Evaluation of the efficacy of commercial protective cultures against mold and yeast in queso fresco.

Abstract: In this study, we evaluated the efficacy of 3 commercial protective cultures designated PC1 (Lactobacillus spp.), PC2 (Lactobacillus rhamnosus), and PC3 (Lactobacillus rhamnosus) as biopreservatives in queso fresco (QF) against 9 yeast strains (Candida zeylanoides, Clavispora lusitaniae, Debaryomyces hansenii, Debaryomyces prosopidis, Kluyveromyces marxianus, Meyerozyma guilliermondii, Pichia fermentans, Rhodotorula mucilaginosa, and Torulaspora delbrueckii) and 11 mold strains (Aspergillus cibarius, Aureobasidium pullulans, Penicillium chrysogenum, Penicillium citrinum, Penicillium commune, Penicillium decumbens, Penicillium roqueforti, Mucor genevensis, Mucor racemosus, Phoma dimorpha, and Trichoderma amazonicum). All fungal spoilage strains were previously isolated from dairy processing environments. A positive control (C) with no protective culture was included. Fungal spoilage organisms were inoculated on cheese surfaces at an inoculum level of 20 cfu/g, and cheeses were stored at 6 ± 2°C throughout the study. For yeast enumeration, cheeses were sampled on d 0, 7, 14, and 21 postinoculation. Significant inhibition was detected for each yeast strain by comparing yeast counts for each cheese treated with protective culture against the control cheese using one-way ANOVA with Bonferroni correction performed individually at d 7, 14, and 21 postinoculation. Mold growth was visually observed and imaged weekly through 70 d postinoculation. Whereas PC3 inhibited Cl. lusitaniae, Mey. guilliermondii, and Ph. dimorpha, PC2 inhibited the outgrowth of Cl. lusitaniae, D. hansenii, and Ph. dimorpha. Protective culture 1 had the broadest spectrum of efficacy across yeast and molds, delaying spoilage caused by 4 distinct yeast strains (Cl. lusitaniae, D. hansenii, D. prosopidis, and Mey. guilliermondii), and inhibiting visible growth of 2 mold strains (P. chrysogenum and Ph. dimorpha). Results demonstrated that commercial protective cultures vary in performance, as indicated by the breadth of mold and yeast inhibition at both the genus and species level. This study suggests that manufacturers looking into using protective cultures should investigate their efficacy against specific fungal strains of concern.

Makki|Ghadeer M|GM|
Kozak|Sarah M|SM|
Jencarelli|Katharine G|KG|
Alcaine|Samuel D|SD|

protective culture
mold and yeast
queso fresco
biopreservative


Nanoencapsulated essential oils embedded in ice improve the quality and shelf life of fresh whole seabream stored on ice.

Abstract: Ice containing essential oils (EOs) nanoencapsulated in β-cyclodextrins (β-CD) (named as EOs+β-CD ice) was used for stunning/slaughtering by hypothermia in ice slurry, and for ice storage of gilthead seabream. Clove essential oil (CEO) was used at fish stunning/slaughtering, while ice storage of whole fish was performed using a combination of carvacrol, bergamot and grapefruit EOs (CBG). Inclusion complexes CBG+β-CD were characterized, and antimicrobial effect was also evaluated. The kneading method used to form inclusion complexes with CBG showed a good complexation efficiency. Microbial, physical-chemical and sensory analyses were carried out to assess the quality changes of fresh whole seabream during ice storage at 2 °C for 17 days. Results (microbial, chemical and sensorial) indicated that seabream stunning/slaughtering and storage using EOs+β-CD ice (in low doses of 15 mg/kg ice for stunning, and 50 mg/kg ice for ice storage) improved the quality of fresh fish and extended the shelf-life up to 4 days.

Navarro-Segura|Laura|L|
Ros-Chumillas|María|M|
López-Cánovas|Amanda E|AE|
García-Ayala|Alfonsa|A|
López-Gómez|Antonio|A|

β-Cyclodextrin
Food microbiology
Food preservation
Food safety
Food technology
Freshness quality
Ice-storage
Microbial quality
Nanotechnology
Sensory quality


Symptomatic partial anomalous pulmonary venous connection in a kitten.

Abstract: A 3-month-old intact female American Shorthair cat, with syncope and tachypnea, underwent cardiac examination which identified no heart murmur or gallop. Thoracic radiography disclosed mild generalized enlargement of the cardiac silhouette and a bronchial and interstitial pattern throughout the lungs. Echocardiography identified tubular structures near the left atrium. After agitated saline contrast imaging, persistent left cranial vena cava with unroofed coronary sinus was suspected. Computed tomography angiography showed the right cranial, right caudal and left caudal pulmonary veins draining into the coronary sinus and flowing into the right atrium. The left cranial pulmonary vein drained normally into the left atrium. Partial anomalous pulmonary venous connection (PAPVC) was diagnosed. The kitten was treated with diuretics but died of heart failure 2 months later. Permission for necropsy was not granted. This case represents symptomatic PAPVC in a kitten. Most pulmonary veins were connected abnormally with the coronary sinus. The prognosis was grave because of refractory heart failure.

agitated saline contrast imaging
computed tomography angiography
heart failure
congenital cardiovascular disease
feline


Stimulation of an anti-tumor immune response with "chromatin-damaging" therapy.

Abstract: Curaxins are small molecules that bind genomic DNA and interfere with DNA-histone interactions leading to the loss of histones and decondensation of chromatin. We named this phenomenon 'chromatin damage'. Curaxins demonstrated anti-cancer activity in multiple pre-clinical tumor models. Here, we present data which reveals, for the first time, a role for the immune system in the anti-cancer effects of curaxins. Using the lead curaxin, CBL0137, we observed elevated expression of several group of genes in CBL0137-treated tumor cells including interferon sensitive genes, MHC molecules, some embryo-specific antigens suggesting that CBL0137 increases tumor cell immunogenicity and improves recognition of tumor cells by the immune system. In support of this, we found that the anti-tumor activity of CBL0137 was reduced in immune deficient SCID mice when compared to immune competent mice. Anti-tumor activity of CBL0137 was abrogated in CD8+ T cell depleted mice but only partially lost when natural killer or CD4+ T cells were depleted. Further support for a key role for the immune system in the anti-tumor activity of CBL0137 is evidenced by an increased antigen-specific effector CD8+ T cell and NK cell response, and an increased ratio of effector T cells to Tregs in the tumor and spleen. CBL0137 also elevated the number of CXCR3-expressing CTLs in the tumor and the level of interferon-γ-inducible protein 10 (IP-10) in serum, suggesting IP-10/CXCR3 controls CBL0137-elicited recruitment of effector CTLs to tumors. Our collective data underscores a previously unrecognized role for both innate and adaptive immunity in the anti-tumor activity of curaxins.

D023041:Xenograft Model Antitumor Assays

Curaxin
Histone
Chromatin damage
CBL0137
Tumor cell immunogenicity
T cells


Effect of three common IL-17 single nucleotide polymorphisms on the risk of developing gastric cancer.

Abstract: A 1:1 matched case-control study was conducted to analyze the association between three common interleukin (IL)-17A and IL-17F single nucleotide polymorphisms (SNPs) and the risk of developing gastric cancer. Genotyping of SNPs rs2275913, rs763780 and rs3748067 within the IL-17 gene were detected by performing polymerase chain reaction-restriction fragment length polymorphism analysis. Gastric cancer patients were more likely to be cigarette smokers, alcohol drinkers and have a family history of cancer in their first-degree relatives. Patients carrying the rs763780 polymorphism were correlated with a significant increased risk of gastric cancer in codominant, dominant and recessive models. Additionally, individuals with the rs763780 polymorphism were correlated with a markedly increased risk of gastric cancer among alcohol drinkers in codominant, dominant and recessive models. Furthermore, a significant correlation was identified between the rs763780 polymorphism and the consumption of alcohol. However, no association was identified between rs2275913 and rs3748067 polymorphisms and the risk of developing gastric cancer. Thus, the present study reported that the rs763780 polymorphism may be associated with risk of developing gastric cancer in the population studied, particularly in alcohol drinkers.

Gao|Ya-Wen|YW| Xu|Meili|M| Xu|Yan|Y| Li|Dan|D| Zhou|Shenghua|S|


A New Signature for Strong Light-Matter Coupling Using Spectroscopic Ellipsometry.

Abstract: Light-matter interactions can occur when an ensemble of molecular resonators is placed in a confined electromagnetic field. In the strong coupling regime the rapid exchange of energy between the molecules and the electromagnetic field results in the emergence of hybrid light-matter states called polaritons. Multiple criteria exist to define the strong coupling regime, usually by comparing the splitting of the polariton bands with the line widths of the uncoupled modes. Here, we highlight the limitations of these criteria and study strong coupling using spectroscopic ellipsometry, a commonly used optical characterization technique. We identify a new signature of strong coupling in ellipsometric phase spectra. The combination of ellipsometric amplitude and phase spectra yields a distinct topological feature that we suggest could serve as a new criterion for strong coupling. Our results introduce the idea of ellipsometric topology and could provide further insight into the transition from the weak to strong coupling regime.

ellipsometry
strong coupling
polaritons
Rabi splitting
optical microcavities
optical phase response


Inflammation Alters Relationship Between High-Density Lipoprotein Cholesterol and Cardiovascular Risk in Patients With Chronic Kidney Disease: Results From KNOW-CKD.

Abstract: Background The function of high-density lipoprotein can change from protective to proatherosclerotic under inflammatory conditions. Herein, we studied whether inflammation could modify the relationship between high-density lipoprotein level and risk of adverse outcomes in patients with chronic kidney disease . Methods and Results In total, 1864 patients from the prospective KNOW-CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease) were enrolled. The main predictor was high-density lipoprotein cholesterol (HDL-C) level. Presence of inflammation was defined by hs-CRP (high-sensitivity C-reactive protein) level of ≥1.0 mg/L. The primary outcome was extended major adverse cardiovascular events. During 9231.2 person-years of follow-up, overall incidence of the primary outcome was 15.8 per 1000 person-years. In multivariable Cox analysis after adjusting for confounders, HDL-C level was not associated with the primary outcome. There was a significant interaction between the inflammatory status and HDL-C for risk of extended major adverse cardiovascular events (P=0.003). In patients without inflammation, the hazard ratios (HRs) (95% CIs) for HDL-C levels <40, 50 to 59, and ≥60 mg/dL were 1.10 (0.50-1.82), 0.95 (0.50-1.82), and 0.42 (0.19-0.95), respectively, compared with HDL-C of 40 to 49 mg/dL. However, the significant association for HDL-C ≥60 mg/dL was not seen after Bonferroni correction. In patients with inflammation, we observed a trend toward increased risk of extended major adverse cardiovascular events in higher HDL-C groups (HRs [95% CIs], 0.73 [0.37-1.43], 1.24 [0.59-2.61], and 1.56 [0.71-3.45], respectively), but without statistical significance. Conclusions The association between HDL-C level and adverse cardiovascular outcomes showed reverse trends based on inflammation status in Korean patients with chronic kidney disease. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01630486.

Kim|Jae Young|JY|
Park|Jung Tak|JT|
Kim|Hyung Woo|HW|
Chang|Tae-Ik|TI|
Kang|Ea Wha|EW|
Ahn|Curie|C|
Oh|Kook-Hwan|KH|
Lee|Joongyub|J|
Chung|Wookyung|W|
Kim|Yong-Soo|YS|
Kim|Soo Wan|SW|
Yoo|Tae-Hyun|TH|
Kang|Shin-Wook|SW|
Han|Seung Hyeok|SH|
|||

inflammation
chronic kidney disease
major adverse cardiovascular events
high‐density lipoprotein cholesterol
high‐sensitivity C‐reactive protein


Comparison of Human Platelet Lysate versus Fetal Bovine Serum for Expansion of Human Articular Cartilage-Derived Chondroprogenitors.

Abstract:
PURPOSE
Articular chondroprogenitors, a suitable contender for cell-based therapy in cartilage repair, routinely employ fetal bovine serum (FBS) for expansion and differentiation. The possibility of transplant rejections or zoonoses transmissions raise a need for xeno-free alternatives. Use of human platelet lysate (hPL), a nutrient supplement abundant in growth factors, has not been reported for human chondroprogenitor expansion thus far. Our aim was to compare the biological profile of chondroprogenitors grown in hPL versus FBS.

METHODS
Chondroprogenitors were isolated from 3 osteoarthritic knee joints. Following differential fibronectin adhesion assay, passage 0 cells grown in (a) 10% FBS and (b) 10% hPL were considered for assessment of growth kinetics, surface marker expression, gene expression, and trilineage differentiation. Latent transforming growth factor-β1 (TGFβ1) levels were also measured for each culture medium used.

RESULTS
Cellular proliferation was significantly higher in cells grown with hPL (P < 0.01). Surface marker expression was comparable except in CD-146 where hPL group had significantly higher values (P = 0.03). Comparison of mRNA expression revealed notably low values of collagen I, collagen X, aggrecan, and collagen II (P < 0.05). Trilineage differentiation was seen in both groups with higher alizarin red uptake noted in hPL. There were also significantly higher levels of latent TGFβ1 in the medium containing hPL as compared to FBS.

CONCLUSIONS
This is the first in vitro xeno-free study to affirm that hPL can serve as an optimal growth supplement for expansion of articular chondroprogenitors, although an in-depth assessment of resident growth factors and evaluation of different dilutions of hPL is required to assess suitability for use in translational research.

human platelet lysate
fetal bovine serum
chondroprogenitors


Self-Erasable Nanocone Antireflection Films Based on the Shape Memory Effect of Polyvinyl Alcohol (PVA) Polymers.

Abstract: Arrays of nanostructure that are capable of broadband antireflection and light trapping properties are implemented in photovoltaic and photonic devices. However, most of the existing antireflection films have been hindered by a complicated fabricated method and structurally rigid. Here, we report a simple preparation method for self-erasable nanocone antireflection films using the surface replication method. Arrays of nanocone with sub-100 nm surface features could be replicated easily on the shape memory polyvinyl alcohol (PVA) film, and are erased by thermal stimulation. The reflectivity of self-erasable antireflection film can be switched from the 4.5% to 0.6% averaged over the visible spectral range by controlling the temperature below or above 80 °C. Theoretical simulations have been demonstrated. The unique smart film is expected to be used to further extend the application of smart optical windows and digital screens.

Li|Peng|P| Han|Yu|Y|0000-0003-3539-9966 Wang|Wenxin|W| Chen|Xinlong|X| Jin|Peng|P| Liu|Shengchun|S|0000-0002-8902-402X

self-erasable
antireflection film
shape memory polymer


An Adeno-Associated Viral Vector Capable of Penetrating the Mucus Barrier to Inhaled Gene Therapy.

Abstract: Diffusion of the viral vectors evaluated in inhaled gene therapy clinical trials to date are largely hindered within airway mucus, which limits their access to, and transduction of, the underlying airway epithelium prior to clearance from the lung. Here, we discovered that adeno-associated virus (AAV) serotype 6 was able to rapidly diffuse through mucus collected from cystic fibrosis (CF) patients, unlike previously tested AAV serotypes. A point mutation of the AAV6 capsid suggests a potential mechanism by which AAV6 avoids adhesion to the mucus mesh. Significantly greater transgene expression was achieved with AAV6 compared to a mucoadhesive serotype, AAV1, in air-liquid interface cultures of human CF bronchial epithelium with naturally secreted mucus or induced mucus hypersecretion. In addition, AAV6 achieved superior distribution and overall level of transgene expression compared to AAV1 in the airways and whole lungs, respectively, of transgenic mice with airway mucus obstruction. Our findings motivate further evaluation and clinical development of AAV6 for inhaled gene therapy.

Duncan|Gregg A|GA|
Kim|Namho|N|
Colon-Cortes|Yanerys|Y|
Rodriguez|Jason|J|
Mazur|Marina|M|
Birket|Susan E|SE|
Rowe|Steven M|SM|
West|Natalie E|NE|
Livraghi-Butrico|Alessandra|A|
Boucher|Richard C|RC|
Hanes|Justin|J|
Aslanidi|George|G|
Suk|Jung Soo|JS|

inhaled gene therapy
airway mucus
adeno-associated virus
muco-obstructive lung disease


Corrigendum: Exploring Physiological Linkage in Same-Sex Male Couples.

Abstract: [This corrects the article DOI: 10.3389/fpsyg.2020.619255.].

Li|Xiaomin|X| Kuelz|Ashley|A| Boyd|Savannah|S| August|Kristin|K| Markey|Charlotte|C| Butler|Emily|E|

physiological linkage
same-sex male couples
conversational context
relationship functioning
rties package


Stereo Video Quality Metric Based on Multi-Dimensional Analysis.

Abstract: Stereo video has been widely applied in various video systems in recent years. Therefore, objective stereo video quality metric (SVQM) is highly necessary for improving the watching experience. However, due to the high dimensional data in stereo video, existing metrics have some defects in accuracy and robustness. Based on the characteristics of stereo video, this paper considers the coexistence and interaction of multi-dimensional information in stereo video and proposes an SVQM based on multi-dimensional analysis (MDA-SVQM). Specifically, a temporal-view joint decomposition (TVJD) model is established by analyzing and comparing correlation in different dimensions and adaptively decomposes stereo group of frames (sGoF) into different subbands. Then, according to the generation mechanism and physical meaning of each subband, histogram-based and LOID-based features are extracted for high and low frequency subband, respectively, and sGoF quality is obtained by regression. Finally, the weight of each sGoF is calculated by spatial-temporal energy weighting (STEW) model, and final stereo video quality is obtained by weighted summation of all sGoF qualities. Experiments on two stereo video databases demonstrate that TVJD and STEW adopted in MDA-SVQM are convincible, and the overall performance of MDA-SVQM is better than several existing SVQMs.

He|Zhouyan|Z| Xu|Haiyong|H| Luo|Ting|T|0000-0003-1762-148X Liu|Yi|Y| Song|Yang|Y|

stereo video
quality metric
image entropy
stereo video decomposition


20(S)-Protopanaxadiol induces apoptosis in human hepatoblastoma HepG2 cells by downregulating the protein kinase B signaling pathway.

Abstract: Hepatoblastoma is the most common primary liver tumor for children aged <5 years old. 20(S)-Protopanaxadiol (PPD) is a ginsenoside extracted from Pananx quinquefolium L., which inhibits tumor growth in several cancer cell lines. The purpose of the present study was to assess the anticancer activities of 20(S)-PPD in human hepatoblastoma HepG2 cells. The cytotoxicity of 20(S)-PPD on HepG2 cells was evaluated using an MTT assay. Apoptosis was detected using DAPI staining and flow cytometry. The expression of apoptosis-associated proteins was identified by western blotting. The results demonstrated that 20(S)-PPD inhibited the viability of HepG2 cell in a dose and time-dependent manner. The IC50 values were 81.35, 73.5, 48.79 µM at 24, 48 and 72 h, respectively. Topical morphological changes of apoptotic body formation following 20(S)-PPD treatment were detected by DAPI staining. The percentage of Annexin V-fluoroscein isothyiocyanate positive cells were 3.73, 17.61, 23.44 and 65.43% in HepG2 cells treated with 0, 40, 50 and 60 µM of 20(S)-PPD, respectively. Furthermore, 20(S)-PPD upregulated the expression of Bax and downregulated the expression of Bcl-2 and also activated caspases-3 and -9, and Poly [ADP-ribose] polymerase cleavage. In addition, 20(S)-PPD inhibited the phosphorylation of protein kinase B (Akt; Ser473). The results indicate that 20(S)-PPD inhibits the viability of HepG2 cells and induces apoptosis in HepG2 cells by inhibiting the phosphoinositide-3-kinase/Akt pathway.

Lu|Zeyuan|Z| Xu|Huali|H| Yu|Xiaofeng|X| Wang|Yuchen|Y| Huang|Long|L| Jin|Xin|X| Sui|Dayun|D|

20(S)-Protopanaxadiol
apoptosis
ginsenoside
caspase
hepatoblastoma cell HepG2


Evidence for the effects of viewing visual artworks on stress outcomes: a scoping review.

Abstract:
OBJECTIVE
To review the existing evidence on the effects of viewing visual artworks on stress outcomes and outline any gaps in the research.

DESIGN
A scoping review was conducted based on the Joanna Briggs Institute methodology for scoping reviews and using the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews. Two independent reviewers performed the screening and data extraction.

DATA SOURCES
Medline, Embase, APA PsycINFO, Cochrane CENTRAL, Scopus, Google Scholar, Google, ProQuest Theses and Dissertations Database, APA PsycExtra and Opengrey.eu were searched in May 2020.

ELIGIBILITY CRITERIA
Studies were included if they investigated the effects of viewing at least one visual artwork on at least one stress outcome measure. Studies involving active engagement with art, review papers or qualitative studies were excluded. There were no limits in terms of year of publication, contexts or population types; however, only studies published in the English language were considered.

DATA EXTRACTION AND SYNTHESIS
Information extracted from manuscripts included: study methodologies, population and setting characteristics, details of the artwork interventions and key findings.

RESULTS
14 primary studies were identified, with heterogeneous study designs, methodologies and artwork interventions. Many studies lacked important methodological details and only four studies were randomised controlled trials. 13 of the 14 studies on self-reported stress reported reductions after viewing artworks, and all of the four studies that examined systolic blood pressure reported reductions. Fewer studies examined heart rate, heart rate variability, cortisol, respiration or other physiological outcomes.

CONCLUSIONS
There is promising evidence for effects of viewing artwork on reducing stress. Moderating factors may include setting, individual characteristics, artwork content and viewing instructions. More robust research, using more standardised methods and randomised controlled trial designs, is needed.

REGISTRATION DETAILS
A protocol for this review is registered with the Open Science Framework (osf.io/gq5d8).

complementary medicine
mental health
psychiatry
social medicine


Ovarian Expression of Adipokines in Polycystic Ovary Syndrome: A Role for Chemerin, Omentin, and Apelin in Follicular Growth Arrest and Ovulatory Dysfunction?

Abstract: Adipokines are a potential link between reproduction and energy metabolism and could partly explain some infertilities related to some pathophysiology, such as polycystic ovary syndrome (PCOS). However, adipokines were predominantly assessed in blood samples, while very little is known concerning their variations in follicular fluid (FF) and ovarian granulosa cells (GCs) of PCOS women. Thus, the objectives of our study were to investigate adiponectin, chemerin, resistin, visfatin, omentin, and apelin ovarian expression in PCOS women in comparison with controls and women with only a polycystic ovary morphology. In total, 78 women undergoing an in vitro fertilization procedure were divided into three groups: 23 PCOS women, 28 women presenting only ≥12 follicles per ovary (ECHO group), and 27 control women. Each group almost equally included normal weight and obese women. Follicular fluid (FF) concentration and granulosa cells (GCs) mRNA expression of adipokines and their receptors were assessed by ELISA and RT-qPCR, respectively. Omentin levels in FF and GC were higher in PCOS than in ECHO and control women, while apelin expression was increased in both PCOS and ECHO groups. FF chemerin concentration was predominant in normal-weight PCOS women compared to BMI (Body Mass Index)-matched ECHO and control women, while GC mRNA levels were higher in the obese PCOS group than in the ECHO one. Compared to PCOS, ECHO women had increased FF adiponectin concentrations and lower plasma AMH levels. The FF concentration of all adipokines was higher in obese subjects except for adiponectin, predominant in normal-weight women. In conclusion, women with PCOS expressed higher GC chemerin and omentin, whereas the ECHO group presented higher levels of FF adiponectin and apelin and lower plasma AMH and LH concentrations. Chemerin, omentin, and apelin expression was differently regulated in women with PCOS, suggesting their possible role in follicular growth arrest and ovulatory dysfunction characterizing PCOS pathogenesis.

Bongrani|Alice|A| Mellouk|Namya|N| Rame|Christelle|C| Cornuau|Marion|M| Guérif|Fabrice|F| Froment|Pascal|P| Dupont|Joëlle|J|0000-0002-8046-7705

adipokines
PCOS
follicular fluid
polycystic ovary morphology
human granulosa cells


Physiological integration enhanced the tolerance of Cynodon dactylon to flooding.

Abstract: Many flooding-tolerant species are clonal plants; however, the effects of physiological integration on plant responses to flooding have received limited attention. We hypothesise that flooding can trigger changes in metabolism of carbohydrates and ROS (reactive oxygen species) in clonal plants, and that physiological integration can ameliorate the adverse effects of stress, subsequently restoring the growth of flooded ramets. In the present study, we conducted a factorial experiment combining flooding to apical ramets and stolon severing (preventing physiological integration) between apical and basal ramets of Cynodon dactylon, which is a stoloniferous perennial grass with considerable flooding tolerance. Flooding-induced responses including decreased root biomass, accumulation of soluble sugar and starch, as well as increased activity of superoxide dismutase (SOD) and ascorbate peroxidase (APX) in apical ramets. Physiological integration relieved growth inhibition, carbohydrate accumulation and induction of antioxidant enzyme activity in stressed ramets, as expected, without any observable cost in unstressed ramets. We speculate that relief of flooding stress in clonal plants may rely on oxidising power and electron acceptors transferred between ramets through physiological integration.

Li|Z J|ZJ|
Fan|D Y|DY|
Chen|F Q|FQ|
Yuan|Q Y|QY|
Chow|W S|WS|
Xie|Z Q|ZQ|

reactive oxygen species scavenging enzymes


Attitudes Toward Clinical Trials Among Physicians in China With Different Levels of Experience.

Abstract:
BACKGROUND
Physicians play an important role in clinical trials, but attitudes toward clinical trials among physicians with different levels of experience have seldom been studied. The objective of this study was to assess the different attitudes toward clinical trials among junior, intermediate, and senior physicians.

METHODS
An anonymous cross-sectional survey was conducted between April 1 and May 1, 2015. A total of 217 physicians (66 junior, 86 intermediate, and 65 senior positions) completed and submitted the validated questionnaires.

RESULTS
The surveyed physicians responded with a high degree of agreement on the necessity of conducting clinical trials. Senior and intermediate physicians considered most about helping patients with new treatments in conducting a clinical trial. For junior physicians, the opportunity to have access to clinical trial methodology and enhancing their reputation in society or in the hospital were the 2 most significant factors. In addition, physicians with lower titles perceived greater difficulties in conducting clinical trials, especially in communicating with the Good Clinical Practice (GCP) office and the trial sponsor, enrolling trial participants, and obtaining informed consent.

CONCLUSIONS
Our results revealed that physicians with different positional titles perceived different benefits and difficulties in conducting clinical trials. Junior physicians need more administrative assistance in clinical trials and related training.

Zheng|Hang|H| Wang|Liqing|L| Wu|Hongyan|H| Wang|Miao|M| Sun|He|H|

attitudes
clinical trials
physician
China


Non-canonical DNA/RNA structures during Transcription-Coupled Double-Strand Break Repair: Roadblocks or Bona fide repair intermediates?

Abstract: Although long overlooked, it is now well understood that DNA does not systematically assemble into a canonical double helix, known as B-DNA, throughout the entire genome but can also accommodate other structures including DNA hairpins, G-quadruplexes and RNA:DNA hybrids. Notably, these non-canonical DNA structures form preferentially at transcriptionally active loci. Acting as replication roadblocks and being targeted by multiple machineries, these structures weaken the genome and render it prone to damage, including DNA double-strand breaks (DSB). In addition, secondary structures also further accumulate upon DSB formation. Here we discuss the potential functions of pre-existing or de novo formed nucleic acid structures, as bona fide repair intermediates or repair roadblocks, especially during Transcription-Coupled DNA Double-Strand Break repair (TC-DSBR), and provide an update on the specialized protein complexes displaying the ability to remove these structures to safeguard genome integrity.

Puget|Nadine|N|
Miller|Kyle M|KM|
Legube|Gaëlle|G|

G-quadruplex
RNA:DNA hybrid
Transcription
DNA double-strand break repair
Chromatin
R-loop


Fluorescent Recognition of 1,2-Diamines by a 1,1'-Binaphthyl-Based Trifluoromethyl Ketone.

Abstract: The fluorescent responses of a 1,1'-binaphthol (BINOL)-based trifluoromethyl aryl ketone toward a variety of amines have been studied. The aliphatic 1,2-diamines, especially ethylenediamine, can greatly enhance the fluorescence of this compound, but under the same conditions, other mono- and diamines cause much smaller fluorescent responses. This compound can be used as a fluorescent sensor for the detection of ethylenediamine at concentrations over micromolar levels. UV absorption and NMR spectroscopic methods have been used to study the interactions of the sensor with ethylenediamine. These studies have demonstrated that the trifluoromethyl ketone of the sensor reacts with ethylenediamine much more favorably than with other amines. The hydroxyl groups of the sensor and those of the hemiaminal adducts formed in the presence of the amines are important for the highly selective fluorescent response.

Xu|Yimang|Y| Yu|Shanshan|S| Chen|Qi|Q| Chen|Xuemin|X| Li|Yinan|Y| Yu|Xiaoqi|X| Pu|Lin|L|

fluorescence
trifluoromethyl ketones
amines
sensors
molecular recognition


Clinical outcome of latissimus dorsi reconstruction after wide resection of soft-tissue sarcoma.

Abstract:
BACKGROUND
We investigated the clinical outcomes of reconstruction using the latissimus dorsi (LD) flap after resection of soft-tissue sarcoma.

MATERIALS AND METHODS
We analyzed 19 patients. Free LD flap was performed in 11 patients and pedicle flap in eight patients. The mean follow-up period after the surgery was 60 months.

RESULTS
The mean age at diagnosis was 57 years. The mean tumor size was 9.8 cm. The median size of the LD flap was 140 × 100 mm. The mean surgical duration and bleeding were 510 min and 602 mL, respectively. Complications included partial skin and soft-tissue necrosis (n = 3) and wound dehiscence (n = 2). No additional free flap was not necessary for the closure of the defect due to the complications. The longer surgical duration was significantly associated with wound complications (P = 0.048). The 5-year survival rate was 80.7%, and the local recurrence-free survival rate was 89.2%. Two patients developed local recurrence, while 6 patients developed metastasis. None of the patients had any restrictions of daily life.

CONCLUSION
The LD flap after surgical tumor resection in patients with soft-tissue sarcoma was useful for the coverage of soft tissue.

Reconstruction
Soft-tissue sarcoma
Bone sarcoma
Latissimus dorsi flap


Management of maxillofacial trauma in the elderly: A European multicenter study.

Abstract:
BACKGROUND/AIMS
Management of maxillofacial trauma in the geriatric population poses a great challenge due to anatomical variations and medical comorbidities. The aim of this study was to analyze the management variables, timing, and outcomes of facial fractures in elderly patients (aged 70 years or more) at several European departments of oral and maxillofacial surgery.

MATERIALS AND METHODS
This study was based on a systematic computer-assisted database that allowed the recording of data from all geriatric patients with facial fractures from the involved maxillofacial surgical units across Europe between 2013 and 2017.

RESULTS
A total of 1334 patients were included in the study: 665 patients underwent closed or open surgical treatment. A significant association (P < .005) was found between the presence of concomitant injuries and a prolonged time between hospital admission and treatment. The absence of indications to treatment was associated with comorbidities and an older age (P < .000005).

CONCLUSIONS
Elderly patients require specific attention and multidisciplinary collaboration in the diagnosis and sequencing of trauma treatment. A prudent attitude may be kept in selected cases, especially when severe comorbidities are associated and function is not impaired.

management
maxillofacial trauma
elderly
geriatric


In Search of a Simple and Reliable Method of Measuring Intra-abdominal Pressure in Peritoneal Dialysis Patients.

Abstract:
Background
Patients treated with peritoneal dialysis (PD) are at increased risk of developing mechanical complications such as dialysate leaks and hernias thought to be partially related to an increase in intra-abdominal pressure (IAP) secondary to dialysate in the abdomen. However, measurement of IAP requires specialized equipment that is not readily available in the home dialysis unit.

Objectives
To develop a reliable method of measuring IAP in PD patients that could be easily used in the home dialysis unit. We hypothesized that the handheld Stryker pressure monitor would be suitable for this purpose via connection to the PD catheter.

Design
Cross-sectional.

Setting
Tertiary Care Hospital, Ottawa, Ontario, Canada.

Patients
Patients who were having a PD catheter inserted via laparoscopic surgery at The Ottawa Hospital were recruited for the study.

Measurements
With the patients at end-expiration, the IAP measured with the Stryker monitor connected to the PD catheter was compared with the insufflator pressures of 15, 10, and 5 mm Hg.

Methods
Bland-Altman plots were constructed and intraclass correlation coefficients were calculated for each pressure.

Results
Twelve patients participated in the study: 9 men and 3 women. They were on average 53 ± 15 years old and 81 ± 13.4 kg. Two patients had to be excluded from the analysis due to difficulties zeroing the Stryker pressure monitor at the time of surgery. There were also rapid fluctuations in the insufflator pressure recording, creating additional challenges in comparing the 2 measurements at end-expiration. The 95% limits of agreement for the Bland-Altman plots ranged from 7.9 (@15 mm Hg) to 12.2 (@10 mm Hg). The intraclass correlation coefficients for reliability of the individual measurements ranged from 0.015 (10 mm Hg) to 0.634 (15 mm Hg).

Limitations
Small sample size and lack of a gold standard comparator may have affected our results.

Conclusions
In our study, we used the operating room insufflator as the gold standard for measuring IAP. By Bland-Altman plots and intraclass correlation coefficients, the pressure values obtained with the Stryker pressure monitor were not a reliable estimate of insufflator IAP especially at lower pressures. Further studies are needed to identify an ideal tool for measurement of IAP to guide PD management.

measurement
intra-abdominal pressure
peritoneal dialysis (PD)
pilot study


A rare case of mechanical bowel obstruction caused by mesh plug migration.

Abstract: Tension-free hernia repair with a mesh plug is currently one of the most popular techniques for open inguinal hernioplasty. It is well tolerated by most patients and is associated with few complications. However, rare mesh migration has been reported. We describe a case of a 72-year-old man who had undergone inguinal hernioplasty with a mesh plug 2 years previously. He visited the emergency department complaining of vomiting. Strangulation ileus was suspected, and an emergency operation was performed. The mesh plug had migrated into the intra-peritoneal cavity, granulation tissue had formed around the plug, and the small intestine was involved in the granulation tissue. The small intestine was strangulated for more than 13 cm, and obstruction was present at this point.


Indirect pulp therapy in a symptomatic mature molar using calcium enriched mixture cement.

Abstract: Dental pulp has the ability of repair/regeneration. Indirect pulp therapy (IPT) is recommended for pulp preservation in asymptomatic teeth with extremely deep caries as well as teeth with clinical symptoms of reversible pulpitis. In this case study, we performed IPT with calcium enriched mixture (CEM) cement on a symptomatic permanent molar. After clinical/radiographic examinations the tooth was diagnosed with irreversible pulpitis and associated apical periodontitis. IPT involved partial caries removal, the placement of CEM cement pulp cap and overlying adhesive permanent restoration. At the 1 week follow-up, patient's spontaneous symptoms had resolved. One-year follow-up demonstrated pulp vitality, clinical function, as well as the absence of pain/tenderness to percussion/palpation/cold sensitivity tests; periapical radiograph showed a healing periradicular lesion with newly formed bone, that is normal pulp with normal periodontium. These favorable results indicate that IPT/CEM may be a good treatment option in comparison to endodontic treatment in young patients. IPT of deep-caries lesion is an easier, more practical and valuable treatment plan than complete caries removal.

calcium enriched mixture cement
pulpitis
Apical periodontitis
pulp cap
endodontic
stepwise excavation


Accuracy of nigrosome-1 detection to discriminate patients with Parkinson's disease and essential tremor.

Abstract:
PURPOSE
The use of susceptibility weighted imaging in high field magnetic resonance imaging scanners can detect the nigrosome-1 area located in the caudo-lateral region of the pars compacta in the substantia nigra. This structure comprises a significant amount of dopaminergic neurons and degenerates in the early stages of Parkinson's disease. Essential tremor is a neurological condition that in some cases could be confused with the early stages of Parkinson's disease with a possible error in clinical diagnosis. Our purpose is to evaluate the accuracy of nigrosome-1 detection by high resolution magnetic resonance imaging to discriminate Parkinson's disease from essential tremor.

METHODS
A case-control study compared patients with a clinical diagnosis of Parkinson's disease and essential tremor. Magnetic resonance imaging studies were performed using a 3T magnetic resonance imaging scanner. The susceptibility weighted imaging sequence was obtained in the axial plane with an isotropic voxel of 0.75 mm. Two independent neuroradiologists evaluated the images without access to clinical patient data.

RESULTS
Sixteen patients were included in each group (Parkinson's disease and essential tremor). Average age: Parkinson's disease group: 71.3 (SD 6.3) and essential tremor group: 68.3 (SD 12.3). For the first evaluator, the nigrosome-1 area was absent in 15 patients with Parkinson's disease and in two with essential tremor and for the second evaluator was absent in 15 patients with Parkinson's disease and four with essential tremor. The sensitivity/specificity for the diagnosis of Parkinson's disease was 93.75%/87.5% for the first evaluator and 93.75%/75% for the second evaluator.

CONCLUSION
The detection of the nigrosome-1 area is a useful tool in the differential diagnosis between Parkinson's disease and essential tremor, with high sensitivity and specificity.

D000368:Aged
D000369:Aged, 80 and over
D016022:Case-Control Studies
D003937:Diagnosis, Differential
D020329:Essential Tremor
D005260:Female
D006801:Humans
D008279:Magnetic Resonance Imaging
D008297:Male
D008875:Middle Aged
D010300:Parkinson Disease
D065842:Pars Compacta
D012680:Sensitivity and Specificity
D013378:Substantia Nigra

nigrosome-1
essential tremor
Parkinson’s disease


Quality of Childbirth Care in Women undergoing Labour: Satisfaction with Care Received and How It Changes over Time.

Abstract: (1) Background: To evaluate women's satisfaction with the care received during childbirth undergoing labour and how this changes over time. (2) Methods: An observational, multicentre and longitudinal study in two public hospitals of Spain with a convenience sample of 248 women during the post-partum period. Satisfaction was evaluated using the Intrapartal-Specific Quality from the Patient's Perspective questionnaire. Socio-demographic and clinical variables were considered. A bivariate analysis evaluated the relationship between satisfaction and the recorded variables to compare the hypotheses, and also to know if there were any significant differences between the scores obtained at the various evaluated time points (three days, 15 days, one year postpartum). The multivariate analysis by binary logistic regression helped complete the study about the variables related to the level of satisfaction; (3) Results: The mean scores for satisfaction at each time point were high, and they lowered with time. The bivariate analysis showed an association between satisfaction and the following variables: 'mother's place of birth', 'level of education', 'type of labour onset', 'type of birth' and 'type of perineal trauma'. For the multivariate analysis, women who gave birth vaginally, began labour spontaneously and had an epidural were more satisfied than those who did not; (4) Conclusions: Women seemed to obtain good levels of satisfaction with the care they received. Even so, based on continuously improved quality, we proposed some improvement measures, particularly regarding the physical environment and the information offered to patients. It is important to know at what time experience while giving birth should be evaluated as scores can lower with time as part of its normal evolution.

childbirth
observational study
patient satisfaction
quality improvement
surveys and questionnaires


Fatal Case of Chronic Jamestown Canyon Virus Encephalitis Diagnosed by Metagenomic Sequencing in Patient Receiving Rituximab.

Abstract: A 56-year-old man receiving rituximab who had months of neurologic symptoms was found to have Jamestown Canyon virus in cerebrospinal fluid by clinical metagenomic sequencing. The patient died, and postmortem examination revealed extensive neuropathologic abnormalities. Deep sequencing enabled detailed characterization of viral genomes from the cerebrospinal fluid, cerebellum, and cerebral cortex.

Solomon|Isaac H|IH|
Ganesh|Vijay S|VS|
Yu|Guixia|G|
Deng|Xian Ding|XD|
Wilson|Michael R|MR|
Miller|Steve|S|
Milligan|Tracey A|TA|
Mukerji|Shibani S|SS|
Mathewson|Abigail|A|
Linxweiler|Justin|J|
Morse|Darlene|D|
Ritter|Jana M|JM|
Staples|J Erin|JE|
Hughes|Holly|H|
Gould|Carolyn V|CV|
Sabeti|Pardis C|PC|
Chiu|Charles Y|CY|
Piantadosi|Anne|A|

Jamestown Canyon virus
encephalitis
rituximab
arbovirus
metagenomic next-generation sequencing
monoclonal antibody
orthobunyavirus
vector-borne infections
viruses


Tannic Acid as a Bio-Based Modifier of Epoxy/Anhydride Thermosets.

Abstract: Toughening an epoxy resin by bio-based modifiers without trade-offs in its modulus, mechanical strength, and other properties is still a big challenge. This paper presents an approach to modify epoxy resin with tannic acid (TA) as a bio-based feedstock. Carboxylic acid-modified tannic acid (TA⁻COOH) was first prepared through a simple esterification between TA and methylhexahydrophthalic anhydride, and then used as a modifier for the epoxy/anhydride curing system. Owing to the chemical modification, TA⁻COOH could easily disperse in epoxy resin and showed adequate interface interaction between TA⁻COOH and epoxy matrix, in avoid of phase separation. The use of TA⁻COOH in different proportions as modifier of epoxy/anhydride thermosets was studied. The results showed that TA⁻COOH could significantly improve the toughness with a great increase in impact strength under a low loading amount. Moreover, the addition of TA⁻COOH also simultaneously improved the tensile strength, elongation at break and glass transition temperature. The toughening and reinforcing mechanism was studied by scanning electron microscopy (SEM), dynamic mechanical analysis (DMA) and thermal mechanical analysis (TMA), which should be owned to the synergistic effect of good interface interaction, aromatic structure, decreasing of cross linking density and increasing of free volume. This approach allows us to utilize the renewable tannic acid as an effective modifier for epoxy resin with good mechanical and thermal properties.

Fei|Xiaoma|X| Zhao|Fangqiao|F| Wei|Wei|W| Luo|Jing|J| Chen|Mingqing|M| Liu|Xiaoya|X|

tannic acid
bio-based
toughening
epoxy resin


Unique Diacidic Fragments Inhibit the OXA-48 Carbapenemase and Enhance the Killing of Escherichia coli Producing OXA-48.

Abstract: Despite the advances in β-lactamase inhibitor development, limited options exist for the class D carbapenemase known as OXA-48. OXA-48 is one of the most prevalent carbapenemases in carbapenem-resistant Enterobacteriaceae infections and is not susceptible to most available β-lactamase inhibitors. Here, we screened various low-molecular-weight compounds (fragments) against OXA-48 to identify functional scaffolds for inhibitor development. Several biphenyl-, naphthalene-, fluorene-, anthraquinone-, and azobenzene-based compounds were found to inhibit OXA-48 with low micromolar potency despite their small size. Co-crystal structures of OXA-48 with several of these compounds revealed key interactions with the carboxylate-binding pocket, Arg214, and various hydrophobic residues of β-lactamase that can be exploited in future inhibitor development. A number of the low-micromolar-potency inhibitors, across different scaffolds, synergize with ampicillin to kill Escherichia coli expressing OXA-48, albeit at high concentrations of the respective inhibitors. Additionally, several compounds demonstrated micromolar potency toward the OXA-24 and OXA-58 class D carbapenemases that are prevalent in Acinetobacter baumannii. This work provides foundational information on a variety of chemical scaffolds that can guide the design of effective OXA-48 inhibitors that maintain efficacy as well as potency toward other major class D carbapenemases.

OXA-48
carbapenemase
Class D carbapenemase
antibiotic resistance
drug discovery
fragment inhibitors
β-lactam
β-lactamase, inhibitor


Is the Efficacy and Safety of Retrograde Flexible Ureteroscopy in the Elderly Population Different from Non-elderly Adults?

Abstract: Background and objectives The population of elderly adults is increasing globally, and due to metabolic changes related to advanced age, many elderly adults experience kidney stones. Flexible ureteroscopy (f-URS) is a minimally invasive procedure to treat kidney stones, but it is not free of complications. The goals of this study were to analyze the efficacy and safety of f-URS in the management of kidney stones in patients aged ≥60 years and compare the outcomes of this surgery with the outcomes of the same surgery in a younger population. Materials and methods We retrospectively reviewed patient data from 1750 patients who met our inclusion criteria and received f-URS at the urology clinic of our hospital from 2012 to 2017. Patients were assigned into two groups: those aged ≥60 years (Group 1, n=291) and those aged 19-59 years (Group 2, n=1459). The perioperative results were evaluated comparatively. We performed multivariable analyses for factors predicting complications. Results When we compared the groups on demographic attributes, we noted statistically significant differences in gender, body mass index (BMI), and American Society of Anesthesiologists scores. Stone size and operation time were higher in the ≥60-year age group (Group 1). Other stone characteristics and operative features were similar. Stone-free rates (SFR) after the first procedure were 88.0% in Group 1 and 89.2% in Group 2. SFR and success rates at three months were similar for both groups. The complication rates were similar, and multivariable regression analysis revealed the most important factor affecting the complications was the presence of residual stones in both groups. The second most important factor affecting the complication was the operation time in Group 1 and the number of stones in Group 2. Conclusion In our study, there were no significant differences in terms of results and complications among elderly and young patients after f-URS except for the duration of the operation. The prolongation of operation time results in worse outcomes in terms of perioperative complications in patients aged ≥60 years. f-URS is a relatively safe and efficient procedure, with a small risk of minor complications even in the elderly population, with increased comorbidity.

Cakici|Mehmet Caglar|MC|
Sari|Sercan|S|
Selmi|Volkan|V|
Sandikci|Fatih|F|
Karakoyunlu|Nihat|N|
Ozok|Ugur|U|

efficacy
flexible
ureteroscopy
elderly
kidney stone
rirs
ureterorenoscopy


Untargeted Metabolomics for Metabolic Diagnostic Screening with Automated Data Interpretation Using a Knowledge-Based Algorithm.

Abstract: Untargeted metabolomics may become a standard approach to address diagnostic requests, but, at present, data interpretation is very labor-intensive. To facilitate its implementation in metabolic diagnostic screening, we developed a method for automated data interpretation that preselects the most likely inborn errors of metabolism (IEM). The input parameters of the knowledge-based algorithm were (1) weight scores assigned to 268 unique metabolites for 119 different IEM based on literature and expert opinion, and (2) metabolite Z-scores and ranks based on direct-infusion high resolution mass spectrometry. The output was a ranked list of differential diagnoses (DD) per sample. The algorithm was first optimized using a training set of 110 dried blood spots (DBS) comprising 23 different IEM and 86 plasma samples comprising 21 different IEM. Further optimization was performed using a set of 96 DBS consisting of 53 different IEM. The diagnostic value was validated in a set of 115 plasma samples, which included 58 different IEM and resulted in the correct diagnosis being included in the DD of 72% of the samples, comprising 44 different IEM. The median length of the DD was 10 IEM, and the correct diagnosis ranked first in 37% of the samples. Here, we demonstrate the accuracy of the diagnostic algorithm in preselecting the most likely IEM, based on the untargeted metabolomics of a single sample. We show, as a proof of principle, that automated data interpretation has the potential to facilitate the implementation of untargeted metabolomics for metabolic diagnostic screening, and we provide suggestions for further optimization of the algorithm to improve diagnostic accuracy.

Prinsen|Hubertus C M T|HCMT|0000-0001-5167-4134

direct-infusion high-resolution mass spectrometry


Reconstruction of the Genomes of Drug-Resistant Pathogens for Outbreak Investigation through Metagenomic Sequencing.

Abstract: Culture-independent methods that target genome fragments have shown promise in identifying certain pathogens, but the holy grail of comprehensive pathogen genome detection from microbiologically complex samples for subsequent forensic analyses remains a challenge. In the context of an investigation of a nosocomial outbreak, we used shotgun metagenomic sequencing of a human fecal sample and a neural network algorithm based on tetranucleotide frequency profiling to reconstruct microbial genomes and tested the same approach using rectal swabs from a second patient. The approach rapidly and readily detected the genome of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae in the patient fecal specimen and in the rectal swab sample, achieving a level of strain resolution that was sufficient for confident transmission inference during a highly clonal outbreak. The analysis also detected previously unrecognized colonization of the patient by vancomycin-resistant Enterococcus faecium, another multidrug-resistant bacterium.IMPORTANCE The study results reported here perfectly demonstrate the power and promise of clinical metagenomics to recover genome sequences of important drug-resistant bacteria and to rapidly provide rich data that inform outbreak investigations and treatment decisions, independently of the need to culture the organisms.

Mu|Andre|A|
Kwong|Jason C|JC|
Isles|Nicole S|NS|
Gonçalves da Silva|Anders|A|
Schultz|Mark B|MB|0000-0002-7689-6531
Ballard|Susan A|SA|
Lane|Courtney R|CR|
Carter|Glen P|GP|
Williamson|Deborah A|DA|
Seemann|Torsten|T|
Stinear|Timothy P|TP|
Howden|Benjamin P|BP|

metagenomics
Klebsiella pneumoniae
antimicrobial resistance
microbiome
vancomycin-resistant enterococci


Lung Cancer with MET exon 14 Skipping Mutation: Genetic Feature, Current Treatments, and Future Challenges.

Abstract: MET exon 14 skipping mutation (MET∆ex14) is present about 3% of non-small cell lung cancers (NSCLCs). NSCLC patients with MET∆ex14 are characterized by an average age of over 70 years at diagnosis, a smoking history and a higher frequency in pleomorphic carcinoma and adenosquamous cell carcinoma than in adenocarcinoma. It has also been reported that NSCLCs with MET∆ex14 often have codriver alterations such as EGFR amplification (6-28%), FGFR1 alterations (5-17%), KRAS alterations (~8%), BRAF alterations (~21%), or PIK3CA mutation/amplification (~14%). In 2020, the approval of two MET-tyrosine kinase inhibitors (TKIs), capmatinib and tepotinib, for NSCLCs carrying MET∆ex14 dawned a new era for MET-targeted therapy. These drugs yielded progression-free survival of 5.4-12.4 months in clinical trials; however, it has also been reported that one-third to half of patients show inherent resistance to MET-TKIs. In addition, the emergence of acquired resistance to MET-TKIs is inevitable. In this review, we summarize the clinical and molecular characteristics of NSCLCs with MET∆ex14, the efficacy and safety of capmatinib and tepotinib, the inherent and acquired resistance mechanisms to MET-TKIs, and new treatment strategies for NSCLCs with MET∆ex14 in the near future.

MET exon 14 skipping
non-small cell lung cancer
capmatinib
tepotinib
resistance mechanisms
immune checkpoint inhibitors


NaFe2PO4(MoO4)2: A Promising NASICON-Type Electrode Material for Sodium-Ion Batteries.

Abstract: Searching for polyanionic electrode materials with high Na+ and electronic conductivity is pivotal to realize high-performance sodium-ion batteries. Here, we report a novel polyanionic-based NASICON-type compound, NaFe2PO4(MoO4)2 (NFPM), that does not crystallize in the common space group R-3c or C2/c but in the rare P2/c. The studies on bond valence sum maps show that NFPM has high Na+ conductivity because the large volumes of MoO4 groups make the interstitial channels wider, thus making the energy barrier of Na+ diffusion decrease along these channels. Density functional theory calculations demonstrate that NFPM has high electronic conductivity because the contribution of Mo 4d orbitals on the formation of the bottom of the conduction band makes the connected MoO4 groups take part in electron transport. Electrochemical tests exhibit that NFPM can deliver a capacity of ∼80 mAh g-1 with good reversible cyclability utilizing the Fe3+/Fe2+ redox couple. In situ X-ray diffraction measurements indicate that NFPM undergoes one-phase reaction mechanism in the process of charge and discharge.

sodium-ion batteries
polyanionic
conductivity
NASICON
cathode


Association of complications with blood transfusions in pediatric cardiac surgery patients.

Abstract:
BACKGROUND
Blood product transfusion during cardiopulmonary bypass has been demonstrated to be associated with increased morbidity and mortality in adult cardiac surgery populations. The aim of this study was to characterize the risk-adjusted occurrence of postoperative complications and mortality in relation to intraoperative blood product transfusion in our pediatric cardiac surgery population.

METHODS
A retrospective review was performed on 1,631 consecutive cardiopulmonary bypass cases to determine the effects of intraoperative blood product transfusion on selected outcomes. After adjusting for patient and operative risk factors, multivariate analysis was performed to determine the association between blood product transfusion and postoperative complications. Cox proportional hazards model was used to examine the relationship of packed red blood cell transfusion to hospital length of stay.

RESULTS
Red blood cell and fresh frozen plasma transfusion was associated with pulmonary complications (adjusted odds ratio, 1.55; 95% confidence interval, 1.05 to 2.28; p=0.03). Red blood cell transfusion also correlated with prolonged hospital stay (p<0.01). Cryoprecipate transfusion was associated with postoperative pulmonary complications (adjusted odds ratio, 1.79; 95% confidence interval, 1.13 to 2.55; p=0.01), but decreased incidence of 30-day mortality (adjusted odds ratio, 0.44; 95% confidence interval, 0.23 to 0.85; p=0.02). Platelet transfusion was associated with decreased 30-day mortality (adjusted odds ratio, 0.51; 95% confidence interval, 0.28 to 0.93; p=0.04), but not overall mortality.

CONCLUSIONS
Blood product transfusion was associated with an increased incidence of postoperative pulmonary complications and prolonged hospital length of stay, but not overall mortality. These findings suggest that minimizing blood product transfusion would be beneficial in the pediatric cardiopulmonary bypass surgery patient population.

Iyengar|Amit|A|
Scipione|Christopher N|CN|
Sheth|Parth|P|
Ohye|Richard G|RG|
Riegger|Lori|L|
Bove|Edward L|EL|
Devaney|Eric J|EJ|
Hirsch-Romano|Jennifer C|JC|

D000293:Adolescent
D006348:Cardiac Surgical Procedures
D002315:Cardiopulmonary Bypass
D002423:Cause of Death
D002648:Child
D002675:Child, Preschool
D015331:Cohort Studies
D016001:Confidence Intervals
D017707:Erythrocyte Transfusion
D005260:Female
D005500:Follow-Up Studies
D017052:Hospital Mortality
D006801:Humans
D015994:Incidence
D007223:Infant
D007430:Intraoperative Care
D008297:Male
D015999:Multivariate Analysis
D016017:Odds Ratio
D011183:Postoperative Complications
D016016:Proportional Hazards Models
D012189:Retrospective Studies
D018570:Risk Assessment
D016896:Treatment Outcome


Advanced cardiovascular life support algorithm for the management of the hospitalized unresponsive patient on continuous flow left ventricular assist device support outside the intensive care unit.

Abstract: Over the past decade, continuous flow left ventricular assist devices (CF-LVADs) have become the mainstay of therapy for end stage heart failure. While the number of patients on support is exponentially growing, at present there are no American Heart Association or European Society of Cardiology Advanced Cardiovascular Life Support guidelines for the management of this unique patient population. We propose an algorithm for the hospitalized unresponsive CF-LVAD patient outside of the intensive care unit setting. Key elements of this algorithm are: creation of a dedicated LVAD code pager and LVAD code team; early assessment and correction of LVAD malfunction; early determination of blood flow using Doppler technique in carotid and femoral arteries; prompt administration of external chest compressions in the absence of Doppler flow; bedside veno-arterial extracorporeal membranous oxygenation support if no response to resuscitation measures; and early consideration for stroke.

Yuzefpolskaya|Melana|M|
Uriel|Nir|N|
Flannery|Margaret|M|
Yip|Natalie|N|
Mody|Kanika|K|
Cagliostro|Barbara|B|
Takayama|Hiroo|H|
Naka|Yoshifumi|Y|
Jorde|Ulrich P|UP|
Goswami|Sumeet|S|
Colombo|Paolo C|PC|

D022561:Advanced Cardiac Life Support
D000465:Algorithms
D019468:Disease Management
D006333:Heart Failure
D006353:Heart-Assist Devices
D006801:Humans
D007362:Intensive Care Units

advanced cardiovascular life support
Left ventricular assist devices
heart failure


Milk lymphocyte profile and macrophage functions: new insights into the immunity of the mammary gland in quarters infected with Corynebacterium bovis.

Abstract:
BACKGROUNDS
The present study explored the viability of bovine milk macrophages, their intracellular production of reactive oxygen and nitrogen species (RONS), and their phagocytosis of Staphylococcus aureus, as well as the profile of lymphocytes, from healthy udder quarters and udder quarters infected by Corynebacterium bovis. The study included 28 healthy udder quarters from 12 dairy cows and 20 udder quarters infected by C. bovis from 10 dairy cows. The percentages of macrophages and lymphocytes were identified by flow cytometry using monoclonal antibodies. Macrophage viability, RONS production, and S. aureus phagocytosis were evaluated by flow cytometry.

RESULTS
Milk samples from quarters infected with C. bovis showed a lower percentage of macrophages but an increased number of milk macrophages per mL and a higher percentage of macrophages that produced intracellular RONS and phagocytosed S. aureus. No effect of C. bovis infection on macrophage viability was found. Udder quarters infected by C. bovis showed a higher percentage of T cells and CD4+ T lymphocytes, but no effect was found on the percentage of CD8+ CD4- T, CD8- CD4- T, or B lymphocytes.

CONCLUSIONS
Thus, our results corroborate, at least in part, the finding that intramammary infections by C. bovis may offer protection against intramammary infections by major pathogens.

Silva|Vitória M|VM|
Souza|Marina T|MT|
Blagitz|Maiara G|MG|
Souza|Fernando N|FN|
Batista|Camila F|CF|
Alves|Alexandre J|AJ|
Fernandes|Artur C C|ACC|
Sanchez|Eduardo M R|EMR|
Ordinola-Ramirez|Carla M|CM|
da Costa|Luciana|L|
Della Libera|Alice M M P|AMMP|

Milk
Dairy cow
T lymphocyte
Immune response
Mastitis
Phagocytes


A case of inflammatory fibroid polyp of the stomach with an "erect penis like appearance" successfully removed by endoscopic submucosal dissection.

Abstract: A 37-year-old woman was diagnosed by esophagogastroduodenoscopy (EGD) as having a 15-mm subepithelial lesion (SEL) in the gastric body. For 2 years, she experienced epigastric pain and anemia; she then underwent emergency EGD, which revealed a significant morphological change of the lesion. The SEL had a disintegrated tip and its submucosal portion was substantially exposed out of the mucosa, showing an "erect penis like appearance". Based on the pathological findings of biopsied samples from the exposed portion and the endoscopic features, an inflammatory fibroid polyp (IFP) was suspected. This lesion was considered responsible for the anemia and was removed by endoscopic submucosal dissection (ESD). The pathological findings confirmed the lesion to be IFP. This report presents a case of gastric IFP that showed a marked morphological change and unique endoscopic features and was successfully removed by ESD.

Inflammatory fibroid polyp
Endoscopic submucosal dissection
Subepithelial lesion
Endoscopic resection
Endoscopic ultrasonography


State of the art of nonthermal and thermal processing for inactivation of micro-organisms.

Abstract: Despite the constant development of novel thermal and nonthermal technologies, knowledge on the mechanisms of microbial inactivation is still very limited. Technologies such as high pressure, ultraviolet light, pulsed light, ozone, power ultrasound and cold plasma (advanced oxidation processes) have shown promising results for inactivation of micro-organisms. The efficacy of inactivation is greatly enhanced by combination of conventional (thermal) with nonthermal, or nonthermal with another nonthermal technique. The key advantages offered by nonthermal processes in combination with sublethal mild temperature (<60°C) can inactivate micro-organisms synergistically. Microbial cells, when subjected to environmental stress, can be either injured or killed. In some cases, cells are believed to be inactivated, but may only be sublethally injured leading to their recovery or, if the injury is lethal, to cell death. It is of major concern when micro-organisms adapt to stress during processing. If the cells adapt to a certain stress, it is associated with enhanced protection against other subsequent stresses. One of the most striking problems during inactivation of micro-organisms is spores. They are the most resistant form of microbial cells and relatively difficult to inactivate by common inactivation techniques, including heat sterilization, radiation, oxidizing agents and various chemicals. Various novel nonthermal processing technologies, alone or in combination, have shown potential for vegetative cells and spores inactivation. Predictive microbiology can be used to focus on the quantitative description of the microbial behaviour in food products, for a given set of environmental conditions.

D000222:Adaptation, Physiological
D005514:Food Irradiation
D005516:Food Microbiology
D006358:Hot Temperature
D050296:Microbial Viability
D058626:Plasma Gases
D011312:Pressure
D013242:Sterilization
D013312:Stress, Physiological
D014465:Ultrasonics

thermal processes
cell injury
modelling
non-thermal processes
stress response


Timely Closure of the Prospore Membrane Requires SPS1 and SPO77 in Saccharomyces cerevisiae.

Abstract: During sporulation in Saccharomyces cerevisiae, a double lipid bilayer called the prospore membrane is formed de novo, growing around each meiotic nucleus and ultimately closing to create four new cells within the mother cell. Here we show that SPS1, which encodes a kinase belonging to the germinal center kinase III family, is involved in prospore membrane development and is required for prospore membrane closure. We find that SPS1 genetically interacts with SPO77 and see that loss of either gene disrupts prospore membrane closure in a similar fashion. Specifically, cells lacking SPS1 and SPO77 produce hyperelongated prospore membranes from which the leading edge protein complex is not removed from the prospore membrane in a timely fashion. The SPS1/SPO77 pathway is required for the proper phosphorylation and stability of Ssp1, a member of the leading edge protein complex that is removed and degraded when the prospore membrane closes. Genetic dissection of prospore membrane closure finds SPS1 and SPO77 act in parallel to a previously described pathway of prospore membrane closure that involves AMA1, an activator of the meiotic anaphase promoting complex.

Paulissen|Scott M|SM|
Slubowski|Christian J|CJ|
Roesner|Joseph M|JM|
Huang|Linda S|LS|0000-0002-9033-4391

prospore membrane
sporulation
germinal center kinase
anaphase promoting complex
cytokinesis
meiotic exit


The BECN1-BCL2 complex regulates insulin secretion and storage in mice.

Abstract: Macroautophagy/autophagy abnormality has been recently associated with metabolic disorders, such as type 2 diabetes (T2D). However, the effect of autophagy activation in systemic energy metabolism was poorly understood. In our recent study, we demonstrated that autophagy plays different roles in distinct metabolic tissues, using an autophagy-hyperactive mouse model. In insulin-producing β cells, excess autophagy degrades insulin-containing vesicles (a process termed vesicophagy), resulting in decreased insulin contents and systemic glucose intolerance; whereas in insulin-responsive cells, activating autophagy decreases endoplasmic reticulum (ER) stress and improves insulin sensitivity.

type 2 diabetes
β cell
vesicophagy
insulin sensitivity
BECN1
ER stress
insulin granules


Inflammatory bowel disease: The role of commensal microbiome in immune regulation.

Abstract: The incidence of inflammatory bowel disease (IBD) is increasing. Microbiome is one of the most important factors in its development and affects the different clinical outcomes of IBD patients depending on its composition and different alterations. We conducted a systematic review to discuss the association between microbiome and IBD in terms of immune regulation, and therapies that can modify microbiota. A comprehensive systematic literature search was performed through April 2020 in PubMed, Web of Science, the Cochrane Library, and clinicaltrials.gov. Inclusion criteria required IBD immune regulation and alternate therapeutics for IBD. This analysis helps explain the multifactorial origin of microbiome diversity including normal immune regulation, immune pathophysiology of IBD, and shows the evidence of several therapeutic targets to change microbiome in patients with IBD, such as prebiotics, probiotics, antibiotics, fecal microbiota transplant, and others.

Wah-Suárez|Martín Ivan|MI|
Vázquez|Manuel Alejandro Martínez|MAM|
Bosques-Padilla|Francisco Javier|FJ|

Inflammatory bowel disease
Microbiome
Microbiota
Microbiota transplantation
Enfermedad inflamatoria intestinal
Microbioma
Trasplante microbiota


Determination of subtypes of Blastocystis sp. in Chilean patients with and without inflammatory bowel syndrome, A preliminary report.

Abstract:
Background & methods
Blastocystis sp. is one of the most prevalent unicellular eukaryote of the human large intestine in Chile and worldwide. It is classified in subtypes (STs), where using the polymorphic sequences of its 18S rRNA genes currently recognizes 22. STs 1-9 and ST12 have been reported in humans. It has been hypothesized that different STs of Blastocystis sp. differentially affect the clinical severity of the digestive disease in Irritable Bowel Syndrome (IBS) patients, but more studies ar4e needed to establish this statement. To contribute in the elucidation of the potential relationship between Blastocystis sp. subtypes and IBS severity, 37 IBS patient fecal samples were collected at hospitals in Santiago (Chile) and were screened for the presence of vacuolated forms of Blastocystis sp. by using conventional microscopy. Positive samples were submitted to PCR and sequencing for determining STs. The same procedure was performed in fecal samples from five non-IBS Blastocystis sp. carriers for preliminary comparative purpose.

Results and discussion
Four out of the 37 samples from the IBS patients were found positive for Blastocystis sp. (10.81%) by using microscopy. The presence of this microorganism in these four samples were confirmed by PCR and sequencing. Subtypes and their respective closest match alleles were searched and the ST1, ST2 and ST4 subtypes were found in these patients. ST4 subtype is scarcely detected in South America countries, being reported previously only in Colombia and Brazil. In this ST4 subtype we determined the allele 42 which is the most frequent allele observed in human Blastocystis isolates. In the non-IBS individuals' carriers, three subtypes were found: ST1, ST2 and ST3, even belonging to the same family group. Closest match alleles: 2, 12 and 34 here detected were also commonly reported globally. Instead of the small number of IBS patients studied here, the frequency of blastocystosis detected (10.81%) was lower than the prevalence of Blastocystis sp. infections described for the Chilean general population (30.4%). In Chile, clear correlation of Blastocystis sp. subtypes and IBS severity is still lacking with this study but it may lead and contribute to a better understanding of its pathogenicity and worldwide epidemiology.

Peña|Sebastián|S|
Carrasco|Gabriela|G|
Rojas|Pamela|P|
Castillo|Douglas|D|
Ozaki|Luiz S|LS|
Mercado|Rubén|R|

Subtypes
Blastocystis
Chile
Irritable bowel syndrome
IBS


Age differences in workplace intervention effects on employees' nighttime and daytime sleep.

Abstract:
OBJECTIVES
To examine the effects of a workplace flexibility/support intervention on employees' sleep quantity and quality during nights and days and whether the effects differ by employee age.

DESIGN
Cluster-randomized controlled trial.

SETTING
Information technology industry workplaces.

PARTICIPANTS
US employees (Mage = 46.9 years) at an information technology firm who provided actigraphy at baseline and a 12-month follow-up (N = 396; n = 195 intervention, n = 201 control).

INTERVENTION
The Work, Family, and Health Study intervention aimed to increase workplace flexibility and support. The intervention consisted of facilitated discussions to help employees increase control over when and where they work as well as manager-specific training sessions to increase manager support for employees' work-family issues.

MEASUREMENTS
Nighttime sleep duration, wake after sleep onset (WASO), and nap duration were measured with wrist actigraphy. Day-to-day variability in these variables (min2) was also estimated.

RESULTS
Intervention employees increased nighttime sleep duration at 12 months, by 9 minutes per day, relative to control employees. There were interaction effects between the intervention and age on daytime nap duration and day-to-day variability in WASO. Older employees (56-70 years) in the intervention condition decreased nap duration at 12 months relative to older employees in the control condition. Older employees in the intervention condition also exhibited a greater decrease in day-to-day variability of WASO at 12 months compared with their baseline.

CONCLUSIONS
The workplace flexibility/support intervention was effective in enhancing employees' sleep health by increasing nighttime sleep duration. Furthermore, the intervention was particularly effective for older employees in decreasing their daytime nap duration and day-to-day variability in WASO.

Lee|Soomi|S|
Almeida|David M|DM|
Berkman|Lisa|L|
Olson|Ryan|R|
Moen|Phyllis|P|
Buxton|Orfeu M|OM|

Workplace intervention
Nighttime sleep duration
Wake after sleep onset
Nap duration
Day-to-day variability in sleep


Country food consumption in Yukon, Northwest Territories and Nunavut, Foodbook study 2014-2015.

Abstract:
Background
This article presents a descriptive summary of the consumption of various country food (i.e. locally harvested plant and animal foods) products by residents of Yukon (YT), Northwest Territories (NT) and Nunavut (NU). Data were collected as part of the Foodbook study in 2014-2015.

Methods
The Foodbook study was conducted by telephone over a one-year period. Respondents were asked about consumption of a wide range of food products over the previous seven days. Residents of the territories were also asked about consumption of regionally-specific country food. Data were weighted to develop territorial estimates of consumption. Data on age, gender, location, income and education were also collected.

Results
The national response rate for the Foodbook survey was 19.9%. In total, 1,235 residents of the territories participated in the study (YT, n=402; NT, n=458; NU, n=375). Consumption of any country food during the previous seven days was reported by 77.5%, 60.7%, and 66.4% of participants in NU, NT and YT, respectively.

Conclusion
Responses to country food questions asked alongside the main Foodbook questionnaire provide insight on country food consumption in YT, NT and NU.

Morton|Vanessa|V| Manore|Anna|A| Ciampa|Nadia|N| Glass-Kaastra|Shiona|S| Hurst|Matt|M| Mullen|Angie|A| Cutler|Jennifer|J|

country food
food consumption
Yukon
Northwest Territories
Nunavut


Hi-C 2.0: An optimized Hi-C procedure for high-resolution genome-wide mapping of chromosome conformation.

Abstract: Chromosome conformation capture-based methods such as Hi-C have become mainstream techniques for the study of the 3D organization of genomes. These methods convert chromatin interactions reflecting topological chromatin structures into digital information (counts of pair-wise interactions). Here, we describe an updated protocol for Hi-C (Hi-C 2.0) that integrates recent improvements into a single protocol for efficient and high-resolution capture of chromatin interactions. This protocol combines chromatin digestion and frequently cutting enzymes to obtain kilobase (kb) resolution. It also includes steps to reduce random ligation and the generation of uninformative molecules, such as unligated ends, to improve the amount of valid intra-chromosomal read pairs. This protocol allows for obtaining information on conformational structures such as compartment and topologically associating domains, as well as high-resolution conformational features such as DNA loops.

Belaghzal|Houda|H|
Dekker|Job|J|
Gibcus|Johan H|JH|

D015252:Deoxyribonucleases, Type II Site-Specific

Hi-C
Chromosome conformation capture
Paired-end sequencing


A retrospective pilot study to examine the feasibility of real-time navigation for laparoscopic liver resections in intrahepatic cholangiocarcinoma using fusion indocyanine green fluorescence imaging.

Abstract:
BACKGROUND AND OBJECTIVES
Recently, PINPOINT, a novel laparoscopic fusion indocyanine green fluorescence imaging (IGFI) system has become available for laparoscopic liver resection. This study aims to characterize fluorescence patterns of intrahepatic cholangiocarcinoma (ICC) using the negative counterstaining method in laparoscopic anatomical hepatectomies of ICC.

METHODS
Eleven consecutive patients, diagnosed with intrahepatic cholangiocarcinoma and underwent laparoscopic liver resection between April 2017 and December 2018, were retrospectively reviewed. A laparoscopic IGFI navigation system was used to characterize fluorescence patterns of ICC with intraoperative liver segment demarcation by means of negative counterstaining.

RESULTS
Fusion IGFI of ICC was successfully obtained from all 11 patients from the surgical specimens. The fluorescence patterns of ICC can be categorized into rim-type fluorescence and segmental fluorescence, depending on tumor growth. In eight patients, indocyanine green fluorescence imaging was used to identify the hepatic lobes or segments by negative counterstaining. In six cases, a valid and persistent demarcation was achieved intraoperatively.

CONCLUSION
Laparoscopic IGFI system could identify different types of ICC lesions and may facilitate real-time navigation for laparoscopic anatomic liver resection of ICC.

D000368:Aged
D000369:Aged, 80 and over
D001650:Bile Duct Neoplasms
D018281:Cholangiocarcinoma
D004396:Coloring Agents
D005240:Feasibility Studies
D005260:Female
D006801:Humans
D007208:Indocyanine Green
D007432:Intraoperative Period
D010535:Laparoscopy
D008297:Male
D008875:Middle Aged
D061848:Optical Imaging
D010865:Pilot Projects
D011300:Preoperative Care
D012189:Retrospective Studies
D013194:Staining and Labeling

intrahepatic cholangiocarcinoma
indocyanine green
fluorescence imaging
laparoscopic anatomical hepatectomies


Patients presenting with metastases: stage IV uveal melanoma, an international study.

Abstract:
OBJECTIVE
To analyse ocular and systemic findings of patients presenting with systemic metastasis.

METHODS AND ANALYSIS
It is an international, multicentre, internet-enabled, registry-based retrospective data analysis. Patients were diagnosed between 2001 and 2011. Data included: primary tumour dimensions, extrascleral extension, ciliary body involvement, American Joint Committee on Cancer (AJCC)-tumour, node, metastasis staging, characteristics of metastases.

RESULTS
Of 3610 patients with uveal melanoma, 69 (1.9%; 95% CI 1.5 to 2.4) presented with clinical metastasis (stage IV). These melanomas originated in the iris, ciliary body and choroid in 4%, 16% and 80% of eyes, respectively. Using eighth edition AJCC, 8 (11%), 20 (29%), 24 (35%), and 17 (25%) belonged to AJCC T-categories T1-T4. Risk of synchronous metastases increased from 0.7% (T1) to 1.5% (T2), 2.6% (T3) and 7.9% (T4). Regional lymph node metastases (N1a) were detected in 9 (13%) patients of whom 6 (67%) had extrascleral extension. Stage of systemic metastases (known for 40 (59%) stage IV patients) revealed 14 (35%), 25 (63%) and 1 (2%) had small (M1a), medium-sized (M1b) and large-sized (M1c) metastases, respectively. Location of metastases in stage IV patients were liver (91%), lung (16%), bone (9%), brain (6%), subcutaneous tissue (4%) and others (5%). Multiple sites of metastases were noted in 24%. Compared with the 98.1% of patients who did not present with metastases, those with synchronous metastases had larger intraocular tumours, more frequent extrascleral extension, ciliary body involvement and thus a higher AJCC T-category.

CONCLUSIONS
Though higher AJCC T-stage was associated with risk for metastases at diagnosis, even small T1 tumours were stage IV at initial presentation. The liver was the most common site of metastases; however, frequent multiorgan involvement supports initial whole-body staging.

ciliary body
Iris
choroid
imaging
retina


Orthopedic implant biomaterials with both osteogenic and anti-infection capacities and associated in vivo evaluation methods.

Abstract: Osteogenicity (i.e., properties that promote new bone formation on and around the implant) has long been a clinical requirement for most orthopedic implants. Recently, anti-infection or antibacterial properties have become critical for orthopedic implants (especially without the use of antibiotics). Ideally, orthopedic implant materials with simultaneous anti-infection and osteogenic capacities are extremely promising for orthopedic applications, but such materials are not widely available to date and have only recently been researched. In the first part of this review, numerous attractive material formulations that exhibit both antibacterial and osteogenic capacities as well as surface modification strategies that enhance such capacities are introduced. Several possible mechanisms underlying simultaneous antibacterial and osteogenic properties are also discussed. In the second part of this review, evaluation methods including animal models, analytical tools and available guidelines for assessing antibacterial and osteogenic properties of implantable materials in vivo are summarized and discussed.

Lin|Xiao|X|
Yang|Shaofeng|S|
Lai|Kalyn|K|
Yang|Huilin|H|
Webster|Thomas J|TJ|
Yang|Lei|L|

Orthopedic implants
Osteogenicity
In vivo evaluation
Anti-bacterial
Infection


Health-related quality of life and social support among Chinese patients with coronary heart disease in mainland China.

Abstract:
AIM
This study aimed to explore and identify the relationship between health-related quality of life (HRQoL) and perceived social support among Chinese patients with coronary heart disease (CHD) in mainland China.

METHODS
A descriptive correlational study was conducted with a convenience sample of 200 Chinese patients with CHD recruited from the cardiac outpatient departments of two university-affiliated hospitals in Xi'an, China. The Chinese Mandarin versions of the Short-form 36-item health survey (CM:SF-36) and the Medical Outcomes Study Social Support Survey (CM:MOS-SSS) were administered to assess HRQoL and perceived social support.

RESULTS
The results indicated that Chinese patients with CHD reported a poorer HRQoL and lower social support compared with their Western and Hong Kong counterparts. Multiple regression analyses identified four significant predictors of deteriorated physical health (increasing age, co-morbidity with heart failure or hypertension, and smoking status) and two significant predictors of poor mental health (co-morbidity with heart failure and perceived social support).

CONCLUSIONS
Health status and social support in Chinese people with CHD should be routinely assessed and, where feasible, addressed through appropriate individually tailored interventions.

Wang|Wenru|W|
Lau|Ying|Y|
Chow|Aloysius|A|
Thompson|David R|DR|
He|Hong-Gu|HG|

Health-related quality of life
social support
Chinese
heart disease


Dengue fever and bone marrow myelofibrosis.

Abstract: Myelofibrosis is characterized by reticulin and/or collagen fibrosis in the bone marrow stroma resulting in secondary cytopenia. In addition to clonal hematologic neoplasms, myelofibrosis may also develop in association with other clinical conditions, including hematological disorders, solid malignancies, Down syndrome, autoimmune diseases and others. We report the first case to our knowledge of myelofibrosis associated with dengue fever. We briefly describe dengue infections and hypothesize the causes of myelofibrosis in this condition.

Qing|Xin|X| Sun|Nora|N| Yeh|James|J| Yue|Changjun|C| Cai|Junchao|J|


The Two Main Olfactory Receptor Families in Drosophila, ORs and IRs: A Comparative Approach.

Abstract: Most insect species rely on the detection of olfactory cues for critical behaviors for the survival of the species, e.g., finding food, suitable mates and appropriate egg-laying sites. Although insects show a diverse array of molecular receptors dedicated to the detection of sensory cues, two main types of molecular receptors have been described as responsible for olfactory reception in Drosophila, the odorant receptors (ORs) and the ionotropic receptors (IRs). Although both receptor families share the role of being the first chemosensors in the insect olfactory system, they show distinct evolutionary origins and several distinct structural and functional characteristics. While ORs are seven-transmembrane-domain receptor proteins, IRs are related to the ionotropic glutamate receptor (iGluR) family. Both types of receptors are expressed on the olfactory sensory neurons (OSNs) of the main olfactory organ, the antenna, but they are housed in different types of sensilla, IRs in coeloconic sensilla and ORs in basiconic and trichoid sensilla. More importantly, from the functional point of view, they display different odorant specificity profiles. Research advances in the last decade have improved our understanding of the molecular basis, evolution and functional roles of these two families, but there are still controversies and unsolved key questions that remain to be answered. Here, we present an updated review on the advances of the genetic basis, evolution, structure, functional response and regulation of both types of chemosensory receptors. We use a comparative approach to highlight the similarities and differences among them. Moreover, we will discuss major open questions in the field of olfactory reception in insects. A comprehensive analysis of the structural and functional convergence and divergence of both types of receptors will help in elucidating the molecular basis of the function and regulation of chemoreception in insects.

Gomez-Diaz|Carolina|C|
Martin|Fernando|F|
Garcia-Fernandez|Jose Manuel|JM|
Alcorta|Esther|E|

receptors Drosophila ORs IRs chemosensation olfaction taste


Meaning before order: Cardinal principle knowledge predicts improvement in understanding the successor principle and exact ordering.

Abstract: Learning the cardinal principle (the last word reached when counting a set represents the size of the whole set) is a major milestone in early mathematics. But researchers disagree about the relationship between cardinal principle knowledge and other concepts, including how counting implements the successor function (for each number word N representing a cardinal value, the next word in the count list represents the cardinal value N + 1) and exact ordering (cardinal values can be ordered such that each is one more than the value before it and one less than the value after it). No studies have investigated acquisition of the successor principle and exact ordering over time, and in relation to cardinal principle knowledge. An open question thus remains: Is the cardinal principle a "gatekeeper" concept children must acquire before learning about succession and exact ordering, or can these concepts develop separately? Preschoolers (N = 127) who knew the cardinal principle (CP-knowers) or who knew the cardinal meanings of number words up to "three" or "four" (3-4-knowers) completed succession and exact ordering tasks at pretest and posttest. In between, children completed one of two trainings: counting only versus counting, cardinal labeling, and comparison. CP-knowers started out better than 3-4-knowers on succession and exact ordering. Controlling for this disparity, we found that CP-knowers improved over time on succession and exact ordering; 3-4-knowers did not. Improvement did not differ between the two training conditions. We conclude that children can learn the cardinal principle without understanding succession or exact ordering and hypothesize that children must understand the cardinal principle before learning these concepts.

Spaepen|Elizabet|E|
Gunderson|Elizabeth A|EA|
Gibson|Dominic|D|
Goldin-Meadow|Susan|S|
Levine|Susan C|SC|

Cardinal principle
Successor principle
Exact ordering
Successor function
Number


Cryptobia iubilans Infections in Discus Fish in Trinidad and Tobago.

Abstract: Discus (Symphysodon spp.) are costly and prized specimens in the international ornamental fish trade. The majority of discus submitted to the Aquatic Animal Health Unit at the University of the West Indies School of Veterinary Medicine for necropsy between September 2010 and September 2015 had lesions consistent with Cryptobia iubilans infection, thus prompting this study. To determine the prevalence of the flagellated gastrointestinal protozoan C. iubilans in discus fish, 32 discus were sourced from 10 suppliers, including breeders, importers, and hobbyists across Trinidad. Fish were euthanized, and the internal organs, particularly the stomach and intestine, were observed under a light microscope for characteristic granulomatous lesions and/or live C. iubilans parasites. All wet-mount slides on which granulomas were observed were also Ziehl-Neelsen acid-fast stained to presumptively exclude the presence of Mycobacterium spp., the main differential when diagnosing C. iubilans-associated granulomatous gastritis or to determine the presence of dual infections. Further histological analyses were performed on stomach and intestinal sections, and transmission electron microscopy was used to confirm the parasite in stomach sections. The prevalence of C. iubilans infection was found to be 81.3%, and the prevalence of presumptive dual infections with Mycobacterium spp. was found to be 21.9%. To the best of our knowledge, this is the first documented study of C. iubilans infections in the wider Caribbean region.

Phillips Savage|Ayanna Carla N|ACN|
Suepaul|Rod|R|
Smith|Stephen A|SA|
Ali|Arianne|A|
Ramcharan|Nirveeta|N|
Ramnarine|Shivana|S|
Sookdeo|Risha|R|

Cryptobia iubilans
Discus
Symphysodon spp.
Mycobacterium spp.
Caribbean


Evidence for a long-term protection of wheel-running exercise against cocaine psychomotor sensitization in adolescent but not in adult mice.

Abstract: Rodents housed with a running wheel can exhibit attenuated cocaine seeking and cocaine-induced psychomotor activation. However, the longevity of such a protection and the influence of the developmental stage during which exercise is displayed received little attention. Here, females and males C57BL/6J mice, aged 28 (adolescents) or 77 (adults) days were housed with (n = 56) or without (n = 28) a running wheel. After 3 weeks in these conditions, half of the exercised mice were deprived of their wheel (n = 28) whereas the other half and the sedentary mice were kept in their respective environments. After 3 additional weeks, mice were tested for initiation of psychomotor sensitization to 9 once-daily intraperitoneal injections of 8 mg/kg cocaine (following 2 drug-free sessions). The expression of sensitization was assessed on a single session 30 days after the last cocaine injection. Continuously exercised mice (wheel throughout experimentation) were less responsive to the initiation and the expression of cocaine effects, regardless of the gender and the developmental period during which exercise was introduced. A 3-week regimen of wheel-running exercise during adolescence (from 28 to 50 days of age) attenuated in later life the initiation and the expression of sensitization in females and its expression in males. In contrast, females and males previously exercised as adults (from 77 to 99 days of age) and their corresponding sedentary counterparts exhibited indiscernible levels of initiation and expression of sensitization. These results suggest that early-life period such as adolescence may be particularly sensitive to the long-term protection of exercise against cocaine vulnerability.

Long-term
Wheel-running
Adolescence
C57BL/6J
Adulthood
Cocaine sensitization


The move from accuracy studies to randomized trials in PET: current status and future directions.

Abstract:
UNLABELLED
Since the influential study by van Tinteren et al. published in The Lancet in 2002, there have been an increasing number of diagnostic randomized controlled trials (RCTs) investigating the benefit of PET. If they provide valid and useful information on the benefit, these studies can play an important role in informing guideline developers and policy makers. Our aim was to investigate how far the nuclear medicine community has come on its way from accuracy studies to RCTs and which issues we have to take into account in planning future studies.

METHODS
We conducted a systematic review of diagnostic randomized trials, in which PET was applied in only one arm. We covered published studies as well as registered unpublished and planned studies. We considered 3 quality indicators related to the usefulness of a trial to generate evidence for a clinical benefit: use of patient-important outcome, sufficient sample size, and current standard as comparator.

RESULTS
Fourteen published and 15 planned studies were identified. Five of the published studies and 12 of the planned studies did not use a patient-important outcome. Sample sizes were often so small that a significant result could be expected only under the assumption of a substantial reduction in the event rate. Comparators typically reflected the current standard.

CONCLUSION
If we consider the traditional areas of primary diagnosis, staging, and follow-up, then the number and quality of RCTs on PET is currently not sufficient to provide a major source for evidence-based decisions on the clinical benefit of PET. There will also be a future need in these traditional areas to deduce the clinical benefit of PET from the results of accuracy studies. The situation may be more favorable for the areas of treatment planning and response evaluation. Choice of patient-important outcomes and sufficient sample sizes are crucial issues in planning RCTs to demonstrate the clinical benefit of using PET.

Siepe|Bettina|B|
Hoilund-Carlsen|Poul Flemming|PF|
Gerke|Oke|O|
Weber|Wolfgang A|WA|
Motschall|Edith|E|
Vach|Werner|W|

D016032:Randomized Controlled Trials as Topic

diagnostic randomized controlled trial
systematic review
patient-important outcome
positron emission tomography


Away from home: the brain of the wandering mind as a model for schizophrenia.

Abstract:
BACKGROUND
The notion that schizophrenia patients' (SZ) sense of being detached from external reality is a core feature of the disorder has existed since the early days of its recognition and is still largely emphasized in first person accounts of SZs; however, its etiology, neurophysiological mechanism, and significance for clinical symptoms are unclear. Mind-wandering is a ubiquitous experience of being detached from reality, the underlying neural mechanism of which closely resembles the brain in a resting-state.

METHODS
The resting-state functional magnetic resonance imaging data of 33 SZs and 33 matched healthy controls (CNT) were acquired. All subjects answered the mind-wandering subscale of the Imaginal Processing Inventory Questionnaire. Functional connectivity maps were constructed using 82 regions of interest comprising default-mode, salience, and frontoparietal networks.

RESULTS
SZs exhibit significantly higher mind-wandering frequency relative to CNT. The elevated mind-wandering frequency in SZs significantly correlated with positive and general symptom severity. The mind-wandering frequency was inversely correlated with connectivity degree in the right ventromedial prefrontal cortex, the brain region involved in self-experience in SZs.

CONCLUSIONS
Our results suggest that self-disturbances in SZs can explain SZs' disconnection to the external world, leading to the manifestation of positive psychotic symptoms. This study demonstrates strong preliminary evidence that contributes significantly to resolve the complex relationship between self, world, and the brain of SZs, which may lie at the "core" of psychotic experiences.

Shin|Da-Jung|DJ|
Lee|Tae Young|TY|
Jung|Wi Hoon|WH|
Kim|Sung Nyun|SN|
Jang|Joon Hwan|JH|
Kwon|Jun Soo|JS|

D001289:Attention Deficit Disorder with Hyperactivity

D011569:Psychiatric Status Rating Scales

Schizophrenia
Mind-wandering
Functional connectivity
Resting-state fMRI
Self-disorder


Neuroanesthetic considerations for emergent extracranial surgeries: What to know?

Abstract: Neuroanaesthetic considerations in non neurosurgical cases are utmost important for the optimal management of such cases. These considerations become even more challenging in patients undergoing emergency surgeries. We have highlighted the neuroanesthetic considerations for three broad categories. The two most important considerations in this type of surgery will be the avoidance of secondary brain insult and maintenance of optimal cerebral perfusion pressure.

Chowdhury|Tumul|T|
Cappellani|Ronald B|RB|
Daya|Jayesh|J|

Extracranial
anesthesia
brain tumor
pregnant
trauma