Left atrial longitudinal strain parameters predict postoperative persistent atrial fibrillation following mitral valve surgery: a speckle tracking echocardiography study.

Abstract: Postoperative atrial fibrillation (POAF) is common after cardiac surgery and is associated with increased morbidity, mortality, and prolonged hospital stay. Speckle tracking echocardiography (STE) has been applied recently for evaluation of LA function. The purpose of this study was to examine whether left atrial longitudinal strain measured by STE is a predictor for the development of POAF following mitral valve surgery for severe mitral regurgitation. We studied 53 patients undergoing mitral valve surgery in sinus rhythm at the time of surgery. Echocardiography with evaluation of LA strain by STE was performed. Detection of POAF was based on documentation of AF episodes by continuous telemetry throughout hospitalization. Patients who did not develop POAF were taken as group 1 and those who had POAF constituted group 2. The echocardiographic and clinical predictors of POAF were investigated. POAF occurred in 28.3% of subjects. Mean age, LAVi and BNP were found higher in group 2 while peak atrial longitudinal strain (PALS) (13.9 ± 3.8% vs. 24.8 ± 7.3%; P < 0.001), peak atrial contraction strain (PACS) (7.6 ± 1.95% vs. 11.3 ± 3.5%; P < 0.001) were significantly lower. By multivariate logistic regression analysis, PALS and LAVi were independent predictor of POAF development. LA longitudinal strain was found to predict POAF in patients undergoing mitral valve surgery. It could be used to better identify patients at greater risk of developing POAF, and thus to guide in risk stratification and to take appropriate intensive prophylactic therapy.

Candan|Ozkan|O|
Ozdemir|Nihal|N|
Aung|Soe Moe|SM|
Dogan|Cem|C|
Karabay|Can Yucel|CY|
Gecmen|Cetin|C|
Omaygenç|Onur|O|
Güler|Ahmet|A|

D019918:Heart Valve Prosthesis Implantation

left atrial longitudinal strain
mitral valve surgery
speckle tracking echocardiography
postoperative atrial fibrillation


Biomimetic Trachea Engineering via a Modular Ring Strategy Based on Bone-Marrow Stem Cells and Atelocollagen for use in Extensive Tracheal Reconstruction.

Abstract: The fabrication of biomimetic tracheas with cartilaginous rings alternately interspersed between vascularized fibrous tissue (CRVFT) architecture has the potential to perfectly recapitulate normal tracheal structure and function. Herein, we describe the development of a customized chondroitin sulfate-incorporated type II atelocollagen (COL II/CS) scaffold with excellent chondrogenic capacity and a type I atelocollagen (COL I) scaffold to facilitate the formation of vascularized fibrous tissue. An efficient modular ring strategy was then adopted to develop a CRVFT-based biomimetic trachea. The in vitro engineering of cartilaginous rings was achieved via the recellularization of ring-shaped COL II/CS scaffolds using bone marrow stem cells as a mimetic for native cartilaginous ring tissue. A CRVFT-based trachea with biomimetic mechanical properties composed of bionic biochemical components was additionally successfully generated in vivo via the alternating stacking of cartilaginous rings and ring-shaped COL I scaffolds on a silicone pipe. The resultant biomimetic trachea with pedicled muscular flaps was used for extensive tracheal reconstruction and exhibited satisfactory therapeutic outcomes with structural and functional properties similar to those of native trachea. This is the first study to utilize stem cells for long-segmental tracheal cartilaginous regeneration and this represents a promising method for extensive tracheal reconstruction. This article is protected by copyright. All rights reserved.

Biomimetic trachea
Stem cell
Atelocollagen
Cartilaginous ring
Vascularization


Natural Materials Assembled, Biodegradable, and Transparent Paper-Based Electret Nanogenerator.

Abstract: Developing eco-friendly and low-cost electronics is an effective strategy to address the electronic waste issue. In this study, transparent cellulose nanopaper (T-paper) and polylactic acid (PLA) electret were used to construct a biodegradable and transparent paper-based electret nanogenerator. The nanogenerator could be assembled with paper products to form a self-powered smart packaging system without impairing the appearance, due to the high transparency and desirable output performance. Furthermore, the self-degradation property in the natural soil of the nanogenerator is demonstrated, indicating that the nanogenerator is recycled and will not pollute the environment. We anticipate that this study will provide new insights to develop eco-friendly power source and paper-based electronics.

biodegradable
transparent
paper-based
electret nanogenerators
self-powered


Molecules to Ecosystems: Actinomycete Natural Products In situ.

Abstract: Actinomycetes, filamentous actinobacteria found in numerous ecosystems around the globe, produce a wide range of clinically useful natural products (NP). In natural environments, actinomycetes live in dynamic communities where environmental cues and ecological interactions likely influence NP biosynthesis. Our current understating of these cues, and the ecological roles of NP, is in its infancy. We postulate that understanding the ecological context in which actinomycete metabolites are made is fundamental to advancing the discovery of novel NP. In this review we explore the ecological relevance of actinomycetes and their secondary metabolites from varying ecosystems, and suggest that investigating the ecology of actinomycete interactions warrants particular attention with respect to metabolite discovery. Furthermore, we focus on the chemical ecology and in situ analysis of actinomycete NP and consider the implications for NP biosynthesis at ecosystem scales.

Behie|Scott W|SW|
Bonet|Bailey|B|
Zacharia|Vineetha M|VM|
McClung|Dylan J|DJ|
Traxler|Matthew F|MF|

actinomycetes
natural products
in situ
chemical ecology
microbial interactions


De novo assembly and annotation of the European abalone Haliotis tuberculata transcriptome.

Abstract: The European abalone Haliotis tuberculata is a delicacy and consequently a commercially valuable gastropod species. Aquaculture production and wild populations are subjected to multiple climate-associated stressors and anthropogenic pressures, including rising sea-surface temperatures, ocean acidification and an emerging pathogenic Vibrio infection. Transcript expression data provides a valuable resource for understanding abalone responses to variation in the biotic and abiotic environment. To generate an extensive transcriptome, we performed next-generation sequencing of RNA on larvae exposed to temperature and pH variation and on haemolymph of adults from two wild populations after experimental infection with Vibrio harveyi. We obtained more than 1.5 billion raw paired-end reads, which were assembled into 328,519 contigs. Filtration and clustering produced a transcriptome of 41,099 transcripts, of which 10,626 (25.85%) were annotated with Blast hits, and 7380 of these were annotated with Gene Ontology (GO) terms in Blast2Go. A differential expression analysis comparing all samples from the two life stages identified 5690 and 10,759 transcripts with significantly higher expression in larvae and adult haemolymph respectively. This is the greatest sequencing effort yet in the Haliotis genus, and provides the first high-throughput transcriptomic resource for H. tuberculata.

Harney|Ewan|E|
Dubief|Bruno|B|
Boudry|Pierre|P|
Basuyaux|Olivier|O|
Schilhabel|Markus B|MB|
Huchette|Sylvain|S|
Paillard|Christine|C|
Nunes|Flavia L D|FLD|

Vibrio harveyi
Climate change
Development
Gastropoda
Mollusca
RNA-Seq


Reference values for salivary testosterone in adolescent boys and girls determined using Isotope-Dilution Liquid-Chromatography Tandem Mass Spectrometry (ID-LC-MS/MS).

Abstract: The measurement of testosterone in saliva is an attractive alternative to serum analysis due to the simple and non-invasive sample collection. In children and adolescents salivary testosterone is mainly measured to investigate whether puberty has started or not. This study aimed to establish reference values for salivary testosterone during puberty in boys and girls. We measured salivary testosterone using ID-LC-MS/MS in a cohort of 131 girls and 123 boys of whom each had salivary testosterone measured at two time points during puberty. Salivary testosterone concentrations start to increase with the start of puberty around eight years and continuously increase up to adult concentrations in the following ten years. Reference values were calculated using the Lambda-Mu-Sigma (LMS)-curve fitting method and provided per year from 8 to 26 years of age in boys and girls. These reference ranges may help clinicians and researchers to interpret salivary testosterone results in both individual patients and study subjects.

Büttler|Rahel M|RM|
Peper|Jiska S|JS|
Crone|Eveline A|EA|
Lentjes|Eef G W|EGW|
Blankenstein|Marinus A|MA|
Heijboer|Annemieke C|AC|

Reference values
Salivary testosterone
Adolescents


Structural modeling of the N-terminal signal-receiving domain of IκBα.

Abstract: The transcription factor nuclear factor-κB (NF-κB) exerts essential roles in many biological processes including cell growth, apoptosis and innate and adaptive immunity. The NF-κB inhibitor (IκBα) retains NF-κB in the cytoplasm and thus inhibits nuclear localization of NF-κB and its association with DNA. Recent protein crystal structures of the C-terminal part of IκBα in complex with NF-κB provided insights into the protein-protein interactions but could not reveal structural details about the N-terminal signal receiving domain (SRD). The SRD of IκBα contains a degron, formed following phosphorylation by IκB kinases (IKK). In current protein X-ray structures, however, the SRD is not resolved and assumed to be disordered. Here, we combined secondary structure annotation and domain threading followed by long molecular dynamics (MD) simulations and showed that the SRD possesses well-defined secondary structure elements. We show that the SRD contains 3 additional stable α-helices supplementing the six ARDs present in crystallized IκBα. The IκBα/NF-κB protein-protein complex remained intact and stable during the entire simulations. Also in solution, free IκBα retains its structural integrity. Differences in structural topology and dynamics were observed by comparing the structures of NF-κB free and NF-κB bound IκBα-complex. This study paves the way for investigating the signaling properties of the SRD in the IκBα degron. A detailed atomic scale understanding of molecular mechanism of NF-κB activation, regulation and the protein-protein interactions may assist to design and develop novel chronic inflammation modulators.

Yazdi|Samira|S| Durdagi|Serdar|S| Naumann|Michael|M| Stein|Matthias|M|

IκBα
NF-κB
signal receiving domain
N-terminal extension
molecular dynamics simulation
protein-protein complex refinement
secondary structure prediction
signal transduction


Role of the Gut Microbiome in Nonalcoholic Fatty Liver Disease.

Abstract: The incidence of nonalcoholic fatty liver disease (NAFLD) continues to increase with prevalence estimates ranging from 17%-33%, making it is the most common cause of chronic liver disease in North America. Its importance is due to not only its prevalence but also its association with increased cardiovascular morbidity and progression to cirrhosis in a subset of patients. NAFLD encompasses a pathologic spectrum of disease, from relatively benign accumulation of lipid (steatosis) to progressive nonalcoholic steatohepatitis associated with inflammation, fibrosis, and necrosis. Nonalcoholic steatohepatitis remains an important phenotypic state because this subgroup of patients is deemed at high risk for developing cirrhosis and progressing to liver failure requiring transplantation or to death. Gut microbiota has recently been identified as regulators of energy homeostasis and fat deposition, thereby implicating them in the development of obesity and associated metabolic diseases. The growing evidence that alteration in gut microbiota (dysbiosis) may affect liver pathology may allow for a better understanding of its role in the pathogenesis of NAFLD, help to identify patients at risk of progression, and expose a microbial target for prevention and therapeutic intervention. In this review, we discuss the growing evidence that highlights the relationship between gut microbiota and its association with NAFLD.

D065626:Non-alcoholic Fatty Liver Disease

nonalcoholic fatty liver disease
fatty liver
liver disease
microbiota
obesity
cytokines
fatty acids
organ transplantation
probiotics


Electrochemical triggering of the Chardonnay wine metabolome.

Abstract: Oxidation of wine upon bottle ageing is a crucial matter of concern for the qualitative long-term storage of white wines. However, understanding the various molecular mechanisms potentially involved, which can impact the wine composition, requires that top-down analytical strategies are implemented. Here, we report the analysis of bottle aged Chardonnay wines made from the same must, but differing by the amount of SO2 initially added to the must at pressing (0 and 8 g·h L-1). Metabolomics fingerprints obtained from electrochemical simulation of oxidative reactions were obtained by coupling of either on-line or off-line electrochemical oxidation to FT-ICR-MS detection. We reveal that, whatever the electrochemical DC voltage is, wines with initial SO2 addition displayed molecular fingerprints, which remained more similar to the non-oxidized wine without initial SO2 addition. We further show that a diversity of sulfur-containing compounds appeared to be the most sensitive to oxidation, whereas nitrogen-containing compounds were mostly formed.

Roullier-Gall|Chloé|C|
Kanawati|Basem|B|
Hemmler|Daniel|D|
Druschel|Gregory K|GK|
Gougeon|Régis D|RD|
Schmitt-Kopplin|Philippe|P|

Chardonnay wine
Oxidation
FT-ICR-MS
SO(2)
electrochemistry (EC)


An emerging problem in clinical practice: how to approach acute psychosis.

Abstract: Limbic encephalitis (LE) is rare, presents with memory impairment, seizures and behavioral disorder. We present a 44-year-old female with an agitation-depressive disorder associated with delusions and hallucinations, admitted to our hospital with the diagnosis of psychosis. A computed tomography (CT) scan of the brain and lumbar puncture on admission were normal. Because of clinical deterioration and addition of seizures in the clinical picture, further workup with serum and repeat cerebrospinal fluid studies, magnetic resonance imaging (MRI), and electroencephalogram disclosed a lesion in the left medial temporal lobe consistent with LE. The patient was treated symptomatically with antidepressive, antipsychotic and anticonvulsant drugs. Aggressive diagnostic tests for the presence of an occult cancer were negative. An 8-year follow up has not revealed a tumor to support a paraneoplasmatic origin of LE. This case, initially diagnosed and treated as psychosis, is a case of non-paraneoplasmatic, non-infective LE, probably caused by an autoimmune mechanism.

Markoula|Sofia|S|
Chatzistefanidis|Dimitrios|D|
Konitsiotis|Spyridon|S|
Kyritsis|Athanassios P|AP|


Long-term serological, virological and histological responses to RNA inhibition by ARC-520 in Chinese chronic hepatitis B patients on entecavir treatment.

Abstract:
OBJECTIVE
We examined the serological, virological (in serum and liver) and histological profiles in chronic hepatitis B virus (HBV) patients during and after completion of multiple dose (MD) ARC-520.

DESIGN
The present phase 1b study was a multidose, open-label extension cohort of patients that had received single dose ARC-520 in our previous study. Eight patients received 4-9 4 weekly doses of MD ARC-520 and entecavir. Liver biopsies were performed in six patients. Intrahepatic and serum HBV DNA, HBV RNA and viral antigens were measured.

RESULTS
All patients had 28.9-30.4 months of follow-up after the last MD. All three hepatitis B e antigen (HBeAg)-positive patients had profound reductions in hepatitis B surface antigen (HBsAg), HBeAg, hepatitis B core-related antigen and HBV RNA with two undergoing HBeAg seroconversion. One further achieved HBsAg seroconversion (anti-HBs level of 25.1 IU/L) and the remaining two had HBsAg reductions of -1.7 and -3.5 log IU/mL >30 months after MD. Among the five HBeAg-negative patients, four had modest HBsAg reduction >29 months after completion of MD and one achieved HBsAg seroconversion (anti-HBs level of 152.5 IU/L) and was negative for liver HBsAg staining. Entecavir was successfully stopped in this patient 12 months after HBsAg seroconversion. Temporally related alanine aminotransferase elevations preceded by HBsAg reductions were observed in three patients suggesting immune activation. HBcAg staining was negative in all six biopsied patients. Two patients with <10% HBsAg positive staining of hepatocytes had correspondingly low serum HBsAg levels of 1.5 and 11.5 IU/mL.

CONCLUSIONS
MD ARC-520 therapy achieved sustained and profound reductions of viral antigens and HBV RNA. HBsAg seroclearance was achievable.

TRIAL REGISTRATION NUMBER
NCT02065336.


Cellulose derived carbon nanofiber: A promising biochar support to enhance the catalytic performance of CoFe2O4 in activating peroxymonosulfate for recycled dimethyl phthalate degradation.

Abstract: We prepared carbon nanofiber (CCNF) using cellulose as the carbon source in this study and utilized for the first time as the support to enhance the catalytic performance of the cobalt ferrite (CoFe2O4) for peroxymonosulfate (PMS) activation. The catalytic capability of the CoFe2O4/CCNF nanocomposites activated PMS was investigated through degrading dimethyl phthalate (DMP), a classical organic pesticide pollutant, in water media. The influence factors like CCNF content, nanocomposite and PMS dosage, DMP content, and pH value on the degradation speed were systematically investigated and analyzed. Since CoFe2O4 is a spinel structured molecule which is magnetically separable, the reusability of the prepared CoFe2O4/CCNF nanocomposites under multiple cycles was also tested. Besides, the degradation intermediates during the catalytic process were also analyzed and identified by liquid chromatography-mass spectrometry (LC-MS) with a possible degradation mechanism. The results indicated that the prepared nanocomposite had promising catalytic capability in degrading DMP, in which the SO4- radicals played the main role as the active oxidation agent. Furthermore, the CoFe2O4/CCNF nanocomposites exhibited very good stability and reusability. The present study provides a clean biochar supported catalyst which could readily enhance the PMS activation efficiency for recycled decontamination of refractory organic pollutants in water media.

Gan|Lu|L| Zhong|Qiang|Q| Geng|Aobo|A| Wang|Linjie|L| Song|Chi|C| Han|Shuguang|S| Cui|Juqing|J| Xu|Lijie|L|

Dimethyl phthalate degradation
Cobalt ferrite
Cellulose carbon nanofiber
Peroxymonosulfate activation
Recyclable catalyst


Focus of Attention in Voice Training.

Abstract:
OBJECTIVE
The vast majority of motor learning studies investigating focus of attention have found that an external focus of attention (focusing on the effect of a movement) results in enhanced performance and learning, compared to an internal focus of attention (focusing on the body movement itself). The present study attempts to determine if the high incidence of internal focus of attention instruction that has been reported in the realm of athletics is replicated in voice training.

METHODS
Two hundred and seventy-eight singers, who were at least 18 years old and taking voice lessons, were recruited to participate in an anonymous research survey entitled "Instructions given to singers in voice lessons." The main six questions asked singers to report phrases or instructions that their studio voice teachers gave them in regard to posture, breathing and/or support, tone clarity and/or onset of tone, space and/or resonance, articulation, and reducing tension.

RESULTS
Approximately 50.83% of the total responses were classified as inducing an external focus, 39.42% were classified as internal focus, 6.48% used a combination of both internal and external focus, and 3.27% were categorized as miscellaneous.

CONCLUSIONS
The results of this study indicate that voice teachers use both external and internal attentional focus directives in the voice studio. Given the robust body of literature supporting the use of external focus, it is noteworthy that the current study found that external focus is used more often than internal focus in voice training.

Voice training
Motor learning
Attentional focus
Vocal pedagogy
Voice performance


Introduction and Establishment of Raccoon Rabies on Islands: Jekyll Island, Georgia, USA as a Case Study.

Abstract: The introduction of rabies virus (RABV) to barrier islands, which are often popular tourist destinations with resource-rich habitats and connectivity and proximity to the mainland, is especially concerning because it can easily become endemic due to factors like dense rabies-vector populations (e.g., raccoons [ Procyon lotor]), high inter- and intraspecies contact rates, and anthropogenic activities such as supplemental feeding of feral cats ( Felis catus). In January 2013, a neurologic raccoon found on the Jekyll Island (JI), Georgia, US causeway tested positive for rabies. Mortality investigations of 29 raccoons have been conducted between December 2012-May 2017. The two most common diagnoses were RABV ( n=11) and canine distemper virus (CDV; n=8). Parvoviral enteritis was diagnosed in four raccoons but no coinfections were diagnosed. There was no apparent seasonality for rabies cases, but all CDV cases occurred in spring-fall. Most (64%) rabies submissions came from residential or recreational use areas located near feral cat feeding stations. Jekyll Island is a popular destination where tourists engage in numerous outdoor activities which facilitate human-wildlife interactions. Concerns regarding public and animal health highlight the importance of rabies surveillance, prevention, and control on islands. This is the first report of rabies on JI and emphasizes the importance of disease investigations because the assumption that neurologic raccoons have CDV, an endemic pathogen, can miss the establishment of novel pathogens such as RABV.

Ortiz|Sebastian|S|
Hernandez|Sonia M|SM|
Yabsley|Michael J|MJ|
Becker|Trista I|TI|
Carswell|Benjamin|B|
Moore|Yank|Y|
Fenton|Heather|H|
Bahnson|Charlie S|CS|
Niedringhaus|Kevin|K|
Elsmo|Elizabeth|E|
Orciari|Lillian|L|
Yager|Pamela|P|
Stedman|Nancy L|NL|
Nelson|Steven E|SE|
Norton|Terry M|TM|

Procyon lotor
Epizootic
infectious disease
island biogeography
public health
urban wildlife
zoonoses


MTORC1 inhibition drives crinophagic degradation of glucagon.

Abstract:
OBJECTIVE
Crinophagy is a secretory granule-specific autophagic process that regulates hormone content and secretion in endocrine cells. However, despite being one of the earliest described autophagic processes, its mechanism of action and regulation in mammalian cells remains unclear.

METHODS AND RESULTS
Here, we examined mammalian crinophagy and its modulation that regulate hormone secretion in a glucagon-producing mouse pancreatic α-cell line, alpha TC1 clone 9 (αTC9), and in vivo. Western blot, electron microscopy, and immunofluorescence analyses were performed to study crinophagy and glucagon secretion in αTC9 cells and C57BL/6 mice, in response to the mammalian target of rapamycin complex 1 (MTORC1) inhibitor rapamycin. Amino acid depletion and pharmacological inhibition of MTORC1 increased the shuttling of glucagon-containing secretory granules into lysosomes for crinophagic degradation to reduce glucagon secretion through a macroautophagy-independent mechanism. Furthermore, MTORC1 inhibition reduced both intracellular and secreted glucagon in rapamycin-treated mice, in response to hypoglycaemia.

CONCLUSION
In summary, we have identified a novel crinophagic mechanism of intracellular glucagon turnover in pancreatic α-cells regulated by MTORC1 signalling.

Rajak|Sangam|S|
Xie|Sherwin|S|
Tewari|Archana|A|
Raza|Sana|S|
Wu|Yajun|Y|
Bay|Boon-Huat|BH|
Yen|Paul M|PM|
Sinha|Rohit A|RA|

MTORC1 Glucagon Crinophagy Rapamycin Lysosomes Autophagy Diabetes


Risk factors for periprosthetic joint infection following total ankle replacement.

Abstract:
BACKGROUND
Identifying preoperative patient characteristics that correlate with an increased risk of periprosthetic joint infection (PJI) following total ankle replacement (TAR) is of great interest to orthopaedic surgeons, as this may assist with appropriate patient selection. The purpose of this study is to systematically review the literature to identify risk factors that are associated with PJI following TAR.

METHODS
Utilizing the terms "(risk factor OR risk OR risks) AND (infection OR infected) AND (ankle replacement OR ankle arthroplasty)" we searched the PubMed/MEDLINE electronic databases. The quality of the included studies was then assessed using the AAOS Clinical Practice Guideline and Systematic Review Methodology. Recommendations were made using the overall strength of evidence.

RESULTS
Eight studies met the inclusion criteria. A limited strength of recommendation can be made that the following preoperative patient characteristics correlate with an increased risk of PJI following TAR: inflammatory arthritis, prior ankle surgery, age less than 65 years, body mass index less than 19, peripheral vascular disease, chronic lung disease, hypothyroidism, and low preoperative AOFAS hindfoot scores. There is conflicting evidence in the literature regarding the effect of obesity, tobacco use, diabetes, and duration of surgery.

CONCLUSIONS
Several risk factors were identified as having an association with PJI following TAR. These factors may alert surgeons that a higher rate of PJI is possible. However, because of the low level of evidence of reported studies, only a limited strength of recommendation can be ascribed to regard these as risk factors for PJI at this time.

Smyth|Niall A|NA|
Kennedy|John G|JG|
Parvizi|Javad|J|
Schon|Lew C|LC|
Aiyer|Amiethab A|AA|

Risk factor
Periprosthetic joint infection
Total ankle replacement
PJI
TAR


The correlation between lipoprotein(a) and coronary atherosclerotic lesion is stronger than LDL-C, when LDL-C is less than 104 mg/dL.

Abstract:
BACKGROUND
Lp(a) and LDL-C are both risk factors of atherosclerotic cardiovascular disease (ASCVD). But there was a contradiction point in LDL-C and Lp(a) control. The appropriate level of LDL-C and Lp(a) in the prevention of ASCVD is still pending.

OBJECTIVE
To investigate the correlation of Lp(a) and coronary atherosclerotic lesion, and find out the balance point in LDL-C and Lp(a) control.

METHOD
3449 patients were divided to coronary atherosclerotic heart disease (CAHD) Group and Non-CAHD Group based on the result of coronary angiography. The clinical characteristics were compared, and Logistic regressions were applied to find the CAHD risk factors in total, High-LDL-C Group (LDL-C ≥ 100 mg/dL) and Low-LDL-C Group (LDL-C < 100 mg/dL) patients. Spearman correlation analysis of Lp(a), LDL-C and Gensini Score was performed in patients with different LDL-C concentration.

RESULTS
Except male and diabetes, the traditional CAHD risk factors were well matched between two groups. But triglyceride, LDL-C and Lp(a) were higher, HDL-C and Apo-A1 were lower in CAHD group (2771). In the Logistic regression analysis, diabetes, LDL-C and Lp(a) are risk factors of CAHD in all patients, while in High-LDL-C Group, they were age, LDL-C, non-HDL-C and ApoB, in Low-LDL-C Group, they were age, Lp(a) and ApoB. Lp(a) correlated with Gensini with coefficient r = 0.41 in all patients, 0.67 in Low-LDL-C Group and 0.32 in High-LDL-C Group. The coefficient r for Lp(a) and Gensini decreased, while the r for LDL-C and Gensini increased with LDL-C concentration increasing. The two fitted lines of rs crossed at LDL-C = 2.7 mmol/L (104 mg/dL).

CONCLUSION
Lp(a) was the risk factor of CAHD in patients with LDL-C < 100 mg/dL. The correlation between Lp(a) and Gensini was influenced by LDL-C concentration, and the correlation was stronger than LDL-C when LDL-C < 104 mg/dl.

Li|Chuang|C| Chen|Qiwen|Q| Zhang|Mei|M|0000-0002-8270-3513 Liu|Yin|Y| Chu|Yushun|Y| Meng|Fanpeng|F| Wang|Jianyu|J| Tang|Jie|J| Luo|Jian|J| Niu|Xiulong|X| Wei|Maoti|M|

Lipoprotein(a)
Gensini score
Acute coronary syndrome
Low-density lipoprotein cholesterol


Economic thermoregulatory response explains mismatch between thermal physiology and behaviour in newts.

Abstract: Temperature is an important factor determining distribution and abundance of organisms. Predicting the impact of warming climate on ectotherm populations requires information about species' thermal requirements, i.e. their so-called 'thermal niche'. The characterization of thermal niche remains a complicated task. We compared the applicability of two indirect approaches, based on reaction norm (aerobic scope curve) and optimality (preferred body temperature) concepts, for indirect estimation of thermal niche while using newts, Ichthyosaura alpestris, as a study system. If the two approaches are linked, then digesting newts should keep their body temperatures close to values maximizing aerobic scope for digestion. After feeding, newts maintained their body temperatures within a narrower range than did hungry individuals. The range of preferred body temperatures was well below the temperature maximizing aerobic scope for digestion. Optimal temperatures for factorial aerobic scope fell within the preferred body temperature range of digesting individuals. We conclude that digesting newts prefer body temperatures that are optimal for the maximum aerobic performance but relative to the maintenance costs. What might be termed the 'economic' thermoregulatory response explains the mismatch between thermal physiology and behaviour in this system.

D000824:Animal Nutritional Physiological Phenomena

Thermal niche
Aerobic scope
Amphibians
Preferred temperature
Specific dynamic action
Thermoregulatory behaviour


Exploiting order effects to improve the quality of decisions.

Abstract:
OBJECTIVE
To examine the effect of ordering information in a patient decision aid (PtDA) about treatments for obstructive sleep apnea (OSA).

METHODS
We recruited 643 individuals to imagine that they had been diagnosed with OSA and to choose between treatment options. A value clarification exercise was used to determine which attributes of treatment mattered most to each individual. Before deciding on their preferred treatment option, we randomly assigned participants to view information with attributes in: a pre-specified order (Group 1), order of what mattered most last (Group 2), and first (Group 3).

RESULTS
Of the 510 participants who provided usable results, viewing information that mattered most first was associated with choosing the treatment option most concordant with their informed values. The order effect was most pronounced in younger individuals.

CONCLUSIONS
In this study of hypothetical patients, order effects were found to improve the information patients focussed on, potentially improving the quality of their decisions.

PRACTICE IMPLICATIONS
The order of information presented in a PtDA can inadvertently influence patients' choices. By tailoring information order for each patient, developers cannot only overcome this dilemma, but also make it simpler for patients to choose the option that is best for them.

Bansback|Nick|N|
Li|Linda C|LC|
Lynd|Larry|L|
Bryan|Stirling|S|

Order effects
Decision aids
Cognitive biases


Cortisol Stress Response Variability in Early Adolescence: Attachment, Affect and Sex.

Abstract: Attachment, affect, and sex shape responsivity to psychosocial stress. Concurrent social contexts influence cortisol secretion, a stress hormone and biological marker of hypothalamic-pituitary-adrenal axis activity. Patterns of attachment, emotion status, and sex were hypothesized to relate to bifurcated, that is, accentuated and attenuated, cortisol reactivity. The theoretical framework for this study posits that multiple individual differences mediate a cortisol stress response. The effects of two psychosocial stress interventions, a modified Trier Social Stress Test for Teens and the Frustration Social Stressor for Adolescents were developed and investigated with early adolescents. Both of these protocols induced a significant stress reaction and evoked predicted bifurcation in cortisol responses; an increase or decrease from baseline to reactivity. In Study I, 120 predominantly middle-class, Euro-Canadian early adolescents with a mean age of 13.43 years were studied. The girls' attenuated cortisol reactivity to the public performance stressor related significantly to their self-reported lower maternal-attachment and higher trait-anger. In Study II, a community sample of 146 predominantly Euro-Canadian middle-class youth, with an average age of 14.5 years participated. Their self-reports of higher trait-anger and trait-anxiety, and lower parental attachment by both sexes related differentially to accentuated and attenuated cortisol reactivity to the frustration stressor. Thus, attachment, affect, sex, and the stressor contextual factors were associated with the adrenal-cortical responses of these adolescents through complex interactions. Further studies of individual differences in physiological responses to stress are called for in order to clarify the identities of concurrent protective and risk factors in the psychosocial stress and physiological stress responses of early adolescents.

Cortisol Stress Adolescence Attachment Affect Sex


Two hundred years of local avian extinctions in eastern Amazonia.

Abstract: Local, regional, and global extinctions caused by habitat loss, degradation, and fragmentation have been widely reported for the tropics. The patterns and drivers of this loss of species are now increasingly well known in Amazonia, but there remains a significant gap in understanding of long-term trends in species persistence and extinction in anthropogenic landscapes. Such a historical perspective is critical for understanding the status and trends of extant biodiversity as well as for identifying priorities to halt further losses. Using extensive historical data sets of specimen records and results of contemporary surveys, we searched for evidence of local extinctions of a terra firma rainforest avifauna over 200 years in a 2500 km(2) eastern Amazonian region around the Brazilian city of Belém. This region has the longest history of ornithological fieldwork in the entire Amazon basin and lies in the highly threatened Belém Centre of Endemism. We also compared our historically inferred extinction events with extensive data on species occurrences in a sample of catchments in a nearby municipality (Paragominas) that encompass a gradient of past forest loss. We found evidence for the possible extinction of 47 species (14% of the regional species pool) that were unreported from 1980 to 2013 (80% last recorded between 1900 and 1980). Seventeen species appear on the International Union for Conservation of Nature Red List, and many of these are large-bodied. The species lost from the region immediately around Belém are similar to those which are currently restricted to well-forested catchments in Paragominas. Although we anticipate the future rediscovery or recolonization of some species inferred to be extinct by our calculations, we also expect that there are likely to be additional local extinctions, not reported here, given the ongoing loss and degradation of remaining areas of native vegetation across eastern Amazonia.

Moura|Nárgila G|NG|
Lees|Alexander C|AC|
Aleixo|Alexandre|A|
Barlow|Jos|J|
Dantas|Sidnei M|SM|
Ferreira|Joice|J|
Lima|Maria de Fátima C|Mde F|
Gardner|Toby A|TA|

D003247:Conservation of Natural Resources

avifauna
IUCN Red List
Lista Roja de la UICN
colonización
colonization
conservación urbana
dependencia de bosque
forest dependency
registro de avistamientos
sighting record
urban conservation


U.S. Dental students' and faculty members' attitudes about technology, instructional strategies, student diversity, and school duration: a comparative study.

Abstract: In this study, attitudes and perceptions of U.S. dental students and faculty members were evaluated regarding four aspects of dental education: technology integration, instructional strategies, student diversity, and school duration. A survey instrument with eight statements using a five-point Likert scale and a free-text comment section was developed and distributed through Survey Monkey. A total of 426 students and 187 faculty members from ten U.S. dental schools participated, a response rate of 17 percent of those surveyed. Faculty and student responses were compared using the Mann-Whitney U test. The results of this analytic procedure revealed that the groups differed in their average responses for seven of the eight statements. Analysis of the faculty and student comments revealed similar themes between the two groups. Both dental students and dental faculty members stated that technology integration should be viewed as only a supplement to conventional instruction and showed mixed opinions about electronic textbooks. Further, both groups had positive views of the roles of problem-based learning, community service, and the integration of research practice into dental education. Both groups also valued diversity in the student body and supported the current four-year duration of dental school.

Abdelkarim|Ahmad|A| Benghuzzi|Hamed|H| Hamadain|Elgenaid|E| Tucci|Michelle|M| Ford|Timothy|T| Sullivan|Donna|D|

D001291:Attitude of Health Personnel
D003149:Community Dentistry
D003197:Computer Literacy
D003205:Computing Methodologies
D018864:Cultural Diversity
D018865:Dental Research
D004497:Education, Dental
D005179:Faculty, Dental
D006801:Humans
D007254:Information Science
D020407:Internet
D018794:Problem-Based Learning
D013335:Students, Dental
D013663:Teaching
D013997:Time Factors
D014481:United States

diversity
dental education
problem-based learning
clinical education
community-based dental education
curriculum
educational methodology
teaching methods


IDENTIFICATION AND EXPRESSION ANALYSIS OF TWO 14-3-3 PROTEINS IN THE MOSQUITO Aedes aegypti, AN IMPORTANT ARBOVIRUSES VECTOR.

Abstract: The 14-3-3 proteins are evolutionarily conserved acidic proteins that form a family with several isoforms in many cell types of plants and animals. In invertebrates, including dipteran and lepidopteran insects, only two isoforms have been reported. 14-3-3 proteins are scaffold molecules that form homo- or heterodimeric complexes, acting as molecular adaptors mediating phosphorylation-dependent interactions with signaling molecules involved in immunity, cell differentiation, cell cycle, proliferation, apoptosis, and cancer. Here, we describe the presence of two isoforms of 14-3-3 in the mosquito Aedes aegypti, the main vector of dengue, yellow fever, chikungunya, and zika viruses. Both isoforms have the conserved characteristics of the family: two protein signatures (PS1 and PS2), an annexin domain, three serine residues, targets for phosphorylation (positions 58, 184, and 233), necessary for their function, and nine alpha helix-forming segments. By sequence alignment and phylogenetic analysis, we found that the molecules correspond to Ɛ and ζ isoforms (Aeae14-3-3ε and Aeae14-3-3ζ). The messengers and protein products were present in all stages of the mosquito life cycle and all the tissues analyzed, with a small predominance of Aeae14-3-3ζ except in the midgut and ovaries of adult females. The 14-3-3 proteins in female midgut epithelial cells were located in the cytoplasm. Our results may provide insights to further investigate the functions of these proteins in mosquitoes.

Hernández-Hernández|Fidel de la Cruz|FC|

D018507:Gene Expression Regulation, Developmental

expression
14-3-3
proteins
Aedes aegypti
RNA


Autonomic healing of acrylic bone cement.

Abstract: Self-healing in orthopedic bone cement is demonstrated with a novel thermoplastic solvent-bonding approach. Low toxicity solvent-filled microcapsules, embedded in a commercial acrylic bone cement matrix, enable recovery of up to 80% of the virgin fracture toughness of the cement at room and body temperature conditions without external stimuli or human intervention.

Gladman|A Sydney|AS|
Celestine|Asha-Dee N|AD|
Sottos|Nancy R|NR|
White|Scott R|SR|

D001843:Bone Cements
D002214:Capsules
D008855:Microscopy, Electron, Scanning
D019904:Polymethyl Methacrylate
D013314:Stress, Mechanical
D013997:Time Factors

bone cement
self-healing
microcapsules
fracture toughness
solvent bonding


Effect of Obstructive Sleep Apnea Treatment on Lipids in Obese Children.

Abstract: Obesity in children is associated with several co-morbidities including dyslipidemia. Obstructive sleep apnea (OSA) is commonly seen in obese children. In adults, diagnosis of OSA independent of obesity is associated with cardiometabolic risk factors including dyslipidemia. There is limited data on the impact of treatment of OSA on lipids in children. The objective of the study was to examine the impact of treatment of OSA on lipids in 24 obese children. Methods: Seventeen children were treated with continuous positive airway pressure (CPAP) and five underwent adenotonsillectomy. Mean apnea hypopnea index prior to treatment was 13.0 + 12.1 and mean body mass index (BMI) was 38.0 + 10.6 kg/m². Results: Treatment of OSA was associated with improvement in total cholesterol (mean change = -11 mg/dL, p < 0.001), and low-density lipoprotein cholesterol (mean change = -8.8 mg/dL, p = 0.021). Conclusion: Obese children should be routinely screened for OSA, as treatment of OSA favorably influences lipids and therefore decreases their cardiovascular risk.

Amini|Zarlasht|Z| Kotagal|Suresh|S| Lohse|Christine|C| Lloyd|Robin|R| Sriram|Swetha|S| Kumar|Seema|S|

obstructive sleep apnea
dyslipidemia
continuous positive airway pressure
cholesterol
childhood obesity


Natural killer/T-cell lymphoma with concomitant syndrome of inappropriate antidiuretic hormone secretion: A case report and review of literature.

Abstract: We report a case of natural killer (NK)/T-cell lymphoma with concomitant syndrome of inappropriate antidiuretic hormone secretion (SIADH). The patient was a 64-year-old woman with a history of nasopharyngeal carcinoma of over 30 years. She was admitted with a chief complaint of intermittent fever for 2 mo. Palpation after admission indicated a swollen lymph node below the left jaw. Multiple imaging examinations on admission indicated multiple enlarged lymph nodes throughout the body. We performed a left submandibular lymph node biopsy, and the results revealed NK/T-cell lymphoma. A biochemical examination indicated Epstein-Barr virus positivity. At the same time, the patient developed hyponatremia. Based on her laboratory examination and clinical manifestation, decreased plasma osmolality, urine osmolality greater than plasma osmolality, lack of skin swelling, normal blood pressure, normal renal function, no adrenal function detected on serology, and no abnormalities in imaging examination of the adrenal glands, the likelihood of SIADH in the patient was high. After fluid restriction and administration of sodium chloride, the patient's blood sodium level gradually increased. Subsequently, the immune function of the patient declined, there were severe symptoms of infection, and she died of respiratory failure. NK/T-cell lymphoma associated with SIADH has not, to our knowledge, been previously reported in PubMed. This case emphasizes the importance of monitoring serum ion levels, especially serum sodium, in patients with NK/T-cell lymphoma.

Syndrome of inappropriate antidiuretic hormone secretion


Effects of Percutaneous LVAD Support on Right Ventricular Load and Adaptation.

Abstract: Both operative and hemodynamic mechanisms have been implicated in right heart failure (RHF) following surgical left ventricular assist device (LVAD) implantation. We investigated the effects of percutaneous LVAD (pLVAD; Impella®, Abiomed) support on right ventricular (RV) load and adaptation. We reviewed all patients receiving a pLVAD for cardiogenic shock at our institution between July 2014 and April 2017, including only those with pre- and post-pLVAD invasive hemodynamic measurements. Hemodynamic data was recorded immediately prior to pLVAD implantation and up to 96 h post-implantation. Twenty-five patients were included. Cardiac output increased progressively during pLVAD support. PAWP improved early post-pLVAD but did not further improve during continued support. Markers of RV adaptation (right ventricular stroke work index, right atrial pressure (RAP), and RAP to pulmonary artery wedge pressure ratio (RAP:PAWP)) were unchanged acutely implant but progressively improved during continued pLVAD support. Total RV load (pulmonary effective arterial elastance; EA) and resistive RV load (pulmonary vascular resistance; PVR) both declined progressively. The relationship between RV load and RV adaptation (EA/RAP and EA/RAP:PAWP) was constant throughout. Median vasoactive-inotrope score declined after pLVAD placement and continued to decline throughout support. Percutaneous LVAD support in patients with cardiogenic shock did not acutely worsen RV adaptation, in contrast to previously described hemodynamic effects of surgically implanted durable LVADs. Further, RV load progressively declined during support, and the noted RV adaptation improvement was load-dependent as depicted by constant EA/RA and EA/RAP:PAWP relationships. These findings further implicate the operative changes associated with surgical LVAD implantation in early RHF following durable LVAD.

Yourshaw|Jeffrey P|JP|
Mishra|Prabodh|P|
Armstrong|M Christopher|MC|
Ramu|Bhavadharini|B|
Craig|Michael L|ML|
Van Bakel|Adrian B|AB|
Steinberg|Daniel H|DH|
DiSalvo|Thomas G|TG|
Tedford|Ryan J|RJ|
Houston|Brian A|BA|

D000222:Adaptation, Physiological
D005260:Female
D006353:Heart-Assist Devices
D006439:Hemodynamics
D006801:Humans
D008297:Male
D008875:Middle Aged
D011474:Prosthesis Design
D019919:Prosthesis Implantation
D020127:Recovery of Function
D012189:Retrospective Studies
D012770:Shock, Cardiogenic
D013997:Time Factors
D016896:Treatment Outcome
D016277:Ventricular Function, Left
D016278:Ventricular Function, Right

Percutaneous LVAD
Right ventricular load
Right ventricular adaptation
Temporary mechanical support


Characteristics of colored passive layers on titanium: morphology, optical properties, and corrosion resistance.

Abstract: Electrochemically formed colored passive layers on titanium and their optical, surface morphology, and corrosion properties are presented and discussed. With the application of progressively higher AC voltages (VAC) during preparation of these passive layers, they are found to become more protective of the underlying metal, as determined from corrosion resistance measurements employing electrochemical polarization curve and inductively coupled plasma mass spectrometry experiments. The passive layers on titanium were found to be uniform in their surface morphology with no apparent cracks or pits. Surface morphology, and its relation to optical properties, was also investigated using visible light microscopy, profilometry, and near-infrared ultraviolet visible reflectance spectroscopy measurements. A correlation between the light reflected from the entire sample surface and the coloration of surface grains was also observed through these measurements. The reflectance spectra showed a red-shift of wavelength maxima (λmax) values as AC voltages and, therefore, thicknesses were increased. Overall, these passive layers are protective of an already remarkable metal, and with greater knowledge of the properties of colored protective layers, their potential may be employed in a wide range of applications.

Holmberg|Rebecca J|RJ|
Beauchemin|Diane|D|
Jerkiewicz|Gregory|G|


Comparative study of oncologic efficacy of cephalomedial to lateral dissection versus medial to lateral dissection in laparoscopic total mesorectal excision for rectal cancer: An RCT study.

Abstract:
BACKGROUND AND OBJECTIVES
We compared the 3-year overall survival between cephalomedial-to-lateral approach proctectomy (CEMP) and medial-to-lateral approach proctectomy (MAP) in patients undergoing laparoscopic total mesorectal excision for rectal cancer. The advantages of CEMP and the clinical value of No. 253 lymph nodes resection have not been objectively analyzed in literature.

METHODS
This was a prospective, two-arm, multicenter, single-blinded, randomized trial. The primary endpoint was 3-year overall survival, and secondary endpoints included safety, feasibility, oncological radicality (including number of No. 253 lymph nodes harvested), short-term outcome, 3-year disease-free survival, rate of postoperative complications, mortality, and rate of recurrence.

RESULTS
From May 2016 to July 2020, 506 patients were enrolled-256 in the CEMP group and 250 in the MAP group. Comparison of overall survival and disease-free survival showed that there was treatment benefit in the CEMP group (28.22 ± 12.12 vs. 27.44 ± 13.06, p = 0.485; 27.24 ± 12.01 vs. 26.42 ± 12.81; p = 0.457). More No. 253 lymph nodes were harvested in the CEMP group, and cases with positive No. 253 lymph nodes had worse prognosis in stage III. Surgical safety was equal for both approaches.

CONCLUSIONS
Dissection of No. 253 lymph nodes may be important to improve clinical prognosis, but further studies with larger samples are needed to confirm this finding.

laparoscopic total mesorectal excision
rectal cancer
no. 253 lymph node
postoperative complication
laparoscopy surgery


(124)I-PET Assessment of Human Sodium Iodide Symporter Reporter Gene Activity for Highly Sensitive In Vivo Monitoring of Teratoma Formation in Mice.

Abstract:
PURPOSE
Pluripotent stem cell (PSC)-based therapies possess great potential to restore the function of irreversibly damaged organs. PSCs can be differentiated in vitro into any cell type. However, pluripotent potential bears the risk of teratoma formation. In vivo monitoring of teratoma formation is indispensable, as 100 % purity of the cell preparation cannot be achieved. We aimed at establishing the human sodium iodide symporter (hNIS) as reporter gene for PET monitoring of teratoma formation.

PROCEDURES
Murine PSC stably expressing hNIS were injected into the hind limbs of SCID mice to induce teratoma formation. Positron emission tomography (PET) scans were acquired weekly between days 14 and 42 after transplantation. Two teratomas were excised at each time point for histology and size measurement. Tracer uptake was correlated with teratoma weight. Specificity of tumoural iodine uptake was assessed by blocking hNIS in vivo with perchlorate.

RESULTS
Neither hNIS expression nor I-124 exposure adversely impacted viability or differentiation potential of PSCs. Iodine uptake was highly specific in teratomas, as in vivo blocking of hNIS with perchlorate led to uptake rates comparable to tracer uptake in non-transgene tumours. Tumour mass and tracer uptake showed a positive correlation.

CONCLUSIONS
This is the first study to generate stably hNIS-expressing murine PSCs. Since the differentiation potential was preserved, hNIS-expressing cells are suitable for PSC-based forward programming approaches. Teratoma formation from undifferentiated cells can be monitored in vivo by PET with high specificity on a quantitative level. Due to its anticipated lack of immunogenicity in humans, hNIS is a promising reporter gene for clinical translation.

Lehner|Sebastian|S|
Lang|Cajetan|C|
Kaissis|Georgios|G|
Todica|Andrei|A|
Zacherl|Mathias Johannes|MJ|
Boening|Guido|G|
Spitzweg|Christine|C|
Herbach|Nadja|N|
Franz|Wolfgang-Michael|WM|
Krause|Bernd Joachim|BJ|
Steinhoff|Gustav|G|
Bartenstein|Peter|P|
Hacker|Marcus|M|
David|Robert|R|

Sodium iodide symporter
Reporter gene
In vivo monitoring
Teratoma formation
Small animal PET
Stem cell therapy


Prevalence of Potentially Traumatic Events, Other Life Events and Subsequent Reactions Indicative for Posttraumatic Stress Disorder in the Netherlands: A General Population Study Based on the Trauma Screening Questionnaire.

Abstract: The 12-month and lifetime prevalence of posttraumatic stress disorder (PTSD) in different country populations has been assessed while using clinical interviews. Because this methodology is relatively time-consuming and resource-intensive, disaster health researchers adopted instruments, like the Trauma Screening Questionnaire (TSQ). This study (1) used the TSQ to estimate the lifetime prevalence of potentially traumatic events and other life events (PTE/OLEs) and the one-week prevalence of subsequent reactions indicative for PTSD (based on DSM-IV PTSD criteria) in The Netherlands and (2) investigated risk and protective factors for the development of PTSD to overcome the lack of baseline comparison data on general populations and subgroups. The data were derived from the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2), a representative study in the Dutch general population aged 18 to 64 years (N = 6646), using face-to-face interviews. Logistic regression modeling was used to assess PTSD correlates. The lifetime PTE/OLE prevalence was 71.1%. Among exposed subjects, one-week PTSD prevalence was estimated at 2.0%. The correlates of PTSD were female gender, Moroccan, or Turkish ethnicity, and exposure to sexual abuse and exposure time less than four years ago. The results are discussed in relation to earlier 12-month and lifetime general population prevalence of PTSD in the Netherlands and other countries, and TSQ-based disaster studies. General population replications can provide additional TSQ baseline data, and shed light on exposure and PTSD prevalence assessed with different instruments.

Knipscheer|Jeroen|J|
Sleijpen|Marieke|M|0000-0002-5143-9828
Frank|Laurence|L|
de Graaf|Ron|R|
Kleber|Rolf|R|
Ten Have|Margreet|M|
Dückers|Michel|M|0000-0001-7746-053X

D039721:Diagnostic and Statistical Manual of Mental Disorders

prevalence
posttraumatic stress disorder
gender
ethnicity
epidemiology


Coupling between the TRPC3 ion channel and the NCX1 transporter contributed to VEGF-induced ERK1/2 activation and angiogenesis in human primary endothelial cells.

Abstract: It has been previously demonstrated that the bi-directional transporter Na+/Ca2+ exchanger (NCX) working in the reverse (Ca2+-influx) - mode promotes the activation of ERK1/2 in response to the key pro-angiogenic cytokine VEGF in human endothelial cells (ECs). However, the molecular event(s) that elicit NCX reversal in VEGF-stimulated ECs remain unclear. Here we investigated whether Na+ influx via the diacylglycerol (DAG) - activated non-selective cation channel TRPC3 was functionally associated with NCX and whether its activity was required for VEGF-induced ERK1/2 activation and angiogenesis. We provide evidence that TRPC3 inhibitors and siRNA attenuated ERK1/2 phosphorylation, reduced PKCα activity and partially suppressed Ca2+ transients in response to VEGF. Additionally, TRPC3 inhibitors and siRNA significantly suppressed endothelial tubular differentiation, an in vitro indicator of angiogenesis. We also report that simulating PLCγ activation downstream of VEGF receptor 2 by application of the cell-permeable DAG analogue 1-oleoyl-2-acetyl-sn-glycerol (OAG) was sufficient to activate ERK1/2 and enhance tubular differentiation. OAG-induced ERK1/2 activation and tubulogenesis were significantly suppressed by TRPC3 and reverse-mode NCX inhibitors and siRNA. Moreover, whilst both reverse-mode NCX and TRPC3 inhibitors attenuated OAG-induced Ca2+ transients, only TRPC3 antagonists blunted Na+ influx in response to OAG. Importantly, when Na+ was increased in ECs by inhibiting the Na+-K+-ATPase, TRPC3 activity was dispensable for OAG-induced ERK1/2 phosphorylation. Collectively, our research suggests that DAG generation downstream of VEGF receptors activatesTRPC3 causing Na+ influx with subsequent reversal of NCX, ERK1/2 activation and ultimately contributes to enhanced angiogenesis. Targeting reverse-mode NCX and its upstream initiator TRPC3 could be clinically relevant in conditions characterised by abnormal VEGF signalling.

Andrikopoulos|Petros|P|
Eccles|Suzanne A|SA|
Yaqoob|Muhammad M|MM|

D061307:Human Umbilical Vein Endothelial Cells

D042461:Vascular Endothelial Growth Factor A


A mutation of MET, encoding hepatocyte growth factor receptor, is associated with human DFNB97 hearing loss.

Abstract:
BACKGROUND
Hearing loss is a heterogeneous neurosensory disorder. Mutations of 56 genes are reported to cause recessively inherited non-syndromic deafness.

OBJECTIVE
We sought to identify the genetic lesion causing hearing loss segregating in a large consanguineous Pakistani family.

METHODS AND RESULTS
Mutations of GJB2 and all other genes reported to underlie recessive deafness were ruled out as the cause of the phenotype in the affected members of the participating family. Homozygosity mapping with a dense array of one million SNP markers allowed us to map the gene for recessively inherited severe hearing loss to chromosome 7q31.2, defining a new deafness locus designated DFNB97 (maximum logarithm of the odds score of 4.8). Whole-exome sequencing revealed a novel missense mutation c.2521T>G (p.F841V) in MET (mesenchymal epithelial transition factor), which encodes the receptor for hepatocyte growth factor. The mutation cosegregated with the hearing loss phenotype in the family and was absent from 800 chromosomes of ethnically matched control individuals as well as from 136 602 chromosomes in public databases of nucleotide variants. Analyses by multiple prediction programmes indicated that p.F841V likely damages MET function.

CONCLUSIONS
We identified a missense mutation of MET, encoding the hepatocyte growth factor receptor, as a likely cause of hearing loss in humans.

Mujtaba|Ghulam|G|
Schultz|Julie M|JM|
Imtiaz|Ayesha|A|
Morell|Robert J|RJ|
Friedman|Thomas B|TB|
Naz|Sadaf|S|

Genetics
Genome-wide
Linkage
Molecular genetics


Effectiveness of a Pre-emptive Preoperative Belladonna and Opium Suppository on Postoperative Urgency and Pain After Ureteroscopy.

Abstract:
PURPOSE
Postoperative ureteroscopy patients can develop bladder spasms, complaints of pain, and the urgent need to void during emergence from anesthesia. Discomfort leads to patient agitation, resulting in a risk to patient safety. The purpose of this study was to determine the effectiveness of a preemptive preoperative belladonna and opium (B + O) suppository on postoperative bladder comfort, narcotic requirements, and length of stay of ureteroscopy patients.

DESIGN
A prospective double-blind study was conducted.

METHODS
Fifty adult outpatients scheduled for ureteroscopy were assigned to routine care or a B + O suppository immediately after anesthesia induction. Urinary urgency and pain were assessed every 15 minutes.

FINDINGS
Urgency significantly decreased in the B+O group, with less than half reporting urgency at discharge.

CONCLUSIONS
Pre-emptive preoperative administration of a B + O suppository before ureteroscopy results in decreased urinary urgency during the postoperative recovery. Pre-emptive preoperative interventions can result in positive outcomes before discharge.

Fetzer|Susan Jane|SJ|
Goodwin|Linda|L|
Stanizzi|Matthew|M|

suppositories
ureteroscopy
postoperative period
urinary bladder


Vasculitides and glomerulonephritis associated with Staphylocococcus aureus infective endocarditis: cases reports and mini-review of the literature.

Abstract: We reported two cases of Staphylococcus aureus Infective Endocarditis associated with vasculitides and glomerulonephritis respectively, before conducting an online search of previously published similar cases reports. Twenty five references were selected: 15 cases of glomerulonephritis; 2 cases of vasculitis and 8 cases involving both glomerulonephritis and vasculitis. Vasculitides and glomerulonephritis associated with Staphylococcus aureus definite Infective Endocarditis have been reported since 1976. All cases except one described clinical symptoms occurring before or during initial antibiotics treatment. Except kidney, organs that were more frequently affected by vasculitis process were skin, gastrointestinal tract and peripheral nerve and the vessels involved were small to medium size vessels. When antineutrophil cytoplasmic antibodies were evidenced (6 out of the 25 cases (24%)), kidney was the most frequently affected organ. The most commonly observed pattern in Kidney biopsy was membranoproliferative glomerulonephritis with endocapillary proliferation sometimes associated with extra capillary crescents, whether or not antineutrophil cytoplasmic antibodies were evidenced. Right-sided Infective Endocarditis (especially in intravenous drug users) were overrepresented (14 of the 25 cases (56.0%)) in this review. Besides antibiotics, corticosteroids were the most frequently prescribed immunosuppressive treatment both for vasculitides or glomerulonephritis. KEY MESSAGES Vasculitides and glomerulonephritis associated with Staphylococcus aureus definite Infective Endocarditis have been reported since 1976. Except kidney, organs that were more frequently affected (by small to medium size vessel vasculitis) were skin, gastrointestinal tract and peripheral nerve. The most commonly observed pattern in Kidney biopsy was membranoproliferative glomerulonephritis with endocapillary proliferation and right-sided Infective Endocarditis (especially in intravenous drug users) were overrepresented in this review.

Brunet|Aurélie|A| Julien|Gautier|G| Cros|Amandine|A| Beaudoux|Olivia|O| Hittinger-Roux|Ambre|A| Bani-Sadr|Firouze|F| Servettaz|Amélie|A| N'Guyen|Yohan|Y|

glomerulonephritis
infective endocarditis
Staphylococcus aureus
vasculitis


Comparative behavioral toxicology with two common larval fish models: Exploring relationships among modes of action and locomotor responses.

Abstract: Behavioral responses inform toxicology studies by rapidly and sensitively detecting molecular initiation events that propagate to physiological changes in individuals. These behavioral responses can be unique to chemical specific mechanisms and modes of action (MOA) and thus present diagnostic utility. In an initial effort to explore the use of larval fish behavioral response patterns in screening environmental contaminants for toxicity and to identify behavioral responses associated with common chemical specific MOAs, we employed the two most common fish models, the zebrafish and the fathead minnow, to define toxicant induced swimming activity alterations during interchanging photoperiods. Though the fathead minnow (Pimephales promelas) is a common model for aquatic toxicology research and regulatory toxicology practice, this model has received little attention in behavioral studies compared to the zebrafish, a common biomedical model. We specifically compared behavioral responses among 7 different chemicals (1-heptanol, phenol, R-(-)-carvone, citalopram, diazinon, pentylenetetrazole (PTZ), and xylazine) that were selected and classified based on anticipated MOA (nonpolar narcosis, polar narcosis, electrophile, specific mechanism) according to traditional approaches to examine whether these comparative responses differ among chemicals with various structure-based predicted toxicity. Following standardized experimental guidelines, zebrafish embryos and fathead minnow larvae were exposed for 96 h to each compound then were observed using digital behavioral analysis. Behavioral observations included photomotor responses, distance traveled, and stimulatory, refractory and cruising locomotor activity. Though fathead minnow larvae displayed greater behavioral sensitivity to 1-heptanol, phenol and citalopram, zebrafish were more sensitive to diazinon and R-(-)-carvone. Both fish models were equally sensitive to xylazine and PTZ. Further, the pharmaceuticals citalopram and xylazine significantly affected behavior at therapeutic hazard values, and each of the seven chemicals elicited unique behavioral response profiles. Larval fish behaviors appear useful as early tier diagnostics to identify mechanisms and pathways associated with diverse biological activities for chemicals lacking mechanistic data.

Steele|W Baylor|WB|
Kristofco|Lauren A|LA|
Corrales|Jone|J|
Saari|Gavin N|GN|
Haddad|Samuel P|SP|
Gallagher|Evan P|EP|
Kavanagh|Terrance J|TJ|
Kostal|Jakub|J|
Zimmerman|Julie B|JB|
Voutchkova-Kostal|Adelina|A|
Anastas|Paul|P|
Brooks|Bryan W|BW|

Behavior
Alternative toxicity testing
Chemical bioactivity
Comparative toxicology
High throughput screening


Neurogenesis-on-Chip: Electric field modulated transdifferentiation of human mesenchymal stem cell and mouse muscle precursor cell coculture.

Abstract: A number of bioengineering strategies, using biophysical stimulation, are being explored to guide the human mesenchymal stem cells (hMScs) into different lineages. In this context, we have limited understanding on the transdifferentiation of matured cells to another functional-cell type, when grown with stem cells, in a constrained cellular microenvironment under biophysical stimulation. While addressing such aspects, the present work reports the influence of the electric field (EF) stimulation on the phenotypic and functionality modulation of the coculture of murine myoblasts (C2C12) with hMScs [hMSc:C2C12=1:10] in a custom designed polymethylmethacrylate (PMMA) based microfluidic device with in-built metal electrodes. The quantitative and qualitative analysis of the immunofluorescence study confirms that the cocultured cells in the conditioned medium with astrocytic feed, exhibit differentiation towards neural-committed cells under biophysical stimulation in the range of the endogenous physiological electric field strength (8 ± 0.06  mV/mm). The control experiments using similar culture protocols revealed that while C2C12 monoculture exhibited myotube-like fused structures, the hMScs exhibited the neurosphere-like clusters with SOX2, nestin, βIII-tubulin expression. The electrophysiological study indicates the significant role of intercellular calcium signalling among the differentiated cells towards transdifferentiation. Furthermore, the depolarization induced calcium influx strongly supports neural-like behaviour for the electric field stimulated cells in coculture. The intriguing results are explained in terms of the paracrine signalling among the transdifferentiated cells in the electric field stimulated cellular microenvironment. In summary, the present study establishes the potential for neurogenesis on-chip for the coculture of hMSc and C2C12 cells under tailored electric field stimulation, in vitro.

Naskar|Sharmistha|S|
Kumaran|Viswanathan|V|
Markandeya|Yogananda S|YS|
Mehta|Bhupesh|B|
Basu|Bikramjit|B|

Electric field
Human mesenchymal stem cell
Coculture
Myoblast
Neurogenesis
Lab-on-a-chip


Post-infarction left ventricular free wall rupture: 12-years experience from the Cardiac Centre of the Institute of Clinical and Experimental Medicine in Prague, Czech Republic.

Abstract:
BACKGROUND
Post-infarction left ventricular free wall rupture (LVFWR) is a feared and catastrophic complication of myocardial infarction that carries a high surgical and hospital mortality. Due to the rarity of this complication, little information exists on surgical treatment and outcomes. Goal and Methods. The goal of this study was to present our experience with LVFWR. We present a retrospective cohort of 19 consecutive patients who were surgically treated in the Cardiac Centre of the Institute of Clinical and Experimental Medicine in Prague between January 2006 and December 2017.

RESULTS
Thirty-day mortality was 26%. Five patients died. Four patients died in the operating theatre and one patient on the ninth postoperative day following re-rupture. Seventy-four percent of the patient cohort survived and were discharged from hospital. The median length of follow-up was 45 months (range 0.75-150). No patient died during follow-up. Median postoperative ejection fraction was 45% (range 25-65%). Angina pectoris and dyspnea were investigated during follow-up and graded according to the Canadian cardiology society (CCS) and the New York Heart Association (NYHA) classifications. Fourteen patients had CCS class I, eight patients had NYHA class I dyspnea and six patients had NYHA class II. Re-rupture occurred after hospital discharge in one patient one month after the original surgery. The patient was treated successfully by urgent surgical intervention.

CONCLUSION
LVFWR is a catastrophic and challenging complication of myocardial infarction. Good outcomes can be achieved by rapid diagnosis and urgent surgical intervention as shown by our results.

Kacer|Petr|P|
Adamkova|Vera|V|
Hubacek|Jaroslav Alois|JA|
Cervinkova|Tereza|T|
Adamek|Vaclav|V|
Kralova Lesna|Ivana|I|
Lanska|Vera|V|
Pirk|Jan|J|

acute myocardial infarction
myocardial rupture
ventricular wall


Non-Newtonian flow-induced deformation from pressurized cavities in absorbing porous tissues.

Abstract: We investigate the behavior of a spherical cavity in a soft biological tissue modeled as a deformable porous material during an injection of non-Newtonian fluid that follows a power law model. Fluid flows into the neighboring tissue due to high cavity pressure where it is absorbed by capillaries and lymphatics at a rate proportional to the local pressure. Power law fluid pressure and displacement of a solid in the tissue are computed as function of radial distance and time. Numerical solutions indicate that shear thickening fluids exhibit less fluid pressure and induce small solid deformation as compared to shear thinning fluids. Absorption in the biological tissue increases as a consequence of flow-induced deformation for power law fluids. In most cases non-Newtonian results are compared with the viscous fluid case to magnify the differences.

Ahmed|Aftab|A|
Siddique|J I|JI|
Mahmood|Asif|A|

biological tissue
Power law fluid
solid deformation
mixture theory
porous medium


CT Angiography Findings Predictive of Kidney Injury in Chronic Aortic Dissection.

Abstract: OBJECTIVE. The purpose of this study was to compare the volume alteration and effective renal plasma flow of kidneys supplied by false lumens (FLs) with those of kidneys supplied by true lumens (TLs), to show the discrepancy in perfusion between the two lumens. We sought to corroborate malperfusion of FL-supplied kidneys with imaging characteristics observed on CT angiography. MATERIALS AND METHODS. A retrospective analysis was conducted using prospectively collected data for 87 patients with a diagnosis of residual chronic aortic dissection between 2005 and 2013 who had one kidney perfused by a TL and the other kidney perfused by a FL. RESULTS. Overall, at follow-up, FL-supplied kidneys had a mean (± SD) effective renal plasma flow (117.5 ± 42.6 vs 146.6 ± 41.0 mL/min; p = 0.004) and volume (131.1 ± 37.1 vs 146.5 ± 33.3 cm3; p = 0.004) that were lower than those of TL-supplied kidneys. Multivariate analysis revealed the presence of a proximal major inlet (odds ratio, 0.306; 95% CI, 0.103-0.910; p = 0.033) and large FL area (odds ratio, 0.104; CI, 0.012-0.880; p = 0.038) as factors protecting against malperfusion of FL-supplied kidneys. In patients with dissected renal arteries, the FL-supplied kidney had low effective renal plasma flow (mean, 88.5 ± 26.8 vs 149.6 ± 43.5 mL/min; p = 0.004) and diminished volume (mean, 120.4 ± 30.4 vs 152.3 ± 24.6 cm3; p = 0.001). CONCLUSION. In the present study, kidneys perfused by FLs showed decreased volume and reduced effective renal plasma flow during follow-up, particularly those kidneys with dissected renal arteries, a small FL area at the renal level, and lack of a proximal major inlet. Further studies are warranted to identify the clinical relevance of malperfusion in FL-supplied kidneys.

Kuo|Tzu-Ting|TT| Chen|Po-Lin|PL| Huang|Chun-Yang|CY| Chen|I-Ming|IM| Shih|Chun-Che|CC|

aortic dissection
effective renal plasma flow
malperfusion
kidney perfusion
renal function


Mid-term follow-up of the TVT-Secur midurethral sling for primary stress incontinence.

Abstract:
OBJECTIVE
The TVT-Secur was introduced in 2006 as a less invasive alternative to retropubic and transobturator suburethral slings. This retrospective cohort study evaluated objective and subjective results in a series of 158 consecutive patients as well as complications and the reoperation rate after TVT-Secur procedure.

STUDY DESIGN
Between November 2006 and June 2010 a total of 158 patients underwent a TVT-Secur procedure at a single institution. All patients underwent preoperative urodynamic testing. All patients were invited for follow-up including physical examination, urodynamic studies and subjective evaluation.

RESULTS
A total of 96 patients (61%) were available for follow-up with a mean follow-up of 29.8 months (range 5-50, median 30). At follow-up, eight (8%) of 96 patients had reoperations for stress incontinence. There were no reoperations for bleeding/hematoma, tape erosions or obstructed micturition and there were no tape erosions or exposures. 29 patients (30%) had a negative cough stress test and 44 patients (46%) subjectively considered themselves "cured". Nine of 43 patients (21%) without urgency symptoms preoperatively developed de novo urgency; 24 of 35 patients (69%) with preoperative urgency complaints were free of urgency symptoms.

CONCLUSION
At 2.4 years, the TVT-Secur appears to have a low adverse events profile but inferior results compared with traditional midurethral slings.

D000328:Adult
D000368:Aged
D000369:Aged, 80 and over
D015331:Cohort Studies
D005260:Female
D005500:Follow-Up Studies
D006801:Humans
D008875:Middle Aged
D017060:Patient Satisfaction
D012086:Reoperation
D012189:Retrospective Studies
D053825:Suburethral Slings
D016896:Treatment Outcome
D014550:Urinary Incontinence, Stress
D013520:Urologic Surgical Procedures

TVT-Secur
Tape
Incontinence surgery
Mini-sling
Stress urinary incontinence
TVT


3β-Isoobeticholic acid efficiently activates the farnesoid X receptor (FXR) due to its epimerization to 3α-epimer by hepatic metabolism.

Abstract: Bile acids (BAs) are important signaling molecules acting via the farnesoid X nuclear receptor (FXR) and the membrane G protein-coupled bile acid receptor 1 (GPBAR1). Besides deconjugation of BAs, the oxidoreductive enzymes of colonic bacteria and hepatocytes enable the conversion of BAs into their epimers or dehydrogenated forms. Obeticholic acid (OCA) is the first-in-class BA-derived FXR agonist approved for the treatment of primary biliary cholangitis. Herein, a library of OCA derivatives, including 7-keto, 6-ethylidene derivatives and 3β-epimers, was synthetized and investigated in terms of interactions with FXR and GPBAR1 in transaction assays and evaluated for FXR target genes expression in human hepatocytes and C57BL/6 mice. The derivatives were further subjected to cell-free analysis employing in silico molecular docking and a TR-FRET assay. The conversion of the 3βhydroxy epimer and its pharmacokinetics in mice were studied using LC-MS. We found that only the 3β-hydroxy epimer of OCA (3β-isoOCA) possesses significant activity to FXR in hepatic cells and mice. However, in a cell-free assay, 3β-isoOCA had about 9-times lower affinity to FXR than did OCA. We observed that 3β-isoOCA readily epimerizes to OCA in hepatocytes and murine liver. This conversion was significantly inhibited by the hydroxy-Δ5-steroid dehydrogenase inhibitor trilostane. In addition, we found that 3,7-dehydroobeticholic acid is a potent GPBAR1 agonist. We conclude that 3β-isoOCA significantly activates FXR due to its epimerization to the more active OCA by hepatic metabolism. Other modifications as well as epimerization on the C3/C7 positions and the introduction of 6-ethylidene in the CDCA scaffold abrogate FXR agonism and alleviate GPBAR1 activation.

Stefela|Alzbeta|A|
Kaspar|Miroslav|M|
Drastik|Martin|M|
Holas|Ondrej|O|
Hroch|Milos|M|
Smutny|Tomas|T|
Skoda|Josef|J|
Hutníková|Miriama|M|
Pandey|Amit V|AV|
Micuda|Stanislav|S|
Kudova|Eva|E|
Pavek|Petr|P|

D018160:Receptors, Cytoplasmic and Nuclear

Metabolism
Bile acids
Nuclear receptors
Pharmacokinetics
Gene regulation


Anatomically-Informed Data Augmentation for Functional MRI with Applications to Deep Learning.

Abstract: The application of deep learning to build accurate predictive models from functional neuroimaging data is often hindered by limited dataset sizes. Though data augmentation can help mitigate such training obstacles, most data augmentation methods have been developed for natural images as in computer vision tasks such as CIFAR, not for medical images. This work helps to fills in this gap by proposing a method for generating new functional Magnetic Resonance Images (fMRI) with realistic brain morphology. This method is tested on a challenging task of predicting antidepressant treatment response from pre-treatment task-based fMRI and demonstrates a 26% improvement in performance in predicting response using augmented images. This improvement compares favorably to state-of-the-art augmentation methods for natural images. Through an ablative test, augmentation is also shown to substantively improve performance when applied before hyperparameter optimization. These results suggest the optimal order of operations and support the role of data augmentation method for improving predictive performance in tasks using fMRI.

Nguyen|Kevin P|KP|
Fatt|Cherise Chin|CC|
Treacher|Alex|A|
Mellema|Cooper|C|
Trivedi|Madhukar H|MH|
Montillo|Albert|A|

data augmentation
deep learning
neuroimaging
fMRI
depression


Toxicity and cost-effectiveness analysis of intensity modulated radiation therapy versus 3-dimensional conformal radiation therapy for postoperative treatment of gynecologic cancers.

Abstract:
OBJECTIVE
To evaluate toxicity and cost-effectiveness of intensity modulated radiation therapy (IMRT) versus 3-dimensional conformal radiation therapy (3DCRT) in the postoperative treatment of uterine and cervical cancer.

METHODS
Between 2000 and 2012, eighty patients at our institution received post-hysterectomy 3DCRT (46) or IMRT (34) for uterine or cervical cancer. Baseline characteristics, outcome, and ≥CTCAE grade 2 toxicities were compared between the two groups. Predictors of toxicity-free survival were identified. A decision analysis model was designed to capture individual health states at 1, 2, and 3 years after treatment. Micro-costing technique and estimated quality-adjusted life years (QALYs) were used to calculate incremental cost-effectiveness ratio (ICER).

RESULTS
Utilization of IMRT increased from 25% (2005-2007) to 75% (2008-2012). Recurrence-free and overall survival rates were not different between the two groups. Toxicity rates were reduced with IMRT versus 3DCRT (HR 0.42, p=0.04). Women who received IMRT had numerically lower rates of late gastrointestinal and genitourinary toxicity and significantly lower rates of late overall toxicity at 3 years (16% vs. 45%, p=0.04). On univariate analysis, IMRT was associated with decreased late toxicity (HR 0.43, p=0.04). Treatment costs were higher and toxicity costs were lower with IMRT. IMRT had an ICER of $235,233 (year 1), $114,270 (year 2), and $75,555 (year 3) per QALY gained.

CONCLUSION
IMRT is associated with reduced late overall toxicity compared to 3DCRT without compromising clinical outcome. IMRT is not cost-effective during the early chronic toxicity phase, but it becomes more cost-effective over time.

Chen|L Andy|LA|
Kim|Jaewhan|J|
Boucher|Kenneth|K|
Terakedis|Breanne|B|
Williams|Britney|B|
Nickman|Nancy A|NA|
Gaffney|David K|DK|

Cost-benefit analysis
Endometrial neoplasms
Health care economics
Radiotherapy, conformal
Radiotherapy, intensity-modulated
Uterine cervical neoplasms


Enhanced performance of the methylerythritol phosphate pathway by manipulation of redox reactions relevant to IspC, IspG, and IspH.

Abstract: The 2C-methyl-D-erythritol 4-phosphate (MEP) pathway is a carbon-efficient route for synthesis of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), the building blocks of isoprenoids. However, practical application of a native or recombinant MEP pathway for the mass production of isoprenoids in Escherichia coli has been unsatisfactory. In this study, the entire recombinant MEP pathway was established with plasmids and used for the production of an isoprenoid, protoilludene. E. coli harboring the recombinant MEP pathway plasmid (ME) and a protoilludene synthesis pathway plasmid (AO) produced 10.4mg/L of protoilludene after 48h of culture. To determine the rate-limiting gene on plasmid ME, each constituent gene of the MEP pathway was additionally overexpressed on the plasmid AO. The additional overexpression of IPP isomerase (IDI) enhanced protoilludene production to 67.4mg/L. Overexpression of the Fpr and FldA protein complex, which could mediate electron transfer from NADPH to Fe-S cluster proteins such as IspG and IspH of the MEP pathway, increased protoilludene production to 318.8mg/L. Given that it is required for IspC as well as IspG/H, the MEP pathway has high demand for NADPH. To increase the supply of NADPH, a NADH kinase from Saccharomyces cerevisiae (tPos5p) that converts NADH to NADPH was introduced along with the deletion of a promiscuous NADPH-dependent aldehyde reductase (YjgB) that consumes NADPH. This resulted in a protoilludene production of 512.7mg/L. The results indicate that IDI, Fpr-FldA redox proteins, and NADPH regenerators are key engineering points for boosting the metabolic flux toward a recombinant MEP pathway.

Zhou|Jia|J| Yang|Liyang|L| Wang|Chonglong|C| Choi|Eui-Sung|ES| Kim|Seon-Won|SW|

Isoprenoid
MEP pathway
Escherichia coli
NADPH
Fe–S cluster protein


The "Goldilocks Zone" from a redox perspective-Adaptive vs. deleterious responses to oxidative stress in striated muscle.

Abstract: Consequences of oxidative stress may be beneficial or detrimental in physiological systems. An organ system's position on the "hormetic curve" is governed by the source and temporality of reactive oxygen species (ROS) production, proximity of ROS to moieties most susceptible to damage, and the capacity of the endogenous cellular ROS scavenging mechanisms. Most importantly, the resilience of the tissue (the capacity to recover from damage) is a decisive factor, and this is reflected in the disparate response to ROS in cardiac and skeletal muscle. In myocytes, a high oxidative capacity invariably results in a significant ROS burden which in homeostasis, is rapidly neutralized by the robust antioxidant network. The up-regulation of key pathways in the antioxidant network is a central component of the hormetic response to ROS. Despite such adaptations, persistent oxidative stress over an extended time-frame (e.g., months to years) inevitably leads to cumulative damages, maladaptation and ultimately the pathogenesis of chronic diseases. Indeed, persistent oxidative stress in heart and skeletal muscle has been repeatedly demonstrated to have causal roles in the etiology of heart disease and insulin resistance, respectively. Deciphering the mechanisms that underlie the divergence between adaptive and maladaptive responses to oxidative stress remains an active area of research for basic scientists and clinicians alike, as this would undoubtedly lead to novel therapeutic approaches. Here, we provide an overview of major types of ROS in striated muscle and the divergent adaptations that occur in response to them. Emphasis is placed on highlighting newly uncovered areas of research on this topic, with particular focus on the mitochondria, and the diverging roles that ROS play in muscle health (e.g., exercise or preconditioning) and disease (e.g., cardiomyopathy, ischemia, metabolic syndrome).

Alleman|Rick J|RJ|
Katunga|Lalage A|LA|
Nelson|Margaret A M|MA|
Brown|David A|DA|
Anderson|Ethan J|EJ|

skeletal muscle
adaptation
heart
mitochondria
carbonyl stress
hormesis
lipid peroxidation
redox environment


MYCOLOGICAL ANALYSIS AND AFLATOXIN B1 CONTAMINANT ESTIMATION OF HERBAL DRUG RAW MATERIALS.

Abstract:
BACKGROUND
The present study explores the fungal contamination of important herbal drug raw materials (HDRM), which are widely used in the preparation of many herbal drugs. Understanding of the microbial contamination status of HDRM is one of the important steps to ensure the safety and efficacy of herbal drugs.

MATERIALS AND METHODS
Eighteen samples of six herbal drug raw materials (HDRM) viz., Acorus calamus Linn., Cassia angustifolia Vahl., Centella asiatica (Linn.) Urban, Myristica fragrans Houtt., Tinospora cardifolia (Wild) Miers and Withania somnifera (Linn.) Dunal, were screened for fungal contamination, by employing serial dilution method. All the isolates of Aspergillus flavus were screened for their ability to produce aflatoxin B1 (AB1) and highly contaminated samples were subjected to AB1 estimation by using Thin Layer Chromatography (TLC), spectrophotometric method and occurrence of Aflatoxin B1 was confirmed by Liquid Chromatography-Mass Spectrometry analysis (LCMS).

RESULTS
A total of 302 isolates of 42 fungal species belonging to 17 genera were found in association with test the samples. More than 61% of A. flavus isolates tested positive for production of AB1 and highest yield recorded was 5008.20 ppb from the isolates of T. cordifolia. Amongthesix highly contaminated samples three samples tested positive for AB1. Highest AB1 was recorded from T. cordifolia (104.19 μg/kg), followed by A. calamus (13.73 μg/kg) and M. fragrans (12.02 μg/kg).

CONCLUSION
Assessment of fungal and mycotoxin contamination should be a part of the quality check while selecting HDRM for manufacture of herbal products. Safe processing and storage practices are necessary.

D016604:Aflatoxin B1
D001231:Aspergillus flavus
D004340:Drug Contamination
D028321:Plant Preparations
D010946:Plants, Medicinal

Aflatoxin B1
Contamination
Herbal drug raw material
Fungi
Tinospora cordifolia


When fear of cancer recurrence becomes a clinical issue: a qualitative analysis of features associated with clinical fear of cancer recurrence.

Abstract:
PURPOSE
Fear of cancer recurrence (FCR) is a common experience for cancer survivors. However, it remains unclear what characteristics differentiate non-clinical from clinical levels of FCR. The goal of this study was to investigate the potential hallmarks of clinical FCR.

METHODS
A convenience sample of 40 participants (n = 19 female) was drawn from another study (Lebel et al. in Qual Life Res 25:311-321. doi: 10.1007/s11136-015-1088-2 , 2016). The semi-structured interview for fear of cancer recurrence (Simard and Savard in J Cancer Surviv 9:481-491. doi: 10.1007/s11764-015-0424-4 , 2015) was used to identify participants with non-clinical and clinical FCR and qualitative analysis of these interviews was performed.

RESULTS
Individuals with clinical FCR reported the following features: death-related thoughts, feeling alone, belief that the cancer would return, experiencing intolerance of uncertainty, having cancer-related thoughts and imagery that were difficult to control, daily and recurrent, lasted 30 minutes or more, increased over time, caused distress and impacted their daily life. Triggers of FCR and coping strategies did not appear to be features of clinical FCR as they were reported by participants with a range of FCR scores.

CONCLUSIONS
While features of clinical FCR found in this analysis such as intrusive thoughts, distress and impact on functioning confirmed previous FCR research, other features spontaneously emerged from the interviews including "death-related thoughts," "feeling alone," and "belief that the cancer will return." The participants' descriptions of cancer-specific fear and worry suggest that FCR is a distinct phenomenon related to cancer survivorship, despite similarities with psychological disorders (e.g., Anxiety Disorders). Future research investigating the construct of FCR, and the distinguishing features of clinical FCR across a range of cancer types and gender is required.

Mutsaers|Brittany|B|
Jones|Georden|G|
Rutkowski|Nicole|N|
Tomei|Christina|C|
Séguin Leclair|Caroline|C|
Petricone-Westwood|Danielle|D|
Simard|Sébastien|S|
Lebel|Sophie|S|

Fear of cancer recurrence
Qualitative analysis
Clinical fear of cancer recurrence
Semi-structured interview
Psychosocial oncology


Mechanical Thrombectomy in Medium Vessel Occlusions: Blind Exchange With Mini-Pinning Technique Versus Mini Stent Retriever Alone.

Abstract:
BACKGROUND AND PURPOSE
Mechanical thrombectomy techniques for intracranial medium vessel occlusions (MeVOs) have evolved in recent years, although the optimal approach is still unclear. The aim of this study was to investigate the effectiveness and safety of mechanical thrombectomy in MeVOs using mini (0.017 inches microcatheter compatible) stent retrievers combined with low-profile (0.035 inches distal inner diameter) distal aspiration catheters through the blind exchange/mini-pinning (BEMP) technique compared with mini stent retrievers alone.

METHODS
Retrospective review of a prospectively maintained database of patients treated with the BEMP technique or mini stent retriever alone for intracranial MeVOs from 2017 to 2020 in a comprehensive stroke center. Both groups were compared about baseline characteristics, occlusion site, clinical presentation, clot cause, procedural outcomes (MeVO first-pass and final expanded Thrombolysis in Cerebral Ischemia score, the mini stent retriever used, number of passes with the front-line approach, and need of rescue therapy), safety outcomes (emboli to unwanted territories and hemorrhagic complications), and clinical outcomes at 90 days. Multivariable logistic regression analysis was performed with potential predictors of vessel recanalization to find independent variables associated with MeVO first-pass expanded Thrombolysis in Cerebral Ischemia 2c/3 recanalization.

RESULTS
We reviewed 102 patients/106 MeVOs treated with the BEMP technique (n=56) or mini stent retriever (n=50). There was a higher rate of MeVO first-pass expanded Thrombolysis in Cerebral Ischemia 2c/3 recanalization (57% versus 34%, P=0.017), lower need of rescue therapy (7.1% versus 22%, P=0.028), and lower rate of emboli to new territory (1.8% versus 12%, P=0.035) and symptomatic intracranial hemorrhage (1.9% versus 12.8%, P=0.038) with the BEMP technique. After multivariable analysis, the sole independent factor associated to MeVO first-pass expanded Thrombolysis in Cerebral Ischemia 2c/3 recanalization was the BEMP technique (odds ratio, 2.72 [95% CI, 1.19-6.22]; P=0.018).

CONCLUSIONS
In the setting of MeVOs, the BEMP technique may lead to higher rates of the first-pass recanalization and a lower incidence of symptomatic intracranial hemorrhage than mini stent retrievers alone.

Pérez-García|Carlos|C|
Moreu|Manuel|M|
Rosati|Santiago|S|
Simal|Patricia|P|
Egido|Jose Antonio|JA|
Gomez-Escalonilla|Carlos|C|
Arrazola|Juan|J|

D020243:Infarction, Anterior Cerebral Artery

D020244:Infarction, Middle Cerebral Artery

D020762:Infarction, Posterior Cerebral Artery

thrombectomy
stents
catheters
intracranial hemorrhages
incidence


Nanopore Sequencing Accurately Identifies the Mutagenic DNA Lesion O6 -Carboxymethyl Guanine and Reveals Its Behavior in Replication.

Abstract: O6 -carboxymethylguanine (O6 -CMG) is a highly mutagenic alkylation product of DNA, triggering transition mutations relevant to gastrointestinal cancer. However, precise localization of a single O6 -CMG with conventional sequencing platforms is challenging. Here nanopore sequencing (NPS), which directly senses single DNA bases according to their physiochemical properties, was employed to detect O6 -CMG. A unique O6 -CMG signal was observed during NPS and a single-event call accuracy of >95 % was achieved. Moreover, O6 -CMG was found to be a replication obstacle for Phi29 DNA polymerase (Phi29 DNAP), suggesting this lesion could cause DNA sequencing biases in next generation sequencing (NGS) approaches.

nanopore sequencing
DNA lesion
gastrointestinal cancer
carboxymethyl guanine


Presepsin as a diagnostic marker for sepsis: evidence from a bivariate meta-analysis.

Abstract:
BACKGROUND
The diagnosis of sepsis remains a clinical challenge. Many studies suggest that presepsin plays a role in diagnosing sepsis, but the results remain controversial. This study aimed to identify the overall diagnostic accuracy of presepsin for sepsis through meta-analysis.

METHODS
A systematic literature search was performed in PubMed and EMBASE to identify studies evaluating the diagnostic accuracy of presepsin in sepsis patients. Data were retrieved and the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio (DOR) were calculated. A summary receiver operating characteristic curve and area under curve (AUC) were used to evaluate the overall diagnostic performance. The statistical analysis was performed using Stata 12.0 and Meta-DiSc 1.4 software.

RESULTS
Eleven publications with 3,106 subjects were included in the meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and DOR were 0.83 (95% confidence interval [CI] 0.77-0.88), 0.81 (95% CI 0.74-0.87), 4.43 (95% CI 3.05-6.43), 0.21 (95% CI 0.14-0.30), and 21.56 (95% CI 10.59-43.88), respectively. The area under the curve was 0.89 (95% CI 0.86-0.92). Estimated positive and negative post-probability values for a sepsis prevalence of 20% were 53% and 5%, respectively. No publication bias was identified.

CONCLUSION
Based on currently available evidence, presepsin may have a valuable role in the diagnosis of sepsis, and its results should be interpreted carefully in the context of clinical condition and traditional markers.

Tong|Xiaomeng|X| Cao|Yongtong|Y| Yu|Min|M| Han|Chengwu|C|

presepsin sepsis meta-analysis diagnosis


Multifactorial positive influence of cochlear implantation on patients with single-sided deafness.

Abstract:
OBJECTIVES
Single-sided deafness (SSD) is an extreme case with profound unilateral hearing loss in the poorer ear and regular hearing in the other ear. The aim of this study is to investigate the impairment in the daily life of SSD patients and the influence of cochlear implants (CI) on their health-related quality of life (HRQoL), the impact on existing tinnitus distress and psychological comorbidities, and audiometric parameters.

METHODS
In total, 21 patients (8 male and 13 female) were included, and the Charité Test Battery was applied for all patients. Data on HRQoL were collected with the Nijmegen Cochlear Implant Questionnaire and the Medical Outcome Study Short Form 36 (SF-36) Survey. Tinnitus distress was assessed with the Tinnitus Questionnaire (TQ). Data with regard to psychological comorbidities were collected using four validated questionnaires. Speech perception was assessed with the Freiburg Monosyllable Test (FMS), the Oldenburg Sentence Test (OLSA), and the Oldenburg Inventory (OI).

RESULTS
HRQoL improved in the subdomain social interactions. Tinnitus distress dropped significantly 6 months postoperatively. SSD patients preoperatively showed elevated levels of stress, depressive symptoms, and anxiety. Postoperatively, these psychological symptoms improved with regard to stress, tension, and demands. The audiometry tools revealed a significant improvement in directional hearing (OI), speech perception in silence, and in the speech intelligibility threshold (OLSA).

CONCLUSION
There was an improvement in HRQoL and a reduction of tinnitus and cognitive distress. The preoperatively elevated stress level decreased significantly, and psychological comorbidities such as depressive symptoms and anxiety all improved postimplantation.

LEVEL OF EVIDENCE
II-2 Laryngoscope, 130:500-506, 2020.

Häußler|Sophia M|SM|0000-0003-4695-3037
Köpke|Vanessa|V|
Knopke|Steffen|S|
Gräbel|Stefan|S|
Olze|Heidi|H|

D000203:Activities of Daily Living
D019929:Cochlear Implantation
D005260:Female
D046088:Hearing Loss, Unilateral
D006320:Hearing Tests
D006801:Humans
D008297:Male
D008875:Middle Aged
D011446:Prospective Studies
D011788:Quality of Life
D011795:Surveys and Questionnaires
D014012:Tinnitus

Cochlear implantation
single-sided deafness
quality of life
tinnitus
stress


The relationship between physical activity and lymphoma: a systematic review and meta analysis.

Abstract:
BACKGROUND
The literature suggests an increased risk between anthropometrics including higher body mass index and lymphoma incidence; however, the association with physical activity remains unclear. A systematic review/meta-analysis was therefore performed to examine this association with physical activity (total, recreational or occupational).

METHODS
PubMed, Web of Science and Embase were reviewed from inception to October 2019 identifying relevant observational studies. Non-Hodgkin lymphoma (NHL) including subtypes diffuse large B cell lymphoma, follicular lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma, and Hodgkin lymphoma (HL) were analyzed. Included studies reported activity, lymphoma cases, effect size and variability measures, and were restricted to human subjects of any age. Data was pooled generating summary relative risk (RR) estimates with 95% confidence intervals (CI) using random-effects models with primary outcome of histologically confirmed incident lymphoma.

RESULTS
One thousand four hundred studies were initially identified with 18 studies (nine cohort, nine case-control) included in final analysis. Comparing highest vs. lowest activity categories was protective for all lymphoma (RR 0.89, 95%CI 0.81-0.98). Sensitivity analysis demonstrated effect persistence within case-control studies (RR 0.82, 95% CI 0.71-0.96), but not cohort studies (RR 0.95, 95%CI 0.84-1.07). Borderline protective effect was seen for NHL (RR 0.92, 95%CI 0.84-1.00), but not HL (RR 0.72, 95%CI 0.50-1.04). Analysis by NHL subtype or gender showed no effect. Dose response analysis demonstrated a protective effect (p = 0.034) with a 1% risk reduction per 3 MET hours/week (RR 0.99, 95%CI 0.98-1.00).

CONCLUSIONS
Physical activity may have a protective effect against lymphoma development; further studies are required to generate recommendations regarding health policy.

TRIAL REGISTRATION
This study was registered prospectively at PROSPERO: CRD42020156242 .

Physical activity
Lymphoma
Meta-analysis