Do Large Uterine Fibroids Impact Pregnancy Outcomes?

Abstract:
Objectives
We sought to assess the prevalence of fibroids complicating pregnancy among Omani women who delivered and were followed-up at Sultan Qaboos University Hospital (SQUH) and correlate the presence of large fibroids (> 5 cm) with maternal and neonatal outcomes.

Methods
This retrospective cohort study was conducted at the Department of Obstetrics and Gynecology, SQUH, from 1 January 2011 to 31 December 2016. Demographic data included maternal age, gravidity, parity, body mass index (BMI), and history of preterm delivery. Ultrasonographic data included the total number of fibroids, number of fibroids > 5 cm in diameter, and location. The main outcomes measured were preterm delivery, preterm premature rupture of membranes (PPROM), malpresentation, intrauterine growth restriction (IUGR), mode of delivery, postpartum hemorrhage, retained placenta, and cesarean myomectomy. Fetal outcomes included birth weight and Apgar score. We used the chi-square test and t-test to calculate significant outcomes.

Results
The total number of deliveries over the study period was 24 800. Among these, 62 women had fibroids complicating pregnancy, giving an overall prevalence of 0.3%. Of the 62 women with documented uterine fibroids, 41 had fibroids > 5 cm in diameter and formed the study group, while the control group included 88 women with no fibroids and normal singleton pregnancies. The mean age, parity, BMI, and history of preterm delivery were comparable. The mean age of the study group was 32.6 years. There was no statistically significant difference in obstetric outcomes between the study and control group in terms of preterm labor (p =0.381), PPROM (p =0.536), malpresentation (p =0.237), IUGR (p =0.059), and retained placenta (p =0.296). Postpartum hemorrhage was significantly higher in the study group (p =0.018), the commonest cause was uterine atony (p =0.007). Women with large fibroids had a significantly increased cesarean section rate (p =0.002), the main indications were obstructed labor and failure to progress (62.5%). Five of the 44 women in the study group (12.8%) underwent cesarean myomectomy. Regarding neonatal outcomes, a statistically significant difference was noted in the Apgar scores.

Conclusions
Fibroids measuring > 5 cm in diameter are more likely to cause obstetric complications and are associated with higher cesarean rates. Pre-conception myomectomy is recommended for women with large fibroids.

Al Sulaimani|Ruqaiya|R|
Machado|Lovina|L|
Al Salmi|Munira|M|

Preterm Premature Rupture of the Membranes


Natural Ingredients Common in the Trás-os-Montes Region (Portugal) for Use in the Cosmetic Industry: A Review about Chemical Composition and Antigenotoxic Properties.

Abstract: The natural cosmetics market has grown since consumers became aware of the concept of natural-based ingredients. A significant number of cosmetics have an ecological impact on the environment and carry noxious and chemically potent substances. Thus, the use of natural and organic cosmetics becomes increasingly important since it is clear that topical treatment with cosmeceuticals can help improve skin rejuvenation. A substantial investigation into the benefits that fruits and plants can bring to health is required. Studies have shown that antigenotoxic properties are linked to anti-aging properties. Several studies have shown potential antigenotoxicity in natural ingredients such as Almonds (Prunus dulcis), Elderberry (Sambucus nigra), Olives (Olea europaea), and Grapes (Vitis vinifera). This review presents an overview of research conducted on these natural ingredients, the most common in the Northeast of Portugal. This region of Portugal possesses the most organic farmers, and ingredients are easily obtained. The Northeast of Portugal also has climatic, topographic, and pedological differences that contribute to agricultural diversity.

natural ingredients
cosmetics
antigenotoxic
almonds
elderberry
olives
grapes
genotoxicity


Enhancing cytochrome P450-mediated non-natural cyclopropanation by mutation of a conserved second-shell residue.

Abstract: Engineered cytochrome P450s are emerging as powerful synthetic tools due to their ability catalyze non-native metallocarbenoid and -nitrenoid insertion reactions. P450-mediated cyclopropanation has garnered particular interest due to the high selectivity demonstrated by engineered scaffolds and their application towards the synthesis of therapeutic agents. We previously reported that mutation of a conserved, first-shell heme-ligating Cys to Ser led to significant improvements in cyclopropanation activity in a model enzyme, P450BM3h . Here, we demonstrate that mutation of a ubiquitously conserved second-shell Phe (F393) to His or Ala, provides complementary increases in the P450 heme reduction potential and conversion to cyclopropanation products when compared to first-shell Cys to Ser mutations. Furthermore, we show that these mutations confer improved non-natural catalysis in 4 diverse P450 scaffolds.

Gober|Joshua G|JG|
Rydeen|Amy E|AE|
Schwochert|Timothy D|TD|
Gibson-O'Grady|Evan J|EJ|
Brustad|Eric M|EM|0000-0002-7031-5433

cyclopropanation
cytochrome P450
non-natural biocatalysis
protein engineering
second-shell mutation


A Rational Designed Novel Bispecific Antibody for the Treatment of GBM.

Abstract: Epidermal growth factor receptor variant III (EGFRvIII) is highly and specifically expressed in a subset of lethal glioblastoma (GBM), making the receptor a unique therapeutic target for GBM. Recently, bispecific antibodies (BsAbs) have shown exciting clinical benefits in cancer immunotherapy. Here, we report remarkable results for GBM treatment with a BsAb constructed by the "BAPTS" method. The BsAb was characterized through LC/MS, SEC-HPLC, and SPR. Furthermore, the BsAb was evaluated in vitro for bioactivities through FACS, antigen-dependent T-cell-mediated cytotoxicity, and a cytokine secretion assay, as well as in vivo for antitumor activity and pharmacokinetic (PK) parameters through immunodeficient NOD/SCID and BALB/c mouse models. The results indicated that the EGFRvIII-BsAb eliminated EGFRvIII-positive GBM cells by recruiting and stimulating effector T cells secreting cytotoxic cytokines that killed GBM cells in vitro. The results demonstrated the antitumor potential and long circulation time of EGFRvIII-BsAb in NOD/SCID mice bearing de2-7 subcutaneously heterotopic transplantation tumors and BALB/c mice. In conclusion, our experiments in both in vitro and in vivo have shown the remarkable antitumor activities of EGFRvIII-BsAb, highlighting its potential in clinical applications for the treatment of GBM. Additional merits, including a long circulation time and low immunogenicity, have also made the novel BsAb a promising therapeutic candidate.

Sun|Rui|R| Zhou|Yuexian|Y| Han|Lei|L| Pan|Zhidi|Z| Chen|Jie|J| Zong|Huifang|H|0000-0002-1498-0631 Bian|Yanlin|Y| Jiang|Hua|H| Zhang|Baohong|B|0000-0001-6453-961X Zhu|Jianwei|J|

bispecific antibody
GBM
EGFRvIII
split intein


Elucidating functional context within microarray data by integrated transcription factor-focused gene-interaction and regulatory network analysis.

Abstract: Microarrays do not yield direct evidence for functional connections between genes. However, transcription factors (TFs) and their binding sites (TFBSs) in promoters are important for inducing and coordinating changes in RNA levels, and thus represent the first layer of functional interaction. Similar to genes, TFs act only in context, which is why a TF/TFBS-based promoter analysis of genes needs to be done in the form of gene(TF)-gene networks, not individual TFs or TFBSs. In addition, integration of the literature and various databases (e.g. GO, MeSH, etc) allows the adding of genes relevant for the functional context of the data even if they were initially missed by the microarray as their RNA levels did not change significantly. Here, we outline a TF-TFBSs network-based strategy to assess the involvement of transcription factors in agonist signaling and demonstrate its utility in deciphering the response of human microvascular endothelial cells (HMEC-1) to leukemia inhibitory factor (LIF). Our strategy identified a central core of eight TFs, of which only STAT3 had previously been definitively linked to LIF in endothelial cells. We also found potential molecular mechanisms of gene regulation in HMEC-1 upon stimulation with LIF that allow for the prediction of changes of genes not used in the analysis. Our approach, which is readily applicable to a wide variety of expression microarray and next generation sequencing RNA-seq results, illustrates the power of a TF-gene networking approach for elucidation of the underlying biology.

Werner|Thomas|T|
Dombrowski|Susan M|SM|
Zgheib|Carlos|C|
Zouein|Fouad A|FA|
Keen|Henry L|HL|
Kurdi|Mazen|M|
Booz|George W|GW|

D020411:Oligonucleotide Array Sequence Analysis

transcription factors
high-throughput (HT) approaches
microarray data analysis
transcription factor binding sites
transcription factor-gene networking


Publication practices of sub-Saharan African Cochrane authors: a bibliometric study.

Abstract:
INTRODUCTION
Cochrane Africa (https://africa.cochrane.org/) aims to increase Cochrane reviews addressing high priority questions in sub-Saharan Africa (SSA). Researchers residing in SSA, despite often drawing on Cochrane methods, training or resources, conduct and publish systematic reviews outside of Cochrane. Our objective was to investigate the extent to which Cochrane authors from SSA publish Cochrane and non-Cochrane reviews.

METHODS
We conducted a bibliometric study of systematic reviews and overviews of systematic reviews from SSA, first by identifying SSA Cochrane authors, then retrieving their first and last author systematic reviews and overviews from PubMed (2008 to April 2019) and using descriptive analyses to investigate the country of origin, types of reviews and trends in publishing Cochrane and non-Cochrane systematic reviews over time. To be eligible, a review had to have predetermined objectives, eligibility criteria, at least two databases searched, data extraction, quality assessment and a first or last author with a SSA affiliation.

RESULTS
We identified 657 Cochrane authors and 757 eligible systematic reviews. Most authors were from South Africa (n=332; 51%), followed by Nigeria (n=126; 19%). Three-quarters of the reviews (71%) were systematic reviews of interventions. The intervention reviews were more likely to be Cochrane reviews (60.3% vs 39.7%). Conversely, the overviews (23.8% vs 76.2%), qualitative reviews (14.8% vs 85.2%), diagnostic test accuracy reviews (16.1% vs 83.9%) and the 'other' reviews (11.1% vs 88.9%) were more likely to be non-Cochrane reviews. During the study period, the number of non-Cochrane reviews increased more than the number of Cochrane reviews. About a quarter of the reviews covered infectious disease topics.

CONCLUSION
Cochrane authors from SSA are increasingly publishing a diverse variety of systematic reviews and overviews of systematic reviews, often opting for non-Cochrane journals.

health informatics
human resource management
statistics & research methods


A two-stage approach to genetic risk assessment in primary care.

Abstract: Genetic risk prediction models such as BRCAPRO are used routinely in genetic counseling for identification of potential BRCA1 and BRCA2 mutation carriers. They require extensive information on the counselee and her family history, and thus are not practical for primary care. To address this gap, we develop and test a two-stage approach to genetic risk assessment by balancing the tradeoff between the amount of information used and accuracy achieved. The first stage is intended for primary care wherein limited information is collected and analyzed using a simplified version of BRCAPRO. If the assessed risk is sufficiently high, more extensive information is collected and the full BRCAPRO is used (stage two: intended for genetic counseling). We consider three first-stage tools: BRCAPROLYTE, BRCAPROLYTE-Plus, and BRCAPROLYTE-Simple. We evaluate the two-stage approach on independent clinical data on probands with family history of breast and ovarian cancers, and BRCA genetic test results. These include population-based data on 1344 probands from Newton-Wellesley Hospital and mostly high-risk family data on 2713 probands from Cancer Genetics Network and MD Anderson Cancer Center. We use discrimination and calibration measures, appropriately modified to evaluate the overall performance of a two-stage approach. We find that the proposed two-stage approach has very limited loss of discrimination and comparable calibration as BRCAPRO. It identifies a similar number of carriers without requiring a full family history evaluation on all probands. We conclude that the two-stage approach allows for practical large-scale genetic risk assessment in primary care.

Biswas|Swati|S|
Atienza|Philamer|P|
Chipman|Jonathan|J|
Blackford|Amanda L|AL|
Arun|Banu|B|
Hughes|Kevin|K|
Parmigiani|Giovanni|G|

D020022:Genetic Predisposition to Disease


The Effect of Interactions of Single Nucleotide Polymorphisms of APOA1/APOC3 with Food Group Intakes on the Risk of Metabolic Syndrome.

Abstract:
BACKGROUND
The aim of this study was to examine the interaction of dietary food groups and genetic variants of APOA1/APOC3, relative to Metabolic Syndrome (MetS) risk in adults.

METHODS
In this matched nested case-control study, 414 MetS subjects and 414 controls were selected from among participants of Tehran Lipid and Glucose Study. Dietary intake was assessed with the use of a valid and reliable semi-quantitative food frequency questionnaire. Single Nucleotide Polymorphisms (SNPs), APOA1 (rs670, -75G>A and rs5069, +83C>T/APOC3 rs5128 C3238>G) were genotyped by the conventional polymerase chain reaction and restriction fragment length polymorphism.

RESULTS
The mean (SD) of age was 40.7 (13) and 41.2 (13) years in male cases and controls versus 44.0 (11) and 44.0 (12) years in female case and controls. A significant interaction between intake quartiles of the sugar group and APOA1 combined group (GA+AA/CT+TT) SNPs was found; The ORs for these genotype carriers were (1, 0.44, 0.36, 0.23; P trend<0.001) in quartiles of intake, relative to other combined genotypes (P interaction=0.02). MetS risk appeared to be increased significantly in higher quartiles of sweet beverages and fish intakes in the GA+AA/CT+TT/CC genotypes of APOA1/APOC3 SNPs, compared to other genotypes (P interaction=0.01). The combined effect of genotypes of APOC3/APOA1 showed further decrease in MetS risk in higher quartiles of sugar group intakes (OR: 1, 0.24, 0.26, 0.14, P trend=0.001) relative to other combinations (P interaction=0.008).

CONCLUSION
Results obtained demonstrate that some dietary food groups (sugar, fish, and sweet beverages) modulate the effect of APOA1/APOC3 SNPs in relation to MetS risk.

Hosseini-Esfahani|Firoozeh|F|
Mirmiran|Parvin|P|
Daneshpour|Maryam S|MS|
Mottaghi|Azadeh|A|
Azizi|Fereidoun|F|

Food
Metabolic Syndrome
Genetic polymorphisms


Multigene engineering of medium-chain fatty acid biosynthesis in transgenic Arabidopsis thaliana by a Cre/LoxP multigene expression system.

Abstract: Medium-chain fatty acids (MCFAs) are an ideal feedstock for biodiesel and a range of oleochemical products. In this study, different combinations of CnFATB3, CnLPAAT-B and CnKASI from coconut (Cocos nucifera L.) were coexpressed in transgenic Arabidopsis thaliana by a Cre/LoxP multigene expression system. Transgenic lines expressing different combinations of these genes were designated FL (FatB3 + LPAAT-B), FK (FatB3 + KASI) and FLK (FatB3 + LPAAT-B + KASI). The homozygous seeds of transgenic Arabidopsis thaliana expressing high levels of these genes were screened, and their fatty acid composition and lipid contents were determined. Compared with its content in wild-type A. thaliana, the lauric acid (C12:0) content was significantly increased by at least 395%, 134% and 124% in FLK, FL and FK seeds, respectively. Meanwhile, the myristic acid (C14:0) content was significantly increased by at least 383%, 106% and 102% in FL, FLK and FK seeds, respectively, compared to its level in wild-type seeds. Therefore, the FLK plants exhibited the best effects to increase the level of C12:0, and FL expressed the optimal combination of genes to increase the level of 14:0 MCFA.

Zheng|Yusheng|Y| Chen|Lizhi|L| Zhu|Zhiyong|Z| Li|Dongdong|D|0000-0003-4006-3551 Zhou|Peng|P|

Medium-chain fatty acids (MCFAs)
CnFatB3
CnLPAAT-B
CnKASI
Combinatorial expression effect
Cre/lox combination system


The Impact of COVID-19 Pandemic on Lung Cancer Community.

Abstract: Since the outbreak of 2019 novel coronavirus disease (COVID-19) induced by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pandemic has become a global catastrophe. Patients with cancer especially lung cancer are more vulnerable and susceptible to get infected by the virus SARS-CoV-2. The overwhelming impact of COVID-19 on lung cancer community may result in rise of the incidence and mortality of lung cancer. It would become more obvious in future retrospective studies. Lung cancer patients are believed at higher risk of COVID-19 due to immunosuppression and should be protected by vaccination with priority. Better understanding of SARS-CoV-2 could help develop more effective vaccines to eradicate this disease in the near future.


Critical role of FANCC in JAK2 V617F mutant-induced resistance to DNA cross-linking drugs.

Abstract: A point mutation (V617F) of tyrosine kinase Janus kinase 2 (JAK2) is found in the majority of patients with myeloproliferative neoplasms (MPNs) and an aberrant signaling pathway induced by constitutively active JAK2 V617F mutant is a hallmark of MPNs. Cells transformed by JAK2 V617F mutant exhibited resistance to anti-cancer drugs such as cisplatin (CDDP), mitomycin C (MMC) and bleomycin (BLM). We first found that the expression of FANCC, a member of the Fanconi anemia (FA) proteins, was significantly induced by JAK2 V617F mutant through activation of signal transducers and activators of transcription 5 (STAT5). In addition, monoubiqitination and foci formation of FANCD2, which are critical for activation of the FA pathway, were increased in cells transformed by JAK2 V617F mutant, compared to cells expressing wild-type JAK2. Interestingly, knockdown of FANCC in cells expressing JAK2 V617F mutant induced not only the reduction of monoubiqitination and foci formation of FANCD2 but also the enhancement of sensitivity to DNA damage induced by CDDP and MMC but not BLM. Taken together, FANCC is most likely to be critical for resistance to DNA cross-linking drug-induced DNA damage in cells transformed by JAK2 V617F mutant.

Ueda|Fumihito|F| Sumi|Kazuya|K| Tago|Kenji|K| Kasahara|Tadashi|T| Funakoshi-Tago|Megumi|M|

D052218:Fanconi Anemia Complementation Group C Protein

D015972:Gene Expression Regulation, Neoplastic

reverse transcriptase-polymerase chain reaction

P P P P P P P P P P P P U U U U U U U U U U U R M U U U P U U U


Network analysis reveals strongly localized impacts of El Niño.

Abstract: Climatic conditions influence the culture and economy of societies and the performance of economies. Specifically, El Niño as an extreme climate event is known to have notable effects on health, agriculture, industry, and conflict. Here, we construct directed and weighted climate networks based on near-surface air temperature to investigate the global impacts of El Niño and La Niña. We find that regions that are characterized by higher positive/negative network "in"-weighted links are exhibiting stronger correlations with the El Niño basin and are warmer/cooler during El Niño/La Niña periods. In contrast to non-El Niño periods, these stronger in-weighted activities are found to be concentrated in very localized areas, whereas a large fraction of the globe is not influenced by the events. The regions of localized activity vary from one El Niño (La Niña) event to another; still, some El Niño (La Niña) events are more similar to each other. We quantify this similarity using network community structure. The results and methodology reported here may be used to improve the understanding and prediction of El Niño/La Niña events and also may be applied in the investigation of other climate variables.

Fan|Jingfang|J|
Meng|Jun|J|
Ashkenazy|Yosef|Y|
Havlin|Shlomo|S|
Schellnhuber|Hans Joachim|HJ|


Relevance of serum sclerostin concentrations in critically ill patients.

Abstract:
PURPOSE
Sclerostin is a negative regulator of bone metabolism and associated with chronic morbidities. We investigated circulating sclerostin in critically ill patients.

METHODS
A total of 264 patients (170 with sepsis) were studied prospectively upon admission to the medical intensive care unit (ICU) and on day 7. Patients' survival was followed for up to 3 years.

RESULTS
Sclerostin serum levels were significantly elevated in critically ill patients at ICU admission compared with 99 healthy controls. Unlike in healthy controls, sclerostin did not depend on sex or age of ICU patients. Sclerostin was associated with disease severity, independent of the presence of sepsis. Sclerostin levels increased during the first week of treatment at the ICU but were not a predictor of mortality. Sclerostin was elevated in patients with preexisting chronic kidney disease or liver cirrhosis, but was not related to diabetes, obesity, or cardiovascular disease. Circulating sclerostin in ICU patients correlated with biomarkers reflecting renal, hepatic and cardiac dysfunction, and biomarkers reflecting bone metabolism.

CONCLUSION
Serum sclerostin concentrations are significantly elevated in critically ill patients, linked to renal or hepatic organ failure, and associated with bone resorption markers, supporting its value as a potential tool for the assessment of ICU-related metabolic bone disease.

Koch|Alexander|A| Weiskirchen|Ralf|R| Ludwig|Sebastian|S| Buendgens|Lukas|L| Bruensing|Jan|J| Yagmur|Eray|E| Baeck|Christer|C| Herbers|Ulf|U| Trautwein|Christian|C| Tacke|Frank|F|

D048868:Adaptor Proteins, Signal Transducing

Sclerostin
Bone metabolism
Sepsis
Cirrhosis
Organ failure
Prognosis


A stabilizer-free and organic solvent-free method to prepare 10-hydroxycamptothecin nanocrystals: in vitro and in vivo evaluation.

Abstract: 10-Hydroxycamptothecin (10-HCPT) is a promising anticancer drug with a wide spectrum of antitumor activities. Due to its poor solubility, the carboxylate form that shows high water solubility but minimal anticancer activity and pharmacokinetic defects is used in the marketed 10-HCPT injections, resulting in its limited clinical application. To develop a simple, safe, and highly effective drug delivery system, a modified acid-base microprecipitation combined with a high-pressure homogenization technique was adopted to prepare 10-HCPT nanocrystals. Neither organic solvents nor stabilizers were employed throughout the preparation process. The in vitro and in vivo performances of the resulting10-HCPT nanocrystals were investigated systematically. The nanocrystals were spherical with a small size of ~130 nm, and the actual drug-loading content was as high as 75%. The nanocrystals displayed a sustained release pattern and were proven to have a higher cell uptake and antiproliferative activity than the 10-HCPT injections. The 10-HCPT nanocrystals also showed enhanced drug accumulation in tumors and better anticancer efficacy in 4T1-bearing mice. In summary, the 10-HCPT nanocrystals prepared in this study seem to be a promising delivery system for a new form of 10-HCPT dosages.

Yang|Xiaofeng|X| Liu|Yingying|Y| Zhao|Yanna|Y| Han|Meihua|M| Guo|Yifei|Y| Kuang|Haixue|H| Wang|Xiangtao|X|

10-hydroxycamptothecin
drug delivery
4T1 cells
high drug payload
poloxamer 188


What Is Your Faction? Multidimensional Evidence for the Divergent Series As the Basis for a New Model of Personality and Work Life.

Abstract: Introduction: The successful "Divergent" sci-fi trilogy by writer Veronica Roth portrays a dystopian and post-apocalyptic society where the population is divided into five groups called "Factions," each with a specific social role and associated to a specific set of psychological traits. Though fictional, such typology is compelling and may provide a significant contribution to personality studies. Objectives: To investigate the accuracy of the classification of psychological and sociocultural traits into five Factions as described in Divergent and their potential practical usefulness for understanding work life choices and experiences in organizations. Method: A total of 217 Brazilian adult men and women of various ages, socioeconomic status and ethnicities were submitted to measures of several psychological and sociocultural variables, as well as of how strongly they supposedly manifest each Faction. The resulting dataset was studied using Smallest Space Analysis (SSA) and Facet Theory. Results: The Factions were shown not only to be associated to psychological variables in ways consistent with the descriptions from Divergent, but also to be related to specific aspects of one's work life in organizations. Conclusion: The five Factions conceived by Roth appear to constitute an original set of constructs that are psychologically valid and, at the same time, of practical use in predicting work life choices and experiences. This justifies engaging in future empirical and theoretical work toward a new scientific model of potential practical value.

work
fiction
Facet Theory
Divergent trilogy
personality dimensions


Scaling Echocardiographic Cardiac Dimensions to Body Size: A Bayesian Analysis in Healthy Men and Women.

Abstract:
BACKGROUND
Proper scaling of cardiac dimensions is of paramount importance in making correct decisions in clinical cardiology. The usual normalization of cardiac dimensions to overall body size assumes an isometric relationship. We sought to investigate these relationships to obtain the best allometric coefficient (AC) for scaling.

METHODS
Ninety-seven healthy volunteers were included. The dimensions to be scaled were the left atrial volume, the end-diastolic and end-systolic left ventricular volumes, and the diameter of the tricuspid annulus. A Bayesian statistical analysis was applied with isometric coefficients as priors.

RESULTS
The linear correlations between cardiac dimensions and body size were modest, ranging from 0.12 (-0.10-0.32) for the left atrial volume and height to 0.70 (0.58-0.80) for the end-diastolic volume and height. The ACs varied across the different cardiac dimensions and body size measurements. For the best linear relationships, the isometric coefficients were outside the 95% highest density interval of the posterior distribution for the left atrial volume-weight (AC: 0.7; 0.4-0.9) and end-diastolic volume-height (AC: 2.3; 1.7-2.9), whereas they were different from 1 for the left atrial volume-weight, end-diastolic volume, and diameter of the tricuspid annulus-body surface area (AC: 0.6; 0.3-0.8). Not scaling the cardiac dimensions to their corresponding ACs can lead to important errors in size estimations of cardiac structure.

CONCLUSIONS
The ACs found in this study are somewhat different from the corresponding isometric coefficients and often different from 1. This finding should be considered when normalizing cardiac structures to body size when making clinical decisions.

Scaling
Cardiac dimensions
Size
Allometry


Giant solitary fibrous tumor of the pleura.

Abstract: Solitary fibrous tumors are rare mesenchymal tumors accounting for <5% of all neoplasms in the pleura and other sites. A 45-year-old man reported to us with cough and dyspnea. Radiological investigations revealed a giant mass displacing the mediastinum to the left. The tumor weighing 3.0 kg was successfully resected via a right thoracotomy. Histology and immunohistochemistry confirmed a benign tumor. Recurrence and malignant transformation of these benign tumors have been reported. Our patient has been followed up for 4 years with no recurrence.

Ludhani|Prakash Manoharlal|PM|
Anathakrishnan|Radha|R|
Muthubaskaran|Venkatadevanathan|V|
Chandrasekar|Padmanabhan|P|
Muralidharan|Srinivasan|S|

Solitary fibrous tumor
Pleural neoplasms
pleural


Cultures that collide: an ethnographic study of the introduction of a palliative care consultation team on acute wards.

Abstract:
BACKGROUND
Acute care and palliative care (PC) are described as different incompatible organisational care cultures. Few studies have observed the actual meeting between these two cultures. In this paper we report part of ethnographic results from an intervention study where a palliative care consultation team (PCCT) used an integrative bedside education approach, trying to embed PC principles and interventions into daily practice in acute wards.

PURPOSE
To study the meeting and interaction of two different care cultures, palliative care and curative acute wards, when a PCCT introduces consulting services to acute wards regarding end-of-life palliative care, focusing on the differences between the cultures.

METHODS
An ethnographic study design was used, including observations, interviews and diary entries. A PCCT visited acute care wards during 1 year. The analysis was inspired by Spradleys ethnography.

RESULTS
Three themes were found: 1) Anticipations meets reality; 2) Valuation of time and prioritising; and 3) The content and creation of palliative care.

CONCLUSION
There are many differences in values, and the way PC are provided in the acute care wards compared to what a PCCT expects. The didactic challenges are many and the PC require effort.

Friedrichsen|Maria|M| Hajradinovic|Yvonne|Y| Jakobsson|Maria|M| Brachfeld|Kerstin|K| Milberg|Anna|A|

D064946:Hospice and Palliative Care Nursing

Palliative care consultation team
Acute wards
End-of-life care
Hospital
Organisational culture


Rational enhancement of enzyme-catalyzed enantioselective reaction by construction of recombinant enzymes based on additive strategy.

Abstract: A rational enhancement of kinetic resolution process for producing (S)-N-(2-ethyl-6-methylphenyl) alanine from racemic methyl ester using lipase B from Candida antarctica (CalB) was investigated. With the benefit results that lipase CalB-catalyzed reactions can be effectively regulated using amino acids (such as histidine and lysine) as additives, CalBs modified (mCalBs) by n-histidines at the N terminal and n-lysines at the C terminal were constructed and expressed. The results show that both soluble and precipitated mCalBs can effectively catalyze the hydrolysis reaction without adding any extra additives. The enantioselective ratio (E value) of soluble and precipitated mCalBs could be improved from 12.1 to 20.3, which were higher than that (E value was only 10.2) of commercial Novozym 435 (immobilized CalB). The study indicated that the amino acid-rich molecules introduced on lipase CalB can produce positive effects on enantioselectivity of enzyme. It provides unusual ideas for reasonable regulation of enzyme-catalyzed reactions.

D002384:Catalysis
D004800:Enzymes, Immobilized
D005656:Fungal Proteins
D008049:Lipase
D000072417:Protein Domains
D011994:Recombinant Proteins

Enantioselective reaction
Amino acid additives
Enhancement of enantioselectivity
Recombinant candida antarctica lipase B


Buruli ulcers in a Spanish aid worker after a stay in Peru.

Abstract: Buruli ulcer (BU) is a chronic and destructive infection of the skin and soft tissues caused by Mycobacterium ulcerans. Recently, population flows have triggered the appearance of several sporadic cases of BU in non-endemic countries. This represents a significant diagnostic challenge for clinicians and microbiologists. We describe the first case of BU imported to Spain. The patient was a Spanish woman who had stayed 5 months in the jungle of Peru.

Guerra Laso|Jose Manuel|JM|
Nebreda Mayoral|Teresa|T|
Palacios Gutiérrez|Juan José|JJ|
Samaniego González|Élia|É|
Rodríguez Martín|Bárbara|B|
Barrio Rodríguez|Leticia|L|
Alonso Orcajo|Nieves|N|
Magaz García|Elena|E|
Stinear|Timothy|T|
Buultjens|Andrew H|AH|
Pérez Molina|Jose Antonio|JA|

Buruli ulcer
Mycobacterium ulcerans
Whole genome sequencing


Preclinical and clinical implications of TERT promoter mutation in glioblastoma multiforme.

Abstract: The promoter region of the telomerase reverse transcriptase gene (TERT) is mutated in a subpopulation of patients with glioblastoma multiforme (GBM). In the present study, preclinical and clinical implications of the mutation were analyzed in 25 GBMs to evaluate its utility as a therapeutic target. Associations between the TERT promoter mutation and a number of preclinical/clinical characteristics were analyzed. Notably, the TERT promoter mutation was identified in 92.3% of GBMs where dissociated cells revealed in vitro sphere formation capacity; while the TERT promoter mutation was identified in 33.3% of GBMs without in vitro sphere formation capacity (P=0.004). In addition, this significantly increased mutation rate was observed in GBMs with in vivo tumorigenic potential (80% vs. 0%; P=0.004). Furthermore, patients with GBM exhibiting the TERT promoter mutation demonstrated significantly decreased overall survival rate compared with patients lacking this mutation (81.7 vs. 152.6 weeks; P=0.026). The results of the present study indicated that the TERT promoter mutation is associated with the self-renewal capacity of GBM cells and clinical aggressiveness of GBMs, which may be translated to a targeting therapy against TERT to inhibit the self-renewal of GBM cells.

Jeong|Da Eun|DE|
Woo|Seon Rang|SR|
Nam|Hyun|H|
Nam|Do-Hyun|DH|
Lee|Jae-Ho|JH|
Joo|Kyeung Min|KM|

telomerase reverse transcriptase promoter mutation


Detection of Non-Small Lung Cell Carcinoma-Associated Genetic Alterations Using a NanoString Gene Expression Platform Approach.

Abstract: In non-small cell lung cancer (NSCLC), mutation detection and fusion gene status are treatment predictive and, hence, key factors in clinical management. Lately, alternate splicing variants of MET have gained focus as NSCLC tumors harboring a MET exon 14 skipping event have proven sensitive toward targeted therapy. Reliable methods for detection of genetic alterations in NSCLC have proven to be of increased importance. This chapter provides with hands-on experience of the NanoString gene expression platform for detection of genetic alterations in NSCLC.

Staaf|Johan|J|
Jönsson|Mats|M|
Karlsson|Anna F|AF|

NanoString
Gene expression
Fusion gene
Non-small cell lung carcinoma


The Emerging Role of Interleukin-21 in Transplantation.

Abstract: Since its discovery in 2000, IL-21 has been shown to play critical roles in the regulation of both innate and adaptive immune responses. IL-21 is produced predominantly by multiple effector CD4+ T-cell types [T helper 17 (Th17), follicular helper T (TFH), and other activated CD4+ cells] and NKT cells. In addition to T cell receptor (TCR) signals, the production of IL-21 by activated CD4+ T cells is intricately regulated by various extrinsic factors and intrinsic molecules, such as IL-6, IL-21, ICOS, Stat3, IRF4, and Batf. Because IL-21 receptor (IL-21R) is broadly expressed on T, B, NK, and dentritic cells (DCs), IL-21 signaling via Jak-Stat and other pathways has direct pleiotropic effects on their proliferation, differentiation, and effector function. For instance, while Th17 and TFH cells produce IL-21, IL-21 also facilitates the development of these cells. IL-21-producing TFH cells are important for the generation and maintenance of germinal centers, and control the differentiation of germinal center B cells and immunoglobulin production. Thus, IL-21R deficiency or IL-21 neutralization with IL-21R-Fc fusion protein prevents B cell-mediated autoimmunity in lupus-prone BXSB.B6-Yaa+ or MRL-Faslpr mouse models, respectively. IL-21 also enhances expansion and cytotoxicity of CD8+ effector T cells. During chronic lymphocytic choriomeningitis viral infection, chronic IL-21 production by antigen-specific CD4+ T cells is needed to sustain CD8+ T cell function for viral control. IL-21 is also required for the development of T cell-mediated type 1 diabetes in NOD mice, possibly through sustaining effector T cell function in a similar manner. Recently, two papers have shown that IL-21R-Fc prevents both auto- and allo-immune responses after islet transplantation. A timely discussion is thus needed to address the immune actions of IL-21 as well as the therapeutic potential of targeting IL-21 in transplantation.

Xie|Aini|A|
Buras|Eric Dale|ED|
Xia|Jiahong|J|
Chen|Wenhao|W|

Transplantation
IL-21
T cells
B cells
Tolerance


Inhibition of Listeria monocytogenes on Ready-to-Eat Meats Using Bacteriocin Mixtures Based on Mode-of-Action.

Abstract:
Bacteriocin-producing (Bac⁺) lactic acid bacteria (LAB) comprising selected strains of Lactobacillus curvatus, Lactococcus lactis, Pediococcus acidilactici, and Enterococcus faecium and thailandicus were examined for inhibition of Listeria monocytogenes during hotdog challenge studies. The Bac⁺ strains, or their cell-free supernatants (CFS), were grouped according to mode-of-action (MOA) as determined from prior studies. Making a mixture of as many MOAs as possible is a practical way to obtain a potent natural antimicrobial mixture to address L. monocytogenes contamination of RTE meat products (i.e., hotdogs). The heat resistance of the bacteriocins allowed the use of pasteurization to eliminate residual producer cells for use as post-process surface application or their inclusion into hotdog meat emulsion during cooking. The use of Bac⁺ LAB comprising 3× MOAs directly as co-inoculants on hotdogs was not effective at inhibiting L. monocytogenes. However, the use of multiple MOA Bac⁺ CFS mixtures in a variety of trials demonstrated the effectiveness of this approach by showing a >2-log decrease of L. monocytogenes in treatment samples and 6-7 log difference vs.

CONTROLS
These data suggest that surface application of multiple mode-of-action bacteriocin mixtures can provide for an Alternative 2, and possibly Alternative 1, process category as specified by USDA-FSIS for control of L. monocytogenes on RTE meat products.

Vijayakumar|Paul Priyesh|PP|
Muriana|Peter M|PM|

Listeria monocytogenes
ready-to-eat meats
bacteriocin
mode-of-action
biopreservatives


Chromosome 19 microRNAs exert antiviral activity independent from type III interferon signaling.

Abstract:
INTRODUCTION
Cultured primary human trophoblasts (PHT), derived from term placentas, are relatively resistant to infection by diverse viruses. The resistance can be conferred to non-trophoblastic cells by pre-exposing them to medium that was conditioned by PHT cells. This antiviral effect is mediated, at least in part, by microRNAs (miRNA) expressed from the chromosome 19 microRNA cluster (C19MC). Recently we showed that PHT cells and cells pre-exposed to PHT medium are also resistant to infection by Zika virus (ZIKV), an effect mediated by the constitutive release of the type III interferons (IFN) IFN lambda-1 and IFN lambda-2 in trophoblastic medium. We hypothesized that trophoblastic C19MC miRNA are active against ZIKV, and assessed the interaction of this pathway with IFN lambda-1 - mediated resistance.

METHODS
Term PHT cells were cultured using standard techniques. An osteosarcoma cell line (U2OS) was used as non-trophoblastic cells, which were infected with either ZIKV or vesicular stomatitis virus (VSV). Trophoblastic extracellular vesicles (EVs) were produced by gradient ultracentrifugation. RT-qPCR was used to determine viral infection, cellular or medium miRNA levels and the expression of interferon-stimulated genes.

RESULTS
We showed that C19MC miRNA attenuate infection of U2OS cells by ZIKV, and that C19MC miRNA or exosomes that contain C19MC miRNA did not influence the type III IFN pathway. Similarly, cell exposure to recombinant IFN lambda-1 had no effect on miRNA expression, and these pathways did not exhibit synergistic interaction.

DISCUSSION
PHT cells exert antiviral activity by at least two independent mechanisms, mediated by C19MC miRNA and by type III IFNs.

Bayer|Avraham|A|
Lennemann|Nicholas J|NJ|
Ouyang|Yingshi|Y|
Sadovsky|Elena|E|
Sheridan|Megan A|MA|
Roberts|R Michael|RM|
Coyne|Carolyn B|CB|
Sadovsky|Yoel|Y|

Placenta
ZIKV
IFN lambda-1
Trophoblast C19MC


The Relationships between Plant Developmental Traits and Winter Field Survival in Rye (Secale cereale L.).

Abstract: Overwintering cereals accumulate low temperature tolerance (LTT) during cold acclimation in the autumn. Simultaneously, the plants adjust to the colder season by making developmental changes at the shoot apical meristem. These processes lead to higher winter hardiness in winter rye varieties (Secale cereale L.) adapted to Northern latitudes as compared to other cereal crops. To dissect the winter-hardiness trait in rye, a panel of 96 genotypes of different origins and growth habits was assessed for winter field survival (WFS), LTT, and six developmental traits. Best Linear Unbiased Estimates for WFS determined from five field trials correlated strongly with LTT (r = 0.90, p < 0.001); thus, cold acclimation efficiency was the major contributor to WFS. WFS also correlated strongly (p < 0.001) with final leaf number (r = 0.80), prostrate growth habit (r = 0.61), plant height (r = 0.34), but showed weaker associations with top internode length (r = 0.30, p < 0.01) and days to anthesis (r = 0.25, p < 0.05). The heritability estimates (h) for WFS-associated traits ranged from 0.45 (prostrate growth habit) to 0.81 (final leaf number) and were overall higher than for WFS (h2 = 0.48). All developmental traits associated with WFS and LTT are postulated to be regulated by phytohormone levels at shoot apical meristem.

Bahrani|Hirbod|H|0000-0002-3318-6775
Båga|Monica|M|
Larsen|Jamie|J|
Graf|Robert J|RJ|
Laroche|Andre|A|
Chibbar|Ravindra N|RN|

winter field survival
low temperature tolerance
final leaf number
prostrate growth habit
plant height
winter cereals


Weekend and off-hour effects on the incidence of cerebral palsy: contribution of consolidated perinatal care.

Abstract:
OBJECTIVE
This study estimated the effects of weekend and off-hour childbirth and the size of perinatal medical care center on the incidence of cerebral palsy.

METHODS
The cases were all children with severe cerebral palsy born in Japan from 2009 to 2012 whose data were stored at the Japan Obstetric Compensation System for Cerebral Palsy database, a nationally representative database. The inclusion criteria were the following: neonates born between January 2009 and December 2012 who had a birth weight of at least 2000 g and gestational age of at least 33 weeks and who had severe disability resulting from cerebral palsy independent of congenital causes or factors during the neonatal period or thereafter. Study participants were restricted to singletons and controls without report of death, scheduled cesarean section, or ambulance transportation. The controls were newborns, randomly selected by year and type of delivery (normal spontaneous delivery without cesarean section and emergency cesarean section) using a 1:10 case to control ratio sampled from the nationwide Japan Society of Obstetrics and Gynecology database.

RESULTS
A total of 90 cerebral palsy cases and 900 controls having normal spontaneous delivery without cesarean section were selected, as were 92 cerebral palsy cases and 920 controls with emergent cesarean section. A significantly higher risk for cerebral palsy was found among cases that underwent emergent cesarean section on weekends (odds ratio [OR] 1.72, 95% confidence interval [CI] 1.06-2.81) and during the night shift (OR 2.29, 95% CI 1.30-4.02). No significant risk was found among normal spontaneous deliveries on weekends (OR 1.63, 95% CI 0.97-2.73) or during the quasi-night shift (OR 1.26, 95% CI 0.70-2.27). Regional perinatal care centers showed significantly higher risk for cerebral palsy in both emergent cesarean section (OR 2.35, 95% CI 1.47-3.77) and normal spontaneous delivery (OR 2.92, 95% CI 1.76-4.84).

CONCLUSION
Labor on weekends, during the night shift, and at regional perinatal medical care centers was associated with significantly elevated risk for cerebral palsy in emergency cesarean section.

D016022:Case-Control Studies
D002547:Cerebral Palsy
D036861:Delivery, Obstetric
D006268:Health Facilities
D006801:Humans
D015994:Incidence
D007231:Infant, Newborn
D007564:Japan
D036801:Parturition
D018743:Perinatal Care
D012189:Retrospective Studies
D013997:Time Factors

Cerebral palsy
Japan
Access to healthcare
Concentration
Intensification
Nightshift


Differential regulation of cardiac excitation-contraction coupling by cAMP phosphodiesterase subtypes.

Abstract:
AIMS
Multiple phosphodiesterases (PDEs) hydrolyze cAMP in cardiomyocytes, but the functional significance of this diversity is not well understood. Our goal here was to characterize the involvement of three different PDEs (PDE2-4) in cardiac excitation-contraction coupling (ECC).

METHODS AND RESULTS
Sarcomere shortening and Ca(2+) transients were recorded simultaneously in adult rat ventricular myocytes and ECC protein phosphorylation by PKA was determined by western blot analysis. Under basal conditions, selective inhibition of PDE2 or PDE3 induced a small but significant increase in Ca(2+) transients, sarcomere shortening, and troponin I phosphorylation, whereas PDE4 inhibition had no effect. PDE3 inhibition, but not PDE2 or PDE4, increased phospholamban phosphorylation. Inhibition of either PDE2, 3, or 4 increased phosphorylation of the myosin-binding protein C, but neither had an effect on L-type Ca(2+) channel or ryanodine receptor phosphorylation. Dual inhibition of PDE2 and PDE3 or PDE2 and PDE4 further increased ECC compared with individual PDE inhibition, but the most potent combination was obtained when inhibiting simultaneously PDE3 and PDE4. This combination also induced a synergistic induction of ECC protein phosphorylation. Submaximal β-adrenergic receptor stimulation increased ECC, and this effect was potentiated by individual PDE inhibition with the rank order of potency PDE4 = PDE3 > PDE2. Identical results were obtained on ECC protein phosphorylation.

CONCLUSION
Our results demonstrate that PDE2, PDE3, and PDE4 differentially regulate ECC in adult cardiomyocytes. PDE2 and PDE3 play a more prominent role than PDE4 in regulating basal cardiac contraction and Ca(2+) transients. However, PDE4 becomes determinant when cAMP levels are elevated, for instance, upon β-adrenergic stimulation or PDE3 inhibition.

Mika|Delphine|D|
Bobin|Pierre|P|
Pomérance|Martine|M|
Lechêne|Patrick|P|
Westenbroek|Ruth E|RE|
Catterall|William A|WA|
Vandecasteele|Grégoire|G|
Leroy|Jérôme|J|
Fischmeister|Rodolphe|R|

D054678:Cyclic Nucleotide Phosphodiesterases, Type 2

D054684:Cyclic Nucleotide Phosphodiesterases, Type 3

D054703:Cyclic Nucleotide Phosphodiesterases, Type 4

cAMP
Phosphodiesterase
Protein phosphorylation
Excitation–contraction coupling


International consensus on clinical severity scale use in evaluating Niemann-Pick disease Type C in paediatric and adult patients: results from a Delphi Study.

Abstract:
BACKGROUND
Several scales have been developed in the past two decades to evaluate Niemann-Pick disease Type C (NPC) severity in clinical practice and trials. However, a lack of clarity concerning which scale to use in each setting is preventing the use of standardised assessments across the world, resulting in incomparable data sets and clinical trial outcome measures. This study aimed to establish agreed approaches for the use of NPC severity scales in clinical practice and research.

METHODS
A Delphi method of consensus development was used, comprising three survey rounds. In Round 1, participants were asked nine multiple-choice and open-ended questions to gather opinions on the six severity scales and domains. In Rounds 2 and 3, questions aimed to gain consensus on the opinions revealed in Round 1 using a typical Likert scale.

RESULTS
Nineteen experts, active in NPC paediatric and adult research and treatment, participated in this study. Of these, 16/19 completed Rounds 1 and 2 and 19/19 completed Round 3. Consensus (defined as ≥ 70% agreement or neutrality, given the study aim to identify the severity scales that the clinical community would accept for international consistency) was achieved for 66.7% of the multiple-choice questions in Round 2 and 83% of the multiple-choice questions in Round 3. Consensus was almost reached (68%) on the use of the 5-domain NPCCSS scale as the first choice in clinical practice. Consensus was reached (74%) for the 17-domain NPCCSS scale as the first choice in clinical trial settings, but the domains measured in the 5-domain scale should be prioritised as the primary endpoints. Experts called for educational and training materials on how to apply the NPCCSS (17- and 5-domains) for clinicians working in NPC.

CONCLUSIONS
In achieving a consensus on the use of the 17-domain NPCCSS scale as the first choice for assessing clinical severity of NPC in clinical trial settings but prioritising the domains in the 5-domain NPCCSS scale for routine clinical practice, this study can help to inform future discussion around the use of the existing NPC clinical severity scales. For routine clinical practice, the study helps provide clarity on which scale is favoured by a significant proportion of a representative body of experts, in this case, the 5-domain NPCCSS scale.

Clinical Severity Scales
Delphi Study
Consensus Paper
Niemann–Pick disease Type C (NPC)


Physalis angulata induces death of promastigotes and amastigotes of Leishmania (Leishmania) amazonensis via the generation of reactive oxygen species.

Abstract: Leishmaniasis are a neglected group of emerging diseases that have been found in 98 countries and are caused by protozoa of the genus Leishmania. The therapy for leishmaniasis causes several side effects and leads to drug-resistant strains. Natural products from plants have exhibited activities against Leishmania in various experimental models. Physalis angulata is a widely used plant in popular medicine, and in the literature it has well-documented leishmanicidal activity. However, its mechanism of action is still unknown. Thus, this study aims to evaluate the mechanism driving the leishmanicidal activity of an aqueous extract of P. angulata root (AEPa). AEPa was effective against both promastigotes and intracellular amastigote forms of Leishmania amazonensis. This effect was mediated by an increase of reactive oxygen species (ROS), but not of nitric oxide (NO). The increased production of ROS induces cell death by phenotypes seems by apoptosis cell death in Leishmania, but not autophagy or necrosis. In addition, morphological analysis of macrophages showed that AEPa induced a high number of cytoplasmic projections, increased the volume of cytoplasm and number of vacuoles, caused cytoskeleton alterations and resulted in high spreading ability. AEPa also promoted superoxide anion (O2(-)) production in both uninfected macrophages and those infected with Leishmania. Therefore, these results revealed that AEPa causes cell death by phenotypes seems by apoptosis cell death in L. amazonensis and modulates macrophage activation through morphofunctional alterations and O2(-) generation to induce Leishmania death.

Da Silva|B J M|BJM|
Da Silva|R R P|RRP|
Rodrigues|A P D|APD|
Farias|L H S|LHS|
Do Nascimento|J L M|JLM|
Silva|E O|EO|

Physalis angulata
Macrophage activation
Antileishmanial activity
L. (L.) amazonensis
ROS production


Joint Venture Healthcare System as Common Practice in Developing Countries: Game Changing on Assessing Health Services.

Abstract:
Background
To explore the essence of game changing on applying joint venture (JV) approach for healthcare system improvement in developing countries.

Methods
This is cross-sectional study exploring the factors influencing the successful implementation of JV for the healthcare services in low- and middle-income countries (LMICs). The study included: Qatar Statistical Authority, CIA fact book, Ministry of Health Annual Report, Hamad Medical Corporation Annual Report, Organization for Economic Cooperation and Development information, and Qatar's healthcare system history.

Results
The research indicated that the LMIC healthcare system would benefit from affiliation with leading technology partner for healthcare reform. The findings support the view of LMIC healthcare systems' needs to incorporate joint venture approach in implementing JV concept for process improvement and knowledge transfer to contribute in country economic growth, development, and stability. Current study explored evidence supporting decision maker and management control of JV trends in different ways in comparison with developed countries. JV can also help the organization to share the risk and cost of large capital investment.

Conclusions
The present study supports observations on expending the use of JVs as approach for improvement in LMIC healthcare system. The current study confirmed the advantages of JV which include helping businesses grow faster, increasing productivity, and generating greater profits, both parties sharing the risks and costs, accessing new markets and distribution networks.

joint venture
Developing countries
low- and middle-income countries
health care


Supporting graduate nurse transition to practice through a quality assurance feedback loop.

Abstract: This mixed-method study focused on new graduate nurses and their transition to practice. Transition to practice can be a time of heightened stress and anxiety, leaving many new graduates disillusioned and dissatisfied with their work. The study explored how satisfaction levels with transition may improve during their first year, using a unique approach of a continuous quality assurance feedback loop. This assurance framework is utilised in hospitality, automotive and supply chain logistics and in health, primarily to monitor patient outcomes. However, an association with graduate nurse satisfaction has not been previously reported. Graduate nurses from two health services completed a short survey questionnaire every four weeks for 12 months. De-identified aggregated data was sent to health service management, giving them an opportunity to integrate the findings with the objective of potentially increasing graduate satisfaction ratings. Quantitative findings showed no statistical significance of graduate nurse satisfaction scores between health services, however, one health service consistently outperformed the other. Qualitative findings drawn from a seminar and interviews confirmed that one health service took a more proactive stance with the monthly reports, communicating the results to ward managers. Outcomes reflected a greater commitment of support and an overall increase of satisfaction scores.

Graduate nurses
Transition to practice
Quality assurance feedback loop


Soluble Urokinase-Type Plasminogen Activator Receptor in Black Americans with CKD.

Abstract:
BACKGROUND AND OBJECTIVES
Black Americans with and without APOL1 kidney disease risk variants face high risk of ESKD. Soluble urokinase-type plasminogen activator receptor (suPAR), a circulating signaling protein and marker of immune activation, constitutes a promising biomarker of CKD-associated risks. We aimed to quantify the associations between serum suPAR concentration and adverse outcomes in Black Americans with and without APOL1 kidney disease risk variants, over and above iodine-125 iothalamate measured GFR and proteinuria.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
Using data from the African-American Study of Kidney Disease and Hypertension, a multicenter clinical trial followed by a cohort phase with a median total follow-up of 9.7 years (interquartile range, 6.5-10.9 years), we examined the associations of suPAR with CKD progression (defined as doubling of serum creatinine or ESKD), ESKD, worsening proteinuria (defined as pre-ESKD doubling of 24-hour urine protein-to-creatinine ratio to ≥220 mg/g), and all-cause death.

RESULTS
At baseline, the median suPAR was 4462 pg/ml, mean measured GFR was 46 ml/min per 1.73 m2, and median 24-hour urine protein-to-creatinine ratio was 80 mg/g. After controlling for baseline demographics, randomization arm, GFR, proteinuria, APOL1 risk status, and clinical risk factors, there was a 1.26-times higher risk for CKD progression per SD higher baseline log-transformed suPAR (hazard ratio [HR], 1.26; 95% confidence interval [95% CI], 1.11 to 1.43; P<0.001). Higher suPAR was also independently associated with risk of ESKD (HR, 1.36; 95% CI, 1.17 to 1.58; P<0.001) and death (HR, 1.25; 95% CI, 1.08 to 1.45; P=0.003). suPAR was only associated with worsening proteinuria in patients with two APOLI risk alleles (HR, 1.46; 95% CI, 1.08 to 1.99; P=0.02).

CONCLUSIONS
Higher suPAR was associated with various adverse outcomes in Black Americans with CKD, with and without APOL1 kidney disease risk variants, independently of proteinuria and GFR.

Luo|Shengyuan|S|0000-0002-3235-6832
Coresh|Josef|J|
Tin|Adrienne|A|
Rebholz|Casey M|CM|
Chen|Teresa K|TK|
Hayek|Salim S|SS|0000-0003-0180-349X
Tracy|Melissa|M|
Lipkowitz|Michael S|MS|
Appel|Lawrence J|LJ|
Levey|Andrew S|AS|
Inker|Lesley A|LA|
Reiser|Jochen|J|
Grams|Morgan Erika|ME|

D055293:Receptors, Urokinase Plasminogen Activator


Metabolomic foundation for differential responses of lipid metabolism to nitrogen and phosphorus deprivation in an arachidonic acid-producing green microalga.

Abstract: The green oleaginous microalga Lobosphaera incisa accumulates storage lipids triacylglycerols (TAG) enriched in the long-chain polyunsaturated fatty acid arachidonic acid under nitrogen (N) deprivation. In contrast, under phosphorous (P) deprivation, the production of the monounsaturated oleic acid prevails. We compared physiological responses, ultrastructural, and metabolic consequences of L. incisa acclimation to N and P deficiency to provide novel insights into the key determinants of ARA accumulation. Differential responses to nutrient deprivation on growth performance, carbon-to-nitrogen stoichiometry, membrane lipid composition and TAG accumulation were demonstrated. Ultrastructural analyses suggested a dynamic role for vacuoles in sustaining cell homeostasis under conditions of different nutrient availability and their involvement in autophagy in L. incisa. Paralleling ARA-rich TAG accumulation in lipid droplets, N deprivation triggered intensive chloroplast dismantling and promoted catabolic processes. Metabolome analysis revealed depletion of amino acids and pyrimidines, and repression of numerous biosynthetic hubs to favour TAG biosynthesis under N deprivation. Under P deprivation, despite the relatively low growth penalties, the presence of the endogenous P reserves and the characteristic lipid remodelling, metabolic signatures of energy deficiency were revealed. Metabolome adjustments to P deprivation included depletion in ATP and phosphorylated nucleotides, increased levels of TCA-cycle intermediates and osmoprotectants. We conclude that characteristic cellular and metabolome adjustments tailor the adaptive responses of L. incisa to N and P deprivation modulating its LC-PUFA production.

Kokabi|Kamilya|K| Gorelova|Olga|O| Ismagulova|Tatiana|T| Itkin|Maxim|M| Malitsky|Sergey|S| Boussiba|Sammy|S| Solovchenko|Alexei|A| Khozin-Goldberg|Inna|I|

Metabolomics
Microalgae
Lobosphaera incisa
Triacylglycerols
LC-PUFA
LC–MS


Deliberations with American Indian and Alaska Native People about the Ethics of Genomics: An Adapted Model of Deliberation Used with Three Tribal Communities in the United States.

Abstract:
BACKGROUND
This paper describes the design, implementation, and process outcomes from three public deliberations held in three tribal communities. Although increasingly used around the globe to address collective challenges, our study is among the first to adapt public deliberation for use with exclusively Indigenous populations. In question was how to design deliberations for tribal communities and whether this adapted model would achieve key deliberative goals and be well received.

METHODS
We adapted democratic deliberation, an approach to stakeholder engagement, for use with three tribal communities to respect tribal values and customs. Public deliberation convenes people from diverse backgrounds in reasoned reflection and dialogue in search of collective solutions. The deliberation planning process and design were informed by frameworks of enclave deliberation and community-based participatory research, which share key egalitarian values. The deliberations were collaboratively designed with tribal leadership and extensive partner input and involvement in the deliberations. Each deliberation posed different, locally relevant questions about genomic research, but used the same deliberation structure and measures to gauge the quality and experience of deliberation.

RESULTS
A total of 52 individuals participated in the deliberations across all three sites. Deliberants were balanced in gender, spanned decades in age, and were diverse in educational attainment and exposure to health research. Overall, the deliberations were positively evaluated. Participant perceptions and external observer datasets depict three deliberations that offered intensive conversation experiences in which participants learned from one another, reported feeling respected and connected to one another, and endorsed this intensive form of engagement.

CONCLUSION
The adapted deliberations achieved key deliberative goals and were generally well received. Limitations of the study are described.

Blacksher|Erika|E|0000-0002-0098-7154
Hiratsuka|Vanessa Y|VY|
Blanchard|Jessica W|JW|
Lund|Justin R|JR|
Reedy|Justin|J|0000-0002-7581-8558
Beans|Julie A|JA|0000-0003-4363-9763
Saunkeah|Bobby|B|
Peercy|Micheal|M|
Byars|Christie|C|
Yracheta|Joseph|J|0000-0002-0691-8504
Tsosie|Krystal S|KS|
O'Leary|Marcia|M|
Ducheneaux|Guthrie|G|
Spicer|Paul G|PG|

D000086562:American Indians or Alaska Natives

deliberation
American Indian
Alaska Native
Genomics
ELSI
community engagement


Molecular dynamics simulations of the effects of lipid oxidation on the permeability of cell membranes.

Abstract: The formation of transient pores in their membranes is a well-known mechanism of permeabilization of cells exposed to high-intensity electric pulses. However, the formation of such pores is not able to explain all aspects of the so-called electroporation phenomenon. In particular, the reasons for sustained permeability of cell membranes, persisting long after the pulses' application, remain elusive. The complete resealing of cell membranes takes indeed orders of magnitude longer than the time for electropore closure as reported from molecular dynamics (MD) investigations. Lipid peroxidation has been suggested as a possible mechanism to explain the sustainable permeability of cell membranes. However, theoretical investigations of membrane lesions containing excess amounts of hydroperoxides have shown that the conductivities of such lesions were not high enough to account for the experimental measurements. Here, expanding on these studies, we investigate quantitatively the permeability of cell membrane lesions that underwent secondary oxidation. MD simulations and free energy calculations of lipid bilayers show that such lesions provide a better model of post-pulse permeable and conductive electropermeabilized cells. These results are further discussed in the context of sonoporation and ferroptosis, respectively a procedure and a phenomenon, among others, in which, alike electroporation, substantial lipid oxidation might be triggered.

Electroporation
Conductance
Free energy calculations
Lipid bilayers
Radical oxygen species
Secondary oxidation products


Agrobacterium spp. nosocomial outbreak assessment using rapid MALDI-TOF MS based typing, confirmed by whole genome sequencing.

Abstract:
Background
A number of episodes of nosocomial Agrobacterium spp. bacteremia (two cases per year) were observed at Bern University Hospital, Switzerland, from 2015 to 2017. This triggered an outbreak investigation.

Methods
Cases of Agrobacterium spp. bacteremias that occurred between August 2011 and February 2017 were investigated employing line lists, environmental sampling, rapid protein- (MALDI-TOF MS), and genome-based typing (pulsed field gel electrophoresis and whole genome sequencing) of the clinical isolates.

Results
We describe a total of eight bacteremia episodes due to A. radiobacter (n = 2), Agrobacterium genomovar G3 (n = 5) and A. pusense (n = 1). Two tight clusters were observed by WGS typing, representing the two A. radiobacter isolates (cluster I, isolated in 2015) and four of the Agrobacterium genomovar G3 isolates (cluster II, isolated in 2016 and 2017), suggesting two different point sources. The epidemiological investigations revealed two computer tomography (CT) rooms as common patient locations, which correlated with the two outbreak clusters. MALDI-TOF MS permitted faster evaluation of strain relatedness than DNA-based methods. High resolution WGS-based typing confirmed the MALDI-TOF MS clustering.

Conclusions
We report clinical and epidemiological characteristics of two outbreak clusters with Agrobacterium. spp. bacteremia likely acquired during CT contrast medium injection and highlight the use of MALDI-TOF MS as a rapid tool to assess relatedness of rare gram-negative pathogens in an outbreak investigation.

Casanova|Carlo|C|0000-0002-7888-6329
Lo Priore|Elia|E|
Egli|Adrian|A|
Seth-Smith|Helena M B|HMB|
Räber|Lorenz|L|
Ott|Daniel|D|
Pflüger|Valentin|V|
Droz|Sara|S|
Marschall|Jonas|J|
Sommerstein|Rami|R|

D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Agrobacterium
Nosocomial outbreak
MALDI-TOF MS
Whole genome sequencing
Rhizobium


Acerihabitans arboris gen. nov., sp. nov., a new member of the family Pectobacteriaceae isolated from sap drawn from Acer pictum.

Abstract: A Gram-negative, facultatively anaerobic bacterium, designated SAP-6T, was isolated from sap extracted from Acer pictum in Mt. Halla in Jeju, Republic of Korea and its precise taxonomic status was determined by a polyphasic approach. Cells were non-sporulating, motile, short rods and showed growth at 4-37 °C, pH 6.0-8.0 and 0-4% NaCl. Phylogenomic analysis based on 92 core gene sequences showed that strain SAP-6T belonged to the family Pectobacteriaceae and formed a distinct clade between members of the genera Sodalis and Biostraticola with gene support index of 89. The closest phylogenetic neighbours were Biostraticola tofi DSM 19580T (97.3% 16S rRNA gene sequence similarity) and Sodalis praecaptivus HS1T (96.8%), with the average amino acid identity values of 75.3% and 74.0%, respectively. The major polar lipids were diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol and an unidentified aminophospholipid. The major isoprenoid quinones were Q-7 and Q-8. The predominant fatty acids were C16:0, C17:0 cyclo and summed feature 3. The DNA G+C content was 57.0%. On the basis of data presented here, strain SAP-6T (=KCTC 52622T=DSM 104038T) represents a novel species of a new genus in the family Pectobacteriaceae, for which the name Acerihabitans arboris gen. nov., sp. nov. is proposed.

Lee|Soon Dong|SD|
Kim|In Seop|IS|
Choe|Hanna|H|
Kim|Ji-Sun|JS|

Acerihabitans gen. nov.
Pecobacteriaceae
core gene analysis
genome information


Genome-wide Identification and Evolutionary Analysis of NBS-LRR Genes From Secale cereale.

Abstract: Secale cereale is an important crop in the Triticeae tribe of the Poaceae family, and it has unique agronomic characteristics and genome properties. It possesses resistance to many diseases and serves as an important resource for the breeding of other Triticeae crops. We performed a genome-wide study on S. cereale to identify the largest group of plant disease resistance genes (R genes), the nucleotide-binding site-leucine-rich repeat receptor (NBS-LRR) genes. In its genome, 582 NBS-LRR genes were identified, including one from the RNL subclass and 581 from the CNL subclass. The NBS-LRR gene number in the S. cereale genome is greater than that in barley and the diploid wheat genomes. S. cereale chromosome 4 contains the largest number of NBS-LRR genes among the seven chromosomes, which is different from the pattern in barley and the genomes B and D of wheat but similar to that in the genome A of wheat. Further synteny analysis suggests that more NBS-LRR genes on chromosome 4 have been inherited from a common ancestor by S. cereale and the wheat genome A than the wheat genomes B and D. Phylogenetic analysis revealed that at least 740 NBS-LRR lineages are present in the common ancestor of S. cereale, Hordeum vulgare and Triticum urartu. However, most of them have only been inherited by one or two species, with only 65 of them preserved in all three species. The S. cereale genome inherited 382 of these ancestral NBS-LRR lineages, but 120 of them have been lost in both H. vulgare and T. urartu. This study provides the full NBS-LRR profile of the S. cereale genome, which is a resource for S. cereale breeding and indicates that S. cereale can be an important material for the molecular breeding of other Triticeae crops.

Qian|Lan-Hua|LH| Wang|Yue|Y| Chen|Min|M| Liu|Jia|J| Lu|Rui-Sen|RS| Zou|Xin|X| Sun|Xiao-Qin|XQ| Zhang|Yan-Mei|YM|

evolutionary analysis
NBS-LRR gene
Secale cereale
triticeae crops
disease resistance


Insights into mammalian morphogen dynamics from embryonic stem cell systems.

Abstract: Morphogens play an essential role in cell fate specification and patterning including in laying out the mammalian body plan during gastrulation. In vivo studies have shed light on the signaling pathways involved in this process and the phenotypes associated with their disruption, however, several important open questions remain regarding how morphogens function in space and time. Self-organized patterning systems based on embryonic stem cells have emerged as a powerful platform for beginning to address these questions that is complementary to in vivo approaches. Here we review recent progress in understanding morphogen signaling dynamics and patterning in early mammalian development by taking advantage of cutting-edge embryonic stem cell technology.

D018507:Gene Expression Regulation, Developmental

Embryonic stem cells
Gastrulation
Self-organization
Signaling dynamics
Mammalian development


Review of midwifery education in Uganda: Toward a framework for integrated learning and midwifery model of care.

Abstract:
OBJECTIVE
To examine the current approach to midwifery education and deployment in Uganda against the backdrop of the evidence presented in the Lancet Series on Midwifery and the International Confederation of Midwives Global Standards for Midwifery Education. To make a distinction between 'Midwifery Model of Care' and training in maternal health nursing and highlight the need for midwifery education that is in alignment with international standards and reflexive to the realities of the Ugandan clinical context.

SETTING/PARTICIPANTS
A review of Ugandan nursing and midwifery education structure, curricula and current workforce configurations. A review of government reports and published literature regarding nursing and midwifery education.

FINDINGS
The pathways for nursing and midwifery education in Uganda are too numerous and without clear pathways for educational advancement. The scope of practice for new graduates is not realistic to the context midwives will practice in. Overall, nursing and midwifery education curricula does not prepare graduates to International Confederation of Midwives Standards and lacks training and mentorship in the 'Midwifery Model of Care' making graduates closer to 'maternity nurses' than midwives.

KEY CONCLUSIONS
The Ugandan midwifery education curricula and model needs to bring education standards into alignment with International Confederation of Midwives such that midwives are equipped to practice using the Quality Maternal Newborn Care Framework. Until this is accomplished maternal and newborn mortality rates will remain high, Uganda will continue to lose one of it's greatest resources, it's human capital, and the Sustainable Development Goal 3 will remain out of reach.

Telfer|Michelle|M|
Zaslow|Rachel|R|
Chalo Nabirye|Rose|R|
Nalugo Mbalinda|Scovia|S|

Midwifery
Midwifery education
Midwifery model of care
Ugandan nursing and midwifery education
Maternal mortality
QMNC framework


The effect of pH adjusted electrolytes on capillary isoelectric focusing assessed by high-resolution dynamic computer simulation.

Abstract: The effect of the composition of electrolytes on capillary IEF is assessed for systems with carrier ampholytes covering 2 pH units and with catholytes of decreased pH, anolytes of increased pH and both electrode solutions with adjusted pH values. For electrolytes composed of formic acid as anolyte and ammonium hydroxide as catholyte, simulation is demonstrated to provide the expected IEF system in which analytes with pI values within the formed pH gradient are focused and become immobile. Addition of formic acid to the catholyte results in the formation of an isotachophoretic zone structure that migrates towards the cathode. With ammonium hydroxide added to the anolyte migration occurs towards the anode. In the two cases, all carrier components and amphoteric analytes migrate isotachophoretically as cations or anions, respectively. The data reveal that mM amounts of a counter ion are sufficient to convert an IEF pattern into an ITP system. With increased amounts of the added counter ion, the overall length of the migrating zone structure shrinks, the range of the pH gradient changes, and the migration rate increases. The studied examples indicate that systems of this type reported in the literature should be classified as ITP and not IEF. When both electrolytes are titrated, a non-uniform background electrolyte composed of formic acid and ammonium hydroxide is established in which analytes migrate according to local pH and conductivity without forming IEF or ITP zone structures. Simulation data are in qualitative agreement with previously published experimental data. This article is protected by copyright. All rights reserved.

Electrolytes
Isoelectric focusing
Simulation
Carrier ampholytes
Isotachophoresis


The Overlapping Area of Non-Celiac Gluten Sensitivity (NCGS) and Wheat-Sensitive Irritable Bowel Syndrome (IBS): An Update.

Abstract: Gluten-related disorders have recently been reclassified with an emerging scientific literature supporting the concept of non-celiac gluten sensitivity (NCGS). New research has specifically addressed prevalence, immune mechanisms, the recognition of non-immunoglobulin E (non-IgE) wheat allergy and overlap of NCGS with irritable bowel syndrome (IBS)-type symptoms. This review article will provide clinicians with an update that directly impacts on the management of a subgroup of their IBS patients whose symptoms are triggered by wheat ingestion.

Catassi|Carlo|C|
Alaedini|Armin|A|
Bojarski|Christian|C|
Bonaz|Bruno|B|
Bouma|Gerd|G|
Carroccio|Antonio|A|0000-0001-8913-7916
Castillejo|Gemma|G|0000-0001-6737-075X
De Magistris|Laura|L|
Dieterich|Walburga|W|
Di Liberto|Diana|D|
Elli|Luca|L|
Fasano|Alessio|A|
Hadjivassiliou|Marios|M|
Kurien|Matthew|M|0000-0002-4227-9500
Lionetti|Elena|E|
Mulder|Chris J|CJ|
Rostami|Kamran|K|
Sapone|Anna|A|
Scherf|Katharina|K|
Schuppan|Detlef|D|
Trott|Nick|N|
Volta|Umberto|U|
Zevallos|Victor|V|
Zopf|Yurdagül|Y|
Sanders|David S|DS|

D016032:Randomized Controlled Trials as Topic

gluten sensitivity
gluten-related disorders
wheat allergy
amylase-trypsin inhibitors (ATIs)
celiac disease
gluten-free diet


Surface modification of zero-valent iron nanoparticles with β-cyclodextrin for 4-nitrophenol conversion.

Abstract: Environmental pollution causes irreversible damage to ecosystems and their structure. Therefore, the development of novel remedial techniques is a must for an effective response to emerging contaminants and those already persisting in the environment. The nanosized zero-valent iron (nZVI) is considered as an important nanostructure for the degradation of toxic compounds. Furthermore, the degradative potential of nZVI may be improved by surface modification. In this work nZVI was functionalized with β-cyclodextrin (β-CD), which is considered to be an environmentally-friendly and cheap adsorbent for toxic pollutants. Such a 'green' improvement not only enhances the activity of nZVI but also enables the conversion of 4-nitrophenol to 4-aminophenol, which under standard conditions is persistent and does not significantly react with bare nZVI. This research may help to find a solution to treat persistent organic pollutants (POPs) in aqueous environment.

Krawczyk|Kamil|K|
Wacławek|Stanisław|S|
Silvestri|Daniele|D|
Padil|Vinod V T|VVT|
Řezanka|Michal|M|
Černík|Miroslav|M|
Jaroniec|Mietek|M|

Zero-valent iron
Cyclodextrins
Modified particles
Water and wastewater treatment


Adherence to Recommended Risk Management among Unaffected Women with a BRCA Mutation.

Abstract: Identifying unaffected women with a BRCA mutation can have a significant individual and population health impact on morbidity and mortality if these women adhere to guidelines for managing cancer risk. But, little is known about whether such women are adherent to current guidelines. We conducted telephone surveys of 97 unaffected BRCA mutation carriers who had genetic counseling at least one year prior to the survey to assess adherence to current guidelines, factors associated with adherence, and common reasons for performing and not performing recommended risk management. More than half of participants reported being adherent with current risk management recommendations for breast cancer (69 %, n = 67), ovarian cancer (82 %, n = 74) and both cancers (66 %, n = 64). Older age (OR = 10.53, p = 0.001), white race (OR = 8.93, p = 0.019), higher breast cancer genetics knowledge (OR = 1.67, p = 0.030), higher cancer-specific distress (OR = 1.07, p = 0.002) and higher physical functioning (OR = 1.09, p = 0.009) were significantly associated with adherence to recommended risk management for both cancers. Responses to open-ended questions about reasons for performing and not performing risk management behaviors indicated that participants recognized the clinical utility of these behaviors. Younger individuals and those with lower physical functioning may require targeted interventions to improve adherence, perhaps in the setting of long-term follow-up at a multi-disciplinary hereditary cancer clinic.

Buchanan|Adam H|AH|
Voils|Corrine I|CI|
Schildkraut|Joellen M|JM|
Fine|Catherine|C|
Horick|Nora K|NK|
Marcom|P Kelly|PK|
Wiggins|Kristi|K|
Skinner|Celette Sugg|CS|

Genetic counseling
Breast cancer
Ovarian cancer
BRCA1 gene
BRCA2 gene


L-Lactate Regulates the Expression of Synaptic Plasticity and Neuroprotection Genes in Cortical Neurons: A Transcriptome Analysis.

Abstract: Lactate, a product of aerobic glycolysis in astrocytes, is required for memory formation and consolidation, and has recently emerged as a signaling molecule for neurons and various cell types in peripheral tissues. In particular lactate stimulates mRNA expression of a few plasticity-related genes. Here, we describe a RNA-seq study that unravels genome-wide transcriptomic responses to this energy metabolite in cortical neurons. Our results show that mRNA expression of 20 immediate-early genes involved in the MAPK signaling pathway and in synaptic plasticity were increased by more than twofold following 1 h of lactate stimulation. This effect was dependent on NMDA receptor (NMDAR) activity since it was prevented by pre-treatment with MK-801. Comparison with published datasets showed that a significant proportion of genes modulated by lactate were similarly regulated by a stimulation protocol activating specifically synaptic NMDARs known to result in upregulation of pro-survival and downregulation of pro-death genes. Remarkably, transcriptional responses to lactate were reproduced by NADH (for 74 of the 113 genes, FDR < 0.05), suggesting a redox-dependent mechanism of action. Longer-term gene expression changes observed after 6 h of lactate treatment affected genes involved in regulating neuronal excitability and genes coding for proteins localized at synapses. Gene set enrichment analyses performed with ranked lists of expressed genes revealed effects on molecular functions involved in epigenetic modulation, and on processes relevant to sleep physiology and behavioral phenotypes such as anxiety and hyperactivity. Overall, these results strengthen the notion that lactate effectively regulates activity-dependent and synaptic genes, and highlight new signaling effects of lactate in plasticity and neuroprotection.

Margineanu|Michael B|MB|
Mahmood|Hanan|H|
Fiumelli|Hubert|H|
Magistretti|Pierre J|PJ|

synaptic plasticity
neuroprotection
transcriptome
lactate
NMDA receptor
NADH
gene expression


Haemaphysalis longicornis: the life-cycle on dogs and cattle, with confirmation of its vector status for Theileria orientalis in Australia.

Abstract: The intracellular protozoal parasite Theileria orientalis ikeda has rapidly spread across South-eastern Australia since 2006, causing deaths and production losses in cattle. The 3-host "bush tick" Haemaphysalis longicornis (Neumann) appears the principal biological vector in the endemic regions. To generate sufficient numbers of ticks to produce stabilate for infection to confirm vector competency and for acaricide trials, the optimal conditions and stage-specific intervals for the generational life-cycle of H.longicornis was defined on two dogs and two steers. To determine whether H.longicornis was a definitive host for Theileria orientalis, nymphal stages were fed on a steer infected with T.orientalis and moulted adults were permitted to feed for 3 days on an uninfected calf prior to harvest. Subsequent detection of infection after inoculation of four naïve calves with stabilate produced from ground-up adult ticks or dissected salivary glands confirmed H.longicornis as one final (definitive) host for T.orientalis in Australia.

Marendy|Dominique|D| Baker|Kim|K| Emery|David|D| Rolls|Peter|P| Stutchbury|Ralph|R|

Haemaphysalis
Theileria orientalis
Ikeda
Ticks
Theileriosis
Transmission


MINTIA: a metagenomic INserT integrated assembly and annotation tool.

Abstract: The earth harbors trillions of bacterial species adapted to very diverse ecosystems thanks to specific metabolic function acquisition. Most of the genes responsible for these functions belong to uncultured bacteria and are still to be discovered. Functional metagenomics based on activity screening is a classical way to retrieve these genes from microbiomes. This approach is based on the insertion of large metagenomic DNA fragments into a vector and transformation of a host to express heterologous genes. Metagenomic libraries are then screened for activities of interest, and the metagenomic DNA inserts of active clones are extracted to be sequenced and analysed to identify genes that are responsible for the detected activity. Hundreds of metagenomics sequences found using this strategy have already been published in public databases. Here we present the MINTIA software package enabling biologists to easily generate and analyze large metagenomic sequence sets, retrieved after activity-based screening. It filters reads, performs assembly, removes cloning vector, annotates open reading frames and generates user friendly reports as well as files ready for submission to international sequence repositories. The software package can be downloaded from https://github.com/Bios4Biol/MINTIA.

Bardou|Philippe|P|
Laguerre|Sandrine|S|
Maman Haddad|Sarah|S|
Legoueix Rodriguez|Sabrina|S|
Laville|Elisabeth|E|
Dumon|Claire|C|
Potocki-Veronese|Gabrielle|G|
Klopp|Christophe|C|

Functional metagenomics
Software package
Activity-based metagenomics
Functional annotation
Metagenomic fosmid
Sequence assembly


Duration of Parathyroid Function Recovery in Patients With Protracted Hypoparathyroidism After Total Thyroidectomy for Papillary Thyroid Carcinoma.

Abstract:
Purpose
The aim of the present study is to investigate the time to recovery of parathyroid function in patients with protracted hypoparathyroidism at 1 month after total thyroidectomy of papillary thyroid carcinoma.

Materials and Methods
Adult patients who underwent total thyroidectomy for papillary thyroid cancer were included. Cases of long-term hypoparathyroidism were studied for recovery of parathyroid function during the follow-up. The duration of recovery and associated variables were recorded.

Results
Out of the 964 patients, 128 (13.28%) developed protracted hypoparathyroidism and of these, 23 (2.39%) developed permanent hypoparathyroidism and 105 (10.89%) recovered: 86 (8.92%) before 6 months, 11 (1.14%) within 6 and 12 months and 8 (0.83%) after 1 year follow-up. Variables significantly associated with the time to parathyroid function recovery were number of autotransplanted parathyroid glands (HR, 1.399; 95% CI, 1.060 - 1.846; P = 0.018), serum calcium concentration >2.07 mmol/L (Hazard ratio [HR], 1.628; 95% confidence interval [CI], 1.009 - 2.628; P = 0.046) and PTH level > 1.2 pmol/L (HR, 1.702; 95% CI, 1.083 - 2.628; P = 0.021) at 1 month postoperatively.

Conclusion
Permanent hypoparathyroidism should not be diagnosed easily by time, since up to one-fifth of the patients will experience recovery after a period of 6 months and a few patients even beyond one year. The number of autotransplanted parathyroid glands is positively associated with the time to parathyroid function recovery.

Qiu|Yuxuan|Y| Xing|Zhichao|Z| Xiang|Qiao|Q| Yang|Qianru|Q| Su|Anping|A| Luo|Yan|Y|

parathyroid function recovery
protracted hypoparathyroidism
total thyroidectomy
papillary thyroid carcinoma
permanent hypoparathyroidism


Corneal Collagen Crosslinking for Post-LASIK Ectasia: An Australian Study.

Abstract:
PURPOSE
Post laser-assisted in situ keratomileusis (LASIK) ectasia is a rare and unpredictable complication after LASIK. Corneal collagen crosslinking (CXL) has emerged as a promising technique to address this complication. Our study evaluates the long-term efficacy of CXL for post-LASIK ectasia in an Australian setting.

DESIGN
Retrospective review of post-LASIK ectasia patients referred to and treated at 3 corneal refractive surgery institutions in Sydney, Australia.

METHODS
Eleven patients (14 eyes; mean age, 39.7 ± 12.6 years) underwent epithelium-off CXL with follow-up ranging from 12-78 months. Best spectacle-corrected visual acuity (BSCVA), simulated keratometry, corneal topography indices, and higher-order aberrations (HOAs) [mean ± standard error of the mean (SEM)] were measured with a rotating Scheimpflug camera (Pentacam, Oculus). Comparisons between baseline measurements and postoperative outcomes were performed using paired t test analysis.

RESULTS
At last follow-up, BSCVA improved significantly by 0.2 ± 0.06 logMAR (P = 0.01), and 12 of 14 eyes showed no keratometric deterioration. Of the corneal topography indices, index of height asymmetry showed a trend toward a significant improvement (P = 0.05). There was no progression of corneal HOAs. Central corneal thickness was not significantly altered (P = 0.6). No major postoperative complications were observed.

CONCLUSIONS
In the Australian setting, CXL has proven effective at stabilizing the progression of post-LASIK ectasia, inducing corneal regularity, and improving visual acuity.

Tong|Jessica Y|JY|
Viswanathan|Deepa|D|
Hodge|Christopher|C|
Sutton|Gerard|G|
Chan|Colin|C|
Males|John J|JJ|

crosslinking
ectasia
LASIK
refractive surgery


Occupational radiation exposure to nursing staff during cardiovascular fluoroscopic procedures: A review of the literature.

Abstract: Fluoroscopy is a method used to provide real time x-ray imaging of the body during medical procedures to assist with medical diagnosis and treatment. Recent technological advances have seen an increase in the number of fluoroscopic examinations being performed. Nurses are an integral part of the team conducting fluoroscopic investigations and are often located close to the patient resulting in an occupational exposure to radiation. The purpose of this review was to examine recent literature which investigates occupational exposure received by nursing staff during cardiovascular fluoroscopic procedures. Articles published between 2011 and 2017 have been searched and comprehensively reviewed on the referenced medical search engines. Twenty-four relevant studies were identified among which seventeen investigated nursing dose comparative to operator dose. Seven researched the effectiveness of interventions in reducing occupational exposure to nursing staff. While doctors remain at the highest risk of exposure during procedures, evidence suggests that nursing staff may be at risk of exceeding recommended dose limits in some circumstances. There is also evidence of inconsistent use of personal protection such as lead glasses and skull caps by nursing staff to minimize radiation exposure. Conclusions: The review has highlighted a lack of published literature focussing on dose to nurses. There is a need for future research in this area to inform nursing staff of factors which may contribute to high occupational doses and of methods for minimizing the risk of exposure, particularly regarding the importance of utilizing radiation protective equipment.

Wilson-Stewart|Kelly|K| Shanahan|Madeleine|M| Fontanarosa|Davide|D| Davidson|Rob|R|

radiation exposure
nursing
fluoroscopy
occupational exposure
systematic review


Evidence for neurogenic inflammation in lichen planopilaris and frontal fibrosing alopecia pathogenic mechanism.

Abstract: Lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA) are lymphocytic scarring alopecias affecting primarily the scalp. Although both diseases may share some clinical and histopathological features, in the last decade, FFA has become an "epidemic" particularly in Europe, North and South America with unique clinical manifestations compared to LPP, thus, raising the idea that this disease may have a different pathogenesis. Symptoms such as scalp burning, pruritus or pain are usually present in both diseases, suggesting a possible role for nerves and neuropeptides in the pathogenesis of both diseases. Based on some previous studies, neuropeptides, such as substance P (SP) and calcitonin gene-related peptide (CGRP), have been associated with lipid metabolism and many chronic inflammatory disorders. In this study, we asked if these neuropeptides are associated with LPP and FFA scalp lesions. Alteration in the expression of SP and CGRP in affected and unaffected scalp skin from patients with both diseases was found with examination of sections using immunohistochemical techniques and confocal microscopy. We then quantitatively assessed and compared SP and CGRP expression from control, LPP and FFA scalp biopsies. Although LPP and FFA share similar histopathologic findings, opposite results were found in affected and unaffected scalp in the ELISA tests, suggesting that these diseases may have different pathogenic mechanisms. We also found presence of histopathological inflammation irrespective of evident clinical lesions, which raises the possibility that both diseases may be more generalized processes affecting the scalp.

Doche|Isabella|I|0000-0003-1124-7175
Wilcox|George L|GL|
Ericson|Marna|M|
Valente|Neusa S|NS|
Romiti|Ricardo|R|
McAdams|Brian D|BD|
Hordinsky|Maria K|MK|

scarring alopecias
nerves
neuropeptide
substance P
calcitonin gene-related peptide


Is there an association between verbal school bullying and possible sleep bruxism in adolescents?

Abstract: The aim of this study was to determine the association between verbal school bullying and possible sleep bruxism (SB) in adolescents. A case-control study was carried out at the population level by recruiting 13- to 15-year-old participants among the attendants of schools of Itabira, Brazil. The case group was composed of 103 adolescents with possible SB (i.e. self- or parental-reported), while the control group included 206 adolescents without possible SB. All participants answered a questionnaire on the occurrence of their involvement in verbal school bullying episodes, based on the National School of Health Research (PeNSE) as well as an evaluation of their economic class according to the criteria of the Brazilian Association of Research Companies. Pearson's chi-square, McNemar test and conditional logistic regression were performed to assess the association between possible SB, verbal school bullying and economic class. There were 134 (43·3%) participants who reported involvement in verbal school bullying episodes as a victim, bully or both. The majority of them were males (90·3%). Adolescents with possible SB were more likely to have been involved in episodes of verbal school bullying (OR: 6·20; 95% CI: 3·67-10·48). Based on these findings, it can be suggested that possible SB in young teenagers is associated with a history of episodes of verbal school bullying.

Serra-Negra|J M|JM|
Pordeus|I A|IA|
Corrêa-Faria|P|P|
Fulgêncio|L B|LB|
Paiva|S M|SM|
Manfredini|D|D|

school
bullying
sleep bruxism
adolescent
behaviour


Discovery of simplified N²-substituted pyrazolo[3,4-d]pyrimidine derivatives as novel adenosine receptor antagonists: efficient synthetic approaches, biological evaluations and molecular docking studies.

Abstract: In the present study, a molecular simplification approach was employed to design novel bicyclic pyrazolo[3,4-d]pyrimidine (PP) derivatives from tricyclic pyrazolo[4,3-e]-1,2,4-triazolo-[1,5-c]pyrimidines (PTP) as promising human A3 adenosine receptor (hA3AR) antagonists. All the target compounds were synthesized using novel and efficient synthetic schemes and the structure-activity relationship studies of these PPs were explored through the synthesis of a series of PTP analogues with various substituents. Substituents with different lipophilicity and steric hindrance (e.g., alkyl and aryl-alkyl) functions were introduced at N(2) position of the pyrazole ring, while acyl groups with different electronic properties were introduced at C(6) position of the bicyclic nucleus to probe both electronic and positional effects. Most of the synthesized derivatives of the PP series presented good affinity at the hA3AR, as indicated by the low micromolar range of Ki values and among them, compound 63 with N(2) neopentyl substituents showed most potent hA3AR affinity with Ki value of 0.9 μM and high selectivity (hA1AR/hA3AR=>111 & hA2AAR/hA3AR=>111) towards other adenosine receptor subtypes. Interestingly, small isopropyl groups at N(2) position displayed high affinity at another receptor subtype (hA2AAR, e.g., compound 55, with Ki hA2AAR=0.8 μM), while they were less favorable at the hA3AR. Molecular docking analysis was also performed to predict the possible binding mode of target compounds inside the hA3AR and hA2AAR. Overall, PP derivatives represent promising starting points for new AR antagonists.

Venkatesan|Gopalakrishnan|G|
Paira|Priyankar|P|
Cheong|Siew Lee|SL|
Vamsikrishna|Kosaraju|K|
Federico|Stephanie|S|
Klotz|Karl-Norbert|KN|
Spalluto|Giampiero|G|
Pastorin|Giorgia|G|

D058915:Purinergic P1 Receptor Antagonists

Pyrazolo[3,4-d]pyrimidine
Adenosine receptor antagonist
Molecular docking
Homology modeling
Structure affinity relationship


Influenza A Viruses in Peridomestic Mammals.

Abstract: During recent years, serological evidence has shown that a number of peridomestic mammals (e.g., those commonly found in or around human structures) are naturally exposed to influenza A viruses (IAVs). In addition, experimental studies have demonstrated that many of these species can successfully replicate several different IAVs, including IAVs of high consequence to public or agricultural health. The replication of some IAVs within this group of mammals could have implications for biosecurity associated with poultry production and live bird markets in some regions of the world. Given this evidence, the need for further study and understanding of the role that peridomestic mammals may play in IAV dynamics is increasingly being recognized. This chapter will provide a general overview on IAV associations in peridomestic mammals, especially as they pertain to avian IAVs, and provide some general views and guidelines for sampling these species in various situations.

Peridomestic
Mammal
Antibodies
Exposure
Influenza A virus
Synanthropic
Transmission


Obesity and diabetes as prognostic factors in patients with colorectal cancer.

Abstract: Colorectal carcinoma is one of the most prevalent cancer types for both men and women. Prognosis of the disease is mostly defined by the stage. Localized disease has a better prognosis especially in earlier stages I and II. In addition most patients with more advanced localized stage III disease are expected to survive with a combination of surgery and adjuvant treatments. Progress in treatment of metastatic disease has led to median survivals exceeding 2 years and a minority of oligometastatic patients may survive even longer or be cured with multimodality therapy. Besides stage of the disease few prognostic factors are available to guide informative discussions with patients or guide therapeutic decisions. One area of research that may provide information in this direction is comorbidity conditions of the metabolic syndrome spectrum. Despite a significant body of literature investigating elements of the metabolic syndrome such as obesity and diabetes in isolation as risk and prognostic factors in colorectal cancer, a more restricted amount of research is dealing with the combination of these two factors as prognosticators of colorectal cancer. This paper will discuss published data on these factors and specifically their combination in the prognosis of colorectal cancer and will address some of their pathogenesis and therapy implications.

Obesity
Colorectal cancer
Prognosis
Metabolic syndrome
Body weight
Diabetes mellitus