Developing Internet-based health interventions: a guide for public health researchers and practitioners.

Abstract:
BACKGROUND
Researchers and practitioners interested in developing online health interventions most often rely on Web-based and print resources to guide them through the process of online intervention development. Although useful for understanding many aspects of best practices for website development, missing from these resources are concrete examples of experiences in online intervention development for health apps from the perspective of those conducting online health interventions.

OBJECTIVE
This study aims to serve as a series of case studies in the development of online health interventions to provide insights for researchers and practitioners who are considering technology-based interventional or programmatic approaches.

METHODS
A convenience sample of six study coordinators and five principal investigators at a large, US-based land grant university were interviewed about the process of developing online interventions in the areas of alcohol policy, adolescent health, medication adherence, and human immunodeficiency virus prevention in transgender persons and in men who have sex with men. Participants were asked questions that broadly addressed each of the four phases of the User-Centered Design Process Map from the US Department of Health and Human Services' Research-Based Web Design & Usability Guidelines. Interviews were audio recorded and transcribed. Qualitative codes were developed using line-by-line open coding for all transcripts, and all transcripts were coded independently by at least 2 authors. Differences among coders were resolved with discussion.

RESULTS
We identified the following seven themes: (1) hire a strong (or at least the right) research team, (2) take time to plan before beginning the design process, (3) recognize that vendors and researchers have differing values, objectives, and language, (4) develop a detailed contract, (5) document all decisions and development activities, (6) use a content management system, and (7) allow extra time for testing and debugging your intervention. Each of these areas is discussed in detail, with supporting quotations from principal investigators and study coordinators.

CONCLUSIONS
The values held by members of each participating organization involved in the development of the online intervention or program, as well as the objectives that are trying to be met with the website, must be considered. These defined values and objectives should prompt an open and explicit discussion about the scope of work, budget, and other needs from the perspectives of each organization. Because of the complexity of developing online interventions, researchers and practitioners should become familiar with the process and how it may differ from the development and implementation of in-person interventions or programs. To assist with this, the intervention team should consider expanding the team to include experts in computer science or learning technologies, as well as taking advantage of institutional resources that will be needed for successful completion of the project. Finally, we describe the tradeoff between funds available for online intervention or program development and the complexity of the project.

D000293:Adolescent
D016497:Adolescent Health Services
D054626:Consumer Health Information
D015658:HIV Infections
D015438:Health Behavior
D006293:Health Promotion
D006801:Humans
D020407:Internet
D007407:Interviews as Topic
D008297:Male
D055118:Medication Adherence
D016730:Program Development
D011634:Public Health
D012108:Research Personnel
D063106:Transgender Persons

development
intervention
public health
Internet


INvestigation on Routine Follow-up in CONgestive HearT FAilure Patients with Remotely Monitored Implanted Cardioverter Defibrillators SysTems (InContact).

Abstract:
BACKGROUND
In heart failure (HF) patients with implantable cardioverter defibrillators (ICD) or cardiac resynchronisation therapy defibrillators (CRT-D), remote monitoring has been shown to result in at least non-inferior outcomes relative to in-clinic visits. We aimed to provide further evidence for this effect, and to assess whether adding telephone follow-ups to remote follow-ups influenced outcomes.

METHODS
InContact was a prospective, randomised, multicentre study. Subjects receiving quarterly automated follow-up only (telemetry group) were compared to those receiving personal physician contact. Personal contact patients were further divided into those receiving automated follow-up plus a telephone call (remote+phone subgroup) or in-clinic visits only.

RESULTS
Two hundred and ten patients underwent randomisation (telemetry n = 102; personal contact n = 108 [remote+phone: n = 53; visit: n = 55]). Baseline characteristics were comparable between groups and subgroups. Over 12 months, 34.8% of patients experienced deterioration of their Packer Clinical Composite Response, with no significant difference between the telemetry group and personal care (p > 0.999), remote+phone (p = 0.937) or visit (p = 0.940) patients; predefined non-inferiority criteria were met. Mortality rates (5.2% overall) were comparable between groups and subgroups (p = 0.832/p = 0.645), as were HF-hospitalisation rates (11.0% overall; p = 0.605/p = 0.851). The proportion of patients requiring ≥1 unscheduled follow-up was nominally higher in telemetry and remote+phone groups (42.2 and 45.3%) compared to the visit group (29.1%). Overall, ≥ 1 ICD therapy was delivered to 15.2% of patients.

CONCLUSION
In HF patients with ICDs/CRT-Ds, quarterly remote follow-up only over 12 months was non-inferior to regular personal contact. Addition of quarterly telephone follow-ups to remote monitoring does not appear to offer any clinical advantage.

TRIAL REGISTRATION
clinicaltrials.gov: NCT01200381 (retrospectively registered on September 13th 2010).

Hansen|Claudius|C| Loges|Christian|C| Seidl|Karlheinz|K| Eberhardt|Frank|F| Tröster|Herbert|H| Petrov|Krum|K| Grönefeld|Gerian|G| Bramlage|Peter|P|0000-0002-4121-6866 Birkenhauer|Frank|F| Weiss|Christian|C|

D000368:Aged
D017147:Defibrillators, Implantable
D004554:Electric Countershock
D005858:Germany
D006333:Heart Failure
D006801:Humans
D008875:Middle Aged
D009819:Office Visits
D011237:Predictive Value of Tests
D011446:Prospective Studies
D058998:Remote Sensing Technology
D013686:Telemetry
D013689:Telephone
D013997:Time Factors
D016896:Treatment Outcome

Cardiac resynchronisation therapy defibrillator

Packer heart failure clinical composite response


Evaluation of spoilage potential and volatile metabolites production by Shewanella baltica isolated from modified atmosphere packaged live mussels.

Abstract: Under the current commercial practice, live mussels only have 10days' shelf-life. Observed spoilage indices reduce consumers' acceptance, palatability and shelf-life of modified atmosphere packaged (MAP) live mussels. The aims of this study are to isolate specific spoilage bacteria from modified atmosphere packaged live mussels, evaluate isolates for microbial spoilage indices using qualitative methods and volatile metabolites production. Forty-six hydrogen sulphide producing bacteria were isolated and evaluated for trimethylamine n-oxide (TMAO) reduction, proteolytic and lipolytic activities and hydrogen sulphide production. Twenty-eight isolates were obtained from pouch water and 18 from mussel meat. All the isolates could produce H2S on Iron agar at 25°C while 30/46 produced H2S at 4°C and tolerate 0-6% NaCl. Four (4/46) isolates could not hydrolyse mussel protein. Over 80% isolates reduced TMAO to TMA in 3days with the production of H2S. Results of this study shows hydrogen sulphide producing bacteria isolated from MAP live mussels produce microbial spoilage indices. Isolate with highest enzymatic activities and hydrogen sulphide production was identified as Shewanella baltica using 16S rRNA gene. Axenic culture of the isolate was inoculated into sterile mussel broth. Inoculated sample was further stored at 4°C for 10days for spoilage study. Volatile metabolites produced during storage were evaluated using headspace solid phase micro-extraction gas chromatography mass spectrometry (HS-SPME GC/MS). A total of 44 compounds were identified in the sample after 10days while 27 compounds were identified in inoculated mussel broth. Group of compounds identified are alcohols, aldehydes, phenol, furans, ketone, esters, organic acid, aromatic hydrocarbons, alkanes, nitrogen and sulphur containing compounds. Dimethyl trisulphide, methyl-phenol, 3,5-octadiene and thiohexene were unique to inoculated mussel broth. Understanding spoilage mechanism and attendant spoilage indices will help in designing effective mussel quality protocols and shelf-life extension.

Odeyemi|Olumide A|OA|
Burke|Christopher M|CM|
Bolch|Christopher J S|CJS|
Stanley|Roger|R|

Volatile metabolites
Microbial shelf-life
Seafood spoilage


The improvement in body composition including subcutaneous and visceral fat reduces ammonia and hepatic encephalopathy after transjugular intrahepatic portosystemic shunt.

Abstract:
BACKGROUND
Sarcopenia and myosteatosis have been associated to a poor prognosis of cirrhosis and to a higher incidence of hepatic encephalopathy (HE). The prognostic implications of visceral and subcutaneous adiposity are less known.

AIM
To evaluate the modifications of visceral and subcutaneous adipose tissue after TIPS and to investigate their relationships with the modification of muscle mass and with the incidence of post-TIPS HE.

PATIENTS AND METHODS
35 cirrhotic patients submitted to TIPS were retrospectively studied. The modification of skeletal muscle index (SMI), muscle attenuation (myosteatosis), subcutaneous adipose tissue index (SATI), visceral adipose tissue index (VATI), assessed by CT-scan and plasma ammonia were evaluated before and after a mean follow-up of 19 ± 15 months after TIPS. The number of episodes of overt HE was also recorded.

RESULTS
During the follow-up, the mean SMI and muscle attenuation increased significantly; SATI significantly increased while VATI significantly decreased, although not uniformly in all patients. By comparing the patients with or without improvement in their nutritional status after TIPS, MELD remained stable while the number of episodes of overt HE was significantly lower in the patients with improved SMI and in the patients with improved SATI. Finally, inverse correlation was observed between the variation of ammonia and SATI (r = -.40; P < .05).

CONCLUSION
In addition to muscle mass, adipose tissue is modified after TIPS. The improvement of subcutaneous adipose tissue as well as of sarcopenia and myosteatosis is associated to the amelioration of cognitive impairment independently of liver function. The correlation between adipose tissue and ammonia modification may suggest an active role of the adipose tissue in the inter-organ ammonia trafficking.

ammonia
hepatic encephalopathy
sarcopenia
adipose tissue
TIPS


Finger-thumb coupling contributes to exaggerated thumb flexion in stroke survivors.

Abstract: The purpose of this study was to investigate altered finger-thumb coupling in individuals with chronic hemiparesis poststroke. First, an external device stretched finger flexor muscles by passively rotating the metacarpophalangeal (MCP) joints. Subjects then performed isometric finger or thumb force generation. Forces/torques and electromyographic signals were recorded for both the thumb and finger muscles. Stroke survivors with moderate (n = 9) and severe (n = 9) chronic hand impairment participated, along with neurologically intact individuals (n = 9). Stroke survivors exhibited strong interactions between finger and thumb flexors. The stretch reflex evoked by stretch of the finger flexors of stroke survivors led to heteronymous reflex activity in the thumb, while attempts to produce isolated voluntary finger MCP flexion torque/thumb flexion force led to increased and undesired thumb force/finger MCP torque production poststroke with a striking asymmetry between voluntary flexion and extension. Coherence between the long finger and thumb flexors estimated using intermuscular electromyographic correlations, however, was small. Coactivation of thumb and finger flexor muscles was common in stroke survivors, whether activation was evoked by passive stretch or voluntary activation. The coupling appears to arise from subcortical or spinal sources. Flexor coupling between the thumb and fingers seems to contribute to undesired thumb flexor activity after stroke and may impact rehabilitation outcomes.

Kamper|Derek G|DG|
Fischer|Heidi C|HC|
Conrad|Megan O|MO|
Towles|Joseph D|JD|
Rymer|William Z|WZ|
Triandafilou|Kristen M|KM|

thumb stroke finger coactivation spasticity


Reductive chemical release of N-glycans as 1-amino-alditols and subsequent 9-fluorenylmethyloxycarbonyl labeling for MS and LC/MS analysis.

Abstract:
Glycoproteins play pivotal roles in a series of biological processes and their glycosylation patterns need to be structurally and functionally characterized. However, the lack of versatile methods to release N-glycans as functionalized forms has been undermining glycomics studies. Here a novel method is developed for dissociation of N-linked glycans from glycoproteins for analysis by MS and online LC/MS. This new method employs aqueous ammonia solution containing NaBH3CN as the reaction medium to release glycans from glycoproteins as 1-amino-alditol forms. The released glycans are conveniently labeled with 9-fluorenylmethyloxycarbonyl (Fmoc) and analyzed by ESI-MS and online LC/MS. Using the method, the neutral and acidic N-glycans were successfully released without peeling degradation of the core α-1,3-fucosylated structure or detectable de-N-acetylation, revealing its general applicability to various types of N-glycans. The Fmoc-derivatized N-glycans derived from chicken ovalbumin, Fagopyrum esculentum Moench Pollen and FBS were successfully analyzed by online LC/MS to distinguish isomers. The 1-amino-alditols were also permethylated to form quaternary ammonium cations at the reducing end, which enhance the MS sensitivity and are compatible with sequential multi-stage mass spectrometry (MSn) fragmentation for glycan sequencing. The Fmoc-labeled N-glycans were further permethylated to produce methylated carbamates for determination of branches and linkages by sequential MSn fragmentation.

SIGNIFICANCE OF THE STUDY
N-Glycosylation represents one of the most common post-translational modification forms and plays pivotal roles in the structural and functional regulation of proteins in various biological activities, relating closely to human health and diseases. As a type of informational molecule, the N-glycans of glycoproteins participate directly in the molecular interactions between glycan epitopes and their corresponding protein receptors. Detailed structural and functional characterization of different types of N-glycans is essential for understanding the functional mechanisms of many biological activities and the pathologies of many diseases. Here we describe a simple, versatile method to indistinguishably release all types of N-glycans as functionalized forms without remarkable side reactions, enabling convenient, rapid analysis and preparation of released N-glycans from various complex biological samples. It is very valuable for studies on the complicated structure-function relationship of N-glycans, as well as for the search of N-glycan biomarkers of some major diseases and N-glycan related targets of some drugs.

Wang|Chengjian|C| Qiang|Shan|S| Jin|Wanjun|W| Song|Xuezheng|X| Zhang|Ying|Y| Huang|Linjuan|L| Wang|Zhongfu|Z|

D021241:Spectrometry, Mass, Electrospray Ionization

Reductive chemical release
N-glycans
LC/MS
Fmoc
Permethylation


Combined therapy with conventional trans-arterial chemoembolization (cTACE) and microwave ablation (MWA) for hepatocellular carcinoma >3-<5 cm.

Abstract:
PURPOSE
To compare safety and efficacy of combined therapy with conventional transarterial chemoembolization (cTACE)+microwave ablation (MWA) versus only TACE or MWA for treatment of hepatocellular carcinoma (HCC) >3-<5 cm.

METHODS
This randomized controlled trial (NCT04721470) screened 278 patients with HCC >3-<5 cm. Patients were randomized into three groups: 90 underwent TACE (Group 1); 95 underwent MWA (Group 2); and 93 underwent combined therapy (Group 3). Patients were followed-up with contrast-enhanced CT or MRI. Images were evaluated and compared for treatment response and adverse events based on modified response evaluation criteria in solid tumor. Serum alpha-fetoprotein (AFP) concentration was measured at baseline and during every follow-up visit.

RESULTS
Final analysis included 265 patients (154 men, 111 women; mean age = 54.5 ± 11.8 years; range = 38-76 years). Complete response was achieved by 86.5% of patients who received combined therapy compared with 54.8% with only TACE and 56.5% with only MWA (p = 0.0002). The recurrence rate after 12 months was significantly lower in Group 3 (22.47%) than Groups 1 (60.7%) and 2 (51.1%) (p = 0.0001). The overall survival rate (three years after therapy) was significantly higher in Group 3 (69.6%) than Groups 1 (54.7%) and 2 (54.3%) (p = 0.02). The mean progression-free survival was significantly higher in Group 3 than groups 1 and 2 (p < 0.001). A decrease in AFP concentration was seen in 75%, 63%, and 48% patients of Group 3, 2, and 1, respectively.

CONCLUSIONS
Combined therapy with cTACE + MWA is safe, well-tolerated, and more effective than TACE or MWA alone for treatment of HCC >3-<5 cm.


Desired improvements of working conditions among medical assistants in Germany: a cross-sectional study.

Abstract:
Background
In outpatient care in Germany, medical assistants (MAs) are the contact persons for patients' concerns and their working conditions are relevant to their own health and the provided quality of care. MAs working conditions have been described as precarious leading to high levels of work stress. Consequently, we aimed to examine MAs' needs for work-related improvements.

Methods
We surveyed 887 employed MAs between September 2016 and April 2017. A 20-item questionnaire measured desired improvements. To measure correlations between variables we computed a matrix of tetrachoric correlations for binary variables and performed an exploratory factor analysis. We ran ordinal logistic regression models employing 11 independent variables to examine determinants of needs.

Results
A total of 97.3% of the participants expressed any need and, on average, 10.27 needs were reported. Most frequently, needs were expressed related to a higher salary (87.0%), less documentation (76.0%) and more recognition from society (75.4%). Exploratory factor analysis suggested three dimensions of needs for work-related improvements (i.e. working conditions, reward from the supervisor and task-related independence). Ordinal logistic regression models only identified determinants for the outcome variable task-related independence, which was more frequent in those with longer work experience or in a leadership position.

Conclusions
The high prevalence of desired workplace-related improvements among MAs highlights the relevance of modifying their working conditions. The fact that we found only few determinants signals that there are no specific high-risk subgroups, but interventions to improve MAs' working conditions should target the entire MA population.

Scharf|Jessica|J| Vu-Eickmann|Patricia|P| Li|Jian|J| Müller|Andreas|A| Wilm|Stefan|S| Angerer|Peter|P| Loerbroks|Adrian|A|0000-0003-2795-8684

Working conditions
Medical assistants
Cross-sectional study
Health occupation
Needs assessment


Real-Time Monitoring and Detection of Single-Cell Level Cytokine Secretion Using LSPR Technology.

Abstract: Cytokine secretion researches have been a main focus of studies among the scientists in the recent decades for its outstanding contribution to clinical diagnostics. Localized surface plasmon resonance (LSPR) technology is one of the conventional methods utilized to analyze these issues, as it could provide fast, label-free and real-time monitoring of biomolecule binding events. However, numerous LSPR-based biosensors in the past are usually utilized to monitor the average performance of cell groups rather than single cells. Meanwhile, the complicated sensor structures will lead to the fabrication and economic budget problems. Thus, in this paper, we report a simple synergistic integration of the cell trapping of microwell chip and gold-capped nanopillar-structured cyclo-olefin-polymer (COP) film for single cell level Interleukin 6 (IL-6) detection. Here, in-situ cytokine secreted from the trapped cell can be directly observed and analyzed through the peak red-shift in the transmittance spectrum. The fabricated device also shows the potential to conduct the real-time monitoring which would greatly help us identify the viability and biological variation of the tested single cell.

Zhu|Chen|C|0000-0003-4589-0257
Luo|Xi|X|0000-0002-8575-2222
Espulgar|Wilfred Villariza|WV|
Koyama|Shohei|S|
Kumanogoh|Atsushi|A|
Saito|Masato|M|
Takamatsu|Hyota|H|
Tamiya|Eiichi|E|

localized surface plasmon resonance (LSPR) technology


Short-term kinesthetic training for sensorimotor rhythms: effects in experts and amateurs.

Abstract: The authors' aim was to examine whether short-term kinesthetic training affects the level of sensorimotor rhythm (SMR) in different frequency band: alpha (8-12 Hz), lower beta (12.5-16 Hz) and beta (16.5-20 Hz) during the execution of a motor imagery task of closing and opening the right and the left hand by experts (jugglers, practicing similar exercises on an everyday basis) and amateurs (individuals not practicing any sports). It was found that the performance of short kinesthetic training increases the power of alpha rhythm when executing imagery tasks only in the group of amateurs. Therefore, kinesthetic training may be successfully used as a method increasing the vividness of motor imagery, for example, in tasks involving the control of brain-computer interfaces based on SMR.

Zapała|Dariusz|D| Zabielska-Mendyk|Emilia|E| Cudo|Andrzej|A| Krzysztofiak|Agnieszka|A| Augustynowicz|Paweł|P| Francuz|Piotr|P|

kinesthetic training
sensorimotor rhythms
motor imagery
EEG
jugglery


Sugar Sensing and Signaling in Candida albicans and Candida glabrata.

Abstract: Candida species, such as Candida albicans and Candida glabrata, cause infections at different host sites because they adapt their metabolism depending on the available nutrients. They are able to proliferate under both nutrient-rich and nutrient-poor conditions. This adaptation is what makes these fungi successful pathogens. For both species, sugars are very important nutrients and as the sugar level differs depending on the host niche, different sugar sensing systems must be present. Saccharomyces cerevisiae has been used as a model for the identification of these sugar sensing systems. One of the main carbon sources for yeast is glucose, for which three different pathways have been described. First, two transporter-like proteins, ScSnf3 and ScRgt2, sense glucose levels resulting in the induction of different hexose transporter genes. This situation is comparable in C. albicans and C. glabrata, where sensing of glucose by CaHgt4 and CgSnf3, respectively, also results in hexose transporter gene induction. The second glucose sensing mechanism in S. cerevisiae is via the G-protein coupled receptor ScGpr1, which causes the activation of the cAMP/PKA pathway, resulting in rapid adaptation to the presence of glucose. The main components of this glucose sensing system are also conserved in C. albicans and C. glabrata. However, it seems that the ligand(s) for CaGpr1 are not sugars but lactate and methionine. In C. glabrata, this pathway has not yet been investigated. Finally, the glucose repression pathway ensures repression of respiration and repression of the use of alternative carbon sources. This pathway is not well characterized in Candida species. It is important to note that, apart from glucose, other sugars and sugar-analogs, such as N-acetylglucosamine in the case of C. albicans, are also important carbon sources. In these fungal pathogens, sensing sugars is important for a number of virulence attributes, including adhesion, oxidative stress resistance, biofilm formation, morphogenesis, invasion, and antifungal drug tolerance. In this review, the sugar sensing and signaling mechanisms in these Candida species are compared to S. cerevisiae.

Van Ende|Mieke|M|
Wijnants|Stefanie|S|
Van Dijck|Patrick|P|


Evaluation of carbapenem use in a tertiary hospital: antimicrobial stewardship urgently needed.

Abstract:
Background
China launched a 3-year rectification scheme for the clinical use of antibiotics in 2011, and a specific scheme for carbapenem use in 2017. The aim of this study was to investigate the effects of government policies on carbapenem use, and their correlation with carbapenem-resistant Pseudomonas aeruginosa (CRPA).

Methods
The study was divided into four stages: preintervention (2010), antimicrobial programme (2011-2013), post-antimicrobial programme (2014-2016) and carbapenem programme (2017). A point-score system was proposed for evaluating the rationality of carbapenem use, and evaluated based on the indications, microbial culture, single dose, interval, and duration. Any prescription without a global score of 10 points was judged as irrational. The trend was analyzed by regression analysis, and Spearman correlation analysis was used for testing the correlation.

Findings
The rate of rational use of carbapenems was 29.7% in 2010, and increased by 55.5, 45.2, and 51.5% during the subsequent three stages. The rationality declined slightly during the post-antimicrobial programme (2014-2016) while the consumption of carbapenems was markedly increased. These two parameters improved slightly in 2017. Moreover, the prevalence of CRPA was significantly negatively correlated with the rate of rational carbapenem use (Coefficient = - 0.553, P < 0.05), and not with the consumption of carbapenems (P > 0.05).

Conclusions
The rational application of carbapenems was related to government policies in this study, with irrational carbapenem use possibly related to the development of CRPA. The current point-score system could be a useful tool for performing assessments.

Zhang|Di|D| Cui|Kai|K| Lu|Wei|W| Bai|Hehe|H| Zhai|Yuyao|Y| Hu|Sasa|S| Li|Hao|H| Dong|Haiyan|H| Feng|Weiyi|W| Dong|Yalin|Y|

D000900:Anti-Bacterial Agents
D000073602:Antimicrobial Stewardship
D015780:Carbapenems
D002681:China
D024881:Drug Resistance, Bacterial
D006801:Humans
D008826:Microbial Sensitivity Tests
D057766:Policy
D011552:Pseudomonas Infections
D011550:Pseudomonas aeruginosa
D012189:Retrospective Studies
D062606:Tertiary Care Centers


Use of a single circuit to provide temporary mechanical respiratory and circulatory support in patients with LV apical thrombus and cardiogenic shock.

Abstract:
INTRODUCTION
Techniques to support patients with cardiogenic shock continue to improve. Patients with intracardiac thrombi pose a potential for additional complications. Novel methods of biventricular support are necessary to manage these patients.

METHODS
Two patients with refractory cardiogenic shock and left ventricular apical thrombi underwent mechanical circulatory support (MCS) as a bridge to decision, with a left ventricular assist device (LVAD) and extracorporeal mechanical oxygenation (ECMO). Instead of the conventional LV apical cannulation for LVAD, the left atrium (LA) was cannulated. The LA cannula was then integrated with the ECMO circuit via a 'Y' connection to a percutaneous right atrial cannula, enabling optimal drainage of both sides into one circuit through a single CentriMag® pump and ECMO into the aorta.

RESULTS
The first patient was converted to a durable LVAD and transplanted, while the second patient was explanted, after demonstrating significant LV recovery.

CONCLUSION
We demonstrated the use of MCS as a bridge to decision in patients with LV thrombi, utilizing biatrial cannulation with a 'Y' connection to drain both right- and left-sided circulation through a single circuit and pump.

single circuit
MCS
LVAD
CentriMag
LA cannulation
LV thrombus
RVAD
VAD


The Effectiveness of a Parent-Training Program for Promoting Cognitive Performance in Preschool Children.

Abstract: The study aims to evaluate the effectiveness of a parent training program for promoting cognitive performance of young children through enriching the parent-child interactions among mothers of preschool-aged children in Mashhad, Iran. A total of 29 couples of mothers and their children were assigned to an experimental group (n = 16 couples) and a control group (n = 13 couples). Mothers in the experimental group participated in 12 weekly sessions and were trained how to enrich their daily parent-child interactions as such. Children's cognitive performance was assessed by three subscales of the Wechsler Preschool and Primary Scale of Intelligence (WPPSI). The results of the analysis of covariance (ANCOVA) indicated a significant difference between the experimental and control group. The findings support the effectiveness of the parent training program for enhancing cognitive performance in preschoolers.

cognitive performance
preschool children
parent training program
parent-child interactions


Preclinical safety evaluation of the aqueous extract from Mangifera indica Linn. (Anacardiaceae): genotoxic, clastogenic and cytotoxic assessment in experimental models of genotoxicity in rats to predict potential human risks.

Abstract:
ETHNOPHARMACOLOGICAL RELEVANCE
Medicinal plants widely used by the population contain significant concentrations of biologically active compounds and, although they have proven pharmacological properties, can cause DNA damage and develop fatal diseases.

AIM OF THE STUDY
The present study aimed to evaluate the genotoxic, cytotoxic potential and clastogenic effects of the aqueous extract from Mangifera indica leaves (EAMI) on rats submitted to experimental genotoxicity models and through the SMART test performed in Drosophila melanogaster.

MATERIAL AND METHODS
The comet assay and the micronucleus test were performed on peripheral and bone marrow blood, respectively, of Wistar rats, orally treated with EAMI at doses of 125, 250, 500 and 1000 mg/kg/bw for 28 days. In the SMART test, the standard cross between three mutant D. melanogaster strains was used. Larvae were treated with EAMI at different concentrations, and the wings of adult flies were evaluated for the presence/frequency of mutant spots and compared to the negative control group.

RESULTS
Phytochemical analysis of EAMI indicated high levels of flavonoids. The tests performed in rats showed that EAMI did not present significant genotoxic or clastogenic effects. The results showed a critical dose-dependent cytoprotective effect exerted by EAMI. This result was attributed to the high content of polyphenols and flavonoids. The biotransformation metabolites of EAMI did not present genotoxic activity, as demonstrated by the SMART test.

CONCLUSIONS
These results are relevant since they provide safety information about a plant species of great therapeutic, economical, nutritious and ethnopharmacological value for the population.

Villas Boas|Gustavo Roberto|GR|
Rodrigues Lemos|João Marcos|JM|
de Oliveira|Matheus William|MW|
Dos Santos|Rafael Claudino|RC|
Stefanello da Silveira|Ana Paula|AP|
Bacha|Flávia Barbieri|FB|
Aguero Ito|Caren Naomi|CN|
Cornelius|Ediane Bortolotte|EB|
Lima|Fernanda Brioli|FB|
Sachilarid Rodrigues|Andrea Marisa|AM|
Costa|Nathália Belmal|NB|
Bittencourt|Felipe Francisco|FF|
Freitas de Lima|Fernando|F|
Paes|Marina Meirelles|MM|
Gubert|Priscila|P|
Oesterreich|Silvia Aparecida|SA|

Preclinical safety
Mangifera indica
Genotoxicity
SMART test
Comet assay
Micronucleus
Mutagenesis


Characterization of the differences in the aroma of cherry wines from different price segments using gas chromatography-mass spectrometry, odor activity values, sensory analysis, and aroma reconstitution.

Abstract: The aroma composition, aroma-active compounds, and sensory attributions of cherry wines from three different price segments were investigated. A total of 48 aroma compounds were identified and quantified using headspace solid-phase microextraction (HS-SPME)/gas chromatography-mass spectrometry (GC-MS), among which 23 aroma compounds were further screened out as important odorants based on their odor activity values (OAVs); then, the previously mentioned 23 volatiles were correlated to sensory attributes using partial least-squares regression (PLSR). The result indicates that the differently priced wines were associated with different compounds and aroma attributions. Finally, aroma reconstitution was performed by mixing odor-active aroma compounds (OAVs>1) on the basis of their measured concentrations in the original sample. The result indicated that the aroma profile of the reconstituted sample was similar to that of the original sample.

Xiao|Qing|Q| Zhou|Xuan|X| Xiao|Zuobing|Z| Niu|Yunwei|Y|

cherry wine
odor activity value
aroma reconstitution
partial least-squares regression
different quality


How Albot0 finds its way home: a novel approach to cognitive mapping using robots.

Abstract: Much of what we know about cognitive mapping comes from observing how biological agents behave in their physical environments, and several of these ideas were implemented on robots, imitating such a process. In this paper a novel approach to cognitive mapping is presented whereby robots are treated as a species of their own and their cognitive mapping is being investigated. Such robots are referred to as Albots. The design of the first Albot, Albot0 , is presented. Albot0 computes an imprecise map and employs a novel method to find its way home. Both the map and the return-home algorithm exhibited characteristics commonly found in biological agents. What we have learned from Albot0 's cognitive mapping are discussed. One major lesson is that the spatiality in a cognitive map affords us rich and useful information and this argues against recent suggestions that the notion of a cognitive map is not a useful one.

D012371:Robotics
D013028:Space Perception
D062206:Spatial Analysis
D065854:Spatial Navigation

Cognitive mapping
Robotics
Inexact map
Spatial cognition


Resolution of an exposed pars plana Baerveldt shunt in a patient with a Boston keratoprosthesis type 1 without surgery.

Abstract: Patients with a keratoprosthesis often develop complications including glaucoma, requiring glaucoma drainage devices. In most of these patients, glaucoma drainage devices have been shown to be safe and effective. However, occasionally, a glaucoma drainage device in the setting of a keratoprosthesis can lead to conjunctival erosion with mechanical trauma. While repeat surgical intervention may appear necessary, we report a case of a patient who had improved conjunctival erosion and glaucoma drainage device exposure after refitting of a therapeutic contact lens. Therapeutic contact lenses can be used to maintain hydration and decrease exposure while improving cosmesis and refractive error. Complications following keratoprosthesis surgery are an understudied area, particularly regarding glaucoma drainage devices, and we seek to show that careful fitting of therapeutic contact lenses may avoid the risks of repeat surgical intervention.

glaucoma drainage device
contact lens
Air Optix
glaucoma drainage implant
keratoprosthesis Kontur


Pathogen profile and MMP-3 levels in areas with varied attachment loss in generalized aggressive and chronic periodontitis.

Abstract:
Introduction
The progression of periodontitis depends on the changes in bone and connective tissue homeostasis and the imbalance of the biofilm and the host immunoinflammatory response, particularly matrix metalloproteinases (MMP).

Aim of the study
To assess the probable relation between subgingival anaerobic flora and the expression of MMP-3 in patients with generalized aggressive periodontitis (AgP), chronic periodontitis (CP) and healthy subjects, and to evaluate these levels according to varied tissue loss severity.

Material and methods
The plaque index (PI), gingival index (GI), probing depth (PD) and clinical attachment levels (CAL) were evaluated. MMP levels obtained from gingival sulcus fluid (GCF) were measured with Enzyme Linked Immuno Assay (ELISA). The bacterial counts were determined with Parocheck®.

Results
Higher levels of MMP-3 in patients with AgP compared to subjects with CP and healthy individuals were observed. The microorganisms responsible of possible tissue destruction in both AgP and CP are red complex bacteria. T. denticola, T. forsythia, P. intermedia and F. nucleatum show positive correlation with MMP-3 levels.

Conclusions
MMP-3 is a biomarker associated with AgP, and red complex bacteria levels are correlated with increasing periodontal tissue loss in both periodontitis forms. The diagnosis of aggressive periodontitis, or site-specific treatment strategies can be orchestrated based on the evaluation of MMP-3 and the bacterial counts in patients with periodontitis.

Yilmaz|Mustafa|M|
Kasnak|GöKHAN|G|
Polat|Nuray G|NG|
Topcuoglu|Nursen E|NE|
KüLEKCI|GüVEN|G|
Firatli|Erhan|E|

pathogens
chronic periodontitis
MMP
aggressive periodontitis
gingival crevicular fluid


Biomimetically enhanced demineralized bone matrix for bone regenerative applications.

Abstract: Demineralized bone matrix (DBM) is one of the most widely used bone graft materials in dentistry. However, the ability of DBM to reliably and predictably induce bone regeneration has always been a cause for concern. The quality of DBM varies greatly depending on several donor dependent factors and also manufacturing techniques. In order to standardize the quality and to enable reliable and predictable bone regeneration, we have generated a biomimetically-enhanced version of DBM (BE-DBM) using clinical grade commercial DBM as a control. We have generated the BE-DBM by incorporating a cell-derived pro-osteogenic extracellular matrix (ECM) within clinical grade DBM. In the present study, we have characterized the BE-DBM and evaluated its ability to induce osteogenic differentiation of human marrow derived stromal cells (HMSCs) with respect to clinical grade commercial DBM. Our results indicate that the BE-DBM contains significantly more pro-osteogenic factors than DBM and enhances HMSC differentiation and mineralized matrix formation in vitro and in vivo. Based on our results, we envision that the BE-DBM has the potential to replace DBM as the bone graft material of choice.

Ravindran|Sriram|S| Huang|Chun-Chieh|CC| Gajendrareddy|Praveen|P| Narayanan|Raghuvaran|R|

demineralized bone matrix
extracellular matrix
biomimetic materials
bone regeneration and repair
mesenchymal stem cells


Single-stage treatment with iliac vein stenting and stripping of great saphenous veins for patients with left iliac vein compression syndrome.

Abstract:
BACKGROUND
We sought to evaluate the safety and feasibility of single-stage treatment with left iliac vein stenting and saphenous stripping in patients with left iliac vein compression (LIVC) and left great saphenous vein (GSV) incompetence.

METHOD
s: We conducted a prospective cohort study of 72 patients diagnosed with LIVC and left GSV incompetence between June 2012 to Oct 2018. We evaluated the periprocedural, 30-day, and 1-year outcomes of venous clinical severity score (VCSS), Chronic Venous Insufficiency Questionnaire 2 (CIVIQ2), the success rate of stent placement, duration of intervention, length of hospital stay, duplex recurrence, and clinically visible recurrence.

RESULTS
There were 43 patients in the two-staged group and 29 patients in the single-staged group. The clinical characteristics of the two groups were similar. There were no differences between the two groups in the technical success rate, perioperative mortality, and surgical morbidity. There was no significant difference in the duplex and clinically visible recurrence. The length of hospital stay was significantly lower in the single-staged group. The single-staged group was associated with a higher complication rate of ecchymosis. There was no death, pulmonary embolism, or contrast-induced nephropathy among the patients. The 1-year primary patency rate was similar.

CONCLUSIONS
Both treatment approaches were equally effective and had a high technical success rate. The single-staged group had a higher complication rate of ecchymosis due to heparin applying during the procedure.

Shao|Changming|C| Yan|Jinlin|J| Zhang|Naiding|N| Zhang|Liang|L| Li|Zhenhua|Z| Yin|Li|L| Liu|Zhenjie|Z|

Stent
Iliac vein compression
Chronic venous disease
Endovascular treatment
Great saphenous vein incompetence


Induction of CD4+ regulatory T cells by stimulation with Staphylococcal Enterotoxin C2 through different signaling pathways.

Abstract: As a member of superantigens, Staphylococcal Enterotoxin C2 (SEC2) can potently activate T cells expressing specific Vβ repertoires and has been applied in clinic for tumor immunotherapy in China for more than 20 years. However, excessive activation of T cells by over-stimulation with superantigen are always followed by eliciting regulatory T cells (Tregs) induction and functional immunosuppression, which brings uncertainties to SEC2 application in tumor immunotherapy. In this study, we found that SEC2 could induce CD4+CD25+Foxp3+ Tregs from the murine splenocytes in dose and time related manners. The induced Tregs with high expression of GITR and CTLA-4 and low expression of CD127 were TCR Vβ8.2-specific and have character of IL-10 production in a SEC2 dose-depended manner. Importantly, SEC2-induced CD4+ Tregs showed the potent capacity of suppressing proliferation of intact murine splenocytes response to SEC2. Furthermore, by using specific inhibitors or neutralizing antibody, we proved that the signaling pathways of TCR-NFAT/AP-1, IL-2-STAT5, and TGF-β-Smad3 play crucial roles in Tregs induction by SEC2. These findings will help us better understand the balance of immune stimulation and immunosuppression mediated by SEC2 and provide valuable guidance for SEC2 application in antitumor immunology.

Li|Yongqiang|Y| Xu|Mingkai|M| Li|Yansheng|Y| Zhang|Zhichun|Z| Gu|Wu|W| Halimu|Gulinare|G| Li|Yuqi|Y| Zhang|Huiwen|H| Zhang|Chenggang|C|

Superantigen
SEC2
Tumor immunotherapy
Immunosuppression
CD4(+) Tregs
Foxp3


Obstetric Patients and Healthcare Providers Perspectives to Inform Mobile App Design for Physical Activity and Weight Control During Pregnancy and Postpartum in a Rural Setting.

Abstract:
Background
Mobile health technology offers the opportunity for women to engage with physical activity promotion programs without many of the barriers commonly associated with exercise during and after pregnancy (eg, childcare concerns, rigid schedules, fear of doing harm to fetus or self, access to fitness facilities, uncomfortable with body in front of others) which may be particularly useful in under-resourced rural environments. We conducted the first known study on perspectives of pregnant women, postpartum women, and obstetric healthcare providers in a rural setting on needs related to the development of a mobile app designed to increase physical activity during pregnancy and postpartum.

Methods
Focus groups and in-depth face-to-face personal interviews were conducted with 14 pregnant women, 13 postpartum women, and 11 healthcare providers in a rural community. Semi-structured questions utilizing constructs of the Health Belief Model were used to identify barriers, facilitators, and other influences on physical activity during pregnancy and postpartum. Recordings of all in-depth interviews and focus groups were transcribed and standard content analyses for qualitative data were conducted.

Results
Rural women and healthcare providers expressed several key perspectives about and recommendations to promote physical activity during and after pregnancy. Broadly, these perspectives encapsulated two main themes: 1) physical activity as critical for weight control and 2) the need for evidence-based exercise information. Key desired features of this app identified include goal setting/progress tracking, evidence-based exercise guidance tailored to specific time points of pregnancy and postpartum, social support via community-based forum, symptom tracking, time-efficient workouts, and push notifications.

Conclusion
The perspectives identified by participants should be utilized when designing mobile health physical activity mobile apps for pregnant and postpartum women in rural areas.

Tinius|Rachel|R|0000-0002-3061-3997 Duchette|Cathryn|C| Beasley|Sia|S| Blankenship|Maire|M| Schoenberg|Nancy|N|

app pregnancy postpartum rural exercise mHealth


Variability among Online Opioid Conversion Calculators Performing Common Palliative Care Conversions.

Abstract: Online opioid conversion calculators (OOCCs) are commonly used to aid conversion between opioids to overcome tolerance, reduce adverse effects, or challenges related to administration. The purpose of this study was to describe and characterize variability among OOCC used by health care practitioners when converting common opioids and doses encountered in the hospice and palliative care setting.  We collected 58 quantitative surveys and performed sentiment analysis on 62 qualitative responses from adult learners primarily practicing in the palliative care setting and enrolled in an online palliative care Master of Science program through the University of Maryland, Baltimore, who were asked to perform opioid conversion calculations using realistic patient cases.  OOCC have substantial variability leading to a wide range of outputs, which may put patients at risk for opioid-related harm. Assessing participant sentiment toward OOCC showed most participants held a "Negative Sentiment" toward these calculators after the activity.  Overall, findings reveal that given the same information, clinicians can come to widely different opioid doses and these differences can be amplified by OOCC. These differences can be particularly dangerous given the higher opioid doses commonly used in the palliative care setting. Considering the significant harm that can arise from an error when converting between opioids, clinicians should avoid the routine use of OOCC in real-world patient care settings. If an OOCC is used, organizations should endorse a specific calculator, provide training and education about the algorithm that supports the calculations, and encourage clinicians to use it only after their own manual calculation, which should be documented in the medical record.

online opioid conversion calculator
opioids
palliative care
hospice
pain management


Potential barriers in the therapeutic relationship in unaccompanied refugee minors in mental health.

Abstract: Background: Unaccompanied refugee minors present with disproportionately high prevalence of emotional and psychological morbidities. However, their utilization of mental health services has been shown to be significantly poorer than the indigenous population of the country they seek asylum in. Despite this, there is limited research exploring their perspectives on the barriers they face. Aims: This research aims to understand unaccompanied refugee minors' and their carers' perceptions of the barriers to utilize mental health services and to explore issues perceived to be related to poor engagement with services. Methods: Semi-structured interviews with 15 unaccompanied refugee minors and their carers were conducted. This was to elicit their views, perceptions and beliefs based on their experience of receiving treatment from a specialist mental health service in the UK. Results: Thematic analysis was used and the findings were categorised into two broad themes; the participants' perceptions of the intervention and perceptions of the professionals. Salient aspects of these are discussed. Conclusions: The findings have potential to stimulate further research into gaining a better understanding of the barriers these young people face in accessing help, and may contribute to developing services that are more efficient in engaging this vulnerable group and meeting their specific needs.

Majumder|Pallab|P| Vostanis|Panos|P| Karim|Khalid|K| O'Reilly|Michelle|M|

D006301:Health Services Needs and Demand

Barriers
unaccompanied refugee minors
mental health
therapy


Residential exposure to radon and DNA methylation across the lifecourse: an exploratory study in the ALSPAC birth cohort.

Abstract: Background: Radon (and its decay products) is a known human carcinogen and the leading cause of lung cancer in never-smokers and the second in ever-smokers. The carcinogenic mechanism from radiation is a combination of genetic and epigenetic processes, but compared to the genetic mechanisms, epigenetic processes remain understudied in humans. This study aimed to explore associations between residential radon exposure and DNA methylation in the general population. Methods: Potential residential radon exposure for 75-metre area buffers was linked to genome-wide DNA methylation measured in peripheral blood from children and mothers of the Accessible Resource for Integrated Epigenomic Studies subsample of the ALSPAC birth cohort. Associations with DNA methylation were tested at over 450,000 CpG sites at ages 0, 7 and 17 years (children) and antenatally and during middle-age (mothers). Analyses were adjusted for potential residential and lifestyle confounding factors and were determined for participants with complete data (n = 786 to 980). Results: Average potential exposure to radon was associated in an exposure-dependent manner with methylation at cg25422346 in mothers during pregnancy, with no associations at middle age. For children, radon potential exposure was associated in an exposure-dependent manner with methylation of cg16451995 at birth, cg01864468 at age 7, and cg04912984, cg16105117, cg23988964, cg04945076, cg08601898, cg16260355 and cg26056703 in adolescence. Conclusions: Residential radon exposure was associated with DNA methylation in an exposure-dependent manner. Although chance and residual confounding cannot be excluded, the identified associations may show biological mechanisms involved in early biological effects from radon exposure.

Radon
DNA methylation
ALSPAC
epigenetics. ARIES
geo-spatial epidemiology


Impact of pH on growth of Staphylococcus epidermidis and Staphylococcus aureus in vitro.

Abstract: The pH of skin is critical for skin health and resilience and plays a key role in controlling the skin microbiome. It has been well reported that under dysbiotic conditions such as atopic dermatitis (AD), eczema, etc. there are significant aberrations of skin pH, along with a higher level of Staphylococcus aureus compared to the commensal Staphylococcus epidermidis on skin. To understand the effect of pH on the relative growth of S. epidermidis and S. aureus, we carried out simple in vitro growth kinetic studies of the individual microbes under varying pH conditions. We demonstrated that the growth kinetics of S. epidermidis is relatively insensitive to pH within the range of 5-7, while S. aureus shows a stronger pH dependence in that range. Gompertz's model was used to fit the pH dependence of the growth kinetics of the two bacteria and showed that the equilibrium bacterial count of S. aureus was the more sensitive parameter. The switch in growth rate happens at a pH of 6.5-7. Our studies are in line with the general hypothesis that keeping the skin pH within an acidic range is advantageous in terms of keeping the skin microbiome in balance and maintaining healthy skin.

D003470:Culture Media
D006801:Humans
D006863:Hydrogen-Ion Concentration
D012867:Skin
D013203:Staphylococcal Infections
D013211:Staphylococcus aureus
D013212:Staphylococcus epidermidis

pH
skin
skin microbiome
commensal
growth kinetics
model


Prehospital management of a non-intubated inhalation injury patient using transcutaneous monitoring of carbon dioxide.

Abstract: A 46-year-old man experienced facial burns due to a fire in his house. In the prehospital setting, suspecting inhalation injury and carbon monoxide poisoning, an emergency physician decided to bring him to the hospital for carbon dioxide (CO2) monitoring without endotracheal intubation for approximately 20 min because of less severe respiratory distress. On the way to the hospital, the patient's end-tidal CO2 monitoring ranged from 19 to 30 mm Hg, and transcutaneous carbon dioxide (TcPCO2) remained between 50 and 55 mm Hg. On arrival at the hospital, PaCO2 showed 51.6 mm Hg. Endotracheal intubation using a bronchoscope was performed in the emergency room, and inhalation injury was observed. He was extubated on day 5 and discharged on day 10. In the prehospital setting, TcPCO2 monitoring is useful for initial management of non-intubated inhalation injury patients even with high concentration oxygen.

D002245:Carbon Dioxide
D004636:Emergency Service, Hospital
D006801:Humans
D007442:Intubation, Intratracheal
D008297:Male
D008875:Middle Aged


A Systematic Review of Nutritional Supplementation in HIV-Infected Children in Resource-Limited Settings.

Abstract:
BACKGROUND
In resource-limited settings, malnutrition is the major cause of death in young children, but the precise benefits of nutritional supplementation for HIV-infected children are not well understood.

METHODS
Two researchers reviewed studies conducted in low- or middle-income countries that involved macro- and micronutrient supplementation in HIV-infected individuals ≤18 years.

RESULTS
Fifteen studies focused on micronutrients, including vitamin A, zinc, multivitamins, and multiple-micronutrient supplementation. The 8 macronutrient studies focused on ready-to-use foods (4 studies), spirulina, whey protein, general food rations, and F75 and F100 starter formulas. Vitamin A was associated with improved mortality rates, ranging from 28% to 63%. Multiple-micronutrient supplementations were not associated with improvement of measured health outcomes. Ready-to-use foods were associated with improvement in certain anthropometrics.

CONCLUSION
Periodic vitamin A supplementation is associated with reduced mortality. Macronutrient supplementation is linked to improved anthropometrics. More research is needed to determine how nutritional supplementation benefits this particularly vulnerable population.

McHenry|Megan S|MS|
Dixit|Avika|A|
Vreeman|Rachel C|RC|

D002664:Child Nutritional Physiological Phenomena

nutrition
nutritional supplementation
children
AIDS
HIV
clinical outcomes


Spinal Cord Ischemia in the Setting of Acute Type B Aortic Dissection: Successful Rescue with Thoracic Endovascular Aortic Repair.

Abstract: We report 2 cases of successful thoracic endovascular aortic repair (TEVAR) for acute type B aortic dissection (ABAD) complicated with spinal cord ischemia (SCI). Case 1. A 70-year-old gentleman found with an uncomplicated ABAD with false lumen occluded, developed SCI shortly after admission during the initial medical management. Cerebrospinal fluid drainage (CSFD) was initiated followed by emergent TEVAR. SCI improved, and the patient was discharged. Case 2. A 52-year-old gentleman developed uncomplicated ABAD with patent false lumen. 5 hours after admission, he developed SCI during the initial medical management. Emergent TEVAR was performed followed by CSFD, and the SCI improved before discharge. These cases prompted us to address prompt TEVAR for primary entry closure and true lumen dilatation with postoperative hypertensive management to relieve the dynamic obstruction of the segmental arteries responsible for the compromised spinal cord circulation in complicated ABAD.

spinal cord ischemia
acute type B aortic dissection
thoracic endovascular aortic repair
complicated type


Deconvoluting the relationships between autophagy and metastasis for potential cancer therapy.

Abstract: Autophagy is a highly conserved lysosome-dependent degradation process that may digest some long-lived proteins and damaged organelles. As an essential homeostasis maintaining system in normal cells, autophagy plays a key role in several pathological settings, especially cancer. Metastasis, known as a crucial hallmark of cancer progression, is the primary cause of cancer lethality. The role of autophagy in metastasis is quite complex as supportive evidence has indicated both pro-metastatic and anti-metastatic functions of autophagy. Autophagy can inhibit metastasis by restricting necrosis and mediating autophagic cell death, whereas it may also promote metastasis by enhancing cancer cell fitness in response to stress. Moreover, the function of autophagy is context- and stage-dependent. Specifically, during the early steps of metastasis, autophagy mainly serves as a suppressor, while it plays a pro-metastatic role in the later steps. Here, we focus on highlighting the dual roles of autophagy in metastasis and address the molecular mechanisms involved in this process, which may provide a new insight into cancer biology. While, we also summarize several anti-metastatic agents manipulating autophagy, in the hope of shedding light on exploration of potential novel drugs for future cancer therapy.

Yao|Dahong|D| Wang|Peiqi|P| Zhang|Jin|J| Fu|Leilei|L| Ouyang|Liang|L| Wang|Jinhui|J|

Autophagy
Metastasis
Cancer therapy
Anti-metastatic agent


Effects of the levonorgestrel-releasing intrauterine system on urinary symptoms in patients with adenomyosis.

Abstract:
OBJECTIVES
We hypothesized that treatment of adenomyosis with the levonorgestrel-releasing intrauterine system (LNG-IUS) can concurrently improve urinary incontinence along with irritative and obstructive symptoms and thus positively affect the patients' quality of life.

STUDY DESIGN
Sixty-five patients suffering from heavy prolonged menstrual bleeding (menorrhagia) with dysmenorrhea diagnosed with uterine adenomyosis by ultrasound were enrolled in this study. LNG-IUS was inserted in the outpatient department for the treatment of the uterine adenomyosis. The patients filled out two validated questionnaires, the Urogenital Distress Inventory (UDI-6) and the Incontinence Impact Questionnaire (IIQ-7), before and 6 months after the insertion of the LNG-IUS. The before and after scores were compared using the non-parametric Mann-Whitney U test.

RESULTS
The mean (± SD) age of the patients was 44.5 ± 6.5 years. Both UDI and IIQ scores were significantly lower at 6 months after treatment with the LNG-IUS (P<0.0001). UDI scores revealed improvement rates of 14.3%, 35.7%, and 22.7% for urinary incontinence, irritative symptoms, and obstructive symptoms, respectively. Moreover, improvements in irritative and obstructive symptoms were significantly correlated with improvements in menorrhagia and dysmenorrhea (P<0.04). IIQ scores demonstrated improvement rates of 18.9%, 14.6%, 19.7%, and 18.5% for physical activity, travel, social relations, and emotional health, respectively.

CONCLUSIONS
LNG-IUS used for treating menorrhagia and dysmenorrhea improved urinary incontinence along with irritative and obstructive symptoms in patients with adenomyosis.

Ekin|Murat|M|
Cengiz|Huseyin|H|
Ayağ|Mehmet Emin|ME|
Kaya|Cihan|C|
Yasar|Levent|L|
Savan|Kadir|K|

Adenomyosis
Menorrhagia
Intrauterine device
Levonorgestrel
Lower urinary tract symptoms


US appearance of partial-thickness supraspinatus tendon tears: Application of the string theory. Pictorial essay.

Abstract: The supraspinatus tendon is composed of 5 different layers consisting of intertwining bundles. On a front portion of the tendon, the layers become coated bundles which insert on the trochanter. At the insertion, the superficial or bursal surface of the tendon corresponding to the tendon fibers in contact with the subacromial bursa can be distinguished from the deep surface corresponding to the fibers in contact with the glenohumeral joint. A tendon tear may involve partial or total disruption of the tendon fibers and is called full-thickness tear if it affects the entire tendon, and partial-thickness tear if it involves only part of the tendon. Partial-thickness tears of the supraspinatus tendon include lesions of the superficial, deep and central surface or tendon delamination.A contrast enhanced examination requires injection of contrast agent into the joint (arthrography followed by computed tomography (CT) or magnetic resonance imaging (MRI)) to study the deep surface, and injection into the subacromial bursa (bursography followed by CT) to study the superficial surface. MRI and ultrasound (US) examination allow the study of these different tendon layers without the use of contrast agent (which is not possible at CT).

Guerini|H|H|
Fermand|M|M|
Godefroy|D|D|
Feydy|A|A|
Chevrot|A|A|
Morvan|G|G|
Gault|N|N|
Drapé|J L|JL|


The impact of high fructose on cardiovascular system: Role of α-lipoic acid.

Abstract: The aim of this study was to evaluate the role of α-lipoic acid (α-LA) on oxidative damage and inflammation that occur in endothelium of aorta and heart while constant consumption of high-fructose corn syrup (HFCS). The rats were randomly divided into three groups with each group containing eight rats. The groups include HFCS, HFCS + α-LA treatment, and control. HFCS was given to the rats at a ratio of 30% of F30 corn syrup in drinking water for 10 weeks. α-LA treatment was given to the rats at a dose of 100 mg/kg/day orally for the last 6 weeks. At the end of the experiment, the rats were killed by cervical dislocation. The blood samples were collected for biochemical studies, and the aortic and cardiac tissues were collected for evaluation of oxidant-antioxidant system, tissue bath, and pathological examination. HFCS had increased the levels of malondialdehyde, creatine kinase MB, lactate dehydrogenase, and uric acid and showed significant structural changes in the heart of the rats by histopathology. Those changes were improved by α-LA treatment as it was found in this treatment group. Immunohistochemical expressions of tumor necrosis factor α and inducible nitric oxide synthase were increased in HFCS group, and these receptor levels were decreased by α-LA treatment. All the tissue bath studies supported these findings. Chronic consumption of HFCS caused several problems like cardiac and endothelial injury of aorta by hyperuricemia and induced oxidative stress and inflammation. α-LA treatment reduced uric acid levels, oxidative stress, and corrected vascular responses. α-LA can be added to cardiac drugs due to its cardiovascular protective effects against the cardiovascular diseases.

Saygin|M|M|
Asci|H|H|
Cankara|F N|FN|
Bayram|D|D|
Yesilot|S|S|
Candan|I A|IA|
Alp|H H|HH|

α-lipoic acid
High-fructose corn syrup
oxidative stress
endothelial dysfunction
heart toxicity


Evaluating the Environmental Health Effect of Bamboo-Derived Volatile Organic Compounds through Analysis the Metabolic Indices of the Disorder Animal Model.

Abstract:
OBJECTIVE
To identify the bamboo VOCs (volatile organic compounds) effect on animal physiological indices, which associated with human health.

METHODS
GC/MS was used to analyze the volatile organic compounds from Moso bamboo (Phyllostachys heterocyla cv. pubescens). The effect of VOCs on environmental health was evaluated by analyzing the metabolic indices of the type 2 diabetic mouse model.

RESULTS
Spectra of VOC generated by GC/MS were blasted against an in-house MS library confirming the identification of 33 major components that were manually validated. The relative constituent compounds as a percentage of total VOCs determined were alcohols (34.63%), followed by ether (22.02%), aldehyde (15.84%), ketone (11.47%), ester (4.98%), terpenoid (4.38%), and acids (3.83%). Further experimentation established that the metabolic incidence of the disease can be improved if treated with vanillin, leaf alcohol, β-ionone and methyl salicylate. The effects of these VOCs on type 2 diabetes were evident in the blood lipid and blood glucose levels.

CONCLUSION
Our model suggests that VOCs can potentially control the metabolic indices in type 2 diabetes mice. This experiment data also provides the scientific basis for the comprehensive utilization of ornamental bamboos and some reference for other similar study of environmental plants.

Guo|Ming|M|
Hu|Zheng Qing|ZQ|
Strong|P James|PJ|
Smit|Anne-Marie|AM|
Xu|Jian Wei|JW|
Fan|Jun|J|
Wang|Hai Long|HL|

Volatile organic compounds
Phyllostachys heterocyla cv. pubescens
Type 2 diabetes
Metabolic index


Lipectomy Technique as a Second-stage Procedure for Primarily Matured, Deep Outflow Vein in Obese Individuals.

Abstract: Prevalence of obesity is growing in the general population as well as among end-stage renal disease (ESRD) patients requiring dialysis. Obesity often leads to a situation when a mature outflow vein is located deeper than 6 mm and is difficult to cannulate. These obese patients usually require additional procedures to able to successfully cannulate the fistula. The available surgical options include: outflow vein elevation, liposuction, and lipectomy. We present a case of a 57-year-old obese female with ESRD and matured, deeply running, inadequate for cannulation arteriovenous fistula. We present a technique of lipectomy with wide resection of adipose tissue from superior and lateral surfaces of outflow vein. Postoperatively, the skin without the underlying adipose tissue collapses allowing easy cannulation of the long segment of outflow vein with two needles. Lipectomy of mature but deeply located outflow vein is a second-stage elective procedure. Wide resection of adipose tissue helps create easy to access cannulation zone in obese individuals.

lipectomy
obesity
end-stage renal disease
Arteriovenous fistula
hemodialysis


Ascorbate uptake enables tubular mitophagy to prevent septic AKI by PINK1-PARK2 axis.

Abstract: Ascorbate (Vitamin C) has been proposed as a promising therapeutic agent against sepsis in clinical trials, but there is little experimental evidence on its anti-septic efficacy. We report that Toll-like receptor 4 (TLR4) activation by LPS stimuli augments ascorbate uptake in murine and human tubular cells through upregulation of two ascorbate transporters SVCT-1 and -2 mediated by Fn14/SCFFbxw7α cascade. Ascorbate restriction, or knockout of SVCT-1 and -2, the circumstance reminiscent to blockade of ascorbate uptake, endows tubular cells more vulnerable to the LPS-inducible apoptosis, whereas exogenous administration of ascorbate overrides the ruin execution, for which the PINK1-PARK2, rather than BNIP3-NIX axis is required. Ascorbate increases, while SVCT-1 and -2 knockout or ascorbate restriction dampens tubular mitophagy upon LPS stimuli. Treatment of endotoxemic mice with high-dose ascorbate confers mitophagy and substantial protection against mortality and septic acute kidney injury (AKI). Our work provides a rationale for clinical management of septic AKI with high doses of ascorbate.

Chen|Zhi-Dong|ZD| Hu|Bang-Chuan|BC| Shao|Xue-Ping|XP| Hong|Jun|J| Zheng|Yang|Y| Zhang|Run|R| Shao|Zi-Qiang|ZQ| Liu|Jin-Quan|JQ| Yang|Xiang-Hong|XH| Sun|Ren-Hua|RH| Mo|Shi-Jing|SJ|

Ascorbate
Mitophagy
Septic AKI
PINK1-PARK2 axis


A unified approach for detection of Clickbait videos on YouTube using cognitive evidences.

Abstract: Clickbait is one of the form of false content, purposely designed to attract the user's attention and make them curious to follow the link and read, view, or listen to the attached content. The teaser aim behind this is to exploit the curiosity gap by giving information within the short statement. Still, the given statement is not sufficient enough to satisfy the curiosity without clicking through the linked content and lure the user to get into the respective page via playing with human psychology and degrades the user experience. To counter this problem, we develop a Clickbait Video Detector (CVD) scheme. The scheme leverages to learn three sets of latent features based on User Profiling, Video-Content, and Human Consensus, these are further used to retrieve cognitive evidence for the detection of clickbait videos on YouTube. The first step is to extract audio from the videos, which is further transformed to textual data, and later on, it is utilized for the extraction of video content-based features. Secondly, the comments are analyzed, and features are extracted based on human responses/reactions over the posted content. Lastly, user profile based features are extracted. Finally, all these features are fed into the classifier. The proposed method is tested on the publicly available fake video corpus [FVC], [FVC-2018] dataset, and a self-generated misleading video dataset [MVD]. The achieved result is compared with other state-of-the-art methods and demonstrates superior performance.

YouTube
Cognitive evidence
User profiling
Dataset
Clickbait detection


CD133 expression in circulating tumor cells from breast cancer patients: potential role in resistance to chemotherapy.

Abstract: CD133 has been associated with cell properties such as self renewal, migration and vasculogenic mimicry, potentially involved in generation of circulating tumor cells (CTCs). We characterized CD133 expression in CTCs of 98 nometastatic breast cancer (BC) patients. CTCs were isolated by immunomagnetic techniques using magnetic beads labeled with a multicytokeratin(CK)-specific antibody (CK3-11D5) and CTCs and CD133 detection through immunocytochemical methods. CK(+) /CD133(+) CTCs were identified in 65% of patients at baseline and 47.8% after systemic therapy (p = 0.53). Correlation of CD133 status in CTCs with classical clinicopathological characteristics and response to therapy was performed. Her2 not amplified and low Ki-67 index were positively correlated with presence of CK(+) /CD133(+) CTCs. Before any treatment, CK(+) /CD133(+) CTCs were more frequently isolated in patients with luminal BC subtype. No statistically significant differences were found between proportion of CK(+) /CD133(+) CTCs and BC subtypes after systemic therapy, implying a relative enrichment of CK(+) /CD133(+) CTCs in triple negative and HER2-amplified tumors. While CK(+) /CTCs decreases after chemotherapy when analyzing the whole population, CK(+) /CD133(+) CTCs were enriched in post-treatment samples in nonluminal BC subtypes. These findings suggest the potential role of CD133 as a promising marker of chemoresistance in nonluminal BC patients. Further prospective studies and extensive preclinical modeling will be needed to confirm whether CD133 is a marker of resistance to chemotherapy, and its role as a target for novel anticancer therapies targeting cancer stem cells and tumor vasculature.

Nadal|Rosa|R|
Ortega|F Gabriel|FG|
Salido|Marta|M|
Lorente|Jose A|JA|
Rodríguez-Rivera|Maria|M|
Delgado-Rodríguez|Miguel|M|
Macià|Marta|M|
Fernández|Ana|A|
Corominas|Josep M|JM|
García-Puche|J Luis|JL|
Sánchez-Rovira|Pedro|P|
Solé|Francesc|F|
Serrano|M Jose|MJ|

D064726:Triple Negative Breast Neoplasms

vasculogenic mimicry and drug resistance


Characterization of the Phospholipid Platelet-Activating Factor As a Mediator of Inflammation in Chickens.

Abstract: Lipid mediators are known to play important roles in the onset and resolution phases of the inflammatory response in mammals. The phospholipid platelet-activating factor (PAF) is a pro-inflammatory lipid mediator which participates in vascular- and innate immunity-associated processes by increasing vascular permeability, by facilitating leukocyte adhesion to the endothelium, and by contributing to phagocyte activation. PAF exerts its function upon binding to its specific receptor, PAF receptor (PAFR), which is abundantly expressed in leukocytes and endothelial cells (ECs). In chickens, lipid mediators and their functions are still poorly characterized, and the role of PAF as an inflammatory mediator has not yet been investigated. In the present study we demonstrate that primary chicken macrophages express PAFR and lysophosphatidylcholine acyltransferase 2 (LPCAT2), the latter being essential to PAF biosynthesis during inflammation. Also, exogenous PAF treatment induces intracellular calcium increase, reactive oxygen species release, and increased phagocytosis by primary chicken macrophages in a PAFR-dependent manner. We also show that PAF contributes to the Escherichia coli lipopolysaccharide (LPS)-induced pro-inflammatory response and boosts the macrophage response to E. coli LPS via phosphatidylinositol 3-kinase/Akt- and calmodulin kinase II-mediated intracellular signaling pathways. Exogenous PAF treatment also increases avian pathogenic E. coli intracellular killing by chicken macrophages, and PAFR and LPCAT2 are upregulated in chicken lungs and liver during experimental pulmonary colibacillosis. Finally, exogenous PAF treatment increases cell permeability and upregulates the expression of genes coding for proteins involved in leukocyte adhesion to the endothelium in primary chicken endothelial cells (chAEC). In addition to these vascular phenomena, PAF boosts the chAEC inflammatory response to bacteria-associated molecular patterns in a PAFR-dependent manner. In conclusion, we identified PAF as an inflammation amplifier in chicken macrophages and ECs, which suggests that PAF could play important roles in the endothelium-innate immunity interface in birds during major bacterial infectious diseases such as colibacillosis.

Garrido|Damien|D|
Chanteloup|Nathalie K|NK|
Trotereau|Angélina|A|
Lion|Adrien|A|
Bailleul|Geoffrey|G|
Esnault|Evelyne|E|
Trapp|Sascha|S|
Quéré|Pascale|P|
Schouler|Catherine|C|
Guabiraba|Rodrigo|R|

platelet-activating factor
inflammation
chicken
endothelial cells
macrophages
colibacillosis
avian pathogenic Escherichia coli
platelet-activating factor receptor


Identification of Genes Related to Immune Infiltration in the Tumor Microenvironment of Cutaneous Melanoma.

Abstract: Cutaneous melanoma (CM) is the leading cause of skin cancer deaths and is typically diagnosed at an advanced stage, resulting in a poor prognosis. The tumor microenvironment (TME) plays a significant role in tumorigenesis and CM progression, but the dynamic regulation of immune and stromal components is not yet fully understood. In the present study, we quantified the ratio between immune and stromal components and the proportion of tumor-infiltrating immune cells (TICs), based on the ESTIMATE and CIBERSORT computational methods, in 471 cases of skin CM (SKCM) obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) were analyzed by univariate Cox regression analysis, least absolute shrinkage, and selection operator (LASSO) regression analysis, and multivariate Cox regression analysis to identify prognosis-related genes. The developed prognosis model contains ten genes, which are all vital for patient prognosis. The areas under the curve (AUC) values for the developed prognostic model at 1, 3, 5, and 10 years were 0.832, 0.831, 0.880, and 0.857 in the training dataset, respectively. The GSE54467 dataset was used as a validation set to determine the predictive ability of the prognostic signature. Protein-protein interaction (PPI) analysis and weighted gene co-expression network analysis (WGCNA) were used to verify "real" hub genes closely related to the TME. These hub genes were verified for differential expression by immunohistochemistry (IHC) analyses. In conclusion, this study might provide potential diagnostic and prognostic biomarkers for CM.

Qin|Rujia|R| Peng|Wen|W| Wang|Xuemin|X| Li|Chunyan|C| Xi|Yan|Y| Zhong|Zhaoming|Z| Sun|Chuanzheng|C|


Intracranial self-stimulation-reward or immobilization-aversion had different effects on neurite extension and the ERK pathway in neurotransmitter-sensitive mutant PC12 cells.

Abstract: Various actions trigger pleasure (reward) or aversion (punishment) as emotional responses. Emotional factors that negatively affect brain neural control processes for long periods of time might cause various mental diseases by inducing neuronal changes. In the present study, newly developed PC12m12 cells which are　highly sensitivity to neurotransmitters such as acetylcholine (ACh), were used. Exposing the cells to plasma from rats that had been subjected to intracranial self-stimulation (ICSS) markedly upregulated neurite outgrowth. In addition, voluntary running in a wheel or forced on a rotating rod was used to induce behavioral excitation in rats, and examinations of their plasma confirmed that the ICSS-induced neurite outgrowth was not associated with the ICSS behavior itself. Furthermore, immunoblotting and treatment with U0126, an ERK (extracellular signal-regulated kinase) antagonist, showed that the ICSS-induced neurite outgrowth was related to neuronal ERK activity. Exposing the same cells to plasma from rats that had been subjected to immobilization (IMM) also increased neurite outgrowth. Although the degree of enhancement was not as great as that seen after the ICSS rat plasma treatment, it was less than that observed after treatment with ACh as a positive control. These results indicate that ICSS or IMM lead to varying degrees of morphological changes, such as enhanced neurite outgrowth, in PC12m12 cells, but the neuronal signal transduction pathways underlying these effects differ; i.e.,the former morphological change might involve the activation of the ERK pathway, whereas the latter changes might not. Using PC12m12 cells which exhibit sensitivity to neurotransmitters, it might be possible to clarify the pathogeneses of mental diseases at the neuronal level and search for therapeutic drugs.

Gomita|Yutaka|Y| Esumi|Satoru|S| Ushio|Soichiro|S| Kitamura|Yoshihisa|Y| Sendo|Toshiaki|T| Motoda|Hirotoshi|H| Inoue|Shigeki|S| Araki|Hiroaki|H| Kano|Yoshio|Y|

D048049:Extracellular Signal-Regulated MAP Kinases

Neurotransmitters
Plasma
Intracranial self-stimulation reward
Neurite-outgrowth
PC12 mutant cells
Restrict immobilization aversion


Habitat collapse due to overgrazing threatens turtle conservation in marine protected areas.

Abstract: Marine protected areas (MPAs) are key tools for combatting the global overexploitation of endangered species. The prevailing paradigm is that MPAs are beneficial in helping to restore ecosystems to more 'natural' conditions. However, MPAs may have unintended negative effects when increasing densities of protected species exert destructive effects on their habitat. Here, we report on severe seagrass degradation in a decade-old MPA where hyper-abundant green turtles adopted a previously undescribed below-ground foraging strategy. By digging for and consuming rhizomes and roots, turtles create abundant bare gaps, thereby enhancing erosion and reducing seagrass regrowth. A fully parametrized model reveals that the ecosystem is approaching a tipping point, where consumption overwhelms regrowth, which could potentially lead to complete collapse of the seagrass habitat. Seagrass recovery will not ensue unless turtle density is reduced to nearly zero, eliminating the MPA's value as a turtle reserve. Our results reveal an unrecognized, yet imminent threat to MPAs, as sea turtle densities are increasing at major nesting sites and the decline of seagrass habitat forces turtles to concentrate on the remaining meadows inside reserves. This emphasizes the need for policy and management approaches that consider the interactions of protected species with their habitat.

Christianen|Marjolijn J A|MJ|
Herman|Peter M J|PM|
Bouma|Tjeerd J|TJ|
Lamers|Leon P M|LP|
van Katwijk|Marieke M|MM|
van der Heide|Tjisse|T|
Mumby|Peter J|PJ|
Silliman|Brian R|BR|
Engelhard|Sarah L|SL|
van de Kerk|Madelon|M|
Kiswara|Wawan|W|
van de Koppel|Johan|J|

D003247:Conservation of Natural Resources

alternate stable states
marine reserves
plant–herbivore interactions


Comparison of a novel anterior-only approach and the conventional posterior-anterior approach for cervical facet dislocation: a retrospective study.

Abstract:
OBJECTIVE
The surgical treatment of lower cervical facet dislocation is controversial. The objective of this study was to compare the surgical trauma and clinical results of a novel anterior-only approach and with those of the conventional posterior-anterior approach to obtain an optimal method to treat lower cervical facet dislocation.

METHODS
From January 2012 to December 2017, 93 patients with lower cervical facet dislocations were enrolled in the study and divided into two groups as follows: 63 conventional patients who enrolled between January 2014 and December 2017 were included in the anterior-only approach group, and 30 conventional patients who enrolled between January 2012 and December 2013 were included in the posterior-anterior approach group. For the anterior-only approach group, two reduction techniques, including Caspar pins kyphotic paramedian distraction and anterior facetectomy, were used in sequence if the former technique failed. The parameters were as follows: the operation time, the intraoperative blood loss, the number of fixed segments, the fusion rate, and the improvement in the ASIA grade and JOA score.

RESULTS
All patients in the anterior-only approach group were successfully reduced by the two techniques. The mean operation time in the posterior-anterior approach group (274.0 ± 114.7 min) was significantly longer than that in the anterior-only approach group (88.6 ± 35.0 min) (p = 0.000). The mean blood loss during the surgery and the number of fixed segments in the posterior-anterior approach group (275.0 ± 183.2 ml; 1.4 ± 0.7, respectively) were significantly greater than those in the anterior-only approach group (92.5 ± 84.0 ml, p = 0.000; 1.2 ± 0.5, p = 0.030, respectively). A 100% fusion rate was observed in both groups after 12-month follow-up. There were no significant differences between the two groups regarding the improvement in the ASIA grade (p = 0.900) or JOA score (p = 0.717).

CONCLUSIONS
Compared with the conventional posterior-anterior approach, the novel anterior-only approach with two reduction techniques, including Caspar pins kyphotic paramedian distraction and anterior facetectomy, achieved a 100% reduction success rate and induced less surgical trauma, indicating that this method can be recommended as an alternative for lower cervical facet dislocation. These slides can be retrieved under Electronic Supplementary Material.

Facet dislocation
Anterior-only procedure
Cervical spine
Posterior–anterior procedure
Surgical approach


High-Mobility Self-Assembling Truxenone-Based n-Type Organic Semiconductors.

Abstract: The synthesis, self-assembly, and semiconducting properties of a series of disk-like truxenone derivatives, functionalized with three peripheral long alkyl chains, either directly attached or distanced by linking phenyl or ethynyl groups, are reported. The strategy of distancing the alkyl chains from the central aromatic cores induces in these discotics well-ordered columnar assemblies and has a favorable effect on their charge-carrier mobility. Electron mobility values above 1 cm2  V-1  S-1 were determined for a truxenone functionalized with three peripheral decynyl chains by means of the space charge-limited current technique. DFT calculations help to rationalize the high mobility values found for these new truxenone-based systems, indicating efficient intermolecular electronic couplings (fostered by a favorable stacking configuration) and moderate intramolecular reorganization energies for electrons in the origin of such high mobilities.

self-assembly
semiconductors
aggregation
density functional calculations
liquid crystals


Monocyte chemoattractant protein-1, macrophage colony stimulating factor, survivin, and tissue inhibitor of matrix metalloproteinases-2 in analysis of damage and repair related to pediatric chronic kidney injury.

Abstract:
BACKGROUND
Kidney injury in the course of chronic kidney disease (CKD) is a consequence of aggravated cell migration, inflammation, apoptosis, and fibrosis. However, the sequence of these phenomena, as well as of the reparatory mechanisms, are not fully known. Monocyte chemoattractant protein 1 (MCP-1) and macrophage colony-stimulating factor (MCSF) trigger monocyte migration to the sites of inflammation and their transition into macrophages. Tissue inhibitor of matrix metalloproteinases-2 (TIMP-2) plays a protective role against excessive matrix remodeling, whereas survivin is known for its anti-apoptotic activity.

OBJECTIVES
To analyze the serum, urine and fractional excretion (FE) values of MCP1, MCSF, TIMP-2, and survivin in children at subsequent stages of CKD being treated conservatively, and to analyze the potential applicability of these markers in the evaluation of CKD-related renal damage and protective mechanisms against it.

MATERIAL AND METHODS
The study group consisted of 70 children with conservatively treated CKD, stages 1-5, and 12 controls. The serum and urine concentrations of MCP1, MCSF, TIMP-2, and survivin were assessed using enzyme-linked immunosorbent assay (ELISA). The FE of these parameters in the urine was also assessed.

RESULTS
The serum values of all parameters were significantly elevated at CKD stage 1 compared to the controls. The urinary concentrations of MCP-1 and MCSF (stages 1-2) rose earlier than TIMP-2 and survivin (stage 4) concentrations. The FE values started increasing at CKD stage 3 (MCP-1) or stage 4 (other parameters).

CONCLUSIONS
The complex analysis of serum/urinary/FE values of the selected parameters revealed a sequence of multifaceted CKD-related phenomena, when the migration of cells and inflammation were followed by delayed and insufficient anti-fibrotic and anti-apoptotic activity.

D019716:Tissue Inhibitor of Metalloproteinase-2

chronic kidney disease
inflammation
apoptosis
fibrosis
urinary fractional excretion


Neurohospitalist Practice, Perspectives, and Burnout.

Abstract:
Background and Purpose
Neurohospitalist neurology is a fast-growing subspecialty with a variety of practice settings featuring neurohospitalist models of care. Since inception, the subspecialty has responded to new challenges in resident training, hospital reimbursement, practice, and burnout.

Methods
To characterize neurohospitalists' current practice and perspectives, we surveyed the neurohospitalists and trainees affiliated with the Neurohospitalist Society using an electronic survey distributed through the society listserv.

Results
Of 501 individuals surveyed by e-mail, 119 began the survey (23.8% response rate), with 88.2% self-identifying as neurohospitalists. Most neurohospitalists (63%) are 10 years or less out of training, devoting 70% of their professional time to inpatient clinical activities while also performing administrative or teaching activities. Only 38% are employed by an academic department. Call schedules are common, with 75% of neurohospitalists participating in a hospital or emergency call schedule, while 55% provide telemedicine services. The majority (97%) of neurohospitalists primarily care for adults, most commonly treating patients with cerebrovascular disease, seizures, and delirium/encephalopathy. The majority (87%) are overall pleased with their work, but 36% report having experienced burnout.

Conclusions
Neurohospitalists are a diverse group of neurologists primarily practicing in the inpatient setting while performing a variety of additional activities. They provide a wide array of clinical expertise for acute neurological diseases and neurological emergencies that require hospitalization, including stroke, seizure, and encephalopathy. Neurohospitalists in general are very pleased with their work, while burnout, as in neurology and other areas of medicine, remains a concern.

Probasco|John C|JC|
Greene|James|J|
Harrison|Amy|A|
Jensen|Judd|J|
Khot|Sandeep|S|
Klein|Joshua P|JP|
Simpson|Jennifer|J|
Wold|Jana|J|
Josephson|S Andrew|SA|
Likosky|David|D|

neurohospitalist
practice
burnout
clinical specialty


17-beta estradiol inhibits oxidative stress-induced accumulation of AIF into nucleolus and PARP1-dependent cell death via estrogen receptor alpha.

Abstract: Oxidative stress-induced DNA damage results in over-activation of poly(ADP-ribose) polymerase 1 (PARP1), leading to parthanatos, a newly discovered cell elimination pathway. Inhibition of PARP1-dependent cell death has shown to improve the outcome of diseases, including stroke, heart ischemia, and neurodegenerative diseases. In the present study we aimed to detect whether estrogen plays a protective role in inhibiting parthanatos. We utilized human mammary adenocarcinoma cells (MCF7) that abundantly express the estrogen receptor alpha and beta (ERα and ERβ). Parthanatos was induced by challenging the cells with hydrogen peroxide (H2O2). Microscopic imaging and molecular biological techniques, such as Western blot analysis and RNA interference, were performed. The results showed 17β estradiol (E2) protected MCF7 cells from PARP1-dependent cell death by decreasing protein PARylation, and AIF translocation into nuclei/nucleoli. Down-regulation of ERα expression by siRNA before E2 addition resulted in the failure of the E2-mediated inhibition of H2O2-induced protein PARylation and AIF nucleolar translocation. Together these data suggest that estrogen via its alpha-type receptor inhibits oxidative stress-induced, PARP1-dependent cell death. The present study provided us insight into how to apply hormone therapy in intervention of parthanatos-implicated ischemic and degenerative diseases.

Batnasan|Enkhzaya|E|
Wang|Ruoxi|R|
Wen|Jitao|J|
Ke|Yueshuang|Y|
Li|Xiaoxue|X|
Bohio|Ameer Ali|AA|
Zeng|Xianlu|X|
Huo|Hongliang|H|
Han|Liping|L|
Boldogh|Istvan|I|
Ba|Xueqing|X|


Mental health and school dropout across educational levels and genders: a 4.8-year follow-up study.

Abstract:
BACKGROUND
Education is a key determinant of future employment and income prospects of young people. Poor mental health is common among young people and is related to risk of dropping out of school (dropout). Educational level and gender might play a role in the association, which remains to be studied.

METHODS
Mental health was measured in 3146 Danish inhabitants aged 16-29 years using the 12-Item Short-Form Health Survey and examined across genders and educational levels. For students, educational level at baseline was used; for young people who were not enrolled in school at baseline (non-students), the highest achieved educational level was used. The risk of dropout in students was investigated in administrative registers over a 4.8-year period (1(st) March 2010-31(th) December 2014). Odds ratios (OR) and 95 % confidence intervals (CI) were calculated for mental health and in relation to dropout in logistic regression models, adjusting for age, gender, educational level, parental education, parental income and ethnicity.

RESULTS
Poor mental health was present in 24 % (n = 753) of the participants, 29 % (n = 468) in females and 19 % (n = 285) in males (p < 0.0001). The prevalence differed from 19 to 39 % across educational levels (p < 0.0001). Females had a statistically significantly higher adjusted risk of poor mental health than males (OR = 1.8, CI = 1.5-2.2). Among the students the lowest risk was found at the elementary level (OR = 1.3, CI = 0.8-2.3), while students in higher education had a statistically significantly higher risk (OR = 1.9, CI = 1.2-2.9). The lowest-educated non-students had the highest OR of poor mental health (OR = 3.3, CI = 2.1-5.4). Dropout occurred in 8 % (n = 124) of the students. Poor mental health was associated to dropout in vocational (OR = 1.8, CI = 1.0-3.2) and higher education (OR = 2.0, CI = 1.0-4.2). For males in higher education, poor mental health was a predictor of dropout (OR = 5.2, CI = 1.6-17.3), which was not seen females in higher education (OR = 1.2, CI = 0.5-3.1).

CONCLUSIONS
Poor mental health was significantly associated to dropout among students in vocational and higher education. Males in higher education had five times the risk of dropout when reporting poor mental health, while no such association was found for females.

Hjorth|Cathrine F|CF|
Bilgrav|Line|L|
Frandsen|Louise Sjørslev|LS|
Overgaard|Charlotte|C|
Torp-Pedersen|Christian|C|
Nielsen|Berit|B|
Bøggild|Henrik|H|

Mental health
Education
Early School Leaving
Educational Dropout
Gender differences
Young Adults


Roseomonas mucosa bacteremia in a neutropenic child: A case report and literature review.

Abstract: Roseomonas species is rarely found to be pathogenic to humans and there are few clinical cases that have been described in the literature. We report a case of Roseomonas mucosa bacteremia that involved a 9-year-old Japanese boy who was in a condition of febrile neutropenia caused by chemotherapy for cerebellar medulloblastoma. Conventional phenotyping failed to identify the organism; however, genetic analysis using 16S rDNA sequencing confirmed the pathogen to be R. mucosa. The patient recovered following treatment by meropenem without any complications. A literature review of pediatric cases of Roseomonas bacteremia identified 12 other documented cases, and these revealed that a common clinical situation for the infection is an immunocompromised state with malignancy and/or an indwelling intravenous catheter. Because of the low number of cases, the overall picture of Roseomonas bacteremia in children remains to be elucidated; however, the prognosis of the infection appears to be satisfactory.

Kimura|Keigo|K| Hagiya|Hideharu|H| Nishi|Isao|I| Yoshida|Hisao|H| Tomono|Kazunori|K|

Roseomonas mucosa
Febrile neutropenia
Bloodstream infection


Induction of CCN1 in Growing Saccular Aneurysms: A Potential Marker Predicting Unstable Lesions.

Abstract: Growing evidence has suggested that inflammatory responses promote the progression of saccular intracranial aneurysms (IAs). However, a biomarker predicting the progression has yet to be established. This study aimed to identify novel molecules upregulated during the progression using a previously established rat aneurysm model. In this model, aneurysms are induced at the surgically created common carotid artery (CCA) bifurcation. Based on sequential morphological data, the observation periods after the surgical manipulations were defined as the growing phase (on the 10th day) or the stable phase (on the 30th day). Total cell lysates from the CCA with or without an aneurysm lesion were prepared to perform protein array analysis. The protein array analysis revealed that the matricellular protein cellular communication network factor 1 (CCN1) is induced in lesions during the growing phase. Immunohistochemistry corroborated the significant upregulation of CCN1 in the growing phase compared with the stable phase. Simultaneously with the induction of CCN1, significant increases in the number of CD68-positive macrophages, myeloperoxidase-positive cells, and proliferating smooth muscle cells in lesions were observed. Immunohistochemistry of human IA specimens reproduced the induction of CCN1 in some lesions. These findings imply a potential role of CCN1 as a marker predicting the progression of saccular aneurysms.

Shimizu|Kampei|K| Imai|Hirohiko|H| Kawashima|Akitsugu|A| Okada|Akihiro|A| Ono|Isao|I| Miyamoto|Susumu|S| Kataoka|Hiroharu|H| Aoki|Tomohiro|T|

CCN1
Intracranial aneurysm
Biomarker
Animal model
Cytokine
Growth


Study on Electrochemical Insulin Sensing Utilizing a DNA Aptamer-Immobilized Gold Electrode.

Abstract: We investigated an insulin-sensing method by utilizing an insulin-binding aptamer IGA3, which forms an anti-parallel G-quadruplex with folded single strands. Spectroscopic observation indicates that some anti-parallel G-quadruplex bind hemin and show peroxidase activity. In this study, the peroxidase activity of IGA3 with hemin was confirmed by spectrophotometric measurements, i.e., the activity was three-times higher than hemin itself. IGA3 was then immobilized onto a gold electrode to determine its electrochemical activity. The peroxidase activity of the immobilized IGA3-hemin complex was determined by cyclic voltammetry, and a cathodic peak current of the electrode showed a dependence on the concentration of H₂O₂. The cathodic peak current of the IGA3-hemin complex decreased by binding it to insulin, and this decrease depended on the concentration of insulin.

insulin
gold electrode
G-quadruplex
hemin
peroxidase activity
DNA aptamer
glucagon


Screening a repurposing library, the Medicines for Malaria Venture Stasis Box, against Schistosoma mansoni.

Abstract:
BACKGROUND
The development of new treatments against schistosomiasis is imperative but lacks commercial interest. Drug repurposing represents a suitable strategy to identify potential treatments, which have already unblocked several essential steps along the drug development path, hence reducing costs and timelines. Promoting this approach, the Medicines for Malaria Venture (MMV) recently distributed a drug repurposing library of 400 advanced lead candidates (Stasis Box).

METHODS
All 400 compounds were initially tested in vitro against the larval stage of Schistosoma mansoni at 10 μM. Hits progressed to screening on adult worms and were further characterised for IC50, cytotoxicity and selectivity. Ten lead compounds were tested in mice harbouring a chronic S. mansoni infection.

RESULTS
Eleven of the 37 compounds active on the larval stage were also highly active on adult worms in vitro (IC50 = 2.0-7.5 μM). IC50 values on adult S. mansoni decreased substantially in the presence of albumin (7.5-123.5 μM). Toxicity to L6 and MRC cells was moderate. A moderate worm burden reduction of 51.6% was observed for MMV690534, while the other 9 compounds showed low activity. None of the in vivo results were statistically significant (P > 0.05).

CONCLUSIONS
Phenotypic screening of advanced lead compounds is a simple and resource-low method to identify novel anthelminthics. None of the promising hits of the Stasis Box identified in vitro against S. mansoni yielded acceptable worm burden reductions in vivo, which might be due to the high plasma protein binding. Since the in vitro hits interfere with different drug targets, they might provide a starting point for target based screening and structure-activity relationship studies.

Schistosoma mansoni
Schistosomiasis
Anthelminthics
Drug discovery