGE. S-sulfhydration assay with the tag-switch technique demonstrate that H2S may directly S-sulfhydrate the C259/C301 residues. Our data suggest that H2S reduces RAGE dimer formation and impairs its membrane stability. The lowered plasma membrane abundance of RAGE therefore helps to protect cells against various RAGE mediated pathological effects.

Graphical abstract

http://ift.tt/2iKBn7I

Sunlight damage to cellular DNA: focus on oxidatively generated lesions

Publication date: Available online 18 January 2017
Source:Free Radical Biology and Medicine
Author(s): André Passaglia Schuch, Natália Cestari Moreno, Natielen Jacques Schuch, Carlos Frederico Martins Menck, Camila Carrião Machado Garcia
The routine and often unavoidable exposure to solar ultraviolet (UV) radiation makes it one of the most significant environmental DNA-damaging agents to which humans are exposed. Sunlight, specifically UVB and UVA, triggers various types of DNA damage. Although sunlight, mainly UVB, is necessary for the production of vitamin D, which is necessary for human health, DNA damage may have several deleterious consequences, such as cell death, mutagenesis, photoaging and cancer. UVA and UVB photons can be directly absorbed not only by DNA, which results in lesions, but also by the chromophores that are present in skin cells. This process leads to the formation of reactive oxygen species, which may indirectly cause DNA damage. Despite many decades of investigation, the discrimination among the consequences of these different types of lesions is not clear. However, human cells have complex systems to avoid the deleterious effects of the reactive species produced by sunlight. These systems include antioxidants, that protect DNA, and mechanisms of DNA damage repair and tolerance. Genetic defects in these mechanisms that have clear harmful effects in the exposed skin are found in several human syndromes. The best known of these is xeroderma pigmentosum (XP), whose patients are defective in the nucleotide excision repair (NER) and translesion synthesis (TLS) pathways. These patients are mainly affected due to UV-induced pyrimidine dimers, but there is growing evidence that XP cells are also defective in the protection against other types of lesions, including oxidized DNA bases. This raises a question regarding the relative roles of the various forms of sunlight-induced DNA damage on skin carcinogenesis and photoaging. Therefore, knowledge of what occurs in XP patients may still bring important contributions to the understanding of the biological impact of sunlight-induced deleterious effects on the skin cells.

Graphical abstract

http://ift.tt/2iKFIYK

Artifacts on temporomandibular joint MR images caused by mascara used as hair dye

Abstract

We report the case of a patient who used mascara in an unusual manner, as hair dye, causing artifacts on magnetic resonance (MR) images. A 60-year-old woman was referred to our hospital because of discomfort and mastication difficulty as a result of dislocation of the mandible on the left side. After a general examination, she was diagnosed with temporomandibular joint disorder and MR imaging was performed. The images showed artifacts in the bilateral temporal regions, although the patient had not undergone surgical treatment in the region and there were no metal hair accessories. However, mascara had been applied to the region to dye the patient's hair black. To verify that mascara could be the cause of the artifacts in the temporomandibular area, we performed mock MR imaging using a phantom and mascara. Artifacts were also observed in the area with mascara, confirming that the mascara caused the artifacts during MR imaging. This case suggests that care should be taken during MR imaging when different cosmetics are used in the head and neck region.

http://ift.tt/2iSJmTM

Pilomatrixoma of the neck: A forgotten entity

Publication date: Available online 18 January 2017
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences
Author(s): Jeyasakthy Saniasiaya, Irfan Mohamad, Zaleha Kamaludin
Pilomatrixoma, also known as pilomatricoma is a rare benign appendageal neoplasm of hair follicle matrix. It usually presents as a superficial, firm mass, commonly found in the head and neck region which may pose a diagnostic challenge as it may resemble other common benign lesions as in this case, sebaceous cyst. Pilomatrixoma remains to be misdiagnosed and are usually not considered in differential diagnosis. We report a case of a young girl with pilomatrixoma of neck, surgical management and histopathological findings.



http://ift.tt/2jysqTO

Preoperative bathing of the surgical site with chlorhexidine for infection prevention: Systematic review with meta-analysis

Publication date: Available online 18 January 2017
Source:American Journal of Infection Control
Author(s): Lúcia Maciel de Castro Franco, Gláucia Fernandes Cota, Tatiana Saraiva Pinto, Flávia Falci Ercole
BackgroundPreoperative bathing with 4% chlorhexidine is recommended as a measure to prevent surgical site infection (SSI) despite uncertainty regarding the effectiveness of the intervention. This review aimed to assess the effect of bathing with 4% chlorhexidine on the prevention of SSIs in clean surgeries compared with bathing with placebo solution or soap.MethodsPreferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for systematic reviews and the Cochrane manual were followed. Sources were MEDLINE and Latin American and Caribbean Health Sciences Literature databases and manual search of references from evaluated studies. We included randomized studies evaluating clean surgical wounds and reporting SSIs after preoperative bathing with 4% chlorhexidine.ResultsA total of 243 primary studies were identified and 8 were considered methodologically appropriate based on the Jadad Scale. Data were gathered from 10,655 patients. The global SSI rate was 7.2%. The SSI rate for chlorhexidine bathing, placebo, and soap without antiseptic groups was 7.1%, 9.1%, and 5.1%, respectively. A significant reduction in the infection rates was not found in the comparison between patients subjected to preoperative bathing with 4% chlorhexidine versus placebo solution (relative risk, 0.91; 95% confidence interval, 0.76-1.09). The same absence of benefit was observed comparing chlorhexidine bathing with soap (relative risk, 1.06; 95% confidence interval, 0.68-1.66).ConclusionsControlled clinical trials are needed to assess the effect of preoperative chlorhexidine bathing on infection rates following clean surgery before the incorporation of this intervention in health care services.



http://ift.tt/2jxWleM

Letter to the Editor on “Evaluating the effectiveness of ultraviolet-C lamps for reducing keyboard contamination in the intensive care unit: A longitudinal analysis”

Publication date: Available online 18 January 2017
Source:American Journal of Infection Control
Author(s): Marko Predic




http://ift.tt/2jy5yn8

Changes in arbuscular mycorrhizal fungal communities along a river delta island in northeastern Brazil

Publication date: February 2017
Source:Acta Oecologica, Volume 79
Author(s): Iolanda Ramalho da Silva, Danielle Karla Alves da Silva, Francisco Adriano de Souza, Fritz Oehl, Leonor Costa Maia
Arbuscular mycorrhizal fungi (AMF) play a key role in the maintenance of the balance of terrestrial ecosystems, but little is known about the biogeography of these fungi, especially on tropical islands. This study aims to compare AMF community structure along a transect crossing a fluvial-marine island and relate these communities with soil and vegetation parameters to shed light on the forces driving AMF community structure on a local scale. We tested the hypothesis that the composition of AMF communities changes across the island, even within short distances among sites, in response to differences in edaphic characteristics and vegetation physiognomies. We sampled roots and soils in five different natural and degraded habitats: preserved mangrove forest (MF), degraded mangrove forest (MD), natural Restinga forest (RF), and two regeneration Restinga forests (RR1 and RR2) on Ilha da Restinga, northeastern Brazil. We determined the mycorrhizal colonization rate and AMF community structure based on morphological spore identification. The island soils were sandy with pH varying from acid to neutral; higher levels of organic matter were registered in RF and lower in MF; other chemical and physical soil attributes differed along the habitat types on the island. In total, 22 AMF species were identified, without any difference in species richness. However, the diversity and composition of AMF communities, spore abundance per families, and mycorrhizal colonization were statistically different among the habitats. The composition of AMF communities was strongly related to soil characteristics, especially the sum of exchangeable bases. Our results indicate that the different habitat types have diverse AMF communities even within short distances among habitats. In conclusion, islands with high spatial heterogeneity in soil parameters and diverse vegetation are potential refuges for the diversity conservation of AM fungi.



http://ift.tt/2jybb4L

Settlements as a source for the spread of non-native plants into Central European suburban forests

Publication date: February 2017
Source:Acta Oecologica, Volume 79
Author(s): Luca Gaggini, Hans-Peter Rusterholz, Bruno Baur
Urbanization is considered as a major driver for biotic homogenization. Urbanization also promotes the dispersal of non-native species. This study examined the roles of suburban settlements and of the surrounding landscape composition for the spread of non-native plant species into adjacent mixed deciduous forests in Southern and Northwestern Switzerland. The number and abundance of native and non-native vascular plant species in both the ground vegetation and shrub layer were recorded in 15 forest sites situated adjacent to settlements and 15 control sites far from settlements. Various site and landscape characteristics were assessed in the surroundings (100 m radius) of the study sites. In both regions we found a higher number and larger abundance of non-native plant species in forest sites adjacent to settlements than in control forest sites. Furthermore, non-native plants were more frequently recorded close to roads and in sites surrounded by a large percentage cover of garden. All these effects were more pronounced in Southern Switzerland, a region with milder winter climate, than in Northwestern Switzerland. Our study showed that settlements are a source for the spread of non-native plant species into Central European suburban forests, and that the composition of the surrounding landscape matrix (e.g. traffic infrastructure, percentage cover of gardens) also affects the establishment of non-native plants.



http://ift.tt/2joG2yq

Nuclear DNA contents of Echinchloa crus-galli and its Gaussian relationships with environments

Publication date: February 2017
Source:Acta Oecologica, Volume 79
Author(s): Dan-Dan Li, Yong-Liang Lu, Shui-Liang Guo, Li-Ping Yin, Ping Zhou, Yu-Xia Lou
Previous studies on plant nuclear DNA content variation and its relationships with environmental gradients produced conflicting results. We speculated that the relationships between nuclear DNA content of a widely-distributed species and its environmental gradients might be non-linear if it was sampled in a large geographical gradient. Echinochloa crus-galli (L.) P. Beauv. is a worldwide species, but without documents on its intraspecific variation of nuclear DNA content. Our objectives are: 1) to detect intraspecific variation scope of E. crus-galli in its nuclear DNA content, and 2) to testify whether nuclear DNA content of the species changes with environmental gradients following Gaussian models if its populations were sampled in a large geographical gradient. We collected seeds of 36 Chinese populations of E. crus-galli across a wide geographical gradient, and sowed them in a homogeneous field to get their offspring to determine their nuclear DNA content. We analyzed the relationships of nuclear DNA content of these populations with latitude, longitude, and nineteen bioclimatic variables by using Gaussian and linear models. (1) Nuclear DNA content varied from 2.113 to 2.410 pg among 36 Chinese populations of E. crus-galli, with a mean value of 2.256 pg. (2) Gaussian correlations of nuclear DNA content (y) with geographical gradients were detected, with latitude (x) following y=2.2923*e−(x−24.9360)22*63.79452 (r = 0.546, P < 0.001), and with longitude (x) following y=2.2933*e−(x−116.1801)22*44.74502 (r = 0.672, P < 0.001). (3) Among the nineteen bioclimatic variables, except temperature isothermality, precipitations of the wettest month, the wettest quarter and the warmest quarter, the others could be better fit with nuclear DNA content by using Gaussian models than by linear models. There exists intra-specific variation among 36 Chinese populations of E. crus-galli, Gaussian models could be applied to fit the correlations of its Nuclear DNA content with geographical and most bioclimatic gradients.



http://ift.tt/2jy3LhU

Editorial Board

Publication date: January 2017
Source:Acta Oecologica, Volume 78





http://ift.tt/2joFRTM

Pilot study: Post-operative rehabilitation pathway changes and implementation of functional closed kinetic chain exercise in total hip and total knee replacement patient

Publication date: Available online 18 January 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): C. Abbas, J. Daher
ObjectiveThe aim of this study was to assess the feasibility of introducing a functional closed kinetic chain exercise program to an acute care setting to reduce length of hospital stay and assess tolerance to exercise immediately following total hip or total knee arthroplasty.MethodsA protocol change implementing a functional closed kinetic chain based exercise program, post total hip (n = 535) and total knee (n = 695) arthroplasty, was performed at Windsor Regional Hospital Ouellette Campus in Windsor, Ontario Canada. A chart review was performed to compare the length of stay, post-surgery, of the new protocol to the length of stay of the previous range of motion and open kinetic chain based protocols of the previous two years.ResultsA significant (P-value <0.05) number of total hip and total knee arthroplasty patients reduced the length of hospital stay to less than 4 days using the closed kinetic chain program.ConclusionEvidence suggests that closed kinetic chain exercises are tolerated in the acute care setting and may be useful in reducing hospital length of stay post total hip and total knee arthroplasty.



http://ift.tt/2iJZVxW

A novel and sensitive fluorescence sensor for glutathione detection by controlling the surface passivation degree of carbon quantum dots

Publication date: 1 May 2017
Source:Talanta, Volume 166
Author(s): Jiahong Pan, Zengyao Zheng, Jianying Yang, Yaoyu Wu, Fushen Lu, Yaowen Chen, Wenhua Gao
A novel fluorescence sensor based on controlling the surface passivation degree of carbon quantum dots (CQDs) was developed for glutathione (GSH) detection. First, we found that the fluorescence intensity of the CQDs which was obtained by directly pyrolyzing citric acid would increased largely after the surface passivation treatment by 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC). In the light of this phenomenon, we designed a simple, rapid and selective fluorescence sensor based on the surface passivated CQDs. A certain and excess amount of EDC were mixed with GSH, part of EDC would form a stable complex with GSH owing to the exposed sulfhydryl group of GSH. As the synthesized CQDs were added into the above mixture solution, the fluorescence intensity of the (EDC/GSH)/CQDs mixture solution could be directly related to the amount of GSH. Compared to other fluorescence analytical methods, the fluorescence sensor we design is neither the traditional fluorescent "turn on" probes nor "turn off" probes. It is a new fluorescence analytical method that target object indirectly control the surface passivation degree of CQDs so that it can realize the detection of the target object. Moreover, the proposed method manifested great advantages including short analysis time, low cost and ease of operation.

Graphical abstract

http://ift.tt/2jA3bQl

Spinel-type manganese ferrite (MnFe2O4) microspheres: A novel affinity probe for selective and fast enrichment of phosphopeptides

Publication date: 1 May 2017
Source:Talanta, Volume 166
Author(s): Xing-Yu Long, Jia-Yuan Li, Dong Sheng, Hong-Zhen Lian
The spinel-type magnetic manganese ferrite (MnFe2O4) microspheres synthesized by simple solvothermal method were used as a novel adsorbent for selective enrichment and effective isolation of phosphopeptides. The uniform MnFe2O4 magnetic affinity microspheres (MAMSs) had a narrow particle size distribution between 250 and 260nm, and displayed superparamagnetism with a saturation magnetization value of 67.0emu/g. Comprehensively, the possible formation mechanism of MnFe2O4 microspheres with ferric and manganous sources as dual precursors was elucidated by comparison with those of Fe3O4 nanoparticles and MnOOH nanosheets respectively with either ferric or manganous source as single precursor. It was suggested that the spherical or sheet nanostructures could be achieved via secondary recrystallization or Ostwald ripening. The MnFe2O4 MAMSs probe exhibited excellent dispersibility in aqueous solution, and rapid magnetic separation within 15s, as well as good reusability. More importantly, MnFe2O4 was highly selective for phosphopeptides because of the strong coordination interaction between metal ions (Fe³⁺ and Mn²⁺) and phosphate groups of phosphopeptdies. This high specificity was demonstrated by effectively enriching phosphopeptides from digest mixture of β-casein and bovine serum albumin (BSA) with high content of non-phosphopeptides, and embodied further in phosphopeptides enrichment from non-fat milk digests and human serum. Consequently, the prepared MnFe2O4 affinity materials are expected to possess great potential in phosphoproteome research.

Graphical abstract

http://ift.tt/2iJWU0p

Contraceptive use and its determinants amongst armed forces personnel

Publication date: Available online 17 January 2017
Source:Medical Journal Armed Forces India
Author(s): R.N. Hiremath, A.K. Yadav, Sandhya Ghodke, Jyoti Yadav
BackgroundNearly 1.5 billion adolescent girls are entering into child bearing age groups without effective knowledge regarding family planning practices which are essential to maintain their reproductive health. Timely and effective knowledge regarding family planning norms and practices among the young women during their initial married days are vital. Therefore the study was carried out with the aim to find out the factors associated with use of contraceptive among Armed Forces Personnel.MethodsA cross sectional survey was carried out among Armed Forces personnel living in a Military station with pre-validated and pre-tested questionnaire. Data was collected from 221 eligible couples. Univariate and logistic regression were done to find out the variables determining family planning.ResultsOut of 221 couples, 65.2% (144) of couples were practicing some or the other methods of family planning while 34.8% (77) didn't practice any methods. Age, age at marriage, sex of first child, type of family, empowerment and parity of women were significantly associated with contraceptive acceptance in univariate model. However in logistic regression analysis age at marriage, empowerment and parity were significant predictors of family planning. Major reason for not adopting any contraception was want of another child (20, 26%), girl child (18, 23%), male child (18, 23%) and worry about side effects (11, 14.3%).ConclusionThe study highlights the gap in preferences and practices of contraceptive and emphasized the need to highlight safety of contraceptive during Information, Education and Communication (IEC) campaign.



http://ift.tt/2joz4JM

Painful immunoglobulin G4-related thyroiditis treated by total thyroidectomy.

Related Articles

Painful immunoglobulin G4-related thyroiditis treated by total thyroidectomy.

Korean J Intern Med. 2016 Mar;31(2):399-402

Authors: Lee IS, Lee JU, Lee KJ, Jang YS, Lee JM, Kim HS

PMID: 26932403 [PubMed - indexed for MEDLINE]

http://ift.tt/2k0NSxg

Evolutionary Dynamics of Pandemic Methicillin-Sensitive Staphylococcus aureus ST398 and Its International Spread via Routes of Human Migration.

Related Articles

Evolutionary Dynamics of Pandemic Methicillin-Sensitive Staphylococcus aureus ST398 and Its International Spread via Routes of Human Migration.

MBio. 2017 Jan 17;8(1):

Authors: Uhlemann AC, McAdam PR, Sullivan SB, Knox JR, Khiabanian H, Rabadan R, Davies PR, Fitzgerald JR, Lowy FD

Abstract
Methicillin-susceptible Staphylococcus aureus (MSSA) accounts for the majority of S. aureus infections globally, and yet surprisingly little is known about its clonal evolution. We applied comparative whole-genome sequencing (WGS) analyses to epidemiologically and geographically diverse ST398-MSSA, a pandemic lineage affecting both humans and livestock. Bayesian phylogenetic analysis predicted divergence of human-associated ST398-MSSA ~40 years ago. Isolates from Midwestern pigs and veterinarians differed substantially from those in New York City (NYC). Pig ST398 strains contained a large region of recombination representing imports from multiple sequence types (STs). Phylogeographic analyses supported the spread of ST398-MSSA along local cultural and migratory links between parts of the Caribbean, North America, and France, respectively. Applying pairwise single-nucleotide polymorphism (SNP) distances as a measure of genetic relatedness between isolates, we observed that ST398 not only clustered in households but also frequently extended across local social networks. Isolates collected from environmental surfaces reflected the full diversity of colonizing individuals, highlighting their potentially critical role as reservoirs for transmission and diversification. Strikingly, we observed high within-host SNP variability compared to our previous studies on the dominant methicillin-resistant Staphylococcus aureus (MRSA) clone USA300. Our data indicate that the dynamics of colonization, persistence, and transmission differ substantially between USA300-MRSA and ST398-MSSA. Taken together, our study reveals local and international routes of transmission for a major MSSA clone, indicating key impacts of recombination and mutation on genetic diversification and highlighting important ecological differences from epidemic USA300. Our study demonstrates extensive local and international routes of transmission for a major MSSA clone despite the lack of substantial antibiotic resistance.
IMPORTANCE: Unlike methicillin-resistant Staphylococcus aureus (MRSA), surprisingly little is known about the clonal evolution of methicillin-susceptible S. aureus (MSSA), although these strains account for the majority of S. aureus infections. To better understand how MSSA spreads and becomes established in communities, we applied comparative bacterial whole-genome sequencing to pandemic ST398-MSSA, a clone of clinical importance affecting humans and livestock in different geographic regions. Phylogeographic analyses identified that ST398-MSSA spread along local cultural and migratory links between parts of the Caribbean, North America, and France, respectively. We observed high within-host SNP variability compared to our previous studies on the dominant MRSA clone USA300. Our data indicate that the dynamics of colonization, persistence, and transmission differ substantially between USA300 MRSA and ST398 MSSA.

PMID: 28096484 [PubMed - in process]

http://ift.tt/2iCtExp

Guided growth of auditory neurons: Bioactive particles towards gapless neural – electrode interface

Publication date: April 2017
Source:Biomaterials, Volume 122
Author(s): Hao Li, Fredrik Edin, Hisamitsu Hayashi, Olafur Gudjonsson, Niklas Danckwardt-Lillieström, Håkan Engqvist, Helge Rask-Andersen, Wei Xia
Cochlear implant (CI) is a successful device to restore hearing. Despite continuous development, frequency discrimination is poor in CI users due to an anatomical gap between the auditory neurons and CI electrode causing current spread and unspecific neural stimulation. One strategy to close this anatomical gap is guiding the growth of neuron dendrites closer to CI electrodes through targeted slow release of neurotrophins. Biodegradable calcium phosphate hollow nanospheres (CPHSs) were produced and their capacity for uptake and release of neurotrophins investigated using ¹²⁵I-conjugated glia cell line-derived neurotrophic factor (GDNF). The CPHSs were coated onto CI electrodes and loaded with neurotrophins. Axon guidance effect of slow-released neurotrophins from the CPHSs was studied in an in vitro 3D culture model. CPHS coating bound and released GDNF with an association rate constant 6.3 × 10³ M⁻¹s⁻¹ and dissociation rate 2.6 × 10⁻⁵ s⁻¹, respectively. Neurites from human vestibulocochlear ganglion explants found and established physical contact with the GDNF-loaded CPHS coating on the CI electrodes placed 0.7 mm away. Our results suggest that neurotrophin delivery through CPHS coating is a plausible way to close the anatomical gap between auditory neurons and electrodes. By overcoming this gap, selective neural activation and the fine hearing for CI users become possible.



http://ift.tt/2jvJQQO

Safety and efficacy of cardiopoietic stem cells in the treatment of post-infarction left-ventricular dysfunction – From cardioprotection to functional repair in a translational pig infarction model

Publication date: April 2017
Source:Biomaterials, Volume 122
Author(s): Maximilian Y. Emmert, Petra Wolint, Andras Jakab, Sean P. Sheehy, Francesco S. Pasqualini, Thi Dan Linh Nguyen, Monika Hilbe, Burkhardt Seifert, Benedikt Weber, Chad E. Brokopp, Dominika Macejovska, Etem Caliskan, Arnold von Eckardstein, Ruth Schwartlander, Viola Vogel, Volkmar Falk, Kevin Kit Parker, Mariann Gyöngyösi, Simon P. Hoerstrup
To date, clinical success of cardiac cell-therapies remains limited. To enhance the cardioreparative properties of stem cells, the concept of lineage-specification through cardiopoietic-guidance has been recently suggested. However, so far, only results from murine studies and from a clinical pilot-trial in chronic heart-failure (CHF) are available, while systematic evidence of its therapeutic-efficacy is still lacking. Importantly, also no data from large animals or for other indications are available. Therefore, we here investigate the therapeutic-efficacy of human cardiopoietic stem cells in the treatment of post-infarction LV-dysfunction using a translational pig-model. Using growth-factor priming, lineage-specification of human bone-marrow derived MSCs was achieved to generate cardiopoietic stem cells according to GMP-compliant protocols. Thereafter, pigs with post-infarction LV-dysfunction (sub-acute phase;1-month) were randomized to either receive transcatheter NOGA 3D electromechanical-mapping guided intramyocardial transplantation of cardiopoietic cells or saline (control). After 30days, cardiac MRI (cMRI) was performed for functional evaluation and in-vivo cell-tracking. This approach was coupled with a comprehensive post-mortem cell-fate and mode-of-repair analysis. Cardiopoietic cell therapy was safe and ejection-fraction was significantly higher when compared to controls (p = 0.012). It further prevented maladaptive LV-remodeling and revealed a significantly lower relative and total infarct-size (p = 0.043 and p = 0.012). As in-vivo tracking and post-mortem analysis displayed only limited intramyocardial cardiopoietic cell-integration, the significant induction of neo-angiogenesis (∼40% higher; p = 0.003) and recruitment of endogenous progenitors (∼2.5x higher; p = 0.008) to the infarct border-zone appeared to be the major modes-of-repair. This is the first report using a pre-clinical large animal-model to demonstrate the safety and efficacy of cardiopoietic stem cells for the treatment of post-infarction LV-dysfunction to prevent negative LV-remodeling and subsequent CHF. It further provides insight into post-delivery cardiopoietic cell-fate and suggests the mechanisms of cardiopoietic cell-induced cardiac-repair. The adoption of GMP-/GLP-compliant methodologies may accelerate the translation into a phase-I clinical-trial in patients with post-ischemic LV-dysfunction broadening the current indication of this interesting cell-type.



http://ift.tt/2jIXiOC

Targeting NF-kB signaling with polymeric hybrid micelles that co-deliver siRNA and dexamethasone for arthritis therapy

Publication date: April 2017
Source:Biomaterials, Volume 122
Author(s): Qin Wang, Hao Jiang, Yan Li, Wenfei Chen, Hanmei Li, Ke Peng, Zhirong Zhang, Xun Sun
The transcription factor NF-kB plays a pivotal role in the pathogenesis of rheumatoid arthritis. Here we attempt to slow arthritis progression by co-delivering the glucocorticoid dexamethasone (Dex) and small-interfering RNA targeting NF-kB p65 using our previously developed polymeric hybrid micelle system. These micelles contain two similar amphiphilic copolymers: polycaprolactone-polyethylenimine (PCL-PEI) and polycaprolactone-polyethyleneglycol (PCL-PEG). The hybrid micelles loaded with Dex and siRNA effectively inhibited NF-kB signaling in murine macrophages more efficiently than micelles containing either Dex or siRNA on their own. In addition, the co-delivery system was able to switch macrophages from the M1 to M2 state. Injecting hybrid micelles containing Dex and siRNA into mice with collagen-induced arthritis led the therapeutic agents to accumulate in inflamed joints and reduce inflammation, without damaging renal or liver function. Thus, blocking NF-kB activation in inflammatory tissue using micelle-based co-delivery may provide a new approach for treating inflammatory disease.



http://ift.tt/2jJuUMb

A π-π conjugation-containing soft and conductive injectable polymer hydrogel highly efficiently rebuilds cardiac function after myocardial infarction

Publication date: April 2017
Source:Biomaterials, Volume 122
Author(s): Rui Bao, Baoyu Tan, Shuang Liang, Ning Zhang, Wei Wang, Wenguang Liu
Previous studies suggested that a stiffer hydrogel system exhibited a better performance to promote heart function after myocardial infarction (MI). However, the nature of myocardium, a tissue that alternately contracts and relaxes with electrical impulses, leads us to hypothesize that a soft and conductive hydrogel may be in favor of mechanical and electrical signals transmission to enhance heart function after MI. In this work, π-π conjugation interaction was first employed to produce a soft injectable hydrogel with conductive property. Melamine with π-π conjugation ring was used as a core to synthesize a multi-armed crosslinker PEGDA700-Melamine (PEG-MEL), which could crosslink with thiol-modified hyaluronic acid (HA-SH) to form an injectable hydrogel rapidly. By incorporating graphene oxide (GO), the injectable PEG-MEL/HA-SH/GO hydrogel exhibited a soft (G' = 25 Pa) and anti-fatigue mechanical property and conductive property (G = 2.84 × 10⁻⁴ S/cm). The hydrogel encapsulating adipose tissue-derived stromal cells (ADSCs) was injected into MI area of rats. The significant increase in α-Smooth Muscle Actin (α-SMA) and Connexin 43 (Cx43) expression confirmed that the gel efficiently promoted the transmission of mechanical and electrical signals. Meanwhile, a significant improvement of heart functions, such as distinct increase of ejection fraction (EF), smaller infarction size, less fibrosis area, and higher vessel density, was achieved.



http://ift.tt/2jvOP3T

A simple and powerful co-delivery system based on pH-responsive metal-organic frameworks for enhanced cancer immunotherapy

Publication date: April 2017
Source:Biomaterials, Volume 122
Author(s): Fei Duan, Xiaochen Feng, Xinjian Yang, Wentong Sun, Yi Jin, Huifang Liu, Kun Ge, Zhenhua Li, Jinchao Zhang
Tumor-associated antigens (TAAs)-loaded nanoparticles are able to be actively internalized by antigen-presenting cells (APCs) and have shown promising potential in cancer immunotherapy. However, current TAAs delivery strategy exhibits limitations of complicated synthesis process, low loading efficiency and inefficient CD8⁺ cytotoxic T lymphocyte activation leading to unsatisfactory therapeutic effect. Thus, the construction of novel TAAs-delivery systems for enhanced cancer therapy is highly desirable. In this work, we fabricated a very simple yet powerful antigens-delivery system for cancer immunotherapy based-on pH-responsive metal-organic frameworks (MOFs) with size about 30 nm. TAAs can be loaded into MOFs in the one-pot synthesis process and released with the degradation of MOFs in the acidic environment of endo/lysosome as the result of relatively labile metal-ligand bonds. The endosomolytic nanoparticles would facilitate protein antigens escape from endo/lysosome and optimal for enhancing antigen cross-presentation. Furthermore, the introduction of immunostimulatory unmethylated cytosine-phosphate-guanine oligonucleotide (CpG) through Watson−Crick base pairing would further enhance CD8⁺ cytotoxic T lymphocyte responses. We demonstrated that the method to co-delivery antigens and immunostimulatory molecules was very simple, convenient and effective and showed no obvious toxicity both in vitro and in vivo. This method gave a high antigens-loading capacity and the maximal antigen encapsulating efficiency was about 55% (w/w). Additionally, the pH-responsive co-delivery system exerted enhanced antitumor outcome (about 100% survival) in B16-OVA melanoma cancers in vivo. Furthermore, we confirmed that this high rating of therapeutic effect was attributed to the recruitment of tumor-killing immunocyte. This work demonstrates the ability of pH-responsive, endosomolytic MOFs to induce strong cellular immune responses for cancer therapy by co-delivery of CpG ODN and antigens.



http://ift.tt/2jJHWsX

Antibacterial anti-oxidant electroactive injectable hydrogel as self-healing wound dressing with hemostasis and adhesiveness for cutaneous wound healing

Publication date: April 2017
Source:Biomaterials, Volume 122
Author(s): Xin Zhao, Hao Wu, Baolin Guo, Ruonan Dong, Yusheng Qiu, Peter X. Ma
Injectable self-healing hydrogel dressing with multifunctional properties including anti-infection, anti-oxidative and conductivity promoting wound healing process will be highly desired in wound healing application and its design is still a challenge. We developed a series of injectable conductive self-healed hydrogels based on quaternized chitosan-g-polyaniline (QCSP) and benzaldehyde group functionalized poly(ethylene glycol)-co-poly(glycerol sebacate) (PEGS-FA) as antibacterial, anti-oxidant and electroactive dressing for cutaneous wound healing. These hydrogels presented good self-healing, electroactivity, free radical scavenging capacity, antibacterial activity, adhesiveness, conductivity, swelling ratio, and biocompatibility. Interestingly, the hydrogel with an optimal crosslinker concentration of 1.5 wt% PEGS-FA showed excellent in vivo blood clotting capacity, and it significantly enhanced in vivo wound healing process in a full-thickness skin defect model than quaternized chitosan/PEGS-FA hydrogel and commercial dressing (Tegaderm™ film) by upregulating the gene expression of growth factors including VEGF, EGF and TGF-β and then promoting granulation tissue thickness and collagen deposition. Taken together, the antibacterial electroactive injectable hydrogel dressing prolonged the lifespan of dressing relying on self-healing ability and significantly promoted the in vivo wound healing process attributed to its multifunctional properties, meaning that they are excellent candidates for full-thickness skin wound healing.



http://ift.tt/2jJr1Xr

TLR9 mediated regulatory B10 cell amplification following sub-total body irradiation: Implications in attenuating EAE

Publication date: March 2017
Source:Molecular Immunology, Volume 83
Author(s): Jinsheng Hong, Jie Fang, Ruilong Lan, Qi Tan, Yeping Tian, Mei Zhang, Paul Okunieff, Lurong Zhang, Jianhua Lin, Deping Han
Autoimmunity and inflammation are controlled in part by regulatory B (Breg) cells, including the recently identified IL-10-competent B10 cell subset that represents 1%–3% of mouse spleen B cells. In this study, the influence of irradiation on Breg/B10 cell generation and IL-10 production mediated by TLR9 signaling pathways was investigated. Spleen and peritoneal cavity Breg/B10 cell frequencies were significantly expanded three weeks after sub-total body irradiation (sub-TBI, 5Gy or 10Gy) in adult male wild type (WT) C57BL/6(B6) mice but not in TLR9^−/− mice. TLR9 agonist ODN1826 stimulation in vitro for 5h induced more B10 cells to express cytoplasmic IL-10 in sub-TBI WT mice than in TLR9^−/− mice. Prolonged ODN1826 stimulation (48h) induced additional spleen CD19^hiCD5⁺CD1d^hi B cells to express IL-10. TLR9-dependent signaling molecules, MyD88, TRAF6 and IRF8 are involved in sub-TBI induced Breg/B10 cells development and expansion. Furthermore, using a mouse model for multiple sclerosis, we show here that sub-TBI induced Breg/B10 cells dramatically inhibit disease onset and severity when transferred into mice with established experimental autoimmune encephalomyelitis (EAE). Adoptively transferred sub-TBI induced Breg cells significantly suppress inflammatory T cell responses of TH17 and TH1 types in EAE mice. In conclusion, sub-TBI can drive Breg/B10 cell development and expansion, which could be used as a novel tool for suppressing undesirable immunity. The ex vivo expansion and reinfusion of autologous Breg/B10 cells may provide a novel and effective in vivo treatment for severe autoimmune diseases that are resistant to current therapies.



http://ift.tt/2jzPWiK

Thiolated polymers as mucoadhesive drug delivery systems

Publication date: 30 March 2017
Source:European Journal of Pharmaceutical Sciences, Volume 100
Author(s): Sarah Duggan, Wayne Cummins, Orla O' Donovan, Helen Hughes, Eleanor Owens
Mucoadhesion is the process of binding a material to the mucosal layer of the body. Utilising both natural and synthetic polymers, mucoadhesive drug delivery is a method of controlled drug release which allows for intimate contact between the polymer and a target tissue. It has the potential to increase bioavailability, decrease potential side effects and offer protection to more sensitive drugs such as proteins and peptide based drugs. The thiolation of polymers has, in the last number of years, come to the fore of mucoadhesive drug delivery, markedly improving mucoadhesion due to the introduction of free thiol groups onto the polymer backbone while also offering a more cohesive polymeric matrix for the slower and more controlled release of drug. This review explores the concept of mucoadhesion and the recent advances in both the polymers and the methods of thiolation used in the synthesis of mucoadhesive drug delivery devices.

Graphical abstract

http://ift.tt/2ij6sCE

An innovative polysaccharide nanobased nail formulation for improvement of onychomycosis treatment

Publication date: 30 March 2017
Source:European Journal of Pharmaceutical Sciences, Volume 100
Author(s): Fernanda C. Flores, Roberta S. Rosso, Letícia Cruz, Ruy C.R. Beck, Cristiane B. Silva
Tioconazole-loaded nanocapsule suspensions and its coating with a cationic polymer were developed for nail drug delivery. The colloidal systems presented a nanometric size around 155nm for uncoated nanoparticles and 162nm for those with the cationic coating, with negative and positive zeta potential values, respectively. Both nanosuspensions showed drug content close to theoretical values (1mgmL⁻¹), association efficiency close to 100% (HPLC) and were able to control tioconazol release. The developed formulations showed in vitro antifungal activity (agar diffusion method) against C. albicans. The cationic nanocapsules were considered bioadhesive, showed higher viscosity and were chosen to be incorporated into an ungueal formulation. Pullulan nanobased nail formulation showed adequate viscosity for nail application and drug content close to the theoretical values. It was equivalent to the commercial formulation Trosid^® in preventing nail infection by T. rubrum in an in vitro onychomycosis model. The nanocapsule suspensions and Pullulan nanobased nail formulation showed lower irritant potential than the commercial formulation and than free drug in an in vitro evaluation. Pullulan nanobased nail formulation is promising for the treatment of onychomycosis.

Graphical abstract

http://ift.tt/2jzQlSe

Generation of quercetin/cellulose acetate phthalate systems for delivery by supercritical antisolvent process

Publication date: 30 March 2017
Source:European Journal of Pharmaceutical Sciences, Volume 100
Author(s): I. García-Casas, A. Montes, C. Pereyra, E.J. Martínez de la Ossa
Supercritical antisolvent process (SAS) has been used to precipitate microparticles of quercetin, a plant pigment found in many foods and used for medical treatments, pharmaceutical and cosmetic industries, together with nanoparticles of cellulose acetate phthalate (CAP), a polymer quite frequently used in drug delivery. Previously, precipitation of nanoparticles of CAP by the same process was studied at different conditions of pressure, temperature, CO2 and solution flow rates, nozzle diameter and initial concentration of the solution. Morphologies of the precipitates were analyzed by scanning electron microscopy (SEM). A range between 84 and 145nm of diameter in spherical particle were achievement in CAP precipitation. A same range of semi-spherical particles of CAP around 145nm and needle-like particle of quercetin was obtained in the coprecipitation experiments. X-ray diffraction (XRD) and Fourier Transform Infrared Spectroscopy (FTIR) were carried out to find out the possible loss of crystallinity of the coprecipitates and the possible interactions between the polymer and quercetin, respectively. Release profiles of quercetin were carried out in simulated gastric and intestinal fluids. Higher quercetin:polymer ratios in the coprecipitates are recommended to achieve faster release and higher solubilities of quercetin in the assayed time. This fact would allow its use in pharmaceutical, cosmetic or nutraceutical applications.

Graphical abstract

http://ift.tt/2jzzUoW

Sorption of organic phosphates and its effects on aggregation of hematite nanoparticles in monovalent and bivalent solutions

Abstract

Sorption of organic phosphates–myo-inositol hexakisphosphate (IHP) and glycerol phosphate (GP) and its effects on the early stage of hematite aggregation kinetics were investigated at different pH and electrolyte composition. KH₂PO₄ (KP) was taken as an inorganic P source for comparison. Results indicated that for all types of P, the sorption amounts decreased with increasing solution pH. Sorption amount of IHP was almost two times that of KP, while those of GP and KP were close. Both organic P and inorganic P interacted with hematite via ligand exchange through their phosphate groups, which conveyed negative charges to mineral surface and significantly decreased the zeta potential of hematite. In Na⁺ solution, critical coagulation concentrations (CCCs) of hematite suspensions increased with increasing P concentration and followed the order of KP < GP < IHP at pH 5.5. Compared with KP, the organic P could more effectively stabilize the hematite suspension not only through increasing the negative charges and electrostatic repulsive force, but also through steric repulsion between P-sorbed hematite nanoparticles. When the pH was increased from 5.5 to 10.0, the CCCs of the hematite suspensions with GP and IHP decreased mainly because of the great reductions in organic P sorption amounts and consequent decreases in electrostatic and steric repulsive forces. However, enhanced aggregation was observed in the presence of IHP at pH 4.5 and above in low Ca²⁺ solutions. The precipitation of calcium phytate formed net-like structure, which served as bridges to bind hematite nanoparticles and resulted in enhanced aggregation. These results have important implications for assessing the fate and transport of organic P and hematite nanoparticles in soil and aquatic environments.

http://ift.tt/2k0NK0A