bluuebunny/crossref_metadata_2025 huggingface dataset:
Myricetin treatment induces apoptosis in canine osteosarcoma cells by inducing DNA fragmentation, disrupting redox homeostasis, and mediating loss of mitochondrial membrane potential
Authors: Park Hahyun , Park Sunwoo , Bazer Fuller W. , Lim Whasun , Song Gwonhwa
Published: April 2018

Canine osteosarcoma is an aggressive primary bone tumor that shows metastasis to distal regions and is associated with a high mortality rate. However, the pathophysiological mechanisms of canine osteosarcoma are not well characterized. In addition, development of prognostic factors and novel therapeutic agents is necessary to efficiently treat osteosarcoma. Therefore, we studied the effects of myricetin, an antioxidant found in berries, nuts, teas, wine, and vegetables, on apoptosis and signal transduction in the canine osteosarcoma cell lines, D‐17 and DSN. Results of the present study demonstrated that treatment with myricetin decreased cell proliferation and DNA replication, while it increased apoptotic DNA fragmentation in D‐17 and DSN cells. In addition, it increased generation of ROS, lipid peroxidation, and depolarization of MMP in both D‐17 and DSN cells. Myricetin treatment activated phosphorylation of AKT, p70S6K, ERK1/2, JNK, and p90RSK in canine osteosarcoma cells. Moreover, inhibition of PI3K and MAPK using LY294002, U0126, or SP600125, in addition to myricetin treatment, effectively suppressed cell proliferation compared to treatment with myricetin or each inhibitor alone. Therefore, we concluded that myricetin may be a potentially effective and less toxic therapeutic agent to prevent and control progression of canine osteosarcoma.
CD69 partially inhibits apoptosis and erythroid differentiation via CD24, and their knockdown increase imatinib sensitivity in BCR‐ABL‐positive cells
Authors: Huang Shih‐Yun , Liu Yu‐Hsiu , Chen Yi‐Ju , Yeh Yi‐Yen , Huang Huei‐Mei
Published: April 2018

Chronic myeloid leukemia (CML) is caused by a constitutively active BCR‐ABL tyrosine kinase. Tyrosine kinase inhibitors (TKIs) imatinib and its derivatives represent a breakthrough for CML therapy, but the use of TKI alone is ineffective for many CML patients. CD69, an early activation marker of lymphocytes, participates in immune and inflammatory responses. Previous studies revealed that BCR‐ABL upregulates CD69 expression; however, the role of CD69 in CML cells is unknown. Here, we demonstrate that BCR‐ABL induced CD69 promoter activity and mRNA and protein expression via the NF‐κB pathway. CD69 knockdown partially increased apoptosis and expression of erythroid differentiation markers, α‐globin, ζ‐globin, and glycophorin A, and increased imatinib sensitivity in K562 and KU812 CML cells. Gene microarray analysis and quantitative real‐time PCR verified that CD24, an oncogenic gene, downregulated in K562 cells upon CD69 knockdown. CD69 overexpression increased, whereas CD69 knockdown inhibited CD24 promoter activity and mRNA and protein levels. CD24 knockdown also partially increased apoptosis, erythroid differentiation, and imatinib sensitivity in K562 cells, whereas its overexpression inhibited the effects of CD69 knockdown on apoptosis, erythroid differentiation, and imatinib sensitivity in K562 cells. Imatinib‐induced apoptosis and erythroid differentiation were also inhibited by CD69 or CD24 overexpression in BCR‐ABL‐expressing CML cell lines and CD34+ cells. Taken together, CD24 is a downstream effector of CD69. CD69 and CD24 partially inhibit apoptosis and erythroid differentiation in CML cells; thus, they may be potential targets to increase imatinib sensitivity.
Predicting Pharmacokinetics/Pharmacodynamics in the Individual Patient: Separating Reality From Hype
Authors: Benet Leslie Z.
Published: April 2018

Individualization of patient drug dosing to maximize efficacy and minimize toxicity is the goal of clinical pharmacology. Here we review the history of drug dosing individualization from early predictions for renally eliminated drugs based on kidney function through the introduction of clearance concepts for metabolic processes, the differentiation of volume of distribution between pharmacokinetics and chemistry, the role of transporters, the unique pharmacokinetic aspects of oral dosing, and the relevance of protein binding to the emergence of pharmacogenomics. The Food and Drug Administration listing of pharmacogenomic markers in approved drug labeling is analyzed with respect to the promise of genomics in terms of picking the right drug for the patient based on genetic information vs selecting or adjusting the dosage regimen based on genetic information: the former resulting in a great advance, whereas the latter has shown less convincing evidence of clinical relevance. Finally, new information on individualized predictive methodologies based on marker drugs for enzymes and transporters is reviewed. We conclude that although individualization of drug dosing will work for most drugs primarily excreted unchanged in the urine, individualization of dosing regimens is not critical for wide‐therapeutic‐index drugs, whereas for narrow‐therapeutic‐index drugs predictions are most often more hype than reality, with therapeutic drug monitoring required. However, continuing advances in discovering and validating biomarkers will lead to predictions of pharmacokinetics/pharmacodynamics in the individualized patient that should result in shifting the hype to reality with time.
Development of continuous cultivation process for oil production through bioconversion of minimally treated waste streams from second‐generation bioethanol production
Authors: Singh Dilip , Mehta Preeti , Saxena Rohit , Barrow Colin J , Puri Munish , Tuli Deepak K , Mathur Anshu S
Published: April 2018

BACKGROUND

Efficient conversion of inhibitor containing pentose rich stream into bioethanol or biogas is still challenging due to several technological challenges; however, this stream can be efficiently assimilated into lipids by oleaginous yeasts such as Rhodotorula. In this work, a continuous and nonsterile process was developed for bioconversion of waste streams into lipids for biodiesel using growth‐inhibitor‐tolerant oleaginous yeast.

RESULTS

An inhibitor‐tolerating property of the strain was used to develop a cyclic and continuous near axenic cultivation process in a 2 L nonsterile bioreactor to enhance valorization of waste streams and to reduce energy requirements for media and vessel sterilization. After media optimization, continuous cultivation resulted in significant increase in biomass (14.90 g L−1 day−1) and lipid productivity (6.15 g L−1 day−1) as compared to flask (biomass ∼3 g L−1 day−1 and lipid productivity ∼0.6 g L−1 day−1) results. Palmitic acid (C16:0) and oleic acid (C18:1) were the major fatty acids, accounting for almost 80% of total lipids, thus making lipid produced in the process suitable for biodiesel production.

CONCLUSION

Inhibitors present in waste streams successfully maintained near axenic conditions during the cultivation. Maximum dilution rate of 1 was achieved after media optimization, which resulted in complete valorization of nutrients into biomass and lipids with high productivity. © 2018 Society of Chemical Industry
Understanding the in vivo fate of radioimmunoconjugates for nuclear imaging
Authors: Vivier Delphine , Sharma Sai Kiran , Zeglis Brian M.
Published: April 2018

Over the past 25 years, antibodies have emerged as extraordinarily promising vectors for the delivery of radionuclides to tumors for nuclear imaging. While radioimmunoconjugates often produce very high activity concentrations in target tissues, they also are frequently characterized by elevated activity concentrations in healthy organs as well. The root of this background uptake lies in the complex network of biological interactions between the radioimmunoconjugate and the subject. In this review, we seek to provide an overview of these interactions and thus paint a general picture of the in vivo fate of radioimmunoconjugates. To cover the entire story, we have divided our discussion into 2 parts. First, we will address the path of the entire radioimmunoconjugate as it travels through the body. And second, we will cover the fate of the radionuclide itself, as its course can diverge from the antibody under certain circumstances. Ultimately, our goal is to provide the nuclear imaging field with a resource covering these important—yet often underestimated—pathways.
Mutations within the major hydrophilic region (MHR) of Hepatitis B virus from individuals with simultaneous HBsAg and anti‐HBs in Guangzhou, Southern China
Authors: Liu Kemin , Xie Mingyu , Lu Xiaomei , Yu Hui , Wang Hui , Xu Yunjian , Yang Qingqing , Lin Yongping , Ma Qiang
Published: April 2018

The mechanism of the coexistence of HBsAg and anti‐HBs is still unclear. This study investigated the variations located in the major hydrophilic region (MHR) of HBV from individuals with simultaneous HBsAg and anti‐HBs in Guangzhou, southern China. Among 4455 samples analyzed, 179 (4.02%) patients were discovered with both HBsAg and anti‐HBs. Finally, 44 individuals with concurrent HBsAg and anti‐HBs (defined as group I), and 88 patients with positive HBsAg and negative anti‐HBs (defined as group II, served as control) were enrolled in the study. The number of residue changes per 100 residues within the MHR in group I was 7.1 times more frequent than group II (P < 0.001) and was discovered mostly in the MHR1 (aa99‐119) (P < 0.001). Two or more residue changes in the MHR were discovered in 15 patients (34.1%) of group I, but were found in only one (1.1%) patient of group II (P < 0.001). The most common variants in group I were at positions s101Q, s133M, s126T/I, s131T, s145G, s120P, and s129Q. In addition, sQ101 K, sT131N, and sM133L were more frequently discovered in group I with significant difference (P < 0.05). In chronic hepatitis B (CHB) patients, the simultaneous of HBsAg and anti‐HBs were accompanied with an increase of MHR variants, and suggested that the HBsAg mutants were selected by naturally acquired anti‐HBs during chronic carriage.
Indeterminate genotypes of hepatitis C virus by the Abbott RealTime HCV Genotype II assay in Morocco. About eight cases resolved by a sequencing method
Authors: Mesbahi Zineb , Kabbaj Hakima , Malki Houcine , Bouihat Najat , Qrafli Mounia , Belefquih Bouchra , Marcil Sarrah , Challine Dominique , Pawlotsky Jean‐Michel , Bouvier Magali , Seffar Myriam
Published: April 2018

The early detection and genotyping of the hepatitis C virus (HCV) are important in the management of this infection. The genotype is the major factor influencing treatment decisions. That's why it is necessary to use fast and accurate methods in its determination. This study reports, over a period of 3 years (from May 2012 to July 2015), the percentage of indeterminate genotypes by the Abbott RealTime HCV Genotype II test and their results using a sequencing technique. Of 309 samples of 309 patients tested, 11 were indeterminate (4.4%). There were three cases of cross‐reactivity (1b/4 in one case, 2/5 in two cases) and a possible co‐infection 1 + 4. Among those indeterminate genotypes, cross‐reactivities and co‐infections, ten samples were tested by sequencing. The results were for four of them a 1d subtype, five were a 2i subtype and one was a 2l subtype. These results support the thesis of complementarity between the two methods: genotyping for the detection of mixed reactions and sequencing for resolving indeterminate cases by genotyping.
Effect of heart rate and pacing mode on QRS fragmentation
Authors: Zagkli Fani , Despotopoulos Stefanos , Spiliotopoulos Christos , Chiladakis John
Published: April 2018

Background

The study was designed to investigate the effect of heart rate and pacing mode on QRS fragmentation (f‐QRS). Moreover, the usefulness of f‐QRS in distinguishing patients with impaired left ventricular ejection function (EF) and ventricular tachycardia (VT) from patients with normal EF was assessed.

Methods

Three hundred and six recipients, with dual‐chamber device, with intrinsic narrow or wide QRS complex and preserved atrioventricular conduction were grouped into normal‐EF or impaired‐EF VT. We analyzed intrinsic narrow f‐QRS and wide f‐QRS as well as ventricular‐paced f‐QRS following different heart rates (baseline, 100 bpm) and pacing modes.

Results

In the baseline state, overall, patients with impaired‐EF VT (35 ± 9%), compared to those with normal‐EF, had more f‐QRS (56% vs 27%, P < .001) and ventricular‐paced f‐QRS (62% vs 16%, P < .0001). Ventricular pacing conferred both at baseline and at higher heart rate more ventricular‐paced f‐QRS in patients with impaired‐EF VT than in normal‐EF (P < .001). Detection of ventricular‐paced f‐QRS markedly improved overall specificity (84%) and positive predictive value (91%) in identifying patients with impaired‐EF VT.

Conclusions

Increased heart rate or/and ventricular pacing uncover QRS fragmentations. Detection of ventricular‐paced f‐QRS adds value toward noninvasive identification of patients with impaired‐EF VT.
Holocene temperature trends in the extratropical Northern Hemisphere based on inter‐model comparisons
Authors: Zhang Yurui , Renssen Hans , Seppä Heikki , Valdes Paul J.
Published: April 2018

Large uncertainties exist in Holocene climate estimates, especially for the early Holocene when large‐scale reorganization occurred in the climate system. To improve our understanding of these uncertainties, we compare four Holocene simulations performed with the LOVECLIM, CCSM3, HadCM3 and FAMOUS climate models. The simulations are generally consistent for the large‐scale Northern Hemisphere extratropics, while the multi‐simulation consistencies are heterogeneous on the sub‐continental scale. Consistently simulated temperature trends are found in Greenland, northern Canada, north‐eastern and north‐western Europe, and central‐west Siberia. These Holocene temperatures show a pattern of an early Holocene warming, mid‐Holocene warmth and gradual decrease towards the pre‐industrial in winter, and the extent of early Holocene warming varies spatially, with 9 °C warming in northern Canada compared with 3 °C warming in central‐west Siberia. In contrast, mismatched temperatures are detected: in Alaska, the warm early Holocene winter in LOVECLIM primarily results from strongly enhanced southerly winds induced by the ice sheets; in eastern Siberia, the intense early‐Holocene summer warmth anomaly in CCSM3 is caused by large negative albedo anomalies due to overestimated snow cover at 0 ka; in the Arctic, cool winter conditons in FAMOUS can be attributed to extensive sea ice coverage probably due to simplified sea ice representations. Thus, the Holocene temperature trends in these regions remain inconclusive.
Polymorphism in ovine ANXA9 gene and the physio‐chemical properties and the fraction of protein in milk
Authors: Pecka‐Kiełb Ewa , Czerniawska‐Piątkowska Ewa , Kowalewska‐Łuczak Inga , Vasil Milan
Published: April 2018

BACKGROUND

Annexin A9 (ANXA9) is a specific fatty acid transport protein. The ANXA9 gene is expressed in various tissues, including secretory tissue and the mammary glands. The association between the three single nucleotide polymorphisms (SNPs) of the ANXA9 gene and sheep's milk composition was assessed.

RESULTS

Genotype analysis was performed using the polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) method. The ANXA9 polymorphisms that were studied had the following major allele frequencies (MAFs): SNP1: allele G 0,66; SNP2: allele G 0,54; SNP3: allele C 0,57. The study found the most favorable profile of protein fractions, namely increased kappa‐casein fractions and a decreased level of whey protein in sheep's milk for the SNP1 and SNP3 polymorphisms. Sheep with the SNP1 GA genotype had the highest (P < 0.05) content of fat and dry matter in milk. AXNA9 gene polymorphism did not influence the levels of protein, lactose, or urea in sheep's milk.

CONCLUSION

The information contained in this study may be useful for determining the impact of the ANXA9 gene on sheep's milk. The ANXA9 SNP1 and SNP3 polymorphism results could be included in breeding programs to select sheep with the genotypes ensuring the highest kappa‐casein levels in milk. However, it is worth conducting further research on ANXA9 and milk composition in larger herds of animals and various breeds of sheep. © 2018 Society of Chemical Industry
Measurement of water absorption capacity in wheat flour by a headspace gas chromatographic technique
Authors: Xie Wei‐Qi , Yu Kong‐Xian , Gong Yi‐Xian
Published: April 2018

The purpose of this work is to introduce a new method for quantitatively analyzing water absorption capacity in wheat flour by a headspace gas chromatographic technique. This headspace gas chromatographic technique was based on measuring the water vapor released from a series of wheat flour samples with different contents of water addition. According to the different trends between the vapor and wheat flour phase before and after the water absorption capacity in wheat flour, a turning point (corresponding to water absorption capacity in wheat flour) can be obtained by fitting the data of the water gas chromatography peak area from different wheat flour samples. The data showed that the phase equilibrium in the vial can be achieved in 25 min at desired temperature (35°C). The relative standard deviation of the reaction headspace gas chromatographic technique in water absorption capacity determination was within 3.48%, the relative differences has been determined by comparing the water absorption capacity obtained from this new analytical technique with the data from the reference technique (i.e., the filtration method), which are less than 8.92%. The new headspace gas chromatographic method is automated, accurate and be a reliable tool for quantifying water absorption capacity in wheat flour in both laboratory research and mill applications.
Preparing the key metabolite of Z‐ligustilide in vivo by a specific electrochemical reaction
Authors: Duan Feipeng , Xu Wenjuan , Liu Jie , Jia Zhixin , Chen Kuikui , Chen Yijun , Wang Mingxia , Ma Kaiyue , Dong Jiaojiao , Chen Lianming , Xiao Hongbin
Published: April 2018

The key in vivo metabolites of a drug play an important role in its efficacy and toxicity. However, due to the low content and instability of these metabolites, they are hard to obtain through in vivo methods. Electrochemical reactions can be an efficient alternative to biotransformation in vivo for the preparation of metabolites. Accordingly, in this study, the metabolism of Z‐ligustilide was investigated in vitro by electrochemistry coupled online to mass spectrometry. This work showed that five oxidation products of the electrochemical reaction were detected and that two of the oxidation products (senkyunolide I and senkyunolide H) were identified from liver microsomal incubation as well. Furthermore, after intragastric administration of Z‐ligustilide in rats, senkyunolide I and senkyunolide H were detected in the rat plasma and liver, while 6,7‐epoxyligustilide, a key intermediate metabolite of Z‐ligustilide, was difficult to detect in vivo. By contrast, 6,7‐epoxyligustilide was obtained from the electrochemical reaction. In addition, for the first time, 6 mg of 6,7‐epoxyligustilide was prepared from 120 mg of Z‐ligustilide. Therefore, electrochemical reactions represent an efficient laboratory method for preparing key drug metabolites.
Neural Tube Defects in Embryonic Life: Lessons Learned From 340 Early Pregnancy Failures
Authors: Hartge David R. , Gembicki Michael , Rody Achim , Weichert Jan
Published: April 2018

Objectives

The aim of this study was to evaluate the feasibility of sonographic assessment of the embryonic/fetal neural tube in nonviable pregnancies and to determine the defect incidence.

Methods

Prospective analysis of transvaginally acquired 3‐dimensional (3D) multiplanar and 3D surface‐rendered volume sets of 340 cases of missed abortion between March 2010 and September 2015 was performed. Data regarding karyotype and postmortem examination as well as demographic features and the outcomes of subsequent pregnancies were evaluated.

Results

In 223 cases, an embryo/fetus was detected and considered suitable for further evaluation: in 37 of 223 (16.6%) embryos/fetuses, a neural tube defect was present: 27 of 37 cephaloceles, 5 of 37 anencephalies/exencepahlies, 3 of 37 spina bifidas, 1 of 37 caudal regression syndrome, and 1 of 37 iniencephaly. Additional alterations were not observed. In 7 of 37 cases karyotyping was carried out and showed no aneuploidy. Eight subsequent pregnancies had a favorable outcome, with 1 ending in an intrauterine fetal death during the 22nd week of gestation. Maternal folic acid supplementation was provided for all subsequent pregnancies. No neural tube defects occurred.

Conclusions

Sonographic 3D evaluation of complete neural tube closure in embryonic/fetal demise is technically feasible and can be achieved in embryos with a crown‐rump length greater than 8 mm. In 26 of 37 cases a defective closure site could be allocated to high‐risk areas known for early embryonic demise. Regardless of the etiology of different neural tube defects, high‐dose folic acid prophylaxis must be recommended in all cases. Sonographic evaluation of the neural tube, including 3D surface‐rendered images, should be offered to every woman with a missed abortion because of the impact on subsequent pregnancies.
Adaptations of Skeletal Muscle Mitochondria to Obesity, Exercise, and Polyunsaturated Fatty Acids
Authors: Chen Phoebe B. , Yang Jason S. , Park Yeonhwa
Published: April 2018

Mitochondria intricately modulate their energy production through the control of mitochondrial adaptation (mitochondrial biogenesis, fusion, and/or fission) to meet energy demands. Nutrient overload may result in dysregulated mitochondrial biogenesis, morphology toward mitochondrial fragmentation, and oxidative stress in the skeletal muscle. In addition, physical activity and diet components influence mitochondrial function. Exercise may stimulate mitochondrial biogenesis and promote mitochondrial fusion/fission in the skeletal muscle. Moreover, some dietary fatty acids, such as n‐3 polyunsaturated fatty acids and conjugated linoleic acid, have been identified to positively regulate mitochondrial adaptation in the skeletal muscle. This review discusses the association of mitochondrial impairments and obesity, and presents an overview of various mechanisms of which exercise training and mitochondrial nutrients promote mitochondrial function in the skeletal muscle.
Superfine Magnetic Resonance Imaging of the Cerebrovasculature Using Self‐Assembled Branched Polyethylene Glycol–Gd Contrast Agent
Authors: Mahara Atsushi , Enmi Jun‐ichiro , Hsu Yu‐I , Kobayashi Naoki , Hirano Yoshiaki , Iida Hidehiro , Yamaoka Tetsuji
Published: April 2018

Magnetic resonance angiography is an attractive method for the visualization of the cerebrovasculature, but small‐sized vessels are hard to visualize with the current clinically approved agents. In this study, a polymeric contrast agent for the superfine imaging of the cerebrovasculature is presented. Eight‐arm polyethylene glycol with a molecular weight of ≈17 000 Da conjugated with a Gd chelate and fluorescein (F‐8‐arm PEG‐Gd) is used. The relaxivity rate is 9.3 × 10−3m−1 s−1, which is threefold higher than that of free Gd chelate. Light scattering analysis reveals that F‐8‐arm PEG‐Gd is formed by self‐assembly. When the F‐8‐arm PEG‐Gd is intravenously injected, cerebrovasculature as small as 100 µm in diameter is clearly visualized. However, signals are not enhanced when Gd chelate and Gd chelate‐conjugated 8‐arm PEG are injected. Furthermore, small vasculature around infarct region in rat stroke model can be visualized. These results suggest that F‐8‐arm PEG‐Gd enhances the MR imaging of cerebrovasculature.
Engineered Hsp Protein Nanocages for siRNA Delivery
Authors: Guan Xingang , Chang Yu , Sun Jinghui , Song Jianxi , Xie Yu
Published: April 2018

The efficient delivery of small interfering RNA (siRNA) to tumor cells still remains a great challenge. Of the various nanocarriers, protein nanocages have attracted extensive interest due to their unique structure and suitable characteristics derived from their proteinaceous nature. However, most reported protein nanocages that are developed are based on virus capsid proteins, which may raise safety concerns, including those related to gene mutation and carcinogenesis. The development of nonviral protein‐based systems for siRNA delivery is greatly needed. In this study, a novel siRNA delivery system based on heat shock protein (Hsp) nanocages is developed by a genetic engineering method. The delivery system could condense siRNA into stable complexes and protect the condensed siRNA from degradation. A cellular uptake analysis shows that siRNA is introduced into tumor cells mediated by Hsp‐R9 nanocages. Green fluorescent protein (GFP) expression in HeLa‐EGFP cells is significantly downregulated by Hsp‐R9/siRNA complexes. The results indicate that Hsp nanocages may be a good platform for siRNA delivery into tumor cells.
Dual‐Functionalization Device for Therapy through Dopamine Release and Monitoring
Authors: Fabregat Georgina , Giménez Alessia , Díaz Angélica , Puiggalí Jordi , Alemán Carlos
Published: April 2018

A dual‐functional device is fabricated to release progressively dopamine (DA) from a biohydrogel under real‐time monitoring via electrochemical detection. For this purpose, a poly‐γ‐glutamic acid biohydrogel is assembled with a poly(3,4‐ethylenedioxythiophene) (PEDOT) layer, previously deposited onto a screen printed electrode. The biohydrogel is formulated to achieve dimensional stability and maximum DA‐loading capacity. Conditions for DA‐loading are influenced by the oxidation of the neurotransmitter in acid environments and the poor resistance of PEDOT to the lyophilization. The performance of the device is proved in a medium with the physiological pH of blood and the cerebrospinal fluid. The progressive release of DA is successfully monitored by the device, the limit of detection and sensitivity of the integrated sensor being 450 × 10−9m and 8 × 10−5 mA µm−1, respectively. The effect of electrochemical stimulation in the kinetics of the DA release is also investigated applying potential ramps in cyclic phase to alter the biohydrogel morphology.
Photo‐Induced Programmable Morphological Transition of the Hybrid Coassembles
Authors: Li Jin , Su Zhilong , Xu Hongjie , Ma Xiaodong , Yin Jie , Jiang Xuesong
Published: April 2018

Morphology and nanoparticle's distribution are both key factors to the hybrid coassemblies. A fancy method to dynamically control the morphology of hybrid core–shell microspheres (CSMs) with UV light is introduced. The CSMs used here are fabricated with azobenzene (AZO) ended hyperbranched poly(ether amine) in the shell and AZO containing polyhedral oligomer silsesquioxane in the core through coassembly. Upon UV irradiation, the dynamic morphology transition from core–shell microsphere to vesicle is realized by synergistic effects and photothermal effects of AZO, resulting in the size of coassemblies increasing from 1.2 to 2.5 µm. And versatile multivesicular structures can be fixed and captured as mid‐states in taking advantage of the easy control of ON/OFF of UV light. This programmable morphology transition provides a new insight for fabricating light‐controlled hybrid materials with ideal structure in soft nanotechnology which matches with requirements in in situ tunable functions, controlled release, and so on.
Clubs on quasi measurable cardinals
Authors: Kumar Ashutosh , Shelah Saharon
Published: April 2018

We construct a model satisfying “κ is quasi measurable”. Here, we call κ quasi measurable if there is an ℵ1‐saturated κ‐additive ideal on κ. We also show that, in this model, forcing with adds one but not κ Cohen reals. We introduce a weak club principle and use it to show that, consistently, for some ℵ1‐saturated κ‐additive ideal on κ, forcing with adds one but not κ random reals.
Bishop's Lemma
Authors: Diener Hannes , Hendtlass Matthew
Published: April 2018

Bishop's Lemma is a centrepiece in the development of constructive analysis. We show that

its proof requires some form of the axiom of choice; and that

the completeness requirement in Bishop's Lemma can be weakened and that there is a vast class of non‐complete spaces that Bishop's Lemma applies to.
Facile Preparation of Polydimethylsiloxane Elastomer with Self‐Healing Property and Remoldability Based on Diels–Alder Chemistry
Authors: Wang Jinke , Lv Chi , Li Zhongxiao , Zheng Junping
Published: April 2018

The polydimethylisioxane elastomer based on Diels–Alder (DA) chemistry is successfully prepared by directly crosslinking bis(3‐aminopropyl)‐terminated polydimethylsiloxane with the bisepoxide containing two DA bonds in one molecule via epoxy‐amine reaction. The elastomer prepared based on DA chemistry exhibits good mechanical property, high self‐healing, and remolded efficiencies. The as‐prepared elastomer can be stretched to over 400% and its tensile strength can reach 0.80 MPa. The self‐healing efficiency and remolded efficiency are up to 93% and 95%, respectively. This work provides a simple and efficient way to fabricate the self‐healing and remolded polydimethylsiloxane elastomer with good mechanical properties. The as‐prepared elastomer has a promising potential in artificial muscles, protective coatings, and intelligent flexible electronics.
Maximal and fractional integral operators on generalized Morrey spaces over metric measure spaces
Authors: Sihwaningrum Idha , Gunawan Hendra , Nakai Eiichi
Published: April 2018

We establish the boundedness and weak boundedness of the maximal operator and generalized fractional integral operators on generalized Morrey spaces over metric measure spaces without the assumption of the growth condition on μ. The results are generalization and improvement of some known results. We also give the vector‐valued boundedness. Moreover we prove the independence of the choice of the parameter in the definition of generalized Morrey spaces by using the geometrically doubling condition in the sense of Hytönen.
Clustering of motor and nonmotor traits in leucine‐rich repeat kinase 2 G2019S Parkinson's disease nonparkinsonian relatives: A multicenter family study
Authors: Mestre Tiago A. , Pont‐Sunyer Claustre , Kausar Farah , Visanji Naomi P. , Ghate Taneera , Connolly Barbara S. , Gasca‐Salas Carmen , Kern Drew S. , Jain Jennifer , Slow Elizabeth J. , Faust‐Socher Achinoam , Kasten Meike , Wadia Pettarusp M. , Zadikoff Cindy , Kumar Prakash , de Bie Ronald M. , Thomsen Teri , Lang Anthony E. , Schüle Birgitt , Klein Christine , Tolosa Eduardo , Marras Connie
Published: April 2018

Objectives

The objective of this study was to determine phenotypic features that differentiate nonparkinsonian first‐degree relatives of PD leucine‐rich repeat kinase 2 (LRRK2) G2019S multiplex families, regardless of carrier status, from healthy controls because nonparkinsonian individuals in multiplex families seem to share a propensity to present neurological features.

Methods

We included nonparkinsonian first‐degree relatives of LRRK2 G2019S familial PD cases and unrelated healthy controls participating in established multiplex family LRRK2 cohorts. Study participants underwent neurologic assessment including cognitive screening, olfaction testing, and questionnaires for daytime sleepiness, depression, and anxiety. We used a multiple logistic regression model with backward variable selection, validated with bootstrap resampling, to establish the best combination of motor and nonmotor features that differentiates nonparkinsonian first‐degree relatives of LRRK2 G2019S familial PD cases from unrelated healthy controls.

Results

We included 142 nonparkinsonian family members and 172 unrelated healthy controls. The combination of past or current symptoms of anxiety (adjusted odds ratio, 4.16; 95% confidence interval, 2.01‐8.63), less daytime sleepiness (adjusted odds ratio [1 unit], 0.90; 95% confidence interval, 0.83‐0.97], and worse motor UPDRS score (adjusted odds ratio [1 unit], 1.4; 95% confidence interval, 1.20‐1.67) distinguished nonparkinsonian family members, regardless of LRRK2 G2019S mutation status, from unrelated healthy controls. The model accuracy was good (area under the curve = 79.3%).

Conclusions

A set of motor and nonmotor features distinguishes first‐degree relatives of LRRK2 G2019S probands, regardless of mutation status, from unrelated healthy controls. Environmental or non‐LRRK2 genetic factors in LRRK2‐associated PD may influence penetrance of the LRRK2 G2019S mutation. The relationship of these features to actual PD risk requires longitudinal observation of LRRK2 familial PD cohorts. © 2018 International Parkinson and Movement Disorder Society
Dynamics of a continuous Hénon model
Authors: Caraballo Tomás , Colucci Renato , Guerrini Luca
Published: April 2018

We study a continuous Hénon system obtained by considering the discrete original model in continuous time. While the dynamics of the continuous model is trivial, we are able to recover the complexity of the discrete model by the introduction of time delays. In particular, high period limit cycles and chaotic attractors are observed. We illustrate the results with some numerical simulations.
Dietary Mannan Oligosaccharides Modulate Gut Microbiota, Increase Fecal Bile Acid Excretion, and Decrease Plasma Cholesterol and Atherosclerosis Development
Authors: Hoving Lisa R. , Katiraei Saeed , Heijink Marieke , Pronk Amanda , van der Wee‐Pals Lianne , Streefland Trea , Giera Martin , Willems van Dijk Ko , van Harmelen Vanessa
Published: April 2018

Scope

Mannan oligosaccharides (MOS) have proven effective at improving growth performance, while also reducing hyperlipidemia and inflammation. As atherosclerosis is accelerated both by hyperlipidemia and inflammation, we aim to determine the effect of dietary MOS on atherosclerosis development in hyperlipidemic ApoE*3‐Leiden.CETP (E3L.CETP) mice, a well‐established model for human‐like lipoprotein metabolism.

Methods and results

Female E3L.CETP mice were fed a high‐cholesterol diet, with or without 1% MOS for 14 weeks. MOS substantially decreased atherosclerotic lesions up to 54%, as assessed in the valve area of the aortic root. In blood, IL‐1RA, monocyte subtypes, lipids, and bile acids (BAs) were not affected by MOS. Gut microbiota composition was determined using 16S rRNA gene sequencing and MOS increased the abundance of cecal Bacteroides ovatus. MOS did not affect fecal excretion of cholesterol, but increased fecal BAs as well as butyrate in cecum as determined by gas chromatography mass spectrometry.

Conclusion

MOS decreased the onset of atherosclerosis development via lowering of plasma cholesterol levels. These effects were accompanied by increased cecal butyrate and fecal excretion of BAs, presumably mediated via interactions of MOS with the gut microbiota.
Technical Note: Iterative megavoltage CT (MVCT) reconstruction using block‐matching 3D‐transform (BM3D) regularization
Authors: Lyu Qihui , Yang Chunlin , Gao Hao , Xue Yi , O'Connor Daniel , Niu Tianye , Sheng Ke
Published: April 2018

Purpose

Megavoltage CT (MVCT) images are noisier than kilovoltage CT (KVCT) due to low detector efficiency to high‐energy x rays. Conventional denoising methods compromise edge resolution and low‐contrast object visibility. In this work, we incorporated block‐matching 3D‐transform shrinkage (BM3D) transformation into MVCT iterative reconstruction as nonlocal patch‐wise regularization.

Methods

The iterative reconstruction was achieved by adding to the existing least square data fidelity objective a regularization term, formulated as the L1 norm of the BM3D transformed image. A Fast Iterative Shrinkage‐Thresholding Algorithm (FISTA) was adopted to accelerate CT reconstruction. The proposed method was compared against total variation (TV) regularization, BM3D postprocess method, and filtered back projection (FBP).

Results

In the Catphan phantom study, BM3D regularization better enhances low‐contrast objects compared with TV regularization and BM3D postprocess method at the same noise level. The spatial resolution using BM3D regularization is 2.79 and 2.55 times higher than that using the TV regularization at 50% of the modulation transfer function (MTF) magnitude, for the fully sampled reconstruction and down‐sampled reconstruction, respectively. The BM3D regularization images show better bony details and low‐contrast soft tissues, on the head and neck (H&N) and prostate patient images.

Conclusions

The proposed iterative BM3D regularization CT reconstruction method takes advantage of both the BM3D denoising capability and iterative reconstruction data fidelity consistency. This novel approach is superior to TV regularized iterative reconstruction or BM3D postprocess for improving noisy MVCT image quality.
Clinical outcomes of detrusor underactivity in female with advanced pelvic organ prolapse following vaginal pelvic reconstructive surgery
Authors: Lo Tsia‐Shu , Chua Sandy , Uy‐Patrimonio Ma. Clarissa , Kao Chuan C. , Lin Chih H.
Published: April 2018

Aim

To determine the impact of vaginal pelvic reconstructive surgery (PRS) on detrusor underactivity (DU) patients having advanced pelvic organ prolapse (POP).

Methods

A retrospective study of patients who underwent PRS for advanced POP (POP‐Q ≥ 3) with DU. Data regarding preoperative evaluation, surgical procedure, and post‐operative management were collated. Patients were considered to have DU when detrusor pressure at maximum flow (PdetQmax) was ≤10 cmH20 and peak flow rate (Qmax) of ≤12 mL/s. Post‐operative values more than the cut‐off were considered objectively cured. Subjective cure was defined as having a negative response to UDI‐6 Question 5, “Do you experience difficulty emptying your bladder?”

Results

A total of 49 patients were evaluated. Majority of the population were post‐menopausal and multiparous. Preoperatively, 38 patients (75%) had stage III prolapse and 13 patients (26%) had stage IV. Subjective cure rate of DU was 76% (37/49) and objective cure rate was 47% (23/49). Post‐operative DU (P < 0.001) significantly improved together with patients having normal urodynamic diagnosis (P < 0.001). Voiding function showed significant increase in Qmax (P < 0.001) and PdetQmax (P < 0.001) while PVR (P < 0.001) and cystometric capacity (P < 0.001) significantly decreased. These findings were observed in 89% (43/49) of patients with post‐void residual urine (PVR) of <200 mL, 63% (31/49) with Qmax > 12 mL/s, and 57% (28/49) with PdetQmax >10 cmH20.

Conclusion

Reversal of short‐term or long‐term obstruction through vaginal pelvic reconstructive surgery enables bladders to regain detrusor muscle function. Although objective cure of DU was at 47%, detrusor function recovered in 57% of patients provided that mechanical obstruction was the cause.
A comparison of the treatment recommendations for neurogenic lower urinary tract dysfunction in the national institute for health and care excellence, European Association of Urology and international consultations on incontinence guidelines
Authors: Jaggi Ashley , Drake Marcus , Siddiqui Emad , Fatoye Francis
Published: April 2018

Aims

Healthcare guidelines are an important vehicle in establishing up‐to‐date evidence based medicine (EBM) in clinical practice. Due to varying development processes, clinical guidelines created by different institutions can often contain contrasting recommendations. This can have implications for optimal and standardized patient care across management settings.

Methods

The similarities and differences of treatment recommendations made in the National Institute for Health and Care Excellence (NICE), The European Association of Urology (EAU), and the International Consultation on Continence (ICI) guidelines for neurogenic lower urinary tract dysfunction (NLUTD) were assessed.

Results

The guidelines generally agree on their approach to conservative management, including behavioral therapies, and catheterization techniques. There was discrepancy on the benefit of using an alpha blocker in NLUTD and bladder outlet obstruction (BOO) and administering Botulinum toxin A (Onabotulinum‐A) in NLUTD. The highest degree of divergence was seen in recommendations for surgical treatments, where the EAU made gender‐specific recommendations, and gave continent urinary diversion higher preference than given in the NICE and ICI guidelines.

Conclusions

In the absence of high‐quality clinical evidence, many of the recommendations made across all three guidelines are based on expert opinion. NICE, the EAU and ICI have similarities but they place differing emphasis on costs and expert opinion, which translated in notably different recommendations. It is evident that increased research efforts, possibly in the form of prospective registries, pragmatic trials, and resource utilization studies are necessary to improve the underlying evidence base for NLUTD, and subsequently the strength and concordance of recommendations across guidelines.
Formal sacrocolpopexy reduces hypercontinence rates in female neobladder formation
Authors: Stearns Gillian , Donahue Timothy , Fathollahi Ali , Dalbagni Guido , Sandhu Jaspreet
Published: April 2018

Aims

Continent urinary diversion is preferred by some patients and orthotopic urinary diversion (OUD) has become the procedure of choice for most men following cystectomy for invasive bladder cancer. OUD in women, however, is less common, likely due to a high rate of hypercontinence (HC), potentially from lax support of pelvic structures similar to pelvic organ prolapse. As such, we evaluated if abdominal sacrocolpopexy (ASC) at the time of OUD in women led to decreased rates of HC.

Methods

A retrospective review of all female patients receiving OUD by a single surgeon and ASC was performed. ASC was performed after RC was complete prior to the urethro‐enteric anastomosis. Peritoneal flap was created to the vaginal apex. The distal leaf was then sutured to the proximal anterior vaginal wall and apex and the proximal end sutured to the anterior longitudinal ligament. HC was defined as the need to perform intermittent catheterization (IC) due to incomplete emptying of the neobladder.

Results

Nine women underwent cystectomy with OUD and concurrent ASC during the specified time period. Average patient age was 54 years (27‐69). Mean followup was 61.6 months (5‐123 months). None of those who underwent ASC had HC or incontinence post‐operatively. No mesh‐related complications were noted in this cohort. Pelvic abscess was noted in one patient who underwent ASC with rectus fascia.

Conclusions

ASC at the time of radical cystectomy and OUD is safe and effective. It appears to be associated with decreased rates of HC and is associated with minimal additional morbidity to the patient.
Test‐retest reliability of the different dynamometric variables used to evaluate pelvic floor musculature during the menstrual cycle
Authors: dos Reis Nagano Reny C. , Biasotto‐Gonzalez Daniela A. , da Costa Gilmar L. , Amorim Karina M. , Fumagalli Marco A. , Amorim César F. , Politti Fabiano
Published: April 2018

Objective

The aim of this study was to evaluate the reliability of different dynamometric variables of the pelvic floor muscles (PFM) in healthy women during different periods of menstrual cycle.

Materials and Methods

Vaginal dynamometric equipment was developed by the authors and its reproducibility was tested. The PFM contractions of 20 healthy women were collected by two independent examiners over three consecutive weeks, always on the same day, with a seven‐day interval between readings, starting from the first day after the end of the menstrual period. For the measurements, the branch of the dynamometer was positioned first on the sagittal plane and then on the frontal plane. Baseline, peak time, maximum PFM strength, impulse contraction, and average contraction force were calculated. Reproducibility was tested using the intra‐class correlation coefficient (ICC) and standard error of measurement. Repeated‐measures ANOVA was used to compare the data from different days.

Results

For intra‐day and inter‐day reliability between examiners, all the parameters collected on the sagittal plane presented good and excellent reproducibility (ICC2,1 = 0.60 to 0.98), whereas reproducibility on the frontal plane was respectively poor and excellent (ICC2,1 = 0.23 to 0.97). The ANOVA revealed significant differences between sessions only for the impulse of contraction for the sagittal (P = 0.005) and frontal (P = 0.03) planes.

Conclusions

Time and contraction force parameters of the PFM are not influenced by hormonal alterations that occur during the menstrual cycle. The impulse of contraction was the only variable to demonstrate a significant difference between the first and second week of the data collection protocol. The baseline, maximum strength value, impulse of contraction, and average contraction force variables presented good to excellent reproducibility and can be safely used as a method of PFM evaluation
Enteral Nutrition and Dementia Integrating Ethics
Authors: Schwartz Denise Baird
Published: April 2018

This narrative review highlights topics related to feeding patients with dementia, including the use of ethical principles and legal precedents; specifies guidelines and practice recommendations; provides an option to assist in applying the recommendations, such as comfort feedings instead of enteral nutrition; promotes the use of early advance care planning to achieve medical therapies based on an individual's wishes; and provides 3 case studies to demonstrate the clinical application of the information presented in the article. Enteral nutrition guidelines and recommendations have been developed by the American Society for Parenteral and Enteral Nutrition and the Academy of Nutrition and Dietetics for individuals with dementia. Predominately these guidelines and recommendations focus on patients with advanced dementia due to the dysphagia and progressive disease process. Despite the research and recommendations to forgo enteral nutrition in advanced dementia, the practice continues. The detailed case studies, integrating an interprofessional approach, provide tools for clinicians to incorporate ethical principles and address the communication aspect when dealing with families and surrogate decision‐makers for individuals with advanced dementia.
Technology in Parenteral Nutrition Compounding
Authors: Curtis Caitlin
Published: April 2018

Technology is constantly being used in novel ways, and its use in the practice of medicine is no exception. Examples of this include computer physician order entry, barcode‐medication scanning, electronic health records (EHRs), and bedside patient charts, to name a few. Compounding parenteral nutrition has been included in this technological revolution, with improvements such as barcode‐assisted medication preparation systems and EHR‐to‐compounder interfaces. Along with some of these electronic advancements come the inevitable improvements and challenges, which are explored in this article.
A polynomial chaos‐based approach to risk‐averse piezoelectric control of random vibrations of beams
Authors: Marín F.J. , Martínez‐Frutos J. , Periago Francisco
Published: April 2018

This paper proposes a risk‐averse formulation for the problem of piezoelectric control of random vibrations of elastic structures. The proposed formulation, inspired by the notion of risk aversion in economy, is applied to the piezoelectric control of a Bernoulli‐Euler beam subjected to uncertainties in its input data. To address the high computational burden associated to the presence of random fields in the model and the discontinuities involved in the cost functional and its gradient, a combination of a nonintrusive anisotropic polynomial chaos approach for uncertainty propagation with a Monte Carlo sampling method is proposed. In the first part, the well‐posedness of the control problem is established by proving the existence of optimal controls. In the second part, an adaptive gradient‐based method is proposed for the numerical resolution of the problem. Several experiments illustrate the performance of the proposed approach and the significant differences that may occur between the classical deterministic formulation of the problem and its stochastic risk‐averse counterpart.