Dapagliflozin Mediates Plin5/PPARα Signaling Axis to Attenuate Cardiac Hypertrophy.

Abstract: Objective: The purpose of this study was to investigate the effect of dapagliflozin (DAPA), a sodium-glucose cotransporter 2 inhibitor, on relieving cardiac hypertrophy and its potential molecular mechanism. Methods: Cardiac hypertrophy induced by abdominal aortic constriction (AAC) in mice, dapagliflozin were administered in the drinking water at a dose of 25 mg/kg/d for 12 weeks was observed. Echocardiography was used to detect the changes of cardiac function, including LVEF, LVFS, LVEDd, LVEDs, HR and LV mass. Histological morphological changes were evaluated by Masson trichrome staining and wheat germ agglutinin (WGA) staining. The enrichment of differential genes and signal pathways after treatment was analyzed by gene microarray cardiomyocyte hypertrophy was induced by AngII (2 μM) and the protective effect of dapagliflozin (1 μM) was observed in vitro. The morphological changes of myocardial cells were detected by cTnI immunofluorescence staining. ELISA and qRT-PCR assays were performed to detect the expressions levels of cardiac hypertrophy related molecules. Results: After 12 weeks of treatment, DAPA significantly ameliorated cardiac function and inhibited cardiac hypertrophy in AAC-induced mice. In vitro, DAPA significantly inhibited abnormal hypertrophy in AngII-induced cardiacmyocytes. Both in vivo and in vitro experiments have confirmed that DAPA could mediate the Plin5/PPARα signaling axis to play a protective role in inhibiting cardiac hypertrophy. Conclusion: Dapagliflozin activated the Plin5/PPARα signaling axis and exerts a protective effect against cardiac hypertrophy.

Yu|Jing|J| Zhao|Huanhuan|H| Qi|Xin|X| Wei|Liping|L| Li|Zihao|Z| Li|Chunpeng|C| Zhang|Xiaoying|X| Wu|Hao|H|

dapagliflozin
Plin5/PPARα signaling
cardiac hypertrophy
mice
AngII


Perylene Bisimide Cyclophanes with High Binding Affinity for Large Planar Polycyclic Aromatic Hydrocarbons: Host-Guest Complexation versus Self-Encapsulation of Side Arms.

Abstract: Binding of guest molecules with high affinity and selectivity requires well-designed hosts to provide optimized interactions in the host-guest complexes. Herein we report the design and synthesis of new cyclophanes 2PBI(2,6-iPr)2 and 2PBI(2,6-Ph)2 based on core-disubstituted perylene bisimide (PBI) chromophores bearing two phenoxy bay-substituents that evoke almost planar PBI scaffolds. This strategy afforded the new cyclophanes with conformationally rigid cavities to ensure strong binding to stiff planar polycyclic aromatic hydrocarbons (PAHs). Our detailed host-guest binding studies with different PAHs by UV/Vis and fluorescence titration experiments revealed record binding strengths for PAHs with binding constants of up to 1.6×106  m-1 in chloroform at room temperature. One- and two-dimensional NMR experiments and solvent-dependent titration studies revealed self-encapsulation of the side arms of PBI bay-substituents into the cavities that attained high fluorescence quantum yields of these cyclophanes close to unity by preventing the interaction of PBI subunits in the excited states. The binding constants and Gibbs free energies of host-guest complexations disclosed significant effects of PBI bay-substituents and core twist on the binding affinity of the cyclophanes.

perylene bisimides
cyclophanes
self-encapsulation
dyes/pigments
host-guest chemistry


Automatic detection of peripheral stimuli in shooters and handball players: an event-related potential study.

Abstract: This study examined the practice-related sensitivity of automatic change detection. The visual mismatch negativity (vMMN) component of event-related potentials was compared in handball players and in sport shooters. Whereas effective performance in handball requires processing of a wide visual field, effective performance in shooting requires concentration to a narrow field. Thus, we hypothesized larger sensitivity to peripheral stimuli violating the regularity of sequential stimulation in handball players. Participants performed a tracking task, while task-irrelevant checkerboard patterns (a frequent and an infrequent type) were presented in the lateral parts of the visual field. We analyzed the vMMN, a signature of automatic detection of violating sequential regularity, and sensory components (P1, N1, and P2). We obtained larger vMMN in the handball players' group indicating larger sensitivity to peripheral stimuli. These results suggest the plasticity of the automatic visual processing, i.e., it can adapt to sport-specific demands, and this can be captured even in a short experimental session in the laboratory.

Handball
Automatic change detection
Visual mismatch negativity
Shooting
Event-related brain potentials (ERPs)
Peripheral visual sensitivity


Transcriptome-wide differences between Saccharomyces cerevisiae and Saccharomyces cerevisiae var. boulardii: Clues on host survival and probiotic activity based on promoter sequence variability.

Abstract: Although Saccharomyces cerevisiae and S. cerevisiae var. boulardii share more than 95% genome sequence homology, only S. cerevisiae var. boulardii displays probiotic activity. In this study, the transcriptomic differences exhibited by S. cerevisiae and S. cerevisiae var. boulardii in intestinal like medium were evaluated. S. cerevisiae was found to display stress response overexpression, consistent with higher ability of S. cerevisiae var. boulardii to survive within the human host, while S. cerevisiae var. boulardii exhibited transcriptional patterns associated with probiotic activity, suggesting increased acetate biosynthesis. Resorting to the creation of a S. cerevisiae var. boulardii genomic database within Yeastract+, a possible correlation between loss or gain of transcription factor binding sites in S. cerevisiae var. boulardii promoters and the transcriptomic pattern is discussed. This study suggests that S. cerevisiae var. boulardii probiotic activity, when compared to S. cerevisiae, relies, at least partially, on differential expression regulation, based on promoter variability.

Pais|Pedro|P|
Oliveira|Jorge|J|
Almeida|Vanda|V|
Yilmaz|Melike|M|
Monteiro|Pedro T|PT|
Teixeira|Miguel C|MC|

Saccharomyces cerevisiae var. boulardii
Boulardii database
Comparative transcriptomics
Global promoter analysis
Probiotic yeast


A two-circular RNA signature as a noninvasive diagnostic biomarker for lung adenocarcinoma.

Abstract:
BACKGROUND
Recently, circular RNAs (circRNAs) have been reported to be microRNA sponges and play essential roles in cancer development. This study aimed to evaluate whether circulating circRNAs could be used as diagnostic biomarkers for lung adenocarcinoma (LUAD).

METHODS
The Gene Expression Omnibus (GEO) dataset was used to investigate differentially expressed circRNAs (DEcircRNAs) in paired LUAD tissues and adjacent nontumor tissues. The expression levels of the host genes were analyzed in The Cancer Genome Atlas (TCGA)-LUAD dataset, and the prognostic value was assessed using the Kaplan-Meier plotter. Quantitative real-time PCR (qRT-PCR) was performed to validate the expression of candidate circRNAs in the LUAD plasma and cells. The CCK8 assay was used to measure the function of circRNAs in cell proliferation. Competing endogenous RNA (ceRNA) network, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to predict the possible mechanisms and functions of circRNAs in LUAD.

RESULTS
Two upregulated and two downregulated circRNAs were identified as candidate circRNAs using bioinformatics analysis. qRT-PCR demonstrated that hsa_circ_0005962 was upregulated in LUAD plasma and cells, whereas hsa_circ_0086414 was downregulated. Receiver operating characteristic (ROC) curve analysis confirmed that a signature comprising the two circRNAs had good diagnostic potential, with an area under the ROC curve (AUC) of 0.81 (P < 0.0001). In addition, we observed that overexpression of plasma hsa_circ_0086414 was related to EGFR mutations (P = 0.001). Plasma hsa_circ_0005962 displayed significantly different expression before and after surgery in patients with LUAD (P < 0.0001). In vitro experiments suggested that hsa_circ_0005962 promoted LUAD cell proliferation. For future studies, we predicted the circRNA-miRNA-mRNA network for hsa_circ_0005962. Bioinformatics analysis revealed that hsa_circ_0005962 might be involved in LUAD development.

CONCLUSION
A circRNA signature was identified as a potential noninvasive biomarker for LUAD diagnosis.

Liu|Xiao-Xia|XX| Yang|Yi-E|YE| Liu|Xiao|X| Zhang|Meng-Yu|MY| Li|Rui|R| Yin|Yun-Hong|YH| Qu|Yi-Qing|YQ|0000-0002-9538-7601

D015972:Gene Expression Regulation, Neoplastic

Biomarker CircRNA LUAD Plasma Hsa_circ_0005962 Hsa_circ_0086414 Diagnosis


Regulation of melanocortin 1 receptor in allergic rhinitis in vitro and in vivo.

Abstract:
BACKGROUND
α-melanocyte-stimulating hormone (α-MSH) was shown to inhibit allergic airway inflammation and exert suppressive effects on human basophils.

OBJECTIVE
This study aims to extend our current knowledge on the melanocortin 1 receptor (MC1R) expression in nasal tissue of patients with allergic rhinitis (AR) and functional effects of α-MSH in human basophils especially from patients with allergic rhinitis.

METHODS
MC1R expression before and after nasal allergen provocation was studied in nasal mucosal tissue of AR patients and in a mouse model of allergic airway inflammation using immunofluorescence. In vitro regulation of the MC1R and CD203c surface expression on whole-blood basophils of patients with AR and controls was assessed with flow cytometry. Functional effects of α-MSH on isolated basophils were analysed regarding apoptosis with flow cytometry and chemotaxis using a Boyden chamber assay.

RESULTS
We detected an accumulation of MC1R-positive basophils in nasal mucosa tissue of patients with AR 24 h after nasal allergen provocation. Such accumulation was not present in mucosa sections from healthy controls. In mice with allergic airway inflammation, we found a clear accumulation of MC1R-positive basophils in the nasal tissue compared to control mice. MC1R expression was inducible in AR patients and controls by stimulation with anti-IgE. α-MSH inhibited anti-IgE and grass pollen induced upregulation of CD203c, but had no effect on chemotaxis or apoptosis of basophils in vitro.

CONCLUSIONS AND CLINICAL RELEVANCE
MC1R-positive basophils accumulate in the nasal mucosa of patients with AR after nasal allergen provocation. Since α-MSH suppresses proinflammatory effector functions in human basophils via the MC1R, it constitutes an interesting novel target for modulating the allergic inflammatory response.

Kleiner|S|S|
Braunstahl|G-J|GJ|
Rüdrich|U|U|
Gehring|M|M|
Eiz-Vesper|B|B|
Luger|T A|TA|
Steelant|B|B|
Seys|S F|SF|
Kapp|A|A|
Böhm|M|M|
Hellings|P W|PW|
Raap|U|U|

allergic rhinitis
basophils
alpha-melanocyte stimulating hormone
melanocortin receptor


Factors That Influence Surgical Margin State in Patients Undergoing Cold Knife Conization - A Single Center Experience.

Abstract:
AIM
To evaluate the factors that influence the surgical margin state in patients undergoing cold knife conization at the University Clinic of Gynecology and Obstetrics in Skopje, Republic of Macedonia Materials and methods: We have retrospectively analyzed the medical records of all patients that underwent a cold knife conization at our Clinic in 2015. We cross-referenced the surgical margin state with the histopathological diagnosis (LSIL, HSIL or micro-invasive/invasive cancer), menopausal status of the patients, number of pregnancies, surgeon experience, operating time and cone depth. The data was analyzed with the Chi square test, Fisher's exact test for categorical data and Student's T test for continuous data and univariate and multivariate logistical regressions were performed.

RESULTS
A total of 246 medical records have neen analyzed, out of which 29 (11.79%) patients had LSIL, 194 (78.86%) had HSIL and 23 (9.34%) patients suffered micro-invasive/invasive cervical cancer. The surgical margins were positive in 78 (31.7%) of the patients. The average age of the patients was 41.13 and 35 (14.23%) of the patients were menopausal. The multivariate logistic regression identified preoperative forceps biopsy of micro-invasive SCC, HSIL or higher cone specimen histology and shorter cone depth as independent predictors of surgical margin involvement in patients undergoing cold knife conization.

CONCLUSION
In the current study, we have found no association between the inherent characteristics of the patient and the surgeon and the surgical margin state after a CKC. The most important predictors for positive margins were the severity of the lesion and the cone depth.

Aluloski|Igor|I| Tanturovski|Mile|M| Petrusevska|Gordana|G| Jovanovic|Rubens|R| Kostadinova-Kunovska|Slavica|S|

D065310:Squamous Intraepithelial Lesions of the Cervix

surgical margin
Cold knife conization
residual disease


Pyrolytic carbon humeral head in hemi-shoulder arthroplasty: preliminary results at 2-year follow-up.

Abstract:
Background
In patients with osteoarthritis (OA) and an intact rotator cuff, hemi-shoulder arthroplasty (HSA) can be a viable option as it offers the advantage of keeping the native glenoid intact. However, glenoid erosion has frequently been reported. The aim of this study was to report preliminary clinical results of HSA with a new pyrolytic carbon (pyrocarbon) humeral head.

Methods
This prospective multicenter study included a continuous series of 65 patients who underwent pyrocarbon HSA in 5 centers.

Results
At the time of analysis, 1 patient was lost to follow-up, 3 patients underwent revision, and 61 patients were evaluated at a mean follow-up of 25.9 ± 3.3 months. The mean age at index surgery was 57.9 ± 13.3 years. The indications were primary glenohumeral OA in 37 patients, osteonecrosis in 11, secondary OA in 11, and rheumatoid arthritis in 2. The mean Constant score increased from 31.0 ± 15.8 points at baseline to 74.6 ± 17 points at last follow-up. Radiographic analyses showed that 86% of glenoids remained unchanged whereas 14% evolved slightly.

Conclusions
Pyrocarbon HSA grants improvement in pain and function in patients with primary OA or secondary OA after instability but at a lower level in patients with post-traumatic sequelae (secondary OA or osteonecrosis). These preliminary clinical and radiologic results are encouraging, although they need to be confirmed by longer-term follow-up observations.

Garret|Jérôme|J|
Harly|Edouard|E|
Le Huec|Jean-Charles|JC|
Brunner|Ulrich|U|
Rotini|Roberto|R|
Godenèche|Arnaud|A|

pyrolytic carbon
glenoid erosion
pyrocarbon
Shoulder arthroplasty
glenohumeral arthritis
hemiarthroplasty
posterior glenoid bone loss
posterior subluxation


Golgi Distribution of Lyn to Caveolin- and Giantin-Positive cis-Golgi Membranes and the Caveolin-Negative, TGN46-Positive trans-Golgi Network.

Abstract: Src-family tyrosine kinases, classified as cytosolic enzymes, have crucial roles in regulating cell proliferation, differentiation, migration and cell-shape changes. Newly synthesized Lyn, a member of Src-family kinases, is biosynthetically accumulated at the cytoplasmic face of caveolin-containing Golgi membranes via posttranslational lipid modifications and then transported to the plasma membrane. However, the precise intra-Golgi localization of Lyn remains elusive. By means of a 19°C block-release technique and short-term brefeldin A treatment, we show here that the distribution of Lyn is not monotonously spread within the Golgi but selectively intensified in two distinct membrane compartments: giantin- and caveolin-positive membranes and trans-Golgi network protein (TGN)46-positive but caveolin-negative membranes. Furthermore, Lyn exits the Golgi from the caveolin-positive cis-Golgi cisternae or the caveolin-negative trans-Golgi network. These results suggest that Lyn moves apart from caveolin, a secretory protein, within the Golgi during Lyn's trafficking to the plasma membrane.

Okamoto|Aya|A| Morinaga|Takao|T| Yamaguchi|Noritaka|N| Yamaguchi|Naoto|N|

D000818:Animals
D019556:COS Cells
D022461:Caveolins
D002522:Chlorocebus aethiops
D006056:Golgi Apparatus
D000077614:Golgi Matrix Proteins
D007425:Intracellular Membranes
D008562:Membrane Glycoproteins
D008565:Membrane Proteins
D021381:Protein Transport
D019061:src-Family Kinases
D021601:trans-Golgi Network

Golgi
Lyn
caveolin
trafficking
giantin
trans-Golgi network protein (TGN)46


Emerging materials for sample preparation.

Abstract: This review provides an update on the implementation of emerging materials as sorbents for sample preparation in combination with chromatographic separation. We have focused on recent applications of metal-organic frameworks, layered double hydroxides, porous carbons obtained from polymers or biomass precursors, and silicates (clays and zeolites). The review is directed toward the strategies followed by the authors to engineer suitable supports enabling the application of materials with unconventional size and shape as high-performance sorbents to explore new boundaries in sample pretreatment in manual or automated modes.

sample preparation
metal-organic frameworks
layered double hydroxides
porous carbons
silicates


Molecular updates in adipocytic neoplasms✰.

Abstract: Adipocytic neoplasms include a diversity of both benign tumors (lipomas) and malignancies (liposarcomas), and each tumor type is characterized by its own unique molecular alterations driving tumorigenesis. Work over the past 30 years has established the diagnostic utility of several of these characteristic molecular alterations (e.g. MDM2 amplification in well- and dedifferentiated liposarcoma, FUS/EWSR1-DDIT3 gene fusions in myxoid liposarcoma, RB1 loss in spindle cell/pleomorphic lipoma). More recent studies have focused on additional molecular alterations which may have therapeutic or prognostic impact. This review will summarize several of the important molecular findings in adipocytic tumors that have been described over the past 10 years.

D014408:Biomarkers, Tumor
D006801:Humans
D018205:Neoplasms, Adipose Tissue

MDM2
Dedifferentiated liposarcoma
Myxoid liposarcoma
RB1
Atypical spindle cell lipomatous tumor
CDK4
Genomics
TERT
Well-differentiated liposarcoma


Effect of total knee arthroplasty on type II diabetes mellitus and hypertension: A prospective study.

Abstract:
CONTEXT
Advanced osteoarthritis of knee joint if bilateral, severely restricts patient mobility. This acts as an aggravating factor for pre existing comorbid elements of metabolical syndrome (MS) like Type II diabetes mellitus and hypertension as patients are unable to carry out therapeutic walks. Successfully implanted total knee arthroplasty (TKA) increases physical activity and enables to carry out therapeutic walks thus may help in better control of type II diabetes mellitus and hypertension. The objective of this prospective study was to find whether TKA for osteoarthritis knee had any effect to improve blood glucose levels and reduce blood pressure.

MATERIALS AND METHODS
A prospective study was done in which patients operated for tricompartmental osteoarthritis of knee with associated comorbidities like Type II diabetes mellitus or hypertension during a period of 2008 and 2009 were studied. One hundred and twenty patients were enrolled (55 diabetics, 65 hypertensives) who met our inclusion criteria. Preoperative knee society score, lower extremity activity scale fasting blood glucose level and systolic and diastolic blood pressure were compared with one year followup values. The KSS and LEAS scores were analysed by the Wilcoxon signed ranked test, while the fasting blood glucose (FBG) levels and systolic and diastolic blood pressure levels were analysed by paired 't' test.

RESULTS
The reduction of systolic blood pressure by 8 mmHg (t = 5.6, P value < 0.05) and diastolic blood pressure by 6 mmHg (t = 7.6, P value < 0.05) was recorded which was statistically significant. However, no statistically significant effect on fasting blood glucose levels was observed (t = -0.77, P value = 0.442). KSS improved in DM from preoperative 29 to 86 and LEAS improved from 6.7 to 11.3.

CONCLUSIONS
Authors are of the opinion that successful total knee replacement results in increased physical activity and reduces blood pressure (systolic and diastolic) in hypertensives. However, the same is not seen in blood glucose level. Increased physical activity and reduced dependence on NSAIDS postoperatively, may be contributing in reduction of systolic and diastolic blood pressure. Further studies in this aspect are necessary.

Vaidya|Shrinand V|SV|
Arora|Arvind|A|
Mathesul|Ambarish A|AA|

total knee arthroplasty
type II diabetes mellitus
Diabetes mellitus
hypertension
metabolic syndrome


Sustainable Aromatic Aliphatic Polyesters and Polyurethanes Prepared from Vanillin-Derived Diols via Green Catalysis.

Abstract: The design and preparation of polymers by using biobased chemicals is regarded as an important strategy towards a sustainable polymer chemistry. Herein, two aromatic diols, 4-(hydroxymethyl)-2-methoxyphenol and 2-(4-(hydroxymethyl)-2-methoxyphenoxy)ethanol, have been prepared in good yields through the direct reduction of vanillin and hydroxyethylated vanillin (4-(2-hydroxyethoxy)-3-methoxybenzaldehyde) using NaBH4, respectively. The diols were submitted to traditional polycondensation and polyaddition with acyl chlorides and diisocyanatos, and serials of new polyesters and polyurethanes were prepared in high yields with moderate molecular weight ranging from 17,000 to 40,000 g mol-1. Their structures were characterized by 1H NMR, 13C NMR and FTIR, and their thermal properties were studied by TGA and differential scanning calorimetry (DSC), indicating that the as-prepared polyesters and polyurethanes have Tg in the range of 16.2 to 81.2 °C and 11.6 to 80.4 °C, respectively.

Zhao|Changbo|C|
Huang|Caijuan|C|
Chen|Qin|Q|
Ingram|Ian D V|IDV|
Zeng|Xiankui|X|
Ren|Tianhua|T|
Xie|Haibo|H|

polyurethane
green catalysis
vanillin
full bio-based polyesters
lignin


Forensic intelligence framework. Part II: Study of the main generic building blocks and challenges through the examples of illicit drugs and false identity documents monitoring.

Abstract: The development of forensic intelligence relies on the expression of suitable models that better represent the contribution of forensic intelligence in relation to the criminal justice system, policing and security. Such models assist in comparing and evaluating methods and new technologies, provide transparency and foster the development of new applications. Interestingly, strong similarities between two separate projects focusing on specific forensic science areas were recently observed. These observations have led to the induction of a general model (Part I) that could guide the use of any forensic science case data in an intelligence perspective. The present article builds upon this general approach by focusing on decisional and organisational issues. The article investigates the comparison process and evaluation system that lay at the heart of the forensic intelligence framework, advocating scientific decision criteria and a structured but flexible and dynamic architecture. These building blocks are crucial and clearly lay within the expertise of forensic scientists. However, it is only part of the problem. Forensic intelligence includes other blocks with their respective interactions, decision points and tensions (e.g. regarding how to guide detection and how to integrate forensic information with other information). Formalising these blocks identifies many questions and potential answers. Addressing these questions is essential for the progress of the discipline. Such a process requires clarifying the role and place of the forensic scientist within the whole process and their relationship to other stakeholders.

Baechler|Simon|S|
Morelato|Marie|M|
Ribaux|Olivier|O|
Beavis|Alison|A|
Tahtouh|Mark|M|
Kirkbride|K Paul|KP|
Esseiva|Pierre|P|
Margot|Pierre|P|
Roux|Claude|C|

D008192:Deception
D044707:Forensic Sciences
D006801:Humans
D063867:Identity Theft
D013287:Illicit Drugs
D016013:Likelihood Functions

Model
Forensic science
Comparison process
Integration
Organisation and decisions


A National Survey of Robotic Surgery Training Among Otolaryngology-Head and Neck Surgery Residents.

Abstract:
OBJECTIVE
The aim of this study is to describe the current state of robotic surgery training among Otolaryngology-Head and Neck Surgery (OHNS) residency programs in the United States.

METHODS
This is a national survey study among OHNS residents. All OHNS residency programs were identified via the Accreditation Council for Graduate Medical Education website. A total of 64/127 (50.3%) of OHNS programs were selected based on a random number generator. The main outcome measure was the number of OHNS residents with access to robotic surgery training and assessment of operative experience in robotic surgery among those residents.

RESULTS
A total of 140 OHNS residents participated in the survey, of which 59.3% (n = 83) were male. Response rate was 40.2%. Respondents came from middle 50.0% (n = 70), southern 17.8% (n = 25), western 17.8% (n = 25), and eastern sections 14.3% (n = 20). Most respondents (94.3%, n = 132) reported that their institution utilized a robot for head and neck surgery. Resident experience at the bedside increased in the junior years of training and console experience increased across the years particularly for more senior residents. However, 63.4% of residents reported no operative experience at the console. Only 11.4% of programs have a structured robotics training program.

CONCLUSION
This survey indicated that nearly all OHNS residencies utilize robotic surgery in their clinical practice with residents receiving little formal education in robotics or experience at the console. OHNS residencies should aim to increase access to training opportunities in order to increase resident competency.

LEVEL OF EVIDENCE
IV.

robotic surgery
residency
head and neck cancer
minimally invasive surgery
surgical education


Identification of Essential Proteins Based on Improved HITS Algorithm.

Abstract: Essential proteins are critical to the development and survival of cells. Identifying and analyzing essential proteins is vital to understand the molecular mechanisms of living cells and design new drugs. With the development of high-throughput technologies, many protein⁻protein interaction (PPI) data are available, which facilitates the studies of essential proteins at the network level. Up to now, although various computational methods have been proposed, the prediction precision still needs to be improved. In this paper, we propose a novel method by applying Hyperlink-Induced Topic Search (HITS) on weighted PPI networks to detect essential proteins, named HSEP. First, an original undirected PPI network is transformed into a bidirectional PPI network. Then, both biological information and network topological characteristics are taken into account to weighted PPI networks. Pieces of biological information include gene expression data, Gene Ontology (GO) annotation and subcellular localization. The edge clustering coefficient is represented as network topological characteristics to measure the closeness of two connected nodes. We conducted experiments on two species, namely Saccharomyces cerevisiae and Drosophila melanogaster, and the experimental results show that HSEP outperformed some state-of-the-art essential proteins detection techniques.

D000465:Algorithms
D000818:Animals
D063990:Gene Ontology
D020043:Genes, Essential
D006801:Humans
D011485:Protein Binding
D025941:Protein Interaction Mapping
D060066:Protein Interaction Maps
D021381:Protein Transport

essential proteins
HITS algorithm
weighted PPI networks
HSEP


Dark Rearing Promotes the Recovery of Visual Cortical Responses but Not the Morphology of Geniculocortical Axons in Amblyopic Cat.

Abstract: Monocular deprivation (MD) of vision during early postnatal life induces amblyopia, and most neurons in the primary visual cortex lose their responses to the closed eye. Anatomically, the somata of neurons in the closed-eye recipient layer of the lateral geniculate nucleus (LGN) shrink and their axons projecting to the visual cortex retract. Although it has been difficult to restore visual acuity after maturation, recent studies in rodents and cats showed that a period of exposure to complete darkness could promote recovery from amblyopia induced by prior MD. However, in cats, which have an organization of central visual pathways similar to humans, the effect of dark rearing only improves monocular vision and does not restore binocular depth perception. To determine whether dark rearing can completely restore the visual pathway, we examined its effect on the three major concomitants of MD in individual visual neurons, eye preference of visual cortical neurons and soma size and axon morphology of LGN neurons. Dark rearing improved the recovery of visual cortical responses to the closed eye compared with the recovery under binocular conditions. However, geniculocortical axons serving the closed eye remained retracted after dark rearing, whereas reopening the closed eye restored the soma size of LGN neurons. These results indicate that dark rearing incompletely restores the visual pathway, and thus exerts a limited restorative effect on visual function.

Gotou|Takahiro|T| Kameyama|Katsuro|K| Kobayashi|Ayane|A| Okamura|Kayoko|K| Ando|Takahiko|T| Terata|Keiko|K| Yamada|Chihiro|C| Ohta|Hiroyuki|H| Morizane|Ayaka|A| Hata|Yoshio|Y|

dark rearing
geniculocortical axons
monocular deprivation
amblyopia
visual cortex
ocular dominance


Cnm is a major virulence factor of invasive Streptococcus mutans and part of a conserved three-gene locus.

Abstract: Cnm, a collagen- and laminin-binding protein present in a subset of Streptococcus mutans strains, mediates binding to extracellular matrices (ECM), intracellular invasion and virulence in the Galleria mellonella model. Antibodies raised against Cnm were used to confirm expression and the cell surface localization of Cnm in the highly invasive OMZ175 strain. Sequence analysis identified two additional genes (cnaB and cbpA) encoding putative surface proteins immediately upstream of cnm. Inactivation of cnaB and cbpA in OMZ175, individually or in combination, did not decrease the ability of this highly invasive and virulent strain to bind to different ECM proteins, invade human coronary artery endothelial cells (HCAEC), or kill G. mellonella. Similarly, expression of cnaB and cbpA in the cnm(-) strain UA159 revealed that these genes did not enhance Cnm-related phenotypes. However, integration of cnm in the chromosome of UA159 significantly increased its ability to bind to collagen and laminin, invade HCAEC, and kill G. mellonella. Moreover, the presence of antibodies against Cnm nearly abolished the ability of OMZ175 to bind to collagen and laminin and invade HCAEC, and significantly protected G. mellonella against OMZ175 infection. We concluded that neither CnaB nor CbpA is necessary for the expression of Cnm-related traits. We also provided definitive evidence that Cnm is an important virulence factor and a suitable target for the development of novel preventive and therapeutic strategies to combat invasive S. mutans strains.

Avilés-Reyes|A|A|
Miller|J H|JH|
Simpson-Haidaris|P J|PJ|
Lemos|J A|JA|
Abranches|J|J|

D018829:Adhesins, Bacterial
D000818:Animals
D000907:Antibodies, Bacterial
D001422:Bacterial Adhesion
D001426:Bacterial Proteins
D002352:Carrier Proteins
D002460:Cell Line
D003094:Collagen
D042783:Endothelial Cells
D005109:Extracellular Matrix
D056426:Genetic Loci
D006801:Humans
D007797:Laminin
D008565:Membrane Proteins
D009036:Moths
D013290:Streptococcal Infections
D013295:Streptococcus mutans
D037521:Virulence Factors

Cnm
Streptococcus mutans
intracellular invasion
collagen-binding protein


Impact of COVID-19 on pregnancy and delivery - current knowledge.

Abstract: The World Health Organization announced on 12 March 2020 a global pandemic of the new SARS-CoV-2 coronavirus causing COVID-19 disease associated with pneumonia and acute respiratory failure. SARS-CoV-2 has caused so far over 6.66 million recorded cases, of which 393,000 ended in death (as of June 1, 2020). Despite the demographic statistics of incidence, there is no current recording of cases in the group of pregnant or perinatal women. Changes occurring in the female body system during pregnancy also affect and alter the immune system, and as studies based on other viral respiratory infections have shown, the population of pregnant women is at risk of having a severe course of the disease. The aim of the study is to summarize current reports on the course of COVID-19 disease in a group of pregnant women and the possible impact of SARS-CoV-2 on the foetus and vertical transmission, taking into account changes occurring in the woman's immune system during pregnancy. Available advice and recommendations for antenatal and perinatal care of pregnant women during the pandemic period are also included.

D018445:Infectious Disease Transmission, Vertical

COVID-19 pregnancy delivery SARS-CoV-2 coronavirus breastfeeding


Traumatic spinal cord injury caused by low falls and high falls: a comparative study.

Abstract:
BACKGROUND
Quite a few traumatic spinal cord injuries (TSCI) were caused by falls. However, the comparison of different causes of TSCI or the epidemiological characteristics of TSCI caused by falls of different heights are rare. This study investigated the epidemiological characteristics of TSCI caused by falls and conducted a comparison between low falls and high falls.

METHOD
Data from cases with TSCI admitted to China Rehabilitation Research Center from 2010 to 2019 were collected, including age, gender, occupation, cause, neurological level, and severity of the injury in admission, combined injuries, complications, and rehabilitation length of stay. Mann-Whitney U and chi-square (χ2) tests were used to assess the differences between two groups at a statistical significance level of 0.05.

RESULT
A total of 1858 TSCI cases were included and 41.7% were caused by falls, 11.4% by low falls and 30.3% by high falls, respectively. Patients with fall-induced TSCI were older and had a shorter rehabilitation length of stay than those with non-fall-induced TSCI. Patients with high fall-induced TSCI were younger and more likely to suffer from paraplegia, severer injuries, and combined injuries, and had longer time from injury to rehabilitation and rehabilitation length of stay, compared with patients with low fall-induced TSCI.

CONCLUSION
Falls is the leading causes of TSCI and high fall is becoming more common. Attention not only should be paid to high falls for the severe injury and longer hospitalization, but also low falls due to the higher neurological level of the injury and the aging of population in China.

Spinal cord injury
Fall
Epidemiology
Length of stay
Functional outcome
Older people
Workplace


Complicating causality: patient and professional perspectives on obstetric fistula in Nigeria.

Abstract: Obstetric fistula, a preventable maternal morbidity characterised by chronic bladder and/or bowel incontinence, is widespread in Nigeria. This qualitative, multi-site study examined the competing narratives on obstetric fistula causality in Nigeria. Research methods were participant observation and in-depth interviews with 86 fistula patients and 43 healthcare professionals. The study found that both patient and professional narratives identified limited access to medical facilities as a major factor leading to obstetric fistula. Patients and professionals beliefs regarding the access problem, however, differed significantly. The majority of fistula patients reported either delivering or attempting to deliver in medical facilities and most patients attributed fistula to a lack of trained medical staff and mismanagement at medical facilities. Conversely, a majority of health professionals believed that women developed obstetric fistula because they chose to deliver at home due to women's traditional beliefs about womanhood and childbirth. Both groups described financial constraints and inadequate transport to medical facilities during complicated labour as related to obstetric fistula onset. Programmatic insights derived from these findings should inform fistula prevention interventions both with healthcare professionals and with Nigerian women.

Phillips|Beth S|BS|
Ononokpono|Dorothy N|DN|
Udofia|Nsikanabasi W|NW|

professional perspectives
obstetric fistula
Nigeria
patient perspectives


The influence of a conductor and co-performer on auditory-motor synchronisation, temporal prediction, and ancillary entrainment in a musical drumming task.

Abstract: Interpersonal coordination is exemplified in ensemble musicians, who coordinate their actions deliberately in order to achieve temporal synchronisation in their performances. However, musicians also move parts of their bodies unintentionally or spontaneously, sometimes in ways that do not directly produce sound from their instruments. Musicians' movements-intentional or otherwise-provide visual signals to co-performers, which might facilitate temporal synchronisation. In large ensembles, a conductor also provides a visual cue, which has been shown to enhance synchronisation. In the present study, we tested how visual cues from a co-performer and a conductor affect processes of temporal anticipation, synchronisation, and ancillary movements in a sample of primarily non-musicians. We used a dyadic synchronisation drumming task, in which paired participants drummed to the beat of tempo-changing music. We manipulated visual access between partners and a virtual conductor. Results showed that the conductor improved synchronisation with the music, but synchrony with the music did not improve when partners could see each other. Temporal prediction was improved when partners saw the conductor, but not each other. Ancillary movements of the head were more synchronised between partners when they could see each other, and greater ancillary synchrony at beat-related frequencies of movement was associated with greater drumming synchrony. These results suggest that compatible audio-visual cues can improve intentional synchronisation, that ancillary movements are affected by seeing a partner, and that attended vs. incidental visual cues thus have partially dissociable effects on temporal coordination during joint action.

Colley|Ian|I|
Varlet|Manuel|M|
MacRitchie|Jennifer|J|
Keller|Peter E|PE|

Entrainment
Ancillary movements
Dyadic synchronisation
Musical synchronisation
Sensorimotor synchronisation


Deficiency of the miR-29a/b-1 cluster leads to ataxic features and cerebellar alterations in mice.

Abstract: miR-29 is expressed strongly in the brain and alterations in expression have been linked to several neurological disorders. To further explore the function of this miRNA in the brain, we generated miR-29a/b-1 knockout animals. Knockout mice develop a progressive disorder characterized by locomotor impairment and ataxia. The different members of the miR-29 family are strongly expressed in neurons of the olfactory bulb, the hippocampus and in the Purkinje cells of the cerebellum. Morphological analysis showed that Purkinje cells are smaller and display less dendritic arborisation compared to their wildtype littermates. In addition, a decreased number of parallel fibers form synapses on the Purkinje cells. We identified several mRNAs significantly up-regulated in the absence of the miR-29a/b-1 cluster. At the protein level, however, the voltage-gated potassium channel Kcnc3 (Kv3.3) was significantly up-regulated in the cerebella of the miR-29a/b knockout mice. Dysregulation of KCNC3 expression may contribute to the ataxic phenotype.

Papadopoulou|Aikaterini S|AS|
Serneels|Lutgarde|L|
Achsel|Tilmann|T|
Mandemakers|Wim|W|
Callaerts-Vegh|Zsuzsanna|Z|
Dooley|James|J|
Lau|Pierre|P|
Ayoubi|Torik|T|
Radaelli|Enrico|E|
Spinazzi|Marco|M|
Neumann|Melanie|M|
Hébert|Sébastien S|SS|
Silahtaroglu|Asli|A|
Liston|Adrian|A|
D'Hooge|Rudi|R|
Glatzel|Markus|M|
De Strooper|Bart|B|

Ataxia
Purkinje cells
Cerebellum
Dendrites
Locomotor behavior
Voltage gated potassium channel
miR-29a/b-1 cluster knockout


Two new compounds from the roots of Ilex pubescens and their cytotoxic activity.

Abstract: A new phenylethanoid, 1-O-β-D-(4-hydroxyphenyl)-ethyl-6-O-vanilloyl-glucopyranoside (1), and a new furofuran lignan, (7R,7'R,7''S,8S,8'S,8''R)-4', 4''-dihydroxy-3,3',3'',5-tetramethoxy-7,9':7'9-diepoxy-4,8''-oxy-8,8'-sesquineolignan-7'',9''-diol (2), along with five known compounds (3-7) were isolated from the roots of Ilex pubescens. Their chemical structures were elucidated on the basis of extensive spectroscopic analysis, including UV, IR, MS, and NMR experiments. In addition, compounds 2-7 were evaluated in vitro for their cytotoxic effects on human HeLa cells; among them, compounds 2, 3, 6, and 7 showed cytotoxic activity against HeLa cells in the test.

Xiong|Huan|H| Zhao|Fang|F| Bi|Jiayi|J| Zhang|Yang|Y| Zhao|Guiyun|G| Chen|Xue|X| Li|Yuncong|Y| Yan|Rui|R| Zhao|Qiang|Q| Qiao|Hua|H| Zhang|Guogang|G|

D006367:HeLa Cells
D006801:Humans
D030017:Ilex
D009682:Magnetic Resonance Spectroscopy
D015394:Molecular Structure
D018517:Plant Roots

Ilex pubescens
Cytotoxic activity
Phenylethanoid
Lignans


Potential Inhibitory Influence of miRNA 210 on Regulatory T Cells during Epicutaneous Chemical Sensitization.

Abstract: Toluene diisocyanate (TDI) is a potent low molecular weight chemical sensitizer and a leading cause of chemical-induced occupational asthma. The regulatory potential of microRNAs (miRNAs) has been recognized in a variety of disease states, including allergic disease; however, the roles of miRNAs in chemical sensitization are largely unknown. In a previous work, increased expression of multiple miRNAs during TDI sensitization was observed and several putative mRNA targets identified for these miRNAs were directly related to regulatory T-cell (Treg) differentiation and function including Foxp3 and Runx3. In this work, we show that miR-210 expression is increased in the mouse draining lymph node (dLN) and Treg subsets following dermal TDI sensitization. Alterations in dLN mRNA and protein expression of Treg related genes/putative miR-210 targets (foxp3, runx3, ctla4, and cd25) were observed at multiple time points following TDI exposure and in ex vivo systems. A Treg suppression assay, including a miR-210 mimic, was utilized to investigate the suppressive ability of Tregs. Cells derived from TDI sensitized mice treated with miR-210 mimic had less expression of miR-210 compared to the acetone control suggesting other factors, such as additional miRNAs, might be involved in the regulation of the functional capabilities of these cells. These novel findings indicate that miR-210 may have an inhibitory role in Treg function during TDI sensitization. Because the functional roles of miRNAs have not been previously elucidated in a model of chemical sensitization, these data contribute to the understanding of the potential immunologic mechanisms of chemical induced allergic disease.

Long|Carrie Mae|CM|
Lukomska|Ewa|E|
Marshall|Nikki B|NB|
Nayak|Ajay|A|
Anderson|Stacey E|SE|

regulatory T cell
toluene diisocyanate
microRNA
miR-210
immunotoxicology
isocyanate


Behavior of Listeria monocytogenes and Other Microorganisms in Sliced Riojano Chorizo (Spanish Dry-Cured Sausage) during Storage under Modified Atmospheres.

Abstract: Sliced ready-to-eat meat products packaged under modified atmospheres are often marketed since they cover consumer demands. The slicing process could be a potential risk for consumers since contamination with Listeria monocytogenes could occur during this stage. The current study evaluated the behavior of L. monocytogenes and other microorganisms in commercial sliced Riojano chorizo. This meat product was sliced and inoculated with L. monocytogenes (3.5 log CFU/g) before packaging under different atmospheres (air, vacuum, 100% N2, 20% CO2/80% N2 and 40% CO2/60% N2) and stored at 4 °C for up to 60 days. Samples were taken on days 0, 7, 21, 28 and 60 of storage. L. monocytogenes, mesophiles, Enterobacteriaceae, lactic acid bacteria, Micrococcaceae, molds and yeast counts were evaluated. Additionally, water activity, humidity and pH were determined. L. monocytogenes counts decreased in inoculated sliced chorizo during storage. Packaging conditions and day of storage influenced microbial counts. After 60 days, a significant reduction (p ≤ 0.05) in the initial Listeria contamination levels (3.5. log CFU/g) between 1.1 and 1.46 logarithmic units was achieved in the sausages packaged in modified atmosphere. The highest reductions were observed in slices packaged in 40% CO2/60% N2 after 60 days of storage at 4 °C.

Listeria monocytogenes
slicing
chorizo
sausages
ready-to-eat
Micrococcaceae
yeasts
LAB
MAP
RTE
dry sausages
food safety
microbial survival


SLNB in cutaneous SCC: A review of the current state of literature and the direction for the future.

Abstract: The concept of the sentinel lymph node biopsy (SLNB) has been universally accepted for melanoma, however, remains controversial for squamous cell carcinoma (SCC). We performed a quantitative review on 260 cases of SCC that had a SLNB. The positivity rate was found to be 14.6%. Literature was qualitatively reviewed to determine whether a positive SLNB has any bearing on prognosis in SCC cases, finding a significant relationship between poor prognosis and a positive SLN (P = 0.0082).

D002294:Carcinoma, Squamous Cell
D006801:Humans
D011237:Predictive Value of Tests
D021701:Sentinel Lymph Node Biopsy
D012878:Skin Neoplasms


Establishment, Validation, and Application of a New World Primate Model of Enterotoxigenic Escherichia coli Disease for Vaccine Development.

Abstract: The establishment of an animal model that closely approximates enterotoxigenic Escherichia coli (ETEC) disease in humans is critical for the development and evaluation of vaccines against this enteropathogen. Here, we evaluated the susceptibility of Aotus nancymaae, a New World monkey species, to ETEC infection. Animals were challenged orogastrically with 109 to 1011 CFU of the human pathogenic CFA/I+ ETEC strain H10407 and examined for evidence of diarrhea and fecal shedding of bacteria. A clear dose-range effect was obtained, with diarrheal attack rates of 40% to 80%, validated in a follow-on study demonstrating an attack rate of 80% with 1011 CFU of H10407 ETEC. To determine whether this model is an effective approach for assessing ETEC vaccine candidates, we used it to evaluate the ability of the donor strand-complemented CFA/I adhesin CfaE (dscCfaE) to protect against H10407 challenge. In a series of experiments, animals were intranasally vaccinated with dscCfaE alone, dscCfaE with either cholera toxin B-subunit (CTB) or heat-labile toxin (LTB), or phosphate-buffered saline (PBS) alone and then challenged with 1011 CFU of H10407. Control animals vaccinated with PBS had attack rates of 70 to 90% on challenge. Vaccination with dscCfaE, or dscCfaE admixed with CTB or LTB, resulted in a reduction of attack rates, with vaccine efficacies of 66.7% (P = 0.02), 77.7% (P = 0.006), and 42.9% (P = 0.370) to 83.3% (P = 0.041), respectively. In conclusion, we have shown the H10407 ETEC challenge of A. nancymaae to be an effective, reproducible model of ETEC disease, and importantly, we have demonstrated that in this model, vaccination with the prototype vaccine candidate dscCfaE is protective against CF-homologous disease.

Rollenhagen|Julianne E|JE|
Jones|Franca|F|
Hall|Eric|E|
Maves|Ryan|R|
Nunez|Gladys|G|
Espinoza|Nereyda|N|
O'Dowd|Aisling|A|
Prouty|Michael G|MG|
Savarino|Stephen J|SJ|

enterotoxigenic Escherichia coli
vaccine
CfaE
nonhuman primates


The relationship between the status and position of third molars and the presence of mandibular angle and condylar fractures.

Abstract:
INTRODUCTION
The aim of this study was to assess the relationship between the status and position of third molars, and the presence of mandibular angle and/or condylar fractures, in a group of patients treated for mandibular fractures, thus hoping to contribute to the knowledge of potential predictors of these fractures.

METHODS
A retrospective study was designated to include all the patients who were diagnosed and treated with open reduction and internal fixation for isolated mandibular angle fractures or isolated mandibular condylar fractures between 1st of January 2012 and 31st of December 2018. The following data were collected for each included patient: gender, age, etiology, site and side of the fracture, and presence and eruption state of third molars in the fracture side.

RESULTS
Seventy patients were diagnosed with a condylar fracture, 48 with an angle fracture. No statistically significant difference was observed as for etiology and gender distribution between angle fracture and condyle fracture patients (p > 0.05). Angle fractures were statistically associated with the presence of third molars, whereas condylar fractures with the absence of third molars (p < 0.000005). The presence of completely erupted 3Ms was associated with condylar fractures (p < 0.05), and partially impacted 3Ms were associated with angle fractures (p < 0.0005).

CONCLUSIONS
Mandibular angle fractures and third molar presence are associated in patients who present with mandibular fractures, especially if the third molar is incompletely erupted. This information should be kept in consideration as for the diagnosis and management of patients with mandibular fractures.

D006801:Humans
D008335:Mandibular Condyle
D008337:Mandibular Fractures
D008964:Molar, Third
D012189:Retrospective Studies
D014095:Tooth, Impacted

Third molar
Angle
Condylar fracture
Facial fracture
Mandible
Maxillofacial trauma


Split-TurboID enables contact-dependent proximity labeling in cells.

Abstract: Proximity labeling catalyzed by promiscuous enzymes, such as TurboID, have enabled the proteomic analysis of subcellular regions difficult or impossible to access by conventional fractionation-based approaches. Yet some cellular regions, such as organelle contact sites, remain out of reach for current PL methods. To address this limitation, we split the enzyme TurboID into two inactive fragments that recombine when driven together by a protein-protein interaction or membrane-membrane apposition. At endoplasmic reticulum-mitochondria contact sites, reconstituted TurboID catalyzed spatially restricted biotinylation, enabling the enrichment and identification of >100 endogenous proteins, including many not previously linked to endoplasmic reticulum-mitochondria contacts. We validated eight candidates by biochemical fractionation and overexpression imaging. Overall, split-TurboID is a versatile tool for conditional and spatially specific proximity labeling in cells.

Cho|Kelvin F|KF|
Branon|Tess C|TC|
Rajeev|Sanjana|S|
Svinkina|Tanya|T|
Udeshi|Namrata D|ND|
Thoudam|Themis|T|0000-0002-3845-2964
Kwak|Chulhwan|C|
Rhee|Hyun-Woo|HW|0000-0002-3817-3455
Lee|In-Kyu|IK|
Carr|Steven A|SA|
Ting|Alice Y|AY|

split-TurboID
proximity labeling
ER–mitochondria contacts


Dignity at stake: Caring for persons with impaired autonomy.

Abstract: Dignity, usually considered an essential ethical value in healthcare, is a relatively complex, multifaceted concept. However, healthcare professionals often have only a vague idea of what it means to respect dignity when providing care, especially for persons with impaired autonomy. This article focuses on two concepts of dignity, human dignity and dignity of identity, and aims to analyse how these concepts can be applied in the care for persons with impaired autonomy and in furthering the practice of respect and protection from harm. Three vignettes were designed to illustrate typical caring situations involving patients with mild to severely impaired autonomy, including patients with cognitive impairments. In situations like these, there is a risk of the patient's dignity being disrespected and violated. The vignettes were then analysed with respect to the two concepts of dignity to find out whether this approach can illuminate what is at stake in these situations and to provide an understanding of which measures could safeguard the dignity of these patients. The analysis showed that there are profound ethical challenges in the daily care of persons with impaired autonomy. We suggest that these two concepts of human dignity could help guide healthcare professionals to develop practical skills in person-centred, ethically grounded care, where the patient's wishes and needs are the starting point.

dignity
Caring
vignettes
cognitive impairment
theoretical analysis


Exposure of Female Rats to an Environmentally Relevant Mixture of Brominated Flame Retardants Targets the Ovary, Affecting Folliculogenesis and Steroidogenesis.

Abstract: Brominated flame retardants (BFRs) are incorporated into various consumer products to prevent flame propagation. These compounds leach into the domestic environment, resulting in chronic exposure and contamination. Pregnancy failure is associated with high levels of BFRs in human follicular fluid, raising serious questions regarding their impact on female reproductive health. The goal of this study is to elucidate the effects of an environmentally relevant BFR mixture on female rat ovarian functions (i.e., folliculogenesis and steroidogenesis). A BFR dietary mixture formulated to mimic the relative BFR congener levels in North American house dust was administered to adult female Sprague-Dawley rats from 2 to 3 wk before mating until Gestational Day 20; these diets were designed to deliver nominal doses of 0, 0.06, 20, or 60 mg/kg/day of the BFR mixture. Exposure to BFRs triggered an approximately 50% increase in the numbers of preantral and antral follicles and an enlargement of the antral follicles in the ovaries of the dams. A significant reduction in the expression of catalase, an antioxidant enzyme, and downregulation of the expression of insulin-like factor 3 (Insl3) and 17alpha-hydroxylase (Cyp17a1) were observed in the ovary. In addition, BFR exposure affected steroidogenesis; we observed a significant decrease in circulating 17-hydroxypregnenolone and an increase in testosterone concentrations in BFR-exposed dams. Thus, BFRs target ovarian function in the rat, adversely affecting both folliculogenesis and steroidogenesis.

Lefèvre|Pavine L C|PL|
Berger|Robert G|RG|
Ernest|Sheila R|SR|
Gaertner|Dean W|DW|
Rawn|Dorothea F K|DF|
Wade|Michael G|MG|
Robaire|Bernard|B|
Hales|Barbara F|BF|

brominated flame retardants
ovary
folliculogenesis
steroidogenesis
catalase
insulin-like factor 3
HBCDD
PBDE
androgens
endocrine disrupters
oxidative stress
toxicology


Dentine microhardness changes following conventional and alternate irrigation regimens: An in vitro study.

Abstract:
AIM
To compare the changes in microhardness of root dentin caused by two novel irrigation regimens with conventional irrigation.

MATERIALS AND METHODS
Forty extracted human permanent incisor teeth were selected. Decoronated roots were separated longitudinally to get 80 specimens that were embedded in autopolymerizing acrylic resin and grounded flat with silicon carbide abrasive papers. Of these, 60 root segments without any cracks or defects were selected and divided into four groups according to the irrigation regimen used (n = 15). Group I: 5% sodium hypochlorite (NaOCl) + 17% ethylenediaminetetraacetic acid (EDTA) + 0.2% chlorhexidine digluconate (CHX) (conventional). Group II: 6% Morinda Citrifolia Juice + 17% EDTA (MCJ). Group III: 5% NaOCl + Q Mix 2 in 1 (QMix). Group IV: Distilled water (control). Irrigation regimens were performed for 5 minutes. Dentin microhardness was measured with a Vickers indenter under a 200-g load and a 20-s dwell time at the midroot level of root dentin. The data were analyzed using Kruskal Wallis test and Dunn's multiple comparison tests.

RESULTS
A significant difference was seen in the median values of the four groups. The control group showed the least reduction in microhardness when comparison with the other groups. Except for Group III (Q Mix), the other groups that were tested (MCJ and conventional regimens) showed statistically significant difference from the control group.

CONCLUSION
Within the limitation of this study, it was concluded that NaOCl + Q Mix were least detrimental to root dentin microhardness when compared with MCJ and conventional irrigation regimens.

Das|Anusree|A| Kottoor|Jojo|J| Mathew|Joy|J| Kumar|Sanjana|S| George|Saira|S|

dentine microhardness
EDTA
Chlorhexidine
Morinda citrifolia juice
Q mix
irrigation regimes


Is local radiotherapy a viable option for patients with an opening of the ventricles during surgical resection of brain metastases?

Abstract:
BACKGROUND
Local hypofractionated stereotactic radiotherapy (HFSRT) of the resection cavity is emerging as the standard of care in the treatment of patients with a limited number of brain metastases as it warrants less neurological impairment compared to whole brain radiotherapy. In periventricular metastases surgical resection can lead to an opening of the ventricles and subsequently carries a potential risk of cerebrospinal tumour cell dissemination. The aim of this study was to assess whether local radiotherapy of the resection cavity is viable in these cases.

METHODS
From our institutional database we analyzed the data of 125 consecutive patients with resected brain metastases treated in our institution with HFSRT between 2009 and 2017. The incidence of LMD, overall survival (OS), local recurrence (LC) and distant recurrence were evaluated depending on ventricular opening (VO) during surgery.

RESULTS
From all 125 patients, the ventricles were opened during surgery in 14 cases (11.2%). None of the patients with VO and 7 patients without VO during surgery developed LMD (p = 0.371). OS (p = 0.817), LC (p = 0.524) and distant recurrence (p = 0.488) did not differ in relation to VO during surgical resection. However, the incidence of distant intraventricular recurrence was slightly increased in patients with VO (14.3% vs. 2.7%, p < 0.01).

CONCLUSION
VO during neurosurgical resection did not affect the outcome after HFSRT of the resection cavity in patients with brain metastases. Particularly, the incidence of LMD was not increased in patients receiving local HFSRT after VO. HFSRT can therefore be offered independently of VO as a local treatment of tumor bed after resection of brain metastases.


Clinical Manifestations and Surgical Management of Spinal Lesions in Patients With Mucopolysaccharidosis: A Report of 52 Cases.

Abstract:
STUDY DESIGN
Descriptive retrospective cohort of 52 pediatric patients with mucopolysaccharidosis (MPS) and spinal cord disease and surgical outcomes in a reference hospital.

OBJECTIVES
To describe clinical manifestations and surgical management and outcomes of spinal lesions.

METHODS
All medical records of 52 patients with mucopolysaccharidosis (I, II, III, IV, and VI) diagnosed between 1992 and 2011 were identified and followed at a single spine center of a pediatric hospital. Demographic, clinical manifestations, spinal cord lesions, and surgical management were the focus of the descriptive report.

RESULTS
A total of 52 patients (32 males and 20 females), mean age at diagnosis of 8 ± 4 years (range 1-19), and with a mean follow-up of 11 ± 8 years were identified. Forty-three had cervical disease (the most frequent affection found was odontoid hypoplasia followed by atlantoaxial instability) and 14 patients had thoracolumbar kyphosis. Twenty-one patients presented neurologic compromise before surgery (quadriparesis as the most frequent manifestation), with the progression of neurologic impairment being the most common surgical indication. Surgery was performed in 38 patients (25 cervical and 13 thoracolumbar). Of the 21 patients with preoperative neurologic deficit, 6 patients showed neurologic improvement. The most common surgical complication found was proximal junctional kyphosis.

CONCLUSION
This is the largest series published of mucopolysaccharidosis pediatric patients with a surgically treated spinal condition. We recommend early spinal cord decompression in mucopolysaccharidosis spine pathology to prevent or potentially reverse neurologic impairment.

LEVEL OF EVIDENCE
Level IV.

Remondino|Rodrigo G|RG|
Tello|Carlos A|CA|
Noel|Mariano|M|
Wilson|Alejandra Francheri|AF|
Galaretto|Eduardo|E|
Bersusky|Ernesto|E|
Piantoni|Lucas|L|

Mucopolysaccharidosis
Spinal cord diseases
Lysosomal storage diseases


Adherence to the Mediterranean diet and risk of bladder cancer in the EPIC cohort study.

Abstract: There is growing evidence of the protective role of the Mediterranean diet (MD) on cancer. However, to date no epidemiological study has investigated the influence of the MD on bladder cancer. We evaluated the association between adherence to the MD and risk of urothelial cell bladder cancer (UCC), according to tumor aggressiveness, in the European Prospective Investigation into Cancer and Nutrition (EPIC). The analysis included 477,312 participants, recruited from ten European countries between 1991 and 2000. Information from validated dietary questionnaires was used to develop a relative Mediterranean diet score (rMED), including nine dietary components. Cox regression models were used to assess the effect of the rMED on UCC risk, while adjusting for dietary energy and tobacco smoking of any kind. Stratified analyses were performed by sex, BMI, smoking status, European region and age at diagnosis. During an average follow-up of 11 years, 1,425 participants (70.9% male) were diagnosed with a first primary UCC. There was a negative but non-significant association between a high versus low rMED score and risk of UCC overall (HR: 0.84 [95% CI 0.69, 1.03]) and risk of aggressive (HR: 0.88 [95% CI 0.61, 1.28]) and non-aggressive tumors (HR: 0.78 [95% CI 0.54, 1.14]). Although there was no effect modification in the stratified analyses, there was a significant 34% (p = 0.043) decreased risk of UCC in current smokers with a high rMED score. In EPIC, the MD was not significantly associated with risk of UCC, although we cannot exclude that a MD may reduce risk in current smokers.

Buckland|G|G|
Ros|M M|MM|
Roswall|N|N|
Bueno-de-Mesquita|H B|HB|
Travier|N|N|
Tjonneland|A|A|
Kiemeney|L A|LA|
Sacerdote|C|C|
Tumino|R|R|
Ljungberg|B|B|
Gram|I T|IT|
Weiderpass|E|E|
Skeie|G|G|
Malm|J|J|
Ehrnström|R|R|
Chang-Claude|J|J|
Mattiello|A|A|
Agnoli|C|C|
Peeters|P H|PH|
Boutron-Ruault|M C|MC|
Fagherazzi|G|G|
Clavel-Chapelon|F|F|
Nilsson|L M|LM|
Amiano|P|P|
Trichopoulou|A|A|
Oikonomou|E|E|
Tsiotas|K|K|
Sánchez|M J|MJ|
Overvad|K|K|
Quirós|J R|JR|
Chirlaque|M D|MD|
Barricarte|A|A|
Key|T J|TJ|
Allen|N E|NE|
Khaw|K T|KT|
Wareham|N|N|
Riboli|E|E|
Kaaks|R|R|
Boeing|H|H|
Palli|D|D|
Romieu|I|I|
Romaguera|D|D|
Gonzalez|C A|CA|

D000368:Aged
D015992:Body Mass Index
D002295:Carcinoma, Transitional Cell
D004034:Diet Surveys
D038441:Diet, Mediterranean
D005060:Europe
D005260:Female
D005518:Food Preferences
D006801:Humans
D008297:Male
D008875:Middle Aged
D017063:Outcome Assessment, Health Care
D016016:Proportional Hazards Models
D011446:Prospective Studies
D018570:Risk Assessment
D012307:Risk Factors
D012907:Smoking
D011795:Surveys and Questionnaires
D013997:Time Factors
D001749:Urinary Bladder Neoplasms

European prospective investigation into cancer and nutrition cohort study


A graphic guide to the percutaneous tripod acetabular reconstruction for metastatic cancer.

Abstract: Symptomatic peri-acetabular metastatic lesions are often treated with open surgery such as modified Harrington procedures. In an effort to avoid surgical complications inherently associated with open surgical approaches, we developed and recently reported a novel Tripod percutaneous screw technique. The tripod technique is minimally invasive and was found to yield excellent outcomes regarding both pain control and functionality. The procedure is performed in a standard operative theater using fluoroscopic guided percutaneous screws. Despite the simplicity of intraoperative set-up and instrumentation, it is technically demanding. Obtaining the correct fluoroscopic views and troubleshooting intraoperative hurdles can be challenging for even an experienced orthopedic surgeon. The technique and bony conduits were previously described in the trauma literature, however, there are key points of difference in the setting of metastatic disease. Here we provide a compilation of a stepwise graphic guide for the tripod model in the setting of metastatic peri-acetabular lesions, as well as the tips and tricks based on our own experience. These encompass preoperative preparation, operating room settings, intraoperative fluoroscopic guidance, postoperative care, and subsequent conversion to a cemented total hip arthroplasty, if needed.

percutaneous
reconstruction
peri-acetabular metastasis


Changes of N6-methyladenosine modulators promote breast cancer progression.

Abstract:
BACKGROUND
Breast cancer (BC) displays striking genetic, epigenetic and phenotypic diversity. N6-methyladenosine (m6A) in mRNA has emerged as a crucial epitranscriptomic modification that controls cancer self-renewal and cell fate. However, the key enzymes of m6A expression and function in human breast carcinogenesis remain unclear.

METHODS
The expression of m6A methylases (METTL3, METTL14 and WTAP) and demethylases (FTO and ALKBH5) were analyzed by using ONCOMINE and The Cancer Genome Atlas databases and in 36 pairs of BC and adjacent non-cancerous tissue. The level of m6A in BC patients was detected by ELISA, and the function of m6A was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay and transwell assay. The database of bc-GenExMiner v4.0, Kaplan-Meier Plotter and cBioPortal were queried for correlation, mutation and prognosis analysis of BC.

RESULTS
The m6A methylases and demethylases were dysregulated in several major malignant tumors. Specifically, the expression of all m6A methylases was reduced in BC as compared with normal controls, but the demethylase ALKBH5 was induced in ONCOMINE databases and confirmed in clinical patients. METTL14 expression was positively correlated with METTL3 expression, and both showed high expression in normal breast-like and luminal-A and -B BC. Functionally, reducing m6A expression by overexpressing METTL14 and/or knockdown of ALKBH5 could inhibit breast cell viability, colony formation and cell migration. Furthermore, Kaplan-Meier, meta-analysis and univariate Cox assay showed that the expression of m6A members including METTL3, METTL14, WTAP and FTO but not their gene mutation and amplification, was tightly associated with cancer progression and poor survival.

CONCLUSIONS
Changes of m6A modulators reduced m6A may promote tumorigenesis and predict poor prognosis in BC.

Wu|Lianpin|L| Wu|Dengying|D| Ning|Jinfeng|J| Liu|Wei|W| Zhang|Donghong|D|

N6-methyladenosine
Breast cancer
Prognosis
Migration
transcription


Prediction of Alzheimer's disease pathophysiology based on cortical thickness patterns.

Abstract:
INTRODUCTION
Recent studies have shown that pathologically defined subtypes of Alzheimer's disease (AD) represent distinctive atrophy patterns and clinical characteristics. We investigated whether a cortical thickness-based clustering method can reflect such findings.

METHODS
A total of 77 AD subjects from the Alzheimer's Disease Neuroimaging Initiative 2 data set who underwent 3-T magnetic resonance imaging, [(18)F]-fluorodeoxyglucose-positron emission tomography (PET), [(18)F]-Florbetapir PET, and cerebrospinal fluid (CSF) tests were enrolled. After clustering based on cortical thickness, diverse imaging and biofluid biomarkers were compared between these groups.

RESULTS
Three cortical thinning patterns were noted: medial temporal (MT; 19.5%), diffuse (55.8%), and parietal dominant (P; 24.7%) atrophy subtypes. The P subtype was the youngest and represented more glucose hypometabolism in the parietal and occipital cortices and marked amyloid-beta accumulation in most brain regions. The MT subtype revealed more glucose hypometabolism in the left hippocampus and bilateral frontal cortices and less performance in memory tests. CSF test results did not differ between the groups.

DISCUSSION
Cortical thickness patterns can reflect pathophysiological and clinical changes in AD.

Hwang|Jihye|J|
Kim|Chan Mi|CM|
Jeon|Seun|S|
Lee|Jong Min|JM|
Hong|Yun Jeong|YJ|
Roh|Jee Hoon|JH|
Lee|Jae-Hong|JH|
Koh|Jae-Young|JY|
Na|Duk L|DL|
|||


Genome-Wide Association Study of Body Mass Index and Body Fat in Mexican-Mestizo Children.

Abstract:
BACKGROUND
Childhood obesity is a major health problem in Mexico. Obesity prevalence estimated by body mass index (BMI) is almost half than that estimated by percent body fat (%BF) in the Childhood Obesity pediatric cohort (COIPIS).

OBJECTIVE
We performed a genome-wide association study (GWAS) of BMI and %BF in 828 children from the COIPIS to identify markers of predisposition to high values for both phenotypes used for obesity classification.

METHODS
For the GWAS we used the LAT Axiom 1, Affymetrix and 2.5 million single loci from the 1000 Genomes Phase 3 imputation panel. We used a linear model, adjusted by age, sex, and Amerindian ancestry assuming an additive inheritance model.

RESULTS
Genome-wide significance (p ≤ 5.0 × 10-8) and 80% of statistical power was reached for associations of two loci in two genes (CERS3 and CYP2E1) to BMI. Also, 11 loci in six genes (ANKS1B, ARNTL2, KCNS3, LMNB1, SRGAP3, TRPC7) reached genome-wide significance for associations to %BF, though not 80% of statistical power.

DISCUSSION
None of the SNPs were previously reported as being associated to BMI or %BF. In addition, different loci were found for BMI and %BF. These results highlight the importance of gaining deeper understanding of genetic markers of predisposition to high values for the phenotypes used for obesity diagnosis.

Costa-Urrutia|Paula|P|
Colistro|Valentina|V|
Jiménez-Osorio|Angélica Saraí|AS|
Cárdenas-Hernández|Helios|H|
Solares-Tlapechco|Jacqueline|J|
Ramirez-Alcántara|Miryam|M|
Granados|Julio|J|
Ascencio-Montiel|Iván de Jesús|IJ|
Rodríguez-Arellano|Martha Eunice|ME|


Data visualization for truth maintenance in clinical decision support systems.

Abstract:
Background and objectives
The goal is to inform proactive initiatives to expand the knowledge base of clinical decision support systems.

Design and setting
We describe an initiative in which research informationists and health services researchers employ visualization tools to map logic models for clinical decision support within an electronic health record.

Materials and methods
We mapped relationships using software for social network analysis: NodeXL and CMAP. We defined relationships by shared observations, such as two Arden rules within medical logic modules that consider the same clinical observation, or by the presence of common keywords that were used to label rules according to standardized vocabularies.

Results
We studied the Child Health Improvement through Computer Automation (CHICA) system, an electronic medical record that contains 170 unique variables representing discrete clinical observations. These variables were used in 300 medical logic modules (MLM's) that prompted health care providers to deliver preventive counseling or otherwise served as clinical decision support. Using data visualization tools, we generated maps that illustrate connections, or lack thereof, between clinical topics within CHICA's MLMs.

Conclusions
The development of such maps may allow multiple disciplines commonly interacting over EMR platforms, and various perspectives (clinicians, programmers, informationists) to work more effectively as teams to refine the EMR by programming logic routines to address co-morbidities or other instances where domains of medical knowledge should be connected.

Liu|Gilbert Chien|GC|
Odell|Jere D|JD|
Whipple|Elizabeth C|EC|
Ralston|Rick|R|
Carroll|Aaron E|AE|
Downs|Stephen M|SM|

Decision support systems
Electronic health records
Information science
Management


AGO2 promotes tumor progression in KRAS-driven mouse models of non-small cell lung cancer.

Abstract: Lung cancer is the deadliest malignancy in the United States. Non-small cell lung cancer (NSCLC) accounts for 85% of cases and is frequently driven by activating mutations in the gene encoding the KRAS GTPase (e.g., KRASG12D). Our previous work demonstrated that Argonaute 2 (AGO2)-a component of the RNA-induced silencing complex (RISC)-physically interacts with RAS and promotes its downstream signaling. We therefore hypothesized that AGO2 could promote KRASG12D-dependent NSCLC in vivo. To test the hypothesis, we evaluated the impact of Ago2 knockout in the KPC (LSL-Kras  ;p53  ;Cre) mouse model of NSCLC. In KPC mice, intratracheal delivery of adenoviral Cre drives lung-specific expression of a stop-floxed KRASG12D allele and biallelic ablation of p53 Simultaneous biallelic ablation of floxed Ago2 inhibited KPC lung nodule growth while reducing proliferative index and improving pathological grade. We next applied the KP  C model, in which the Clara cell-specific CCSP-driven Cre activates KRASG12D and ablates a single p53 allele. In these mice, Ago2 ablation also reduced tumor size and grade. In both models, Ago2 knockout inhibited ERK phosphorylation (pERK) in tumor cells, indicating impaired KRAS signaling. RNA sequencing (RNA-seq) of KPC nodules and nodule-derived organoids demonstrated impaired canonical KRAS signaling with Ago2 ablation. Strikingly, accumulation of pERK in KPC organoids depended on physical interaction of AGO2 and KRAS. Taken together, our data demonstrate a pathogenic role for AGO2 in KRAS-dependent NSCLC. Given the prevalence of this malignancy and current difficulties in therapeutically targeting KRAS signaling, our work may have future translational relevance.

Tien|Jean Ching-Yi|JC|
Chugh|Seema|S|
Goodrum|Andrew E|AE|
Cheng|Yunhui|Y|
Mannan|Rahul|R|0000-0002-6642-0468
Zhang|Yuping|Y|
Wang|Lisha|L|
Dommeti|Vijaya L|VL|
Wang|Xiaoming|X|0000-0001-9697-5571
Xu|Alice|A|
Hon|Jennifer|J|
Kenum|Carson|C|
Su|Fengyun|F|
Wang|Rui|R|0000-0002-5356-9685
Cao|Xuhong|X|
Shankar|Sunita|S|0000-0001-8743-7480
Chinnaiyan|Arul M|AM|


Improvements in the multidisciplinary care are beneficial for survival in amyotrophic lateral sclerosis (ALS): experience from a tertiary ALS center.

Abstract: Objective: The Ljubljana ALS Centre, established in 2002, is the only tertiary center for amyotrophic lateral sclerosis (ALS) in Slovenia. The aim of our study was to evaluate the impact of therapeutic interventions and improvements in the multidisciplinary care on the survival of our patients.Methods: All patients diagnosed with ALS at our center during years 2003-2005 (early group) and 2011-2012 (late group) were included in this retrospective cohort study (n = 124). Kaplan-Meier survival analysis and multiple regression analysis with Cox proportional hazards model were performed to compare survival and to evaluate the differences between the two cohorts.Results: Median survival from the time of diagnosis was 13.0 (95% CI 10.2-15.8) months in the early group and 21.8 (95% CI 17.2-26.4) months in the late group (p = 0.005). In the Cox proportional hazards analysis, the late group of patients was associated with better survival independently of all other prognostic factors (hazard ratio (HR)=0.51, 95% CI = 0.32-0.81, p = 0.004). Survival was also associated with patients' age, use of noninvasive ventilation (NIV) and gastrostomy. The model fit significantly improved when the interaction between the NIV use and the observed time period was added to the model (HR = 0.34, 95% CI = 0.12-0.96, p = 0.041).Conclusions: Our findings suggest that improvements in the multidisciplinary care were beneficial for survival of our patients with ALS. The survival benefit in the late group of our patients could be partially explained by the improvements in the NIV use at our center.

Klavžar|Polona|P|0000-0001-6974-2115
Koritnik|Blaž|B|0000-0002-5083-8261
Leonardis|Lea|L|
Dolenc Grošelj|Leja|L|
Kirbiš|Mojca|M|0000-0003-1794-8829
Ristić Kovačič|Stanka|S|
Klinar|Polona|P|
Pohar Perme|Maja|M|0000-0002-3412-2642
Zidar|Janez|J|

D018691:Excitatory Amino Acid Antagonists

multidisciplinary care
survival
Amyotrophic lateral sclerosis
noninvasive ventilation
multidisciplinary approach


Development of Balanced Whole System Value Measures for Inflammatory Bowel Disease Care in the IBD Qorus Collaborative Using a Modified Delphi Process.

Abstract:
BACKGROUND
The IBD Qorus Collaborative aims to reduce variation and increase the value of care for the adult inflammatory bowel disease (IBD) community. To evaluate the success of the collaborative, we aimed to develop a balanced set of outcome measures that reflect a multistakeholder view of value in IBD care. To achieve this, we used the Clinical Value Compass framework and engaged a mixed-stakeholder group to conduct a modified Delphi process. The end result was a 10-measure set to assess the value of IBD care.

METHOD
The modified Delphi process included 3 iterative rounds of blinded voting and interactive webinar-style discussion. We recruited 18 participants for the Delphi panel, including clinicians, researchers, patients, Crohn's & Colitis Foundation staff, and payers. Participants first identified constructs to measure, then identified the tools to measure those constructs. A literature review and environmental scan of current measures in 4 domains were performed, and relevant measures were proposed for discussion and voting in each domain. Throughout the process, participants were invited to contribute additional measures.

CONCLUSION
The modified Delphi process led to selection of 10 value measures across 4 domains: (1) patient experience; (2) functional status; (3) clinical status; and (4) health care costs and utilization. We have successfully completed a 3-stage modified Delphi process to develop a balanced set of value measures for adult IBD care. The value measure set expands upon prior efforts that have established quality measures for IBD care by adding cost and experience of care elements. This work positions IBD Qorus to better assess, study, improve, and demonstrate value at individual, system, and population levels and will inform and empower related research, improvement, and implementation efforts.

Oliver|Brant J|BJ|
Kennedy|Alice M|AM|0000-0002-4729-0282
van Deen|Welmoed K|WK|
Weaver|S Alandra|SA|
Heller|Caren|C|
Holthoff|Megan M|MM|
Bank|Jeffrey|J|
Melmed|Gil Y|GY|
Siegel|Corey A|CA|
Nelson|Eugene C|EC|

value measures
inflammatory bowel disease
modified delphi process
value compass
patient-reported experience measures
patient-reported outcome measures
patient-reported outcomes
quality improvement


Modelling driver acceptance of driver support systems.

Abstract: Driver support systems are intended to enhance driver performance and improve transportation safety. Even though these systems afford safety advantages, they challenge the traditional role of drivers in operating vehicles. Driver acceptance, therefore, is essential for the adoption of new in-vehicle technologies into the transportation system. In this study, a model of driver acceptance of driver support systems was developed. A conceptual driver acceptance model, including several components, was proposed based on a review of current literature. An empirical study was subsequently carried out using an online survey approach. The study collected data on participants' perceptions of two driver support systems (a fatigue monitoring system and an adaptive cruise control system combined with a lane-keeping system) in terms of attitude, perceived usefulness, and other components of driver acceptance. Results identified five components of driver acceptance (attitude, perceived usefulness, endorsement, compatibility, and affordability). The results also confirmed several mediating effects. The developed model was able to explain 85% of the variability in driver acceptance. The model provides an improved understanding how driver acceptance is formed, including which factors affect driver acceptance and how they affect it. The model can also help automakers and researchers to assess the design and estimate the potential use of a driver support system. The model could also be highly beneficial in developing a questionnaire to assess driver acceptance.

Rahman|Md Mahmudur|MM|
Strawderman|Lesley|L|
Lesch|Mary F|MF|
Horrey|William J|WJ|
Babski-Reeves|Kari|K|
Garrison|Teena|T|

D000063:Accidents, Traffic
D001334:Automobile Driving
D036262:Empirical Research
D005260:Female
D006801:Humans
D008297:Male
D008962:Models, Theoretical
D011482:Protective Devices
D011795:Surveys and Questionnaires

Driver acceptability
Advanced driver assistance systems
Intelligent transport technology
Vehicle automation


Using the Findings of a National Survey to Inform the Work of England's Genomics Education Programme.

Abstract: A national coordinated approach to workforce education and training in genomics is essential for the successful implementation of whole genome sequencing and, more broadly, genomic medicine within the National Health Service (NHS) in England. However, there have been no workforce wide assessments of genomics education and training needs that can be used to inform the strategic approach to be taken. In order to assess these needs the Genomics Education Programme (GEP) undertook a cross-professional training needs analysis. Responses from 2,814 individuals allowed the identification of four themes related to NHS staff's perceived education and training needs in genomics, those who: a) have a role in genomics and are competent; b) have a role in genomics but identified a specific learning need; c) could not identify whether genomics is relevant, but want to know more, and; d) do not see genomics as relevant to their role and do not believe they need to learn about it. Individuals are motivated to undertake training for their own continuing professional development and if they perceive training to have a direct impact on patient care. Overall, online learning is the preferred mode of delivery, but there are still many individuals who value face-to-face teaching. This paper demonstrates how the GEP has used these findings to provide an evidence base to inform the ongoing strategy for genomics education and training in the NHS, including the development of competency frameworks and a range of resources to address the diverse genomics learning needs of the healthcare workforce.

survey
genomics education
genomic medicine
education strategy
multidisciplinary
training needs assessment


Macrophages engulf apoptotic and primary necrotic thymocytes through similar phosphatidylserine-dependent mechanisms.

Abstract: One of the major roles of professional phagocytes is the removal of dead cells in the body. We know less about the clearance of necrotic cells than apoptotic cell phagocytosis, despite the fact that both types of dead cells need to be cleared together and necrotic cells appear often in pathological settings. In the present study, we examined phagocytosis of heat- or H2O2-killed necrotic and apoptotic thymocytes by mouse bone marrow-derived macrophages (BMDMs) in vitro and found that the two cell types are engulfed at equal efficiency and compete with each other when added together to BMDMs. Phagocytosis of both apoptotic and necrotic thymocytes was decreased by (a) blocking phosphatidylserine on the surface of dying cells; (b) inhibition of Mer tyrosine kinase, Tim-4, integrin β3 receptor signaling, or Ras-related C3 botulinum toxin substrate 1 activity; or (c) using BMDMs deficient for transglutaminase 2. Stimulation of liver X, retinoid X, retinoic acid or glucocorticoid nuclear receptors in BMDMs enhanced not only apoptotic, but also necrotic cell uptake. Electron microscopic analysis of the engulfment process revealed that the morphology of phagosomes and the phagocytic cup formed during the uptake of dying thymocytes is similar for apoptotic and necrotic cells. Our data indicate that apoptotic and necrotic cells are cleared via the same mechanisms, and removal of necrotic cells in vivo can be facilitated by molecules known to enhance the uptake of apoptotic cells.

Budai|Zsófia|Z|
Ujlaky-Nagy|László|L|
Kis|Gréta Nikoletta|GN|
Antal|Miklós|M|
Bankó|Csaba|C|
Bacsó|Zsolt|Z|
Szondy|Zsuzsa|Z|
Sarang|Zsolt|Z|

macrophages
phagocytosis
phosphatidylserine
apoptosis
primary necrosis


Phyto-synthesis and structural characterization of catalytically active gold nanoparticles biosynthesized using Delonix regia leaf extract.

Abstract: Biological methods of nanoparticles synthesis are ecologically sound and sustainable alternative to the conventional methods. On the basis of aforesaid premise, the present study deals with the optimization and fabrication of gold nanoparticles (Au-NPs) using easily available bio-resource, Delonix regia leaf extract. The use of practically nontoxic natural extracts and water allows the synthesis pathways presented to be considered as ''green'' and so permitting the synthesized Au-NPs to be used in sensitive areas, such as bioremediation. Various characterization techniques are adopted for the evaluation of size, stability, morphology, crystal nature, and purity of nanoparticles. Ultraviolet-visible spectroscopy analysis showed a surface Plasmon resonance peak for prepared Au-NPs at 542 nm, and its absorbance increased with increasing the interaction time. Transmission electron microscopy analysis showed that the particles were spherical and 4-24 nm in size. Energy dispersive X-ray spectroscopy analysis displayed a 2.2 keV peak corresponding to the pure phase gold nanocrystal. X-ray diffraction analysis proved the fabrication of crystalline Au-NPs with face-centered cubic geometry within 10 min. Furthermore, ζ potential (-15 mV) and Fourier transform infrared data suggested the role of polar polyphenolic compounds of leaf extract in fabrication and stabilization process. Biofabricated nanoparticles are demonstrated to have catalytic activity for the reduction of toxic nitro-organic pollutant o-nitroaniline. Therefore, the present study offers a straightforward, cost-efficient, eco-friendly, and sustainable alternative for the fabrication of catalytically active Au-NPs.

Gold
Nanoparticle
Delonix regia
Biofabrication
Nitroaniline


Cryptococcal Meningoencephalitis 10 Years After Bone Marrow Transplant in a Patient With Multiple Myeloma.

Abstract: Cryptococcosis is a fungal infection that mostly affects immunocompromised patients. Diagnosis is based on the detection of cryptococcal antigen in the cerebrospinal fluid (CSF) or serum. Antifungal resistance is emerging, making treatment difficult and long. We report a case of cryptococcosis in a patient with multiple myeloma, years after undergoing a bone marrow transplant. Symptoms were mild, and imaging studies were nonspecific. CSF analysis revealed positive cryptococcal antigen. The patient was started on the standard three-phase antifungal therapy and recovered.

Stepman|Gauthier|G| Sanapati|Jaya|J| Dabb|Kulveer|K| Angelo|Debra|D| Frunzi|Johnathan|J|

cryptococcal meningoencephalitis
meningoencephalitis
cryptococcus
encephalitis


Human responses to high levels of carbon dioxide and air temperature.

Abstract: In this study, 30 subjects were exposed to different combinations of air temperature (Ta : 24, 27, and 30°C) and CO2 level (8000, 10 000, and 12 000 ppm) in a high-humidity (RH: 85%) underground climate chamber. Subjective assessments, physiological responses, and cognitive performance were investigated. The results showed that as compared with exposure to Ta  = 24°C, exposure to 30°C at all CO2 levels caused subjects to feel uncomfortably warm and experience stronger odor intensity, while increased mental effort and greater intensity of acute health symptoms were reported. However, no significant effects of Ta on task performance or physiological responses were found. This indicated that subjects had to exert more effort to maintain their performance in an uncomfortably warm environment. Increasing CO2 from 8000 to 12 000 ppm at all Ta caused subjects to report higher rates of headache, fatigue, agitation, and feeling depressed, although the results were statistically significant only at 24 and 27°C. The text typing performance and systolic blood pressure (SBP) decreased significantly at this exposure, whereas diastolic blood pressure (DBP) and thermal discomfort increased significantly. These effects suggest higher arousal/stress. No significant interaction effect of Ta and CO2 concentration on human responses was identified.

Tu|Zhijun|Z|0000-0002-9645-9216 Li|Yong|Y| Geng|Shibin|S| Zhou|Kun|K| Wang|Ruihai|R| Dong|Xian|X|

air temperature
physiological responses
cognitive performance
CO2 concentration
subjective ratings
underground confined space


Covalently Connected Carbon Nanostructures for Current Collectors in Both the Cathode and Anode of Li-S Batteries.

Abstract: A 3D current collector made of covalently connected carbon nanostructures is presented, which can significantly improve battery performance when used as the cathode and/or anode. A Li-S cell assembled using these current collectors, with the cathode loaded with elemental sulfur and the anode loaded with lithium metal, delivers a high-rate capacity of 860 mA h g-1 at 12 C.

Jin|Song|S|
Xin|Sen|S|
Wang|Linjun|L|
Du|Zhenzhen|Z|
Cao|Lina|L|
Chen|Jiafeng|J|
Kong|Xianghua|X|
Gong|Ming|M|
Lu|Junling|J|
Zhu|Yanwu|Y|
Ji|Hengxing|H|
Ruoff|Rodney S|RS|

covalently connected
current collectors
Li-S batteries
sp2-hybridized carbon nanostructures


A Longitudinal Study of Family Functioning in Offspring of Parents Diagnosed With Bipolar Disorder.

Abstract:
OBJECTIVE
To compare the longitudinal course of family functioning in offspring of parents with bipolar disorder (BD), offspring of parents with non-BD psychopathology, and offspring of healthy control (HC) parents.

METHOD
Offspring of parents with BD (256 parents and 481 offspring), parents without BD (82 parents and 162 offspring), and HC parents (88 parents and 175 offspring) 7 to 18 years of age at intake, from the Bipolar Offspring Study (BIOS), were followed for an average of 4.3 years. Family functioning was evaluated using the child- and parent-reported Family Adaptability and Cohesion Scale-II and the Conflict Behavior Questionnaire. The data were analyzed using multivariate multilevel regression, generalized linear estimating equation models, and path analysis.

RESULTS
Families of parents with BD and parents with non-BD psychopathology showed lower cohesion and adaptability and higher conflict compared with HC families. There were no significant differences in cohesion and adaptability between families of parents with psychopathology. The effect of parental psychopathology on family functioning was mediated by parental psychosocial functioning and, to a lesser extent, offspring disorders. In all 3 groups, parent-reported family conflict was significantly higher than child-reported conflict. Across groups, family cohesion decreased over follow-up, whereas conflict increased.

CONCLUSION
Any parental psychopathology predicted family impairment. These results were influenced by the offspring's age and were mediated by parental psychosocial functioning and, to a lesser degree, by offspring psychopathology. These findings emphasize the need to routinely assess family functioning in addition to psychopathology and provide appropriate interventions to parents and offspring.

Shalev|Amit|A|
Merranko|John|J|
Goldstein|Tina|T|
Miklowitz|David J|DJ|
Axelson|David|D|
Goldstein|Benjamin I|BI|
Brent|David|D|
Monk|Kelly|K|
Hickey|Mary Beth|MB|
Hafeman|Danella M|DM|
Sakolsky|Dara|D|
Diler|Rasim|R|
Birmaher|Boris|B|

longitudinal study
family functioning
bipolar disorder
family conflict


Emerging treatments in management of prostate cancer: biomarker validation and endpoints for immunotherapy clinical trial design.

Abstract: The rapidly emerging field of immunotherapy and the development of novel immunologic agents that have been approved in melanoma and successfully studied in lung cancer, kidney cancer, and prostate cancer have mandated that there be uniformity in clinical trial analysis beyond conventional survival endpoints and imaging. This includes some measure of determining whether the immunologic target is hit and how the treatment has impacted on the immune system in toto. While melanoma is leading the field towards these ends, there is some doubt that not all of the recent successes with immune therapies, for example, checkpoint inhibitors, will be effective for every cancer, and that the toxicities may also be different depending on the malignancy. This review serves to elucidate the current issues facing clinical investigators who perform immunologic trials targeted at patients with prostate cancer and discusses the challenges in assessing the right immunologic endpoints to demonstrate biologic/immunologic targeting leading to clinical benefit.

prostate cancer
biomarkers
cellular therapy
monoclonal antibodies
prostate-specific antigen
sipuleucel-T
vaccines


Ber-EP4 staining in effusion cytology: A potential source of false positives.

Abstract: The distinction between reactive mesothelium and carcinoma in serous effusions can be very difficult. Immunocytochemistry (ICC) is the most widely used tool to improve the diagnostic accuracy of body fluid cytology, with several ICC markers being proposed. Ber-EP4 antibody has shown high sensitivity and specificity rates for diagnosing metastatic carcinoma. In our department, we have detected Ber-EP4 positivity in mesothelium in some cytological specimens. We reviewed all articles on Ber-EP4 staining in effusion cytology, summarized current findings and analyzed the staining pattern of all cases expressing Ber-EP4. Some cases showing Ber-EP4 positivity in mesothelium have been reported, most of which showed only weak Ber-EP4 staining or staining of less than 50% of mesothelial cells. However, some cases may show strong positivity both in cytological and histological specimens. Clinicians and pathologists should be aware of this source of misdiagnosis, and ICC results in mesothelium should be always interpreted cautiously and correlated with clinical tests, other ICC markers and patient's previous history.

Díaz Del Arco|Cristina|C|
Saiz-Pardo Sanz|Melchor|M|
Ortega Medina|Luis|L|
Fernández Aceñero|Mª Jesús|MJ|

Ber-EP4 Cytology Mesothelium Carcinoma Histology Citología Histología Mesotelio


Distal radioulnar joint instability with three different injury patterns assessed by three-dimensional C-arm scans: a cadaveric study.

Abstract: The aim of this study was to establish a radiographic method for detecting distal radioulnar joint instability intraoperatively. We created three successive instabilities in 12 intact Thiel-fixed upper limb specimens: lesion of the triangular fibrocartilage complex, Galeazzi injury and Essex-Lopresti injury. We made three-dimensional scans of the wrists in pronation and supination with a mobile C-arm. We used four validated measurement methods to quantify ulnar migration in the standard axial planes: the radioulnar line method, the subluxation ratio method, the epicentre method and the radioulnar ratio method. All types of instability showed significantly increased migration of the ulna compared with the control group. The subluxation ratio and the radioulnar ratio methods showed the highest sensitivity and specificity in detecting the instabilities. We conclude that these two methods are feasible for radiographically assessing distal radioulnar joint instability. Instability may be assumed if the migration of the ulna in the sigmoid notch is at least 45% of the length of the sigmoid notch, in which case wire transfixation of the distal radioulnar joint is advised.

Swartman|Benedict|B|
Benner|Laura|L|
Franke|Jochen|J|
Grützner|Paul A|PA|
Vetter|Sven Y|SY|
Schnetzke|Marc|M|

D000368:Aged
D000369:Aged, 80 and over
D001696:Biomechanical Phenomena
D002102:Cadaver
D006801:Humans
D021621:Imaging, Three-Dimensional
D007593:Joint Instability
D015203:Reproducibility of Results
D012680:Sensitivity and Specificity
D014057:Tomography, X-Ray Computed
D051478:Triangular Fibrocartilage
D014955:Wrist Joint

Distal radioulnar joint instability
triangular fibrocartilage complex
Galeazzi
Essex–Lopresti injury
intraoperative 3-D imaging


Phylogenetic Analyses of Fowl Adenoviruses (FAdV) Isolated in China and Pathogenicity of a FAdV-8 Isolate.

Abstract: Fowl adenoviruses (FAdVs) have a worldwide distribution and are associated with a variety of diseases, causing considerable economic losses to the poultry industry. We characterized 10 FAdVs isolated from China in 2015-2016 and assessed the pathogenicity of a FAdV-8 strain in specific-pathogen-free (SPF) chickens. Phylogenetic analysis of a hexon gene revealed that only 1 of the 10 isolates belonged to FAdV-8, whereas others belonged to FAdV-4, indicating that Chinese FAdVs were mainly FAdV-4 in recent years. The pathogenicity experiment of the FAdV-8 strain CH/SD/2015/09 showed that no clinical signs were observed in infected chickens. Necropsy displayed mild necrotic foci and petechial hemorrhage of livers collected at 5 days postinfection (dpi). Histopathologic examination identified the presence of intranuclear inclusion bodies in hepatocytes. No virus was detected in oral and cloacal swabs at 5 dpi, and only viral DNA could be measured in kidneys collected at the same time. The results revealed that CH/SD/2015/09 had no obvious pathogenicity in 5-wk-old SPF chickens, which could provide a better understanding about the pathogenicity of the FAdV-8 serotype.

Ruan|Si-Fan|SF| Zhao|Jing|J| Ren|Ying-Chao|YC| Feng|Jin-Ling|JL| Zhang|Guo-Zhong|GZ|

pathogenicity
FAdV-8
phylogenetic analysis
hexon
fowl adenovirus