Anti-Inflammatory Effect for Atherosclerosis Progression by Sodium-Glucose Cotransporter 2 (SGLT-2) Inhibitor in a Normoglycemic Rabbit Model.

Abstract:
BACKGROUND AND OBJECTIVES
We sought to investigate an anti-atherosclerotic and anti-inflammatory effect of sodium-glucose cotransporter-2 (SGLT-2) inhibitors in normoglycemic atherosclerotic rabbit model.

METHODS
Male New Zealand white rabbits (n=26) were fed with a 1% high-cholesterol diet for 7 weeks followed by normal diet for 2 weeks. After balloon catheter injury, the rabbits were administered with the Dapagliflozin (1mg/kg/day) or control-medium for 8 weeks (n=13 for each group). All lesions were assessed with angiography, optical coherence tomography (OCT), and histological assessment.

RESULTS
Atheroma burden (38.51±3.16% vs. 21.91±1.22%, p<0.01) and lipid accumulation (18.90±3.63% vs. 10.20±2.03%, p=0.047) was significantly decreased by SGLT-2 inhibitor treatment. The SGLT-2 inhibitor group showed lower macrophage infiltration (20.23±1.89% vs. 12.72±1.95%, p=0.01) as well as tumor necrosis factor (TNF)-α expression (31.17±4.40% vs. 19.47±2.10%, p=0.025). Relative area of inducible nitric oxide synthase⁺ macrophages was tended to be lower in the SGLT-2 inhibitor-treated group (1.00±0.16% vs. 0.71±0.10%, p=0.13), while relative proportion of Arg1⁺ macrophage was markedly increased (1.00±0.27% vs. 2.43±0.64%, p=0.04). As a result, progression of atherosclerosis was markedly attenuated in SGLT-2 inhibitor treated group (OCT area stenosis, 32.13±1.20% vs. 22.77±0.88%, p<0.01). Mechanistically, SGLT-2 treatment mitigated the inflammatory responses in macrophage. Especially, Toll-like receptor 4/nuclear factor-kappa B signaling pathway, and their downstream effectors such as interleukin-6 and TNF-α were markedly suppressed by SGLT-2 inhibitor treatment.

CONCLUSIONS
These results together suggest that SGLT-2 inhibitor exerts an anti-atherosclerotic effect through favorable modulation of inflammatory response as well as macrophage characteristics in non-diabetic situation.

Atherosclerosis
Macrophages
Sodium-glucose transporter 2 inhibitors
Sodium-glucose transporter-2


Beyond Maternal Mortality: A Systematic Review of Evidences on Mistreatment and Disrespect During Childbirth in Health Facilities in India.

Abstract: The aim of this systematic review is to examine current evidence on the nature and extent of disrespect and abuse (D&A), mistreatment and practices of respectful maternity care of women during childbirth in India. Electronic databases were searched for published studies relevant to the topic. The search was conducted from May to September 2018. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to conduct the review. A results synthesis was done using the Bowser and Hill landscape analytical framework for D&A of women during childbirth. Eleven studies are included in this review of which six were cross-sectional, four were qualitative, and one used a mixed-method approach. The type of abuse most frequently reported was the lack of respect and dignity (nondignified care) experienced by the women, usually in the form of negative and unfriendly attitudes of the providers. The least frequent form of mistreatment was physical abuse and detention in the facilities. The frequency of reported D&A was high, ranging from 10% to 77.3%. These behaviors were influenced by lack of education and empowerment of the women, their low socioeconomic status, poor training of providers and supervision, and a lack of accountability. Overall, disrespectful and abusive behavior had adverse impact on the utilization of health facilities for childbirth. It created a psychological distance between women and health providers. To our knowledge, this is the first systematic literature review to be conducted on respectful maternity care in India.

mistreatment
childbirth
health facility
India
disrespect and abuse (D&A)
dignity
quality of care


Influence of polymer additives on gas-phase emissions from 3D printer filaments.

Abstract: A collection of six commercially available, 3D printer filaments were analyzed with respect to their gas-phase emissions, specifically volatile organic compounds (VOCs), during simulated fused filament fabrication (FFF). Filaments were chosen because they were advertised to contain metal particles or carbon nanotubes. During experimentation, some were found to contain other non-advertised additives that greatly influenced gas-phase emissions. Three polylactic acid (PLA) filaments containing either copper, bronze, or stainless steel particles were studied along in addition to three carbon nanotube (CNT) filaments made from PLA, acrylonitrile-butadiene-styrene (ABS), and polycarbonate (PC). The metal-additive PLA filaments were found to emit primarily lactide, acetaldehyde, and 1-chlorododecane. The presence of metal particles in the PLA is a possible cause of the increased total emissions, which were higher than any other PLA filament reported in the literature. In addition, the filament with stainless steel particles had a threefold increase in total VOCs compared to the copper and bronze particles. Two of three CNT-containing filaments emitted compounds that have not been reported before for PLA and PC. A comparison between certain emitted VOCs and their suggested maximum inhalation limits shows that printing as little as 20 g of certain filaments in a small, unventilated room can subject the user to hazardous concentrations of multiple toxic VOCs with carcinogenic properties (e.g., acetaldehyde, 1,4-dioxane, and bis(2-ethylhexyl) phthalate). The use of certain additives, whether advertised or not, should be reevaluated due to their effects on VOC emissions during 3D printing.

Potter|Phillip M|PM|
Al-Abed|Souhail R|SR|
Hasan|Farhana|F|
Lomnicki|Slawomir M|SM|

D016902:Air Pollution, Indoor
D037742:Nanotubes, Carbon
D052638:Particulate Matter
D011108:Polymers
D055549:Volatile Organic Compounds

Volatile organic compounds
VOCs
3D printing
Additive manufacturing
Indoor air quality
Polymer degradation


Neurotransmitter transporters in schistosomes: structure, function and prospects for drug discovery.

Abstract: Neurotransmitter transporters (NTTs) play a fundamental role in the control of neurotransmitter signaling and homeostasis. Sodium symporters of the plasma membrane mediate the cellular uptake of neurotransmitter from the synaptic cleft, whereas proton-driven vesicular transporters sequester the neurotransmitter into synaptic vesicles for subsequent release. Together these transporters control how much transmitter is released and how long it remains in the synaptic cleft, thereby regulating the intensity and duration of signaling. NTTs have been the subject of much research in mammals and there is growing interest in their activities among invertebrates as well. In this review we will focus our attention on NTTs of the parasitic flatworm Schistosoma mansoni. Bloodflukes of the genus Schistosoma are the causative agents of human schistosomiasis, a devastating disease that afflicts over 200 million people worldwide. Schistosomes have a well-developed nervous system and a rich diversity of neurotransmitters, including many of the small-molecule ("classical") neurotransmitters that normally employ NTTs in their mechanism of signaling. Recent advances in schistosome genomics have unveiled numerous NTTs in this parasite, some of which have now been cloned and characterized in vitro. Moreover new genetic and pharmacological evidence suggests that NTTs are required for proper control of neuromuscular signaling and movement of the worm. Among these carriers are proteins that have been successfully targeted for drug discovery in other organisms, in particular sodium symporters for biogenic amine neurotransmitters such as serotonin and dopamine. Our goal in this chapter is to review the current status of research on schistosome NTTs, with emphasis on biogenic amine sodium symporters, and to evaluate their potential for anti-schistosomal drug targeting. Through this discussion we hope to draw attention to this important superfamily of parasite proteins and to identify new directions for future research.

D050483:Dopamine Plasma Membrane Transport Proteins

D050486:Serotonin Plasma Membrane Transport Proteins

gamma-aminobutyric acid (GABA) transporter

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


Redo Aortic Root Operations in Patients with Marfan Syndrome.

Abstract: Aortic root aneurysm is the most common cardiovascular manifestation requiring surgical intervention in patients with Marfan syndrome (MFS), a heritable thoracic aortic disease. Elective replacement of the aortic root is the treatment of choice for patients with aneurysmal complications of the aortic root and ascending aorta. There are two basic approaches to aortic root replacement: valve-sparing (VS) and valve-replacing (VR) techniques. After successful aortic root replacement surgery, several patients with MFS may develop a late complication related to their aortic disease process, such as developing a pseudoaneurysm of the coronary artery reattachment buttons, aneurysmal expansion, or aortic dissection in the remaining native aorta. These patients may also develop other late complications that are not specifically related to the heritable thoracic aortic disease, such as infections that can lead to dehiscence of some or all of the distal or proximal anastomosis. Because these complications are rare, the clinical volume of reoperations of the aortic root in patients with MFS is low, making it difficult to assess contemporary experiences with these procedures. Only a few published reports have examined reoperative aortic root surgery in patients with MFS, each of which had only a small series of patients. Herein, we describe our contemporary experience with reoperative aortic root replacement in patients with MFS and provide our operative approach for these uncommon procedures.

Orozco-Sevilla|Vicente|V|
Whitlock|Richard|R|
Preventza|Ourania|O|
de la Cruz|Kim I|KI|
Coselli|Joseph S|JS|

redo aortic root operation
Marfan syndrome
heritable thoracic aortic disease
reoperation
Yacoub
remodeling
valve-sparing aortic root replacement


Tumor microenvironment - Unknown niche with powerful therapeutic potential.

Abstract: Head and neck squamous cell carcinomas (HNSCC) are in a group of cancers that are the most resistant to treatment. The survival rate of HNSCC patients has been still very low since last 20 years. The existence of relationship between oncogenic and surrounding cells is probably the reason for a poor response to treatment. Fibroblasts are an important element of tumor stroma which increases tumor cells ability to proliferate. Another highly resistance, tumorigenic and metastatic cell population in tumor microenvironment are cancer initiating cells (CICs). The population of cancer initiating cells can be found regardless of differentiation status of cancer and they seem to be crucial for HNSCC development. In this review, we describe the current state of knowledge about HNSCC biological and physiological tumor microenvironment.

Kolenda|Tomasz|T|
Przybyła|Weronika|W|
Kapałczyńska|Marta|M|
Teresiak|Anna|A|
Zajączkowska|Maria|M|
Bliźniak|Renata|R|
Lamperska|Katarzyna M|KM|

Tumor microenvironment
HNSCC
Cancer stem cells
Metastasis
Resistance to therapy
Tumor initiating cells


Calcium impacts carbon and nitrogen balance in the filamentous cyanobacterium Anabaena sp. PCC 7120.

Abstract: Calcium is integral to the perception, communication and adjustment of cellular responses to environmental changes. However, the role of Ca(2+) in fine-tuning cellular responses of wild-type cyanobacteria under favourable growth conditions has not been examined. In this study, extracellular Ca(2+) has been altered, and changes in the whole transcriptome of Anabaena sp. PCC 7120 have been evaluated under conditions replete of carbon and combined nitrogen. Ca(2+) induced differential expression of many genes driving primary cellular metabolism, with transcriptional regulation of carbon- and nitrogen-related processes responding with opposing trends. However, physiological effects of these transcriptional responses on biomass accumulation, biomass composition, and photosynthetic activity over the 24h period following Ca(2+) adjustment were found to be minor. It is well known that intracellular carbon:nitrogen balance is integral to optimal cell growth and that Ca(2+) plays an important role in the response of heterocystous cyanobacteria to combined-nitrogen deprivation. This work adds to the current knowledge by demonstrating a signalling role of Ca(2+) for making sensitive transcriptional adjustments required for optimal growth under non-limiting conditions.

Walter|Julia|J|
Lynch|Fiona|F|
Battchikova|Natalia|N|
Aro|Eva-Mari|EM|
Gollan|Peter J|PJ|

calcium nitrogen Anabaena cyanobacteria bicarbonate cmpA nirA transcriptomics.


Robotic surgery in obese patients with early-stage endometrial cancer.

Abstract:
Aim
The objective of this study was to assess the clinical effectiveness of robotic surgery for obese patients (body mass index (BMI) ≥ 30 kg/m2) with early stage endometrial cancer.

Material and methods
This study is a retrospective review of women who underwent robotic surgery for early-stage endometrial cancer from 2008 to 2017. Patients were subdivided into those with BMI < 30 kg/m2 (group 1), and those with BMI ≥ 30 kg/m2 (group 2). Basic demographics and perioperative period outcomes were extracted from the medical records and compared.

Results
Group 1 included fifty patients and group 2 included 24 patients. There were no significant differences in surgical outcomes or complication rates between the two groups (p > 0.05 for all). There were no differences in pelvic nodal counts or length of stay.

Conclusions
Robotic surgery was found to be feasible and safe for obese patients with endometrial cancer. Its widespread application needs a larger sample with longer follow-up.

Zhao|Yanyan|Y| Liu|Zhongyu|Z| Yu|Ling|L| Liu|Sai|S| Yan|Hong|H| Zhang|Yan|Y| Yao|Yuanqing|Y|

robotic surgery
obese
endometrial cancer
body mass index


Scapular fractures: a common diagnostic pitfall.

Abstract: Scapular fractures are one of the most difficult fractures to diagnose on radiographs. Detection can be challenging because of the obscuration by the overlying structures or incomplete imaging due to difficult patient collaboration. Familiarity with imaging characteristics of these abnormalities will allow radiologists to better diagnose and characterize scapular fractures. Three-dimensional computed tomographic scans are considered the gold standard for scapular diagnoses. Treatment strategies differ depending on the type of scapular fractures, but the site and degree of displacement will determine whether surgical intervention should be considered. Complications can occur in fractures that are undiagnosed or improperly evaluated. The purpose of this article is to describe imaging features of traumatic scapular injury, and discuss the role of diagnostic imaging in clinical decision making after shoulder trauma.

Berritto|Daniela|D|
Pinto|Antonio|A|
Russo|Anna|A|
Urraro|Fabrizio|F|
Laporta|Antonella|A|
Belfiore|Maria Paola|MP|
Grassi|Roberto|R|

D050723:Fractures, Bone
D006801:Humans
D021621:Imaging, Three-Dimensional
D057072:Intra-Articular Fractures
D056888:Patient Positioning
D011859:Radiography
D012540:Scapula
D000070599:Shoulder Injuries
D014057:Tomography, X-Ray Computed


Lineage tracing of the bivalve shell field with special interest in the descendants of the 2d blastomere.

Abstract: By evolving bilaterally separated shell plates, bivalves acquired a unique body plan in which their soft tissues are completely protected by hard shell plates. In this unique body plan, mobility between the separated shell plates is provided by novel structures such as a ligament and adductor muscles. As a first step towards understanding how the bivalve body plan was established, we investigated the development of the separated shell plates and ligament. Over 100 years ago, it was hypothesized that the development of separated shell plates is tightly linked with the unique cell cleavage (division) pattern of bivalves during development, wherein each bilateral daughter cell of the 2d descendant 2d(1121) develops into one of the bilateral shell fields. In this study, we tested this hypothesis by tracing the cell lineages of the Japanese purple mussel Septifer virgatus. Although the shell fields were found to be exclusively derived from the bilateral descendant cells of 2d: 2d(11211) and 2d(11212), the descendants of these cells were not restricted to shell fields alone, nor were they confined to the left or right side of the shell field based on their lineage. Our study demonstrated that ligament cells are also derived from 2d(11211) and 2d(11212), indicating that the ligament cells emerged as a subpopulation of shell field cells. This also suggests that the establishment of the novel developmental system for the ligament cells was critical for the evolution of the unique body plan of bivalves.

bivalve
cell lineage
Kaede
spiral cleavage


The HeartQoL: Part I. Development of a new core health-related quality of life questionnaire for patients with ischemic heart disease.

Abstract:
BACKGROUND
Evaluation of health-related quality of life (HRQL) is important in improving the quality of patient care.

METHODS
The HeartQoL Project, with cross-sectional and longitudinal phases, was designed to develop a core ischemic heart disease (IHD) specific HRQL questionnaire, to be called the HeartQoL, for patients with angina, myocardial infarction (MI), or ischemic heart failure. Patients completed a battery of questionnaires and Mokken scaling analysis was used to identify items in the HeartQoL questionnaire.

RESULTS
We enrolled 6384 patients (angina, n = 2111, 33.1%; MI, n = 2351, 36.8%; heart failure, n = 1922, 30.1%) across 22 countries and 15 languages. The HeartQoL questionnaire comprises 14-items with 10-item physical and 4-item emotional subscales which are scored from 0 (poor HRQL) to 3 (better HRQL) with a global score if needed. The mean baseline HeartQoL global score was 2.2 (±0.5) in the total group and was different (p < 0.001) by diagnosis (MI, 2.4 ± 0.5; angina, 2.2 ± 0.6; and heart failure, 2.1 ± 0.6).

CONCLUSION
The HeartQoL questionnaire, with global and subscale scores, has the potential to allow clinicians and researchers to (a) assess baseline HRQL, (b) make between-diagnosis comparisons of HRQL, and (c) evaluate change in HRQL in patients with angina, MI, or heart failure with a single IHD-specific HRQL instrument.

Oldridge|Neil|N| Höfer|Stefan|S| McGee|Hannah|H| Conroy|Ronan|R| Doyle|Frank|F| Saner|Hugo|H| |||

health-related quality of life
Ischemic heart disease
angina
myocardial infarction
heart failure


A family-centered prevention ameliorates the associations of low self-control during childhood with employment income and poverty status in young African American adults.

Abstract:
OBJECTIVE
Children with low self-control who grow up in poverty are at elevated risk for living in poverty when they are adults. The purpose of this study was to further understanding of the intergenerational continuity of poverty by (a) examining the likelihood that children with low levels of self-control at age 11 earn less employment income and are more likely to live in poverty 14 years later, at age 25; and (b) determining, via a preventive intervention, whether enhancing supportive parenting during childhood will ameliorate these associations.

METHODS
Parents and their 11-year-old children from 381 families participated in the Strong African American Families (SAAF) program or a control condition. Teachers assessed children's self-control at 11 years; parents reported their use of supportive parenting when children were 11 and 13 years; emerging adults provided data on cognitive and emotional self-control at 19, 20, and 21 years; and young adults indicated their employment income at 25 years.

RESULTS
Significant two-way interactions were detected between children's self-control and prevention condition for employment income (b = -183.18, 95% CI [-363.82, -2.53], p < .05) and poverty status (b = 0.257, 95% CI [0.018, 0.497], p < .05). Low self-control at age 11 forecast less employment income and a greater likelihood of living in poverty among children in the control condition, but not among low self-control SAAF participants. Mediated moderation analyses confirmed that enhanced supportive parenting accounted for SAAF's effects on employment income (indirect effect = 63.057, 95% BCA [19.385, 124.748]) and poverty status (indirect effect = -0.071, 95% BCA [-0.165, -0.016]).

CONCLUSIONS
This study is unique in using a randomized controlled trial to show that preventive interventions designed to enhance parenting and strengthen families can buffer the long-term economic consequences of low self-control.

Brody|Gene H|GH|0000-0002-2244-6797
Yu|Tianyi|T|
Miller|Gregory E|GE|
Chen|Edith|E|

self-control
African American
preventive intervention
Parent-child relations


Steroid phosphate esters and phosphonosteroids and their biological activities.

Abstract: Steroid phosphate esters are very rare natural lipids that have been comparatively recently isolated from fractions of polar lipids of marine sponges and starfish. These steroids exhibit interesting biological activities. When using the PASS computer program, we showed that many of steroid phosphate esters showed antifungal, antihypercholesterolemic, anesthetic, and other activities with a confidence of 73 to 93%. In addition, some of them can be used as inhibitors of cholesterol synthesis and show hepatoprotection properties. Phosphonosteroids demonstrate antineoplastic and antihypercholesterolemic activities with a certainty of 85 to 90%. And also, they can be used as ovulation inhibitors or female steroid contraceptives with confidence from 86 to 98%.

Dembitsky|Valery M|VM|
Gloriozova|Tatyana A|TA|
Savidov|Nick|N|

Steroid phosphate esters
Steroids
Phosphonosteroids
Lipids
Marine sponges
Starfish


A study of the substance dependence effect of the ethanolic extract and iridoid-rich fraction from Valeriana jatamansi Jones in mice.

Abstract:
BACKGROUND
Recently we found the ethanolic extract and iridoid-rich fraction from Valeriana jatamansi Jones, which is a traditional Chinese medicine exhibited anxiolytic properties.

OBJECTIVE
This study aims to the substance dependence effect of the ethanolic extract and iridoid-rich fraction.

MATERIALS AND METHODS
The study included two experiments: Mice were given orally with ethanolic extract for 12 weeks or iridoid-rich fraction for 16 weeks in experiment I and experiment II, respectively. Diazepam was used as a control drug and the normal mice groups were administered with 0.5% carboxymethyl cellulose Na in both experiments. All groups were administered twice daily. Natural withdrawal symptoms, withdrawal-induced body weight change, audiogenic tail-erection test (in experiment I), and pentylenetetrazol (PTZ)-induced convulsion test (in experiment II) were measured.

RESULTS
(1) Compared to normal group in both experiments, the diazepam-treated group exhibited obvious withdrawal symptoms of tail-erection, irritability, teeth chattering, etc; the body weight of them after withdrawal had a period of significant loss (P < 0.05 or P < 0.01); and the ratios of tail-erection and seizure in two experiments were improved significantly when mice were induced by mixer noise ringtone (experiment I) or PTZ (experiment II) (P < 0.05 or P < 0.01).(2) In experiment I and II, there were no significant differences between mice that received ethanolic extract or iridoid-rich fraction and normal group in terms of natural withdrawal symptoms and withdrawal-induced body weight change (P > 0.05); in audiogenic tail-erection test, it found that the significant difference compared with normal group was just in ethanolic extract 900 mg/kg dose group on week 8 (P < 0.05); in PTZ-induced convulsion test, mice in iridoid-rich fraction groups had a slightly tail-erection and seizure, all results of them were with no significant difference compare to normal mice (P > 0.05), while significant lower than diazepam group (P < 0.01).

CONCLUSION
(1) The two experiments successfully established the physical dependence of diazepam by gradually increasing the dose.(2)There were just a few mice received with ethanolic extract for 12 weeks or iridoid-rich fraction for 16 weeks appearing some slight withdrawal symptoms after precipitated withdrawal, but it didn't show significant difference compared to normal mice. Therefore, these indicated that the risks of potential drug dependence about ethanolic extract and iridoid-rich fraction were far lower than that of diazepam.

Yu|Lin|L| Ke-Ke|Xu|X| Chao-Yong|Chen|C| Rui-Tong|Zhang|Z| Ming|Lan|L| Shao-Hua|Li|L| Ling-Zhen|Pan|P| Tian-E|Zhang|Z| Zhi-Yong|Yan|Y|

dependence
extract
Valeriana jatamansi Jones
Audiogenic tail-erection
iridoids
pentylenetetrazol-induced convulsion


Report on the First Symposium on Invertebrate Neuroscience held on 13-17th August 2019 at the Balaton Limnological Institute, MTA Centre for Ecological Research, Tihany, Hungary.

Abstract: This meeting report provides an overview of the oral and poster presentations at the first international symposium for invertebrate neuroscience. The contents reflect the contributions of invertebrate neuroscience in addressing fundamental and fascinating challenges in understanding the neural substrates of animal behaviour.

Invertebrate Neuroscience Tihany International Conference


Divergence of Desiccation-Related Traits in Sitobion avenae from Northwestern China.

Abstract: The impact of drought on insects has become increasingly evident in the context of global climate change, but the physiological mechanisms of aphids' responses to desiccating environments are still not well understood. We sampled the wheat aphid Sitobion avenae (Fabricius) (Hemiptera: Aphididae) from arid areas of northwestern China. Both desiccation-resistant and -nonresistant genotypes were identified, providing direct evidence of genetic divergence in desiccation resistance of S. avenae. Resistant genotypes of wingless S. avenae showed longer survival time and LT50 under the desiccation stress (i.e., 10% relative humidity) than nonresistant genotypes, and wingless individuals tended to have higher desiccation resistance than winged ones. Both absolute and relative water contents did not differ between the two kinds of genotypes. Resistant genotypes had lower water loss rates than nonresistant genotypes for both winged and wingless individuals, suggesting that modulation of water loss rates could be the primary strategy in resistance of this aphid against desiccation stress. Contents of cuticular hydrocarbons (CHC) (especially methyl-branched alkanes) showed significant increase for both resistant and nonresistant genotypes after exposure to the desiccation stress for 24 h. Under desiccation stress, survival time was positively correlated with contents of methyl-branched alkanes for resistant genotypes. Thus, the content of methyl-branched alkanes and their high plasticity could be closely linked to water loss rate and desiccation resistance in S. avenae. Our results provide insights into fundamental aspects and underlying mechanisms of desiccation resistance in aphids, and have significant implications for the evolution of aphid populations in the context of global warming.

Yang|Yujing|Y| Liu|Deguang|D|0000-0002-2216-9830 Liu|Xiaoming|X| Wang|Biyao|B| Shi|Xiaoqin|X|

wheat aphids
desiccation resistance
cuticular hydrocarbons
adaptive response
population divergence
water balance traits


Emerging therapies for the treatment of nonalcoholic steatohepatitis: A systematic review.

Abstract: To describe the mechanism, efficacy, and safety of novel agents that have reached phase 3 clinical trials for the treatment of biopsy-proven nonalcoholic steatohepatitis (NASH). A literature search was conducted using the PRISMA guidelines of MEDLINE databases (1990 to October 2020) with the following MeSH terms: NASH, nonalcoholic liver disease, fatty liver, liver diseases, steatohepatitis, liver fibrosis; combined with obeticholic acid, FXR agonist, cenicriviroc, CCR5 receptor antagonist, elafibranor, PPAR, selonsertib, ASK-1 inhibitor, resmetirom, THR-β receptor, arachidyl amido cholanoic acid (Aramchol™), and SCD-1 modulator. Results were verified via clinicaltrials.gov, Google Scholar, and Google. Articles were included if the medications of interest had ongoing or completed phase 3 trials in biopsy-proven NASH with outcomes directly related to NASH resolution. Eleven studies were identified involving obeticholic acid (OCA), elafibranor, cenicriviroc, Aramchol, and resmetirom. Two agents have reported data from phase 3 trials: OCA and elafibranor. OCA demonstrated safety and efficacy in NASH with a primary end point of improvement or NASH resolution; a new drug approval has been submitted. Elafibranor failed to show efficacy in NASH in the preliminary report from the RESOLVE-IT trial; however, the study is being extended to reassess outcomes. The remaining agents demonstrated positive results in phase 2b studies and have initiated phase 3 trials. With projections for increased prevalence of patients with NASH and the current lack of treatment options, novel agents with targeted mechanisms could potentially change the treatment landscape. The manufacturer of OCA is first to submit a new drug application for the treatment of NASH. These novel agents may fill a pharmacotherapy gap in patients with NASH and possibly prevent progression to advanced liver disease.

Guirguis|Erenie|E|0000-0003-0542-936X
Grace|Yasmin|Y|
Bolson|Anthony|A|
DellaVecchia|Matthew J|MJ|
Ruble|Melissa|M|

NASH
obeticholic acid
cenicriviroc
elafibranor
selonsertib
resmetirom
Aramchol


Production, Purification, and Characterization of Antibody-TNF Superfamily Ligand Fusion Proteins.

Abstract: Antibody-fusion proteins with ligands, e.g., of the TNF superfamily (TNFSF) can be adequately produced in mammalian expression systems. Here, we describe the transient production in adherent and suspension human embryonic kidney cells at laboratory scale, followed by purification procedures applying protein A and immobilized metal affinity chromatography for proteins with Fc domain and 6 × histidine-tag, respectively. In addition, characterization of the purified proteins by size exclusion chromatography is described.

Antibody-fusion protein
Protein A
Size exclusion chromatography
Fc fusion
IMAC


Electrocardiographic criteria of epicardial ventricular tachycardia with anterior origin.

Abstract:
BACKGROUND
ECG criteria for identifying an epicardial origin of ventricular tachycardia (VT) have mainly been described for VTs with basal-superior and lateral origin.

OBJECTIVE
The aim of this study was to determine ECG criteria for epicardial VTs with anterior origin as a guide for trans-pericardial ablation.

RESULTS
Among 22 patients undergoing successful ablation of VTs from the anterior myocardial wall, 14 patients underwent endocardial ablation and 8 patients underwent epicardial ablation. VTs with anterior origin ablated epicardially had widened QS complexes in precordial leads with staircase-shaped notching and slowing of the descent to the nadir of S. In comparison, endocardial VTs with anterior origin usually had narrower QS complexes with a smooth and fast downstroke to the nadir of S. The duration of the negative pseudodelta wave was longer in epicardial VTs (55 ± 12 ms) compared to endocardial VTs (22 ± 12 ms). The interval "time to the nadir of S" in patients with anterior VT origin was longer in epicardial VTs (121 ± 16 ms) than in endocardial VTs (80 ± 22 ms). The QRS duration was also longer in patients with epicardial origin (212 ± 19 ms) than with endocardial VT origin (166 ± 30 ms).

CONCLUSIONS
Epicardial origin of VTs arising from the anterior myocardial wall produces a slowing, widening and staircase-shaped notching in the initial VT-QS complex. Thus, the morphology of the initial part of the QS complex in precordial leads can be used as a guide for trans-pericardial ablation of VTs with anterior origin.

D019028:Magnetic Resonance Imaging, Cine

Ventricular tachycardia
ECG
Epicardial ablation
Anterior myocardial infarction
Nonischemic cardiomyopathy


How Sensitive Is the Upper Gastrointestinal Tract to 90Y Radioembolization? A Histologic and Dosimetric Analysis in a Porcine Model.

Abstract:
In 90Y radioembolization, nontarget embolization to the stomach or small bowel can result in gastrointestinal injury, a rare but difficult to manage clinical complication. However, dosimetric thresholds for toxicity to these tissues from radioembolization have never been evaluated in a controlled setting. We performed an analysis of the effect of 90Y radioembolization in a porcine model at different absorbed-dose endpoints.

METHODS
Six female pigs underwent transfemoral angiography and infusion of 90Y-resin microspheres into arteries supplying part of the gastric wall. Esophagogastroduodenoscopy was performed after 4 wk to assess interim gastrointestinal health. Animals were monitored for side effects for 9 wk after 90Y infusion, after which they were euthanized and their upper gastrointestinal tracts were excised for analysis. Histologic sections were used to map microsphere location, and a microdosimetric evaluation was performed to determine the absorbed-dose profile within the gastrointestinal wall.

RESULTS
90Y radioembolization dosages from 46.3 to 105.1 MBq were infused, resulting in average absorbed doses of between 35.5 and 91.9 Gy to the gastric wall. No animal exhibited any signs of pain or gastrointestinal distress through the duration of the study. Excised tissue showed 1-2 small (<3.0 cm2) healed or healing superficial gastric lesions in 5 of 6 animals. Histologic analysis demonstrated that lesion location was superficial to areas of abnormally high microsphere deposition. An analysis of microsphere deposition patterns within the gastrointestinal wall indicated a high preference for submucosal deposition. Dosimetric evaluation at the luminal mucosa performed on the basis of microscopic microsphere distribution confirmed that 90Y dosimetry techniques conventionally used in hepatic dosimetry provide a first-order estimate of absorbed dose.

CONCLUSION
The upper gastrointestinal tract may be less sensitive to 90Y radioembolization than previously thought. Lack of charged-particle equilibrium at the luminal mucosa may contribute to decreased toxicity of 90Y radioembolization compared with external-beam radiation therapy in gastrointestinal tissue. Clinical examples of injury from 90Y nontarget embolization have likely resulted from relatively large 90Y activities being deposited in small tissue volumes, resulting in absorbed doses in excess of 100 Gy.

Pasciak|Alexander S|AS|
Nodit|Laurentia|L|
Bourgeois|Austin C|AC|
Paxton|Ben E|BE|
Coan|Patricia N|PN|
Clark|Christopher T|CT|
Tolbert|M Katherine|MK|
Adams|Joleen K|JK|
Arepally|Aravind|A|
Bradley|Yong C|YC|

90Y
radioembolization
SIRT
interventional oncology


Equine Endometrial Explants Undergo Significant Degenerative Changes in Culture.

Abstract: This study evaluated equine endometrial explants following 12, 24, and 48 hr in culture. Measurement of an indicator of cell death in explant supernatant, light microscopy, and gene expression of biomarkers of endometrial function and cellular stress were used to compare the effect of six different media on explant viability and morphology. Viability of explants was assessed indirectly through measuring LDH activity in the culture supernatant. Regardless of culture medium composition, a significant increase in LDH activity was observed within 12 hr of culture, indicating occurrence of cell damage. Morphological analysis through light microscopy revealed degenerative changes occurring within 12 hr and, after 48 hr, there is nearly complete loss of luminal and superficial glandular epithelium and diffuse detachment of deep glandular epithelium. Transcript abundance of prostaglandin-endoperoxide synthase 2 (PTGS2), estrogen receptor 1 (ESR1), and vascular endothelial growth factor (VEGF) was assessed as biomarkers of endometrial function. A marked increase in PTGS2 and VEGF expression occurred; ESR1 displayed more or less steady expression levels. Above-described changes were seen irrespective of cell culture medium used. The marked increase in expression in PTGS2 expression presents a limitation to using endometrial explants in the current culture system to study aspects of endometrial function such as the inflammatory response to insemination. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 301:148-153, 2018. © 2017 Wiley Periodicals, Inc.

D042461:Vascular Endothelial Growth Factor A

degeneration
endometrium
explant culture
mare


Human Brain Imaging Links Dopaminergic Systems to Impulsivity.

Abstract: Molecular and functional imaging techniques have been used and combined with pharmacological probes to evaluate the role of dopamine in impulsivity. Overall, strong evidence links striatal dopaminergic function with impulsivity, measured by self-reports and laboratory tests of cognitive control and reward-based decision-making. The combination of molecular imaging using positron emission tomography (PET) with functional magnetic resonance imaging (fMRI) specifically implicates striatal D2-type dopamine receptors (i.e., D2 and D3) and corticostriatal connectivity in cognitive control. Low levels of striatal and midbrain D2-type receptor availability correlate with self-reported impulsivity, whereas striatal D2-type receptor availability shows positive correlation with motor response inhibition and cognitive flexibility. Impulsive choice on reward-based decision-making tasks also is related to deficits in striatal D2-type dopamine receptor availability, and there is evidence for an inverted U-shaped function in this relationship, reflecting an optimum of striatal dopaminergic activity. Findings from studies of clinical populations that present striatal dopamine D2-type receptor deficits as well as healthy control research participants identify D2-type receptors as therapeutic targets to improve cognitive control.

Positron emission tomography
Functional magnetic resonance imaging
Response inhibition
Cognitive flexibility
D2 receptor
Delay discounting


Results from a randomized trial evaluating a hospital-school transition support model for students hospitalized with traumatic brain injury.

Abstract:
OBJECTIVE
To evaluate the utility of the STEP model, a systematic hospital-school transition protocol for children hospitalized for TBI.

SETTING
Five children's hospitals in Colorado, Ohio, and Oregon.

PARTICIPANTS
Hundred families of children with mild, complicated mild, moderate, or severe TBI.

DESIGN
Randomized controlled trial (RCT); participants were randomized while hospitalized to the STEP (a standardized hospital-school transition protocol for children treated for TBI) or usual care condition.

MAIN MEASURES
Questionnaire about child's special education eligibility status, support services, and academic accommodations; Achenbach Child Behaviour Checklist (CBCL); Behaviour Rating Inventory of Executive Function (BRIEF); Child and Adolescent Scale of Participation (CASP); Child and Adolescent Scales of Environment (CASE) Results: There were no significant effects, indicating that STEP participants did not differ from usual care participants on any study outcome at one month post-discharge or at one-year follow-up.

CONCLUSION
The lack of significant findings in this study does not imply that effective hospital-to-school transition programming is unnecessary. Rather, the findings raise important questions regarding timing and dosage/intensity of intervention, appropriate measurement of outcomes, and fidelity of programme delivery. The study highlights difficulties involved in the conduct of community-based RCTs in the paediatric TBI population.

Glang|Ann|A|
Todis|Bonnie|B|
Ettel|Debbie|D|
Wade|Shari L|SL|
Yeates|Keith Owen|KO|

D016032:Randomized Controlled Trials as Topic

hospitals
child
Education
brain injuries/*rehabilitation
disabled children/*education
programme development
programme evaluation
school health services
schools
surveys and questionnaires


Regulation of transposable elements: Interplay between TE-encoded regulatory sequences and host-specific trans-acting factors in Drosophila melanogaster.

Abstract: Transposable elements (TEs) are mobile genetic elements that can move around the genome, and their expression is one precondition for this mobility. Because the insertion of TEs in new genomic positions is largely deleterious, the molecular mechanisms for transcriptional suppression have been extensively studied. In contrast, very little is known about their primary transcriptional regulation. Here, we characterize the expression dynamics of TE families in Drosophila melanogaster across a broad temperature range (13-29°C). In 71% of the expressed TE families, the expression is modulated by temperature. We show that this temperature-dependent regulation is specific for TE families and strongly affected by the genetic background. We deduce that TEs carry family-specific regulatory sequences, which are targeted by host-specific trans-acting factors, such as transcription factors. Consistent with the widespread dominant inheritance of gene expression, we also find the prevailing dominance of TE family expression. We conclude that TE family expression across a range of temperatures is regulated by an interaction between TE family-specific regulatory elements and trans-acting factors of the host.

transposable elements
Drosophila
expression
temperature
trans-acting regulation


Right hemicolectomy with D3 lymph node dissection for right-sided transverse colon cancer using the Senhance robotic system: a case report.

Abstract:
BACKGROUND
The evolution of remote systems and artificial intelligence technology has led to increase in robotic surgeries. One system used in this case report is the Senhance robotic system. The most important premise for using robotic surgery in cancer therapeutics is to ensure oncological safety. Similar to conventional laparoscopic surgery, robotic surgery needs to be a reliable and secure surgical procedure, such as complete mesocolic excisions with central vascular ligations in Western countries or D3 lymph node dissections (dissection of the lymph nodes that locates from the origin to the terminal branch of the main feeding artery of cancer) in Japan.

CASE PRESENTATION
A 76-year-old man underwent clinical examination for severe anemia. He was diagnosed with transverse colon cancer of tumor (T)3, node (N)1a, metastasis (M)0 cancer stage IIIA. A right hemicolectomy with D3 lymph node dissection using the Senhance surgical system was performed. The operative time was 313 min and the estimated blood loss was 5 ml. He was discharged from our hospital 12 days after the surgery without any complications. What is the remarkable of this report, not only mobilization of right colon but also D3 lymph node dissection and vascular ligation were performed intraperitoneally by using Senhance robotic system as conventional laparoscopic surgery. We tried using fourth robotic arm to accomplish lymphadenectomies and middle colic artery dissection. A right hemicolectomy with D3 dissection using the Da Vinci surgical system was reported. Another report of a right hemicolectomy performed with the Senhance robotic system was identified; however, in that study, lymph node dissections were not performed intraperitoneally.

CONCLUSIONS
Therefore, to our knowledge, this is the first report using the Senhance robotic system for right hemicolectomy with D3 dissection. We hope that our case report will assist in the establishment of this robotic procedure in surgical practice.

Robotic surgery
Oncology
Laparoscopic surgery
Complete mesocolic excision


Changing the environment to improve population health: a framework for considering exposure in natural experimental studies.

Abstract: There is renewed optimism regarding the use of natural experimental studies to generate evidence as to the effectiveness of population health interventions. Natural experimental studies capitalise on environmental and policy events that alter exposure to certain social, economic or environmental factors that influence health. Natural experimental studies can be useful for examining the impact of changes to 'upstream' determinants, which may not be amenable to controlled experiments. However, while natural experiments provide opportunities to generate evidence, they often present certain conceptual and methodological obstacles. Population health interventions that alter the physical or social environment are usually administered broadly across populations and communities. The breadth of these interventions means that variation in exposure, uptake and impact may be complex. Yet many evaluations of natural experiments focus narrowly on identifying suitable 'exposed' and 'unexposed' populations for comparison. In this paper, we discuss conceptual and analytical issues relating to defining and measuring exposure to interventions in this context, including how recent advances in technology may enable researchers to better understand the nature of population exposure to changes in the built environment. We argue that when it is unclear whether populations are exposed to an intervention, it may be advantageous to supplement traditional impact assessments with observational approaches that investigate differing levels of exposure. We suggest that an improved understanding of changes in exposure will assist the investigation of the impact of complex natural experiments in population health.

Humphreys|David K|DK|
Panter|Jenna|J|
Sahlqvist|Shannon|S|
Goodman|Anna|A|0000-0001-9995-6659
Ogilvie|David|D|

D006293:Health Promotion
D006801:Humans
D000075485:Population Health
D012107:Research Design
D012931:Social Environment

Environmental epidemiology
Neighborhood/place
Outcome Research Evaluation
PUBLIC HEALTH
RESEARCH METHODS


Recommendations for ophthalmologic practice during the easing of COVID-19 control measures.

Abstract: In the context of the COVID-19 pandemic, this paper provides recommendations for medical eye care during the easing of control measures after lockdown. The guidelines presented are based on a literature review and consensus among all Spanish Ophthalmology Societies regarding protection measures recommended for the ophthalmologic care of patients with or without confirmed COVID-19 in outpatient, inpatient, emergency and surgery settings. We recommend that all measures be adapted to the circumstances and availability of personal protective equipment at each centre and also highlight the need to periodically update recommendations as we may need to readopt more restrictive measures depending on the local epidemiology of the virus. These guidelines are designed to avoid the transmission of SARS-CoV-2 among both patients and healthcare staff as we gradually return to normal medical practice, to prevent postoperative complications and try to reduce possible deficiencies in the diagnosis, treatment and follow-up of the ophthalmic diseases. With this update (5th ) the Spanish Society of Ophthalmology is placed as one of the major ophthalmology societies providing periodic and systematized recommendations for ophthalmic care during the COVID-19 pandemic.

Benítez Del Castillo Sánchez|José Manuel|JM|

COVID-19
pandemic
eye care
personal protective equipment
eye health
lockdown easing


Functional Activity of Four Autochthonous Strains L. paraplantarum AB362736.1, L. plantarum MF369875.1, W. paramesenteroides CP023501.1, and E. faecalis HQ802261.1 in a Probiotic Grape Marmalade during Storage.

Abstract: Grape foods with probiotics are sources of beneficial bacteria for the gastrointestinal (GI) tract and also have a high antioxidant capacity. The addition of probiotics to dairy food is a traditional process; therefore, probiotic non-dairy products might contribute to a daily antioxidant diet to improve consumer life quality and health. This research was undertaken to develop a grape marmalade with a probiotic base to investigate the potential antioxidant activity in the probiotic non-dairy product. Thus, changes in active culture numbers, pH level, glucose concentration, and antioxidant properties were evaluated. Most of the isolates demonstrated higher growth in the grape marmalade than the synthetic grape marmalade, which was greater than 7 log colony-forming units (CFU)/g within 90 days of storage at 4 °C. In addition, most of the wild isolates grew beyond the critical count of 106 CFU/g in sampling between 60 and 90 days of storage. Moreover, probiotic grape marmalade with probiotics showed a strong antioxidant capacity that failed to differ significantly with the synthetic medium. The study confirmed Lactobacillus paraplantarum AB362736.1, Lactobacillus plantarum MF369875.1, Weissella paramesenteroides CP023501.1, and Enterococcus faecalis HQ802261.1 were ideal bacteria for the probiotic process of grape marmalade.

probiotics
grape marmalade
antioxidative properties
Lactobacillus
2,2-diphenyl-1-picrylhydrazyl (DPPH)


DA-9801, a standardized Dioscorea extract, improves memory function via the activation of nerve growth factor-mediated signaling.

Abstract: Objectives: Nerve growth factor (NGF) is a neurotrophin that plays a critical role in mammalian learning and memory functions. NGF also regulates neuronal cell differentiation and neurite outgrowth by activating ERK/CREB signaling. This present study examined the effects of a standardized Dioscorea extract (DA-9801), which is composed of Dioscorea japonica Thunb and Dioscorea nipponica Makino on memory function via its NGF-potentiating activities using an in vitro and in vivo paradigm.Methods: Cells were incubated with or without different concentrations of DA-9801 (10, 25, and 50 μg/ml) extract for 24 h. The cultured conditioned medium from C6 glioma cells was used for NGF production assay, and neurite length in N2a cells was measured after every 2 h. Mice were orally treated with DA-9801 (10 and 100 mg/kg/day) once daily for 7 days. They were subjected to passive avoidance test to evaluate memory functions. The question of whether DA-9801 induced NGF synthesis was assessed by measuring the levels of NGF in the mouse cortical and hippocampal tissues. Hippocampal cell differentiation and NGF-mediated ERK/CREB signaling were evaluated by performing immunohistochemical analysis using BrdU, ki67, DCX, phosphorylated ERK and CREB in the mouse hippocampus.Results: DA-9801 treatment increased the NGF contents and neurite length, respectively. Mice with DA-9801 administration showed memory enhancement in the passive avoidance test. DA-9801 also increased newborn cell differentiation, neurite length, NGF secretion, and ERK/CREB phosphorylation in the mouse hippocampus.Discussion: These results suggest that DA-9801 treatment could improve memory function by inducing hippocampal NGF synthesis and ERK/CREB signaling.

Choi|Jin Gyu|JG|
Khan|Zahra|Z|
Choi|Sang-Zin|SZ|
Kim|Sun Yeou|SY|
Oh|Myung Sook|MS|

DA-9801
memory function
nerve growth factor
cell differentiation
ERK/CREB signaling
Dioscorea japonica
Dioscorea nipponica
memory enhancement


Retinoids in Embryonic Development.

Abstract: Retinoids constitute a class of compounds chemically related to vitamin A [...].

origin and evolution of retinoic acid functions


The Mediating Effect of Spiritual Well-being on Depressive Symptoms and Health-related Quality of Life Among Elders.

Abstract: The purpose of this study was to investigate the mediating effect of spiritual well-being (SWB) on depressive symptoms (DS) and health-related quality of life (HRQOL) among Taiwanese elders. A convenience sample of 150 Taiwanese elders completed self-administrated questionnaires participated in this cross-sectional study. This study revealed that SWB was positively related to HRQOL but negatively correlated with DS. Results of hieratical regression analyses suggested that SWB significantly mediated the relationship between DS and mental components of HRQOL. Findings from this study suggest that nurses and health care providers should develop strategies to enhance spiritual well-being when caring for elders to maintain good health and promote quality of life.

Spiritual well-being
Depressive symptoms
Quality of life
Elders
Taiwanese


Accelerating drug development in pediatric cancer: a novel Phase I study design of venetoclax in relapsed/refractory malignancies.

Abstract: Venetoclax is a highly selective, potent BCL-2 inhibitor that is approved for some patients previously treated for chronic lymphocytic leukemia, and has shown promising activity in adult studies across several hematologic malignancies. Preclinical studies have demonstrated venetoclax activity in pediatric patient-derived xenograft models and cell lines; however, clinical studies in pediatric patients have yet to be conducted. The prognosis is poor for children with most relapsed/refractory malignancies, and limited treatment options result in unmet clinical need. Herein, we describe the rationale and design of the first study of venetoclax in pediatric patients with relapsed/refractory malignancies: a Phase I trial investigating the safety and pharmacokinetics of venetoclax monotherapy followed by the addition of chemotherapy (Trial registration: EudraCT 2017-000439-14; NCT03236857).

Place|Andrew E|AE|
Goldsmith|Kelly|K|
Bourquin|Jean-Pierre|JP|
Loh|Mignon L|ML|
Gore|Lia|L|
Morgenstern|Daniel A|DA|
Sanzgiri|Yeshwant|Y|
Hoffman|David|D|
Zhou|Ying|Y|
Ross|Jeremy A|JA|
Prine|Betty|B|
Shebley|Mohamad|M|
McNamee|Megan|M|
Farazi|Thalia|T|
Kim|Su Young|SY|
Verdugo|Maria|M|
Lash-Fleming|Leanne|L|
Zwaan|C Michel|CM|
Vormoor|Josef|J|

D019086:Bridged Bicyclo Compounds, Heterocyclic

pediatric cancer
venetoclax
relapsed/refractory
BCL-2
ALL
AML
NHL
neuroblastoma


Qualitative evaluation of a self-management intervention for people in the early stage of dementia.

Abstract: Self-management programs are effective for people living with chronic illnesses. However, there has been little research addressing self-management for people with dementia in the early stages. This study presents a qualitative evaluation of the experiences of attending a novel self-management program and initial process evaluation. The program was designed with and for people with dementia. It addresses: (a) relationship with family, (b) maintenance of an active lifestyle, (c) psychological well-being, (d) techniques to cope with memory changes and (e) information about dementia. Six participants with early stage dementia completed the intervention that was co-delivered by lay and clinical professional tutors. Participants and tutors attended focus group and interviews at the end of the program to explore their perceptions of the intervention. These were audio-recorded, transcribed verbatim and analysed thematically. Participants reported enjoyment and benefits from the intervention. This was despite some reporting concerns relating to their memory difficulties. The program's flexible nature, focus on strengths and the opportunity to spend time with other people living with dementia were particularly well received. Participants and tutors outlined areas for further improvement. The program was feasible and its flexible delivery appeared to facilitate participant benefit. Emphasis should be placed on maintaining activity and relationships, improving positive well-being and social interaction during the program. Memory of the pleasant experience and strengths focus was evidenced, which may impact positively on quality of life. The results highlight the usefulness and acceptability of self-management for people with early stage dementia and provide initial support for the program's structure and content.

Martin|Faith|F|
Turner|Andrew|A|
Wallace|Louise M|LM|
Stanley|Damian|D|
Jesuthasan|Jana|J|
Bradbury|Nicola|N|

evaluation
self-management
dementia
qualitative research


Papillary thyroid carcinoma with bilateral axillary lymph node involvement: a case report outlining hypothesis for locoregional spread and therapeutic implications.

Abstract: Axillary lymph node involvement (ALNI) in well differentiated papillary thyroid carcinoma (WDPTC) is a rare sequela of disease presentation. We report a case of PTC with extensive cervical lymph node involvement, local extension to the skin of the neck and bilateral ALNI without evidence of distant disease. We posit that ALNI represents local extension of disease rather than distant metastasis. Therefore, in the absence of distant spread, ALNI should result in surgical intervention. This optimizes removal of all bulky disease and increases effectiveness of radioactive iodine (RAI) therapy. Future research centered on genomics should focus on ascertaining the behavior and prognosis of such cases, especially when anatomic spread is discordant with biologic behavior.

Caso|Raul|R|
Villano|Anthony M|AM|
Sutton|Whitney|W|
Alexander|Randi|R|
Caragacianu|Diana L|DL|

axillary lymph node involvement (ALNI)
local extension
Papillary thyroid carcinoma (PTC)
thyroid cancer


Preliminary evidence that different mechanisms underlie the anger superiority effect in children with and without Autism Spectrum Disorders.

Abstract: Previous studies have demonstrated that angry faces capture humans' attention more rapidly than emotionally positive faces. This phenomenon is referred to as the anger superiority effect (ASE). Despite atypical emotional processing, adults and children with Autism Spectrum Disorders (ASD) have been reported to show ASE as well as typically developed (TD) individuals. So far, however, few studies have clarified whether or not the mechanisms underlying ASE are the same for both TD and ASD individuals. Here, we tested how TD and ASD children process schematic emotional faces during detection by employing a recognition task in combination with a face-in-the-crowd task. Results of the face-in-the-crowd task revealed the prevalence of ASE both in TD and ASD children. However, the results of the recognition task revealed group differences: In TD children, detection of angry faces required more configural face processing and disrupted the processing of local features. In ASD children, on the other hand, it required more feature-based processing rather than configural processing. Despite the small sample sizes, these findings provide preliminary evidence that children with ASD, in contrast to TD children, show quick detection of angry faces by extracting local features in faces.

Isomura|Tomoko|T| Ogawa|Shino|S| Yamada|Satoko|S| Shibasaki|Masahiro|M| Masataka|Nobuo|N|

anger superiority effect
children
Autism Spectrum Disorders
attention
emotion
face-in-the-crowd effect
facial expressions
visual search


Poly(L-lactic acid) nanofibers containing Cissus quadrangularis induced osteogenic differentiation in vitro.

Abstract: Cissus quadrangularis (CQ) is known as "bone setter" in Ayurvedic Medicine because of its ability to promote fracture healing. Polymers incorporated with CQ at lower concentration have shown to enhance osteogenic differentiation of mesenchymal stem cells (MSCs) in vitro. However, for the healing of clinically relevant critical sized bone defects, large amount of CQ would be required. Based on this perception, a herbal fibrous sheet containing high weight percentage of CQ [20,40 and 60wt/wt% in poly (L-lactic acid) (PLLA)] was fabricated through electrospinning. The solution concentration, flow rate, voltage and tip-target distance was optimized to obtain nanofibers. The hydrophobicity of PLLA fibers was reduced through CQ incorporation. There was considerable increase in the adhesion, proliferation and osteogenic differentiation of MSCs on herbal fibers than normal fibers, mainly on P-Q20 and P-CQ40. MSCs were differentiated into osteoblasts without providing any osteogenic supplements in the medium, indicating its osteoinductive capability. The herbal sheet also could promote mineralization when immersed in simulated body fluid for 14days. These studies specify that PLLA nanofibers loaded with 20 and 40wt% of CQ could serve as a potential candidate for bone tissue engineering applications.

Parvathi|K|K|
Krishnan|Amit G|AG|
Anitha|A|A|
Jayakumar|R|R|
Nair|Manitha B|MB|

Cissus quadrangularis
Electrospinning
Osteoinduction


Nitrate reduction by mixed iron(II-III) hydroxycarbonate green rust in the presence of phosphate anions: the key parameters influencing the ammonium selectivity.

Abstract: The reduction of nitrate anions by a mixed Fe(II)-Fe(III) carbonated green rust (GR) in aqueous medium is studied as a function of the initial pH and the initial concentrations of iron, phosphate and nitrate. The influence of these parameters on the fraction of nitrate removed and the production of ammonium is investigated by the help of statistical experimental designs. The goal is to determine experimental conditions that maximize the fraction of NO3(-) removed and concomitantly minimize the production of NH4(+). Increasing the phosphate concentration relatively to the initial Fe(II) concentration inhibits the reduction of nitrate probably due to a surface saturation of the lateral sites of the GR crystals. The kinetics of the reaction is greatly enhanced by increasing the initial pH at 10.5, however it leads to a global increase of the NH4(+) production. A partial saturation of the surface sites by phosphate leads to a global decrease of selectivity of the reaction towards ammonium. The evolution of the ratio of the NH4(+) concentration to the Fe(II) concentration confirms that the NO3(-) species are only partially transformed into ammonium. Interestingly at an initial pH of 7.5, the selectivity of the reaction towards NH4(+) is often lower than ∼30%. The reduction of nitrate by carbonated GR differs from the behavior of other GRs incorporating Cl(-), F(-) and SO4(2-) anions that fully transform nitrate into ammonium. Finally, if GR is intended to be used during a passive water denitrification process, complementary dephosphatation and ammonium treatments should be considered.

Etique|Marjorie|M| Zegeye|Asfaw|A| Grégoire|Brian|B| Carteret|Cédric|C| Ruby|Christian|C|

Green rust
Iron
Denitrification
Layered double hydroxide
Passive treatment


Hydrogen bond-induced bright enhancement of fluorescent silica cross-linked micellar nanoparticles.

Abstract: This work demonstrated the synthesis and design of ultra-bright and ultra-small fluorescent nanoparticles, which were prepared by encapsulating 4-(diphenylamino)benzaldehyde (DPB) in silica cross-linked micellar nanoparticles (SCMNPs). The DPB-doped SCMNPs (DPB-SCMNPs) exhibited ultra-bright fluorescence in an aqueous medium that was 22 times brighter than that of free DPB molecules in an organic solvent. For the first time, density functional theory (DFT) and time-dependent density functional theory (TDDFT) calculations were used to confirm that the enhanced brightness of the DPB-SCMNPs was due to a hydrogen bond-induced mechanism. In addition, the 3D fluorescence spectra and the Commission Internationale de L'Eclairage (CIE) diagram were employed to determine the optical properties and emission colour of the DPB-SCMNPs. Moreover, the DPB-SCMNPs were water-soluble, monodisperse and ultra-small (∼12 nm) and should be robust and stable in aqueous media and biological systems.

Gai|Fangyuan|F| Fan|Mengmeng|M| Yang|Xudong|X| Hao|Ce|C| Ao|Yuhui|Y| Duan|Chunying|C| Liu|Yunling|Y| Huo|Qisheng|Q|

Brightness-enhancement
Hydrogen-bond induced
Ulrasmall
Water-compatible


The Role of Nitric Oxide-Induced ATILL6 in Growth and Disease Resistance in Arabidopsis thaliana.

Abstract: Nitric oxide (NO) is a signaling molecule that regulates various processes, including plant growth and development, immunity, and environmental interactions. Using high throughput RNA-seq data, we explored the role of the NO-induced ATILL6 gene in plant growth and defense using functional genomics. The atill6 mutant and wild-types were challenged with either oxidative (H2O2, MV) or nitro-oxidative (CySNO, GSNO) stress conditions, and the phenotypic results showed that ATILL6 gene differentially regulates cotyledon development frequency (CDF) as well as the root and shoot lengths of the plants. To investigate whether ATILL6 plays a role in plant basal or resistance (R)-gene-mediated defense, the plants were challenged with either virulent or avirulent strains of Pseudomonas syringae pathovar tomato (Pst) DC3000. The atill6 line showed a susceptible phenotype, higher pathogen growth, and highly reduced transcript accumulation of PR1 and PR2 genes. These results suggested that ATILL6 positively regulates plant basal defense. Furthermore, after the inoculation of atill6 with avirulent Pst (DC3000), the expressions of the PR1 and PR2 genes decreased, suggesting a positive role in R-gene-mediated resistance in protecting the plant from further spread of disease. We also investigated the role of ATILL6 in systemic acquired resistance (SAR), and the results showed that ATILL6 positively regulates SAR, as the mutant line atill6 has significantly (p ≤ 0.05) lower transcript accumulation of PR, G3DPH, and AZI genes. Overall, these results indicate that the NO-induced ATILL6 gene differentially regulates plant growth and positively regulates plant basal defense, R-gene-mediated resistance, and SAR.

Khan|Murtaza|M|
Al Azawi|Tiba Nazar Ibrahim|TNI|
Pande|Anjali|A|
Mun|Bong-Gyu|BG|
Lee|Da-Sol|DS|
Hussain|Adil|A|
Lee|Byung-Hyun|BH|
Yun|Byung-Wook|BW|

Arabidopsis thaliana
growth under control
nitro-oxidative stress
oxidative stress
plant defense


Exosomes: From Garbage Bins to Promising Therapeutic Targets.

Abstract: Intercellular communication via cell-released vesicles is a very important process for both normal and tumor cells. Cell communication may involve exosomes, small vesicles of endocytic origin that are released by all types of cells and are found in abundance in body fluids, including blood, saliva, urine, and breast milk. Exosomes have been shown to carry lipids, proteins, mRNAs, non-coding RNAs, and even DNA out of cells. They are more than simply molecular garbage bins, however, in that the molecules they carry can be taken up by other cells. Thus, exosomes transfer biological information to neighboring cells and through this cell-to-cell communication are involved not only in physiological functions such as cell-to-cell communication, but also in the pathogenesis of some diseases, including tumors and neurodegenerative conditions. Our increasing understanding of why cells release exosomes and their role in intercellular communication has revealed the very complex and sophisticated contribution of exosomes to health and disease. The aim of this review is to reveal the emerging roles of exosomes in normal and pathological conditions and describe the controversial biological role of exosomes, as it is now understood, in carcinogenesis. We also summarize what is known about exosome biogenesis, composition, functions, and pathways and discuss the potential clinical applications of exosomes, especially as biomarkers and novel therapeutic agents.

H Rashed|Mohammed|M|
Bayraktar|Emine|E|
K Helal|Gouda|G|
Abd-Ellah|Mohamed F|MF|
Amero|Paola|P|
Chavez-Reyes|Arturo|A|
Rodriguez-Aguayo|Cristian|C|

intercellular communication
non-coding RNAs
biomarkers
exosome-based therapeutics
tumor-derived exosomes


Association of gallbladder polyp with the risk of colorectal adenoma.

Abstract:
BACKGROUND/AIMS
Gallbladder polyps and colorectal adenomas share many common risk factors; however, their association has never been studied. The aim of this study was to investigate this association in asymptomatic healthy subjects.

METHODS
Consecutive asymptomatic subjects who underwent both screening colonoscopy and abdominal ultrasonography at Kyung Hee University Hospital in Gang Dong between July 2010 and April 2011 were prospectively enrolled. The prevalence of colorectal adenoma was compared between subjects with or without gallbladder polyps. Furthermore, a logistic regression analysis was performed to determine the independent risk factors for colorectal adenoma in these subjects.

RESULTS
Of the 581 participants, 55 presented with gallbladder polyps and 526 did not have gallbladder polyps. Participants with gallbladder polyps showed a trend toward a higher prevalence of colorectal adenoma than those without gallbladder polyps (52.7% vs. 39.2%, P=0.051). Although the result was not statistically significant, gallbladder polyps were found to be a possible risk factor for colorectal adenoma (odds ratio=1.796, 95% confidence interval=0.986-3.269, P=0.055), even after adjusting for potential confounding factors. There was no difference observed in colorectal adenoma characteristics between the two groups.

CONCLUSIONS
Our results suggest a possible association between gallbladder polyps and colorectal adenomas. Future studies with larger cohorts are warranted to further investigate this matter.

Jeun|Jung Won|JW|
Cha|Jae Myung|JM|
Lee|Joung Il|JI|
Joo|Kwang Ro|KR|
Shin|Hyun Phil|HP|
Lim|Jun Uk|JU|

Gallbladder polyp
Colonoscopy
Abdominal ultrasonography
Colorectal neoplasm
Mass screening


Modulation of immune responses of Rhynchophorus ferrugineus (Insecta: Coleoptera) induced by the entomopathogenic nematode Steinernema carpocapsae (Nematoda: Rhabditida).

Abstract: Aim of this study was to investigate relationships between the red palm weevil (RPW) Rhynchophorus ferrugineus (Olivier) and the entomopathogenic nematode Steinernema carpocapsae (EPN); particularly, the work was focused on the immune response of the insect host in naive larvae and after infection with the EPN. Two main immunological processes have been addressed: the activity and modulation of host prophenoloxidase-phenoloxidase (proPO) system, involved in melanization of not-self and hemocytes recognition processes responsible for not-self encapsulation. Moreover, immune depressive and immune evasive strategies of the parasite have been investigated. Our results suggest that RPW possess an efficient immune system, however in the early phase of infection, S. carpocapsae induces a strong inhibition of the host proPO system. In addition, host cell-mediated mechanisms of encapsulation, are completely avoided by the parasite, the elusive strategies of S. carpocapsae seem to be related to the structure of its body-surface, since induced alterations of the parasite cuticle resulted in the loss of its mimetic properties. S. carpocapsae before the release of its symbiotic bacteria, depress and elude RPW immune defenses, with the aim to arrange a favorable environment for its bacteria responsible of the septicemic death of the insect target.

Mastore|Maristella|M|
Arizza|Vincenzo|V|
Manachini|Barbara|B|
Brivio|Maurizio F|MF|

Rhynchophorus ferrugineus
Steinernema carpocapsae
encapsulation
immune depression
immune evasion
proPO system


Post-traumatic osteoarthritis diagnosed within 5 years following ACL reconstruction.

Abstract:
PURPOSE
The purpose was to calculate the incidence of osteoarthritis in individuals following Anterior Cruciate Ligament Reconstruction (ACLR) in a large, national database and to examine the risk factors associated with OA development.

METHODS
A commercially available insurance database was queried to identify new diagnoses of knee OA in patients with ACLR. The cumulative incidence of knee OA diagnoses in patients after ACLR was calculated and stratified by time from reconstruction. Odds ratios were calculated using logistic regression to describe factors associated with a new OA diagnosis including age, sex, BMI, meniscus involvement, osteochondral graft use, and tobacco use.

RESULTS
A total of 10,565 patients with ACLR were identified that did not have an existing diagnosis of OA, 517 of which had a documented new diagnosis of knee OA 5 years after ACL reconstruction. When stratified by follow-up time points, the incidence of a new OA diagnosis within 6 months was 2.3%; within a 1-year follow-up was 4.1%; within 2 years, follow-up was 6.2%, within 3 years, follow-up was 8.4%; within 4 years, follow-up was 10.4%; and within 5 years, follow-up was 12.3%. Risk factors for new OA diagnoses were age (OR 2.44, P < 0.001), sex (OR 1.2, P = 0.002), obesity (OR 1.4, P < 0.001), tobacco use (OR = 1.3, P = 0.001), and meniscal involvement (OR 1.2, P = 0.005).

CONCLUSION
Approximately 12% of patients presenting within 5 years following ACLR are diagnosed with OA. Demographic factors associated with an increased risk of a diagnosis of PTOA within 5 years after ACLR are age, sex, BMI, tobacco use, and concomitant meniscal surgery. Clinicians should be cognizant of these risk factors to develop risk profiles in patients with the common goal to achieve optimal long-term outcomes after ACLR.

LEVEL OF EVIDENCE
III.

D000070598:Anterior Cruciate Ligament Injuries

D059549:Anterior Cruciate Ligament Reconstruction

Post-traumatic osteoarthritis
ACL reconstruction
Risk factors
Outcomes
Knee injury


Analgesic effect of a single dose of betamethasone after ambulatory knee arthroscopy: a randomized controlled trial.

Abstract:
PURPOSE
Glucocorticoids are reported to improve postoperative analgesia. The purpose of the study was to investigate whether a preoperative, single dose of betamethasone could reduce pain after ambulatory arthroscopic knee surgery.

METHODS
This was a randomized, double-blind, placebo-controlled trial including patients scheduled for knee arthroscopy. The intervention was an intravenous injection of betamethasone 8 mg or placebo. The primary outcome was pain day 1 evaluated by a verbal descriptor scale (VDS).

RESULTS
In total, 74 patients (betamethasone = 34; placebo = 40) were randomized. One patient in each group was excluded from analysis. During activity day 1 following surgery, the proportion with no or minor pain was significantly (p = 0.030) higher in the betamethasone group (22 of 33; 67 %) compared with the placebo group (17 of 39; 44 %). At rest, the corresponding figures were 26 of 33 (79 %) for betamethasone and 24 of 39 (62 %) for placebo (p = 0.062). After 3 months of follow-up, no patient receiving betamethasone experienced adverse events while six receiving placebo did (postoperative nausea and vomiting in five and delayed wound healing in one).

CONCLUSIONS
An analgesic benefit was seen day 1 following surgery. This indicates that betamethasone has a place in ambulatory arthroscopic knee surgery.

TRIAL REGISTRATION
https://www.clinicaltrialsregister.eu/ (identifier 2009-014717-27).

Segelman|Jerker|J|0000-0002-5098-6977
Pettersson|Hans Järnbert|HJ|
Svensén|Christer|C|
Divander|Mona-Britt|MB|
Barenius|Björn|B|
Segelman|Josefin|J|

D020250:Postoperative Nausea and Vomiting

Betamethasone
Arthroscopy
Randomized controlled trial
Pain


Sepsis Inflammation Impairs the Generation of Functional Dendritic Cells by Targeting Their Progenitors.

Abstract:
Background
Sepsis is a complex systemic immune dysfunction syndrome induced by infection. Sepsis has a high mortality rate, with most patients dying due to systemic organ failure or secondary infection. Dendritic cells (DCs) are professional antigen-presenting cells. Upon infection with microbes, DCs are activated to induce adaptive immune responses for controlling infection. DC generation and function are impaired during sepsis; however, the underlying mechanisms remain largely unknown.

Methods
Peripheral blood samples from sepsis patients were collected to examine DC subsets, DC progenitors, and apoptosis of DCs by flow cytometer. In vitro induction of DCs from hematopoietic stem/progenitor cells were established and a variety of sepsis-associated inflammatory mediators [e.g., interferon-gamma (IFN-γ), interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and granulocyte-colony stimulating factor (G-CSF)] and Lipopolysaccharide (LPS) were determined for the impact on DC generation and function in vitro.

Results
Our results demonstrate that sepsis-induced systemic inflammation impairs the capacity of hematopoietic stem and progenitor cells (HSPCs) to produce DCs, including conventional DCs (cDCs) and plasmacytoid DCs (pDCs). We investigated peripheral blood (PB) samples from 34 pediatric patients on days 1 to 7 following diagnosis. Compared to healthy donors (n = 18), the sepsis patients exhibited a significantly fewer percentage and number of pDCs and cDCs, and a lower expression of antigen presenting molecule HLD-DR and co-stimulatory molecules (e.g., CD86) on the surface of DCs. This sepsis-induced DC impairment was associated with significantly increased apoptotic death of DCs and marked decreases of progenitor cells that give rise to DCs. Furthermore, we observed that among the tested sepsis-associated cytokines (e.g., IFN-γ, IL-1β, TNF-α, and G-CSF), G-CSF and IFN-γ impaired DC development from cultured HSPCs. G-CSF also markedly decreased the expression of HLA-DR on HSPC-derived DCs and their cytokine production, including IL-12 and IFN-β.

Conclusions
Collectively, these findings indicate that sepsis impairs the survival of functional DCs and their development from HSPCs. Strategies for improving DC reconstitution following sepsis may restore DC progenitors and their associated function.

Lu|Jie|J| Sun|Kun|K| Yang|Huiping|H| Fan|Dan|D| Huang|He|H| Hong|Yi|Y| Wu|Shuiyan|S| Zhou|HuiTing|H| Fang|Fang|F| Li|YanHong|Y| Meng|Lijun|L| Huang|Jie|J| Bai|Zhenjiang|Z|

sepsis
dendritic cells
IFN-γ
G-CSF
common dendritic cell progenitors
dendritic cell progenitors


Model-based comorbidity clusters in patients with heart failure: association with clinical outcomes and healthcare utilization.

Abstract:
BACKGROUND
Comorbidities affect outcomes in heart failure (HF), but are not reflected in current HF classification. The aim of this study is to characterize HF groups that account for higher-order interactions between comorbidities and to investigate the association between comorbidity groups and outcomes.

METHODS
Latent class analysis (LCA) was performed on 12 comorbidities from patients with HF identified from administrative claims data in the USA (OptumLabs Data Warehouse®) between 2008 and 2018. Associations with admission to hospital and mortality were assessed with Cox regression. Negative binomial regression was used to examine rates of healthcare use.

RESULTS
In a population of 318,384 individuals, we identified five comorbidity clusters, named according to their dominant features: low-burden, metabolic-vascular, anemic, ischemic, and metabolic. Compared to the low-burden group (minimal comorbidities), patients in the metabolic-vascular group (exhibiting a pattern of diabetes, obesity, and vascular disease) had the worst prognosis for admission (HR 2.21, 95% CI 2.17-2.25) and death (HR 1.87, 95% CI 1.74-2.01), followed by the ischemic, anemic, and metabolic groups. The anemic group experienced an intermediate risk of admission (HR 1.49, 95% CI 1.44-1.54) and death (HR 1.46, 95% CI 1.30-1.64). Healthcare use also varied: the anemic group had the highest rate of outpatient visits, compared to the low-burden group (IRR 2.11, 95% CI 2.06-2.16); the metabolic-vascular and ischemic groups had the highest rate of admissions (IRR 2.11, 95% CI 2.08-2.15, and 2.11, 95% CI 2.07-2.15) and healthcare costs.

CONCLUSIONS
These data demonstrate the feasibility of using LCA to classify HF based on comorbidities alone and should encourage investigation of multidimensional approaches in comorbidity management to reduce admission and mortality risk among patients with HF.

Gulea|Claudia|C|0000-0001-9607-5901
Zakeri|Rosita|R|
Quint|Jennifer K|JK|

D010342:Patient Acceptance of Health Care

Comorbidity
Hospitalization
Mortality
Resource use


Optimisation of glutathione conjugation to liposomes quantified with a validated HPLC assay.

Abstract: Glutathione (GSH) grafted onto nanoliposomes (GSH-liposomes) have the potential to enhance drug delivery into the brain. GSH is known to be an unstable tripeptide, however, despite widespread use to promote active transport its stability has been largely ignored to date. Therefore this study focuses on the optimisation of GSH conjugation with liposomes, supported with a validated HPLC assay for GSH. An isocratic stability-indicating HPLC assay of GSH was developed after derivatisation of GSH with 5,5'-dithio-bis-2-nitrobenzoic acid and applied for efficient conjugation of GSH to DSPE-PEG2000-maleimide lipid, either in solution or in preformed liposomes (4% molar ratio) at pH 7.4. The conjugation rate was monitored by the HPLC assay to optimise the conjugation conditions, including GSH concentration, GSH:lipid ratio, reaction time, temperature and medium. The physiochemical properties of the resulting GSH-liposomes and their GSH densities were characterised. The HPLC method was linear in the range of 0.05-50 µg/ml, highly sensitive (limit of quantification 50 ng/ml), and accurate (98-102% recoveries) with less than 4% intra-day and inter-day variability. Interestingly, enhanced GSH stability was observed at higher GSH concentrations ≥2 mg/ml and mass spectroscopy confirmed that GSH degradation occurred predominantly by oxidation. Both the proton nuclear magnetic resonance (1H NMR) spectra and HPLC analysis of GSH concentrations confirmed the formation of GSH-PEG-DSPE conjugate. Under the optimal conditions, complete conjugation was attained either by post-insertion or direct conjugation methods with the resulting GSH-liposomes attaining a GSH density of 4% with similar size (120 nm) and zeta potential (-26.7 ± 0.9 mV or -29.8 ± 1.5 mV). The study provides useful information on GSH stability for the optimisation of its conjugation in liposomal formulation.

Reginald-Opara|Joy N|JN|
Svirskis|Darren|D|
O'Carroll|Simon J|SJ|
Sreebhavan|Sreevalsan|S|
Dean|Justin M|JM|
Wu|Zimei|Z|

D002851:Chromatography, High Pressure Liquid

Optimisation
Glutathione conjugation
Liposomes
Blood-brain barrier
Elman’s derivatisation
Glutathione stability
Glutathione-liposomes
HPLC validation


Bioavailability of Aflatoxins in Cultured Fish and Animal Livers Using an In Vitro Dialyzability Approach.

Abstract: The objective of the present study was to investigate the bioavailability of aflatoxins (AFs) from fish, and chicken and rabbit livers using an in vitro dialyzability approach. Ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was used to assess the aflatoxin content in samples, as well as in dialyzate and residue fractions after the in vitro procedure. A vortex-assisted dispersive liquid-liquid microextraction (VALLME) technique was used for preconcentrating AFs before determination. Raw samples showed bioavailability ratios of 41-45% for aflatoxin B1 (AFB1), 28-38% for aflatoxin B2 (AFB2), and 42% for aflatoxin G2 (AFG2). Aflatoxin G1 (AFG1) was not detected. The culinary process (steaming or grilling) was found to change AFs' bioavailability (higher bioavailability ratios were found in cooked samples). AFB2 was found to be transformed into other compounds during the in vitro process, and the presence of AFB2 and AFB2 transformation/degradation products was investigated and confirmed by high-resolution mass spectrometry (HRMS).

Jayasinghe|G D Thilini Madurangika|GDTM|

bioavailability
aflatoxins
fish
high-resolution mass spectrometry
transformation products


Key Decision Makers and Actors in Selected Newborn Care Practices: A Community-Based Survey in Northern Uganda.

Abstract: Knowledge of key decision makers and actors in newborn care is necessary to ensure that health interventions are targeted at the right people. This was a cross-sectional study carried out in Lira district, Northern Uganda. Multivariable logistic regression was used to determine factors associated with mothers being the key decision maker regarding where to give birth from and when to initiate breastfeeding. Fathers were the key decision makers on the place of birth (54.3%, n = 505) and on whether to seek care for a sick newborn child (47.7%, n = 92). Grandmothers most commonly bathed the baby immediately after birth (55.5%, n = 516), whereas mothers and health workers were common decision makers regarding breastfeeding initiation. Predictors for a mother being the key decision maker on the place of birth included: Mother having a secondary education (AOR 1.9: 95% C.I (1.0-3.6)) and mother being formally employed (AOR 2.0: 95% (1.5-2.9)). Mothers, fathers, grandmothers, health-workers, and traditional birth attendants were the most influential in the selected newborn care practices. Programs that aim to promote newborn care need to involve husbands, grandmothers, and health workers in addition to mothers.

actors newborn Uganda behavior decision-making implementation influencers neonatal post-conflict


Expressional studies of the aldehyde oxidase (AOX1) gene during myogenic differentiation in C2C12 cells.

Abstract: Aldehyde oxidases (AOXs), which catalyze the hydroxylation of heterocycles and oxidation of a wide variety of aldehydic compounds, have been present throughout evolution from bacteria to humans. While humans have only a single functional aldehyde oxidase (AOX1) gene, rodents are endowed with four AOXs; AOX1 and three aldehyde oxidase homologs (AOH1, AOH2 and AOH3). In continuation of our previous study conducted to identify genes differentially expressed during myogenesis using a microarray approach, we investigated AOX1 with respect to its role in myogenesis to conceptualize how it is regulated in C2C12 cells. The results obtained were validated by silencing of the AOX1 gene. Analysis of their fusion index revealed that formation of myotubes showed a marked reduction of up to 40% in AOX1kd cells. Expression of myogenin (MYOG), one of the marker genes used to study myogenesis, was also found to be reduced in AOX1kd cells. AOX1 is an enzyme of pharmacological and toxicological importance that metabolizes numerous xenobiotics to their respective carboxylic acids. Hydrogen peroxide (H2O2) produced as a by-product in this reaction is considered to be involved as a part of the signaling mechanism during differentiation. An observed reduction in the level of H2O2 among AOX1kd cells confirmed production of H2O2 in the reaction catalyzed by AOX1. Taken together, these findings suggest that AOX1 acts as a contributor to the process of myogenesis by influencing the level of H2O2.

Kamli|Majid Rasool|MR|
Kim|Jihoe|J|
Pokharel|Smritee|S|
Jan|Arif Tasleem|AT|
Lee|Eun Ju|EJ|
Choi|Inho|I|

D060888:Real-Time Polymerase Chain Reaction

Oxidase
Differentiation
C2C12 cell
Myogenesis
Hydrogen peroxide


Behavioral inhibition and posttrauma symptomatology: Moderating effects of safety behaviors and biological sex.

Abstract:
OBJECTIVES
Behavioral inhibition is a trait-level factor associated with posttraumatic stress. Safety behaviors may impact this link by interfering with anxiety habituation. The current study examined the unique and interactive effects of behavioral inhibition, safety behaviors, and participant sex on posttrauma symptom clusters.

METHOD
Participants (N = 131; 75.6% female; M = 19.9 years) completed a trauma history interview and questionnaires assessing behavioral inhibition, safety behavior, and posttrauma symptom severity.

RESULTS
Safety behaviors were associated with intrusion (partial correlations [pr] = 0.319), avoidance (pr = 0.274), cognition-mood (pr = 0.274), and arousal-reactivity (pr = 0.538) symptoms (all p ≤ 0.001). An interaction of sex and safety behaviors was noted for avoidance (p = 0.047, pr = -0.159) with a significant relation observed only among women ( p < 0.001, pr = 0.442). Safety behaviors also moderated the link between behavioral inhibition and arousal-reactivity (p = 0.002, pr = 0.272) with inhibition predicting symptoms at high levels of safety behavior (p = 0.024, pr = 0.171).

CONCLUSION
Trauma-related safety behaviors are associated with greater posttrauma symptoms and evidence differential effects across individual symptom domains.

McClure|Kenneth E|KE|
Blakey|Shannon M|SM|
Kozina|Ryan M|RM|
Ripley|Adam J|AJ|
Kern|Shira M|SM|0000-0003-4227-9954
Clapp|Joshua D|JD|0000-0003-2897-5363

behavioral inhibition
safety behaviors
trauma
PTSD
sex differences


Value of systematic analysis of the olfactory cleft in case of cerebrospinal rhinorrhea: incidence of olfactory arachnoid dilatation.

Abstract: To report on the presence of olfactory arachnoid dilatations (OAD), a previously undescribed radiologic feature of spontaneous cerebrospinal fluid (CSF) rhinorrhea originating from the cribriform plate of the ethmoid bone. The medical records of all patients treated between 2001 and 2011 at a tertiary care center for a spontaneous CSF rhinorrhea originating from the cribriform plate were retrospectively reviewed. The radiological work-up included high-resolution computed tomography and magnetic resonance imaging with at least the following sequences: T1, T2, and T2 with fast imaging employing steady state acquisition (FIESTA). Thirty cases were identified. The mean age at diagnosis was 49. Fourteen patients (47 %) had a body mass index (BMI) of 30 or more and 3 patients (10 %) had a BMI between 25 and 29.9. Five patients had a history of meningitis. The imaging work-up revealed a bone defect of the cribriform plate in 6 cases (20 %), associated to a typical meningocele in 14 cases (47 %). In ten patients (33 %), there was no defect of the cribriform plate, but ultrathin coronal T2-FIESTA sequences revealed an OAD, i.e. a dilatation of the arachnoid sheath of the olfactory fibers, in nine cases (30 %), or a "pseudo-polyp" outlined by a thin layer of arachnoid (1 patient, 3 %). Preoperative imaging should be carefully analyzed for the presence of OAD or "pseudo-polyp" in patients presenting with a CSF rhinorrhea without bony defect of the cribriform plate.

Gharzouli|Imen|I| Verillaud|Benjamin|B| Tran|Hugo|H| Blancal|Jean-Philippe|JP| Sauvaget|Elisabeth|E| Kania|Romain|R| Guichard|Jean-Pierre|JP| Herman|Philippe|P|

Olfactory cleft
Cribriform plate
Meningocele
CSF leak
Endoscopic repair


Live birth after PGD with confirmation by a comprehensive approach (karyomapping) for simultaneous detection of monogenic and chromosomal disorders.

Abstract: Preimplantation genetic diagnosis (PGD) for monogenic disorders has the drawback of time and cost associated with tailoring a specific test for each couple, disorder, or both. The inability of any single assay to detect the monogenic disorder in question and simultaneously the chromosomal complement of the embryo also limits its application as separate tests may need to be carried out on the amplified material. The first clinical use of a novel approach ('karyomapping') was designed to circumvent this problem. In this example, karyomapping was used to confirm the results of an existing PGD case detecting both chromosomal abnormalities and a monogenic disorder (Smith-Lemli-Opitz [SLO] syndrome) simultaneously. The family underwent IVF, ICSI and PGD, and both polar body and cleavage stage biopsy were carried out. Following whole genome amplification, array comparative genomic hybridisation of the polar bodies and minisequencing and STR analysis of single blastomeres were used to diagnose maternal aneuploidies and SLO status, respectively. This was confirmed, by karyomapping. Unlike standard PGD, karyomapping required no a-priori test development. A singleton pregnancy and live birth, unaffected with SLO syndrome and with no chromosome abnormality, ensued. Karyomapping is potentially capable of detecting a wide spectrum of monogenic and chromosome disorders and, in this context, can be considered a comprehensive approach to PGD.

Natesan|Senthilkumar A|SA|
Handyside|Alan H|AH|
Thornhill|Alan R|AR|
Ottolini|Christian S|CS|
Sage|Karen|K|
Summers|Michael C|MC|
Konstantinidis|Michalis|M|
Wells|Dagan|D|
Griffin|Darren K|DK|

PGD
Karyomapping
polar body
aneuploidy
Smith Lemli Opitz syndrome
embryo biopsy


Murine Bronchoalveolar Lavage.

Abstract: A basic Bronchoalveolar lavage (BAL) procedure in mouse is described here. Cells and fluids obtained from BAL can be analyzed by Hema3-staining, immunostaining, Fluorescence-activated cell sorting (FACS), PCR, bicinchoninic acid protein assay, enzyme-linked immunosorbent assay (ELISA), luminex assays, etc., to examine the immune cells, pathogens, proteins such as cytokines/chemokines, and the expression levels of inflammation-related and other genes in the cells. This will help to understand the underlying mechanisms of these lung diseases and develop specific and effective drugs.

Bronchoalveolar lavage
Hema3-staining
Lung cancer


Estimating the public economic consequences of introducing varenicline smoking cessation therapy in South Korea using a fiscal analytic framework.

Abstract:
BACKGROUND AND AIMS
Smoking gives rise to many cross-sectorial public costs and benefits for government. Costs arise from increased healthcare spending and work-related social benefits, while smoking itself provides significant revenue for government from tobacco taxes. To better understand the public economic impact of smoking and smoking cessation therapies, this study developed a government perspective framework for assessing smoking-attributable morbidity and mortality and associated public costs. This framework includes changes in lifetime tax revenue and health costs, as well as changes in tobacco tax revenue, from fewer smokers.

METHODS
A modified generational accounting framework was developed to assess relationships between smoking-attributable morbidity and mortality and public economic consequences of smoking, including lifetime tax revenue gains/losses, government social transfers, and health spending. Based on the current prevalence of smoking in South Korean males, a cohort model was developed for smokers, former-smokers, and never-smokers. The model simulated the lifetime discounted fiscal transfers for different age cohorts in 5 year age bands, and the return on investment (ROI) from smoking cessation therapy.

RESULTS
Former smokers are estimated to generate higher lifetime earnings and direct tax revenues and lower lifetime healthcare costs due to the reduction of smoking-attributable mortality and morbidity compared to smokers, even after accounting for reduced tobacco taxes paid. Based on the costs of public investments in varenicline, this study estimated a ROI from 1.4-1.7, depending on treatment age, with higher ROI in younger cohorts, with an average ROI of 1.6 for those aged less than 65.

CONCLUSIONS
This analysis suggests that reductions in smoking can generate positive public economic benefits for government, even after accounting for lost tobacco tax revenues. The results described here are likely applicable to countries having similar underlying smoking prevalence, comparable taxation rates, and social benefit protection provided to individuals with smoking-related conditions.

Connolly|Mark P|MP|
Baker|Christine L|CL|
Kotsopoulos|Nikolaos|N|

Public economics
smoking cessation
tax
smoking-attributable mortality
smoking policy


Comparison of Logistic Regression and Bayesian Networks for Risk Prediction of Breast Cancer Recurrence.

Abstract:
PURPOSE
For individualized follow-up, accurate prediction of locoregional recurrence (LRR) and second primary (SP) breast cancer risk is required. Current prediction models employ regression, but with large data sets, machine-learning techniques such as Bayesian Networks (BNs) may be better alternatives. In this study, logistic regression was compared with different BNs, built with network classifiers and constraint- and score-based algorithms.

METHODS
Women diagnosed with early breast cancer between 2003 and 2006 were selected from the Netherlands Cancer Registry (NCR) ( N = 37,320). BN structures were developed using 1) Bayesian network classifiers, 2) correlation coefficients with different cutoffs, 3) constraint-based learning algorithms, and 4) score-based learning algorithms. The different models were compared with logistic regression using the area under the receiver operating characteristic curve, an external validation set obtained from the NCR from 2007 and 2008 ( N = 12,308), and subgroup analyses for a high- and low-risk group.

RESULTS
The BNs with the most links showed the best performance in both LRR and SP prediction (c-statistic of 0.76 for LRR and 0.69 for SP). In the external validation, logistic regression generally outperformed the BNs in both SP and LRR (c-statistic of 0.71 for LRR and 0.64 for SP). The differences were nonetheless small. Although logistic regression performed best on most parts of the subgroup analysis, BNs outperformed regression with respect to average risk for SP prediction in low- and high-risk groups.

CONCLUSIONS
Although estimates of regression coefficients depend on other independent variables, there is no assumed dependence relationship between coefficient estimators and the change in value of other variables as in the case of BNs. Nonetheless, this analysis suggests that regression is still more accurate or at least as accurate as BNs for risk estimation for both LRRs and SP tumors.

logistic regression
Bayesian network
risk prediction
breast cancer
locoregional recurrence
second primary
machine learning


Crosstalk between Peroxisome Proliferator-Activated Receptors and Toll-Like Receptors: A Systematic Review.

Abstract: As one of the four major families of pattern recognition receptors (PRRs), toll like receptors (TLRs) are crucial and important components of the innate immune system. Peroxisome proliferatoractivated receptors (PPARs) with three isoforms are transcription factors classified as a subfamily of nuclear receptor proteins, and are of significant regulatory activity in cellular differentiation, development, metabolism, and tumorigenesis. It is well established that PPARs agonists display anti-inflammatory effects through inhibition of the nuclear factor-kappa B (NF-κB) pathway, a key regulator of immune and inflammatory responses, in a sense that TLRs signaling pathways are mainly toward activation of NF-κB. Through a systematic review of previous studies, we aimed to address and clarify the reciprocal interaction between TLRs and PPARs in hope to find alternative therapeutic approaches for inflammatory diseases. Among the available scientific database, 31 articles were selected for this review. A comprehensive review of this database confirms the presence of a cross-talk between PPARs and TLRs, indicating that not only PPARs stimulation may affect the expression level of TLRs via several mechanisms leading to modulating TLRs activities, but also TLRs have the potential to moderate the expression of PPARs. We, therefore, conclude that, as a key regulator of the innate immune system, the interaction between PPARs and TLRs is a potential therapeutic target in disease treatment.