bluuebunny/crossref_metadata_2025 huggingface dataset:
Cyclodextrins reduce the ability of Pseudomonas aeruginosa outer-membrane vesicles to reduce CFTR Cl− secretion
Authors: Barnaby Roxanna , Koeppen Katja , Stanton Bruce A.
Published: October 2018

Pseudomonas aeruginosa secretes outer-membrane vesicles (OMVs) that fuse with cholesterol-rich lipid rafts in the apical membrane of airway epithelial cells and decrease wt-CFTR Cl− secretion. Herein, we tested the hypothesis that a reduction of the cholesterol content of CF human airway epithelial cells by cyclodextrins reduces the inhibitory effect of OMVs on VX-809 (lumacaftor)-stimulated Phe508del CFTR Cl− secretion. Primary CF bronchial epithelial cells and CFBE cells were treated with vehicle, hydroxypropyl-β-cyclodextrin (HPβCD), or methyl-β-cyclodextrin (MβCD), and the effects of OMVs secreted by P. aeruginosa on VX-809 stimulated Phe508del CFTR Cl− secretion were measured in Ussing chambers. Neither HPβCD nor MβCD were cytotoxic, and neither altered Phe508del CFTR Cl− secretion. Both cyclodextrins reduced OMV inhibition of VX-809-stimulated Phe508del-CFTR Cl− secretion when added to the apical side of CF monolayers. Both cyclodextrins also reduced the ability of P. aeruginosa to form biofilms and suppressed planktonic growth of P. aeruginosa. Our data suggest that HPβCD, which is in clinical trials for Niemann-Pick Type C disease, and MβCD, which has been approved by the U.S. Food and Drug Administration for use in solubilizing lipophilic drugs, may enhance the clinical efficacy of VX-809 in CF patients when added to the apical side of airway epithelial cells, and reduce planktonic growth and biofilm formation by P. aeruginosa. Both effects would be beneficial to CF patients.
HDAC8 inhibition ameliorates pulmonary fibrosis
Authors: Saito Shigeki , Zhuang Yan , Suzuki Takayoshi , Ota Yosuke , Bateman Marjorie E. , Alkhatib Ala L. , Morris Gilbert F. , Lasky Joseph A.
Published: October 2018

Idiopathic pulmonary fibrosis (IPF) is a fibroproliferative lung disease, and fibroblast-myofibroblast differentiation (FMD) is thought to be a key event in the pathogenesis of IPF. Histone deacetylase-8 (HDAC8) has been shown to associate with α-smooth muscle actin (α-SMA; a marker of FMD) and regulates cell contractility in vascular smooth muscle cells. However, the role of HDAC8 in FMD or pulmonary fibrosis has never been reported. This study investigated the role of HDAC8 in pulmonary fibrosis with a focus on FMD. We observed that HDAC8 expression was increased in IPF lung tissue as well as transforming growth factor (TGF)β1-treated normal human lung fibroblasts (NHLFs). Immunoprecipitation experiments revealed that HDAC8 was associated with α-SMA in TGFβ1-treated NHLFs. HDAC8 inhibition with NCC170 (HDAC8-selective inhibitor) repressed TGFβ1-induced fibroblast contraction and α-SMA protein expression in NHLFs cultured in collagen gels. HDAC8 inhibition with HDAC8 siRNA also repressed TGFβ1-induced expression of profibrotic molecules such as fibronectin and increased expression of antifibrotic molecules such as peroxisome proliferator-activated receptor-γ (PPARγ). Chromatin immunoprecipitation quantitative PCR using an antibody against H3K27ac (histone H3 acetylated at lysine 27; a known HDAC8 substrate and a marker for active enhancers) suggested that HDAC8 inhibition with NCC170 ameliorated TGFβ1-induced loss of H3K27ac at the PPARγ gene enhancer. Furthermore, NCC170 treatment significantly decreased fibrosis measured by Ashcroft score as well as expression of type 1 collagen and fibronectin in bleomycin-treated mouse lungs. These data suggest that HDAC8 contributes to pulmonary fibrosis and that there is a therapeutic potential for HDAC8 inhibitors to treat IPF as well as other fibrotic lung diseases.
Acute pulmonary effects of aerosolized nicotine
Authors: Ahmad Shama , Zafar Iram , Mariappan Nithya , Husain Maroof , Wei Chih-Chang , Vetal Nilam , Eltoum Isam A. , Ahmad Aftab
Published: October 2018

Nicotine is a highly addictive principal component of both tobacco and electronic cigarette that is readily absorbed in blood. Nicotine-containing electronic cigarettes are promoted as a safe alternative to cigarette smoking. However, the isolated effects of inhaled nicotine are largely unknown. Here we report a novel rat model of aerosolized nicotine with a particle size (~1 μm) in the respirable diameter range. Acute nicotine inhalation caused increased pulmonary edema and lung injury as measured by enhanced bronchoalveolar lavage fluid protein, IgM, lung wet-to-dry weight ratio, and high-mobility group box 1 (HMGB1) protein and decreased lung E-cadherin protein. Immunohistochemical analysis revealed congested blood vessels and increased neutrophil infiltration. Lung myeloperoxidase mRNA and protein increased in the nicotine-exposed rats. Complete blood counts also showed an increase in neutrophils, white blood cells, eosinophils, and basophils. Arterial blood gas measurements showed an increase in lactate. Lungs of nicotine-inhaling animals revealed increased mRNA levels of IL-1A and CXCL1. There was also an increase in IL-1α protein. In in vitro air-liquid interface cultures of airway epithelial cells, there was a dose dependent increase in HMGB1 release with nicotine treatment. Air-liquid cultures exposed to nicotine also resulted in a dose-dependent loss of barrier as measured by transepithelial electrical resistance and a decrease in E-cadherin expression. Nicotine also caused a dose-dependent increase in epithelial cell death and an increase in caspase-3/7 activities. These results show that the nicotine content of electronic cigarettes may have adverse pulmonary and systemic effects.
Chemopreventive Effects of Silibinin on Colitis-Associated Tumorigenesis by Inhibiting IL-6/STAT3 Signaling Pathway
Authors: Zheng Rongjuan , Ma Jiaheng , Wang Dan , Dong Wenxiao , Wang Sinan , Liu Tianyu , Xie Runxiang , Liu Li , Wang Bangmao , Cao Hailong
Published: October 2018

Inflammatory bowel disease (IBD), characterized by sustained inflammation, is a latent risk factor of colon tumorigenesis. Silibinin has been reported to be anti-inflammatory and antineoplastic, but its efficacy on colitis-associated cancer (CAC) has not been reported. Interlukin-6/signal transducer and activator of transcription 3 (IL-6/STAT3) is the key signaling pathway involved in CAC. We evaluated the chemopreventive effect of silibinin on a CAC mouse model and determined its impact on IL-6/STAT3 signaling. Intestinal tumor cells (IMCE and HCT-116 cell lines) were also treated by graded concentration of silibinin, and cellular viability was determined. Silibinin (750 mg/kg/day) was administered to an azoxymethane/dextran sulfate sodium (AOM/DSS) C57BL/6 mouse model for 10 weeks by gavage. Body weight, colon length, and the amount and diameter of colon tumors were documented, respectively. Specimens were subjected to H&E staining for colitis and tumor scoring, immunohistochemical staining and terminal deoxynucleotidyl transferase dUTP nick end labeling for proliferation assessment, and immunofluorescent staining for intestinal mucosa barrier assessment. Production of inflammatory cytokines was determined by real-time PCR. IL-6/STAT3 pathway activation was evaluated through immunohistochemical staining and western blot. In the current study, silibinin significantly inhibited the viability of intestinal tumor cells. The production of inflammatory cytokines and the phosphorylation of STAT3 were both inhibited in intestinal tumor cells. Meanwhile, silibinin decreased the amount and size of tumors in AOM/DSS mice. Colitis and tumor scores were decreased accompanying with inhibition of colonic tumor cell proliferation and promotion of cellular apoptosis. Additionally, silibinin could reduce the production of inflammatory cytokines and attenuate the impairment of colonic mucosal barrier. Furthermore, STAT3 phosphorylation was significantly suppressed by silibinin. In conclusion, silibinin could protect against colitis-associated tumorigenesis in mice via inhibiting IL-6/STAT3, which showed promising chemopreventive potential of CAC.
Surgical Treatment of Intrapelvic Pseudotumour after Hip Resurfacing Arthroplasty: Case Report and Literature Review
Authors: Barrientos Cristian , Brañes Julian , Llanos José-Luis , Martinez Alvaro , Barahona Maximiliano
Published: October 2018

Hip replacement is the surgery of the last century due to its impact on the quality of life. A pseudotumour is a rare complication of hip arthroplasty, and it is related to a metal-bearing surface. Pseudotumour is a challenging scenario for hip surgeons due to poor clinical outcomes. The patient consulted for hip pain and paresthesia in the left lower extremity, and analyses showed that the cause was a sizeable intrapelvic pseudotumour. A multidisciplinary team surgery was planned. At first, an infraumbilical approach was made to resect the intrapelvic-retroperitoneum portion of the pseudotumour. Then, a posterolateral hip approach was performed, to resect the remaining portion of the pseudotumour and revision arthroplasty. At five years of follow-up, there are no clinical or imaging signs of recurrence of the pseudotumour. Treatment evidence is limited to a series of cases and expert opinions; we encourage complete resection and revision arthroplasty.
Study of Binding Kinetics and Specificity of 99mTc-SSS-Complex and 99mTc-HMPAO to Blood Cells
Authors: Auletta S. , Iodice V. , Galli F. , Lepareur N. , Devillers A. , Signore A.
Published: October 2018

Nuclear medicine offers several techniques and procedures to image infection, but radiolabelled autologous white blood cells (WBCs) are still the gold standard. These cells are usually labelled with 111In or 99mTc bound to a hydrophobic chelating agent that allows these isotopes to pass through the plasma membrane and enter in the cytoplasm. The most common compound in Europe is HMPAO that efficiently chelates 99mTc. However, up to 20–40% of the complex is released from the cells in the first few hours. The aim of this study was to radiolabel a new compound, (S3CPh)2 (S2CPh)-complex (SSS-complex) with 99mTc and compare its binding kinetics and specificity for WBC with HMPAO. The SSS-complex was labelled with 99mTc and analysed by iTLC and RP-HPLC. In vitro quality controls included a stability assay in serum and saline. Results showed a labelling efficiency of 95 ± 1.2% and 98 ± 1.4% for 99mTc-SSS-complex and 99mTc-HMPAO, respectively (p=ns). 99mTc-SSS-complex was stable in serum and in saline up to 24 h (94 ± 0.1%). Cell labelling experiments showed a higher incorporation of 99mTc-SSS-complex than 99mTc-HMPAO by granulocytes (62.6 ± 17.8% vs 40.5 ± 15%, p=0.05), lymphocytes (59.9 ± 22.2% vs 29.4 ± 13.5%; p=0.03), and platelets (44.4 ± 24% vs 20.5 ± 10.7%; p=ns), but the release of radiopharmaceutical from granulocytes at 1 h was lower for HMPAO than for SSS-complex (10.3 ± 1.9% vs 21.3 ± 1.8%; p=0.001). In conclusion, 99mTc-SSS-complex, although showing high labelling efficiency, radiochemical purity, and stability, is not a valid alternative to 99mTc-HMPAO, for example, in vivo white blood cells labelling because of high lymphocyte and platelet uptake and rapid washout from granulocytes.
Tuberculous Distal Biceps Tendon Rupture: Case Report and Review of the Literature
Authors: Boonrod Artit , Sugaya Hiroyuki , Takahashi Norimasa , Boonrod Arunnit , Sumananont Chat
Published: October 2018

Tuberculous distal biceps tendon rupture is a rare condition in orthopedics. Musculoskeletal tuberculosis usually presents with bursitis, synovitis, myositis, and osteomyelitis, conditions which demonstrate an excellent response to antituberculosis chemotherapy. Tendon rupture is often associated with delayed diagnosis and treatment. We report a rare manifestation of musculoskeletal tuberculosis in the distal biceps tendon with delayed diagnosis.
Vocal Cord Palsy as a Complication of Epidural Anaesthesia
Authors: Mc Loughlin Laura , Young Orla
Published: October 2018

Cranial nerve palsy is a rare but recognised complication of epidural anaesthesia, most commonly presenting as diplopia secondary to abducens nerve palsy. While upper cranial nerve palsies have been documented on numerous occasions, lower cranial nerve palsies, including recurrent laryngeal nerve palsy, are exceedingly rare. This case describes a 37-year-old female who, following epidural anaesthesia for spontaneous vaginal delivery of her first child, presented with dysphonia. Flexible laryngoscopy confirmed a left vocal cord palsy, and computed tomography ruled out any mass lesions along the course of the recurrent laryngeal nerve. Here, we discuss a case of vocal cord palsy secondary to epidural anaesthesia, an extremely rare complication. We also discuss the proposed etiology, treatment, and outcomes in patients with this condition. Cranial nerve palsy should be an important differential in patients presenting with dysphonia following spinal or epidural anaesthesia.
Gastrointestinal Malignancy Presenting with a Virchow’s Node in a Patient with Rothmund-Thomson Syndrome
Authors: Nadeau Kara , Brule Michele
Published: October 2018

Rothmund-Thomson syndrome is a genetic disorder with characteristic findings in childhood as well as a predisposition to osteosarcoma, skin cancer, and hematological malignancy. We present the first reported case of duodenal malignancy in a patient with Rothmund-Thompson syndrome. An enlarged Virchow’s node was noted and an advanced duodenal adenocarcinoma was diagnosed shortly thereafter. The features of Rothmund-Thomson syndrome are discussed, as well as current management and screening guidelines for duodenal adenocarcinoma.
Hyphema from Iris Melanocytoma
Authors: Pasricha Neel D. , Seider Michael I.
Published: October 2018

Using multimodal imaging, we demonstrate a classic iris melanocytoma presenting with recurrent, spontaneous hyphema in a young female patient. The patient has been observed without tumor growth. Hyphema has not been previously reported to occur with iris melanocytoma.
Spectrophotometry, Physiochemical Properties, and Histological Staining Potential of Aqueous and Ethanol Extracts of Beetroot on Various Tissues of an Albino Rat
Authors: Udonkang Mfoniso I. , Inyang Imeobong J. , Ukorebi Affiong N. , Effiong Faith , Akpan Uwem , Bassey Iya E.
Published: October 2018

Background and Aims: Natural dyes and pigments are nontoxic, ecofriendly alternatives to synthetic counterparts and beetroot is one such natural dye. The red color of beetroot derived from betalain pigments confers great advantage to this plant. In this study, the physiochemical and spectrophotometric characteristics of beetroot as well as the histological staining potential of various tissues were carried out to determine its tissue specificity. Methods: The aqueous and ethanol extracts of beetroot were prepared using distilled water and 95% ethanol, respectively. Spectrophotometry, pH, and concentration of both extracts were determined before histological staining with 10% neutral-buffered formalin-fixed, paraffin-wax-embedded tissue sections. Stained sections were viewed with a photomicroscope. Results: The aqueous and ethanol extracts of beetroot were slightly acidic and soluble at concentrations of 381.5 mg/100 g and 253.7 mg/100 g fresh beetroot sample, respectively. Both extracts consist of three betalain pigments with absorbances at different spectrophotometric wavelengths, namely betaxanthins (475 nm), betanin (525 nm), and betanidin (575 nm). The maximum absorbance was 0.925 and 0.615 for the aqueous and ethanol extracts, respectively, at a peak wavelength of 525 nm for each extract. Both extracts stained various tissue structures such as muscles, mucins, red blood cells, keratin, and nerve fibers. Conclusion: Thus, beetroot stain is slightly acidic, contains betalain pigments, stains basic histological tissue structures, and can be used as an ecofriendly alternative to hematoxylin and eosin.
Comparative Pharmacokinetic Study of Mangiferin in Normal and Alloxan-Induced Diabetic Rats after Oral and Intravenous Administration by UPLC-MS/MS
Authors: Gu Peng-Cheng , Wang Lan , Han Mei-Na , Peng Jun , Shang Jing-Chuan , Pan Yong-Quan , Han Wen-Li
Published: October 2018

Backgrounds: Diabetes mellitus (DM)-induced morphological and/or functional complications may alter the pharmacokinetic profiles of mangiferin. This study aims to compare pharmacokinetic profiles of mangiferin in normal and alloxan-induced diabetic rats after oral and intravenous administration. Methods: Mangiferin was administered orally (10 mg/kg) and intravenously (2 mg/kg) to normal and alloxan-induced diabetic Sprague-Dawley (SD) rats (n = 8). Blood samples were collected at different time points post-dose. Mangiferin and esculentoside (internal standard)  were analyzed by Waters Acquity ultra-performance liquid chromatography system and TSQ Quantum Ultra triple quadrupole mass spectrometer (UPLC-MS/MS). Results: Mangiferin in normal and alloxan-induced diabetic rats experienced serious first-pass effect, which resulted in 1.71 and 0.80% of oral bioavailability respectively. Meanwhile, mangiferin was predominantly restricted to blood but not extensively distributed to organ tissues after intravenous administration. Compared with normal rats, the diabetic condition induced 53.26 and 50.90% decreases in Cmax and AUC0–t, respectively, for mangiferin after oral administration, and 63.08% decreases in Cmax after intravenous administration. Conclusions: Compared to normal rats, pharmacokinetic parameters of mangiferin were altered in diabetic condition induced by alloxan. The findings might help to provide useful evidence for modeling of diabetic rats and the clinical applications of mangiferin.
Iris Morphological Features in Patients with 360° Angle-Closure Neovascular Glaucoma: An Anterior Segment Optical Coherence Tomography Study
Authors: Kobayashi Yui , Nakakura Shunsuke , Terao Etsuko , Fujio Yuki , Matsuya Kanae , Tabuchi Hitoshi , Takahashi Yasuhiro , Kiuchi Yoshiaki
Published: October 2018

Purpose: To investigate iris morphological features in 360° angle-closure neovascular glaucoma (NVG) by swept-source anterior segment optical coherence tomography (ASOCT). Patients and Methods: In this retrospective, clinic-based, comparative study, 14 patients with 360° angle-closure NVG and 14 healthy age-matched control subjects were enrolled. All patients enrolled had no prior glaucoma surgery but underwent cataract surgery with intraocular lens implantation. Horizontal scanning images of swept-source ASOCT were analyzed using software calipers in temporal and nasal angle areas. The iris thickness at 1 and 2 mm from the pupil edge, iris length, trabecular meshwork length, peripheral anterior synechia (PAS) length, PAS height ratio (PAS length/trabecular meshwork length), and pupil diameter were measured. Results: Between the groups, there were no statistically significant differences in iris length, trabecular meshwork length, and pupil diameter (p > 0.05). However, the iris thickness was significantly reduced in the NVG group compared with the control group in the temporal and nasal areas (0.306 vs. 0.563 mm/0.326 vs. 0.645 mm at 1 mm, 0.278 vs. 0.523 mm/0.282 vs. 0.546 mm at 2 mm, respectively) (mean, all p < 0.001). In the NVG group, PAS height ratios were 1.55 ± 0.45 (mean ± standard deviation) (range, 0.58–2.30) and 1.55 ± 0.78 (range, 0.68–3.68) at the temporal and nasal angles, respectively. Conclusions: In patients with 360° angle-closure NVG, the iris thickness decreased to about 50% of that in healthy subjects, and the PAS length exceeded the trabecular meshwork length by about 1.5 times.
Structural and Functional Analyses of Retinal Ischemia in Eyes with Retinal Vein Occlusion: Relationship with Macular Edema or Microaneurysm Formation
Authors: Tomiyasu Taneto , Hirano Yoshio , Suzuki Norihiro , Esaki Yuya , Yasuda Yusuke , Uemura Akiyoshi , Yasukawa Tsutomu , Yoshida Munenori , Ogura Yuichiro
Published: October 2018

Purpose: To study the structural and functional changes of retinal ischemia and investigate their association with macular edema (ME) or microaneurysm (MA) formation in eyes with retinal vein occlusion (RVO). Methods: Sixty eyes of 30 patients (27 eyes with branch [b]RVO, 3 with central RVO, and 30 fellow eyes) were retrospectively reviewed. Optical coherence tomography (OCT), OCT angiography (OCTA), and microperimetry were performed simultaneously to measure retinal thickness and sensitivity. The presence of ME or MA was also assessed using OCT and fluorescein angiography. Results: The mean retinal sensitivity in the nonperfused areas (NPAs) deteriorated, and this was significantly (r = –0.379, p = 0.0391*) and inversely correlated with duration from disease onset. ME and MA were unlikely to be observed around the area where the retinal sensitivity decreased. In the NPAs, the mean retinal thickness of the superficial capillary plexus (SCP) (p < 0.0001), deep capillary plexus (DCP) (p = 0.0323), and outer retina (p = 0.0008) were significantly thinner than those in the fellow eyes, respectively. Multivariate regression analysis revealed that the thicknesses of the DCP (β: 0.3107, p = 0.0007) and outer retina (β: 0.3482, p = 0.0001) were the independent correlative factors of the retinal sensitivity, but that SCP thickness was not. Conclusion: Deep retinal thinning in NPAs was correlated significantly with a decreased retinal sensitivity, which might be a negative predictor of ME and MA in eyes with RVO.
Demographics, Clinical Characteristics, and Therapeutic Approaches among Older Adults Referred to Mobile Psychiatric Crisis Intervention Teams: A Retrospective Study
Authors: Gillès de Pélichy Estelle , Ebbing Karsten , Matos Queiros  Alcina , Hanon Cécile , von Gunten Armin , Sellah Zaia , Verloo Henk
Published: October 2018

Background / Aims: The advent of mobile old age psychiatry intervention teams supports policies maintaining older adults in their habitual living environments, even those who are very old and suffering from acute cognitive and psychiatric impairments. Analyzing sociodemographic data, clinical and health characteristics, reasons for crisis-oriented psychiatric consultations, and other therapeutic suggestions for supporting home- or nursing home-dwelling older adult patients suffering from an onset of a psychiatric crisis. Methods: Reviews of the medical records and discharge letters of home- or nursing home-dwelling older adults who had undergone a consultation with the Lausanne region’s Mobile Old Age Psychiatry Teams (MOAPTs), between May 2016 and December 2017. Results: Of 570 older adult patients referred for consultation with MOAPTs, 333 had medical records and discharge letters eligible for retrospective analysis (59%). The majority of these older adult patients were women aged over 80 years suffering from dementia, mood disorders with and without a risk of suicide, and delirium. Challenging behaviors related to different stages of cognitive impairment were the most important clinical reason for crisis consultations. Nonpharmacological and pharmacological treatments were delivered concurrently in 68% of crisis consultations. Conclusion: Appropriate responses by dual nurse-psychiatrist teams using crisis-oriented nonpharmacological and pharmacological interventions decreased hospitalization.
Plasmapheresis Combined with Continuous Plasma Filtration Adsorption Rescues Severe Acute Liver Failure in Wilson’s Disease before Liver Transplantation
Authors: Zhang Yu , Li Liang , Zhang Xiaole , Xu Wen , Guo Qun , Zhou Jianhua
Published: October 2018

Wilsonian crisis (hemolytic crisis and acute liver failure [ALF] in Wilson’s disease) is fatal and almost all patients ultimately need a timely liver transplantation to save their lives. How to safely pass the critical period to liver transplantation is still a big challenge to doctors especially to pediatricians facing more difficult situations in blood purification. Here, we report about a 7-year-old child (weight 21 kg) presenting with severe hemolysis and impending ALF that made a rapid recovery with prompt initiation of plasmapheresis combined with continuous plasma filtration adsorption (CPFA) and chelation therapy. Rapidly efficient removal of copper, bilirubin, and albumin-binding toxins by hybrid blood purification alleviated hemolysis and liver injury and successfully bridged the patient over the critical period to late liver transplantation. Moreover, a review of the literature was performed examining the use of plasmapheresis, molecular adsorbent recirculation system, single-pass albumin dialysis, and continuous veno-venous hemodiafiltration in Wilson disease. The experience of our case points to that plasmapheresis combined with CPFA treatment can improve clinical symptoms and bridge children over through Wilsonian crisis to late live transplantation, and CPFA treatment is feasible and safe in children weighing more than 20 kg.
Comprehensive Analysis of the Relationship Between RAS and RAF Mutations and MSI Status of Colorectal Cancer in Northeastern China
Authors: Li Wenqi , Li Huining , Liu Ruiqi , Yang Xinxin , Gao Yuhui , Niu Yangyang , Geng Jiashi , Xue Yingwei , Jin Xiaoming , You Qi , Geng Jingshu , Meng Hongxue
Published: October 2018

Background/Aims: Colorectal cancer (CRC) is mainly caused by chromosomal instability (CIN) and microsatellite instability (MSI). The RAS and RAF genes are essential components of the CIN pathway, and several studies have found that RAS and RAF mutations are associated with MSI status in CRC. Here, we examined these three factors in CRC in Northeast China and aimed to reveal new details of the relationship between these mutations and MSI status. Methods: This study involved 290 patients with CRC who had RAS or RAF gene mutation detected using fluorescence-based allele-specific polymerase chain reaction or Sanger sequencing. The majority of the identified patients were found to harbor MSI (MSI status). Accurate molecular detection was carried out using formalin-fixed paraffin-embedded tissue or blood samples. Results: The rates of RAS and RAF mutations were 58.5% and 4.1%, respectively. The prevalence of RAS mutation in CRC was clearly higher and that of RAF mutation was lower in Northeast China compared with previously reported cohorts in other locations. High MSI level (MSI-H status) was more complex, at around 10%. This was consistent with previous data from China. However, compared with data reported from other continents, MSI-H was higher than that of Japan or South Korea in Asia, and lower than that of Europe or the United States. Conclusion: RAS/RAF mutations and MSI status in CRC are closely associated with tumor location and ethnicity. Further studies investigating the relationship between these three factors can help in the development of treatment strategies for patients with CRC.
Cathepsin B-Mediated NLRP3 Inflammasome Formation and Activation in Angiotensin II -Induced Hypertensive Mice: Role of Macrophage Digestion Dysfunction
Authors: Lian Dawei , Lai Jieqing , Wu Yanjiao , Wang Lei , Chen Yongjun , Zhang Yang , Boini Krishna M. , Huang Yi , Chen Yang
Published: October 2018

Background/Aims: Angiotensin II (Ang II) is an octapeptide hormone that plays a significant role in mediating hypertension. Although hypertension is considered a chronic inflammatory disease, the molecular basis of the sterile inflammatory response involved in hypertension remains unclear. Methods: We investigated the role of macrophage NLRP3 inflammasomes in engulfing and digesting microbes, a key macrophage function, and in early onset of hypertension-associated macrophage injury using biochemical analyses, gene silencing, molecular biotechnology, immunofluorescence, and microbiology. Results: Ang II stimulation decreased nitric oxide (NO) release and macrophage digestion in cultured THP-1 cells and markedly increased NLRP3 inflammasome formation and activation. NO release and macrophage digestion were restored by NLRP3 inflammasome inhibition with isoliquiritigenin and gene silencing. This Ang II-induced upregulation of NLRP3 inflammasomes in macrophages was attributed to lysosomal damage and release of cathepsin B. Mechanistically, losartan, a nonpeptide Ang II receptor antagonist, decreased Ang II-induced NLRP3 inflammasome activation, lysosomal membrane permeability, lysosomal cathepsin B release, and macrophage digestion dysfunction. Similarly, Ang II-induced macrophage microbe digestion and NO production, which were blocked by ATI gene silencing. In addition, in vivo experiments showed that the bacteria scavenging function was clearly decreased in macrophages from Ang II-induced hypertensive mice. Conclusion: Angiotensin II enhances lysosomal membrane permeabilization and the consequent release of lysosomal cathepsin B, resulting in activation of the macrophage NLRP3 inflammasome. This may contribute to NO mediation of dysfunction in digesting microbes.
Faster Hypothermia Induced by Esophageal Cooling Improves Early Markers of Cardiac and Neurological Injury After Cardiac Arrest in Swine
Authors: Xu Jiefeng , Jin Xiaohong , Chen Qijiang , Wu Chunshuang , Li Zilong , Zhou Guangju , Xu Yongan , Qian Anyu , Li Yulin , Zhang Mao
Published: October 2018

Background

After cardiopulmonary resuscitation, the protective effects of therapeutic hypothermia induced by conventional cooling are limited. Recently, esophageal cooling (
EC
) has been shown to be an effective, easily performed approach to induce therapeutic hypothermia. In this study we investigated the efficacy of
EC
and its effects on early markers of postresuscitation cardiac and neurological injury in a porcine model of cardiac arrest.

Methods and Results

Thirty‐two male domestic swine were randomized into 4 groups: sham control, normothermia, surface cooling, and
EC
. Sham animals underwent the surgical preparation only. Ventricular fibrillation was induced and untreated for 8 minutes while defibrillation was attempted after 5 minutes of cardiopulmonary resuscitation. At 5 minutes after resuscitation, therapeutic hypothermia was induced by either
EC
or surface cooling to reach a target temperature of 33°C until 24 hours postresuscitation, followed by a rewarming rate of 1°C/h for 5 hours. The temperature was normally maintained in the control and normothermia groups. After resuscitation, a significantly faster decrease in blood temperature was observed in the
EC
group than in the surface cooling group (2.8±0.7°C/h versus 1.5±0.4°C/h;
P
<0.05). During the maintenance and rewarming phases the temperature was maintained at an even level between the 2 groups. Postresuscitation cardiac and neurological damage was significantly improved in the 2 hypothermic groups compared with the normothermia group; however, the protective effects were significantly greater in the
EC
group.

Conclusions

In a porcine model of cardiac arrest, faster hypothermia successfully induced by
EC
was significantly better than conventional cooling in improving early markers of postresuscitation cardiac and neurological injury.
VEGF‐C and Mortality in Patients With Suspected or Known Coronary Artery Disease
Authors: Wada Hiromichi , Suzuki Masahiro , Matsuda Morihiro , Ajiro Yoichi , Shinozaki Tsuyoshi , Sakagami Satoru , Yonezawa Kazuya , Shimizu Masatoshi , Funada Junichi , Takenaka Takashi , Morita Yukiko , Nakamura Toshihiro , Fujimoto Kazuteru , Matsubara Hiromi , Kato Toru , Unoki Takashi , Takagi Daisuke , Ura Shuichi , Wada Kyohma , Iguchi Moritake , Masunaga Nobutoyo , Ishii Mitsuru , Yamakage Hajime , Shimatsu Akira , Kotani Kazuhiko , Satoh‐Asahara Noriko , Abe Mitsuru , Akao Masaharu , Hasegawa Koji ,   the ANOX Study Investigators
Published: October 2018

Background

The lymphatic system has been suggested to play an important role in cholesterol metabolism and cardiovascular disease. However, the relationships of vascular endothelial growth factor‐C (
VEGF
‐C), a central player in lymphangiogenesis, with mortality and cardiovascular events in patients with suspected or known coronary artery disease are unknown.

Methods and Results

We performed a multicenter, prospective cohort study of 2418 patients with suspected or known coronary artery disease undergoing elective coronary angiography. The primary predictor was serum levels of
VEGF
‐C. The primary outcome was all‐cause death. The secondary outcomes were cardiovascular death, and major adverse cardiovascular events defined as a composite of cardiovascular death, non‐fatal myocardial infarction, and non‐fatal stroke. During the 3‐year follow‐up, 254 patients died from any cause, 88 died from cardiovascular disease, and 165 developed major adverse cardiovascular events. After adjustment for established risk factors,
VEGF
‐C levels were significantly and inversely associated with all‐cause death (hazard ratio for 1‐
SD
increase, 0.69; 95% confidence interval, 0.60–0.80) and cardiovascular death (hazard ratio, 0.67; 95% confidence interval, 0.53–0.87), but not with major adverse cardiovascular events (hazard ratio, 0.85; 95% confidence interval, 0.72–1.01). Even after incorporation of N‐terminal pro‐brain natriuretic peptide, contemporary sensitive cardiac troponin‐I, and high‐sensitivity C‐reactive protein into a model with established risk factors, the addition of
VEGF
‐C levels further improved the prediction of all‐cause death, but not that of cardiovascular death or major adverse cardiovascular events. Consistent results were observed within 1717 patients with suspected coronary artery disease.

Conclusions

In patients with suspected or known coronary artery disease, a low
VEGF
‐C value may independently predict all‐cause mortality.
Individual variation in the dear enemy phenomenon via territorial vocalizations in red squirrels
Authors: Robertson Jack G. , Boutin Stan , Humphries Murray M. , Dantzer Ben , Lane Jeffrey E. , McAdam Andrew G.
Published: October 2018

Territoriality arises when the benefits of resources exceed the costs of defending them. The dear enemy phenomenon, where familiar territorial neighbours refrain from intruding on one another and mutually reduce their defensive efforts, allows for reduction of these costs but requires discrimination between conspecifics. We hypothesized that territorial vocalizations in red squirrels (Tamiasciurus hudsonicus) are used for this discrimination. We performed a speaker replacement experiment where red squirrels () were temporarily removed from their territories and replaced with a speaker broadcasting their own call, an unfamiliar call, or silence. Contrary to our prediction, there were no differences in overall intrusion risk among our three playbacks, but the identity of intruders did vary. Existing variation in familiarity within territorial neighbourhoods should be considered, rather than the binary classification of familiar or stranger, when studying dear enemy effects. We also discuss the variable importance of silence in acoustic territorial populations.
Estimation of lipid reserves in different life stages of Meloidogyne incognita using image analysis of Nile Red-stained nematodes
Authors: Shivakumara Tagginahalli N. , Dutta Tushar K. , Mandal Abhishek , Rao Uma
Published: October 2018

Biochemical analyses of nematodes have revealed that neutral lipids (especially triglycerides) are the main source of energy reserves, which is depleted as the nematodes age. Several methodologies have been developed to visualise triglyceride-rich fat stores in plant-parasitic nematodes using non-fluorescent, lipophilic dyes, such as Oil Red O. Here, we propose a robust and reproducible fluorescence-based Nile Red staining method (followed by image analysis) for rapid detection of neutral lipid droplets inMeloidogyne incognita. This unique lipophilic dye selectively fluoresces in red and green spectra in a lipid-rich environment. The neutral lipid content ofM. incognitajuveniles gradually diminished during different periods of food deprivation, and this was significantly correlated with reduction in parasitic success ofM. incognitain eggplant. Additionally, variation in fat reserves in different developmental stages ofM. incognitainfecting adzuki bean was also demonstrated. This investigation may aid future metabolic research, including functional analysis of lipid regulatory genes in plant-parasitic nematodes.
Inter se Modification of the UN Drug Control Conventions
Authors: Boister Neil , Jelsma Martin
Published: October 2018

Legal tensions are growing as more jurisdictions move towards legal regulation of the cannabis market in contravention of the obligation under UN drug control treaties to limit cannabis exclusively to medical and scientific purposes. Reaching a global consensus to amend the conventions does not appear to be a viable political option in the foreseeable future. Amongst the limited options not requiring consensus, inter se modification – based on article 41 of the Vienna Convention on the Law of Treaties – provides a useful safety valve for collective action to adjust a treaty regime arguably frozen in time. Restrictions imposed on inter se modification require a clear commitment to the original treaty aim to promote the health and welfare of humankind and to the original treaty obligations vis-à-vis states not party to the agreement. A coordinated collective response has benefits compared to a chaotic scenario of multiple unilateral reservations and questionable re-interpretations.
More Beautiful Than Necessary
Authors: Ritchie David
Published: October 2018

What was it about the First World War that brought on Modernism? Like the simplified poppy form and the sword-within-a-cross which both came to memorialize the First World War in British culture, materiel from that era—shells, rifle stocks, helmets, bullets, bunkers— have a thoroughly modern, almost Bauhaus aesthetic. This was not entirely new in the history of weapons; the common soldier had often fought with unadorned weapons. In this war, however, there was nothing else to see; soldiers could safely regard only the sky, their comrades, their weapons and—viewed through a periscope’s framing—a landscape stripped of nature’s adornments. The inference is that this limited vision and consequent focus on unadorned form were key to the modern aesthetic taking hold.
Prophet of Poison Gas
Authors: Johnson Ian
Published: October 2018

This article explores the formation and growth of the Soviet chemical weapons program from 1924 to 1937. Seen as a symbol of modernity by the Soviet government, the Red Army’s chemical weapons directorate became a priority area of research and development. Initially, however, the Red Army’s investment in chemical weapons production encountered a variety of difficulties exacerbated by early Soviet policies, such as the lack of capital and skilled labor. But thanks to Stalin’s broader political aims, Yakov Fishman—the head of the chemical weapons directorate—managed to draw in vast resources to achieve his vision for the Soviet chemical weapons program. In the end, Fishman’s success in building huge chemical weapons production capacities for the Red Army would have a major impact on the course of the Second World War. Drawing from Russian and German military archives, this article offers new insight into a long-hidden, top-secret military program of colossal dimensions.
Atomic Dysfunction
Authors: Curatola John M.
Published: October 2018

Following World War II the US believed its atomic monopoly was the primary tool to offset large, standing communist ground forces within the Soviet orbit. However, both the newly established and civilian-run Atomic Energy Commission (AEC) along with the nascent US Air Forces’ Strategic Air Command (SAC) were models of dysfunction. In the late 1940s neither the civilians nor the military were capable of fulfilling the requirements outlined in the envisioned atomic air offensives of the time. Apart from their internal problems, both the AEC and SAC failed to properly coordinate with each other for effective transfer of bomb material, requisite training, and standing up the required number of atomic ordnance assembly teams. As a result, the American atomic monopoly from 1945–1950 was largely a bluff with few men, materials, and resources to serve as the nation’s primary strategic offense.
Review of the genus Earinus Wesmael (Hymenoptera, Braconidae, Agathidinae) from China
Authors: TANG PU , VAN ACHTERBERG CORNELIS , CHEN XUE-XIN
Published: October 2018

The Chinese species of Earinus Wesmael, 1837 (Braconidae, Agathidinae) are revised and eight species are recognized. Three new species, namely, E. longigena sp. nov., E. pallitarsus sp. nov. and E. protinus sp. nov., are described and illustrated, and two species are recorded from China for the first time, i.e., E. brevistigmus van Achterberg et Long, 2010 and E. elator (Fabricius, 1804). A new synonym is proposed, Earinus albopilosus Chen et Yang, 2006, with Therophilus festivus (Muesebeck, 1953). A key to the Chinese species of the genus Earinus is provided.
New species of Trichomycterus (Siluriformes: Trichomycteridae) from the High Andean Plateau of Argentina
Authors: FERNÁNDEZ LUIS , BIZE JULIETA ANDREOLI
Published: October 2018

Trichomycterus varii new species, is described from a small tributary of the High Andean Plateau Region, Jujuy, Argentina. The new species is distinguished from other species of Trichomycterus by the following characters: the caudal peduncle expanded in the area of procurrent caudal-fin rays, distal tip of pelvic fin not reaching the anus when depressed, the presence of fronto-lachrymal tendon bone without lateral process, the first pectoral-fin ray terminating at the margin of the fin, the distal margin of pectoral-fin rounded, seven pectoral fin rays, 15–19 interopercular odontodes, the supraorbital sensory canal with the presence of pore s3, the infraorbital sensory canal segment with the presence of pores i1 and i3, the laterosensory canal of trunk with three sensory pores, 16 pairs of ribs, 11 precaudal vertebrae, and 25 caudal vertebrae. It closely resembles T. yuska and T. pseudosilvinichthys from northwestern Argentina and western Bolivia, but differs in head canal sensory pattern.
Two new species of the Genus Clathria (Demospongiae: Poecilosclerida: Microcionidae) from Jeju Island, Korea
Authors: KANG DONG WON , KIM HYUNG JUNE
Published: October 2018

Two new species of sponge, Clathria (Clathria) ramus sp. nov. and Clathria (Clathria) ieoensis sp. nov. are described from Jeju Island of Korea. Clathria (Clathria) ramus sp. nov. is branching with a stalk, yellow in life, with small oscules. Clathria (C.) ieoensis sp. nov. is thickly encrusting, soft and compressible texture, and color is red and dark brown after fixation in ethanol. The new species are compared to other microcionids from the Korean region, and similar species from elsewhere.
Chironomus rishii sp. n., an enigmatic non-biting midge (Diptera: Chironomidae: Chironominae) from Neotropical region
Authors: TRIVINHO-STRIXINO SUSANA , DA SILVA FABIO LAURINDO
Published: October 2018

A new species of Chironomus Meigen, C. rishii (Diptera: Chironomidae: Chironominae) from Brazil, is described and figured as adults male and female, pupa and larva. Adults of C. rishii sp. n. can be recognized by the prominent scutal tubercle and the hypopygium with narrow, elongated and strongly hooked superior volsella. Pupae of this new species are indistinguishable from most of the described Neotropical species, while larvae may be separated by the mentum with deeply incised trifid median tooth and 7 pairs of lateral teeth and the absence of lateral and ventral tubules. This last feature would place C. rishii sp. n. within the 'salinarius group'. However, this is not a group in the systematic sense, but an artificial grouping equivalent to a morphotype that reflects only the tubule character state. It is suggested that the absence of tubules is an adaptation for tolerating a wide range of salinity levels, however the 'salinarius group' had been also recorded in freshwater environments. Here, larvae without abdominal tubules were found in an environment with low levels of salinity, which indicates that the tubule condition may be result of further abiotic pressures, and configures a rather enigmatic scenario to this feature, particularly when considered the fact that larvae of Chironomus having tubules had also been recorded at the same habitat, living under similar conditions of C. rishi sp. n.
Evaluation of the Quasi-Biweekly Oscillation over the South China Sea in Early and Late Summer in CAM5
Authors: Wang Xu , Zhang Guang J.
Published: October 2018

Low-frequency intraseasonal oscillations in the tropical atmosphere in general circulation models (GCMs) were studied extensively in many previous studies. However, the simulation of the quasi-biweekly oscillation (QBWO), which is an important component of the intraseasonal oscillations, in GCMs has not received much attention. This paper evaluates the QBWO features over the South China Sea in early [May–June (MJ)] and late [August–September (AS)] summer in the National Center for Atmospheric Research (NCAR) Community Atmosphere Model, version 5.3 (CAM5), using observations and reanalysis data. Results show that the major features of the spatial distribution of the QBWO in both MJ and AS are simulated reasonably well by the model, although the amplitude of the variation is overestimated. CAM5 captures the local oscillation in MJ and the westward propagation in AS of the QBWO. Although there are important biases in geographical location and intensity in MJ, the model represents the QBWO horizontal and vertical structure qualitatively well in AS. The diagnosis of the eddy vorticity budget is conducted to better understand the QBWO activities in the model. Both horizontal advection of relative vorticity and that of planetary vorticity (Coriolis parameter) are important for the local evolution of the QBWO in MJ in observations as well as model simulation, whereas advection of planetary vorticity contributes to the westward propagation of QBWO vorticity anomalies in AS. Since the Coriolis parameter f only changes with latitude, this suggests that the correct simulation of anomalous meridional wind is a key factor in the realistic simulation of the QBWO in the model.
Perception of American–English Vowels by Early and Late Spanish–English Bilinguals
Authors: Baigorri Miriam , Campanelli Luca , Levy Erika S.
Published: October 2018

Increasing numbers of Hispanic immigrants are entering the US and learning American–English (AE) as a second language (L2). Previous studies investigating the relationship between AE and Spanish vowels have revealed an advantage for early L2 learners for their accuracy of L2 vowel perception. Replicating and extending such previous research, this study examined the patterns with which early and late Spanish–English bilingual adults assimilated naturally-produced AE vowels to their native vowel inventory and the accuracy with which they discriminated the vowels. Twelve early Spanish–English bilingual, 12 late Spanish–English bilingual, and 10 monolingual listeners performed perceptual-assimilation and categorical-discrimination tasks involving AE /i,ɪ,ɛ,ʌ,æ,ɑ,o/. Early bilinguals demonstrated similar assimilation patterns to late bilinguals. Late bilinguals’ discrimination was less accurate than early bilinguals’ and AE monolinguals’. Certain contrasts, such as /æ-ɑ/, /ʌ-ɑ/, and /ʌ-æ/, were particularly difficult to discriminate for both bilingual groups. Consistent with previous research, findings suggest that early L2 learning heightens Spanish–English bilinguals’ ability to perceive cross-language phonetic differences. However, even early bilinguals’ native-vowel system continues to influence their L2 perception.