More on the Best Evolutionary Rate for Phylogenetic Analysis.

Abstract: The accumulation of genome-scale molecular data sets for nonmodel taxa brings us ever closer to resolving the tree of life of all living organisms. However, despite the depth of data available, a number of studies that each used thousands of genes have reported conflicting results. The focus of phylogenomic projects must thus shift to more careful experimental design. Even though we still have a limited understanding of what are the best predictors of the phylogenetic informativeness of a gene, there is wide agreement that one key factor is its evolutionary rate; but there is no consensus as to whether the rates derived as optimal in various analytical, empirical, and simulation approaches have any general applicability. We here use simulations to infer optimal rates in a set of realistic phylogenetic scenarios with varying tree sizes, numbers of terminals, and tree shapes. Furthermore, we study the relationship between the optimal rate and rate variation among sites and among lineages. Finally, we examine how well the predictions made by a range of experimental design methods correlate with the observed performance in our simulations.We find that the optimal level of divergence is surprisingly robust to differences in taxon sampling and even to among-site and among-lineage rate variation as often encountered in empirical data sets. This finding encourages the use of methods that rely on a single optimal rate to predict a gene's utility. Focusing on correct recovery either of the most basal node in the phylogeny or of the entire topology, the optimal rate is about 0.45 substitutions from root to tip in average Yule trees and about 0.2 in difficult trees with short basal and long-apical branches, but all rates leading to divergence levels between about 0.1 and 0.5 perform reasonably well.Testing the performance of six methods that can be used to predict a gene's utility against our simulation results, we find that the probability of resolution, signal-noise analysis, and Fisher information are good predictors of phylogenetic informativeness, but they require specification of at least part of a model tree. Likelihood quartet mapping also shows very good performance but only requires sequence alignments and is thus applicable without making assumptions about the phylogeny. Despite them being the most commonly used methods for experimental design, geometric quartet mapping and the integration of phylogenetic informativeness curves perform rather poorly in our comparison. Instead of derived predictors of phylogenetic informativeness, we suggest that the number of sites in a gene that evolve at near-optimal rates (as inferred here) could be used directly to prioritize genes for phylogenetic inference. In combination with measures of model fit, especially with respect to compositional biases and among-site and among-lineage rate variation, such an approach has the potential to greatly improve marker choice and should be tested on empirical data.


Acid-Induced Gelation of Caseins Glycated with Lactose: Impact of Maillard Reaction-Based Glycoconjugation and Protein Cross-Linking.

Abstract: During food processing or storage, milk proteins can react with reducing sugars via the Maillard reaction (glycation), which may alter their techno-functional properties. The aim of this study was to investigate the relationship between molecular changes of casein occurring during different stages of the Maillard reaction and its acid-induced gelling properties. Therefore, sodium caseinate was heated in a dry state at 60 °C in the presence of lactose and analyzed for structural modifications by determining Amadori compounds (glycoconjugation) indirectly as furosine, the total lysine modification, and the extent of protein cross-linking. For techno-functional characterization, acid-induced gels were prepared by the addition of glucono-δ-lactone and evaluated by measuring pH kinetics during gel formation, gel strength, and water holding capacity. The time to reach pH 4.6 during the gelation process was significantly delayed with increasing extent of the Maillard reaction. Glycation with lactose also led to a significant increase in gel strength and water holding capacity. The increase in gel stability was rather independent from the amount of sugars covalently bound to the proteins during the early phase of the Maillard reaction but strongly correlated to the degree of protein polymerization. Small- and medium-sized casein oligomers, formed during advanced stages of the Maillard reaction, contributed considerably to the formation of stronger gels with higher water holding capacity, whereas a sharp increase in the relative amount of the polymer fraction observed during prolonged cross-linking processes caused a spontaneous destabilization of the gel network. Knowledge about structure-function relationships on a molecular level can provide useful information to control food texture by raw material quality.

gelation
glycation
glycoconjugation
protein cross-linking
Maillard reaction
sodium caseinate
techno-functionality


The effects of elevated CO2 and nitrogen nutrition on root dynamics.

Abstract: Ambient CO2 concentration is currently 400 μmol mol-1, and projections forecast an increase up to 970 μmol mol-1 by century's end. Elevated CO2 can stimulate C3 plant growth, whereas nitrogen is the main nutrient plants acquire from soils and often limits growth. Plants primarily obtain two nitrogen sources from the soil, ammonium (NH4+) and nitrate (NO3-). At elevated CO2 levels, plant growth and nitrogen metabolism is affected by the nitrogen source. Most research has focused on shoot traits, while neglecting the plants' hidden half, the root. We studied the effects of elevated CO2 and nitrogen source on hydroponically grown tomato plants, a C3 model and crop plant. Our main objective was to determine how the nitrogen source and elevated CO2 affect root development. Our results indicate they affect development in terms of the size and anatomy of different root orders. Specifically, root xylem development was found sensitive to the nitrogen source, whereas NO3--supplied plants displayed greater xylem development compared to their NH4+ counterparts, and also to a lesser extent, to elevated CO2, which we found inhibits this development. Additionally, elevated CO2 decreased root respiration in different root orders exclusively in plants supplied with NH4+as the sole nitrogen source.

Cohen|Itay|I|
Rapaport|Tal|T|
Berger|Reut Tal|RT|
Rachmilevitch|Shimon|S|

D002245:Carbon Dioxide
D019069:Cell Respiration
D018551:Lycopersicon esculentum
D009584:Nitrogen
D018517:Plant Roots
D018520:Plant Shoots
D036226:Seedlings

Roots
Nitrogen source
Anatomy
Root orders
Xylem
Root respiration
Elevated CO(2)


An Iron-Catalyzed Bond-Making/Bond-Breaking Cascade Merges Cycloisomerization and Cross-Coupling Chemistry.

Abstract: Treatment of readily available enynes with alkyl-Grignard reagents in the presence of catalytic amounts of Fe(acac)3 engenders a remarkably facile and efficient reaction cascade that results in the net formation of two new C-C bonds while a C-Z bond in the substrate backbone is broken. Not only does this new manifold lend itself to the extrusion of heteroelements (Z=O, NR), but it can even be used for the cleavage of activated C-C bonds. The reaction likely proceeds via metallacyclic intermediates, the iron center of which gains ate character before reductive elimination occurs. The overall transformation represents a previously unknown merger of cycloisomerization and cross-coupling chemistry. It provides ready access to highly functionalized 1,3-dienes comprising a stereodefined tetrasubstituted alkene unit, which are difficult to make by conventional means.

cycloisomerization
cross-coupling
enynes
1,3-dienes
Grignard reagents
iron catalysis


My life as a pupil: The autobiographical memories of adolescents excluded from school.

Abstract: Narrative psychology is founded on the premise that substantial insight can be gained into individuals' self-understanding and behaviour by studying the content of their autobiographical memories. This article contributes to this field of inquiry by suggesting that our understanding of adolescents' exclusion from mainstream education can be enhanced by examining their recollections of school using a narrative dialogical approach. In a research project the autobiographical memories of fifteen female and twenty male students, aged 15-16 years, who had been excluded from secondary schools in London, England were collected and analysed. The aim was to examine how in their narrated depictions of the past, the adolescents explained and justified their position and behaviour at different times in their lives at school. The findings highlight how adolescents perceive themselves to have become positioned by the voices of significant others, schools as institutions and themselves at earlier or later stages in their lives.

Adolescence
Narrative psychology
Dialogical self
School exclusion


Schwannoma on the nasal dorsum and tip with sensory changes.

Abstract: Schwannomas, which originate from Schwann cells in the peripheral nervous system, are slowgrowing and uncommon benign tumors. Most schwannomas (90%) occur in isolation, and multiple occurrences are a characteristic feature of neurofibromas. Schwannomas of the nose and nasal tip are particularly unusual. Although a few cases of schwannomas of the sinusoidal tract and nasal septum have been reported, schwannomas arising from the nasal dorsum area and tip are extremely rare. Sensory abnormalities are also a very rare symptom. We excised a schwannoma on the nasal dorsum through direct incision and a schwannoma on the nasal tip through open rhinoplasty. No postoperative complications involving recurrence, hematoma, or infection occurred. The possibility of neurological changes should be considered in cases of an abnormality in the peripheral nervous system. Schwannoma must be kept in mind as a possible cause of neurological changes localized to a specific dermatome, and should always be considered in the differential diagnosis of a mass on the nose.

Yoon|Sung Ho|SH|
Kim|Cha Soo|CS|
Oh|Jae Wook|JW|
Lee|Keun Cheol|KC|


An overview on personalisation of radiotherapy prescriptions in locally advanced non-small cell lung cancer: Are we there yet?

Abstract: Standard of care radiotherapy in LA-NSCLC is 60-66 Gy in 30-33 fractions. However outcomes for these patients are poor with 5-year survival in the range of 10-20%. Randomised controlled trials have shown that dose escalation in a linear fashion does not improve outcomes for all patients, thus there is a need to tailor the prescription to the individual patient. This review assesses the strategies published to personalise the radiation therapy dose prescription in LA-NSCLC. A systematic and scoping search of the literature was performed to identify studies that met the inclusion criteria. 19 relevant studies were identified ranging from prospective clinical trials to mathematically modelled concept studies. Heterogeneity existed between all clinical studies. Nine heterogeneous publications proposed methodology to adapt the dose prescription to the individual patient. A number of encouraging strategies have been identified but fall short of the evidence level required to influence clinical practice.

Barrett|Sarah|S|
Hanna|Gerard G|GG|
Marignol|Laure|L|

D002289:Carcinoma, Non-Small-Cell Lung
D006801:Humans
D008175:Lung Neoplasms
D057285:Precision Medicine
D011446:Prospective Studies
D011879:Radiotherapy Dosage

Radiotherapy
Dose fractionation
Non-small-cell lung cancer
Personalised medicine
Personalised prescriptions


Mitochondria and mitochondrial DNA in porcine oocytes and cumulus cells--A search for developmental competence marker.

Abstract: The development of mammalian oocytes is dependent on bidirectional signaling with the surrounding cumulus cells. Among the numerous factors that contribute to oocyte developmental competence, the mitochondria and the mitochondrial DNA play pivotal roles. Although these highly abundant organelles have been well-studied in oocytes, their roles, abundance and metabolism remain elusive in cumulus cells. Therefore, the aim of our study was to analyze the correlation between the mtDNA copy number in cumulus cells and oocytes, as well as the mitochondrial distribution patterns in oocytes, using two groups of animals that differ in terms of the developmental competence of their oocytes. We determined a positive correlation between the mtDNA copy number in the cumulus cells and mtDNA copy number in oocytes of prepubertal pigs and negative correlation in cyclic gilts. These opposing correlations may reflect the differences in the developmental competence of the prepubertal and cyclic oocytes. We also hypothesize that observed differences may reflect different metabolism and energy requirements of the cumulus-oocyte complexes from prepubertal and cyclic gilts. The mitochondrial distribution patterns in the prepubertal and cyclic gilts were not different.

Pawlak|Piotr|P| Chabowska|Agnieszka|A| Malyszka|Natalia|N| Lechniak|Dorota|D|

Mitochondria
Oocyte
Cumulus
Developmental competence
mtDNA
Puberty
Quality


Molecular Fluorescence and Photoacoustic Imaging in the Second Near-Infrared Optical Window Using Organic Contrast Agents.

Abstract: Noninvasive near-infrared (NIR) light ranging from 650 to 1000 nm (NIR-I) is widely employed in fundamental research and clinical applications; however, a recently discovered second NIR (NIR-II) window from 1000 to 1700 nm exhibits even better deep-tissue imaging capability due to reduced photon scattering, minimized tissue autofluorescence, and increased applicable power at longer wavelengths. This review focuses on recent advances of organic contrast agents developed for in vivo fluorescence and photoacoustic imaging in the NIR-II optical window. The superiority of the NIR-II over the NIR-I window for molecular imaging is first discussed in detail, followed by discussion of fluorescence and photoacoustic imaging of cancer, vasculature, and the brain using organic contrast agents in the NIR-II window. At last, challenges and perspectives of organic contrast agents for NIR-II in vivo imaging are suggested.

photoacoustic imaging
fluorescence imaging
organic nanoparticles
second near-infrared window


Underwater Acoustic Impulsive Noise Monitoring in Port Facilities: Case Study of the Port of Cartagena.

Abstract: Recording underwater impulsive noise data is an important aspect of mitigating its environmental impact and improving maritime environmental management systems. This paper describes the method used and results of the spatial monitoring of both the baseline noise level and the impulsive noise sources in the Port of Cartagena. An autonomous vessel was equipped with a smart digital hydrophone with a working frequency range between 10 and 200 kHz and a received voltage response (RVR) of, approximately, -170 dB re 1V/µPa. A GIS map was drawn up with the spatiotemporal distribution of the basal sound pressure levels by coupling the acoustic data with the vessel's GPS positions to identify the sources of the impulsive noise of interest and their temporal characteristics. The loading of cargo containers was identified as the main source of impulse noise. This study is the first of a series designed to obtain accurate information on underwater noise pollution and its potential impact on biodiversity in the Port of Cartagena.

hydrophone
ASV
continuous underwater noise
impulsive underwater noise
marine contamination
marine strategy framework directive
underwater noise monitoring


Association between timely initiation of hepatitis B vaccine and completion of the hepatitis B vaccine and national immunization program vaccine series.

Abstract:
BACKGROUND
Little is known about the association between the initiation of hepatitis B vaccine (HB vaccine) at birth and completion of the HB vaccine and the national immunization program vaccine (NIPV) series in Fujian, China.

METHODS
A provincial survey, including children in the community and newborns in hospital, was conducted to evaluate coverage with a timely first dose of HB vaccine and the completion of three doses of HB vaccine and the NIPV series in 2013. A proportion of the samples was rechecked to investigate the relationship between the administration of a timely first dose of HB vaccine and completion of the HB vaccine series and the NIPV series (three doses of HB vaccine, one dose of Bacillus Calmette-Guérin vaccine, three doses of oral poliomyelitis vaccine, three doses of diphtheria-tetanus-pertussis vaccine, one dose of measles-containing vaccine, one dose of Japanese encephalitis attenuated live vaccine, and two doses of group A meningococcal polysaccharide vaccine).

RESULTS
A total of 6589 subjects (including 3785 community children and 2804 hospital newborns) were included in this study; 97.34% of them received a timely first dose of HB vaccine (≤24h after birth) and 99.10% and 88.27% completed the HB vaccine series and the NIPV series, respectively. Among the 1680 children from eight counties who were rechecked, those with a timely first dose of HB vaccine had higher completion rates of the HB vaccine series and the NIPV series than those with a delayed first dose of HB vaccine (99.69% and 88.90% vs. 83.05% and 79.66%, respectively; both p<0.001). Compared to those with a delayed HB vaccine first dose, the odds ratios for completing the HB vaccine series and the NIPV series among children who received a timely first dose of HB vaccine were 65.96 (95% confidence interval (CI) 21.73-200.25) and 3.24 (95% CI 1.81-5.81), respectively.

CONCLUSIONS
Coverage with a timely first dose of HB vaccine is high in children in the community and newborns in hospital, and timely receipt of the first dose of HB vaccine is associated with an increased likelihood of completing the HB vaccine series and the NIPV series in Fujian, China.

Hepatitis B vaccine
National immunization program vaccine
Birth dose


Addition of Flucytosine to Fluconazole for the Treatment of Cryptococcal Meningitis in Africa: A Multicountry Cost-effectiveness Analysis.

Abstract:
BACKGROUND
Mortality from cryptococcal meningitis remains very high in Africa. In the Advancing Cryptococcal Meningitis Treatment for Africa (ACTA) trial, 2 weeks of fluconazole (FLU) plus flucytosine (5FC) was as effective and less costly than 2 weeks of amphotericin-based regimens. However, many African settings treat with FLU monotherapy, and the cost-effectiveness of adding 5FC to FLU is uncertain.

METHODS
The effectiveness and costs of FLU+5FC were taken from ACTA, which included a costing analysis at the Zambian site. The effectiveness of FLU was derived from cohorts of consecutively enrolled patients, managed in respects other than drug therapy, as were participants in ACTA. FLU costs were derived from costs of FLU+5FC in ACTA, by subtracting 5FC drug and monitoring costs. The cost-effectiveness of FLU+5FC vs FLU alone was measured as the incremental cost-effectiveness ratio (ICER). A probabilistic sensitivity analysis assessed uncertainties and a bivariate deterministic sensitivity analysis examined the impact of varying mortality and 5FC drug costs on the ICER.

RESULTS
The mean costs per patient were US $847 (95% confidence interval [CI] $776-927) for FLU+5FC, and US $628 (95% CI $557-709) for FLU. The 10-week mortality rate was 35.1% (95% CI 28.9-41.7%) with FLU+5FC and 53.8% (95% CI 43.1-64.1%) with FLU. At the current 5FC price of US $1.30 per 500 mg tablet, the ICER of 5FC+FLU versus FLU alone was US $65 (95% CI $28-208) per life-year saved. Reducing the 5FC cost to between US $0.80 and US $0.40 per 500 mg resulted in an ICER between US $44 and US $28 per life-year saved.

CONCLUSIONS
The addition of 5FC to FLU is cost-effective for cryptococcal meningitis treatment in Africa and, if made available widely, could substantially reduce mortality rates among human immunodeficiency virus-infected persons in Africa.

Shiri|Tinevimbo|T|
Loyse|Angela|A|
Mwenge|Lawrence|L|
Chen|Tao|T|
Lakhi|Shabir|S|
Chanda|Duncan|D|
Mwaba|Peter|P|
Molloy|Síle F|SF|
Heyderman|Robert S|RS|
Kanyama|Cecilia|C|
Hosseinipour|Mina C|MC|
Kouanfack|Charles|C|
Temfack|Elvis|E|
Mfinanga|Sayoki|S|
Kivuyo|Sokoine|S|
Chan|Adrienne K|AK|
Jarvis|Joseph N|JN|
Lortholary|Olivier|O|
Jaffar|Shabbar|S|
Niessen|Louis W|LW|
Harrison|Thomas S|TS|

flucytosine
fluconazole
treatment
cryptococcal meningitis
cost-effectiveness


Technical note: Feasibility of near infrared transmittance spectroscopy to predict cheese ripeness.

Abstract: The aim of the study was to evaluate the feasibility of near infrared (NIR) transmittance spectroscopy to predict cheese ripeness using the ratio of water-soluble nitrogen (WSN) to total nitrogen (TN) as an index of cheese maturity (WSN/TN). Fifty-two Protected Designation of Origin cow milk cheeses of 5 varieties (Asiago, Grana Padano, Montasio, Parmigiano Reggiano, and Piave) and different ripening times were available for laboratory and chemometric analyses. Reference measures of WSN and TN were matched with cheese spectral information obtained from ground samples by a NIR instrument that operated in transmittance mode for wavelengths from 850 to 1,050 nm. Prediction equations for WSN and TN were developed using (1) cross-validation on the whole data set and (2) external validation on a subset of the entire data. The WSN/TN was calculated as ratio of predicted WSN to predicted TN in cross-validation. The coefficients of determination for WSN and TN were >0.85 both in cross- and external validation. The high accuracy of the prediction equations for WSN and TN could facilitate implementation of NIR transmittance spectroscopy in the dairy industry to objectively, rapidly, and accurately monitor the ripeness of cheese through WSN/TN.

Currò|S|S|
Manuelian|C L|CL|
Penasa|M|M|
Cassandro|M|M|
De Marchi|M|M|

water-soluble nitrogen
ripening time
chemometric
cheese quality


APOE-ε4 Carrier Status and Gut Microbiota Dysbiosis in Patients With Alzheimer Disease.

Abstract:
Background
Alternations in gut microbiota and a number of genes have been implicated as risk factors for the development of Alzheimer disease (AD). However, the interactions between the altered bacteria and risk genetic variants remain unclear.

Objective
We aimed to explore associations of the risk genetic variants with altered gut bacteria in the onset of AD.

Methods
We collected baseline data and stool and blood samples from 30 AD patients and 47 healthy controls in a case-control study. The rs42358/rs4512 (ApoE), rs3851179 (PICALM), rs744373 (BIN1), rs9331888 (CLU), rs670139 (MS4A4E), rs3764650 (ABCA7), rs3865444 (CD33), rs9349407 (CD2AP), rs11771145 (EPHA1), and rs3818361/rs6656401 (CR1) were sequenced, and microbiota composition was characterized using 16S rRNA gene sequencing. The associations of the altered gut bacteria with the risk genetics were analyzed.

Results
Apolipoprotein ε4 allele and rs744373 were risk loci for the AD among 12 genetic variants. Phylum Proteobacteria; orders Enterobacteriales, Deltaproteobacteria, and Desulfovibrionales; families Enterobacteriaceae and Desulfovibrionaceae; and genera Escherichia-Shigella, Ruminococcaceae_UCG_002, Shuttleworthia, Anaerofustis, Morganelia, Finegoldia, and Anaerotruncus were increased in AD subjects, whereas family Enterococcaceae and genera Megamonas, Enterococcus, and Anaerostipes were more abundant in controls (P < 0.05). Among the altered microbiota, APOE ε4 allele was positively associated with pathogens: Proteobacteria.

Conclusion
The interaction of APOE ε4 gene and the AD-promoting pathogens might be an important factor requiring for the promotion of AD. Targeting to microbiota might be an effective therapeutic strategy for AD susceptible to APOE ε4 allele. This needs further investigation.

Hou|Min|M| Xu|Gaolian|G| Ran|Maosheng|M| Luo|Wei|W| Wang|Hui|H|

dysbiosis
Alzheimer disease
genetic variants
apolipoprotein E
gut microbiome


Endoscopic Approaches to the Frontal Sinus: Modifications of the Existing Techniques and Proposed Classification.

Abstract: Frontal sinus surgery has long been technically challenging in terms of access and chronic disease management. Decades of experience and advances in technology have led to the widespread use of various surgical approaches to the frontal sinus. Modifications to these existing procedures have been described to minimize unnecessarily invasive approaches. The lack of a classification that incorporates the newly described modifications prompts the proposal of a new classification. Eloy I-III incorporates all the previously described approaches as well as 3 recently published, and 1 newly described, procedures.

Eloy|Jean Anderson|JA|
Vázquez|Alejandro|A|
Liu|James K|JK|
Baredes|Soly|S|

Frontal sinus
Endoscopic modified Lothrop procedure
Extended Draf IIB
Frontal sinusotomy
Lothrop procedure
Modified hemi-Lothrop procedure
Modified mini-Lothrop procedure
Modified subtotal-Lothrop procedure


Temporal structure of human magnetic evoked fields.

Abstract: Nonlinear analysis of the multifocal cortical visual evoked potential has allowed the identification of neural generation of higher-order nonlinear components by magnocellular and parvocellular neural streams. However, the location of individual brain sources that make such contributions to these evoked responses has not been studied. Thus, an m-sequence pseudorandom stimulus system was developed for use in magnetoencephalographic (MEG) studies. Five normal young adults were recorded using an Elekta TRIUX MEG with 306 sensors. Visual stimuli comprised a nine-patch dartboard stimulus, and each patch fluctuated between two luminance levels with separate recordings carried out at low (24 %) and high (96 %) temporal contrast. Sensor-space analysis of MEG evoked fields identified components of the first- and second-order Wiener kernel decomposition that showed qualitative similarity with EEG-based cortical VEP recordings. The first slice of the second-order response (K2.1) was already saturated at 24 % contrast, while the major waveform of the second slice of the second-order response (K2.2) grew strongly with contrast, consistent with properties of the magnocellular and parvocellular neurons. Minimum norm estimates of cortical source localization showed almost simultaneous activation of V1 and MT+ activations with latencies only a little greater that those reported for first neural spikes in primate single cell studies. Time-frequency analysis of the kernel responses from five minimum norm estimate scout sources shows contributions from higher-frequency bands for the first compared with the second slice response, consistent with the proposed neural sources. In support of this magno/parvo break-up, the onset latencies of the K2.2 responses were delayed by approximately 30 ms compared with K2.1 responses.

Crewther|David P|DP|
Brown|Alyse|A|
Hugrass|Laila|L|

D000328:Adult
D002540:Cerebral Cortex
D005074:Evoked Potentials, Visual
D005829:Geniculate Bodies
D006801:Humans
D015225:Magnetoencephalography
D017711:Nonlinear Dynamics
D014796:Visual Perception
D055815:Young Adult

Nonlinearity Magnocellular Parvocellular MEG MT+ Latency


Evaluation of Proliferation and Osteogenic Differentiation of Human Umbilical Cord-Derived Mesenchymal Stem Cells in Porous Scaffolds.

Abstract:
INTRODUCTION
Human umbilical cord-derived mesenchymal stem cells (UCMSCs) are multiple potential stem cells that can differentiate into various kinds of functional cells, including adipocytes, osteoblasts, and chondroblasts. Thus, UCMSCs have recently been used in both stem cell therapy and tissue engineering applications to produce various functional tissues. This study aimed to evaluate the proliferation and differentiation of UCMSCs on porous scaffolds.

METHODS
UCMSCs were established in a previous study and kept in liquid nitrogen. They were thawed and expanded in vitro to yield enough cells for further experiments. The cells were characterized as having MSC phenotype. They were seeded onto culture medium-treated porous scaffolds or on non-treated porous scaffolds at different densities of UCMSCs (105, 2.1 × 105, and 5 × 105 cells/0.005 g scaffold). The existence of UCMSCs on the scaffold was evaluated by nucleic staining using Hoechst 33342 dye, while cell proliferation on the scaffold was determined by MTT assay. Osteogenic differentiation was evaluated by changes in cellular morphology, accumulation of extracellular calcium, and expression of osteoblast-specific genes (including runx2, osteopontin (OPN), and osteocalcin (OCN)).

RESULTS
The data showed that UCMSCs could attach, proliferate, and differentiate on both treated and non-treated scaffolds but were better on the treated scaffold. At a cell density of 105 cells/0.005 g scaffold, the adherent and proliferative abilities of UCMSCs were higher than that of the other densities after 14 days of culture (p < 0.05). Adherent UCMSCs on the scaffold could be induced into osteoblasts in the osteogenic medium after 21 days of induction. These cells accumulated calcium in the extracellular matrix that was positive with Alizarin Red staining. They also expressed some genes related to osteoblasts, including runx2, OPN, and OCN.

CONCLUSION
UCMSCs could adhere, proliferate, and differentiate into osteoblasts on porous scaffolds. Therefore, porous scaffolds (such as Variotis) may be suitable scaffolds for producing bone tissue in combination with UCMSCs.

Dao|Thuy Thi-Thanh|TT|
Nguyen|Chau Thi-Hong|CT|
Vu|Ngoc Bich|NB|
Le|Ha Thi-Ngan|HT|
Nguyen|Phuc Dang-Ngoc|PD|
Van Pham|Phuc|P|

D049109:Cell Proliferation
D002478:Cells, Cultured
D006801:Humans
D059630:Mesenchymal Stem Cells
D010012:Osteogenesis
D023822:Tissue Engineering
D054457:Tissue Scaffolds
D014470:Umbilical Cord

Osteogenic differentiation
UCMSCs
Variotis
3D porous scaffold


What makes cancer stem cell markers different?

Abstract: Since the cancer stem cell concept has been widely accepted, several strategies have been proposed to attack cancer stem cells (CSC). Accordingly, stem cell markers are now preferred therapeutic targets. However, the problem of tumor specificity has not disappeared but shifted to another question: how can cancer stem cells be distinguished from normal stem cells, or more specifically, how do CSC markers differ from normal stem cell markers? A hypothesis is proposed which might help to solve this problem in at least a subgroup of stem cell markers. Glycosylation may provide the key.

Cancer stem cells
Stem cells
Therapeutic targets
Glycosylation
Thomsen-Friedenreich antigen


Dissemination and Acceptance of COVID-19 Misinformation in Iran: A Qualitative Study.

Abstract:
INTRODUCTION
Misinformation refers to unclear information from unreliable resources, and it is a common phenomenon of society; it can even constitute a part of family and social conversations due to the relative damages. Misinformation dissemination under the circumstances of the COVID-19 pandemic can be considered a cause of health-related anxieties and severe harm to the countries. The present study aims to explain factors related to the dissemination and acceptance of coronavirus misinformation in Iran.

MATERIAL AND METHODS
This qualitative study was carried out through content analysis in the year 2020. The population included Iranian experts in Information and Communication Sciences, among whom 19 experts were selected through the purposive sampling method. The data were collected through semi-structured interviews and analyzed through Continuous Thematic Analysis. Such criteria authenticated data trustworthiness as credibility, confirmability, dependability, and transferability proposed by Guba and Lincoln.

FINDINGS
Based on the experiences of participants, six major categories and 18 subcategories were identified regarding the major theme. The major categories included the official news and informing system, misinformation nature, users, media, misinformation source, and social determinants.

CONCLUSION
Concurrent with the Covid-19 outbreak, a sort of information tsunami occurs. Unavoidably, a significant amount of misinformation regarding the various aspects of the virus, such as its origin, transmission methods, control, and treatment, are published. In many cases, the spreading information is not checked and verified in terms of accuracy and authenticity. The spread and acceptance of Covid-19 related misinformation happen under the impact of various factors. Being familiar with these factors will boost the culture of health and pave the path toward establishing evidence-based information public awareness schemes.

COVID-19
misinformation
Iran
social media


Touch-free measurement of body temperature using close-up thermography of the ocular surface.

Abstract: In experimental animal research body temperature (BT) is measured for the objective determination of an animals' physiological condition. Invasive, probe-based measurements are stressful and can influence experimental outcome. Alternatively BT can be determined touch-free from the emitted heat of the organism at a single spot using infrared thermometers [1]. To get visual confirmation and find more appropriate surfaces for measurement a hand-held thermal imager was equipped with a self-made, cheap, 3D-printable close-up lens system that reproducibly creates eight-time magnified thermal images and improves sensitivity. This setup was used to establish ocular surface temperature (OST), representing the temperature of the brain-heart axis, as a touch-free alternative for measurement of BT in mice, rats, rabbits and humans.OST measurement after isoflurane exposure and myocardial infarction (MI) experiments in mice revealed high physiological relevance and sensitivity, the possibility to discriminate between MI and sham operations in one hour and even long-term outcome-predictive capabilities of OST after MI. Summarized here we present: •Self-made close-up lens for thermal imaging cameras for eight-time magnification•Establishment of OST for touch-free determination of BT in rodents and humans•Short- and long-term predictive capabilities of OST in experimental MI in mice.

Vogel|Benjamin|B| Wagner|Heike|H| Gmoser|Johanna|J| Wörner|Anja|A| Löschberger|Anna|A| Peters|Laura|L| Frey|Anna|A| Hofmann|Ulrich|U| Frantz|Stefan|S|

Close-up thermal imager for temperature measurement and detail investigations

rOSTd, relative ocular surface temperature decline


Autocrined leptin promotes proliferation of non-small cell lung cancer (NSCLC) via PI3K/AKT and p53 pathways.

Abstract:
Background
Circulating leptin can directly act on tumor cells. However, a recent meta-analysis showed that plasma leptin concentration had no significant effect on the survival of lung cancer patients. So does Leptin have an effect on lung cancer? Or there may be other factors that influence the effect.

Methods
Genome sequencing database Oncomine was searched to learn the differential expression of leptin between tumors and normal lungs. Fresh tumor specimens and paired normal lung tissue from six lung adenocarcinoma patients were collected, and validate the expression level of leptin. Clinicopathological information and tumor slices from 60 non-small cell lung cancer (NSCLC) patients were analyzed to evaluate the prognostic value of autocrined leptin. Whole genome sequencing data from the cancer genome atlas (TCGA) was analyzed to predict the underlying mechanism of leptin regulating tumor proliferation. Finally, these findings were confirmed by using cell lines H1299, A549, H460, and H322 to explore the promoting effect and mechanism of leptin on cell proliferation in vitro.

Results
Five datasets in Oncomine reported the expression of the LEP gene in NSCLC, and 4 datasets showed that leptin was up-regulated in tumors compared with normal lungs. Leptin was also overexpressed in 5 out of 6 clinical lung adenocarcinoma specimens. The analysis of the 60 NSCLC patients revealed that autocrined leptin could serve as an auxiliary prognostic factor, and a higher expression of leptin indicated a higher survival risk. Gene set enrichment analysis (GSEA) showed that the PI3K/AKT/mTOR signaling pathway was positively enriched when the LEP gene was highly expressed, while the P53 signaling pathway was negatively enriched. Leptin promoted cell cycle and clone formation in H1299 and A549 cells, up-regulation or down-regulation of leptin in these two cell lines led to enhanced or declined proliferation. Finally, it was confirmed that the PI3K/AKT/mTOR signaling pathway was positively regulated by leptin expression, while the P53 signaling pathway was negatively regulated.

Conclusions
Autocrined leptin was observed in majority of NSCLC tissue, which could serve as an auxiliary prognostic factor for NSCLC patients. Autocrined leptin had a promoting effect on the proliferation of NSCLC cells, which probably positively regulating the PI3K/AKT/mTOR signaling pathway and negatively regulate the P53 signaling pathway.

Wang|Jin|J| Zhou|Fachen|F| Li|Fengzhou|F| Wang|Bing|B| Hu|Yiying|Y| Li|Xia|X|


Electronic medical record: research tool for pancreatic cancer?

Abstract:
BACKGROUND
A novel data warehouse based on automated retrieval from an institutional health care information system (HIS) was made available to be compared with a traditional prospectively maintained surgical database.

METHODS
A newly established institutional data warehouse at a single-institution academic medical center autopopulated by HIS was queried for International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) diagnosis codes for pancreatic neoplasm. Patients with ICD-9-CM diagnosis codes for pancreatic neoplasm were captured. A parallel query was performed using a prospective database populated by manual entry. Duplicated patients and those unique to either data set were identified. All patients were manually reviewed to determine the accuracy of diagnosis.

RESULTS
A total of 1107 patients were identified from the HIS-linked data set with pancreatic neoplasm from 1999-2009. Of these, 254 (22.9%) patients were also captured by the surgical database, whereas 853 (77.1%) patients were only in the HIS-linked data set. Manual review of the HIS-only group demonstrated that 45.0% of patients were without identifiable pancreatic pathology, suggesting erroneous capture, whereas 36.3% of patients were consistent with pancreatic neoplasm and 18.7% with other pancreatic pathology. Of the 394 patients identified by the surgical database, 254 (64.5%) patients were captured by HIS, whereas 140 (35.5%) patients were not. Manual review of patients only captured by the surgical database demonstrated 85.9% with pancreatic neoplasm and 14.1% with other pancreatic pathology. Finally, review of the 254 patient overlap demonstrated that 80.3% of patients had pancreatic neoplasm and 19.7% had other pancreatic pathology.

CONCLUSIONS
These results suggest that cautious interpretation of administrative data rely only on ICD-9-CM diagnosis codes and clinical correlation through previously validated mechanisms.

Arous|Edward J|EJ|
McDade|Theodore P|TP|
Smith|Jillian K|JK|
Ng|Sing Chau|SC|
Sullivan|Mary E|ME|
Zottola|Ralph J|RJ|
Ranauro|Paul J|PJ|
Shah|Shimul A|SA|
Whalen|Giles F|GF|
Tseng|Jennifer F|JF|

D038801:International Classification of Diseases

Electronic medical record
Pancreatic cancer
Data warehouse
Database
EMR


Montane ecosystem productivity responds more to global circulation patterns than climatic trends.

Abstract: Regional ecosystem productivity is highly sensitive to inter-annual climate variability, both within and outside the primary carbon uptake period. However, Earth system models lack sufficient spatial scales and ecosystem processes to resolve how these processes may change in a warming climate. Here, we show, how for the European Alps, mid-latitude Atlantic ocean winter circulation anomalies drive high-altitude summer forest and grassland productivity, through feedbacks among orographic wind circulation patterns, snowfall, winter and spring temperatures, and vegetation activity. Therefore, to understand future global climate change influence to regional ecosystem productivity, Earth systems models need to focus on improvements towards topographic downscaling of changes in regional atmospheric circulation patterns and to lagged responses in vegetation dynamics to non-growing season climate anomalies.

Desai|A R|AR|
Wohlfahrt|G|G|
Zeeman|M J|MJ|
Katata|G|G|
Eugster|W|W|
Montagnani|L|L|
Gianelle|D|D|
Mauder|M|M|
Schmid|H-P|HP|

atmospheric circulation
Alpine ecology
Foehn
climatic change and variability
ecosystem carbon uptake


Bilateral spontaneous inter-trochanteric fractures of proximal femurs.

Abstract:
INTRODUCTION
Bilateral spontaneous inter-trochanteric fractures of the proximal femur are rare. We report an unusual case of bilateral intertrochanteric fractures of the proximal femur in a 92 year old lady.

PRESENTATION OF CASE
A 92 year old lady presented to us with one week history of pain in both hips and poor mobilisation. There was no history of mechanical fall. The initial plain films of the hips did not show any fractures and the diagnosis was made by MRI scans. She underwent bilateral fixation of the fractures with dynamic hip screws. After a period of rehabilitation she returned to the pre injury mobilisation status.

DISCUSSION
Bilateral spontaneous intertrochanteric fractures of the hip due to osteoporosis are not that common. These rare fractures are usually associated with major trauma, renal disease, osteoporosis, osteomalacia, long term corticosteroid treatment and epilepsy.

CONCLUSION
Early diagnosis with high index of suspicion and appropriate investigations are mandatory in the management of these fractures.

Bilateral
Inter-trochanteric fractures
Insufficiency


Energy utilization, nutrient digestibility and bone quality of broiler chickens fed Tanzania-type diets in different forms with enzymes.

Abstract: A study was conducted to determine the influence of feed form and microbial enzyme supplementation on energy utilization, bone quality, and amino acid and mineral digestibility of broiler chickens. Four hundred and eighty Ross 308, day-old broiler chickens were randomly assigned to eight diets formulated from commonly used ingredients in Tanzania. A 2 (pellet or mash) × 4 (control, Axtra XB, Quantum Blue (QB) and Axtra XB + QB enzyme) factorial array in a completely randomized design having six replicates per treatment (10 birds per replicate) was used. Birds were raised in climate-controlled rooms in a 3-phase; starter (0-10 days), grower (11-24 days) and finisher (25-35 days). Apparent metabolizable energy (AME), metabolizable energy intake, net energy of production, energy retained as protein (REp), and efficiency of metabolizable energy use for energy and protein retention were higher (p < 0.05) in birds fed pelleted diets. The AME and REp was higher (p < 0.05) with enzyme supplementation. Ash content, weight, length, width and breaking strength of tibia bones were highest (p < 0.05) in birds on pelleted diets. Tibia bone traits were improved (p < 0.05) when enzymes were included, particularly in a combination of QB and Axtra XB. However, potassium, magnesium, and zinc contents were highest (p < 0.05) when QB was supplemented. Digestibility of all amino acids was higher (p < 0.05) in birds supplied with pellets and with enzyme supplementation for most amino acids, except for serine. There was a positive interaction (p < 0.05) between feed form and enzymes on lysine and phenylalanine digestibility. Digestibility of Ca, P, K, S, Zn, and Fe was higher (p < 0.05) in birds fed pelleted diets, while those on mashed diets had higher (p < 0.05) digestibility of Cu and B. The digestibility of P, K, and Zn was highest (p < 0.001) when QB was added, while Ca, P, S, and B digestibility was highest when a combination of Axtra XB + QB was applied. Pelleted diets with or without enzymes improved energy utilization, digestibility of amino acids, and minerals, and increased bone strength in broiler chickens.

Enzymes
Pellets
Mash
Feed efficiency
Meat chickens


Consequences of community water fluoridation cessation for Medicaid-eligible children and adolescents in Juneau, Alaska.

Abstract:
BACKGROUND
The general aim of this research was to determine whether cessation of community water fluoridation (CWF) increased oral health disparities, as measured by dental caries procedures and restoration costs for children and adolescents.

METHODS
The analysis was based on all Medicaid dental claims records of 0- to 18-year-old patients residing in zip code 99801 (Juneau, Alaska) during an optimal CWF year (2003, n = 853) compared to all claims for the same age group from 2012 (n = 1052), five years after cessation of CWF. A bivariate analysis (Mann-Whitney U test) of the mean number of caries procedures performed per client was conducted in the study groups under both independent CWF conditions. Furthermore, logistic regression was performed using the dependent variables of caries procedures and the cost of caries-related procedures, with adjustments for CWF group, gender, and race.

RESULTS
The statistically significant results included a higher mean number of caries-related procedures among 0- to 18-year-old and < 7-year-old patients in the suboptimal CWF group (2.35 vs. 2.02, p < 0.001; 2.68 vs. 2.01, p = 0.004, respectively). The mean caries-related treatment costs per patient were also significantly higher for all age groups, ranging from a 28 to 111% increase among the suboptimal CWF cohorts after adjusting for inflation. The binary logistic regression analysis results indicated a protective effect of optimal CWF for the 0- to 18-year-old and < 7-year-old age groups (OR = 0.748, 95% CI [0.62, 0.90], p = 0.002; OR = 0.699, 95% CI [0.52, 0.95], p = 0.02, respectively). Additionally, the age group that underwent the most dental caries procedures and incurred the highest caries treatment costs on average were those born after CWF cessation.

CONCLUSIONS
These results expand our understanding of caries epidemiology under CWF cessation conditions and reaffirm that optimal CWF exposure prevents dental decay. These findings can offer fiscal estimates of the cost burden associated with CWF cessation policies and help decision-makers advance oral health, prevent dental caries, and promote equity in oral health outcomes.


Gonadotropin dose is negatively correlated with live birth rate: analysis of more than 650,000 assisted reproductive technology cycles.

Abstract:
OBJECTIVE
To evaluate the correlation between total gonadotropin dose and live birth rate.

DESIGN
Retrospective analysis.

SETTING
Not applicable.

PATIENT(S)
A total of 658,519 fresh autologous cycles of in vitro fertilization (IVF) reported to the Society for Assisted Reproductive Technology from 2004 to 2012.

INTERVENTION(S)
None.

MAIN OUTCOME MEASURE(S)
Logistic regression models were fitted to live birth rates with the use of categorized values for total FSH dose and number of oocytes retrieved as the primary predictor variables. To reduce the effect of the most significant confounders that may lead physicians to prescribe higher doses of FSH, additional analyses were performed limited to good-prognosis patients (<35 years of age, body mass index <30 kg/m(2), and no diagnosis of diminished ovarian reserve, endometriosis, or ovulatory disorder) and including duration of gonadotropin treatment.

RESULT(S)
Live birth rate significantly decreased with increasing FSH dose, regardless of the number of oocytes retrieved. The statistically significant decrease in live birth rate with increasing FSH dose remained in patients with good prognosis, and regardless of female age, except for women aged ≥ 35 years with 1-5 oocytes retrieved.

CONCLUSION(S)
This analysis suggests that physicians may wish to avoid prescribing a high dose of FSH. However, the results of this study do not justify the use of minimal-stimulation or natural-cycle IVF.

Baker|Valerie L|VL|
Brown|Morton B|MB|
Luke|Barbara|B|
Smith|George W|GW|
Ireland|James J|JJ|

gonadotropin dose
live birth rate
In vitro fertilization


Plasticity of Promoter-Core Sequences Allows Bacteria to Compensate for the Loss of a Key Global Regulatory Gene.

Abstract: Transcription regulatory networks (TRNs) are of central importance for both short-term phenotypic adaptation in response to environmental fluctuations and long-term evolutionary adaptation, with global regulatory genes often being targets of natural selection in laboratory experiments. Here, we combined evolution experiments, whole-genome resequencing, and molecular genetics to investigate the driving forces, genetic constraints, and molecular mechanisms that dictate how bacteria can cope with a drastic perturbation of their TRNs. The crp gene, encoding a major global regulator in Escherichia coli, was deleted in four different genetic backgrounds, all derived from the Long-Term Evolution Experiment (LTEE) but with different TRN architectures. We confirmed that crp deletion had a more deleterious effect on growth rate in the LTEE-adapted genotypes; and we showed that the ptsG gene, which encodes the major glucose-PTS transporter, gained CRP (cyclic AMP receptor protein) dependence over time in the LTEE. We then further evolved the four crp-deleted genotypes in glucose minimal medium, and we found that they all quickly recovered from their growth defects by increasing glucose uptake. We showed that this recovery was specific to the selective environment and consistently relied on mutations in the cis-regulatory region of ptsG, regardless of the initial genotype. These mutations affected the interplay of transcription factors acting at the promoters, changed the intrinsic properties of the existing promoters, or produced new transcription initiation sites. Therefore, the plasticity of even a single promoter region can compensate by three different mechanisms for the loss of a key regulatory hub in the E. coli TRN.

Lamrabet|Otmane|O|
Plumbridge|Jacqueline|J|
Martin|Mikaël|M|
Lenski|Richard E|RE|
Schneider|Dominique|D|
Hindré|Thomas|T|

D015964:Gene Expression Regulation, Bacterial

bacteria
transcription regulatory networks
cAMP receptor protein
compensatory mutations
experimental evolution
fitness


Flying and midface fractures: the truth is out there.

Abstract: There are no clear, evidence-based guidelines that dictate when it is safe for a patient to fly after sustaining a midface fracture. From January 2006 to December 2009, the Royal Darwin Hospital Maxillofacial Unit had 48 out of 201 patients with an orbital fracture that involved a paranasal air sinus transported by a variety of aircraft to the unit for definitive management. No orbital complications were recorded for the 24% of patients requiring air travel to our tertiary referral centre. Furthermore, there were no recorded deviations from the standard flight plan. We believe that this demonstrates there are no absolute contraindications to flying on a variety of aircraft with a midface fracture, but clinical assessment remains crucial for an informed decision to transport these patients by air.

Tan-Gore|E|E|
Thanigaivel|R|R|
Wilson|B|B|
Thomas|A|A|
Thomas|M E|ME|

D064870:Air Travel
D001315:Australia
D005147:Facial Bones
D006801:Humans
D009917:Orbital Fractures
D010256:Paranasal Sinuses
D010360:Patient Transfer
D062606:Tertiary Care Centers

flying
midface
guidelines
maxillofacial
air travel
recommendations
trauma


Replisome activity slowdown after exposure to ultraviolet light in Escherichia coli.

Abstract: The replisome is a multiprotein machine that is responsible for replicating DNA. During active DNA synthesis, the replisome tightly associates with DNA. In contrast, after DNA damage, the replisome may disassemble, exposing DNA to breaks and threatening cell survival. Using live cell imaging, we studied the effect of UV light on the replisome of Escherichia coli Surprisingly, our results showed an increase in Pol III holoenzyme (Pol III HE) foci post-UV that do not colocalize with the DnaB helicase. Formation of these foci is independent of active replication forks and dependent on the presence of the χ subunit of the clamp loader, suggesting recruitment of Pol III HE at sites of DNA repair. Our results also showed a decrease of DnaB helicase foci per cell after UV, consistent with the disassembly of a fraction of the replisomes. By labeling newly synthesized DNA, we demonstrated that a drop in the rate of synthesis is not explained by replisome disassembly alone. Instead, we show that most replisomes continue synthesizing DNA at a slower rate after UV. We propose that the slowdown in replisome activity is a strategy to prevent clashes with engaged DNA repair proteins and preserve the integrity of the replication fork.

D004249:DNA Damage
D004260:DNA Repair
D004261:DNA Replication
D004269:DNA, Bacterial
D053488:DnaB Helicases
D004926:Escherichia coli
D014466:Ultraviolet Rays

replisome
Escherichia coli
UV
DNA replication
fluorescence microscopy


Genomic positional conservation identifies topological anchor point RNAs linked to developmental loci.

Abstract:
BACKGROUND
The mammalian genome is transcribed into large numbers of long noncoding RNAs (lncRNAs), but the definition of functional lncRNA groups has proven difficult, partly due to their low sequence conservation and lack of identified shared properties. Here we consider promoter conservation and positional conservation as indicators of functional commonality.

RESULTS
We identify 665 conserved lncRNA promoters in mouse and human that are preserved in genomic position relative to orthologous coding genes. These positionally conserved lncRNA genes are primarily associated with developmental transcription factor loci with which they are coexpressed in a tissue-specific manner. Over half of positionally conserved RNAs in this set are linked to chromatin organization structures, overlapping binding sites for the CTCF chromatin organiser and located at chromatin loop anchor points and borders of topologically associating domains (TADs). We define these RNAs as topological anchor point RNAs (tapRNAs). Characterization of these noncoding RNAs and their associated coding genes shows that they are functionally connected: they regulate each other's expression and influence the metastatic phenotype of cancer cells in vitro in a similar fashion. Furthermore, we find that tapRNAs contain conserved sequence domains that are enriched in motifs for zinc finger domain-containing RNA-binding proteins and transcription factors, whose binding sites are found mutated in cancers.

CONCLUSIONS
This work leverages positional conservation to identify lncRNAs with potential importance in genome organization, development and disease. The evidence that many developmental transcription factors are physically and functionally connected to lncRNAs represents an exciting stepping-stone to further our understanding of genome regulation.

Amaral|Paulo P|PP|
Leonardi|Tommaso|T|
Han|Namshik|N|
Viré|Emmanuelle|E|
Gascoigne|Dennis K|DK|
Arias-Carrasco|Raúl|R|
Büscher|Magdalena|M|
Pandolfini|Luca|L|
Zhang|Anda|A|
Pluchino|Stefano|S|
Maracaja-Coutinho|Vinicius|V|
Nakaya|Helder I|HI|
Hemberg|Martin|M|
Shiekhattar|Ramin|R|
Enright|Anton J|AJ|
Kouzarides|Tony|T|

D018507:Gene Expression Regulation, Developmental

Topology
lncRNAs
Cancer
Zinc finger
Development
Chromatin architecture


Extracellular vesicles and pancreatitis: mechanisms, status and perspectives.

Abstract: Comprehensive reviews and large population-based cohort studies have played an important role in the diagnosis and treatment of pancreatitis and its sequelae. The incidence and mortality of pancreatitis have been reduced significantly due to substantial advancements in the pathophysiological mechanisms and clinically effective treatments. The study of extracellular vesicles (EVs) has the potential to identify cell-to-cell communication in diseases such as pancreatitis. Exosomes are a subset of EVs with an average diameter of 50~150 nm. Their diverse and unique constituents include nucleic acids, proteins, and lipids, which can be transferred to trigger phenotypic changes of recipient cells. In recent years, many reports have indicated the role of EVs in pancreatitis, including acute pancreatitis, chronic pancreatitis and autoimmune pancreatitis, suggesting their potential influence on the development and progression of pancreatitis. Plasma exosomes of acute pancreatitis can effectively reach the alveolar cavity and activate alveolar macrophages to cause acute lung injury. Furthermore, upregulated exosomal miRNAs can be used as biomarkers for acute pancreatitis. Here, we summarized the current understanding of EVs in pancreatitis with an emphasis on their biological roles and their potential use as diagnostic biomarkers and therapeutic agents for this disease.

Jia|Yu-Chen|YC| Ding|Yi-Xuan|YX| Mei|Wen-Tong|WT| Wang|Yu-Ting|YT| Zheng|Zhi|Z| Qu|Yuan-Xu|YX| Liang|Kuo|K| Li|Jia|J| Cao|Feng|F| Li|Fei|F|

extracellular vesicles
pancreatitis
exosomes
biomarkers


Predictors of Loss to Follow-Up Among Pediatric and Adult Hematopoietic Cell Transplantation Survivors: A Report from the Center for International Blood and Marrow Transplant Research.

Abstract: Follow-up is integral for hematopoietic cell transplantation (HCT) care to ensure surveillance and intervention for complications. We characterized the incidence of and predictors for being lost to follow-up. Two-year survivors of first allogeneic HCT (10,367 adults and 3865 children) or autologous HCT (7291 adults and 467 children) for malignant/nonmalignant disorders between 2002 and 2013 reported to the Center for International Blood and Marrow Transplant Research were selected. The cumulative incidence of being lost to follow-up (defined as having missed 2 consecutive follow-up reporting periods) was calculated. Marginal Cox models (adjusted for center effect) were fit to evaluate predictors. The 10-year cumulative incidence of being lost to follow-up was 13% (95% confidence interval [CI], 12% to 14%) in adult allogeneic HCT survivors, 15% (95% CI, 14% to 16%) in adult autologous HCT survivors, 25% (95% CI, 24% to 27%) in pediatric allogeneic HCT survivors, and 24% (95% CI, 20% to 29%) in pediatric autologous HCT survivors. Factors associated with being lost to follow-up include younger age, nonmalignant disease, public/no insurance (reference: private), residence farther from the tranplantation center, and being unmarried in adult allogeneic HCT survivors; older age and testicular/germ cell tumor (reference: non-Hodgkin lymphoma) in adult autologous HCT survivors; older age, public/no insurance (reference: private), and nonmalignant disease in pediatric allogeneic HCT survivors; and older age in pediatric autologous HCT survivors. Follow-up focusing on minimizing attrition in high-risk groups is needed to ensure surveillance for late effects.

Buchbinder|David|D|
Brazauskas|Ruta|R|
Bo-Subait|Khalid|K|
Ballen|Karen|K|
Parsons|Susan|S|
John|Tami|T|
Hahn|Theresa|T|
Sharma|Akshay|A|
Steinberg|Amir|A|
D'Souza|Anita|A|
Kumar|Anita J|AJ|
Yoshimi|Ayami|A|
Wirk|Baldeep|B|
Shaw|Bronwen|B|
Freytes|César|C|
LeMaistre|Charles|C|
Bredeson|Christopher|C|
Dandoy|Christopher|C|
Almaguer|David|D|
Marks|David I|DI|
Szwajcer|David|D|
Hale|Gregory|G|
Schouten|Harry|H|
Hashem|Hasan|H|
Schoemans|Hélène|H|
Murthy|Hemant S|HS|
Lazarus|Hillard M|HM|
Cerny|Jan|J|
Tay|Jason|J|
Yared|Jean A|JA|
Adekola|Kehinde|K|
Schultz|Kirk R|KR|
Lehmann|Leslie|L|
Burns|Linda|L|
Aljurf|Mahmoud|M|
Diaz|Miguel Angel|MA|
Majhail|Navneet|N|
Farhadfar|Nosha|N|
Kamble|Rammurti|R|
Olsson|Richard|R|
Schears|Raquel|R|
Seo|Sachiko|S|
Beattie|Sara|S|
Chhabra|Saurabh|S|
Savani|Bipin N|BN|
Badawy|Sherif|S|
Ganguly|Siddhartha|S|
Ciurea|Stefan|S|
Marino|Susana|S|
Gergis|Usama|U|
Kuwatsuka|Yachiyo|Y|
Inamoto|Yoshihiro|Y|
Khera|Nandita|N|
Hashmi|Shahrukh|S|
Wood|William|W|
Saber|Wael|W|

D018380:Hematopoietic Stem Cell Transplantation

Survivor
Lost to follow-up
Bone marrow transplantation
Stem cell transplantation


Variability in total shoulder arthroplasty planning software compared to a control CT-derived 3D printed scapula.

Abstract:
Background
Two techniques exist from which all 3D preoperative planning software for total shoulder arthroplasty are based. One technique is based on measurements constructed on the mid-glenoid and scapular landmarks (Landmark). The second is an automated system using a best-fit sphere technique (Automated). The purpose was to compare glenoid measurements from the two techniques against a control computed tomography-derived 3D printed scapula.

Methods
Computed tomography scans of osteoarthritic shoulders of 20 patients undergoing primary total shoulder arthroplasty were analyzed with both 3D planning software techniques. Measurements from a 3D printed scapula (Scapula) from the true 3D computed tomography scan served as controls. Glenoid version and inclination measurements from each group were blinded and reviewed.

Results
In 65% (Automated) and 45% (Landmark) of cases, either inclination or version varied by 5° or more versus 3D printed scapula. Significant variability in version differences compared to the scapula group existed (p = 0.007). Glenoid version from the Scapula = 13.0° ± 10.6°, Automated = 15.0° ± 13.9°, and Landmark = 12.2° ± 7.8°. Inclination from Scapula = 5.4° ± 7.9°, Automated = 6.1° ± 12.6°, and Landmark = 6.2° ± 9.1°.

Discussion
A high percentage of cases showed discrepancies in glenoid inclination and version values from both techniques. Surgeons should be aware that regardless of software technique, there is variability compared to measurements from a control 3D computed tomography printed scapula.

Total shoulder arthroplasty
preoperative planning
glenoid version
glenoid inclination
patient-specific instrumentation
three-dimensional analysis


How do Swiss general practitioners agree with and report adhering to a top-five list of unnecessary tests and treatments? Results of a cross-sectional survey.

Abstract:
BACKGROUND
In 2014, the 'Smarter Medicine' campaign released a top five list of unnecessary tests and treatments in Swiss primary care, such as imaging for acute low-back pain and long-term prescribing of proton pump inhibitors.

OBJECTIVES
Measure general practitioners' (GPs) agreement with the recommendations and self-reported adherence.

METHODS
Cross-sectional, online survey of GPs in the 'Swiss primary care active monitoring' (SPAM) network, which assessed awareness of 'Smarter Medicine' and views on each recommendation. Questions included whether the clinical situation is common, whether the recommendation is followed, whether GPs agree with the recommendation and reasons why the recommendation would not be followed.

RESULTS
One-hundred-and-sixty-seven of 277 GPs from the SPAM network participated (60%), of which 104 (62%) knew of 'Smarter Medicine', including 79% in German areas, 49% in French areas and 38% in Italian areas (P < 0.001). Agreement with the five recommendations was high, with scores around nine out of 10. The proportion saying they typically follow each recommendation was 68 to 74%, except not continuing long-term PPI prescriptions without attempting dose reduction, with only 34%. Common reasons for not following the recommendations were patient or other provider requests and situations that might suggest the need for more aggressive care.

CONCLUSION
Two years after the launch of the campaign, awareness and acceptance of 'Smarter Medicine' appear to be high among Swiss GPs. By self-report, the recommendations are adhered to by most of the respondents but there may be room for improvement, especially for long-term PPI prescriptions.

Selby|Kevin|K| Cornuz|Jacques|J| Cohidon|Christine|C| Gaspoz|Jean-Michel|JM| Senn|Nicolas|N|

D001291:Attitude of Health Personnel
D003430:Cross-Sectional Studies
D005260:Female
D058005:General Practitioners
D019983:Guideline Adherence
D006801:Humans
D057970:Inappropriate Prescribing
D008297:Male
D008875:Middle Aged
D010818:Practice Patterns, Physicians'
D011320:Primary Health Care
D054328:Proton Pump Inhibitors
D057566:Self Report
D011795:Surveys and Questionnaires
D013557:Switzerland
D019564:Unnecessary Procedures

proton pump inhibitors
Clinical decision-making
general practice
medical overuse
rational use of medications


Phycoremediation and valorization of synthetic dairy wastewater using microalgal consortia of Chlorella variabilis and Scenedesmus obliquus.

Abstract: Microalgae are known to grow on wastewater utilizing their available nutrients. The residual algal biomass thus obtained could be used for producing value-added products thereby making it an economically viable and sustainable option for the dairy industry. The present study evaluates the ability of the microalgal consortia composed of Chlorella variabilis and Scenedesmus obliquus to treat and valorize diluted synthetic dairy wastewater under controlled laboratory conditions. The effect of time, inoculum concentration and light intensity on five responses, namely phosphate removal, ammoniacal nitrogen removal, COD removal, biomass productivity and lutein content, are studied by response surface methodology utilizing central composite design. The quadratic models are found to be suitable for phosphate removal, ammoniacal nitrogen removal, COD removal and biomass productivity. At optimized experimental conditions, the microalgal consortia exhibited phosphate removal of 70.19%, ammoniacal nitrogen removal of 86.22%, COD removal of 54.72%, biomass productivity of 29.13 mg/L/day and lutein content of 12.59 mg/g respectively. This study is of high importance as the lutein content exhibited by the microalgal consortia is higher when compared to other microalgal species and could be considered in the future as a commercial source of lutein.

Gatamaneni Loganathan|Bhalamurugan|B|
Orsat|Valerie|V|
Lefsrud|Mark|M|

Dairy wastewater
microalgal consortia
biomass productivity
lutein content
nutrient removal


How can proteomics elucidate the complexity of multiple sclerosis?

Abstract: Multiple sclerosis affects more than 2.5 million people worldwide. Although multiple sclerosis was described almost 150 years ago, there are many knowledge gaps regarding its etiology, diagnosis, prognosis, and pathogenesis. Multiple sclerosis is an inflammatory, demyelinating, neurodegenerative disease of the CNS. During the last several decades, experimental models of multiple sclerosis have contributed to our understanding of the inflammatory disease mechanisms and have aided drug testing and development. However, little is known about the neurodegenerative mechanisms that operate during the evolution of the disease. Currently, all therapeutic approaches are primarily based on the inflammatory aspect of the disease. During the last decade, proteomics has emerged as a promising tool for revealing molecular pathways as well as identifying and quantifying differentially expressed proteins. Therefore, proteomics may be used for the discovery of biomarkers, potential drug targets, and new regulatory mechanisms. To date, a considerable number of proteomics studies have been conducted on samples from experimental models and patients with multiple sclerosis. These data form a solid base for further careful analysis and validation.

Farias|Alessandro S|AS|
Santos|Leonilda M B|LM|


Direct α-arylation of ethers through the combination of photoredox-mediated C-H functionalization and the Minisci reaction.

Abstract: The direct α-arylation of cyclic and acyclic ethers with heteroarenes has been accomplished through the design of a photoredox-mediated CH functionalization pathway. Transiently generated α-oxyalkyl radicals, produced from a variety of widely available ethers through hydrogen atom transfer (HAT), were coupled with a range of electron-deficient heteroarenes in a Minisci-type mechanism. This mild, visible-light-driven protocol allows direct access to medicinal pharmacophores of broad utility using feedstock substrates and a commercial photocatalyst.

ethers
CH functionalization
alkylation
heterocycles
photoredox catalysis


Detection and characterization of purified antigenic proteins from culture filtrate of Mycobacterium bovis strain AN5.

Abstract:
Background and Objectives
Bovine tuberculosis diagnosis is usually performed by various tests with specific limitations. Mycobacterium bovis culture filtrate contains antigenic proteins that could be used to improve the sensitivity of bovine tuberculosis diagnosis. The objective of this study was to identify and purify antigenic proteins from culture filtrates of M. bovis strain AN5 for use in immunological assays.

Materials and Methods
Secreted proteins were purified from the heat-treated culture filtrate of M. bovis strain AN5. Proteins were precipitated with ammonium sulfate, fractionated by Sephadex G50 chromatography. The protein concentrations and the approximate molecular weight were determined by lowry method and 12% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), respectively. Immunological methods, including dot-blotting and western blotting, assessed the quality of the isolated proteins.

Results
The quantity of antigenic proteins in the culture medium was measured at far more than 15% of the amount of proteins secreted into medium. Three main chromatographic fractions obtained and showed concentrations of proteins ranging from 14 to 60 μg/ μl with molecular weights in the 10 to 180 kDa range. The purified antigens showed positive reactions to the infected cattle serum throughout dot-blotting. Western blotting revealed a total of 15 to 70 kDa molecular weight proteins.

Conclusion
Immunoblotting analysis made it possible to detect and recognize novel antigens that are useful for bovine tuberculosis diagnosis improvement. This is significant since non-specific reactions were not observed when we utilized serum of cattle experimentally infected with M. bovis as a polyclonal antibody.

Kashi|Malihe Honarmand|MH|
Mosavari|Nader|N|
Salehi|Mitra|M|
Mojgani|Naheed|N|

Purified antigenic proteins
Mycobacterium bovis
Dot-blot
Western blot


Gender differences in factors associated with body weight misperception.

Abstract:
OBJECTIVE
Gender analysis in health research is important to strengthen our health system. The current study aimed to explore factors related to body weight misperception in a national sample of the general Korean population.

DESIGN
Cross-sectional study.

SETTING
South Korea, general population.

PARTICIPANTS
12,900 adults enrolled from the Seventh Korea National Health and Nutrition Examination Survey (2016-2018).

RESULTS
Disadvantageous socio-economic status was considered a predictor of participants' misperceptions of themselves as being of a healthy weight despite being overweight and as underweight despite being of a healthy weight, mainly in men. Favourable socio-economic status was considered a predictor of participants' misperceptions of themselves as being of a healthy weight despite being underweight and as overweight despite being of a healthy weight, mainly in women. Living in an urban area was an independent predictor of men's misperception of themselves as being of a healthy weight despite being overweight and women's misperception of themselves as being underweight despite being of a healthy weight. Physical inactivity was a predictor of most misperceptions in women. Psychological variables, such as stress and depression, were not significant predictors of misperception.

CONCLUSIONS
The current study highlighted the gender differences in factors related to body weight misperception. These differences suggested that more sophisticated policies should be formulated to identify solutions to health problems related to body weight.

Gender
Factors
Body weight misperception
BMI


Size-Dependent Ag2S Nanodots for Second Near-Infrared Fluorescence/Photoacoustics Imaging and Simultaneous Photothermal Therapy.

Abstract: Ag2S nanoparticles are increasingly important in biomedicine, such as in cancer imaging. However, there has been only limited success in the exploration of theranostic Ag2S nanoparticles for photoinduced cancer imaging and simultaneous therapy. Here we report size-dependent Ag2S nanodots (NDs) with well-defined nanostructure as a theranostic agent for multimodal imaging and simultaneous photothermal therapy. The NDs are precisely synthesized through carefully controlled growth of Ag2S in hollow human serum albumin nanocages. These NDs produce effective fluorescence in second near-infrared (NIR-II) region, distinct photoacoustic intensity, and good photothermal conversion in a size-dependent manner under light irradiation, thereby generating sufficient in vivo fluorescence and photoacoustic signals as well as potent hyperthermia at tumors. Moreover, Ag2S NDs possess ideal resistance to photobleaching, effective cellular uptake, preferable tumor accumulation, and in vivo elimination, thus facilitating NIR-II fluorescence/photoacoustics imaging with both ultrasensitivity and microscopic spatial resolution and simultaneous photothermal tumor ablation. These findings provide insight into the clinical potential of Ag2S nanodots for cancer theranostics.

Yang|Tao|T| Tang|Yong'an|Y| Liu|Ling|L| Lv|Xiaoyan|X| Wang|Qiaoli|Q| Ke|Hengte|H| Deng|Yibin|Y| Yang|Hong|H| Yang|Xiangliang|X| Liu|Gang|G|0000-0003-2613-7286 Zhao|Yuliang|Y|0000-0002-9586-9360 Chen|Huabing|H|0000-0003-1637-2872

D000818:Animals
D045744:Cell Line, Tumor
D002470:Cell Survival
D006801:Humans
D007259:Infrared Rays
D051379:Mice
D064847:Multimodal Imaging
D049329:Nanostructures
D009374:Neoplasms, Experimental
D061848:Optical Imaging
D010316:Particle Size
D055668:Photochemical Processes
D010789:Phototherapy
D016062:Porosity
D045663:Quantum Dots
D000075462:Serum Albumin, Human
D018030:Silver Compounds
D013499:Surface Properties

Ag2S nanodot
second near-infrared fluorescence
photothermal therapy
albumin nanocage
tumor ablation


Pneumocephalus patterns following endonasal endoscopic skull base surgery as predictors of postoperative CSF leaks.

Abstract:
OBJECTIVES
Postoperative pneumocephalus is a common occurrence after endoscopic endonasal skull base surgery (ESBS). The risk of cerebrospinal fluid (CSF) leaks can be high and the presence of postoperative pneumocephalus associated with serosanguineous nasal drainage may raise suspicion for a CSF leak. The authors hypothesized that specific patterns of pneumocephalus on postoperative imaging could be predictive of CSF leaks. Identification of these patterns could guide the postoperative management of patients undergoing ESBS.

METHODS
The authors queried a prospectively acquired database of 526 consecutive ESBS cases at a single center between December 1, 2003, and May 31, 2012, and identified 258 patients with an intraoperative CSF leak documented using intrathecal fluorescein. Postoperative CT and MRI scans obtained within 1-10 days were examined and pneumocephalus was graded based on location and amount. A discrete 0-4 scale was used to classify pneumocephalus patterns based on size and morphology. Pneumocephalus was correlated with the surgical approach, histopathological diagnosis, and presence of a postoperative CSF leak.

RESULTS
The mean follow-up duration was 56.7 months. Of the 258 patients, 102 (39.5%) demonstrated pneumocephalus on postoperative imaging. The most frequent location of pneumocephalus was frontal (73 [71.5%] of 102), intraventricular (34 [33.3%]), and convexity (22 [21.6%]). Patients with craniopharyngioma (27 [87%] of 31) and meningioma (23 [68%] of 34) had the highest incidence of postoperative pneumocephalus compared with patients with pituitary adenomas (29 [20.6%] of 141) (p < 0.0001). The incidence of pneumocephalus was higher with transcribriform and transethmoidal approaches (8 of [73%] 11) than with a transsellar approach (9 of [7%] 131). There were 15 (5.8%) of 258 cases of postoperative CSF leak, of which 10 (66.7%) had pneumocephalus, compared with 92 (38%) of 243 patients without a postoperative CSF leak (OR 3.3, p = 0.027). Pneumocephalus located in the convexity, interhemispheric fissure, sellar region, parasellar region, and perimesencephalic region was significantly correlated with a postoperative CSF leak (OR 4.9, p = 0.006) and was therefore termed "suspicious" pneumocephalus. In contrast, frontal or intraventricular pneumocephalus was not correlated with postoperative CSF leak (not significant) and was defined as "benign" pneumocephalus. The amount of convexity pneumocephalus (p = 0.002), interhemispheric pneumocephalus (p = 0.005), and parasellar pneumocephalus (p = 0.007) (determined using a scale score of 0-4) was also significantly related to postoperative CSF leaks. Using a series of permutation-based multivariate analyses, the authors established that a model containing the learning curve, the transclival/transcavernous approach, and the presence of "suspicious" pneumocephalus provides the best overall prediction for postoperative CSF leaks.

CONCLUSIONS
Postoperative pneumocephalus is much more common following extended approaches than following transsellar surgery. Merely the presence of pneumocephalus, particularly in the frontal or intraventricular locations, is not necessarily associated with a postoperative CSF leak. A "suspicious" pattern of air, namely pneumocephalus in the convexity, interhemispheric fissure, sella, parasellar, or perimesencephalic locations, is significantly associated with a postoperative CSF leak. The presence and the score of "suspicious" pneumocephalus on postoperative imaging, in conjunction with the learning curve and the type of endoscopic approach, provide the best predictive model for postoperative CSF leaks.

Banu|Matei A|MA|
Szentirmai|Oszkar|O|
Mascarenhas|Lino|L|
Salek|Al Amin|AA|
Anand|Vijay K|VK|
Schwartz|Theodore H|TH|

pneumocephalus
endonasal
endoscopic
skull base
CSF leak
transsellar
transclival
transcavernous
BMI = body mass index
ESBS = endonasal skull base surgery
NTR = near-total resection
STR = subtotal resection


Furthering the debate on the role of interstitial cells of Cajal in enteric inhibitory neuromuscular neurotransmission.

Abstract: The gut, a muscular organ, performs a critical role in transporting ingested contents, yet it is also controlled to periodically stop transport to maximize digestion and toxin detection. The complex intraluminal composition and rheology challenge the mechanistic requirements of inhibitory neuromuscular neurotransmission. The interstitial cells of Cajal (ICCs)-generated slow wave may tune the promiscuous luminal chemical environment, which prepares the smooth muscle membrane potential for a depolarizing or hyperpolarizing response as needed. Slow waves are abolished during stimulation-induced inhibitory junction potentials (IJPs) due to purinergic-nitrergic tandem neurotransmission. Recent data demonstrating intact IJPs in a genomic knockout of ICCs provide rigorous evidence of the noncontribution of ICCs during evoked neurotransmission. This perspective article discusses the priority areas of investigations in enteric musculomotor transmission, for understanding its near-perfect design for chemical space sensing, as well as diseases in which the luminal transport braking process becomes dysfunctional, leading to delayed gastric emptying or intestinal transit.

D000818:Animals
D004558:Electric Stimulation
D006801:Humans
D056885:Interstitial Cells of Cajal
D008564:Membrane Potentials
D009130:Muscle, Smooth
D009469:Neuromuscular Junction
D009435:Synaptic Transmission

interstitial cells of Cajal
neurotransmission
ICC
nitrergic
nitric oxide


Adolescents' self-perceived and actual weight: Which plays a dominant role in weight loss behaviour in Lebanon?

Abstract:
BACKGROUND
The decision to lose weight among adolescents is complex and is guided by a number of body-related factors. This study examined the extent of agreement between actual weight, measured as body mass index, and self-perceived weight and assessed their relative importance in weight loss behaviour among Lebanese adolescents.

METHODS
Data on 278 adolescents aged 13-17 years were drawn from the nationwide Nutrition and Non-Communicable Disease Risk Factor Survey (Lebanon, 2009). Binary multivariable logistic regressions were conducted to test associations with "effort to lose weight" as the outcome variable, controlling for a number of potential confounders.

RESULTS
Close to 36% reported trying to lose weight. Around 21% and 13% were overweight and obese, respectively, and 40% and 10% perceived their weight as slightly high and very high, respectively. Inaccurate perceivers, those underestimating or overestimating their weight, constituted 39%, with overall percent agreement between actual and self-perceived weight being 60.8% (kappa statistic = 0.319, 95% CI [0.242, 0.396]). About a third of the overweight adolescents (30.5%) and more than half of the obese (56.8%) underestimated their weight. In the multivariable analysis, self-perceived weight was statistically significant and a stronger predictor of weight loss effort than body mass index (adjusted odds ratios = 14.42 and 6.42 for slightly high and very high perceived weight, respectively, compared to odds ratios = 1.47 and 2.31 for overweight and obese adolescents, respectively).

CONCLUSION
Health professionals need to consider self-perceived weight in conjunction with actual weight in their pursuit of weight management goals and in planning prevention programmes that guide weight loss behaviours for adolescents.

weight loss
Lebanon
body mass index
weight perception


Effect on mode of death of heart failure treatment started with bisoprolol followed by Enalapril, compared to the opposite order: results of the randomized CIBIS III trial.

Abstract:
BACKGROUND
Mode of death in chronic heart failure (CHF) may be of relevance to choice of therapy for this condition. Sudden death is particularly common in patients with early and/or mild/moderate CHF. β-Blockade may provide better protection against sudden death than ACE inhibition (ACEI) in this setting.

METHODS
We randomized 1010 patients with mild or moderate, stable CHF and left ventricular ejection fraction ≤35%, without ACEI, β-blocker or angiotensin-receptor-blocker therapy, to either bisoprolol (n = 505) or enalapril (n = 505) for 6 months, followed by their combination for 6-24 months. The two strategies were blindly compared regarding adjudicated mode of death, including sudden death and progressive pump failure death.

RESULTS
During the monotherapy phase, 8 of 23 deaths in the bisoprolol-first group were sudden, compared to 16 of 32 in the enalapril-first group: hazard ratio (HR) for sudden death 0.50; 95% confidence interval (CI) 0.21-1.16; P= 0.107. At 1 year, 16 of 42 versus 29 of 60 deaths were sudden: HR 0.54; 95% CI 0.29-1.00; P= 0.049. At study end, 29 of 65 versus 34 of 73 deaths were sudden: HR 0.84; 95% CI 0.51-1.38; P= 0.487. Comparable figures for pump failure death were: monotherapy, 7 of 23 deaths versus 2 of 32: HR 3.43; 95% CI 0.71-16.53; P= 0.124, at 1 year, 13 of 42 versus 5 of 60: HR 2.57; 95% CI 0.92-7.20; P= 0.073, at study end, 17 of 65 versus 7 of 73: HR 2.39; 95% CI 0.99-5.75; P= 0.053. There were no significant between-group differences in any other fatal events.

CONCLUSION
Initiating therapy with bisoprolol compared to enalapril decreased the risk of sudden death during the first year in this mild systolic CHF cohort. This was somewhat offset by an increase in pump failure deaths in the bisoprolol-first cohort.

Krum|Henry|H|
van Veldhuisen|Dirk J|DJ|
Funck-Brentano|Christian|C|
Vanoli|Emilio|E|
Silke|Bernard|B|
Erdmann|Erland|E|
Follath|Ferenc|F|
Ponikowski|Piotr|P|
Goulder|Michael|M|
Meyer|Wilfried|W|
Lechat|Philippe|P|
Willenheimer|Ronnie|R|
|||


Venous Thromboembolism While on Anticoagulation With Apixaban.

Abstract: Venous thromboembolism (VTE) is a common condition whose pathophysiology is explained by Virchow's triad with stasis, hypercoagulability, and endothelial injury. Direct oral anticoagulants (DOACs) showed non-inferiority when compared with conventional treatment using subcutaneous low molecular weight heparin (LMWH) and warfarin, but treatment failure is a concern and remains a challenge for physicians. In our case report, we present a patient who had VTE in the form of a saddle pulmonary embolus while on apixaban.

venous thromboembolism (vte)
cardiovascular diseases / blood
failed anticoagulation
saddle pulmonary embolism


A choline chloride-acrylic acid deep eutectic solvent polymer based on Fe3O4 particles and MoS2 sheets (poly(ChCl-AA DES)@Fe3O4@MoS2) with specific recognition and good antibacterial properties for β-lactoglobulin in milk.

Abstract: With the development of deep eutectic solvents (DESs), more DES-based functional materials have been explored and applied in various areas. In this work, a novel choline chloride-acrylic acid (ChCl-AA) DES polymer, on a 2D magnetic base, was prepared for the recognition of β-lactoglobulin (β-LG) biomacromolecules in milk and for the inhibition of common bacteria such as Escherichia coli (E. coli), Pseudomonas fluorescens (P. fluorescens), Staphylococcus aureus (S. aureus), and Bacillus subtilis (B. subtilis). The ChCl-AA DESs were polymerized on the surface of 2D MoS2 sheets doped with nano Fe3O4 particles, and the resulting polymer was abbreviated poly(ChCl-AA DES)@Fe3O4@MoS2. The free energy (ΔG=-92) of ChCl-AA DES was calculated using the Gaussian software, the composition and structure of poly(ChCl-AA DES)@Fe3O4@MoS2 were characterized by field emission scanning electron microscopy, transmission electron microscopy, etc., the qualitative and quantitative analyses of β-LG were done by fluorescence spectra, sodium dodecyl sulfate polyacrylamide gel electrophoresis and high performance liquid chromatography, and the bioactivity of bacteria was analyzed by flat colony counting. Based on the present analysis, poly(ChCl-AA DES)@Fe3O4@MoS2 specifically recognized β-LG in a good fitting Langmuir isotherm (R2 = 0.9909) and second-order kinetic model (R2 = 0.9989) by affinity, and evidently inhibited three bacteria, namely, E. coil (65%), S. aureus (50%), and B. subtilis (54%), effectively reducing the relative colony number. As the poly(ChCl-AA DES)@Fe3O4@MoS2 material did not only exhibit specific recognition of biomacromolecules, but also had an antimicrobial effect against common bacteria, it could be an ideal separation media or carrier for biomacromolecules in real samples.

Fu|Najing|N|
Li|Liteng|L|
Liu|Kaijing|K|
Kim|Chan Kyung|CK|
Li|Jun|J|
Zhu|Tao|T|
Li|Jianheng|J|
Tang|Baokun|B|

Deep eutectic solvent
Specific recognition
Biomacromolecule
2D material
Antibacterial activity


MiR-448-5p/VEGFA Axis Protects Cardiomyocytes from Hypoxia Through Regulating the FAS/FAS-L Signaling Pathway.

Abstract: Bioinformatics analysis showed that miR-448-5p expression in the myocardial tissue of rats with myocardial infarction significantly increased, suggesting that it may participate in myocardial cell apoptosis in myocardial infarction. This study aimed to explore the protective effects of miR-448-5p on hypoxic myocardial cells.H9C2 cells were cultured and subjected to anoxia for 2, 4, and 8 hours to establish a hypoxia model. MiR-448-5p mimic and inhibitor were transfected into the cells; then, a dual-luciferase experiment was conducted to verify the targeting relationship between miR-448-5p and VEGFA. Cell viability and apoptosis was detected by cell counting kit-8 and ﬂow cytometry, respectively. The expressions of apoptosis-related proteins, miR-448-5p, FAS, and FAS-L were measured using western blotting and quantitative reverse transcription-polymerase chain reaction (qRT-PCR).Hypoxia-reduced H9C2 cell viability and promoted apoptosis. MiR-448-5p expression was increased after H9C2 cell hypoxia. MiR-448-5p mimic significantly inhibited the viability and promoted the apoptosis of hypoxia-induced model cells. Hypoxia promoted the expression of apoptosis-related protein B-cell lymphoma-2 (Bcl-2) and inhibited the expressions of Bcl-2-associated x protein (Bax), cleaved caspase-3, and caspase-3, whereas the effect of inhibitor on hypoxia-reduced H9C2 cell and apoptotic protein expression were opposite to miR-448-5p mimic. MiR-448-5p targeted VEGFA and regulated its expression. Silenced VEGFA expression significantly inhibited inhibitor effect on increasing cell viability and promoted apoptosis. In addition, miR-448-5p mimic inhibited the effect of hypoxia on promoting the expressions of FAS and FAS-L of H9C2 cells. Inhibitors had the opposite effect on cell hypoxia model.The miR-448-5p/VEGFA axis could protect cardiomyocytes from hypoxia through inhibiting the FAS/FAS-L signaling pathway.

Tang|Hanqing|H| Zhang|Shitian|S| Huang|Cenhan|C| Li|Keming|K| Zhao|Qiuhua|Q| Li|Xiaohua|X|

D042461:Vascular Endothelial Growth Factor A


Conditional Learning Deficits in Children with ADHD can be Reduced Through Reward Optimization and Response-Specific Reinforcement.

Abstract: When children with ADHD are presented with behavioral choices, they struggle more than Typically Developing [TD] children to take into account contextual information necessary for making adaptive choices. The challenge presented by this type of behavioral decision making can be operationalized as a Conditional Discrimination Learning [CDL] task. We previously showed that CDL is impaired in children with ADHD. The present study explores whether this impairment can be remediated by increasing reward for correct responding or by reinforcing correct conditional choice behavior with situationally specific outcomes (Differential Outcomes). An arbitrary Delayed Matching-To-Sample [aDMTS] procedure was used, in which children had to learn to select the correct response given the sample stimulus presented (CDL). We compared children with ADHD (N = 45) and TD children (N = 49) on a baseline aDMTS task and sequentially adapted the aDMTS task so that correct choice behavior was rewarded with a more potent reinforcer (reward manipulation) or with sample-specific (and hence response-specific) reinforcers (Differential Outcomes manipulation). At baseline, children with ADHD performed significantly worse than TD children. Both manipulations (reward optimization and Differential Outcomes) improved performance in the ADHD group, resulting in a similar level of performance to the TD group. Increasing the reward value or the response-specificity of reinforcement enhances Conditional Discrimination Learning in children with ADHD. These behavioral techniques may be effective in promoting the learning of adaptive behavioral choices in children with ADHD.

D001289:Attention Deficit Disorder with Hyperactivity

Attention Deficit Hyperactivity Disorder


Prebiotic Lipidic Amphiphiles and Condensing Agents on the Early Earth.

Abstract: It is still uncertain how the first minimal cellular systems evolved to the complexity required for life to begin, but it is obvious that the role of amphiphilic compounds in the origin of life is one of huge relevance. Over the last four decades a number of studies have demonstrated how amphiphilic molecules can be synthesized under plausibly prebiotic conditions. The majority of these experiments also gave evidence for the ability of so formed amphiphiles to assemble in closed membranes of vesicles that, in principle, could have compartmented first biological processes on early Earth, including the emergence of self-replicating systems. For a competitive selection of the best performing molecular replicators to become operative, some kind of bounded units capable of harboring them are indispensable. Without the competition between dynamic populations of different compartments, life itself could not be distinguished from an otherwise disparate array or network of molecular interactions. In this review, we describe experiments that demonstrate how different prebiotically-available building blocks can become precursors of phospholipids that form vesicles. We discuss the experimental conditions that resemble plausibly those of the early Earth (or elsewhere) and consider the analytical methods that were used to characterize synthetic products. Two brief sections focus on phosphorylating agents, catalysts and coupling agents with particular attention given to their geochemical context. In Section 5, we describe how condensing agents such as cyanamide and urea can promote the abiotic synthesis of phospholipids. We conclude the review by reflecting on future studies of phospholipid compartments, particularly, on evolvable chemical systems that include giant vesicles composed of different lipidic amphiphiles.

lipids
amphiphiles
origin of life
vesicles
phosphorylation
cyanamide
urea
hydrothermal conditions
phosphite
prebiotic chemistry


Naming famous people through face and voice: a normative study.

Abstract:
OBJECTIVES
Within the large topic of naming disorders, an important and separated chapter belongs to proper names. Defects of proper naming could be a selective linguistic problem. Sometimes, it includes names belonging to various kinds of semantically unique entities, but other times, it has been observed for famous people proper names only. According to Bruce and Young's model, different stages allow to recognize, identify, and name famous people from their faces and voices, subsuming different anatomical pathways, both in right temporal lobe, and their different efficiency in this task. The present study aimed to report the normative data concerning the naming of the same famous people from voice and face.

SUBJECTS AND METHODS
One hundred fifty-three normal subjects underwent a test in which they were requested to name famous people from their face and from their voice. The stimuli belonged to the previously published Famous People Recognition Battery.

RESULTS
The mean percentage score on naming from face was 84.42 ± 12.03% (range 55.26-100%) and the mean percentage score on naming from voice was 66.04 ± 16.81% (range 28.13-100%). The difference observed in performance by face and by voice resulted significant (t|153 = 15.973; p < 0.001). Regression analyses showed that the percentage score obtained on naming from faces was predicted by education, whereas naming from voice was predicted by education and gender.

DISCUSSION
Naming from voice is more difficult than from face, confirming a different difficulty of the two tasks. Education showed high predicting value for faces and less for voices, whereas gender contributed to predict results only for voices.

Naming
Famous people
Face
Voice
Temporal lobe
Famous person


Durable Benefit of Particle Occlusion of Systemic to Pulmonary Collaterals in Select Patients After Superior Cavopulmonary Connection.

Abstract: Systemic to pulmonary arterial collaterals (SPC) are commonly found in patients undergoing staged operative palliation for single ventricle heart disease. Occlusion of SPC as part of pre-Fontan catheterization has been shown to improve hemodynamics acutely. Anecdotally, the effect of this intervention appears to be transient, and to our knowledge there is no data supporting its durability in these patients. Between 1/1/2016 and 5/1/2017, 24 children underwent Glenn operations at our institution. Of these, 3 patients had signs and symptoms deteriorating clinical status suggestive of volume overload in the period between their Glenn operation and Fontan completion, prompting heart catheterization. SPC were occluded with a combination of polyvinyl alcohol embolization particles, and in some cases coils or vascular plugs. Clinical course and data from echocardiograms and serial catheterizations are presented. SPC occlusion was performed over 6 procedures in 3 subjects with technical success in each case. Hemodynamic evaluation was repeated in 2/3 patients with improvement in collateral burden and hemodynamics in both cases. One patient previously thought to be unsuitable for Fontan completion improved sufficiently to undergo late Fontan completion, which was ultimately successful. In all patients, there was improvement in clinical status. In patients with severe SPC collateral durable benefit was seen, suggesting that in certain cases intervention on SPC remote from Fontan completion may have clinical benefit.

O'Byrne|Michael L|ML|
Schidlow|David N|DN|

Pulmonary atresia intact ventricular septum


NMR studies of daidzein and puerarin: active anti-oxidants in traditional Chinese medicine.

Abstract: Radix puerariae-a popular traditional Chinese medicine-is used for the treatment of diarrhea, acute dysentery, deafness, and cardiovascular diseases. It can also be used as an effective antioxidant and has been tested as an anticancer drug. Daidzein and puerarin are its main active compounds. The present contribution was focused on experimental and theoretical studies of the 1H and 13C NMR chemical shifts and nuclear magnetic shielding parameters of daidzein and puerarin. Experimental data were gained by exploring standard one-dimensional spectra and a set of two-dimensional measurements: COSY, HSQC, and HMBC. The theoretical gauge independent atomic orbital density functional theory supporting studies, were performed to determine shielding constants and chemical shifts in vacuum and methanol-d4 solvent. The correlation between experimental and theoretical data was fairly good, especially when the DFT/PBE0 approach was used. The molecular properties of daidzein and puerine related to antiradical activity were studied in the context of a single-step hydrogen atom transfer mechanism and its correlation with 13C NMR chemical shifts. Graphical abstract Electron spin density distribution for daidzein radical.

D019906:Nuclear Magnetic Resonance, Biomolecular

Daidzein
Puerarin
Chemical shifts
Nuclear magnetic shielding
Density functional theory
NMR measurements
Radix puerariae