Analysis of corn and sorghum flour mixtures using laser-induced breakdown spectroscopy.

Abstract:
BACKGROUND
In a world constantly challenged by climate change, corn and sorghum are two important grains because of their high productivity and adaptability, and their multifunctional use for different purposes such as human food, animal feed, and feedstock for many industrial products and biofuels. Corn and sorghum can be utilized interchangeably in certain applications; one grain may be preferred over the other for several reasons. The determination of the composition corn and sorghum flour mixtures may be necessary for economic, regulatory, environmental, functional, or nutritional reasons.

RESULTS
Laser-induced breakdown spectroscopy (LIBS) in combination with chemometrics, was used for the classification of flour samples based on the LIBS spectra of flour types and mixtures using partial least squares discriminant analysis (PLS-DA) and the determination of the sorghum ratio in sorghum / corn flour mixture based on their elemental composition using partial least squares (PLS) regression. Laser-induced breakdown spectroscopy with PLS-DA successfully identified the samples as either pure corn, pure sorghum, or corn-sorghum mixtures. Moreover, the addition of various levels of sorghum flour to mixtures of corn-sorghum flour were used for PLS analysis. The coefficient of determination values of calibration and validation PLS models are 0.979 and 0.965, respectively. The limit of detection of the PLS models is 4.36%.

CONCLUSION
This study offers a rapid method for the determination of the sorghum level in corn-sorghum flour mixtures and the classification of flour samples with high accuracy, a short analysis time, and no requirement for time-consuming sample preparation procedures. © 2020 Society of Chemical Industry.

D016002:Discriminant Analysis
D005433:Flour
D005504:Food Analysis
D005506:Food Contamination
D028321:Plant Preparations
D045868:Sorghum
D013057:Spectrum Analysis
D003313:Zea mays


High-dose infliximab therapy in Crohn's disease: clinical experience, safety, and efficacy.

Abstract:
BACKGROUND
Inadequate response to infliximab [IFX] therapy in Crohn's disease [CD] may necessitate dose intensification. We evaluated safety and efficacy of high-dose IFX [HD IFX] [greater than 10mg/kg every 8 weeks] in CD and characterized predictors of response to HD IFX intensification.

METHODS
Electronic medical records were queried for CD patients between 2010 and 2012 who received HD IFX and were reviewed for history, medications, laboratory data, efficacy, and safety.

RESULTS
In all, 86 patients received HD IFX for CD at doses between 10 and 22.5mg/kg every 4 to 7 weeks. In early HD IFX therapy [week 1-16], 25.8% and 59.1% experienced full and partial response, respectively. In later HD IFX therapy [week 38-100], 27.9% and 34.4% experienced full and partial response, respectively. Median serum IFX levels increased from 1.7 to 7.3 µ/mL [p = 0.017], and median C-reactive protein [CRP] values decreased from 20.5 at baseline to 4.7 mg/L after 16 weeks [p < 0.001]. Baseline CRP values were significantly elevated in the group that responded at 1-16 weeks compared with nonresponders [22.0 vs 3.5mg/L, p < 0.01]. HD IFX therapy was discontinued in 26% and 7.3% of patients for inadequate response and adverse events, respectively. Eleven cases of infection required hospitalization for a serious infection rate of 7.41 events per 100 patient-years.

CONCLUSIONS
HD IFX therapy may benefit CD patients who have failed standard doses of IFX. HD IFX therapy may be associated with more serious adverse events compared with standard dosing. Baseline CRP value may predict clinical response to HD IFX.

Hendler|Steven A|SA|
Cohen|Benjamin L|BL|
Colombel|Jean-Frédéric|JF|
Sands|Bruce E|BE|
Mayer|Lloyd|L|
Agarwal|Shradha|S|

infliximab
dose intensification
Crohn’s disease
anti-TNF
biologic therapy
loss of response


Turning the Page on Pen-and-Paper Questionnaires: Combining Ecological Momentary Assessment and Computer Adaptive Testing to Transform Psychological Assessment in the 21st Century.

Abstract: The current paper describes new opportunities for patient-centred assessment methods which have come about by the increased adoption of affordable smart technologies in biopsychosocial research and medical care. In this commentary, we review modern assessment methods including item response theory (IRT), computer adaptive testing (CAT), and ecological momentary assessment (EMA) and explain how these methods may be combined to improve psychological assessment. We demonstrate both how a 'naïve' selection of a small group of items in an EMA can lead to unacceptably unreliable assessments and how IRT can provide detailed information on the individual information that each item gives thus allowing short form assessments to be selected with acceptable reliability. The combination of CAT and IRT can ensure assessments are precise, efficient, and well targeted to the individual; allowing EMAs to be both brief and accurate.

ecological momentary assessment
computer adaptive testing
item response theory
electronic assessment
patient reported outcomes
rasch analysis


Prediction of Lower Flammability Limits for Binary Hydrocarbon Gases by Quantitative Structure-A Property Relationship Approach.

Abstract: The lower flammability limit (LFL) is one of the most important parameters for evaluating the fire and explosion hazards of flammable gases or vapors. This study proposed quantitative structure-property relationship (QSPR) models to predict the LFL of binary hydrocarbon gases from their molecular structures. Twelve different mixing rules were employed to derive mixture descriptors for describing the structures characteristics of a series of 181 binary hydrocarbon mixtures. Genetic algorithm (GA)-based multiple linear regression (MLR) was used to select the most statistically effective mixture descriptors on the LFL of binary hydrocarbon gases. A total of 12 multilinear models were obtained based on the different mathematical formulas. The best model, issued from the norm of the molar contribution formula, was achieved as a six-parameter model. The best model was then rigorously validated using multiple strategies and further extensively compared to the previously published model. The results demonstrated the robustness, validity, and satisfactory predictivity of the proposed model. The applicability domain (AD) of the model was defined as well. The proposed best model would be expected to present an alternative to predict the LFL values of existing or new binary hydrocarbon gases, and provide some guidance for prioritizing the design of safer blended gases with desired properties.

Pan|Yong|Y| Ji|Xianke|X| Ding|Li|L| Jiang|Juncheng|J|

quantitative structure–property relationship (QSPR)


Genetic polymorphisms in the microRNA binding-sites of the thymidylate synthase gene predict risk and survival in gastric cancer.

Abstract: Thymidylate synthase (TYMS) plays a crucial role in folate metabolism as well as DNA synthesis and repair. We hypothesized that functional polymorphisms in the 3' UTR of TYMS are associated with gastric cancer risk and survival. In the present study, we tested our hypothesis by genotyping three potentially functional (at miRNA binding sites) TYMS SNPs (rs16430 6bp del/ins, rs2790 A>G and rs1059394 C>T) in 379 gastric cancer patients and 431 cancer-free controls. Compared with the rs16430 6bp/6bp + 6bp/0bp genotypes, the 0bp/0bp genotype was associated with significantly increased gastric cancer risk (adjusted OR = 1.72, 95% CI = 1.15-2.58). Similarly, rs2790 GG and rs1059394 TT genotypes were also associated with significantly increased risk (adjusted OR = 2.52, 95% CI = 1.25-5.10 and adjusted OR = 1.57, 95% CI = 1.04-2.35, respectively), compared with AA + AG and CC + CT genotypes, respectively. In the haplotype analysis, the T-G-0bp haplotype was associated with significantly increased gastric cancer risk, compared with the C-A-6bp haplotype (adjusted OR = 1.34, 95% CI = 1.05-1.72). Survival analysis revealed that rs16430 0bp/0bp and rs1059394 TT genotypes were also associated with poor survival in gastric cancer patients who received chemotherapy treatment (adjusted HR = 1.61, 95% CI = 1.05-2.48 and adjusted HR = 1.59, 95% CI = 1.02-2.48, respectively). These results suggest that these three variants in the miRNA binding sites of TYMS may be associated with cancer risk and survival of gastric cancer patients. Larger population studies are warranted to verify these findings.

Shen|Rong|R|
Liu|Hongliang|H|
Wen|Juyi|J|
Liu|Zhensheng|Z|
Wang|Li-E|LE|
Wang|Qiming|Q|
Tan|Dongfeng|D|
Ajani|Jaffer A|JA|
Wei|Qingyi|Q|

D020022:Genetic Predisposition to Disease

polymorphism
microRNA
thymidylate synthase
survival
gastric cancer
genetic susceptibility


Linkage analysis of rice bacterial blight resistance gene xa20 in XM6, a mutant line from IR24.

Abstract: Bacterial blight caused by Xanthomonas oryzae pv. oryzae (Xoo) is an important disease constraining rice (Oryza sativa L.) production worldwide. The XM6 line was induced by N-methyl-N-nitrosourea from IR24, an Indica cultivar that is susceptible to Philippine and Japanese Xoo races. XM6 was confirmed to carry a recessive gene named xa20, resistant to six Philippine and five Japanese Xoo races. The chromosomal gene location was found using 10 plants with the shortest lesion length in an F2 population consisting of 298 plants from a susceptible Japonica variety Koshihikari × XM6. Analysis using PCR-based DNA markers covering the whole rice genome indicated the gene as located on the distal region of the long arm of chromosome 3. The IKC3 line carries IR24 genetic background with Koshihikari fragment on chromosome 3 where a resistance gene was thought to be located. The F2 population from IKC3 × XM6 clearly showed a bimodal distribution separating resistant and susceptible plants. Further linkage analysis conducted using this F2 population revealed that xa20 is located within the 0.8 cM region flanked by DNA markers KIC3-33.88 (33.0 Mb) and KIC3-34.06 (33.2 Mb). This study yields important findings for resistance breeding and for the genetic mechanism of Xoo resistance.

Msami|Jessey Anderson|JA|
Kawaguchi|Yoshiki|Y|
Ichitani|Katsuyuki|K|
Taura|Satoru|S|

Xanthomonas oryzae pv. oryzae
Oryza sativa
DNA marker
mapping
resistance by a recessive gene


The Best Digital Biomarkers Papers of 2017.

Abstract: The use and evaluation of digital biomarkers, objective and quantifiable measures of biology, and health collected through digital devices is growing rapidly. To highlight some of the most promising work in the field, we have compiled a list of the top digital biomarkers papers from the past year. Eligible papers reported on original research that evaluated a digital sensor (e.g., smartphone, wearable sensor, implantable device) in humans and was published in a peer-reviewed journal in 2017. Nominations were solicited from the editorial board of Digital Biomarkers and supplemented by papers the editorial team identified from Web of Science, Google Scholar, and PubMed. The editorial board then selected up to ten papers to be recognized among 28 nominations. Here, we present all of the nominated papers and profile the eight that received the most votes. The top eight papers evaluated 1,290 individuals with digital pills, smartwatches, wearable devices, and electronic inhalers in disease states ranging from dementia to diabetes and from Parkinson disease to pain.

Snyder|Christopher W|CW|
Dorsey|E Ray|ER|
Atreja|Ashish|A|

Wearable sensors
Digital pills
Parkinson disease
Bipolar disorder
Chronic obstructive pulmonary disease
Digital divide
Huntington disease
Hypertension
Mental health
Passive monitoring


Impact of the Everolimus-eluting Bioresorbable Scaffold in Coronary Atherosclerosis.

Abstract:
INTRODUCTION AND OBJECTIVES
The Absorb bioresorbable vascular scaffold has been shown to decrease total plaque areas in the treated segment. However, it is unknown whether plaque size is modified in scaffolded segments only or whether the modification extends to other coronary segments.

METHODS
Absorb Cohort A is a single-arm, prospective study, with safety and imaging endpoints, in which 30 patients underwent percutaneous coronary intervention with the first generation Absorb bioresorbable vascular scaffold. Noninvasive multislice computed tomography imaging was performed in 18 patients at 18 months and 5 years of follow-up. The present study was an intrapatient comparison of matched segments (normalized by the segment length) of the scaffolded region with nonintervened segments for lumen volume, vessel volume, plaque volume, plaque burden, and percent change in plaque atheroma volume.

RESULTS
All 18 scaffolded segments could be analyzed. In the nonintervened segments, 1 of 72 segments had a motion artifact and was excluded. Serial comparison showed that the scaffolded segments showed no significant change in the mean plaque burden, total atheroma volume, total lumen volume, or vessel volume between 18 months and 5 years. Conversely, the untreated segments showed a significant increase in plaque burden (2.7 ± 6.5%; P < .01) and normalized plaque volumes (8.0 ± 22.8mm(3); P < .01). This resulted in a significant difference in plaque burden between scaffolded and nonintervened segments (P = .03).

CONCLUSIONS
In this small series, the Absorb bioresorbable vascular scaffold showed the potential to provide an additional benefit to pharmacological therapy in locally reducing progression of percent plaque burden. These findings need to be confirmed in larger studies.

Campos|Carlos M|CM|
Garcia-Garcia|Hector M|HM|
Muramatsu|Takashi|T|
de Araujo Gonçalves|Pedro|P|
Onuma|Yoshinobu|Y|
Dudek|Dariusz|D|
Thuesen|Leif|L|
Webster|Mark W I|MW|
Kitslaar|Pieter|P|
Veldhof|Susan|S|
Reiber|Johan H C|JH|
Nieman|Koen|K|
Ormiston|John A|JA|
Serruys|Patrick W|PW|

Angiografía coronaria con tomografía computarizada

Computed tomography coronary angiography


Integrated analysis of differentially expressed long noncoding RNAs and mRNAs associated with high-fat diet-induced hepatic insulin resistance in mice.

Abstract:
Background
Hepatic insulin resistance (IR) is an early pathological characteristic of many metabolic diseases, such as type 2 diabetes. Long noncoding RNAs (lncRNAs) have been identified as mediators of IR and related diseases. However, the roles of lncRNAs in hepatic IR remain largely unknown.

Method
High-throughput sequencing was performed on ten liver tissue samples from five normal diet (ND)-fed mice and five high-fat diet (HFD)-induced hepatic IR mice, respectively. lncRNAs and mRNAs that were differentially expressed (DE) between the two groups were identified by bioinformatic analyses. Seven DE lncRNAs were validated by quantitative real-time PCR (q-PCR). The potential functions of the DE lncRNAs were predicted by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses of target genes. In addition, integrated analysis was performed for the DE lncRNAs and mRNAs to predict their interaction relationships.

Results
A total of 232 DE lncRNAs were identified in the HFD-induced hepatic IR mice compared with the ND-fed mice. These DE lncRNAs included 108 upregulated and 124 downregulated lncRNAs, and 7 of the DE lncRNAs were validated by q-PCR. In addition, 291 DE mRNAs including 166 upregulated and 125 downregulated mRNAs were identified in the HFD group. Furthermore, target genes of the DE lncRNAs were predicted, and functional enrichment results showed that the enriched genes were involved in IR- and glycolipid metabolism-related processes. Additionally, the coexpression network was also constructed to further reflect the potential functions of the DE lncRNAs.

Conclusion
The study describes the expression profiles of lncRNAs and mRNAs and the functional networks involved in HFD-induced hepatic IR. These findings may provide a new perspective for the study of lncRNAs in hepatic IR- and glycolipid metabolism-related diseases.

Zhou|Zengyuan|Z|0000-0001-7216-3165 Zhao|Xue|X| Chen|Liang|L| Li|Yuzheng|Y| Chen|Zhao|Z| Wang|Yuanyuan|Y| Zhou|Zihao|Z| Chu|Xia|X|

Long noncoding RNAs
Hepatic insulin resistance
High-throughput sequencing


Nephroblastoma overexpressed gene (NOV) enhances RCC cell motility through upregulation of ICAM-1 and COX-2 expression via Akt pathway.

Abstract: Renal cell carcinoma (RCC) carries a high risk of malignancy and metastasis. The inducible isoform of prostaglandin synthase, cyclooxygenase (COX)-2, and ICAM-1 may be involved in tumor metastasis. CCN3, also called nephroblastoma overexpressed gene (NOV), has been found to regulate the proliferation and differentiation of cancer cells. The effects of NOV on RCC cell migration and expression of COX-2 and ICAM-1 have not described yet in detail. But here, NOV was found to promote the migration and expression of COX-2 and ICAM-1 in human RCC cells. Akt inhibitor was found to interfere with this NOV-induced migration and up-regulation of COX-2 and ICAM-1 in RCC cells. NOV stimulation was here found to promote the phosphorylation of Akt. RCC tissue chips were subjected to IHC staining, which showed COX-2 expression in RCC tissues to be a significantly closely correlated with NOV expression, with significance determined using Pearson correlation testing (P < 0.05). The results of the current work indicate that NOV activates COX-2 and ICAM-1 through Akt, promoting the migration of RCC cells.

Liu|Shuai|S| Han|Liping|L| Wang|Xiaoqing|X| Liu|Zheng|Z| Ding|Sentai|S| Lu|Jiaju|J| Bi|Dongbin|D| Mei|Yikun|Y| Niu|Zhihong|Z|

D015972:Gene Expression Regulation, Neoplastic

NOV
cell motility
ICAM-1
COX-2
akt pathway
renal cell carcinoma


Borderline personality disorder, trauma, and the hypothalamus-pituitary-adrenal axis.

Abstract: Borderline personality disorder (BPD) is a complex psychiatric illness for which treatment poses a significant challenge due to limited effective pharmacologic treatments, and under-resourced psychological interventions. BPD is one of the most stigmatized conditions in psychiatry today, but can be understood as a modifiable, neurodevelopmental disorder that arises from maladaptive responses to trauma and stress. Stress susceptibility and reactivity in BPD is thought to mediate both the development and maintenance of BPD symptomatology, with trauma exposure considered an early life risk factor of development, and acute stress moderating symptom trajectory. An altered stress response has been characterized in BPD at the structural, neural, and neurobiological level, and is believed to underlie the maladaptive behavioral and cognitive symptomatology presented in BPD. The endocrine hypothalamus-pituitary-adrenal (HPA) axis represents a key stress response system, and growing evidence suggests it is dysfunctional in the BPD patient population. This theoretical review examines BPD in the context of a neurodevelopmental stress-related disorder, providing an overview of measurements of stress with a focus on HPA-axis measurement. Potential confounding factors associated with measurement of the HPA system are discussed, including sex and sex hormones, genetic factors, and the influence of sample collection methods. HPA-axis dysfunction in BPD largely mirrors findings demonstrated in post-traumatic stress disorder and may represent a valuable neuroendocrine target for diagnostic or treatment response biomarkers, or for which novel treatments can be investigated.

borderline personality disorder
trauma
stress
hypothalamus–pituitary–adrenal axis


Combination of Endoglin and ASCVD Risk Assessment Improves Carotid Subclinical Atherosclerosis Recognition.

Abstract:
AIM
Our study investigated the association between soluble endoglin and carotid subclinical atherosclerosis.

METHODS
We used endoglin as an adjunct to atherosclerotic cardiovascular disease (ASCVD) risk, in recognition of carotid clinical atherosclerosis, in order to explore a new model to refine risk assessment. Out of 3,452 participants, 978 subjects with detected soluble endoglin were enrolled in a cross-sectional investigation in Fujian Province were enrolled. Soluble endoglin concentration in serum samples was evaluated using an enzyme-linked immunosorbent assay method. Carotid ultrasonography was used to detect intima-media thickness and carotid plaque.

RESULTS
The mean 10-year ASCVD risk by the new Pooled Cohort Equations accounted for 10.04% (±12.35). The mean soluble endoglin level was 15.35 ng/ml (±6.64). Multivariable regression demonstrated that age, systolic blood pressure, diastolic blood pressure, total cholesterol, high density lipoprotein cholesterol, and serum uric acid were independent determinants of soluble endoglin. Adding tests of ASCVD and endoglin together, in parallel, will increase the sensitivity and decrease specificity in recognizing carotid subclinical atherosclerosis. Evaluating the added value of endoglin to the ASCVD risk model showed significantly improved discrimination with analysis of C-statistics, continuous net reclassification index and integrated discrimination index. Both ASCVD risk and soluble endoglin showed positively linear correlation with carotid intima-media thickness (cIMT) (β=0.006, P＜0.001; β=0.485, P＜0.001). Even with adjustment for other factors, the relationship between log-transformed soluble endoglin with cIMT was still significant (β=0.369, P＜0.001).

CONCLUSIONS
The combination of ASCVD risk and endoglin levels increases carotid atherosclerosis recognition.

Li|Qiaowei|Q| Lin|Fan|F| Ke|Douli|D| Cheng|Qiong|Q| Gui|Yongzhi|Y| Zhou|Yuyan|Y| Wu|Yicheng|Y| Wang|Yinzhou|Y| Zhu|Pengli|P|

Endoglin
Carotid subclinical atherosclerosis
Cardiovascular disease risk factors


Ophiodiaporthe cyatheae gen. et sp. nov., a diaporthalean pathogen causing a devastating wilt disease of Cyathea lepifera in Taiwan.

Abstract: The scaly tree fern, Cyathea lepifera, in Taiwan has been devastated by an ascomycetous pathogen in recent years. This fungus resembles species of Diaporthe, but unlike anamorphs of Diaporthe that produce two types of conidia, its anamorph produces one conidium type. It is described herein as Ophiodiaporthe cyatheae gen. et sp. nov. Through pathogenicity tests, O. cyatheae was demonstrated to be the causal agent of the C. lepifera wilt disease. Of interest, sporulating structures of O. cyatheae have not been found on C. lepifera plants but in culture thus far. The mating system is homothallic. Phylogenetic analyses based on combined sequences of nSSU-rDNA, nLSU-rDNA, EF1-α-1 and RPB2 placed O. cyatheae in Diaporthaceae. Combined sequences of EF1-α-2 and TUB indicated that O. cyatheae had its origin within Diaporthe.

Fu|Chuen-Hsu|CH| Hsieh|Huei-Mei|HM| Chen|Chi-Yu|CY| Chang|Tun-Tschu|TT| Huang|Yao-Moan|YM| Ju|Yu-Ming|YM|

pathogen
scaly tree fern
Diaporthaceae
Ascomycota
Diaporthales
systematics


Building skill in heart failure self-care among community dwelling older adults: results of a pilot study.

Abstract:
OBJECTIVE
Most of the day-to-day care for heart failure (HF) is done by the patient at home and requires skill in self-care. In this randomized controlled trial (RCT) we tested the efficacy of a community-based skill-building intervention on HF self-care, knowledge and health-related quality of life (HRQL) at 1- and 3-months.

METHODS
An ethnically diverse sample (n=75) of patients with HF (53% female; 32% Hispanic, 27% Black; mean age 69.9±10 years) was randomized to the intervention group (IG) or a wait-list control group (CG). The protocol intervention focused on tactical and situational HF self-care skill development delivered by lay health educators in community senior centers. Data were analyzed using mixed (between-within subjects) ANOVA.

RESULTS
There was a significant improvement in self-care maintenance [F(2,47)=3.42, p=.04, (Cohen's f=.38)], self-care management [F(2,41)=4.10, p=.02, (Cohen's f=.45) and HF knowledge [F(2,53)=8.00, p=.001 (Cohen's f=.54)] in the IG compared to the CG.

CONCLUSIONS
The skill-building intervention improved self-care and knowledge but not HRQL in this community-dwelling sample.

PRACTICE IMPLICATIONS
Delivering an intervention in a community setting using lay health educators provides an alternative to clinic- or home-based teaching that may be useful across diverse populations and geographically varied settings.

Dickson|Victoria Vaughan|VV|
Melkus|Gail D'Eramo|GD|
Katz|Stuart|S|
Levine-Wong|Alissa|A|
Dillworth|Judy|J|
Cleland|Charles M|CM|
Riegel|Barbara|B|

D007722:Health Knowledge, Attitudes, Practice

Heart failure
Self-care
Health educators
Symptom monitoring decision-making
Treatment adherence


Using a Modified Theory of Planned Behavior to Examine Adolescents' Workplace Safety and Health Knowledge, Perceptions, and Behavioral Intention: A Structural Equation Modeling Approach.

Abstract: Work, a defining feature of adolescence in the United States, has many benefits. Work also has risks, as adolescents experience a higher rate of serious job-related injuries compared to adults. Talking Safety, a free curriculum from the National Institute for Occupational Safety and Health, is one tool educators may adopt to provide teens with essential workplace safety and health education. Adolescents (N = 2503; female, 50.1%; Hispanic, 50.0%) in a large urban school district received Talking Safety from their eighth-grade science teachers. This study used a modified theory of planned behavior (which included a knowledge construct), to examine students' pre- and post-intervention scores on workplace safety and health knowledge, attitude, self-efficacy, and behavioral intention to enact job safety skills. The results from confirmatory factor analyses indicate three unique dimensions reflecting the theory, with a separate knowledge factor. Reliability estimates are ω ≥ .83. The findings from the structural equation models demonstrate that all paths, except pre- to posttest behavioral intention, are statistically significant. Self-efficacy is the largest contributor to the total effect of these associations. As hypothesized, knowledge has indirect effects on behavioral intention. Hispanic students scored lower at posttest on all but the behavioral intention measure, possibly suggesting the need for tailored materials to reach some teens. Overall the findings support the use of a modified theory of planned behavior to evaluate the effectiveness of a foundational workplace safety and health curriculum. This study may inform future efforts to ensure that safe and healthy work becomes integral to the adolescent experience.

Guerin|Rebecca J|RJ|
Toland|Michael D|MD|
Okun|Andrea H|AH|
Rojas-Guyler|Liliana|L|
Bernard|Amy L|AL|

Theory of planned behavior
Adolescents
Structural equation modeling
Occupational safety and health
Injury prevention
Young workers


Provisionally pregnant: uncertainty and interpretive work in accounts of home pregnancy testing.

Abstract: Upon their availability for purchase in the 1970s, home pregnancy testing devices were hailed as a 'revolution' for women's reproductive rights. Some authors, however, have described these technologies as further enabling the medicalisation of pregnancy and as contributing to the devaluing of women's embodied knowledge. The home pregnancy test is one of many technological devices encountered by women experiencing pregnancy in the United Kingdom today. Existing literature has described how engagement with medical technologies during pregnancy might address uncertainties experienced at this time, providing women with reassurance and alleviating anxieties. Drawing on interviews with women living in Scotland, this article explores accounts of testing for a first pregnancy, and women's descriptions of the impacts of home pregnancy testing upon experiences of early gestation. Participants engaged with pregnancy tests in varying ways, with uses shaping and shaped by their experiences of early pregnancy more broadly. Particular technical characteristics of the home pregnancy test led many participants to question their interpretation of a positive result, as well as the accuracy of the test itself. Rather than addressing the unknowns of early gestation by confirming a suspected pregnancy, a positive result could thus exacerbate uncertainty. Through participants' accounts, this article shows how uncertainty is lived out by users of mundane techno-medical artefacts and sheds new light on women's experiences of the first trimester of pregnancy.

uncertainty
home pregnancy test
pregnancy
qualitative research
technological scripts


Hepatitis C virus infection stimulates transforming growth factor-β1 expression through up-regulating miR-192.

Abstract: The objective of this study was to determine the molecular mechanisms underlying chronic liver injury and fibrosis caused by hepatitis C virus (HCV). This study revealed that miR-192 expreßsion was induced by HCV infection without affecting viral replication. However, viral-induced miR-192 up-regulated transforming growth factor-ß1 (TGF-ß1) expreßsion in liver cells at transcriptional level. TGF-ß1 stimulation by HCV-induced miR-192 was caused through ZEB1 down-regulation and TGF-ß1 increased miR-192 level via positive feedback pathway. Increase in miR-192 expreßsion by HCV infection was due to HCV core protein released and/or expressed by viral infection. TGF-ß1 promoter activity was also increased by HCV core protein in liver cells. Taken together, HCV infection resulted in increased TGF-ß1 transcription in hepatocytes through ZEB1 down-regulation by HCV core-mediated miR-192 stimulation. Importantly, miR-192 inhibition with anti-miR-192 rescued ZEB1 expression down-regulated by HCV infection, thus reducing the level of TGF-ß1 expression increased by HCV infection in hepatocytes. These results suggest a novel mechanism of HCV-mediated liver fibrogenesis with miR-192 being a potential molecular target to ameliorate viral pathogenesis.

Kim|Ji Hyun|JH|
Lee|Chang Ho|CH|
Lee|Seong-Wook|SW|

D053773:Transforming Growth Factor beta1

D000071799:Zinc Finger E-box-Binding Homeobox 1


Adaptations in muscle oxidative capacity, fiber size, and oxygen supply capacity after repeated-sprint training in hypoxia combined with chronic hypoxic exposure.

Abstract: In this study, we investigate adaptations in muscle oxidative capacity, fiber size and oxygen supply capacity in team-sport athletes after six repeated-sprint sessions in normobaric hypoxia or normoxia combined with 14 days of chronic normobaric hypoxic exposure. Lowland elite field hockey players resided at simulated altitude (≥14 h/day at 2,800-3,000 m) and performed regular training plus six repeated-sprint sessions in normobaric hypoxia (3,000 m; LHTLH; n = 6) or normoxia (0 m; LHTL; n = 6) or lived at sea level with regular training only (LLTL; n = 6). Muscle biopsies were obtained from the m. vastus lateralis before (pre), immediately after (post-1), and 3 wk after the intervention (post-2). Changes over time between groups were compared, including likelihood of the effect size (ES). Succinate dehydrogenase activity in LHTLH largely increased from pre to post-1 (~35%), likely more than LHTL and LLTL (ESs = large-very large), and remained elevated in LHTLH at post-2 (~12%) vs. LHTL (ESs = moderate-large). Fiber cross-sectional area remained fairly similar in LHTLH from pre to post-1 and post-2 but was increased at post-1 and post-2 in LHTL and LLTL (ES = moderate-large). A unique observation was that LHTLH and LHTL, but not LLTL, improved their combination of fiber size and oxidative capacity. Small-to-moderate differences in oxygen supply capacity (i.e., myoglobin and capillarization) were observed between groups. In conclusion, elite team-sport athletes substantially increased their skeletal muscle oxidative capacity, while maintaining fiber size, after only 14 days of chronic hypoxic residence combined with six repeated-sprint training sessions in hypoxia. NEW & NOTEWORTHY Our novel findings show that elite team-sport athletes were able to substantially increase the skeletal muscle oxidative capacity in type I and II fibers (+37 and +32%, respectively), while maintaining fiber size after only 14 days of chronic hypoxic residence combined with six repeated-sprint sessions in hypoxia. This increase in oxidative capacity was superior to groups performing chronic hypoxic residence with repeated sprints in normoxia and residence at sea level with regular training only.

van der Zwaard|S|S|0000-0002-8296-828X
Brocherie|F|F|
Kom|B L G|BLG|
Millet|G P|GP|0000-0001-8081-4423
Deldicque|L|L|
van der Laarse|W J|WJ|
Girard|O|O|
Jaspers|R T|RT|

skeletal muscle
altitude training
angiogenesis
hypertrophy
oxygen transport


Neuroprotective effects of angiotensin receptor blockers.

Abstract: Angiotensin II receptor blockers (ARBs, collectively called sartans) are widely used compounds therapeutically effective in cardiovascular disorders, renal disease, the metabolic syndrome, and diabetes. It has been more recently recognized that ARBs are neuroprotective and have potential therapeutic use in many brain disorders. ARBs ameliorate inflammatory and apoptotic responses to glutamate, interleukin 1β and bacterial endotoxin in cultured neurons, astrocytes, microglial, and endothelial cerebrovascular cells. When administered systemically, ARBs enter the brain, protecting cerebral blood flow, maintaining blood brain barrier function and decreasing cerebral hemorrhage, excessive brain inflammation and neuronal injury in animal models of stroke, traumatic brain injury, Alzheimer's and Parkinson's disease and other brain conditions. Epidemiological analyses reported that ARBs reduced the progression of Alzheimer's disease, and clinical studies suggested amelioration of cognitive loss following stroke and aging. ARBs are pharmacologically heterogeneous; their effects are not only the result of Ang II type 1(AT1) receptor blockade but also of additional mechanisms selective for only some compounds of the class. These include peroxisome proliferator-activated receptor gamma activation and other still poorly defined mechanisms. However, the complete pharmacological spectrum and therapeutic efficacy of individual ARBs have never been systematically compared, and the neuroprotective efficacy of these compounds has not been rigorously determined in controlled clinical studies. The accumulation of pre-clinical evidence should promote further epidemiological and controlled clinical studies. Repurposing ARBs for the treatment of brain disorders, currently without effective therapy, may be of immediate and major translational value.

neuroprotection
angiotensin receptor blockers
angiotensin II
sartans
brain inflammation
neuronal injury
Alzheimer’s disease
Parkinson’s disease
blood pressure
hypertension
neurodegenerative disorders
renin–angiotensin system
traumatic brain injury.


Effectiveness of stop smoking interventions among adults: protocol for an overview of systematic reviews and an updated systematic review.

Abstract:
BACKGROUND
Tobacco smoking is the leading cause of cancer, preventable death, and disability. Smoking cessation can increase life expectancy by nearly a decade if achieved in the third or fourth decades of life. Various stop smoking interventions are available including pharmacotherapies, electronic cigarettes, behavioural support, and alternative therapies. This protocol outlines an evidence review which will evaluate the benefits and harms of stop smoking interventions in adults.

METHODS
The evidence review will consist of two stages. First, an overview of systematic reviews evaluating the benefits and harms of various stop smoking interventions delivered in or referred from the primary care setting will be conducted. The second stage will involve updating a systematic review on electronic cigarettes identified in the overview; randomized controlled trials will be considered for outcomes relating to benefits while randomized controlled trials, non-randomized controlled trials, and comparative observational studies will be considered for evaluating harms. Search strategies will be developed and peer-reviewed by medical information specialists. The search strategy for the updated review on e-cigarettes will be developed using that of the candidate systematic review. The MEDLINE®, PsycINFO, Embase, and the Cochrane Library electronic databases will be searched as of 2008 for the overview of reviews and from the last search date of the selected review for the updated review. Organizational websites and trial registries will be searched for unpublished or ongoing reviews/studies. Two reviewers will independently screen the title and abstracts of citations using the liberal accelerated method. Full-text screening will be performed independently by two reviewers. Extracted data will be verified by a second reviewer. Disagreements regarding full-text screening and data extraction will be resolved by consensus or third-party adjudication. The methodological quality of systematic reviews, risk of bias of randomized and non-randomized trials, and methodological quality of cohort studies will be evaluated using AMSTAR 2, the Cochrane risk of bias tool, and a modified version of the Scottish Intercollegiate Guidelines Network critical appraisal tool, respectively. The GRADE framework will be used to assess the quality of the evidence for outcomes.

DISCUSSION
The evidence review will evaluate the benefits and harms of various stop smoking interventions for adults. Findings will be used to inform a national tobacco cessation guideline by the Canadian Task Force on Preventive Health Care.

SYSTEMATIC REVIEW REGISTRATION
PROSPERO (CRD42018099691, CRD42018099692).

Hersi|Mona|M|0000-0003-1784-1167
Traversy|Gregory|G|
Thombs|Brett D|BD|
Beck|Andrew|A|
Skidmore|Becky|B|
Groulx|Stéphane|S|
Lang|Eddy|E|
Reynolds|Donna L|DL|
Wilson|Brenda|B|
Bernstein|Steven L|SL|
Selby|Peter|P|
Johnson-Obaseki|Stephanie|S|
Manuel|Douglas|D|
Pakhale|Smita|S|
Presseau|Justin|J|
Courage|Susan|S|
Hutton|Brian|B|
Shea|Beverley J|BJ|
Welch|Vivian|V|
Morrow|Matt|M|
Little|Julian|J|
Stevens|Adrienne|A|

D066300:Electronic Nicotine Delivery Systems

D016032:Randomized Controlled Trials as Topic

Stop smoking
Adults
Systematic review
Tobacco
Cessation


Synaptic and network consequences of monosynaptic nociceptive inputs of parabrachial nucleus origin in the central amygdala.

Abstract: A large majority of neurons in the superficial layer of the dorsal horn projects to the lateral parabrachial nucleus (LPB). LPB neurons then project to the capsular part of the central amygdala (CeA; CeC), a key structure underlying the nociception-emotion link. LPB-CeC synaptic transmission is enhanced in various pain models by using electrical stimulation of putative fibers of LPB origin in brain slices. However, this approach has limitations for examining direct monosynaptic connections devoid of directly stimulating fibers from other structures and local GABAergic neurons. To overcome these limitations, we infected the LPB of rats with an adeno-associated virus vector expressing channelrhodopsin-2 and prepared coronal and horizontal brain slices containing the amygdala. We found that blue light stimulation resulted in monosynaptic excitatory postsynaptic currents (EPSCs), with very small latency fluctuations, followed by a large polysynaptic inhibitory postsynaptic current in CeC neurons, regardless of the firing pattern type. Intraplantar formalin injection at 24 h before slice preparation significantly increased EPSC amplitude in late firing-type CeC neurons. These results indicate that direct monosynaptic glutamatergic inputs from the LPB not only excite CeC neurons but also regulate CeA network signaling through robust feed-forward inhibition, which is under plastic modulation in response to persistent inflammatory pain.

Sugimura|Yae K|YK|
Takahashi|Yukari|Y|
Watabe|Ayako M|AM|
Kato|Fusao|F|0000-0003-0031-9946

pain
rat
channelrhodopsin-2
excitatory postsynaptic current
feed-forward inhibition


An evaluation of the Sennheiser HDA 280-CL circumaural headphone for use in audiometric testing.

Abstract: Objective: Evaluation of the Sennheiser HDA 280-CL circumaural headphone for the determination of (1) equivalent threshold sound pressure levels (ETSPL) for 125-18,000 Hz.; (2) real ear attenuation (250-8000 Hz); (3) insertion loss (63-18,000 Hz); (4) frequency response (125-18,000 Hz); (5) total harmonic distortion (THD) (125-10,000 Hz); and, (6) linearity (11,200-18,000 Hz).Study Sample: Twenty-five normal hearing adults aged 18-25 participated in (1) and (2).Design: (1) Hearing thresholds were measured using the Sennheiser HDA 280-CL. Frequency specific ETSPL values were calculated in an artificial ear. (2) Sound field thresholds were measured with the ears open and covered with the headphone to obtain the real ear attenuation thresholds (REAT). These values were used to determine the maximum permissible ambient noise levels (MPANL). (3) A B&K HATS mannequin recorded the output levels of a broadband pink noise with the ears open and covered with the headphones. (4, 5) The frequency response, THD and linearity were measured in an artificial ear.Results: Values for ETSPL, REAT, MPANL, insertion loss, as well as measures of frequency response, THD and linearity are presented.Conclusions: The Sennheiser HDA 280-CL meets the requirements for audiometric testing and the values presented can be used for calibration.

Folkeard|Paula|P| Hawkins|Marianne|M| Scollie|Susan|S| Sheikh|Bilal|B| Parsa|Vijay|V|

D055615:Electrical Equipment and Supplies

Circumaural headphone
ETSPL
REAT
extended high frequencies


Antioxidant and Anti-Inflammatory Activities in Relation to the Flavonoids Composition of Pepper (Capsicum annuum L.).

Abstract: The chili pepper (Capsicum annuum L.) is a food source that is rich in flavonoids such as luteolin and apigenin. Flavonoids are known to have anti-inflammatory and antioxidant activities; however, studies on the flavonoids composition identified and the anti-inflammatory and antioxidant effects in pepper leaves (PL) and fruits (PF) are insufficient. In the present study, we investigated the antioxidant and anti-inflammatory effects in vitro, and the flavonoids contents of the PL and PF. Pepper extracts showed radical scavenging activities and ameliorated the lipopolysaccharide (LPS)-stimulated inflammatory response by decreasing nitric oxide production and interluekin-6 and tumor necrosis factor alpha levels in RAW 264.7 cells, with more effective activities noted for PL than for PF. Furthermore, PL extracts markedly inhibited the LPS-induced production of reactive oxygen species accumulation. The flavonoid profile and content of pepper were dependent on the part, with PL showing higher total flavonoids than PF. In particular, the content of luteolin glycosides in PL was twice that in PF. Thus, PL may be useful to prevent oxidative stress and inflammation-related diseases.

luteolin
reactive oxygen species
pepper fruit
pepper leaf


Protective Effects of p53 Regulatory Agents Against High-LET Radiation-Induced Injury in Mice.

Abstract: Radiation damage to normal tissues is one of the most serious concerns in radiation therapy, and the tolerance dose of the normal tissues limits the therapeutic dose to the patients. p53 is well known as a transcription factor closely associated with radiation-induced cell death. We recently demonstrated the protective effects of several p53 regulatory agents against low-LET X- or γ-ray-induced damage. Although it was reported that high-LET heavy ion radiation (>85 keV/μm) could cause p53-independent cell death in some cancer cell lines, whether there is any radioprotective effect of the p53 regulatory agents against the high-LET radiation injury in vivo is still unclear. In the present study, we verified the efficacy of these agents on bone marrow and intestinal damages induced by high-LET heavy-ion irradiation in mice. We used a carbon-beam (14 keV/μm) that was shown to induce a p53-dependent effect and an iron-beam (189 keV/μm) that was shown to induce a p53-independent effect in a previous study. Vanadate significantly improved 60-day survival rate in mice treated with total-body carbon-ion (p < 0.0001) or iron-ion (p < 0.05) irradiation, indicating its effective protection of the hematopoietic system from radiation injury after high-LET irradiation over 85 keV/μm. 5CHQ also significantly increased the survival rate after abdominal carbon-ion (p < 0.02), but not iron-ion irradiation, suggesting the moderate relief of the intestinal damage. These results demonstrated the effectiveness of p53 regulators on acute radiation syndrome induced by high-LET radiation.

Morita|Akinori|A| Wang|Bing|B| Tanaka|Kaoru|K| Katsube|Takanori|T| Murakami|Masahiro|M| Shimokawa|Takashi|T| Nishiyama|Yuichi|Y| Ochi|Shintaro|S| Satoh|Hidetoshi|H| Nenoi|Mitsuru|M| Aoki|Shin|S|

p53
cell death
gastrointestinal syndrome
hematopoietic syndrome
radioprotector


Correction of problematic hypospadias with dartos fascia-reinforced flap and slanted incision of fistula.

Abstract:
BACKGROUND
Hypospadias is the most common congenital malformation of the male urinary tract, wherein the urethral opening is located proximal to the normal site. Tubularized incised-plate urethroplasty reconstruction, and its efficacy, remains controversial due to the high recurrence rate. This study aimed to evaluate the results of dartos fascia-reinforced flap surgery in hypospadias patients with previous operative complications.

METHODS
Nine patients (mean age, 12 years) who had previous one- or two-stage repair with TIP urethroplasty and suffered from urethrocutaneous fistulas or fissures as complications, underwent dartos fascia-reinforced flap surgery in our clinic between January 2010 and December 2012. The mean postoperative follow-up period was 6 months.

RESULTS
Among the 9 patients, 7 had complete correction. In all the patients, the maximum uroflow angle was >45°. No patient complained of an unnatural urinating position. The patients and parents gave very high satisfaction scores (4.7 points) with regard to the appearance of the outer genitalia.

CONCLUSION
The dartos fascia-reinforced flap could be a useful and reliable option for complications of hypospadias repair or fissure with the prepuce preserved, given that histological aspects vary and that the possibility of recurrence in the glanular region is high.

Choi|Dong Sik|DS|
Lee|Jeong Woo|JW|
Yang|Jung Dug|JD|
Chung|Ho Yun|HY|
Cho|Byung Chae|BC|
Byun|Jin Suk|JS|
Choi|Kang Young|KY|

Hypospadias
Fistula
Surgical flaps
Urethra


Full-length ORF2 sequence-based genetic and phylogenetic characterization of Korean feline caliciviruses.

Abstract: Feline calicivirus (FCV) is a highly infectious pathogen in cats and widely distributed worldwide with high genetic variation. Full-length open reading frame 2 of 5 from recently isolated Korean FCV isolates were sequenced and compared with those of global isolates. The results of phylogenetic analysis supported dividing global FCV isolates into two genogroups (type I and II) and demonstrated the presence of genogroup II in Korea, indicating their geographic spread in East Asia. High sequence variations in region E of the FCV isolates emphasizes that a novel vaccine needs to be developed to induce protective immunity against various FCV strains.

D000595:Amino Acid Sequence
D000818:Animals
D017250:Caliciviridae Infections
D017927:Calicivirus, Feline
D036022:Capsid Proteins
D002371:Cat Diseases
D002415:Cats
D010802:Phylogeny
D056910:Republic of Korea

Feline calicivirus
open reading frame 2
phylogenetic analysis
genogroup


Proyecto piloto de promoción de la salud en consumo dual de cannabis y tabaco en universitarios: ÉVICT-Universidad.

Abstract:
INTRODUCCIÓN
La universidad es el lugar de formación de los futuros profesionales de los ámbitos educativo, sanitario y social. La implementación de programas de formación, prevención de adicciones y promoción de la salud con universitarios provoca un doble impacto, sobre el propio individuo y, dado su papel mediador, sobre la comunidad universitaria en general. El objetivo del trabajo es, partiendo de un proyecto piloto de investigación-acción, establecer un marco de promoción de la salud en contraposición al consumo dual de cannabis y tabaco en el contexto universitario, involucrando a la comunidad universitaria como agente de cambio.

METODOLOGÍA
Estudio descriptivo de la implementación, cobertura y resultados preliminares del Proyecto piloto ÉVICT-Universidad.

RESULTADOS
Entre el 2018 y el 2020 se implementó el Proyecto ÉVICT-Universidad en 11 universidades. Se formó a estudiantes universitarios como mediadores y se realizaron actividades comunitarias de sensibilización e información orientadas a la promoción de la salud y la prevención del uso de cannabis y tabaco, con especial foco en el consumo dual de estas sustancias, alcanzando a un total de 1471 beneficiarios en los tres años de implementación.

CONCLUSIONES
La experiencia piloto permite detectar fortalezas, aspectos de mejora y resultados prometedores sobre el nivel de conocimientos, contribuyendo a la adopción de estilos de vida saludables en el ámbito universitario. En especial, se destaca la contribución a la formación como agentes promotores de salud de estudiantes y, por tanto, el empoderamiento en salud desde la propia comunidad universitaria.

promoción de la salud
cannabis
tabaco
Educación superior
prevención de drogas
universidades promotoras de salud


Polypyrimidine tract binding protein 1 protects mRNAs from recognition by the nonsense-mediated mRNA decay pathway.

Abstract: The nonsense-mediated mRNA decay (NMD) pathway degrades mRNAs containing long 3'UTRs to perform dual roles in mRNA quality control and gene expression regulation. However, expansion of vertebrate 3'UTR functions has required a physical expansion of 3'UTR lengths, complicating the process of detecting nonsense mutations. We show that the polypyrimidine tract binding protein 1 (PTBP1) shields specific retroviral and cellular transcripts from NMD. When bound near a stop codon, PTBP1 blocks the NMD protein UPF1 from binding 3'UTRs. PTBP1 can thus mark specific stop codons as genuine, preserving both the ability of NMD to accurately detect aberrant mRNAs and the capacity of long 3'UTRs to regulate gene expression. Illustrating the wide scope of this mechanism, we use RNA-seq and transcriptome-wide analysis of PTBP1 binding sites to show that many human mRNAs are protected by PTBP1 and that PTBP1 enrichment near stop codons correlates with 3'UTR length and resistance to NMD.

nonsense-mediated mRNA decay
3'UTR
PTBP1
human
Rous sarcoma virus
biochemistry
chicken
infectious disease
microbiology
retrovirus


Determinants of viral load rebound on HIV/AIDS patients receiving antiretroviral therapy: results from South Africa.

Abstract:
BACKGROUND
Antiretroviral therapy (ART) has become the standard of care for patients with HIV infection in South Africa and has led to the reduction in AIDS related morbidity and mortality. In developing countries, the nucleosides reverse transcriptase inhibitors (NRTIs) class are widely used because of their low production costs. However patients treated with NRTIs develop varying degree of toxicity after long-term therapy. For this study patients are administered with a triple therapy of two NRTIs and one non-nucleoside reverse transcriptase inhibitor (NNRTI).

METHOD
In this study the progression of HIV in vivo is divided into some viral load states and a continuous time-homogeneous model is fitted to assess the effects of covariates namely gender, age, CD4 baseline, viral load baseline, lactic acidosis, peripheral neuropathy, non-adherence and resistance to treatment on transition intensities between the states. Effects of different drug combinations on transition intensities are also assessed.

RESULTS
The results show no gender differences on transition intensities. The likelihood ratio test shows that the continuous time Markov model for the effects of the covariates including combination give a significantly better fit to the observed data. From almost all states, rates of viral suppression were higher than rates of viral rebound except for patients in state 2 (viral load between 50 and 10,000 copies/mL) where rates of viral rebound to state 3 (viral load between 10,000 and 100,000 copies/mL) were higher than rates of viral suppression to undetectable levels. For this transition, confidence intervals were very small. This was quite notable for patients who were administered with AZT-3TC-LPV/r and FTC-TDF-EFV. Although patients on d4T-3TC-EFV also had higher rates of viral rebound from state 2 than suppression, the difference was not significant.

CONCLUSION
From these findings, we can conclude that administering of any HIV drug regimen is better when based on the viral load level of an HIV+ patient. Before initiation of treatment, patients should be well equipped on how antiretroviral drugs operate including possibilities of toxicity in order to reduce chances of non-adherence to treatment. There should also be a good relationship between patient and health-care-giver to ensure proper adherence to treatment. Uptake of therapy by young patients should be closely monitored by adopting pill counting every time they come for review.

Viral load
Triple therapy
Lactic acidosis
Peripheral neuropathy
Non-adherence
HIV progression


Effect of riociguat on pulmonary arterial compliance in the PATENT and CHEST studies.

Abstract: Pulmonary arterial compliance is a measure of the pulsatile afterload of the right ventricle. Lower pulmonary arterial compliance is associated with reduced right ventricular function and worse prognosis in pulmonary hypertension. The effect of pulmonary vasodilators on pulmonary arterial compliance has not been evaluated in detail in pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. In this post hoc analysis of patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension in the PATENT and CHEST studies, we evaluated the change in pulmonary arterial compliance with riociguat versus placebo. Association of pulmonary arterial compliance with clinical outcomes was assessed using Kaplan-Meier and Cox proportional hazards analyses. Compared with placebo, riociguat significantly improved pulmonary arterial compliance in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. Pulmonary arterial compliance at baseline was associated with survival and clinical worsening-free survival in pulmonary arterial hypertension but only with clinical worsening-free survival in chronic thromboembolic pulmonary hypertension. In patients with pulmonary arterial hypertension, pulmonary arterial compliance at follow-up ≥1.6 mL/mmHg was associated with better outcomes than pulmonary arterial compliance <1.6 mL/mmHg. In patients with chronic thromboembolic pulmonary hypertension, pulmonary arterial compliance at follow-up did not predict outcomes. Cox proportional hazards analyses showed no association between change in pulmonary arterial compliance and outcomes in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. In conclusion, riociguat improved pulmonary arterial compliance in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. Pulmonary arterial compliance at baseline or follow-up, rather than change in pulmonary arterial compliance, is of prognostic importance for outcomes.


Deoxynivalenol exposure assessment through a modelling approach of food intake and biomonitoring data - A contribution to the risk assessment of an enteropathogenic mycotoxin.

Abstract: Deoxynivalenol (DON), an enteropathogenic mycotoxin produced by Fusarium species, is usually associated with adverse health outcomes such as gastrointestinal diseases and immunotoxicity. To estimate DON exposure of the Portuguese population at national level, a modelling approach, based on data from 94 Portuguese volunteers, was developed considering the inputs of the food consumption data generated within the National Food and Physical Activity Survey and the human biomonitoring data used to assess the exposure to DON. Ten models of association between DON urinary biomarkers and food items (pasta, cookies, biscuits, sweets, bread, rusks, nuts, oilseeds, beer, meat, milk) were established. Applying the most adequate model to the consumption data (n = 5811) of the general population, the exposure estimates of the Probable Daily Intake revealed that a fraction (0.1%) of the Portuguese population might exceed the Tolerable Daily Intake defined for DON. The analysis stratified by age revealed children (3.2%) and adolescents (6.0%) are more likely to exceed the Tolerable Daily Intake for DON. Although the unavoidable uncertainties, these results are important contributions to understand the exposure to this mycotoxin in Portugal, to assess the associated risk and the potential public health consequences.

Martins|Carla|C|
Torres|Duarte|D|
Lopes|Carla|C|
Correia|Daniela|D|
Goios|Ana|A|
Assunção|Ricardo|R|
Alvito|Paula|P|
Vidal|Arnau|A|
De Boevre|Marthe|M|
De Saeger|Sarah|S|
Nunes|Carla|C|

Modelling
Mycotoxins
Food consumption
Urinary biomarkers
Public health


Effect of coating over the handle of a drill machine on vibration transmissibility.

Abstract: This study was to see the effect of different coatings on the handle of hand-held drilling machines. Out of five different handles chosen for this study, including one handle uncoated. Root mean square (rms) values of the vibration levels (acceleration) were recorded at the surface of handle and wrist of the operators. Results showed that maximum vibrations were reduced by coating of handle coated with rubber sheet and Rexene (H4) followed by handle coated with cotton sandwiched between jeans cloth (H5). Equivalent vibrations transmitted through coating of handles coated with sponge and velvet (H2) and jute and cotton (H3) were of almost same magnitude and these two coated handles were able to reduce least vibration transmitted. Transmissibility of vibrations along dominant (Z) direction was analyzed using ANOVA. Results showed that coating on handles significantly affected vibration transmitted in Z direction. Vibration transmissibility ratios were found to be 0.354, 0.571, 0.408, 0.4326, and 0.3555 for handles H1, H2, H3, H4 and H5 respectively.

Coating
Vibration transmissibility
Work related musculoskeletal disorders


Healthful plant-based dietary patterns, genetic risk of obesity, and cardiovascular risk in the UK biobank study.

Abstract:
BACKGROUND & AIMS
People with a higher genetic risk for obesity are more likely to develop cardiovascular disease (CVD), and healthy plant-based dietary patterns may be associated with decreased risks of obesity and cardiovascular events. We investigated whether adherence to healthy plant-foods-rich dietary patterns might attenuate risks of obesity and related cardiovascular abnormalities for people at genetically higher risk of obesity.

METHODS
This study included 121,799 middle-aged adults in UK Biobank who were initially free of metabolic diseases and cancer. We calculated a healthful plant-based diet index (hPDI) based on 17 major food groups as well as a genetic risk score (GRS) for obesity consisting of body mass index (BMI)-associated variants. The incidence of cardiovascular events (myocardial infarction, MI, or stroke) was prospectively followed during a mean (SD) 5.1 (0.9) years.

RESULTS
We found significant interactions between GRS and hPDI on adiposity (Pinteraction <0.0001); adherence to hPDI was more strongly associated with lower levels of adiposity among participants with higher GRS than those with lower GRS. Further, we found a similar pattern of GRS-hPDI interactions on untreated hypertension (Pinteraction = 0.0036). When we tested GRS-hPDI interactions on cardiovascular events, adherence to hPDI was more strongly associated with a decreased risk of MI among people with high GRS (above median) than those with low GRS (Pinteraction = 0.006). Among participants with high GRS, high adherence to hPDI (the top tertile of hPDI) was associated with an HR 0.54 (95% CI: 0.39, 0.74) for MI, as compared to low adherence.

CONCLUSIONS
Adherence to healthy plant-based dietary patterns significantly attenuated risks of cardiovascular abnormalities for people at genetically higher risk of obesity. Our results support the precision medicine strategies considering genetics and dietary habits to modify cardiovascular health for people at higher risk of genetically determined obesity.

Heianza|Yoriko|Y|
Zhou|Tao|T|
Sun|Dianjianyi|D|
Hu|Frank B|FB|
Qi|Lu|L|

Obesity
Cardiovascular events
Genetic predisposition
Plant-based nutrition
Risk factors


Downregulation of SFRP1 is a protumorigenic event in hepatoblastoma and correlates with beta-catenin mutations.

Abstract:
BACKGROUND
Hepatoblastoma (HB) and pediatric hepatocellular carcinoma (HCC) are the most common malignant liver tumors in childhood. Both tumor types exhibit genetic and epigenetic alterations in the WNT/β-catenin signaling pathway, which is a key regulator of liver progenitor cells in embryonic development. The tumors demonstrate a high rate of β-catenin mutations and gene expression changes of several WNT antagonists. However, the role of the WNT inhibitory factor secreted frizzled-related protein 1 (SFRP1) has not been addressed in pediatric liver cancer so far.

RESULTS
In our study, we investigated the gene expression level, DNA methylation status and functional relevance of SFRP1 in HB cell lines and in pediatric liver tumor patient samples. SFRP1 was downregulated due to DNA promoter methylation in all tested HB cell lines. Overexpression of SFRP1 in HB cell lines diminished tumor cell proliferation, colony formation and migration potential. In addition, the SFRP1-expressing HB cell lines showed reduced WNT/β-catenin signaling pathway activity and decreased expression of WNT target genes. To evaluate the utility of SFRP1 as a biomarker in pediatric liver cancer, we determined the gene expression level and DNA methylation status of SFRP1 in 45 pediatric liver tumor patient samples. The correlation analysis of different clinical parameters and tumor characteristics revealed a significant correlation of reduced SFRP1 expression with the presence of mutant β-catenin. The methylation status of SFRP1 was furthermore associated to a pediatric liver tumor type with HCC-like characteristics, TERT mutations and an older age at diagnosis.

CONCLUSION
Altogether, our data demonstrate that the epigenetic suppression of the WNT/β-catenin antagonist SFRP1 has an important impact on the malignant behavior of HB cells. Although SFRP1 methylation is a common event in HCC-like pediatric liver tumors, its potential as a prognostic or diagnostic biomarker needs to be further investigated.

Regel|Ivonne|I|
Eichenmüller|Melanie|M|
Mahajan|Ujjwal Mukund|UM|
Hagl|Beate|B|
Benitz|Simone|S|
Häberle|Beate|B|
Vokuhl|Christian|C|
von Schweinitz|Dietrich|D|
Kappler|Roland|R|

D036341:Intercellular Signaling Peptides and Proteins

SFRP1
Hepatoblastoma
Hepatocellular carcinoma
Epigenetics
Pediatric liver cancer
DNA methylation
APC
DKK1
WIF1
WNT signaling


Evolutionary mechanism unifies the hallmarks of cancer.

Abstract: The basis for the gene mutation theory of cancer that dominates current molecular cancer research consists of: the belief that gene-level aberrations such as mutations are the main cause of cancers, the concept that stepwise gene mutation accumulation drives cancer progression, and the hallmarks of cancer. The research community swiftly embraced the hallmarks of cancer, as such synthesis has supported the notions that common cancer genes are responsible for the majority of cancers and the complexity of cancer can be dissected into simplified molecular principles. The gene/pathway classification based on individual hallmarks provides explanation for the large number of diverse gene mutations, which is in contrast to the original estimation that only a handful of gene mutations would be discovered. Further, these hallmarks have been highly influential as they also provide the rationale and research direction for continued gene-based cancer research. While the molecular knowledge of these hallmarks is drastically increasing, the clinical implication remains limited, as cancer dynamics cannot be summarized by a few isolated/fixed molecular principles. Furthermore, the highly heterogeneous genetic signature of cancers, including massive stochastic genome alterations, challenges the utility of continuously studying each individual gene mutation under the framework of these hallmarks. It is therefore necessary to re-evaluate the concept of cancer hallmarks through the lens of cancer evolution. In this analysis, the evolutionary basis for the hallmarks of cancer will be discussed and the evolutionary mechanism of cancer suggested by the genome theory will be employed to unify the diverse molecular mechanisms of cancer.

Horne|Steven D|SD|
Pollick|Sarah A|SA|
Heng|Henry H Q|HH|

hallmarks of cancer
cancer evolution
evolutionary mechanism of cancer
genome theory
cancer genomics
cancer heterogeneity
genome chaos
genome instability
system inheritance


Effect of IV Acetaminophen Usage on Opioid Requirements, Outcomes and Costs of Care for Postoperative Children in a Pediatric Intensive Care Unit.

Abstract:
OBJECTIVE
Children admitted to the ICU are commonly treated with opioids for postoperative pain. We hypothesized that administration of IV acetaminophen in the immediate postoperative period is effective in lowering cumulative opioid use leading to other benefits.

METHODS
This was a retrospective chart review of patients admitted to the PICU between December 2016 and April 2019. For each patient, data including demographics, cumulative opioid usage per kilogram, oral or rectal acetaminophen, x-ray findings, hospital costs, and surgical procedure were collected. Cumulative opioid usage was determined by converting all opioids to morphine equivalents (MEs) per kg. Standard descriptive and comparative analyses were conducted using SAS 9.4 (SAS Institute, Inc, Cary, NC).

RESULTS
A total of 200 patients met inclusion and exclusion criteria (N = 92 in IV acetaminophen group and N = 108 in no IV acetaminophen group). There was no significant difference in ME per kilogram between the groups (0.3 ME/kg in IV acetaminophen group, IQR 0.5 ME/kg versus 0.4 ME/kg in no IV acetaminophen group, IQR 0.5 ME/kg, adjusted p = 0.38). Rate of atelectasis was not significant between the groups (47.8% in IV acetaminophen versus 45.4% in no acetaminophen group, p = 0.28). There was a significant difference in median total hospital costs between the groups ($22,456 in IV acetaminophen group, IQR $18,650 versus $18,552 in no IV acetaminophen group, IQR $13,361, adjusted p = 0.04).

CONCLUSIONS
IV acetaminophen in the immediate postoperative period did not lead to a decrease in cumulative opioid usage or rate of atelectasis. IV acetaminophen usage was associated with increase in overall hospital costs per patient.

Taylor|Brock M|BM|
Chakraborty|Shawn R|SR|
Harthan|Aaron A|AA|
Tripathi|Sandeep|S|
Wang|Huaping|H|
Swayampakula|Anil Kumar|AK|

acetaminophen
opioid
pediatrics
analgesics
critical care


Slotted labyrinthotomy approach with customized electrode for patients with common cavity deformity.

Abstract:
OBJECTIVES/HYPOTHESIS
Cochlear implantation for patients with common cavity deformity (CCD) can be difficult, with a higher incidence of intra- and postoperative complications; outcomes with CCD patients are also highly variable. In this study, surgical time was compared between the traditional facial recess approach (TFRA) and the transmastoid slotted labyrinthotomy approach (TSLA). Audiological outcomes and the benefit of using customized electrode arrays for CCD patients are also discussed.

STUDY DESIGN
Retrospective review of 13 cochlear implant (CI) patients with CCD.

METHODS
Six patients were implanted with the TFRA using traditional electrodes, and seven patients were implanted with the TSLA using customized electrodes. Intra- and postoperative complications were reviewed. Audiological outcomes were measured 3 months to 2 years after CI activation.

RESULTS
The mean surgical time for TSLA group was nearly half as long as for the TRFA group (P < .05). Although mean audiological outcomes were better for the TSLA group, there was no significant difference between groups (P > .05).

CONCLUSIONS
For CCD patients, TSLA for cochlear implantation is recommended due to shortened surgical time; customized electrode arrays may be additionally advantageous in terms of audiological outcomes.

LEVEL OF EVIDENCE
4. Laryngoscope, 128:468-472, 2018.

Wei|Xingmei|X|0000-0001-7188-485X Li|Yongxin|Y| Fu|Qian-Jie|QJ| Gong|Yue|Y| Chen|Biao|B| Chen|Jingyuan|J| Shi|Ying|Y| Su|Qiaotong|Q| Cui|Danmo|D| Liu|Ting|T|

common cavity deformity
Cochlear implantation
customized electrode array
surgical approach


Primary Central Nervous System Leukemia Presenting as Altered Mental Status.

Abstract:
BACKGROUND
Altered mental status is a common cause for presentation to the emergency department with a broad differential diagnosis.

CASE REPORT
We present a unique case of altered mental status in a previously healthy man that was found to be secondary to primary central nervous system acute lymphoblastic leukemia. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Lumbar puncture remains a critical tool for emergency physicians in the diagnosis of central nervous system pathologies.

altered mental status
acute lymphoblastic leukemia
lumbar puncture
central nervous system malignancy


Organic-inorganic epoxide hydrolase hybrid nanoflowers with enhanced catalytic activity: Hydrolysis of styrene oxide to 1-phenyl-1,2-ethanediol.

Abstract: Epoxide hydrolases are ubiquitous in nature and are utilized to catalyze the cofactor-independent hydrolysis of epoxides to their corresponding diols. These enzymes have tremendous potential and have been applied in the synthesis of bulk and fine chemical industry and utilized as chiral building blocks. Herein, we report a green, facile, and economical method for immobilization of epoxide hydrolase based on biomimetic mineralization. The organic-inorganic hybrid nanoflowers have received tremendous attention due to their higher catalytic activity and stability. The nanoflowers were synthesized, with the organic component being enzyme epoxide hydrolase and the inorganic component being Ca2+ ions. A unique hierarchical flower-like spherical structure with hundreds of spiked petals was observed. The synthesized nanoflowers were applied for styrene oxide hydrolysis, producing 1-phenyl-1,2-ethanediol. Further, the factors influencing the morphology, catalytic activity, and stability studies were performed to study the activity recovery of the synthesized organic-inorganic hybrid epoxide hydrolase nanoflowers. The findings will have interesting applications.

Salvi|Harshada M|HM|
Yadav|Ganapati D|GD|

D004851:Epoxide Hydrolases
D004852:Epoxy Compounds
D005026:Ethylene Glycols
D006868:Hydrolysis

Epoxide hydrolase
Hybrids
Nanoflower
Immobilization
Glycine max


Predicting risk of adverse drug reactions in older adults.

Abstract: Adverse drug reactions (ADRs) are common in older adults, with falls, orthostatic hypotension, delirium, renal failure, gastrointestinal and intracranial bleeding being amongst the most common clinical manifestations. ADR risk increases with age-related changes in pharmacokinetics and pharmacodynamics, increasing burden of comorbidity, polypharmacy, inappropriate prescribing and suboptimal monitoring of drugs. ADRs are a preventable cause of harm to patients and an unnecessary waste of healthcare resources. Several ADR risk tools exist but none has sufficient predictive value for clinical practice. Good clinical practice for detecting and predicting ADRs in vulnerable patients includes detailed documentation and regular review of prescribed and over-the-counter medications through standardized medication reconciliation. New medications should be prescribed cautiously with clear therapeutic goals and recognition of the impact a drug can have on multiple organ systems. Prescribers should regularly review medication efficacy and be vigilant for ADRs and their contributory risk factors. Deprescribing should occur at an individual level when drugs are no longer efficacious or beneficial or when safer alternatives exist. Inappropriate prescribing and unnecessary polypharmacy should be minimized. Comprehensive geriatric assessment and the use of explicit prescribing criteria can be useful in this regard.

adverse drug reaction
polypharmacy
inappropriate prescribing
predictive value
risk assessment


Inhibition of the glucocorticoid receptor results in an enhanced miR-99a/100-mediated radiation response in stem-like cells from human prostate cancers.

Abstract: Radiation therapy is a major primary treatment option for both localized early stage prostate cancer, and for advanced, regionally un-resectable, cancer. However, around 30% of patients still experience biochemical recurrence after radiation therapy within 10 years. Thus, identification of better biomarkers and new targets are urgently required to improve current therapeutic strategies. The miR-99 family has been shown to play an important role in the regulation of the DNA damage response, via targeting of the SWI/SNF chromatin remodeling factors, SMARCA5 and SMARCD1 in cell line models. In the present study, we have demonstrated that low expression of miR-99a and miR-100 is present in cell populations which are relatively radiation insensitive, for example in prostate cancer stem cells and in castration-resistant prostate cancer. Additionally, treatment of cells with the synthetic glucocorticoid, Dexamethasone resulted in decreased miR-99a and 100 expression, suggesting a new mechanism of miR-99a and 100 regulation in androgen-independent prostate cells. Strikingly, treatment of prostate cells with the glucocorticoid receptor inhibitor, Mifepristone was found to sensitize prostate cells to radiation by increasing the levels of miR-99a and miR-100. These results qualify the miR99 family as markers of radiation sensitivity and as potential therapeutic targets to improve efficiency of radiotherapy.

Rane|Jayant K|JK|
Erb|Holger H H|HH|
Nappo|Giovanna|G|
Mann|Vincent M|VM|
Simms|Matthew S|MS|
Collins|Anne T|AT|
Visakorpi|Tapio|T|
Maitland|Norman J|NJ|

cancer stem cells
mifepristone
radiotherapy
DNA damage repair
miRNA


Light wine consumption is associated with a lower odd for cardiovascular disease in chronic kidney disease.

Abstract:
AIMS
To examine the association between wine consumption and the prevalence of chronic kidney disease (CKD) and cardiovascular disease (CVD).

DATA SYNTHESIS
We performed a cross-sectional logistic regression analysis of National Health and Nutrition Examination Survey (NHANES) in participants 21 years of age or older from 2003 to 2006 in a large representative study of the U.S.

POPULATION
Wine consumption was categorized as none (0 glass per day), light (<1 glass per day), or moderate (≥1 glasses per day). Prevalent CKD was defined as a urine albumin/creatinine ratio (UACR) ≥30 mg/g or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. CVD was defined as history of CVD including angina, myocardial infarction, or stroke. Only 27 (0.5%) individuals reported moderate wine consumption, whereas 57.5% and 42% reported abstinence and light wine consumption, respectively. Light wine consumption was associated with a lower prevalence of CKD as opposed to abstinence in unadjusted analysis. After adjusting for demographics and CVD risk factors light wine consumption was associated with lower prevalence of CKD defined as UACR ≥30 mg/g but not with low eGFR. Furthermore, light wine consumption was associated with significantly lower rates of CVD in the general population and in subjects with CKD. The adjusted odd of CVD for those with light wine consumption was 0.72 (CI 0.52-0.99, p = 0.046) for the subjects with CKD.

CONCLUSION
These data suggest that light wine consumption (compared to abstinence) is associated with lower prevalence of CKD and a lower odd of CVD in those with CKD in the U.S.

POPULATION

Jespersen|T|T| Kruse|N|N| Mehta|T|T| Kuwabara|M|M| Noureddine|L|L| Jalal|D|D|


Multiple changes of functional connectivity between sensorimotor areas in focal hand dystonia.

Abstract:
BACKGROUND
Task-specific focal hand dystonia impairs the control of arm muscles during fine motor skills such as writing (writer's cramp (WC)). Functional imaging found abnormal task-related activation of sensorimotor areas in this disorder, but little is known on their functional connectivity (FC).

METHODS
Resting-state fMRI and regions of interest (ROI)-voxel cross-correlation analyses were used for systematically analysing the FC between multiple ROIs within the cerebello-basal ganglia-thalamocortical network in 15 patients with right-sided WC and 15 healthy volunteers.

RESULTS
Patients with WC showed a lower positive FC of several seed ROIs (left lateral premotor cortex, left thalamus, left/right pallidum) to the symptomatic left primary sensorimotor cortex compared with controls. The FC of the left primary motor cortex to prefrontal areas, pre- supplementary motor area and right somatosensory cortex was reduced and correlated with disease severity. Several cerebellar seed ROIs (right dentate nucleus, right crus I and bilateral crus II) revealed a stronger negative FC to primary and secondary sensorimotor areas.

CONCLUSIONS
An increase of negative cerebello-cortical FC at rest is in line with the hypothesis of a pathogenetic role of the cerebellum in dystonia. The deficit of positive subcortico-cortical FC indicates more generalised changes within the basal ganglia-thalamocortical motor loops beyond primary sensorimotor areas in WC. As patients with WC are asymptomatic during rest, these functional network changes could reflect an underlying abnormality or compensatory neuroplastic changes of network architecture in this disorder.

Dresel|Christian|C| Li|Yong|Y| Wilzeck|Verena|V| Castrop|Florian|F| Zimmer|Claus|C| Haslinger|Bernhard|B|

D016022:Case-Control Studies
D020821:Dystonic Disorders
D005260:Female
D007839:Functional Laterality
D059907:Functional Neuroimaging
D005917:Globus Pallidus
D006801:Humans
D008279:Magnetic Resonance Imaging
D008297:Male
D008875:Middle Aged
D009044:Motor Cortex
D009434:Neural Pathways
D066191:Sensorimotor Cortex
D013788:Thalamus

DYSTONIA
FUNCTIONAL IMAGING
MOTOR CONTROL
MOVEMENT DISORDERS
MRI


Type III CRISPR-Cas systems can provide redundancy to counteract viral escape from type I systems.

Abstract: CRISPR-Cas-mediated defense utilizes information stored as spacers in CRISPR arrays to defend against genetic invaders. We define the mode of target interference and role in antiviral defense for two CRISPR-Cas systems in Marinomonas mediterranea. One system (type I-F) targets DNA. A second system (type III-B) is broadly capable of acquiring spacers in either orientation from RNA and DNA, and exhibits transcription-dependent DNA interference. Examining resistance to phages isolated from Mediterranean seagrass meadows, we found that the type III-B machinery co-opts type I-F CRISPR-RNAs. Sequencing and infectivity assessments of related bacterial and phage strains suggests an 'arms race' in which phage escape from the type I-F system can be overcome through use of type I-F spacers by a horizontally-acquired type III-B system. We propose that the phage-host arms race can drive selection for horizontal uptake and maintenance of promiscuous type III interference modules that supplement existing host type I CRISPR-Cas systems.

D064112:Clustered Regularly Interspaced Short Palindromic Repeats

CRISPR
Marinomonas mediterranea
phage
phage-host arms race
bacteria
evolutionary biology
genomics
immunity
infectious disease
microbiology


Detection of gastric inflation using transesophageal echocardiography after different level of pressure-controlled mask ventilation: a prospective randomized trial.

Abstract: This study aimed to assess the technique of using transesophageal echocardiography (TEE) to detect gastric inflation and to determine the optimal level of inspiratory pressure during face mask ventilation (FMV). In this prospective and randomized trial, seventy-five adults scheduled for cardiac surgery were enrolled to one of the three groups (P12, P15, P20) defined by the applied inspiratory pressure during FMV. After induction, mask ventilation was performed with the corresponding level of pressure-control ventilation for 2 min in each patient. Respiratory and hemodynamic parameters were recorded every 15 s. Arterial blood gases were tested before induction and at the time of intubation. Gastric cross-section area was detected using transesophageal echocardiography after intubation. The gastric cross-section areas were 3.1 ± 0.81, 3.8 ± 1.37 and 4.8 ± 2.29 cm2 respectively. It statistically increased in group P20 compared with group P12 and P15. PaCO2 before intubation statistically increased compared with the baseline in groups P12 and P15, while decreased in group P20. The mean values of PaCO2 equaled to 44.4 mmHg (40-51.5), 42.9 mmHg (34-50.5) and 36.9 mmHg (30.9-46) respectively in three groups. Peak airway pressure of 12-20 cmH2O could provide acceptable sufficient ventilation during mask ventilation, but 20 cmH2O result in higher incidence of gastric inflation. TEE is useful to detect the gastric inflation related to the entry of air into the stomach during pressure-controlled face mask ventilation.Trial Registration Number ChiCTR-IOR-14005325.

Gastric inflation
Transesophageal echocardiography
Mask ventilation


Newly Developed Aneurysm at the Anastomosis Site of a Superficial Temporal Artery to Middle Cerebral Artery Bypass Successfully Treated by Endovascular Embolization.

Abstract:
BACKGROUND
The superficial temporal artery (STA) to middle cerebral artery (MCA) bypass is an effective treatment procedure for steno-occlusive severe ischemic disease of the anterior circulation. The formation of an aneurysm at the anastomosis site is a rare complication, and the mechanism underlying this condition and the appropriate treatment strategy, have not yet been established. We describe a case of an unruptured anastomosis aneurysm that was treated by endovascular embolization 7 years after bypass surgery.

CASE DESCRIPTION
A 62-year-old woman presented with slurred speech, with magnetic resonance imaging and angiography showing multiple infarctions in her left cerebral hemisphere and severe stenosis in the left internal carotid artery and left MCA. An STA-MCA anastomosis was performed without neurologic sequelae. Five years later, follow-up magnetic resonance imaging showed that an aneurysm had formed at the MCA side of the anastomosis site. After 2 years, the saccular aneurysm had grown and was embedded in the brain parenchyma. Because the patient had experienced repeated problems with surgical wound healing, an endovascular intervention was performed, achieving obliteration of the aneurysm by coil embolization.

CONCLUSIONS
Endovascular treatment is a feasible and efficacious treatment option for an aneurysm at the anastomosis site of an STA-MCA bypass.

Isono|Naofumi|N| Matsubara|Noriaki|N| Takeuchi|Koji|K| Hiramatsu|Ryo|R| Kawabata|Shinji|S| Tsujiguchi|Kounosuke|K|

D000714:Anastomosis, Surgical
D002548:Cerebral Revascularization
D004621:Embolization, Therapeutic
D057510:Endovascular Procedures
D005260:Female
D006801:Humans
D002532:Intracranial Aneurysm
D008875:Middle Aged
D020768:Middle Cerebral Artery
D013699:Temporal Arteries

Aneurysm
Endovascular embolization
STA-MCA anastomosis


Impact of intestinal dysbiosis-related drugs on the efficacy of immune checkpoint inhibitors in clinical practice.

Abstract:
PURPOSE
Intestinal dysbiosis has emerged as a biomarker of response to immune checkpoint inhibitors (ICIs). It can be caused by antibiotics, although it may also result from the use of other drugs that have been studied to a lesser extent. The objective of our study was to analyze the association between the use of potentially dysbiosis-related drugs and survival in patients treated with ICIs in the clinical practice.

MATERIALS AND METHODS
A retrospective, multicenter, cohort study was conducted. Clinicopathological variables were collected and the concomitant use of drugs was analyzed. A descriptive analysis of variables and overall survival, estimated by the Kaplan-Meier method, was performed, and association with various independent variables was assessed using Cox regression.

RESULTS
We included 253 patients, mainly with non-small cell lung cancer and melanoma. The most commonly used drugs were acid reducers, prescribed to 55.3% of patients, followed by corticosteroids (37.9%), anxiolytic drugs (35.6%), and antibiotics (20.5%). The use of acid reducers (9 vs. 18 months, P < .0001), antibiotics (7 vs. 15 months, P < .017), anxiolytic drugs (8 vs. 16 months, P < .015), and corticosteroids (6 vs. 19 months, P < .00001) was associated with poorer overall survival. Furthermore, the greater the number of drugs used concomitantly with ICIs, the higher the risk of death (1 drug: hazard ratio, 1.88; CI 95%, 1.07-3.30; 4 drugs: hazard ratio, 4.19; CI9 5%, 1.77-9.92; P < .001).

CONCLUSION
Response to ICIs may be influenced by the use of drugs that lead to intestinal dysbiosis. Although a confirmatory prospective controlled study is required, our findings should be taken into account when analyzing ICI efficacy.

Immune checkpoints inhibitors
Intestinal dysbiosis
Clinical response


EFTUD2 missense variants disrupt protein function and splicing in mandibulofacial dysostosis Guion-Almeida type.

Abstract: Pathogenic variants in the core spliceosome U5 small nuclear ribonucleoprotein gene EFTUD2/SNU114 cause the craniofacial disorder mandibulofacial dysostosis Guion-Almeida type (MFDGA). MFDGA-associated variants in EFTUD2 comprise large deletions encompassing EFTUD2, intragenic deletions and single nucleotide truncating or missense variants. These variants are predicted to result in haploinsufficiency by loss-of-function of the variant allele. While the contribution of deletions within EFTUD2 to allele loss-of-function are self-evident, the mechanisms by which missense variants are disease-causing have not been characterized functionally. Combining bioinformatics software prediction, yeast functional growth assays, and a minigene (MG) splicing assay, we have characterized how MFDGA missense variants result in EFTUD2 loss-of-function. Only four of 19 assessed missense variants cause EFTUD2 loss-of-function through altered protein function when modeled in yeast. Of the remaining 15 missense variants, five altered the normal splicing pattern of EFTUD2 pre-messenger RNA predominantly through exon skipping or cryptic splice site activation, leading to the introduction of a premature termination codon. Comparison of bioinformatic predictors for each missense variant revealed a disparity amongst different software packages and, in many cases, an inability to correctly predict changes in splicing subsequently determined by MG interrogation. This study highlights the need for laboratory-based validation of bioinformatic predictions for EFTUD2 missense variants.

D017415:Ribonucleoprotein, U5 Small Nuclear


Smoke-Free Sports in The Netherlands: Why Most Sports Clubs Have Not Adopted an Outdoor Smoke-Free Policy.

Abstract: Background: Outdoor smoke-free policies (SFPs) at sports clubs represent an important new area of tobacco control, as many people, including youth, spend a large portion of their free time participating in sports. Nevertheless, the majority of sports clubs worldwide still have not adopted an outdoor SFP. The aim of this study is to explore the perceptions of key stakeholders at different Dutch sports clubs concerning the adoption of an outdoor SFP. Methods: Semi-structured interviews were held with 41 key stakeholders at seven Dutch sports clubs (in field hockey, football, tennis, or korfball) without an outdoor SFP. A thematic approach was used to analyze the data. Results: The majority of respondents reported considerations that were favorable towards adoption of an outdoor SFP, including expected support from club members, changing social norms with regard to smoking, and few members who smoke. Most of all, respondents valued the protection of children from the harmful effects of smoking. However, they also foresaw a number of problems in case of adoption, including impaired social functioning of the sports club, problems with compliance and enforcement, conflict with smokers' interest, and low priority in club management. Conclusions: Although stakeholders at sports clubs recognize the intrinsic value of an outdoor SFP, they foresee practical problems that are inherent to sports clubs. Adoption could be enhanced by articulating the importance of protecting children from the harmful effects of smoking, referring to 'success stories' at sports clubs that are already smoke-free, and actively involving smokers in the adoption process.


Ecosystem response to earlier ice break-up date: Climate-driven changes to water temperature, lake-habitat-specific production, and trout habitat and resource use.

Abstract: Climate warming has yielded earlier ice break-up dates in recent decades for lakes leading to water temperature increases, altered habitat, and both increases and decreases to ecosystem productivity. Within lakes, the effect of climate warming on secondary production in littoral and pelagic habitats remains unclear. The intersection of changing habitat productivity and warming water temperatures on salmonids is important for understanding how climate warming will impact mountain ecosystems. We develop and test a conceptual model that expresses how earlier ice break-up dates influence within lake habitat production, water temperatures and the habitat utilized by, resources obtained and behavior of salmonids in a mountain lake. We measured zoobenthic and zooplankton production from the littoral and pelagic habitats, thermal conditions, and the habitat use, resource use, and fitness of Brook Trout (Salvelinus fontinalis). We show that earlier ice break-up conditions created a "resource-rich" littoral-benthic habitat with increases in zoobenthic production compared to the pelagic habitat which decreased in zooplankton production. Despite the increases in littoral-benthic food resources, trout did not utilize littoral habitat or zoobenthic resources due to longer durations of warm water temperatures in the littoral zone. In addition, 87% of their resources were supported by the pelagic habitat during periods with earlier ice break-up when pelagic resources were least abundant. The decreased reliance on littoral-benthic resources during earlier ice break-up caused reduced fitness (mean reduction of 12 g) to trout. Our data show that changes to ice break-up drive multi-directional results for resource production within lake habitats and increase the duration of warmer water temperatures in food-rich littoral habitats. The increased duration of warmer littoral water temperatures reduces the use of energetically efficient habitats culminating in decreased trout fitness.

ecosystems
ecosystem production
mountain lakes
climate change
fish ecology
ice phenology
stable isotopes


Micro-RNAs in cognition and cognitive disorders: Potential for novel biomarkers and therapeutics.

Abstract: Micro-RNAs (miRNAs) are small regulatory non-coding RNAs involved in the regulation of many biological functions. In the brain, they have distinct expression patterns depending on region, cell-type and developmental stage. Their expression profile is altered by neuronal activation in response to behavioral training or chemical/electrical stimulation. The dynamic changes in miRNA level regulate the expression of genes required for cognitive processes such as learning and memory. In addition, in cognitive dysfunctions such as dementias, expression levels of many miRNAs are perturbed, not only in brain areas affected by the pathology, but also in peripheral body fluids such as serum and cerebrospinal fluid. This presents an opportunity to utilize miRNAs as biomarkers for early detection and assessment of cognitive dysfunctions. Further, since miRNAs target many genes and pathways, they may represent key molecular signatures that can help understand the mechanisms of cognitive disorders and the development of potential therapeutic agents.

Woldemichael|Bisrat T|BT|
Mansuy|Isabelle M|IM|

Biomarkers
miRNA
Learning and memory
Cognitive dysfunctions
Alzheimer’s disease


Challenges with multi-objective QSAR in drug discovery.

Abstract: The complexity in the drug discovery pipeline, in combination with the exponential growth of experimental and computational data, the technological achievements, and the access to large data sets, has led to a continuous evolution and transformation of quantitative structure-activity relationships (QSAR) to compete with the challenges of multi-objective drug discovery. Areas covered: After a short overview of the multiple objectives involved in drug discovery, this review focuses on definition of the drug-like space and the construction of local and/or global models, platforms and workflows for step-by-step single-objective optimization (SOO) of the different and often conflicting processes. Multi-targeted drug design is a particular case of multi-objective QSAR integrated into the new era of polypharmacology. Multi-objective optimization (MOO), based on desirability functions or Pareto surfaces and its application in QSAR, as an alternative optimization philosophy, is also discussed. Expert opinion: Access to large databases as well as to software services by means of cloud technology facilitates research for more efficient and safer drugs. QSAR models implemented in web platforms and workflows provide sequential SOO for multiple biological and toxicity end points, while MOO, still restricted to a limited number of objectives, is helpful for multi-target or selectivity design, as well as for model prioritization.

QSAR
drug-like space
multi-target drug design
multi-objective optimization
multi-objective drug design
single objective optimization


Longitudinal Genomic Characterization of Carbapenemase-producing Enterobacteriaceae (CPE) Reveals Changing Pattern of CPE Isolated in Hong Kong Hospitals.

Abstract: An active, territory-wide, CPE surveillance program implemented from 2011 showed increasing levels of carbapenemase-producing Enterobacteriaceae (CPE) isolates from patients in Hong Kong hospitals. The molecular epidemiology of 567 CPE from patients of three of seven public hospital clusters in Hong Kong are described. During a 7-year period, the incidence of CPE isolation increased from 0.05 to 9.6/100 000 patient-days. The carbapenemase genes identified were polyclonal, including blaKPC, blaNDM and blaIMP, which were mainly associated with hospitalization overseas in previous years. However, increasing CPE isolation from patients without hospitalization overseas occurred in 2015, with blaNDM (52.6%) predominant followed by blaIMP (30.0%). Escherichia coli (46.4%) and Klebsiella spp. (38.3%) were the dominant species. Whole-genome sequencing was performed on 169 representative isolates with a combination of short and long reads using Illumina and Nanopore technology. Two distinct lineages of blaKPC-2-positive Klebsiella pneumoniae (ST11 and ST258) were identified with ST11 carrying yersiniabactin gene ybt-9 on ICEKp3. ST131 E. coli producing IMP-4 was present throughout the study period. The blaNDM and blaIMP genes were mainly carried in IncX3 and IncN-ST7 plasmids, respectively. blaOXA-48-like gene was carried in the IncX3 plasmid in E. coli and in the ColKP3 plasmid in K. pneumoniae. A lineage of K. pneumoniae with blaNDM-1 plus blaOXA-232 in distinct plasmids of IncF1B/IncHI1B was identified and associated with prior hospitalization overseas. This study highlights the threat of multiple types of CPE, with the predominance of blaNDM and blaIMP among CPE in our hospitals. Enhanced containment strategies are needed to mitigate the trend of rapidly rising CPE in healthcare settings.

Zhu|Chendi|C|
Li|Carmen|C|
Lai|Christopher K C|CKC|
Ng|Rita|R|
Chau|Ka Yee|KY|
Wong|Kam Tak|KT|
Lo|Norman W S|NWS|
Barua|Nilakshi|N|
Yang|Ying|Y|
Liyanapathirana|Veranja|V|
Hui|Mamie|M|
Lai|Raymond W|RW|
Fung|Kitty S C|KSC|
Tsang|Dominic N|DN|
Ip|Margaret|M|

Enterobacteriaceae
surveillance
Carbapenemase
whole-genome sequencing
plasmids


Prognostic value of pre- and post-treatment health-related quality of life in predicting survival of patients with brain metastases.

Abstract:
AIM
The present study aimed to determine the prognostic survival value of pretreatment health-related quality of life (HRQOL) and changes in HRQOL following whole-brain radiation treatment in patients with brain metastases.

METHODS
Patients who were treated with whole-brain radiation treatment and completed HRQOL questionnaires were included. Univariate and multivariate Cox proportional hazard models of overall survival (OS) were conducted for overall HRQOL and domain scores.

RESULTS & CONCLUSION
Patients with lower HRQOL at baseline, especially lower physical functioning and motor dysfunction domains, were more likely to have poorer survival. Changes in overall HRQOL and its domains were not significantly related to OS. Pretreatment HRQOL, especially physical functioning and motor dysfunction, has added prognostic value in patients with brain metastases.

Wong|Erin|E| Rowbottom|Leigha|L| Tsao|May|M| Zhang|Liying|L| McDonald|Rachel|R| Danjoux|Cyril|C| Barnes|Elizabeth|E| Chan|Stephanie|S| Chow|Edward|E|

quality of life
brain metastases
overall survival
prognosis