Dietary Patterns Are Associated with Serum Metabolite Patterns and Their Association Is Influenced by Gut Bacteria among Older German Adults.

Abstract:
BACKGROUND
Although dietary intakes and dietary intake patterns (DPs) have been associated with single metabolites, it is unclear whether DPs are also reflected in specific metabolite patterns (MPs). Moreover, the influence of groups of gut bacteria on the relationship between DPs and MPs is underexplored.

OBJECTIVES
We aimed to investigate the association of DPs and serum MPs and also the modifying effect of the gut bacteria compositional patterns (BCPs).

METHODS
This is a cross-sectional investigation among 225 individuals (median age: 63 y; 53% women) from the European Prospective Investigation into Cancer and Nutrition study. Dietary intakes were assessed by three 24-h dietary recalls, gut bacteria composition was quantified by 16S rRNA gene sequencing, and the serum metabolome was profiled by an untargeted approach. We identified DPs and BCPs by the treelet transform analysis. We modeled associations between DPs and 8 previously published MPs and the modifying effect of BCPs by fitting generalized linear models using DataSHIELD R.

RESULTS
We identified 5 DPs and 7 BCPs. The "bread, margarine, and processed meat" and "fruiting vegetables and vegetable oils" DPs were positively associated with the "amino acids" (β = 0.35; 95% CI: 0.02, 0.69; P = 0.03) and "fatty acids" MPs (β = 0.45; 95% CI: 0.16, 0.74; P = 0.01), respectively. The "tea and miscellaneous" was inversely associated with the "amino acids" (β = -0.28; 95% CI: -0.52, -0.05; P = 0.02) and "amino acid derivatives" MPs (β = -0.21; 95% CI: -0.39, -0.02; P = 0.03). One BCP negatively modified the association between the "bread, margarine, and processed meat" DP and the "amino acids" MP (P-interaction = 0.01).

CONCLUSIONS
In older German adults, DPs are reflected in MPs, and the gut bacteria attenuate 1 DP-MP association. These MPs should be explored as biomarkers of these jointly consumed foods while taking into account a potentially modifying role of the gut bacteria.

Oluwagbemigun|Kolade|K|
Foerster|Jana|J|
Watkins|Claire|C|
Fouhy|Fiona|F|
Stanton|Catherine|C|
Bergmann|Manuela M|MM|
Boeing|Heiner|H|
Nöthlings|Ute|U|

serum metabolite patterns
dietary intake patterns
gut bacteria compositional patterns
treelet transform analysis
DataSHIELD


Hyperpolarizing Water with Parahydrogen.

Abstract: Studies of water-based systems are of fundamental interest for nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) as water is the most abundant and important medium for global living. Hence, increasing the polarization of water and dissolved compounds is particularly attractive for biomedical applications such as investigations of intermolecular interactions and metabolite structures as well as for imaging purposes. In this work, we show a new approach based on para enriched hydrogen (p-H2 ) that enables the hyperpolarization of bulk water if a suitable catalytic system is employed. The results indicate that the polarization is transferred by a new exchange mechanism.

hyperpolarization
parahydrogen
NMR spectroscopy
PHIP
SABRE


Assessing Cyberbiosecurity Vulnerabilities and Infrastructure Resilience.

Abstract: The convergence of advances in biotechnology with laboratory automation, access to data, and computational biology has democratized biotechnology and accelerated the development of new therapeutics. However, increased access to biotechnology in the digital age has also introduced additional security concerns and ultimately, spawned the new discipline of cyberbiosecurity, which encompasses cybersecurity, cyber-physical security, and biosecurity considerations. With the emergence of this new discipline comes the need for a logical, repeatable, and shared approach for evaluating facility and system vulnerabilities to cyberbiosecurity threats. In this paper, we outline the foundation of an assessment framework for cyberbiosecurity, accounting for both security and resilience factors in the physical and cyber domains. This is a unique problem set, but despite the complexity of the cyberbiosecurity field in terms of operations and governance, previous experience developing and implementing physical and cyber assessments applicable to a wide spectrum of critical infrastructure sectors provides a validated point of departure for a cyberbiosecurity assessment framework. This approach proposes to integrate existing capabilities and proven methodologies from the infrastructure assessment realm (e.g., decision science, physical security, infrastructure resilience, cybersecurity) with new expertise and requirements in the cyberbiosecurity space (e.g., biotechnology, biomanufacturing, genomics) in order to forge a flexible and defensible approach to identifying and mitigating vulnerabilities. Determining where vulnerabilities reside within cyberbiosecurity business processes can help public and private sector partners create an assessment framework to identify mitigation options for consideration that are both economically and practically viable and ultimately, allow them to manage risk more effectively.

Schabacker|Daniel S|DS|
Levy|Leslie-Anne|LA|
Evans|Nate J|NJ|
Fowler|Jennifer M|JM|
Dickey|Ellen A|EA|

cyberbiosecurity vulnerability resilience convergence convergence emerging risk converging technology


Large animals as potential models of human mental and behavioral disorders.

Abstract: Many animal models in different species have been developed for mental and behavioral disorders. This review presents large animals (dog, ovine, swine, horse) as potential models of this disorders. The article was based on the researches that were published in the peer-reviewed journals. Aliterature research was carried out using the PubMed database. The above issues were discussed in the several problem groups in accordance with the WHO International Statistical Classification of Diseases and Related Health Problems 10thRevision (ICD-10), in particular regarding: organic, including symptomatic, disorders; mental disorders (Alzheimer's disease and Huntington's disease, pernicious anemia and hepatic encephalopathy, epilepsy, Parkinson's disease, Creutzfeldt-Jakob disease); behavioral disorders due to psychoactive substance use (alcoholic intoxication, abuse of morphine); schizophrenia and other schizotypal disorders (puerperal psychosis); mood (affective) disorders (depressive episode); neurotic, stress-related and somatoform disorders (posttraumatic stress disorder, obsessive-compulsive disorder); behavioral syndromes associated with physiological disturbances and physical factors (anxiety disorders, anorexia nervosa, narcolepsy); mental retardation (Cohen syndrome, Down syndrome, Hunter syndrome); behavioral and emotional disorders (attention deficit hyperactivity disorder). This data indicates many large animal disorders which can be models to examine the above human mental and behavioral disorders.

behavioral disorders
mental disorders
large animal models


The Sensorimotor Basis of Whisker-Guided Anteroposterior Object Localization in Head-Fixed Mice.

Abstract: Active tactile perception combines directed motion with sensory signals to generate mental representations of objects in space. Competing models exist for how mice use these signals to determine the precise location of objects along their face. We tested six of these models using behavioral manipulations and statistical learning in head-fixed mice. Trained mice used a whisker to locate a pole in a continuous range of locations along the anteroposterior axis. Mice discriminated locations to ≤0.5 mm (<2°) resolution. Their motor program was noisy, adaptive to touch, and directed to the rewarded range. This exploration produced several sets of sensorimotor features that could discriminate location. Integration of two features, touch count and whisking midpoint at touch, was the simplest model that explained behavior best. These results show how mice locate objects at hyperacute resolution using a learned motor strategy and minimal set of mentally accessible sensorimotor features.

Cheung|Jonathan|J|
Maire|Phillip|P|
Kim|Jinho|J|
Sy|Jonathan|J|
Hires|Samuel Andrew|SA|

localization
head-fixed
statistical learning
touch
whisking
barrel cortex
mouse
quantitative behavior
sensorimotor integration
somatosensation


Metabolic Health Index (MHI): Assessment of Comorbidity in Bariatric Patients Based on Biomarkers.

Abstract:
PURPOSE
The focus of bariatric surgery is reduction of weight, reflected in body mass index (BMI). However, the resolution of comorbidity is a second important outcome indicator. The degree of comorbidity is hard to quantify objectively as comorbidities develop gradually and are interdependent. Multiple scoring systems quantifying comorbidity exist but they lack continuity and objectivity. In analogy with BMI as index for weight, the Metabolic Health Index (MHI) is developed as objective quantification of metabolic health status. Laboratory data were used as comorbidities affect biomarkers. Conversely, laboratory data can be used as objectively obtained variables to describe comorbidity.

METHODS
Laboratory data were collected and crosschecked by national quality registry entries. Machine learning was applied to develop an ordinal logistic regression model, using 4 clinical and 32 laboratory input variables. The output was mathematically transformed into a continuous score for intuitive interpretation, ranging from 1 to 6 (MHI).

RESULTS
In total, 4778 data records of 1595 patients were used. The degree of comorbidity is best described by age at phlebotomy, estimated Glomerular Filtration Rate (eGFR), and concentrations of glycated hemoglobin (HbA1c), triglycerides, and potassium. The model is independent of day of sampling and type of surgery. Mean MHI was significantly different between patient subgroups with increasing number of comorbidities.

CONCLUSION
The MHI reflects severity of comorbidity, enabling objective assessment of a bariatric patient's metabolic health state, regardless day of sampling and surgery type. Next to weight-focused outcome measures like %TWL, the MHI can serve as outcome measure for metabolic health.

Biomarkers
Bariatric surgery
Machine learning
Outcome measure
Diabetes
Dyslipidemia
Hypertension
METABOLIC SURGERY
Metabolic syndrome
Value based health care


Modification of Chitosan Membranes via Methane Ion Beam.

Abstract: Chitosan has been used for biomedical applications in recent years, primarily because of its biocompatibility. A chitosan membrane with a 30 μm thickness was prepared and investigated for its surface modification using methane ions. Methane ions were implanted into the chitosan membrane using a Kaufman ion source; bombardment was accomplished using three accelerating voltages of ion beams-30, 55, and 80 keV. The influence of the ion bombardment on morphology, crystallinity, and hydrophilicity was investigated. Attenuated total reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy analysis showed that a triplet bond appeared after the implantation of methane ions (acceleration voltage: 80 keV), culminating in the creation of a more amorphous membrane structure. The analyses of atomic force microscopy (AFM) images showed that, with the increase in bombardment energy, the roughness of the surface changed. These results revealed that ion bombardment improved the hydrophilicity of the membranes and the water fluxes of chitosan membranes altered after methane ion bombardment.

Gholami|Nasim|N|
Jaleh|Babak|B|
Golbedaghi|Reza|R|
Larijani|Majid Mojtahedzadeh|MM|
Wanichapichart|Pikul|P|
Nasrollahzadeh|Mahmoud|M|
Varma|Rajender S|RS|0000-0001-9731-6228

D057927:Hydrophobic and Hydrophilic Interactions

D017550:Spectroscopy, Fourier Transform Infrared

chitosan membrane
methane ion
surface modification
ATR-FTIR
characterization


Effects of electronic medical records on patient safety culture: The perspective of nurses.

Abstract:
OBJECTIVES
This study investigates the effects of nurses' views regarding electronic medical records on patient safety culture.

METHODS
The implementation part of the study was conducted with nurses working in seven state hospitals in the Burdur province of Turkey. The data were collected between 15 March and 20 April 2018. Correlation and multiple regression analyses were performed to evaluate the relationships among the variables in the study. In addition, descriptive analyses (mean, standard deviation) and Cronbach α coefficients of reliability of the scales were also used.

RESULTS
The results of the analyses revealed that control variables (gender, educational level, age, etc) and all dimensions of electronic medical records affected all three dimensions of patient safety culture. The control variables and all dimensions of electronic medical records explained 41% of the total variance in perceptions of process, 42.5% of the total variance in management support for patient safety, and 27.9% of the total variance in perceptions of safety.

DISCUSSION
This study provides insight concerning the effects of nurses' views of electronic medical records on patient safety culture. The results of the study reveal that nurses' views of electronic medical records affect the perception of patient safety culture positively.

CONCLUSIONS
It is recommended that further studies be conducted on topics such as the use of medical records and the development of patient safety. Health care managers should encourage nurses to undergo training and educational efforts on electronic medical records and patient safety.

D001291:Attitude of Health Personnel
D003430:Cross-Sectional Studies
D057286:Electronic Health Records
D006801:Humans
D009726:Nurses
D009741:Nursing Staff, Hospital
D061214:Patient Safety
D015203:Reproducibility of Results
D017751:Safety Management
D011795:Surveys and Questionnaires
D014421:Turkey

electronic medical records
patient safety culture
health sector


Biocrust-forming mosses mitigate the impact of aridity on soil microbial communities in drylands: observational evidence from three continents.

Abstract: Recent research indicates that increased aridity linked to climate change will reduce the diversity of soil microbial communities and shift their community composition in drylands, Earth's largest biome. However, we lack both a theoretical framework and solid empirical evidence of how important biotic components from drylands, such as biocrust-forming mosses, will regulate the responses of microbial communities to expected increases in aridity with climate change. Here we report results from a cross-continental (North America, Europe and Australia) survey of 39 locations from arid to humid ecosystems, where we evaluated how biocrust-forming mosses regulate the relationship between aridity and the community composition and diversity of soil bacteria and fungi in dryland ecosystems. Increasing aridity was negatively related to the richness of fungi, and either positively or negatively related to the relative abundance of selected microbial phyla, when biocrust-forming mosses were absent. Conversely, we found an overall lack of relationship between aridity and the relative abundance and richness of microbial communities under biocrust-forming mosses. Our results suggest that biocrust-forming mosses mitigate the impact of aridity on the community composition of globally distributed microbial taxa, and the diversity of fungi. They emphasize the importance of maintaining biocrusts as a sanctuary for soil microbes in drylands.

aridity
drylands
bacteria
fungi
biodiversity
microbial composition


Determination of the chiral status of different novel psychoactive substance classes by capillary electrophoresis and β-cyclodextrin derivatives.

Abstract: Besides the abuse of well-known illicit drugs, consumers discovered new synthetic compounds with similar effects but minor alterations in their chemical structure. Originally, these so-called novel psychoactive substances (NPS) have been created to circumvent law of prosecution because of illicit drug abuse. During the past decade, such compounds came up in generations, the most popular compound was a synthetic cathinone derivative named mephedrone. Cathinones are structurally related to amphetamines; to date, more than 120 completely new derivatives have been synthesized and are traded via the Internet. Cathinones possess a chiral center; however, only little is known about the pharmacology of their enantiomers. However, NPS comprise further chiral compound classes such as amphetamine derivatives, ketamines, 2-(aminopropyl)benzofurans, and phenidines. In continuation of our project, a cheap and easy-to-perform chiral capillary zone electrophoresis method for enantioseparation of cathinones presented previously was extended to the aforementioned compound classes. Enantioresolution was achieved by simply adding native β-cyclodextrin, acetyl-β-cyclodextrin, 2-hydroxypropyl-β-cyclodextrin, or carboxymethyl-β-cyclodextrin as chiral selector additives to the background electrolyte. Fifty-one chiral NPS served as analytes mainly purchased from online vendors via the Internet. Using 10 mM of the aforementioned β-cyclodextrins in a 10 mM sodium phosphate buffer (pH 2.5), overall, 50 of 51 NPS were resolved. However, chiral separation ability of the selectors differed depending on the analyte. Additionally, simultaneous enantioseparations, the determination of enantiomeric migration orders of selected analytes, and a repeatability study were performed successfully. It was proven that all separated NPS were traded as racemic mixtures.

Hägele|Johannes S|JS|
Hubner|Eva-Maria|EM|
Schmid|Martin G|MG|0000-0003-0055-660X

novel psychoactive substances
capillary electrophoresis
native β-cyclodextrin
acetyl-β-cyclodextrin
2-hydroxypropyl-β-cyclodextrin
carboxymethyl-β-cyclodextrin


AGC2 (Citrin) Deficiency-From Recognition of the Disease till Construction of Therapeutic Procedures.

Abstract: Can you imagine a disease in which intake of an excess amount of sugars or carbohydrates causes hyperammonemia? It is hard to imagine the intake causing hyperammonemia. AGC2 or citrin deficiency shows their symptoms following sugar/carbohydrates intake excess and this disease is now known as a pan-ethnic disease. AGC2 (aspartate glutamate carrier 2) or citrin is a mitochondrial transporter which transports aspartate (Asp) from mitochondria to cytosol in exchange with glutamate (Glu) and H+. Asp is originally supplied from mitochondria to cytosol where it is necessary for synthesis of proteins, nucleotides, and urea. In cytosol, Asp can be synthesized from oxaloacetate and Glu by cytosolic Asp aminotransferase, but oxaloacetate formation is limited by the amount of NAD+. This means an increase in NADH causes suppression of Asp formation in the cytosol. Metabolism of carbohydrates and other substances which produce cytosolic NADH such as alcohol and glycerol suppress oxaloacetate formation. It is forced under citrin deficiency since citrin is a member of malate/Asp shuttle. In this review, we will describe history of identification of the SLC25A13 gene as the causative gene for adult-onset type II citrullinemia (CTLN2), a type of citrin deficiency, pathophysiology of citrin deficiency together with animal models and possible treatments for citrin deficiency newly developing.

Saheki|Takeyori|T| Moriyama|Mitsuaki|M| Funahashi|Aki|A| Kuroda|Eishi|E|

D020022:Genetic Predisposition to Disease

D033681:Mitochondrial Membrane Transport Proteins

neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD)


"Not Just Right Experiences" as a psychological endophenotype for obsessive-compulsive disorder: Evidence from an Italian family study.

Abstract: The heart of the obsessional process may be considered the subject's underlying impression that "something is wrong" or "that something is not just as it should be". This phenomenon, labeled "not just right experiences" (NJREs), has increasingly been receiving attention as a possible marker of obsessive-compulsive disorder (OCD). The present study sought to add to the evidence that NJREs may be a putative endophenotype of obsessional symptoms. To this aim, measures of NJREs, obsessive-compulsive (OC) symptoms and psychological distress were compared in offspring of parents with and without OC symptoms. The offspring of parents with OC symptoms (N=120) reported higher frequency and severity of NJREs compared to offspring of parents without OC symptoms (N=106). Such differences remained significant for NJREs frequency and close to significance for NJREs severity, when general distress (i.e., anxiety and depression) was controlled. The possible role of NJREs as an endophenotype for OCD is discussed in reference to Gottesman and Gould criteria and the National Institute of Mental Health RDoC initiative.

Sica|Claudio|C| Bottesi|Gioia|G| Caudek|Corrado|C| Orsucci|Antonella|A| Ghisi|Marta|M|

Not just right experiences
Endophenotype
Obsessive-compulsive disorder
Family study
At risk population
Research domain criterion


Structure-based approach for the study of thyroid hormone receptor binding affinity and subtype selectivity.

Abstract: Thyroid hormone (TH) possesses the ability to lower cholesterol and improve cardiac performance, which have prompted the efforts to design analogs that can utilize the cholesterol-lowering property without adversely affecting heart function. In order to gain insights into the interaction mechanism for agonists at the active site of thyroid hormone receptor β (TRβ), quantitative structure-activity relationship (QSAR) models have been developed on TRβ agonists, significant statistical coefficients were obtained (CoMFA, R(2)cv, .732), (CoMSIA, R(2)cv, .853), indicating the internal consistency of the models, the obtained models were further validated using the test set, the acquired R(2)pred values .7054 and .7129 were in good agreement with the experimental results. The key amino acids affecting ligand binding were identified by molecular docking, and the detailed binding modes of the compounds with different activities were also determined. Furthermore, molecular dynamics (MD) simulations were conducted to assess the reliability of the derived models and the docking results. Moreover, TH exerts significant physiological effects through modulation of the two human thyroid hormone receptor subtypes. Because TRβ and TRα locate in different target cells, selective TR ligands would target specific tissues regulated by one receptor without affecting the other. Thus, the 3D information was analyzed to reveal the most relevant structural features involved in selectivity. The findings serve as the basis for further investigation into selective TRβ/TRα agonists.

Wang|Fang-Fang|FF| Yang|Wei|W| Shi|Yong-Hui|YH| Cheng|Xiang-Rong|XR| Le|Guo-Wei|GW|


Effects of Olfactory Training in Patients With Postinfectious Olfactory Dysfunction.

Abstract:
OBJECTIVES
Postinfectious olfactory dysfunction (PIOD) is the most common etiology of olfactory dysfunction, and olfactory training (OT) is an accepted treatment modality for PIOD. Some studies have investigated OT in Korean patients, but they involved odorants unfamiliar to Koreans or had no control group. The aim of this study was to verify the efficacy of OT in PIOD patients, using odorants familiar to Koreans and including a control group.

METHODS
We enrolled a total of 104 Korean patients with PIOD over the 3-year study period. All participants were assessed using endoscopy and an olfactory function test at the baseline assessment and 3 months after OT. The olfactory function test was performed using the Korean version of Sniffin' stick (KVSS) II. Nasal and psychological function was evaluated using a visual analog scale and the Mini-Mental State Examination. OT was performed over a period of 3 months, using five odorants (rose, lemon, cinnamon, orange, and peach).

RESULTS
OT improved olfactory function in approximately 40% of subjects over a period of 12 weeks compared to non-OT subjects. A comparison of changes between the initial and follow-up assessments demonstrated that the OT group had significantly better olfactory results for the total KVSS II, threshold, and identification scores than the non-OT group. The degree of olfactory improvement after OT was affected by the initial score.

CONCLUSION
The effects of OT in patients with PIOD were demonstrated in this study. A meaningful contribution of this study is that Korean patients were tested using odors familiar to them in comparison with a control group.

Choi|Bo Yoon|BY|
Jeong|Hamin|H|
Noh|Haemin|H|
Park|Joon Yong|JY|
Cho|Jae Hoon|JH|
Kim|Jin Kook|JK|

Anosmia Postviral Regeneration Smell Therapy


Targeting CXCR4/SDF-1 axis by lipopolymer complexes of siRNA in acute myeloid leukemia.

Abstract: In spite of high complete remission rates in Acute Myeloid Leukemia (AML), little progress has been made in the long-term survival of relapsing AML patients, urging for the development of novel therapies. The CXCR4/SDF-1 axis is a potential therapeutic target in AML to reduce the enhanced survival and proliferation of leukemic cells, with current drug development efforts focusing on antagonists and blocking antibodies. The RNAi technology mediated by siRNA is a promising alternative; however, further development of clinically relevant siRNA carriers is needed since siRNA on its own is an incompetent silencing agent. Here, we report on lipid-substituted polymeric carriers for siRNA delivery to AML cells, specifically targeting CXCR4. Our results demonstrate an effective suppression of CXCR4 protein with the polymeric siRNA delivery in AML THP-1 cells. The suppression of CXCR4 as well as its ligand, SDF-1 (CXCL12), decreased THP-1 cell numbers due to reduced cell proliferation. The reduced proliferation was also observed in the presence of human bone marrow stromal cells (hBMSC), suggesting that our approach would be effective in the protective bone marrow microenvironment. The combination of CXCR4 silencing and cytarabine treatment resulted in more effective cytotoxicity when the cells were co-incubated with hBMSC. We observed a decrease in the toxicity of the lipopolymer/siRNA complexes when THP-1 cells were treated in the presence of hBMSC but this effect did not negatively affect CXCR4 silencing. In addition, siRNA delivery to mononuclear cells derived from AML patients led to significant CXCR4 silencing in 2 out of 5 samples, providing a proof-of-concept for clinical translation. We conclude that decreasing CXCR4 expression via lipopolymer/siRNA complexes is a promising option for AML therapy and could provide an effective alternative to current CXCR4 inhibition strategies.

Landry|Breanne|B|
Gül-Uludağ|Hilal|H|
Plianwong|Samarwadee|S|
Kucharski|Cezary|C|
Zak|Zoulika|Z|
Parmar|Manoj B|MB|
Kutsch|Olaf|O|
Jiang|Hongxing|H|
Brandwein|Joseph|J|
Uludağ|Hasan|H|

D000963:Antimetabolites
D001854:Bone Marrow Cells
D002448:Cell Adhesion
D045744:Cell Line, Tumor
D049109:Cell Proliferation
D054377:Chemokine CXCL12
D003561:Cytarabine
D016503:Drug Delivery Systems
D020868:Gene Silencing
D006801:Humans
D015470:Leukemia, Myeloid, Acute
D008055:Lipids
D011108:Polymers
D034741:RNA, Small Interfering
D019718:Receptors, CXCR4
D017154:Stromal Cells

CXCR4
Lipopolymer
SiRNA
Acute myeloid leukemia (AML)
RNAi
THP-1
SDF-1 (CXCL12)
Cell proliferation
Bone marrow stromal cell attachment
Cell adhesion
Co-culture
Drug delivery
Gene expression
Gene therapy
Lipid
Non-viral delivery


Soybean Yield Formation Physiology - A Foundation for Precision Breeding Based Improvement.

Abstract: The continued improvement of crop yield is a fundamental driver in agriculture and is the goal of both plant breeders and researchers. Plant breeders have been remarkably successful in improving crop yield, as demonstrated by the continued release of varieties with improved yield potential. This has largely been accomplished through performance-based selection, without specific knowledge of the molecular mechanisms underpinning these improvements. Insight into molecular mechanisms has been provided by plant molecular, genetic, and biochemical research through elucidation of the function of genes and pathways that underlie many of the physiological processes that contribute to yield potential. Despite this knowledge, the impact of most genes and pathways on yield components have not been tested in key crops or in a field environment for yield assessment. This gap is difficult to bridge, but field-based physiological knowledge offers a starting point for leveraging molecular targets to successfully apply precision breeding technologies such as genome editing. A better understanding of both the molecular mechanisms underlying crop yield physiology and yield limiting processes under field conditions is essential for elucidating which combinations of favorable alleles are required for yield improvement. Consequently, one goal in plant biology should be to more fully integrate crop physiology, breeding, genetics, and molecular knowledge to identify impactful precision breeding targets for relevant yield traits. The foundation for this is an understanding of yield formation physiology. Here, using soybean as an example, we provide a top-down review of yield physiology, starting with the fact that yield is derived from a population of plants growing together in a community. We review yield and yield-related components to provide a basic overview of yield physiology, synthesizing these concepts to highlight how such knowledge can be leveraged for soybean improvement. Using genome editing as an example, we discuss why multiple disciplines must be brought together to fully realize the promise of precision breeding-based crop improvement.

Vogel|Jonathan T|JT|
Liu|Weidong|W|
Olhoft|Paula|P|
Crafts-Brandner|Steven J|SJ|
Pennycooke|Joyce C|JC|
Christiansen|Nicole|N|

soybean
yield
precision breeding
genome editing
crop growth rate
duration of flowering
leaf area duration
seed filling period


Skin dose estimation using virtual structures for Contura Multi-Lumen Balloon breast brachytherapy.

Abstract:
PURPOSE
To propose a workflow that uses ultrasound (US)-measured skin-balloon distances and virtual structure creations in the treatment planning system to evaluate the maximum skin dose for patients treated with Contura Multi-Lumen Balloon applicators.

METHODS AND MATERIALS
Twenty-three patients were analyzed in this study. CT and US were used to investigate the interfractional skin-balloon distance variations. Virtual structures were created on the planning CT to predict the maximum skin doses. Fitted curves and its equation can be obtained from the skin-balloon distance vs. maximum skin dose plot using virtual structure information. The fidelity of US-measured skin distance and the skin dose prediction using virtual structures were assessed.

RESULTS
The differences between CT- and US-measured skin-balloon distances values had an average of -0.5 ± 1.1 mm (95% confidence interval [CI] = -1.0 to 0.1 mm). Using virtual structure created on CT, the average difference between the predicted and the actual dose overlay maximum skin dose was -1.7% (95% CI = -3.0 to -0.4%). Furthermore, when applying the US-measured skin distance values in the virtual structure trendline equation, the differences between predicted and actual maximum skin dose had an average of 0.7 ± 6.4% (95% CI = -2.3% to 3.7%).

CONCLUSIONS
It is possible to use US to observe interfraction skin-balloon distance variation to replace CT acquisition. With the proposed workflow, based on the creation of virtual structures defined on the planning CT- and US-measured skin-balloon distances, the maximum skin doses can be reasonably estimated.

Huang|YuHuei Jessica|YJ|
Su|Fan-Chi Frances|FF|
Gaffney|David K|DK|
Kokeny|Kristine E|KE|
Zhao|Hui|H|
Rassiah-Szegedi|Prema|P|
Salter|Bill J|BJ|
Poppe|Matthew M|MM|

Skin dose
Contura
Brachytherapy
Accelerated partial breast irradiation


Cell Type-Specific Transcriptomics in the Plant Embryo Using an Adapted INTACT Protocol.

Abstract: Cells differentiate from undifferentiated precursors in order to establish the tissues of vascular plants. The different cell types and stem cells are first specified in the early embryo. How cell type specification is instructed by transcriptional control on a genome-wide level is poorly understood. A major hurdle has been the technical challenge associated with obtaining cellular transcriptomes in this inaccessible tissue. Recently, we adapted a two-component genetic labeling system called INTACT to isolate nuclei and generate a microarray-based expression atlas of the cell types in the early Arabidopsis thaliana embryo. Here we present a step-by-step description of the adapted INTACT protocol, as well as the approach to generate transcriptomic profiles. This protocol has been adapted to account for using seeds with embryos of various developmental stages as a starting material, and the relatively few cell type-specific nuclei that can be isolated from embryos.

D018506:Gene Expression Regulation, Plant

Cell type-specific
Transcriptome
Embryo
Isolation
Nucleus


Microbiology of bile in extrahepatic biliary obstruction: A tropical experience.

Abstract:
PURPOSE
Bile is considered sterile, but in obstructed biliary system, growth of micro-organisms results in bacteraemia and toxaemia. We analysed bacterial profile of patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) and evaluated antibiotic resistance patterns to formulate strategy for antibiotics in patients undergoing ERCP.

MATERIALS AND METHODS
Patients with cholestasis who underwent ERCP were enrolled. Bile, collected aseptically, was cultured. Positive cultures were processed for isolate identification and antibiotic susceptibility.

RESULTS
One hundred and sixty-three patients (78 females; mean age - 55.1 ± 15.8 years) were enrolled and divided into two groups: Group I (n = 99) were naïve and Group II (n = 64) had undergone ERCP and stenting previously. Positive culture was seen in 68.1% (n = 111) with monomicrobial growth in 74.8% (n = 83) and poly-microbial growth in 25.2% (n = 28). Culture positivity was common in Group II vis-a-vis Group I (84.4% vs. 57.5%). Poly-microbial growth was significantly more common in Group II (35.2% vs. 15.8%, P = 0.028). Gram-negative bacilli were the predominant organisms isolated with Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae comprising 70% of the isolates. The most sensitive antibiotics were piperacillin-tazobactam and imipenem. The sensitivity of vancomycin, against Enterococcus spp. was in the range of 60%-70%.

CONCLUSION
Cholestasis leads to bacterial colonisation in most cases, regardless of the presence of a biliary stent. Biliary stent however predisposes to a polymicrobial growth. Most of the commonly used antibiotics continue to have significant sensitivity and may be used empirically. However, previously stented patients may have a higher incidence of infection with Enterococcus spp. and may require specific therapy.

Manrai|Manish|M|
Jha|Atul A|AA|
Singh Shergill|Shelinder Pal|SP|
Thareja|Sandeep|S|
Sood|Atul K|AK|
Shukla|Rajat|R|
Jain|Rahul|R|
Dhiman|Priyank|P|
Gaurab|||


Simulating Erosion-Induced Soil and Carbon Delivery From Uplands to Rivers in a Global Land Surface Model.

Abstract: Global water erosion strongly affects the terrestrial carbon balance. However, this process is currently ignored by most global land surface models (LSMs) that are used to project the responses of terrestrial carbon storage to climate and land use changes. One of the main obstacles to implement erosion processes in LSMs is the high spatial resolution needed to accurately represent the effect of topography on soil erosion and sediment delivery to rivers. In this study, we present an upscaling scheme for including erosion-induced lateral soil organic carbon (SOC) movements into the ORCHIDEE LSM. This upscaling scheme integrates information from high-resolution (3″) topographic and soil erodibility data into a LSM forcing file at 0.5° spatial resolution. Evaluation of our model for the Rhine catchment indicates that it reproduces well the observed spatial and temporal (both seasonal and interannual) variations in river runoff and the sediment delivery from uplands to the river network. Although the average annual lateral SOC flux from uplands to the Rhine River network only amounts to 0.5% of the annual net primary production and 0.01% of the total SOC stock in the whole catchment, SOC loss caused by soil erosion over a long period (e.g., thousands of years) has the potential to cause a 12% reduction in the simulated equilibrium SOC stocks. Overall, this study presents a promising approach for including the erosion-induced lateral carbon flux from the land to aquatic systems into LSMs and highlights the important role of erosion processes in the terrestrial carbon balance.

land surface model
soil erosion
upscaling
carbon cycle
lateral carbon transport


High MCM6 Expression as a Potential Prognostic Marker in Clear-cell Renal Cell Carcinoma.

Abstract:
AIM
Minichromosome maintenance (MCM) proteins are involved in initiation of DNA replication and cell-cycle progression. Loss of MCM function results in genomic instability and causes carcinogenesis. Among MCM genes, the role and prognostic value of MCM6 expression in clear-cell renal cell carcinoma (ccRCC) has not been elucidated.

MATERIALS AND METHODS
We assessed the mRNA expression level of MCM6 using the Gene Expression Profiling Interactive Analysis database and investigated MCM6 protein expression by immunohistochemistry in 238 ccRCC cases.

RESULTS
High MCM6 expression was significantly associated with increasing tumor size, pT, stage, tumor necrosis, and metastasis. Furthermore, high MCM6 expression was significantly associated with shorter overall and disease-free survival, and was an independent unfavorable prognostic marker. Regarding patients with metastasis, high MCM6-expressing ccRCC conferred significantly shorter survival than for those with low expression.

CONCLUSION
A high MCM6 expression level may be a promising biomarker to predict tumor progression, metastasis, and survival in patients with ccRCC.

Jang|Nu-Ri|NR|
Baek|Jina|J|
Ko|Younghwii|Y|
Song|Phil Hyun|PH|
Gu|Mi-Jin|MJ|

D064151:Minichromosome Maintenance Complex Component 6

MCM6
biomarker
clear cell renal cell carcinoma
prognosis


Effect of age and caponization on blood parameters and bone development of male native chickens in taiwan.

Abstract: An experiment was carried out to determine the effect of age and caponization on the development blood and bone characteristics development in male country chickens in Taiwan. A total of two hundred 8-wk-old LRI native chicken cockerels, Taishi meat No.13 from LRI-COA, were used as experimental animals. Cockerels were surgically caponized at 8 wks of age. Twelve birds in each group were bled and dressed from 8 wks to 35 wks of age at 1 to 5 wk intervals. The results indicated that the plasma testosterone concentration was significantly (p<0.05) lower in capons after 12 wks of age (caponized treatment after 4 wks) than that of the intact males. The relative tibia weight, bone breaking strength, cortical thickness, bone ash, bone calcium, bone phosphorus and bone magnesium contents were significantly (p<0.05) higher in intact males, while capons had higher (p<0.05) plasma ionized calcium, inorganic phosphorus and alkaline phosphatase concentration. The plasma testosterone concentration, relative tibia weight, tibia length, breaking strength, cortical thickness, bone ash, calcium, and phosphorus contents of intact males chickens increased significantly (p<0.05) with the advance of age. In addition, the relative tibia weight of capons peaked at 18 wks of age, and declined at 35 wks of age. The bone ash, calcium and phosphorus content increased most after 14 wks of age in male native chickens in Taiwan. Also, tibia length and cortical thickness peaked at 22 wks of age. However, the peak of bone strength was found at 26 wks of age. These findings support the assertion that androgens can directly influence bone composition fluxes in male chickens. Caponization caused a significant increase in bone loss at 4 wks post treatment, which reflected bone cell damage, and demonstrated reductions in the relative tibia weight, breaking strength, cortical thickness, bone ash, calcium, phosphorus and magnesium contents, and increases in plasma ionized calcium, inorganic phosphorus and alkaline phosphatase concentration.

Age
Caponization
Bone Development
Testosterone
Male Chicken


Progress in teaching physician-patient communication in medical school; personal observations and experience of a medical educator.

Abstract: In spite of the enormous progress of Western medicine during the past century there has not be a concomitant rise in the public's satisfaction with the medical profession. Much of the discontent relates to problems in physician-patient communication. The multiple advantages of good communication have been clearly demonstrated by numerous careful studies. While the past few decades have witnessed much more attention given to teaching communication skills in medical schools, there are a number of factors that create new problems in physician-patient communication and counteract the positive teaching efforts. The "hidden curriculum", the increased emphasis on technology, the greater time pressures, and the introduction of the computer in the interface between physician and patient present new challenges for the teaching of physician-patient communication.

Physician-patient communication
medical education
communication skills
medical school curriculum


An assessment of voting knowledge and related decisions amongst hospitalised mental healthcare users in South Africa.

Abstract:
Background
The South African Constitution protects the right to vote for every citizen. The Electoral Act (No. 73 of 1998) limits registration on the voter's roll on the basis of being declared of 'unsound mind' or 'mentally disordered' by the high court or detention under the Mental Health Care Act (No. 17 of 2002). There is limited information regarding voting knowledge and subsequent voting-related decisions amongst South African involuntary mental healthcare users (MHCUs).

Aim
To compare voting knowledge and related decisions between hospitalised MHCUs and non-psychiatric hospitalised patients (controls).

Setting
Participants were recruited from Sterkfontein Psychiatric Hospital (MHCUs) and Chris Hani Baragawanth Academic Hospital orthopaedic wards (controls) in Gauteng, South Africa.

Method
A cross-sectional survey was conducted using a modified Cognitive Assessment Tool for Voting (MCAT-V) questionnaire. Scores on the MCAT-V were compared between the MHCU and control groups, along with socio-demographic variables and clinical variables.

Results
There was a significant association between group (MHCU vs. control) and HLOE (p = 0.016). Although the median overall score for the controls (11; interquartile range [IQR] 10-12) was significantly higher than that for the MHCUs (10; IQR 8-12) (p = 0.043), when controlling for education level, there was no significant association between group (MHCU/control) and MCAT-V scores (p = 0.011). The MCAT-V scores of the 'Doe questions' between the MHCUs and controls were not significantly different (p = 0.063). There was a difference in 'reasoning scores' between MHCUs and controls (p = 0.0082) and this was associated with level of educational attainment (p = 0.013).

Conclusion
The limitations regarding voter registration legislated in the South African Electoral Act, are not supported by the findings of this study. The MCAT-V demonstrates a possible educational bias and therefore is not recommended as a screening tool for assessing voting competency.

voting
cognitive assessment tool
CAT-V questionnaire
doe scoring
schizophrenia


Thermally Induced Structural Transition of Peptide Nanofibers into Nanoparticles with Enhanced Fluorescence Properties.

Abstract: A heating treatment method for the synthesis of fluorescent nanoparticles using simple N-(9-fluorenylmethoxycarbonyl) (Fmoc)-protected tripeptides is reported. Two pairs of Fmoc-protected tripeptides (Fmoc-FR1 R2 , R1 =F or W, R2 =H or Y) were designed by changing the amino acid sequences of the peptides. The peptides can self-assemble into nanofibers at lower temperatures, which will spontaneously transform into fluorescent nanoparticles under heating treatment. Moreover, the fluorescence properties of the self-assembled structures can be affected by changing amino acids in the middle of the tripeptide. Specifically, tryptophan (W) can promote fluorescence of the assemblies incubated at high temperatures. Thus, the temperatures and amino sequences of the Fmoc-protected tripeptides have significant effects on the fluorescence of the assembled nanostructures. The results provide a design principle for self-assembled fluorescent peptide nanostructures with potential biomedical applications.

Li|Qing|Q| Yang|Xin|X| Zhang|Liwei|L| Wang|Yuefei|Y|0000-0002-5736-7431 Kong|Jia|J| Qi|Wei|W| Liang|Yaoyu|Y| Su|Rongxin|R| He|Zhimin|Z|

peptides
fluorescence
amino acid sequences
self-assembly
nanomaterials


Prevalence of methicillin-resistant Staphylococcus aureus and pattern of antimicrobial resistance in mastitis milk of cattle in Chitwan, Nepal.

Abstract:
BACKGROUND
The threat of methicillin-resistant Staphylococcus aureus (MRSA) exists globally and has been listed as a priority pathogen by the World Health Organization. One of the sources of MRSA emergence is livestock and its products, often raised in poor husbandry conditions. There are limited studies in Nepal to understand the prevalence of MRSA in dairy animals and its antimicrobial resistance (AMR) profile. A cross-sectional study was conducted in Chitwan, one of the major milk-producing districts of Nepal, from February 2018 to September 2019 to estimate the prevalence of MRSA in milk samples and its AMR profile. The collected milk samples (n = 460) were screened using the California Mastitis Test (CMT) and positive samples were subjected to microbiological analysis to isolate and identify S. aureus. Polymerase Chain Reaction (PCR) was used to identify the presence of the mecA gene and screen for MRSA.

RESULTS
In total, 41.5% (191/460) of milk samples were positive in the CMT test. Out of 191 CMT positive milk samples, the biochemical tests showed that the prevalence of S. aureus was 15.2% (29/191). Among the 29 S. aureus isolates, 6.9% (2/29) were identified as MRSA based on the detection of a mecA gene. This indicates that that 1.05% (2/191) of mastitis milk samples had MRSA. The antibiotic sensitivity test showed that 75.9% (22/29) and 48.3% (14/29) S. aureus isolates were found to be sensitive to Cefazolin and Tetracycline respectively (48.3%), whereas 100% of the isolates were resistant to Ampicillin. In total 96.6% (28/29) of S. aureus isolates were multidrug-resistant (MDR).

CONCLUSIONS
This study revealed a high prevalence of S. aureus-mediated subclinical mastitis in dairy herds in Chitwan, Nepal, with a small proportion of it being MRSA carrying a mecA gene. This S. aureus, CoNS, and MRSA contaminated milk poses a public health risk due to the presence of a phenotype that is resistant to very commonly used antibiotics. It is suggested that dairy herds be screened for subclinical mastitis and treatments for the animals be based on antibiotic susceptibility tests to reduce the prevalence of AMR. Furthermore, future studies should focus on the Staphylococcus spp. to explore the antibiotic resistance genes in addition to the mecA gene to ensure public health.

Antimicrobial resistance
Mastitis
MRSA
S. aureus
mecA


Subtype classification and functional annotation of L1Md retrotransposon promoters.

Abstract:
Background
L1Md retrotransposons are the most abundant and active transposable elements in the mouse genome. The promoters of many L1Md retrotransposons are composed of tandem repeats called monomers. The number of monomers varies between retrotransposon copies, thus making it difficult to annotate L1Md promoters. Duplication of monomers contributes to the maintenance of L1Md promoters during truncation-prone retrotranspositions, but the associated mechanism remains unclear. Since the current classification of monomers is based on limited data, a comprehensive monomer annotation is needed for supporting functional studies of L1Md promoters genome-wide.

Results
We developed a pipeline for de novo monomer detection and classification. Identified monomers are further classified into subtypes based on their sequence profiles. We applied this pipeline to genome assemblies of various rodent species. A major monomer subtype of the lab mouse was also found in other Mus species, implying that such subtype has emerged in the common ancestor of involved species. We also characterized the positioning pattern of monomer subtypes within individual promoters. Our analyses indicate that the subtype composition of an L1Md promoter can be used to infer its transcriptional activity during male germ cell development.

Conclusions
We identified subtypes for all monomer types using comprehensive data, greatly expanding the spectrum of monomer variants. The analysis of monomer subtype positioning provides evidence supporting both previously proposed models of L1Md promoter expansion. The transcription silencing of L1Md promoters differs between promoter types, which supports a model involving distinct suppressive pathways rather than a universal mechanism for retrotransposon repression in gametogenesis.

Classification
Annotation
Retrotransposon
L1Md monomer


Video-Assisted Thoracoscopic Surgery Lobectomy Performed Satisfaction and Complications of Patients During Hands-On Training Courses.

Abstract:
AIM
It was aimed to concern about the satisfaction and procedural complications of patients during the thoracoscopy exist of hands-on training in this present study.

PATIENTS AND METHODS
The patients with non-small-cell carcinoma underwent video-assisted thoracoscopic surgery (VATS) lobectomy during hands-on training courses at thoracoscopic center in our hospital and collected from January 2009 and December 2014. The rates of satisfaction and complications of patients were compared from hands-on training group and control group. Potential risk factors associated with post-VATS complications of patients and thoracoscopist-related variables were analyzed. There were 54 patients join in six meetings with hands-on thoracoscopy training in our center.

RESULTS
There was no significant difference between patients for hands-on training group (n = 54) and control group (n = 54), including sex, age, BMI, smoking, PpoFEV1 and comorbidities. The satisfaction rate and the incidence of complication were similar between the two groups.

CONCLUSION
Univariate analyses showed that elder age, heart disease, chronic obstructive pulmonary disease, long operative time, and first-time mentorship were significantly associated with post-VATS complications of patients in hands-on training group. We should pay more attention to the characteristics of patent and the experience of mentor before VATS hands-on training courses.

Ma|Dongjie|D| Song|Xiaonan|X| Li|Shanqing|S| Liu|Hongsheng|H| Cui|Yushang|Y| Huang|Cheng|C| Zhou|Xiaoyun|X| Qin|Yingzhi|Y| Li|Li|L| Chen|Yeye|Y|

video-assisted thoracoscopic surgery
lobectomy
complication
hands-on training
risk factors


Structural and Functional Characterization of a Cross-Reactive Dengue Virus Neutralizing Antibody that Recognizes a Cryptic Epitope.

Abstract: Understanding the molecular basis of the neutralizing antibody response to dengue virus (DENV) is an essential component in the design and development of effective vaccines and immunotherapeutics. Here we present the structure of a cross-reactive, neutralizing antibody, 3E31, in complex with domain III (DIII) of the DENV envelope (E) protein and reveal a conserved, temperature-sensitive, cryptic epitope on DIII that is not available in any of the known conformations of E on the dengue virion. We observed that 3E31 inhibits E-mediated membrane fusion, suggesting that the antibody is able to neutralize virus through binding an as-yet uncharacterized intermediate conformation of DENV E and sterically block trimer formation. Finally, we show that, unlike cross-reactive fusion peptide-specific antibodies, 3E31 does not promote antibody-dependent enhancement of infection at sub-neutralizing concentrations. Our results highlight the 3E31 epitope on the E protein DIII as a promising target for immunotherapeutics or vaccine design.

Li|Jie|J|
Watterson|Daniel|D|
Chang|Chiung-Wen|CW|
Che|Xiao-Yan|XY|
Li|Xiao-Quan|XQ|
Ericsson|Daniel J|DJ|
Qiu|Li-Wen|LW|
Cai|Jian-Piao|JP|
Chen|Jing|J|
Fry|Scott R|SR|
Cheung|Stacey T M|STM|
Cooper|Matthew A|MA|
Young|Paul R|PR|
Kobe|Bostjan|B|

D054730:Protein Interaction Domains and Motifs

cross-reactive
dengue
neutralizing antibody
cryptic epitope
membrane fusion
antibody-dependent enhancement
temperature sensitive


Acute appendicitis in overweight patients: the role of preoperative imaging.

Abstract:
BACKGROUND
The diagnosis of acute appendicitis in overweight patients is challenging due to the limited value of the clinical examination. The benefits of ultrasonography and abdominal CT have been studied in the general population, but there is limited data regarding their use in overweight and obese patients with suspected appendicitis. This study analyzes the role of preoperative radiological modalities in overweight patients with suspected appendicitis.

METHODS
Retrospective analysis of a prospectively acquired database including 705 patients operated for suspected acute appendicitis. Patients were divided into two groups according to their BMI (BMI ≥25 kg/m(2) (n = 242) and BMI <25 kg/m(2) (n = 463)). The use of preoperative radiological modalities, laboratory findings and outcome parameters were analyzed.

RESULTS
Ultrasonography was the preferred radiological assessment in our cohort (68 % in BMI <25 kg/m and 52.4 % in BMI ≥25 kg/m(2)). However, it was non-conclusive in 42 % of overweight as compared to 6 % in patients with a BMI < 25 (p < 0.0001). This difference was particularly obvious between female patients (8 % of non-conclusive US for BMI <25 kg/m(2) vs 52 % for BMI ≥25 kg/m(2), p < 0.0001). Significantly more CT scans were performed in overweight patients (37 % vs. 20 %; p <0.0001). The accuracy of CT did not differ according to BMI (85 % vs. 88 %; p = 0.76). Preoperative radiological imaging did not significantly delay surgery. Laparoscopy was the preferred approach for both groups (98.2 % vs 98.7 %, P = 0.86) with an overall conversion rate of 4 %. The overall rate of negative appendectomy was 10 %.

CONCLUSIONS
The role of ultrasonography in patients with BMI ≥25 kg/m(2) with suspected acute appendicitis is questionable due to its high rate of non-conclusive findings. Therefore, abdominal CT scans should be preferred to investigate suspected appendicitis in overweight patient if clinical findings are not conclusive.

Sauvain|Marc-Olivier|MO|
Tschirky|Sandra|S|
Patak|Michael A|MA|
Clavien|Pierre-Alain|PA|
Hahnloser|Dieter|D|
Muller|Markus K|MK|

Appendicitis
BMI
CT scan
Appendectomy
Ultrasound


Isolation and characterization of mesenchymal progenitor cells from human orbital adipose tissue.

Abstract:
PURPOSE
Adipose-derived stem cells (ASCs) have gained importance due to their myriad potential clinical applications. We hypothesize that progenitor cells also exist besides those conventionally isolated from the stromal vascular fraction (SVF).

METHOD
Central and medial orbital adipose tissues obtained from patients during eyelid surgery were digested with collagenase for 3 or 16 hours at 37°C with or without shaking. After centrifugation, the remaining cell pellet was resuspended and filtered to yield flow through in SVF and retained cells (RC) on the filter. Single cells from RC and SVF were cultured on 5% coated Matrigel in serum-free modified embryonic stem cells medium (MESCM) for 10 passages. The progenitor status was evaluated by the expression of a number of markers by qPCR and immunofluorescence staining as well as their plasticity for endothelial and tri-lineage differentiation.

RESULTS
Type I collagenase digestion for 3 hours under shaking was significantly less effective in releasing progenitor cells than collagenase A digestion for 16 hours without shaking. Following filtration, cells in SVF and RC, of which the latter were tangled in collagen IV-containing matrix, expressed different markers of progenitor cells. Cells from SVF and RC could be expanded for 10 passages on coated Matrigel in MESCM and exhibited similar or better potential to differentiate into vascular endothelial cells, chondrocytes, osteocytes, and adipocytes than SVF cells expanded on plastic in Dulbecco's modified Eagle's medium (DMEM) with 10% fetal bovine serum (FBS).

CONCLUSIONS
Different progenitor cells can be isolated and expanded from orbital adipose tissues. Further characterization of their mesodermal or neuroectodermal origin might enhance clinical outcome when used as a source of autologous stem cells for ocular surface regeneration.

Chen|Szu-Yu|SY|
Mahabole|Megha|M|
Horesh|Elan|E|
Wester|Sara|S|
Goldberg|Jeffrey L|JL|
Tseng|Scheffer C G|SC|

isolation
orbital adipose tissue
stromal vascular fraction
adipose stem cells
basement membrane
mesenchymal stem cells


Olive cultivar and maturation process on the oviposition preference of Bactrocera oleae (Rossi) (Diptera: Tephritidae).

Abstract: The olive fly, Bactrocera oleae (Rossi) (Diptera: Tephritidae), is a key-pest in the main olives producing areas worldwide, and displays distinct preference to different olive cultivars. The present work intended to study oviposition preference towards three Portuguese cultivars (Cobrançosa, Madural, and Verdeal Transmontana) at different maturation indexes. Multiple oviposition bioassays (multiple-choice and no-choice) were conducted to assess cultivar preference. No-choice bioassays were conducted to assess the influence of different maturation indexes (MI 2; MI 3, and MI 4) in single cultivars. The longevity of olive fly adults according to the cultivar in which its larvae developed was also evaluated through survival assays.Cultivar and maturation are crucial aspects in olive fly preference. Field and laboratory assays revealed a preference towards cv. Verdeal Transmontana olives and a lower susceptibility to cv. Cobrançosa olives. A higher preference was observed for olives at MI 2 and MI 3. The slower maturation process in cv. Verdeal Transmontana (still green while the other cultivars are reddish or at black stage) seems to have an attractive effect on olive fly females, thus increasing its infestation levels. Olive fly adults from both sexes live longer if emerged from pupae developed from cv. Verdeal Transmontana fruits and live less if emerged from cv. Cobrançosa. Therefore, olive cultivar and maturation process are crucial aspects in olive fly preference, also influencing the longevity of adults.

Malheiro|R|R|
Casal|S|S|
Pinheiro|L|L|
Baptista|P|P|
Pereira|J A|JA|

oviposition
olive fly
cultivar preference
adult longevity
olive ripening


Segmentation error in spectral domain optical coherence tomography measures of the retinal nerve fibre layer thickness in idiopathic intracranial hypertension.

Abstract:
BACKGROUND
Optical Coherence Tomography (OCT) imaging is being increasingly used in clinical practice for the monitoring of papilloedema. The aim is to characterise the extent and location of the Retinal Nerve Fibre Layer (RNFL) Thickness automated segmentation error (SegE) by manual refinement, in a cohort of Idiopathic Intracranial Hypertension (IIH) patients with papilloedema and compare this to controls.

METHODS
Baseline Spectral Domain OCT (SDOCT) scans from patients with IIH, and controls with no retinal or optic nerve pathology, were examined. The internal limiting membrane and RNFL thickness of the most severely affected eye was examined for SegE and re-segmented. Using ImageJ, the total area of the RNFL thickness was calculated pre and post re-segmentation and the percentage change was determined. The distribution of RNFL thickness error was qualitatively assessed.

RESULTS
Significantly greater SegE (p = 0.009) was present in RNFL thickness total area, assessed using ImageJ, in IIH patients (n = 46, 5% ± 0-58%) compared to controls (n = 14, 1% ± 0-6%). This was particularly evident in moderate to severe optic disc swelling (n = 23, 10% ± 0-58%, p < 0.001). RNFL thickness was unable to be quantified using SDOCT in patients with severe papilloedema.

CONCLUSIONS
SegE remain a concern for clinicians using SDOCT to monitor papilloedema in IIH, particularly in the assessment of eyes with moderate to severe oedema. Systematic assessment and manual refinement of SegE is therefore important to ensure the accuracy in longitudinal monitoring of patients.

Aojula|Anuriti|A|
Mollan|Susan P|SP|
Horsburgh|John|J|
Yiangou|Andreas|A|
Markey|Kiera A|KA|
Mitchell|James L|JL|
Scotton|William J|WJ|
Keane|Pearse A|PA|
Sinclair|Alexandra J|AJ|

D000328:Adult
D005260:Female
D006801:Humans
D009412:Nerve Fibers
D009898:Optic Disk
D010211:Papilledema
D011559:Pseudotumor Cerebri
D015203:Reproducibility of Results
D012165:Retinal Ganglion Cells
D012720:Severity of Illness Index
D041623:Tomography, Optical Coherence
D014794:Visual Fields

Optical coherence tomography
Retinal nerve fibre layer
Idiopathic intracranial hypertension
Imaging
Monitoring
Papilloedema
Artefact
Pseudotumour Cerebri


Mosquito species composition and Plasmodium vivax infection rates on Baengnyeong-do (island), Republic of Korea.

Abstract: Vivax malaria is a significant military and civilian health threat in the north of the Republic of Korea (ROK). The island of Baengnyeong-do is the westernmost point of the ROK and is located close to the southwestern coast of the Democratic People's Republic of Korea (DPRK). Mosquitoes were collected using a black light trap on Baengnyeong-do, and Anopheles spp. were assayed by PCR, to identify the species, and screened for sporozoites of Plasmodium vivax. Of a subsample of 257 mosquitoes, Anopheles lesteri was the most frequently collected (49.8%), followed by Anopheles sinensis (22.6%), Anopheles pullus (18.7%), Anopheles kleini (7.8%), and Anopheles belenrae (1.2%). The overall sporozoite rate was 3.1%, with the highest rates observed in An. kleini (15.0%), An. sinensis (5.2%), and An. lesteri (1.6%). No sporozoite positive An. pullus or An. belenrae were observed. The results extend our knowledge of the distribution and potential role in malaria transmission of An. kleini, An. lesteri, and An. sinensis, for an area previously considered to be at a low risk for contracting vivax malaria.

Foley|Desmond H|DH|
Klein|Terry A|TA|
Lee|In-Yong|IY|
Kim|Myung-Soon|MS|
Wilkerson|Richard C|RC|
Harrison|Genelle|G|
Rueda|Leopoldo M|LM|
Kim|Heung Chul|HC|

Plasmodium vivax
Baengnyeong-do (Island)
malaria
sporozoite
Anopheles lesteri
Anopheles sinensis
Anopheles kleini


Air pollution and decreased semen quality: a comparative study of Chongqing urban and rural areas.

Abstract: To investigate the association and effects of air pollution level on male semen quality in urban and rural areas, this study examines the outdoor concentrations of particulate matter (PM10), sulfur dioxide (SO2), nitrous dioxide (NO2) and semen quality outcomes for 1346 volunteers in both urban and rural areas in Chongqing, China. We found the urban area has a higher pollution level than the rural area, contrasted with better semen quality in the rural residents, especially for sperm morphology and computer assistant semen analysis (CASA) motility parameters. A multivariate linear regression analysis demonstrates that concentrations of PM10, SO2, and NO2 significantly and negatively are associated with normal sperm morphology percentage (P < 0.001) and sperm kinetic parameters. In conclusion, exposure to higher concentrations of PM10, SO2, and NO2 in urban ambient air may account for worse semen quality in urban males.

Zhou|Niya|N| Cui|Zhihong|Z| Yang|Sanming|S| Han|Xue|X| Chen|Gangcai|G| Zhou|Ziyuan|Z| Zhai|Chongzhi|C| Ma|Mingfu|M| Li|Lianbing|L| Cai|Min|M| Li|Yafei|Y| Ao|Lin|L| Shu|Weiqun|W| Liu|Jinyi|J| Cao|Jia|J|

D000328:Adult
D000393:Air Pollutants
D000397:Air Pollution
D002681:China
D004781:Environmental Exposure
D006801:Humans
D016014:Linear Models
D008297:Male
D052638:Particulate Matter
D012424:Rural Population
D055101:Semen Analysis
D013458:Sulfur Dioxide
D014505:Urban Population


Two new species of Ripella (Amoebozoa, Vannellida) and unusual intragenomic variability in the SSU rRNA gene of this genus.

Abstract: Two new species, Ripella decalvata and R. tribonemae (Amoebozoa, Vannellida), are described and the diversity of known strains assigned to the genus analyzed. Ripella spp. are closely similar to each other in the light microscopic characters and sequences of small-subunit (SSU) ribosomal RNA gene, but differences in the cell coat structure and cytochrome oxidase (COI) gene sequences are more prominent. SSU rRNA in R. platypodia CCAP1589/2, R. decalvata and R. tribonemae demonstrates an unusual pattern of intragenomic variation. Sequencing of multiple molecular clones of this gene produced numerous sequence variants in a number of specific sites. These sites were usually terminal parts of several variable helices in all studied strains. Analysis of all known Ripella strains shows that SSU rRNA sites differing between strains of different origin are mainly restricted to these areas of the gene. There are only two sites, which differ between strains, but not within genomes. This intragenomic variability of the SSU rRNA gene, seemingly characteristic of all Ripella spp., was never reported to be so extensive in Amoebozoa. The data obtained show another example of complex organization of rRNA gene cluster in protists and emphasize caution needed when interpreting the metagenomic data based on this marker.

D056894:Amoebozoa
D003576:Electron Transport Complex IV
D014644:Genetic Variation
D010802:Phylogeny
D012337:RNA, Ribosomal, 18S
D013045:Species Specificity

Ripella
Amoebozoa
Vannellida
rRNA
Molecular phylogeny
Taxonomy


Starting a new residency program: a step-by-step guide for institutions, hospitals, and program directors.

Abstract: Although our country faces a looming shortage of doctors, constraints of space, funding, and patient volume in many existing residency programs limit training opportunities for medical graduates. New residency programs need to be created for the expansion of graduate medical education training positions. Partnerships between existing academic institutions and community hospitals with a need for physicians can be a very successful means toward this end. Baylor College of Medicine and The Children's Hospital of San Antonio were affiliated in 2012, and subsequently, we developed and received accreditation for a new categorical pediatric residency program at that site in 2014. We share below a step-by-step guide through the process that includes building of the infrastructure, educational development, accreditation, marketing, and recruitment. It is our hope that the description of this process will help others to spur growth in graduate medical training positions.

D000068:Accreditation
D003479:Curriculum
D005180:Faculty, Medical
D006764:Hospitals, Community
D006801:Humans
D007373:Interinstitutional Relations
D007396:Internship and Residency
D012577:Schools, Medical
D013192:Staff Development

funding
graduate medical education
physician shortage


Children and adolescents with marginal zone lymphoma have an excellent prognosis with limited chemotherapy or a watch-and-wait strategy after complete resection.

Abstract: Data on management of pediatric marginal zone lymphoma (MZL) are scarce. This retrospective study assessed characteristics and outcome in 66 patients who were <18 years old. Forty-four (67%) had an extranodal MZL (EMZL), 21 (32%) a nodal MZL (NMZL), and one patient a splenic MZL. Thirty-three patients (50%) received a variable combination of adjuvant chemotherapy/immunotherapy/radiotherapy, while the remainder, including 20 of 21 with NMZL, entered an active observation period. Overall survival was excellent (98 ± 2%), although 11 patients relapsed (17%; NMZL, n = 1; EMZL, n = 10), seven after any therapy and four after complete resection only. In conclusion, outcome of NZML, in particular, seems to be excellent after (in)complete resection and observation only.

marginal zone lymphoma
watch-and-wait
complete resection
outcome


IMRT with Stereotactic Body Radiotherapy Boost for High Risk Malignant Salivary Gland Malignancies: A Case Series.

Abstract: Patients with high risk salivary gland malignancies are at increased risk of local failure. We present our institutional experience with dose escalation using hypofractionated stereotactic body radiotherapy (SBRT) in a subset of this rare disease. Over the course of 9 years, 10 patients presenting with skull base invasion, gross disease with one or more adverse features, or those treated with adjuvant radiation with three or more pathologic features were treated with intensity-modulated radiation therapy followed by hypofractionated SBRT boost. Patients presented with variable tumor histologies, and in all but one, the tumors were classified as poorly differentiated high grade. Four patients had gross disease, three had gross residual disease, three had skull base invasion, and two patients had rapidly recurrent disease (≤6 months) that had been previously treated with surgical resection. The median stereotactic radiosurgery boost dose was 17.5 Gy (range 10-30 Gy) given in a median of five fractions (range 3-6 fractions) for a total median cumulative dose of 81.2 Gy (range 73.2-95.6 Gy). The majority of the patients received platinum based concurrent chemotherapy with their radiation. At a median follow-up of 32 months (range 12-120) for all patients and 43 months for surviving patients (range 12-120), actuarial 3-year locoregional control, distant control, progression-free survival, and overall survival were 88, 81, 68, and 79%, respectively. Only one patient failed locally and two failed distantly. Serious late toxicity included graft ulceration in one patient and osteoradionecrosis in another patient, both of which underwent surgical reconstruction. Six patients developed fibrosis. In a subset of patients with salivary gland malignancies with skull base invasion, gross disease, or those treated adjuvantly with three or more adverse pathologic features, hypofractionated SBRT boost to intensity-modulated radiotherapy yields good local control rates and acceptable toxicity.

Karam|Sana D|SD|
Rashid|Abdul|A|
Snider|James W|JW|
Wooster|Margaux|M|
Bhatia|Shilpa|S|
Jay|Ann K|AK|
Newkirk|Kenneth|K|
Davidson|Bruce|B|
Harter|William K|WK|


Fabrication of SrGe2 thin films on Ge (100), (110), and (111) substrates.

Abstract: Semiconductor strontium digermanide (SrGe2) has a large absorption coefficient in the near-infrared light region and is expected to be useful for multijunction solar cells. This study firstly demonstrates the formation of SrGe2 thin films via a reactive deposition epitaxy on Ge substrates. The growth morphology of SrGe2 dramatically changed depending on the growth temperature (300-700 °C) and the crystal orientation of the Ge substrate. We succeeded in obtaining single-oriented SrGe2 using a Ge (110) substrate at 500 °C. Development on Si or glass substrates will lead to the application of SrGe2 to high-efficiency thin-film solar cells.

Imajo|T|T| Toko|K|K| Takabe|R|R| Saitoh|N|N| Yoshizawa|N|N| Suemasu|T|T|

Solar cells
Epitaxy
Germanides
Nanostructures


Post-ablation syndrome after percutaneous cryoablation of small renal tumors: A prospective study of incidence, severity, duration, and effect on lifestyle.

Abstract:
PURPOSE
To prospectively investigate the incidence, severity, duration, and effect on lifestyle of post-ablation syndrome (PAS) after percutaneous renal cryoablation.

MATERIALS AND METHODS
We enrolled 39 patients (27 male and 12 female; mean age, 62 years) who underwent 40 CT-guided cryoablation sessions for pathologically proven renal cancer (mean size, 20 mm) between December 2015 and December 2017. Four symptoms attributable to PAS, i.e., fever, nausea, vomiting, malaise, and the synergistic effect of these symptoms on lifestyle by 21 days after ablation were evaluated using a questionnaire. Symptoms were graded according to the common toxicity criteria of adverse events.

RESULTS
The incidences of fever, nausea, vomiting, and malaise were 100% (40/40), 20% (8/40), 20% (8/40), and 63% (25/40), respectively. Most (78/81, 96%) symptoms had begun by day 2. The highest grade of fever per session was 0 (defined as ≥37.0 °C and <38.0 °C) (n = 24), 1 (n = 15), or 2 (n = 1); that of nausea was 2 (n = 8); that of vomiting was 1 (n = 7) or 3 (n = 1); and that of malaise was 1 (n = 14) or 2 (n = 11). Most (76/81, 94%) symptoms had resolved by day 8. The average values for the maximum scores of interference with general activity and work were 3.6 and 1.1, respectively.

CONCLUSION
All symptoms were generally early-onset and self-limiting, with minimal impact on lifestyle and resolution by day 8. The clinical course and impact of PAS should be acknowledged by practitioners who manage patients undergoing renal cryoablation.

Kawabata|Takahiro|T| Hiraki|Takao|T| Iguchi|Toshihiro|T| Matsui|Yusuke|Y| Uka|Mayu|M| Masaoka|Yoshihisa|Y| Komaki|Toshiyuki|T| Sakurai|Jun|J| Gobara|Hideo|H| Araki|Motoo|M| Nasu|Yasutomo|Y| Kanazawa|Susumu|S|

Post-ablation syndrome
Cryoablation
CT-guided
Renal cancer


Effects of acrylamide in the presence of vitamin E on sperm parameters, chromatin quality, and testosterone levels in mice.

Abstract:
OBJECTIVE
The present study investigated sperm chromatin quality and testosterone levels in acrylamide-treated mice and the possible protective effects of vitamin E on the fertility potential of spermatozoa.

METHODS
Thirty-two adult male mice were divided equally into four groups. Group 1 was the control, group 2 received acrylamide (10 mg/kg, water solution), group 3 received vitamin E (100 mg/kg, intraperitoneal), and group 4 received both acrylamide and vitamin E. After 35 days, spermatozoa from the right cauda epididymis were analyzed in terms of count, motility, morphology, and viability. Sperm DNA integrity and chromatin condensation were assessed by acridine orange (AO), aniline blue (AB), toluidine blue (TB), and chromomycin A3 (CMA3) staining.

RESULTS
In acrylamide-treated mice, significantly lower sperm concentration, viability, motility, and testosterone levels were found in comparison with the control and acrylamide+vitamin E groups (p<0.05). In the vitamin E group, significantly more favorable sperm parameters and testosterone levels were found than in the other groups (p<0.05). There were also significantly more spermatozoa with less condensed chromatin in the acrylamide-treated mice than in the other groups. Moreover, significantly more spermatozoa with mature nuclei (assessed by AB, CMA3, AO, and TB staining) were present in the vitamin E group than in the control and acrylamide+vitamin E groups.

CONCLUSION
This study revealed the deleterious effects of acrylamide on sperm parameters and sperm chromatin quality. Vitamin E can not only compensate for the toxic effects of acrylamide, but also improve sperm chromatin quality in mice.

Anvari|Morteza|M|
Talebi|Ali Reza|AR|
Mangoli|Esmat|E|
Shahedi|Abbas|A|
Ghasemi|Mohammad Rasool|MR|
Pourentezari|Majid|M|

Acrylamide
Vitamin E
Chromatin
Testosterone
Mice
Spermatozoa


Outcome of neoadjuvant chemotherapy in BRCA1/2 mutation positive women with advanced-stage Müllerian cancer.

Abstract:
OBJECTIVES
To investigate whether patients with germline BRCA1/2 mutations who received neoadjuvant chemotherapy (NAC) for advanced-stage Müllerian cancer (MC) have an improved outcome compared to patients who did not undergo genetic testing.

METHODS
Three hundred and two patients who received NAC for stage III-IV MC were identified from a multi-institutional study involving Cleveland Clinic and Brigham and Women's Hospital for 2000-2014 and 2010-2014 respectively. Patients were divided into 3 cohorts: patients with germline BRCA1/2 mutations (BRCA_mut+; N=30), patients with no genetic testing (BRCA_mut_unk; N=166) and patients with negative genetic testing (BRCA_mut-, N=106).

RESULTS
There were no differences in the clinical characteristics and rates of complete cytoreduction and bowel resection between the three groups. BRCA_mut+ had longer PFS compared to BRCA_mut_unk and BRCA_mut- (19.1 vs. 15.1 vs. 15.7months respectively. However, this difference was not statistically significant (p=0.48). Patients with BRCA2 mutation had non-significant trend toward longer PFS compared to patients with unknown BRCA or BRCA1 mutation (20.2 vs. 15.1 vs. 14.8months respectively, p=0.58). BRCA_mut+ and BRCA_mut- had longer overall survivals (OS) compared to BRCA_mut_unk patients (50.5 vs. 54.1 vs. 36.5months respectively, p=0.009). In multivariable analyses, controlling for age, stage and complete cytoreduction, BRCA_mut_unk was associated with worse PFS (HR 1.44, 95% CI 1.01-2.05, p=0.045) and OS (HR 2.67, 95% CI 1.33-5.36, p=0.006).

CONCLUSIONS
Patients with germline BRCA mutations had improved outcomes with NAC compared to patients with unknown BRCA status. These outcomes were more favorable compared to the outcome of NAC in prior studies.

Mahdi|Haider|H|
Gockley|Allison|A|
Esselen|Katherine|K|
Marquard|Jessica|J|
Nutter|Benjamin|B|
Yang|Bin|B|
Hinchcliff|Emily|E|
Horowitz|Neil|N|
Rose|Peter G|PG|

Advanced-stage cancer of Müllerian origin


Current management of cryptoglandular fistula-in-ano.

Abstract: Fistula-in-ano is a difficult problem that physicians have struggled with for centuries. Appropriate treatment is based on 3 central tenets: (1) control of sepsis; (2) closure of the fistula; and (3) maintenance of continence. Treatment options continue to evolve - as a result, it is important to review old and new options on a regular basis to ensure that our patients are provided with up to date information and options. This paper will briefly cover some of the traditional approaches that have been used as well as some newer promising procedures.

D001003:Anal Canal
D019468:Disease Management
D015718:Fibrin Tissue Adhesive
D006801:Humans
D012003:Rectal Fistula
D013524:Surgical Flaps
D016896:Treatment Outcome

Ligation of the intersphincteric fistula tract procedure


Primary Immunodeficiencies and Oncological Risk: The Experience of the Children's Hospital of Brescia.

Abstract: Background and aims: Primary immunodeficiencies (PID) are characterized by recurrent infections and increased risk of malignancies because of the reduced immunological surveillance against cancer cells and oncogenic viruses. Methods: We report the incidence of tumors among 690 patients with PID, diagnosed from 1990 until 2017 in Brescia. Results: Out of 690 patients, 25 patients (3.6%) developed 33 tumors. Of the 25 affected patients, 8 patients suffered from common variable immunodeficiency (CVID), 5 from combined immunodeficiency (CID), 3 from Ataxia-telangectasia (AT), 2 from Hermanksy-Pudlak type 2 (HSP2), 2 from gammaglobulinemia X-linked (XLA), 2 from Wiskott-Aldrich syndrome (WAS), 2 from Hyper IgE syndrome (HIES), 1 from severe combined immunodeficiency (SCID). The age at diagnosis ranged from 1 to 52 years, with a median age of 19.6 years. The time between the diagnosis of PID and onset of tumor was short, often <1 year between diagnosis and the appearance of cancer in the case of CID. Moreover, in two cases of CID, the diagnosis of cancer was made before the diagnosis of PID, so cancer was the onset clinical manifestation. Hematological malignancies were prevalent (22/33, 66.7%) with a minority of solid tumors (11/33, 33.33%). In particular Non-Hodgkin lymphomas were the most frequent (16/33, 48.48%). In total 13 patients survived (52%) and tumor was the main cause of death (7 cases). Two patients underwent BMT once the disease was in remission. Conclusions: Therefore, the correct management of tumors that arise in patients with primitive immunodeficiency still represents a challenge in the pediatric field. For this reason now it is mandatory to collect in a unique international registry the cases of malignancies in PID that could lead to a better understanding of the etiopathogenesis and of the biological and clinical characteristics of these tumors, with the aim of defining adequate preventive measures and guaranteeing an early diagnosis which also creating a shared and specific therapeutic strategy, with the prospect of obtaining a better prognosis for these patients.

Maffeis|Marianna|M|
Notarangelo|Lucia Dora|LD|
Schumacher|Richard Fabian|RF|
Soncini|Elena|E|
Soresina|Annarosa|A|
Lanfranchi|Arnalda|A|
Porta|Fulvio|F|

tumors
pediatric
bone marrow transplant (BMT)
primary immumunodeficiencies
rare diseases


Microcontainers for oral insulin delivery - In vitro studies of permeation enhancement.

Abstract: Oral delivery of peptides is challenging due to their low uptake through the small intestinal epithelium. Tight junctions, connecting the enterocytes, impede permeability, often necessitating the use of permeation enhancers in the formulation. Loading of peptide and permeation enhancer into micro-scale devices, such as microcontainers, can potentially confine the effective absorptive area through unidirectional release and thereby enhance absorption. This concept is investigated by in vitro permeation studies of insulin across Caco-2 cell and Caco-2/HT29-MTX-E12 co-culture monolayers mimicking the intestinal absorption barrier. The importance of proximity between the microcontainers and the barrier is assessed, by keeping the amounts of insulin and sodium caprate fixed throughout all experiments, while collectively orienting the unidirectional release towards the cell monolayers. Increasing the distance is observed to have a negative effect on insulin permeation matching a one-phase exponential decay function, while no difference in insulin transport is observed between Caco-2 and co-culture monolayers. Although there are no signs of cytotoxicity caused by the microcontainer material, reversible cell deterioration, as a consequence of high local concentrations of sodium caprate, becomes evident upon qualitative assessment of the cell monolayers. These results both suggest a potential of increasing oral bioavailability of peptides by the use of microcontainers, while simultaneously visualising the ability of regaining monolayer integrity upon local permeation enhancer induced toxicity.

Jørgensen|Jacob Rune|JR|
Jepsen|Morten Leth|ML|
Nielsen|Line Hagner|LH|
Dufva|Martin|M|
Nielsen|Hanne Mørck|HM|
Rades|Thomas|T|
Boisen|Anja|A|
Müllertz|Anette|A|

D000284:Administration, Oral
D001682:Biological Availability
D001692:Biological Transport
D018938:Caco-2 Cells
D045744:Cell Line, Tumor
D018920:Coculture Techniques
D006801:Humans
D007328:Insulin
D007408:Intestinal Absorption
D007413:Intestinal Mucosa
D010455:Peptides
D010539:Permeability
D019108:Tight Junctions

Permeation enhancers
Caco-2 cells
Micro devices
Oral peptides
Sodium caprate (C(10))


Mesenchymal stem cells desensitize castration-resistant prostate cancer to docetaxel chemotherapy via inducing TGF-β1-mediated cell autophagy.

Abstract:
BACKGROUND
Mesenchymal stem cells (MSCs) have been proved to drive castration resistant prostate cancer (CRPC). In this study, we aim to investigate the contribution of MSCs to the development of docetaxel resistance in CRPC cells and its potential mechanisms.

METHODS
The effect of MSCs on CRPC cells resistance to docetaxel was determined using in vivo and in vitro approaches. CCK8 and PI/Annexin V-FITC assay were used to examined the cell viability and apoptosis. The concentration of transforming growth factor-β1 was measured by enzyme-linked immunosorbent assay and small interfering RNA was used for functional analyses.

RESULTS
MSCs significantly reduced the sensitivity of CRPC cells to docetaxel-induced proliferation inhibition and apoptosis promotion in vivo and in vitro. CRPC cells cocultured with MSCs under docetaxel administration have an increased autophagy activation, while autophagy inhibitor could effectively reversed MSCs-induced resistance to docetaxel. Additionally, MSCs-induced CRPC cell autophagy increase under docetaxel administration depends on MSCs secreting TGF-β1 and inhibition of TGF-β1 secretion in MSCs could consequently increase the sensitivity of CRPC cells to docetaxel.

CONCLUSIONS
These results suggest that docetaxel administrated CRPC cells may elicit MSCs secreting TGF-β1 increase, which desensitizes CRPC to docetaxel chemotherapy accelerating chemoresistance occurrence via inducing cell autophagy.

Mesenchymal stem cells
Prostate cancer
Autophagy
Docetaxel resistance
Transforming growth factor-β1


Assessing the levels of intraspecific admixture and interspecific hybridization in Iberian wild goats (Capra pyrenaica).

Abstract: Iberian wild goats (Capra pyrenaica, also known as Iberian ibex, Spanish ibex, and Spanish wild goat) underwent strong genetic bottlenecks during the 19th and 20th centuries due to overhunting and habitat destruction. From the 1970s to 1990s, augmentation translocations were frequently carried out to restock Iberian wild goat populations (very often with hunting purposes), but they were not systematically planned or recorded. On the other hand, recent data suggest the occurrence of hybridization events between Iberian wild goats and domestic goats (Capra hircus). Augmentation translocations and interspecific hybridization might have contributed to increase the diversity of Iberian wild goats. With the aim of investigating this issue, we have genotyped 118 Iberian wild goats from Tortosa-Beceite, Sierra Nevada, Muela de Cortes, Gredos, Batuecas, and Ordesa and Monte Perdido by using the Goat SNP50 BeadChip (Illumina). The analysis of genotypic data indicated that Iberian wild goat populations are strongly differentiated and display low diversity. Only three Iberian wild goats out from 118 show genomic signatures of mixed ancestry, a result consistent with a scenario in which past augmentation translocations have had a limited impact on the diversity of Iberian wild goats. Besides, we have detected eight Iberian wild goats from Tortosa-Beceite with signs of domestic goat introgression. Although rare, hybridization with domestic goats could become a potential threat to the genetic integrity of Iberian wild goats; hence, measures should be taken to avoid the presence of uncontrolled herds of domestic or feral goats in mountainous areas inhabited by this iconic wild ungulate.

Capra pyrenaica
Iberian ibex
introgression
genetic diversity
high‐density SNP arrays


Age-Related Changes in Cortical Connectivity During Surgical Anesthesia.

Abstract: An advanced understanding of the neurophysiologic changes that occur with aging may help improve care for older, vulnerable surgical patients. The objective of this study was to determine age-related changes in cortical connectivity patterns during surgical anesthesia. This was a substudy analysis of a prospective, observational study characterizing cortical connectivity during surgical anesthesia in adult patients (n = 45) via whole-scalp (16-channel) electroencephalography. Functional connectivity was estimated using a weighted phase lag index (wPLI), which was classified into a discrete set of states through k-means analysis. Temporal dynamics were quantified by occurrence rate and state transition probabilities. The mean global connectivity state transition probability [13.4% (±8.1)] was not correlated with age (ρ = 0.100, p = 0.513). Increasing age was inversely correlated with prefrontal-frontal alpha-beta connectivity (ρ = -0.446, p = 0.002) and positively correlated with frontal-parietal theta connectivity (ρ = 0.414, p = 0.005). After adjusting for anesthetic-related confounders, prefrontal-frontal alpha-beta connectivity remained significantly associated with age (β = -0.625, 95% CI -0.99 to -0.26; p = 0.001), while frontal-parietal theta connectivity was no longer significant (β = 0.436, 95% CI -0.03 to 0.90; p = 0.066). Specific transition states were also examined. Between frontal-parietal connectivity states, transitioning from theta-alpha to theta-dominated connectivity positively correlated with age (ρ = 0.545, p = 0.001). Dynamic connectivity states during surgical anesthesia, particularly involving alpha and theta bandwidths, maybe an informative measure to assess neurophysiologic changes that occur with aging.

Li|Duan|D|
Puglia|Mike P|MP|
Lapointe|Andrew P|AP|
Ip|Ka I|KI|
Zierau|Mackenzie|M|
McKinney|Amy|A|
Vlisides|Phillip E|PE|

neurophysiology
aging
electroencephalography
intraoperative monitoring
neurophysiological monitoring


Exposure treatment in multiple contexts attenuates return of fear via renewal in high spider fearful individuals.

Abstract:
BACKGROUND AND OBJECTIVES
Research has demonstrated that after exposure treatment, re-exposure to a previously feared stimulus outside of the treatment context can result in renewal of fear. The current study investigated whether conducting exposure treatment in multiple real-life contexts can attenuate renewal of fear.

METHODS
Forty-six moderate to high spider fearful individuals were randomly allocated to groups that received exposure treatment in either one context or three contexts. Follow-up testing was conducted one week and four weeks after exposure in the treatment context or a novel context.

RESULTS
Renewal of fear was found for the single extinction context group when exposed to the feared object in a novel context with self-report of fear, heart rate, and behavioural avoidance. However, renewal of fear was attenuated for the multiple extinction context group.

LIMITATIONS
The sample included moderate to high spider fearful participants rather than clients with spider phobia, potentially limiting the generalisability of the findings to clinical populations.

CONCLUSIONS
Using multiple extinction contexts in combination with other methods of attenuating renewal (e.g., context similarity) may provide a means to reduce the risk of renewal of fear.

Bandarian-Balooch|Siavash|S|
Neumann|David L|DL|
Boschen|Mark J|MJ|

Context
Return of fear
Renewal
Extinction
Exposure therapy


Epithelioid hemangioendothelioma: evaluation by 18F-FDG PET/CT.

Abstract:
PURPOSE
The purpose of this study was to evaluate the imaging characteristics of epithelioid hemangioendothelioma (EHE) on staging 18F-FDG PET/CT.

MATERIALS AND METHODS
An IRB-approved retrospective review was conducted for patients with biopsy-proven EHE who underwent FDG PET/CT at our institution between 2005 and 2019. Patients with a history of surgery, chemotherapy, or radiotherapy prior to PET/CT were excluded. PET/CT exams were analyzed, noting metabolic activity, distribution of involvement, and CT morphologic features. PET/CT findings were correlated with comparative CT and MRI performed within three months.

RESULTS
There were 35 patients [21 females, 14 males; average age 55.1±16.9 years (range 15-82 years)]. 18/35 patients (52%) had more than one organ affected on PET/CT. The most common sites were liver [21/35 (60%)], lung [(19/35 (54%)], bone [5/35 (14%)], lymph nodes [4/35 (11%)], and vasculature [4/35 (11%)]. Most patients [30/35, (86%)] presented with multiple lesions. The average largest lesion dimension was 4.0±3.6 cm (range 0.6-15.0 cm). The average SUVmax of the most metabolically active lesion at any site was 5.3±3.3 (range 1.2-17.1), and for bone was 7.9±5.4 (range 3.5-17.1), liver was 5.1±2.1 (range 2.6-10.5), and lung was 3.0±1.9 (range 1.2-8.5). Of patients with pulmonary lesions, 9/19 (47%) showed calcification, and 4/19 (21%) had nodules that were either non FDG-avid or too small for accurate SUV assessment. Of patients with hepatic lesions, 11/21 (52%) demonstrated capsular retraction, and 12/21 (57%) were found to have additional hepatic lesions on contrast-enhanced CT or MRI that were occult on PET/CT.

CONCLUSION
EHE demonstrates variable, but most commonly moderate FDG activity on PET/CT. The most common sites of disease are the liver, lungs, and bones, and most patients present with multiple lesions and more than one organ involved. Given the intrinsic metabolic activity and multi-organ involvement, FDG PET/CT represents an attractive modality for EHE evaluation. However, it may be best used in combination with CT or MRI given that EHE pulmonary or hepatic lesions may be missed by PET/CT.

Frota Lima|Livia Maria|LM|
Packard|Annie T|AT|
Broski|Stephen M|SM|

Epithelioid hemangioendothelioma
PET/CT
EHE
staging


Association Between Children's Hospital Visitor Restrictions and Healthcare-Associated Viral Respiratory Infections: A Quasi-Experimental Study.

Abstract: We investigated the effect of annual winter visitor restrictions on hospital respiratory virus transmission. The healthcare-associated (HA) viral respiratory infection (VRI) transmission index (number of HA VRIs per 100 inpatient community-associated VRIs) was 59% lower during the months in which visitor restrictions were implemented. These data prompt consideration for instituting year-round visitor restrictions.

Forkpa|Hawa|H|
Rupp|Angela H|AH|
Shulman|Stanford T|ST|
Patel|Sameer J|SJ|
Gray|Elizabeth L|EL|
Zheng|Xiaotian|X|
Bovee|Maria|M|
Kociolek|Larry K|LK|

visitors
respiratory virus
enterovirus
healthcare-associated infection
rhinovirus


Changes in Corneal Subbasal Nerve Morphology and Sensitivity During Orthokeratology: Onset of Change.

Abstract:
PURPOSE
To investigate changes in corneal subbasal nerve fiber density and orientation during a 3-month orthokeratology (OK) lens wear period and their relationship with concurrent changes in corneal sensitivity.

METHODS
Sixteen subjects wore overnight OK lenses for 90 days and were assessed at baseline, Day 30, and Day 90. Nerve images at the corneal apex and temporal mid-periphery were captured from the right eye only using in vivo confocal microscopy and analyzed to calculate nerve fiber density (NFD) and global nerve fiber orientation (GNFO). Corneal sensitivity was measured using the Cochet-Bonnet aesthesiometer at similar corneal locations. Control groups of non-lens (NL) wearing and conventional rigid gas-permeable (GP) lens-wearing subjects were also examined.

RESULTS
Significant changes in NFD, GNFO and corneal sensitivity were observed during OK lens wear over the study period. In the central cornea, both NFD and corneal sensitivity decreased by Day 30, with further reductions at Day 90. Reduced NFD was associated with reduced corneal sensitivity. In the mid-peripheral cornea only, GNFO was rotated in a clockwise direction at Day 30, with further rotation at Day 90. Corneal sensitivity reduction plateaued by Day 30. In the GP lens-wearing subjects, only corneal sensitivity decreased by Day 30 at both corneal locations. No changes were observed in the NL control subjects.

CONCLUSIONS
Alterations in corneal nerve morphology occur rapidly with commencement of OK lens wear and appear to underpin functional sensitivity loss. Nerve fiber orientation can provide a useful index for changes in corneal nerve morphology.

Lum|Edward|E|
Golebiowski|Blanka|B|
Swarbrick|Helen A|HA|

D003261:Contact Lenses
D003315:Cornea
D006801:Humans
D009412:Nerve Fibers
D054158:Orthokeratologic Procedures
D013997:Time Factors

orthokeratology
corneal sensitivity
in vivo confocal microscopy
subbasal nerve plexus


Comparative Transcriptome and Weighted Gene Co-expression Network Analysis Identify Key Transcription Factors of Rosa chinensis 'Old Blush' After Exposure to a Gradual Drought Stress Followed by Recovery.

Abstract: Rose is one of the most fundamental ornamental crops, but its yield and quality are highly limited by drought. The key transcription factors (TFs) and co-expression networks during rose's response to drought stress and recovery after drought stress are still limited. In this study, the transcriptomes of leaves of 2-year-old cutting seedlings of Rosa chinensis 'Old Blush' from three continuous droughted stages (30, 60, 90 days after full watering) and rewatering were analyzed using RNA sequencing. Weighted gene co-expression network analysis (WGCNA) was used to construct a co-expression network, which was associated with the physiological traits of drought response to discovering the hub TFs involved in drought response. More than 45 million high-quality clean reads were generated from the sample and used for comparison with the rose reference genome. A total of 46433 differentially expressed genes (DEGs) were identified. Gene Ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that drought stress caused significant changes in signal transduction, plant hormones including ABA, auxin, brassinosteroid (BR), cytokinin, ethylene (ET), jasmonic acid (JA) and salicylic acid (SA), primary and secondary metabolism, and a certain degree of recovery after rewatering. Gene co-expression analysis identified 18 modules, in which four modules showed a high degree of correlation with physiological traits. In addition, 42 TFs including members of NACs, WRKYs, MYBs, AP2/ERFs, ARFs, and bHLHs with high connectivity in navajowhite1 and blue modules were screened. This study provides the transcriptome sequencing report of R. chinensis 'Old Blush' during drought stress and rewatering process. The study also identifies the response of candidate TFs to drought stress, providing guidelines for improving the drought tolerance of the rose through molecular breeding in the future.

Jia|Xin|X| Feng|Hui|H| Bu|Yanhua|Y| Ji|Naizhe|N| Lyu|Yingmin|Y| Zhao|Shiwei|S|

weighted gene co-expression network analysis