B-type natriuretic peptide in patients with asymptomatic severe aortic stenosis.

Abstract:
OBJECTIVES
We sought to evaluate the prognostic impact of the B-type natriuretic peptide (BNP) levels in patients with asymptomatic severe aortic stenosis (AS), who were not referred for aortic valve replacement (AVR).

METHODS
We used data from a Japanese multicentre registry, the Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe Aortic Stenosis Registry, which enrolled 3815 consecutive patients with severe AS. Of those, 387 asymptomatic patients who were not referred for AVR without left ventricular dysfunction and very severe AS were subdivided into four groups based on their BNP levels (BNP<100 pg/mL, n=201; 100≤BNP<200 pg/mL, n=94; 200≤BNP<300 pg/mL, n=42 and BNP>300 pg/mL, n=50).

RESULTS
The cumulative 5-year incidence of AS-related events (aortic valve-related death or heart failure hospitalisation) was incrementally higher with increasing BNP level (14.2%, 29.6%, 46.3% and 47.0%, p<0.001). After adjusting for confounders, the risk for AS-related events was incrementally greater with increasing BNP levels (HR: 1.97, 95% CI: 0.97 to 3.98, p=0.06; HR: 3.59, 95% CI: 1.55 to 8.32, p=0.03 and HR: 7.38, 95% CI: 3.21 to 16.9, p<0.001, respectively). Notably, asymptomatic patients with BNPlevels of <100 pg/mL had an event rate of only 2.1% at 1 year.

CONCLUSIONS
Increased BNP level was associated with a higher risk for AS-related adverse events in patients with asymptomatic severe AS with normal left ventricular ejection fraction who were not referred for AVR. Asymptomatic patients with BNP levels of <100 pg/mL had relatively low event rate, who might be safely followed with watchful waiting strategy.

TRAIL REGISTRATION NUMBER
UMIN000012140.

Nakatsuma|Kenji|K| Taniguchi|Tomohiko|T| Morimoto|Takeshi|T| Shiomi|Hiroki|H| Ando|Kenji|K| Kanamori|Norio|N| Murata|Koichiro|K| Kitai|Takeshi|T| Kawase|Yuichi|Y| Izumi|Chisato|C| Miyake|Makoto|M| Mitsuoka|Hirokazu|H| Kato|Masashi|M| Hirano|Yutaka|Y| Matsuda|Shintaro|S| Inada|Tsukasa|T| Nagao|Kazuya|K| Mabuchi|Hiroshi|H| Takeuchi|Yasuyo|Y| Yamane|Keiichiro|K| Toyofuku|Mamoru|M| Ishii|Mitsuru|M| Minamino-Muta|Eri|E| Kato|Takao|T| Inoko|Moriaki|M| Ikeda|Tomoyuki|T| Komasa|Akihiro|A| Ishii|Katsuhisa|K| Hotta|Kozo|K| Higashitani|Nobuya|N| Kato|Yoshihiro|Y| Inuzuka|Yasutaka|Y| Maeda|Chiyo|C| Jinnai|Toshikazu|T| Morikami|Yuko|Y| Saito|Naritatsu|N| Minatoya|Kenji|K| Kimura|Takeshi|T| |||


Cytotoxicity and Chemotherapeutic Potential of Natural Rosin Abietane Diterpenoids and their Synthetic Derivatives.

Abstract: Cancer is a major cause of morbidity and mortality worldwide. Chemotherapeutic agents currently used in cancer treatment are associated with severe side effects and development of resistance. Thus, there is a pressing need for novel and more potent anticancer drugs with high selectivity for tumor cells and reduced toxicity to normal tissue. Natural products remain an important source of bioactive compounds and drug prototypes that can lead to new and more effective antitumor agents. Coniferous plants are rich in abietane diterpenoids with a wide range of biological activities that provide useful templates for synthetic modification. Abietic acid and dehydroabietic acid (DHA), the major diterpenic resin acids from Pinus rosin, and dehydroabietylamine found in commercial disproportionated rosin amine, display antibacterial and antitumor properties. These compounds and their synthetic derivatives have been reported as promising anticancer agents with potent growth inhibitory activity against several types of human cancer cell lines, including breast, ovarian, prostate, colon, liver, lung and cervical carcinoma cells. Their mechanisms of action are diverse and include DNA binding, induction of apoptosis or oncosis, tubulin polymerization inhibition and disruption of intracellular cholesterol transport. This review covers the main aspects of natural rosin abietane diterpenoids (abietic acid, DHA and DHAA) and synthetic derivatives concerning their anti-proliferative, cytotoxic and antitumor activities, mechanisms of action and structure- activity relationships relevant for the development of novel anticancer agents for cancer chemotherapy.

Faustino|Célia|C| Neto|Íris|Í| Fonte|Pedro|P| Macedo|Ana|A|

cytotoxicity
Rosin
cancer
abietic acid
dehydroabietic acid
diterpenes
dehydroabietylamine
natural products.


Gestational diabetes affects fetal autophagy.

Abstract: Autophagy is a catabolic process involved in the preservation of energy homeostasis and its dysregulation has been implicated in the development of metabolic disorders, including diabetes mellitus. Gestational diabetes mellitus represents a risk for fetal morbidity and mortality. The present study focuses on the autophagy process in human diabetic placenta and fetal pancreas, compared with controls. Analysis of the autophagy markers LC3, Beclin-1 and p62 suggests an impairment of the autophagy process in diabetic placentas. Results indicate an association between gestational diabetes and autophagy, emphasizing the importance of unravelling the mechanisms regulating this relationship.

Avagliano|Laura|L|
Massa|Valentina|V|
Terraneo|Laura|L|
Samaja|Michele|M|
Doi|Patrizia|P|
Bulfamante|Gaetano Pietro|GP|
Marconi|Anna Maria|AM|


Neurohemodynamic correlates of 'OM' chanting: A pilot functional magnetic resonance imaging study.

Abstract:
BACKGROUND
A sensation of vibration is experienced during audible 'OM' chanting. This has the potential for vagus nerve stimulation through its auricular branches and the effects on the brain thereof. The neurohemodynamic correlates of 'OM' chanting are yet to be explored.

MATERIALS AND METHODS
Using functional Magnetic Resonance Imaging (fMRI), the neurohemodynamic correlates of audible 'OM' chanting were examined in right-handed healthy volunteers (n=12; nine men). The 'OM' chanting condition was compared with pronunciation of "ssss" as well as a rest state. fMRI analysis was done using Statistical Parametric Mapping 5 (SPM5).

RESULTS
In this study, significant deactivation was observed bilaterally during 'OM' chanting in comparison to the resting brain state in bilateral orbitofrontal, anterior cingulate, parahippocampal gyri, thalami and hippocampi. The right amygdala too demonstrated significant deactivation. No significant activation was observed during 'OM' chanting. In contrast, neither activation nor deactivation occurred in these brain regions during the comparative task - namely the 'ssss' pronunciation condition.

CONCLUSION
The neurohemodynamic correlates of 'OM' chanting indicate limbic deactivation. As similar observations have been recorded with vagus nerve stimulation treatment used in depression and epilepsy, the study findings argue for a potential role of this 'OM' chanting in clinical practice.

Kalyani|Bangalore G|BG|
Venkatasubramanian|Ganesan|G|
Arasappa|Rashmi|R|
Rao|Naren P|NP|
Kalmady|Sunil V|SV|
Behere|Rishikesh V|RV|
Rao|Hariprasad|H|
Vasudev|Mandapati K|MK|
Gangadhar|Bangalore N|BN|

vagus nerve stimulation
fMRI
Meditation
‘OM’ chanting


Sustaining implementation facilitation: a model for facilitator resilience.

Abstract:
BACKGROUND
Implementation facilitators enable healthcare staff to effectively implement change, yet little is known about their affective (e.g., emotional, mental, physical) experiences of facilitation. We propose an expansion to the Integrated Promoting Action on Research in Health Services (i-PARIHS) framework that introduces facilitation intensity and facilitator resilience to better assess facilitators' affective experiences.

METHODS
We used an instrumental case study and facilitator data (logged reflections and debrief session notes) from the Coordination Toolkit and Coaching initiative to conceptualize facilitation intensity and facilitator resilience and to better understand the psychological impact of the facilitation process on facilitator effectiveness and implementation success.

RESULTS
We define facilitation intensity as both the quantitative and/or qualitative measure of the volume of tasks and activities needed to engage and motivate recipients in implementation, and the psychological impact on the facilitator of conducting facilitation tasks and activities. We define facilitator resilience as the ability to cope with and adapt to the complexities of facilitation in order to effectively engage and motivate staff, while nurturing and sustaining hope, self-efficacy, and adaptive coping behaviors in oneself.

CONCLUSIONS
Facilitators' affective experience may help to identify potential relationships between the facilitation factors we propose (facilitation intensity and facilitator resilience). Future studies should test ways of reliably measuring facilitation intensity and facilitator resilience and specify their relationships in greater detail. By supporting facilitator resilience, healthcare delivery systems may help sustain the skilled facilitator workforce necessary for continued practice improvement.

TRIAL REGISTRATION
The project was registered with ClinicalTrials.gov ( NCT03063294 ) on February 24, 2017.

Implementation facilitation
Care coordination
Primary care
Quality improvement
Workforce support


Translational new approaches for investigating mood disorders in rodents and what they may reveal about the underlying neurobiology of major depressive disorder.

Abstract: Mood disorders represent one of society's most costly and challenging health burdens. The drug treatments used today were initially discovered serendipitously in the 1950s. Animal models were then developed based on the ability of these drugs to alter specific behaviours. These models have played a major role in the development of the second generation of antidepressants. However, their use has been heavily criticized, particularly in relation to whether they recapitulate similar underlying biology to the psychiatric disorder they are proposed to represent. This article considers our work in the field of affective bias and the development of a translational research programme to try to develop and validate better animal models. We discuss whether the new data that have arisen from these studies support an alternative perspective on the underlying neurobiological processes that lead to major depressive disorder (MDD). Specifically, this article will consider whether a neuropsychological mechanism involving affective biases plays a causal role in the development of MDD and its associated emotional and behavioural symptoms. These animal studies also raise the possibility that neuropsychological mechanisms involving affective biases are a precursor to, rather than a consequence of, the neurotrophic changes linked to MDD.This article is part of a discussion meeting issue 'Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists'.

major depressive disorder
animal model
affective bias
neuropsychology
neurotrophic


Dual-color dual-hapten in situ hybridization (D-DISH) - Comparison with fluorescence in situ hybridization (FISH) for HER2/neu testing in breast cancer.

Abstract:
Context
HER2/neu testing in breast cancer is a mandate due to availability of trastuzumab, a monoclonal antibody targeted against this biomarker. Dual-color dual-hapten in situ hybridization (D-DISH) is a new test for assessment of HER2/neu gene overexpression on light microscopy.

Aims
This was a validation study for D-DISH in our laboratory and was conducted to study the concordance between fluorescence in situ hybridization (FISH) and D-DISH for HER2/neu testing in breast cancer.

Materials and Methods
In all, 150 cases of invasive breast carcinoma requested for FISH analysis were selected. Immunohistochemistry by Ventana PATHWAY anti-HER2/neu (4B5) antibody, FISH by ZytoLight SPEC ERBB2/CEN17 Dual Color Probe, and D-DISH using the Ventana INFORM HER2 Dual ISH DNA Probe Cocktail Assay was carried out.

Statistical Analysis
Cohen's kappa coefficient was used to calculate concordance between FISH and D-DISH assays. The ratios and average number of signals were compared with Lin's concordance correlation coefficient.

Results
About 93.1% of the cases showed concordance between FISH and D-DISH results. Cohen's kappa correlation coefficient was 0.836, indicating almost perfect level of agreement. Lin's concordance correlation coefficient (ρc) showed moderate strength of agreement for HER2/chromosome 17 ratios between FISH and D-DISH assays (ρc 0.9452). As per the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) 2018 updated guidelines, four of the cases that were nonamplified on FISH showed low-level amplification on D-DISH due to counting errors caused by faint signals or background dust. Genomic heterogeneity and larger red chromosome 17 signals on D-DISH led to discordance of the six cases amplified by FISH. D-DISH failure rate was 3.33%.

Conclusion
Overall, D-DISH showed good concordance with FISH but needs expertise for reporting.

Gajaria|Pooja K|PK|
Tambe|Sonali|S|
Pai|Trupti|T|
Patil|Asawari|A|
Desai|Sangeeta B|SB|
Shet|Tanuja M|TM|

D017404:In Situ Hybridization, Fluorescence

dual-color dual-hapten in situ hybridization


Reversible and Selective CO2 to HCO2 - Electrocatalysis near the Thermodynamic Potential.

Abstract: Reversible catalysis is a hallmark of energy-efficient chemical transformations, but can only be achieved if the changes in free energy of intermediate steps are minimized and the catalytic cycle is devoid of high transition-state barriers. Using these criteria, we demonstrate reversible CO2 /HCO2 - conversion catalyzed by [Pt(depe)2 ]2+ (depe=1,2-bis(diethylphosphino)ethane). Direct measurement of the free energies associated with each catalytic step correctly predicts a slight bias towards CO2 reduction. We demonstrate how the experimentally measured free energy of each step directly contributes to the <50 mV overpotential. We also find that for CO2 reduction, H2 evolution is negligible and the Faradaic efficiency for HCO2 - production is nearly quantitative. A free-energy analysis reveals H2 evolution is endergonic, providing a thermodynamic basis for highly selective CO2 reduction.

electrocatalysis
reversible catalysis
Carbon dioxide reduction
formate
thermochemistry


Do Faith Communities Have a Role in Addressing Childhood Obesity?

Abstract:
OBJECTIVES
Pediatric obesity is a multifaceted phenomenon. A partnership with faith-based communities to address the issue has been suggested. The purpose of this study was to describe the cultural beliefs of faith community leaders regarding childhood obesity and to examine attitudes about their role in addressing the issue.

DESIGN AND SAMPLE
A qualitative descriptive design informed by ethnographic methods and triangulation of multiple data sources was utilized to assess the cultural beliefs of faith community leaders. A purposive sample of 13 leaders (nine females, four males) from seven multicultural and multigenerational local faith communities participated in the study. No more than three participants from any one faith community were enrolled in the study.

RESULTS
Twenty-first century lifestyle challenges, accountability of behaviors (a dichotomy that fluctuated between individual responsibility to community and/or social responsibility), and the need for intentionality emerged as themes from the data.

CONCLUSIONS
Faith community leaders envisioned a role for faith communities in addressing childhood obesity. Findings support the ongoing development of population based health promotion programs through faith community engagement. The findings provide a foundation for nurses partnering with faith communities on health promotion programs targeting childhood obesity to address family health issues in a holistic way.

pediatric obesity
culture
social responsibility
health promotion
family health
parish nursing
public health nursing


Pain, fatigue, depressive symptoms and sleep disturbance in young adults with cerebral palsy.

Abstract:
PURPOSE
Investigate pain, fatigue, depressive symptoms and sleep disturbance in young adults with cerebral palsy compared to references.

MATERIALS AND METHODS
Young adults with cerebral palsy (n = 97, aged 21-34 years) and age-matched references from the general population (n = 190) rated pain using a numeric rating scale and fatigue, depressive symptoms, sleep disturbance and global health using Patient-Reported Outcomes Measurement Information System® short forms. Scores were compared between cerebral palsy subgroups and the reference population. Correlation coefficients and linear regression analyses assessed interrelationships of health issues and associations with global health.

RESULTS
Individuals with Gross Motor Function Classification System level I had less pain, fatigue and depressive symptoms, while individuals with levels II and III-V had more pain (53% and 56%, p < 0.001) and those with levels III-V more fatigue (39%, p = 0.035) than references (pain: 26%, fatigue: 14%). Pain and fatigue were more interrelated (correlation coefficients: 0.71 vs. 0.41) and stronger associated with global mental health in individuals with cerebral palsy.

CONCLUSIONS
Young adults with Gross Motor Function Classification System levels II-V report more pain and those with levels III-V report more fatigue than references. Pain and fatigue are highly interrelated and specifically relate to mental health in individuals with cerebral palsy.Implications for rehabilitationExcept for those in the highest level of motor function, young adults with cerebral palsy report higher levels of pain and fatigue compared to the general population of the same age.Pain and fatigue are strongly interrelated and associated with mental health in young adults with cerebral palsy.The present study recommends to monitor pain and fatigue in young adults with cerebral palsy with low levels of gross motor function.We advise rehabilitation professionals to consider combined treatment for both pain and fatigue.

van Gorp|Marloes|M|
Dallmeijer|Annet J|AJ|
van Wely|Leontien|L|
de Groot|Vincent|V|
Terwee|Caroline B|CB|
Flens|Gerard|G|
Stam|Henk J|HJ|
van der Slot|Wilma|W|
Roebroeck|Marij E|ME|
|||

pain
fatigue
depressive symptoms
sleep disturbance
young adult
Cerebral palsy


Gemcitabine/Nab-Paclitaxel versus FOLFIRINOX in Locally Advanced Pancreatic Cancer: A European Multicenter Study.

Abstract:
BACKGROUND
Gemcitabine/nab-paclitaxel (GN) and FOLFIRINOX (FFX) are two standard first-line therapies for metastatic pancreatic cancer (PC) but have rarely been compared, especially in patients with locally advanced PC (LAPC).

METHODS
This is a retrospective European multicenter study including patients with LAPC treated with either GN or FFX as the first-line therapy between 2010 and 2019. Coprimary objectives were progression-free survival (PFS) and overall survival (OS), both estimated using the Kaplan-Meier method.

RESULTS
A total of 147 patients (GN: n = 60; FFX: n = 87) were included. Tumor resection rates were similar between the two groups (16.7% vs. 16.1%; p = 1), with similar R0 resection rates (88.9%). Median PFS rates were not statistically different: 9 months (95% CI: 8-13.5) vs. 12.1 months (95% CI: 10.1-14.6; p = 0.8), respectively. Median OS rates were 15.7 months (95% CI: 12.6-20.2) and 16.7 months (95% CI: 14.8-20.4; p = 0.7), respectively. Abdominal pain at the baseline (HR = 2.03, p = 0.03), tumors located in the tail of the pancreas (HR = 4.35, p = 0.01), CA19-9 > 200 UI/L (HR = 2.03, p = 0.004) and tumor resection (HR = 0.37, p = 0.007) were independent prognostic factors for PFS, similarly to OS. CA19-9 ≤ 200 UI/L (OR = 2.6, p = 0.047) was predictive of the tumor response. Consolidation chemoradiotherapy, more often used in the FFX group (11.7% vs. 50.6%; p < 0.001), was not predictive.

CONCLUSION
This retrospective study did not show any difference between GN and FFX as the first-line treatment in patients with LAPC.

Williet|Nicolas|N|
Petrillo|Angelica|A|0000-0001-5489-5733
Roth|Gaël|G|0000-0001-5822-4320
Ghidini|Michele|M|0000-0001-5435-1218
Petrova|Mila|M|
Forestier|Julien|J|
Lopez|Anthony|A|
Thoor|Audrey|A|
Weislinger|Lucie|L|
De Vita|Ferdinando|F|
Taieb|Julien|J|0000-0002-9955-4753
Phelip|Jean Marc|JM|

gemcitabine/nab-paclitaxel
FOLFIRINOX
pancreatic cancer
prognostic factors
predictors of response


Age-Related Changes in Hair Shaft Protein Profiling and Genetically Variant Peptides.

Abstract: Recent reports highlight possible improvements in individual identification using proteomic information from human hair evidence. These reports have stimulated investigation of parameters that affect the utility of proteomic information. In addition to variables already studied relating to processing technique and anatomic origin of hair shafts, an important variable is hair ageing. Present work focuses on the effect of age on protein profiling and analysis of genetically variant peptides (GVPs). Hair protein profiles may be affected by developmental and physiological changes with age of the donor, exposure to different environmental conditions and intrinsic processes, including during storage. First, to explore whether general trends were evident in the population at different ages, hair samples were analyzed from groups of different subjects in their 20's, 40's and 60's. No significant differences were seen as a function of age, but consistent differences were evident between European American and African American hair profiles. Second, samples collected from single individuals at different ages were analyzed. Mostly, these showed few protein expression level differences over periods of 10 years or less, but samples from subjects at 44 and 65 year intervals were distinctly different in profile. The results indicate that use of protein profiling for personal identification, if practical, would be limited to decadal time intervals. Moreover, batch effects were clearly evident in samples processed by different staff. To investigate the contribution of storage (at room temperature) in affecting the outcomes, the same proteomic digests were analyzed for GVPs. In samples stored over 10 years, GVPs were reduced in number in parallel with the yield of identified proteins and unique peptides. However, a very different picture emerged with respect to personal identification. Numbers of GVPs sufficed to distinguish individuals despite the age differences of the samples. As a practical matter, three hair samples per person provided nearly the maximal number obtained from 5 or 6 samples. The random match probability (where the log increased in proportion to the number of GVPs) reached as high as 1 in 108. The data indicate that GVP results are dependent on the single nucleotide polymorphism profile of the donor genome, where environmental/processing factors affect only the yield, and thus are consistent despite the ages of the donors and samples and batchwise effects in processing. This conclusion is critical for application to casework where the samples may be in storage for long periods and used to match samples recently collected.

Plott|Tempest J|TJ|
Karim|Noreen|N|
Durbin-Johnson|Blythe P|BP|
Swift|Dionne P|DP|
Scott Youngquist|R|R|
Salemi|Michelle|M|
Phinney|Brett S|BS|
Rocke|David M|DM|
Davis|Michael G|MG|
Parker|Glendon J|GJ|
Rice|Robert H|RH|

genetically variant peptides
human hair
ageing
Proteomic profiling
forensic investigation


Bacteria causing pyometra in bitch and queen induce neutrophil extracellular traps.

Abstract: Neutrophils are capable of releasing their DNA in response to infectious agents to form neutrophil extracellular traps (NETs) to destroy pathogens. Even though pyometra in queens and bitches is a common disease, its pathogenesis is not fully understood. The aim of this study was to assess the presence of NETs in the endometrium of queens and bitches suffering from pyometra. Pyometra and normal uteri were obtained after ovariohysterectomy from adult queens and bitches in diestrus. Uterine contents were evaluated for bacterial isolation and identification and for NETs presence. Escherichia coli were isolated in 5/5 queens and 4/5 bitches, and Streptococcus spp in one bitch. Sterile glass coverslips were placed on the endometrium surface to obtain material for NETs that were evaluated by immunocytochemistry (histone, neutrophil elastase or myeloperoxidase), fluorescence microscopy or scanning electron microscopy. NETs in endometrium content were positively stained by DNA histone DAPI, myeloperoxidase and by neutrophil elastase. NETs were spread in all observed queen and bitch endometria of pyometra cases. Ultrastructure images of NETs depicted clusters of globular material with fine filaments deposited on or around thick filaments and trapped bacteria. To the best of our knowledge these are the first findings confirming NETs endometrial presence in queen and bitch pyometra. Nevertheless, the precise role of NETs in pyometra in the bitch and queen, either to contribute to the defeat of infection or to its persistence remains to be unraveled.

Rebordão|M R|MR|
Alexandre-Pires|G|G|
Carreira|M|M|
Adriano|L|L|
Carneiro|C|C|
Nunes|T|T|
Mateus|L|L|
Ferreira-Dias|G|G|

Pyometra
Bitch
Queen
Neutrophil extracellular traps (NETs)
Escherichia coli
Streptococcus spp


Perirenal Adipose Tissue-Current Knowledge and Future Opportunities.

Abstract: The perirenal adipose tissue (PRAT), a component of visceral adipose tissue, has been recently recognized as an important factor that contributes to the maintenance of the cardiovascular system and kidney homeostasis. PRAT is a complex microenvironment consisting of a mixture of white adipocytes and dormant and active brown adipocytes, associated with predipocytes, sympathetic nerve endings, vascular structures, and different types of inflammatory cells. In this review, we summarize the current knowledge about PRAT and discuss its role as a major contributing factor in the pathogenesis of hypertension, obesity, chronic renal diseases, and involvement in tumor progression. The new perspectives of PRAT as an endocrine organ and recent knowledge regarding the possible activation of dormant brown adipocytes are nowadays considered as new areas of research in obesity, in close correlation with renal and cardiovascular pathology. Supplementary PRAT complex intervention in tumor progression may reveal new pathways involved in carcinogenesis and, implicitly, may identify additional targets for tailored cancer therapy.

perirenal adipose tissue
obesity
cardiovascular diseases
chronic kidney disease


Assessing awareness and knowledge of hypertension in an at-risk population in the Karen ethnic rural community, Thasongyang, Thailand.

Abstract:
BACKGROUND
Hypertension is currently a global health concern. Rural and minority populations are increasingly exposed to risk factors as a result of urbanization, leading to hypertension and cardiovascular disease. We conducted a survey in the rural Karen community in Thasongyang District, Tak Province, Thailand, with the aims of determining: the distribution of blood pressure across different age groups; the prevalence of hypertension and other risk factors for cardiovascular diseases (CVDs), including diabetes, smoking, sedentary lifestyle, and excess alcohol use; knowledge and awareness of hypertension as a disease; and knowledge and awareness of risk factors for hypertension among the population at risk.

METHODS
This was a community-based, cross-sectional survey of 298 rural Karen residents. A set of questionnaires assessing lifestyle-related health risk behaviors and awareness and knowledge of hypertension were used. Blood pressure, fasting plasma glucose, weight, height, and waist circumference were measured.

RESULTS
Median systolic and diastolic blood pressures were 110 (range 100-120) mmHg and 70 (range 60-80) mmHg, respectively. High blood pressure was observed in more than 27% of the population, with 15% being hypertensive and 12% being prehypertensive. Multinomial logistic regression analysis showed that people in the Karen community who were aware of hypertension were less likely to be current smokers (odds ratio [OR] 0.53, confidence interval [CI] 0.29-0.97) and those with primary school education were more likely to be aware of hypertension than those who did not have a primary school education (OR 6.5, CI 1.9-22.24). Overall, our survey showed that less than half of the Karen community had such knowledge and awareness.

CONCLUSION
It is urgently necessary to promote knowledge, awareness, and health literacy among the ethnic Karen tribes to prevent hypertension and associated CVDs.

Aung|Myo Nyein|MN|
Lorga|Thaworn|T|
Srikrajang|Janthila|J|
Promtingkran|Nongluk|N|
Kreuangchai|Suchart|S|
Tonpanya|Wilawan|W|
Vivarakanon|Phatchanan|P|
Jaiin|Puangpet|P|
Praipaksin|Nara|N|
Payaprom|Apiradee|A|

awareness knowledge hypertension Karen CVDs smoking


Corrigendum: ncRNAs: New Players in Mitochondrial Health and Disease?

Abstract: [This corrects the article DOI: 10.3389/fgene.2020.00095.].

ncRNA lncRNA miRNA micropeptide mitochondria mtDNA


Postural stability in subjects with whiplash injury symptoms: results of a pilot study.

Abstract:
CONCLUSIONS
Posturographic tests can be used to assess and confirm the body's imbalance in subjects with whiplash injury. Further studies with larger cohorts are necessary to confirm this pilot study.

OBJECTIVES
To verify through a posturographic exam the qualitative and quantitative alterations of postural stability in subjects with previous cervical trauma in comparison with healthy subjects.

METHODS
A total of 42 subjects were analysed for the study; 22 as the control group (NM) and 20 (WM) with a positive anamnesis of whiplash injury from 3 to 12 month from diagnosis through a force platform. Centre of pressure (CoP) movements of the two groups with their eyes open and closed were recorded.

RESULTS
During the closed eye test, the subjects with cervical injuries displayed a significant increase in the anterior-posterior oscillation velocity (p < 0.05) compared with the control group, with a significant reduction (p < 0.01) of the ratio between the shifting length (SL) of CoP on the polygon support and the total envelope area (EA, mm(2)) of CoP movements in the polygon support (SL/EA-ratio, mm(-1)).

Bianco|Antonino|A| Pomara|Francesco|F| Petrucci|Marco|M| Battaglia|Giuseppe|G| Filingeri|Davide|D| Bellafiore|Marianna|M| Thomas|Ewan|E| Paoli|Antonio|A| Palma|Antonio|A|

force platform
centre of pressure
Vertigo
posturography


Mortality among patients due to adverse drug reactions that lead to hospitalization: a meta-analysis.

Abstract:
PURPOSE
The aim of this study was to estimate the prevalence of mortality among patients due to adverse drug reactions that lead to hospitalisation (fatal ADRAd), to explore the heterogeneity in its estimation through subgroup analysis of study characteristics, and to identify system-organ classes involved and causative drugs for fatal ADRAd.

METHODS
We identified prospective ADRAd-related studies via screening of the PubMed and Google Scholar databases with appropriate key terms. We estimated the prevalence of fatal ADRAd using a double arcsine method and explored heterogeneity using the following study characteristics: age groups, wards, study region, ADR definitions, ADR identification methods, study duration and sample size. We examined patterns of fatal ADRAd and causative drugs.

RESULTS
Among 312 full-text articles assessed, 49 studies satisfied the selection criteria and were included in the analysis. The mean prevalence of fatal ADRAd was 0.20% (95% CI: 0.13-0.27%; I2 = 93%). The age groups and study wards were the important heterogeneity modifiers. The mean fatal ADRAd prevalence varied from 0.01% in paediatric patients to 0.44% in the elderly. Subgroup analysis showed a higher prevalence of fatal ADRAd in intensive care units, emergency departments, multispecialty wards and whole hospitals. Computer-based monitoring systems in combination with other methods detected higher mortality. Intracranial haemorrhage, renal failure and gastrointestinal bleeding accounted for more than 50% of fatal ADRAdcases. Warfarin, aspirin, renin-angiotensin system (RAS) inhibitors and digoxin accounted for 60% of fatal ADRAd.

CONCLUSIONS
ADRAd is an important cause of mortality. Strategies targeting the safer use of warfarin, aspirin, RAS inhibitors and digoxin could reduce the large number of fatal ADRAdcases.

D064420:Drug-Related Side Effects and Adverse Reactions

Adverse drug reaction
Hospital
Meta-analysis
Prevalence
Causative drugs
Fatal reaction


Effects of sesame seed extract as a natural antioxidant on the oxidative stability of sunflower oil.

Abstract: Natural and de-novo biosynthesized phyto-compounds have gained much significance because of their non-controversial nutritional, health and safety benefits as compared with chemically synthesized commercially rivalry antioxidants. However, none of natural de-novo biosynthesized phyto-compounds has been commercially available and used in customary food business and processing. In this study, efficacy of sesame seed extracts (SSEs) in stabilizing sunflower oil during storage has been studied. Fine powder of sesame seed was extracted in different solvents. The results showed that significant differences in extractability of different solvents and maximum extraction yield (29.48%) were achieved with methanol. The antioxidant components and capability of different extracts were further investigated and evaluated via total phenolic contents, DPPH radical scavenging activity and β-carotene/linoleic acid calorimetric assays respectively. Being highest in yield and antioxidant potential, methanolic extract was used; three different concentrations of SSE (500, 750, and 1000 μL) were added in 100 mL of sunflower oil to further evaluate its oxidative stability. Sensory and oxidative analysis of baked product from these groups was also evaluated.

Hussain|Syed Ammar|SA|
Hameed|Ahsan|A|
Ajmal|Iqra|I|
Nosheen|Shaista|S|
Suleria|Hafiz Ansar Rasul|HAR|
Song|Yuanda|Y|0000-0002-8565-6724

Sesame seed extracts
Natural antioxidants
Oxidative stability
Sunflower oil


A blood-brain barrier overview on structure, function, impairment, and biomarkers of integrity.

Abstract: The blood-brain barrier is playing a critical role in controlling the influx and efflux of biological substances essential for the brain's metabolic activity as well as neuronal function. Thus, the functional and structural integrity of the BBB is pivotal to maintain the homeostasis of the brain microenvironment. The different cells and structures contributing to developing this barrier are summarized along with the different functions that BBB plays at the brain-blood interface. We also explained the role of shear stress in maintaining BBB integrity. Furthermore, we elaborated on the clinical aspects that correlate between BBB disruption and different neurological and pathological conditions. Finally, we discussed several biomarkers that can help to assess the BBB permeability and integrity in-vitro or in-vivo and briefly explain their advantages and disadvantages.

Integrity
Disruption
Permeability
Blood–brain barrier
CNS
Degenerative
Markers
Neuroinflammation
TEER
Tight junctions
Transcytosis


Activation of ventral tegmental area dopaminergic neurons reverses pathological allodynia resulting from nerve injury or bone cancer.

Abstract: Chronic pain induced by nerve damage due to trauma or invasion of cancer to the bone elicits severe ongoing pain as well as hyperalgesia and allodynia likely reflecting adaptive changes within central circuits that amplify nociceptive signals. The present study explored the possible contribution of the mesolimbic dopaminergic circuit in promoting allodynia related to neuropathic and cancer pain. Mice with ligation of the sciatic nerve or treated with intrafemoral osteosarcoma cells showed allodynia to a thermal stimulus applied to the paw on the injured side. Patch clamp electrophysiology revealed that the intrinsic neuronal excitability of ventral tegmental area (VTA) dopamine neurons projecting to the nucleus accumbens (N.Acc.) was significantly reduced in those mice. We used tyrosine hydroxylase (TH)-cre mice that were microinjected with adeno-associated virus (AAV) to express channelrhodopsin-2 (ChR2) to allow optogenetic stimulation of VTA dopaminergic neurons in the VTA or in their N.Acc. terminals. Optogenetic activation of these cells produced a significant but transient anti-allodynic effect in nerve injured or tumor-bearing mice without increasing response thresholds to thermal stimulation in sham-operated animals. Suppressed activity of mesolimbic dopaminergic neurons is likely to contribute to decreased inhibition of N.Acc. output neurons and to neuropathic or cancer pain-induced allodynia suggesting strategies for modulation of pathological pain states.

Watanabe|Moe|M|
Narita|Michiko|M|
Hamada|Yusuke|Y|
Yamashita|Akira|A|
Tamura|Hideki|H|
Ikegami|Daigo|D|
Kondo|Takashige|T|
Shinzato|Tatsuto|T|
Shimizu|Takatsune|T|
Fukuchi|Yumi|Y|
Muto|Akihiro|A|
Okano|Hideyuki|H|
Yamanaka|Akihiro|A|
Tawfik|Vivianne L|VL|
Kuzumaki|Naoko|N|
Navratilova|Edita|E|
Porreca|Frank|F|
Narita|Minoru|M|

cancer pain
dopamine
optogenetics
mesolimbic dopaminergic neurons
Neuropathic pain


Peter J Derrick and the Grand Scale 'Magnificent Mass Machine' mass spectrometer at Warwick.

Abstract: The value of the Grand Scale 'Magnificent Mass Machine' mass spectrometer in investigating the reactivity of ions in the gas phase is illustrated by a brief analysis of previously unpublished work on metastable ionised n-pentyl methyl ether, which loses predominantly methanol and an ethyl radical, with very minor contributions for elimination of ethane and water. Expulsion of an ethyl radical is interpreted in terms of isomerisation to ionised 3-pentyl methyl ether, via distonic ions and, possibly, an ion-neutral complex comprising ionised ethylcyclopropane and methanol. This explanation is consistent with the closely similar behaviour of the labelled analogues, C3H7CH2CD2OCH3+. and C3H7CD2CH2OCH3+., and is supported by the greater kinetic energy release associated with loss of ethane from ionised n-propyl methyl ether compared to that starting from directly generated ionised 3-pentyl methyl ether.

Colburn|A W|AW|
Derrick|Peter J|PJ|
Bowen|Richard D|RD|

methyl
isomerisation
distonic ions
ion-neutral complex
Grand Scale mass spectrometer
MMM
Peter Derrick
ionised ether
pentyl


Evaluation of SEPT2 and SEPT4 transcript contents in spermatozoa from men with asthenozoospermia and teratozoospermia.

Abstract:
Background and aims
Motility and morphological defects of spermatozoa can cause male infertility. Sperm RNAs are related to sperm quality. They are considered to have clinical values as a biomarker for assessing sperm quality and fertility potential. The annulus, located in the mammalian sperm tail, is required for motility and terminal differentiation of the spermatozoa. SEPT2, 4, 6, 7, and 12 proteins are the main components of the annulus in the sperm tail. The study aimed to evaluate SEPT2 and SEPT4 mRNA contents in the spermatozoa of patients with asthenozoospermia and teratozoospermia.

Methods
We evaluated transcript levels of SEPT2 and SEPT4 in the sperm samples of 20 asthenozoospermic, 20 teratozoospermic, and 20 normozoospermic samples using quantitative PCR.

Results
The SEPT2 transcript level was significantly decreased in the asthenozoospermia samples compared with the normal group (P = .013). However, SEPT4 was not significantly different between these two groups. The transcript levels of SEPT2 and SEPT4 were not statistically different between teratozoospermic and normozoospermic groups.

Conclusion
In conclusion, downregulation of SEPT2 in patients with asthenozoospermia appears to be associated with poor sperm motility.


Rates and risk factors of unplanned 30-day readmission following general and thoracic pediatric surgical procedures.

Abstract:
BACKGROUND/PURPOSE
Postoperative unplanned readmissions are costly and decrease patient satisfaction; however, little is known about this complication in pediatric surgery. The purpose of this study was to determine rates and predictors of unplanned readmission in a multi-institutional cohort of pediatric surgical patients.

METHODS
Unplanned 30-day readmissions following general and thoracic surgical procedures in children <18 were identified from the 2012-2014 National Surgical Quality Improvement Program- Pediatric. Time-dependent rates of readmission per 30 person-days were determined to account for varied postoperative length of stay (pLOS). Patients were randomly divided into 70% derivation and 30% validation cohorts which were used for creation and validation of a risk model for readmission.

RESULTS
Readmission occurred in 1948 (3.6%) of 54,870 children for a rate of 4.3% per 30 person-days. Adjusted predictors of readmission included hepatobiliary procedures, increased wound class, operative duration, complications, and pLOS. The predictive model discriminated well in the derivation and validation cohorts (AUROC 0.710 and 0.701) with good calibration between observed and expected readmission events in both cohorts (p>.05).

CONCLUSIONS
Unplanned readmission occurs less frequently in pediatric surgery than what is described in adults, calling into question its use as a quality indicator in this population. Factors that predict readmission including type of procedure, complications, and pLOS can be used to identify at-risk children and develop prevention strategies.

LEVEL OF EVIDENCE
III.

Polites|Stephanie F|SF|
Potter|Donald D|DD|
Glasgow|Amy E|AE|
Klinkner|Denise B|DB|
Moir|Christopher R|CR|
Ishitani|Michael B|MB|
Habermann|Elizabeth B|EB|

D002648:Child
D015331:Cohort Studies
D005260:Female
D006801:Humans
D007902:Length of Stay
D008297:Male
D010359:Patient Readmission
D011183:Postoperative Complications
D011184:Postoperative Period
D058996:Quality Improvement
D019984:Quality Indicators, Health Care
D012189:Retrospective Studies
D012307:Risk Factors
D013514:Surgical Procedures, Operative
D019616:Thoracic Surgical Procedures


Human sLZIP promotes atherosclerosis via MMP-9 transcription and vascular smooth muscle cell migration.

Abstract: Atherosclerosis is a chronic inflammatory response of the vascular wall, and immune responses are involved in every phase of atherosclerosis, from initiation, to progression, and finally to plaque rupture. Cytokines are the major atherogenic mediators that promote plaque formation and progression by activation of inflammatory cells. They induce expressions of matrix metalloproteinases (MMPs), leading to vascular smooth muscle cell (VSMC) migration in atherosclerotic lesions. Although chronic inflammatory mediators, including tumor necrosis factor α (TNF-α) and MMPs, exacerbate atherosclerosis, the molecular mechanism of atherogenesis remains unclear. In this study we investigated the role of a novel transcription factor the human small leucine zipper protein (sLZIP) in TNF-α-induced MMP expression, VSMC migration, and atherosclerosis progression. The proinflammatory cytokine TNF-α enhanced sLZIP expression by 3-fold via activation of NF-κB signaling. sLZIP induced MMP-9 transcription and the proteolytic activity of MMP-9 by 2.8- and 3.2-fold (P< 0.05), respectively, in macrophages, leading to enhancement of VSMC migration by 2.7-fold (P<0.005). sLZIP(OE/+) (sLZIP transgenic); LDLR(-/-) mice fed a high-cholesterol diet exhibited enhanced arterial plaque formation and increased VSMC migration from the media into the intima by 2.8- and 2.6-fold (P<0.01), respectively, compared with atherosclerosis-prone LDLR(-/-) mice. These results indicate that human sLZIP plays a critical role in development of atherosclerosis and can be used as a therapeutic target molecule for treatment of atherosclerosis.

D017362:Cyclic AMP Response Element-Binding Protein

D015971:Gene Expression Regulation, Enzymologic

sLZIP
atherosclerosis
vascular smooth muscle cell
matrix metalloproteinase
macrophage


Multicenter retrospective comparison of spontaneous intestinal perforation outcomes between primary peritoneal drain and primary laparotomy.

Abstract:
PURPOSE
The purpose of our study was to compare outcomes of infants with spontaneous intestinal perforation (SIP) treated with primary peritoneal drain versus primary laparotomy.

METHODS
We performed a multi-institution retrospective review of infants with diagnosis of SIP from 2012 to 2016. Clinical characteristics and outcomes were compared between infants treated with primary peritoneal drain vs infants treated with laparotomy.

RESULTS
We identified 171 patients treated for SIP (drain n = 110 vs. laparotomy n = 61). There were no differences in maternal or prenatal characteristics. There were no clinically significant differences in vital signs, white blood cell or platelet measures, up to 48 h after intervention. Patients who were treated primarily with a drain were more premature (24.9 vs. 27.2 weeks, p < 0.001) and had lower median birth weight (710 g vs. 896 g, p < 0.001). No significant differences were found in complications, time to full feeds, length of stay (LOS) or mortality between the groups. Primary laparotomy group had more procedures (median number 1 vs. 2, p = 0.002). There were 32 (29%) primary drain failures whereby a laparotomy was ultimately needed.

CONCLUSIONS
SIP treated with primary drain is successful in the majority of patients with no significant differences in outcomes when compared to laparotomy with stoma.

THE LEVEL OF EVIDENCE
III.

Ahle|Samantha|S|
Badru|Faidah|F|
Damle|Rachelle|R|
Osei|Hector|H|
Munoz-Abraham|Armando Salim|AS|
Bajinting|Adam|A|
Barbian|Maria Estefania|ME|
Bhatia|Amina M|AM|
Gingalewski|Cindy|C|
Greenspon|Jose|J|
Hamilton|Nicholas|N|
Stitelman|David|D|
Strand|Marya|M|
Warner|Brad W|BW|
Villalona|Gustavo A|GA|

Spontaneous intestinal perforation
Peritoneal drain
Necrotizing enterocolitis


Improving Team Performance Through Simulation-Based Learning.

Abstract: American health care is facing an epidemic of medical errors. A major cause of these errors is poor teamwork. Crisis resource management (CRM) is a set of teamwork principles derived from the airline industry. Medical simulation is an educational tool that affords health care providers a means of improving teamwork by learning and practicing CRM. This article (1) discusses the case for teaching team training, (2) reviews the principles of medical simulation as they pertain to team training, (3) provides practical guidelines for using medical simulation in otolaryngology education, (4) discusses current evidence for the efficacy of medical simulation.

D002983:Clinical Competence
D006801:Humans
D033183:Interdisciplinary Communication
D019300:Medical Errors
D010036:Otolaryngology
D010348:Patient Care Team
D000066908:Simulation Training

Medical errors
Teamwork
Medical culture
SimZones
Simulation based


Aggregated Amphiphilic Antimicrobial Peptides Embedded in Bacterial Membranes.

Abstract: Molecular dynamics (MD) simulations, stochastic optical reconstruction microscopy (STORM), and neutron reflection (NR) were combined to explore how antimicrobial peptides (AMPs) can be designed to promote the formation of nanoaggregates in bacterial membranes and impose effective bactericidal actions. Changes in the hydrophobicity of the designed AMPs were found to have a strong influence on their bactericidal potency and cytotoxicity. G(IIKK)3I-NH2 (G3) achieved low minimum inhibition concentrations (MICs) and effective dynamic kills against both antibiotic-resistant and -susceptible bacteria. However, a G3 derivative with weaker hydrophobicity, KI(KKII)2I-NH2 (KI), exhibited considerably lower membrane-lytic activity. In contrast, the more hydrophobic G(ILKK)3L-NH2 (GL) peptide achieved MICs similar to those observed for G3 but with worsened hemolysis. Both the model membranes studied by Brewster angle microscopy, zeta potential measurements, and NR and the real bacterial membranes examined with direct STORM contained membrane-inserted peptide aggregates upon AMP exposure. These structural features were well supported by MD simulations. By revealing how AMPs self-assemble in microbial membranes, this work provides important insights into AMP mechanistic actions and allows further fine-tuning of antimicrobial potency and cytotoxicity.

D023181:Antimicrobial Cationic Peptides
D001672:Biocompatible Materials
D004926:Escherichia coli
D008826:Microbial Sensitivity Tests
D056004:Molecular Dynamics Simulation
D010316:Particle Size
D066329:Protein Aggregates
D013211:Staphylococcus aureus
D013499:Surface Properties
D013501:Surface-Active Agents

antimicrobial peptides
membranes
nanoaggregates
antibiotics
antimicrobial resistance
nanostructures
pathogens
peptide design


A sustained systemic inflammatory response syndrome is associated with shunt-dependent hydrocephalus after aneurysmal subarachnoid hemorrhage.

Abstract: OBJECTIVEThe authors sought to evaluate whether a sustained systemic inflammatory response was associated with shunt-dependent hydrocephalus following aneurysmal subarachnoid hemorrhage.METHODSA retrospective analysis of 193 consecutive patients with aneurysmal subarachnoid hemorrhage was performed. Management of hydrocephalus followed a stepwise algorithm to determine the need for external CSF drainage and subsequent shunt placement. Systemic inflammatory response syndrome (SIRS) data were collected for all patients during the first 7 days of hospitalization. Patients who met the SIRS criteria every day for the first 7 days of hospitalization were considered as having a sustained SIRS. Univariate and multivariate regression analyses were used to determine predictors of shunt dependence.RESULTSSixteen percent of patients required shunt placement. Sustained SIRS was observed in 35% of shunt-dependent patients compared to 14% in non-shunt-dependent patients (p = 0.004). On multivariate logistic regression, female sex (OR 0.35, 95% CI 0.142-0.885), moderate to severe vasospasm (OR 3.78, 95% CI 1.333-10.745), acute hydrocephalus (OR 21.39, 95% CI 2.260-202.417), and sustained SIRS (OR 2.94, 95% CI 1.125-7.689) were significantly associated with shunt dependence after aneurysmal subarachnoid hemorrhage. Receiver operating characteristic analysis revealed an area under the curve of 0.83 for the final regression model.CONCLUSIONSSustained SIRS was a predictor of shunt-dependent hydrocephalus following aneurysmal subarachnoid hemorrhage even after adjustment for potential confounding variables in a multivariate logistic regression model.

Wessell|Aaron P|AP|
Kole|Matthew J|MJ|
Cannarsa|Gregory|G|
Oliver|Jeffrey|J|
Jindal|Gaurav|G|
Miller|Timothy|T|
Gandhi|Dheeraj|D|
Parikh|Gunjan|G|
Badjatia|Neeraj|N|
Aldrich|E Francois|EF|
Simard|J Marc|JM|

SIRS = systemic inflammatory response syndrome

WFNS = World Federation of Neurosurgical Societies


Birthweight predicts individual differences in adult face recognition ability.

Abstract: It has long been known that premature birth and/or low birthweight can lead to general difficulties in cognitive and emotional functioning throughout childhood. However, the influence of these factors on more specific processes has seldom been addressed, despite their potential to account for wide individual differences in performance that often appear innate. Here, we examined the influence of gestation and birthweight on adults' face perception and face memory skills. Performance on both sub-processes was predicted by birthweight and birthweight-for-gestation, but not gestation alone. Evidence was also found for the domain-specificity of these effects: No perinatal measure correlated with performance on object perception or memory tasks, but they were related to the size of the face inversion effect on the perceptual test. This evidence indicates a novel, very early influence on individual differences in face recognition ability, which persists into adulthood, influences face-processing strategy itself, and may be domain-specific.

individual differences
face recognition
gestation
face perception
birth weight


Do thermal treatments affect the mechanical behavior of porcelain-veneered zirconia? A systematic review and meta-analysis.

Abstract:
OBJECTIVES
A systematic review of in vitro studies was conducted to assess the effect of thermal treatments on flexural strength or critical load to failure of porcelain-veneered zirconia (PVZ).

SOURCES
Literature searches were performed up to June 2018 in PubMed/MEDLINE, Scopus and Web of Science databases, with no publication year or language limits.

DATA
From 393 relevant studies, 21 were selected for full-text analysis, from which 7 failed to meet the inclusion criteria. The 14 remaining papers were included in the systematic review: 8 for meta-analysis and 6 restricted to descriptive analyses. Hand searching of reference lists resulted in no additional papers.

STUDY SELECTION
In vitro studies using PVZ specimens testing the influence of thermal treatments on the fracture resistance to monotonic or cyclic loading. Papers evaluating cooling rate were divided into those applying fast cooling from above the porcelain glass transition temperature (Tg), or from below it. Meta-analyses were performed separately for flexural strength and critical load to failure, using random effects at a 5% significance level.

CONCLUSIONS
Delaying furnace opening at a temperature below the porcelain Tg is advised for PVZ restorations, in order to improve their fracture resistance. Additional information is required to confirm the apparent beneficial effect of self-glaze and repeated veneer firings on the mechanical properties of these restorations. Finally, in order to obtain conclusive and relevant evidence regarding thermal treatments and the fracture resistance of PVZs, future studies should concentrate on anatomically-correct crown specimens.

Rodrigues|Camila da Silva|CDS|
Aurélio|Iana Lamadrid|IL|
Kaizer|Marina da Rosa|MDR|
Zhang|Yu|Y|
May|Liliana Gressler|LG|

D003442:Crowns
D003776:Dental Porcelain
D003799:Dental Stress Analysis
D003801:Dental Veneers
D008422:Materials Testing
D013314:Stress, Mechanical
D013499:Surface Properties
D015040:Zirconium

Porcelain-veneered zirconia
Mechanical properties
Cooling protocols
Glaze firings
Heat treatment
Repeated firings


Somatic mutations and increased lymphangiogenesis observed in a rare case of intramucosal gastric carcinoma with lymph node metastasis.

Abstract:
Background and aim
Intramucosal gastric adenocarcinoma of the well-moderately differentiated type only exhibits lymph node metastasis in extremely rare cases. We encountered such case and investigated both the lymphangiogenic properties and somatic mutations in the cancer to understand the prometastatic features of early-stage gastric cancer.

Methods
We quantitatively measured the density of lymphatic vessels and identified mutations in 412 cancer-associated genes through next-generation target resequencing of DNA extracted from tumor cells in a formalin-fixed and paraffin-embedded tissue. Functional consequence of the identified mutation was examined in vitro by means of gene transfection, immunoblot, and the quantitative real-time polymerase chain reaction assay.

Results
The intramucosal carcinoma was accompanied by abundant lymphatic vessels. The metastatic tumor harbored somatic mutations in NBN, p.P6S, and PAX8, p.R49H. The PAX8R49H showed significantly higher transactivation activity toward E2F1 than the wild-type PAX8 (P< 0.001).

Conclusions
Our data suggest that increased lymphangiogenesis and somatic mutations of NBN and/or PAX8 could facilitate lymph node metastasis from an intramucosal gastric carcinoma. These findings may potentially inform evaluations of the risk of developing lymph node metastasis in patients with intramucosal gastric cancer.

Ikari|Naoki|N| Aoyama|Shota|S| Seshimo|Akiyoshi|A| Suehiro|Yuji|Y| Motohashi|Tomoko|T| Mitani|Shohei|S| Yoshina|Sawako|S| Tanji|Etsuko|E| Serizawa|Akiko|A| Yamada|Takuji|T| Taniguchi|Kiyoaki|K| Yamamoto|Masakazu|M| Furukawa|Toru|T|

lymphangiogenesis
lymph node metastasis
NBN
PAX8
early gastric cancer


Extraction and quantification of SO2 content in wines using a hollow fiber contactor.

Abstract: Sulfites [Formula: see text] or sulfur dioxide (SO2) is a preservative widely used in fruits and fruit-derived products. This study aims to propose a membrane contactor process for the selective removal and recovery of SO2 from wines in order to obtain its reliable quantification. Currently, the aspiration and Ripper methods offer a difficult quantification of the sulfite content in red wines because they involve evaporation steps of diluted compounds and a colorimetric assay, respectively. Therefore, an inexpensive and accurate methodology is not currently available for continuous monitoring of SO2 in the liquids food industry. Red wine initially acidified at pH < 1 was treated by membrane extraction at 25 ℃. This operation is based on a hydrophobic Hollow Fiber Contactor, which separates the acidified red wine in the shell side and a diluted aqueous sodium hydroxide solution as receiving solution into the lumenside in countercurrent. Sulfite and bisulfite in the acidified red wine become molecular SO2, which is evaporated through the membrane pores filled with gas. Thus, SO2 is trapped in a colorless solution and the membrane contactor controls its transfer, decreasing experimental error induced in classical methods. Experimental results using model solutions with known concentration values of [Formula: see text] show an average extraction percentage of 98.91 after 4 min. On the other hand, two types of Chilean Cabernet Sauvignon wines were analyzed with the same system to quantify the content of free and total sulfites. Results show a good agreement between these methods and the proposed technique, which shows a lower experimental variability.

Plaza|Andrea|A|
Romero|Julio|J|
Silva|Wladimir|W|
Morales|Elizabeth|E|
Torres|Alejandra|A|
Aguirre|María J|MJ|

Wines
sulfite
sulfur dioxide
membrane contactor
Ripper method
aspiration method


Neural and physiological relations observed in musical beat and meter processing.

Abstract:
INTRODUCTION
Music is ubiquitous and powerful in the world's cultures. Music listening involves abundant information processing (e.g., pitch, rhythm) in the central nervous system and can also induce changes in the physiology, such as heart rate and perspiration. Yet, previous studies tended to examine music information processing in the brain separately from physiological changes. In the current study, we focused on the temporal structure of music (i.e., beat and meter) and examined the physiology, neural processing, and, most importantly, the relation between the two areas.

METHODS
Simultaneous MEG and ECG data were collected from a group of adults (N = 15) while they passively listened to duple and triple rhythmic patterns. To characterize physiology, we measured heart rate variability (HRV), indexing the parasympathetic nervous system function (PSNS). To characterize neural processing of beat and meter, we examined the neural entertainment and calculated the beat-to-meter ratio to index the relation between beat-level and meter-level entrainment. Specifically, the current study investigated three related questions: (a) whether listening to musical rhythms affects HRV; (b) whether the neural beat-to-meter ratio differed between metrical conditions, and (c) whether neural beat-to-meter ratio is related to HRV.

RESULTS
Results suggest that while at the group level, both HRV and neural processing are highly similar across metrical conditions, at the individual level, neural beat-to-meter ratio significantly predicts HRV, establishing a neural-physiological link.

CONCLUSION
This observed link is discussed under the theoretical "neurovisceral integration model," and it provides important new perspectives in music cognition and auditory neuroscience research.

Zhao|T Christina|TC|0000-0003-1165-909X
Kuhl|Patricia K|PK|

physiology
beat and meter
rhythm
heart rate variability
music processing
neural entrainment


The role of surgical intervention for isolated breast cancer liver metastasis: Results of case-control study with comparison to medical treatment.

Abstract:
BACKGROUND
Combined with systemic therapy, the surgical intervention for breast cancer liver metastases (BCLM) is increasingly accepted but lacks convincing evidence. The aim of this study was to evaluate the disease control efficacy of hepatic surgery in isolated BCLM patients.

METHODS
Between 2012 and 2017, metastatic breast cancer patients with isolated liver metastasis and regular follow-up were identified. Cohort design was conducted to compare the progression-free survival (PFS) between the surgical and nonsurgical BCLM patients. Univariate analysis and multivariate Cox regression survival analyses were performed to identify significant prognostic factors.

RESULT
In all, 148 isolated BCLM patients were enrolled and 95 participants received hepatic surgery for metastatic lesions. With median follow-up of 36.47 months, there was no significant difference between hepatic surgical group and nonsurgical group for PFS (median PFS: 11.17 months vs 10.10 m, P = .092). Based on the multivariate analysis, the disease-free interval (DFI) was an independent prognostic factor for isolated BCLM patients. Among the surgical group, BCLM patients who had ideal response after first salvage systemic treatment experienced the best long-term survival (median PFS: 14.20 months).

CONCLUSION
For isolated BCLM patients with ideal response in first-line medical treatment, surgical intervention (hepatectomy, radiofrequency ablation) combining with systemic treatment could bring improved progression-free survival compared to sole systemic treatment, indicating that hepatic surgery may be considered as a therapeutic choice for selected isolated BCLM patients in clinical practice.

Wen|Jiahuai|J|0000-0001-7326-5980 Ye|Feng|F| Xie|Fengfeng|F| Liu|Dan|D| Huang|LeZhen|L| Fang|Chen|C| Zhong|Shaowen|S| Ren|Liping|L|

D000328:Adult
D000970:Antineoplastic Agents
D001943:Breast Neoplasms
D016022:Case-Control Studies
D018572:Disease-Free Survival
D005260:Female
D006498:Hepatectomy
D006801:Humans
D008113:Liver Neoplasms
D008875:Middle Aged
D000077982:Progression-Free Survival
D000078703:Radiofrequency Ablation
D012044:Regression Analysis
D012189:Retrospective Studies
D016879:Salvage Therapy

surgical intervention
breast cancer
liver metastasis


Shifts in the importance of the species pool and environmental controls of epiphytic bryophyte richness across multiple scales.

Abstract: Species richness is influenced by a nested set of environmental factors, but how do these factors interact across several scales? Our main aim is to disentangle the relative importance of environmental filters and the species pool on the richness of epiphytic bryophytes across spatial scales. To do so, we sampled epiphytic bryophytes in 43 oak forests across the northwest of the Iberian Peninsula. As predictors we used climate, descriptors of forest structure and micro-environment. We applied structural equation modeling to relate these variables with richness and cover at three scales: locality (forest), stand (three stands per forest), and sample (a quadrate in a tree). We assumed top-down relationships, so that large-scale variables influenced lower scale variables, and in which cover directly influenced richness. Richness at the next larger scale (locality to stand and stand to sample) is considered a surrogate of the species pool and included as a predictor of richness at the next smaller scale. Environmental variables explain locality richness, but as we decrease the spatial scale, its importance decreases and the dependence on species pool increases. In addition, we found unexpected bottom-up relationships (between micro-scale environment to locality richness). Our results point to the scale dependence of niche vs. neutral processes: niche processes are important at the locality (forest) scale, while neutral processes are significant at the small (sample) scale. We propose a modified conceptualization of the factors influencing biodiversity at different spatial scales by adding links across different scales (between micro-environment and locality-scale richness in our study).

Medina|Nagore G|NG|
Bowker|Matthew A|MA|
Hortal|Joaquín|J|
Mazimpaka|Vicente|V|
Lara|Francisco|F|

Scale
Neutral processes
Diversity
Plant
Regional species pool


Ballistic research techniques: visualizing gunshot wounding patterns.

Abstract: There are difficulties associated with mapping gunshot wound (GSW) patterns within opaque models. Depending on the damage measurement parameters required, there are multiple techniques that can provide methods of "seeing" the GSW pattern within an opaque model. The aim of this paper was to test several of these techniques within a cadaveric animal limb model to determine the most effective. The techniques of interest were flash X-ray, ultrasound, physical dissection, and computed-tomography (CT). Fallow deer hind limbs were chosen for the model with four limbs used for each technique tested. Quarantined 7.62 × 39 mm ammunition was used for each shot, and each limb was only shot once, on an outdoor range with shots impacting at muzzle velocity. Flash X-ray provided evidence of yaw within the limb during the projectile's flight; ultrasound though able to visualise the GSW track, was too subjective and was abandoned; dissection proved too unreliable due to the tissue being cadaveric so also too subjective; and lastly, CT with contrast provided excellent imaging in multiple viewing planes and 3D image reconstruction; this allowed versatile measurement of the GSW pattern to collect dimensions of damage as required. Of the different techniques examined in this study, CT with contrast proved the most effective to allow precise GSW pattern analysis within a cadaveric animal limb model. These findings may be beneficial to others wishing to undertake further ballistic study both within clinical and forensic fields.


Ocular surface microvascular response and its relation to contact lens fitting and ocular comfort: an update of recent research.

Abstract: This review examines vascular responses in the ocular surface to contact lens wear and its relation to lens fitting characteristics and contact lens-related discomfort. A search of PubMed was performed to find original research in English, within the past 10 years, that studied the ocular surface, including lid-wiper vascular responses to the lens. The interaction between the lens and ocular surface triggers vascular responses, impacting the lens fitting and contact lens-related discomfort. Contact lens-related discomfort is a multifactorial event, which is affected by lens characteristics. Overall, contact lenses with low modulus and a relatively tight fit produce significant ocular comfort. If an appropriate lens fit is achieved, lens fitting characteristics may not play a critical role in contact lens-related discomfort. On the other hand, the pathogenic and vascular changes of lid-wiper vascular responses appear to play an essential role in developing contact lens-related discomfort, in concert with reactions of the cornea (compression and staining) and conjunctiva (indentation and staining). Robust evaluation of lid-wiper changes at the cellular and microvascular level may hold the key to better understanding the mechanism of contact lens-related discomfort and reveal strategies for eliminating lid wiper epitheliopathy and improving ocular comfort in contact lens wearers.

Fang|Min|M| Airen|Shriya|S| Jiang|Hong|H| Wang|Jianhua|J|

ocular surface
Comfort
vascular response
lid-wiper
contact lenses


A microsatellite-based genetic linkage map and putative sex-determining genomic regions in Lake Victoria cichlids.

Abstract: Cichlid fishes in East Africa have undergone extensive adaptive radiation, which has led to spectacular diversity in their morphology and ecology. To date, genetic linkage maps have been constructed for several tilapias (riverine), Astatotilapia burtoni (Lake Tanganyika), and hybrid lines of Lake Malawi cichlids to facilitate genome-wide comparative analyses. In the present study, we constructed a genetic linkage map of the hybrid line of Lake Victoria cichlids, so that maps of cichlids from all the major areas of East Africa will be available. The genetic linkage map shown here is derived from the F2 progeny of an interspecific cross between Haplochromis chilotes and Haplochromis sauvagei and is based on 184 microsatellite and two single-nucleotide polymorphism (SNP) markers. Most of the microsatellite markers used in the present study were originally designed for other genetic linkage maps, allowing us to directly compare each linkage group (LG) among different cichlid groups. We found 25 LGs, the total length of which was 1133.2cM with an average marker spacing of about 6.09cM. Our subsequent linkage mapping analysis identified two putative sex-determining loci in cichlids. Interestingly, one of these two loci is located on cichlid LG5, on which the female heterogametic ZW locus and several quantitative trait loci (QTLs) related to adaptive evolution have been reported in Lake Malawi cichlids. We also found that V1R1 and V1R2, candidate genes for the fish pheromone receptor, are located very close to the recently detected sex-determining locus on cichlid LG5. The genetic linkage map study presented here may provide a valuable foundation for studying the chromosomal evolution of East African cichlids and the possible role of sex chromosomes in generating their genomic diversity.

Kudo|Yu|Y| Nikaido|Masato|M| Kondo|Azusa|A| Suzuki|Hikoyu|H| Yoshida|Kohta|K| Kikuchi|Kiyoshi|K| Okada|Norihiro|N|

Linkage mapping
Hybrid line
Linkage group


An experiment study on temperature characteristics of a linear ultrasonic motor using longitudinal transducers.

Abstract: The temperature characteristics of a T-shaped linear ultrasonic motor using longitudinal vibration transducers are reported. When the ultrasonic motor is excited by different voltages, the surface temperatures at the driving foot, PZT ceramic and end cap are tested by a thermal imager for obtaining the thermal characteristics of the motor under no-load condition. PZT ceramic shows the maximum temperature increase. Then, the variations of resonant frequencies, electromechanical coupling factors and mechanical Q-factors versus time, as well as the effect of the temperature on the resonance frequencies, electromechanical coupling factors and mechanical Q-factors, is measured and analysed under the long-term running. It is found that all the resonance frequencies and electromechanical coupling factors decrease as the increase of the temperature, as well as the mechanical Q-factors. In addition, the change of the output speed over temperature is tested and the obtained result shows the trend of decline. This work can provide useful guidelines for the design and optimization of linear ultrasonic motor operating in wide temperature range.

Li|He|H| Chen|Weishan|W| Tian|Xinqi|X| Liu|Junkao|J|

Temperature characteristics
Ultrasonic motor
Transducers


Complete mitochondrial genome and the phylogenetic position of the pelagic octopus Tremoctopus violaceus (Mollusca: Tremoctopodidae).

Abstract: Tremoctopus violaceus is a small species of pelagic octopods which inhabit in subtropical and tropical open oceans. The mitogenome of T. violaceus is 16,015 base pairs (bp) in length and contained 13 protein-coding genes, two rRNA genes, and 22 tRNA genes. Sequence analysis showed that the overall base composition is 31.5% for A, 40.47% for T, 7.79% for C, and 20.24% for G. The newly characterized complete mitochondrial genome of T. violaceus will provide essential data for further studies of this endangered species.

Chiu|Yuh-Wen|YW| Chang|Chih-Wei|CW| Shen|Kang-Ning|KN| Ju|Yu-Min|YM| Lin|Hung-Du|HD|

Tremoctopus violaceus
octopods
mitogenome
Argonautoidea


A link to better care: The effect of remote monitoring on long-term adverse cardiac events in a propensity score-matched cohort.

Abstract:
AIMS
There are conflicting data regarding the clinical benefits of device-based remote monitoring (RM). We sought to assess the effect of device-based RM on long-term clinical outcomes in recipients of implantable cardioverter-defibrillators (ICDs).

METHODS
We assessed the incidence of adverse cardiac events, overall mortality and device therapy efficacy and safety in a propensity score-matched cohort of patients under RM compared to patients under conventional follow-up. Data on hospitalizations, mortality and cause of death were systematically assessed using a nationwide healthcare platform. The primary outcome was time to a composite outcome of first hospital admission for heart failure or cardiovascular death.

RESULTS
Of a total of 923 implantable device recipients, 164 matched patients were identified (84 under RM, 84 under conventional follow-up). The mean follow-up was 44 months (range 1-123). There were no significant differences regarding baseline characteristics in the matched cohorts. Patients under RM had a significantly lower incidence of the primary outcome (hazard ratio [HR] 0.42, confidence interval [CI] 0.20-0.88, p=0.022); there was a non-significant trend towards lower overall mortality (HR 0.53, CI 0.27-1.04, p=0.066). No significant differences between cohorts were found regarding appropriate therapies (RM vs. conventional follow-up, 8.1 vs. 8.2%, p=NS) or inappropriate therapies (6.8 vs. 5.0%, p=NS).

CONCLUSION
In a propensity score-matched cohort of ICD recipients with long-term follow-up, RM was associated with a lower rate of a combined endpoint of hospital admission for heart failure or cardiovascular death.

Portugal|Guilherme|G|
Cunha|Pedro|P|
Valente|Bruno|B|
Feliciano|Joana|J|
Lousinha|Ana|A|
Alves|Sandra|S|
Braz|Manuel|M|
Pimenta|Ricardo|R|
Delgado|Ana Sofia|AS|
Oliveira|Mário|M|
Ferreira|Rui C|RC|

D015331:Cohort Studies
D016757:Death, Sudden, Cardiac
D017147:Defibrillators, Implantable
D005260:Female
D006801:Humans
D008297:Male
D008875:Middle Aged
D010343:Patient Admission
D057216:Propensity Score
D058996:Quality Improvement
D058998:Remote Sensing Technology
D012189:Retrospective Studies
D013997:Time Factors

Remote monitoring
Implantable cardioverter-defibrillator
Heart failure
Cardioversor-desfibrilhador implantável
Insuficiência cardíaca
Monitorização remota


Association of overweight and obesity with cardiovascular risk factors in patients with atherosclerotic diseases.

Abstract:
Background
The aim of this study was to compare demographic, clinical and biochemical characteristics, including inflammatory markers, according to the nutritional status of patients with verified atherosclerotic disease.

Methods
This cross-sectional study involved 1045 consecutive patients with verified carotid disease or peripheral arterial disease (PAD). Anthropometric parameters and data on cardiovascular risk factors and therapy for hypertension and hyperlipidemia were collected for all participants.

Results
Carotid disease was positively and PAD was negatively associated with body mass index (BMI). Negative association between obesity and PAD was significant only in former smokers, not in current smokers or in patients who never smoked. Overweight and general obesity were significantly related to metabolic syndrome (p < 0.001), lower values of high - density lipoprotein cholesterol (p < 0.001), increased triglycerides (p < 0.001), hyperglycemia (p < 0.001), self-reported diabetes (p < 0.001), hypertension (p < 0.001), high serum uric acid (p < 0.001), increased high sensitivity C-reactive protein (p = 0.020) and former smoking (p = 0.005) after adjustment for age, gender and type of disease. Antihypertensive therapy seems to be less effective in patients who are overweight and obese.

Conclusions
In conclusion, overweight and general obesity were significantly related to several cardiovascular risk factors.

Maksimovic|Milos|M| Vlajinac|Hristina|H| Radak|Djordje|D| Marinkovic|Jelena|J| Maksimovic|Jadranka|J| Jorga|Jagoda|J|

obesity
risk factors
carotid disease
peripheral arterial disease
atherosclerosis


Circumpolar contamination in eggs of the high-Arctic ivory gull Pagophila eburnea.

Abstract: The ivory gull Pagophila eburnea is a high-Arctic species threatened by climate change and contaminants. The objective of the present study was to assess spatial variation of contaminant levels (organochlorines [OCs], brominated flame retardants [BFRs], perfluorinated alkyl substances [PFASs], and mercury [Hg]) in ivory gulls breeding in different areas across the Arctic region as a baseline for potential future changes associated with climate change. Contaminants were already determined in eggs from Canada (Seymour Island; except PFASs), Svalbard in Norway (Svenskøya), and 3 sites in Russia (Nagurskoe, Cape Klyuv, and Domashny). New data from Greenland allowed the investigation of a possible longitudinal gradient of contamination. The most quantitatively abundant OCs were p,p'-dichlorodiphenyldichloroethylene (DDE) and polychlorobiphenyls. Mercury concentrations were higher in Canada compared with other colonies. Eggs from Nagurskoe often were characterized by higher OC and BFR concentrations. Concentrations gradually decreased in colonies situated east of Nagurskoe. In contrast, PFAS concentrations, especially perfluorooctanoate and perfluorononanoate, were higher in Greenland. Some of the contaminants, especially Hg and p,p'-DDE, exceeded published thresholds known to disrupt the reproductive success of avian species. Overall, the levels of OCs, BFRs, and PFASs did not suggest direct lethal exposure to these compounds, but their potential synergetic/additive sublethal effects warrant monitoring.

Lucia|Magali|M|
Verboven|Nanette|N|
Strøm|Hallvard|H|
Miljeteig|Cecilie|C|
Gavrilo|Maria V|MV|
Braune|Birgit M|BM|
Boertmann|David|D|
Gabrielsen|Geir W|GW|

D002851:Chromatography, High Pressure Liquid

Ivory gull
Perfluorinated alkyl substances
Arctic
Persistent organic pollutants


Dyspnea in Amyotrophic Lateral Sclerosis: Rasch-Based Development and Validation of a Patient-Reported Outcome (DALS-15).

Abstract:
CONTEXT
Dyspnea is a cardinal but often underestimated symptom in amyotrophic lateral sclerosis (ALS). The lack of a satisfying assessment tool leads to diagnostic uncertainty and bears the risk that established life-prolonging and symptom-relieving therapeutic options will not be adequately applied.

OBJECTIVES
The objective of this study was to develop and validate a German language disease-specific patient-reported outcome measure to assess dyspnea in ALS by combination of a qualitative and quantitative approach using Rasch analysis.

METHODS
Based on input from clinical experts and patients, a preliminary 35-item questionnaire was developed and completed by 94 patients with ALS having dyspnea. Data were subjected to Rasch analysis and tested for required measurement issues such as appropriate response categories, the absence of differential item functioning, local independence, and unidimensionality.

RESULTS
After iterative Rasch analyses, the final 15-item Dyspnea-ALS-Scale (DALS-15) was obtained. The scale satisfies the axioms of the Rasch model with good fit statistics, the absence of local dependency, and differential item functioning as well as acceptable unidimensionality. The DALS-15 is optimally targeted and suitable for group and individual use. It shows excellent test-retest reliability and convergent validity.

CONCLUSION
The DALS-15 satisfies strictest modern measurement criteria and has interval scale properties. It fills an important gap in assessment and could be most helpful to optimize symptom management in patients with ALS.

Vogt|Susanne|S| Petri|Susanne|S| Dengler|Reinhard|R| Heinze|Hans-Jochen|HJ| Vielhaber|Stefan|S|

D000071066:Patient Reported Outcome Measures

dyspnea
Amyotrophic lateral sclerosis
assessment
patient-reported outcome measure
Rasch analysis
motor neuron disease


m6A Reader: Epitranscriptome Target Prediction and Functional Characterization of N 6-Methyladenosine (m6A) Readers.

Abstract: N 6-methyladenosine (m6A) is the most abundant post-transcriptional modification in mRNA, and regulates critical biological functions via m6A reader proteins that bind to m6A-containing transcripts. There exist multiple m6A reader proteins in the human genome, but their respective binding specificity and functional relevance under different biological contexts are not yet fully understood due to the limitation of experimental approaches. An in silico study was devised to unveil the target specificity and regulatory functions of different m6A readers. We established a support vector machine-based computational framework to predict the epitranscriptome-wide targets of six m6A reader proteins (YTHDF1-3, YTHDC1-2, and EIF3A) based on 58 genomic features as well as the conventional sequence-derived features. Our model achieved an average AUC of 0.981 and 0.893 under the full-transcript and mature mRNA model, respectively, marking a substantial improvement in accuracy compared to the sequence encoding schemes tested. Additionally, the distinct biological characteristics of each individual m6A reader were explored via the distribution, conservation, Gene Ontology enrichment, cellular components and molecular functions of their target m6A sites. A web server was constructed for predicting the putative binding readers of m6A sites to serve the research community, and is freely accessible at: http://m6areader.rnamd.com.

Zhen|Di|D| Wu|Yuxuan|Y| Zhang|Yuxin|Y| Chen|Kunqi|K| Song|Bowen|B| Xu|Haiqi|H| Tang|Yujiao|Y| Wei|Zhen|Z| Meng|Jia|J|


CO ameliorates endothelial senescence induced by 5-fluorouracil through SIRT1 activation.

Abstract: Endothelial senescence is the main risk factor that contributes to vascular dysfunction and the progression of vascular disease. Carbon monoxide (CO) plays an important role in preventing vascular dysfunction and in maintaining vascular physiology or homeostasis. The application of exogenous CO has been shown to confer protection in several models of cardiovascular injury or disease, including hypertension, atherosclerosis, balloon-catheter injury, and graft rejection. However, the mechanism by which CO prevents endothelial senescence has been largely unexplored. The aim of this study was to evaluate the effects of CO on endothelial senescence and to investigate the possible mechanisms underlying this process. We measured the levels of senescence-associated-β-galactosidase activity, senescence-associated secretory phenotype, reactive oxygen species (ROS) production, and stress granule in human umbilical vein endothelial cells and the WI-38 human diploid fibroblast cell line. We found that 5-fluorouracil (5FU)-induced ROS generation was inhibited by CO-releasing molecules (CORM)-A1 treatment, and endothelial senescence induced by 5FU was attenuated by CORM-A1 treatment. The SIRT1 inhibitor EX527 reversed the inhibitory effect of CO on the 5FU-induced endothelial senescence. Furthermore, SIRT1 deficiency abolished the stress granule formation by CO. Our results suggest that CO alleviates the endothelial senescence induced by 5FU through SIRT1 activation and may hence have therapeutic potential for the treatment of vascular diseases.

Zheng|Min|M|
Chen|Yubing|Y|
Park|Jeongmin|J|
Song|Hyun-Chul|HC|
Chen|Yingqing|Y|
Park|Jeong Woo|JW|
Joe|Yeonsoo|Y|
Chung|Hun Taeg|HT|

D061307:Human Umbilical Vein Endothelial Cells


ORBITAL PSEUDOTUMOR CAN MIMIC GRAVES' OPHTHALMOPATHY.

Abstract:
Context
Orbital pseudotumor (OP) is a benign inflammatory process of the orbit with a large polymorphous lymphoid infiltrate, associated with fibrosis in variable amounts, localized or diffuse. Graves' ophthalmopathy (GO) is the most common cause of proptosis, unilateral or bilateral.

Case report
We report a patient with unilateral proptosis who was initially treated with antithyroid drugs for an euthyroid Graves disease, but the extension of the investigation infirmed this. The MRI findings (inflammation of fat, muscle and the left lacrimal gland) in conjunction with the biopsy infirmed the initial diagnostic and confirmed the OP.

Conclusions
Orbital pseudotumor is a rare disorder that can image and clinically mimics some inflammatory disease especialy Graves' ophthalmopathy. Orbital MRI represents the most important test for diagnostic. A negative TRAb in euthyroid cases of proptosis can be a serious starting point for investigating an OP.

Stanciu|M|M|
Popa|F L|FL|
Totoian|I G|IG|
Bera|L G|LG|

orbital pseudotumor
MRI
TRAb
Graves’ ophtalmopathy
differential diagnosis


Improvement of the performance of simultaneous nitrification denitrification and phosphorus removal (SNDPR) system by nitrite stress.

Abstract: This study investigated a new way to improve the performance of simultaneous nitrification denitrification and phosphorus removal (SNDPR) system by regularly changing the anaerobic/micro-aerobic/anoxic mode to the anaerobic/anoxic mode with 30 mg/L of nitrite dosing. The results indicated that the removal efficiency of total inorganic nitrogen and PO43--P was improved from 75.44% and 85.14% to 98.89% and 98.17%, respectively. And the good performance of the SNDPR showed a long-time sustainability when the C/N ratio was 5. The results of microbial community illustrated that the abundance of the main nitrite-oxidizing bacteria (NOB), Nitrospira sp., dropped from 5.71% to 0.85% and the abundance of denitrifying polyphosphate-accumulating organisms (DPAOs), Pseudomonas sp. and Acinetobacter sp., increased by 5 times after nitrite stress. The high level of nitric oxide (NO) and free nitrite acid produced by addition of nitrite strongly suppressed the undesired organisms NOB and ordinary heterotrophic denitrifying organisms, and promoted the enrichment of DPAOs. The NO accumulated in the nitrite denitrification process could inhibit NOB and promote AOB. This study revealed that NO plays an important role in regulating the microbial community in the SNDPR system.

Xie|Shuting|S| Zhao|Jianqiang|J| Zhang|Qianqian|Q| Zhao|Junkai|J| Lei|Shuhan|S| Ma|Xiaoqing|X| Yan|Chunxiao|C|

Simultaneous nitrification denitrification and phosphorus removal (SNDPR)


Utilization of causal reasoning of hepatic gene expression in rats to identify molecular pathways of idiosyncratic drug-induced liver injury.

Abstract: Drug-induced liver injury (DILI) represents a leading cause of acute liver failure. Although DILI can be discovered in preclinical animal toxicology studies and/or early clinical trials, some human DILI reactions, termed idiosyncratic DILI (IDILI), are less predictable, occur in a small number of individuals, and do not follow a clear dose-response relationship. The emergence of IDILI poses a critical health challenge for patients and a financial challenge for the pharmaceutical industry. Understanding the cellular and molecular mechanisms underlying IDILI is key to the development of models that can assess potential IDILI risk. This study used Reverse Causal Reasoning (RCR), a method to assess activation of molecular signaling pathways, on gene expression data from rats treated with IDILI or pharmacologic/chemical comparators (NON-DILI) at the maximum tolerated dose to identify mechanistic pathways underlying IDILI. Detailed molecular networks involved in mitochondrial injury, inflammation, and endoplasmic reticulum (ER) stress were found in response to IDILI drugs but not negative controls (NON-DILI). In vitro assays assessing mitochondrial or ER function confirmed the effect of IDILI compounds on these systems. Together our work suggests that using gene expression data can aid in understanding mechanisms underlying IDILI and can guide in vitro screening for IDILI. Specifically, RCR should be considered for compounds that do not show evidence of DILI in preclinical animal studies positive for mitochondrial dysfunction and ER stress assays, especially when the therapeutic index toward projected human maximum drug plasma concentration is low.

Laifenfeld|Daphna|D|
Qiu|Luping|L|
Swiss|Rachel|R|
Park|Jennifer|J|
Macoritto|Michael|M|
Will|Yvonne|Y|
Younis|Husam S|HS|
Lawton|Michael|M|

D056486:Chemical and Drug Induced Liver Injury

liver
biological modeling
risk assessment
safety evaluation
systems biology
systems toxicology.
toxicogenomics


Reduction of radiation and contrast agent exposure in a cryoballoon ablation procedure with integration of electromagnetic mapping and intracardiac echocardiography: a single center experience.

Abstract:
BACKGROUND
Pulmonary vein isolation (PVI) with cryoballoon ablation (CBA) is routinely guided by fluoroscopy and utilizes contrast injection to ensure catheter positioning and pulmonary vein occlusion. Non-fluoroscopic imaging techniques including electromagnetic mapping (EM) and intracardiac echocardiography (ICE) have demonstrated reduced fluoroscopy times and contrast exposure. Utilization of color flow Doppler to evaluate vein occlusion with the balloon has not been evaluated as an alternative to contrast injection. In this study we evaluate the effectiveness of cryoablation guided by EM and ICE along with color Doppler to achieve PVI.

METHODS
We designed a retrospective cohort study comparing patients who were treated before and after implementation of EM (Carto 3, Biosense Webster) and ICE during CBA (AF Solutions, Medtronic). We analyzed patients receiving CBA with fluoroscopy plus EM and ICE (group 2; N = 24) versus fluoroscopy alone (group 1; N = 25). Procedural success was defined as freedom from atrial fibrillation or other atrial arrhythmias at 1 year post ablation. Primary outcomes were radiation time and contrast exposure.

RESULTS
Procedural success was achieved in all cases. Total fluoroscopy time was reduced from 22.4 ± 9.8 min to 8.9 ± 5.1 min (P < 0.001) in patients receiving CBA guided by EM and ICE. Furthermore, exposure to contrast media was significantly lower at 75.4 ± 24.1 ml and 16.5 ± 21.1 ml (P ≤ 0.001) in group 1 and group 2, respectively. Neither the number of required cryotherapy treatments nor procedure duration was negatively impacted by the implementation of non-fluoroscopic techniques. The 1-year success rate was identical between both groups at 72% and 79%. There was no difference in complication rates.

CONCLUSION
This single-center cohort study demonstrates that CBA guided by EM and ICE can markedly reduce radiation and contrast exposure with excellent rates of acute PVI. This technique may be particularly effective in patients sensitive to intravenous contrast exposure.

Cryoballoon ablation
Pulmonary vein isolation
Fluoroscopy
Radiation exposure


General Anesthesia Versus Local Anesthesia in Carotid Endarterectomy: A Systematic Review and Meta-Analysis.

Abstract:
OBJECTIVE
The choice of anesthetic technique in carotid endarterectomy (CEA) has been controversial. This study compared the outcomes of general anesthesia (GA) and local anesthesia (LA) in CEA.

DESIGN
Systematic review and meta-analysis of comparative studies.

SETTING
Hospitals.

PARTICIPANTS
Adult patients undergoing CEA with either LA or GA.

INTERVENTIONS
The effects of GA and LA on CEA outcomes were compared.

MEASUREMENTS AND MAIN RESULTS
PubMed, OVID, Scopus, and Embase were searched to June 2018. Thirty-one studies with 152,376 patients were analyzed. A random effect model was used, and heterogeneity was assessed with the I2 and chi-square tests. LA was associated with shorter surgical time (weighted mean difference -9.15 min [-15.55 to -2.75]; p = 0.005) and less stroke (odds ratio [OR] 0.76 [0.62-0.92]; p = 0.006), cardiac complications (OR 0.59 [0.47-0.73]; p < 0.00001), and in-hospital mortality (OR 0.72 [0.59-0.90]; p = 0.003). Transient neurologic deficit rates were similar (OR 0.69 [0.46-1.04]; p = 0.07). Heterogeneity was significant for surgical time (I2 = 0.99, chi-square = 1,336.04; p < 0.00001), transient neurologic deficit (I2 = 0.41, chi-square = 28.81; p = 0.04), and cardiac complications (I2 = 0.42, chi-square = 43.32; p = 0.01) but not for stroke (I2 = 0.22, chi-square = 30.72; p = 0.16) and mortality (I2 = 0.00, chi-square = 21.69; p = 0.65). Randomized controlled trial subgroup analysis was performed, and all the aforementioned variables were not significantly different or heterogenous.

CONCLUSION
The results from this study showed no inferiority of using LA to GA in patients undergoing CEA. Future investigations should be reported more systematically, preferably with randomization or propensity-matched analysis, and thus registries will facilitate investigation of this subject. Anesthetic choice in CEA should be individualized and encouraged where applicable.

Harky|Amer|A|
Chan|Jeffrey Shi Kai|JSK|
Kot|Thompson Ka Ming|TKM|
Sanli|Dilan|D|
Rahimli|Rashad|R|
Belamaric|Zlatka|Z|
Ng|Marcus|M|
Kwan|Ian Yu Young|IYY|
Bithas|Christiana|C|
Makar|Ragai|R|
Chandrasekar|Ramasubramanyan|R|
Dimitri|Sameh|S|

D000328:Adult
D000768:Anesthesia, General
D000772:Anesthesia, Local
D016893:Carotid Stenosis
D016894:Endarterectomy, Carotid
D006801:Humans
D012307:Risk Factors
D020521:Stroke
D016896:Treatment Outcome

general anesthesia
local anesthesia
carotid endarterectomy
anesthetic technique


Association between left ventricular function and paraprotein type in patients with multiple myeloma.

Abstract:
BACKGROUND/AIMS
Multiple myeloma (MM)-associated cardiac damage, particularly according to the type of monoclonal (M) protein has not been elucidated. We sought to investigate relationship between elevated serum M protein levels and echocardiographic indices of cardiac structure and function in patients with MM.

METHODS
We evaluated a total of 184 consecutive MM patients who underwent echocardiography for bone marrow pre-transplant screening. Serum levels of intact immunoglobulin M protein and free light chain kappa/lambda (FLC-κ/-λ) were measured.

RESULTS
One hundred thirty-nine patients were non-light chain MM (non-LCMM) and 45 patients belonged to LCMM. In patients with non-LCMM, significant correlations were found between serum M protein and left atrial volume index (LAVi; r = 0.720, p < 0.0001), E/e' (r = 0.511, p < 0.0001), and systolic pulmonary arterial pressure (r = 0.485, p < 0.0001). In patients with LCMM, log-transformed FLC-λ (log-λ) was correlated with left ventricular ejection fraction (LVEF, r = -0.536, p = 0.010), left ventricular (LV) end-systolic dimension (r = 0.500, p = 0.018), and LV end-systolic volume (r = 0.444, p = 0.038). On multivariate analyses, hematocrit and serum M protein were independent predictors of LAVi in patients with non-LCMM. In patient with LCMM, FLC-λ isotype was only found to be an independent determinant of LVEF.

CONCLUSIONS
An increase in serum M protein was associated with LV diastolic dysfunction, whereas an increase in serum FLC-λ concentration showed a negative correlation with the echocardiographic parameters of LV systolic function. These findings also suggest that serum M protein has different effects on LV function according to the type of paraproteins in patients with MM.

Yi|Jeong-Eun|JE| Lee|Sung-Eun|SE| Jung|Hae-Ok|HO| Min|Chang-Ki|CK| Youn|Ho-Joong|HJ|

Multiple myeloma
Serum monoclonal paraprotein
Ventricular function, left


A de novo CTNNB1 nonsense mutation associated with syndromic atypical hyperekplexia, microcephaly and intellectual disability: a case report.

Abstract:
BACKGROUND
In addition to its role in cell adhesion and gene expression in the canonical Wingless/integrated Wnt signaling pathway, β-catenin also regulates genes that underlie the transmission of nerve impulses. Mutations of CTNNB1 (β-catenin) have recently been described in patients with a wide range of neurodevelopmental disorders (intellectual disability, microcephaly and other syndromic features). We for the first time associate CTNNB1 mutation with hyperekplexia identifying it as an additional candidate for consideration in patients with startle syndrome.

CASE PRESENTATION
We describe an 11 year old male Polish patient with a de novo nonsense mutation in CTNNB1 who in addition to the major features of CTNNB1-related syndrome including intellectual disability and microcephaly, exhibited hyperekplexia and apraxia of upward gaze. The patient became symptomatic at the age of 20 months exhibiting delayed speech and psychomotor development. Social and emotional development was normal but mild hyperactivity was noted. Episodic falls when startled by noise or touch were observed from the age of 8.5 years, progressively increasing but never with loss of consciousness. Targeted gene panel next generation sequencing (NGS) and patient-parents trio analysis revealed a heterozygous de novo nonsense mutation in exon 3 of CTNNB1 identifying a novel association of β-catenin with hyperekplexia.

CONCLUSION
We report for the first time a clear association of mutation in CTNNB1 with an atypical syndromic heperekplexia expanding the phenotype of CTNNB1-related syndrome. Consequently CTNNB1 should be added to the growing list of genes to be considered as a cause of startle disease or syndromic hyperekplexia.

Winczewska-Wiktor|Anna|A|
Badura-Stronka|Magdalena|M|
Monies-Nowicka|Anna|A|
Nowicki|Michal Maciej|MM|
Steinborn|Barbara|B|
Latos-Bieleńska|Anna|A|
Monies|Dorota|D|

Hyperekplexia
Microcephaly
Intellectual disability
β-catenin