Cyperus Rotundus L. extract suppresses RANKL-induced osteoclastogenesis through NFATc1/c-fos downregulation and prevent bone loss in OVX-induced osteoporosis rat

Publication date: Available online 15 March 2017
Source:Journal of Ethnopharmacology
Author(s): Chang-Jun Kum, Eun-Young Kim, Jae-Hyun Kim, Bina Lee, Ju-Hee Min, Jun Heo, Jong-Hyun Kim, Mijung Yeom, Youngjoo Sohn, Hyuk-Sang Jung
Ethnopharmacological relevanceCyperus Rotundus L. (CyR) has been widely used for the treatment of gynecologic disorder. Recent studies have reported that CyR can prevent the formation of cystic follicles and ovarian malfunction. However, the effects of CyR on osteoclastogenesis and postmenopausal osteoporosis remain unknown.Aim of the studyThis study was aimed to investigate the preventive effects of CyR on RANKL-induced osteoclast formation and ovariectomy (OVX)-induced bone loss.Materials and methodsIn this in vitro study, we investigate the anti-osteoporotic effect of CyR on receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis, the formation of tartrate-resistant acid phosphatase (TRAP) multinucleated cells, pit formation, transcription factors such as NFATc1 and c-Fos, and mRNA expression of osteoclast-associated genes were investigated. Forty 12-weeks female Sprague-Dawley rats for in vivo effect of CyR were used and OVX rat model was determined. The rats were randomly assigned into sham group and four OVX groups, i.e. OVX with D.W; OVX with estradiol (E2, 100 μg/kg/day), OVX with CyR-L (16mg/kg/day), OVX with CyR-H (160mg/kg/day). The treatment lasted for 8weeks.ResultsCyR inhibited osteoclast differentiation and pit formation in the RANKL-induced osteoclastogenesis of RAW 264.7 cells. Reverse transcription polymerase chain reaction analysis also showed that CyR reduced the mRNA expression of osteoclast-associated genes such as carbonic anhydrase II, TRAP, RANK, cathepsin K, matrix metalloproteinase 9, nuclear factor of activated T cells cytoplasmic 1 (NFATc1), and c-Fos. In addition, CyR decreased protein levels of NFATc1 and c-Fos. CyR inhibited trabecular bone loss in the femur caused by OVX.ConclusionThe results of this study indicate that CyR inhibits the RANKL-induced osteoclast differentiation in RAW 264.7 cells and trabecular bone loss in OVX rats.

Graphical abstract

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An update of dens invaginatus in the diagnosis and treatment

Abstract

Dens invaginatus is a malformation with varying anatomical features, posing challenges to treatment. Early and accurate diagnosis plays a significant role in selecting the appropriate treatment. The diagnosis of teeth with a complex root canal system including dens invaginatus has made progress with the application of three-dimensional imaging techniques in endodontics. Advanced treatment options provide hope for teeth that could not be saved before. This review discusses diagnostic methods and treatment options for teeth with dens invaginatus, and provides guidelines for the management of dens invaginatus cases in clinic. Current as well as traditional diagnostic techniques are summarised. Treatment options including state-of-the-art alternatives are presented for coronal dens invaginatus and radicular dens invaginatus.

This article is protected by copyright. All rights reserved.

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Non-invasive Liver Ablation Using Histotripsy: Preclinical Safety Study in an in Vivo Porcine Model

Publication date: Available online 17 March 2017
Source:Ultrasound in Medicine & Biology
Author(s): Eli Vlaisavljevich, Gabe Owens, Jonathan Lundt, Dejan Teofilovic, Kimberly Ives, Alexander Duryea, Jim Bertolina, Theodore H. Welling, Zhen Xu
This study investigates the safety profile for use of histotripsy, a non-invasive ultrasonic ablation method currently being developed for the treatment of liver cancer, for liver ablation in an in vivo porcine model. Histotripsy treatments were applied to the liver and hepatic veins of 22 porcine subjects, with half of the subjects receiving systemic heparinization. Vital signs (heart rate, blood pressure, temperature, electrocardiogram and SpO2) were monitored throughout the procedure and for 1 h post-treatment. Blood was drawn at six points during the experiment to analyze blood gases, liver function and free hemoglobin levels. All treatments were guided and monitored by real-time ultrasound imaging. After treatment, the tissue was harvested for histological analysis. Results indicated that histotripsy generated well-defined lesions inside the liver and around the treated hepatic veins of all subjects in both treatment groups. Vital signs and blood analysis revealed that animals responded well to histotripsy, with all animals surviving the treatment. One animal in the non-heparinized group had a transient increase in pH and decreases in blood pressure, heart rate and PCO2 during the 15-min vessel treatment, with these changes returning to baseline levels soon after the treatment. Overall, the results indicate that histotripsy can safely be performed on the liver without the need for systemic heparinization, even in regions containing large hepatic vessels, supporting its future use for the treatment of liver cancer.



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Measuring Endotracheal Tube Depth by Bedside Ultrasound in Adult Patients in an Intensive Care Unit: A Pilot Study

Publication date: Available online 17 March 2017
Source:Ultrasound in Medicine & Biology
Author(s): Fenglin Dong, Canhong Zhu, Huiwen Xu, Jiajia Wang, Yehan Zhu, Qingmin Fan, Jian'an Huang, Wei Lei
The aim of the study described here was to evaluate the feasibility and accuracy of measuring endotracheal tube (ETT) depth with ultrasound in adult patients in an intensive care unit (ICU). The distance between the upper margin of the cuff and the upper margin of the aortic arch (Duc-ua) of 67 ICU patients was measured by ultrasound, and the time of measurement was recorded. The level of agreement between the distance between the tip of the ETT and the carina (Dtt-c) measured by ultrasound (U-Dtt-c) and Dtt-c measured by bronchoscopy (B-Dtt-c) was assessed using linear regression and a Bland–Altman plot. There was a significant correlation between B-Dtt-c and U-Dtt-c (r = 0.844, p < 0.001). Also, the Bland–Altman plot revealed strong agreement between B-Dtt-c and U-Dtt-c. The time it took to measure ETT depth by ultrasound was 33.91 ± 5.43 s. In conclusion, bedside ultrasound provides a novel and convenient method for measuring the depth of ETT in ICU patients.



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Characterization of the Lung Parenchyma Using Ultrasound Multiple Scattering

Publication date: Available online 16 March 2017
Source:Ultrasound in Medicine & Biology
Author(s): Kaustav Mohanty, John Blackwell, Thomas Egan, Marie Muller
The purpose of the study described here was to showcase the application of ultrasound to quantitative characterization of the micro-architecture of the lung parenchyma to predict the extent of pulmonary edema. The lung parenchyma is a highly complex and diffusive medium for which ultrasound techniques have remained qualitative. The approach presented here is based on ultrasound multiple scattering and exploits the complexity of ultrasound propagation in the lung structure. The experimental setup consisted of a linear transducer array with an 8-MHz central frequency placed in contact with the lung surface. The diffusion constant D and transport mean free path L* of the lung parenchyma were estimated by separating the incoherent and coherent intensities in the near field and measuring the growth of the incoherent diffusive halo over time. Significant differences were observed between the L* values obtained in healthy and edematous rat lungs in vivo. In the control rat lung, L* was found to be 332 μm (±48.8 μm), whereas in the edematous lung, it was 1040 μm (±90 μm). The reproducibility of the measurements of L* and D was tested in vivo and in phantoms made of melamine sponge with varying air volume fractions. Two-dimensional finite difference time domain numerical simulations were carried out on rabbit lung histology images with varying degrees of lung collapse. Significant correlations were observed between air volume fraction and L* in simulation (r = −0.9542, p < 0.0117) and sponge phantom (r = −0.9932, p < 0.0068) experiments. Ex vivo measurements of a rat lung in which edema was simulated by adding phosphate-buffered saline revealed a linear relationship between the fluid volume fraction and L*. These results illustrate the potential of methods based on ultrasound multiple scattering for the quantitative characterization of the lung parenchyma.



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Cued uncertainty modulates later recognition of emotional pictures: An ERP study

Publication date: Available online 16 March 2017
Source:International Journal of Psychophysiology
Author(s): Huiyan Lin, Jing Xiang, Saili Li, Jiafeng Liang, Dongmei Zhao, Desheng Yin, Hua Jin
Previous studies have shown that uncertainty about the emotional content of an upcoming event modulates event-related potentials (ERPs) during the encoding of the event, and this modulation is affected by whether there are cues (i.e., cued uncertainty) or not (i.e., uncued uncertainty) prior to the encoding of the uncertain event. Recently, we showed that uncued uncertainty affected ERPs in later recognition of the emotional event. However, it is as yet unknown how the ERP effects of recognition are modulated by cued uncertainty. To address this issue, participants were asked to view emotional (negative and neutral) pictures that were presented after cues. The cues either indicated the emotional content of the pictures (the certain condition) or not (the cued uncertain condition). Subsequently, participants had to perform an unexpected old/new task in which old and novel pictures were shown without any cues. ERP data in the old/new task showed smaller P2 amplitudes for neutral pictures in the cued uncertain condition compared to the certain condition, but this uncertainty effect was not observed for negative pictures. Additionally, P3 amplitudes were generally enlarged for pictures in the cued uncertain condition. Taken together, the present findings indicate that cued uncertainty alters later recognition of emotional events in relevance to feature processing and attention allocation.



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Effects of anticipated emotional category and temporal predictability on the startle reflex

Publication date: Available online 14 March 2017
Source:International Journal of Psychophysiology
Author(s): Elizabeth A. Parisi, Greg Hajcak, Eleni Aneziris, Brady D. Nelson
Anticipated emotional category and temporal predictability are key characteristics that have both been shown to impact psychophysiological indices of defensive motivation (e.g., the startle reflex). To date, research has primarily examined these features in isolation, and it is unclear whether they have additive or interactive effects on defensive motivation. In the present study, the startle reflex was measured in anticipation of low arousal neutral, moderate arousal pleasant, and high arousal unpleasant pictures that were presented with either predictable or unpredictable timing. Linear mixed-effects modeling was conducted to examine startle magnitude across time, and the intercept at the beginning and end of the task. Across the entire task, the anticipation of temporally unpredictable (relative to predictable) pictures and emotional (relative to neutral) pictures potentiated startle magnitude, but there was no interaction between the two features. However, examination of the intercept at the beginning of the task indicated a Predictability by Emotional Category interaction, such that temporal unpredictability enhanced startle potentiation in anticipation of unpleasant pictures only. Examination of the intercept at the end of the task indicated that the effects of predictability and emotional category on startle magnitude were largely diminished. The present study replicates previous reports demonstrating that emotional category and temporal predictability impact the startle reflex, and provides novel evidence suggesting an interactive effect on defensive motivation at the beginning of the task. This study also highlights the importance of examining the time course of the startle reflex.



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Pyrroloquinoline quinone from Gluconobacter oxydans fermentation broth enhances superoxide anion-scavenging capacity of Cu/Zn-SOD

Publication date: 1 September 2017
Source:Food Chemistry, Volume 230
Author(s): Ke Ma, Jun-Zhu Cui, Jian-Bin Ye, Xian-Mei Hu, Ge-Li Ma, Xue-Peng Yang
A bioassay-guided fractionation of extract from Gluconobacter oxydans fermentation broth afforded Compound 1, which was identified as pyrroloquinoline quinone (PQQ) by spectroscopic methods. PQQ has been shown to enhance the superoxide anion-scavenging capacity significantly for Cu/Zn-SOD. To illustrate the mechanism, the interaction between PQQ and Cu/Zn-SOD was investigated. The multiple binding sites involving hydrogen bonds and van der Waals force between PQQ and Cu/Zn-SOD were revealed by isothermal titration calorimetry. The α-helix content was increased in the Cu/Zn-SOD structure with the addition of PQQ into the solution through ultraviolet (UV) spectroscopy. These results indicated that PQQ could change the conformation of Cu/Zn-SOD through interaction, which could enhance its superoxide anion-scavenging capacity. Therefore, PQQ is a potential natural antioxidant.



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Zn-Li alloy after extrusion and drawing: Structural, mechanical characterization, and biodegradation in abdominal aorta of rat

Publication date: 1 July 2017
Source:Materials Science and Engineering: C, Volume 76
Author(s): Shan Zhao, Jan-M. Seitz, Rainer Eifler, Hans J. Maier, Roger J. Guillory, Elisha J. Earley, Adam Drelich, Jeremy Goldman, Jaroslaw W. Drelich
Zinc shows great promise as a bio-degradable metal. Our early in vivo investigations implanting pure zinc wires into the abdominal aorta of Sprague-Dawley rats revealed that metallic zinc does not promote restenotic responses and may suppress the activities of inflammatory and smooth muscle cells. However, the low tensile strength of zinc remains a major concern.A cast billet of the Zn-Li alloy was produced in a vacuum induction caster under argon atmosphere, followed by a wire drawing process. Two phases of the binary alloy identified by x-ray diffraction include the zinc phase and intermetallic LiZn4 phase. Mechanical testing proved that incorporating 0.1wt% of Li into Zn increased its ultimate tensile strength from 116±13MPa (pure Zn) to 274±61MPa while the ductility was held at 17±7%. Implantation of 10mm Zn-Li wire segments into abdominal aorta of rats revealed an excellent biocompatibility of this material in the arterial environment. The biodegradation rate for Zn-Li was found to be about 0.008mm/yr and 0.045mm/yr at 2 and 12months, respectively.

Graphical abstract

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ZnO/ZnGaNO heterostructure with enhanced photocatalytic properties prepared from a LDH precursor using a coprecipitation method

Publication date: 30 June 2017
Source:Journal of Alloys and Compounds, Volume 709
Author(s): Yan-Ling Hu, Zhi Wu, Xianting Zheng, Nan Lin, Youhuang Yang, Juan Zuo, Dongya Sun, Chunhai Jiang, Lan Sun, Changjian Lin, Yongsheng Fu
Wurtzite Zinc-gallium oxynitrides (ZnGaNO) particles were synthesized by nitridation of Zn/Ga/CO3 layered double hydroxides (LDHs) using three different coprecipitation methods, called Decreasing-pH method, Constant-pH method, and Increasing-pH Method, respectively. The obtained particles were found to be a ZnO/ZnGaNO composite, a single-phase ZnGaNO, and a porous ZnGaNO/ZnGa2O4 composite, respectively, as characterized by X-ray diffraction, scanning electron microscope, scanning and transmission electron microscope, Raman Spectroscopy, UV–vis diffuse refection spectra, and room temperature photoluminescence (PL). Photocatalytic activities of the obtained particles were evaluated under visible-light irradiation against the photodegradation of methylene blue (MB) and phenol. The ZnO/ZnGaNO heterostructure, which was formed due to sequential precipitation of Zn and Ga ions in the Decreasing-pH method, exhibited significant advance in the photocatalytic activity compared to other ZnGaNO particles. The enhanced photoactivity of ZnO/ZnGaNO particles was attributed to efficient separation of photogenerated electron-hole pairs driven by the matched band edges. The predominant active species for the phenol photodegradation over the ZnO/ZnGaNO particles were determined to be superoxide radicals and holes. The facile synthesis of the ZnO/ZnGaNO heterostructure makes it as a potential efficient visible-light responsive photocatalyst for water pollutant degradation.

Graphical abstract

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Synthesis, structure and luminescent properties of halogenated isophthalic acid-directed frameworks in virtue of flexible and semiflexible N-containing ligands

Publication date: 5 July 2017
Source:Journal of Molecular Structure, Volume 1139
Author(s): Yong-Mei Pan, Bao-Xia Dong, Meng Tang, Yi-Chen Wu, Fan-Yan Bu, Wen-Long Liu, Yun-Lei Teng
Four three-dimensional (3D) coordination complexes on the basis of 4-halogenated isophthalic acid and two types of flexible and semiflexible N-donor ligands, formulated as {[Zn(bix)(4-Br-ip)]·H2O}n (1), {[Co(bix)(4-Br-ip)]·0.5H2O}n (2), [Zn(bbi)(4-Br-ip)]n (3) and [Co(bbi)(4-Cl-ip)]n (4), (4-Br-H2ip = 4-bromoisophthalic acid, 4-Cl-H2ip = 4-chloroisophthalic acid, bix = 1,4-bis(imidazol-1-yl-methyl)benzene, bbi = 1,1′-(1,4-butanediyl)bis(imidazole)), have been synthesized and characterized by elemental analyses, IR spectra, single-crystal and powder X-ray diffraction analyses. Compounds 1 and 2 possess the same 4-connected 6⁶ net. Compounds 3 and 4 are isostructural and exhibit the 4-connected 4¹² topology. The thermal stabilities for 1–4 and photoluminescence properties for the d¹⁰ metal centers were discussed in detail.

Graphical abstract

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Evaluation of Fe(II)EDTA-NO reduction by zinc powder in wet flue gas denitrification technology with Fe(II)EDTA

Publication date: 1 July 2017
Source:Fuel, Volume 199
Author(s): Feiqiang He, Xianhe Deng, Min Chen
Regeneration of Fe(II)EDTA, converting Fe(III)-EDTA and Fe(II)EDTA-NO to Fe(II)EDTA, is the key process in a wet flue gas denitrification technology with Fe(II)EDTA solution. In this paper, Zn powder was first employed as a reductant to reduce Fe(II)EDTA-NO. The stoichiometry and kinetics of Fe(II)EDTA-NO reduction by Zn powder were investigated with respect to Zn powder concentration, pH value, and temperature. The effect of the particle size of the Zn powder on Fe(II)EDTA-NO reduction was also investigated. The experimental results indicated that Fe(II)EDTA-NO reduction rate increased with the decrease of pH value and elevated temperature, and small particle size is beneficial to Fe(II)EDTA NO reduction. Fe(II)EDTA-NO reduction with Zn powder showed a pseudo-second-order reaction concerning Fe(II)EDTA-NO. In addition, the energy of activation (Ea) and the entropy of activation (ΔS^‡) of the Fe(II)EDTA-NO reduction with Zn powder were estimated to be 19.853kJmol⁻¹ and −135.557JK⁻¹mol⁻¹, respectively. Finally, the simultaneous reduction of Fe(III)EDTA and Fe(II)EDTA-NO with Zn powder was investigated. Results showed that Zn powder had better performance on simultaneous Fe(III)EDTA and Fe(II)EDTA-NO reduction as compared to the earlier related research. These fundamental researches can offer valuable guidance for industrial denitrification using mixed Fe(II)EDTA and Zn powder system.



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Oxysterols: players in different metabolic leagues

Publication date: Available online 16 March 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Dieter Lütjohann, Gérard Lizard, Luigi Iuliano




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A comparative study of bio-inspired protective scales using 3D printing and mechanical testing

Publication date: Available online 16 March 2017
Source:Acta Biomaterialia
Author(s): Roberto Martini, Yanis Balit, Francois Barthelat
Flexible natural armors from fish, alligators or armadillo are attracting an increasing amount of attention for their unique combinations of hardness, flexibility and light weight. The extreme contrast of stiffness between hard scales and surrounding soft tissues gives rise to unusual and attractive mechanisms, which now serve as models for the design of bio-inspired armors. Despite this growing interest, there is little guideline for the choice of materials, optimum thickness, size, shape and arrangement for the protective scales. In this work, we explore how the geometry and arrangement of hard scales can be tailored to promote scale-scale interactions. We use 3D printing to fabricate arrays of scales with increasingly complex geometries and arrangements, from simple squares with no overlap to complex ganoid-scales with overlaps and interlocking features. We performed puncture tests and flexural tests on each of the 3D printed materials, and we report the puncture resistance – compliance characteristics of each design on an Ashby chart. The interactions between the scales can significantly increase the resistance to puncture, and these interactions can be maximized by tuning the geometry and arrangement of the scales. Interestingly, the designs that offer the best combinations of puncture resistance and flexural compliance are similar to the geometry and arrangement of natural teleost and ganoid scales, which suggests that natural evolution has shaped these systems to maximize flexible protection. This study yields new insights into the mechanisms of natural dermal armor, and also suggests new designs for personal protective systems.Statement of significanceFlexible natural armors from fish, alligators or armadillo are attracting an increasing amount of attention from their unique and attractive combinations of hardness, flexibility and low weight. Despite a growing interest in bio-inspired flexible protection, there is still little guideline for the choice of materials, optimum thickness, size, shape and arrangement for the protective scales. In this work, we explored how the geometry and arrangement of hard scales affect puncture resistance and flexural compliance, using 3D printing and mechanical testing. Our main finding is that the performance of the scaled skin in terms of puncture resistance can be significantly improved by slight changes in their geometry and arrangement. Our results also suggest that natural evolution has shaped scaled skins to maximize flexible protection. This study yields new insights into the mechanisms of natural dermal armor, and also suggests new designs for personal protective systems.

Graphical abstract

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A closer look at the in vitro electrochemical characterisation of titanium alloys for biomedical applications using in-situ methods

Publication date: Available online 16 March 2017
Source:Acta Biomaterialia
Author(s): J-L. Wang, R.L. Liu, T. Majumdar, S.A. Mantri, V.A. Ravi, R. Banerjee, N. Birbilis
Titanium (Ti) and its alloys are widely used in several biomedical applications, particularly as permanent orthopaedic implants. Electrochemical testing provides a means to perform accelerated corrosion testing, however whilst results from polarisation testing for Ti and its alloys to date have been generally useful, they are also rather limited on the basis of several reasons. One reason is that the polarisation curves for Ti and its alloys in simulated body fluids all appear rather similar, and they do not present a classical 'breakdown' or pitting potential, making discrimination between alloys difficult. Of practical relevance however, are two key issues; (1) how do Ti alloys respond to a breakdown event? (i.e. do they readily 'repassivate'?), and, (2) what is that actual rate of Ti ion loss from exposure to physiological conditions? The answers to these questions are probed herein. Several Ti alloys of either unique composition or different fabrication method were studied, including commercially pure Ti (cp-Ti), Ti-6Al-4V, Ti-29Nb-13Ta-4.5Zr (TNTZ), selective laser melted Ti-6Al-4V, direct laser deposited cp-Ti, Ti-35Nb-15Zr, and Ti-25Nb-8Zr. Results reveal that both fabrication method and alloying influence 'repassivation' behaviour. Furthermore, atomic emission spectroelectrochemistry as applied to cp-Ti indicated actual dissolution currents of ∼2-3 μA/cm^-2 (i.e. ∼9 μm/yr) in the range of the corrosion potential, also revealing such dissolution is persistent, even with cathodic polarisation, and definitively revealing that the presence of hydrogen peroxide and albumin activate anodic dissolution of Ti.Statement of SignificanceWe believe the paper makes a significant and important contribution to the field of permanent implant biomaterials. Whilst we concede that the paper does not include any in vivo work, the timeliness of the work, and the completely new nature of the findings, we believe carries the impact required for Acta Biomaterialia.Key highlights include:- A means of assessment of 'repassivation' of Ti-alloys used as biomaterials (for the first time)- Reportage of the performance of various Ti-alloys fabricated by 3D printing (for the first time)- The first unambiguous reporting of the TRUE corrosion rate of Ti in biological environments, employing the advanced AESEC method (for the first time).- Demonstration of the real, and important, effect of the combination of albumin and H2O2 upon dissolution kinetics of Ti (recently revealed to be critically important in this journal: F. Yu, O. Addison, A.J. Davenport, A synergistic effect of albumin and H2O2 accelerates corrosion of Ti6Al4V, Acta Biomater, 26 (2015) 355-365)All of the above combine to produce a manuscript that we believe has wide appeal, and can be used as both a port of reference to those working with Ti biomaterials, and also those wishing to apply useful characterisation techniques to their own work (with two very novel methods demonstrated herein, along with the unique information they provide).

Graphical abstract

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Fascicles and the interfascicular matrix show decreased fatigue life with ageing in energy storing tendons

Publication date: Available online 16 March 2017
Source:Acta Biomaterialia
Author(s): Chavaunne T Thorpe, Graham P Riley, Helen L Birch, Peter D Clegg, Hazel RC Screen
Tendon is composed of rope-like fascicles bound together by interfascicular matrix (IFM). The IFM is critical for the function of energy storing tendons, facilitating sliding between fascicles to allow these tendons to cyclically stretch and recoil. This capacity is required to a lesser degree in positional tendons. We have previously demonstrated that both fascicles and IFM in energy storing tendons have superior fatigue resistance compared with positional tendons, but the effect of ageing on the fatigue properties of these different tendon subunits has not been determined. Energy storing tendons become more injury-prone with ageing, indicating reduced fatigue resistance, hence we tested the hypothesis that the decline in fatigue life with ageing in energy storing tendons would be more pronounced in the IFM than in fascicles. We further hypothesised that tendon subunit fatigue resistance would not alter with ageing in positional tendons. Fascicles and IFM from young and old energy storing and positional tendons were subjected to cyclic fatigue testing until failure, and mechanical properties were calculated. The results show that both IFM and fascicles from the SDFT exhibit a similar magnitude of reduced fatigue life with ageing. By contrast, the fatigue life of positional tendon subunits was unaffected by ageing. The age-related decline in fatigue life of tendon subunits in energy storing tendons is likely to contribute to the increased risk of injury in aged tendons. Full understanding of the mechanisms resulting in this reduced fatigue life will aid in the development of treatments and interventions to prevent age-related tendinopathy.Statement of SignificanceUnderstanding the effect of ageing on tendon-structure function relationships is crucial for the development of effective preventative measures and treatments for age-related tendon injury. In this study, we demonstrate for the first time that the fatigue resistance of the interfascicular matrix decreases with ageing in energy storing tendons. This is likely to contribute to the increased risk of injury in aged tendons. Full understanding of the mechanisms that result in this reduced fatigue resistance will aid in the development of treatments and interventions to prevent age-related tendinopathy.

Graphical abstract

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Self-assembled photoadditives in polyester films allow stop and go chemical release

Publication date: Available online 16 March 2017
Source:Acta Biomaterialia
Author(s): Ting Cheng, Richard O'Rorke, Raphael Francois Ortiz, Tay Yee Yan, Eva Hemmer, Fiorenzo Vetrone, Robert S. Marks, Terry W.J. Steele
Near-infrared (NIR) triggered chemical delivery allows on-demand release with the advantage of external tissue stimulation. Bioresorbable polyester poly-L-lactic acid (PLLA) was compounded with photoadditives of neat zinc oxide (ZnO) nanoparticles and 980 → 365 nm LiYF4:Tm³⁺, Yb³⁺ upconverting nanoparticles (UCNP). Subsequently, neat ZnO and UCNP blended PLLA films of sub-50 μm thickness were knife casted with a hydrophobic small molecule drug mimic, fluorescein diacetate. The PLLA films displayed a 500 times increase in fluorescein diacetate release from the 50 mW NIR irradiated PLLA/photoadditive film compared to non-irradiated PLLA control films. Larger ratios of UCNP/neat ZnO increased photocatalysis efficiency at low NIR duty cycles. The synergistic increase results from the self-assembled photoadditives of neat zinc oxide and upconverting nanoparticles (UCNPs), as seen in transmission electron microscopy. Colloidal ZnO, which does not self-assemble with UCNPs, had less than half the release kinetics of the self-assembled PLLA films under similar conditions, advocating Förster resonance energy transfer as the mechanism responsible for the synergistic increase. Alternative to intensity modulation, pulse width modulation (duty cycles from 0.1 to 1) of the low intensity 50 mW NIR laser diode allowed tailorable release rates from 0.01 to 1.4% per day. With the low intensity NIR activation, tailorable release rates, and favourable biocompatibility of the constituents, implanted PLLA photoadditive thin films could allow feedback mediated chemical delivery.Statement of SignificanceUpconverting nanoparticles and zinc oxide nanorods were found to spontaneously self-assemble into submicron particles in organic solvents. Exposure of the submicron particles to near-infrared light allows stop and go chemical release from biocompatible polymers. Sample preparation of thin films is done with ease through physical mixing of the photoadditives followed by air-dried knife casting. A colloidal ZnO variant that does not self-assemble with upconverting nanoparticles had slower chemical release, suggesting that synergistic chemical release is brought upon by highly efficient energy transfer mechanisms when the nanoparticles are less than 10 nanometers apart. Never before seen composite particles of UCNP/ZnO are displayed, which shows the close interaction of the photoadditives within the polymer matrix.

Graphical abstract

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The Case for Applying Tissue Engineering Methodologies to Instruct Human Organoid Morphogenesis

Publication date: Available online 16 March 2017
Source:Acta Biomaterialia
Author(s): Carlos R. Marti-Figueroa, Randolph S. Ashton
Three-dimensional organoids derived from human pluripotent stem cell (hPSC) derivatives have become widely used in vitro models for studying development and disease. Their ability to recapitulate facets of normal human development during in vitro morphogenesis produces tissue structures with unprecedented biomimicry. Current organoid derivation protocols primarily rely on spontaneous morphogenesis processes to occur within 3-D spherical cell aggregates with minimal to no exogenous control. This yields organoids containing microscale regions of biomimetic tissues, but at the macroscale (i.e. 100's of microns to millimeters), the organoids' morphology, cytoarchitecture, and cellular composition are non-biomimetic and variable. The current lack of control over in vitro organoid morphogenesis at the microscale induces aberrations at the macroscale, which impedes realization of the technology's potential to reproducibly form anatomically correct human tissue units that could serve as optimal human in vitro models and even transplants. Here, we review tissue engineering methodologies that could be used to develop powerful approaches for instructing multiscale, 3-D human organoid morphogenesis. Such technological mergers are critically needed to harness organoid morphogenesis as a tool for engineering functional human tissues with biomimetic anatomy and physiology.Statement of SignificanceHuman PSC-derived 3-D organoids are revolutionizing the biomedical sciences. They enable the study of development and disease within patient-specific genetic backgrounds and unprecedented biomimetic tissue microenvironments. However, their uncontrolled, spontaneous morphogenesis at the microscale yields inconsistences in macroscale organoid morphology, cytoarchitecture, and cellular composition that limits their standardization and application. Integration of tissue engineering methods with organoid derivation protocols could allow us to harness their potential by instructing standardized in vitro morphogenesis to generate organoids with biomimicry at all scales. Such advancements would enable the use of organoids as a basis for 'next-generation' tissue engineering of functional, anatomically mimetic human tissues and potentially novel organ transplants. Here, we discuss critical aspects of organoid morphogenesis where application of innovative tissue engineering methodologies would yield significant advancement towards this goal.

Graphical abstract

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Motion corrected DWI with integrated T2-mapping for simultaneous estimation of ADC, T2-relaxation and perfusion in prostate cancer

Publication date: June 2017
Source:Magnetic Resonance Imaging, Volume 39
Author(s): M. Skorpil, P. Brynolfsson, M. Engström
ObjectiveMultiparametric magnetic resonance imaging (MRI) and PI-RADS (Prostate Imaging – Reporting and Data System) has become the standard to determine a probability score for a lesion being a clinically significant prostate cancer. T2-weighted and diffusion-weighted imaging (DWI) are essential in PI-RADS, depending partly on visual assessment of signal intensity, while dynamic-contrast enhanced imaging is less important. To decrease inter-rater variability and further standardize image evaluation, complementary objective measures are in need.MethodsWe here demonstrate a sequence enabling simultaneous quantification of apparent diffusion coefficient (ADC) and T2-relaxation, as well as calculation of the perfusion fraction f from low b-value intravoxel incoherent motion data. Expandable wait pulses were added to a FOCUS DW SE-EPI sequence, allowing the effective echo time to change at run time. To calculate both ADC and f, b-values 200s/mm² and 600s/mm² were chosen, and for T2-estimation 6 echo times between 64.9ms and 114.9ms were used.ResultsThree patients with prostate cancer were examined and all had significantly decreased ADC and T2-values, while f was significantly increased in 2 of 3 tumors. T2 maps obtained in phantom measurements and in a healthy volunteer were compared to T2 maps from a SE sequence with consecutive scans, showing good agreement. In addition, a motion correction procedure was implemented to reduce the effects of prostate motion, which improved T2-estimation.ConclusionsThis sequence could potentially enable more objective tumor grading, and decrease the inter-rater variability in the PI-RADS classification.



http://ift.tt/2nvsqWG

Is GH dosing optimal in female patients with adult-onset GH deficiency? An analysis from the NordiNet® International Outcome Study

Summary

Objective

To evaluate gender differences in GH dosing, IGF-I and cardiovascular risk markers in adults with GH deficiency (GHD).

Design

NordiNet^® International Outcome Study (NCT00960128), a non-interventional, multicentre study, evaluates the long-term effectiveness and safety of Norditropin^® (Novo Nordisk A/S) in the real-life clinical setting.

Patients

Non-diabetic patients (n=252; 41.7% female) with adult-onset GHD (age ≥20 years at GH start), ≥4 years' GH therapy, and glycosylated haemoglobin (HbA_1c) data at baseline and 4 years.

Measurements

Effects of gender (adjusted for baseline age and body mass index [BMI], average GH dose, treatment duration, and concomitant medication) on change from baseline to 4 years (∆) in HbA_1c, fasting plasma glucose (FPG), IGF-I, lipids and waist circumference were evaluated.

Results

GH dose (mean [SE]; mg/day) was similar between females (0.22 [0.02]) and males (0.21 [0.01]) at baseline, but higher in females from year 1 (year 4, females, 0.45 [0.03]; males, 0.32 [0.02]). Mean IGF-I standard deviation score [SDS] was lower in females vs males at each treatment year; more than one-third of females still had an IGF-I SDS below 0 at year 4, compared with only 21.8% of men. An adverse lipid profile at baseline remained poor in more females than males at 4 years. Improvement in total cholesterol was significantly associated with gender (P < 0.0001), improving less in females than in males.

Conclusions

These data highlight that, even after 4 years, GH dose is sub-optimal in many female patients, which may impact clinical outcomes; therefore, GH titration for women requires further improvement.

This article is protected by copyright. All rights reserved.

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A review of 4D printing

Publication date: 15 May 2017
Source:Materials & Design, Volume 122
Author(s): Farhang Momeni, Seyed M.Mehdi Hassani.N, Xun Liu, Jun Ni
Research into 4D printing has attracted unprecedented interest since 2013 when the idea was first introduced. It is based on 3D printing technology, but requires additional stimulus and stimulus-responsive materials. Based on certain interaction mechanisms between the stimulus and smart materials, as well as appropriate design of multi-material structures from mathematical modeling, 4D printed structures evolve as a function of time and exhibit intelligent behavior. Unlike 3D printing, 4D printing is time-dependent, printer-independent, predictable, and targets shape/property/functionality evolution. This allows for self-assembly, multi-functionality, and self-repair. This paper presents a comprehensive review of the 4D printing process and summarizes the practical concepts and related tools that have a prominent role in this field. Unsought aspects of 4D printing are also studied and organized for future research.

Graphical abstract

http://ift.tt/2ma9uwH

VPPAW penetration monitoring based on fusion of visual and acoustic signals using t-SNE and DBN model

Publication date: 5 June 2017
Source:Materials & Design, Volume 123
Author(s): Di Wu, Yiming Huang, Huabin Chen, Yinshui He, Shanben Chen
It is a big challenge to identify the joint penetration status for obtaining high-quality weld joints during variable polarity plasma arc welding (VPPAW). This paper addresses "t-stochastic neighbor embedding" (t-SNE) and deep belief network (DBN) to perform VPPAW process monitoring and penetration status identification. The multi-source weld information under different conditions is simultaneously received by using visual and acoustic sensors. Time and frequency domains features extracting from the sensors constitute a fusing feature set to reflect the variation trend of weld penetration status. Using the obtained feature vectors, t-SNE method is proposed to acquire the intrinsic features corresponding to different penetration states and map them into a 3-dimensional space to realize visualization. The visualization result produced by t-SNE is significantly better than PCA or Isomap technique. Then the DBN classification model with the optimal structure is developed to guarantee effective identification of penetration status. Experimental verification and comparisons show that the classification performance of DBN can reach 97.62% which indicates DBN outperforms back-propagation neural network (BPNN) and support vector machine (SVM) models. The proposed methodology based on the combination of t-SNE and DBN might be regarded as a promising technique for VPPAW penetration status identification.

Graphical abstract

http://ift.tt/2mao4V1

Extended application of a unified creep-ageing constitutive model to multistep heat treatment of aluminium alloys

Publication date: 15 May 2017
Source:Materials & Design, Volume 122
Author(s): Yong Li, Zhusheng Shi, Jianguo Lin, Yo-Lun Yang, Qi Rong
A recently developed unified constitutive model for creep-ageing of an Al-Cu-Li alloy (AA2050-T34) has been successfully extended to applications of multistep heat treatments of aluminium alloys, including natural and artificial ageing with simple and complex hardening evolution and creep-ageing with different initial temper conditions. An age hardening model for both natural and artificial ageing was proposed based on the unified creep-ageing constitutive model and methods to determine the initial and equilibrium values of both micro and macro variables of aluminium alloys under general heat-treated conditions were presented. By unifying normalised microstructural variables throughout the multistep heat treatments, the model was able to predict both the simple and complex strengthening evolution of various aluminium alloys during ageing and creep-ageing. A number of case studies were carried out for natural ageing, artificial ageing and creep-ageing of some typical heat-treatable aluminium alloys, including 2xxx (Al-Cu-Mg and Al-Cu-Li) and 7xxx (Al-Zn-Mg) alloys with as-quenched, naturally-aged (T3/T4) and peak-aged (T6/T8) initial temper conditions. Excellent agreement has been achieved between experimental and simulation results.

Graphical abstract

http://ift.tt/2mabo05

Surface electromyogram and muscle ultrasonography for detection of muscle fasciculations in pediatric peripheral neuropathy

Publication date: Available online 16 March 2017
Source:Brain and Development
Author(s): Masayoshi Oguri, Yoshiaki Saito, Tetsuya Okazaki, Wataru Matsumura, Koyo Ohno, Masami Togawa, Chisako Fukuda, Yuko Saito, Ichizo Nishino, Yoshihiro Maegaki
A 12-year-old girl presented with talipes equinus of both legs, attenuation of upper and lower limb tendon reflexes, thermal hyperalgesia, and reduction of vibratory sensation. On clinical examination, muscle twitches of fingers of both hands, as well as the abductor halluces and the dorsal interossei muscles of the right foot were observed. Nerve conduction velocity was significantly declined in the upper and lower extremities. Needle electromyography (EMG) was not performed; however, ultrasonography revealed repetitive, semi-regular muscle twitches lasting 0.2–0.4s, concomitant with muscle discharges on surface EMG in the right foot muscles. These findings were compatible with contraction fasciculation in muscles under chronic reinnervation. Nerve and muscle biopsies were suggestive of chronic motor, sensory, and autonomic neuropathy. This is the first case of pediatric peripheral neuropathy where muscle fasciculation was noninvasively identified by simultaneous surface EMG and ultrasonography.



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Spinal fusion in a patient with Fukuyama congenital muscular dystrophy

Publication date: Available online 16 March 2017
Source:Brain and Development
Author(s): Kaori Hino, Mitsumasa Fukuda, Tadao Morino, Tadanori Ogata, Masanori Ito, Eiichi Ishii
Many studies have evaluated surgical treatments for spinal deformities in patients with neuromuscular disease. However, few reports have described patients with Fukuyama congenital muscular dystrophy (FCMD). A 13-year-old boy with FCMD was unable to sit for long periods or sleep in the supine position because of progressive scoliosis. His Cobb angle worsened from 27° to 41° in 5months. He underwent standard posterior spinal fusion and pedicle-screw-alone fixation from T5 to S1. Postoperatively, his Cobb angle improved from 41° to 25° without exacerbation for 2years. After the surgery, he was able to sit for longer periods without pain, and he and his family were satisfied with the efficacy of the spinal fusion. Some patients with mild FCMD can sit at the age of puberty, but progression to scoliosis is possible. Therefore, spinal fusion for progressive scoliosis in patients with FCMD should be considered.



http://ift.tt/2mX07Pu

Radiation Dose Escalation in Esophageal Cancer

Condition:   Esophageal Cancer
Intervention:   Radiation: radiotherapy plus chemotherapy
Sponsor:   Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Recruiting - verified March 2017

http://ift.tt/2mzZSqc

Pembrolizumab Combined With Cetuximab for Treatment of Recurrent/Metastatic Head & Neck Squamous Cell Carcinoma

Conditions:   HNSCC;   Lip SCC;   Oral Cavity Cancer;   Oropharynx Cancer;   Larynx Cancer;   Hypopharynx Cancer;   Nasopharynx Cancer;   Sinonasal Carcinoma;   Cutaneous Squamous Cell Carcinoma;   Head and Neck Neoplasms;   Head and Neck Cancer;   Head and Neck Squamous Cell Carcinoma
Intervention:   Drug: Pembrolizumab, Cetuximab
Sponsors:   Assuntina G. Sacco;   Merck Sharp & Dohme Corp.
Not yet recruiting - verified March 2017

http://ift.tt/2nvlatX

Prediction Model of Response for CCRT in Esophageal Cancer

Condition:   Esophageal Cancer
Intervention:   Other: chemoradiotherapy
Sponsor:   Kyungpook National University
Recruiting - verified March 2017

http://ift.tt/2mA0gVJ

Longitudinal Evaluation of Hip Cartilage Degeneration: FAI

Condition:   Femoroacetabular Impingement
Intervention:   Other: dGEMERIC MRI technique
Sponsors:   Hospital for Special Surgery, New York;   National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Recruiting - verified March 2017

http://ift.tt/2mzTGi5

Letter to the Editor: A late response from a female scientist to Hoy, ‘Gender Imbalance at Brain Stimulation Conferences: We Have a Problem and it is Everyone’s Problem’

Publication date: Available online 16 March 2017
Source:Brain Stimulation
Author(s): Andrea Antal




http://ift.tt/2nMFWSa

Transcutaneous and invasive vagal nerve stimulations engage the same neural pathways: in-vivo human evidence

Publication date: Available online 16 March 2017
Source:Brain Stimulation
Author(s): Giovanni Assenza, Chiara Campana, Gabriella Colicchio, Mario Tombini, Federica Assenza, Giovanni Di Pino, Vincenzo Di Lazzaro




http://ift.tt/2mX613r

Colon-targeted delivery of solubilized bisacodyl by doubly enteric-coated multiple-unit tablet

Publication date: 1 May 2017
Source:European Journal of Pharmaceutical Sciences, Volume 102
Author(s): Hee J. Park, Hyuck J. Jung, Myoung J. Ho, Dae R. Lee, Ha R. Cho, Yong S. Choi, Joonho Jun, Miwon Son, Myung J. Kang
A doubly enteric-coated multiple-unit tablet (DET) of bisacodyl (BD) was formulated to selectively deliver the stimulant laxative to the large intestine. Solubilized BD in surfactants was adsorbed into the porous carrier and primarily coated with different combinations of pH-sensitive polymers (Eudragit S and Eudragit L) and time-dependent release polymer (Eudragit RS). BD-loaded granules were compressed into tablets and coated again with pH-sensitive polymers (Eudragit S:Eudragit L=1:1). The multiple-unit tablet was optimized with respect to the granular coating compositions (Eudragit S:Eudragit L:Eudragit RS=5:1:4) and coating level (12.5%), and coating level on the tablet (25%), by evaluating in vitro release profile in continuous dissolution medium. Drug release from the optimized tablet was effectively retarded in the simulated gastric and small intestinal fluids (below 7%), but profound drug liberation was attained in the colonic fluid (over 50%). On the other hand, drug release from the marketed product (Dulcolax®, Boehringer Ingelheim Pharma), a reference drug, in the gastric and small intestinal fluids was reached to 30%, while that in the colonic fluid was only 7%. In an in vivo efficacy study in loperamide-induced constipated rabbits, a remarkable recovery in fecal secretion was observed in the DET-treated group 24h post-dosing, compared to vehicle-treated (p<0.05) and the marketed product-treated groups (p<0.05). Moreover, pharmacokinetic evaluation in the constipated rabbits revealed that the DET system significantly lowered the systemic exposure compared with the marketed product (p<0.05), by hindering drug release in the upper intestine, a preferential absorption site. Therefore, the novel colon-targeted delivery system may be an alternative for boosting pharmacological responses in the colon, while diminishing the intestinal irritation and/or systemic adverse effect of the stimulant laxative.

Graphical abstract

http://ift.tt/2mX4hH9

Multifunctional LUV liposomes decorated for BBB and amyloid targeting - B. In vivo brain targeting potential in wild-type and APP/PS1 mice

Publication date: 1 May 2017
Source:European Journal of Pharmaceutical Sciences, Volume 102
Author(s): Konstantina Papadia, Anastasios D. Giannou, Eleni Markoutsa, Christian Bigot, Greejte Vanhoute, Spyridon Mourtas, Annemie Van der Linded, Georgios T. Stathopoulos, Sophia G. Antimisiaris
Multifunctional liposomes (mf-LIPs) having a curcumin-lipid ligand (to target amyloids) together with two ligands to target the transferrin, and the low-density apolipoprotein receptor of the blood-brain-barrier (BBB) on their surface, were previously studied (in vitro) as potential theranostic systems for Alzheimer's disease (AD) (Papadia et al., 2017, Eur. J. Pharm. Sciences; 101:140–148). Herein, the targeting potential of mf-LIPs was compared to that of BBB-LIPs (liposomes having only the two BBB-specific ligands) in FVB mice (normal), as well as in double transgenic mice (APP/PS1) and their corresponding littermates (WT), by live-animal (in vivo) and explanted organ (ex vivo) imaging. In FVB mice, the head-signals of mf-LIPs and BBB-LIPs are either similar, or signals from mf-LIP are higher, suggesting that the co-presence of the curcumin derivative on the liposome surface does not disturb the functionality of the BBB-specific ligands. Higher brain/liver+spleen ratios (ex vivo) were calculated post-injection of mf-LIP, compared to those found after BBB-LIP injection, due to the reduced distribution of mf-LIPs in the liver and spleen; showing that the curcumin ligand increases the stealth properties of liposomes by reducing their uptake by liver and spleen. The later effect is more pronounced when the density of the BBB-specific ligands on the mf-LIPs is 0.1mol%, compared to 0.2%, highlighting the importance of this parameter. When a high lipid dose (4mg/mouse) is injected in WT and APP/PS1 mice, the head-signals of mf-LIPs are significantly higher than those of BBB-LIPs, but no differences are observed between WT and APP/PS1 mice. However, after administration of a low liposome dose (0.05mg/mouse) of mf-LIPs, significant differences in the head-signals are found between WT and transgenic mice, highlighting the AD theranostic potential of the multifunctional liposomes, as well as the importance of the experimental parameters used in such in vivo screening studies.

Graphical abstract

http://ift.tt/2mXjTun

Surface area, volume and shape descriptors as a novel tool for polymer lead design and discovery

Publication date: 1 May 2017
Source:European Journal of Pharmaceutical Sciences, Volume 102
Author(s): Jonatan Riis Christensen, Helena Meng-Lund, Holger Grohganz, Antti Poso, Tuomo Laitinen, Ossi Korhonen, Lene Jørgensen, Jari Pajander
In recent years, the demand and interest for functionalized polymers have increased for drug delivery purposes. Because of the increased interest, methods that can be used to predict physical and chemical properties of polymers prior to synthesis would be of high value for the design and development of novel polymer structures. Through use of molecular descriptors and Principal Component Analysis, this study explores the possibilities of using in silico methods for polymer design and characterization for property prediction. The results presented in this paper suggest that it is possible to produce a model, which can successfully distinguish between a set of both structurally similar and different polymers based on their surface properties.

Graphical abstract

http://ift.tt/2mX9KxT

Exploring the State of the Science in the Field of Regenerative Medicine: Challenges of and Opportunities for Cellular Therapies: Proceedings of a Workshop [Prepublication Draft].

Regenerative medicine holds the potential to create living, functional cells and tissues that can be used to repair or replace those that have suffered potentially irreparable damage due to disease, age, traumatic injury, or genetic and congenital defects. The field of regenerative medicine is broad and includes research and development components of gene and cell therapies, tissue engineering, and non-biologic constructs. Although regenerative medicine has the potential to improve health and deliver economic benefits, this relatively new field faces challenges to developing policies and procedures to support the development of novel therapies are both safe and effective.

http://ift.tt/2nMJqnE

Role of AHR and HIF-1α in Glioblastoma Metabolism

Publication date: Available online 16 March 2017
Source:Trends in Endocrinology & Metabolism
Author(s): Galina Gabriely, Michael A. Wheeler, Maisa C. Takenaka, Francisco J. Quintana
Glioblastoma (GBM) progression is associated with metabolic remodeling in both glioma and immune cells, resulting in the use of aerobic glycolysis as the main source of energy and biosynthetic molecules. The transcription factor hypoxia-inducible factor (HIF)-1α drives this metabolic reorganization. Oxygen levels, as well as other factors, control the activity of HIF-1α. In addition, the ligand-activated transcription factor aryl hydrocarbon receptor (AHR) modulates tumor-specific immunity and can also participate in metabolic remodeling. AHR activity is regulated by tryptophan derivatives present in the tumor microenvironment. Thus, the tumor microenvironment and signaling via HIF-1α and AHR regulate the metabolism of gliomas and immune cells, modulating tumor-specific immunity and, consequently, tumor growth. Here, we review the roles of HIF-1α and AHR in cancer and immune cell metabolism in GBM.



http://ift.tt/2mQlTmi

Adipocyte Accumulation in the Bone Marrow during Obesity and Aging Impairs Stem Cell-Based Hematopoietic and Bone Regeneration

Publication date: Available online 16 March 2017
Source:Cell Stem Cell
Author(s): Thomas H. Ambrosi, Antonio Scialdone, Antonia Graja, Sabrina Gohlke, Anne-Marie Jank, Carla Bocian, Lena Woelk, Hua Fan, Darren W. Logan, Annette Schürmann, Luis R. Saraiva, Tim J. Schulz
Aging and obesity induce ectopic adipocyte accumulation in bone marrow cavities. This process is thought to impair osteogenic and hematopoietic regeneration. Here we specify the cellular identities of the adipogenic and osteogenic lineages of the bone. While aging impairs the osteogenic lineage, high-fat diet feeding activates expansion of the adipogenic lineage, an effect that is significantly enhanced in aged animals. We further describe a mesenchymal sub-population with stem cell-like characteristics that gives rise to both lineages and, at the same time, acts as a principal component of the hematopoietic niche by promoting competitive repopulation following lethal irradiation. Conversely, bone-resident cells committed to the adipocytic lineage inhibit hematopoiesis and bone healing, potentially by producing excessive amounts of Dipeptidyl peptidase-4, a protease that is a target of diabetes therapies. These studies delineate the molecular identity of the bone-resident adipocytic lineage, and they establish its involvement in age-dependent dysfunction of bone and hematopoietic regeneration.

Graphical abstract

Teaser

Ambrosi, Schulz, and colleagues define a stem cell-like population that gives rise to osteogenic progeny and promotes hematopoietic reconstitution. Aging and high-fat diet reprogram the mesenchymal lineage to preferentially give rise to adipogenic cells that impair reconstitution and bone fracture healing. Bone tissue repair is fully restored by DPP4 inhibition.


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An experimental examination of the effort-reward imbalance model of occupational stress: Increased financial reward is related to reduced stress physiology

Publication date: Available online 16 March 2017
Source:Biological Psychology
Author(s): Kathleen Landolt, Emma O'Donnell, Agnes Hazi, Nico Dragano, Bradley J. Wright
Effort-reward imbalance in the workplace is linked to a variety of negative health and organisational outcomes, but it has rarely been assessed experimentally. We manipulated reward (while keeping effort constant) in a within-subjects design with female participants (N= 60) who were randomly assigned to high and standard reward conditions within a simulated office environment. Self-report, behavioural (task performance), and physiological (heart rate variability, salivary alpha amylase) measures assessed the impact of increased financial reward. Participants reported increased perceptions of reward, performed moderately better on the task, and were less physiologically reactive in the high reward versus the standard condition. These findings highlight the importance of assessing both subjective self-reports of stress together with objective physiological measures of stress, and suggest that increasing monetary rewards has the potential to decrease stress physiological reactivity, and in turn, reduce the risk of ill-health in employees, and may also positively influence task efficacy.



http://ift.tt/2n5Xk77

Measurement reliability of atypical language lateralisation assessed using functional transcranial Doppler ultrasound

Publication date: Available online 16 March 2017
Source:Biological Psychology
Author(s): Jessica C. Hodgson, John M. Hudson
It is well established that some individuals present with atypical, non-left hemisphere, cerebral lateralisation for language processing. However previous studies exploring the reliability of functional blood flow responses to detect lateralised activation during speech have focused only on individuals with typical left sided dominance. Here we report test-retest and between-task reliability measures obtained with functional transcranial Doppler ultrasound in 47 participants, including 9 with atypical language presentation. Results showed good test-retest reliability in atypically lateralised individuals, even after an interval of 120 days. Between-task reliability was weaker, but still within acceptable ranges.



http://ift.tt/2mQmm87

Erectile dysfunction in patients with nonalcoholic fatty liver disease

Publication date: Available online 16 March 2017
Source:Arab Journal of Gastroenterology
Author(s): Ahmad Farooq Alsayed Hasanain, Reem Ezzat Mahdy, Ali Mohamed Abdel-Rahman Mahran, Ahmed Serag Mahmoud Safwat, Asmaa Omar Mohamed, Sherif Mohamed Abdel-Aal
Background and study aimsThere is a lack of studies on erectile dysfunction (ED) in patients diagnosed with nonalcoholic fatty liver disease (NAFLD). The present study aimed to estimate the prevalence of ED in patients with NAFLD and to determine the independent predictors of ED in these patients.Patients and methodsWe conducted a prospective, hospital-based study of 192 consecutive male patients with NAFLD. All patients underwent clinical evaluation; abdominal ultrasonography; test for viral hepatitis markers; and estimation of liver chemistry panel, complete blood count, prothrombin time, serum lipids panel, serum testosterone, and fasting serum levels of glucose, insulin, and C-peptide.ResultsThe mean age of the study population was 42.4±7.7years (79.1%≥40years). Of the 192 patients with NAFLD, 88 (45.8%) had ED, 28 (14.6%) had metabolic syndrome, 25 (13%) had type-2 diabetes mellitus (DM), and 131 (68.2%) had insulin resistance (IR). The mean level of serum testosterone was 3.17±2.94ng/mL, while the mean insulin resistance index was 2.9±1.7. Mild ED (38.6%) was the most frequent grade of ED. Age≥40years (odds ratio [OR] 6.4; 95% confidence interval [CI] 1.7–24.1; p- 0.006), IR (OR 5.9; 95% CI 1.7–20.6; p- 0.005), and low serum testosterone (OR 5.1; 95% CI 1.5–17.1; p- 0.009) were the predictors of ED.ConclusionsED is a common disorder in male patients with NAFLD; both IR and low serum testosterone contribute to its development. Treatment of IR may carry a dual benefit of improving erectile function and decreasing the grade of hepatic steatosis.



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Prospective evaluation of peripherally inserted central catheter complications in both inpatient and outpatient settings

Publication date: Available online 16 March 2017
Source:American Journal of Infection Control
Author(s): Christina Liscynesky, Jessica Johnston, Kelci E. Haydocy, Kurt B. Stevenson
We describe a prospective observational cohort (N = 187) to evaluate peripherally inserted central catheter line complications concurrently from the time of placement until removal. A significantly higher percentage of patients who experienced intraluminal thrombosis were receiving total parenteral nutrition (P ≤ .001) and had a dual lumen catheter (P = .01). Among patients with a confirmed or suspected infection, a significantly higher proportion received total parenteral nutrition (P = .01), had dual-lumen catheters (P = .04), and were neutropenic (P = .04).



http://ift.tt/2mWDwm8

Rates of central line–associated bloodstream infection in tertiary care hospitals in 3 Arabian gulf countries: 6-year surveillance study

Publication date: Available online 16 March 2017
Source:American Journal of Infection Control
Author(s): Hanan H. Balkhy, Aiman El-Saed, Seif S. Al-Abri, Jameela Alsalman, Huda Alansari, Zaina AL Maskari, Ayman El Gammal, Wafa Al Nasser, Amina AlJardani, Abdulhakeem Althaqafi
The objective of this study was to compare central line–associated bloodstream infection (CLABSI) rates in Gulf Cooperation Council (GCC) states with those of the U.S. National Healthcare Safety Network (NHSN) and International Nosocomial Infection Control Consortium (INICC) using pooled data from 6 hospitals in 3 GCC countries. The overall CLABSI rate was 3.1 per 1,000 central line days. After adjusting for differences in intensive care unit types, the risk of CLABSI in GCC hospitals was 146% higher than NHSN hospitals but 33% lower than INICC hospitals.



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A novel cytogenetic and molecular characterization of renal metanephric adenoma: identification of partner genes involved in translocation t(9;15)(p24;q24)

Publication date: Available online 16 March 2017
Source:Cancer Genetics
Author(s): Aida Catic, Amina Kozaric, Sarah H. Johnson, George Vasmatzis, Michael R. Pins, Jillene Kogan
Renal metanephric adenoma (MA) is a rare benign tumor frequently misclassified when microscopic features alone are applied. The correct classification of a renal tumor is critical for diagnostic, prognostic, and therapeutic purposes. Despite the advancements in cancer genomics, up until recently relatively few genetic alterations critical to the MA development have been recognized. Recent data suggest that 90% of MA have BRAF^V600E mutations; the genetics of the remaining 10 % are unclear. To date, only one case of a chromosomal translocation, t(9;15)(p24;q24) associated with MA has been reported. However, the potential role of the KANK1 gene, which lies near the breakpoint of the short arm of chromosome 9p24, in the etiology of MA was not examined. We identified the same cytogenetic aberration utilizing molecular cytogenetic techniques in a 22-year-old female patient, and further investigated the genes involved in the translocation that might have contributed to tumorgenesis. A series of fluorescence in situ hybridization (FISH) probes identified the rearranged genes to be KANK1 on chromosome 9 (9p24.3) and NTRK3 on chromosome 15 (15q25.3). Mate-Pair genome sequencing validated the balanced translocation between 9p24.3 and 15q25.3, involving genes KANK1 and NTRK3, respectively. BRAF^V600E mutational analysis was normal. Our findings indicate that, gene fusions may be one mechanism by which functionally relevant genes are altered in the development of MA. Molecular and cytogenetic analyses have elucidated a novel genetic aberration, which helps to provide a better understanding of this genomic change and assist in diagnosis and classification of new subgroups/ entities in metanephric adenomas.



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In vivo electroporation in DNA-VLP prime-boost preferentially enhances HIV-1 envelope-specific IgG2a, neutralizing antibody and CD8 T cell responses

Publication date: Available online 17 March 2017
Source:Vaccine
Author(s): Xun Huang, Qianqian Zhu, Xiaoxing Huang, Lifei Yang, Yufeng Song, Ping Zhu, Paul Zhou
Although in vivo electroporation (EP) has been utilized to improve immunogenicity in DNA vaccines alone or in prime-boost regimens with both proteins and viral-vectors, no studies on in vivo EP in DNA-VLP prime-boost regimens against HIV-1 have been reported. Previously we developed stably transfected Drosophila S2 clones to produce HIV-1 virus-like particles (VLP) and demonstrated that priming mice twice with DNA plasmids encoding HIV-1 gp120 and gag and boosting twice with HIV-1 VLP (i.e. DDVV immunization) elicited both envelope-specific antibody and envelope and gag-specific CD8 T cell responses. However, the potency and the breadth of immunogenicity still need to be improved. In this study we tested the effect of in vivo EP during DNA priming on immunogenicity of this DNA-VLP prime-boost regimen. Here we report that although both DDVV and DDVV+EP elicited gp120-specific ELISA-binding antibody responses, average EC50 values of gp120-specific ELISA-binding total IgG, IgG2a, but not IgG1, antibody responses were significantly higher in DDVV+EP than in DDVV. Moreover, while DDVV elicited neutralizing antibody responses against autologous, but not other five, strains tested, DDVV+EP not only elicited significantly higher anti-autologous neutralizing antibody responses, but also cross-neutralizes four of five other HIV-1 strains tested, including two tier 2 strains. Finally, although CD4 and CD8 T cells from both DDVV and DDVV+EP immunizations secreted IFN-γ, IL-2, TNF-α upon HIV-1 envelope peptide stimulation, average HIV-1 envelope-specific CD8 T cells that secreted IFN-γ, IL-2 and/or TNF-α were significantly higher in DDVV+EP than in DDVV. Thus we conclude that DDVV+EP immunization preferentially increases HIV-1 envelope-specific TH1 cytokine-mediated IgG2a responses and significantly enhances the potency and the breadth of neutralizing antibody responses including tier 2 viruses. Further study on this heterologous regimen in large animals is warranted.



http://ift.tt/2n5A9tC

Expression of Cathepsin S in BCG converts it into a pro-apoptotic and highly immunogenic strain

Publication date: Available online 17 March 2017
Source:Vaccine
Author(s): Alice Lau, Vijender Singh, Hafid Soualhine, Zakaria Hmama
BackgroundBCG vaccine, introduced almost 100years ago, is the only option to prevent TB disease. It effectively protects newborns from meningeal TB but fails to prevent adult pulmonary TB. TB kills 1.3million people annually in areas where BCG vaccination is widely practiced. Thus, more effective TB vaccines are urgently needed. Others and we have shown that BCG mimics features of virulent M. tuberculosis, in particular attenuation of essential macrophage functions such as phagosome maturation and antigen presentation. One of these studies revealed that defect in antigen presentation is largely due to down-regulation of the cysteine protease Cathepsin S (CatS), which prevents MHC II molecule maturation and proper antigen peptide loading. Recent studies also suggested a potential role for cysteine proteases in the regulation of apoptosis, a key cellular process used by the macrophage to (i) contain and process ingested bacteria and (ii) facilitate cross-talk antigen presentation between the macrophage and dendritic cells.MethodTo reverse the phenotype of vaccine-mediated macrophage attenuation, we engineered a novel BCG strain that expresses and secretes active CatS (rBCG-CatS) to examine its pro-apoptotic properties in vitro, and subsequently, immunogenicity in mice.ResultsTranscriptomic profiling of macrophages infected with rBCG-CatS, but not BCG, revealed upregulation of key pro-apoptotic genes and downregulation of anti-apoptotic genes, which were further confirmed by RT-qPCR analyses of expression of selected genes. Macrophages infected with rBCG-CatS undergo apoptosis as indicated by increased levels of annexin V staining and intracellular caspase-3 cleavage. Consistent with these findings, mice vaccinated with rBCG-CatS showed increased antigen-specific CD4⁺ T-cell responses, as well as enhanced cytokine production and proliferation in CD4⁺ upon ex vivo re-stimulation.ConclusionCollectively, this study shows that a pro-apoptotic BCG strain alleviates adverse traits of the wild-type strain, resulting in a highly immunogenic TB vaccine.



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Clinical development strategy for a candidate group A streptococcal vaccine

Publication date: Available online 16 March 2017
Source:Vaccine
Author(s): Florian Schödel, Nicole J. Moreland, Janet T. Wittes, Kim Mulholland, Ian Frazer, Andrew C. Steer, John D. Fraser, Jonathan Carapetis
GroupA streptococci (GAS) cause a wide spectrum of diseases ranging from benign pharyngitis and skin infections to severe invasive disease and the immune sequelae rheumatic fever and rheumatic heart disease. Pharyngitis, one of the most frequent diseases caused by GAS, is highly prevalent in school-age children in temperate climates and a major cause of antibiotic use. An efficacious vaccine would reduce disease burden associated with pharyngitis and the need of care for sick children. Importantly, GAS pharyngitis is recognised as the main precursor for acute rheumatic fever so a vaccine that is efficacious against GAS pharyngitis should also prevent acute rheumatic fever and rheumatic heart disease. It may also prevent post-streptococcal glomerulonephritis and invasive disease since GAS pharyngitis is one of the precursors for these clinical syndromes. There has been no clearly articulated pathway for clinical trial design leading to GAS vaccine registration. This review outlines a clinical development strategy detailing the phases of development required for registration of a candidate GAS vaccine for GAS pharyngitis initially, followed by impetigo and associated sequelae. The major advantages of a strategy first focused on GAS pharyngitis is an early proof of principle, that can be followed by studies for other clinical syndromes. The end goal being the availability of a preventive tool for the most prevalent GAS-associated diseases globally.



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Stereolithography: A new method for processing dental ceramics by additive computer-aided manufacturing

Publication date: Available online 17 March 2017
Source:Dental Materials
Author(s): Marion Dehurtevent, Lieven Robberecht, Jean-Christophe Hornez, Anthony Thuault, Etienne Deveaux, Pascal Béhin
ObjectivesThe aim of this study was to compare the physical and mechanical properties of stereolithography (SLA)- manufactured alumina ceramics of different composition to those of subtractive- manufactured ceramics and to produce suitable dental crown frameworks.MethodsThe physical and mechanical properties of a control and six experimental SLA ceramics prepared from slurries with small (S) and large (L) particles (0.46±0.03 and 1.56±0.04μm, respectively) and three dry matter contents (70%, 75%, 80%) were evaluated by dynamic rheometry, hydrostatic weighing, three3-point flexural strength measurements, and Weibull analyses, and by the micrometrics measurement of shrinkage ratio before and after the heat treatments.ResultsS75 was the only small particle slurry with a significantly higher viscosity than L70. The viscosity of the S80 slurry made it impossible to take rheological measurements. The viscosities of the S75 and S80 slurries caused deformations in the printed layers during SLA manufacturing and were excluded from further consideration. SLA samples with low dry matter content had significantly lower and densityflexural strengths. Only SLA samples with a large particle size and high dry matter content (L75 and L80) were similar in density and flexural strength to the subtractive- manufactured samples. The 95% confidence intervals of the Weibull modulus of the L80 ceramic were higher (no overlap fraction) than those of the L75 ceramic and were similar to the control (overlap fraction). The Weibull characteristics of L80 ceramic were higher than those of L75 ceramic and the control. SLA can be used to process suitable crown frameworks but shows results in anisotropic shrinkage.SignificanceThe hH High particle size and dry matter content of the L80 slurry allowed made it possible to produce a reliable ceramic by SLA manufacturing with an anisotropic shrinkage, and a density, and flexural strength similar to those of a subtractive-manufactured ceramic. SLA allowed made it possible to build up a dense 3D alumina crown framework with controlled shape. Further studies on the marginal adaptation and shrinkage model of alumina crown frameworks will be required to optimize the process.



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Chitinase 3-like-1 deficient donor splenocytes accentuated the pathogenesis of acute graft-versus-host diseases through regulating T cell expansion and type I inflammation

Publication date: May 2017
Source:International Immunopharmacology, Volume 46
Author(s): Zengyao Li, Jian Gu, Jing Liu, Qin Zhu, Hao Lu, Yunjie Lu, Jianhua Rao, Ling Lu, Xuehao Wang
Acute graft-versus-host disease (aGVHD) is a major complication following transplantation, limiting the success of this therapy. Chitinase 3-like-1 (CHI3L1), a member of the glycosyl hydrolase 18 family, plays a critical role in bacterial infections, allergic disease and a variety of malignancies. Here, we investigated whether CHI3L1 could affect the pathogenesis of aGVHD in a mouse allo-HCT model. In this study, we show that CHI3L1 deficiency in donor T cells increased the severity of aGVHD through enhancing systemic and local inflammation. In addition, we found that aGVHD induced by CHI3L1-knockout (CHI3L1-KO) donors resulted in massive expansion of donor CD3⁺ T cells, release of Th1-related cytokines and chemokines, and significant inhibition of CD4⁺CD25⁺Foxp3⁺ regulatory T cells (Tregs) without changing the suppressive ability of donor Tregs remarkably. Expression of PERK1/2 and PAkt increased both in the skin and intestine from CHI3L1-KO splenocytes-treated aGVHD mice. Moreover, at mRNA and protein levels, we defined several molecules that may account for the enhanced ability of CHI3L1-KO splenocytes to migrate into target organs and produce Th1-related cytokines and chemokines, such as CXCL9, CXCL11, IFN-γ and TNF-α. Therefore, these results imply that CHI3L1 levels in donor cells may be related to the risk of aGVHD and targeting CHI3L1 may be a promising clinical strategy to control aGVHD.



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Incorporation of Autopsy Case-Based Learning into PhD Graduate Education: a Novel Approach to Bridging the ‘Bench to Bedside’ Gap

Publication date: Available online 16 March 2017
Source:Human Pathology
Author(s): Erin G. Brooks, Joanne M. Thornton, Erik A. Ranheim, Zsuzsanna Fabry
Given the current rapid expansion of biological knowledge and the challenges of translating that knowledge into clinical practice, finding effective methods of teaching graduate students clinical medicine concepts has become even more critical. The utility of autopsy in medical student and resident education has been well-established. Multiple studies have reported it to be a helpful means of teaching anatomy, pathophysiology, clinical problem-solving skills, and medical diagnostic techniques. While various models of training Ph.D. candidates in clinical medicine have been reported, an autopsy-based curriculum has not been previously described. For over four years, our pathology department has offered a novel semester-long autopsy-based course to educate future Cellular and Molecular Pathology (CMP) scientists about clinical medicine. Our results indicating that this 'hands-on' approach is a popular as well as effective means of teaching the pathogenesis of disease at the level of the cell, organ, and patient. The course reputation has recently led to requests to open registration to graduate students from other university programs as well as undergraduate students. Additionally, it has played an important role in our CMP program's recent receipt of a 5-year renewal National Institutes of Health funded T32 award. Overall, this course model has been successful at our own institution, and could provide a useful template for other institutions seeking to provide graduate investigators with in-depth exposure to clinical medicine.



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Prognostic impact of GATA binding protein-3 expression in primary lung adenocarcinoma

Publication date: Available online 16 March 2017
Source:Human Pathology
Author(s): Toshihiro Hashiguchi, Hiroaki Miyoshi, Kazutaka Nakashima, Shintaro Yokoyama, Ryoichi Matsumoto, Daigo Murakami, Masahiro Mitsuoka, Shinzo Takamori, Yoshito Akagi, Koichi Ohshima
GATA binding protein-3 (GATA3) is a transcription factor that regulates cell differentiation and maintenance in some types of normal cells. This study aimed to investigate the association between GATA3 expression and primary lung adenocarcinoma and to clarify the clinical significance of GATA3 expression in lung adenocarcinoma. Immunohistochemical GATA3 expression was evaluated using completely resected lung adenocarcinoma samples from 95 cases. GATA3 immunohistochemical staining was performed and scored. Associations between clinicopathological factors and GATA3 expression were analyzed by using the χ²-test and Fisher's exact test. The Kaplan–Meier method was used to analyze overall survival (OS) and disease free survival (DFS). Forty-nine cases expressed high levels of GATA3, which were associated with lymphatic invasion (P=.003). In univariate and multivariate analyses, vascular invasion (P<.001) and high GATA3 expression (P=.023) were identified as independent risk factors for OS. Higher pathological stages (P=.012), vascular invasion (P=.010), and high GATA3 expression (P=.009) were identified as independent risk factors for DFS. The high GATA3 expression group exhibited statistically worse OS (P=.031) and DFS (P=.011) than the low expression group based on the Kaplan–Meier curves. In resected lung adenocarcinoma, high GATA3 expression is associated with poorer prognosis for both OS and DFS. Therefore, the immunohistochemical evaluation of GATA3 represents a potentially useful prognostic tool for postoperative patients.



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Malignant transformation of polyostotic fibrous dysplasia with aberrant keratin expression

Publication date: April 2017
Source:Human Pathology, Volume 62
Author(s): Riyam T. Zreik, Laurel A. Littrell, Long Jin, Andre M. Oliveira, Karen J. Fritchie
Malignant transformation of fibrous dysplasia (FD) is exceedingly rare, occurring in less than 1% of all FD cases, and has been described in both monostotic and polyostotic forms of this entity. We report a case of a large proximal femur mass arising in a 45-year-old man. The biopsy revealed a high-grade pleomorphic malignancy that focally expressed multiple keratins. Based on the presence of keratin immunoreactivity, the morphologic differential diagnosis included metastatic sarcomatoid carcinoma. However, review of the clinical information revealed a history of polyostotic FD, and imaging findings were compatible with malignant transformation of FD. The resected neoplasm was biphasic and composed of areas of conventional FD admixed with a high-grade pleomorphic malignancy. Activating GNAS mutations were identified in both components. To the best of our knowledge, this is the first description of keratin expression in malignant transformation of FD.



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An unusual primary malignant tumor of the stomach: Fetal gut-like Gastric adenocarcinoma with “blastoma”-like component

Publication date: Available online 16 March 2017
Source:Human Pathology
Author(s): Altaf Taher, Nebojsa Denic, Sangeetha N Kalimuthu, Runjan Chetty
An unusual case of a polypoid, malignant gastric tumor in a 62-year man is presented. Endoscopy and subsequent polypectomy revealed an 8.5 x 6.5 x 4.5cm lesion in the body of the stomach. Microscopy showed surface dysplasia with an invasive adenocarcinoma displaying prominent tubulopapillary areas composed of large vacuolated cells, pleomorphic nuclei and occasional cytoplasmic hyaline globules. This component then blended with tubular structures lined by more primitive appearing vacuolated cells embedded within a stroma made up of cellular primitive, high-grade blastema-like areas and, less cellular more pleomorphic foci with spindle and several bizarre, large cells. Immunohistochemistry showed the adenocarcinoma and primitive tubules to be strongly SALL4 and epithelial marker positive, but only focal expression of α-fetoprotein and glypican-3. The stromal component made up of blastema-like areas displayed strong immunoreactivity for glypican-3. The pleomorphic stromal areas were negative for all markers, including epithelial and muscle markers. The overall morphology and expression of primitive oncofetal proteins, especially SALL4 and glypican-3, are in keeping with this being a primitive adenocarcinoma showing fetal gut-like differentiation with an accompanying blastoma-like component, a combination not previously described in a primary gastric cancer.



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Recent advances of magneto-thermal capabilities of nanoparticles: From design principles to biomedical applications

Publication date: Available online 16 March 2017
Source:Nano Today
Author(s): Seung-hyun Noh, Seung Ho Moon, Tae-Hyun Shin, Yongjun Lim, Jinwoo Cheon
Magnetic nanoparticle (MNP)-mediated heating systems have emerged as an effective strategy for the fine control of biological systems from hyperthermia to cell signaling in a spatiotemporally controlled fashion. To achieve satisfactory performance, advanced design concepts have been developed to tailor the magnetism that directly affects the heating properties of nanoparticles. In this review, we focus on recent advances in magnetism-engineered nanoparticles. Fundamental principles of magnetic heating mechanisms and related key magnetic parameters are discussed first to provide instructive guidelines for the design of MNPs with enhanced heating efficiency. Then, we highlight recent progress in MNPs for optimized heat generation with unique design approaches to control magnetism. Finally, we discuss highly effective biomedical application studies such as dual-mode magnetic hyperthermia, magnetothermally triggered drug delivery, and the magnetothermal control of cellular activities.

Graphical abstract

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Oxygen defective metal oxides for energy conversion and storage

Publication date: Available online 17 March 2017
Source:Nano Today
Author(s): Gongming Wang, Yi Yang, Dongdong Han, Yat Li
Controlled creation of intrinsic defects such as oxygen vacancies can effectively modulate the optical and electronic properties of metal oxide nanomaterials. In the past few years, a number of oxygen defective metal oxides have been developed and implemented as electrode materials for energy conversion and storage applications. They show significantly enhanced performance for photoelectrochemical water splitting, electrochemical charge storage, and (photo)electrochemical catalysis. In this review, we present an overview of progress made in preparing oxygen defective metal oxide nanostructures and probing the role of oxygen vacancies on the performance of metal oxides, and identify the key challenges and future opportunities for oxygen defective metal oxides.

Graphical abstract

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Masthead

Publication date: March–April 2017
Source:Journal of Surgical Education, Volume 74, Issue 2





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Table of Contents & Bacode

Publication date: March–April 2017
Source:Journal of Surgical Education, Volume 74, Issue 2





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Pasireotide versus pituitary surgery: a retrospective analysis of 12 months of treatment in patients with Cushing’s disease

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Euglycemic ketosis in patients with type 2 diabetes on SGLT2-inhibitor therapy—an emerging problem and solutions offered by diabetes technology

Abstract

Diabetic ketoacidosis is an infrequent but life-threatening acute complication of diabetes, affecting predominantly patients with type 1 diabetes, children, and pregnant women, where ketosis is usually associated with marked hyperglycemia. Recently, an increasing number of cases have been reported of euglycemic diabetic ketoacidosis in patients with type 2 diabetes receiving sodium-glucose cotransporter 2 inhibitor treatment in routine practice. There is a minor, but not negligible diabetic ketoacidosis risk associated with this drug class, which was not seen in randomized clinical trials. However, sodium-glucose cotransporter2 inhibitors increase the risk of ketosis by increasing glucagon secretion in the pancreas and decreasing the renal excretion of 3-hydroxybutyrate and acetoacetate. When used in addition to insulin, any insulin dose reduction required to avoid hypoglycemia may lead to insufficient suppression of lipolysis and ketogenesis. sodium-glucose cotransporter2 inhibitor-induced loss of urinary glucose encourages euglycemia. Normo-glycemic or near-normoglycemic diabetic ketoacidosis represents a major threat to the health and well-being of a patient, because it may occur undetected and without any indicative hyperglycemia. In consequence, patients on sodium-glucose cotransporter2 inhibitors are recommended to perform regular blood ketone tests since they are not alerted to incipient diabetic ketoacidosis by glucose testing alone. This option is offered by several blood glucose meters that can also measure ketones with a separate ketone strip or in one case by an automatic parallel ketone assessment from the same strip. The need for extra testing and the associated costs may be a barrier to patient acceptance of this risk mitigation procedure. However, patients who are at risk for euglycemic diabetic ketoacidosis when being treated with sodium-glucose cotransporter2 inhibitors should be specially advised to monitor blood ketone levels on a regular basis.

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Technical note: Mining data from on-farm electronic equipment to identify the time dairy cows spend away from the pen

Publication date: Available online 17 March 2017
Source:Journal of Dairy Science
Author(s): A.J. Thompson, D.M. Weary, M.A.G. von Keyserlingk
The electronic equipment used on farms can be creatively co-opted to collect data for which it was not originally designed. In the current study, we describe 2 novel algorithms that harvest data from electronic feeding equipment and data loggers used to record standing and lying behavior, to estimate the time that dairy cows spend away from their pen to be milked. Our 2 objectives were to (1) measure the ability of the first algorithm to estimate the time cows spend away from the pen as a group and (2) determine the capability of a second algorithm to estimate the time it takes for individual cows to return to their pen after being milked. To achieve these objectives, we conducted 2 separate experiments: first, to estimate group time away, the feeding behavior of 1 pen of 20 Holstein cows was monitored electronically for 1 mo; second, to measure individual latency to return to the pen, feeding and lying behavior of 12 healthy Holstein cows was monitored electronically from parturition to 21 d in milk. For both experiments, we monitored the time each individual cow exited the pen before each milking and when she returned to the pen after milking using video recordings. Estimates generated by our algorithms were then compared with the times captured from the video recordings. Our first algorithm provided reliable pen-based estimates for the minimum time cows spent away from the pen to be milked in the morning [coefficient of determination (R²) = 0.92] and afternoon (R² = 0.96). The second algorithm was able to estimate of the time it took for individual cows to return to the pen after being milked in the morning (R² = 0.98), but less so in the afternoon (R² = 0.67). This study illustrates how data from electronic systems used to assess feeding and lying behavior can be mined to estimate novel measures. New work is now required to improve the estimates of our algorithm for individuals, for example by adding data from other electronic monitoring systems on the farm.



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Short communication: Early modification of the circadian organization of cow activity in relation to disease or estrus

Publication date: Available online 17 March 2017
Source:Journal of Dairy Science
Author(s): Isabelle Veissier, Marie-Madeleine Mialon, Karen Helle Sloth
Biological rhythms are an essential regulator of life. There is evidence that circadian rhythm of activity is disrupted under chronic stress in animals and humans, and it may also be less marked during diseases. Here we investigated whether a detectable circadian rhythm of activity exists in dairy cows in commercial settings using a real-time positioning system. We used CowView (GEA Farm Technologies) to regularly record the individual positions of 350 cows in a Danish dairy farm over 5 mo and to infer the cows' activity (resting, feeding, in alley). We ran a factorial correspondence analysis on the cows' activities and used the first component of this analysis to express the variations in activity. On this axis, the activities obtained the following weights: resting = −0.15; in alleys = +0.12; feeding = +0.34. By applying these weights to the proportions of time each cow spent on each of the 3 activities, we were able to chart a circadian rhythm of activity. We found that average level of activity of a cow on a given day and its variations during that day varied with specific states (i.e., estrus, lameness, mastitis). More specifically, circadian variations in activity appeared to be particularly sensitive and to vary 1 to 2 d before the farmer detected a disorder. These findings offer promising avenues for further research to design models to predict physiological or pathological states of cows from real-time positioning data.



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Evaluation of prostaglandin F2α versus prostaglandin F2α plus gonadotropin-releasing hormone as Presynch methods preceding an Ovsynch in lactating dairy cows: A meta-analysis

Publication date: Available online 17 March 2017
Source:Journal of Dairy Science
Author(s): S. Borchardt, P. Haimerl, A. Pohl, W. Heuwieser
Presynchronization of cows with 2 injections of prostaglandin administered 14 d apart (Presynch-Ovsynch) is a widely adopted procedure to increase pregnancy per artificial insemination (P/AI) at first service. Recently, a presynchronization protocol including GnRH and PGF2α (Double-Ovsynch; GnRH, 7 d, PGF2α, 3 d, GnRH) followed 7 d later by an Ovsynch protocol was introduced to overcome the limitations of PGF2α-based protocols for presynchronization of anovular cows and to precisely set up cows on d 7 of the estrous cycle when the Ovsynch is initiated. A systematic review of the literature and a meta-analytical assessment was performed with the objective to compare the reproductive performance of lactating dairy cows presynchronized with these 2 protocols for the first timed AI (TAI) considering parity-specific effects. A fixed or a random effects meta-analysis was used based on the heterogeneity among the experimental groups. Reproductive outcomes of interest were P/AI measured on d 32 (28–42) and pregnancy loss between d 32 and 60 (42–74) of gestation. A total of 25 articles with 27 experimental groups from 63 herds including 21,046 cows submitted to first TAI using either a Presynch-Ovsynch or a Double-Ovsynch protocol were reviewed. Results for P/AI were then categorized by parity if available. Information was available for P/AI for 7,400 and 10,999 primiparous and multiparous cows, respectively. Information regarding pregnancy loss was available for 7,477 cows. In the random effects model for all cows, the overall proportion of P/AI was 41.7% [95% confidence interval (CI): 39.1–44.3; n = 8,213] and 46.2% (95% CI: 41.9–50.5; n = 12,833) on d 32 after TAI for Presynch-Ovsynch and Double-Ovsynch, respectively. In the random effects model for primiparous cows, the overall proportion of P/AI was 43.4% (95% CI: 36.2–47.7; n = 2,614) and 51.4% (95% CI: 47.4–55.4; n = 4,786) on d 32 after TAI for Presynch-Ovsynch and Double-Ovsynch, respectively. In the random effects model for multiparous cows, the overall proportion of P/AI was 39.2% (95% CI: 36.2–42.3; n = 3,411) and 41.4% (95% CI: 36.4–46.4; n = 7,588) on d 32 after TAI for Presynch-Ovsynch and Double-Ovsynch, respectively. The overall proportion of pregnancy loss was 11.3% (95% CI: 7.6–15.7; n = 3,247) and 11.7% (95% CI: 9.3–14.3; n = 4,230) on d 60 after AI for Presynch-Ovsynch to and Double-Ovsynch, respectively. Substantial heterogeneity existed among the experimental groups regarding P/AI and pregnancy loss. In summary, a benefit was detected for P/AI in primiparous cows presynchronized with a Double-Ovsynch protocol for the first TAI, but this benefit was not observed in multiparous cows.



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Reduction of Mycobacterium avium ssp. paratuberculosis in colostrum: Development and validation of 2 methods, one based on curdling and one based on centrifugation

Publication date: Available online 17 March 2017
Source:Journal of Dairy Science
Author(s): M. Verhegghe, G. Rasschaert, L. Herman, K. Goossens, L. Vandaele, K. De Bleecker, G. Vlaemynck, M. Heyndrickx, J. De Block
The aim of this study was to develop and validate 2 protocols (for use on-farm and at a central location) for the reduction of Mycobacterium avium ssp. paratuberculosis (MAP) in colostrum while preserving beneficial immunoglobulins (IgG). The on-farm protocol was based on curdling of the colostrum, where the IgG remain in the whey and the MAP bacteria are trapped in the curd. First, the colostrum was diluted with water (2 volumes colostrum to 1 volume water) and 2% rennet was added. After incubation (1 h at 32°C), the curd was cut and incubated again, after which whey and curd were separated using a cheesecloth. The curd was removed and milk powder was added to the whey. Approximately 1 log reduction in MAP counts was achieved. A reduction in total proteins and IgG was observed due to initial dilution of the colostrum. After curd formation, more than 95% of the immunoglobulins remained in the whey fraction. The semi-industrial protocol was based on centrifugation, which causes MAP to precipitate, while the IgG remain in the supernatant. This protocol was first developed in the laboratory. The colostrum was diluted with skimmed colostrum (2 volumes colostrum to 1 volume skimmed colostrum), then skimmed and centrifuged (at 15,600 × g for 30 min at room temperature). We observed on average 1.5 log reduction in the MAP counts and a limited reduction in proteins and IgG in the supernatant. To obtain a semi-industrial protocol, dairy pilot appliances were evaluated and the following changes were applied to the protocol: after 2:1 dilution as above, the colostrum was skimmed and subsequently clarified, after which the cream was heat treated and added to the supernatant. To investigate the effect of the colostrum treatment on the nutritional value and palatability of the colostrum and the IgG transfer, an animal experiment was conducted with 24 calves. Six received the dam's colostrum, 6 were given untreated purchased colostrum (control), and 2 groups of 6 calves received colostrum treated according to both of the above-mentioned methods. No significant differences were found between the test groups and the dam's colostrum group in terms of animal health, IgG uptake in the blood serum, milk, or forage uptake. Two protocols to reduce MAP in colostrum (for use on-farm or at a central location) were developed. Both methods preserve the vital IgG.



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Supplementation with rumen-protected methionine or choline during the transition period influences whole-blood immune response in periparturient dairy cows

Publication date: Available online 17 March 2017
Source:Journal of Dairy Science
Author(s): M. Vailati-Riboni, Z. Zhou, C.B. Jacometo, A. Minuti, E. Trevisi, D.N. Luchini, J.J. Loor
Methionine, together with Lys, is the most limiting AA for milk production in dairy cows. Besides its crucial role in milk production, Met and its derivate metabolites (e.g., glutathione, taurine, polyamines) are well-known immunonutrients in nonruminants, helping support and boost immune function and activity. In the present study, the effects of Met or choline, as its precursor, were investigated using an ex vivo whole blood challenge. The study involved 33 multiparous Holstein cows (from a larger cohort with a factorial arrangement of treatments) assigned from d −21 to +30 relative to parturition to a basal control (CON) diet, CON plus rumen-protected Met (MET, Smartamine M, Adisseo NA, Alpharetta, GA) at a rate of 0.08% of dry matter, or CON plus rumen-protected choline (CHOL, ReaShure, Balchem Inc., New Hampton, NY) at 60 g/d. Blood was sampled on d −15, −7, 2, 7, and 20 for ex vivo lipopolysaccharide (LPS) challenge, and on d 1, 4, 14, and 28 relative to parturition for phagocytosis and oxidative burst assays. The MET cows had greater energy-corrected milk production and milk protein content. Overall, IL-6 response to LPS increased around parturition, whereas IL-1β remained constant, casting doubt on the existence of systemic immunosuppression in the peripartal period. Supplementation with MET dampened the postpartal blood response to LPS (lower IL-1β), while improving postpartum neutrophil and monocyte phagocytosis capacity and oxidative burst activity. In contrast, CHOL supplementation increased monocyte phagocytosis capacity. Overall, the data revealed a peripartal immune hyper-response, which appeared to have been mitigated by MET supplementation. Both MET and CHOL effectively improved immune function; however, MET affected the immune and antioxidant status before parturition, which might have been beneficial to prepare the cow to respond to metabolic challenges after parturition. These results provide insights on potential differences in the immunomodulatory action of methionine and choline in dairy cows. As such, the effects observed could have implications for ration formulation and dietary strategies.



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