Empowering Citizens through Perceptual Sensing of Urban Environmental and Health Data Following a Participative Citizen Science Approach.

Abstract: The growth of the urban population together with a high concentration of air pollution have important health impacts on citizens who are exposed to them, causing serious risks of the development and evolution of different chronic diseases. This paper presents the design and development of a novel participatory citizen science-based application and data ecosystem model. These developments are imperative and scientifically designed to gather and process perceptual sensing of urban, environmental, and health data. This data acquisition approach allows citizens to gather and generate environment- and health-related data through mobile devices. The sum of all citizens' data will continuously enrich and increase the volumes of data coming from the city sensors and sources across geographical locations. These scientifically generated data, coupled with data from the city sensors and sources, will enable specialized predictive analytic solutions to empower citizens with urban, environmental, and health recommendations, while enabling new data-driven policies. Although it is difficult for citizens to relate their personal behaviour to large-scale problems such as climate change, pollution, or public health, the developed ecosystem provides the necessary tools to enable a greener and healthier lifestyle, improve quality of life, and contribute towards a more sustainable local environment.

Ottaviano|Manuel|M|
Beltrán-Jaunsarás|María Eugenia|ME|
Teriús-Padrón|José Gabriel|JG|
García-Betances|Rebeca I|RI|
González-Martínez|Sergio|S|
Cea|Gloria|G|
Vera|Cecilia|C|
Cabrera-Umpiérrez|María Fernanda|MF|
Waldmeyer|María Teresa Arredondo|MTA|

D000397:Air Pollution
D002947:Cities
D000080029:Citizen Science
D003256:Community Participation
D017753:Ecosystem
D004784:Environmental Monitoring
D040362:Geographic Information Systems
D000070497:Healthy Lifestyle
D006801:Humans
D063731:Mobile Applications
D010865:Pilot Projects
D014584:User-Computer Interface
D057188:Workflow

citizen science
pollution
public health
environmental sensors
green behaviour
sustainable lifestyle
user empowerment


Preliminary study on alginate/NIPAM hydrogel-based soft microrobot for controlled drug delivery using electromagnetic actuation and near-infrared stimulus.

Abstract: Currently, microrobots are receiving attention because of their small size and motility, which can be applied to minimal invasive therapy. Additionally, various microrobots using hydrogel with the characteristics of biocompatibility and biodegradability are also being developed. Among them, microrobots that swell and deswell in response to temperature changes caused by external near infrared (NIR) stimuli, focused ultrasound, and an alternating magnetic field, have been receiving a great amount of interest as drug carriers for therapeutic cell delivery. In this study, we propose a spring type medical microrobot that can be manipulated by an electromagnetic actuation (EMA) system and respond to an external stimulus (NIR). Additionally, we verified its feasibility with regard to targeting and drug delivery. There exist various methods of fabricating a spring type microrobot. In this study, we adopted a simple method that entails using a perfluoroalkoxy (PFA) microtube and a syringe pump. Moreover, we also used a hydrogel mixture composed of natural alginate, N-Isopropylacrylamide (NIPAM) for temperature responsiveness, and magnetic nanoparticles (MNPs) for electromagnetic control. Then, we fabricated a spring type alginate/NIPAM hydrogel-based soft microrobot. Additionally, we encapsulated doxorubicin (DOX) for tumor therapy in the microrobot. To verify the feasibility of the proposed spring type hydrogel-based soft microrobot's targeting and drug delivery, we developed an EMA and NIR integrated system. Finally, we observed the swelling and deswelling of the soft microrobot under NIR stimulation and verified the EMA controlled targeting. Moreover, we implemented a control function to release the encapsulated anticancer drug (DOX) through the swelling and deswelling of the soft microrobot by NIR, and evaluated the feasibility of cancer cell therapy by controlling the release of the drug from the soft microrobot.

Lee|Hyoryong|H| Choi|Hyunchul|H| Lee|Mikyoung|M| Park|Sukho|S|0000-0002-8699-897X

Electromagnetic actuation
Near-infrared stimulus
Temperature responsive
Magnetic nanoparticles
Controlled drug releasing
Hydrogel-based microrobot


A diagnostic pitfall of a sternal mass.

Abstract: Primary sternal lymphoma represents a rare entity which must be evoked in front of a sternal mass especially as its treatment is different from that of sarcomas, the principal etiology of sternal masses.


Bacteria and Competing Herbivores Weaken Top-Down and Bottom-Up Aphid Suppression.

Abstract: Herbivore suppression is mediated by both plant defenses and predators. In turn, plant defenses are impacted by soil fertility and interactions with soil bacteria. Measuring the relative importance of nutritional and microbial drivers of herbivore resistance has proven problematic, in part because it is difficult to manipulate soil-bacterial community composition. Here, we exploit variation in soil fertility and microbial biodiversity across 20 farms to untangle suppression of aphids (Brevicoryne brassicae) through bottom-up and top-down channels. We planted Brassica oleracea plants in soil from each farm, manipulated single and dual infestations of aphids alone or with caterpillars (Pieris rapae), and exposed aphids to parasitoid wasps (Diaeretiella rapae) in the open field. We then used multi-model inference to identify the strongest soil-based predictors of herbivore growth and parasitism. We found that densities of Bacillus spp., a genus known to include plant-growth-promoting rhizobacteria, negatively correlated with aphid suppression by specialist parasitoids. Aphid parasitism also was disrupted on plants that had caterpillar damage, compared to plants attacked only by aphids. Relative abundance of Pseudomonas spp. bacteria correlated with higher aphid growth, although this appeared to be a direct effect, as aphid parasitism was not associated with this group of bacteria. Non-pathogenic soil bacteria are often shown to deliver benefits to plants, improving plant nutrition and the deployment of anti-herbivore defenses. However, our results suggest that these plant growth-promoting bacteria may also indirectly weaken top-down aphid suppression by parasitoids and directly improve aphid performance. Against a background of varying soil fertility, microbial biodiversity, competing herbivores, and natural enemies, we found that effects of non-pathogenic soil microbes on aphid growth outweighed those of nutritional factors. Therefore, predictions about the strength of plant defenses along resource gradients must be expanded to include microbial associates.

Blubaugh|Carmen K|CK|
Carpenter-Boggs|Lynne|L|
Reganold|John P|JP|
Schaeffer|Robert N|RN|
Snyder|William E|WE|

Brevicoryne brassicae
Brassica oleracea
Bacillus spp.
Pseudomonas spp.
growth-defense tradeoff
tritrophic interactions


Differential expression of miR-21 and miR-75 in esophageal carcinoma patients and its clinical implication.

Abstract: In Xinjiang, China, esophageal carcinoma has a high incidence in Kazak and Uighur populations. MicroRNA (miR)-21 and miR-375 are related to esophageal carcinoma. This study thus investigated their potencials in early diagnosis and prognosis in Kazak and Uighur populations, to provide evidences for serum markers of esophageal cancer. A total of 126 Kazak or Uighur esophageal cancer patients were enrolled as the disease group, along with 86 local Han patients as disease control cohort, and 80 healthy Kazak or Uighur individuals. MiRNA expression was detected by in situ hybridization in tissues and by qRT-PCR in serum. ROC approach was used to evaluate the diagnostic value of miRNA on esophageal carcinoma. Cox analysis was performed to screen factors governing prognosis. MiR-21 level was significantly elevated in both tissue and serum samples of esophageal cancer patients, while miR-375 was down-regulated. Such difference was more potent in disease group compared to disease control group. MiR expression was correlated with infiltration depth, TNM stage, vascular invasion, and lymph node metastasis. Elevated expression of miR-21 reduced the sensitivity of radio-therapy, and increased recurrence frequency. The diagnostic value of single assay for miR-21 or miR-375 was lower than the combined assay (AUC=0.812 or 0.739 vs. 0.858). They also affected patient prognosis (OR=1.53 or 0.652). MiR-21 and miR-375 presented abnormal expression in Kazak or Uighur esophageal carcinoma patients and were independent factors affecting prognosis. The combined assay of miR-21 and miR-375 may help to make early diagnosis of esophageal cancer.

Lv|Hongbo|H| He|Zhanao|Z| Wang|Hongjiang|H| Du|Tongxin|T| Pang|Zuoliang|Z|


Synthesis and antiviral activity of diverse heterocyclic scaffolds.

Abstract: Heterocyclic moieties form a major part of organic chemistry as they are widely distributed in nature and have wide scale practical applications ranging from extensive clinical use to diverse fields such as medicine, agriculture, photochemistry, biocidal formulations, and polymer science. By virtue of their therapeutic properties, they could be employed in combating many infectious diseases. Among the common infectious diseases, viral infections are of great public health importance worldwide. Thus, there is an urgent need for the discovery and development of antiviral drugs and clinical methods to prevent various viral infections so as to increase the life expectancy. This review presents the comprehensive overview of the synthesis and antiviral activity of different heterocyclic compounds 2015 onwards, which aids in present knowledge and helps the researchers and other stakeholders to explore their field.

antiviral
heterocyclic
inhibitors
plant virus
structure-activity relationships


Diversity and Reassortment Rate of Influenza A Viruses in Wild Ducks and Gulls.

Abstract: Influenza A viruses (IAVs) evolve via point mutations and reassortment of viral gene segments. The patterns of reassortment in different host species differ considerably. We investigated the genetic diversity of IAVs in wild ducks and compared it with the viral diversity in gulls. The complete genomes of 38 IAVs of H1N1, H1N2, H3N1, H3N2, H3N6, H3N8, H4N6, H5N3, H6N2, H11N6, and H11N9 subtypes isolated from wild mallard ducks and gulls resting in a city pond in Moscow, Russia were sequenced. The analysis of phylogenetic trees showed that stable viral genotypes do not persist from year to year in ducks owing to frequent gene reassortment. For comparison, similar analyses were carried out using sequences of IAVs isolated in the same period from ducks and gulls in The Netherlands. Our results revealed a significant difference in diversity and rates of reassortment of IAVs in ducks and gulls.

Postnikova|Yulia|Y|
Treshchalina|Anastasia|A|
Boravleva|Elizaveta|E|
Gambaryan|Alexandra|A|
Ishmukhametov|Aydar|A|
Matrosovich|Mikhail|M|
Fouchier|Ron A M|RAM|
Sadykova|Galina|G|
Prilipov|Alexey|A|
Lomakina|Natalia|N|0000-0003-2638-4244


Pheromones mediating copulation and attraction in Drosophila.

Abstract: Intraspecific olfactory signals known as pheromones play important roles in insect mating systems. In the model Drosophila melanogaster, a key part of the pheromone-detecting system has remained enigmatic through many years of research in terms of both its behavioral significance and its activating ligands. Here we show that Or47b-and Or88a-expressing olfactory sensory neurons (OSNs) detect the fly-produced odorants methyl laurate (ML), methyl myristate, and methyl palmitate. Fruitless (fru(M))-positive Or47b-expressing OSNs detect ML exclusively, and Or47b- and Or47b-expressing OSNs are required for optimal male copulation behavior. In addition, activation of Or47b-expressing OSNs in the male is sufficient to provide a competitive mating advantage. We further find that the vigorous male courtship displayed toward oenocyte-less flies is attributed to an oenocyte-independent sustained production of the Or47b ligand, ML. In addition, we reveal that Or88a-expressing OSNs respond to all three compounds, and that these neurons are necessary and sufficient for attraction behavior in both males and females. Beyond the OSN level, information regarding the three fly odorants is transferred from the antennal lobe to higher brain centers in two dedicated neural lines. Finally, we find that both Or47b- and Or88a-based systems and their ligands are remarkably conserved over a number of drosophilid species. Taken together, our results close a significant gap in the understanding of the olfactory background to Drosophila mating and attraction behavior; while reproductive isolation barriers between species are created mainly by species-specific signals, the mating enhancing signal in several Drosophila species is conserved.

Dweck|Hany K M|HK|
Ebrahim|Shimaa A M|SA|
Thoma|Michael|M|
Mohamed|Ahmed A M|AA|
Keesey|Ian W|IW|
Trona|Federica|F|
Lavista-Llanos|Sofia|S|
Svatoš|Aleš|A|
Sachse|Silke|S|
Knaden|Markus|M|
Hansson|Bill S|BS|

pheromone
Drosophila
mating
olfaction
olfactory circuit


Overexpression of CHI3L1 is associated with chemoresistance and poor outcome of epithelial ovarian carcinoma.

Abstract: We propose CHI3L1 as a prognostic biomarker for patients with epithelial ovarian carcinoma (EOC) and also suggest possible biological functions of CHI3L1. We measured CHI3L1 expression with quantitative real time-polymerase chain reaction (qRT-PCR) in 180 women with EOC and evaluated correlations between CHI3L1 expression, clinicopathological characteristics, and the outcomes of the patients. The expression of CHI3L1 was higher in cancerous tissues than in normal tissues. The expression of CHI3L1 was also higher in patients with a serous histological type, advanced stage, and chemoresistance. Patients with high CHI3L1 expression had a shorter progression-free survival (p < 0.001)and overall survival (p < 0.001). Patients with high CHI3L1 expression also had a high risk of recurrence (p < 0.001)and death (p < 0.001). In vitro studies showed that CHI3L1 up-regulated the expression of anti-apoptotic Mcl-1 protein and hampered paclitaxel-induced apoptosis of ovarian cancer cells. These results suggest that CHI3L1 shows potential as a prognostic biomarker for EOC. CHI3L1 may promote chemoresistance via inhibition of drug-induced apoptosis by up-regulating Mcl-1.

Chiang|Ying-Cheng|YC| Lin|Han-Wei|HW| Chang|Chi-Fang|CF| Chang|Ming-Cheng|MC| Fu|Chi-Feng|CF| Chen|Tsung-Ching|TC| Hsieh|Shu-Feng|SF| Chen|Chi-An|CA| Cheng|Wen-Fang|WF|

D015972:Gene Expression Regulation, Neoplastic

D064549:Myeloid Cell Leukemia Sequence 1 Protein

D009375:Neoplasms, Glandular and Epithelial

D020133:Reverse Transcriptase Polymerase Chain Reaction

CHI3L1
chemoresistance
epithelial ovarian carcinoma
apoptosis


Effect of dietary vitamin E on oxidative stress-related gene-mediated differences in anxiety-like behavior in inbred strains of mice.

Abstract: It has been reported that the degree of anxiety-like behavior differs between inbred strains of mice, and that this phenomenon was linked to the expression levels of the oxidative stress-related genes glyoxalase 1 (Glo1) and glutathione reductase 1 (Gsr) in the brain. Therefore, we investigated whether antioxidative activity in the brain affects the Glo1 and Gsr mRNA expressions and strain-dependent anxiety-like behavior using mice fed different amounts of vitamin E. First, we measured brain Glo1 and Gsr mRNA levels and evaluated the anxiety-like behaviors presented by C57BL/6J (B6) and DBA/2C (D2) mice. We demonstrated that D2 mice presented both significantly elevated Glo1 and Gsr mRNA levels as well as more prominent anxiety-like behavior in elevated plus-maze and open field tests. Next, we fed mice from these two strains either a control, vitamin E-free, or vitamin E-supplemented diet for four weeks. Plasma, liver, and brain α-tocopherol concentrations changed in a dose-dependent manner. However, neither brain Glo1 and Gsr mRNA levels nor anxiety-like behavior were affected by dietary vitamin E intake. These results demonstrated that while strain-dependent anxiety-like behavior in mice was related to oxidative stress-related gene expression, the regulatory mechanisms for these genes and anxiety-like behaviors were independent of antioxidative activity in the brain. Strain-dependent differences of the anxiety in mice are probably related to the anxiolytic effects of methylglyoxal, a substrate for Glo1 and Gsr.

D017392:Thiobarbituric Acid Reactive Substances

Vitamin E
Anxiety-like behavior
Mouse strains
Oxidative stress
Tocopherol


Delayed presentation of compartment syndrome of the thigh secondary to quadriceps trauma and vascular injury in a soccer athlete.

Abstract:
INTRODUCTION
Compartment syndrome isolated to the anterior thigh is a rare complication of soccer injury. Previous reports in the English literature on sports trauma-related compartment syndrome of the thigh are vague in their description of the response of thigh musculature to blunt trauma, magnetic resonance imaging (MRI) findings of high-risk features of compartment syndrome, vascular injury in quadriceps trauma, and the role of vascular study in blunt thigh injury.

CASE REPORT
We present herein the rare case of a 30-year-old man who developed thigh compartment syndrome 8 days after soccer injury due to severe edema of vastus intermedius and large thigh hematoma secondary to rupture of the profunda femoris vein. MRI revealed "blow-out" rupture of the vastus lateralis. Decompressive fasciotomy and vein repair performed with subsequent split-skin grafting of the wound defect resulted in a good functional outcome at 2-years follow-up.

CONCLUSION
A high index of suspicion for compartment syndrome is needed in all severe quadriceps contusion. Vascular injury can cause thigh compartment syndrome in sports trauma. MRI findings of deep thigh muscle swelling and "blow-out" tear of the vastus lateralis are strongly suggestive of severe quadriceps injury, and may be a harbinger of delayed thigh compartment syndrome.

How|Moo Ing|MI|
Lee|Puah Ken|PK|
Wei|Tan See|TS|
Chong|Chua Tai|CT|

Soccer
Fasciotomy
Quadriceps injury
Acute compartment syndrome


Temporal and spatial impact of Spartina alterniflora invasion on methanogens community in Chongming Island, China.

Abstract: Methane production by methanogens in wetland is recognized as a significant contributor to global warming. Spartina alterniflora (S. alterniflora), which is an invasion plant in China's wetland, was reported to have enormous effects on methane production. But studies on shifts in the methanogen community in response to S. alterniflora invasion at temporal and spatial scales in the initial invasion years are rare. Sediments derived from the invasive species S. alterniflora and the native species Phragmites australis (P. australis) in pairwise sites and an invasion chronosequence patch (4 years) were analyzed to investigate the abundance and community structure of methanogens using quantitative real-time PCR (qPCR) and Denaturing gradient gel electrophoresis (DGGE) cloning of the methyl-coenzyme M reductase A (mcrA) gene. For the pairwise sites, the abundance of methanogens in S. alterniflora soils was lower than that of P. australis soils. For the chronosequence patch, the abundance and diversity of methanogens was highest in the soil subjected to two years invasion, in which we detected some rare groups including Methanocellales and Methanococcales. These results indicated a priming effect at the initial invasion stages of S. alterniflora for microorganisms in the soil, which was also supported by the diverse root exudates. The shifts of methanogen communities after S. alterniflora invasion were due to changes in pH, salinity and sulfate. The results indicate that root exudates from S. alterniflora have a priming effect on methanogens in the initial years after invasion, and the predominate methylotrophic groups (Methanosarcinales) may adapt to the availability of diverse substrates and reflects the potential for high methane production after invasion by S. alterniflora.

Chen|Xue Ping|XP|
Sun|Jing|J|
Wang|Yi|Y|
Zhang|Heng Yang|HY|
He|Chi Quan|CQ|
Liu|Xiao Yan|XY|
Bu|Nai Shun|NS|
Long|Xi-En|XE|

Spartina alterniflora
methanogens
Phragmites australis
chronosequence
methyl-coenzyme M reductase A (mcrA)
priming effect


An Electrochemical Amperometric Ethylene Sensor with Solid Polymer Electrolyte Based on Ionic Liquid.

Abstract: An electrochemical amperometric ethylene sensor with solid polymer electrolyte (SPE) and semi-planar three electrode topology involving a working, pseudoreference, and counter electrode is presented. The polymer electrolyte is based on the ionic liquid 1-butyl 3-methylimidazolium bis(trifluoromethylsulfonyl)imide [BMIM][NTf2] immobilized in a poly(vinylidene fluoride) matrix. An innovative aerosol-jet printing technique was used to deposit the gold working electrode (WE) on the solid polymer electrolyte layer to make a unique electrochemical active SPE/WE interface. The analyte, gaseous ethylene, was detected by oxidation at 800 mV vs. the platinum pseudoreference electrode. The sensor parameters such as sensitivity, response/recovery time, repeatability, hysteresis, and limits of detection and quantification were determined and their relation to the morphology and microstructure of the SPE/WE interface examined. The use of additive printing techniques for sensor preparation demonstrates the potential of polymer electrolytes with respect to the mass production of printed electrochemical gas sensors.

Kuberský|Petr|P| Navrátil|Jiří|J| Syrový|Tomáš|T|0000-0003-3943-8643 Sedlák|Petr|P|0000-0003-2454-7951 Nešpůrek|Stanislav|S| Hamáček|Aleš|A|

ethylene
solid polymer electrolyte
ionic liquid
printed electrochemical sensor


Differential gene expression in the mesocorticolimbic system of innately high- and low-impulsive rats.

Abstract: Impulsivity is an important component of many psychiatric illnesses and has been associated with a number of psychiatric disorders such as bipolar disorder and attention deficit / hyperactivity disorder (ADHD). Exploring the different aspects of impulsive behaviour and assigning these to specific neurobiological pathways would advance our interpretation of disorders for which impulsivity is key. Pharmacological studies have implicated a number of neurotransmitters in impulsivity, which in turn have been shown to be affected by several genes in both rodent and human studies of impulsivity. Here, we examine impulsivity-related differences in gene expression in finer detail, using the 2-choice serial reaction time task (2-CSRTT) to assess the molecular signature of impulsivity in brain regions previously linked to impulsive behaviour. Wistar rats were rated as high, (n = 6), intermediate, (n = 12) or low impulsive (n = 6), based on premature responses in the 2-CSRTT, after which RNA was extracted from the nucleus accumbens core (NAcc) and ventral prefrontal cortex (vPFC). RNA from the NAcc and vPFC of high and low impulsivity rats (n = 6 per group) was analysed for differential gene expression patterns and exon usage using RNA poly-A tail sequencing. Pnisr, Mal, and Tspan2 were significantly increased in the NAcc of highly impulsive rats, whereas Ube3a was significantly decreased. No differences were seen in the vPFC. In addition to changes in gene expression, Tspan2 displayed differential exon usage in impulsive rats, while functionally, gene expression changes were related to membrane depolarisation and changes in exon usage were linked to sphingolipid breakdown. The changes in gene expression and exon usage observed in this study represent an important step towards defining the molecular architecture of impulsivity. This study therefore represents an important starting point for analysis of the biological role of impulsivity in addiction and other neurological conditions associated with impulsive phenotypes.

Moloney|Gerard M|GM|
van Oeffelen|Wesley E P A|WEPA|
Ryan|Feargal J|FJ|
van de Wouw|Marcel|M|
Cowan|Caitlin|C|
Claesson|Marcus J|MJ|
Schellekens|Harriet|H|
Dinan|Timothy G|TG|
Cryan|John F|JF|

D001289:Attention Deficit Disorder with Hyperactivity

D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins

Impulsivity
Nucleus accumbens core
Ventral Prefrontal cortex
Genomics
RNA-sequencing


Moebius sequence -a multidisciplinary clinical approach.

Abstract:
BACKGROUND
Moebius Sequence (MS) is a rare disorder defined by bilateral congenital paralysis of the abducens and facial nerves in combination with various odontological, craniofacial, ophthalmological and orthopaedic conditions. The aetiology is still unknown; but both genetic (de novo mutations) and vascular events in utero are reported. The purpose of present study was through a multidisciplinary clinical approach to examine children diagnosed with Moebius-like symptoms. Ten children underwent odontological, ophthalmological, obstetric, paediatric, orthopaedic, genetic, radiological and photographical evaluation. Five patients maintained the diagnosis of MS according to the diagnostic criteria.

RESULTS
All five patients had bilateral facial and abducens paralysis confirmed by ophthalmological examination. Three of five had normal brain MR imaging. Two had missing facial nerves and one had missing abducens nerves. The Strengths and Difficulties Questionnaire (SDQ) showed normal scores in three of five patients. Interestingly, two of five children were born to mothers with uterine abnormalities (unicornuate/bicornuate uterus). In the odontological examination three of five showed enamel hypomineralisation. All five had abnormal orofacial motor function and maxillary prognathism. Two patients had adactyly, syndactyly and brachydactyly. None of the five patients had Poland anomaly, hip dislocation or dysplasia but all had a mild degree of scoliosis. We observed congenital club-feet, calcaneovalgus deformities, macrodactyly of one or more toes or curly toes. Pedobarography showed plantar pressures within normal ranges.

CONCLUSIONS
Adherence to standard diagnostic criteria is central in the diagnosis of MS. An accurate diagnosis is the basis for correct discussion of other relevant concomitant symptoms of MS, genetic testing and evaluation of prognosis. The multidisciplinary approach and adherence to diagnostic criteria taken in present study increases the knowledge on the relationship between genotype, phenotype and symptomatology of MS.

Pedersen|Line Kjeldgaard|LK|
Maimburg|Rikke Damkjær|RD|
Hertz|Jens Michael|JM|
Gjørup|Hans|H|
Pedersen|Thomas Klit|TK|
Møller-Madsen|Bjarne|B|
Østergaard|John Rosendahl|JR|

Moebius Sequence
Children
Multidisciplinary Approach
Rare Disease


Percutaneous endoscopic gastrostomy for nutritional support in dementia patients.

Abstract:
BACKGROUND
A link between aging, dementia and malnutrition is established and leads to poor prognosis. Endoscopic gastrostomy (PEG) is used without clear benefit on survival, nutritional status or quality of life.

AIMS
This work aims to assess the effectiveness of PEG-feeding for nutritional support in patients with dementia.

METHODS
We conducted an observational, longitudinal and retrospective study using records from patients with moderate-severe dementia that underwent PEG. Age, gender, dementia subtype and mortality were considered. Body mass index (BMI), serum albumin, transferrin and total cholesterol were recorded at the time of the PEG procedure (T0) and repeated after 3 months (T3). The evolution of those parameters was analysed and compared to survival.

RESULTS
We obtained data from 46 patients (16 men/30 women) between 50 and 94 years (M = 79 years). Most had Alzheimer's. Mean survival was 21 months. Mortality rate at 3 months was 15 %. At T0, 30 patients were undernourished according to BMI and 29, 31 and 16 patients displayed low albumin, transferrin and total cholesterol, respectively. Albumin (p < 0.01) and transferrin levels (p < 0.05) were significantly increased from T0 to T3. High albumin (r = 0.2), transferrin (r = 0.3) and cholesterol (r = 0.1) at T0 were positively correlated with longer survival.

CONCLUSIONS
Low albumin, transferrin and cholesterol were predictors of a poor survival. PEG improves low albumin and transferrin, serum markers of malnutrition and poor outcome. PEG should be considered on an individual basis in patients with moderate-severe dementia when risk of malnutrition and aspiration is present.

Nunes|Gonçalo|G|
Santos|Carla Adriana|CA|
Santos|Carla|C|
Fonseca|Jorge|J|


Identification of Phenolic Compounds by LC-MS/MS and Evaluation of Bioactive Properties of Two Edible Halophytes: Limonium effusum and L. sinuatum.

Abstract: This work aimed to evaluate the phenolic content and in vitro antioxidant, antimicrobial and enzyme inhibitory activities of the methanol extracts and their fractions of two edible halophytic Limonium species, L. effusum (LE) and L. sinuatum (LS). The total phenolic content resulted about two-fold higher in the ethyl acetate fraction of LE (522.82 ± 5.67 mg GAE/g extract) than in that of LS (274.87 ± 1.87 mg GAE/g extract). LC-MS/MS analysis indicated that tannic acid was the most abundant phenolic acid in both species (71,439.56 ± 3643.3 µg/g extract in LE and 105,453.5 ± 5328.1 µg/g extract in LS), whereas hyperoside was the most abundant flavonoid (14,006.90 ± 686.1 µg/g extract in LE and 1708.51 ± 83.6 µg/g extract in LS). The antioxidant capacity was evaluated by DPPH and TAC assays, and the stronger antioxidant activity in ethyl acetate fractions was highlighted. Both species were more active against Gram-positive bacteria than Gram negatives and showed considerable growth inhibitions against tested fungi. Interestingly, selective acetylcholinesterase (AChE) activity was observed with LE and LS. Particularly, the water fraction of LS strongly inhibited AChE (IC50 = 0.199 ± 0.009 µg/mL). The ethyl acetate fractions of LE and LS, as well as the n-hexane fraction of LE, exhibited significant antityrosinase activity (IC50 = 245.56 ± 3.6, 295.18 ± 10.57 and 148.27 ± 3.33 µg/mL, respectively). The ethyl acetate fraction and methanol extract of LS also significantly inhibited pancreatic lipase (IC50 = 83.76 ± 4.19 and 162.2 ± 7.29 µg/mL, respectively). Taken together, these findings warrant further investigations to assess the potential of LE and LS as a bioactive source that can be exploited in pharmaceutical, cosmetics and food industries.

phenolics
LC-MS/MS
Limonium effusum
antioxidant
antimicrobial
antityrosinase
pancreatic lipase
Limonium sinuatum
Plumbaginaceae
anticholinesterase
enzyme inhibition


Inhaled corticosteroid beliefs, complementary and alternative medicine in children presenting to the emergency department for asthma.

Abstract:
OBJECTIVE
Negative beliefs about inhaled corticosteroids (ICS) and endorsement of complementary and alternative medicine (CAM) have been associated with medication non-adherence and uncontrolled asthma. The association of CAM and negative health beliefs is not described in children in acute care settings. Our study objective is to determine the relationship between negative ICS beliefs, CAM use and poorly controlled asthma among a predominantly Latino population in an acute care setting.

METHODS
The study was conducted in the pediatric emergency department of a children's hospital. During an ED asthma encounter, validated questionnaires surveyed parents about negative ICS beliefs, CAM use, and asthma health and control. We compared asthma health reports between parents who did or did not endorse negative ICS beliefs or CAM use, by chi-squared test (or a Fisher's exact test where appropriate).

RESULTS
Parents of 174 children identified mostly as Latino with Medicaid insurance and high asthma morbidity. CAM endorsement and negative ICS beliefs were both associated with increased use of lifetime glucocorticoid (p = 0.03 and p=0.01 respectively). While CAM endorsement was associated with less hospitalizations (p = 0.04) and parental report of asthma "getting better" (p = 0.01), CAM users reported trouble with paying for rent or food (p = 0.02). Negative ICS beliefs and CAM endorsement were not associated with medication adherence.

CONCLUSIONS
Negative ICS beliefs are associated with higher number of oral glucocorticoid courses. The association between CAM endorsement and asthma control is varied, but mostly in favor of improved control. Financial difficulties may make CAM use more likely.

D007722:Health Knowledge, Attitudes, Practice

negative health beliefs
pediatric
medication adherence
asthma control


Seasonal variability of metabolic markers and oxidative balance in freshwater amphipod Hyalella kaingang (Crustacea, Amphipoda).

Abstract: Amphipods are widely used as bioindicator organisms, in view of their ease of collection and cultivation, sexual dimorphism and abundance, in aquatic environments. In the present study male (n=30) and female (n=30) amphipod Hyalella kaingang were collected during the middle of each season from a nature preserve (Research Center PRÓ-MATA) in São Francisco de Paula, Southern Brazil. Proteins, glycogen, lipids, triglycerides, glycerol, and lipid peroxidation (superoxide dismutase, catalase, and glutathione S-transferase activity) were measured. The results obtained for the markers of energy metabolism, antioxidant enzymes, and lipid peroxidation revealed a clear seasonal variation. The patterns of proteins, glycerol, and glutathione S-transferase activity did not differ between sexes; conversely, differential responses in males and females over the year were observed for all other parameters (glycogen, lipids, triglycerides, lipid peroxidation, and superoxide dismutase and catalase activity). These responses appear to be strongly influenced by a prolonged reproductive period (autumn through spring, peaking in autumn); by the degree of exploratory activity, particularly in the summer and autumn; and by abiotic factors, such as temperature and photoperiod. The responses observed in the summer and autumn (decrease in levels of proteins, glycogen and fats, and increase in lipid peroxidation levels and glutathione S-transferase activity), suggest that this season represents a critical time point for these animals. The parameters studied herein may be used as biomarkers to assess the environmental conditions in the aquatic habitat.

Braghirolli|Fernando Machado|FM|
Oliveira|Maiara Rodriguez|MR|
Oliveira|Guendalina Turcato|GT|

Amphipod
Lipid peroxidation
Antioxidant enzymes
Seasonal variation
Biomarkers
Intermediary metabolism


Microalgae-based swine wastewater treatment: Strain screening, conditions optimization, physiological activity and biomass potential.

Abstract: Using microalgae to treat swine wastewater (SW) can achieve wastewater purification and biomass recovery at the same time. The algae species suitable for growth in SW were screened in this study, and the response surface combined with the desirability function method was used for multi-objective optimization to obtain high algal biomass and pollutant removal. Chlorophyll fluorescence parameters and biomass composition were analyzed to evaluate the cell physiological activity and its application potential. Chlorella sp. HL was selected as the most suitable species for growth in SW, and after 9 d of cultivation, the maximum specific growth rate and highest algal density were achieved 0.51 d-1 and 2.43 × 107 cells/mL, respectively. In addition, the removal of total phosphate and chemical oxygen demand were reached 69.13% and 72.95%, respectively. The optimum conditions for maximum algal density and highest pollutant removal were determined as the light intensity of 58.73 μmol/m2/s, inoculation density of 5.0 × 106 cells/mL, and a light/dark ratio of 3 using response surface model, and the predicted overall desirability value was 0.96. The potential maximum quantum yield of PSII (Fv/Fm) of Chlorella sp. HL in the early stage of cultivation was 0.60-0.70, while under high light and long photoperiod, the value of Fv/Fm and performance index of Chlorella decreased, trapped and dissipated energy flux per reaction center increased. The higher heating value of 18.25 MJ/kg indicated that the Chlorella cultivated in SW could be a good feedstock for biofuel production.

Liu|Xiao-Ya|XY| Hong|Yu|Y| Zhao|Guang-Pu|GP| Zhang|Hong-Kai|HK| Zhai|Qing-Yu|QY| Wang|Qiao|Q|

Swine wastewater
Chlorophyll fluorescence parameters
Chlorella sp. HL
Box–Behnken design
Nutrient removal


Molecular and Evolutionary Determinants of Bacteriophage Host Range.

Abstract: The host range of a bacteriophage is the taxonomic diversity of hosts it can successfully infect. Host range, one of the central traits to understand in phages, is determined by a range of molecular interactions between phage and host throughout the infection cycle. While many well studied model phages seem to exhibit a narrow host range, recent ecological and metagenomics studies indicate that phages may have specificities that range from narrow to broad. There is a growing body of studies on the molecular mechanisms that enable phages to infect multiple hosts. These mechanisms, and their evolution, are of considerable importance to understanding phage ecology and the various clinical, industrial, and biotechnological applications of phage. Here we review knowledge of the molecular mechanisms that determine host range, provide a framework defining broad host range in an evolutionary context, and highlight areas for additional research.

de Jonge|Patrick A|PA|
Nobrega|Franklin L|FL|
Brouns|Stan J J|SJJ|
Dutilh|Bas E|BE|

bacteriophage
specificity
broad-host-range phages
phage therapy
virus–host interaction


Heat sensitisation in suspended moxibustion: features and clinical relevance.

Abstract: We have observed a 'heat-sensitisation' phenomenon in a large proportion of patients receiving suspended moxibustion treatment. Patients become thermally sensitised to moxibustion stimulation at certain locations on the body, indicated by sensations of strong warmth or heat penetrating into the body (heat penetration), warmth spreading around the stimulation site (heat expansion), warmth conducting in certain directions and reaching some body regions or even internal organs remote from stimulation sites (heat transmission), or other non-thermal sensations such as aching, heaviness, pressure etc. These heat-sensitised locations are not fixed, but may, during the progression of disease, dynamically change within a certain range centred on acupuncture points. Each condition seems to have its specific set of such sensitised acupuncture points and such phenomena are not commonly observed in other body regions or in healthy subjects. A number of clinical trials have shown that the appearance of heat sensitisation is correlated with better therapeutic effects in various diseases, indicating the clinical significance of such responses. Further investigation is required to elucidate the epidemiological characteristics and biological mechanisms of the heat sensitisation in suspended moxibustion.

Xie|Dingyi|D| Liu|Zhongyong|Z| Hou|Xiaoqin|X| Zhang|Bo|B| Xiong|Jun|J| Yi|Ming|M| Chen|Rixin|R|


Traffic Intensity of Patients and Physicians in the Emergency Department: A Queueing Approach for Physician Utilization.

Abstract:
BACKGROUND
The unpredictable nature of patient visits poses considerable challenges to the staffing of emergency department (ED) medical personnel. There is a lack of common physician usage parameters at present.

OBJECTIVE
The aim of this study was to quantify the ED traffic intensity of patients and physicians using a queueing model approach.

METHODS
A retrospective administrative electronic data analysis was conducted in a tertiary medical center. All patients who registered at the ED in 2013 were included. Precisely recorded patient waiting time, service time, and disposition time were obtained. An M/M/s (Markovian patient arrival, Markovian patient service, s servers) queueing model was used, while taking account of the actual physician number and number of patients managed simultaneously. Physician utilization and performance indicators were measured.

RESULTS
A total of 148,581 patients were analyzed after exclusion. The overall mean waiting time, service time, and disposition time were 0.23 (standard deviation [SD] = 0.24), 2.31 (SD = 3.89), and 2.54 (SD = 3.90) hours, respectively. Hourly physician utilization (ρ), stratified by different patient entities, was ρ = 0.75 ± 0.17 for adult non-trauma, ρ = 0.75 ± 0.28 for pediatric, and ρ = 0.53 ± 0.18 for trauma (p = 0.0004). There was a surge of utility for pediatric non-trauma patients in the late evening (ρ = 1.4 at 11 pm). The distribution of number of patients in the system was derived and compared by different patient entities and time points.

CONCLUSIONS
A queueing model was built to model traffic intensity of physicians and patients, the physician utility trend disclosed the fluctuation of manpower utility. The estimated parameters serve as important factors for developing tailored staffing policies for minimizing ED waiting and improving ED crowding.

Chaou|Chung-Hsien|CH|
Chen|Hsiu-Hsi|HH|
Tang|Petrus|P|
Yen|Amy Ming-Fang|AM|
Wu|Kuan-Han|KH|
Hsiao|Cheng-Ting|CT|
Chiu|Te-Fa|TF|

traffic intensity
emergency department
physician utilization
queueing model
waiting time
service time
staffing policy
crowding


Anti-STMN1 therapy improves sensitivity to antimicrotubule drugs in esophageal squamous cell carcinoma.

Abstract: Stathmin (STMN1) regulates microtubule dynamics by promoting depolymerization of microtubules and/or preventing polymerization of tubulin heterodimers. Several studies have shown that overexpression of STMN1 has been linked to chemoresistance of paclitaxel and vinblastine in tumor cells. This study aimed to investigate the effects of STMN1 silencing on chemosensitivities of paclitaxel or vinblastine in esophageal squamous cell carcinoma (ESCC). Immunocytochemistry and immunofluorescence assays showed that STMN1 gene was highly expressed in Eca109 and TE-1 cells. We demonstrated that lentiviral-mediated STMN1 short hairpin RNA (shRNA) specifically and efficiently downregulated STMN1 expression in Eca109 and TE-1 cells. The sensitivity of STMN1-silencing shRNA-transfected Eca109 and TE-1 cells increased 191.4- and 179.3-fold to paclitaxel, and 21.3- and 28.4-fold to vincristine, respectively. Flow cytometry and mitotic index assays showed that knockdown of STMN1 in Eca109 and TE-1 cells led to cell cycle arrest in G2/M phase. After treatment with paclitaxel or vincristine, STMN1-silencing shRNA-transfected Eca109 and TE-1 cells were more likely to enter G2 but less likely to enter mitosis than control cells. Therefore, these data suggests that silencing STMN1 gene could increase sensitivity of ESCC to paclitaxel and vincristine through G2/M phase block.

D060888:Real-Time Polymerase Chain Reaction

D023041:Xenograft Model Antitumor Assays

Antimicrotubule drugs
Esophageal squamous cell carcinoma
Stathmin
Resistance


Macronutrients, Phytochemicals, and Antioxidant Activity of Soybean Sprout Germinated with or without Light Exposure.

Abstract: This study examined the macronutrients, phytochemicals, and antioxidant activities of yellow soybean sprout (YSS) and green soybean sprout (GSS) with different germination days. YSS and GSS were obtained by sprouting soybean in darkness or with light exposure at 21 °C. Lipid, protein, carbohydrate, and ash contents were analyzed before and after soybean germination. Phytochemicals (total phenolic compounds, saponin, and isoflavone) were also determined. DPPH, ferric reducing antioxidant power (FRAP), and oxygen radical absorbance capacity (ORAC) were determined to examine the antioxidant activities of soybean sprout. Results showed YSS had a higher yield than GSS. Based on dry mass composition, 7-d germination of GSS decreased 14% protein, 37% lipid, 22% carbohydrate, and 16% ash, whereas 7-d germination of YSS decreased 6% protein and 47% lipid. Carbohydrate did not change and ash significantly increased for the 7-d germinated YSS. Lipid was greatly metabolized in germination, which explained why the protein relative percentage in dried soybean sprout was higher than that in the corresponding soybean. Total phenolic compounds and saponin (mg/g soybean sprout, dry basis) had the same accumulation trend in soybean sprout with the increases in germination days. Aglycone isoflavones (genistein, glycitein, and daidzein) and daidzin showed an increased trend, whereas malonylgenistin and malonylglycitin showed a decreased trend with germination days for both GSS and YSS. The change in other isoflavones did not show definite trends. GSS had 20% more antioxidant activities than YSS (7-d germinated soybean sprout). The increases in ORAC antioxidant activity suggest eating GSS may be more beneficial than GSS for promoting human health.

Antioxidant activity
soybean sprout
germination
light exposure
protein


Synthesis and characterization of diphenyl quinoline and bromine-activated diphenyl quinoline organic phosphors.

Abstract: A diphenyl quinoline (DPQ)-conjugated derivative and bromine-activated DPQ (Br-DPQ) were synthesized in an inert gas atmosphere at 140 °C using Friedlander condensation. The compounds showed blue emission under a UV source. The structures were characterized by X-ray diffraction and Fourier transform infrared spectroscopy. The photoluminescence properties of the compounds were analysed using excitation and emission spectra. The synthesized organic phosphors shows bright emission in the blue region, with peaks at 445 and 453 nm, respectively, for DPQ and Br-DPQ in the powder form. The physical and photoluminescence properties of these organic compounds reveal promising blue emitters for high-efficiency organic light-emitting diodes.

D017550:Spectroscopy, Fourier Transform Infrared

synthesis
DPQ
Br-DPQ
UV
FTIR
OLEDs
PL
XRD
lamp phosphor


Ecological and agriculture impacts of bakery yeast wastewater use on weed communities and crops in an arid environment.

Abstract: The goal of this study was to evaluate the impact of using yeast wastewater (YW) on weed communities. The study showed that all ecological parameters including species richness, dispersion, density, frequency, and % of vegetation cover were significantly increased in the site irrigated with YW compared to a natural rain fed site and another site irrigated with fresh water. The vegetation cover (%) was significantly increased by 2-folds in the site irrigated with YW (52%) than the one irrigated with fresh water (27%). Species richness increases to 23 in the site irrigated with yeast wastewater compared to 12 species in natural rain fed site and 7 species in areas irrigated with fresh water. The 10 studied weed species germinated better at 10 and 20% dilutions of baker's YW. However, only five species achieved few germination (3-25%) at 50% of YW and the two species Sisymbrim irio and Cardariia droba achieved (6-13%) germination using 100% YW. No germination occurred for the crop seeds (tomato, squash, lentil, and barley) at 50 and 100% YW. For tomato, 10 and 20% of YW achieved better germination (82 and 63%, respectively) than the seeds of other species, followed by barley with 80 and 53% of germination. Squash showed the lowest germination percentage with 59 and 42% at 10 and 20% of YW, respectively. Yeast wastewater seems to be crop specific and can affect weed species composition and relative abundances and care should be taken before using the effluent for irrigation of tree plantations and crops.

Abu-Dieyeh|Mohammed H|MH|
Diab|Mahmoud|M|
Al-Ghouti|Mohammad A|MA|

Agriculture
Weeds
Germination
Bakery factories
Wastewater re-use


miR-22 suppresses cell viability and EMT of ovarian cancer cells via NLRP3 and inhibits PI3K/AKT signaling pathway.

Abstract:
PURPOSE
miR-22 plays a great role in inhibiting cell growth, metastasis and enhanced cell apoptosis in several cancers. The purpose of this study was to investigate the functions of miR-22 in ovarian cancer.

METHODS
The proliferative ability was measured using CCK-8 assay. The protein expression associated with EMT and PI3K/AKT signaling biomarkers were measured by western blot. Luciferase assay applied to measure the luciferase activity. Kaplan-Meier method was performed to evaluate the overall survival rate of ovarian cancers.

RESULTS
miR-22 was low expressed and NLRP3 was overexpressed in ovarian cancer tissues and cells, and downregulation of miR-22 was associated with poor prognosis. The expression of NLRP3 had a negative correlation with miR-22 expression in ovarian cancer. miR-22 promoted cell viability and EMT through directly binding to the 3'-UTR of NLRP3 mRNA and inhibited PI3K/AKT signaling pathway. NLRP3 partially restored functions of miR-22 on cell proliferation and EMT in ovarian cancer.

CONCLUSION
miR-22 impaired cell viability and EMT by NLRP3 and inhibited PI3K/AKT signaling pathway in ovarian cancer. The newly identified miR-22/NLRP3/PI3K/AKT axis provides novel insight into the pathogenesis of ovarian cancer.

D000071199:NLR Family, Pyrin Domain-Containing 3 Protein


A benchmark of transposon insertion detection tools using real data.

Abstract:
Background
Transposable elements (TEs) are an important source of genomic variability in eukaryotic genomes. Their activity impacts genome architecture and gene expression and can lead to drastic phenotypic changes. Therefore, identifying TE polymorphisms is key to better understand the link between genotype and phenotype. However, most genotype-to-phenotype analyses have concentrated on single nucleotide polymorphisms as they are easier to reliable detect using short-read data. Many bioinformatic tools have been developed to identify transposon insertions from resequencing data using short reads. Nevertheless, the performance of most of these tools has been tested using simulated insertions, which do not accurately reproduce the complexity of natural insertions.

Results
We have overcome this limitation by building a dataset of insertions from the comparison of two high-quality rice genomes, followed by extensive manual curation. This dataset contains validated insertions of two very different types of TEs, LTR-retrotransposons and MITEs. Using this dataset, we have benchmarked the sensitivity and precision of 12 commonly used tools, and our results suggest that in general their sensitivity was previously overestimated when using simulated data. Our results also show that, increasing coverage leads to a better sensitivity but with a cost in precision. Moreover, we found important differences in tool performance, with some tools performing better on a specific type of TEs. We have also used two sets of experimentally validated insertions in Drosophila and humans and show that this trend is maintained in genomes of different size and complexity.

Conclusions
We discuss the possible choice of tools depending on the goals of the study and show that the appropriate combination of tools could be an option for most approaches, increasing the sensitivity while maintaining a good precision.

Vendrell-Mir|Pol|P|
Barteri|Fabio|F|
Merenciano|Miriam|M|
González|Josefa|J|
Casacuberta|Josep M|JM|
Castanera|Raúl|R|0000-0002-3772-7727

Benchmark
Transposon insertion
Transposable elements
Polymorphism
Resequencing


Platelets in pregnancy.

Abstract: As stated in this review, platelets functions and their important role in coagulabity in pregnancy must be well understood, not only in thrombosis related complications in pregnancy (i.e., hypertension, diabetes, thrombophilia).Clinical findings suggest that a periodical monitoring of haematological markers such as MPV and coagulation markers may be associated to Doppler velocimetry, keeping in mind also that the incidence of complications is increased in women who have heritable platelet function disorders.

Juan|Piazze|P| Stefano|Gioia|G| Antonella|Spagnuolo|S| Albana|Cerekja|C|

platelets
coagulation
high risk pregnancies


Bacteriophages Promote Metabolic Changes in Bacteria Biofilm.

Abstract: Bacterial biofilm provides bacteria with resistance and protection against conventional antimicrobial agents and the host immune system. Bacteriophages are known to move across the biofilm to make it permeable to antimicrobials. Mineral hydroxyapatite (HA) can improve the lytic activity of bacteriophages, and, together with eicosanoic acid (C20:0), can destroy the biofilm structure. Here, we demonstrate the efficacy of the combined use of phage, HA and C20:0 against Xanthomonas campestris pv campestris (Xcc) biofilm. We used nuclear magnetic resonance (NMR)-based metabolomics to investigate the molecular determinants related to the lytic action, aiming at identifying the metabolic pathways dysregulated by phage treatment. Furthermore, we identified specific markers (amino acids, lactate and galactomannan) which are involved in the control of biofilm stability. Our data show that Xccφ1, alone or in combination with HA and C20:0, interferes with the metabolic pathways involved in biofilm formation. The approach described here might be extended to other biofilm-producing bacteria.


Arrhythmogenic Substrates for Atrial Fibrillation in Obesity.

Abstract: Global obesity rates have nearly tripled since 1975. This obesity rate increase is mirrored by increases in atrial fibrillation (AF) that now impacts nearly 10% of Americans over the age of 65. Numerous epidemiologic studies have linked incidence of AF and obesity and other obesity-related diseases, including hypertension and diabetes. Due to the wealth of epidemiologic data linking AF with obesity-related disease, mechanisms of AF pathogenesis in the context of obesity are an area of ongoing investigation. However, progress has been somewhat slowed by the complex phenotype of obesity; separating the effects of obesity from those of related sequelae is problematic. While the initiation of pathogenic pathways leading to AF varies with disease (including increased glycosylation in diabetes, increased renin angiotensin aldosterone system activation in hypertension, atrial ischemia in coronary artery disease, and sleep apnea) the pathogenesis of AF is united by shared mediators of altered conduction in the atria. We suggest focusing on these downstream mediators of AF in obesity is likely to yield more broadly applicable data. In the context of obesity, AF is driven by the interrelated processes of inflammation, atrial remodeling, and oxidative stress. Obesity is characterized by a constant low-grade inflammation that leads to increased expression of pro-inflammatory cytokines. These cytokines contribute to changes in cardiomyocyte excitability. Atrial structural remodeling, including fibrosis, enlargement, and fatty infiltration is a prominent feature of AF and contributes to the altered conduction. Finally, obesity impacts oxidative stress. Within the cardiomyocyte, oxidative stress is increased through both increased production of reactive oxygen species and by downregulation of scavenging enzymes. This increased oxidative stress modulates of cardiomyocyte excitability, increasing susceptibility to AF. Although the initiating insults vary, inflammation, atrial remodeling, and oxidative stress are conserved mechanisms in the pathophysiology of AF in the obese patients. In this review, we highlight mechanisms that have been shown to be relevant in the pathogenesis of AF across obesity-related disease.

Lubbers|Ellen R|ER|
Price|Morgan V|MV|
Mohler|Peter J|PJ|

atrial fibrillation
obesity
inflammation
remodeling
oxidative stress
arrhythmia


Update on infective complications in patients treated with alemtuzumab for multiple sclerosis: review and meta-analysis of real-world and randomized studies.

Abstract:
OBJECTIVE
We aimed to systematically assess the pooled prevalence of infective complications in randomized controlled trials (RCTs) and real-world studies (RWSs) investigating alemtuzumab treatment in multiple sclerosis (MS), also looking at selected infections and their severity.

METHODS
We included in the analysis RCTs and RWSs investigating the use of alemtuzumab in MS in which infective complications were reported, as well as case reports of rare infections. We conducted a meta-analysis of proportions and a random effect model meta-regression to investigate heterogeneity.

RESULTS
The pooled prevalence of infective complications in alemtuzumab treated MS patients is 24%. The most common reported infections are respiratory tract infections (47%) and the most part of the infections are mild-to-moderate (85%). Severe infections account for 6% of the total estimate. We found first-time-reported cases of invasive aspergillosis, hepatitis E virus infection, EBV hepatitis, and cerebral toxoplasmosis. The prevalence of infections is higher in studies conducted before 2009, and in studies with higher proportion of male participants.

CONCLUSIONS
Clinicians should be aware that the prevalence of serious infections during alemtuzumab can be higher than expected from RCTs. Peculiar opportunistic infections should be considered when evaluating a patient treated with alemtuzumab who develops signs of infection.

Buonomo|Antonio Riccardo|AR|
Viceconte|Giulio|G|
Zappulo|Emanuela|E|
Maraolo|Alberto Enrico|AE|
Russo|Cinzia Valeria|CV|
Carotenuto|Antonio|A|
Moccia|Marcello|M|
Gentile|Ivan|I|

D016032:Randomized Controlled Trials as Topic

Alemtuzumab
multiple sclerosis
opportunistic infections
monoclonal antibodies


Clinical, physical, physiological, and dietary patterns of obese and sedentary adults with primary hypertension characterized by sex and cardiorespiratory fitness: EXERDIET-HTA study.

Abstract: The main purpose of this study was to determine some key physical, physiological, clinical, and nutritional markers of health status in obese and sedentary adults (54.0 ± 8.1 years, 141 men and 68 women) with primary hypertension (HTN) characterized by sex and cardiorespiratory fitness (CRF) level. The studied population showed a high cardiovascular risk (CVR) profile including metabolically abnormal obese, with poor CRF level (22.5 ± 5.6 mL·kg-1·min-1), exercise-induced HTN (Systolic Blood Pressure>210 mmHg in men and >190 mmHg in women at the end of the exercise test) and with non-healthy adherence to dietary pattern (Dietary Approaches to Stop Hypertension, 46.3%; Mediterranean Diet, 41.1%; and Healthy Diet Indicator, 37.1%). Women showed a better biochemical and dietary pattern profile than men (lower values, P < 0.05, in triglycerides, mean difference = 26.3; 95% CI = 0.9-51.7 mg/dL, aspartate transaminase, mean difference = 4.2; 95% CI = 0.3-8.0 U/L; alanine transaminase, mean difference = 8.2; 95% CI = 1.6-14.8 U/L; gamma-glutamyl transpeptidase, mean difference = 11.0; 95% CI = -1.1-23.2 U/L and higher values, P = 0.002, in high-density lipoprotein cholesterol, mean difference = 5.0, 95% CI = -13.3-3.3 mg/dL), but physical and peak exercise physiological characteristics were poorer. A higher CRF level might contribute to the attenuation of some CVR factors, such as high body mass index, non-dipping profile, and high hepatic fat. The results strongly suggest that targeting key behaviors such as improving nutritional quality and CRF via regular physical activity will contribute to improving the health with independent beneficial effects on CVR factors.

dietary pattern
Cardiorespiratory fitness
cardiovascular risk
metabolically abnormal obese
sex differences


Long non-coding RNA HOTAIR acts as a competing endogenous RNA to promote glioma progression by sponging miR-126-5p.

Abstract: LncRNA HOX transcript antisense intergenic RNA (HOTAIR) has been shown to play prominent roles in tumorigenesis. However, its precise molecular mechanism in glioma has not been completely elucidated. In this study, we found that HOTAIR was aberrantly up-regulated in glioma tissues and was negatively correlated with miR-126-5p expression. Next, we determined that HOTAIR promote glioma progression by sponging miR-126-5p. Subsequently, glutaminase (GLS) was confirmed to be a direct target of miR-126-5p using bioinformatics software and a luciferase reporter assay. Moreover, HOTAIR could modulate GLS expression by functioning as a competing endogenous RNA (ceRNA) for miR-126-5p. Taken together, our study clarified that the HOTAIR/miR-126/GLS pathway is involved in glioma progression and may potentially serve as a target for glioma therapy.

Liu|Liang|L| Cui|Sitong|S| Wan|Teng|T| Li|Xiaojian|X| Tian|Wei|W| Zhang|Rui|R| Luo|Liangsheng|L|0000-0002-6091-1944 Shi|Yan|Y|

HOTAIR
glioma
MiR-126-5p
GLS
ceRNA
glutamine metabolism


Self-reported music perception is related to quality of life and self-reported hearing abilities in cochlear implant users.

Abstract:
OBJECTIVES
To investigate the relationship between self-reported music perception and appreciation and (1) quality of life (QoL), and (2) self-assessed hearing ability in 98 post-lingually deafened cochlear implant (CI) users with a wide age range.

METHODS
Participants filled three questionnaires: (1) the Dutch Musical Background Questionnaire (DMBQ), which measures the music listening habits, the quality of the sound of music and the self-assessed perception of elements of music; (2) the Nijmegen Cochlear Implant Questionnaire (NCIQ), which measures health-related QoL; (3) the Speech, Spatial and Qualities (SSQ) of hearing scale, which measures self-assessed hearing ability. Additionally, speech perception was behaviorally measured with a phoneme-in-word identification.

RESULTS
A decline in music listening habits and a low rating of the quality of music after implantation are reported in DMBQ. A significant relationship is found between the music measures and the NCIQ and SSQ; no significant relationships are observed between the DMBQ and speech perception scores.

CONCLUSIONS
The findings suggest some relationship between CI users' self-reported music perception ability and QoL and self-reported hearing ability. While the causal relationship is not currently evaluated, the findings may imply that music training programs and/or device improvements that improve music perception may improve QoL and hearing ability.

Fuller|Christina|C| Free|Rolien|R| Maat|Bert|B| Başkent|Deniz|D|

Music perception
Self-reported hearing abilities
Cochlear implant
Speech perception


Opportunities and challenges in development of phosphoantigens as Vγ9Vδ2 T cell agonists.

Abstract: In contrast to T cells that express the more prevalent αβ T cell receptor and respond to peptide antigens, T cells that express the Vγ9Vδ2 T cell receptor detect and respond to non-peptide phosphorous-containing small molecules known as phosphoantigens. Because γδ T cells are early responders to infections and malignancies, it has been suggested that stimulation of their activity with small molecule phosphoantigen drugs may hold promise for therapeutic interventions. Recent studies have greatly advanced our knowledge of phosphoantigens as well as their cellular receptors. At the same time, clinical trials of phosphoantigens have suggested that development of these Vγ9Vδ2 T cell agonists has met unexpected challenges. In this commentary, we summarize the biology that underlies phosphoantigen activity and discuss the structural features of synthetic phosphoantigens that affect both their ability to stimulate Vγ9Vδ2 T cells and their potential as therapeutic agents.

D016692:Receptors, Antigen, T-Cell, gamma-delta

Phosphoantigen
Bisphosphonate
Gamma delta T cell
Immunotherapy
Isoprenoid
Statin


Morphological features of the yolk processing pattern in the eastern fence lizard, Sceloporus undulatus (Phrynosomatidae).

Abstract: Features of embryonic development in birds traditionally have been assumed to be shared by sauropsids in general. Herein, we document a pattern of yolk processing and cellularization in the Eastern fence lizard (Sceloporus undulatus) that is fundamentally different from that of birds. In the avian pattern, cells of the yolk sac lining phagocytose, and digest yolk material. These cells release products of digestion into underlying blood vessels for transport back to the embryo. In contrast, microscopic examination of the developing eggs of S. undulatus reveals that the yolk mass is converted into vascularized, "spaghetti-like" strands that fill the yolk sac cavity. Three successive developmental stages are involved. First, the liquid yolk is invaded by proliferating endodermal cells, which phagocytose and digest the yolk material. These cells form clumps that progressively fill the yolk sac cavity. Second, small blood vessels derived from the yolk sac vasculature invade the yolk sac cavity. Third, the endodermal cells become organized in monolayers around these vessels. This arrangement provides a means by which large numbers of endodermal cells can digest yolk, with each cell being positioned to release products of digestion into an adjacent blood vessel for transport to the embryo. The mechanism of yolk processing in this lizard species is similar to that of recently studied snakes. From its phylogenetic distribution, we infer that this pattern probably is ancestral for squamate sauropsids.

D000818:Animals
D001808:Blood Vessels
D002449:Cell Aggregation
D049109:Cell Proliferation
D004625:Embryo, Nonmammalian
D008116:Lizards
D018919:Neovascularization, Physiologic
D015017:Yolk Sac

yolk
embryonic development
yolk sac
embryo nutrition
yolk digestion


Comparison of the Properties of Natural Sorbents for the Calcium Looping Process.

Abstract: Capturing CO2 from industrial processes may be one of the main ways to control global temperature increases. One of the proposed methods is the calcium looping technology (CaL). The aim of this research was to assess the sequestration capacity of selected carbonate rocks, serpentinite, and basalt using a TGA-DSC analysis, thus simulating the CaL process. The highest degrees of conversion were obtained for limestones, lower degrees were obtained for magnesite and serpentinite, and the lowest were obtained for basalt. The decrease in the conversion rate, along with the subsequent CaL cycles, was most intense for the sorbents with the highest values. Thermally pretreated limestone samples demonstrated different degrees of conversion, which were the highest for the calcium-carbonate-rich limestones. The cumulative carbonation of the pretreated samples was more than twice as low as that of the raw ones. The thermal pretreatment was effective for the examined rocks.

natural sorbents
calcium looping
carbonate rock
TGA-DSC
CO2 capture
mineral carbonation
serpentine


Specific sorting and post-Golgi trafficking of dendritic potassium channels in living neurons.

Abstract: Proper membrane localization of ion channels is essential for the function of neuronal cells. Particularly, the computational ability of dendrites depends on the localization of different ion channels in specific subcompartments. However, the molecular mechanisms that control ion channel localization in distinct dendritic subcompartments are largely unknown. Here, we developed a quantitative live cell imaging method to analyze protein sorting and post-Golgi vesicular trafficking. We focused on two dendritic voltage-gated potassium channels that exhibit distinct localizations: Kv2.1 in proximal dendrites and Kv4.2 in distal dendrites. Our results show that Kv2.1 and Kv4.2 channels are sorted into two distinct populations of vesicles at the Golgi apparatus. The targeting of Kv2.1 and Kv4.2 vesicles occurred by distinct mechanisms as evidenced by their requirement for specific peptide motifs, cytoskeletal elements, and motor proteins. By live cell and super-resolution imaging, we identified a novel trafficking machinery important for the localization of Kv2.1 channels. Particularly, we identified non-muscle myosin II as an important factor in Kv2.1 trafficking. These findings reveal that the sorting of ion channels at the Golgi apparatus and their subsequent trafficking by unique molecular mechanisms are crucial for their specific localizations within dendrites.

Jensen|Camilla Stampe|CS|
Watanabe|Shoji|S|
Rasmussen|Hanne Borger|HB|
Schmitt|Nicole|N|
Olesen|Søren-Peter|SP|
Frost|Nicholas A|NA|
Blanpied|Thomas A|TA|
Misonou|Hiroaki|H|

Ion Channels
Protein Sorting
Golgi
Myosin
Actin
Intracellular Trafficking


Protocol for Psychosocial Interventions Based on Integrative Body-Mind-Spirit (IBMS) Model for Children with Eczema and Their Parent Caregivers.

Abstract:
PURPOSE
Eczema is a pediatric skin disease that affects the psychosocial well-being of both children and their parent caregivers. This paper outlines a protocol for an experimental study that evaluates the effectiveness of a psychosocial empowerment program for children with eczema and their parent caregivers.

METHOD
A multi-center randomized controlled trial is proposed, where parent-child dyads are randomized into two arms: an intervention group and wait-list control group. The intervention is delivered to participants in a parallel group format based on the Integrative Body-Mind-Spirit model which focuses on holistic well-being. Quality of life is measured before and after the intervention is provided, and five weeks after the intervention has been completed.

DISCUSSION
The suggested model fills a research gap in existing interventions, and provides new knowledge by evaluating the effectiveness of a tailored psychosocial intervention, delivered in group settings, for parent-child dyads affected by eczema.

psychosocial
intervention
Integrative Body-Mind-Spirit
children
Eczema
parent caregivers


Multivariate genetic analysis of plant responses to water deficit and high temperature revealed contrasting adaptive strategies.

Abstract: How genetic factors control plant performance under stressful environmental conditions is a central question in ecology and for crop breeding. A multivariate framework was developed to examine the genetic architecture of performance-related traits in response to interacting environmental stresses. Ecophysiological and life history traits were quantified in the Arabidopsis thaliana Ler × Cvi mapping population exposed to constant soil water deficit and high air temperature. The plasticity of the genetic variance-covariance matrix (G-matrix) was examined using mixed-effects models after regression into principal components. Quantitative trait locus (QTL) analysis was performed on the predictors of genotype effects and genotype by environment interactions (G × E). Three QTLs previously identified for flowering time had antagonistic G × E effects on carbon acquisition and the other traits (phenology, growth, leaf morphology, and transpiration). This resulted in a size-dependent response of water use efficiency (WUE) to high temperature but not soil water deficit, indicating that most of the plasticity of carbon acquisition and WUE to temperature is controlled by the loci that control variation of development, size, growth, and transpiration. A fourth QTL, MSAT2.22, controlled the response of carbon acquisition to specific combinations of watering and temperature irrespective of plant size and development, growth, and transpiration rate, which resulted in size-independent plasticity of WUE. These findings highlight how the strategies to optimize plant performance may differ in response to water deficit and high temperature (or their combination), and how different G × E effects could be targeted to improve plant tolerance to these stresses.

Vasseur|François|F| Bontpart|Thibaut|T| Dauzat|Myriam|M| Granier|Christine|C| Vile|Denis|D|

Arabidopsis thaliana
G-matrix
mixed-effects model
QTL
genotype by environment interactions
Antagonistic pleiotropy
photosynthesis
water use efficiency.


Superior Survival of Black Versus White Patients Following Post-Transplant Cyclophosphamide-Based Haploidentical Transplantation for Adults with Hematologic Malignancy.

Abstract: Available evidence from large registry studies has shown inferior survival for black adult patients following both unrelated donor and cord blood transplantation. Post-transplant cyclophosphamide (PTCy)-based haploidentical donor transplantation (HIDT) is being increasingly used in ethnic minorities. However, no studies of the impact of race on outcomes following HIDT have been reported. We analyzed 203 consecutive patients (123 white, 80 black) who underwent first HIDT using PTCy for hematologic malignancy at a single institution. Median recipient age was 53 (range, 19-75) years. Peripheral blood stem cells (PBSCs) were used as the stem cell source in 66% of patients, and conditioning intensity was myeloablative (MA) in 41%. After a median follow-up of 36 months, the estimated 3-year overall survival (OS), disease-free survival (DFS), and cumulative incidence of relapse (CIR) were significantly better in black patients, compared with white patients (72% [95% confidence interval (CI), 60% to 81%], 65% [95% CI, 52% to 75%], and 25% [95% CI, 16% to 35] versus 50% [95% CI, 40% to 59%], 45% [95% CI, 36% to 54%], and 39% [95% CI, 31% to 47%], respectively; P < .001 for OS and DFS, P = .015 for CIR). In contrast, 3-year nonrelapse mortality was similar between black (11%) and white (16%) patients, as were the incidences of acute graft-versus-host disease (GVHD) and moderate-to-severe chronic GVHD. Improved survival was noted in all subgroups of black patients-younger versus older, male versus female, lower versus higher disease risk index, MA versus non-MA conditioning, or PBSC versus marrow stem cell source. In multivariate analysis, black race was independently associated with better OS (hazard ratio [HR], .47; P = .003), DFS (HR, .49; P = .003), and relapse (HR, .49; P = .01). Black patients achieve superior outcomes to their white counterparts following PTCy-based HIDT due to a decreased incidence of disease relapse.

Solomon|Scott R|SR|
Zhang|Xu|X|
Holland|H Kent|HK|
Morris|Lawrence E|LE|
Solh|Melhem|M|
Bashey|Asad|A|

Haploidentical transplantation
Post-transplant cyclophosphamide
Race


Self-Reported Hearing Loss and Longitudinal Cognitive Function in a Cohort Enriched with Risk for Alzheimer's Disease.

Abstract:
BACKGROUND
Growing evidence suggests hearing loss is a risk factor for mild cognitive impairment and dementia, but few studies have examined its relationship to sub-clinical cognitive outcomes.

OBJECTIVE
To investigate the effect of self-reported hearing loss on longitudinal cognitive function in a risk-enriched cohort of clinically-unimpaired, late middle-aged adults.

METHODS
579 participants from the Wisconsin Registry for Alzheimer's Prevention (WRAP) were included. Hearing status was determined via self-reported history of diagnosed hearing loss. Each participant with self-reported hearing loss was age- and sex-matched to two participants who never reported hearing loss using nearest-neighbor matching. Linear mixed-effects models were used to examine associations between self-reported hearing loss and age-related cognitive trajectories with covariates of sex, literacy, and ethnicity, person-level random intercepts and age-related slopes. Cognitive outcomes encompassed measures of speed and flexibility, visuospatial memory, and verbal fluency.

RESULTS
Participants with self-reported hearing loss exhibited significantly poorer performance on a speed and flexibility factor score and single test of psychomotor speed and executive function, relative to participants who never reported hearing loss. There was no association between self-reported hearing loss and visuospatial memory or verbal fluency. Longitudinally, self-reported hearing loss was associated with less rapid decline in speed and flexibility and no difference in rate of decline for any other cognitive measure.

CONCLUSION
Self-reported hearing loss was associated with poorer speed and flexibility but not with accelerated decline in any domain studied, contrary to previous findings. Further studies involving behavioral auditory measures in this cohort would clarify the robustness of these findings.

Fields|Taylor N|TN|
Mueller|Kimberly D|KD|
Koscik|Rebecca L|RL|
Johnson|Sterling C|SC|
Okonkwo|Ozioma C|OC|
Litovsky|Ruth Y|RY|

hearing
hearing loss
cognition
cognitive impairment
executive function
Alzheimer’s disease
longitudinal studies


Sentinel lymph node biopsy may be unnecessary for ductal carcinoma in situ of the breast that is small and diagnosed by preoperative biopsy.

Abstract:
BACKGROUND
Current guidelines do not recommend that sentinel lymph node biopsy is routinely performed for ductal carcinoma in situ; thus, indications for sentinel lymph node biopsy in patients with ductal carcinoma in situ remain controversial. In this study, we investigated whether sentinel lymph node biopsy can be safely omitted when ductal carcinoma in situ has been diagnosed by preoperative biopsy.

METHODS
We retrospectively analysed sentinel lymph node metastasis rates and upstaging to invasive cancer in surgical specimens, performed receiver operating characteristic analysis for ductal carcinoma in situ lesion size and assessed correlations with preoperative clinicopathological factors of 277 patients with ductal carcinoma in situ diagnosed by preoperative biopsy at our institution.

RESULTS
Among 277 patients with sentinel lymph node biopsy, six (2.2%) had sentinel lymph node metastasis. All six were upstaged to invasive cancer by pathological examination of surgical specimens. In total, 69 patients (24.9%) were upstaged to invasive cancer. The mean size of ductal carcinoma in situ lesions on preoperative imaging was significantly larger for the 69 upstaged patients (50.0 mm) than for the non-upstaged patients (34.4 mm; P < 0.0001). Of the 277 patients with sentinel lymph node biopsy, 117 (42.2%) had preoperative ductal carcinoma in situ lesions <31.8 mm, which was identified as the optimal cut-off size by receiver operating characteristic analysis. Of these 117 patients, 96 (82.1%, 95% confidence interval: 73.9-88.5%) could be safely omitted from sentinel lymph node biopsy because all of them remained as ductal carcinoma in situ and had negative sentinel lymph nodes at surgery.

CONCLUSIONS
Size of ductal carcinoma in situ lesions on preoperative diagnostic imaging is a predictor of diagnosis of invasive cancer on pathological examination of surgical specimens. Sentinel lymph node biopsy may be unnecessary in ductal carcinoma in situ diagnosed by preoperative biopsy in patients with small lesions.

Uemoto|Yasuaki|Y| Kondo|Naoto|N| Wanifuchi-Endo|Yumi|Y| Asano|Tomoko|T| Hisada|Tomoka|T| Nishikawa|Sayaka|S| Katagiri|Yusuke|Y| Terada|Mitsuo|M| Kato|Akiko|A| Okuda|Katsuhiro|K| Sugiura|Hiroshi|H| Kato|Hiroyuki|H| Takahashi|Satoru|S| Toyama|Tatsuya|T|

sentinel lymph node biopsy
ductal carcinoma in situ
breast cancer
treatment


Crack Restraining Methods and their Effects on the Microstructures and Properties of Laser Cladded WC/Fe Coatings.

Abstract: Laser cladded WC/Fe coatings have the advantages of low cost and high abrasion wear resistance. However, cracks always appear in WC/Fe coatings, which limits their industrial application. In this paper, the co-effects of the re-melting process, heat treatments, and amount of Co element on the cracking susceptibility, microstructures, and mechanical properties of WC/Fe laser cladding coatings were studied. Experimental results show that re-melting process is helpful to improve the surface quality of the coating and to reduce the cracking susceptibility. The hardness of the coating decreases slightly but distributes more uniformly. Cracks in the coating can be inhibited effectively by preheating the substrate to 250 °C and maintaining the temperature during the laser cladding process, as well as applying an annealing treatment at 300 °C for 1 h. Heat treatment also results in a slight decrease in the hardness. Crack initiation cannot be restrained completely by applying the above two methods when laser cladding a big area of coating. On the basis of the above two methods, addition of Co element to the coating can further improve its toughness and decrease the crack susceptibility. Crack-free WC/Fe coating can be manufactured when 8% Co is added, and its wear resistance is much better than that of the hardened medium steel, especially when the wear time is long.

crack restraining methods
microstructures
Laser Cladding
WC/Fe coating
mechanical properties


Compression Garment Reduces Orthostatic Tachycardia and Symptoms in Patients With Postural Orthostatic Tachycardia Syndrome.

Abstract:
BACKGROUND
Postural orthostatic tachycardia syndrome (POTS) is a chronic form of orthostatic intolerance associated with a significant symptom burden. Compression garments are a frequently prescribed treatment, but the effectiveness of waist-high compression has not been evaluated in adults with POTS.

OBJECTIVES
This study evaluated compression garments as a treatment for POTS using a head-up tilt test (HUT), and a noninflatable core and lower body compression garment.

METHODS
Thirty participants completed 10-min HUT with each of 4 compression conditions in a randomized crossover design. The conditions were no compression (NONE), lower leg compression (LEG), abdominal/thigh compression (ABDO), and full abdominal/leg compression (FULL). Heart rate, beat-to-beat blood pressure, and Vanderbilt Orthostatic Symptom Score ratings were measured during each HUT.

RESULTS
The compression garment reduced heart rate (NONE: 109 ± 19 beats/min; LEG: 103 ± 16 beats/min; ABDO: 97 ± 15 beats/min; FULL: 92 ± 14 beats/min; p < 0.001) and improved symptoms (p < 0.001) during HUT in a dose-dependent manner. During HUT, stroke volume and systolic blood pressure were better maintained with FULL and ABDO compression compared with LEG and NONE compression.

CONCLUSIONS
Abdominal and lower body compression reduced heart rate and improved symptoms during HUT in adult patients with POTS. These effects were driven by improved stroke volume with compression. Abdominal compression alone might also provide a clinical benefit if full lower body compression is not well tolerated. (Hemodynamic Effects of Compression in POTS; NCT03484273).

Bourne|Kate M|KM|
Sheldon|Robert S|RS|
Hall|Juliette|J|
Lloyd|Matthew|M|
Kogut|Karolina|K|
Sheikh|Nasia|N|
Jorge|Juliana|J|
Ng|Jessica|J|
Exner|Derek V|DV|
Tyberg|John V|JV|
Raj|Satish R|SR|

D054972:Postural Orthostatic Tachycardia Syndrome

compression
POTS
orthostatic intolerance
non-pharmacological treatment


Changes in plasma bile acid profiles after partial internal biliary diversion in PFIC2 patients.

Abstract:
Background
We ask if plasma bile acid profiles can be used to monitor the effectiveness of partial internal biliary diversion (PIBD) for treating uncontrolled cholestasis in progressive familial intrahepatic cholestasis type 2 (PFIC2) patients.

Methods
Plasma bile acids were profiled in 3 cases of ATP-binding cassette, sub-family B member 11 (ABCB11)-mutated PFIC2 children before and after PIBD compared to healthy controls and 8 PFIC2 patients. The quantitation of bile acids was performed by reversed-phase ultrahigh-performance liquid chromatography/multiple-reaction monitoring-mass spectrometry (UPLC/MRM-MS) with negative ion detection.

Results
Before PIBD, all three patients presented with >50-fold higher levels of total plasma bile acids, 2-7 folds higher ratios of taurine: glycine conjugated primary bile acids, and unchanged secondary bile acids levels compared to healthy controls. After PIBD, only one of the three patients (P3) showed relief of cholestasis. The bile acid profiles of the two nonresponding patients showed little change while that of the responding patient showed a 5-fold reduction in total plasma primary bile acids, a reduced taurine: glycine conjugate ratio, and an unexpected 26- and 12-fold increase in secondary bile acids DCA and LCA respectively. One year later, the responder suffered a recurrence of cholestasis, and the bile acid profile shifted back to a more pre-PIBD-like profile.

Conclusions
Plasma bile acid profiles may potentially be useful as sensitive biomarkers for monitoring the clinical course of PIBD patients. Relief of cholestasis after PIBD appears to be associated with significantly increased circulating toxic secondary bile acids and this may limit the utility of PIBD in PFIC2 patients in the long run.

Liu|Teng|T|
Wang|Ren-Xue|RX|
Han|Jun|J|
Qiu|Yi-Ling|YL|
Borchers|Christoph H|CH|
Ling|Victor|V|
Wang|Jian-She|JS|

Biliary diversion
bile salt export pump (BSEP)
jaundice
liquid chromatography-mass spectrometry


Wood frog adaptations to overwintering in Alaska: new limits to freezing tolerance.

Abstract: We investigated the ecological physiology and behavior of free-living wood frogs [Lithobates (Rana) sylvaticus] overwintering in Interior Alaska by tracking animals into natural hibernacula, recording microclimate, and determining frog survival in spring. We measured cryoprotectant (glucose) concentrations and identified the presence of antifreeze glycolipids in tissues from subsamples of naturally freezing frogs. We also recorded the behavior of wood frogs preparing to freeze in artificial hibernacula, and tissue glucose concentrations in captive wood frogs frozen in the laboratory to -2.5°C. Wood frogs in natural hibernacula remained frozen for 193 ± 11 consecutive days and experienced average (October-May) temperatures of -6.3°C and average minimum temperatures of -14.6 ± 2.8°C (range -8.9 to -18.1°C) with 100% survival (N=18). Mean glucose concentrations were 13-fold higher in muscle, 10-fold higher in heart and 3.3-fold higher in liver in naturally freezing compared with laboratory frozen frogs. Antifreeze glycolipid was present in extracts from muscle and internal organs, but not skin, of frozen frogs. Wood frogs in Interior Alaska survive freezing to extreme limits and durations compared with those described in animals collected in southern Canada or the Midwestern United States. We hypothesize that this enhancement of freeze tolerance in Alaskan wood frogs is due to higher cryoprotectant levels that are produced by repeated freezing and thawing cycles experienced under natural conditions during early autumn.

Larson|Don J|DJ|
Middle|Luke|L|
Vu|Henry|H|
Zhang|Wenhui|W|
Serianni|Anthony S|AS|
Duman|John|J|
Barnes|Brian M|BM|

Wood frog
Freeze tolerance
Cryoprotectant
Antifreeze glycolipid


Robot training for hand motor recovery in subacute stroke patients: A randomized controlled trial.

Abstract:
BACKGROUND
Evidence of superiority of robot training for the hand over classical therapies in stroke patients remains controversial. During the subacute stage, hand training is likely to be the most useful.

AIM
To establish whether robot active assisted therapies provides any additional motor recovery for the hand when administered during the subacute stage (<4 months from event) in a Mexican adult population diagnosed with stroke.

HYPOTHESIS
Compared to classical occupational therapy, robot based therapies for hand recovery will show significant differences at subacute stages.

TRIAL DESIGN
A randomized clinical trial.

METHODS
A between subjects randomized controlled trial was carried out on subacute stroke patients (n = 17) comparing robot active assisted therapy (RT) with a classical occupational therapy (OT). Both groups received 40 sessions ensuring at least 300 repetitions per session. Treatment duration was (mean ± std) 2.18 ± 1.25 months for the control group and 2.44 ± 0.88 months for the study group. The primary outcome was motor dexterity changes assessed with the Fugl-Meyer (FMA) and the Motricity Index (MI).

RESULTS
Both groups (OT: n = 8; RT: n = 9) exhibited significant improvements over time (Non-parametric Cliff's delta-within effect sizes: dwOT-FMA = 0.5, dwOT-MI = 0.5, dwRT-FMA = 1, dwRT-MI = 1). Regarding differences between the therapies; the Fugl-Meyer score indicated a significant advantage for the hand training with the robot (FMA hand: WRS: W = 8, p <0.01), whilst the Motricity index suggested a greater improvement (size effect) in hand prehension for RT with respect to OT but failed to reach significance (MI prehension: W = 17.5, p = 0.080). No harm occurred.

CONCLUSIONS
Robotic therapies may be useful during the subacute stages of stroke - both endpoints (FM hand and MI prehension) showed the expected trend with bigger effect size for the robotic intervention. Additional benefit of the robotic therapy over the control therapy was only significant when the difference was measured with FM, demanding further investigation with larger samples. Implications of this study are important for decision making during therapy administration and resource allocation.

Orihuela-Espina|Felipe|F|
Roldán|Giovana Femat|GF|
Sánchez-Villavicencio|Israel|I|
Palafox|Lorena|L|
Leder|Ronald|R|
Sucar|Luis Enrique|LE|
Hernández-Franco|Jorge|J|

Subacute
Stroke
Motor training
Robotic rehabilitation


Morphologic and functional abnormalities in patients with Ebstein's anomaly with cardiac magnetic resonance imaging: Correlation with tricuspid regurgitation.

Abstract:
PURPOSE
The aim of this study was to assess the correlations of functional and dimensional parameters with the severity of tricuspid regurgitation in patients with Ebstein's anomaly (EA) by using cardiac magnetic resonance (CMR) imaging.

MATERIALS AND METHODS
Thirty-three patients with EA without previous cardiac surgery and 25 normal individuals were recruited and underwent both cardiac MR imaging and preoperative transthoracic echocardiography. The left ventricular (LV) functional parameters and dimensions of the right ventricle (RV) and LV were measured using 3.0-T cardiac MR imaging. Tricuspid regurgitation severity grading was estimated by echocardiography. The functional and dimensional parameters were compared between EA patients and controls using independent sample t-tests. Spearman's rank correlation was used to determine the correlations between the functional and dimensional parameters and tricuspid regurgitation. Receiver operating characteristic (ROC) analysis was used to predict tricuspid regurgitation severity using individual functional and dimensional parameters.

RESULTS
Statistical analysis revealed significant differences in the functional and dimensional parameters between EA patients and controls. Within the EA group, tricuspid valve regurgitation negatively correlated well with the left ventricular ejection fraction (LVEF) (r=-0.558, p=0.001). The ratio of the right ventricular (functional right ventricle) end-diastolic dimension to the left ventricle end-diastolic dimension (RVEDD/LVEDD) in EA patients also correlated well with the severity of tricuspid valve regurgitation (r=0.492, p=0.004). Moreover, ROC analysis revealed that high sensitivity and specificity were obtained for predicting the severity of tricuspid valve regurgitation with LVEF (78.3%, 90.0%) and RVEDD/LVEDD (78.3%, 94.3%).

CONCLUSION
In EA patients, the left and right ventricular functional and dimensional parameters from MRI correlated well with tricuspid regurgitation, which helped predict the severity of EA.

Liu|Xi|X| Zhang|Qin|Q| Yang|Zhi-Gang|ZG| Guo|Ying-Kun|YK| Shi|Ke|K| Xu|Hua-Yan|HY| Wen|Ling-Yi|LY| Li|Rui|R| Chen|Jing|J|

Cardiac magnetic resonance
Tricuspid regurgitation
LVEF
Ebstein’s anomaly


Inhibiting effect of Radix Hedysari Polysaccharide (HPS) on endotoxin-induced uveitis in rats.

Abstract:
PURPOSE
The aim of this study is to investigate the anti-inflammatory effect of Radix Hedysari Polysaccharide (HPS) on clinical indicators, the expression of Toll-like receptor-4 (TLR4) and its downstream transduction molecules during endotoxin-induced uveitis in rats.

METHODS
EIU was induced through the intraperitoneal injection of male Wistar rats with lipopolysaccharide (LPS 200 μg). HPS (400mg/kg), DXM (1mg/kg) or an equivalent volume of normal saline was injected intraperitoneally 1h before the LPS induction. The clinical manifestation was observed and scored at 2-h intervals using a slit microscope. The degree of inflammatory reaction was determined by routine histological examinations, and the expression of TLR4 and MyD88 in the iris-ciliary body complex was detected through a double-labeled immunofluorescence study. Real-time RT-PCR was used to assess the effects of HPS on the expression of the TLR4 complex, MyD88 and NF-κB p65 mRNA. The protein expression levels of TLR4, MyD88 and NF-κB p65 were examined by western blot.

RESULTS
HPS treatment produced similar therapeutic results with dexamethasone by significantly reducing the clinical severity of EIU as well as fibrin exudations and inflammatory cell infiltration in the eye. Correspondingly, according to the immunofluorescence results, HPS treatment significantly suppressed the expression of TLR4 and MyD88 in the iris-ciliary body complex. HPS treatment could also remarkably reduce the mRNA and protein expression of the TLR4 complex, MyD88 and NF-κB p65.

CONCLUSION
HPS can suppress the intraocular inflammation observed in EIU by inhibiting TLR4 and its downstream signal transduction pathway.

Yu|Shuo|S| Zhang|Wei|W| Yu|Jinyi|J| Feng|Shilan|S| Guo|Tiankang|T| Lu|Hong|H|

D053594:Myeloid Differentiation Factor 88

Radix Hedysari Polysaccharide
Endotoxin-induced uveitis
Anti-inflammatory
TLR-4


Early impact of the DREAMS partnership on young women's knowledge of their HIV status: causal analysis of population-based surveys in Kenya and South Africa.

Abstract:
BACKGROUND
Knowledge of one's HIV status is the gateway to treatment and prevention, but remains low among young people. We investigated the early impact (2016-2017) of Determined, Resilient, Empowered, AIDS-free, Mentored and Safe (DREAMS), a multisectoral HIV prevention package, on knowledge of HIV status among adolescent girls and young women (AGYW).

METHODS
In 2017, randomly selected AGYW were enrolled into surveys, N=1081 aged 15-22 years in Nairobi slum settlements, and N=2174 aged 13-22 years in rural KwaZulu-Natal. We estimated the causal effect of being a DREAMS beneficiary on knowledge of HIV status (those who self-reported as HIV-positive or tested HIV-negative in the past year), accounting for an AGYW's propensity to be a DREAMS beneficiary.

RESULTS
In Nairobi, knowledge of HIV status was higher among DREAMS beneficiaries compared with non-beneficiaries (92% vs 69%, adjusted OR=8.7; 95% CI 5.8 to 12.9), with DREAMS predicted to increase the outcome by 28%, from 65% if none were a DREAMS beneficiary to 93% if all were beneficiaries. The increase attributable to DREAMS was larger among younger participants: 32% and 23% among those aged 15-17 and 18-22 years, respectively. In KwaZulu-Natal, knowledge of status was higher among DREAMS beneficiaries aged 13-17 years (37% vs 26% among non-beneficiaries), with a 9% difference due to DREAMS (95% CI 4.8% to 14.4%), and no evidence of effect among 18-22 years (-2.8%; 95% CI -11.1% to 5.7%).

CONCLUSION
DREAMS substantially increased knowledge of HIV status among AGYW in Nairobi, and among younger but not older AGYW in KwaZulu-Natal. Adolescent girls can be reached early (before age 18) with community-based HIV testing programmes in diverse high-prevalence settings, with a large impact on the proportion who know their HIV status.

HIV
adolescent
epidemiology
inequalities
sexual health


An upper bound computational model for investigation of fusion effects on adjacent segment biomechanics of the lumbar spine.

Abstract: Prediction of the biomechanical effects of fusion surgery on adjacent segments is a challenge in computational biomechanics of the spine. In this study, a two-segment L3-L4-L5 computational model was developed to simulate the effects of spinal fusion on adjacent segment biomechanical responses under a follower load condition. The interaction between the degenerative segment (L4-5) and the adjacent segment (L3-4) was simulated using an equivalent follower spring. The spring stiffness was calibrated using a rigid fusion of a completely degenerated disc model at the L4-5 level, resulting in an upper bound response at the adjacent (L3-4) segment. The obtained upper bound equivalent follower spring was used to simulate the upper bound biomechanical responses of fusion of the disc with different degeneration grades. It was predicted that as the disc degeneration grade at the degenerative segment decreased, the effect on the adjacent segment responses decreased accordingly after fusion. The data indicated that the upper bound computational model can be a useful computational tool for evaluation of the interaction between segments and for investigation of the biomechanical mechanisms of adjacent segment degeneration after fusion.

D001696:Biomechanical Phenomena
D003198:Computer Simulation
D020342:Finite Element Analysis
D006801:Humans
D008159:Lumbar Vertebrae
D013123:Spinal Fusion
D013314:Stress, Mechanical

Upper bound
Lumbar spine
Spinal fusion
Disc degeneration
Adjacent segment responses
Finite element analysis


Computational modeling and simulation of genital tubercle development.

Abstract: Hypospadias is a developmental defect of urethral tube closure that has a complex etiology involving genetic and environmental factors, including anti-androgenic and estrogenic disrupting chemicals; however, little is known about the morphoregulatory consequences of androgen/estrogen balance during genital tubercle (GT) development. Computer models that predictively model sexual dimorphism of the GT may provide a useful resource to translate chemical-target bipartite networks and their developmental consequences across the human-relevant chemical universe. Here, we describe a multicellular agent-based model of genital tubercle (GT) development that simulates urethrogenesis from the sexually-indifferent urethral plate stage to urethral tube closure. The prototype model, constructed in CompuCell3D, recapitulates key aspects of GT morphogenesis controlled by SHH, FGF10, and androgen pathways through modulation of stochastic cell behaviors, including differential adhesion, motility, proliferation, and apoptosis. Proper urethral tube closure in the model was shown to depend quantitatively on SHH- and FGF10-induced effects on mesenchymal proliferation and epithelial apoptosis-both ultimately linked to androgen signaling. In the absence of androgen, GT development was feminized and with partial androgen deficiency, the model resolved with incomplete urethral tube closure, thereby providing an in silico platform for probabilistic prediction of hypospadias risk across combinations of minor perturbations to the GT system at various stages of embryonic development.

Leung|Maxwell C K|MC|
Hutson|M Shane|MS|
Seifert|Ashley W|AW|
Spencer|Richard M|RM|
Knudsen|Thomas B|TB|

Genital tubercle
Hypospadias
Agent-based model
Computational toxicology