bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary Fatty Acids Differentially Regulate Secretion of Adiponectin and Interleukin‐6 in Primary Canine Adipose Tissue Culture
Authors: Mazaki‐Tovi Michal , Bolin Steven R. , Schenck Patricia A.
Published: March 2018

The aim of this study was to determine the effect of n3 polyunsaturated fatty acids (PUFA) on canine adipose tissue secretion of adiponectin, interleukin‐6 (IL6), and tumor necrosis factor‐α (TNFα). Subcutaneous and omental visceral adipose tissue samples were collected from 16 healthy intact female dogs. Concentrations of adiponectin were measured in mature adipocyte cultures, and concentrations of IL6 and TNFα were measured in undifferentiated stromovascular cell (SVC) cultures following treatment with eicosapentaenic acid (EPA, 20:5n‐3), arachidonic acid (ARA, 20:4n‐6), or palmitic acid (PAM, 16:0) at 25, 50, or 100 μM. Secretion of adiponectin from mature adipocytes was higher (p < 0.001) following EPA treatment at 50 μM compared to control in subcutaneous tissue, and higher following EPA treatment compared to PAM treatment at 25 μM in both subcutaneous (p < 0.001) and visceral tissues (p = 0.010). Secretion of IL6 from SVC derived from subcutaneous tissue was lower following EPA treatment and higher following PAM treatment compared to control both at 50 μM (p = 0.001 and p = 0.041, respectively) and 100 μM (p = 0.013 and p < 0.001, respectively). These findings of stimulation of adiponectin secretion and inhibition of IL6 secretion by EPA, and stimulation of IL6 secretion by PAM, are consistent with findings of increased circulating concentrations of adiponectin and decreased circulating concentration of IL6 in dogs supplemented with dietary fish oil, and show that the effect of fish oil on circulating concentrations of adiponectin and IL6 is, at least partially, the result of local effects of EPA and PAM on adipose tissue.
Heterozygosity for the alpha‐1‐antitrypsin Z allele in cirrhosis is associated with more advanced disease
Authors: Schaefer Benedikt , Mandorfer Mattias , Viveiros André , Finkenstedt Armin , Ferenci Peter , Schneeberger Stefan , Tilg Herbert , Zoller Heinz
Published: March 2018

Alpha‐1‐antitrypsin deficiency (A1ATD) due to homozygosity for the Z allele (ZZ) is an established risk factor for cirrhosis, but the liver disease risk in heterozygous Z allele carriers (MZ) is controversial. The aim of the present study was to determine the prevalence of the MZ genotype among patients with cirrhosis and the associated risk of decompensation and liver transplantation/mortality. An unselected cohort of 561 patients with cirrhosis and 248 deceased liver donors were genotyped for the A1ATD risk alleles Z and S using a validated allelic discrimination assay. Clinical and biochemical parameters were assessed in 488 genotype MM and 52 MZ patients at baseline when cirrhosis was diagnosed and at the last contact, before liver transplantation or death, as study endpoints. MZ prevalence was 2.8% among liver donors, 5.8%, 9.1%, 10.9%, and 19.0% in patients with cirrhosis and Model for End‐Stage Liver Disease–sodium (MELD‐Na) ≤10, 11‐20, 21‐30, and >30, respectively. Among liver transplant recipients, MZ prevalence was 9.7%. MS prevalence was not different between donors, patients with cirrhosis, or transplant recipients. At the end of follow‐up, MELD‐Na scores were higher among heterozygous Z risk allele carriers (16 versus 19; P = 0.03). Decompensation of cirrhosis with ascites or encephalopathy was significantly more frequent in patients with MZ than in MM patients. In the subgroup with transferrin (Tf) saturation >50% or Tf <180 mg/dL, MZ patients had a significantly higher risk of liver transplantation or death than MM patients. In conclusion, the genotype MZ is a genetic risk factor for more advanced cirrhosis and decompensation. MZ patients with cirrhosis and hypotransferrinemia or increased Tf saturation are at higher risk of death and liver transplantation. Liver Transplantation 24 744–751 2018 AASLD.
Propensity‐Matched Analysis of Patients with Mixed Hepatocellular‐Cholangiocarcinoma and Hepatocellular Carcinoma Undergoing Liver Transplantation†
Authors: Lunsford Keri E. , Court Colin , Seok Lee Yong , Lu David S. , Naini Bita V. , Harlander‐Locke Michael P. , Busuttil Ronald W. , Agopian Vatche G.
Published: March 2018

Mixed hepatocellular‐cholangiocarcinomas (HCC‐CCAs) are rare tumors with both hepatocellular and biliary differentiation. While liver transplantation (LT) is the gold standard treatment for patients with unresectable hepatocellular carcinoma (HCC), it is contraindicated in known HCC‐CCA because of concerns of poor prognosis. We sought to compare posttransplant oncologic outcomes for HCC‐CCA and a matched cohort of HCC LT recipients. A retrospective, single‐center analysis (1984‐2015) identified 12 patients with mixed HCC‐CCA who were matched 1:3 to patients with HCC on both pretransplant (radiologic diameter and alpha‐fetoprotein) and explant (pathologic diameter, grade/differentiation, and vascular invasion) tumor characteristics. Compared with HCC patients matched on pretransplant characteristics (n = 36), HCC‐CCA had higher explant tumor grade, more poorly differentiated tumors, but similar T stage and vascular invasion. HCC‐CCA recipients trended toward inferior recurrence‐free survival at 5 years (28% versus 61%; P = 0.12) and greater recurrence (HCC‐CCA: 50%, median time to recurrence 297 days versus HCC: 22%, median time to recurrence 347 days; P = 0.07). However, when matched to a separate HCC cohort with similar explant pathology, HCC‐CCA had similar 5‐year recurrence‐free survival (42% versus 44%; P = 0.45) and posttransplant recurrence (50% versus 27%; P = 0.13). All 6 HCC‐CCA recurrences occurred with poorly differentiated tumors (median survival 21.3 months), without a single recurrence in 5 of the 12 HCC‐CCA patients with well‐moderately differentiated tumors (median survival 60.2 months). Mixed HCC‐CCA tumors are more likely poorly differentiated tumors compared with HCC with similar pretransplant characteristics. However, compared with HCC with similar pathologic characteristics, they display similar recurrence‐free survival and are not inherently more aggressive tumors. Low‐grade, well‐moderately differentiated HCC‐CCAs have excellent survival with a low risk for post‐LT recurrence, and they should not be excluded from LT. Improved pretransplant identification of pathologic characteristics in HCC‐CCA may allow for successful utilization of LT in this subset of patients.
Achieving Sustained Virological Response in Liver Transplant Recipients With Hepatitis C Decreases Risk of Decline in Renal Function
Authors: Satapathy Sanjaya K. , Joglekar Kiran , Molnar Miklos Z. , Ali Bilal , Gonzalez Humberto C. , Vanatta Jason M. , Eason James D. , Nair Satheesh P.
Published: March 2018

The effect of antiviral therapy (AVT) on kidney function in liver transplantation (LT) recipients has not been well described despite known association of hepatitis C virus (HCV) infection with chronic kidney disease (CKD). We compared the incidence of CKD and end‐stage renal disease (ESRD) in 204 LT recipients with HCV based on treatment response to AVT. The mean estimated glomerular filtration rate (eGFR) at baseline (3 months after LT) was similar in the sustained virological response (SVR; n = 145) and non‐SVR group (n = 59; 69 ± 21 versus 65 ± 33 mL/minute/1.73 m2; P = 0.27). In the unadjusted Cox proportional regression analysis, the presence of SVR was associated with an 88% lower risk of CKD (hazard ratio, 0.12; 95% confidence interval [CI], 0.05‐0.31) and 86% lower risk of ESRD (odds ratio, 0.14; 95% CI, 0.05‐0.35). Similar results were found after adjusting for propensity score and time‐dependent Cox regression analyses. The estimated slopes of eGFR based on a 2‐stage mixed model of eGFR were calculated. Patients with SVR had a less steep slope in eGFR (–0.60 mL/minute/1.73 m2/year; 95% CI, –1.50 to 0.30; P = 0.190) than recipients without SVR (–2.53 mL/minute/1.73 m2/year; 95% CI, –3.99 to –1.07; P = 0.001), and the differences in the slopes were statistically significant (P = 0.026). In conclusion, in LT recipients with chronic HCV infection, achieving SVR significantly lowers the risk of decline in renal function and progression to ESRD independent of the AVT therapy used.
An Inexpensive, Portable Device for Point‐of‐Need Generation of Silver‐Nanoparticle Doped Cellulose Acetate Nanofibers for Advanced Wound Dressing
Authors: Brako Francis , Luo Chaojie , Craig Duncan Q. M. , Edirisinghe Mohan
Published: March 2018

This short communication describes the design and assembly of a new, miniaturized electrospinner to produce nanofibers at the site of need for drug delivery and wound dressing applications. The portable apparatus would eliminate the storage and transportation concerns with regards to the delicate nature of drug‐loaded nanofibers, thereby preserving product integrity at the site of use. Furthermore, the setup features a smaller size, a cheaper price, and components that are readily obtainable off‐the‐shelf, compared to those of available devices that are custom‐built and more expensive, making it desirable and accessible for other users in the field. As a proof‐of‐concept for wound care, the device is successfully used to electrospin three types of nanofibers comprised of pure cellulose acetate (CA), and CA respectively doped with 0.75 and 1.5 wt% silver nanoparticles. The miniaturized device is useful on account of the popularity of electrospinning as well as the potential to minimize wound infection due to the reduced manipulation of both the dressing and the wound from product generation to the point of need. Work is in progress to further develop the portable device and compare its product performance with traditional wound dressing materials for clinical translation.
Naphtho[1,2‐b:5,6‐b′]dithiophene‐Based Conjugated Polymers for Fullerene‐Free Inverted Polymer Solar Cells
Authors: Jiang Zhaoyan , Li Huan , Wang Zhen , Zhang Jianqi , Zhang Yajie , Lu Kun , Wei Zhixiang
Published: March 2018

Three novel copolymers based on zigzag naphthodithiophene (zNDT) with different aromatic rings as π bridges and different core side substitutions are designed and synthesized (PzNDT‐T‐1,3‐bis(4‐(2‐ethylhexyl)‐thiophen‐2‐yl)‐5,7‐bis(2‐ethylhexyl)benzo[1,2‐c:4,5‐c′]‐dithiophene‐4,8‐dione (BDD), PzNDT‐TT‐BDD, and PzNDTP‐T‐BDD, respectively). The 2D conjugation structure and molecular planarity of the polymers can be effectively altered through the modification of conjugated side chains and π‐bridges. These alterations contribute to the variation in energy levels, light absorption capacity, and morphology compatibility of the polymers. When blended with the nonfullerene acceptor (2,2′‐[(4,4,9,9‐tetrahexyl‐4,9‐dihydro‐sindaceno[1,2‐b:5,6‐b′]dithiophene‐2,7‐diyl)bis[methylidyne(3‐oxo‐1H‐indene‐2,1(3H)‐diylidene)]]bis‐propanedinitrile) (IDIC), PzNDT‐T‐BDD exhibits the highest power conversion efficiency (PCE) of 9.72% among the three polymers. This result can be attributed to its superior crystallinity and more obvious face‐on orientation in blending film. PzNDT‐TT‐BDD and PzNDTP‐T‐BDD present PCE values of 8.20% and 4.62%, respectively. The alteration of polymer structure, particularly the modification of conjugated side chains and π‐bridges, is an effective strategy for designing NDT‐based polymers with high photovoltaic performance and potential applications in fullerene‐free solar cells.
Localization and dynamics of Wolbachia infection in Asian citrus psyllid Diaphorina citri, the insect vector of the causal pathogens of Huanglongbing
Authors: Ren Su‐Li , Li Yi‐Han , Ou Da , Guo Yan‐Jun , Qureshi Jawwad A. , Stansly Philip A. , Qiu Bao‐Li
Published: March 2018

Wolbachia is a group of intracellular bacteria that infect a wide range of arthropods including the Asian citrus psyllid (ACP), Diaphorina citri Kuwayama. This insect is the vector of Candidatus Liberibacter asiaticus (CLas), the causal pathogen of Huanglongbing or citrus greening disease. Here, we investigated the localization pattern and infection dynamics of Wolbachia in different developmental stages of ACP. Results revealed that all developmental stages of ACP including egg, 1st–5th instar nymphs, and adults of both gender were infected with Wolbachia. FISH visualization of an ACP egg showed that Wolbachia moved from the egg stalk of newly laid eggs to a randomly distributed pattern throughout the egg prior to hatching. The infection rate varied between nymphal instars. The titers of Wolbachia in fourth and fifth instar nymphs were significantly higher than those in the first and second instar nymphs. Wolbachia were scattered in all nymphal stages, but with highest intensity in the U‐shaped bacteriome located in the abdomen of the nymph. Wolbachia was confined to two symmetrical organizations in the abdomen of newly emerged female and male adults. The potential mechanisms of Wolbachia infection dynamics are discussed.
The role of conserved charged residues in the bidirectional rotation of the bacterial flagellar motor
Authors: Onoue Yasuhiro , Takekawa Norihiro , Nishikino Tatsuro , Kojima Seiji , Homma Michio
Published: March 2018

Many bacteria rotate their flagella both counterclockwise (CCW) and clockwise (CW) to achieve swimming toward attractants or away from repellents. Highly conserved charged residues are important for that motility, which suggests that electrostatic interactions are crucial for the rotor–stator function. It remains unclear if those residues contribute equally to rotation in the CCW and CW directions. To address this uncertainty, in this study, we expressed chimeric rotors and stators from Vibrio alginolyticus and Escherichia coli in E. coli, and measured the rotational speed of each motor in both directions using a tethered‐cell assay. In wild‐type cells, the rotational speeds in both directions were equal, as demonstrated previously. Some charge‐neutralizing residue replacements in the stator decreased the rotational speed in both directions to the same extent. However, mutations in two charged residues in the rotor decreased the rotational speed only in the CCW direction. Subsequent analysis and previous results suggest that these amino acid residues are involved in supporting the conformation of the rotor, which is important for proper torque generation in the CCW direction.
Effect of hydraulic retention time on microbial community structure in wastewater treatment electro‐bioreactors
Authors: ElNaker Nancy A. , Yousef Ahmed F. , Hasan Shadi W.
Published: March 2018

The impact of hydraulic retention time (HRT) on the performance and microbial community structure of control and electro‐bioreactors was investigated. Control bioreactors and electro‐bioreactors were operated at HRT ranging between 6 and 75 hr. The total bacterial counts in addition to the removal efficiency of NH4+–N, sCOD, and PO43−–P was assessed in all the reactors tested. In addition, Illumina sequencing was performed to determine the microbial communities that developed in these reactors under each HRT condition. Phylogenetic analysis showed that Proteobacteria and Bacteroidetes were the dominant phyla in those reactors. In addition, Nitrospira sp. and Pseudomonas sp. were found to be present in electro‐bioreactors with higher relative abundance than in control bioreactors. The results presented here are the first to determine what different microbial communities in wastewater electro‐bioreactors due to the application of an electric current under different HRTs.
Responses of fungal community composition to long‐term chemical and organic fertilization strategies in Chinese Mollisols
Authors: Ma Mingchao , Jiang Xin , Wang Qingfeng , Ongena Marc , Wei Dan , Ding Jianli , Guan Dawei , Cao Fengming , Zhao Baisuo , Li Jun
Published: March 2018

How fungi respond to long‐term fertilization in Chinese Mollisols as sensitive indicators of soil fertility has received limited attention. To broaden our knowledge, we used high‐throughput pyrosequencing and quantitative PCR to explore the response of soil fungal community to long‐term chemical and organic fertilization strategies. Soils were collected in a 35‐year field experiment with four treatments: no fertilizer, chemical phosphorus, and potassium fertilizer (PK), chemical phosphorus, potassium, and nitrogen fertilizer (NPK), and chemical phosphorus and potassium fertilizer plus manure (MPK). All fertilization differently changed soil properties and fungal community. The MPK application benefited soil acidification alleviation and organic matter accumulation, as well as soybean yield. Moreover, the community richness indices (Chao1 and ACE) were higher under the MPK regimes, indicating the resilience of microbial diversity and stability. With regards to fungal community composition, the phylum Ascomycota was dominant in all samples, followed by Zygomycota, Basidiomycota, Chytridiomycota, and Glomeromycota. At each taxonomic level, the community composition dramatically differed under different fertilization strategies, leading to different soil quality. The NPK application caused a loss of Leotiomycetes but an increase in Eurotiomycetes, which might reduce the plant–fungal symbioses and increase nitrogen losses and greenhouse gas emissions. According to the linear discriminant analysis (LDA) coupled with effect size (LDA score > 3.0), the NPK application significantly increased the abundances of fungal taxa with known pathogenic traits, such as order Chaetothyriales, family Chaetothyriaceae and Pleosporaceae, and genera Corynespora, Bipolaris, and Cyphellophora. In contrast, these fungi were detected at low levels under the MPK regime. Soil organic matter and pH were the two most important contributors to fungal community composition.
Regulatory role of the RstB‐RstA system in adhesion, biofilm production, motility, and hemolysis
Authors: Huang Lixing , Xu Wei , Su Yongquan , Zhao Lingmin , Yan Qingpi
Published: March 2018

For infection, initial invasion of the host is of great importance, with adhesion playing a critical role. We previously demonstrated rstA and rstB are remarkably downregulated in Vibrio alginolyticus cultured under heavy metal and acidic stresses, with impaired adhesion, suggesting that rstA and rstB might be involved in adhesion regulation. The present study showed that rstA and rstB silencing resulted in impaired adhesion, biofilm production, motility, hemolysis, and virulence. Meanwhile, changes of temperature, starvation, and pH remarkably affected rstA and rstB expression. These findings indicated that (1) rstA and rstB are critical regulators of adhesion in V. alginolyticus; (2) rstA and rstB have remarkable effects on biofilm production, motility, hemolysis, and virulence in V. alginolyticus; (3) rstA and rstB modulate adhesion in response to environmental changes of temperature, pH, and starvation.
Dynamics of coral‐associated microbiomes during a thermal bleaching event
Authors: Pootakham Wirulda , Mhuantong Wuttichai , Putchim Lalita , Yoocha Thippawan , Sonthirod Chutima , Kongkachana Wasitthee , Sangsrakru Duangjai , Naktang Chaiwat , Jomchai Nukoon , Thongtham Nalinee , Tangphatsornruang Sithichoke
Published: March 2018

Coral‐associated microorganisms play an important role in their host fitness and survival. A number of studies have demonstrated connections between thermal tolerance in corals and the type/relative abundance of Symbiodinium they harbor. More recently, the shifts in coral‐associated bacterial profiles were also shown to be linked to the patterns of coral heat tolerance. Here, we investigated the dynamics of Porites lutea‐associated bacterial and algal communities throughout a natural bleaching event, using full‐length 16S rRNA and internal transcribed spacer sequences (ITS) obtained from PacBio circular consensus sequencing. We provided evidence of significant changes in the structure and diversity of coral‐associated microbiomes during thermal stress. The balance of the symbiosis shifted from a predominant association between corals and Gammaproteobacteria to a predominance of Alphaproteobacteria and to a lesser extent Betaproteobacteria following the bleaching event. On the contrary, the composition and diversity of Symbiodinium communities remained unaltered throughout the bleaching event. It appears that the switching and/or shuffling of Symbiodinium types may not be the primary mechanism used by P. lutea to cope with increasing seawater temperature. The shifts in the structure and diversity of associated bacterial communities may contribute more to the survival of the coral holobiont under heat stress.
Large buoyant particles dominated by cyanobacterial colonies harbor distinct bacterial communities from small suspended particles and free‐living bacteria in the water column
Authors: Shi Limei , Huang Yaxin , Zhang Min , Shi Xiaoli , Cai Yuanfeng , Gao Shengling , Tang Xiangming , Chen Feizhou , Lu Yaping , Kong Fanxiang
Published: March 2018

Worldwide cyanobacterial blooms greatly impair ecosystems in many eutrophic lakes and impact the microbial environment. In particular, large cyanobacterial colonies that are buoyant on the water surface may provide a distinct habitat for bacteria from other small particles that are suspended stably in the water column. To test this hypothesis, bacterial communities (excluding cyanobacteria) attached to large particles dominated by cyanobacterial colonies (>120 μm, LA), small particles (3–36 μm, SA), and free‐living bacteria (0.2–3 μm, FL) were investigated monthly for a year in Lake Taihu, China. Results confirmed that the Shannon diversity index of LA was significantly lower than that of FL, which was lower than that of SA. Cytophagia and Alphaproteobacteria were specially enriched in LA. Although samples in each habitat collected during high‐ (May to November) and low‐bloom seasons (December to April) were separated, all samples in LA were clustered and separated from SA and FL, which were also clustered during the same sampling seasons. In addition, the bacterial communities in LA were correlated with nitrate level, whereas FL and SA were correlated with nitrate level and temperature. Mantel analysis revealed that bacterial composition significantly correlated with the cyanobacterial composition in LA and FL but not in SA. These results indicate that LA provides distinct niches to bacteria, whereas the differentiation of bacterial communities in FL and SA is seasonally dependent.
Treatment of colon cancer with liver X receptor agonists induces immunogenic cell death
Authors: Wang Qiang , Ren Meijia , Feng Fan , Chen Keping , Ju Xiaoli
Published: March 2018

Liver X receptor (LXR) agonists inhibit various types of tumor growth and have been applied to preclinical research. In colon cancer cells, LXR agonists induce pyroptotic cell death through the predominant cytoplasmic localisation of LXRβ. In the present study, we determined whether tumor cell death induced by LXR agonists in colon cancer cells could elicit immunogenic cell death (ICD). LXR agonist‐treated‐colon cancer cells exhibited translocation of calreticulin (CRT) and release of HMGB1 and ATP into the medium. Expression levels of CRT and HMGB1 were also increased in T0901317‐treated Balb/c mice. Furthermore, compared with control mice, mice vaccinated with T0901317‐treated CT26 cells showed reduced tumor volumes and protection against a challenge with live tumor cells. Inhibition of CRT or HMGB1 expression in CT26 cells abolished this protection in Balb/c mice. In conclusion, the LXR agonist T0901317 induces ICD in colon cancer cells. CRT exposure and HMGB1 release play a critical role in the immunogenicity of this treatment.
Low dose irradiation facilitates hepatocellular carcinoma genesis involving HULC
Authors: Li Yuan , Ge Chang , Feng Guoxing , Xiao Huiwen , Dong Jiali , Zhu Changchun , Jiang Mian , Cui Ming , Fan Saijun
Published: March 2018

Irradiation exposure positive correlates with tumor formation, such as breast cancer and lung cancer. However, whether low dose irradiation induces hepatocarcinogenesis and the underlying mechanism remain poorly defined. In the present study, we reported that low dose irradiation facilitated the proliferation of hepatocyte through up‐regulating HULC in vitro and in vivo. Low dose irradiation exposure elevated HULC expression level in hepatocyte. Deletion of heightened HULC erased the cells growth accelerated following low dose irradiation exposure. CDKN1, the neighbor gene of HULC, was down‐regulated by overexpression of HULC following low dose irradiation exposure via complementary base pairing, resulting in promoting cell cycle process. Thus, our findings provide new insights into the mechanism of low dose irradiation‐induced hepatocarcinogenesis through HULC/CDKN1 signaling, and shed light on the potential risk of low dose irradiation for the development of hepatocellular carcinoma in pre‐clinical settings.
Stool Immune Profiles Evince Gastrointestinal Inflammation in Parkinson's Disease
Authors: Houser Madelyn C. , Chang Jianjun , Factor Stewart A. , Molho Eric S. , Zabetian Cyrus P. , Hill‐Burns Erin M. , Payami Haydeh , Hertzberg Vicki S. , Tansey Malú G.
Published: March 2018

Background: Gastrointestinal symptoms are common in Parkinson's disease and frequently precede the development of motor impairments. Intestinal inflammation has been proposed as a driver of disease pathology, and evaluation of inflammatory mediators in stool could possibly identify valuable early‐stage biomarkers. We measured immune‐ and angiogenesis‐related proteins in human stool to examine inflammatory profiles associated with Parkinson's disease.

Methods: Stool samples and subjects' self‐reported metadata were obtained from 156 individuals with Parkinson's disease and 110 without, including spouse and nonhousehold controls. Metadata were probed for disease‐associated differences, and levels of 37 immune and angiogenesis factors in stool homogenates were measured by multiplexed immunoassay and compared across experimental groups.

Results: Parkinson's disease patients reported greater incidence of intestinal disease and digestive problems than controls. Direct comparison of levels of stool analytes in patients and controls revealed elevated vascular endothelial growth factor receptor 1, interleukin‐1α, and CXCL8 in patients' stool. Paired comparison of patients and spouses suggested higher levels of multiple factors in patients, but this was complicated by sex differences. Sex, body mass index, a history of smoking, and use of probiotics were found to strongly influence levels of stool analytes. Multivariate analysis accounting for these and other potential confounders confirmed elevated levels of interleukin‐1α and CXCL8 and also revealed increased interleukin‐1β and C‐reactive protein in stool in Parkinson's disease. These differences were not dependent on subject age or disease duration.

Conclusions: Levels of stool immune factors indicate that intestinal inflammation is present in patients with Parkinson's disease. © 2018 International Parkinson and Movement Disorder Society
Longitudinal Change of Clinical and Biological Measures in Early Parkinson's Disease: Parkinson's Progression Markers Initiative Cohort
Authors: Simuni Tanya , Siderowf Andrew , Lasch Shirley , Coffey Chris S. , Caspell‐Garcia Chelsea , Jennings Danna , Tanner Caroline M. , Trojanowski John Q. , Shaw Leslie M. , Seibyl John , Schuff Norbert , Singleton Andrew , Kieburtz Karl , Toga Arthur W. , Mollenhauer Brit , Galasko Doug , Chahine Lana M. , Weintraub Daniel , Foroud Tatiana , Tosun Duygu , Poston Kathleen , Arnedo Vanessa , Frasier Mark , Sherer Todd , Chowdhury Sohini , Marek Kenneth ,   the Parkinson's Progression Marker Initiative*
Published: March 2018

Objective: The objective of this study was to assess longitudinal change in clinical and dopamine transporter imaging outcomes in early, untreated PD.

Methods: We describe 5‐year longitudinal change of the MDS‐UPDRS and other clinical measures using results from the Parkinson's Progression Markers Initiative, a longitudinal cohort study of early Parkinson's disease (PD) participants untreated at baseline. We also provide data on the longitudinal change in dopamine transporter 123‐I Ioflupane striatal binding and correlation between the 2 measures.

Results: A total of 423 PD participants were recruited, and 358 remain in the study at year 5. Baseline MDS‐UPDRS total score was 32.4 (standard deviation 13.1), and the average annual change (assessed medications OFF for the treated participants) was 7.45 (11.6), 3.11 (11.7), 4(11.9), 4.7 (11.1), and 1.74(11.9) for years 1, 2, 3, 4, and 5, respectively (P < .0001 for the change over time), with a steeper change in year 1. Dopaminergic therapy had a significant effect on the change of MDS‐UPDRS. There was a significant longitudinal change in dopamine transporter binding in all striatal regions (P < .001). There was a significant but weak correlation between MDS‐UPDRS and dopamine transporter binding at baseline and years 1, 2, and 4, but no correlation between the rate of change of the 2 variables.

Conclusions: We present 5‐year longitudinal data on the change of the MDS‐UPDRS and other clinical and dopamine transporter imaging outcome measures in early PD. These data can be used for sample size estimates for interventional studies in the de novo PD population. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Structural variations causing inherited peripheral neuropathies: A paradigm for understanding genomic organization, chromatin interactions, and gene dysregulation
Authors: Cutrupi Anthony N. , Brewer Megan H. , Nicholson Garth A. , Kennerson Marina L.
Published: March 2018

Inherited peripheral neuropathies (IPNs) are a clinically and genetically heterogeneous group of diseases affecting the motor and sensory peripheral nerves. IPNs have benefited from gene discovery and genetic diagnosis using next‐generation sequencing with over 80 causative genes available for testing. Despite this success, up to 50% of cases remain genetically unsolved. In the absence of protein coding mutations, noncoding DNA or structural variation (SV) mutations are a possible explanation. The most common IPN, Charcot‐Marie‐Tooth neuropathy type 1A (CMT1A), is caused by a 1.5 Mb duplication causing trisomy of the dosage sensitive gene PMP22. Using genome sequencing, we recently identified two large genomic rearrangements causing IPN subtypes X‐linked CMT (CMTX3) and distal hereditary motor neuropathy (DHMN1), thereby expanding the spectrum of SV mutations causing IPN. Understanding how newly discovered SVs can cause IPN may serve as a useful paradigm to examine the role of topologically associated domains (TADs), chromatin interactions, and gene dysregulation in disease. This review will describe the growing role of SV in the pathogenesis of IPN and the importance of considering this type of mutation in Mendelian diseases where protein coding mutations cannot be identified.
Intraoperative evaluation of perfusion in free flap surgery: A systematic review and meta‐analysis
Authors: Smit Jan Maerten , Negenborn Vera L. , Jansen Sanne M. , Jaspers Mariëlle E. H. , de Vries Ralph , Heymans Martijn W. , Winters Hay A. H. , van Leeuwen Ton G. , Mullender Margriet G. , Krekel Nicole M. A.
Published: March 2018

Background

Free flap survival relies on adequate tissue perfusion. We aim to give an overview of the available literature of all objective methods to intraoperatively assess free flap tissue perfusion, and the effects on (partial) flap loss.

Methods

A systematic review and meta‐analysis according to the PRISMA guidelines was performed (PubMed, Cochrane Library, Embase) regarding English language articles. Meta‐analyses were performed by pooling means and slopes using random‐effect models.

Results

Sixty‐four articles were included reporting on 2369 procedures in 2009 patients with various indications. Reported methods were fluorescence imaging (FI), laser Doppler, oxygen saturation, ultrasound, (dynamic) infrared thermography, venous pressure, and microdialysis. Intraoperative tissue perfusion was adequately measured by the use of FI and laser Doppler, leading to surgical intervention or altered flap design, and increased flap survival. Meta‐analysis showed a mean time until onset of the dye to become visible of 18.4 (7.27; 29.46, Q P < 0.001) sec. The relative intensity of the flap compared to the intensity curve of normal tissue was 75.92% (65.85; 85.98, Q P = 0.719). The mean difference in the slope value of the oxygen tensions before and after the anastomosis was −0.09 (–0.12; −0;06 Q P = 0.982). No convincing evidence was found for the use of other methods.

Conclusions

Based on the current literature, FI and laser Doppler are most suitable to intraoperatively measure free flap tissue perfusion, resulting in improved flap survival. However, this review was limited by the available literature. Additional studies are necessary to investigate the predictive value of intraoperative perfusion measurement.
Analyticity for a class of nonlocal Kuramoto‐Sivashinsky equations arising in interfacial electrohydrodynamics
Authors: Ioakim Xenakis
Published: March 2018

In this article, we study the analyticity properties of solutions of the nonlocal Kuramoto‐Sivashinsky equations,

urn:x-wiley:mma:media:mma4844:mma4844-math-0001
defined on 2π‐periodic intervals, where ν is a positive constant; μ is a nonnegative constant; p is an arbitrary but fixed real number in the interval [3,4); and
is an operator defined by its symbol in Fourier space, with
be the Hilbert transform. We establish spatial analyticity in a strip around the real axis for the solutions of such equations, which possess universal attractors. Also, a lower bound for the width of the strip of analyticity is obtained.
Transcriptome‐Based Analysis in Lactobacillus plantarum WCFS1 Reveals New Insights into Resveratrol Effects at System Level
Authors: Reverón Inés , Plaza‐Vinuesa Laura , Franch Mónica , de las Rivas Blanca , Muñoz Rosario , López de Felipe Félix
Published: March 2018

Scope

This study was undertaken to expand our insights into the mechanisms involved in the tolerance to resveratrol (RSV) that operate at system‐level in gut microorganisms and advance knowledge on new RSV‐responsive gene circuits.

Methods and results

Whole genome transcriptional profiling was used to characterize the molecular response of Lactobacillus plantarum WCFS1 to RSV. DNA repair mechanisms were induced by RSV and responses were triggered to decrease the load of copper, a metal required for RSV‐mediated DNA cleavage, and H2S, a genotoxic gas. To counter the effects of RSV, L. plantarum strongly up‐ or downregulated efflux systems and ABC transporters pointing to transport control of RSV across the membrane as a key mechanism for RSV tolerance. L. plantarum also downregulated tRNAs, induced chaperones, and reprogrammed its transcriptome to tightly control ammonia levels. RSV induced a probiotic effector gene and a likely deoxycholate transporter, two functions that improve the host health status.

Conclusion

Our data identify novel protective mechanisms involved in RSV tolerance operating at system level in a gut microbe. These insights could influence the way RSV is used for a better management of gut microbial ecosystems to obtain associated health benefits.
Cruciferous Vegetables and Risk of Cancers of the Gastrointestinal Tract
Authors: Johnson Ian T.
Published: March 2018

Cancers of the oropharyngeal tissues, oesophagus, stomach, and colorectum are amongst the most common causes of death from cancer throughout the world. Higher consumption of fruits and vegetables is thought to be protective, and cruciferous vegetables are of particular interest because of their unique role as a source of biologically active glucosinolate breakdown products. A literature review of primary studies and meta‐analyses indicates that higher consumption of cruciferous vegetables probably reduces the risk of colorectal and gastric cancers by approximately 8% and 19%, respectively. Some studies support the hypothesis that the protective effect against colorectal cancer is modified by genetic polymorphisms of genes regulating the expression of enzymes of the glutathione S‐transferase family, but due to contradictory findings the evidence is currently inconclusive. Despite these promising findings, future epidemiological research on the protective effects of cruciferous plants will depend critically upon accurate measurement of dietary exposure, both to the vegetables themselves, and to their active constituents. The development of sensitive chemical assays has facilitated the measurement of urinary excretion of isothiocyanate metabolites as an objective biomarker of intake, but sampling strategies need to be optimized in order to assess long‐term exposures at the population level.
The Influence of Dietary Habits and Meat Consumption on Plasma 3‐Methylhistidine—A Potential Marker for Muscle Protein Turnover
Authors: Kochlik Bastian , Gerbracht Christiana , Grune Tilman , Weber Daniela
Published: March 2018

Scope

3‐Methylhistidine (3‐MH) as a potential biomarker for muscle protein turnover is influenced by meat intake but data on the impact of meat on plasma 3‐MH are scarce. We determined the association of plasma 3‐MH, 1‐methylhistidine (1‐MH), and creatinine with dietary habits and assessed the impact of a single white meat intervention during a meat‐free period.

Methods and results

Plasma 3‐MH, 1‐MH, and creatinine concentrations of healthy young omnivores (n = 19) and vegetarians (n = 16) were analyzed together with data on anthropometry, body composition, grip strength, and nutrition. After baseline measurements omnivores adhered to a meat‐free diet for 6 days and received a defined administration of chicken breast on day four. At baseline, omnivores had higher plasma 3‐MH and 1‐MH concentrations than vegetarians. White meat administration led to a slight increase in plasma 3‐MH in omnivores. The elevated 3‐MH concentrations significantly declined within 24 h after white meat intake.

Conclusion

1‐MH concentrations in plasma seem to be suitable to display (white) meat consumption and its influence on 3‐MH plasma concentration. 3‐MH in plasma may be used as a biomarker for muscle protein turnover if subjects have not consumed meat in the previous 24 h.
Activation of the IGF1 receptor stimulates glycogen synthesis by mink uterine epithelial cells
Authors: Dean Matthew , Rose Jack
Published: March 2018

Glycogen synthesis by mink uterine epithelial cells is stimulated by estradiol (E2) during estrus, although the mechanism/s through which the steroid promotes glycogen accumulation are unknown. Our aim was to determine if insulin is required for E2 induced glycogen synthesis by an immortalized mink uterine epithelial cell line (GMMe). We show that the cells expressed the genes for glycogen metabolizing enzymes (hexokinase 1, glucose‐6‐phosphatase 3, glycogen synthase 1, and glycogen phosphorylase‐muscle), receptors for insulin, insulin‐like growth factor 1 and E2 (Esr1). Interestingly, treatment of cells with E2 alone failed to stimulate glycogen production, whereas supraphysiological concentrations of insulin (50 μg/ml) only, significantly increased glycogen content. Moreover, insulin + E2 increased glycogen content when compared to insulin alone (p < 0.05), an affect that was blocked when cells were treated with the pure E2 receptor antagonist ICI 182,780. Glycogen synthesis in response to insulin was significantly inhibited when cells were pre‐treated with picropodophyllotoxin, an IGF1R antagonist. Treatment of cells with LY294002, a phosphatidylinositol 3‐kinase (PI3K) antagonist, blocked insulin's effects on glycogen production whereas treatment with U0126, an inhibitor of mitogen activated kinase‐kinase (MEK1/2) was without effect. These findings suggest to us that the affects of E2 on glycogen synthesis by GMMe cells is mediated through Esr1 and increased responsiveness of the cells to insulin. Because picropodophylotoxin blocked the effects of insulin on glycogen production, and both insulin and IGF1 act through PI3K, it is possible that IGF1 plays a role in glycogen production by these cells.
Optimization of selective inversion recovery magnetization transfer imaging for macromolecular content mapping in the human brain
Authors: Dortch Richard D. , Bagnato Francesca , Gochberg Daniel F. , Gore John C. , Smith Seth A.
Published: March 2018

Purpose

To optimize a selective inversion recovery (SIR) sequence for macromolecular content mapping in the human brain at 3.0T.

Theory and Methods

SIR is a quantitative method for measuring magnetization transfer (qMT) that uses a low‐power, on‐resonance inversion pulse. This results in a biexponential recovery of free water signal that can be sampled at various inversion/predelay times (tI/tD) to estimate a subset of qMT parameters, including the macromolecular‐to‐free pool‐size‐ratio (PSR), the R1 of free water (R1f), and the rate of MT exchange (kmf). The adoption of SIR has been limited by long acquisition times (≈4 min/slice). Here, we use Cramér‐Rao lower bound theory and data reduction strategies to select optimal tI/tD combinations to reduce imaging times. The schemes were experimentally validated in phantoms, and tested in healthy volunteers (N = 4) and a multiple sclerosis patient.

Results

Two optimal sampling schemes were determined: (i) a 5‐point scheme (kmf estimated) and (ii) a 4‐point scheme (kmf assumed). In phantoms, the 5/4‐point schemes yielded parameter estimates with similar SNRs as our previous 16‐point scheme, but with 4.1/6.1‐fold shorter scan times. Pair‐wise comparisons between schemes did not detect significant differences for any scheme/parameter. In humans, parameter values were consistent with published values, and similar levels of precision were obtained from all schemes. Furthermore, fixing kmf reduced the sensitivity of PSR to partial‐volume averaging, yielding more consistent estimates throughout the brain.

Conclusions

qMT parameters can be robustly estimated in ≤1 min/slice (without independent measures of ΔB0,
, and T1) when optimized tI‐tD combinations are selected.
A diffusion model‐free framework with echo time dependence for free‐water elimination and brain tissue microstructure characterization
Authors: Molina‐Romero Miguel , Gómez Pedro A. , Sperl Jonathan I. , Czisch Michael , Sämann Philipp G. , Jones Derek K. , Menzel Marion I. , Menze Bjoern H.
Published: March 2018

Purpose

The compartmental nature of brain tissue microstructure is typically studied by diffusion MRI, MR relaxometry or their correlation. Diffusion MRI relies on signal representations or biophysical models, while MR relaxometry and correlation studies are based on regularized inverse Laplace transforms (ILTs). Here we introduce a general framework for characterizing microstructure that does not depend on diffusion modeling and replaces ill‐posed ILTs with blind source separation (BSS). This framework yields proton density, relaxation times, volume fractions, and signal disentanglement, allowing for separation of the free‐water component.

Theory and Methods

Diffusion experiments repeated for several different echo times, contain entangled diffusion and relaxation compartmental information. These can be disentangled by BSS using a physically constrained nonnegative matrix factorization.

Results

Computer simulations, phantom studies, together with repeatability and reproducibility experiments demonstrated that BSS is capable of estimating proton density, compartmental volume fractions and transversal relaxations. In vivo results proved its potential to correct for free‐water contamination and to estimate tissue parameters.

Conclusion

Formulation of the diffusion‐relaxation dependence as a BSS problem introduces a new framework for studying microstructure compartmentalization, and a novel tool for free‐water elimination.
A highly decoupled transmit–receive array design with triangular elements at 7T
Authors: Chen Gang , Zhang Bei , Cloos Martijn A. , Sodickson Daniel K. , Wiggins Graham C.
Published: March 2018

Purpose

Transmit arrays are essential tools for various RF shimming or parallel excitation techniques at 7T. Here we present an array design with triangular coils to improve diversity in the B1 profiles in the longitudinal (z) direction and allow for next‐nearest neighbor decoupling.

Methods

Two cylindrical 8‐channel arrays having the same length and diameter, 1 of triangular coils and the other of rectangular coils, were constructed and compared in phantom imaging experiments using measures of excitation distribution for a variety of RF shim settings and geometry factor maps for different accelerations on different planes.

Results

Coupling between elements was −20 dB or better for all triangular coil pairs, but worse than −12 dB for several of the rectangular coil pairs. Both coils could produce adequate shims on a central transverse plane, but the same shim produced worse results off center for the triangular coil array than for the rectangular coil array. Compared to the rectangular coil array, the maximum geometry factor for the triangular coil array was reduced by a factor of 13.1 when using a 2‐fold acceleration in the z‐direction.

Conclusion

An array design with triangular coils provides effective decoupling mechanisms for nearest and next‐nearest neighboring elements, as well as diversity in B1 profiles along the z‐direction, although this also means that individual slices must be shimmed separately. This design is well suited for parallel transmit applications while also having high receive sensitivity.
The correlation between the Childhood Health Assessment Questionnaire and disease activity in juvenile idiopathic arthritis
Authors: Sontichai Watchareewan , Vilaiyuk Soamarat
Published: March 2018

Background

The Childhood Health Assessment Questionnaire (CHAQ) has been adapted from the Stanford Health Assessment Questionnaire for assessing functional ability in children. The present study aimed to determine the correlation between CHAQ and disease activity in juvenile idiopathic arthritis (JIA) during active and inactive disease.

Methods

JIA patients in the Pediatric Department, Ramathibodi Hospital, between January 2011 and December 2013, were included in the study. The CHAQ disability index (DI) and disease activity variables, including active and limited joint count, erythrocyte sedimentation rate, patient's global assessment (PtGA), physician's global assessment (PGA) and 27‐joint Juvenile Arthritis Disease Activity Score (JADAS27), were collected from medical records for each patient over six visits. At each visit, each patient was classified as having either active or inactive disease. The correlations between CHAQ‐DI and disease activity variables were analysed using Spearman's correlation.

Results

The classification of 139 JIA patients consisted of enthesitis‐related arthritis (30.9%), systemic JIA (28.1%), oligoarthritis (16.5%), rheumatoid factor (RF)‐negative polyarthritis (15.1%), RF‐positive polyarthritis (6.5%) and undifferentiated arthritis (2.9%). Out of 812 patient visits, 606 were in active disease and 206 were in inactive disease. RF‐negative polyarthritis had the highest CHAQ‐DI (0.39 ± 0.66), while oligoarthritis had the lowest (0.20 ± 0.32). There was a good correlation between CHAQ‐DI and JADAS27, PGA and PtGA in all JIA subtypes (p < 0.05) during active disease, but a poor correlation between CHAQ‐DI and disease activity variables during inactive disease.

Conclusions

CHAQ‐DI had a good correlation with disease activity during active disease but a poor correlation during inactive disease. Therefore, CHAQ is only useful for assessing functional ability during active disease.