Application of multifold characteristic ion filtering combined with statistical analysis for comprehensive profiling of chemical constituents in anti-renal interstitial fibrosis I decoction by ultra-high performance liquid chromatography coupled with hybrid quadrupole-orbitrap high resolution mass spectrometry.

Abstract: A Chinese herbal formula of Anti-Renal Interstitial Fibrosis I Decoction (ARIF I) is composed of Eucommia ulmoides Oliv., Scutellaria baicalensis Georgi, and Rheum. officinale Baill., and it has been used for the treatment of chronic kidney disease for many years. However, the comprehensive chemical analysis of the formulated ARIF I has yet to be clarified. In this study, an ultra-high performance liquid chromatography coupled with hybrid quadrupole-orbitrap high resolution mass spectrometry (UHPLC/Q-orbitrap HRMS) method executed in full scan/data-dependent MS2 (full MS/dd-MS2) mode has been established in negative ion mode to analyze the major chemical constituents in ARIF I as well as in its three constituent herbs. To rapidly and efficient identify these compounds, we employed a combination of statistical analysis of the MS2 data and fragmentation pathway method to screen for elementary characteristic ions and sub-characteristic ions. Then, we applied multifold characteristic ion filtering to comprehensively profile ARIF I extract chemical constituents with diverse structures. A total of 360 compounds, including anthraquinones, sennosides, galloyl glucoside derivatives, catechin and its derivatives, flavonoids, iridoids, phenylpropanoids, lignan, organic acid, and other compounds were rapidly identified or tentatively characterized by multifold characteristic ion filtering based on their accurate mass spectra (within 5 ppm error) and structure types or by comparison with reference standards. All the ARIF I compounds were also detected in the individual constituent herbs. This study provides a basis for further pharmacokinetic studies of ARIF I and may help in the discovery of new chemical drugs to treat chronic kidney disease. This study also provides a more efficient approach for the screening of appropriate characteristic ions, and a practical strategy for the detection of the types of compounds identified in this study in other herbal medicines.

Jiang|Yueping|Y| Liu|Rui|R| Chen|Jingjing|J| Liu|Manhua|M| Liu|Min|M| Liu|Bin|B| Yi|Lunzhao|L| Liu|Shao|S|

D002851:Chromatography, High Pressure Liquid

Anti-Renal interstitial fibrosis I decoction


Structure and concept of ICU rounds: the VIS-ITS survey.

Abstract:
OBJECTIVE
To gather data about structural and procedural characteristics of patient rounds in the intensive care unit (ICU) setting.

DESIGN
A structured online survey was offered to members of two German intensive care medicine societies.

MEASUREMENTS AND MAIN RESULTS
Intensivists representing 390 German ICUs participated in this study (university hospitals 25%, tertiary hospitals 23%, secondary hospitals 36%, primary hospitals 16%). In 90% of participating ICUs, rounds were reported to take place in the morning and cover an average of 12 intensive care beds and 6 intermediate care beds within 60 min. With an estimated bed occupancy of 80%, this averaged to 4.3 min spent per patient during rounds. In 96% of ICUs, rounds were stated to include a bedside visit. On weekdays, 86% of the respondents reported holding a second ICU round with the attendance of a qualified decision-maker (e.g. board-certified intensivist). On weekends, 79% of the ICUs performed at least one round with a decision-maker per day. In 18%, only one ICU round per weekend was reported, mostly on Sundays. The highest-qualified decision-maker present during rounds on most ICUs was an ICU attending (57%). Residents (96%) and intensive care nurses (87%) were stated to be always or usually present during rounds. In contrast, physiotherapists, respiratory therapists or medical specialists such as pharmacists or microbiologist were not regular members of the rounding team on most ICUs. In the majority of cases, the participants reported examining the medical chart directly before or during the bedside visit (84%). An electronic patient data management system (PDMS) was available on 31% of ICUs. Daily goals were always (55%) or usually (39%) set during rounds.

CONCLUSION
This survey gives a broad overview of the structure and processes of ICU rounds in different sized hospitals in Germany. Compared to other mostly Anglo-American studies, German ICU rounds appear to be shorter and less interdisciplinary.

Hillmann|Bastian|B| Schwarzkopf|Daniel|D| Manser|Tanja|T| Waydhas|Christian|C| Riessen|Reimer|R|

Intensive care unit
Decision-maker
Patient data managment system
Daily goals
Electronic health record


Low-dose aspirin reduces hypoxia-induced sFlt1 release via the JNK/AP-1 pathway in human trophoblast and endothelial cells.

Abstract: Pre-eclampsia (PE) is a serious hypertensive disorder of pregnancy that remains a leading cause of perinatal and maternal morbidity and mortality worldwide. Placental ischemia/hypoxia and the secretion of soluble fms-like tyrosine kinase 1 (sFlt1) into maternal circulation are involved in the pathogenesis of PE. Although low-dose aspirin (LDA) has beneficial effects on the prevention of PE, the exact mechanisms of action of LDA, particularly on placental dysfunction, and sFlt1 release, have not been well investigated. This study aimed to determine whether LDA exists the protective effects on placental trophoblast and endothelial functions and prevents PE-associated sFlt1 release. First, we observed that LDA mitigated hypoxia-induced trophoblast apoptosis, showed positive effects on trophoblast cells migration and invasion activity, and increased the tube-forming activity of human umbilical vein endothelial cells (HUVECs). In addition, LDA decreased hypoxia-induced sFlt1 production, and the c-Jun NH2 -terminal kinase/activator protein-1 (JNK/AP-1) pathway was shown to mediate the induction of sFlt1. Moreover, the transcription factor AP-1 was confirmed to regulate the Flt1 gene expression by directly binding to the Flt1 promoter in luciferase assays. The result of chromatin immunoprecipitation assays further demonstrated that LDA could directly decrease the expression of the transcription factor AP-1, and thus decrease sFlt1 production. Finally, the effects of LDA on sFlt1 production were proved in human placental explants. Taken together, our data show the protective effects of LDA against trophoblast and endothelial cell dysfunction and reveal that the LDA-mediated inhibition of sFlt1 via the JNK/AP-1 pathway may be a potential cellular/molecular mechanism for the prevention of PE.

Lin|Li|L|0000-0002-4117-2314 Li|Guanlin|G| Zhang|Wanyi|W| Wang|Yan-Ling|YL| Yang|Huixia|H|

D061307:Human Umbilical Vein Endothelial Cells

D048031:JNK Mitogen-Activated Protein Kinases

D040281:Vascular Endothelial Growth Factor Receptor-1

c-Jun NH2-terminal kinase/activator protein-1 (JNK/AP-1) pathway


High-resolution mapping of traffic related air pollution with Google street view cars and incidence of cardiovascular events within neighborhoods in Oakland, CA.

Abstract:
BACKGROUND
Some studies have linked long-term exposure to traffic related air pollutants (TRAP) with adverse cardiovascular health outcomes; however, previous studies have not linked highly variable concentrations of TRAP measured at street-level within neighborhoods to cardiovascular health outcomes.

METHODS
Long-term pollutant concentrations for nitrogen dioxide [NO2], nitric oxide [NO], and black carbon [BC] were obtained by street-level mobile monitoring on 30 m road segments and linked to residential addresses of 41,869 adults living in Oakland during 2010 to 2015. We fit Cox proportional hazard models to estimate the relationship between air pollution exposures and time to first cardiovascular event. Secondary analyses examined effect modification by diabetes and age.

RESULTS
Long-term pollutant concentrations [mean, (standard deviation; SD)] for NO2, NO and BC were 9.9 ppb (SD 3.8), 4.9 ppb (SD 3.8), and 0.36 μg/m3 (0.17) respectively. A one SD increase in NO2, NO and BC, was associated with a change in risk of a cardiovascular event of 3% (95% confidence interval [CI] -6% to 12%), 3% (95% CI -5% to 12%), and - 1% (95% CI -8% to 7%), respectively. Among the elderly (≥65 yrs), we found an increased risk of a cardiovascular event of 12% for NO2 (95% CI: 2%, 24%), 12% for NO (95% CI: 3%, 22%), and 7% for BC (95% CI: -3%, 17%) per one SD increase. We found no effect modification by diabetes.

CONCLUSIONS
Street-level differences in long-term exposure to TRAP were associated with higher risk of cardiovascular events among the elderly, indicating that within-neighborhood differences in TRAP are important to cardiovascular health. Associations among the general population were consistent with results found in previous studies, though not statistically significant.

Alexeeff|Stacey E|SE|
Roy|Ananya|A|
Shan|Jun|J|
Liu|Xi|X|
Messier|Kyle|K|
Apte|Joshua S|JS|
Portier|Christopher|C|
Sidney|Stephen|S|
Van Den Eeden|Stephen K|SK|

Air pollution
Mobile monitoring
Cardiovascular disease
Coronary heart disease
Mortality


Molecular mechanisms underlying the anti-proliferative and anti-migratory effects of folate on homocysteine-challenged rat aortic smooth muscle cells.

Abstract:
BACKGROUND AND PURPOSE
Homocysteine is an intermediate product formed during the metabolism of methionine, and is increased in cells with folate deficiency. Patients with hyperhomocysteinemia tend to develop cardiovascular disease. Here, we have examined the molecular mechanisms underlying the anti-proliferative and anti-migratory effects of folate on homocysteine-challenged rat aortic smooth muscle cells (RASMCs).

EXPERIMENTAL APPROACH
Cultures of RASMC were challenged with homocysteine and then incubated with folate added. Changes in p21/p27, AKT and RhoA were followed by RT-PCR, Western blotting and immunocytochemistry. Transfection and anti-sense techniques were also used. Cell viability, growth and migration were measured.

KEY RESULTS
Folate up-regulated p21/p27 through a Src/ERK-dependent mechanism that accounted for its anti-proliferative effects on RASMC. Folate protected RASMC from the effects of homocysteine by reducing AKT1, focal adhesion kinase (FAK), paxillin, and p190RhoGAP activation/phosphorylation, along with cytosolic levels of p21 and p27, and increasing RhoA activation. Overexpression of AKT1, but not of AKT2, induced p21/p27 phosphorylation and increased cytosolic p21/p27 levels, as did homocysteine treatment. By contrast, and similarly to folate treatment, transfection with dominant negative (DN) AKT1 counteracted these effects. Additionally, AKT was shown to be an upstream target of FAK activation. In RASMC overexpressing constitutively active RhoA, activation of RhoA mediated the anti-migratory effects of folate. Addition of Y27632 (a RhoA inhibitor) and DNRhoA counteracted the anti-migratory effects, confirming RhoA involvement.

CONCLUSION AND IMPLICATIONS
Folate was anti-proliferative and anti-migratory in homocysteine-challenged RASMC. Mechanisms underlying folate-mediated protection against the proatherosclerotic effects of homocysteine have been delineated.

Chou|Ying|Y| Lin|Hui-Chen|HC| Chen|Kuan-Chou|KC| Chang|Chi-Cheng|CC| Lee|Wen-Sen|WS| Juan|Shu-Hui|SH|

D050759:Cyclin-Dependent Kinase Inhibitor p21


Optimization of the epithermal neutronic beam for BNCT at a 22 MW MTR reactor.

Abstract: The design of an Epithermal Neutronic Beam (ENB) at a 22 MW MTR reactor for the Boron Neutron Capture Therapy (BNCT) is discussed in this paper(Calculations were made for the ETRR-2 reactor). Along the beam a moderator made from the materials: Pb + Al + Cd + Al + FLUENTAL + Al + FLUENTAl + Air + Cd + Bi with Pb was used as reflector. Following the moderator is air + Pb + Air with Bi lined collimator and Li2CO3-Polyethelene at the beam exit. The collimator is surrounded by layers of water, heavy concrete and Pb. The calculated values of the beam at the head phantom were: Фepith = 2.402 х 109 n/cm2.s, Df/Фepith = 1.724 х 10-11 cGy cm2/n and Dγ/Фepith = 0.196 х 10-11 cGy cm2/n, where the head phantom was placed at 5 cm from the beam exit. The obtained values by using the MCNP code of the Advantage Depth (AD), the Advantage Ratio (AR), the Advantage Depth Dose Ratio (ADDR), the treatment time and the therapeutic ratio were: 8.75 cm, 5.62, 36.37 cGy/min, 34.37 and 5.62, respectively. The MCNP geometry plotting resources were used to plot all geometrical cross sections of the simulated reactor.

D016754:Boron Neutron Capture Therapy
D019047:Phantoms, Imaging
D011878:Radiotherapy

Epithermal neutronic beam
MCNPcode
MTR-Reactor


Young People, Adult Worries: Randomized Controlled Trial and Feasibility Study of the Internet-Based Self-Support Method "Feel the ViBe" for Adolescents and Young Adults Exposed to Family Violence.

Abstract:
BACKGROUND
Adolescents and young adults (AYAs) are of special interest in a group of children exposed to family violence (FV). Past-year prevalence of exposure to FV is known to be highest in AYAs and has severe consequences. Peer support is an effective approach to behavior change and the Internet is considered suitable as a mode of delivery.

OBJECTIVE
The study aimed to evaluate both effectiveness and feasibility of a randomized controlled trial (RCT) and feasibility study of the Internet-based self-support method "Feel the ViBe" (FtV) using mixed-methods approach to fully understand the strengths and weaknesses of a new intervention.

METHODS
AYAs aged 12-25 years and exposed to FV were randomized in an intervention group (access to FtV + usual care) and a control group (minimally enhanced usual care) after they self-registered themselves. From June 2012 to July 2014, participants completed the Impact of Event Scale (IES) and Depression (DEP) and Anxiety (ANX) subscales of the Symptom CheckList-90-R (SCL-90) every 6 weeks. The Web Evaluation Questionnaire was completed after 12 weeks. Quantitative usage data were collected using Google analytics and content management system (CMS) logs and data files. A univariate analysis of variance (UNIANOVA) and mixed model analysis (intention-to-treat [ITT], complete case) were used to compare groups. Pre-post t tests were used to find within-group effects. Feasibility measures structurally address the findings. The CONsolidated Standards Of Reporting Trials of Electronic and Mobile HEalth Applications and onLine TeleHealth (CONSORT-EHEALTH) checklist was closely followed.

RESULTS
In total, 31 out of 46 participants in the intervention group and 26 out of 47 participants in the control group started FtV. Seventeen participants (intervention: n=8, control: n=9) completed all questionnaires. Mixed model analysis showed significant differences between groups on the SCL-90 DEP (P=.04) and ANX (P=.049) subscales between 6 and 12 weeks after participation started. UNIANOVA showed no significant differences. Pre-post paired sample t tests showed significant improvements after 12 weeks for the SCL-90 DEP (P=.03) and ANX (P=.046) subscales. Reported mean Web-based time per week was 2.83 with a session time of 36 min. FtV was rated a mean 7.47 (1-10 Likert scale) with a helpfulness score of 3.16 (1-5 Likert scale). All participants felt safe. Two-thirds of the intervention participants started regular health care.

CONCLUSIONS
No changes on the IES were found. SCL-90 DEP and ANX showed promising results; however, the calculated sample size was not reached (n=18). FtV functions best as a first step for adolescents and young adults in an early stage of change. FtV can be easily implemented without extensive resources and fits best in the field of public health care or national governmental care.

TRIAL REGISTRATION
Netherlands National Trial Register (NTR): NTR3692; http://www.trialregister.nl/trialreg/admin/ rctview.asp?TC=3692 (Archived by WebCite at http://www.webcitation.org/6qIeKyjA4).

randomized controlled trial
feasibility studies
adolescent
young adult
Internet
child abuse
delivery of health care
domestic violence
exposure to violence
peer group
peer influence
telemedicine


Time-course of changes in key catecholaminergic receptors and trophic systems in rat brain after antidepressant administration.

Abstract: Several biochemical parameters within the brain are altered by antidepressants. However, it is still uncertain which parameters are important for the evaluation of the effectiveness of these drugs. What seems certain is that the response of the nervous system is dynamic. The dynamic nature of the nervous system is still poorly understood, although it has implications in clinical management. Criteria for evaluating treatment resistant depression are based on this temporal variability. The present study was designed to evaluate dynamic alterations in catecholaminergic receptors and calcyon (associated with monoaminergic theory of depression) in the rat brain as well as brain-derived neurotrophic factor (BDNF) and tyrosine kinase beta (TRKB; related to neurotrophin theory) induced by three antidepressant drugs (ADs) with various pharmacological profiles (imipramine, desipramine, and citalopram) administered for 21 days or acutely, followed by various drug-free periods. Receptor autoradiography and in situ hybridization studies allowed us to identify changes in various brain regions simultaneously in each rat. Repeated treatment with ADs induced biochemical alterations, which were in agreement with the results of previous studies. These alterations include the downregulation of β1, β2, and α1 adrenergic receptors, upregulation of α2-adrenergic receptors and dopamine D2 receptors, and increased expression of BDNF in the hippocampus. Additionally, we observed dynamic alterations in the measured parameters after acute drug administration, particularly at the level of dopamine receptors, which were extremely sensitive to a single dose of ADs followed by various drug-free periods. All three ADs induced the upregulation of dopamine D2 receptor mRNA levels in the nucleus accumbens. The same effect was induced by single doses of ADs followed by various drug-free periods. The obtained results indicate that alterations in the availability of neurotransmitters at synapses induced by ADs are strong enough to induce immediate and long-lasting adaptive changes in the neuronal network.

Kusmider|M|M| Faron-Górecka|A|A| Solich|J|J| Pabian|P|P| Dziedzicka-Wasylewska|M|M|

Antidepressants
Receptor autoradiography
Delayed effect
Hybridization in situ
Time-dependent sensitization


Early postnatal feed restriction reduces liver connective tissue levels and affects H3K9 acetylation state of regulated genes associated with protein metabolism in low birth weight pigs.

Abstract: Intrauterine growth retardation is associated with metabolic consequences in adulthood. Since our previous data indicate birth weight-dependent effects of feed restriction (R) on protein degradation processes in the liver, it should be investigated whether effects on connective tissue turnover are obvious and could be explained by global changes of histone H3K9me3 and H3K9ac states in regulated genes. For this purpose, female littermate pigs with low (U) or normal (N) birth weight were subjected to 3-week R (60% of ad libitum fed controls) with subsequent refeeding (REF) for further 5 weeks. The 3-week R-period induced a significant reduction of connective tissue area by 43% in the liver of U animals at 98 d of age, which was not found in age-matched N animals. Of note, after REF at 131 d of age, in previously feed-restricted U animals (UR), the percentage of mean connective tissue was only 53% of ad libitum fed controls (UK), indicating a persistent effect. In U animals, R induced H3K9 acetylation of regulated genes (e.g. XBP1, ERLEC1, GALNT2, PTRH2), which were inter alia associated with protein metabolism. In contrast, REF was mostly accompanied by deacetylation in U and N animals. Thus, our epigenetic data may give a first explanation for the observed birth weight-dependent differences in this connective tissue phenotype.

Nebendahl|Constance|C|
Görs|Solvig|S|
Albrecht|Elke|E|
Krüger|Ricarda|R|
Martens|Karen|K|
Giller|Katrin|K|
Hammon|Harald M|HM|
Rimbach|Gerald|G|
Metges|Cornelia C|CC|

H3K9me3
H3K9ac
Epigenetics
Connective liver tissue
Gene expression
IUGR


Fractionation of Hydrogen Isotopes by Sulfate- and Nitrate-Reducing Bacteria.

Abstract: Hydrogen atoms from water and food are incorporated into biomass during cellular metabolism and biosynthesis, fractionating the isotopes of hydrogen-protium and deuterium-that are recorded in biomolecules. While these fractionations are often relatively constant in plants, large variations in the magnitude of fractionation are observed for many heterotrophic microbes utilizing different central metabolic pathways. The correlation between metabolism and lipid δ(2)H provides a potential basis for reconstructing environmental and ecological parameters, but the calibration dataset has thus far been limited mainly to aerobes. Here we report on the hydrogen isotopic fractionations of lipids produced by nitrate-respiring and sulfate-reducing bacteria. We observe only small differences in fractionation between oxygen- and nitrate-respiring growth conditions, with a typical pattern of variation between substrates that is broadly consistent with previously described trends. In contrast, fractionation by sulfate-reducing bacteria does not vary significantly between different substrates, even when autotrophic and heterotrophic growth conditions are compared. This result is in marked contrast to previously published observations and has significant implications for the interpretation of environmental hydrogen isotope data. We evaluate these trends in light of metabolic gene content of each strain, growth rate, and potential flux and reservoir-size effects of cellular hydrogen, but find no single variable that can account for the differences between nitrate- and sulfate-respiring bacteria. The emerging picture of bacterial hydrogen isotope fractionation is therefore more complex than the simple correspondence between δ(2)H and metabolic pathway previously understood from aerobes. Despite the complexity, the large signals and rich variability of observed lipid δ(2)H suggest much potential as an environmental recorder of metabolism.

Osburn|Magdalena R|MR|
Dawson|Katherine S|KS|
Fogel|Marilyn L|ML|
Sessions|Alex L|AL|

hydrogen isotopes
sulfate-reducing bacteria
NAD(P)H
anaerobic microbial metabolism
fatty acids
transhydrogenase


Crystallization and preliminary X-ray diffraction analysis of FabG from Yersinia pestis.

Abstract: The type II fatty-acid biosynthesis pathway of bacteria provides enormous potential for antibacterial drug development owing to the structural differences between this and the type I fatty-acid biosynthesis system found in mammals. β-Ketoacyl-ACP reductase (FabG) is responsible for the reduction of the β-ketoacyl group linked to acyl carrier protein (ACP), and is essential for the formation of fatty acids and bacterial survival. Here, the cloning, expression, purification, crystallization and diffraction of FabG from Yersinia pestis (ypFabG), the highly virulent causative agent of plague, are reported. Recombinant FabG was expressed, purified to homogeneity and crystallized via the hanging-drop vapour-diffusion technique. Diffraction data were collected at the Australian Synchrotron to 2.30 Å resolution. The crystal displayed P2(1)2(1)2(1) symmetry, with unit-cell parameters a = 68.22, b = 98.68, c = 169.84 Å, and four ypFabG molecules in the asymmetric unit.

Nanson|Jeffrey David|JD|
Forwood|Jade Kenneth|JK|

FabG
β-ketoacyl-ACP reductase
Yersina pestis


Paraproteinaemia in Primary Cutaneous Marginal Zone Lymphoma.

Abstract: Primary cutaneous marginal zone lymphomas (PCMZL) frequently exhibit lymphoplasmacytoid/plasmacytic differentiation, implying the capacity to produce monoclonal immunoglobulins. As these paraproteins are secreted, and thus are measurable in blood and urine, they may correlate with disease burden and serve as tumour markers reflecting therapeutic response. This study retrospectively analysed the records of 23 patients with PCMZL. During treatment and follow-up, laboratory tests, including full blood count, lactate dehydrogenase, serum protein electrophoresis and turbidimetric analyses, were conducted. Thirty-nine percent of cases showed a suspicious serum protein electrophoresis in terms of paraproteinaemia. In 44% of cases the heavy and light chain restriction in tissue samples correlated with serological findings. Altogether, 89% of the PCMZL patients with paraproteinaemia eventually experienced a relapse, in contrast to 62% of the group without paraproteinaemia. This study analysed the incidence and clinical implications of paraproteinaemia in patients with PCMZL. A clear correlation was found between paraproteinaemia, tumour relapse and therapeutic intervention.

Frings|Verena G|VG|
Röding|Kristina|K|
Strate|Alexander|A|
Rosenwald|Andreas|A|
Roth|Sabine|S|
Kneitz|Hermann|H|
Goebeler|Matthias|M|
Geissinger|Eva|E|
Wobser|Marion|M|

lymphoma immunofixation monoclonalgammopathy monoclonalimmunoglobulins


Subcutaneous phaeohyphomycosis due to Alternaria infectoria in a renal transplant patient: surgical treatment with no long-term relapse.

Abstract:
BACKGROUND
Phaeohyphomycosis can be caused by a number of different species, being the most common Alternaria alternata and Alternaria infectoria. The biggest risk factor for the development of the infection is immunosuppression.

AIMS
We present the case of a 64-year-old male renal transplant patient who came to hospital for presenting a tumour in the Achilles region which had been gradually growing in size.

METHODS
A skin biopsy was taken for histological study and culture of fungi and mycobacteria. Blood tests and imaging studies were performed.

RESULTS
Histopathology study and cultures identified A. infectoria as the causal agent. Imaging studies ruled out internal foci of infection. The lesion was surgically removed with no signs of recurrence after 24 months of follow-up.

CONCLUSIONS
There are no treatment guidelines at present for cutaneous and subcutaneous Alternaria spp. infections. Various systemic antifungals have been used, either in combination with surgical removal or alone, with varying results. Surgery alone could be useful in the treatment of solitary, localised lesions in transplant patients in whom there are difficulties in controlling immunosuppression.

Salido-Vallejo|Rafael|R|
Linares-Sicilia|María José|MJ|
Garnacho-Saucedo|Gloria|G|
Sánchez-Frías|Marina|M|
Solís-Cuesta|Francisco|F|
Gené|Josepa|J|
Moreno-Giménez|José Carlos|JC|

Phaeohyphomycosis
Alternaria infectoria
Feohifomicosis
Kidney transplantation
Trasplante de riñón


Metastatic breast carcinoma to the urinary bladder-a report of 11 cases including a tumor to tumor metastasis.

Abstract: Metastatic breast carcinoma to the urinary bladder is rare. Eleven cases of metastatic breast carcinoma to the bladder are described in this report, including one case with a tumor to tumor metastasis. The patients ranged from 51 to 83 years of age. The time intervals between the diagnosis of primary breast cancer and the occurrence of bladder metastases ranged from 41 to 336 months. There were seven cases of invasive ductal carcinoma and four cases of invasive lobular carcinoma. In one case, a lobular carcinoma of the breast metastasized to a concurrent squamous cell carcinoma of the bladder. The immunophenotypic status of estrogen receptor and Her2 expression of the metastatic carcinomas were all concordant with the primary tumors. In nine patients with follow-up available, seven patients died of the disease ranging from 1 to 23 months after the diagnosis of the bladder metastasis and two patients were alive at 5 months of follow-up. To date, this report is the largest single series of patients with breast carcinoma metastatic to the bladder. It is the first reported instance of lobular carcinoma of the breast metastasizing to a squamous cell carcinoma of the bladder.

Breast carcinoma
Tumor to tumor metastasis
Metastasis
Bladder


Prospective memory in bipolar disorder: A meta-analysis.

Abstract: There are conflicting findings about prospective memory (PM) performance in bipolar disorder. This meta-analysis systematically examined PM in patients with bipolar disorders. Articles were systematically searched in both English and Chinese databases, from their inception to Nov 15, 2016. Only case-control studies on PM in bipolar patients were included for analyses. The random effect model was used in all meta-analytic outcomes. Four studies (n = 390) comparing PM performance between patients with bipolar disorder (n = 208) and healthy controls (n = 182) were included. Three studies were rated as "high quality", while the quality of evidence in 3 meta-analyzable outcomes ranged from "moderate" (67%) to "high" (33%). Compared to healthy controls, bipolar disorder patients showed impairments in overall PM [2 studies, n = 196; SMD: - 1.08 (95%CI: - 1.61, - 0.55), P < 0.0001; I2 = 65%], event-based PM [4 studies, n = 367; SMD: - 0.51 (95%CI: - 0.78, - 0.23), P = 0.0003; I2 = 37%] and time-based PM performance [4 studies, n = 367; SMD: - 0.82 (95%CI: - 1.11, - 0.52), P < 0.0001; I2 = 41%]. In this meta-analysis, both time-based PM and event-based PM deficits appeared to be evident in bipolar disorder.

Zhou|Fu-Chun|FC|
Wang|Yuan-Yuan|YY|
Zheng|Wei|W|
Ungvari|Gabor S|GS|
Ng|Chee H|CH|
Yuan|Zhen|Z|
Xiang|Yu-Tao|YT|

Prospective memory
Bipolar disorder
Meta-analysis


iSulfoTyr-PseAAC: Identify Tyrosine Sulfation Sites by Incorporating Statistical Moments via Chou's 5-steps Rule and Pseudo Components.

Abstract:
Background
The amino acid residues, in protein, undergo post-translation modification (PTM) during protein synthesis, a process of chemical and physical change in an amino acid that in turn alters behavioral properties of proteins. Tyrosine sulfation is a ubiquitous posttranslational modification which is known to be associated with regulation of various biological functions and pathological pro-cesses. Thus its identification is necessary to understand its mechanism. Experimental determination through site-directed mutagenesis and high throughput mass spectrometry is a costly and time taking process, thus, the reliable computational model is required for identification of sulfotyrosine sites.

Methodology
In this paper, we present a computational model for the prediction of the sulfotyrosine sites named iSulfoTyr-PseAAC in which feature vectors are constructed using statistical moments of protein amino acid sequences and various position/composition relative features. These features are in-corporated into PseAAC. The model is validated by jackknife, cross-validation, self-consistency and in-dependent testing.

Results
Accuracy determined through validation was 93.93% for jackknife test, 95.16% for cross-validation, 94.3% for self-consistency and 94.3% for independent testing.

Conclusion
The proposed model has better performance as compared to the existing predictors, how-ever, the accuracy can be improved further, in future, due to increasing number of sulfotyrosine sites in proteins.

Barukab|Omar|O|
Khan|Yaser Daanial|YD|
Khan|Sher Afzal|SA|
Chou|Kuo-Chen|KC|

Sulfation
statistical moments
5-step rule
pseudo components
sulfotyrosine
PseAAC


Inhibiting Heat Shock Proteins Can Potentiate the Cytotoxic Effect of Cannabidiol in Human Glioma Cells.

Abstract: Cannabinoids possess a number of characteristics that make them putative anticancer drugs, and their value as such is currently being explored in a number of clinical studies. To further understand the roles that cannabinoids may have, we performed gene expression profiling in glioma cell lines cultured with cannabidiol (CBD) and/or Δ9-tetrahydrocannabinol (THC), and pursued targets identified by this screening. Results showed that a large number of genes belonging to the heat shock protein (HSP) super-family were up-regulated following treatment, specifically with CBD. Increases were observed both at the gene and protein levels and arose as a consequence of increased generation of ROS by CBD, and correlated with an increase in a number of HSP client proteins. Furthermore, increases impeded the cytotoxic effect of CBD; an effect that was improved by co-culture with pharmacalogical inhibitors of HSPs. Similarly, culturing glioma cells with CBD and HSP inhibitors increased radiosensitivity when compared to CBD-alone. Taken together, these data indicate that the cytotoxic effects of CBD can be diminished by HSPs that indirectly rise as a result of CBD use, and that the inclusion of HSP inhibitors in CBD treatment regimens can enhance the overall effect.

Scott|Katherine A|KA|
Dennis|Jayne L|JL|
Dalgleish|Angus G|AG|
Liu|Wai M|WM|

D015972:Gene Expression Regulation, Neoplastic

D020411:Oligonucleotide Array Sequence Analysis

D060888:Real-Time Polymerase Chain Reaction

D020133:Reverse Transcriptase Polymerase Chain Reaction

Heat shock proteins
cannabidiol
glioma
reactive oxygen species
tetrahydrocannabinol


How Active Mechanics and Regulatory Biochemistry Combine to Form Patterns in Development.

Abstract: The development of organisms starting from their zygotic state involves a tight integration of the myriad biochemical signaling interactions with the mechanical forces that eventually pattern and shape the resulting embryo. In the past decade, it has become increasingly evident that several important developmental processes involve mechanical forces in an essential manner. In this review, we highlight the multifaceted role of mechanics in pattern formation, from protein and cell sorting to the generation of tissue shape. We then review the ways in which the active cellular cytoskeleton self-organizes to form dynamic patterns. Finally, we focus on mechanochemical feedback, where signaling proteins can establish patterns via coupling to the activity of the cytoskeleton. Throughout the review, we focus on the generic physical principles of the establishment of active mechanochemical patterns and point toward future directions in studying how the principles of mechanics and chemistry combine to drive morphogenetic pattern formation.

Gross|Peter|P|
Kumar|K Vijay|KV|
Grill|Stephan W|SW|

pattern formation
mechanochemical patterns
active matter
morphogenesis


Protein Hydrolysates from Fenugreek (Trigonella foenum graecum) as Nutraceutical Molecules in Colon Cancer Treatment.

Abstract: The application of plant extracts for therapeutic purposes has been used in traditional medicine since the plants are a source of a great variety of chemical compounds that possess biological activity. Actually, the effect of these extracts on diseases such as cancer is being widely studied. Colorectal adenocarcinoma is one of the main causes of cancer related to death and the second most prevalent carcinoma in Western countries. The aim of this work is to study the possible effect of two fenugreek (Trigonella foenum graecum) protein hydrolysates on treatment and progression of colorectal cancer. Fenugreek proteins from seeds were hydrolysed by using two enzymes separately, which are named Purafect and Esperase, and were then tested on differentiated and undifferentiated human colonic adenocarcinoma Caco2/TC7 cells. Both hydrolysates did not affect the growth of differentiated cells, while they caused a decrease in undifferentiated cell proliferation by early apoptosis and cell cycle arrest in phase G1. This was triggered by a mitochondrial membrane permeabilization, cytochrome C release to cytoplasm, and caspase-3 activation. In addition, the hydrolysates of fenugreek proteins displayed antioxidant activity since they reduce the intracellular levels of ROS. These findings suggest that fenugreek protein hydrolysates could be used as nutraceutical molecules in colorectal cancer treatment.

Allaoui|Amine|A|
Gascón|Sonia|S|
Benomar|Souhila|S|
Quero|Javier|J|
Osada|Jesús|J|
Nasri|Moncef|M|
Rodríguez-Yoldi|María Jesús|MJ|
Boualga|Ahmed|A|

protein hydrolysate
fenugreek
apoptosis
antioxidant
Caco2 cells
antiproliferative


Spectral Characteristics of Square-Wave-Modulated Type II Long-Period Fiber Gratings Inscribed by a Femtosecond Laser.

Abstract: We study here the spectral characteristics of square-wave-modulated type II long-period fiber gratings (LPFGs) inscribed by a femtosecond laser. Both theoretical and experimental results indicate that higher-order harmonics refractive index (RI) modulation commonly exists together with the fundamental harmonic RI modulation in such LPFGs, and the duty cycle of a square wave has a great influence on the number and amplitudes of higher-order harmonics. A linear increase in the duty cycle in a series of square wave pulses will induce another LPFG with a minor difference in periods, which is useful for expanding the bandwidth of LPFGs. We also propose a method to reduce insertion loss by fabricating type II LPFGs without higher-order harmonic resonances. This work intensifies our comprehension of type II fiber gratings with which novel optical fiber sensors can be fabricated.

Zhao|Xiaofan|X| Li|Hongye|H| Rao|Binyu|B| Wang|Meng|M| Wu|Baiyi|B| Wang|Zefeng|Z|

long-period fiber gratings
femtosecond laser
higher-order harmonics


In vivo evaluation of the CB1 allosteric modulator LDK1258 reveals CB1-receptor independent behavioral effects.

Abstract: In the present study, we examined whether LDK1258, which produces strong CB1 receptor allosteric effects in in vitro assays, would elicit in vivo effects consistent with allosteric activity. In initial studies, LDK1258 reduced food consumption and elicited delayed antinociceptive effects in the chronic constrictive injury of the sciatic nerve (CCI) model of neuropathic pain, which unexpectedly emerged 4 h post-injection. UPLC-MS/MS analysis quantified significant levels of LDK1258 in both blood and brain tissue at 30 min post-administration that remained stable up to 4 h. The observation that LDK1258 also produced respective antinociceptive and anorectic effects in rimonabant-treated wild type mice and CB1 (-/-) mice suggests an off-target mechanism of action. Likewise, LDK1258 produced a partial array of common cannabimimetic effects in the tetrad assay, which were not CB1 receptor mediated. Additionally, LDK1258 did not substitute for the CB1 receptor orthosteric agonists CP55,940 or anandamide in the drug discrimination paradigm. In other in vivo assays sensitive to CB1 receptor allosteric modulators, LDK1258 failed to shift the dose-response curves of either CP55,940 or anandamide in producing thermal antinociception, catalepsy, or hypothermia, and did not alter the generalization curve of either drug in the drug discrimination assay. Thus, this battery of tests yielded results demonstrating that LDK1258 produces antinociceptive effects in the CCI model of neuropathic pain, anorectic effects, and other in vivo pharmacological effects in a manner inconsistent with CB1 receptor allosterism. More generally, this study offers a straightforward screening assay to determine whether newly synthesized CB1 receptor allosteric modulators translate to the whole animal.

Mustafa|Mohammed|M|
Donvito|Giulia|G|
Moncayo|Lauren|L|
Swafford|Amelia|A|
Poklis|Justin|J|
Grauer|Ralph|R|
Olszewska|Teresa|T|
Ignatowska-Jankowska|Bogna|B|
Kendall|Debra A|DA|
Lu|Dai|D|
Lichtman|Aron H|AH|

Allosteric modulator
Neuropathic pain
Anandamide
Drug discrimination
CB(1) receptor
CP55
940
Cannabinoid
Rimonabant


Strain-Dependent Activation and Inhibition of Human Immunodeficiency Virus Entry by a Specific PF-68742 Stereoisomer.

Abstract: Human immunodeficiency virus (HIV-1) entry into cells is mediated by the viral envelope glycoprotein (Env) trimer, which consists of three gp120 exterior glycoproteins and three gp41 transmembrane glycoproteins. When gp120 binds sequentially to the receptors CD4 and CCR5 on the target cell, the metastable Env trimer is triggered to undergo entry-related conformational changes. PF-68742 is a small molecule that inhibits the infection of a subset of HIV-1 strains by interfering with an Env function other than receptor binding. Determinants of HIV-1 resistance to PF-68742 map to the disulfide loop and fusion peptide of gp41. Of the four possible PF-68742 stereoisomers, only one, MF275, inhibited the infection of CD4-positive CCR5-positive cells by some HIV-1 strains. MF275 inhibition of these HIV-1 strains occurred after CD4 binding but before the formation of the gp41 six-helix bundle. Unexpectedly, MF275 activated the infection of CD4-negative CCR5-positive cells by several HIV-1 strains resistant to the inhibitory effects of the compound in CD4-positive target cells. In contrast to CD4 complementation by CD4-mimetic compounds, activation of CD4-independent infection by MF275 did not depend upon the availability of the gp120 Phe 43 cavity. Sensitivity to inhibitors indicates that MF275-activated virus entry requires formation/exposure of the gp41 heptad repeat (HR1) as well as CCR5 binding. MF275 apparently activates a virus entry pathway parallel to that triggered by CD4 and CD4-mimetic compounds. Strain-dependent divergence in Env conformational transitions allows different outcomes, inhibition or activation, in response to MF275. Understanding the mechanisms of MF275 activity should assist efforts to optimize its utility.IMPORTANCE Envelope glycoprotein (Env) spikes on the surface of human immunodeficiency virus (HIV-1) bind target cell receptors, triggering changes in the shape of Env. We studied a small molecule, MF275, that also induced shape changes in Env. The consequences of MF275 interaction with Env depended on the HIV-1 strain, with infection by some viruses inhibited and infection by other viruses enhanced. These studies reveal the strain-dependent diversity of HIV-1 Envs as they undergo shape changes in proceeding down the entry pathway. Appreciation of this diversity will assist attempts to develop broadly active inhibitors of HIV-1 entry.

Zhao|Connie|C|
Princiotto|Amy M|AM|
Nguyen|Hanh T|HT|
Zou|Shitao|S|
Zhao|Meiqing Lily|ML|
Zhang|Shijian|S|
Herschhorn|Alon|A|
Farrell|Mark|M|
Pahil|Karanbir|K|
Melillo|Bruno|B|
Sambasivarao|Somisetti V|SV|
Abrams|Cameron|C|
Smith|Amos B|AB|
Madani|Navid|N|
Sodroski|Joseph|J|

D000998:Antiviral Agents
D015496:CD4-Positive T-Lymphocytes
D015699:HIV Envelope Protein gp120
D015700:HIV Envelope Protein gp41
D015658:HIV Infections
D015497:HIV-1
D006801:Humans
D011485:Protein Binding
D011487:Protein Conformation
D055503:Protein Multimerization
D011728:Pyridones
D019713:Receptors, CCR5
D013237:Stereoisomerism
D013449:Sulfonamides
D053586:Virus Internalization
D014779:Virus Replication

Env
conformational change
sensitization
inhibitor
CD4 independent
antibody
mutant
retrovirus
variation


Rationale and pre-clinical evidences for the use of autologous cartilage micrografts in cartilage repair.

Abstract:
BACKGROUND
The management of cartilage lesions is an open issue in clinical practice, and regenerative medicine represents a promising approach, including the use of autologous micrografts whose efficacy was already tested in different clinical settings. The aim of this study was to characterize in vitro the effect of autologous cartilage micrografts on chondrocyte viability and differentiation and perform an evaluation of their application in racehorses affected by joint diseases.

MATERIALS AND METHODS
Matched human chondrocytes and micrografts were obtained from articular cartilage using Rigenera® procedure. Chondrocytes were cultured in the presence or absence of micrografts and chondrogenic medium to assess cell viability and cell differentiation. For the pre-clinical evaluation, three racehorses affected by joint diseases were treated with a suspension of autologous micrografts and PRP in arthroscopy interventions. Clinical and radiographic follow-ups were performed up to 4 months after the procedure.

RESULTS
Autologous micrografts support the formation of chondrogenic micromasses thanks to their content of matrix and growth factors, such as transforming growth factor β (TGFβ) and insulin-like growth factor 1 (IGF-1). On the other hand, no significant differences were observed on the gene expression of type II collagen, aggrecan, and SOX9. Preliminary data in the treatment of racehorses are suggestive of a potential in vivo use of micrografts to treat cartilage lesions.

CONCLUSION
The results reported in this study showed the role of articular micrografts in the promoting chondrocyte differentiation suggesting their potential use in the clinical practice to treat articular lesions.

Viganò|Marco|M|
Tessaro|Irene|I|
Trovato|Letizia|L|
Colombini|Alessandra|A|
Scala|Marco|M|
Magi|Alberto|A|
Toto|Andrea|A|
Peretti|Giuseppe|G|
de Girolamo|Laura|L|

Micrografts
Cartilage repair
Regenerative medicine
Rigenera
Cartilage defects


Vein of foramen caecum: imaging findings.

Abstract: Vein of foramen caecum has been classically described as a vein that connects nasal mucosa to the superior sagittal sinus in classic anatomy textbooks. However, its existence is controversial in literature. Herein, we demonstrated computed tomography and contrast enhanced magnetic resonance imaging findings of a tubular vascular structure extending to nasal mucosa and superior sagittal sinus.

Tutar|Onur|O|
Kandemirli|Sedat Giray|SG|
Yildirim|Duzgun|D|
Memis|Emine Sebnem|ES|
Bakan|Selim|S|

D000328:Adult
D063405:Anatomic Variation
D059350:Chronic Pain
D003287:Contrast Media
D005260:Female
D005624:Frontal Bone
D006261:Headache
D006801:Humans
D008279:Magnetic Resonance Imaging
D009297:Nasal Mucosa
D054063:Superior Sagittal Sinus
D014057:Tomography, X-Ray Computed
D055815:Young Adult

Computed tomography
Magnetic resonance imaging
Foramen caecum (cecum)
Vein of foramen caecum (cecum)


ERBB signaling attenuates proinflammatory activation of nonclassical monocytes.

Abstract: Immune activation in chronic systolic heart failure (HF) correlates with disease severity and prognosis. Recombinant neuregulin-1 (rNRG-1) is being developed as a possible therapy for HF, based on the activation of ERBB receptors in cardiac cells. Work in animal models of HF led us to hypothesize that there may be direct effects of NRG-1 on immune system activation and inflammation. We investigated the expression of ERBB receptors and the effect of rNRG-1 isoform glial growth factor 2 (GGF2) in subpopulations of peripheral blood mononuclear cells (PB MNCs) in subjects with HF. We found that human monocytes express both ERBB2 and ERBB3 receptors, with high interindividual variability among subjects. Monocyte surface ERBB3 and TNF-α mRNA expression were inversely correlated in subjects with HF but not in human subjects without HF. GGF2 activation of ERBB signaling ex vivo inhibited LPS-induced TNF-α production, specifically in the CD14lowCD16+ population of monocytes in a phosphoinositide 3-kinase-dependent manner. GGF2 suppression of TNF-α correlated directly with the expression of ERBB3. In vivo, a single dose of intravenous GGF2 reduced TNF-α expression in PB MNCs of HF subjects participating in a phase I safety study of GGF2. These results support a role for ERBB3 signaling in the regulation of TNF-α production from CD14lowCD16+ monocytes and a need for further investigation into the clinical significance of NRG-1/ERBB signaling as a modulator of immune system function.NEW & NOTEWORTHY This study identified a novel role of neuregulin-1 (NRG-1)/ERBB signaling in the control of proinflammatory activation of monocytes. These results further improve our fundamental understanding of cardioprotective effects of NRG-1 in patients with heart failure.

Ryzhov|Sergey|S|
Matafonov|Anton|A|
Galindo|Cristi L|CL|
Zhang|Qinkun|Q|
Tran|Truc-Linh|TL|
Lenihan|Daniel J|DJ|
Lenneman|Carrie Geisberg|CG|
Feoktistov|Igor|I|
Sawyer|Douglas B|DB|

heart failure
inflammation
ERBB receptor tyrosine kinase
inflammatory cytokine
neuregulin


Mortality and Macrovascular Risk in Elderly With Hypertension and Diabetes: Effect of Intensive Drug Therapy.

Abstract:
BACKGROUND
This study identifies the effect of intensive drug therapy (IDT) in individuals age 65+ with diabetes (type 2 diabetes mellitus (T2D)) and hypertension on all-cause death, congestive heart failure (CHF), hospitalization for myocardial infarction (MI), and stroke or transient ischemic attack (TIA).

METHODS
Individuals from the Medicare 5% dataset with hypertension and T2D undergoing IDT for these conditions were propensity score matched to a nonintensive drug-therapy group. Hazard ratios (HRs) were obtained using the Cox proportional hazard model.

RESULTS
IDT was associated with increased risk of CHF (HR 2.32; 95% confidence interval (CI) 2.32-2.38), MI (HR 4.27; 95% CI 4.05-4.52), and stroke or TIA (HR 1.80; 95% CI 1.70-1.89) but decreased risk of death (HR 0.95; 95% CI 0.93-0.97). Risk for CHF (HR 0.73; 95% CI 0.71-0.73), MI (HR 0.64; 95% CI 0.62-0.67), stroke or TIA (HR 0.82; 95% CI 0.78-0.86), and death (HR 0.29; 95% CI 0.28-0.29) was decreased by adherence to diabetes management guidelines.

CONCLUSIONS
Use of IDT in a high-risk population delays death but not severe macrovascular outcomes. Protective effects of IDT in high-risk patients likely outweigh polypharmacy-related health concerns.

Yashkin|Arseniy P|AP|
Kravchenko|Julia|J|
Yashin|Anatoliy I|AI|
Sloan|Frank|F|

mortality
hypertension
intensive drug therapy
diabetes mellitus
adherence
macrovascular outcomes
blood pressure


Effect of fish and krill oil supplementation on glucose tolerance in rabbits with experimentally induced obesity.

Abstract:
PURPOSE
This study was conducted to investigate the effect of fish oil (FO) and krill oil (KO) supplementation on glucose tolerance in obese New Zealand white rabbits.

METHODS
The experiments were carried out with 24 male rabbits randomly divided into four groups: KO-castrated, treated with KO; FO-castrated, treated with FO; C-castrated, non-treated; NC-non-castrated, non-treated. At the end of treatment period (2 months), an intravenous glucose tolerance test (IVGTT) was performed in all rabbits.

RESULTS
Fasting blood glucose concentrations in FO and KO animals were significantly lower than in group C. The blood glucose concentrations in FO- and KO-treated animals returned to initial values after 30 and 60 min of IVGTT, respectively. In liver, carnitine palmitoyltransferase 2 (Cpt2) and 3-hydroxy-3-methyl-glutaryl-CoA synthase 2 (Hmgcs2) genes were significantly increased in FO-fed rabbits compared with the C group. Acetyl-CoA carboxylase alpha (Acaca) expression was significantly reduced in both KO- and FO-fed rabbits. In skeletal muscle, Hmgcs2 and Cd36 were significantly higher in KO-fed rabbits compared with the C group. Acaca expression was significantly lower in KO- and FO-fed rabbits compared with the C group.

CONCLUSION
The present results indicate that FO and KO supplementation decreases fasting blood glucose and improves glucose tolerance in obese New Zealand white rabbits. This could be ascribed to the ameliorated insulin sensitivity and insulin secretion and modified gene expressions of some key enzymes involved in β-oxidation and lipogenesis in liver and skeletal muscle.

Ivanova|Zhenya|Z|
Bjørndal|Bodil|B|
Grigorova|Natalia|N|
Roussenov|Anton|A|
Vachkova|Ekaterina|E|
Berge|Kjetil|K|
Burri|Lena|L|
Berge|Rolf|R|
Stanilova|Spaska|S|
Milanova|Anelia|A|
Penchev|Georgi|G|
Vik|Rita|R|
Petrov|Vladimir|V|
Georgieva|Teodora Mircheva|TM|
Bivolraski|Boycho|B|
Georgiev|Ivan Penchev|IP|

Krill oil
Glucose tolerance
Obesity
Fish oil
Gene expression
Lipogenesis


Copper and zinc in rhizospheric soil of wild plants growing in long-term acid vineyard soils. Insights on availability and metal remediation.

Abstract: Total and available Cu and Zn levels were assessed in plant biomass, as well as in two rhizosphere fractions (tightly adhering rhizosphere (TAR), and loosely adhering rhizosphere (LAR)), in wild plants species from vineyard soils. Both TAR and LAR fractions were enriched in total Cu and Zn (1.7 and 1.6 times, respectively), and in available Cu and Zn (2.2 and 19.5 times, respectively), with the former being significantly higher for TAR than for LAR fractions. Mean values for total Cu accumulation in root and aerial biomass of the studied wild plants were 84 and 66 mg kg-1, respectively, being 57 and 79 mg kg-1 for Zn. No correlations were found among metal contents in plant biomass and available Cu and Zn concentrations in the rhizosphere fractions. Translocation factor (TF) values for Zn (range 1.0-3.5) indicate preferential accumulation in the aerial biomass in all the studied wild plants. On the contrary, TF for Cu shows a greater variability, depending on plant species, and ranging from 0.2 to 5.9. Regarding bioaccumulation factor (BAF), ranges were 0.03-0.27 and 0.13-0.58, for Cu and Zn, respectively. Results suggest that D. sanguinalis, P. hieracioides, S. viridis, and T. barbata could be useful for Cu remediation in the studied soils, by means of phytostabilization processes.

Campillo-Cora|C|C|
Fernández-Calviño|D|D|
Pérez-Rodríguez|P|P|
Fernández-Sanjurjo|M J|MJ|
Núñez-Delgado|A|A|
Álvarez-Rodríguez|E|E|
Arias-Estévez|M|M|
Nóvoa-Muñoz|J C|JC|

D052918:Environmental Restoration and Remediation

Rhizosphere
Vineyard soils
Availability
Phytostabilization
Cu and Zn pollution


TBAI/TBHP-Promoted Generation of Malonyl Radicals: Oxidative Coupling with Styrenes Leads to γ-Keto Diesters.

Abstract: A metal-free protocol for oxidative coupling of malonic esters with styrenes to form γ-keto diesters has been developed. Key to the success of this process is the generation of malonyl radicals from unfunctionalized malonic esters under organo-catalysis conditions with TBAI and TBHP. This process tolerates both terminal and internal olefins with diverse malonic esters. It provides a new green metal-free alternative to traditional metal mediated process for generation of malonyl radicals and there by γ-keto diesters.

malonyl radical
oxidative coupling
TBAI/TBHP
ketodiester
metal-free conditions


Use of infrared spectroscopy and geospatial techniques for measurement and spatial prediction of soil properties.

Abstract: The main aim of this research was to assess the use of mid-infrared (MIR) spectroscopy and geostatistical model for the evaluation and mapping of the spatial variability of some selected soil properties across a field. It is with the view of aiding site-specific soil management decisions. The performance of the model for the prediction of the components (soil parameters) was reported using the coefficient of determination (R2) and root mean square error (RMSE) values of the validation data set. Results revealed that least square regression model performed better in predicting cation exchange capacity-CEC (R2 = 0.88 and RMSE = 8.98), soil organic carbon-OC (R2 = 0.88, RMSE = 0.55), and total nitrogen-TN (R2 = 0.91 and RMSE = 0.04). The first five principal components (PC) accounted for 78.17% of the total variance (PC1 = 25.75%, PC2 = 18.06%, PC3 = 13.85%, PC4 = 11.12%, and PC5 = 9.39%) and represented most of the variation within the data set. The coefficient of variation ranged from 6.73% for soil pH to 57.02% for available phosphorus (av. P). The soil pH values ranged from 4.21 to 6.57. The mean soil OC density was 2.14 kg m-2 within 50 cm soil depth. Nearly 96-97% of the soils contained av. P and sulfur (   -S) below the critical levels. The overall results revealed that soil properties varied spatially. Hence, we suggest that mapping the spatial variability of soils across a field is a cost-effective solution for soil management.

Infrared spectroscopy
Geostatistical model
Soil management
Agricultural science
Biogeochemistry
Biological sciences
Chemistry
Digital soil mapping
Earth sciences
Environmental geochemistry
Environmental science
Precision agriculture
Soil science
Soil survey
Soil variability
Variable rate technology


Workplace bullying and violence as risk factors for type 2 diabetes: a multicohort study and meta-analysis.

Abstract:
AIMS/HYPOTHESIS
The aim of this multicohort study was to examine whether employees exposed to social stressors at work, such as workplace bullying and violence, have an increased risk of type 2 diabetes.

METHODS
The study included 45,905 men and women (40-65 years of age and free of diabetes at baseline) from four studies in Sweden, Denmark and Finland. Workplace bullying and violence were self-reported at baseline. Incident diabetes was ascertained through national health and medication records and death registers. Marginal structural Cox models adjusted for age, sex, country of birth, marital status and educational level were used for the analyses.

RESULTS
Nine per cent of the population reported being bullied at work and 12% were exposed to workplace violence or threats of violence. Bullied participants had a 1.46 (95% CI 1.23, 1.74) times higher risk of developing diabetes compared with non-bullied participants. Exposure to violence or threats of violence was also associated with a higher risk of diabetes (HR 1.26 [95% CI 1.02, 1.56]). The risk estimates attenuated slightly when taking BMI into account, especially for bullying. The results were similar for men and women, and were consistent across cohorts.

CONCLUSIONS/INTERPRETATION
We found a higher risk of incident type 2 diabetes among employees exposed to bullying or violence in the workplace. Further research is needed to determine whether policies to reduce bullying and violence at work may reduce the incidence of type 2 diabetes in working populations. Research on the mechanisms is also highly warranted.

Xu|Tianwei|T|
Magnusson Hanson|Linda L|LL|
Lange|Theis|T|
Starkopf|Liis|L|
Westerlund|Hugo|H|
Madsen|Ida E H|IEH|
Rugulies|Reiner|R|
Pentti|Jaana|J|
Stenholm|Sari|S|
Vahtera|Jussi|J|
Hansen|Åse M|ÅM|
Kivimäki|Mika|M|
Rod|Naja H|NH|

Workplace
Bullying
Violence
Diabetes
Meta-analysis
Occupational health
Stress


Clinical Value of Inflammation-Based Prognostic Scores to Predict the Resectability of Hyperbilirubinemia Patients with Potentially Resectable Hilar Cholangiocarcinoma.

Abstract:
BACKGROUND
We aimed to examine whether inflammation-based prognostic scores could predict tumor resectability in a cohort of hilar cholangiocarcinoma patients with preoperative hyperbilirubinemia. We also sought to investigate the prognostic factors associated with overall survival in the subgroup of patients with an R0 resection.

METHODS
A total of 173 patients with potentially resectable hilar cholangiocarcinoma, as judged by radiological examinations, were included. The potential relationship of the Glasgow prognostic score (GPS), modified GPS, platelet lymphocyte ratio (PLR), neutrophil lymphocyte ratio (NLR), prognostic nutritional index (PNI), and prognostic index (PI) with tumor resectability were investigated using univariate and multivariate analysis.

RESULTS
Among the 173 patients, 134 had R0 resection margins. Univariate analysis identified that patients with PLR ≥ 150, NLR ≥ 3, PNI ≥ 45, GPS (0.1/2), modified GPS (0.1/2), preoperative CA 125 > 35 U/mL, and a tumor size ≥ 3 cm were more likely to have unresectable tumors. Multivariate analysis indicated that tumor size ≥ 3 cm (OR = 2.422, 95% CI: 1.053-5.573; P = 0.037), PLR ≥ 150 (OR = 3.324, 95% CI: 1.143-9.667; P = 0.027), preoperative CA 125 > 35 U/mL (OR = 3.184, 95% CI: 1.316-7.704; P = 0.010), and GPS (0.1/2) (OR = 2.440, 95% CI: 1.450-4.107; P = 0.001) were independent factors associated with tumor resectability. In selected patients with an R0 resection in this cohort, nodal status (P = 0.010) and tumor differentiation (P = 0.025) were predictive of poor survival outcome.

CONCLUSION
Patients with higher GPS, CA 125, and PLR levels, and a larger tumor size, tend to have unresectable tumors even if they were judged as potentially resectable using preoperative radiological examinations.

Hu|Hai-Jie|HJ| Jin|Yan-Wen|YW| Zhou|Rong-Xing|RX| Ma|Wen-Jie|WJ| Yang|Qin|Q| Wang|Jun-Ke|JK| Liu|Fei|F| Cheng|Nan-Sheng|NS| Li|Fu-Yu|FY|0000-0003-2755-2887

Inflammation-based prognostic score
Hilar cholangiocarcinoma
Tumor resectability
Prognosis


Characteristics of Patients with End-Stage Kidney Disease in ADPKD.

Abstract:
Introduction
Cystic expansion damaging the parenchyma is thought to lead to end-stage kidney disease (ESKD) in autosomal dominant polycystic kidney disease (ADPKD). Here we characterized genotypic and phenotypic attributes of ADPKD at time of ESKD.

Methods
This is a retrospective cross-sectional study of patients with ADPKD with ESKD evaluated at Mayo Clinic with available abdominal computed tomography (CT) or magnetic resonance imaging (MRI). Kidney volumes were measured (total kidney volume adjusted for height [HtTKV]), Mayo Image Class (MIC) calculated, ADPKD genotype determined, and clinical and laboratory features obtained from medical records.

Results
Differences in HtTKV at ESKD were associated with patient age and sex; older patients and women had smaller HtTKV at ESKD. HtTKV at ESKD was observed to be 12.3% smaller with each decade of age (P < 0.01); but significant only in women (17.8%, P < 0.01; men 6.9%, P = 0.06). Patients with onset of ESKD at <47, 47-61, or >61 years had different characteristics, with a shift from youngest to oldest in male to female enrichment, MIC from 1D/1E to 1B/1C, likely fully penetrant PKD1 mutations from 95% to 42%, and presence of macrovascular disease from 8% to 40%. Macrovascular disease was associated with smaller kidneys in female patients.

Conclusion
HtTKV at ESKD was smaller with advancing age in patients with ADPKD, particularly in women. These novel findings provide insight into possible underlying mechanisms leading to ESKD, which differ between younger and older individuals. Cystic growth is the predominant mechanism in younger patients with ESKD, whereas aging-related factors, including vascular disease, becomes potentially important as patients age.

Shukoor|Shehbaz S|SS|
Vaughan|Lisa E|LE|
Edwards|Marie E|ME|
Lavu|Sravanthi|S|
Kline|Timothy L|TL|
Senum|Sarah R|SR|
Mkhaimer|Yaman|Y|
Zaatari|Ghaith|G|
Irazabal|Maria V|MV|
Neal|Reem|R|
Hogan|Marie C|MC|
Zoghby|Ziad M|ZM|
Harris|Peter C|PC|
Torres|Vicente E|VE|
Chebib|Fouad T|FT|

ADPKD
ESKD
Polycystic Kidney Disease
Total Kidney Volume
Aging
Characteristics of ESKD in ADPKD
Gender
TKV


First Metatarsophalangeal Joint Arthrodesis: A Narrative Review of Fixation Constructs and Their Evolution.

Abstract: First metatarsophalangeal (MTP) joint arthrodesis is a surgical procedure in which the first metatarsal head is fused to the proximal phalanx of the great toe in order to permanently stiffen the first MTP joint. It was originally proposed as a treatment for severe cases of hallux valgus deformity, but the procedure's indications and utilization have expanded since its initial development. Despite a wide variety of indications, first MTP arthrodesis has been shown to have reliable, satisfactory outcomes. As a result, the development of a wide array of surgical approaches, joint preparation techniques, and fixation devices used in the procedure has occurred. In this narrative review, we highlight the evolution of fixation constructs used in first MTP arthrodesis in order to provide a frame of reference for the various types of fixation constructs available.

LaCoste|Ketrick L|KL|
Andrews|Nicholas A|NA|
Ray|Jessyca|J|
Harrelson|Whitt M|WM|
Shah|Ashish|A|

fixation
construct
first metatarsophalangeal arthrodesis
foot and ankle
fusion
orthopaedic surgery
plate
screw
staple


Intrafraction tumor motion during deep inspiration breath hold pancreatic cancer treatment.

Abstract:
PURPOSE
Beam gating with deep inspiration breath hold (DIBH) has been widely used for motion management in radiotherapy. Normally it relies on some external surrogate for estimating the internal target motion, while the exact internal motion is unknown. In this study, we used the intrafraction motion review (IMR) application to directly track an internal target and characterized the residual motion during DIBH treatment for pancreatic cancer patients through their full treatment courses.

METHODS AND MATERIALS
Eight patients with pancreatic cancer treated with DIBH volumetric modulated arc therapy in 2017 and 2018 were selected for this study, each with some radiopaque markers (fiducial or surgical clips) implanted near or inside the target. The Varian Real-time Position Management (RPM) system was used to monitor the breath hold, represented by the anterior-posterior displacement of an external surrogate, namely reflective markers mounted on a plastic block placed on the patient's abdomen. Before each treatment, a cone beam computed tomography (CBCT) scan under DIBH was acquired for patient setup. For scan and treatment, the breath hold reported by RPM had to lie within a 3 mm window. IMR kV images were taken every 20° or 40° gantry rotation during dose delivery, resulting in over 5000 images for the cohort. The internal markers were manually identified in the IMR images. The residual motion amplitudes of the markers as well as the displacement from their initial positions located in the setup CBCT images were analyzed.

RESULTS
Even though the external markers indicated that the respiratory motion was within 3 mm in DIBH treatment, significant residual internal target motion was observed for some patients. The range of average motion was from 3.4 to 7.9 mm, with standard deviation ranging from 1.2 to 3.5 mm. For all patients, the target residual motions seemed to be random with mean positions around their initial setup positions. Therefore, the absolute target displacement relative to the initial position was small during DIBH treatment, with the mean and the standard deviation 0.6 and 2.9 mm, respectively.

CONCLUSIONS
Internal target motion may differ from external surrogate motion in DIBH treatment. Radiographic verification of target position at the beginning and during each fraction is necessary for precise RT delivery. IMR can serve as a useful tool to directly monitor the internal target motion.

Zeng|Chuan|C|
Xiong|Weijun|W|
Li|Xiang|X|
Reyngold|Marsha|M|
Gewanter|Richard M|RM|
Cuaron|John J|JJ|
Yorke|Ellen D|ED|
Li|Tianfang|T|

deep inspiration breath hold
pancreatic cancer
intrafraction motion
radiation therapy


Effects of Advanced Pharmacy Practice Experience Characteristics on Postgraduate Year 1 Residency Match Rates.

Abstract:
BACKGROUND
Mentors often provide advice to students regarding selection of Advanced Pharmacy Practice Experience (APPE) rotations to strengthen their candidacy for a residency position. However, the impact of APPE characteristics on the chances of matching is unknown.

OBJECTIVE
To determine the impact of APPE characteristics on Post Graduate Year-1 (PGY1) residency match rates at a Midwest US college of pharmacy.

METHODS
Graduates from a single college of pharmacy who participated in the PGY1 match in 2015 or 2016 were included. Match data were obtained from National Matching Services. APPE characteristics (e.g., rotation timing relative to the Midyear Clinical Meeting [MCM], rotation type, and setting) were stratified by matched status. Independent predictors were identified using multivariate logistic regression and tree-based models.

RESULTS
Ninety-nine students were included with 57 matching (57.6%). Students completing an infectious diseases rotation (75 vs. 51%; p = 0.028), a hospital rotation before the MCM (67 vs. 47%; p = 0.039), or a rotation in an ambulatory care clinic (67 vs. 47%; p = 0.045) were more likely to match. Students completing an independent community pharmacy rotation were less likely to match (8.3 vs. 64%; p < 0.001). After multivariate adjustment, all of these factors were associated with the likelihood of matching except completion of an infectious diseases (p = 0.077) or ambulatory care rotation (p = 0.073).

CONCLUSION
A hospital rotation prior to the MCM was positively associated with matching while completion of an independent community pharmacy rotation was associated with non-matched status. The utility of these findings in guiding APPE selections for students pursing residency should be explored.

advanced pharmacy practice experience
match
pharmacy match
postgraduate year 1 pharmacy residency


Lipidomics Unravels the Role of Leaf Lipids in Thyme Plant Response to Drought Stress.

Abstract: Thymus is one of the best known genera within the Labiatae (Lamiaceae) family, with more than 200 species and many medicinal and culinary uses. The effects of prolonged drought on lipid profile were investigated in tolerant and sensitive thyme plants (Thymus serpyllum L. and Thymus vulgaris L., respectively). Non-targeted non-polar metabolite profiling was carried out using Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry with one-month-old plants exposed to drought stress, and their morpho-physiological parameters were also evaluated. Tolerant and sensitive plants exhibited clearly different responses at a physiological level. In addition, different trends for a number of non-polar metabolites were observed when comparing stressed and control samples, for both sensitive and tolerant plants. Sensitive plants showed the highest decrease (55%) in main lipid components such as galactolipids and phospholipids. In tolerant plants, the level of lipids involved in signaling increased, while intensities of those induced by stress (e.g., oxylipins) dramatically decreased (50-60%), in particular with respect to metabolites with m/z values of 519.3331, 521.3488, and 581.3709. Partial least square discriminant analysis separated all the samples into four groups: tolerant watered, tolerant stressed, sensitive watered and sensitive stressed. The combination of lipid profiling and physiological parameters represented a promising tool for investigating the mechanisms of plant response to drought stress at non-polar metabolome level.

Moradi|Parviz|P| Mahdavi|Atiyeh|A| Khoshkam|Maryam|M| Iriti|Marcello|M|0000-0002-5063-1236

D000222:Adaptation, Physiological
D016000:Cluster Analysis
D055864:Droughts
D050356:Lipid Metabolism
D053858:Metabolic Networks and Pathways
D055442:Metabolome
D055432:Metabolomics
D018515:Plant Leaves
D013312:Stress, Physiological
D046930:Thymus Plant

lipidome
Thymus
FT-ICR
lipid signaling
stress physiology
water deficit


Reacquisition of New Meristematic Sites Determines the Development of a New Organ, the Cecidomyiidae Gall on Copaifera langsdorffii Desf. (Fabaceae).

Abstract: The development of gall shapes has been attributed to the feeding behavior of the galling insects and how the host tissues react to galling stimuli, which ultimately culminate in a variable set of structural responses. A superhost of galling herbivores, Copaifera langsdorffii, hosts a bizarre "horn-shaped" leaflet gall morphotype induced by an unidentified species of Diptera: Cecidomyiidae. By studying the development of this gall morphotype under the anatomical and physiological perspectives, we demonstrate the symptoms of the Cecidomyiidae manipulation over plant tissues, toward the cell redifferentiation and tissue neoformation. The most prominent feature of this gall is the shifting in shape from growth and development phase toward maturation, which imply in metabolites accumulation detected by histochemical tests in meristem-like group of cells within gall structure. We hypothesize that the development of complex galls, such as the horn-shaped demands the reacquisition of cell meristematic competence. Also, as mature galls are green, their photosynthetic activity should be sufficient for their oxygenation, thus compensating the low gas diffusion through the compacted gall parenchyma. We currently conclude that the galling Cecidomyiidae triggers the establishment of new sites of meristematic tissues, which are ultimately responsible for shifting from the young conical to the mature horn-shaped gall morphotype. Accordingly, the conservative photosynthesis activity in gall site maintains tissue homeostasis by avoiding hypoxia and hipercarbia in the highly compacted gall tissues.

Carneiro|Renê G S|RGS|
Isaias|Rosy M S|RMS|
Moreira|Ana S F P|ASFP|
Oliveira|Denis C|DC|

gall shape
cell redifferentiation
photosynthesis
hystochemistry


The Disconnected Brain and Executive Function Decline in Aging.

Abstract: Higher order speeded cognitive abilities depend on efficient coordination of activity across the brain, rendering them vulnerable to age reductions in structural and functional brain connectivity. The concept of "disconnected aging" has been invoked, suggesting that degeneration of connections between distant brain regions cause cognitive reductions. However, it has not been shown that changes in cognitive functions over time can be explained by simultaneous changes in brain connectivity. We followed 119 young and middle-aged (23-52 years) and older (63-86 years) adults for 3.3 years with repeated assessments of structural and functional brain connectivity and executive functions. We found unique age-related longitudinal reductions in executive function over and above changes in more basic cognitive processes. Intriguingly, 82.5% of the age-related decline in executive function could be explained by changes in connectivity over time. While both structural and functional connectivity changes were related to longitudinal reductions in executive function, only structural connectivity change could explain the age-specific decline. This suggests that the major part of the age-related reductions in executive function can be attributed to micro- and macrostructural alterations in brain connectivity. Although correlational in nature, we believe the present results constitute evidence for a "disconnected brain" view on cognitive aging.

Fjell|Anders M|AM|
Sneve|Markus H|MH|
Grydeland|Håkon|H|
Storsve|Andreas B|AB|
Walhovd|Kristine B|KB|

D000328:Adult
D000368:Aged
D000369:Aged, 80 and over
D001921:Brain
D001931:Brain Mapping
D000066492:Cognitive Aging
D056324:Diffusion Tensor Imaging
D056344:Executive Function
D005260:Female
D005500:Follow-Up Studies
D006801:Humans
D008137:Longitudinal Studies
D008279:Magnetic Resonance Imaging
D008297:Male
D008609:Mental Status Schedule
D008875:Middle Aged
D009434:Neural Pathways
D057190:Stroop Test
D055815:Young Adult

executive function
aging
functional connectivity
structural connectivity
diffusion tensor imaging


Mechanical Thrombectomy in Strokes with Large-Vessel Occlusion Beyond 6 Hours: A Pooled Analysis of Randomized Trials.

Abstract:
BACKGROUND AND PURPOSE
Mechanical thrombectomy with or without intravenous thrombolysis is indicated in the acute treatment of ischemic strokes caused by an emergent large-vessel occlusion (ELVO) within 6 hours from symptom onset. However, a significant proportion of patients are referred to comprehensive stroke centers beyond this therapeutic time window. This study performed a pooled analysis of data from trials in which mechanical thrombectomy was performed beyond 6 hours from symptom onset.

METHODS
We searched for randomized controlled trials that compared mechanical thrombectomy with the best medical treatment beyond 6 hours for ischemic strokes due to ELVO and reported on between 1990 and April 2018. The intervention group comprised patients treated with mechanical thrombectomy. Statistical analysis was conducted while pooling data and analyzing fixed- or random-effects models as appropriate.

RESULTS
Four trials involving 518 stroke patients met the eligibility criteria. There were 267 strokes treated with mechanical thrombectomy, with a median time of 10.8 hours between when the patient was last known to be well to randomization. We observed a significant difference between groups concerning the rate of functional independence at 90 days from stroke, with an absolute difference of 27.5% (odds ratio=3.33, 95% CI=1.81-6.12, p<0.001) and good recanalization (odds ratio=13.17, 95% CI=4.17-41.60, p<0.001) favoring the intervention group.

CONCLUSIONS
This meta-analysis confirms the efficacy of mechanical thrombectomy in selected ischemic stroke patients beyond 6 hours from symptom onset. The selection is mainly based on the limited core infarct detected by emergent assessment using neuroimaging techniques.

Vidale|Simone|S| Longoni|Marco|M| Valvassori|Luca|L| Agostoni|Elio|E|

mechanical thrombectomy
stroke
large-vessel occlusion
6 hours
therapeutic time window
meta-analysis


Keratin nanoparticles obtained from human hair for removal of crystal violet from aqueous solution: Optimized by Taguchi method.

Abstract: Developing the cheap but superior adsorbents is of importance for environmental applications. In this paper, the Taguchi experimental design was applied to establish the optimum condition for the removal of crystal violet (CV) dye using keratin nanoparticles obtained from human hair waste. The average diameter of keratin particles was found about 63.7 nm, using DLS. Effective factors on the removal of CV dye including pH, adsorbent dose, temperature and contact time were considered using an L16 orthogonal array. The optimum condition was found to be pH = 9, adsorbent dose = 0.004 g, temperature = 25 °C and contact time = 10 h in the studied range for different parameters. ANOVA results indicated that the pH has the highest contribution percentage (75.97%) on the adsorption process. Moreover, the equilibrium data were well described by Freundlich Isotherm, indicating a multilayer adsorption process with a maximum adsorption capacity of 555.56 mg/g through an endothermic and spontaneous adsorption process that could be used for up to 5 cycles of adsorption process. The kinetic adsorption data were evaluated by different kinetic models, where the data followed a pseudo-second-order model with three steps of diffusion indicated by the intra-particle diffusion model. The obtained results clearly show the high potential of human hair-obtained keratin nanoparticles for removal of cationic dyes from wastewater.

Abbasi|Fereshteh|F|
Tavakkoli Yaraki|Mohammad|M|
Farrokhnia|Abdolhadi|A|
Bamdad|Mehrdad|M|

Keratin nanoparticles
Crystal Violet
Taguchi method
Wastewater
Biosorption


Health-related quality of life and functional impairment in acute vestibular disorders.

Abstract:
BACKGROUND AND PURPOSE
Acute vestibular symptoms have a profound impact on patients' well-being. In this study, health-related quality of life (HRQoL) and functional impairment were investigated prospectively in patients with different peripheral and central vestibular disorders during the acute symptomatic stage to decipher the most relevant underlying factors.

METHODS
In all, 175 patients with acute vestibular disorders were categorized as central vestibular (CV, n = 40), peripheral vestibular (PV, n = 68) and episodic vestibular disorders (EV, n = 67). All patients completed scores to quantify generic HRQoL (European Quality of Life Score Five Dimensions Five Levels, EQ-5D-5L) and disease-specific HRQoL (Dizziness Handicap Inventory, DHI). Vestibular-ocular motor signs were assessed by video-oculography, vestibular-spinal control by posturography and verticality perception by measurement of subjective visual vertical.

RESULTS
Patients with PV had a poorer HRQoL compared to patients with CV and EV (EQ-5D-5L/DHI: PV, 0.53 ± 0.31/56.1 ± 19.7; CV, 0.66 ± 0.28/43.3 ± 24.0; EV, 0.75 ± 0.24/46.7 ± 21.4). After adjusting for age, gender, cardiovascular risk factors and non-vestibular brainstem/cerebellar dysfunction patients with PV persisted to have poorer generic and disease-specific HRQoL (EQ-5D-5L -0.17, DHI +11.2) than patients with CV. Horizontal spontaneous nystagmus was a highly relevant factor for subgroup differences in EQ-5D-5L and DHI, whilst vertical spontaneous nystagmus, subjective visual vertical and sway path were not. EQ-5D-5L decreased significantly with more intense horizontal subjective visual vertical in CV (rho = -0.57) and PV (rho = -0.5) but not EV (rho = -0.13).

CONCLUSIONS
Patients with PV have the highest functional impairment of all patients with acute vestibular disorders. Vestibular-ocular motor disturbance in the yaw plane has more impact than vestibular-spinal or vestibular-perceptive asymmetry in the roll and pitch plane, suggesting that horizontal visual stability is the most critical for HRQoL.

Möhwald|K|K| Hadzhikolev|H|H| Bardins|S|S| Becker-Bense|S|S| Brandt|T|T| Grill|E|E| Jahn|K|K| Dieterich|M|M| Zwergal|A|A|0000-0002-3839-8398

acute unilateral peripheral vestibulopathy


Chitosan beads immobilized manganese peroxidase catalytic potential for detoxification and decolorization of textile effluent.

Abstract: Textile industry has led to severe environmental pollution and is posing a serious threat to the ecosystems. Immobilized biocatalysts have gained importance as potential bio-remediating agent. Manganese peroxidase (MnP) was immobilized onto glutaraldehyde activated chitosan beads by crosslinking and employed for the degradation and detoxification of dyes in textile effluents. The efficiency of chitosan-immobilized MnP (CI-MnP) was evaluated on the basis of decolorization, water quality improvement and toxicity reduction. Maximum color removal of 97.31% was recorded and up to 82.40%, 78.30% and 91.7% reductions in COD, TOC, and BOD were achieved, respectively. The cytotoxicity of bio-treated effluents reduced significantly and 38.46%, 43.47% and 41.83% Allium cepa root length, root count and mitotic index were increased, respectively, whereas brine shrimp nauplii death reduced up to 63.64%. Mutagenicity (Ames test) reduced up to 73.44% and 75.43% for TA98 and TA100 strains, respectively. The CI-MnP retained 60% activity after 10 repeated decolorization batches. The CI-MnP showed excellent efficiency for the bioremediation of textile effluents and can be used for the remediation of toxic agents in wastewater. The monitoring of processed wastewater using bioassays is suggested to evaluate bio-efficiency of treatment method for safe disposal of effluents into water bodies.

Bilal|Muhammad|M| Asgher|Muhammad|M| Iqbal|Munawar|M| Hu|Hongbo|H| Zhang|Xuehong|X|

Chitosan beads
Manganese peroxidase
Textile effluent
Crosslinking
Color removal
Cytotoxicity
Mutagenicity


Dehydration-responsive miRNAs in foxtail millet: genome-wide identification, characterization and expression profiling.

Abstract: A set of novel and known dehydration-responsive miRNAs have been identified in foxtail millet. These findings provide new insights into understanding the functional role of miRNAs and their respective targets in regulating plant response to dehydration stress. MicroRNAs perform significant regulatory roles in growth, development and stress response of plants. Though the miRNA-mediated gene regulatory networks under dehydration stress remain largely unexplored in plant including foxtail millet (Setaria italica), which is a natural abiotic stress tolerant crop. To find out the dehydration-responsive miRNAs at the global level, four small RNA libraries were constructed from control and dehydration stress treated seedlings of two foxtail millet cultivars showing contrasting tolerance behavior towards dehydration stress. Using Illumina sequencing technology, 55 known and 136 novel miRNAs were identified, representing 22 and 48 miRNA families, respectively. Eighteen known and 33 novel miRNAs were differentially expressed during dehydration stress. After the stress treatment, 32 dehydration-responsive miRNAs were up-regulated in tolerant cultivar and 22 miRNAs were down-regulated in sensitive cultivar, suggesting that miRNA-mediated molecular regulation might play important roles in providing contrasting characteristics to these cultivars. Predicted targets of identified miRNAs were found to encode various transcription factors and functional enzymes, indicating their involvement in broad spectrum regulatory functions and biological processes. Further, differential expression patterns of seven known miRNAs were validated by northern blot and expression of ten novel dehydration-responsive miRNAs were confirmed by SL-qRT PCR. Differential expression behavior of five miRNA-target genes was verified under dehydration stress treatment and two of them also validated by RLM RACE. Overall, the present study highlights the importance of dehydration stress-associated post-transcriptional regulation governed by miRNAs and their targets in a naturally stress-tolerant model crop.

D018506:Gene Expression Regulation, Plant

miRNAs
Dehydration
Small RNA library
Post-transcriptional regulation
Contrasting cultivars
Drought stress
Next generation sequencing
Water deficit


Cost-effectiveness of transcarotid artery revascularization versus carotid endarterectomy.

Abstract:
OBJECTIVE
Recent studies have demonstrated that transcarotid artery revascularization (TCAR) has comparable outcomes to the surgical gold standard, carotid endarterectomy (CEA). However, few studies have analyzed the cost of TCAR, and no study has evaluated its cost-effectiveness. The purpose of this study is to conduct a cost-effectiveness analysis comparing TCAR with CEA for carotid artery stenosis.

METHODS
We built a Markov microsimulation using transition probabilities and utilities from existing literature for symptomatic patients undergoing TCAR or CEA. Costs were derived from literature then converted to 2019 dollars. The model included six health states with monthly cycle lengths: surgery, death, alive after surgery, alive after myocardial infarction, alive after stroke, and alive after stroke and death. Quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratio (ICER) were analyzed over a 5-year period. One-way sensitivity and probabilistic sensitivity analyses were conducted to study the impact of parameter variability on cost effectiveness.

RESULTS
For symptomatic patients, CEA cost $7821 for 2.85 QALYs, whereas TCAR cost $19154 for 2.92 QALYs, leading to an ICER of $152,229 per QALY gained in the TCAR arm. Sensitivity analysis demonstrated that our model was most sensitive to probability of restenosis, costs of TCAR, and costs of CEA. Probabilistic sensitivity analysis demonstrated TCAR would be considered cost-effective in 49% of iterations.

CONCLUSIONS
This study found that, although 5-year costs for TCAR were greater than CEA, TCAR afforded greater QALYs than CEA. TCAR became cost-effective at 6 years of follow-up.

Cui|Christina|C|
Ramakrishnan|Ganesh|G|
Murphy|James|J|
Malas|Mahmoud B|MB|

Cost effectiveness
Carotid revascularization costs
TCAR vs CEA
TCAR with flow reversal


A β2-Integrin/MRTF-A/SRF Pathway Regulates Dendritic Cell Gene Expression, Adhesion, and Traction Force Generation.

Abstract: β2-integrins are essential for immune system function because they mediate immune cell adhesion and signaling. Consequently, a loss of β2-integrin expression or function causes the immunodeficiency disorders, Leukocyte Adhesion Deficiency (LAD) type I and III. LAD-III is caused by mutations in an important integrin regulator, kindlin-3, but exactly how kindlin-3 regulates leukocyte adhesion has remained incompletely understood. Here we demonstrate that mutation of the kindlin-3 binding site in the β2-integrin (TTT/AAA-β2-integrin knock-in mouse/KI) abolishes activation of the actin-regulated myocardin related transcription factor A/serum response factor (MRTF-A/SRF) signaling pathway in dendritic cells and MRTF-A/SRF-dependent gene expression. We show that Ras homolog gene family, member A (RhoA) activation and filamentous-actin (F-actin) polymerization is abolished in murine TTT/AAA-β2-integrin KI dendritic cells, which leads to a failure of MRTF-A to localize to the cell nucleus to coactivate genes together with SRF. In addition, we show that dendritic cell gene expression, adhesion and integrin-mediated traction forces on ligand coated surfaces is dependent on the MRTF-A/SRF signaling pathway. The participation of β2-integrin and kindlin-3-mediated cell adhesion in the regulation of the ubiquitous MRTF-A/SRF signaling pathway in immune cells may help explain the role of β2-integrin and kindlin-3 in integrin-mediated gene regulation and immune system function.

Guenther|Carla|C|
Faisal|Imrul|I|
Uotila|Liisa M|LM|
Asens|Marc Llort|ML|
Harjunpää|Heidi|H|
Savinko|Terhi|T|
Öhman|Tiina|T|
Yao|Sean|S|
Moser|Markus|M|
Morris|Stephan W|SW|
Tojkander|Sari|S|
Fagerholm|Susanna Carola|SC|

D000818:Animals
D001696:Biomechanical Phenomena
D018821:CD18 Antigens
D002448:Cell Adhesion
D002465:Cell Movement
D002478:Cells, Cultured
D003598:Cytoskeletal Proteins
D003713:Dendritic Cells
D020869:Gene Expression Profiling
D063990:Gene Ontology
D053263:Gene Regulatory Networks
D008810:Mice, Inbred C57BL
D018345:Mice, Knockout
D008822:Mice, Transgenic
D026362:Serum Response Factor
D015398:Signal Transduction
D015534:Trans-Activators
D020742:rhoA GTP-Binding Protein

MRTF-A
SRF
dendritic cells
adhesion
traction force
LAD-III
MKL-1


Mechanics of Total Drum Replacement Tympanoplasty Studied With Wideband Acoustic Immittance.

Abstract:
OBJECTIVE
Poor hearing outcomes often persist following total drum replacement tympanoplasty. To understand the mechanics of the reconstructed eardrum, we measured wideband acoustic immittance and compared the mechanical characteristics of fascia-grafted ears with the normal tympanic membrane.

STUDY DESIGN
Prospective comparison study.

SETTING
Tertiary care center.

METHODS
Patients who underwent uncomplicated total drum replacement with temporalis fascia grafts were identified. Ears with healed grafts, an aerated middle ear, and no other conductive abnormalities were included. All patients underwent pre- and postoperative audiometry. Wideband acoustic immittance was measured with absorbance and impedance computed. Fascia-grafted ears were compared with normal unoperated ears.

RESULTS
Eleven fascia-grafted ears without complications were included. Postoperatively, the median air-bone gap was 15 dB (250-4000 Hz), with variation across frequency and between ears. Fifty-six control ears were included. Absorbance of fascia-grafted ears was significantly lower than that of normal ears at 1 to 4 kHz (P < .05) but similar below 1 kHz. Impedance magnitude demonstrated deeper and sharper resonant notches in fascia-grafted ears than normal ears (P < .05), suggesting lower mechanical resistance of the fascia graft.

CONCLUSION
The mechanics of fascia-grafted ears differ from the normal tympanic membrane by having lower absorbance at mid- to high frequencies and thus poor sound transmission. The lower resistance in fascia-grafted ears may be due to poor coupling of the graft to the malleus. To improve sound transmission, grafts for tympanic membrane reconstructions would benefit from refined mechanical properties.

Eberhard|Kristine Elisabeth|KE|
Masud|Salwa Fatima|SF|
Knudson|Inge M|IM|
Kirubalingam|Keshinisuthan|K|
Khalid|Hamza|H|
Remenschneider|Aaron K|AK|
Nakajima|Hideko Heidi|HH|

total drum replacement
tympanoplasty
wideband acoustic immittance
fascia graft
absorbance
conductive hearing loss
reflectance


Utility of the EAT-10 in the detection of dysphagia in high-risk hospitalisation units at a university hospital: a cross-sectional study.

Abstract: Introduction: the objective was to assess the utility of the Eating Assessment Tool (EAT-10) in hospitalisation units with patients at high risk of dysphagia. Patients and methods: a cross-sectional study was conducted in the Neurology and Internal Medicine wards; patients with admission < 24 hours and in a terminal stage of disease were excluded. In the first 24-48 hours of admission the presence of dysphagia as assessed with the EAT-10, the risk of malnutrition as assessed with the Malnutrition Universal Screening Tools (MUST), and comorbidities using the Charlson index were screened. Results: a total of 169 patients were recruited (76.0 years, 52 % women); 19.5 % were at risk of malnutrition. The EAT-10 instrument could be administered in 80.6 % of the patients, and was positive in 26.6 % (women 34.1 % vs. men 18.4 %; p = 0.025). When comparing patients with higher comorbidity with those with a lower Charlson index, a lower response rate to EAT-10 was observed (78.4 % vs. 93.9 %; p = 0.038), without differences in screening positivity (28.3 % vs. 19.4 %; p = 0.310). The prevalence of dysphagia risk was higher in the Internal Medicine unit than in the Neurology unit (30.4 % vs. 19.6 %; p = 0.133), as was the percentage of cases in which screening could not be performed (21.1 % vs. 11.1 %; p = 0.011). There were no significant differences in risk of malnutrition, mortality, hospital stay, or readmission according to the EAT-10. Conclusions: The EAT-10 has limited utility in the studied hospitalisation units due to a high rate of unfeasible tests, especially among patients at higher risk of dysphagia.

Vidal Casariego|Alfonso|A|
Suárez Silva|Carla|C|
Lugo Rodríguez|Gloria|G|
Pita Gutiérrez|Francisco|F|
Almeida Seoane|M ª Carmen|MªC|
Rodríguez Ramos|M ª Josefa|MªJ|
Martínez Ramonde|Teresa|T|

Disfagia. Cribado. Eating Assessment Tool. Desnutrición.


Molecular Insights into the Flavivirus Replication Complex.

Abstract: Flaviviruses are vector-borne RNA viruses, many of which are clinically relevant human viral pathogens, such as dengue, Zika, Japanese encephalitis, West Nile and yellow fever viruses. Millions of people are infected with these viruses around the world each year. Vaccines are only available for some members of this large virus family, and there are no effective antiviral drugs to treat flavivirus infections. The unmet need for vaccines and therapies against these flaviviral infections drives research towards a better understanding of the epidemiology, biology and immunology of flaviviruses. In this review, we discuss the basic biology of the flavivirus replication process and focus on the molecular aspects of viral genome replication. Within the virus-induced intracellular membranous compartments, flaviviral RNA genome replication takes place, starting from viral poly protein expression and processing to the assembly of the virus RNA replication complex, followed by the delivery of the progeny viral RNA to the viral particle assembly sites. We attempt to update the latest understanding of the key molecular events during this process and highlight knowledge gaps for future studies.

van den Elsen|Kaïn|K|
Quek|Jun Ping|JP|0000-0002-3827-8580
Luo|Dahai|D|

D002352:Carrier Proteins
D005416:Flavivirus
D018177:Flavivirus Infections
D054884:Host-Pathogen Interactions
D006801:Humans
D008958:Models, Molecular
D046912:Multiprotein Complexes
D011485:Protein Binding
D060066:Protein Interaction Maps
D012367:RNA, Viral
D013329:Structure-Activity Relationship
D014764:Viral Proteins
D014779:Virus Replication

flavivirus
replication complex
RNA replication
non-structural protein


Curvature Induced by Deflection in Thick Meta-Plates.

Abstract: The design of advanced functional devices often requires the use of intrinsically curved geometries that belong to the realm of non-Euclidean geometry and remain a challenge for traditional engineering approaches. Here, it is shown how the simple deflection of thick meta-plates based on hexagonal cellular mesostructures can be used to achieve a wide range of intrinsic (i.e., Gaussian) curvatures, including dome-like and saddle-like shapes. Depending on the unit cell structure, non-auxetic (i.e., positive Poisson ratio) or auxetic (i.e., negative Poisson ratio) plates can be obtained, leading to a negative or positive value of the Gaussian curvature upon bending, respectively. It is found that bending such meta-plates along their longitudinal direction induces a curvature along their transverse direction. Experimentally and numerically, it is shown how the amplitude of this induced curvature is related to the longitudinal bending and the geometry of the meta-plate. The approach proposed here constitutes a general route for the rational design of advanced functional devices with intrinsically curved geometries. To demonstrate the merits of this approach, a scaling relationship is presented, and its validity is demonstrated by applying it to 3D-printed microscale meta-plates. Several applications for adaptive optical devices with adjustable focal length and soft wearable robotics are presented.

auxeticity
Gaussian curvature
3D printing
functional materials
mechanical metamaterials


Antithyroid Drug Treatment in Graves' Disease.

Abstract: Graves' disease is associated with thyrotropin (TSH) receptor stimulating antibody, for which there is no therapeutic agent. This disease is currently treated through inhibition of thyroid hormone synthesis or destruction of the thyroid gland. Recurrence after antithyroid drug (ATD) treatment is common. Recent studies have shown that the longer is the duration of use of ATD, the higher is the remission rate. Considering the relationship between clinical outcomes and iodine intake, recurrence of Graves' disease is more common in iodine-deficient areas than in iodine-sufficient areas. Iodine restriction in an iodine-excessive area does not improve the effectiveness of ATD or increase remission rates. Recently, Danish and Korean nationwide studies noted significantly higher prevalence of birth defects in newborns exposed to ATD during the first trimester compared to that of those who did not have such exposure. The prevalence of birth defects was lowest when propylthiouracil (PTU) was used and decreased by only 0.15% when methimazole was changed to PTU in the first trimester. Therefore, it is best not to use ATD in the first trimester or to change to PTU before pregnancy.

Recurrence
Iodine
Pregnancy
Antithyroid agents
Congenital abnormalities
Graves disease


Automatic diet monitoring: a review of computer vision and wearable sensor-based methods.

Abstract: Food intake and eating habits have a significant impact on people's health. Widespread diseases, such as diabetes and obesity, are directly related to eating habits. Therefore, monitoring diet can be a substantial base for developing methods and services to promote healthy lifestyle and improve personal and national health economy. Studies have demonstrated that manual reporting of food intake is inaccurate and often impractical. Thus, several methods have been proposed to automate the process. This article reviews the most relevant and recent researches on automatic diet monitoring, discussing their strengths and weaknesses. In particular, the article reviews two approaches to this problem, accounting for most of the work in the area. The first approach is based on image analysis and aims at extracting information about food content automatically from food images. The second one relies on wearable sensors and has the detection of eating behaviours as its main goal.

Automatic diet monitoring
image analysis
food image
wearable sensors