Type I Interferon Production of Plasmacytoid Dendritic Cells under Control.

Abstract: One of the most powerful and multifaceted cytokines produced by immune cells are type I interferons (IFNs), the basal secretion of which contributes to the maintenance of immune homeostasis, while their activation-induced production is essential to effective immune responses. Although, each cell is capable of producing type I IFNs, plasmacytoid dendritic cells (pDCs) possess a unique ability to rapidly produce large amounts of them. Importantly, type I IFNs have a prominent role in the pathomechanism of various pDC-associated diseases. Deficiency in type I IFN production increases the risk of more severe viral infections and the development of certain allergic reactions, and supports tumor resistance; nevertheless, its overproduction promotes autoimmune reactions. Therefore, the tight regulation of type I IFN responses of pDCs is essential to maintain an adequate level of immune response without causing adverse effects. Here, our goal was to summarize those endogenous factors that can influence the type I IFN responses of pDCs, and thus might serve as possible therapeutic targets in pDC-associated diseases. Furthermore, we briefly discuss the current therapeutic approaches targeting the pDC-type I IFN axis in viral infections, cancer, autoimmunity, and allergy, together with their limitations defined by the Janus-faced nature of pDC-derived type I IFNs.

type I interferon
plasmacytoid dendritic cells
viral infection
autoimmunity
regulation
cancer
allergy
IFN gene signature
antiviral response
therapy


A longitudinal study of pre- and post-weaning tail damage in non-docked pigs.

Abstract: Tail-biting occurs pre-weaning, but literature on tail damage during lactation and on the development of damage over time is sparse, especially for non-docked piglets. We assessed the prevalence of tail damage in non-docked piglets in a commercial Danish piggery during the lactation and weaning period, and investigated the within-animal association of tail lesions pre- and post-weaning. Non-docked piglets (n = 741) from 51 loose-housed sows were individually marked and tracked from birth to 9 weeks (w9) of age. Tail damage was scored during lactation at w1 and w4, and once a week post-weaning (average weaning age 30 days) at w6 to w9. The within-animal association of tail damage before and after weaning was investigated at pig level using generalized mixed models. Tail damage was prevalent already pre-weaning. During the lactation period, the prevalence of tail lesions was 5% at w1 and 42% at w4, with the most prevalent score being 'superficial damages' (66.7%, score 1; pre-weaning scheme: 0 = no damage, 3 = tail wound). Post-weaning, 45% of pigs had a tail lesion at least once over the four assessments, with 16.7% of pigs having a tail lesion at least at two assessments. The majority of lesions were 'minor scratches' (34.2%, score 1; post-weaning scheme: 0 = no damage, 4 = wound - necrotic tail end) and a 'scabbed wound' (19.9%, score 3). The number of pigs with lesions as well as wound severity increased over time. More pigs had a tail wound at w8 (15%, P < 0.001 and < 0.01) and w9 (19%, P < 0.001 and < 0.001) compared to w6 (2.7%) and w7 (5.6%). Pigs with tail lesions pre-weaning (w1: OR 3.0, 95% CI 0.9 to 10.2; w4: OR 3.4, 95% CI 2.0 to 5.8) had a significantly higher risk of having a wound post-weaning, and pigs with lesions at w4 additionally were at a higher risk (OR 3.0, 95% CI 1.8 to 5.1) of having a lesion over several assessments. Females compared to castrated males had a significantly lower risk of having tail lesions at w1 (OR 0.3, 95% CI 0.1 to 0.8). Similarly, females were at a significantly lower risk (OR 0.5, 95% CI 0.4 to 0.9) of having a wound post-weaning, and tended to have a lower risk of having lesions over several assessments (OR 0.7, 95% CI 0.5 to 1.2). Our study confirmed that tail damage is prevalent already during the lactation period, and that pre-weaning tail damage is predictive of tail wounds post-weaning.

piglets
tail lesion
early life
intact tails
tail-biting behaviour


Gaze-holding and anti-GAD antibody: prototypic heterogeneous motor dysfunction in immune disease.

Abstract: The variability in motor dysfunction is not uncommon in autoimmune disorders. Antibody-mediated system-wide malfunction or effects on the neural network shared by two independent pathophysiological processes can cause such heterogeneity. We tested this prediction for motor dysfunction during gaze holding in 11 patients with increased titers of glutamic acid decarboxylase (anti-GAD) antibody. High-resolution oculography measured horizontal and vertical eye positions. The analysis was performed with customized signal processing algorithms. Downbeat and gaze-evoked nystagmus commonly coexisted; one patient had a combination of upbeat and gaze-evoked nystagmus. The nystagmus was associated with saccadic intrusions in 10 patients; all had squarewaves, but five also had saccadic oscillations. The nystagmus and saccadic intrusions, both in the same axis of eye rotations, were not uncommon. Tandem appearance of the episodes of nystagmus and saccadic intrusions suggested a coupling between the two abnormalities. We speculated a unifying framework where the anti-GAD antibody inhibited (GAD mediated) conversion of glutamate to gamma-aminobutyric acid (GABA). Paucity GABA and excess of glutamate cause nystagmus (less GABA) and high-frequency saccadic oscillations (excessive glutamate).

Nystagmus Saccades Cerebellum Integrator Opsoclonus


Positively-charged polyethersulfone nanofibrous membranes for bacteria and anionic dyes removal.

Abstract: Given the complexity of pollutants in wastewater, development of facile and effective multifunctional materials, which can not only kill bacteria but also remove dyes from wastewater, is in high demand. Herein, a facile strategy for the preparation of positively-charged nanofibrous membranes (NFMs) is reported via the combination of electrospinning and in-situ cross-linked polymerization of poly ([2-(methacryloyloxy)-ethyl] trimethyl ammonium chloride) (PMETAC) in poly (ether sulfone) (PES) solution. The quaternary ammonium salt polymer of PMETAC enabled the NFMs with positive charge to kill bacteria and remove anionic dyes. The antibacterial tests including agar plate counting and live/dead staining indicate that the NFMs show strong antibacterial ability with bacterial killing ratios of nearly 99% for both Escherichia coli and Staphylococcus aureus, as well as remarkable recyclability towards killing bacteria. The dyes adsorption experiments show that the NFMs exhibit high adsorption capacity for anionic dyes up to 208 mg g-1 for Congo Red (CR) and good reusability toward CR. Impressively, the membrane adsorption column test indicates that the CR dye removal ratio is up to 100% for the first time, and that is still as high as 96.5% for the third time with a fresh dye solution. Given the above advantages, such fascinating NFMs may provide new perspectives in the exploitation of multifunctional membrane materials for complex water remediation.

Lv|Chunyan|C| Chen|Shengqiu|S| Xie|Yi|Y| Wei|Zhiwei|Z| Chen|Lei|L| Bao|Jianxu|J| He|Chao|C| Zhao|Weifeng|W| Sun|Shudong|S| Zhao|Changsheng|C|

Nanofibrous membrane
Anionic dyes
Quaternary ammonium salt
Positive charge
Antibacterial activity


Sex-specific epigenetic alterations of the hypothalamic Agrp-Pomc system do not explain 'diabesity' in the offspring of high-fat diet (HFD) overfed maternal rats.

Abstract: Maternal high-fat diet (HFD) overfeeding pre- and during pregnancy and lactation may 'program' a 'diabesity' predisposition in the offspring, for inconclusive reasons. Acquired alterations of the hypothalamic promoter methylation and mRNA expression of the satiety neurohormone Pomc are possibly of critical importance here. We investigated within one developmental approach, including male and female rats, the sex-specific DNA methylation pattern and corresponding mRNA expression of both Pomc and its endogenous functional antagonist Agrp in the hypothalamus of adult HFD offspring. Obesity and diabetic disturbances occurred in both male and female HFD offspring, accompanied by altered Pomc promoter methylation pattern. However, this was not related to significant Pomc mRNA expression alterations. In contrast, male-specific alterations of Agrp promoter methylation were found, even associated with reduced mRNA expression of this orexigenic/anabolic Pomc antagonist. In conclusion, acquired epigenetic alterations of the hypothalamic Agrp-Pomc system hardly explain the 'diabesity' phenotype in HFD offspring, while distinct vulnerability and functionality of Agrp promoter and related genomic regions methylation should be further investigated.

Schellong|Karen|K|
Melchior|Kerstin|K|
Ziska|Thomas|T|
Henrich|Wolfgang|W|
Rancourt|Rebecca C|RC|
Plagemann|Andreas|A|

D039382:Maternal Nutritional Physiological Phenomena

D011297:Prenatal Exposure Delayed Effects

Epigenetics
Maternal high-fat diet
Hypothalamic arcuate nucleus
Neuropeptide expression
Nutritional programming
Offspring ‘diabesity’


Vocal tract shaping of emotional speech.

Abstract: Emotional speech production has been previously studied using fleshpoint tracking data in speaker-specific experiment setups. The present study introduces a real-time magnetic resonance imaging database of emotional speech production from 10 speakers and presents articulatory analysis results of speech emotional expression using the database. Midsagittal vocal tract parameters (midsagittal distances and the vocal tract length) were parameterized based on a two-dimensional grid-line system, using image segmentation software. The principal feature analysis technique was applied to the grid-line system in order to find the major movement locations. Results reveal both speaker-dependent and speaker-independent variation patterns. For example, sad speech, a low arousal emotion, tends to show smaller opening for low vowels in the front cavity than the high arousal emotions more consistently than the other regions of the vocal tract. Happiness shows significantly shorter vocal tract length than anger and sadness in most speakers. Further details of speaker-dependent and speaker-independent speech articulation variation in emotional expression and their implications are described.

Kim|Jangwon|J|
Toutios|Asterios|A|
Lee|Sungbok|S|
Narayanan|Shrikanth S|SS|

vocal tract shaping
emotional speech production
MR image segmentation
USC-EMO-MRI corpus


An index-based robust decision making framework for watershed management in a changing climate.

Abstract: This study developed an index-based robust decision making framework for watershed management dealing with water quantity and quality issues in a changing climate. It consists of two parts of management alternative development and analysis. The first part for alternative development consists of six steps: 1) to understand the watershed components and process using HSPF model, 2) to identify the spatial vulnerability ranking using two indices: potential streamflow depletion (PSD) and potential water quality deterioration (PWQD), 3) to quantify the residents' preferences on water management demands and calculate the watershed evaluation index which is the weighted combinations of PSD and PWQD, 4) to set the quantitative targets for water quantity and quality, 5) to develop a list of feasible alternatives and 6) to eliminate the unacceptable alternatives. The second part for alternative analysis has three steps: 7) to analyze all selected alternatives with a hydrologic simulation model considering various climate change scenarios, 8) to quantify the alternative evaluation index including social and hydrologic criteria with utilizing multi-criteria decision analysis methods and 9) to prioritize all options based on a minimax regret strategy for robust decision. This framework considers the uncertainty inherent in climate models and climate change scenarios with utilizing the minimax regret strategy, a decision making strategy under deep uncertainty and thus this procedure derives the robust prioritization based on the multiple utilities of alternatives from various scenarios. In this study, the proposed procedure was applied to the Korean urban watershed, which has suffered from streamflow depletion and water quality deterioration. Our application shows that the framework provides a useful watershed management tool for incorporating quantitative and qualitative information into the evaluation of various policies with regard to water resource planning and management.

D003247:Conservation of Natural Resources

Index-based robust decision making
Watershed management
Climate change
Multi-criteria decision analysis


Circulating tumor DNA for malignant peripheral nerve sheath tumors in neurofibromatosis type 1.

Abstract: The leading cause of early death in patients with neurofibromatosis type 1 (NF1) is malignant peripheral nerve sheath tumor (MPNST). The principles of management include early diagnosis, surgical clearance and close monitoring for tumor recurrence. Current methods for diagnosis, detection of residual disease and monitoring tumor burden are inadequate, as clinical and radiological features are non-specific for malignancy in patients with multiple tumors and lack the sensitivity to identify early evidence of malignant transformation or tumor recurrence. Circulating tumor DNA (ctDNA) is a promising tool in cancer management and has the potential to improve the care of patients with NF1. In the following article we summarise the current understanding of the genomic landscape of MPNST, report on the previous literature of ctDNA in MPNST and outline the potential clinical applications for ctDNA in NF1 associated MPNST. Finally, we describe our prospective cohort study protocol investigating the utility of using ctDNA as an early diagnostic tool for MPNSTs in NF1 patients.

Circulating tumor DNA
Malignant peripheral nerve sheath tumor
Neurofibromatosis type 1
Biomarkers
Liquid biopsy


COVID-19-associated acute transverse myelitis: a rare entity.

Abstract: SARS-CoV-2 has wreaked havoc globally and has claimed innumerable lives all over the world. Apart from the characteristic respiratory illness, this disease has been associated with florid extrapulmonary manifestations and complications. A 59-year-old female healthcare worker presented with features of acute-onset non-compressive myelopathy with a sensory level at T10 segment along with high-grade fever for 4 days. MRI of dorsal spine was suggestive of myelitis at T7 vertebral level. She was initiated on injectable steroids and did show some initial signs of recovery. A day later, she developed an acute-onset respiratory failure but could not be revived despite our best efforts. Her nasopharyngeal and oropharyngeal swab turned out to be positive for SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR). We hereby report a case of acute transverse myelitis with COVID-19 as a probable aetiology.


Physical interaction between neurofibromin and serotonin 5-HT6 receptor promotes receptor constitutive activity.

Abstract: Active G protein-coupled receptor (GPCR) conformations not only are promoted by agonists but also occur in their absence, leading to constitutive activity. Association of GPCRs with intracellular protein partners might be one of the mechanisms underlying GPCR constitutive activity. Here, we show that serotonin 5 hydroxytryptamine 6 (5-HT6) receptor constitutively activates the Gs/adenylyl cyclase pathway in various cell types, including neurons. Constitutive activity is strongly reduced by silencing expression of the Ras-GTPase activating protein (Ras-GAP) neurofibromin, a 5-HT6 receptor partner. Neurofibromin is a multidomain protein encoded by the NF1 gene, the mutation of which causes Neurofibromatosis type 1 (NF1), a genetic disorder characterized by multiple benign and malignant nervous system tumors and cognitive deficits. Disrupting association of 5-HT6 receptor with neurofibromin Pleckstrin Homology (PH) domain also inhibits receptor constitutive activity, and PH domain expression rescues 5-HT6 receptor-operated cAMP signaling in neurofibromin-deficient cells. Furthermore, PH domains carrying mutations identified in NF1 patients that prevent interaction with the 5-HT6 receptor fail to rescue receptor constitutive activity in neurofibromin-depleted cells. Further supporting a role of neurofibromin in agonist-independent Gs signaling elicited by native receptors, the phosphorylation of cAMP-responsive element-binding protein (CREB) is strongly decreased in prefrontal cortex of Nf1+/- mice compared with WT mice. Moreover, systemic administration of a 5-HT6 receptor inverse agonist reduces CREB phosphorylation in prefrontal cortex of WT mice but not Nf1+/- mice. Collectively, these findings suggest that disrupting 5-HT6 receptor-neurofibromin interaction prevents agonist-independent 5-HT6 receptor-operated cAMP signaling in prefrontal cortex, an effect that might underlie neuronal abnormalities in NF1 patients.

Deraredj Nadim|Wissem|W|
Chaumont-Dubel|Séverine|S|
Madouri|Fahima|F|
Cobret|Laetitia|L|
De Tauzia|Marie-Ludivine|ML|
Zajdel|Pawel|P|
Bénédetti|Hélène|H|
Marin|Philippe|P|
Morisset-Lopez|Séverine|S|

neurofibromin
5-HT6 receptor
constitutive activity
G protein-coupled receptor
neurofibromatosis type 1


[(18-Crown-6)K][Fe(1)Cl(1)4 ]0.5 [Fe(2)Cl(2)4 ]0.5 : A Multifunctional Molecular Switch of Dielectric, Conductivity and Magnetic Properties.

Abstract: Multifunctional materials that exhibit different physical properties in a single phase have potential for use in multifunctional devices. Herein, we reported an organic-inorganic hybrid compound [(18-crown-6)K][Fe(1)Cl(1)4 ]0.5 [Fe(2)Cl(2)4 ]0.5 (1) by incorporating KCl and FeCl3 into a 18-crown-6 molecule, which acts as a host of the six O atoms providing a lone pair of electrons to anchor the guest potassium cation, and [FeCl4 ]- as a counterion for charge balance to construct a complex salt. This salt exhibited a one-step reversible structural transformation giving two separate high and low temperature phases at 373 K, which was confirmed by systematic characterizations including differential scanning calorimetry (DSC) measurements, variable-temperature structural analyses, and dielectric, impedance, variable-temperature magnetic susceptibility measurements. Interestingly, the structural transformation was coupled to both hysteretic dielectric phase transition, conductivity switch and magnetic-phase transition at 373 K. This result gives an idea for designing a new type of phase-transition materials harboring technologically important magnetic, conductivity and dielectric properties.

crystal engineering
heterometallic complexes
organic-inorganic hybrid composites
structure-phase transition
supramolecular chemistry


Nitrogen Containing Bisphosphonates Impair the Release of Bone Homeostasis Mediators and Matrix Production by Human Primary Pre-Osteoblasts.

Abstract: Bisphosphonates (BPs) represent the first-line treatment for a wide array of bone disorders. Despite their well-known action on osteoclasts, the effects they induce on osteoblasts are still unclear. In order to shed light on this aspect we evaluated the impact of two nitrogen containing bisphosphonates, Alendronate (ALN) and Zoledronate (ZOL), on human primary pre-osteoblasts. At first, we showed an inhibitory effect on cell viability and alkaline phosphatase activity starting from µM concentrations of both drugs. In addition, an inhibitory trend on mineralized nodules deposition was observed. Then low doses of both ALN and ZOL rapidly increased the release of the pro-inflammatory mediators TNFα and IL-1β, while increased DKK-1 and Sclerostin, both inhibitors of osteoblastogenesis. Finally, ALN and 10-7M ZOL decreased the expression of type I Collagen and Osteopontin, while both drugs slightly stimulated SPARC production. With these results, we would like to suggest a direct inhibitory action on bone-forming cells by nitrogen containing bisphosphonates.

Giannasi|Chiara|C|
Niada|Stefania|S|
Farronato|Davide|D|
Lombardi|Giovanni|G|
Manfredi|Barbara|B|
Farronato|Giampietro|G|
Brini|Anna Teresa|AT|

D050071:Bone Density Conservation Agents

bisphosphonates
human primary pre-osteoblasts
bone formation


Aquaporins facilitate hydrogen peroxide entry into guard cells to mediate ABA- and pathogen-triggered stomatal closure.

Abstract: Stomatal movements are crucial for the control of plant water status and protection against pathogens. Assays on epidermal peels revealed that, similar to abscisic acid (ABA), pathogen-associated molecular pattern (PAMP) flg22 requires the AtPIP2;1 aquaporin to induce stomatal closure. Flg22 also induced an increase in osmotic water permeability (Pf) of guard cell protoplasts through activation of AtPIP2;1. The use of HyPer, a genetic probe for intracellular hydrogen peroxide (H2O2), revealed that both ABA and flg22 triggered an accumulation of H2O2 in wild-type but not pip2;1 guard cells. Pretreatment of guard cells with flg22 or ABA facilitated the influx of exogenous H2O2 Brassinosteroid insensitive 1-associated receptor kinase 1 (BAK1) and open stomata 1 (OST1)/Snf1-related protein kinase 2.6 (SnRK2.6) were both necessary to flg22-induced Pf and both phosphorylated AtPIP2;1 on Ser121 in vitro. Accumulation of H2O2 and stomatal closure as induced by flg22 was restored in pip2;1 guard cells by a phosphomimetic form (Ser121Asp) but not by a phosphodeficient form (Ser121Ala) of AtPIP2;1. We propose a mechanism whereby phosphorylation of AtPIP2;1 Ser121 by BAK1 and/or OST1 is triggered in response to flg22 to activate its water and H2O2 transport activities. This work establishes a signaling role of plasma membrane aquaporins in guard cells and potentially in other cellular context involving H2O2 signaling.

D000069452:Pathogen-Associated Molecular Pattern Molecules

aquaporin
hydrogen peroxide
stomatal movement
pathogen
guard cell signaling


Bone plates for osteosynthesis - a systematic review of test methods and parameters for biomechanical testing.

Abstract: Bone plates for osteosynthesis are subject to biomechanical testing for safety and regulatory purposes. International standards applicable for those devices are designed for bone plates used in the surgical fixation of the skeletal system but not necessarily for all device variants available. We intend to summarize the test methods and parameters presented in the literature to evaluate bone plates in a clinical environment, especially for modern anatomically shaped implants. We conducted a systematic review on published biomechanical studies for lower and upper extremities (clavicle, humerus, ulna, radius, metacarpal, femur, tibia, fibula, metatarsal). The search process led to the identification of 159 relevant articles containing 330 individual tests, which were analyzed concerning various test criteria including test methods and parameters per bone segment for static and dynamic loading tests, as well as number of cycles, chosen bone model and outcome variables. The biomechanical literature for bone plates is diverse, inconsistent and heterogeneous. Test methods are not commonly applied per bone plate location and test parameters are not uniformly specified and displayed. They vary in particular for bending and torsion tests as well as for the number of loading cycles for dynamic testing. Outcome variables are not commonly applied nor defined. Consequently this paper is the first in a planned chronological series of three to identify the need (this publication), to develop a systematic procedural approach (2. publication) and to apply the process exemplary on a bone plate sample (3. publication).

Schorler|Hendrik|H| Capanni|Felix|F| Gaashan|Muneer|M| Wendlandt|Robert|R| Jürgens|Christian|C| Schulz|Arndt-Peter|AP|

D001696:Biomechanical Phenomena
D001860:Bone Plates
D005593:Fracture Fixation, Internal
D006801:Humans
D008422:Materials Testing

upper extremity
lower extremity
quality assurance
regulatory compliance
state of the art
surgical implant


Rural-Urban Disparities in Pancreatic Cancer Stage of Diagnosis: Understanding the Interaction With Medically Underserved Areas.

Abstract:
PURPOSE
To estimate differences in pancreatic cancer diagnosis stage by rurality of patient residence and residence in a medically underserved area (MUA).

METHODS
Using 2010-2016 Pennsylvania Cancer Registry data, we restrict our analysis to adults diagnosed with pancreatic cancer. We categorize each patient's residence by Rural-Urban Continuum Codes (RUCC): (1) metro; (2) nonmetro adjacent with population ≥20,000; (3) nonmetro adjacent with population <20,000; (4) nonmetro nonadjacent, and (5) completely rural; also by whether the county was a full MUA, partial MUA, or non-MUA. We examine the percent of patients diagnosed with local and locoregional stage of disease for each residential rurality and MUA status grouping. We estimate multivariate linear probability models of local and locoregional stage of diagnosis while controlling for demographics, insurance type, year, rurality, and MUA status. Finally, we estimate models interacting rurality with MUA status to disentangle the relative impact of each on diagnostic stage.

FINDINGS
We find that no pancreatic patients living in completely rural areas were diagnosed at the local stage, the lowest of all categories of rurality. In adjusted models, we find that patients living in completely rural areas have significantly lower rates of local and local/regional stage of diagnosis. The estimates are attenuated slightly when controlling for MUA.

CONCLUSIONS
We find significantly lower rates of early stage pancreatic cancer diagnosis for patients living in completely rural areas. While lack of primary medical care resources is an important factor, rural residence remains an important independent predictor in later stage of diagnosis.

Segel|Joel E|JE|0000-0001-8937-0531
Hollenbeak|Christopher S|CS|
Gusani|Niraj J|NJ|0000-0002-7695-5108

D006801:Humans
D008507:Medically Underserved Area
D010190:Pancreatic Neoplasms
D012042:Registries
D012424:Rural Population
D014505:Urban Population

rural-urban disparities
pancreatic cancer
cancer stage
medically underserved areas
access to care


Sex and Employment-Setting Differences in Work-Family Conflict in Athletic Training.

Abstract:
CONTEXT
Work-family conflict (WFC) has received much attention in athletic training, yet several factors related to this phenomenon have not been examined, specifically a practitioner's sex, occupational setting, willingness to leave the profession, and willingness to use work-leave benefits.

OBJECTIVE
To examine how sex and occupational differences in athletic training affect WFC and to examine willingness to leave the profession and use work-leave benefits.

DESIGN
Cross-sectional study.

SETTING
Multiple occupational settings, including clinic/outreach, education, collegiate, industrial, professional sports, secondary school, and sales.

PATIENTS OR OTHER PARTICIPANTS
A total of 246 athletic trainers (ATs) (men = 110, women = 136) participated. Of these, 61.4% (n = 151) were between 20 and 39 years old.

MAIN OUTCOME MEASURES(S)
Participants responded to a previously validated and reliable WFC instrument. We created and validated a 3-item instrument that assessed willingness to use work-leave benefits, which demonstrated good internal consistency (Cronbach α = 0.88), as well as a single question about willingness to leave the profession.

RESULTS
The mean (± SD) WFC score was 16.88 ± 4.4 (range = 5 [least amount of conflict] to 25 [highest amount of conflict]). Men scored 17.01 ± 4.5, and women scored 16.76 ± 4.36, indicating above-average WFC. We observed no difference between men and women based on conflict scores (t244 = 0.492, P = .95) or their willingness to leave the profession (t244 = -1.27, P = .21). We noted differences among ATs in different practice settings (F8,245 = 5.015, P <.001); those in collegiate and secondary school settings had higher reported WFC scores. A negative relationship existed between WFC score and comfort using work-leave benefits (2-tailed r = -0.533, P < .001). Comfort with using work-leave benefits was different among practice settings (F8,245 = 3.01, P = .003).

CONCLUSIONS
The ATs employed in traditional practice settings reported higher levels of WFC. Male and female ATs had comparable experiences of WFC and willingness to leave the profession.

Mazerolle|Stephanie M|SM|
Eason|Christianne M|CM|
Pitney|William A|WA|
Mueller|Megan N|MN|

work-leave benefits
attrition
retention
work-life balance


Screening of Anti-Biofilm Compounds from Marine-Derived Fungi and the Effects of Secalonic Acid D on Staphylococcus aureus Biofilm.

Abstract: Biofilm formation of Staphylococcus aureus is one of its mechanisms of drug resistance. Antibiofilm screening of 106 compounds from marine-derived fungi displayed that 12 compounds inhibited S. aureus biofilm formation by >50% at the concentration of 100 μg/ml, and only secalonic acid D (SAD) and B inhibited by >90% at 6.25 μg/ml without inhibiting cell growth after 24-h incubation. Meanwhile, it was found that the double bond between C-1 and C-10 of citrinin derivatives and the C-C connection position of two chromone monomers may be important for their anti-biofilm activities. Moreover, SAD slightly facilitated biofilm eradication and influenced its architecture. Furthermore, SAD slowed the cell growth rate in the preceding 18-h incubation and differentially regulated transcriptional expression of several genes, such as agr, isaA, icaA, and icaD, associated with biofilm formation in planktonic and biofilm cells, which may be the reason for the anti-biofilm activity of SAD. Finally, SAD acted synergistically against S. aureus growth and biofilm formation with other antibiotics. These findings indicated that various natural products from marine-derived fungi, such as SAD, could be used as a potential biofilm inhibitor against S. aureus.

Wang|Jie|J| Nong|Xu-Hua|XH| Zhang|Xiao-Yong|XY| Xu|Xin-Ya|XY| Amin|Muhammad|M| Qi|Shu-Hua|SH|

D015964:Gene Expression Regulation, Bacterial

secalonic acid D
Staphylococcus aureus
Anti-biofilm activity
marine natural product
mechanism of action


Significant bone microarchitecture impairment in premenopausal women with active celiac disease.

Abstract: Patients with active celiac disease (CD) are more likely to have osteoporosis and increased risk of fractures. High-resolution peripheral quantitative computed tomography (HR-pQCT) permits three-dimensional exploration of bone microarchitectural characteristics measuring separately cortical and trabecular compartments, and giving a more profound insight into bone disease pathophysiology and fracture. We aimed to determine the volumetric and microarchitectural characteristics of peripheral bones-distal radius and tibia-in an adult premenopausal cohort with active CD assessed at diagnosis. We prospectively enrolled 31 consecutive premenopausal women with newly diagnosed CD (median age 29 years, range: 18-49) and 22 healthy women of similar age (median age 30 years, range 21-41) and body mass index. Compared with controls, peripheral bones of CD patients were significantly lower in terms of total volumetric density mg/cm(3) (mean ± SD: 274.7 ± 51.7 vs. 324.7 ± 45.8, p 0.0006 at the radius; 264.4 ± 48.7 vs. 307 ± 40.7, p 0.002 at the tibia), trabecular density mg/cm(3) (118.6 ± 31.5 vs. 161.9 ± 33.6, p<0.0001 at the radius; 127.9 ± 28.7 vs. 157.6 ± 15.6, p < 0.0001 at the tibia); bone volume/trabecular volume ratio % (9.9 ± 2.6 vs. 13.5 ± 2.8, p<0.0001 at the radius; 10.6 ± 2.4 vs. 13.1 ± 1.3, p < 0.0001 at the tibia); number of trabeculae 1/mm (1.69 ± 0.27 vs. 1.89 ± 0.26, p 0.009 at the radius; 1.53 ± 0.32 vs. 1.80 ± 0.26, p 0.002 at the tibia); and trabecular thickness mm (0.058 ± 0.010 vs. 0.071 ± 0.008, p < 0.0001 at the radius with no significant difference at the tibia). Cortical density was significantly lower in both regions (D comp mg/cm(3) 860 ± 57.2 vs. 893.9 ± 43, p 0.02; 902.7 ± 48.7 vs. 932.6 ± 32.6, p 0.01 in radius and tibia respectively). Although cortical thickness was lower in CD patients, it failed to show any significant inter-group difference (a-8% decay with p 0.11 in both bones). Patients with symptomatic CD (n = 22) had a greater bone microarchitectural deficit than those with subclinical CD. HR-pQCT was used to successfully identify significant deterioration in the microarchitecture of trabecular and cortical compartments of peripheral bones. Impairment was characterized by lower trabecular number and thickness-which increased trabecular network heterogeneity-and lower cortical density and thickness. In the prospective follow-up of this group of patients we expect to be able to assess whether bone microarchitecture recovers and to what extend after gluten-free diet.

Zanchetta|María Belén|MB|
Costa|Florencia|F|
Longobardi|Vanesa|V|
Longarini|Gabriela|G|
Mazure|Roberto Martín|RM|
Moreno|María Laura|ML|
Vázquez|Horacio|H|
Silveira|Fernando|F|
Niveloni|Sonia|S|
Smecuol|Edgardo|E|
Temprano|María de la Paz|Mde L|
Hwang|Hui Jer|HJ|
González|Andrea|A|
Mauriño|Eduardo César|EC|
Bogado|Cesar|C|
Zanchetta|Jose R|JR|
Bai|Julio César|JC|

Bone microarchitecture
Celiac disease
Osteoporosis
Fractures
HRp-QCT


Postmortem computed tomography and magnetic resonance imaging facilitates forensic autopsy in a fatal case of poisoning with formic acid, diphenhydramine, and ethanol.

Abstract: A case of fatal poisoning by ingesting formic acid, diphenhydramine, and ethanol by a 25-year-old woman who committed suicide is presented. Prior to autopsy, postmortem computed tomography and postmortem magnetic resonance tomography were performed and revealed severe damage to the stomach, the left thoracic wall, and parts of the liver. Imaging detected acid-induced fluid-fluid level within the thoracic cavity (fat-equivalent fluid and necrotic pleural effusion). This case report illustrates that postmortem cross-sectional imaging may facilitate dissection of severely damaged or complex regions, and may provide additional information compared to autopsy and toxicological examinations alone.

Berger|Florian|F|
Steuer|Andrea E|AE|
Rentsch|Katharina|K|
Gascho|Dominic|D|
Stamou|Stamatios|S|
Schärli|Sarah|S|
Thali|Michael J|MJ|
Krämer|Thomas|T|
Flach|Patricia M|PM|

D002492:Central Nervous System Depressants

Postmortem magnetic resonance tomography


A call for transformation: Exit, Voice, Loyalty and Neglect (EVLN) in response to workplace incivility.

Abstract:
BACKGROUND
Interrelations between incivility and its precursors or consequences, as well as the role of these interrelations in employees' reactions to incivility are still poorly understood.

OBJECTIVE
The purpose of the present study was to assess different reactions to workplace incivility while identifying specific and individual-based appraisals and emotions associated with these reactions.

METHOD
A qualitative research approach using semi-structured in-depth interviews, with a sample of 42 employees in a beverage manufacturing corporation in Israel to capture employees' voices regarding their incivility experiences.

RESULTS
Analysis of the interviews indicated four reaction-categories: (1) Exit; (2) Voice; (3) Loyalty; and (4) Neglect, in line with the theoretical EVLN model for describing reactions to stressful conditions. In particular, the interviews revealed a dynamic reaction process and suggested that intentionality of reaction provides a third, new dimension. Additionally, an underlying emotional process rooted in appraisals and aroused emotions was evident in each of the reactions.

CONCLUSIONS
Organizations that wish to reduce incivility events may wish to examine the emotions of targets of incivility, explore the underlying appraisals associated with these emotions, and be mindful of the dynamic and highly individual reaction processes involved.

appraisals
Mistreatment
exit/voice/loyalty/neglect model
work-related stress
workplace emotions


1,25-Dihydroxyvitamin D3 attenuates disease severity and induces synoviocyte apoptosis in a concentration-dependent manner in rats with adjuvant-induced arthritis by inactivating the NF-κB signaling pathway.

Abstract: An aggressive proliferation of synoviocytes is the hallmark of rheumatoid arthritis (RA). Emerging evidence shows that inhibiting the NF-κB signaling pathway with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] may be a therapeutic approach for controlling inflammatory diseases. In this study, we demonstrated the protective effects of three different 1,25(OH)2D3 concentration on adjuvant-induced arthritis (AA) rats through the NF-κB signaling pathway and their pro-apoptotic roles in cultured adjuvant-induced arthritis synoviocytes (AIASs). AA rats were prepared by injecting complete Freund's adjuvant and independently given daily intraperitoneal injection of 1,25(OH)2D3 at concentrations of 50, 100, and 300 ng/day/kg. Subsequently, AIASs were isolated from the inflamed joints of AA rats to test the effects of 1,25(OH)2D3 on AIASs in vitro. Intraperitoneal injection of 1,25-(OH)2D3 was found to induce a concentration- and time-dependent improvement in relieving the symptoms of AA. We found an increased paw withdrawal thermal latency (PWTL) in the affected paw of AA rats as the concentration of 1,25-(OH)2D3 increased. 1,25-(OH)2D3 treatment reduced levels of inflammatory factors in synovial tissues of AA rats. In the case of cultured AIASs, 1,25-(OH)2D3 was shown to inhibit cell proliferation and induce cell apoptosis in a concentration-dependent manner. Additionally, 1,25-(OH)2D3 inhibited the activation of the NF-κB signaling pathway. In conclusion, our study provides evidence emphasizing that 1,25(OH)2D3 has the potential to attenuate disease severity in RA potentially due to its contributory role in synoviocyte proliferation and apoptosis. The protective role of 1,25(OH)2D3 against RA depends on the NF-κB signaling pathway.

Sun|Hua-Qiang|HQ| Yan|Dong|D| Wang|Qin-Nan|QN| Meng|Hong-Zheng|HZ| Zhang|Ye-Yong|YY| Yin|Lu-Xu|LX| Yan|Xin-Feng|XF| Li|Shu-Feng|SF|

Synoviocyte
Adjuvant-induced arthritis
NF-κB signaling pathway
Rheumatoid arthritis
1,25(OH)2D3


Do we see how they perceive risk? An integrated analysis of risk perception and its effect on workplace safety behavior.

Abstract: While risk perception is a key factor influencing safety behavior, the academia lacks specific attention to the ways that workers perceive risk, and thus little is known about the mechanisms through which different risk perceptions influence safety behavior. Most previous research in the workplace safety domain argues that people tend to perceive risk based on rational formulations of risk criticality. However, individuals' emotions can be also useful in understanding their perceptions. Therefore, this research employs an integrated analysis concerning the rational and emotional perspectives. Specifically, it was expected that the identified three rational ways of perceiving risk, i.e., perceived probability, severity, and negative utility, would influence the direct emotional risk perception. Furthermore, these four risk perceptions were all expected to positively but differently influence safety behavior. The hypotheses were tested using a sample of 120 construction workers. It was found that all the three rational risk perceptions significantly influenced workers' direct perception of risk that is mainly based on emotions. Furthermore, safety behavior among workers relied mainly on emotional perception but not rational calculations of risk. This research contributes to workplace safety research by highlighting the importance of integrating the emotional assessment of risk, especially when workers' risk perception and behavior are concerned. Suggested avenues for improving safety behavior through improvement in risk perception include being aware of the possibility of different ways of perceiving risk, promoting experience sharing and accident simulation, and uncovering risk information.

Xia|Nini|N|
Wang|Xueqing|X|
Griffin|Mark A|MA|
Wu|Chunlin|C|
Liu|Bingsheng|B|

Risk perception
Safety behavior
Construction industry
Rational risk assessment


Influence of exercise on the structure of the anterior chamber of the eye.

Abstract:
PURPOSE
To measure changes in anterior chamber structure before and after exercise in healthy individuals using anterior segment optical coherence tomography (ASOCT).

METHODS
Thirty-two healthy young individuals performed jogging for 20 min. Eye blinking rate was recorded during rest and exercise. The anterior chamber angle (ACA), angle opening distance at 500 μm from the scleral spur (AOD500), trabecular-iris space area at 500 μm from the scleral spur (TISA500), iris concavity (IC), iris concavity ratio (CR), iris thickness at 750 μm from the scleral spur (IT750), anterior chamber depth (ACD), anterior chamber width (ACW), pupil diameter (PD), intraocular pressure (IOP), blood pressure (BP) and heart rate (HR) were recorded before and after exercise. Anterior chamber angle (ACA), AOD500, TISA500, IC, IT750, ACD, ACW and PD were measured with ASOCT.

RESULTS
Compared with rest, the blinking rate during exercise did not change significantly (13.04 ± 5.80 versus 13.52 ± 5.87 blinks/min, p = 0.645). The average IOP (15.4 ± 2.4 versus 12.4 ± 2.1 mmHg), ACA (35.96 ± 11.35 versus 40.25 ± 12.64 degrees), AOD500 (0.800 ± 0.348 versus 0.942 ± 0.387 mm), TISA500 (0.308 ± 0.155 versus 0.374 ± 0.193 mm2 ), IC (-0.078 ± 0.148 versus -0.153 ± 0.159 mm) and CR (-0.027 ± 0.050 versus -0.054 ± 0.056) changed significantly (all p < 0.001), while the average IT750 (0.463 ± 0.084 versus 0.465 ± 0.086 mm; p = 0.492), ACD (3.171 ± 0.229 versus 3.175 ± 0.238 mm; p = 0.543) and ACW (11.768 ± 0.377 versus 11.755 ± 0.378 mm; p = 0.122) showed no significant change after exercise.

CONCLUSION
The blinking rate did not change significantly during exercise, while ACA, AOD500 and TISA500 increased after exercise. Exercise also induced or increased IC. These changes in anterior chamber structure were only associated with exercise, but not with the postexercise change in PD or IOP.

exercise
anterior chamber structure
iris concavity
reverse pupillary block


Implications of Pubertal Timing for Romantic Relationship Quality Among Heterosexual and Sexual Minority Young Adults.

Abstract:
PURPOSE
Relative to on-time or late-maturing peers, girls who begin puberty early typically begin romantic and sexual experiences earlier; however, advanced pubertal status does not necessarily coincide with commensurate interpersonal skills necessary for healthy romantic relationships. Research is limited on the long-term implications of early puberty for relationship quality, and virtually nothing is known about the social implications of early timing for sexual minority females.

METHODS
Using linear regression, we examine longitudinal associations between two measures of girls' pubertal timing (self-perceived timing and menarcheal age) and romantic relationship quality in young adulthood, stratified by sexual orientation, among 5,568 females in waves I and IV of the National Longitudinal Study of Adolescent to Adult Health. We also examine whether identified associations are mediated by parent-adolescent relationship quality.

RESULTS
Among sexual minorities, early self-perceived pubertal timing was associated with lower adult romantic relationship quality compared with on-time maturers (β = -2.32; standard error = 1.44; p = .05); this association was mediated by parent-adolescent relationship quality. Among heterosexuals, girls experiencing menarche before age 12 (early maturers) reported lower adult relationship quality compared to on-time maturers (β = -.43; standard error = .22; p = .03); parent-adolescent relationship quality did not mediate this association.

CONCLUSIONS
Early maturation is associated with lower romantic relationship quality in young adulthood. However, evidence of the association varies by measure of pubertal timing, and the processes by which pubertal timing is linked to later relationship quality may be different for sexual minority and heterosexual females. Potential explanations and public health implications are discussed.

Reese|Bianka M|BM|
Trinh|Sarah L|SL|
Halpern|Carolyn T|CT|

Pubertal timing
Relationship quality
Sexual minorities
Longitudinal
Menarche
Parental relationship quality


Effect of Electrode Waterproof Coating on Quality of Underwater Wet Welded Joints.

Abstract: In this paper, the effects of different hydrophobic coatings on the surface of covered electrodes on the quality of wet welded carbon steel joints were discussed. Commonly available hydrophobic substances used in industrial applications were selected for the research. The aim of using waterproof coatings was to check the possibility to decreasing the susceptibility of high-strength low-alloy S460N steel to cold cracking. During experiments diffusible hydrogen content in deposited metal determination by mercury method, metallographic macro- and microscopic testing and hardness measurements were performed. Investigations showed that waterproof coatings laid on covered electrodes can improve the quality of wet welded joints, by decreasing the Vickers HV10 hardness in heat-affected zone and decreasing the diffusible hydrogen content in deposited metal, which minimalize possibility of cold cracking.

wet welding
hydrophobic coatings
covered electrode
cold cracking
diffusible hydrogen
underwater welding


Effects of phytate and minerals on the bioavailability of oxalate from food.

Abstract: Phytate and mineral cations are both considered as important dietary factors for inhibiting the crystallisation of calcium oxalate kidney stones in susceptible individuals. In this paper, the phytate and mineral composition of whole bran cereals (wheat, barley and oat) and legumes were determined together with their soluble and insoluble oxalate concentrations in order to investigate the effects on oxalate solubility. The oat bran sample had the highest soluble oxalate concentration at 79±1.3 mg/100 g, while total and soluble oxalate concentrations in the food samples studied range from 33 to 199 mg/100 g and 14 to 79 mg/100 g, respectively. The phytate concentration was in the range from 227 to 4393 mg/100 g and the concentrations of cations were in the range 54-70 mg/100 g for calcium, 75-398 mg/100 g for magnesium, 244-1529 mg/100 g for potassium and 4-11 mg/100 g for iron. Soluble oxalate concentration did not increase in proportion to total oxalate, and the phytate concentration in all foods was sufficient to contribute to an increase in soluble oxalate concentration by binding calcium.

Israr|Beenish|B|
Frazier|Richard A|RA|
Gordon|Michael H|MH|

Minerals
Bioavailability
Calcium
Oxalate and phytate


Multidisciplinary diagnostic approach combining fine needle aspiration, core needle biopsy and imaging features of a presacral myelolipoma in a patient with concurrent breast cancer.

Abstract: Myelolipomas are uncommon benign tumors composed of mature adipose tissue mixed with hematopoietic elements; these tumors can occur in both the adrenal glands and extra-adrenal locations, the presacral region being the most frequent extra-adrenal site. We present a case of presacral myelolipoma diagnosed by fine needle aspiration (FNA) and core needle biopsy (CNB) in a 55-year-old woman with concurrent invasive ductal breast cancer. TC and RM imaging were consistent with the diagnosis of presacral myelolipoma. The lesion was discovered incidentally during the staging procedure for breast malignancy. The purpose of our work is to describe the FNA and CNB finding in combination with the imaging features of this uncommon lesion.

Varone|Valeria|V| Ciancia|Giuseppe|G| Bracale|Umberto|U| Merola|Giovanni|G| Vetrani|Antonio|A| Pettinato|Guido|G| Cozzolino|Immacolata|I|

Imaging features
FNA
CNB
Extradrenal myelolipoma


Friendly help for clinical use of maternal hemodynamics.

Abstract:
OBJECTIVES
Maternal hemodynamics plays a major role during pregnancy and its evaluation is fundamental to understand obstetric conditions. The modern opinion about maternal hemodynamics assessment is to shift focus from single hemodynamic parameters to the whole hemodynamic profile. Our aim is to create a simple, intuitive, and easily understandable graphing technique to evaluate the main hemodynamic parameters.

METHODS
We enrolled 531 pregnant women without maternal or fetal disease. One hundred and forty five in the first trimester of pregnancy, 258 in the second one and 128 in the third one. We performed hemodynamic assessment with ultrasonic cardiac output monitor method. We selected the six main parameters: cardiac output, systemic vascular resistance, heart rate, potential-to-kinetic energy ratio, inotropy index, and stroke volume variation. We chose the radar chart to display the multivariate data of the hemodynamic measurement of the patient in evaluation.

RESULTS
We have obtained mean and deviation standard values for the six main hemodynamic parameters in every trimester. They deeply change during the pregnancy, so it is correct to compare a new hemodynamic measurement with the mean values for the specific trimester in order to evaluate any possible alterations. In fact, once a new hemodynamic assessment is performed, we calculate the Z-score in order to fix the positions of the six measured parameters in their specific axis of radar chart.

CONCLUSIONS
At the end of a hemodynamic exam, the physician can input the data in the program obtaining a graphic representation. Using this technique, which simultaneously evaluates six hemodynamic parameters, it is possible to easily understand the patient's hemodynamic status. By converting the parameters values in Z-score, it is easier to understand when hemodynamics is altered, even if the physician does not have any experience in maternal hemodynamics.

maternal hemodynamics
Cardiac output
systemic vascular resistance
radar chart


Effects of offset values for artificial teeth positions in CAD/CAM complete denture.

Abstract: Recently, computer-aided design/computer-aided manufacturing (CAD/CAM) technology has been applied to the field of removable complete denture prosthodontics. We developed a system for fabricating complete dentures applying CAD/CAM technology. In this system, artificial teeth were bonded to the recesses of a milled denture base. However, the offset values needed for the recesses are not known. The purpose of the present study was to evaluate the accuracy of bonded artificial teeth positions in 0.00 (control), 0.10, 0.15, 0.20, and 0.25mm offset recess groups. Four types of artificial teeth, upper left central incisor (UL1), upper left canine (UL3), upper left first premolar (UL4), and upper left first molar (UL6), were used. Each type of artificial tooth was arranged at regular intervals on the denture base model with the CAD software. These data were defined as the master data. The artificial teeth parts were subtracted from the denture base model by Boolean logic operations in order to make recesses, and the recesses were then offset in five values. Based on these denture base data, prepolymerized resin blocks were milled (n=3). After bonding artificial teeth on the milled denture base model, a cone beam computed tomography (CBCT) scan was performed to obtain scanned data. Deviations between the master data and the scanned data were calculated. Based on the results, the optimal offset values were found to be 0.15-0.25mm for UL1, 0.15 and 0.25mm for UL3, 0.25mm for UL4, and 0.10-0.25mm for UL6.

Yamamoto|Shinta|S| Kanazawa|Manabu|M| Iwaki|Maiko|M| Jokanovic|Ana|A| Minakuchi|Shunsuke|S|

D017076:Computer-Aided Design
D003824:Denture, Complete
D006801:Humans
D000090822:Ribosomal Protein L3
D014093:Tooth, Artificial

Offset
Artificial teeth
Complete denture
Accuracy
Measurement


Psychosexual Characteristics of Women Reporting Sexual Aggression Against Men.

Abstract: Sexual aggression as committed by women has been the target of little empirical research and is still regarded as a myth by many people. The aim of this study was to evaluate the psychosexual profile of young and educated women reporting sexual aggression against men. This is a cross-sectional study; a total of 260 female college students answered to an online survey. Among them, 93 (35.8%) reported having committed some form of sexual aggression against men: 46.2% of sexually aggressive women fell into the category of sexual coercion, 34.1% fell into the category of sexual abuse, and 19.8% reported having used physical force. Findings revealed that sexually aggressive women reported significantly higher levels of sociosexuality, sexual fantasies of dominance and submission, sexual compulsivity, sexual excitation, and sexual inhibition due to the threat of sexual performance failure. Data are expected to affect prevention strategies for a relevant yet understudied social concern.

sexual aggression
females
college students
sexual functioning


The mechanism of Lactobacillus strains for their ability to remove fumonisins B1 and B2.

Abstract: Two Lactobacillus strains, L. plantarum B7 and L. pentosus X8, exhibited high efficiency in removing fumonisins (FB1 and FB2) from aqueous medium. 52.9% FB1 and 85.2% FB2 were bound by L. plantarum B7, and 58.0% FB1 and 86.5% FB2 by L. pentosus X8, respectively. Temperature, incubation time, and pH affected the binding ability of two strains. Cell viability was not necessary for the binding ability. The various components of cell wall were determined for their ability to absorb FBS. The results revealed that the intact peptidoglycans exhibited the greatest capacity in binding FBs. Especially the better structural integrity of the peptidoglycans the more FBs was bound. Thus, the absorption of two bacterial cells to FBs is proposed to be a physical process, and peptidoglycans should be the main binding site. Additionally, Caco-2 cell lines were used to evaluate the ability of the two strains to reduce the damage of FBs in vitro. Caco-2 cell's death was reduced after the cell lines were subjected to both viable and non-viable L. pentosus X8, respectively. The two Lactobacillus strains might be used as a biological detoxification for the removal of FBs from diet and feed in the future.

Zhao|Hongfei|H| Wang|Xiao|X| Zhang|Junwen|J| Zhang|Jun|J| Zhang|Bolin|B|

Lactobacillus
Binding
Caco-2 cells
Fumonisins (FB1, FB2)


Arsenic treatment increase Aurora-A overexpression through E2F1 activation in bladder cells.

Abstract:
BACKGROUND
Arsenic is a widely distributed metalloid compound that has biphasic effects on cultured cells. In large doses, arsenic can be toxic enough to trigger cell death. In smaller amounts, non-toxic doses may promote cell proliferation and induces carcinogenesis. Aberration of chromosome is frequently detected in epithelial cells and lymphocytes of individuals from arsenic contaminated areas. Overexpression of Aurora-A, a mitotic kinase, results in chromosomal instability and cell transformation. We have reported that low concentration (≦1 μM) of arsenic treatment increases Aurora-A expression in immortalized bladder urothelial E7 cells. However, how arsenic induces carcinogenesis through Aurora-A activation remaining unclear.

METHODS
Bromodeoxyuridine (BrdU) staining, MTT assay, and flow cytometry assay were conducted to determine cell proliferation. Messenger RNA and protein expression levels of Aurora-A were detected by reverse transcriptional-PCR and Western blotting, respectively. Centrosome of cells was observed by immunofluorescent staining. The transcription factor of Aurora-A was investigated by promoter activity, chromosome immunoprecipitation (ChIP), and small interfering RNA (shRNA) assays. Mouse model was utilized to confirm the relationship between arsenic and Aurora-A.

RESULTS
We reveal that low dosage of arsenic treatment increased cell proliferation is associated with accumulated cell population at S phase. We also detected increased Aurora-A expression at mRNA and protein levels in immortalized bladder urothelial E7 cells exposed to low doses of arsenic. Arsenic-treated cells displayed increased multiple centrosome which is resulted from overexpressed Aurora-A. Furthermore, the transcription factor, E2F1, is responsible for Aurora-A overexpression after arsenic treatment. We further disclosed that Aurora-A expression and cell proliferation were increased in bladder and uterus tissues of the BALB/c mice after long-term arsenic (1 mg/L) exposure for 2 months.

CONCLUSION
We reveal that low dose of arsenic induced cell proliferation is through Aurora-A overexpression, which is transcriptionally regulated by E2F1 both in vitro and in vivo. Our findings disclose a new possibility that arsenic at low concentration activates Aurora-A to induce carcinogenesis.

Kao|Yu-Ting|YT| Wu|Chin-Han|CH| Wu|Shan-Ying|SY| Lan|Sheng-Hui|SH| Liu|Hsiao-Sheng|HS| Tseng|Ya-Shih|YS|

D020133:Reverse Transcriptase Polymerase Chain Reaction


The Effect of Noise Exposure on Cognitive Performance and Brain Activity Patterns.

Abstract:
BACKGROUND
It seems qualitative measurements of subjective reactions are not appropriate indicators to assess the effect of noise on cognitive performance.

AIM
In this study, quantitative and combined indicators were applied to study the effect of noise on cognitive performance.

MATERIAL AND METHODS
A total of 54 young subjects were included in this experimental study. The participants' mental workload and attention were evaluated under different levels of noise exposure including, background noise, 75, 85 and 95 dBA noise levels. The study subject's EEG signals were recorded for 10 minutes while they were performing the IVA test. The EEG signals were used to estimate the relative power of their brain frequency bands.

RESULTS
Results revealed that mental workload and visual/auditory attention is significantly reduced when the participants are exposed to noise at 95 dBA level (P < 0.05). Results also showed that with the rise in noise levels, the relative power of the Alpha band increases while the relative power of the Beta band decreases as compared to background noise. The most prominent change in the relative power of the Alpha and Beta bands occurs in the occipital and frontal regions of the brain respectively.

CONCLUSION
The application of new indicators, including brain signal analysis and power spectral density analysis, is strongly recommended in the assessment of cognitive performance during noise exposure. Further studies are suggested regarding the effects of other psychoacoustic parameters such as tonality, noise pitch (treble or bass) at extended exposure levels.

Jafari|Mohammad Javad|MJ|
Khosrowabadi|Reza|R|
Khodakarim|Soheila|S|
Mohammadian|Farough|F|

Noise
Cognitive Performance
Brain Activity
Attention
Electroencephalogram


Potassium chlorido-tris-(hypersil-oxy)aluminate dimer.

Abstract: The tris-(tri-methyl-silylsiloxide) ligand, also known as hypersiloxide, is an extremely bulky group. In an attempt to make the monomeric Al(OSi(SiMe3)3)3, AlCl3 was combined with 3 equiv. of potassium hypersiloxide. The crystalline product isolated (40% yield), namely di-μ3-chlorido-bis-[μ2-tris-(tri-methyl-sil-yl)silanolato]tetra-kis-[tris-(tri-methyl-sil-yl)silanolato]dialuminium-dipotassium, [Al2K2Cl2(C19H27OSi4)6], is a KCl adduct of aluminium tris(hypersilyloxide) that is dimerized through a planar K2Cl2 ring, with K-Cl distances of 3.1131 (8) and 3.319 (3) Å, and ring angles of 77.41 (2) and 102.60 (2)°. This ring is on an inversion center, and there is no supra-molecular coordination.


Three-Dimensional-Ordered Porous Nanostructures for Lithium-Sulfur Battery Anodes and Cathodes Confer Superior Energy Storage Performance.

Abstract: The nonuniformity of microscopic electrochemical reaction of electrodes essentially results in the partial reaction discrepancy and subsequent partial overheating, which is the most critical safety problem of the battery system in electric vehicles. Herein, we report a class of DLPC@S/DLPC@Li full cell based on a distinctly constructed double-layer photonic crystal (DLPC) with a three-dimensional-ordered interconnected structure. This full cell not only ensures the uniformity of microscopic electrochemical reaction but also solves common problems such as low conductivity of sulfur, poor cycle life, and lithium dendrite growth. Impressively, the full cell exhibits superior electrochemical performance pertaining to high reversible capacity of 703.3 mAh g-1 even at an extremely high rate of 10 C and excellent cycle performance with 1200 cycles with about 0.0317% capacity loss per cycle at 0.5 C.

interconnected
lithium−sulfur batteries
ordered
three-dimensional
uniform electrochemical reaction


Heart failure exacerbation as only presenting sign of COVID-19.

Abstract: With the increasing number of confirmed cases and accumulating clinical data, our understanding of COVID-19 continues to evolve. Here we describe the case of a patient who was initially admitted for decompensated heart failure with reduced ejection fraction (HFrEF). Only later in his course did he develop fever that led to testing for severe acute respiratory syndrome coronavirus-2 (SARS-COV-2). Although we are aware of the common respiratory failure induced by SARS-COV-2, we have scant information that describes cardiac manifestations caused by this novel virus.

Villanueva|Daphne-Dominique H|DH|
Lusby|Heather P|HP|
Islam|Shehla P|SP|
Gupte|Asmita A|AA|
Beatty|Norman L|NL|


Developmental neurotoxicity of the organophosphorus insecticide chlorpyrifos: from clinical findings to preclinical models and potential mechanisms.

Abstract: Organophosphorus (OP) insecticides are pest-control agents heavily used worldwide. Unfortunately, they are also well known for the toxic effects that they can trigger in humans. Clinical manifestations of an acute exposure of humans to OP insecticides include a well-defined cholinergic crisis that develops as a result of the irreversible inhibition of acetylcholinesterase (AChE), the enzyme that hydrolyzes the neurotransmitter acetylcholine (ACh). Prolonged exposures to levels of OP insecticides that are insufficient to trigger signs of acute intoxication, which are hereafter referred to as subacute exposures, have also been associated with neurological deficits. In particular, epidemiological studies have reported statistically significant correlations between prenatal subacute exposures to OP insecticides, including chlorpyrifos, and neurological deficits that range from cognitive impairments to tremors in childhood. The primary objectives of this article are: (i) to address the short- and long-term neurological issues that have been associated with acute and subacute exposures of humans to OP insecticides, especially early in life (ii) to discuss the translational relevance of animal models of developmental exposure to OP insecticides, and (iii) to review mechanisms that are likely to contribute to the developmental neurotoxicity of OP insecticides. Most of the discussion will be focused on chlorpyrifos, the top-selling OP insecticide in the United States and throughout the world. These points are critical for the identification and development of safe and effective interventions to counter and/or prevent the neurotoxic effects of these chemicals in the developing brain. This is an article for the special issue XVth International Symposium on Cholinergic Mechanisms.

Burke|Richard D|RD|
Todd|Spencer W|SW|
Lumsden|Eric|E|
Mullins|Roger J|RJ|
Mamczarz|Jacek|J|
Fawcett|William P|WP|
Gullapalli|Rao P|RP|
Randall|William R|WR|
Pereira|Edna F R|EFR|
Albuquerque|Edson X|EX|

chlorpyrifos development acetylcholinesterase brain learning memory


Highly efficient detection of paclobutrazol in environmental water and soil samples by time-resolved fluoroimmunoassay.

Abstract: A fast and ultrasensitive indirect competitive time-resolved fluoroimmunoassay (TRFIA) was developed for the analysis of paclobutrazol in environmental water and soil samples. Paclobutrazol hapten was synthesized and conjugated to bovine serum albumin (BSA) for producing polyclonal antibodies. Under optimal conditions, the 50% inhibitory concentration (IC50 value) and limit of detection (LOD, IC20 value) were 1.09μgL(-1) and 0.067μgL(-1), respectively. The LOD of TRFIA was improved 30-fold compared to the already reported ELISA. There was almost no cross-reactivity of the antibody with the other structural analogues of triazole compounds, indicating that the antibody had high specificity. The average recoveries from spiked samples were in the range from 80.2% to 104.7% with a relative standard deviation of 1.0-9.5%. The TRFIA results for the real samples were in good agreement with that obtained by high-performance liquid chromatography analyses. The results indicate that the established TRFIA has potential application for screening paclobutrazol in environmental samples.

Liu|Zhenjiang|Z| Wei|Xi|X| Ren|Kewei|K| Zhu|Gangbing|G| Zhang|Zhen|Z| Wang|Jiagao|J| Du|Daolin|D|

Paclobutrazol
Time-resolved fluoroimmunoassay
Hapten
Polyclonal antibody
Environmental samples
Enzyme-linked immunosorbent assay


Comparative analysis of serum proteome in congenital scoliosis patients with TBX6 haploinsufficiency - a first report pointing to lipid metabolism.

Abstract: Congenital scoliosis (CS) is a three-dimensional deformity of the spine affecting quality of life. We have demonstrated TBX6 haploinsufficiency is the most important contributor to CS. However, the pathophysiology at the protein level remains unclear. Therefore, this study was to explore the differential proteome in serum of CS patients with TBX6 haploinsufficiency. Sera from nine CS patients with TBX6 haploinsufficiency and nine age- and gender-matched healthy controls were collected and analysed by isobaric tagged relative and absolute quantification (iTRAQ) labelling coupled with mass spectrometry (MS). In total, 277 proteins were detected and 20 proteins were designated as differentially expressed proteins, which were submitted to subsequent bioinformatics analysis. Gene Ontology classification analysis showed the biological process was primarily related to 'cellular process', molecular function 'structural molecule activity' and cellular component 'extracellular region'. IPA analysis revealed 'LXR/RXR activation' was the top pathway, which is a crucial pathway in lipid metabolism. Hierarchical clustering analysis generated two clusters. In summary, this study is the first proteomic research to delineate the total and differential serum proteins in TBX6 haploinsufficiency-caused CS. The proteins discovered in this experiment may serve as potential biomarkers for CS, and lipid metabolism might play important roles in the pathogenesis of CS.

Zhu|Qiankun|Q| Wu|Nan|N|0000-0003-4137-2030 Liu|Gang|G| Zhou|Yangzhong|Y| Liu|Sen|S| Chen|Jun|J| Liu|Jiaqi|J| Zuo|Yuzhi|Y| Liu|Zhenlei|Z| Chen|Weisheng|W| Chen|Yixin|Y| Chen|Jia|J| Lin|Mao|M| Zhao|Yanxue|Y| Yang|Yang|Y| Wang|Shensgru|S| Yang|Xu|X| Ma|Yufen|Y| Wang|Jian|J| Chen|Xiaoli|X| Zhang|Jianguo|J| Shen|Jianxiong|J| Wu|Zhihong|Z| Qiu|Guixing|G|


Effect of P-glycoprotein regulation on cadmium exhaustion from Crassostrea gigas.

Abstract: P-glycoprotein (P-gp) is a molecular pump, responsible for extruding xenobiotics. The aim of the study was to demonstrate the role of P-glycoprotein (P-gp) in cadmium (Cd) exhaustion. The activity of P-gp was regulated in Crassostrea gigas, which was previously exposed to Cd by using rifampicin (inducer) and verapamil (inhibitor), respectively. Comparing with Crassostrea gigas depurated in natural seawater, Cd content increased significantly from 14.28 mg/kg dw to 17.49 mg/kg dw accompanied by a changed metallothionein level from 9.84 μg/g fw to 10.67 μg/g fw after 25 μg/L verapamil treatment, while Cd content after 25 μg/L rifampicin treatment reduced to 12.21 mg/kg dw. Moreover, after treatment with rifampicin and verapamil, beneficial metal elements, fats, and proteins were maintained, and the tissue-dependent difference was found in the variation of antioxidant defenses and oxidative damage in Crassostrea gigas. In brief, the study provided new evidence on possibility of Cd removal by inducing P-glycoprotein.

Yang|Chao|C| Liu|Qingkang|Q| Li|Guangzhen|G| Meng|Xianghong|X| Liu|Bingjie|B|

D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1

P-glycoprotein
Cadmium
Exhaustion
Crassostrea gigas
Rifampicin induce


Alveolar soft part sarcoma of the forearm.

Abstract: Alveolar soft part sarcoma (ASPS) is a rare form of soft-tissue sarcoma arising from connective tissue. It is most often seen in adolescents and young adults and has high propensity for recurrence and metastasis. Clinically, it mimics haemangioma or arteriovenous malformations. In our case report, an 18-year-old female presented with markedly vascular tumour in the left forearm, for which excision biopsy was done. Histopathological report revealed ASPS. The patient was screened for metastasis. Ultrasound abdomen, computed tomography (CT) chest, CT brain and whole-body skeletal survey was done. The patient was found to have bilateral pulmonary metastasis. The patient was given 6 cycles of chemotherapy with adriamycin, cyclophosphamide and vincristine. There was no locoregional and pulmonary recurrence for 11 months after being treated by excision of the tumour followed by chemotherapy.

Asokan|B|B| Ramanan|P|P| Sundararaj|M|M| Kovarthini|E|E|

Alveolar soft part sarcoma
pulmonary metastasis
extremity soft part sarcoma


Pathological changes of distal motor neurons after complete spinal cord injury.

Abstract: Traumatic spinal cord injury (SCI) causes serious disruption of neuronal circuits that leads to motor functional deficits. Regeneration of disrupted circuits back to their original target is necessary for the restoration of function after SCI, but the pathophysiological condition of the caudal spinal cord has not been sufficiently studied. Here we investigated the histological and biological changes in the distal part of the injured spinal cord, using a mice model of complete thoracic SCI in the chronic stage (3 months after injury). Atrophic changes were widely observed in the injured spinal cord both rostral and caudal to the lesion, but the decrease in area was mainly in the white matter in the rostral spinal cord while both the white and gray matter decreased in the caudal spinal cord. The number of the motor neurons was maintained in the chronic phase of injury, but the number of presynaptic boutons decreased in the lumbar motor neurons caudal to the lesion. Using laser microdissection, to investigate gene expressions in motor neurons caudal to the lesion, we observed a decrease in the expressions of neuronal activity markers. However, we found that the synaptogenic potential of postsynapse molecules was maintained in the motor neurons after SCI with the expression of acetylcholine-related molecules actually higher after SCI. Collectively, our results show that the potential of synaptogenesis is maintained in the motor neurons caudal to the lesion, even though presynaptic input is decreased. Although researches into SCI concentrate their effort on the lesion epicenter, our findings suggest that the area caudal to the lesion could be an original therapeutic target for the chronically injured spinal cord.

Yokota|Kazuya|K| Kubota|Kensuke|K| Kobayakawa|Kazu|K| Saito|Takeyuki|T| Hara|Masamitsu|M| Kijima|Ken|K| Maeda|Takeshi|T| Katoh|Hiroyuki|H| Ohkawa|Yasuyuki|Y| Nakashima|Yasuharu|Y| Okada|Seiji|S|

D000109:Acetylcholine
D000818:Animals
D001284:Atrophy
D000071437:Axon Guidance
D059329:Cholinergic Neurons
D002908:Chronic Disease
D005260:Female
D005786:Gene Expression Regulation
D061346:Laser Capture Microdissection
D008159:Lumbar Vertebrae
D008810:Mice, Inbred C57BL
D009046:Motor Neurons
D018377:Neurotransmitter Agents
D017729:Presynaptic Terminals
D013116:Spinal Cord
D013119:Spinal Cord Injuries
D013569:Synapses

Motor neurons
Spinal cord injury
Chronic phase
Laser microdissection
Synaptogenic potential
Cell-selective gene expression


The Emerging Role of PD-1/PD-L1-Targeting Immunotherapy in the Treatment of Metastatic Urothelial Carcinoma.

Abstract:
OBJECTIVE
To summarize and evaluate immunotherapy agents targeting programmed cell death protein-1 (PD-1) and programmed death ligand-1 (PD-L1) recently approved for the treatment of metastatic urothelial carcinomas (UC).

DATA SOURCES
A literature review was performed using PubMed (2012 to June 2017), the American Society of Clinical Oncology abstract databases (2012 to June 2017 Annual Meetings/symposia), and the America Association for Cancer Research symposia (2012 to June 2017). A search using clinicaltrials.gov was conducted to identify studies for atezolizumab, avelumab, durvalumab, nivolumab, and pembrolizumab.

STUDY SELECTION AND DATA EXTRACTION
English language phase I to III studies assessing PD-1 and PD-L1 in UC were incorporated.

DATA SYNTHESIS
Atezolizumab, avelumab, durvalumab, nivolumab, and pembrolizumab have demonstrated clinical efficacy with tolerable toxicities in patients with metastatic UC with disease progression following platinum-based chemotherapy. Anti-PD-1/PD-L1 therapies may provide overall survival advantage; these are currently being evaluated in ongoing phase 3 studies. Greater objective response rates seem to be observed in PD-L1-positive patients versus PD-L1-negative patients, but methodologies in this assessment differ among clinical trials. The identification of biomarkers that provide greater insight into patients who positively respond to PD-1/PD-L1 therapies are needed.

CONCLUSIONS
Treatment options for metastatic UC have expanded to include PD-1/PD-L1 therapies. These agents should be strongly considered as second-line therapy over single-agent chemotherapy for patients who fail or progress after platinum-based treatment.

D061026:Programmed Cell Death 1 Receptor

urothelial carcinoma
atezolizumab
avelumab
durvalumab
nivolumab
pembrolizumab
programmed death protein 1 (PD-1)


Is there an association between the nutritional and functional parameters and congestive heart failure severity?

Abstract:
BACKGROUND & AIMS
The association between markers of nutritional status (handgrip strength [HGS] and adductor pollicis muscle thickness [APMT]) and clinical markers of congestive heart failure (CHF) severity is currently unclear. The objective of this study was to evaluate the association between HGS, APMT, as markers of nutritional status and CHF severity.

METHODS
APMT and muscle strength was measured in 500 CHF patients bilaterally. Nutritional status was assessed by Subjective Global Assessment (SGA). Functional classification was performed according to guidelines provided by the New York Heart Association (NYHA) and ejection fraction (EF) was measured to classify CHF severity. Poisson regression, adjusted for sex and age, was performed to verify the association between nutritional factors and CHF severity markers.

RESULTS
The majority of patients (75.8%) were ≥60 years old and 53.6% were either overweight or obese. SGA identified 42.2% of the patients as malnourished, 12.6% with low APMT, and 29.0% with low HGS. Most of the patients were classified as NYHA III/IV (56.8%) and almost one third of patients (31.1%) had EF ≤ 40%. HGS and APMT were significantly lower in malnourished male patients and in male patients with a lower EF or worse NYHA classification. Even after controlling for the EF, malnourished patients showed a 2.5-fold increased risk of CHF severity by NYHA classification and for each kilogram of increase in the HGS, there was a significant decrease of 2% in the risk (RR: 0.98 p < 0.001). Malnourished patients presented a 52% higher risk (RR: 1.52 p = 0.016) of having a low EF, whereas for each APMT increase, there was a 5% decrease in the risk (RR: 0.95 p < 0.001), even after controlling for NYHA classification.

CONCLUSIONS
Malnutrition is highly prevalent among patients with CHF and it is associated with the functional class and the severity of the disease. Objective markers of strength (HGS) and muscle (APMT) are independently associated with the CHF severity, assessed by NYHA classification and EF, respectively, even after adjustment for other confounding variables. Thus, the implementation of these nutritional assessment methods in hospital routines, either by SGA or by objective methods, such as HGS and APMT, can configure effective measurements for early detection of malnutrition in patients at higher risk, and possibly a way to avoid their further functional decline.

Duarte|Rodrigo R P|RRP|
Gonzalez|M Cristina|MC|
Oliveira|Jacqueline F|JF|
Goulart|Maíra Ribas|MR|
Castro|Iran|I|

Heart failure
Handgrip strength
Adductor pollicis muscle thickness
Malnutrition
Nutritional assessment


Facile incorporation of REDV into porous silk fibroin scaffolds for enhancing vascularization of thick tissues.

Abstract: Rapid neovascularization within scaffolds is critical for the regeneration of thick complex tissues. The surface immobilization of peptides and other active molecules have been explored to improve the vascularization capacity of implants. However, the rapid degradation of these molecules, the reaction conditions and cross-linking usually result in decreased vascularization capability. Here, we introduced a temperate, all-aqueous process to achieve bulk porous silk fibroin (SF) scaffolds. A temperature controlled process was used to induce the water stable structure by SF self-assembly. Arg-Glu-Asp-Val (REDV) peptides were added into SF solution and fixed within SF scaffolds during the self-assembly process. The results showed that the functionalized scaffolds markedly promoted the adhesion of endothelial cells in vitro. Moreover, the in vivo studies indicated enhanced cell infiltration in the bulk functionalized SF scaffolds and impressive vascularization at 4 weeks post-implantation. The functionalized scaffolds demonstrated excellent vascularization capability, providing an exciting biomaterial option for thick tissue regeneration.

Yao|Danyu|D| Qian|Zhiyong|Z| Zhou|Jin|J| Peng|Ge|G| Zhou|Gang|G| Liu|Haifeng|H| Fan|Yubo|Y|

D061307:Human Umbilical Vein Endothelial Cells

Facile incorporation
REDV
Silk fibroin
Vascularization
Thick tissues


Identification of Aedes aegypti cis-regulatory elements that promote gene expression in olfactory receptor neurons of distantly related dipteran insects.

Abstract:
BACKGROUND
Sophisticated tools for manipulation of gene expression in select neurons, including neurons that regulate sexually dimorphic behaviors, are increasingly available for analysis of genetic model organisms. However, we lack comparable genetic tools for analysis of non-model organisms, including Aedes aegypti, a vector mosquito which displays sexually dimorphic behaviors that contribute to pathogen transmission. Formaldehyde-assisted isolation of regulatory elements followed by sequencing (FAIRE-seq) recently facilitated genome-wide discovery of putative A. aegypti cis-regulatory elements (CREs), many of which could be used to manipulate gene expression in mosquito neurons and other tissues. The goal of this investigation was to identify FAIRE DNA elements that promote gene expression in the olfactory system, a tissue of vector importance.

RESULTS
Eight A. aegypti CREs that promote gene expression in antennal olfactory receptor neurons (ORNs) were identified in a Drosophila melanogaster transgenic reporter screen. Four CREs identified in the screen were cloned upstream of GAL4 in a transgenic construct that is compatible with transformation of a variety of insect species. These constructs, which contained FAIRE DNA elements associated with the A. aegypti odorant coreceptor (orco), odorant receptor 1 (Or1), odorant receptor 8 (Or8) and fruitless (fru) genes, were used for transformation of A. aegypti. Six A. aegypti strains, including strains displaying transgene expression in all ORNs, subsets of these neurons, or in a sex-specific fashion, were isolated. The CREs drove transgene expression in A. aegypti that corresponded to endogenous gene expression patterns of the orco, Or1, Or8 and fru genes in the mosquito antenna. CRE activity in A. aegypti was found to be comparable to that observed in D. melanogaster reporter assays.

CONCLUSIONS
These results provide further evidence that FAIRE-seq, which can be paired with D. melanogaster reporter screening to test FAIRE DNA element activity in select tissues, is a useful method for identification of mosquito cis-regulatory elements. These findings expand the genetic toolkit available for the study of Aedes neurobiology. Moreover, given that the CREs drive comparable olfactory neural expression in both A. aegypti and D. melanogaster, it is likely that they may function similarly in multiple dipteran insects, including other disease vector mosquito species.

Aedes aegypti
Neuron
Mosquito
FAIRE
Drosophila melanogaster
Antenna
Dengue
Enhancer
Sensory
Zika


Exosomal linc-ROR mediates crosstalk between cancer cells and adipocytes to promote tumor growth in pancreatic cancer.

Abstract: Exosomes are emerging as important mediators of the crosstalk between tumor cells and stromal cells in the microenvironment. However, the underlying molecular mechanism of pancreatic cancer (PC)-derived exosomes in the progression of the tumor microenvironment (TME) and crosstalk with adipocytes has not been elucidated. Exosomes isolated from PC cell culture supernatant through ultracentrifugation were rich in long intergenic non-coding ROR (linc-ROR). After constructing PC cell lines with stable linc-ROR knockdown or overexpression via the transfection of short hairpin RNA (shRNA) and pLent-U6-GFP-Puro, direct and indirect coculture systems were established to simulate the interaction between adipocytes and PC cells. Next, the effects of conditioned medium collected from dedifferentiated adipocytes on PC cell proliferation, motility, metastasis, and epithelial-mesenchymal transition (EMT) were evaluated by western blot analysis, colony forming, real-time cell analysis (RTCA), 5-ethynyl-2'-deoxyuridine (EdU), immunofluorescence (IF), Transwell, and wound-healing assays in vitro. Xenograft models were employed to identify whether conditioned medium loaded with interleukin-1β (IL-1β) promoted PC cell growth in vivo. Our results demonstrate that linc-ROR delivery via exosomes represents a brand-new perspective of dedifferentiating adipocytes in the TME of PC, which further induce PC cell EMT via the hypoxia inducible factor 1α (HIF1α)-ZEB1 axis. Moreover, exosomal linc-ROR may become a novel diagnostic marker for PC patients.

Sun|Zhaowei|Z| Sun|Dong|D| Feng|Yujie|Y| Zhang|Bingyuan|B| Sun|Peng|P| Zhou|Bin|B| Du|Lutao|L| Wang|Yunshan|Y| Fan|Zhiyao|Z| Yang|Jian|J| Li|Yongzheng|Y| Hu|Sanyuan|S| Zhan|Hanxiang|H|

exosomes
linc-ROR
adipocytes
pancreatic cancer
coculture system
epithelial-mesenchymal transition
IL-1β
HIF1α
ZEB1


Patient-reported satisfaction after robot-assisted hysterectomy among Korean patients with benign uterine disease.

Abstract:
Objective
This study aimed to evaluate patient-reported satisfaction following robot-assisted hysterectomy due to benign uterine disease, and to identify the factors associated.

Methods
We used a questionnaire to evaluate patients' satisfaction with robot-assisted hysterectomy. The questions concerned overall patient-reported satisfaction and specific factors affecting satisfaction, including postoperative pain, return to daily life, the hospital experience, wounds, cost, the doctor-patient relationship, whether expectations were met, and whether detailed information was provided. We also collected data from patient records, such as uterine weight, rate of pelvic adhesion, operation time, rate of transfusion, delayed discharge, and readmission. One hundred patients who underwent robot-assisted hysterectomy participated in the study. Seventy-three fully completed questionnaires were returned.

Results
The majority of patients (95.9%) were satisfied with robot-assisted hysterectomy. The doctor-patient relationship, whether expectations were met, the hospital experience, wounds, and whether detailed information was provided were statistically significant factors influencing patients' overall satisfaction. Payment of fees and clinical and surgical outcomes did not significantly influence patients' overall satisfaction.

Conclusion
Our findings show that most patients reported high levels of satisfaction following robot-assisted hysterectomy, regardless of cost or clinical and surgical outcomes. Therefore, if gynecologists consider robot-assisted hysterectomy suitable for patients they need not hesitate based on potential costs; they should feel confident in recommending the procedure to patients.

Hysterectomy
Patient satisfaction
Robot surgical procedures


Association between change in brain gray matter volume, cognition, and depression severity: Pre- and post- antidepressant pharmacotherapy for late-life depression.

Abstract: Late-life depression (LLD) is associated with cognitive impairments and reduced gray matter volume (GMV); however the mechanisms underlying this association are not well understood. The goal of this study was to characterize changes in depression severity, cognitive function, and brain structure associated with pharmacologic antidepressant treatment for LLD. We administered a detailed neurocognitive battery and conducted structural magnetic resonance imaging (MRI) on 26 individuals with LLD, pre-/post-a 12-week treatment trial with venlafaxine. After calculating changes in cognitive performance, GMV, and depression severity, we calculated Pearson's correlations, performed permutation testing, and false discovery rate correction. We found that loss of GMV over 12 weeks in the superior orbital frontal gyrus was associated with less improvement in depression severity and that increased GMV in the same was associated with greater improvement in depression severity. We detected no associations between changes in cognitive performance and improvements in either depressive symptoms or changes in GMV.

Droppa|K|K|
Karim|H T|HT|
Tudorascu|D L|DL|
Karp|J F|JF|
Reynolds|C F|CF|
Aizenstein|H J|HJ|
Butters|M A|MA|


Rare anatomical variation of the brachiocephalic trunk encountered in tracheostomy.

Abstract: Tracheostomy is a common procedure in head and neck surgery and emergency medicine to secure a patent airway. Surgeons should always be aware of anatomical variants of the branches of the aortic arch, which could lead to life-threatening complications. Open tracheostomy is the safest emergency procedure.


miR-140-5p attenuates chemotherapeutic drug-induced cell death by regulating autophagy through inositol 1,4,5-trisphosphate kinase 2 (IP3k2) in human osteosarcoma cells.

Abstract: Acquisition of drug-resistant phenotypes is often associated with chemotherapy in osteosarcoma. A number of studies have demonstrated a critical role for autophagy in osteosarcoma development, therapy and drug resistance. However, the molecular mechanisms underlying the autophagy-mediated chemotherapy resistance of osteosarcoma cells remain largely unknown. In the present study, we determined the autophagy and microRNA-140 (miR-140-5p, miRBase ID: MIMAT0000431) expression induced by chemotherapeutic drugs in osteosarcoma cells. Then we determined the promotory role of miR-140-5p to the chemotherapy-induced autophagy. Our results demonstrated that miR-140-5p expression was highly induced during chemotherapy of osteosarcoma cells, and this was accompanied by up-regulated autophagy. The increased miR-140-5p expression levels up-regulated anticancer drug-induced autophagy in osteosarcoma cells and ameliorated the anticancer drug-induced cell proliferation and viability decrease. Importantly, miR-140-5p regulates this context-specific autophagy through its target, inositol 1,4,5-trisphosphate kinase 2 (IP3k2). Therefore, the results of the present study demonstrated that miR-140-5p mediated drug-resistance in osteosarcoma cells by inducing autophagy. The present study provides evidence of miRNA regulation of autophagy through modulation of IP3 signalling. The present study recognized a novel mechanism of chemoresistance in osteosarcoma cancers.

Wei|Renxiong|R| Cao|Gang|G| Deng|Zhouming|Z| Su|Jiajia|J| Cai|Lin|L|

D015972:Gene Expression Regulation, Neoplastic

D017853:Phosphotransferases (Alcohol Group Acceptor)


Bilateral high- and low-frequency rTMS in acute stroke patients with hemiparesis: a comparative study with unilateral high-frequency rTMS.

Abstract:
BACKGROUND
High- and low-frequency repetitive transcranial magnetic stimulation (HF-rTMS and LF-rTMS) has been shown to be beneficial for upper limb hemiparesis in patients with acute stroke. However, no study has examined the usefulness of bilateral application of HF- and LF-rTMS (BL-rTMS).

METHODS
Fifty-eight hemiparetic patients with acute stroke were randomly assigned into two groups: HF-rTMS group and BL-rTMS group. All patients were scheduled to receive five sessions of either HF-rTMS over the lesional hemisphere or BL-rTMS over both hemispheres for 5 days. Motor function of the affected upper limb was evaluated using the Brunnstrom Recovery Stage (BRS) for upper-limb and hand-fingers, grip strength and tapping frequency, before the first session and after the last session of rTMS.

RESULTS
Improvement of BRS for the upper limb and hand/finger was significantly greater in the BL-rTMS group than the HF-rTMS group (p < 0.01). Improvement in grip strength and tapping frequency was also greater in the BL-rTMS group, although the differences were not statistically significant.

CONCLUSIONS
The proposed BL-rTMS is safe and feasible and showed a greater improvement of BRS of the affected upper limb compared to HF-rTMS. This novel rTMS approach may be a useful intervention for hemiparetic patients with acute stroke.

stroke
Neurological
rehabilitation
sub-acute care


Clinically indicated replacement of peripheral cannulas.

Abstract: Insertion of peripheral venous cannulas is one of the most frequently performed procedures in hospitals. In the UK, one in three patients will have at least one cannula inserted while in hospital. Cannula insertion is uncomfortable and causes anxiety and distress to patients. The risks associated with this include infection, phlebitis and infiltration. In the UK, it is widely accepted that cannulas should be routinely changed every 72--96 hours in line with national guidelines ( Department of Health (DH) 2007). The updated epic3 guidelines recommend to change cannulas when clinically indicated, rather than routinely. The objective in a local NHS trust, was to look at the evidence for this, with an aim to change local policy and practice to reflect the new recommendation. The primary outcomes of the first 6 months from implementation suggest that patients have not been adversely affected. The change to practice has provided a significant reduction in financial costs to the trust, enabling a stock reduction of 25%. It is estimated that a total of 11 750 clinical hours have been saved for busy clinical staff. The most important outcome has been for patients, who have been spared the unnecessary pain and potential risks associated with repeated insertion of cannulas when there has been no clinical indication to do this.

Peripheral cannula
Phlebitis
Cost savings
Infection prevention
Prevalence


Safety Evaluation of PQ Birch Allergy Immunotherapy to Support Product Development.

Abstract: PQ Birch represents an allergen-specific immunotherapy for the treatment of birch pollinosis. It consists of native birch pollen extract chemically modified with glutaldehyde adsorbed to L-tyrosine in its microcrystalline form with addition of the adjuvant Monophosphoryl Lipid A (MPL®). A nonclinical safety testing strategy was designed based upon interpretation of current legislation and regulatory intelligence and comprised genotoxicity studies (bacterial reverse mutation and Chinese hamster ovary micronucleus assays), a rat repeat dose toxicology study and a rabbit local tolerance study. No safety findings of concern were found. Thus, no evidence of genotoxicity was found. Relatively minor, immunostimulatory effects were seen following repeated subcutaneous dosing (once every 2 weeks for 13 weeks) as reversible increased white cell count (notably neutrophils), increased globulin level (resulting in decreased albumin/globulin [A/G] ratio) and increased fibrinogen, as well as minor dose site reaction in the form of inflammatory cell infiltrate. These findings are likely due to the immunostimulatory nature of MPL® and/or the presence of L-tyrosine within the adjuvanted vaccine. Similar dose site inflammatory changes to the injected formulation were also noted in the rabbit local tolerance study.

Baldrick|Paul|P|
Hutchings|James W|JW|
Heath|Matthew D|MD|
Skinner|Murray A|MA|

PQ birch
Birch pollen
Genotoxicity
Toxicology study
Allergy vaccine


Cyclin-Dependent Kinases 8 and 19 Regulate Host Cell Metabolism during Dengue Virus Serotype 2 Infection.

Abstract: Dengue virus infection is associated with the upregulation of metabolic pathways within infected cells. This effect is common to infection by a broad array of viruses. These metabolic changes, including increased glucose metabolism, oxidative phosphorylation and autophagy, support the demands of viral genome replication and infectious particle formation. The mechanisms by which these changes occur are known to be, in part, directed by viral nonstructural proteins that contact and control cellular structures and metabolic enzymes. We investigated the roles of host proteins with overarching control of metabolic processes, the transcriptional regulators, cyclin-dependent kinase 8 (CDK8) and its paralog, CDK19, as mediators of virally induced metabolic changes. Here, we show that expression of CDK8, but not CDK19, is increased during dengue virus infection in Huh7 human hepatocellular carcinoma cells, although both are required for efficient viral replication. Chemical inhibition of CDK8 and CDK19 with Senexin A during infection blocks virus-induced expression of select metabolic and autophagic genes, hexokinase 2 (HK2) and microtubule-associated protein 1 light chain 3 (LC3), and reduces viral genome replication and infectious particle production. The results further define the dependence of virus replication on increased metabolic capacity in target cells and identify CDK8 and CDK19 as master regulators of key metabolic genes. The common inhibition of CDK8 and CDK19 offers a host-directed therapeutic intervention that is unlikely to be overcome by viral evolution.

Butler|Molly|M|
Chotiwan|Nunya|N|
Brewster|Connie D|CD|
DiLisio|James E|JE|
Ackart|David F|DF|
Podell|Brendan K|BK|
Basaraba|Randall J|RJ|
Perera|Rushika|R|0000-0001-6798-2537
Quackenbush|Sandra L|SL|
Rovnak|Joel|J|0000-0003-4518-9030


Electrocatalytic NiCo2O4 Nanofiber Arrays on Carbon Cloth for Flexible and High-Loading Lithium-Sulfur Batteries.

Abstract: Lithium-sulfur batteries have ultrahigh theoretical energy densities, which makes them one of the most promising next-generation energy storage systems. However, it is still difficult to achieve large-scale commercialization because of the severe lithium polysulfide (LiPS) shuttle effect and low sulfur loading. Here, we report a flexible lithium-sulfur battery of a high sulfur loading with the assistance of NiCo2O4 nanofiber array grown carbon cloth. The NiCo2O4 nanofibers are ideal electrocatalysts for accelerating LiPS conversion kinetics through strong chemical interactions. Therefore, the composite cathode delivers a high specific capacity of 1280 mAh g-1 at 0.2 C with a sulfur loading of 3.5 mg cm-2, and it can maintain a high specific capacity of 660 mAh g-1 after 200 cycles, showing a good cycle stability. The "layer-by-layer" stacking strategy enables the Li-S battery with a high S loading of ∼9.0 mg cm-2 to deliver a high areal capacity of 8.9 mAh cm-2.

shuttle effect
flexible battery
high mass loading
lithium sulfur battery


Study on the Mechanical and Leaching Characteristics of Permeable Reactive Barrier Waste Solidified by Cement-Based Materials.

Abstract: The durability against wet-dry (w-d) cycles is an important parameter for the service life design of solidified permeable reactive barrier (PRB) waste. This study introduces the potential use of cement, fly ash, and carbide slag (CFC) for the stabilization/solidification (S/S) of PRB waste. In this study, solidified PRB waste was subjected to different w-d cycles ranging in times from 0 to 10. By analyzing the mass loss, the unconfined compressive strength (UCS), initial resistivity (IR), and the Mn2+ leaching concentration under different durability conditions, the results demonstrate that these variables increased and then tended to decrease with the number of w-d cycles. The UCS of contaminated soil is significantly correlated with IR. Moreover, scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and X-ray diffraction (XRD) analyses indicate that the hydration products calcium silicate hydrate (C-S-H) and ettringite (AFt) are the main reasons for the enhancement of the UCS. However, the increase in Mn2+ concentration leads to a decrease in hydration products and the compactness of solidified soil, which has negative effects for the UCS and the leaching ion concentration. In general, the durability exhibited by the PRB waste treated with S/S in this paper was satisfactory. This study can provide theoretical guidance for practical engineering applications.

Chen|Xuan|X| Feng|Wenkui|W| Wen|Hao|H| Duan|Wei|W| Suo|Chongxian|C| Xie|Mingxing|M| Dong|Xiaoqiang|X|

leaching characteristics
PRB waste
unconfined compressive strength
initial resistivity
microstructural characteristics
wet-dry cycle