Temperature differentially regulates the two kisspeptin systems in the brain of zebrafish.

Abstract: Kisspeptins encoded by the kiss1 and kiss2 genes play an important role in reproduction through the stimulation of gonadotropin-releasing hormone (GnRH) secretion by activating their receptors (KissR1 EU047918 and KissR2 EU047917). To understand the mechanism through which temperature affects reproduction, we examined kiss1 and kiss2 and their respective receptor (kissr1 and kissr2) gene expression in the brain of male zebrafish exposed to a low temperature (15°C), normal temperature (27°C), and high temperature (35°C) for 7-days. kiss1 mRNA levels in the brain were significantly increased (2.9-fold) in the low temperature compared to the control (27°C), while no noticeable change was observed in the high temperature conditions. Similarly, kissr1 mRNA levels were significantly increased (1.5-2.2-folds) in the low temperature conditions in the habenula, the nucleus of the medial longitudinal fascicle, oculomotor nucleus, and the interpeduncular nucleus. kiss2 mRNA levels were significantly decreased (0.5-fold) in the low and high temperature conditions, concomitant with kissr2 mRNA levels (0.5-fold) in the caudal zone of the periventricular hypothalamus and the posterior tuberal nucleus. gnrh3 but not gnrh2 mRNA levels were also decreased (0.5-fold) in the low and high temperature conditions. These findings suggest that while the kiss1/kissr1 system is sensitive to low temperature, the kiss2/kissr2 system is sensitive to both extremes of temperature, which leads to failure in reproduction.

Shahjahan|Md|M|
Kitahashi|Takashi|T|
Ogawa|Satoshi|S|
Parhar|Ishwar S|IS|

Temperature Reproduction Adaptation Environment GPR54 Metastin


High-Performance Green OLEDs Using Thermally Activated Delayed Fluorescence with a Power Efficiency of over 100 lm W(-1).

Abstract: A green organic light-emitting device (OLED) with an extremely high power efficiency of over 100 lm W(-1) is realized through energy transfer from an exciplex. An optimized OLED showed a maximum external efficiency of 25.7%, and a power efficiency of 79.4 lm W(-1) at 1000 cd m(-2) , which is 1.6-times higher than that of state-of-the-art green thermally activated delayed fluorescence (TADF) OLEDs.

Seino|Yuki|Y| Inomata|Susumu|S| Sasabe|Hisahiro|H| Pu|Yong-Jin|YJ| Kido|Junji|J|


CB1 receptor-dependent desensitisation of TRPV1 channels contributes to the analgesic effect of dipyrone in sensitised primary sensory neurons.

Abstract:
BACKGROUND AND PURPOSE
While dipyrone is a widely used analgesic, its mechanism of action is not completely understood. Recently, we have reported that the dipyrone metabolite 4-aminoantipyrine (4-AA) reduces PGE2 -induced pain-related behaviour through cannabinoid CB1 receptors. Here, we ascertained, in naive and PGE2 -induced "inflamed" conditions, both in vivo and in vitro, the molecular mechanisms involved in the 4-AA-induced analgesic effects.

EXPERIMENTAL APPROACH
The effect of local administration of 4-AA (160 μg per paw) on capsaicin (0.12 μg per paw) injection-induced pain-related behaviour and 4-AA's effect on 500-nM capsaicin-induced changes in intracellular calcium concentration ([Ca2+ ]i ) in cultured primary sensory neurons were assessed in vivo and in vitro, respectively.

KEY RESULTS
4-AA reduced capsaicin-induced nociceptive behaviour in naive and inflamed conditions through CB1 receptors. 4-AA (100 μM) reduced capsaicin-induced increase in [Ca2+ ]i in a CB1 receptor-dependent manner, when PGE2 was not present. Following PGE2 application, 4-AA (1-50 μM) increased the [Ca2+ ]i . Although 4-AA activated both TRPV1 and TRPA1 channels, increased [Ca2+ ]i was mediated through TRPV1 channels. Activation of TRPV1 channels resulted in their desensitisation. Blocking CB1 receptors reduced both the excitatory and desensitising effects of 4-AA.

CONCLUSION AND IMPLICATIONS
CB1 receptor-mediated inhibition of TRPV1 channels and TRPV1-mediated Ca2+ -influx- and CB1 receptor-dependent desensitisation of TRPV1 channels contribute to the anti-nociceptive effect of 4-AA in naive and inflamed conditions respectively. Agonists active at both CB1 receptors and TRPV1 channels might be useful as analgesics, particularly in inflammatory conditions.


The evaluation of surface topography changes in nanoscaled 2,6-diphenyl anthracene thin films by atomic force microscopy.

Abstract: The physical properties of electronic devices made by 2,6-diphenyl anthracene (DPA) are influenced by the microtexture of DPA surfaces. This work focused on the experimental investigation of the 3-D surface microtexture of DPA thin films deposited on OTS (octadecyltrichlorosilane), HMDS (Hexamethyldisilasane), OTMS (octadecyltrimethoxysilane), and Si/SiO2 (300 nm SiO2 thickness) substrates with 5 and 50 nm thicknesses and 5 and 10 μm scan size. The thin film surfaces were recorded using atomic force microscopy (AFM) and their images were stereometrically analyzed to obtain statistical parameters, in accordance with ASME B46.1-2009 and ISO 25178-2: 2012. The results showed the effect of different manufacturing parameters on microtexture values where the granular structure is confirmed in all films. In addition, root mean square is increased by increasing the thickness from 5 to 50 nm for all types of substrates.

atomic force microscopy
2,6-diphenyl anthracene (DPA)
surface microtexture
statistical parameters
stereometric analysis
thin film field-effect transistors


Escaping aversive exposure.

Abstract: This research examined human defensive reactivity when exposure to an aversive event could be escaped but not entirely avoided. Prolonged visual cues indicated whether exposure to an upcoming aversive (i.e., disgusting) picture could be terminated after onset (escaped) or not, or that a neutral go signal would appear. Acoustically elicited startle reflexes were measured during each cue interval, as were cardiac and skin conductance activity. Early in the cuing interval, startle reflexes were potentiated during both escape and inescapable exposure trials, compared to the simple motor context. Later in the interval, reflexes remained potentiated for both escapable and inescapable trials, with potentiation further enhanced when aversive exposure could not be escaped compared to when exposure could be escaped. Heart rate deceleration in the cuing interval indicated increased vigilance when preparing any (escape or neutral) action, whereas skin conductance responding indicated enhanced sympathetic action mobilization particularly in an escape context. These data suggest that startle reflexes engaged in an escape context reflect both motor-related response inhibition and aversive potentiation, and they indicate that defensive motivation is engaged whenever aversive exposure is guaranteed, regardless of whether it can be escaped or not.

Sege|Christopher T|CT|
Bradley|Margaret M|MM|
Lang|Peter J|PJ|

Escape
Autonomic
Defensive behavior
Startle blink


The colour of paternity: extra-pair paternity in the wild Gouldian finch does not appear to be driven by genetic incompatibility between morphs.

Abstract: In socially monogamous species, individuals can use extra-pair paternity and offspring sex allocation as adaptive strategies to ameliorate costs of genetic incompatibility with their partner. Previous studies on domesticated Gouldian finches (Erythrura gouldiae) demonstrated a genetic incompatibility between head colour morphs, the effects of which are more severe in female offspring. Domesticated females use differential sex allocation, and extra-pair paternity with males of compatible head colour, to reduce fitness costs associated with incompatibility in mixed-morph pairings. However, laboratory studies are an oversimplification of the complex ecological factors experienced in the wild and may only reflect the biology of a domesticated species. This study aimed to examine the patterns of parentage and sex ratio bias with respect to colour pairing combinations in a wild population of the Gouldian finch. We utilized a novel PCR assay that allowed us to genotype the morph of offspring before the morph phenotype develops and to explore bias in morph paternity and selection at the nest. Contrary to previous findings in the laboratory, we found no effect of pairing combinations on patterns of extra-pair paternity, offspring sex ratio or selection on morphs in nestlings. In the wild, the effect of morph incompatibility is likely much smaller, or absent, than was observed in the domesticated birds. Furthermore, the previously studied domesticated population is genetically differentiated from the wild population, consistent with the effects of domestication. It is possible that the domestication process fostered the emergence (or enhancement) of incompatibility between colour morphs previously demonstrated in the laboratory.

Bolton|P E|PE|0000-0002-2057-1973
Rollins|L A|LA|
Brazill-Boast|J|J|
Kim|K-W|KW|
Burke|T|T|
Griffith|S C|SC|

domestication
Estrildidae
colour polymorphism
mate choice
polyandry
post-zygotic isolation


Microwave conductance in random waveguides in the cross-over to Anderson localization and single-parameter scaling.

Abstract: The nature of transport of electrons and classical waves in disordered systems depends upon the proximity to the Anderson localization transition between freely diffusing and localized waves. The suppression of average transport and the enhancement of relative fluctuations in conductance in one-dimensional samples with lengths greatly exceeding the localization length, L>>ξ, are related in the single-parameter scaling (SPS) theory of localization. However, the difficulty of producing an ensemble of statistically equivalent samples in which the electron wave function is temporally coherent has so-far precluded the experimental demonstration of SPS. Here we demonstrate SPS in random multichannel systems for the transmittance T of microwave radiation, which is the analog of the dimensionless conductance. We show that for L∼4ξ, a single eigenvalue of the transmission matrix (TM) dominates transmission, and the distribution of the T is Gaussian with a variance equal to the average of −ln T, as conjectured by SPS. For samples in the cross-over to localization, L∼ξ, we find a one-sided distribution for T. This anomalous distribution is explained in terms of a charge model for the eigenvalues of the TM τ in which the Coulomb interaction between charges mimics the repulsion between the eigenvalues of TM. We show in the localization limit that the joint distribution of T and the effective number of transmission eigenvalues determines the probability distributions of intensity and total transmission for a single-incident channel.

Shi|Zhou|Z|
Wang|Jing|J|
Genack|Azriel Z|AZ|

mesoscopic physics
quasi-one-dimension
random media
transmission distribution


Apoptosis-Inducing Activity and Antiproliferative Effect of Gossypin on PC-3 Prostate Cancer Cells.

Abstract:
AIM
The rapid growth, morbidity and mortality of prostate cancer, and the lack of effective treatment have attracted great interest of researchers to find novel cancer therapies aiming at the effect of gossypin on cell proliferation and apoptosis of PC-3 cells.

METHODS
The effect of gossypin on cell viability was determined using MTT assay at 5-100μg/ml and cisplatin (50μM) in a time-dependent manner in PC-3 cell lines. The expression levels of caspase-3 (CASP3) and caspase-9 (CASP9) for apoptosis and Nuclear Factor Kappa B (NFKB1) for survival, inflammation, and growth were evaluated by real-time PCR. Hoechst staining was used to analyze apoptosis.

RESULTS
Gossypin showed an anti-proliferative effect on PC3 cell line in a time- and dose-dependent manner. In addition, gossypin led to a significant increase in apoptosis genes (CASP3, CASP9) when compared to control while it caused a decrease in the level of NFKB1, which is accepted as apoptosis inhibitor (p<0.05) (cisplatin-like). Gossypin 50 and 100μM significantly induced apoptotic mechanism in PC-3 cells. However, no apoptotic or commonly stained nuclei have been observed in control group cells.

CONCLUSION
The results indicated that gossypin can be defined as a promising anticancer agent for PC-3 human prostate cancer cell line.

D004354:Drug Screening Assays, Antitumor

Gossypin
apoptosis
MTT assay
anticancer
caspase
prostate cancer cells (PC-3)


Is the COVID-19 pandemic even darker for some? Examining dark personality and affective, cognitive, and behavioral responses to the COVID-19 pandemic.

Abstract: As the COVID-19 pandemic and interventions intended to minimize its spread continue to impact daily life, personality research may help to address the different ways in which people respond to a major global health crisis. The present study assessed the role of dark personality traits in predicting different responses to the pandemic. A nationally representative sample of 412 Americans completed measures of the Dark Tetrad as well as perceptions of COVID-19 threat, emergency beliefs, and positive and negative affect in response to COVID-19. Narcissism and Machiavellianism predicted greater negative affect and perceptions of threat during the pandemic, while psychopathy predicted positive affect. Conversely, sadism predicted greater positive affect. Dark personality also showed some predictive ability in explaining pandemic-related behaviors (e.g., more frequent cleaning) but not others (e.g., social distancing). Our findings provide evidence for differences in how dark personality traits predict individual responses to global crises.

Hardin|Benjamin S|BS|
Smith|C Veronica|CV|
Jordan|Lauren N|LN|

COVID-19
Pandemic
Dark personality
Dark Tetrad


HLA-B influences integrin beta-1 expression and pancreatic cancer cell migration.

Abstract: Human leukocyte antigen (HLA) class I molecules present antigenic peptides to cytotoxic T cells, causing lysis of malignant cells. Transplantation biology studies have implicated HLA class I molecules in cell migration, but there has been little evidence presented that they influence cancer cell migration, a contributing factor in metastasis. In this study, we examined the effect of HLA-B on pancreatic cancer cell migration. HLA-B siRNA transfection increased the migration of the S2-013 pancreatic cancer cells but, in contrast, reduced migration of the PANC-1 and MIA PaCa-2 pancreatic cancer cell lines. Integrin molecules have previously been implicated in the upregulation of pancreatic cancer cell migration, and knockdown of HLA-B in S2-013 cells heightened the expression of integrin beta 1 (ITGB1), but in the PANC-1 and MIA PaCa-2 cells HLA-B knockdown diminished ITGB1 expression. A transmembrane sequence in an S2-013 HLA-B heavy chain matches a corresponding sequence in HLA-B in the BxPC-3 pancreatic cancer cell line, and knockdown of BxPC-3 HLA-B mimics the effect of S2-013 HLA-B knockdown on migration. In total, our findings indicate that HLA-B influences the expression of ITGB1 in pancreatic cancer cells, with concurrent distinctions in transmembrane sequences and effects on the migration of the cells.

Sliker|Bailee H|BH|
Goetz|Benjamin T|BT|
Barnes|Raina|R|
King|Hannah|H|
Maurer|H Carlo|HC|
Olive|Kenneth P|KP|
Solheim|Joyce C|JC|

D015972:Gene Expression Regulation, Neoplastic

Major histocompatibility complex class I


Deficiency in the nuclear long noncoding RNA Charme causes myogenic defects and heart remodeling in mice.

Abstract: Myogenesis is a highly regulated process that involves the conversion of progenitor cells into multinucleated myofibers. Besides proteins and miRNAs, long noncoding RNAs (lncRNAs) have been shown to participate in myogenic regulatory circuitries. Here, we characterize a murine chromatin-associated muscle-specific lncRNA, Charme, which contributes to the robustness of the myogenic program in vitro and in vivo In myocytes, Charme depletion triggers the disassembly of a specific chromosomal domain and the downregulation of myogenic genes contained therein. Notably, several Charme-sensitive genes are associated with human cardiomyopathies and Charme depletion in mice results in a peculiar cardiac remodeling phenotype with changes in size, structure, and shape of the heart. Moreover, the existence of an orthologous transcript in human, regulating the same subset of target genes, suggests an important and evolutionarily conserved function for Charme Altogether, these data describe a new example of a chromatin-associated lncRNA regulating the robustness of skeletal and cardiac myogenesis.

Ballarino|Monica|M|
Cipriano|Andrea|A|
Tita|Rossella|R|
Santini|Tiziana|T|
Desideri|Fabio|F|
Morlando|Mariangela|M|
Colantoni|Alessio|A|
Carrieri|Claudia|C|
Nicoletti|Carmine|C|
Musarò|Antonio|A|
Carroll|Dònal O'|DO|0000-0002-8626-2217
Bozzoni|Irene|I|0000-0002-3485-8537

myogenesis
lncRNAs
CRISPR/Cas9
epigenetic control
heart development


Evaluation of larvicidal efficacy of Ricinus communis (Castor) and synthesized green silver nanoparticles against Aedes aegypti L.

Abstract: Aedes mosquitoes are the most important group of vectors that transmit pathogens, including arboviruses, and cause human diseases such as dengue fever, yellow fever, Zika virus, and Chikungunya. Biosynthesis and the use of green silver nanoparticles (AgNPs) is a vital step to identify reliable and eco-friendly controls for these vectors. In this study, Aedes (Ae.) aegypti larvae (2nd and 3rd instar) were exposed to leaf extracts of Ricinus communis (Castor) and AgNPs synthesized from the extract to evaluate their larvicidal potential. Synthesized AgNPs were characterized by UV-Vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), and energy-dispersive X-ray spectroscopy (XRD). Ae. aegypti larvae were treated with different concentrations (50-250 ppm) of the leaf extract and synthesized AgNPs. There were five replicates per treatment, in addition to a positive (temephos) and negative control (dechlorinated water). Mortality was recorded after 12, 24, 36, and 48 h and the data were subjected to Probit analysis. The nanoparticles were more toxic (LC50 = 46.22 ppm and LC90 = 85.30 ppm) than the plant extract (106.24 and 175.73 ppm, respectively). The leaf extracts of Ricinus communis were subjected to HPLC analysis to identify their chemical constituents. This study suggests that plant extracts and synthesized nanoparticles are excellent alternatives to hazardous chemical pesticides used to control vector mosquitoes. This is a potentially useful technique that can reduce aquatic toxicity from insecticide use.

Waris|Muhammad|M|
Nasir|Shabab|S|
Abbas|Sadia|S|
Azeem|Muhammad|M|
Ahmad|Bilal|B|
Khan|Naveed Ahmad|NA|
Hussain|Bilal|B|
Al-Ghanim|K A|KA|
Al-Misned|F|F|
Mulahim|N|N|
Mahboob|Shahid|S|

Larvicidal
Ricinus communis
AgNPs
Mosquito larvae
Yellow fever mosquito


The Potential Therapeutic Role of the HMGB1-TLR Pathway in Epilepsy.

Abstract: Epilepsy is one of the most common serious neurological disorders, affecting over 70 million people worldwide. For the treatment of epilepsy, antiepileptic drugs (AEDs) and surgeries are widely used. However, drug resistance and adverse effects indicate the need to develop targeted AEDs based on further exploration of the epileptogenic mechanism. Currently, many efforts have been made to elucidate the neuroinflammation theory in epileptogenesis, which may show potential in the treatment of epilepsy. In this respect, an important target protein, high mobility group box 1 (HMGB1), has received increased attention and has been developed rapidly. HMGB1 is expressed in various eukaryotic cells and localized in the cell nucleus. When HMGB1 is released by injuries or diseases, it participates in inflammation. Recent studies suggest that HMGB1 via Toll-like receptor (TLR) pathways can trigger inflammatory responses and play an important role in epilepsy. In addition, studies of HMGB1 have shown its potential in the treatment of epilepsy. Herein, the authors analyzed the experimental and clinical evidence of the HMGB1-TLR pathway in epilepsy to summarize the theory of epileptogenesis and provide insights into antiepileptic therapy in this novel field.

HMGB1-TLR pathway
epilepsy
antiepileptic drugs
Neuroinflammation
HMGB1
TLR


Superior laryngeal nerve block for neurogenic cough: A case series.

Abstract:
Objectives
To demonstrate that an in-office superior laryngeal nerve (SLN) block with lidocaine and steroids is an effective alternative to neuromodulators for patients with neurogenic cough.

Study Design
Retrospective study.

Methods
A retrospective review of 10 patients who underwent in office nerve block to the laryngeal nerve (SLN) for neurogenic cough. Demographic data and pre- and postcough survey index are the measure outcomes. Follow-up was 3-6 months.

Results
We find that all patients in this study that underwent an SLN block showed significant improvement in cough severity index (CSI). The average number of blocks was 2.3. The mean follow-up time from the first SLN block is 3.4 months. The mean CSI improvement 16.30. 95% confidence interval, 11.44-21.16; P < .0001. All patients in this study completed at least one session of cough suppression therapy with speech language pathology (SLP). No patients were on neuromodulators at the time of the SLN block.

Conclusions
There is a role for in-office SLN block with lidocaine and steroids for patients with neurogenic cough, and can be an effective alternative to neuromodulators.

Level of Evidence
NA.

superior laryngeal nerve block
Neurogenic cough
cough survey index


GAG replenishment therapy for bladder pain syndrome/interstitial cystitis.

Abstract:
AIMS
To present a rationale for the inclusion of urothelial coating dysfunction in the etipathogenesis of bladder pain syndrome/interstitial cystitis (BPS/IC) and the preclinical and clinical evidence in support of glycosaminoglycan (GAG) replenishment therapy in the treatment of BPS/IC, supplemented by the clinical experience of medical experts in the field and patient advocates attending a symposium on GAG replenishment at ESSIC'17, the annual Meeting of the International Society for the Study of Bladder Pain Syndrome, held in Budapest, Hungary in 2017.

RESULTS
The urothelial GAG layer has a primary role in providing a permeability barrier to prevent penetration of urinary toxins and pathogens into the bladder wall. Disruption of the GAG layer contributes to the development of BPS/IC. The evidence shows that replenishment of GAGs can restore the GAG layer in BPS/IC, reducing inflammation, pain, and other symptoms.

CONCLUSIONS
Although data from large randomized controlled studies are limited, long clinical observation and the experience of clinicians and patients support the beneficial effects of intravesical GAG replenishment therapy for providing symptomatic relief for patients with BPS/IC.

Wyndaele|Jean Jacques J|JJJ|
Riedl|Claus|C|
Taneja|Rajesh|R|0000-0002-1726-9263
Lovász|Sándor|S|
Ueda|Tomohiro|T|
Cervigni|Mauro|M|

bladder pain syndrome
interstitial cystitis
glycosaminoglycans
chondroitin sulfate
clinical practice
diagnosis
gag layer replenishment
hyaluronic acid


Molecular analysis of alternative transcripts of equine AXL receptor tyrosine kinase gene.

Abstract:
OBJECTIVE
Since athletic performance is a most importance trait in horses, most research focused on physiological and physical studies of horse athletic abilities. In contrast, the molecular analysis as well as the regulatory pathway studies remain insufficient for evaluation and prediction of horse athletic abilities. In our previous study, we identified AXL receptor tyrosine kinase (AXL) gene which was expressed as alternative spliced isoforms in skeletal muscle during exercise. In the present study, we validated two AXL alternative splicing transcripts (named as AXLa for long form and AXLb for short form) in equine skeletal muscle to gain insight(s) into the role of each alternative transcript during exercise.

METHODS
We validated two isoforms of AXL transcripts in horse tissues by reverse transcriptase polymerase chain reaction (RT-PCR), and then cloned the transcripts to confirm the alternative locus and its sequences. Additionally, we examined the expression patterns of AXLa and AXLb transcripts in horse tissues by quantitative RT-PCR (qRT-PCR).

RESULTS
Both of AXLa and AXLb transcripts were expressed in horse skeletal muscle and the expression levels were significantly increased after exercise. The sequencing analysis showed that there was an alternative splicing event at exon 11 between AXLa and AXLb transcripts. 3-dimentional (3D) prediction of the alternative protein structures revealed that the structural distance of the connective region between fibronectin type 3 (FN3) and immunoglobin (Ig) domain was different between two alternative isoforms.

CONCLUSION
It is assumed that the expression patterns of AXLa and AXLb transcripts would be involved in regulation of exercise-induced stress in horse muscle possibly through an NF-κB signaling pathway. Further study is necessary to uncover biological function(s) and significance of the alternative splicing isoforms in race horse skeletal muscle.

Park|Jeong-Woong|JW|
Song|Ki-Duk|KD|
Kim|Nam Young|NY|
Choi|Jae-Young|JY|
Hong|Seul A|SA|
Oh|Jin Hyeog|JH|
Kim|Si Won|SW|
Lee|Jeong Hyo|JH|
Park|Tae Sub|TS|
Kim|Jin-Kyoo|JK|
Kim|Jong Geun|JG|
Cho|Byung-Wook|BW|

AXL Receptor Tyrosine Kinase
Athletic Performance
Horse
Alternative Splicing
Muscle
RNA-Sequence


Eicosanoid biosynthesis influences the virulence of Candida parapsilosis.

Abstract: Lipid mediators, derived from arachidonic acid metabolism, play an important role in immune regulation. The functions of bioactive eicosanoids range from modulating cytokine signaling and inflammasome formation to anti-inflammatory and pro-resolving activities. Human pathogenic fungi such as Candida albicans, Candida parapsilosis, Cryptococcus neoformans and Aspergillus fumigatus have been shown to produce such lipid mediators, associated with their virulence. To date, investigations into the molecular mechanisms of fungal eicosanoid biosynthesis in different species have revealed that several genes are associated with prostaglandin production. However, these routes remain uncharacterized in C. parapsilosis with early results suggesting it uses pathways distinct from those found in C. albicans. Therefore, we aimed to identify and characterize C. parapsilosis genes involved in eicosanoid biosynthesis. Following arachidonic acid treatment of C. parapsilosis cells, we identified several genes interfering with prostaglandin production. Out of the identified genes, homologues of a multi copper oxidase (FET3), an Acyl-CoA thiolase (POT1) and an Acyl-CoA oxidase (POX1-3) were found to play a significant role in prostaglandin synthesis. Furthermore, all three genes were confirmed to enhance C. parapsilosis pathogenicity, as the corresponding deletion mutants were cleared more efficiently by human macrophages and induced higher levels of pro-inflammatory cytokines. In addition, the mutants were less virulent than the wild-type strain in a mouse model of systemic infection. Taken together, we identified three genes that regulate eicosanoid biosynthesis in C. parapsilosis and impact the fungus' virulence.

Chakraborty|Tanmoy|T| Thuer|Ernst|E| Heijink|Marieke|M| Tóth|Renáta|R| Bodai|László|L| Vágvölgyi|Csaba|C| Giera|Martin|M| Gabaldón|Toni|T| Gácser|Attila|A|0000-0003-2939-9580

virulence
Candida parapsilosis
fungal eicosanoids
host-pathogen interaction
immunomodulation


The relationships between particulate and soluble alkaline phosphatase activities and the concentration of phosphorus dissolved in the seawater of Toulon Bay (NW Mediterranean).

Abstract: The activities of particulate and soluble phosphatase were analyzed monthly for 1 year in the coastal ecosystems of the NW Mediterranean Sea. The mean contribution of the particulate activity increased from 56% at an MUF-P concentration of 30 μM to 77% at 0.04 μM. This particulate activity was negatively correlated with the DIP, DOP and TDP concentrations when the activities were related to the seawater volume, chlorophyll a or the protein concentration. The TDP correlations were highly significant (p: 0.001). The DOP correlations were significant (p: 0.04) and became highly significant (p: 0.009) at low DIP concentrations (<0.13 μM). The DIP correlations were significant (p: 0.04) only at low DOP concentrations (<0.18 μM). Thus, the effects of seawater DIP and DOP were found to be linked. The soluble activity exhibited distinct phosphatase fractions with high (0.5-29.5 μM) and low (0.02-2 μM) Km values, but none exhibited significant correlations with phosphorus compounds.

Bogé|Gérard|G| Lespilette|Magali|M| Jamet|Dominique|D| Jamet|Jean-Louis|JL|

Alkaline phosphatase
Phosphorus
Mediterranean Sea
MUF-P
DIP
DOP
TDP
Kinetics
MUF
Methyl umbelliferyl phosphate
Plankton
SRP
dissolved inorganic phosphorus
dissolved organic phosphorus
methylumbelliferone
soluble reactive phosphorus
total dissolved phosphorus


Characteristic of drug-related problems and pharmacists' interventions in a stroke unit in Thailand.

Abstract: Background Little information is available regarding pharmacist's intervention to solve drug-related problems (DRPs) in a stroke unit. Objective To investigate the nature and frequency of DRPs along with the role of pharmacists in a stroke unit. Setting The study was conducted at the stroke unit of Siriraj hospital, a university affiliated tertiary care hospital in Thailand. Method A retrospective descriptive study of DRPs and pharmacists' interventions for stroke patients was performed during July 2015 to December 2016. Data were collected from patient's medical records and pharmacist's intervention record forms. DRPs were categorized using the Hepler-Strand classification. The stroke pharmacist team, consisting of a board-certified pharmacotherapy specialist, neurology pharmacy residents and stroke unit pharmacists, participated in the multidisciplinary ward round in the stroke unit 5 days a week. All patients were visited by a member of the stroke pharmacist team within the first two days of their admission to conduct a thorough review of drug therapy for every patient and provided appropriate recommendation to the multidisciplinary team either verbally during the ward round or with written information in the patients' medical charts, as appropriate. Main Outcome Measure (a) incidence and characteristics of DRPs (b) types and the acceptance of pharmacists' interventions. Results A total of 859 patients were admitted, of those, 768 patients had ≥ 1 DRPs and a total of 796 DRPs were identified. Clinical pharmacists provided 659 interventions to the multidisciplinary team. The most common DRPs identified were "untreated indications" (22.6%) and "non-compliance" (21.0%). Of all DRPs, 74.6% were stroke related issues. The most implicated drugs were antihypertensive drugs, followed by antithrombotic therapies. The multidisciplinary team accepted 84.7% of pharmacists' interventions. Conclusion DRP in a stroke unit is common. Clinical pharmacists in a stroke unit can effectively reduce and prevent DRPs with the focus on performing medication reconciliation, providing recommendation on dosage adjustment and proper drug selection for stroke patients.

Semcharoen|Kannikar|K| Supornpun|Sajja|S| Nathisuwan|Surakit|S| Kongwatcharapong|Junporn|J|

D064420:Drug-Related Side Effects and Adverse Reactions

Drug-related problems
Pharmacist
Stroke
Thailand
Hospital
Pharmacist’s intervention


Outcomes of Arthroscopic Fixation of Unstable Distal Clavicle Fractures: A Systematic Review.

Abstract:
Background
Surgical management of unstable distal clavicle fractures (DCFs) remains controversial. Traditional open techniques result in acceptable union rates but are fraught with complications. In response to these limitations, arthroscopic techniques have been developed; however, clinical outcome data are limited.

Purpose
The primary purpose was to systematically evaluate the clinical and radiographic outcomes of arthroscopic fixation of unstable DCFs. The secondary purpose was to characterize the overall complication rate, focusing on major complications and subsequent reoperations.

Study Design
Systematic review; Level of evidence, 4.

Methods
A systematic review of the literature was performed following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and included a search of the PubMed, Web of Science, Cochrane Register of Controlled Trials, EMBASE, and Scopus databases. English-language studies between 2008 and 2019 that reported on outcomes of patients with DCFs who underwent operative fixation using an arthroscopic or arthroscopically assisted surgical technique were included. Data consisted of patient characteristics, fracture type, surgical technique, concomitant injuries, union rates, functional outcomes, and complications.

Results
A total of 15 studies consisting of 226 DCFs treated using an arthroscopically based technique were included in the systematic review. The majority of fractures were classified as Neer type II. Most (97%) of the fractures underwent arthroscopic fixation using a cortical button coracoclavicular stabilization surgical technique. Bony union was reported in 94.1% of the fractures. Good to excellent outcomes were recorded in most patients at the final follow-up. The Constant-Murley score was the most widely used functional outcome score; the pooled mean Constant score was 93.06 (95% CI, 91.48-94.64). Complications were reported in 14 of the 15 studies, and the overall complication rate was 27.4%. However, only 12% of these were considered major complications, and only 6% required a reoperation for hardware-related complications.

Conclusion
Arthroscopic fixation of DCFs resulted in good functional outcomes with union rates comparable to those of traditional open techniques. While the overall complication profile was similar to that of other described techniques, there was a much lower incidence of major complications, including hardware-related complications and reoperations.

Yagnik|Gautam P|GP|
Seiler|Jacob R|JR|
Vargas|Luis A|LA|
Saxena|Anshul|A|
Narvel|Raed I|RI|
Hassan|Robert|R|

arthroscopic
distal clavicle fracture
coracoclavicular stabilization


Zinc abrogates anticancer drug tamoxifen-induced hepatotoxicity by suppressing redox imbalance, NO/iNOS/NF-ĸB signaling, and caspase-3-dependent apoptosis in female rats.

Abstract: Tamoxifen (TAM) is used in breast cancer chemotherapy since its approval by the Food and Drug Administration in 1977. However, TAM therapy is accompanied with hepatotoxicity - a source of worry to clinicians. Oxidative stress and inflammation are the major implicated mechanisms contributing to TAM hepatotoxicity. In this study, we explored whether zinc (Zn) supplementation could prevent TAM-induced hepatotoxicity in female Wistar rats. Rats were subjected to oral pretreatment of Zn (100 mg/kg body weight (b.w.)/day) for 14 days against hepatic toxicity induced by single intraperitoneal administration of TAM (50 mg/kg b.w.) on day 13. TAM markedly elevated serum liver enzymes, whereas total protein and albumin considerably reduced. TAM caused prominent depletion of hepatic-reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activity. Also, TAM significantly increased malondialdehyde (MDA) level. Further, it raised liver levels of tumor necrosis factor-α (TNF-α), interleukin-1β, (IL-1β), interleukin-6 (IL-6), and nitric oxide (NO) confirmed by the liver histopathological alterations. The mechanistic inflammatory expression of inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-ĸB), and expression of caspase-3 protein prominently increased. Zinc supplementation significantly modulated serum liver function markers, antioxidant enzymes, and GSH and MDA levels. Zinc downregulated the expression of cytokines, NO, iNOS, NF-ĸB and caspase-3, and ameliorated histopathological changes. Zinc protects against TAM-induced hepatotoxicity; it may serve as an adjuvant supplement for female patients undergoing TAM chemotherapy.

D056486:Chemical and Drug Induced Liver Injury

zinc
hepatotoxicity
Tamoxifen
chemotherapy
oxidative stress
inflammation


Dexmedetomidine alleviates cerebral ischemia-induced short-term memory impairment by inhibiting the expression of apoptosis-related molecules in the hippocampus of gerbils.

Abstract: Cerebral ischemia results from cerebrovascular occlusion, which leads to neuronal cell death and eventually causes neurological impairments. Dexmedetomidine is a potent and highly selective α2-adrenoreceptor agonist with actions such as sedation, anxiolysis, analgesia and anesthetic-sparing effects. We investigated the effect of dexmedetomidine on apoptosis in the hippocampus after transient global ischemia in gerbils. Transient global ischemia was induced by ligation of both common carotid arteries. Dexmedetomidine was administrated intraperitoneally at three respective doses (0.1, 1 and 10 µg/kg) once per day for 14 consecutive days beginning a day after surgery. Short-term memory was assessed by use of a step-down avoidance task. Apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay, immunohistochemistry for caspase-3, and western blot analysis of Bcl-2-associated X protein, B-cell lymphoma 2, Bid, cytochrome c, apoptotic protease activating factor-1 and caspase-9 in the hippocampus. Induction of global ischemia deteriorated short-term memory by enhancing the expression of apoptosis-related molecules in the hippocampus. Treatment with dexmedetomidine suppressed the expression of apoptosis-related molecules under ischemic conditions, resulting in short-term memory improvement. Under normal conditions, dexmedetomidine exerted no significant effect on apoptosis in the hippocampus. The present results suggest that the α2-adrenoceptor agonist dexmedetomidine may be a useful therapeutic agent for the treatment of ischemic brain diseases.

Choi|In-Young|IY| Hwang|Lakkyong|L| Jin|Jun-Jang|JJ| Ko|Il-Gyu|IG| Kim|Sung-Eun|SE| Shin|Mal-Soon|MS| Shin|Key-Moon|KM| Kim|Chang-Ju|CJ| Park|Sung-Wook|SW| Han|Jin-Hee|JH| Yi|Jae-Woo|JW|

dexmedetomidine
short-term memory
gerbils
apoptosis
transient global ischemia
α2-adrenergic receptor


Risk of Myocardial Infarction and Ischemic Stroke after Dental Treatments.

Abstract: The association between invasive dental treatments (IDTs) and a short-term risk of myocardial infarction (MI) and ischemic stroke (IS) remains controversial. Bacterial dissemination from the oral cavity and systemic inflammation linked to IDT can induce a state of acute vascular dysfunction. The aim of study is to investigate the relation of IDTs to MI and IS by using case-only study designs to analyze data from a large Taiwanese cohort. A nationwide population-based study was undertaken by using the case-crossover and self-controlled case series design to analyze the Taiwanese National Health Care Claim database. Conditional logistic regression model and conditional Poisson regression model were used to estimate the risks of MI/IS. In addition, we used burn patients as negative controls to explore the potential effect of residual confounding. In total, 123,819 MI patients and 327,179 IS patients in the case-crossover design and 117,655 MI patients and 298,757 IS patients were included in the self-controlled case series design. Results from both study designs showed that the risk of MI within the first 24 wk after IDT was not significantly different from or close to unity except for a modest risk during the first week for patients without other comorbidities (odds ratios [95% confidence intervals] of 1.31 [1.08-1.58] and 1.15 [1.01-1.31] for 3 d and 7 d, respectively). We also observed no association between IDTs and IS, or the risk ratio was close to unity. IDTs did not appear to be associated with a transient risk of MI and IS in the Taiwanese population, with consistent findings from both case-only study designs. However, we cannot exclude that dental infections and diseases may yield a long-term risk of MI and IS.

Chen|T T|TT|
D'Aiuto|F|F|
Yeh|Y C|YC|
Lai|M S|MS|
Chien|K L|KL|
Tu|Y K|YK|

case-only study
case-crossover
self-controlled case series
cardiovascular diseases
epidemiologic studies
retrospective studies


In-Line Rheo-Optical Investigation of the Dispersion of Organoclay in a Polymer Matrix during Twin-Screw Compounding.

Abstract: The dispersion mechanisms in a clay-based polymer nanocomposite (CPNC) during twin-screw extrusion are studied by in-situ rheo-optical techniques, which relate the CPNC morphology with its viscosity. This methodology avoids the problems associated with post extrusion structural rearrangement. The polydimethylsiloxane (PDMS) matrix, which can be processed at ambient and low temperatures, is used to bypass any issues associated with thermal degradation. Local heating in the first part of the extruder allows testing of the usefulness of low matrix viscosity to enhance polymer intercalation before applying larger stresses for clay dispersion. The comparison of clay particle sizes measured in line with models for the kinetics of particle dispersion indicates that larger screw speeds promote the break-up of clay particles, whereas smaller screw speeds favor the erosion of the clay tactoids. Thus, different levels of clay dispersion are generated, which do not simply relate to a progressively better PDMS intercalation and higher clay exfoliation as screw speed is increased. Reducing the PDMS viscosity in the first mixing zone of the screw facilitates dispersion at lower screw speeds, but a complex interplay between stresses and residence times at larger screw speeds is observed. More importantly, the results underline that the use of larger stresses is inefficient per se in dispersing clay if sufficient time is not given for PDMS to intercalate the clay galleries and thus facilitate tactoid disruption or erosion.

rheo-optics
dispersion
organoclay
polymer nanocomposites
extrusion
in-process monitoring
rheology


A systematic review and meta-analysis of pregnancy and COVID-19: Signs and symptoms, laboratory tests, and perinatal outcomes.

Abstract:
Background
Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 appeared in December 2019 in Wuhan, China.

Objective
To investigate the clinical manifestations including signs and symptoms, laboratory results, and perinatal outcomes in pregnant women with COVID-19.

Materials and Methods
Scholarly databases such as PubMed via LitCovid hub, Embase, Scopus, Web of sciences, and Google scholar were searched on April 7, 2020. Meta-analysis was performed via comprehensive meta-analysis software using the Mantel-Haenszel method. The event rate with 95% CI was calculated for each variable.

Results
Ten studies were selected. The pooled prevalence for fever, post-partum fever, cough, myalgia, fatigue, dyspnea, sore throat, and diarrhea were 66.8%, 37.1%, 35%, 24.6 %, 14.9%, 14.6%, 11.5%, and 7.6%, respectively. Laboratory test results were 49.8% for lymphopenia, 47.7% for leukocytosis, 83.7% for elevated neutrophil ratio, 57% for elevated C-reactive protein, and 71.4% for decreased lymphocyte ratio. The rate of cesarean section for delivery in all cases was 84%. Of the newborns of the corona-positive mothers, only one had a positive test result. Also, there was only one death due to a decreased lymphocyte ratio.

Conclusion
Fever was the most common sign and symptom in pregnant women with COVID-19. Among the laboratory tests, the highest amount was related to elevated neutrophil ratio. It seems that due to the differences between pregnant women and the general population, special measures should be considered to treat these patients.

Hassanipour|Soheil|S|
Faradonbeh|Saeed Bagheri|SB|
Momeni|Khalil|K|
Heidarifard|Zahra|Z|
Khosousi|Mohammad-Javad|MJ|
Khosousi|Leila|L|
Ameri|Hosein|H|
Arab-Zozani|Morteza|M|

Pregnancy
COVID-19
Signs and symptoms
Diagnosis
Meta-analysis.


Dissection of the RET/β-catenin interaction in the TPC1 thyroid cancer cell line.

Abstract: The RET receptor tyrosine kinase is a member of the cadherin superfamily and plays a pivotal role in cell survival, differentiation and proliferation. Currently, 12 ret/ptc chimeric oncogenes, characterized by the fusion between the intracellular domain of RET and different activating genes, which can cause ligand-independent dimerization and constitutive activation, have been described. β-catenin is usually involved in the maintenance of cell-to-cell adhesion and mediates the Wnt/β-catenin pathway important during embryogenesis and in cellular malignant transformation. Recently, a novel mechanism of RET-mediated function through the β-catenin pathway has been reported in multiple endocrine neoplasia type 2 and in sporadic thyroid carcinomas. Here, we investigated the effects of the ZD6474, a small molecule RET-inhibitor, on RET/β-catenin interaction. We confirmed the ZD6474 mediated-inhibition of recombinant RET kinase and of growth of cells expressing RET/PTC. Interestingly, we firstly observed reduced cellular mobility and changed morphology of TPC1 treated cells suggesting that RET-inhibitor could affect β-catenin cellular distribution as resulted in its co-immunoprecipitation with E-cadherin. We further investigated this hypothesis showing that TPC1 treated cells displayed predominantly β-catenin cytosolic localization. Surprisingly, RET and β-catenin co-immunoprecipitated in both ZD6474-treated and untreated TPC1 cells, suggesting that RET/β-catenin interaction might not be affected by RET kinase inactivation. All together these results suggest that RET kinase activation is crucial for β-catenin stabilization (pY654), localization and its signaling pathway activation but not for β-catenin/RET physical interactions, in human papillary thyroid carcinomas. In conclusion, ZD6474, by inhibiting RET kinase, down-modulates β-catenin pathway leading its recruitment to the membrane by E-cadherin.

Tartari|Carmen J|CJ|
Donadoni|Carla|C|
Manieri|Elisa|E|
Mologni|Luca|L|
Mina|Pamela Della|PD|
Villa|Antonello|A|
Gambacorti-Passerini|Carlo|C|

RET
β-catenin
ZD6474
RET-inhibitor
protein interaction


Speech production abilities of 4- to 5-year-old children with and without a history of late talking: The tricky tyrannosaurus.

Abstract: Purpose: Research on the speech production abilities of children with a history of late talking (HLT) is limited. We compared 4- to 5-year-old children with and without a HLT on a routine speech assessment and a single-word polysyllable assessment.Method: The two speech assessments were administered to 13 children with a HLT (4;4-5;9 years) and 11 children with a history of typical development (HTD) (4;1-5;10 years). Data were analysed using descriptive and inferential statistics.Result: The HLT group had significantly poorer speech accuracy than the HTD group on both the routine speech and polysyllable assessments. The HLT group also showed a significantly higher percentage occurrence of consonant omissions on both speech assessments compared to the HTD group. Descriptive analysis of participants' polysyllable productions indicated that the HLT group showed a higher percentage occurrence of a range of error types compared to the HTD group.Conclusion: By 4-5 years of age, children who were late to talk had speech production abilities that were significantly poorer than their peers who were not late to talk, suggesting continued underlying differences.

children
assessment
polysyllables
late talkers
outcomes


Assessment of the maxilla-mandible-nasion angle in normal and aneuploid foetuses in the first trimester of pregnancy.

Abstract:
PURPOSE
This retrospective study aims to determine whether the maxilla-mandible-nasion (MMN) angle can be reliably measured in the first trimester, to describe normal ranges, and to determine if significant changes occur in foetuses with aneuploidies.

METHODS
The MMN angle was measured in stored 2D-ultrasound images of 200 normal fetal profiles between 11+0 and 13+6 weeks of gestation. Each image was analyzed by two observers at two independent time points. Bland-Altmann analysis was performed to evaluate the reliability of the measurements. Additionally, the MMN angle was measured on sonograms from 140 aneuploid foetuses.

RESULTS
The mean MMN angle in normal foetuses from 11 to 14 weeks of gestation was 15.4°. Reliability of the measurement was high when repeatedly measured by the same observer (ICC = 0.92 and 0.82) and between two observers (ICC = 0.77 and 0.63). Average MMN values in foetuses with trisomy 21, 13, and Turner syndrome were significantly higher than those measured in normal foetuses. The highest differences were observed in foetuses with trisomy 13. Among those, 62% had an MMN angle above the 95th percentile and 92% above the normal mean.

CONCLUSION
The MMN angle can be reliably measured in early pregnancy and is abnormal in about 60% of foetuses with trisomy 13.

maxilla-mandible-nasion angle
aneuploidy
first trimester pregnancy
prenatal diagnosis
ultrasound


Development and function of Foxp3(+) regulatory T cells.

Abstract: Regulatory T cells (Tregs) have been recognized as having a major role in maintaining peripheral tolerance and preventing and limiting autoimmune and chronic inflammatory diseases. Tregs derive from the thymus and also develop peripherally. In this review, we discuss recent progress in our understanding of the basic mechanisms involved in Treg development and function in protecting against autoimmunity in the periphery, including thymic selection, peripheral induction and the many mechanisms of Treg suppression. Specifically in kidney disease, Tregs have been shown to play a role in limiting injury and may potentially have a therapeutic role.

Wang|Yuan Min|YM|
Ghali|Joanna|J|
Zhang|Geoff Yu|GY|
Hu|Min|M|
Wang|Ya|Y|
Sawyer|Andrew|A|
Zhou|Jimmy Jianheng|JJ|
Hapudeniya|Dhanushka A|DA|
Wang|Yiping|Y|
Cao|Qi|Q|
Zheng|Guoping|G|
Harris|David C|DC|
Alexander|Stephen I|SI|


Cultural Similarities and Differences in the Development of Sociomoral Judgments: An Eye-Tracking Study.

Abstract: People integrate the valence of behavior and that of outcome when making moral judgments. However, the role of culture in the development of this integration among young children remains unclear. We investigated cultural similarities and differences in moral judgments by measuring both visual attention and verbal evaluations. Three- and four-year-olds from Japan and the U.S. (N = 141) were shown sociomoral scenarios that varied in agents' behavior which reflected prosocial or antisocial intention and recipients' emotional outcome (happy, neutral, or sad); then, they were asked to evaluate agents' moral trait. Their eye fixations while observing moral scenarios were measured using an eye-tracker. We found culturally similar tendencies in the integration of behavior and outcome; however, a cultural difference was shown in their verbal evaluation. The link between implicit attention and explicit verbal evaluation was negligible. Both culturally shared and specific aspects of sociomoral development are discussed.

Shimizu|Yuki|Y|
Senzaki|Sawa|S|
Cowell|Jason M|JM|

young children
attention
cross-cultural comparison
implicit and explicit processes
moral development
sociomoral trait evaluation


Detector-based spectral CT with a novel dual-layer technology: principles and applications.

Abstract: Detector-based spectral computed tomography is a novel dual-energy CT technology that employs two layers of detectors to simultaneously collect low- and high-energy data in all patients using standard CT protocols. In addition to the conventional polyenergetic images created for each patient, projection-space decomposition is used to generate spectral basis images (photoelectric and Compton scatter) for creating multiple spectral images, including material decomposition (iodine-only, virtual non-contrast, effective atomic number) and virtual monoenergetic images, on-demand according to clinical need. These images are useful in multiple clinical applications, including- improving vascular contrast, improving lesion conspicuity, decreasing artefacts, material characterisation and reducing radiation dose. In this article, we discuss the principles of this novel technology and also illustrate the common clinical applications. Teaching points • The top and bottom layers of dual-layer CT absorb low- and high-energy photons, respectively.• Multiple spectral images are generated by projection-space decomposition.• Spectral images can be generated in all patients scanned in this scanner.

Rassouli|Negin|N| Etesami|Maryam|M| Dhanantwari|Amar|A| Rajiah|Prabhakar|P|

Spectral CT Dual-energy Contrast Cardiac


A Novel Mean-Value Model of the Cardiovascular System Including a Left Ventricular Assist Device.

Abstract: Time-varying elastance models (TVEMs) are often used for simulation studies of the cardiovascular system with a left ventricular assist device (LVAD). Because these models are computationally expensive, they cannot be used for long-term simulation studies. In addition, their equilibria are periodic solutions, which prevent the extraction of a linear time-invariant model that could be used e.g. for the design of a physiological controller. In the current paper, we present a new type of model to overcome these problems: the mean-value model (MVM). The MVM captures the behavior of the cardiovascular system by representative mean values that do not change within the cardiac cycle. For this purpose, each time-varying element is manually converted to its mean-value counterpart. We compare the derived MVM to a similar TVEM in two simulation experiments. In both cases, the MVM is able to fully capture the inter-cycle dynamics of the TVEM. We hope that the new MVM will become a useful tool for researchers working on physiological control algorithms. This paper provides a plant model that enables for the first time the use of tools from classical control theory in the field of physiological LVAD control.

Ochsner|Gregor|G|
Amacher|Raffael|R|
Schmid Daners|Marianne|M|

D000465:Algorithms
D002319:Cardiovascular System
D003198:Computer Simulation
D006353:Heart-Assist Devices
D006801:Humans
D008955:Models, Cardiovascular

Time-varying elastance model
Linear time-invariant model
Physiological control
Model-based controller design


An oscillopathic approach to developmental dyslexia: From genes to speech processing.

Abstract: Developmental dyslexia is a heterogeneous condition entailing problems with reading and spelling. Several genes have been linked or associated to the disease, many of which contribute to the development and function of brain areas important for auditory and phonological processing. Nonetheless, a clear link between genes, the brain, and the symptoms of dyslexia is still pending. The goal of this paper is contributing to bridge this gap. With this aim, we have focused on how the dyslexic brain fails to process speech sounds and reading cues. We have adopted an oscillatory perspective, according to which dyslexia may result from a deficient integration of different brain rhythms during reading/spellings tasks. Moreover, we show that some candidate genes for this condition are related to brain rhythms. This fresh approach is expected to provide a better understanding of the aetiology and the clinical presentation of developmental dyslexia, but also to achieve an earlier and more accurate diagnosis of the disease.

Developmental dyslexia
Reading
Spelling
Speech sounds
Brain rhythms
Candidate genes


Acetylation of polysaccharide from Morchella angusticeps peck enhances its immune activation and anti-inflammatory activities in macrophage RAW264.7 cells.

Abstract: Morchella angusticeps Peck has been recognized as a resource of nutraceuticals and drug discovery. Three acetylated polysaccharides (Ac-PMEP1-3) with appropriate degree of substitution were obtained from Morchella angusticeps Peck, chemically characterized, and cultured with macrophage RAW264.7 cells to evaluate their immune activation and anti-inflammatory activities. Results of ultraviolet-visible spectroscopy and fourier-transform infrared showed these modifications were successful. Compared with the control group, PMEP and Ac-PMEP1-3 enhanced cell proliferation and the production of nitric oxide and tumor necrosis factor-α of RAW264.7 macrophages (cultured without lipopolysaccharide). Compared with PMEP, Ac-PMEP3 enhanced cell viability and NO production by inducing the degradation of cytoplasmic IκBα and nuclear translocation of NF-κB subunit p65 as well as the expression of iNOS and phosphorylated-p38. Moreover, in lipopolysaccharide-stimulated RAW264.7 macrophages, Ac-PMEP3 showed a stronger ability to suppress the overproduction of nitric oxide and tumor necrosis factor-α by down-regulating the level of nuclear NF-κB p65, iNOS, and phosphorylated-p38 and inhibiting the degradation of cytoplasmic IκBα. Therefore, Ac-PMEP enhanced immune activation and anti-inflammatory activities via nuclear factor κB and p38/mitogen-activated protein kinase signaling pathways.

Yang|Yaxuan|Y| Chen|Jinlong|J| Lei|Lin|L| Li|Fuhua|F| Tang|Yu|Y| Yuan|Ya|Y| Zhang|Yueqiao|Y| Wu|Surui|S| Yin|Ran|R| Ming|Jian|J|

D017550:Spectroscopy, Fourier Transform Infrared

Morchella angusticepes peck
Anti-inflammatory
RAW264.7 cells
Acetylated polysaccharide
Nuclear NF-κB
Immunomodulatory


Shifting eating to the circadian rest phase misaligns the peripheral clocks with the master SCN clock and leads to a metabolic syndrome.

Abstract: The light-entrained master central circadian clock (CC) located in the suprachiasmatic nucleus (SCN) not only controls the diurnal alternance of the active phase (the light period of the human light-dark cycle, but the mouse dark period) and the rest phase (the human dark period, but the mouse light period), but also synchronizes the ubiquitous peripheral CCs (PCCs) with these phases to maintain homeostasis. We recently elucidated in mice the molecular signals through which metabolic alterations induced on an unusual feeding schedule, taking place during the rest phase [i.e., restricted feeding (RF)], creates a 12-h PCC shift. Importantly, a previous study showed that the SCN CC is unaltered during RF, which creates a misalignment between the RF-shifted PCCs and the SCN CC-controlled phases of activity and rest. However, the molecular basis of SCN CC insensitivity to RF and its possible pathological consequences are mostly unknown. Here we deciphered, at the molecular level, how RF creates this misalignment. We demonstrate that the PPARα and glucagon receptors, the two instrumental transducers in the RF-induced shift of PCCs, are not expressed in the SCN, thereby preventing on RF a shift of the master SCN CC and creating the misalignment. Most importantly, this RF-induced misalignment leads to a misexpression (with respect to their normal physiological phase of expression) of numerous CC-controlled homeostatic genes, which in the long term generates in RF mice a number of metabolic pathologies including diabetes, obesity, and metabolic syndrome, which have been reported in humans engaged in shift work schedules.

Mukherji|Atish|A| Kobiita|Ahmad|A| Damara|Manohar|M| Misra|Nisha|N| Meziane|Hamid|H| Champy|Marie-France|MF| Chambon|Pierre|P|

D000071679:Glycogen Synthase Kinase 3 beta

D051780:Sterol Regulatory Element Binding Protein 1

metabolic syndrome
mouse
diabetes
shift work
circadian clocks misalignment


Induction of smell through transethmoid electrical stimulation of the olfactory bulb.

Abstract:
BACKGROUND
Anosmia has an estimated prevalence of 5% of the general population. Outside of inflammatory causes, therapeutic options are limited despite research advances. Bypassing peripheral neuronal damage through central stimulation is a potential therapeutic option that has shown success in other sensory systems, most notably with hearing. We performed a pilot study to determine the feasibility of inducing smell through artificial electrical stimulation of the olfactory bulbs in humans.

METHODS
Subjects with a history of sinus surgery, including total ethmoidectomy, with intact ability to smell were enrolled. The ability to smell was confirmed with a 40-item smell identification test. Awake subjects underwent nasal endoscopy and either a monopolar or bipolar electrode was positioned at 3 areas along the lateral lamella of the cribriform plate within the ethmoid sinus cavity. A graded stimulation current of 1-20 mA at 3.17 Hz was administered while cortical evoked potential (CEP) recordings were collected. Subjective responses of perceived smell along with reports of discomfort were recorded. Subjects with artificially induced smell underwent repeat stimulation after medically induced anosmia.

RESULTS
Five subjects (age, 43-72 years) were enrolled. Three subjects reported smell perception smell with electrical stimulation. This was reproducible after inducing anosmia, but CEP recordings could not provide objective support. All subjects tolerated the study with minimal discomfort.

CONCLUSION
This is the first report of induced smell through transethmoid electrical stimulation of the olfactory bulb. These results provide a proof of concept for efforts in development of an olfactory implant system.

Holbrook|Eric H|EH|0000-0002-7632-2204
Puram|Sidharth V|SV|0000-0003-3543-889X
See|Reiner B|RB|
Tripp|Aaron G|AG|
Nair|Dinesh G|DG|

humans
endoscopy
ethmoid sinus
ethmoid bone
olfactory perception
olfactory receptor neurons


Physicochemical Properties of Various 2-Hydroxyethylammonium Sulfonate -Based Protic Ionic Liquids and Their Potential Application in Hydrodeoxygenation.

Abstract: In order to obtain the regularities of physicochemical properties of hydroxy protic ionic liquids (PILs) and broaden their potential application, a series of 2-hydroxyethylammonium sulfonate-based PILs were synthesized through proton transfer reaction and characterized by NMR and FT-IR and elemental analysis. Their phase transfer behavior (T m) and initial decomposition point (T d) were characterized by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), respectively. Meanwhile, the regularities of density (ρ), viscosity (η) and electrical conductivity (σ) of synthesized PILs at different temperatures were measured. The results indicated that their physicochemical properties were tightly related with their structures and the interactions between cations and anions. In addition, the dissociation constants (pKa) of synthesized PILs were obtained by acid-base titration, which revealed that all synthesized PILs had pKa exceeding 7 and their cations were the crux of determining the pKa value. Moreover, several synthesized PILs with a low melting temperature also showed potential application in the deoxidation reaction of cyclohexanol, as they had conversion rates approximating 100% and the selectivity of cyclohexane or cyclohexene was about 80%.

Cai|Guangming|G| Yang|Shaoqi|S| Zhou|Qing|Q| Liu|Lifei|L| Lu|Xingmei|X| Xu|Junli|J| Zhang|Suojiang|S|

protic ionic liquids
density
viscosity
electrical conductivity
dissociation constants
deoxidation reaction


Assessing access to care for transgender and gender nonconforming people: a consideration of diversity in combating discrimination.

Abstract: Transgender and gender nonconforming people face stigma and discrimination from a wide variety of sources and through numerous social realms. Stigma and discrimination originating from biomedicine and health care provision may impact this group's access to primary care. Such stigma and discrimination may originate not only from direct events and past negative experiences, but also through medicine's role in providing treatments of transitioning, the development of formal diagnoses to provide access to such treatments, and the medical language used to describe this diverse group. This paper examines the postponement of primary curative care among this marginalized group of people by drawing from the National Transgender Discrimination Survey, one of the largest available datasets for this underserved group. This paper also proposes an innovate categorization system to account for differences in self-conceptualization and identity, which has been of considerable concern for transgender and gender nonconforming communities but remains underexplored in social and health research. Results suggest that experience, identity, state of transition, and disclosure of transgender or gender nonconforming status are associated with postponement due to discrimination. Other findings suggest that postponement associated with primary place of seeking care and health insurance has ties to both discrimination and affordability. These findings highlight the importance of combating stigma and discrimination generated from within or experienced at sites of biomedicine or health care provision in improving access to care for this group of people. Improving access to care for all gender variant people requires a critical evaluation of existing research practices and health care provision to ensure that care is tailored as needed to each person's perspective in relation to larger social processes.

D005260:Female
D005783:Gender Identity
D019538:Health Care Surveys
D006297:Health Services Accessibility
D006801:Humans
D008297:Male
D011320:Primary Health Care
D063508:Social Discrimination
D057545:Social Stigma
D063106:Transgender Persons
D014481:United States

Access to care
Transgender
Gender nonconforming
Stigma
United States


Enlargement of the human adrenal zona fasciculata and chronic psychiatric illness - an autopsy-based study.

Abstract: Severe mental illness (SMI) is associated with a reduced life expectancy of up to 20 years. One possible contributor to this fact is dysregulation of the hypothalamus-pituitary-adrenal (HPA)-axis. Looking at the morphology of effector organs, such as the adrenal glands themselves, could reveal insights into organ function and response to possible HPA-dysregulation. This forensic autopsy-based study investigated if there were any morphological changes in adrenal glands between decedents who had previously been submitted to a psychiatric hospital with a diagnosis of schizophrenia (n = 34), bipolar (n = 5), or depressive disorder (n = 20), any other psychiatric diagnosis (n = 36) compared with decedents who had no previous psychiatric admission (n = 40). Length of admissions to psychiatric wards and admission in the 180 days preceding death was included in regression as proxy variables for severity of illness. On the macroscopic level, we found no difference in gland weight or volume. On the microscopic level, we found a 25% increase in cross-sectional area of the zona fasciculata (ZF) in decedents who had a diagnosis of schizophrenia compared with controls (p = 0.033). Other diagnosis groups did not differ from controls. Total admission length was positively correlated with area of the ZF.Lay SummaryPeople with a severe mental disorder may be in a constant state of increased stress, which is harmful. This study looked at the adrenal gland, which produces stress hormones, to see if they were different in deceased persons who had suffered from a severe mental illness. We found that the part of the adrenal gland that produces stress hormones is larger in deceased patients who suffered from schizophrenia, but not other types of psychiatric illnesses, compared to deceased persons with no history of psychiatric illness.

zona fasciculata
morphology
Adrenal gland
autopsy
chronic mental illness
histology


Wheat RING E3 ubiquitin ligase TaDIS1 degrade TaSTP via the 26S proteasome pathway.

Abstract: Drought stress has a great impact on wheat yields. The ubiquitin/26S proteasome system is one of the most important mechanisms employed by plants for responding to stress. E3 ubiquitin ligase is an important part of the ubiquitin/26S proteasome system. In wheat, the mechanism of E3 ubiquitin ligase TaDIS1 has not been investigated in great detail. In this study, TaSTP was identified as an interacting partner using yeast two-hybrid screening. The results obtained from bimolecular fluorescence complementation, pull-down, and co-immunoprecipitation assays also demonstrated that TaDIS1 interacts with TaSTP. In vitro ubiquitination assays showed that TaDIS1 has an E3 ubiquitin ligase activity and the results based on two TaDIS1 mutants suggested that the RING domain is essential for its E3 ubiquitin ligase activity. In addition, we used MG132 to show that TaSTP can be degraded by TaDIS1 via the 26S proteasome pathway. The transcript levels of TaSTP showed that it can also respond to different abiotic stresses, such as drought, salt, and abscisic acid treatment. RING E3 ubiquitin ligase TaDIS1 may through the posttranslational regulation of TaSTP to play an important role in drought tolerance.

Lv|Qian|Q| Zhang|Li|L| Zan|Ting|T| Li|Liqun|L| Li|Xuejun|X|

D018506:Gene Expression Regulation, Plant

Wheat
E3 ubiquitin ligase
Drought stress
Protein degradation


The measurement of in vivo joint angles during a squat using a single camera markerless motion capture system as compared to a marker based system.

Abstract: Markerless motion capture may have the potential to make motion capture technology widely clinically practical. However, the ability of a single markerless camera system to quantify clinically relevant, lower extremity joint angles has not been studied in vivo. Therefore, the goal of this study was to compare in vivo joint angles calculated using a marker-based motion capture system and a Microsoft Kinect during a squat. Fifteen individuals participated in the study: 8 male, 7 female, height 1.702±0.089m, mass 67.9±10.4kg, age 24±4 years, BMI 23.4±2.2kg/m(2). Marker trajectories and Kinect depth map data of the leg were collected while each subject performed a slow squat motion. Custom code was used to export virtual marker trajectories for the Kinect data. Each set of marker trajectories was utilized to calculate Cardan knee and hip angles. The patterns of motion were similar between systems with average absolute differences of <5 deg. Peak joint angles showed high between-trial reliability with ICC>0.9 for both systems. The peak angles calculated by the marker-based and Kinect systems were largely correlated (r>0.55). These results suggest the data from the Kinect can be post processed in way that it may be a feasible markerless motion capture system that can be used in the clinic.

Schmitz|Anne|A| Ye|Mao|M| Boggess|Grant|G| Shapiro|Robert|R| Yang|Ruigang|R| Noehren|Brian|B|

Squat
Markerless motion capture
Kinect
Hip and knee angles


Analysis and critique of 'Transforming children and young people's mental health provision: A green paper': Some implications for refugee children and young people.

Abstract: Adopting a children's rights perspective, a critique and analysis underpinned by documentary research methodology was undertaken in order to assess the extent to which the government's Green Paper (Department of Health and Social Care and Department of Education, 2017. Transforming children and young people's mental health provision: a green paper. Available at: https://www.gov.uk/government/consultations/transforming-children-and-young-peoples-mental-health-provision-a-green-paper (accessed 7 December 2017)) addresses the mental health and well-being needs of refugee children and young people in England and Wales, identifying strengths, limitations and challenges for future policy and practice. Findings suggest that there is much of potential benefit to refugee children and young people's future mental health and well-being. However, a paradigm shift, explicit in implications, scale and time frame, will be required, if the Green Paper is to achieve those changes in attitudes, practice and service delivery which it anticipates. We argue that this Green Paper's overarching challenge is that it is premised on Western-centric models in its understanding of the experiences of refugee children and young people, and management of trauma and mental health. It fails to recognize the meanings and significance of culture, and of diversity and difference, and the need to invest in all communities in facilitating engagement and support for children and young people's mental health issues.


An unprecedented occult non-communicating rudimentary uterine horn treated with laparoscopic excision and preservation of both fallopian tubes: a case report and review of the literature.

Abstract:
BACKGROUND
Müllerian duct anomalies are congenital malformations of the female genital tract and may be of various types. For decades they have been classified according to the American Society of Reproductive Medicine, which mentions unicornuate uterine malformations as the second subgroup. They result from the arrested development of one of the Müllerian ducts and appear in approximately 1/1000 women. These anomalies are usually diagnosed in the second decade of life, because they tend to remain asymptomatic until adolescence and their initial symptoms may vary. Patients present with symptoms such as dysmenorrhea, infertility, and chronic or acute abdominal pain.

CASE PRESENTATION
We report on a 21-year-old Caucasian German patient who suffered from dysmenorrhea for 7 years. After a transvaginal ultrasound and magnetic resonance tomography of the pelvis was performed, the patient underwent a diagnostic hysteroscopy and operative laparoscopy, and was finally diagnosed with a Müllerian duct anomaly presenting with a non-communicating rudimentary uterine horn. The left tube arose directly in orthotopic location from the cornua of uterus, with no connection to the rudimentary uterine horn or structure.

CONCLUSION
The anatomic features of this case have not been reported previously and were not consistent with any existing classification. More cases are needed in order to confirm our hypothesis. Gynecologists should always consider Müllerian anomalies as an important differential diagnosis in young patients with abdominal pain.

Rudimentary uterine horn
Laparoscopic excision
Müllerian anomalies


The substituent effects on the [3+2] cycloaddition of nitrile oxides generated by photooxidation of arylazides to acetonitrile.

Abstract: The DFT approach in M06L/6-311 + G(d,p) approximation was used to study the transformation of unsaturated nitrile oxides (RCNO), which were generated by photooxidation of the corresponding aromatic azide, to oxadiazoles via [3 + 2]cyclization with acetonitrile. It was found that the cycloaddition activation enthalpy was within 60-93 kJ/mol, depending on the structure of the nitrile oxide. A significant mesomeric effect of the substituent and its position in the conjugated molecular system on the activation barrier of the reaction studied was identified. The relationship between the thermodynamic characteristics of [3 + 2] cycloaddition and electron density distribution in RCNO was demonstrated by a representative set of compounds including mono- and disubstituted nitrile oxides.

Yarullin|Aidar R|AR|
Ovchinnikov|Mikhail Yu|MY|
Khursan|Sergey L|SL|
Chainikova|Ekaterina M|EM|
Safiullin|Rustam L|RL|

[3+2] cycloaddition
Nitrile oxides
DFT approximation
Nitroso oxides


Title: Gene transfer by pyro-drive jet injector is a novel therapeutic approach for muscle diseases.

Abstract: The angiogenic gene therapy is an attractive approach for the treatment of ischemic muscle diseases, including peripheral arterial disease and ischemic heart diseases. Although a variety of gene transfer methods have been developed, the efficiency of gene transfer is still limited. We have been developing the needleless high-energy bioinjector device, Pyro-drive Jet Injector (PJI), based on pyrotechnics using a combination of ignition powder and gunpowder, however, the utility of PJI in gene transfer into muscle tissues remains unclear. pcDNA3.1 plasmid containing Flag was injected to the thigh muscles of C57BL/6J mice using PJI or needle, as a control. Histological analysis demonstrated that the protein expression of Flag was observed in a wider range in PJI group than in needle group. To assess the validity of PJI for gene therapy, pcDNA3.1-human fibroblast growth factor 2 (FGF2), which has angiogenic activity and tissue protective properties, was injected into the ischemic thigh muscles with PJI or needle. ELISA assay revealed that the protein expression of FGF2 was increased in the thigh muscle tissues by PJI-mediated gene delivery. Significantly, histological analyses revealed that muscle fiber cross-sectional area and the number of endothelial marker CD31 (+) cells was increased in ischemic hind-limb tissues of the PJI-FGF2 group but not in those of needle-FGF2 group. To expand the applicability of the PJI-mediated gene transfer, pcDNA3.1-venus plasmid was injected into murine hearts with PJI or needle. PJI method was successful in gene transfer into murine hearts, especially into cardiomyocytes, with high efficiency when compared to needle method. Collectively, the non-needle, non-liposomal and non-viral gene transfer by PJI could be a novel therapeutic approach for muscle diseases.

Nakae|Takafumi|T| Obana|Masanori|M| Maeda|Takahiro|T| Ikeda|Akari|A| Miyazaki|Hiroshi|H| Tanaka|Shota|S| Maeda|Makiko|M| Yamashita|Kunihiko|K| Terai|Kazuhiro|K| Obika|Satoshi|S| Fujio|Yasushi|Y|

Pyro-drive Jet Injector
Gene delivery
Cardiac muscles
Skeletal muscles


Extracorporeal membrane oxygenation for life-threatening asthma refractory to mechanical ventilation: analysis of the Extracorporeal Life Support Organization registry.

Abstract:
BACKGROUND
The use of extracorporeal membrane oxygenation (ECMO) in cases of near-fatal asthma (NFA) has increased, but the benefits and potential complications of this therapy have yet to be fully investigated.

METHODS
Cases were extracted from the Extracorporeal Life Support Organization Registry between March 1992 and March 2016. All patients with a diagnosis of asthma (according to the International Classification of Diseases 9th edition), who also received ECMO, were extracted. Exclusion criteria included patients who underwent multiple courses of ECMO; those who received ECMO for cardiopulmonary resuscitation or cardiac dysfunction; and those with another primary diagnosis, such as sepsis. We analyzed survival to hospital discharge, complications, and clinical factors associated with in-hospital mortality, in patients with severe life-threatening NFA requiring ECMO support.

RESULTS
In total 272 patients were included. The mean time spent on ECMO was 176.4 hours. Ventilator settings, including rate, fraction of inspired oxygen (FiO2), peak inspiratory pressure (PIP), and mean airway pressure, significantly improved after ECMO initiation (rate (breaths/min), 19.0 vs. 11.3, p < 0.001; FiO2 (%), 81.2 vs. 48.8, p < 0.001; PIP (cmH2O), 38.2 vs. 25.0, p < 0.001; mean airway pressure (cmH2O): 21.4 vs. 14.2, p < 0.001). In particular, driving pressure was significantly decreased after ECMO support (29.5 vs. 16.8 cmH2O, p < 0.001). The weaning success rate was 86.7%, and the rate of survival to hospital discharge was 83.5%. The total complication rate was 65.1%, with hemorrhagic complications being the most common (28.3%). Other complications included renal (26.8%), cardiovascular (26.1%), mechanical (24.6%), metabolic (22.4%), infection (16.5%), neurologic (4.8%), and limb ischemia (2.6%). Of the hemorrhagic complications, cannulation site hemorrhage was the most common (13.6%). Using multivariate logistic regression analysis, it was found that hemorrhage was associated with increased in-hospital mortality (odds ratio, 2.97; 95% confidence interval, 1.07-8.24; p = 0.036). Hemorrhage-induced death occurred in four patients (1.5%). The most common reason for death was organ failure (37.8%).

CONCLUSIONS
ECMO can provide adequate gas exchange and prevent lung injury induced by mechanical ventilation, and may be an effective bridging strategy to avoid aggressive ventilation in refractory NFA. However, careful management is required to avoid complications.

Yeo|Hye Ju|HJ|
Kim|Dohyung|D|
Jeon|Doosoo|D|
Kim|Yun Seong|YS|
Rycus|Peter|P|
Cho|Woo Hyun|WH|

D038801:International Classification of Diseases


Anisotropic Effective Mass, Optical Property, and Enhanced Band Gap in BN/Phosphorene/BN Heterostructures.

Abstract: Phosphorene is receiving great research interests because of its peculiar physical properties. Nonetheless, the phosphorus has a trouble of degradation due to oxidation. Hereby, we propose that the electrical and optical anisotropic properties can be preserved by encapsulating into hexagonal boron nitride (h-BN). We found that the h-BN contributed to enhancing the band gap of the phosphorene layer. Comparing the band gap of the pristine phosphorene layer, the band gap of the phosphorene/BN(1ML) system was enhanced by 0.15 eV. It was further enhanced by 0.31 eV in the BN(1ML)/phosphorene/BN(1ML) trilayer structure. However, the band gap was not further enhanced when we increased the thickness of the h-BN layers even up to 4 MLs. Interestingly, the anisotropic effective mass and optical property were still preserved in BN/phosphorene/BN heterostructures. Overall, we predict that the capping of phosphorene by the h-BN layers can be an excellent solution to protect the intrinsic properties of the phosphorene.

optical property
band gap
phosphorene
heterostructure
anisotropic transport


Two phase 3, double-blind, placebo-controlled studies of the efficacy and safety of Astodrimer 1% Gel for the treatment of bacterial vaginosis.

Abstract:
OBJECTIVE
Astodrimer is a dendrimer formulated in a vaginal gel to treat bacterial vaginosis (BV) and prevent recurrence. The objective of these studies was to confirm the efficacy and safety of Astodrimer 1 % Gel for treatment of BV.

STUDY DESIGN
Women with bacterial vaginosis were randomized 1:1 to Astodrimer 1 % Gel (Study 1 conducted in the United States, N = 127; Study 2 conducted in the United States, Germany and Belgium, N = 128) or placebo gel (Study 1, N = 123; Study 2, N = 123) at a dose of 5 g vaginally once daily for 7 days. The primary endpoint was clinical cure, defined as i) absence of bacterial vaginosis vaginal discharge; ii) <20 % clue cells; and iii) negative whiff test at day 9-12. Secondary efficacy analyses included clinical cure at day 21-30. Other endpoints at days 9-12 and 21-30 included Nugent cure (Nugent score ≤3), absence of symptoms, and adverse events. The primary analysis in the modified intent-to-treat population used the Cochran Mantel Haenszel test stratified by analysis center with a two-sided significance level of α = .05.

RESULTS
Astodrimer 1 % Gel was superior to placebo for the primary and selected secondary efficacy measures. Clinical cure rates at day 9-12 were 50.4 % (59/117) vs 16.5 % (19/115, P < .001) (Study 1) and 56.7 % (68/120) vs 21.4 % (25/117, P < .001) (Study 2) for astodrimer vs placebo. At day 21-30, clinical cure results showed a similar trend but the difference to placebo was not statistically significant. Nugent cure rates at day 9-12 were 12.8 % (15/117) vs 2.6 % (3/115, P = .004) (Study 1) and 13.3 % (16/120) vs 5.1 % (6/117, P = .030) (Study 2) for astodrimer vs placebo. A greater proportion of women receiving astodrimer reported absence of vaginal discharge and absence of vaginal odor at day 9-12 and day 21-30 compared with placebo. Adverse events were generally mild and self-limiting. For the combined studies, adverse events potentially related to treatment occurred in 14.7 % (37/252) of astodrimer patients vs 9.4 % (23/244) for placebo, including vulvovaginal candidiasis reported for 2.4 % (6/252) of astodrimer patients.

CONCLUSION
These results support a role for Astodrimer 1 % Gel as an effective, safe and well-tolerated treatment for women with bacterial vaginosis.

Chavoustie|Steven E|SE|
Carter|Belvia A|BA|
Waldbaum|Arthur S|AS|
Donders|Gilbert G G|GGG|
Peters|Klaus H|KH|
Schwebke|Jane R|JR|
Paull|Jeremy R A|JRA|
Price|Clare F|CF|
Castellarnau|Alex|A|
McCloud|Philip|P|
Kinghorn|George R|GR|

D014622:Vaginal Creams, Foams, and Jellies

Treatment
Bacterial vaginosis
Dendrimer
Astodrimer gel
Biofilm
SPL7013
VivaGel®


The pattern of shikimate pathway and phenylpropanoids after inhibition by glyphosate or quinate feeding in pea roots.

Abstract: The shikimate pathway is a metabolic route for the biosynthesis of aromatic amino acids (AAAs) (i.e. phenylalanine, tyrosine, and tryptophan). A key enzyme of shikimate pathway (5-enolpyruvylshikimate-3-phosphate synthase, EPSPS) is the target of the widely used herbicide glyphosate. Quinate is a compound synthesized in plants through a side branch of the shikimate pathway. Glyphosate provokes quinate accumulation and exogenous quinate application to plants shows a potential role of quinate in the toxicity of the herbicide glyphosate. Based on this, we hypothesized that the role of quinate accumulation in the toxicity of the glyphosate would be mediated by a deregulation of the shikimate pathway. In this study the effect of the glyphosate and of the exogenous quinate was evaluated in roots of pea plants by analyzing the time course of a full metabolic map of several metabolites of shikimate and phenylpropanoid pathways. Glyphosate application induced an increase of the 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase (DAHPS, first enzyme of the shikimate pathway) protein and accumulation of metabolites upstream of the enzyme EPSPS. No common effects on the metabolites and regulation of shikimate pathway were detected between quinate and glyphosate treatments, supporting that the importance of quinate in the mode of action of glyphosate is not mediated by a common alteration of the regulation of the shikimate pathway. Contrary to glyphosate, the exogenous quinate supplied was probably incorporated into the main trunk from the branch pathway and accumulated in the final products, such as lignin, concomitant with a decrease in the amount of DAHPS protein.

Zabalza|Ana|A| Orcaray|Luis|L| Fernández-Escalada|Manuel|M| Zulet-González|Ainhoa|A| Royuela|Mercedes|M|

Aromatic amino acids
EPSPS
DAHPS
Hydroxybenzoic acids
Hydroxycinnamic acids
Phenylpropanoid metabolism


Early myocardial and skeletal muscle interstitial remodelling in systemic sclerosis: insights from extracellular volume quantification using cardiovascular magnetic resonance.

Abstract:
AIMS
Systemic sclerosis (SSc) may induce cardiac fibrosis and systo-diastolic dysfunction. Cardiovascular magnetic resonance (CMR) can detect replacement myocardial fibrosis with late gadolinium enhancement (LGE) and interstitial myocardial fibrosis with T1 mapping techniques. The aim of the study was to detect subclinical cardiac involvement with CMR in paucisymptomatic SSc patients with no previous history of myocardial disease, comparing it with skeletal muscle remodelling.

METHODS AND RESULTS
Thirty consecutive SSc patients (mean age: 51 ± 12 years, all women) and 10 healthy controls (mean age: 48 ± 15 years, all women) underwent clinical, biohumoral assessment, and CMR. Extracellular volume fraction (ECV) was calculated from pre- and post-contrast T1 values in the myocardium and skeletal muscle. Seventeen patients (57%) were asymptomatic, 13 (43%) paucisymptomatic (effort dyspnoea). All patients had normal biventricular volumes and systolic function, while LGE was present in seven patients (23%). Myocardial ECV was significantly increased in patients with SSc (30 ± 4%) than controls (28 ± 4%, P = 0.03), as was skeletal muscle ECV (23 ± 6% vs. 18 ± 4%, P < 0.01). Myocardial ECV did not differ between patients with and without LGE (P = NS) and showed no significant correlations with clinical data, biventricular volumes, systolic, or diastolic function. Overall, myocardial ECV showed a significant correlation with skeletal muscle ECV (R = 0.58, P < 0.001).

CONCLUSION
SSc is associated not only with myocardial replacement fibrosis, as detected by LGE, but also with interstitial remodelling of the myocardium and skeletal muscles, as detected by an increased ECV also in patients with normal biventricular function, with potential diagnostic, prognostic, and therapeutic clinical implications.

Barison|Andrea|A|
Gargani|Luna|L|
De Marchi|Daniele|D|
Aquaro|Giovanni Donato|GD|
Guiducci|Serena|S|
Picano|Eugenio|E|
Cerinic|Marco Matucci|MM|
Pingitore|Alessandro|A|

D019028:Magnetic Resonance Imaging, Cine

Systemic sclerosis
Cardiovascular magnetic resonance
Myocardial fibrosis
Late gadolinium enhancement
Cardiac T1 mapping


DNA Methylation Reorganization of Skeletal Muscle-Specific Genes in Response to Gestational Obesity.

Abstract: The goals were to investigate in umbilical cord tissue if gestational obesity: (1) was associated with changes in DNA methylation of skeletal muscle-specific genes; (2) could modulate the co-methylation interactions among these genes. Additionally, we assessed the associations between DNA methylation levels and infant's variables at birth and at age 6. DNA methylation was measured in sixteen pregnant women [8-gestational obesity group; 8-control group] in umbilical cord using the Infinium Methylation EPIC Bead Chip microarray. Differentially methylated CpGs were identified with Beta Regression Models [false discovery rate (FDR) < 0.05 and an Odds Ratio > 1.5 or < 0.67]. DNA methylation interactions between CpGs of skeletal muscle-specific genes were studied using data from Pearson correlation matrices. In order to quantify the interactions within each network, the number of links was computed. This identification analysis reported 38 differential methylated CpGs within skeletal muscle-specific genes (comprising 4 categories: contractibility, structure, myokines, and myogenesis). Compared to control group, gestational obesity (1) promotes hypermethylation in highly methylated genes and hypomethylation in low methylated genes; (2) CpGs in regions close to transcription sites and with high CpG density are hypomethylated while regions distant to transcriptions sites and with low CpG density are hypermethylated; (3) diminishes the number of total interactions in the co-methylation network. Interestingly, the associations between infant's fasting glucose at age 6 and MYL6, MYH11, TNNT3, TPM2, CXCL2, and NCAM1 were still relevant after correcting for multiple testing. In conclusion, our study showed a complex interaction between gestational obesity and the epigenetic status of muscle-specific genes in umbilical cord tissue. Additionally, gestational obesity may alter the functional co-methylation connectivity of CpG within skeletal muscle-specific genes interactions, our results revealing an extensive reorganization of methylation in response to maternal overweight. Finally, changes in methylation levels of skeletal muscle specific genes may have persistent effects on the offspring of mothers with gestational obesity.

Prats-Puig|Anna|A| García-Retortillo|Sergi|S| Puig-Parnau|Miquel|M| Vasileva|Fidanka|F| Font-Lladó|Raquel|R| Xargay-Torrent|Sílvia|S| Carreras-Badosa|Gemma|G| Mas-Parés|Berta|B| Bassols|Judit|J| López-Bermejo|Abel|A|

methylation
gestational obesity
umbilical cord tissue
skeletal muscle
network physiology


Long-term improvement of psoriasis patients' adherence to topical drugs: testing a patient-supporting intervention delivered by healthcare professionals.

Abstract:
BACKGROUND
Psoriasis affects 2-4% of the Western adult population and is a socio-economic burden for patients and society. Topical drugs are recommended as first-line treatment for mild-to-moderate psoriasis, but low adherence is a barrier to treatment success. Psoriasis patients require support, in order to improve their long-term use of topical drugs. The project aims to test whether a patient-supporting intervention delivered by dermatology nurses can reduce the severity of psoriasis, improve the use of topical drugs, and is cost-effective compared to standard procedure.

METHODS
The intervention consists of improved support delivered to patients by three experienced dermatology nurses, who will support patients on a regular basis by consultations with a focus on providing reminder systems, accountability, reinforcement, and building trust in the treatment. Each patient will be supported by the same dermatology nurse throughout the entire study period. The effect will be compared with standard procedure. The intervention will be tested in a randomized controlled trial during a 48-week period. A group of patients with moderate-to-severe psoriasis (psoriasis affecting ≥ 4% of the total body surface area) and 18-85 years of age who are prescribed topical treatment will be randomized to a non-intervention (n ≈ 57) or intervention group (n ≈ 57). Participants in both arms will be prescribed topical preparations containing corticosteroid and/or calcipotriol. The primary outcome will be a change in the severity of psoriasis, measured as reduction in the Lattice-System Physician's Global Assessment. Secondary outcomes will include changes in health-related quality of life (measured by disease specific and generic questionnaires), primary adherence (i.e., proportion of filled prescriptions), and secondary adherence by objective measure (rate of topical drug consumption (obtained by weighing medication packages) compared to estimated recommended consumption). A health economic evaluation is planned to run alongside the trial. Participants' total health costs will be estimated on the basis of health costs reported to the national health registries and costs spent on the intervention, after which a cost-utility and cost-effectiveness analysis will be carried out.

DISCUSSION
If the intervention can reduce the severity of psoriasis in a significant manner and is economically favorable compared to standard treatment, there is potential for implementing the intervention in dermatology clinics.

TRIAL REGISTRATION
Clinicaltrials.gov NCT04220554 . Registered on January 7, 2020. Study results, either positive, negative, or inconclusive, will be published on www.clinicaltrials.gov . Trial registration no. with the Danish Regional Committee on Health Research Ethics, registration no. 72613.

Psoriasis
Adherence
Support
Health-care professionals
Randomized controlled trial (RCT)


Preferential central venous catheter access with concurrent IVC filter use.

Abstract: In our aging population, there is an increased incidence of concurrent IVC filter and central venous catheter use. One of the risks of concurrent use is filter embolization, which almost always occurs due to the J-tipped guidewire. In this case, we describe the successful placement of a central venous catheter in the femoral vein in a patient with an IVC filter. Some guidelines exist concerning CVC placement in patients with IVC filters, and this case highlights the benefits of placing a CVC in the femoral vein. While little research exists regarding higher rates of IVC filter embolization in internal jugular and subclavian vein access sites, we hypothesize it is due to the conical shape of IVC filters.

Catheters
dialysis access
intensive care
techniques and procedures


Subcutaneous Versus Sublingual Immunotherapy for Adults with Allergic Rhinitis: A Systematic Review with Meta-Analyses.

Abstract:
OBJECTIVES
To determine whether subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT) better improves patient outcomes and quality of life for adults with allergic rhinitis or rhinoconjunctivitis (AR/C) with or without mild to moderate asthma.

METHODS
Systematic review methodology was based on the Cochrane Collaboration handbook and Preferred Reporting Items for Systematic Reviews and Meta-analyses. Four databases (PubMed, Cochrane Library, EMBASE, and Web of Science) were queried from inception to July 30, 2020. Two independent reviewers screened potentially relevant studies and assessed risk of bias. Outcomes of interest were symptom score (SS), medication score (MS), combined symptom medication score (CSMS), and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). Meta-analyses with an adjusted indirect comparison were conducted in RevMan 5.4.1.

RESULTS
Seven SCIT versus SLIT randomized controlled trials (RCTs) demonstrated no significant differences for any outcomes, but insufficient data precluded direct meta-analysis. For the adjusted indirect comparison, 46 RCTs over 39 studies were included for SCIT versus placebo (n = 13) and SLIT versus placebo (n = 33). Statistically significant results favoring SCIT were found for SS (standardized mean difference [SMD] = 0.40; 95% confidence interval [CI] = 0.31-0.49), MS (SMD = 0.26; 95% CI = 0.14-0.39), CSMS (SMD = 0.42; 95% CI = 0.17-0.67), and RQLQ (MD = 0.24; 95% CI = 0.04-0.44). Statistically significant results favoring SLIT were found for SS (SMD = 0.42; 95% CI = 0.32-0.53), MS (SMD = 0.40; 95% CI = 0.28-0.53), CSMS (SMD = 0.37; 95% CI = 0.29-0.45), and RQLQ (MD = 0.32; 95% CI = 0.20-0.43). No significant differences were found between SCIT and SLIT for SS (SMD = -0.02; 95% CI = -0.15 to 0.11), MS (SMD = -0.14; 95% CI = -0.31 to 0.03), CSMS (SMD = 0.05; 95% CI = -0.21 to 0.31), or RQLQ (MD = -0.08; 95% CI = -0.31 to 0.15).

CONCLUSION
SCIT and SLIT are comparably effective treatments for adults with AR/C. More RCTs analyzing SCIT versus SLIT are needed to directly compare the two. Laryngoscope, 2021.