Comparative effectiveness of buprenorphine-naloxone versus methadone for treatment of opioid use disorder: a population-based observational study protocol in British Columbia, Canada.

Abstract:
INTRODUCTION
Despite a recent meta-analysis including 31 randomised controlled trials comparing methadone and buprenorphine for the treatment of opioid use disorder, important knowledge gaps remain regarding the long-term effectiveness of different treatment modalities across individuals, including rigorously collected data on retention rates and other treatment outcomes. Evidence from real-world data represents a valuable opportunity to improve personalised treatment and patient-centred guidelines for vulnerable populations and inform strategies to reduce opioid-related mortality. Our objective is to determine the comparative effectiveness of methadone versus buprenorphine/naloxone, both overall and within key populations, in a setting where both medications are simultaneously available in office-based practices and specialised clinics.

METHODS AND ANALYSIS
We propose a retrospective cohort study of all adults living in British Columbia receiving opioid agonist treatment (OAT) with methadone or buprenorphine/naloxone between 1 January 2008 and 30 September 2018. The study will draw on seven linked population-level administrative databases. The primary outcomes include retention in OAT and all-cause mortality. We will determine the effectiveness of buprenorphine/naloxone vs methadone using intention-to-treat and per-protocol analyses-the former emulating flexible-dose trials and the latter focusing on the comparison of the two medication regimens offered at the optimal dose. Sensitivity analyses will be used to assess the robustness of results to heterogeneity in the patient population and threats to internal validity.

ETHICS AND DISSEMINATION
The protocol, cohort creation and analysis plan have been approved and classified as a quality improvement initiative exempt from ethical review (Providence Health Care Research Institute and the Simon Fraser University Office of Research Ethics). Dissemination is planned via conferences and publications, and through direct engagement and collaboration with entities that issue clinical guidelines, such as professional medical societies and public health organisations.

Piske|Micah|M|
Thomson|Trevor|T|
Krebs|Emanuel|E|
Hongdilokkul|Natt|N|
Bruneau|Julie|J|
Greenland|Sander|S|
Gustafson|Paul|P|
Karim|M Ehsan|ME|
McCandless|Lawrence C|LC|
Maclure|Malcolm|M|
Platt|Robert W|RW|
Siebert|Uwe|U|
Socías|M Eugenia|ME|
Tsui|Judith I|JI|
Wood|Evan|E|
Nosyk|Bohdan|B|0000-0003-2513-3718

D000069479:Buprenorphine, Naloxone Drug Combination

public health
epidemiology
primary care
statistics & research methods
substance misuse


The Increase of Simple Sequence Repeats during Diversification of Marchantiidae, An Early Land Plant Lineage, Leads to the First Known Expansion of Inverted Repeats in the Evolutionarily-Stable Structure of Liverwort Plastomes.

Abstract: The chloroplast genomes of liverworts, an early land plant lineage, exhibit stable structure and gene content, however the known resources are very limited. The newly sequenced plastomes of Conocephalum, Riccia and Sphaerocarpos species revealed an increase of simple sequence repeats during the diversification of complex thalloid liverwort lineage. The presence of long TA motifs forced applying the long-read nanopore sequencing method for proper and dependable plastome assembly, since the length of dinucleotide repeats overcome the length of Illumina short reads. The accumulation of SSRs (simple sequence repeats) enabled the expansion of inverted repeats by the incorporation of rps12 and rps7 genes, which were part of large single copy (LSC) regions in the previously sequenced plastomes. The expansion of inverted repeat (IR) at the genus level is reported for the first time for non-flowering plants. Moreover, comparative analyses with remaining liverwort lineages revealed that the presence of SSR in plastomes is specific for simple thalloid species. Phylogenomic analysis resulted in trees confirming monophyly of Marchantiidae and partially congruent with previous studies, due to dataset-dependent results of Dumortiera-Reboulia relationships. Despite the lower evolutionary rate of Marchantiales plastomes, significant barcoding gap was detected, even for recently divergent holarctic Conocephalum species. The sliding window analyses revealed the presence of 18 optimal (500 bp long) barcodes that enable the molecular identification of all studied species.

Sawicki|Jakub|J| Bączkiewicz|Alina|A| Buczkowska|Katarzyna|K| Górski|Piotr|P| Krawczyk|Katarzyna|K| Mizia|Patryk|P| Myszczyński|Kamil|K|0000-0002-3118-0900 Ślipiko|Monika|M|0000-0002-7759-2193 Szczecińska|Monika|M|

liverworts
chloroplast genome
nanopore sequencing
cpSSR
inverted repeats expansion
phylogeny
super-barcoding


Outcomes of an emergency department intensive care unit in a tertiary medical center in Taiwan: An observational study.

Abstract:
PURPOSE
The boarding of critically ill patients in the emergency department (ED) could reduce quality of care and increase mortality. An ED intensive care unit (ICU) was set up in a 3715-bed medical center to facilitate timely delivery of critical care. This study reports comparative outcomes of EDICU patients with specialty ICU patients.

MATERIALS AND METHODS
Medical records of adult nontrauma ED patients admitted to nonsurgical ICUs (EDICU, medical, cardiac, alimentary, and neurological units) between January 2007 and July 2011 were retrospectively reviewed. The respective number of admissions, bed turnover rate, and length of stay were compared. Cox regression models were also applied to compare inhospital mortality risks among these patients.

RESULTS
With only 13% (14/108) of all ICU beds, EDICU admitted 36% (3711/10449) of patients. Emergency department ICU patients had an unfavorable adjusted hazard ratio for inhospital mortality compared with medical ICU and cardiac ICU patients, but after excluding patients with an ICU length of stay of 2 days or less, the difference in hazard ratio became nonsignificant.

CONCLUSIONS
Emergency department ICU has admitted a disproportionately higher proportion of patients without sacrificing quality of care. Specialty care could be secured through direct communication between EDICU and specialty physicians and forming close collaboration between departments and ICUs.

Tseng|Jo-Chi|JC| Li|Chih-Huang|CH| Chen|Kuan-Fu|KF| Chan|Yi-Ling|YL| Chang|Shy-Shin|SS| Wang|Feng-Lin|FL| Chiu|Te-Fa|TF| Chen|Jih-Chang|JC|

D000328:Adult
D000369:Aged, 80 and over
D016638:Critical Illness
D004636:Emergency Service, Hospital
D005260:Female
D017052:Hospital Mortality
D006772:Hospitals, Military
D006801:Humans
D007362:Intensive Care Units
D007902:Length of Stay
D017063:Outcome Assessment, Health Care
D011787:Quality of Health Care
D013624:Taiwan
D014481:United States

Emergency department
Intensive care unit
Boarding
Critically ill patients
Hazard ratio
In-hospital mortality


Multimodal connectivity mapping of the human left anterior and posterior lateral prefrontal cortex.

Abstract: Working memory is essential for many of our distinctly human abilities, including reasoning, problem solving, and planning. Research spanning many decades has helped to refine our understanding of this high-level function as comprising several hierarchically organized components, some which maintain information in the conscious mind, and others which manipulate and reorganize this information in useful ways. In the neocortex, these processes are likely implemented by a distributed frontoparietal network, with more posterior regions serving to maintain volatile information, and more anterior regions subserving the manipulation of this information. Recent meta-analytic findings have identified the anterior lateral prefrontal cortex, in particular, as being generally engaged by working memory tasks, while the posterior lateral prefrontal cortex was more strongly associated with the cognitive load required by these tasks. These findings suggest specific roles for these regions in the cognitive control processes underlying working memory. To further characterize these regions, we applied three distinct seed-based methods for determining cortical connectivity. Specifically, we employed meta-analytic connectivity mapping across task-based fMRI experiments, resting-state BOLD correlations, and VBM-based structural covariance. We found a frontoparietal pattern of convergence which strongly resembled the working memory networks identified in previous research. A contrast between anterior and posterior parts of the lateral prefrontal cortex revealed distinct connectivity patterns consistent with the idea of a hierarchical organization of frontoparietal networks. Moreover, we found a distributed network that was anticorrelated with the anterior seed region, which included most of the default mode network and a subcomponent related to social and emotional processing. These findings fit well with the internal attention model of working memory, in which representation of information is processed according to an anteroposterior gradient of abstract-to-concrete representations.

Reid|Andrew T|AT|
Bzdok|Danilo|D|
Langner|Robert|R|
Fox|Peter T|PT|
Laird|Angela R|AR|
Amunts|Katrin|K|
Eickhoff|Simon B|SB|
Eickhoff|Claudia R|CR|

D000328:Adult
D001931:Brain Mapping
D016208:Databases, Factual
D005260:Female
D007839:Functional Laterality
D006801:Humans
D008279:Magnetic Resonance Imaging
D008297:Male
D008570:Memory, Short-Term
D008875:Middle Aged
D064847:Multimodal Imaging
D009434:Neural Pathways
D017397:Prefrontal Cortex

Posterior lateral prefrontal cortex
Working memory
Anterior lateral prefrontal cortex
Structural covariance
Functional connectivity
Meta-analytic connectivity modeling


Long non-coding RNA SNHG16 regulates human aortic smooth muscle cell proliferation and migration via sponging miR-205 and modulating Smad2.

Abstract: The present study investigated the role of long non-coding RNA (lncRNA) small nucleolar RNA host gene 16 (SNHG16) in the human aortic smooth muscle cell (HASMC) proliferation and migration and explored the potential link between SNHG16 and atherosclerosis. Our results showed that platelet-derived growth factor (PDGF)-bb treatment promoted cell proliferation and migration with concurrent up-regulation of SNHG16 in HASMCs. Small nucleolar RNA host gene 16 overexpression promoted HASMC proliferation and migration, while SNHG16 knockdown suppressed cell proliferation and migration in PDGF-bb-stimulated HASMCs. The bioinformatic analyses showed that SNHG16 possessed the complementary binding sequence with miR-205, where the interaction was confirmed by luciferase reporter assay and RNA pull-down assay in HASMCs, and SNHG16 inversely regulated miR-205 expression. MiR-205 overexpression attenuated the enhanced effects of PDGF-bb treatment on HASMC proliferation and migration. Moreover, Smad2 was targeted and inversely regulated by miR-205, while being positively regulated by SNHG16 in HASMCs. Smad2 knockdown attenuated PDGF-bb-mediated actions on HASMC proliferation and migration. Both miR-205 overexpression and Smad2 knockdown partially reversed the effects of SNHG16 overexpression on HASMC proliferation and migration. Moreover, SNHG16 and Smad2 mRNA were up-regulated, while miR-205 was down-regulated in the plasma from patients with atherosclerosis. Small nucleolar RNA host gene 16 expression was inversely correlated with miR-205 expression and positively correlated with Smad2 expression in the plasma from atherosclerotic patients. In conclusion, our data showed the up-regulation of SNHG16 in pathogenic-stimulated HASMCs and clinical samples from atherosclerotic patients. Small nucleolar RNA host gene 16 regulated HASMC proliferation and migration possibly via regulating Smad2 expression by acting as a competing endogenous RNA for miR-205.

Lin|Yongqing|Y| Tian|Guoping|G| Zhang|Haifeng|H| Yuan|Woliang|W| Xie|Yong|Y| Yang|Ying|Y| Wang|Jingfeng|J| Liang|Ying|Y|0000-0002-2939-3210


The Effect of Social Support on Psychological Flourishing and Distress Among Migrants in Australia.

Abstract: We examine the access that culturally diverse migrant groups in Australia have to different sources of social support and how this access, or lack thereof, is associated with psychological flourishing and distress. A national online survey was conducted with 1334 migrants in Australia, examining 11 different sources of social support, including family, friends, relationship partner, acquaintances, work colleagues, health professionals, government agencies, community organisations, religious groups, social groups and online groups. We also examined migrants from different cultural groups. All sources of support were significantly associated with mental health, but somewhat differently for the dimensions of distress and flourishing. Flourishing was linked to higher support from all 11 sources, though not for all cultural groups. High psychological distress was linked to lower support only from family, friends, a partner, acquaintances, work colleagues and social groups, and only for some cultural groups. In particular, for distress, there was no link between migrants from Southern Asia and family support, as well as Confucian Asia groups and friend support. Understanding where migrants from different cultural origins draw their support from could help policymakers and support workers improve health and well-being in migrant populations, especially by focusing on sources of support that are linked to lower distress and greater flourishing, as indicated in this study.

du Plooy|Daniel R|DR|
Lyons|Anthony|A|
Kashima|Emiko S|ES|

Social support
Flourishing
Distress
Migrants
Mental health


Assessment of acute mild hypoxia on retinal oxygen saturation using snapshot retinal oximetry.

Abstract:
PURPOSE
To study the effect of acute mild hypoxia on retinal oxygen saturation.

METHODS
Spectral retinal images were acquired under normoxic and hypoxic conditions for 10 healthy human volunteers (six male, four female, aged 25 ± 5 years [mean ± SD]) using a modified fundus camera fitted with an image-replicating imaging spectrometer (IRIS). Acute, mild hypoxia was induced by changing the oxygen saturation of inhaled air from 21% to 15% using a hypoxia generator with subjects breathing the hypoxic gas mixture for 10 minutes. Peripheral arterial oxygen saturation of the subjects was monitored using fingertip-pulse oximetry. Images were processed to calculate oxygen saturation, arteriovenous difference in oxygen saturation, and vessel diameter. Data are presented as mean ± SD and were analyzed using paired sample t-test with significance accepted at P < 0.05.

RESULTS
The retinal arterial and venous oxygen saturation was 98.5% ± 1.6% and 70.7% ± 2.7% during normoxia. A reduction in the fraction of inspired oxygen resulted in a decline (P < 0.001) in both retinal-arterial and venous oxygen saturation to 90.3% ± 2.0% and 62.4% ± 2.2%, respectively. The arteriovenous oxygen saturation difference in normoxia (27.8% ± 2.9%) and hypoxia (27.9% ± 2.1%) did not change. Retinal arteriolar and venular diameters increased (P < 0.001) by 4% and 3%, respectively, under hypoxia.

CONCLUSIONS
The acute inhalation of a hypoxic gas mixture resulted in a decline in both retinal-arterial and venous saturation, while arteriovenous oxygen difference was maintained with an accompanying significant increase in retinal vessel diameter. This may suggest an autoregulatory response to acute mild hypoxia.

Choudhary|Tushar R|TR|
Ball|Derek|D|
Fernandez Ramos|Javier|J|
McNaught|Andrew I|AI|
Harvey|Andrew R|AR|

hypoxia
oximetry
autoregulation
hemoglobin
retina
spectral imaging


Isoniazid-induced control of Mycobacterium tuberculosis by primary human cells requires interleukin-1 receptor and tumor necrosis factor.

Abstract: Proinflammatory cytokines are critical mediators that control Mycobacterium tuberculosis (Mtb) growth during active tuberculosis (ATB). To further inhibit bacterial proliferation in diseased individuals, drug inhibitors of cell wall synthesis such as isoniazid (INH) are employed. However, whether INH presents an indirect effect on bacterial growth by regulating host cytokines during ATB is not well known. To examine this hypothesis, we used an in vitro human granuloma system generated with primary leukocytes from healthy donors adapted to model ATB. Intense Mtb proliferation in cell cultures was associated with monocyte/macrophage activation and secretion of IL-1β and TNF. Treatment with INH significantly reduced Mtb survival, but altered neither T-cell-mediated Mtb killing, nor production of IL-1β and TNF. However, blockade of both IL-1R1 and TNF signaling rescued INH-induced killing, suggesting synergistic roles of these cytokines in mediating control of Mtb proliferation. Additionally, mycobacterial killing by INH was highly dependent upon drug activation by the pathogen catalase-peroxidase KatG and involved a host PI3K-dependent pathway. Finally, experiments using coinfected (KatG-mutated and H37Rv strains) cells suggested that active INH does not directly enhance host-mediated killing of Mtb. Our results thus indicate that Mtb-stimulated host IL-1 and TNF have potential roles in TB chemotherapy.

Yamashiro|Lívia H|LH|
Eto|Carolina|C|
Soncini|Marina|M|
Horewicz|Verônica|V|
Garcia|Magno|M|
Schlindwein|Aline D|AD|
Grisard|Edmundo C|EC|
Rovaris|Darcita B|DB|
Báfica|André|A|

Mycobacterium tuberculosis
Human
Isoniazid
Leukocytes
TNF
IL-1


Enantioselective separation and dissipation of pydiflumetofen enantiomers in grape and soil by supercritical fluid chromatography-tandem mass spectrometry.

Abstract: Pydiflumetofen is registered in many countries and is widely used in crop production in the racemate form. However, the environmental behavior of the enantiomers has not been studied. An effective and sensitive chiral analytical method was first established for analyzing the pydiflumetofen enantiomers by supercritical fluid chromatography with tandem triple quadrupole mass spectrometry. The enantiomers could be separated and detected using the Chiralcel OD-3 column in less than 3 min. The separation conditions were as follows: mobile phase, CO2 /methanol (80:20); flow rate, 1.0 mL/min; column temperature, 30°C, auto back-pressure regulator pressure, 2000 psi with modified quick, easy, cheap, effective, rugged, and safe sample treatment method. The average recoveries of analytes from both matrices at three spiking levels were in the range of 84.1-103.0%. The limit of quantitation for each enantiomer was 0.005 mg/kg with a baseline resolution of approximately 1.64. The method was applied to monitor the enantioselective dissipation of pydiflumetofen in grape and soil. In grapes, (-)-pydiflumetofen was degraded more rapidly than (+)-pydiflumetofen. In soil, (+)-pydiflumetofen was preferentially degraded. The data provided useful references for the risk assessment and rational use of pydiflumetofen in agriculture.

dissipation
pydiflumetofen
grape
enantioseparation
field soil


Prevalence of Comorbidity among People with Hypertension: The Korea National Health and Nutrition Examination Survey 2007-2013.

Abstract:
BACKGROUND AND OBJECTIVES
Joint National Committee guidelines attempt to vary treatment recommendations for patients based on considerations of their comorbidities. The aim of the present study is to estimate the age-standardized prevalence of common comorbidities among Korean hypertension patients.

SUBJECTS AND METHODS
We analyzed the Korea National Health and Nutrition Examination Survey from 2007 to 2013. Among the 58423 participants, 30092 adults, aged ≥30 yrs who completed a health examination and interview survey, were selected. The survey procedures were used to estimate weighted prevalence and odds ratios for 8 comorbidities, including obesity, diabetes mellitus, dyslipidemia, cardiovascular disease, chronic kidney disease, and thyroid disease.

RESULTS
Most chronic conditions were more prevalent in adults with hypertension than in those without hypertension. Common comorbidities were obesity (60.1%), dyslipidemia (57.6%), and impaired fasting glucose (45.1%). Hypertensive patients with two or more comorbid diseases were 42.2% and those with three or more diseases were 17.7%. The age- and sex-specific prevalence of three or more comorbid diseases among male hypertension patients was significantly higher than those patients in the 30-59 (p<0.05) age group.

CONCLUSION
Comorbidity is highly prevalent in Korean patients with hypertension.

Noh|Juhwan|J|
Kim|Hyeon Chang|HC|
Shin|Anna|A|
Yeom|Hyungseon|H|
Jang|Suk-Yong|SY|
Lee|Jung Hyun|JH|
Kim|Changsoo|C|
Suh|Il|I|

Prevalence
Hypertension
Korea
Chronic disease
Epidemiology


Phytochemistry and pharmacology of genus Ephedra.

Abstract: The genus Ephedra of the Ephedraceae family contains more than 60 species of nonflowering seed plants distributed throughout Asia, America, Europe, and North Africa. These Ephedra species have medicinal, ecological, and economic value. This review aims to summarize the chemical constituents and pharmacological activities of the Ephedra species to unveil opportunities for future research. Comprehensive information on the Ephedra species was collected by electronic search (e.g., GoogleScholar, Pubmed, SciFinder, and Web of Science) and phytochemical books. The chemical compounds isolated from the Ephedra species include alkaloids, flavonoids, tannins, polysaccharides, and others. The in vitro and in vivo pharmacological studies on the crude extracts, fractions and few isolated compounds of Ephedra species showed anti-inflammatory, anticancer, antibacterial, antioxidant, hepatoprotective, anti-obesity, antiviral, and diuretic activities. After chemical and pharmacological profiling, current research is focused on the antibacterial and antifungal effects of the phenolic acid compounds, the immunosuppressive activity of the polysaccharides, and the antitumor activity of flavonoids.

Zhang|Ben-Mei|BM| Wang|Zhi-Bin|ZB| Xin|Ping|P| Wang|Qiu-Hong|QH| Bu|He|H| Kuang|Hai-Xue|HX|


BHLHE40 promotes macrophage pro-inflammatory gene expression and functions.

Abstract: Macrophages are the principal innate immune cells that populate all major organs and provide the first line of cellular defense against infections and/or injuries. The immediate and early-responding macrophages must mount a robust pro-inflammatory response to protect the host by eliminating deleterious agents. The effective pro-inflammatory macrophage response requires the activation of complex transcriptional programs that modulate the dynamic regulation of inflammatory and metabolic gene expression. Therefore, transcription factors that govern pro-inflammatory and metabolic gene expression play an essential role in shaping the macrophage inflammatory response. Herein, we identify the basic helix-loop-helix family member e40 (BHLHE40), as a critical transcription factor that promotes broad pro-inflammatory and glycolytic gene expression by elevating HIF1α levels in macrophages. Our in vivo studies revealed that myeloid-BHLHE40 deficiency significantly attenuates macrophage and neutrophil recruitment to the site of inflammation. Our integrated transcriptomics and gene set enrichment analysis (GSEA) studies show that BHLHE40 deficiency broadly curtails inflammatory signaling pathways, hypoxia response, and glycolytic gene expression in macrophages. Utilizing complementary gain- and loss-of-function studies, our analyses uncovered that BHLHE40 promotes LPS-induced HIF1α mRNA and protein expression in macrophages. More importantly, forced overexpression of oxygen stable form of HIF1α completely reversed attenuated pro-inflammatory and glycolytic gene expression in BHLHE40-deficient macrophages. Collectively, these results demonstrate that BHLHE40 promotes macrophage pro-inflammatory gene expression and functions by elevating HIF1α expression in macrophages.

Zafar|Atif|A|
Ng|Hang Pong|HP|
Kim|Gun-Dong|GD|0000-0001-8518-5267
Chan|E Ricky|ER|
Mahabeleshwar|Ganapati H|GH|

D051792:Basic Helix-Loop-Helix Transcription Factors

D051795:Hypoxia-Inducible Factor 1, alpha Subunit

BHLHE40 macrophages HIF1α inflammation hypoxia glycolysis


How biological attention mechanisms improve task performance in a large-scale visual system model.

Abstract: How does attentional modulation of neural activity enhance performance? Here we use a deep convolutional neural network as a large-scale model of the visual system to address this question. We model the feature similarity gain model of attention, in which attentional modulation is applied according to neural stimulus tuning. Using a variety of visual tasks, we show that neural modulations of the kind and magnitude observed experimentally lead to performance changes of the kind and magnitude observed experimentally. We find that, at earlier layers, attention applied according to tuning does not successfully propagate through the network, and has a weaker impact on performance than attention applied according to values computed for optimally modulating higher areas. This raises the question of whether biological attention might be applied at least in part to optimize function rather than strictly according to tuning. We suggest a simple experiment to distinguish these alternatives.

convolutional neural networks
gain modulation
neuroscience
visual attention


Communication and Working with Authorities During Natural Disasters.

Abstract: Keeping people and animals out of harm's way, preventing property loss, and working together in the community with other animal stakeholders and officials are important in building community resilience during disasters. Developing plans for neighbors helping each other evacuate animals is important. Producer helping producer, veterinarian helping veterinarian, and community helping community build resilience by preventing loss, responding to needs, and recovering and restoring livelihoods.

Communication
Working with authorities
Natural disasters


Reduced pectin content of cell walls prevents stress-induced root cell elongation in Arabidopsis.

Abstract: The primary cell walls of plants provide mechanical strength while maintaining the flexibility needed for cell extension growth. Cell extension involves loosening the bonds between cellulose microfibrils, hemicelluloses and pectins. Pectins have been implicated in this process, but it remains unclear if this depends on the abundance of certain pectins, their modifications, and/or structure. Here, cell wall-related mutants of the model plant Arabidopsis were characterized by biochemical and immunohistochemical methods and Fourier-transform infrared microspectroscopy. Mutants with reduced pectin or hemicellulose content showed no root cell elongation in response to simulated drought stress, in contrast to wild-type plants or mutants with reduced cellulose content. While no association was found between the degrees of pectin methylesterification and cell elongation, cell wall composition analysis suggested an important role of the pectin rhamnogalacturonan II (RGII), which was corroborated in experiments with the RGII-modifying chemical 2β-deoxy-Kdo. The results were complemented by expression analysis of cell wall synthesis genes and microscopic analysis of cell wall porosity. It is concluded that a certain amount of pectin is necessary for stress-induced root cell elongation, and hypotheses regarding the mechanistic basis of this result are formulated.

Liu|Xiaohui|X| Cui|Huiying|H| Zhang|Bochao|B| Song|Min|M| Chen|Shaolin|S| Xiao|Chaowen|C| Tang|Yunjia|Y| Liesche|Johannes|J|

Cellulose
hemicellulose
drought stress
rhamnogalacturonan
wall porosity
FTIR spectroscopy
polysaccharides
root growth


Protective effect of Flos puerariae extract following acute alcohol intoxication in mice.

Abstract:
BACKGROUND
The effect of Flos Puerariae extract (FPE) on alcohol metabolism, hepatic injury, and memory impairment was assessed following acute ethanol (EtOH) intoxication in mice.

METHODS
The model of acute EtOH intoxication was established by intragastric administration with 8 g/kg EtOH in mice. FPE was orally administrated (gavage) once a day for 7 consecutive days. Mice were randomly divided into 4 groups: control group, model group, and FPE groups (100, 200 mg/kg). Alcohol tolerance and intoxication time, blood alcohol concentration, the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in liver, aspartate amino transferase (AST) and alanine amino transferase (ALT) in serum, superoxide dismutase (SOD), glutathione peroxidase (GSH-px), catalase and the formation of malondialdehyde (MDA) in both liver and brain, as well as memory ability were determined after acute alcohol exposure.

RESULTS
Compared with model group, pretreatment with FPE significantly prolonged alcohol tolerance time and shortened intoxication time, which is accompanied by decreased blood alcohol concentration and elevated activities of ADH and ALDH in liver. Moreover, the index of hepatic injury, ALT, and AST activities in serum was markedly decreased by pretreatment with FPE. Additionally, decreased MDA level, enhanced GSH-px and catalase activities in liver, as well as enhanced SOD and catalase activities in brain were found in FPE pretreated mice after acute exposure to EtOH. Furthermore, FPE pretreated mice showed markedly relieved memory disruption following acute EtOH intoxication.

CONCLUSIONS
This study suggests that FPE pretreatment could enhance alcohol metabolism, prevent hepatic injury, and relieve memory impairment after acute alcohol intoxication and that this effect is likely related to its modulation on the alcohol metabolizing and antioxidant enzymes.

Chen|Xiao|X| Cai|Fei|F| Guo|Shuang|S| Ding|Fang|F| He|Yi|Y| Wu|Jiliang|J| Liu|Chao|C|

D056486:Chemical and Drug Induced Liver Injury

Flos Puerariae
Alcoholism
Alcohol Dehydrogenase
Aldehyde Dehydrogenase
Antioxidant


Profile of catering staff at a tertiary care hospital in Mumbai.

Abstract:
BACKGROUND
Food borne illnesses, even today, continue to be a major public health problem in both developing and developed nations. Food handlers play an important role in ensuring food safety throughout the chain of production, processing, storage and preparation.Health of food handlers is of great importance for maintaining hygienic quality of food prepared and served by them. Thus, the present study was conducted to study socio-demographic characteristics, morbidity pattern and immunization status of catering staff at a tertiary care hospital in Mumbai

METHOD
A cross sectional study was conducted from August 2010 to November 2010. Out of the total of 162 food handlers working in 11 food service establishments, 137 were interviewed face to face using a semi-structured questionnaire, while remaining 25 food handlers were excluded because of either their absence or not giving consent. The food handlers were assessed clinically for personal hygiene and investigated for hemoglobin, stool routine and sputum AFB examination.

RESULTS
82 (59.8%) food handlers were from the age group 10 - 29 years, 113 (82.5%) male, 95 (69%) married, 59 (43.1%) educated up to primary level. Only 7 (5.1%) had ever received a dose of typhoid vaccine. 103 (75.2%) had an addiction, majority consuming gutkha 59 (57.3%). Dental caries 32 (23.4%) was the most common morbidity identified. Entamoeba histolytica was isolated in 13 (9.5%) subjects.

CONCLUSION
This study has confirmed an association between educational status and personal hygiene suggesting the need for greater personal hygiene in this group. Preemployment and periodical medical examination should be encouraged.

Bobhate|Prateek S|PS|
R Shrivastava|Saurabh|S|
Gupta|Pankaj|P|

Food handler
personal hygiene
dental caries
periodic medical examination


Preparation for Meaningful Work and Life: Urban High School Youth's Reflections on Work-Based Learning 1 Year Post-Graduation.

Abstract: The challenges confronted by low-income high school students throughout school and across the transition to higher education and employment are well-documented in the US and many other nations. Adopting a positive youth development perspective (Lerner et al., 2005), this study reports findings from interviews with 18 low-income, racially and ethnically diverse graduates of an urban Catholic high school in the US. The interviews were designed to shed light on the post-high school experiences of urban high school graduates and to understand how students construct meaning about the value of school and work-based learning (WBL) in their preparation for meaningful work and life. The interviews highlight the perceived value of the academic and non-cognitive preparation students experienced through high school and WBL in relation to the challenges they encountered along the pathway to post-high school success and decent work. Overall, the findings suggest the potential of WBL for low-income youth in facilitating access to resources that build academic and psychological/non-cognitive assets, while also illustrating the role of structural and contextual factors in shaping post-high school transitions and access to meaningful work and life opportunities.

Kenny|Maureen E|ME|
Catraio|Christine|C|
Bempechat|Janine|J|
Minor|Kelly|K|
Olle|Chad|C|
Blustein|David L|DL|
Seltzer|Joanne|J|

work-based learning
decent work
post-high school transition
college access
employability of low-income youth
school to work transition


Imaging the Role of Multinucleate Pancreatic Cancer Cells and Cancer-Associated Fibroblasts in Peritoneal Metastasis in Mouse Models.

Abstract:
BACKGROUND/AIM
The interaction between pancreatic-cancer cells and stromal cells in the tumor microenvironment (TME) is of particular importance in cancer progression and metastasis. The present report demonstrates the role of cancer-associated fibroblasts (CAFs) and multinucleate pancreatic-cancer cells in peritoneal metastasis.

MATERIALS AND METHODS
An orthotopic mouse model of pancreatic cancer was established with the human pancreatic cancer cell line BxPC3, which stably expresses green fluorescent protein (GFP).

RESULTS
BxPC3-GFP cells formed peritoneal metastases by week 18 after orthotopic implantation. Using an Olympus FV1000 confocal microscope, multi-nucleated cancer cells were frequently observed in the peritoneal metastases. The primary pancreatic tumor and peritoneal-metastases were harvested, cultured and then transplanted subcutaneously. Subcutaneous tumors established from peritoneal-metastatic cells were larger than subcutaneous tumors established from primary-tumor cells. Subcutaneous tumors of each type were subsequently cultured in vitro. CAFs were observed growing out from the tumors established from peritoneal-metastatic cells, but not the tumors established from the primary cancer.

CONCLUSION
The results of the present study suggest that multi-nucleated cancer cells and CAFs were related to peritoneal metastasis of pancreatic cancer.

Hasegawa|Kosuke|K|
Suetsugu|Atsushi|A|
Nakamura|Miki|M|
Matsumoto|Takuro|T|
Aoki|Hitomi|H|
Kunisada|Takahiro|T|
Shimizu|Masahito|M|
Saji|Shigetoyo|S|
Moriwaki|Hisataka|H|
Hoffman|Robert M|RM|

imaging
Pancreatic cancer
cancer-associated fibroblasts
peritoneal metastasis
orthotopic
green fluorescent protein
nude mice


Iningainema tapete sp. nov. (Scytonemataceae, Cyanobacteria) from greenhouses in central Florida (USA) produces two types of nodularin with biosynthetic potential for microcystin-LR and anabaenopeptin production.

Abstract: Iningainema is a recently described genus of heterocytous, false-branching cyanobacteria originally described from Australia. In this work, we present Iningainema tapete sp. nov., isolated from subaerial and terrestrial environments in central Florida (USA). In comparison to the sister species, our novel cyanobacterium produces nodularin-R (NOD-R) and a methylated isoform [MeAdda3] NOD previously not reported within this genus; in addition to possessing the biosynthetic gene clusters for microcystin and anabaenopeptins production. Nodularin accumulation by this cyanobacterium exceeded 500 µg g-1 dry weight in cultures grown in nitrogen-depleted media. Such elevated toxin concentrations are alarming as the cyanobacterium was isolated from a food production greenhouse and poses a potential risk for food products and for workforce exposure. Using morphology, 16S rRNA gene phylogeny, and 16S-23S rRNA internal transcribed spacer (ITS) secondary structure, coupled with toxin detection and toxin gene presence, we provide evidence for the establishment of a novel toxic species of cyanobacteria, Iningainema tapete.

Berthold|David E|DE|
Lefler|Forrest W|FW|
Huang|I-Shuo|IS|
Abdulla|Hussain|H|
Zimba|Paul V|PV|
Laughinghouse|H Dail|HD|

Terrestrial
Phylogeny
Cyanotoxins
Genome
Taxonomy
Tribrid orbitrap mass spectrometer


High nevus counts confer a favorable prognosis in melanoma patients.

Abstract: A high number of nevi is the most significant phenotypic risk factor for melanoma and is in part genetically determined. The number of nevi decreases from middle age onward but this senescence can be delayed in patients with melanoma. We investigated the effects of nevus number count on sentinel node status and melanoma survival in a large cohort of melanoma cases. Out of 2,184 melanoma cases, 684 (31.3%) had a high nevus count (>50). High nevus counts were associated with favorable prognostic factors such as lower Breslow thickness, less ulceration and lower mitotic rate, despite adjustment for age. Nevus count was not predictive of sentinel node status. The crude 5- and 10-year melanoma-specific survival rate was higher in melanomas cases with a high nevus count compared to those with a low nevus count (91.2 vs. 86.4% and 87.2 vs. 79%, respectively). The difference in survival remained significant after adjusting for all known melanoma prognostic factors (hazard ratio [HR] = 0.43, confidence interval [CI] = 0.21-0.89). The favorable prognostic value of a high nevus count was also seen within the positive sentinel node subgroup of patients (HR = 0.22, CI = 0.08-0.60). High nevus count is associated with a better melanoma survival, even in the subgroup of patients with positive sentinel lymph node. This suggests a different biological behavior of melanoma tumors in patients with an excess of nevi.

Ribero|Simone|S|
Davies|John R|JR|
Requena|Celia|C|
Carrera|Cristina|C|
Glass|Daniel|D|
Rull|Ramon|R|
Vidal-Sicart|Sergi|S|
Vilalta|Antonio|A|
Alos|Lucia|L|
Soriano|Virtudes|V|
Quaglino|Pietro|P|
Traves|Victor|V|
Newton-Bishop|Julia A|JA|
Nagore|Eduardo|E|
Malvehy|Josep|J|
Puig|Susana|S|
Bataille|Veronique|V|

nevus count
melanoma
survival
sentinel lymph node


Bound phenolics in foods, a review.

Abstract: Among phytochemicals, phenolic compounds have been extensively researched due to their diverse health benefits. Phenolic compounds occur mostly as soluble conjugates and insoluble forms, covalently bound to sugar moieties or cell wall structural components. Absorption mechanisms for bound phenolic compounds in the gastrointestinal tract greatly depend on the liberation of sugar moieties. Food processes such as fermentation, malting, thermoplastic extrusion or enzymatic, alkaline and acid hydrolyses occasionally assisted with microwave or ultrasound have potential to release phenolics associated to cell walls. Different kinds of wet chemistry methodologies to release and detect bound phenolic have been developed. These include harsh heat treatments, chemical modifications or biocatalysis. New protocols for processing and determining phenolics in food matrices must be devised in order to release bound phenolics and for quality control in the growing functional food industry.

Acosta-Estrada|Beatriz A|BA|
Gutiérrez-Uribe|Janet A|JA|
Serna-Saldívar|Sergio O|SO|

D002473:Cell Wall
D005504:Food Analysis
D005511:Food Handling
D010636:Phenols

Bound phenolics
Fermentation
Malting
Thermoplastic extrusion
Chemical hydrolysis
Ultrasound assisted hydrolysis


Seminal Plasma Lipidomics Profiling to Identify Signatures of Kallmann Syndrome.

Abstract:
Background
Kallmann syndrome (KS) is a rare developmental disorder. Our previous metabolomics work showed substantial changes in linoleic acid and glycerophospholipid metabolism in KS. Here, we performed targeted lipidomics to further identify the differential lipid species in KS.

Methods
Twenty-one patients with KS (treatment group) and twenty-two age-matched healthy controls (HC, control group) were enrolled. Seminal plasma samples and medical records were collected. Targeted lipidomics analysis of these samples was performed using ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS).

Results
Lipidomics profiling of patients with KS and the HCs showed clear separation in the orthogonal projections to latent structures-discriminant analysis (OPLS-DA). There were many differential lipids identified, with the main differential lipid species being triacylglycerols (TAGs), phosphatidylcholines (PCs) and phosphatidylethanolamine (PE).

Conclusions
The lipidomics profile of patients with KS changed. It was also determined that TAGs, PCs and PE are promising biomarkers for KS diagnosis. To our knowledge, this is the first report to analyze lipidomics in men with Kallmann syndrome.

Li|Xiaogang|X| Wang|Xi|X| Li|Haolong|H| Li|Yongzhe|Y| Guo|Ye|Y|

Kallmann syndrome
targeted lipidomics
biomarker
UPLC-MS/MS
rare disease


Extracting ligands from receptors by reversed targeted molecular dynamics.

Abstract: Short targeted MD trajectories are used to expel ligands from binding sites. The expulsion is governed by a linear increase of the target RMSD value, growing from zero to an arbitrary chosen final RMSD that forces the ligand to a selected distance outside of the receptor. The RMSD lag (i.e., the difference between the imposed and the actual RMSD) can be used to follow barriers encountered by the ligand during its way out of the receptor. The force constant used for the targeted MD can transform the RMSD lag into a strain energy. Integration of the (time-dependent) strain energy over time yields a value with the dimensions of "action" (i.e, energy multiplied by time) and can serve as a measure for the overall effort required to extract the ligand from its binding site. Possibilities to compare (numerically and graphically) the randomly detected exit pathways are discussed. As an example, the method is tested on the exit of bisphenol A from the human estrogen-related receptor [Formula: see text] and of GW0072 from the peroxysome proliferator activated receptor.

Ligand exit pathways
Nuclear receptors
Reversed targeted MD


Biophysical characterization and structural determination of the potent cytotoxic Psathyrella asperospora lectin.

Abstract: A lectin with strong cytotoxic effect on human colon cancer HT29 and monkey kidney VERO cells was recently identified from the Australian indigenous mushroom Psathyrella asperospora and named PAL. We herein present its biochemical and structural analysis using a multidisciplinary approach. Glycan arrays revealed binding preference towards N-acetylglucosamine (GlcNAc) and, to a lesser extent, towards sialic acid (Neu5Ac). Submicromolar and millimolar affinity was measured by surface plasmon resonance for GlcNAc and NeuAc, respectively. The structure of PAL was resolved by X-ray crystallography, elucidating both the protein's amino acid sequence as well as the molecular basis rationalizing its binding specificity. Proteins 2017; 85:969-975. © 2016 Wiley Periodicals, Inc.

Ribeiro|João P|JP|
Ali Abol Hassan|Mohamed|M|
Rouf|Razina|R|
Tiralongo|Evelin|E|
May|Tom W|TW|
Day|Christopher J|CJ|
Imberty|Anne|A|
Tiralongo|Joe|J|
Varrot|Annabelle|A|

D054730:Protein Interaction Domains and Motifs

GlcNAc recognition
beta-propeller
fungal lectins


Maintenance phase of a physical activity intervention in older kidney transplant recipients: A 12-month follow-up.

Abstract: Daily walking activities are associated with improving cardiovascular outcomes in older kidney transplant recipients. However, little is known regarding physical activity adherence outcomes in older kidney recipients. The purpose of this randomized controlled trial 12-month follow-up study was to evaluate the feasibility of the intervention (SystemCHANGE™ + activity tracker) during the maintenance period (7-12 months), compared to an attention-control group (activity tracker only) in older kidney recipients (age 60 and older). The sample included 60 participants (n = 30 IG; n = 30 ACG). Adherence rates for wearing the activity tracker daily were 96.5% in the IG and 80.8% in the ACG. The IG demonstrated within-group improvements for blood pressure at 12 months. Overall, there was a decrease in the average daily steps observed in both groups. These data suggest this intervention is feasible and additional boosters should be considered during the maintenance period to encourage physical activity.

O'Brien|Tara|T| Tan|Alai|A| Rose|Karen|K| Focht|Brian|B| Daloul|Reem|R|

Physical activity
Kidney transplant recipients
Adherence
Older adults


Mandibular ramus shape of Australopithecus sediba suggests a single variable species.

Abstract: The fossils from Malapa cave, South Africa, attributed to Australopithecus sediba, include two partial skeletons-MH1, a subadult, and MH2, an adult. Previous research noted differences in the mandibular rami of these individuals. This study tests three hypotheses that could explain these differences. The first two state that the differences are due to ontogenetic variation and sexual dimorphism, respectively. The third hypothesis, which is relevant to arguments suggesting that MH1 belongs in the genus Australopithecus and MH2 in Homo, is that the differences are due to the two individuals representing more than one taxon. To test these hypotheses, we digitized two-dimensional sliding semilandmarks in samples of Gorilla, Pan, Pongo, and Homo, as well as MH1 and MH2. We document large amounts of shape variation within all extant species, which is related neither to ontogeny nor sexual dimorphism. Extant species nevertheless form clusters in shape space, albeit with some overlap. The shape differences in extant taxa between individuals in the relevant age categories are minimal, indicating that it is unlikely that ontogeny explains the differences between MH1 and MH2. Similarly, the pattern of differences between MH1 and MH2 is inconsistent with those found between males and females in the extant sample, suggesting that it is unlikely that sexual dimorphism explains these differences. While the difference between MH1 and MH2 is large relative to within-species comparisons, it does not generally fall outside of the confidence intervals for extant intraspecific variation. However, the MH1-MH2 distance also does not plot outside and below the between-species confidence intervals. Based on these results, as well as the contextual and depositional evidence, we conclude that MH1 and MH2 represent a single species and that the relatively large degree of variation in this species is due to neither ontogeny nor sexual dimorphism.

Ritzman|Terrence B|TB|
Terhune|Claire E|CE|
Gunz|Philipp|P|
Robinson|Chris A|CA|

Australopithecus sediba
Malapa
Ontogeny
Geometric morphometrics
Origins of Homo


Molecular characterization of gdf9 and bmp15 genes in rare minnow Gobiocypris rarus and their expression upon bisphenol A exposure in adult females.

Abstract: Growth differentiation factor 9 (Gdf9) and bone morphogenetic protein 15 (Bmp15) are members of transforming growth factor β (TGFβ) superfamily that plays important roles in regulating ovarian functions. We cloned the cDNAs of gdf9 and bmp15 in rare minnow Gobiocypris rarus. The full length cDNAs of gdf9 and bmp15 were 1999 and 1721 bp, encoding 431 and 384 amino acids respectively. They both contained conserved TGFβ superfamily domain, with six conserved cysteine residues. Tissue distribution showed that both gdf9 and bmp15 are highly expressed in the G. rarus ovary. Following bisphenol A (BPA) treatment, ovarian transcripts of gdf9 and bmp15 together with the gonadosomatic index and the ovarian histology were altered. It suggests that the altered gdf9 and bmp15 expression may play roles in the weight gain and abnormal development of the ovary following BPA exposure.

Zhang|Yingying|Y| Yuan|Cong|C| Qin|Fang|F| Hu|Guojun|G| Wang|Zaizhao|Z|

Gobiocypris rarus
Bisphenol A
Growth differentiation factor 9
Bone morphogenetic protein 15
Ovarian development


The Protective Mechanism of Cannabidiol in Cardiac Injury: A Systematic Review of Non-Clinical Studies.

Abstract:
BACKGROUND
Cardiac disease is accounted as the leading cause of worldwide morbidity and mortality. The disease is characterized by the overproduction of reactive oxygen and/or nitrogen species (ROS/RNS), and induction of oxidative stress. Cannabidiol (CBD) is a non-psychoactive ingredient of marijuana that has been reported to be safe and well tolerated in patients. Due to its pleiotropic effect, CBD has been shown to exert cytoprotective effects. This study intended to clarify the mechanisms and the potential role of CBD regarding cardiac injuries treatment.

METHODS
A systematic literature search was conducted, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, in the electronic databases including PubMed, Web of Science, Scopus, and Embase up to June 2019 using predefined search terms in the titles and abstracts. Accordingly, a set of pre-specified inclusion and exclusion criteria were considered and 8 articles were ultimately included in this study.

RESULTS
Our findings demonstrate that CBD has multi-functional protective assets to improve cardiac injuries; preliminary through scavenging of free radicals, and reduction of oxidative stress, apoptosis, and inflammation.

CONCLUSION
CBD can protect against cardiac injuries, mainly through its antioxidative and antiapoptotic effects on the basis of non-clinical studies. The cardioprotective effects of the CBD need to be further studied in welldesigned clinical trials.

Shayesteh|Mohammad R H|MRH|
Haghi-Aminjan|Hamed|H|
Mousavi|Mohammad J|MJ|
Momtaz|Saeideh|S|
Abdollahi|Mohammad|M|

cardiac injury
oxidative stress
free radicals
cardioprotective effects
Cannabinoids
systematic review.


Investigation of angucycline compounds as potential drug candidates against SARS Cov-2 main protease using docking and molecular dynamic approaches.

Abstract: The emerged Coronavirus disease (COVID-19) causes severe or even fatal respiratory tract infection, and to date there is no FDA-approved therapeutics or effective treatment available to effectively combat this viral infection. This urgent situation is an attractive research area in the field of drug design and development. One of the most important targets of SARS-coronavirus-2 (SARS Cov-2) is the main protease (3CLpro). Actinomycetes are important resources for drug discovery. The angucylines that are mainly produced by Streptomyces genus of actinomycetes exhibit a broad range of biological activities such as anticancer, antibacterial and antiviral. This study aims to investigate the binding affinity and molecular interactions of 157 available angucycline compounds with 3CLpro using docking and molecular dynamics simulations. MM-PBSA calculations showed that moromycin A has a better binding energy (- 30.42 kcal mol-1) compared with other ligands (in a range of - 18.66 to - 22.89 kcal mol-1) including saquayamycin K4 (- 21.27 kcal mol-1) except the co-crystallized ligand N3. However, in vitro and in vivo studies are essential to assess the effectiveness of angucycline compounds against coronavirus.

Angucycline compounds
Main protease
Docking
COVID-19
3CLpro
Molecular dynamics simulation
MM-PBSA
Inhibitors
Molecular modelling


Diagnostic value of beclin-1 and mTOR in ovarian cancer.

Abstract: This study described the expression of beclin-1 and mTOR proteins in 86 ovarian tumor tissue samples (n=25 benign ovarian tumor tissues; n=16 borderline ovarian tumor tissues; n=45 malignant epithelial ovarian tumor tissues) and 20 normal ovarian tissue samples and determined the diagnostic value of serum beclin-1 and mTOR protein levels for ovarian tumors. Serum and tissue beclin-1 and mTOR protein levels were detected with enzyme-linked immunosorbent assay, western blot, and immunohistochemistry. Receiver operating characteristic (ROC) curves were constructed to determine the significance of serum beclin-1 and mTOR protein levels for diagnosing borderline and malignant epithelial ovarian tumor. Mean beclin-1 protein levels were highest in normal ovarian tissue and were progressively decreased in benign, borderline, and malignant epithelial ovarian tumor. Mean mTOR protein levels were lowest in normal ovarian tissue and were progressively increased in benign, borderline, and malignant epithelial ovarian tumor. The area under the ROC curve was 0.93 or 0.97 when a combination of serum beclin-1 and mTOR protein levels was used to diagnose borderline or malignant epithelial ovarian tumor. There was a significant negative correlation between beclin-1 and mTOR protein expression in malignant epithelial ovarian tumor (rs=-0.78, P<0.05), but no correlation between beclin-1 and mTOR protein expression in borderline ovarian tumor. Combined detection of serum beclin-1 and mTOR protein levels may have improved diagnostic accuracy for malignant epithelial ovarian tumor compared to each marker alone.

diagnostic value
beclin-1
mTOR
ovarian cancer
Ovarian tumor


Visco-hyperelastic characterization of human brain white matter micro-level constituents in different strain rates.

Abstract: In this study, we propose a computational characterization technique for obtaining the material properties of axons and extracellular matrix (ECM) in human brain white matter. To account for the dynamic behavior of the brain tissue, data from time-dependent relaxation tests of human brain white matter in different strain rates are extracted and formulated by a visco-hyperelastic constitutive model consisting of the Ogden hyperelastic model and the Prony series expansion. Through micromechanical finite element simulation, a derivative-free optimization framework designed to minimize the difference between the numerical and experimental data is used to identify the material properties of the axons and ECM. The Prony series expansion parameters of axons and ECM are found to be highly affected by the Prony series expansion coefficients of the brain white matter. The optimal parameters of axons and ECM are verified through micromechanical simulation by comparing the averaged numerical response with that of the experimental data. Moreover, the initial shear modulus and the reduced shear modulus of the axons are found for different strain rates of 0.0001, 0.01, and 1 s-1. Consequently, first- and second-order regressions are used to find relations for the prediction of the shear modulus at the intermediate strain rates. Graphical Abstract The applied procedure for characterization of brain white matter micro-level constituents. The macro-level experimental data in different strain rates are used in the context of simulation-based optimization to obtain the properties of axons and extracellular matrix material.

Ramzanpour|Mohammadreza|M| Hosseini-Farid|Mohammad|M| McLean|Jayse|J| Ziejewski|Mariusz|M| Karami|Ghodrat|G|

Visco-hyperelastic
Strain rate
Micromechanical simulation
Simulation-based optimization


PINK1: A Bridge between Mitochondria and Parkinson's Disease.

Abstract: Mitochondria are known as highly dynamic organelles essential for energy production. Intriguingly, in the recent years, mitochondria have revealed the ability to maintain cell homeostasis and ultimately regulate cell fate. This regulation is achieved by evoking mitochondrial quality control pathways that are capable of sensing the overall status of the cellular environment. In a first instance, actions to maintain a robust pool of mitochondria take place; however, if unsuccessful, measures that lead to overall cell death occur. One of the central key players of these mitochondrial quality control pathways is PINK1 (PTEN-induce putative kinase), a mitochondrial targeted kinase. PINK1 is known to interact with several substrates to regulate mitochondrial functions, and not only is responsible for triggering mitochondrial clearance via mitophagy, but also participates in maintenance of mitochondrial functions and homeostasis, under healthy conditions. Moreover, PINK1 has been associated with the familial form of Parkinson's disease (PD). Growing evidence has strongly linked mitochondrial homeostasis to the central nervous system (CNS), a system that is replenished with high energy demanding long-lasting neuronal cells. Moreover, sporadic cases of PD have also revealed mitochondrial impairments. Thus, one could speculate that mitochondrial homeostasis is the common denominator in these two forms of the disease, and PINK1 may play a central role in maintaining mitochondrial homeostasis. In this review, we will discuss the role of PINK1 in the mitochondrial physiology and scrutinize its role in the cascade of PD pathology.

PINK1
Parkinson’s disease
mitochondria homeostasis


A folded viral noncoding RNA blocks host cell exoribonucleases through a conformationally dynamic RNA structure.

Abstract: Folded RNA elements that block processive 5' → 3' cellular exoribonucleases (xrRNAs) to produce biologically active viral noncoding RNAs have been discovered in flaviviruses, potentially revealing a new mode of RNA maturation. However, whether this RNA structure-dependent mechanism exists elsewhere and, if so, whether a singular RNA fold is required, have been unclear. Here we demonstrate the existence of authentic RNA structure-dependent xrRNAs in dianthoviruses, plant-infecting viruses unrelated to animal-infecting flaviviruses. These xrRNAs have no sequence similarity to known xrRNAs; thus, we used a combination of biochemistry and virology to characterize their sequence requirements and mechanism of stopping exoribonucleases. By solving the structure of a dianthovirus xrRNA by X-ray crystallography, we reveal a complex fold that is very different from that of the flavivirus xrRNAs. However, both versions of xrRNAs contain a unique topological feature, a pseudoknot that creates a protective ring around the 5' end of the RNA structure; this may be a defining structural feature of xrRNAs. Single-molecule FRET experiments reveal that the dianthovirus xrRNAs undergo conformational changes and can use "codegradational remodeling," exploiting the exoribonucleases' degradation-linked helicase activity to help form their resistant structure; such a mechanism has not previously been reported. Convergent evolution has created RNA structure-dependent exoribonuclease resistance in different contexts, which establishes it as a general RNA maturation mechanism and defines xrRNAs as an authentic functional class of RNAs.

Steckelberg|Anna-Lena|AL|
Akiyama|Benjamin M|BM|
Costantino|David A|DA|
Sit|Tim L|TL|
Nix|Jay C|JC|
Kieft|Jeffrey S|JS|

D020413:3' Untranslated Regions
D000818:Animals
D001483:Base Sequence
D005095:Exoribonucleases
D005416:Flavivirus
D054884:Host-Pathogen Interactions
D009690:Nucleic Acid Conformation
D059370:RNA Folding
D020871:RNA Stability
D012367:RNA, Viral

RNA structure
single-molecule FRET
exoribonuclease resistance
RNA dynamics
noncoding RNA maturation


Chronic Illness Management in Culturally and Linguistically Diverse Patients: Exploring the Needs, Access, and Understanding of Information.

Abstract: In Canada, people from culturally and linguistically diverse (CALD) backgrounds are at a greater risk of developing a chronic illness, and are more likely to experience adverse health effects and challenges in accessing high-quality care compared with Canadian-born individuals. This, in part, has been attributed to having inadequate access to information and resources needed to manage their illness(es). A qualitative descriptive design and inductive content analysis were used to explore the information needs of 24 CALD patients with chronic illnesses. Participants identified medical, lifestyle, and psychosocial information needs. How much information was needed depended on such antecedents as illness trajectory, severity, and perception. Most information needs remained unmet. A number of communication strategies were identified to bridge language barriers that go beyond translation and are based on effective health education strategies. Findings can help health care professionals better identify CALD patients' information needs and provide strategies that go beyond translation.

Lambert|Sylvie|S|0000-0002-9202-9251
Loban|Ekaterina|E|
Li|Jane|J|0000-0003-4988-4436
Nghiem|Tracy|T|
Schaffler|Jamie|J|
Maheu|Christine|C|
Dubois|Sylvie|S|
Folch|Nathalie|N|
Gélinas-Phaneuf|Elisa|E|
Laizner|Andréa Maria|AM|

culturally and linguistically diverse communities


A phantom-based forward projection approach in support of model-based iterative reconstructions for HAADF-STEM tomography.

Abstract: We introduce a forward model for the computation of high angle annular dark field (HAADF) images of nano-crystalline spherical particles and apply it to image simulations for assemblies of nano-spheres of Al, Cu, and Au with a range of sizes, as well as an artificial bi-sphere, consisting of solid hemispheres of Al and Cu or Al and Au. Comparison of computed intensity profiles with experimental observations on Al spheres at different microscope accelerating voltages provides confidence in the forward model. Simulated tomographic tilt series for both HAADF and bright field (BF) images are then used to illustrate that the model-based iterative reconstruction (MBIR) approach is capable of reconstructing sphere configurations of mixed atomic number, with the correct relative reconstructed intensity ratio proportional to the square of the atomic number ratio.

Venkatakrishnan|S V|SV|
Drummy|L F|LF|
Jackson|M A|MA|
Bouman|C A|CA|
Simmons|J P|JP|
De Graef|M|M|

Forward model
High angle annular dark field
Image simulation
Nano-particles
Tomographic reconstruction


Human Phase 1 trial of low-dose inactivated seasonal influenza vaccine formulated with Advax™ delta inulin adjuvant.

Abstract: Influenza vaccines are usually non-adjuvanted but addition of adjuvant may improve immunogenicity and permit dose-sparing, critical for vaccine supply in the event of an influenza pandemic. The aim of this first-in-man study was to determine the effect of delta inulin adjuvant on the safety and immunogenicity of a reduced dose seasonal influenza vaccine. Healthy male and female adults aged 18-65years were recruited to participate in a randomized controlled study to compare the safety, tolerability and immunogenicity of a reduced-dose 2007 Southern Hemisphere trivalent inactivated influenza vaccine formulated with Advax™ delta inulin adjuvant (LTIV+Adj) when compared to a full-dose of the standard TIV vaccine which does not contain an adjuvant. LTIV+Adj provided equivalent immunogenicity to standard TIV vaccine as assessed by hemagglutination inhibition (HI) assays against each vaccine strain as well as against a number of heterosubtypic strains. HI responses were sustained at 3months post-immunisation in both groups. Antibody landscapes against a large panel of H3N2 influenza viruses showed distinct age effects whereby subjects over 40years old had a bimodal baseline HI distribution pattern, with the highest HI titers against the very oldest H3N2 isolates and with a second HI peak against influenza isolates from the last 5-10years. By contrast, subjects >40years had a unimodal baseline HI distribution with peak recognition of H3N2 isolates from approximately 20years ago. The reduced dose TIV vaccine containing Advax adjuvant was well tolerated and no safety issues were identified. Hence, delta inulin may be a useful adjuvant for use in seasonal or pandemic influenza vaccines. Australia New Zealand Clinical Trial Registry: ACTRN12607000599471.

Gordon|David L|DL|
Sajkov|Dimitar|D|
Honda-Okubo|Yoshikazu|Y|
Wilks|Samuel H|SH|
Aban|Malet|M|
Barr|Ian G|IG|
Petrovsky|Nikolai|N|

Influenza
Vaccine
Advax
Delta inulin
Adjuvant
Immunogenicity
Safety


Perceptions of emergency nurses during the human swine influenza outbreak: a qualitative study.

Abstract:
INTRODUCTION
The primary aim of this study was to explore the perception of Hong Kong emergency nurses regarding their work during the human swine influenza pandemic outbreak.

METHODS
In this exploratory, qualitative study, 10 emergency nurses from a regional hospital in Hong Kong were recruited using purposive sampling. Semi-structured, face-to-face individual interviews were conducted. Qualitative content analysis was utilized to analyze the transcripts.

RESULTS
The three following categories emerged from the interview data: concerns about health, comments on the administration, and attitudes of professionalism. Nurses viewed the human swine influenza as a threat to their personal and families' health. However, nurses perceived that the severity of the disease was exaggerated by the public. Improvements in planning the circulation of information, allocation of manpower, and utilization of personal protective equipment were indicated. The emergency nurses demonstrated a sense of commitment and professional morale in promoting a high quality of nursing care.

DISCUSSION
Various factors affecting the perceptions of emergency nurses toward their professional duties during the influenza pandemic were identified. By understanding these perceptions, appropriate planning, policies, and guidelines can be formulated to meet the healthcare needs of patients during future pandemic outbreaks.

D000328:Adult
D004196:Disease Outbreaks
D016529:Emergency Nursing
D005260:Female
D006723:Hong Kong
D006801:Humans
D053118:Influenza A Virus, H1N1 Subtype
D007251:Influenza, Human
D007407:Interviews as Topic
D009741:Nursing Staff, Hospital
D036301:Qualitative Research

Perception
Emergency nursing
Qualitative
Influenza pandemic


Temporal Regulation of Natural Killer T Cell Interferon Gamma Responses by β-Catenin-Dependent and -Independent Wnt Signaling.

Abstract: Natural killer T (NKT) cells are prominent innate-like lymphocytes in the liver with critical roles in immune responses during infection, cancer, and autoimmunity. Interferon gamma (IFN-γ) and IL-4 are key cytokines rapidly produced by NKT cells upon recognition of glycolipid antigens presented by antigen-presenting cells (APCs). It has previously been reported that the transcriptional coactivator β-catenin regulates NKT cell differentiation and functionally biases NKT cell responses toward IL-4, at the expense of IFN-γ production. β-Catenin is not only a central effector of Wnt signaling but also contributes to other signaling networks. It is currently unknown whether Wnt ligands regulate NKT cell functions. We thus investigated how Wnt ligands and β-catenin activity shape liver NKT cell functions in vivo in response to the glycolipid antigen, α-galactosylceramide (α-GalCer) using a mouse model. Pharmacologic targeting of β-catenin activity with ICG001, as well as myeloid-specific genetic ablation of Wntless (Wls), to specifically target Wnt protein release by APCs, enhanced early IFN-γ responses. By contrast, within several hours of α-GalCer challenge, myeloid-specific Wls deficiency, as well as pharmacologic targeting of Wnt release using the small molecule inhibitor IWP-2 impaired α-GalCer-induced IFN-γ responses, independent of β-catenin activity. These data suggest that myeloid cell-derived Wnt ligands drive early Wnt/β-catenin signaling that curbs IFN-γ responses, but that, subsequently, Wnt ligands sustain IFN-γ expression independent of β-catenin activity. Our analyses in ICG001-treated mice confirmed a role for β-catenin activity in driving early IL-4 responses by liver NKT cells. However, neither pharmacologic nor genetic perturbation of Wnt production affected the IL-4 response, suggesting that IL-4 production by NKT cells in response to α-GalCer is not driven by released Wnt ligands. Collectively, these data reveal complex temporal roles of Wnt ligands and β-catenin signaling in the regulation of liver NKT cell activation, and highlight Wnt-dependent and -independent contributions of β-catenin to NKT cell functions.

Kling|Jessica C|JC|
Jordan|Margaret A|MA|
Pitt|Lauren A|LA|
Meiners|Jana|J|
Thanh-Tran|Thao|T|
Tran|Le Son|LS|
Nguyen|Tam T K|TTK|
Mittal|Deepak|D|
Villani|Rehan|R|
Steptoe|Raymond J|RJ|
Khosrotehrani|Kiarash|K|
Berzins|Stuart P|SP|
Baxter|Alan G|AG|
Godfrey|Dale I|DI|
Blumenthal|Antje|A|

D019086:Bridged Bicyclo Compounds, Heterocyclic

D047908:Intracellular Signaling Peptides and Proteins

natural killer T cell
interferon gamma
Wnt
IL-4
β-catenin
α-galactosylceramide
IL-12


Confronting, Representing, and Believing Counterintuitive Concepts: Navigating the Natural and the Supernatural.

Abstract: Recent research shows that even preschoolers are skeptical; they frequently reject claims from other people when the claims conflict with their own perceptions and concepts. Yet, despite their skepticism, both children and adults come to believe in a variety of phenomena that defy their first-hand perceptions and intuitive conceptions of the world. In this review, we explore how children and adults acquire such concepts. We describe how a similar developmental process underlies mental representation of both the natural and the supernatural world, and we detail this process for two prominent supernatural counterintuitive ideas-God and the afterlife. In doing so, we highlight the fact that conceptual development does not always move in the direction of greater empirical truth, as described within naturalistic domains. We consider factors that likely help overcome skepticism and, in doing so, promote belief in counterintuitive phenomena. These factors include qualities of the learners, aspects of the context, qualities of the informants, and qualities of the information.

counterintuitive concepts
conceptual development
belief
trust in testimony


Identifying a Deletion Affecting Total Lung Capacity Among Subjects in the COPDGene Study Cohort.

Abstract: Chronic obstructive pulmonary disease (COPD) is a progressive disease with both environmental and genetic risk factors. Genome-wide association studies (GWAS) have identified multiple genomic regions influencing risk of COPD. To thoroughly investigate the genetic etiology of COPD, however, it is also important to explore the role of copy number variants (CNVs) because the presence of structural variants can alter gene expression and can be causal for some diseases. Here, we investigated effects of polymorphic CNVs on quantitative measures of pulmonary function and chest computed tomography (CT) phenotypes among subjects enrolled in COPDGene, a multisite study. COPDGene subjects consist of roughly one-third African American (AA) and two-thirds non-Hispanic white adult smokers (with or without COPD). We estimated CNVs using PennCNV on 9,076 COPDGene subjects using Illumina's Omni-Express genome-wide marker array. We tested for association between polymorphic CNV components (defined as disjoint intervals of copy number regions) for several quantitative phenotypes associated with COPD within each racial group. Among the AAs, we identified a polymorphic CNV on chromosome 5q35.2 located between two genes (FAM153B and SIMK1, but also harboring several pseudo-genes) giving genome-wide significance in tests of association with total lung capacity (TLCCT ) as measured by chest CT scans. This is the first study of genome-wide association tests of polymorphic CNVs and TLCCT . Although the ARIC cohort did not have the phenotype of TLCCT , we found similar counts of CNV deletions and amplifications among AA and European subjects in this second cohort.

Begum|Ferdouse|F|
Ruczinski|Ingo|I|
Li|Shengchao|S|
Silverman|Edwin K|EK|
Cho|Michael H|MH|
Lynch|David A|DA|
Curran-Everett|Douglas|D|
Crapo|James|J|
Scharpf|Robert B|RB|
Parker|Margaret M|MM|
Hetmanski|Jacqueline B|JB|
Beaty|Terri H|TH|

D020022:Genetic Predisposition to Disease

D029424:Pulmonary Disease, Chronic Obstructive

COPD
genome-wide association study (GWAS)
copy number variant (CNV)
pulmonary function
total lung capacity (TLCCT)
lung hyperinflation


Systematic underestimation of the age of selected alleles.

Abstract: A common interpretation of genome-wide selection scans is that the dispersal of anatomically modern humans out of Africa and into diverse environments led to a number of genetic adaptations. If so, patterns of polymorphism from non-African individuals should show the signature of adaptations dating to 40,000-100,000 Kya, coinciding with the main exodus from Africa. However, scans of polymorphism data from a few populations have yielded conflicting results about the chronology of local, population-specific adaptations. In particular, a number of papers report very recent ages for selected alleles in humans, which postdate the development of agriculture 10 Kya, and suggest that adaptive differences among human populations are much more recent. I present an analysis of simulations suggesting a downward bias in methods commonly used to estimate the age of selected alleles. These findings indicate that an estimate of a time to the most recent common ancestor (tMRCA) obtained using standard methods (used as a proxy for the age of an allele) of less than 10 Kya is consistent with an allele that actually became selected before the onset of agriculture and potentially as early as 50 Kya. These findings suggest that the genomic scans for selection may be consistent with selective pressures tied to the Out of Africa expansion of modern human populations.

selected allele
tMRCA
allele age
haplotype length
selective sweep
time to most recent common ancestor


NMR Studies of the Ion Channel-Forming Human Amyloid-β with Zinc Ion Concentrations.

Abstract: Alzheimer's disease (AD) is classified as an amyloid-related disease. Amyloid beta (Aβ) is a transmembrane protein known to play a major role in the pathogenesis of AD. These Aβ proteins can form ion channels or pores in the cell membrane. Studies have elucidated the structure of the transmembrane domain of Aβ ion channels. In addition, various studies have investigated substances that block or inhibit the formation of Aβ ion channels. Zinc ions are considered as potential inhibitors of AD. In this study, we focused on the transmembrane domain and some external domains of the Aβ protein (hAPP-TM), and solution-state NMR was used to confirm the effect on residues of the protein in the presence of zinc ions. In addition, we sought to confirm the structure and orientation of the protein in the presence of the bicelle using solid-state NMR.

transmembrane protein
solution-state NMR
solid-state NMR
Alzheimer’s disease
amyloid channel


Anti-diabetic effect mediated by Ramulus mori polysaccharides.

Abstract: Diabetes mellitus is a complicated metabolic disease, whose pathogenesis is related to apoptosis within pancreatic tissue. In this study, the potential therapeutic benefits of Ramulus mori polysaccharides (RMP) on streptozotocin (STZ)-induced diabetic mice were evaluated. Our experiments indicated that RMP lowered hyperglycemia and increased insulin levels in diabetic mice. Histopathological examination revealed that RMP contributed to the reduction of STZ-lesioned pancreatic cells. In addition, the serum level of HbA1c was decreased. RMP treatment also showed increased Bcl-2 expression and reduced Bax protein level in pancreatic tissue. Furthermore, intrapancreatic expressions of p-JNK, p-p38 and cleaved-caspase-3 were down-regulated by RMP treatment. Collectively, the findings demonstrate that RMP exerts the pronounced hypoglycemic effect via regulation of the intrapancreatic JNK/p38 pathway to protect against STZ-induced apoptosis in pancreatic tissue, eventually ameliorating metabolic function in the pancreas.

Xu|Lingyuan|L| Yang|Fenglian|F| Wang|Junli|J| Huang|Hao|H| Huang|Yanqiang|Y|

D015971:Gene Expression Regulation, Enzymologic

D048031:JNK Mitogen-Activated Protein Kinases

D048051:p38 Mitogen-Activated Protein Kinases

Ramulus mori polysaccharides
Metabolism
Apoptosis
Hyperglycemia


Rapid and extensive collapse from electrically responsive macroporous hydrogels.

Abstract: Electrically responsive hydrogels are created with interconnected macropores, which greatly enhance their ability to rapidly undergo volumetric collapse when subjected to moderate electric fields. When optimized, these electrogels are easily integrated into arrays capable of rapid configurational and chromatic optical modulations, and when loaded with drugs, are able to coordinate the delivery profile of multiple drugs.

Kennedy|Stephen|S| Bencherif|Sidi|S| Norton|Daniel|D| Weinstock|Laura|L| Mehta|Manav|M| Mooney|David|D|

hydrogels
drug delivery
electroactivity
stimuli responsiveness
tissue engineering


Capital Investment by Independent and System-Affiliated Hospitals.

Abstract: Capital expenditures are a critical part of hospitals' efforts to maintain quality of patient care and financial stability. Over the past 20 years, finding capital to fund these expenditures has become increasingly challenging for hospitals, particularly independent hospitals. Independent hospitals struggling to find ways to fund necessary capital investment are often advised that their best strategy is to join a multi-hospital system. There is scant empirical evidence to support the idea that system membership improves independent hospitals' ability to make capital expenditures. Using data from the American Hospital Association and Medicare Cost Reports, we use difference-in-difference methods to examine changes in capital expenditures for independent hospitals that joined multi-hospital systems between 1997 and 2008. We find that in the first 5 years after acquisition, capital expenditures increase by an average of almost $16,000 per bed annually, as compared with non-acquired hospitals. In later years, the difference in capital expenditure is smaller and not statistically significant. Our results do not suggest that increases in capital expenditures vary by asset age or the size of the acquiring system.

Carroll|Nathan W|NW|
Smith|Dean G|DG|
Wheeler|John R C|JR|

D002202:Capital Financing
D016208:Databases, Factual
D005377:Financial Management, Hospital
D016304:Hospitals, Private
D017059:Models, Econometric
D009096:Multi-Institutional Systems
D014481:United States

capital investment
capital access
health finance
hospital system


Frequency-dependent changes in fractional amplitude of low-frequency oscillations in Alzheimer's disease: a resting-state fMRI study.

Abstract: Alzheimer's disease (AD) is the most common neurodegenerative disease in elderly individuals. We conducted this study to examine whether alterations in the fractional amplitudes of low-frequency fluctuations (fALFF) in the AD spectrum were frequency-dependent and symptom-relevant. A total of 43 patients with subjective cognitive decline (SCD), 52 with amnestic mild cognitive impairment (aMCI), 44 with Alzheimer's dementia (d-AD) and 55 well-matched controls participated in resting-state functional magnetic resonance imaging (rs-fMRI) scans. The amplitudes were measured using fALFF within the slow-4 (0.027-0.073 Hz) and slow-5 (0.01-0.027 Hz) bands. Repeated-measures analysis of variance was performed on fALFF within two bands and correlated with neuropsychological test scores. The significant main effects of frequency and group on fALFF differed widely across brain regions. There were more varied areas in the slow-5 band than the slow-4 band. The fALFF associated with primary disease effects was mainly distributed in the parietal lobe. Obvious frequency band and group interaction effects were observed in the left angular gyrus, left calcarine fissure and surrounding cortex, left superior cerebellum, left cuneus and right lingual gyrus. Neuropsychological tests scores were significantly correlated with the fALFF magnitude of the left cuneus and right lingual in the slow-5 band. Our results suggested that the AD continuum had abnormal amplitudes in intrinsic brain activity, and these abnormalities were frequency-dependent and mainly associated with the slow-5 band rather than the slow-4 band. This may guide the frequency choice of future rs-fMRI studies and provide new insights into the neuropathophysiology of AD.

Yang|Liu|L| Yan|Yan|Y| Li|Yuxia|Y| Hu|Xiaochen|X| Lu|Jie|J| Chan|Piu|P| Yan|Tianyi|T| Han|Ying|Y|

fALFF
Subjective cognitive decline
Alzheimer’s disease
Frequency dependence
Resting-state functional MRI


One-year risk of opioid use disorder after index hospitalization for inflammatory bowel disease.

Abstract:
PURPOSE
Patients with inflammatory bowel disease are commonly prescribed opiates for pain. We sought to determine the incidence of opiate use disorder after inflammatory bowel disease (IBD) admission over a 1-year period as well as its impact on mortality and hospital resource utilization.

METHODS
The Nationwide Readmission Database 2016 was used to identify adult patients with a principal diagnosis of IBD who were subsequently readmitted with a primary diagnosis of opioid use disorder. The primary outcome was 1-year readmission rate for opiate use disorder. Predictors were analyzed using multivariate logistic regression. Secondary outcomes were mortality rate, length of stay, and total hospital costs and charges.

RESULTS
Among the 6340 index hospitalizations for IBD, 4.7% (6.0% Crohn's and 2.6% ulcerative colitis) were readmitted within 1 year for opiate use disorder. Readmission hospitalizations were associated with additional mortality (0.32%) and hospital utilization (length of stay 4.80 days, mean total costs $9503, and mean total charges $38,288). Ulcerative colitis had significantly higher mortality and hospital utilization costs compared with Crohn's disease. In multivariable analysis, odds of readmission were associated with female sex (OR 1.51, CI 1.19-1.92), private insurance (OR 0.20, CI 0.11-0.37), Charlson Comorbidity Index (OR 0.20, CI 0.11-0.37), anxiety (OR 1.65, CI 1.02-2.63), and depression (OR 2.07, CI 1.28-3.34). On stratification analysis, psychiatric comorbidities were associated with both Crohn's and ulcerative colitis.

CONCLUSION
Patients with IBD were often readmitted for opiate use disorder and sustained significant mortality and hospital costs. Psychiatric comorbidities, gender, and insurance status impacted the odds of readmission and represent targets for intervention.

Reja|Mishal|M| Hajela|Nitya|N| Makar|Michael|M| Marino|Daniel|D| Bhurwal|Abhishek|A| Rustgi|Vinod|V|

Opiate use disorder
Ulcerative colitis
Crohn’s disease


Changing the stability conditions in a back squat: the effect on maximum load lifted and erector spinae muscle activity.

Abstract: The aim of this study was to identify how changes in the stability conditions of a back squat affect maximal loads lifted and erector spinae muscle activity. Fourteen male participants performed a Smith Machine (SM) squat, the most stable condition, a barbell back (BB) squat, and Tendo-destabilizing bar (TBB) squat, the least stable condition. A one repetition max (1-RM) was established in each squat condition, before electromyography (EMG) activity of the erector spinae was measured at 85% of 1-RM. Results indicated that the SM squat 1-RM load was significantly (p = 0.006) greater (10.9%) than the BB squat, but not greater than the TBB squat. EMG results indicated significantly greater (p < 0.05) muscle activation in the TBB condition compared to other conditions. The BB squat produced significantly greater (p = 0.036) EMG activity compared to the SM squat. A greater stability challenge applied to the torso seems to increase muscle activation. The maximum loads lifted in the most stable and unstable squats were similar. However, the lift with greater stability challenge required greatest muscle activation. The implications of this study may be important for training programmes; if coaches wish to challenge trunk stability, while their athletes lift maximal loads designed to increase strength.

D000704:Analysis of Variance
D054874:Athletic Performance
D004576:Electromyography
D006801:Humans
D008297:Male
D009119:Muscle Contraction
D064170:Paraspinal Muscles
D011187:Posture
D055070:Resistance Training
D019876:Sports Equipment
D014891:Weight Lifting
D055815:Young Adult

muscle activity
Electromyography
squat performance
torso instability


The effect of DPP-4-protected GLP-1 (7-36) on coronary microvascular function in obese adults.

Abstract:
Objective
Glucagon-like-peptide-1 (GLP-1) receptor analogues have been shown to reduce cardiovascular events in patients with type 2 diabetes. However, the mechanism behind is still unknown. The aim of the study was to investigate the effect of intact GLP-1 (7-36) on coronary microcirculation in overweight adults.

Design and methods
A double-blinded randomized cross-over study was performed, with 12 overweight participants. Effects of intact GLP-1 (7-36) infusion were compared with a saline infusion on separate days. A DPP-4 inhibitor was administered to block degradation of intact GLP-1 (7-36) to the GLP-1 metabolite (9-36). Coronary microcirculation was assessed by Doppler coronary flow velocity reserve (CFVR) before and after 2 h of infusion. Peripheral endothelial function was assessed by flow mediated dilation (FMD) before and after one hour of infusion.

Results
CFVR was 3.77 ± 1.25 during GLP-1 infusion and 3.85 ± 1.32 during saline infusion, endothelial function was 16.3 ± 15.5 % during GLP-1 infusion and 7.85 ± 7.76 % during saline infusion. When adjusting for baseline values no significant differences in CFVR (ΔCFVR 0.38 ± 0.92 vs. ΔCFVR 0.71 ± 1.03, p = 0.43) and no difference in peripheral endothelial function (ΔFMD 7.34 ± 11.5 % vs. ΔFMD -1.25 ± 9.23%, p = 0.14) was found.

Conclusions
We found no effect of intact GLP-1 (7-36), protected from DPP4 mediated degradation on coronary microcirculation in overweight adults.

Nilsson|Malin|M|
Bové|Kira Bang|KB|
Suhrs|Elena|E|
Hermann|Thomas|T|
Madsbad|Sten|S|
Holst|Jens Juul|JJ|
Prescott|Eva|E|
Zander|Mette|M|

TTDE, trans-thoracic Doppler echocardiography


Incorporation of telehealth into a multidisciplinary ALS Clinic: feasibility and acceptability.

Abstract:
OBJECTIVE
The practice of telehealth in the care of patients with ALS has received little attention, but has the potential to change the multidisciplinary care model. This study was carried out to assess the feasibility and acceptability of telehealth for ALS care via real-time videoconferencing from the clinic to patients' homes.

METHODS
Patients and caregivers engaged in live telehealth videoconferencing from their homes with members of a multidisciplinary ALS care team who were located in an ALS clinic, in place of their usual in-person visit to the clinic. Participating patients, their caregivers, and health care providers (HCPs) completed surveys assessing satisfaction with the visit, quality of care, and confidence with the interface. Mixed methods analysis was used for survey responses.

RESULTS
Surveys from 11 patients, 12 caregivers, and 15 HCPs were completed. All patients and caregivers, and most HCPs, agreed that the system allowed for good communication, description of concerns, and provision of care recommendations. The most common sentiment conveyed by each group was that telehealth removed the burdens of travel, resulting in lower stress and more comfortable interactions. Caregivers and HCPs expressed more concerns than patients about the ways in which telehealth fell short of in-person care.

CONCLUSIONS
Telehealth was generally viewed favourably by ALS patients, caregivers, and multidisciplinary team members. Improvements in technology and in methods to provide satisfactory remote care without person-to-person contact should be explored.

Geronimo|Andrew|A| Wright|Courtney|C| Morris|Anne|A| Walsh|Susan|S| Snyder|Bethany|B| Simmons|Zachary|Z|

D010342:Patient Acceptance of Health Care

telehealth
Multidisciplinary care
amyotrophic lateral sclerosis
caregiver burden
quality of life


Gabapentin-saccharin co-crystals with enhanced physicochemical properties and in vivo absorption formulated as oro-dispersible tablets.

Abstract: The physicochemical properties and in vivo absorption of a drug can be altered through cocrystallization with a suitable coformer. The aim of this study was to prepare and characterize Gabapentin (Gaba)-saccharine (sacch) sweet cocrystals for improvement of Gaba physicochemical properties, stability and in vivo absorption in addition to masking its taste. The prepared cocrystals were incorporated into oro-dispersible tablets as an attractive dosage form for pediatrics and adults. Gaba-sacch sweet cocrystals were prepared and characterized using FTIR, DSC, XRD and SEM analysis. They enhanced Gaba solubility and particle size distribution. Oro-dispersible tablets of the sweet cocrystals were prepared and evaluated in comparison to tablets prepared by Gaba-sacch physical mixture (PM). The tablets prepared by the cocrystals had lower wetting and disintegration time with enhanced drug release than those prepared with the physical mixture. The optimized formulation was evaluated for Gaba pharmacokinetics in rabbits in comparison to Gaba-sacch PM tablet and Gaba commercial oral capsules. This formulation had enhanced in vivo drug absorption through significant higher Cmax and AUC0-24 with shorter Tmax. The prepared Gaba-sacch sweet cocrystals oro-dispersible tablets, in addition to its enhanced in vitro and in vivo performance, can also enhance patient compliance through its palatable taste and ease of administration.

oro-dispersible gabapentin Cocrystal pediatric saccharine


Impact of Medical Doctors Global Health and Tropical Medicine on decision-making in caesarean section: a pre- and post-implementation study in a rural hospital in Malawi.

Abstract:
BACKGROUND
Medical doctors with postgraduate training in Global Health and Tropical Medicine (MDGHTM) from the Netherlands, a high-income country with a relatively low caesarean section rate, assist associate clinicians in low-income countries regarding decision-making during labour. Objective of this study was to assess impact of the presence of MDGHTMs in a rural Malawian hospital on caesarean section rate and indications.

METHODS
This retrospective pre- and post-implementation study was conducted in a rural hospital in Malawi, where MDGHTMs were employed from April 2015. Indications for caesarean section were audited against national protocols and defined as supported or unsupported by these protocols. Caesarean section rates and numbers of unsupported indications for the years 2015 and 2016 per quarter for different staff cadres were assessed by linear regression.

RESULTS
Six hundred forty-five women gave birth by caesarean section in the study period. The caesarean rate dropped from 20.1 to 12.8% (p < 0.05, R2 = 0.53, y = - 0.0086x + 0.2295). Overall 132 of 501 (26.3%) auditable indications were not supported by documentation in medical records. The proportion of unsupported indications dropped significantly over time from 47.0 to 4.4% (p < 0.01, R2 = 0.71, y = - 0.0481x + 0.4759). Stratified analysis for associate clinicians only (excluding caesarean sections performed by medical doctors) showed a similar decrease from 48.3 to 6.5% (p < 0.05, R2 = 0.55, y = - 0.0442x + 0.4805).

CONCLUSIONS
Our results indicate that presence of MDGHTMs was accompanied by considerable decreases in caesarean section rate and proportion of unsupported indications for caesarean section in this facility. Their presence is likely to have influenced decision-making by associate clinicians.

Bakker|Wouter|W|0000-0001-6470-243X
Bakker|Emma|E|
Huigens|Christiaan|C|
Kaunda|Emily|E|
Phiri|Timothy|T|
Beltman|Jogchum|J|
van Roosmalen|Jos|J|
van den Akker|Thomas|T|

Caesarean section
MDGHTM
Associate clinicians
Audit
Unnecessary caesareans


An economic evaluation of vagus nerve stimulation as an adjunctive treatment to anti-seizure medications for the treatment of drug-resistant epilepsy in England.

Abstract:
INTRODUCTION
Anti-seizure medications (ASMs) are commonly used to prevent recurring epileptic seizures, but around a third of people with epilepsy fail to achieve an adequate response. Vagus nerve stimulation (VNS) is clinically recommended for people with drug-resistant epilepsy (DRE) who are not suitable for surgery, but the cost-effectiveness of the intervention has not recently been evaluated. The study objective is to estimate costs and quality-adjusted life-years (QALYs) associated with using VNS as an adjunct to ongoing ASM therapy, compared to the strategy of using only ASMs in the treatment of people with DRE, from an English National Health Service perspective.

METHODS
A cohort state transition model was developed in Microsoft Excel to simulate costs and QALYs of the VNS + ASM and ASM only strategies. Patients could transition between five health states, using a 3-month cycle length. Health states were defined by an expected percentage reduction in seizure frequency, derived from randomized control trial data. Costs included the VNS device as well as its installation, setup, and removal; ASM therapy; adverse events associated with VNS (dyspnea, hoarseness, and cough); and health-state costs associated with epilepsy including hospitalizations, emergency department visits, neurologist visits, and primary care visits. A range of sensitivity analyses, including probabilistic sensitivity analysis, were run to assess the impact of parameter and structural uncertainty.

RESULTS
In the base case, VNS + ASM had an estimated incremental cost-effectiveness ratio (ICER) of £17,771 per QALY gained compared to ASMs alone. The cost-effective ICER was driven by relative reductions in expected seizure frequency and the differences in health care resource use associated therewith. Sensitivity analyses found that the amount of resource use per epilepsy-related health state was a key driver of the cost component.

CONCLUSIONS
VNS is expected to be a cost-effective intervention in the treatment of DRE in the English National Health Service.

D003362:Cost-Benefit Analysis
D004827:Epilepsy
D006801:Humans
D004364:Pharmaceutical Preparations
D013222:State Medicine
D016896:Treatment Outcome
D055536:Vagus Nerve Stimulation

economic evaluation
vagus nerve stimulation
drug-resistant epilepsy
epilepsy
Cost-effectiveness model
Markov model
anti-epileptic drugs


Oculopathologic findings in flavivirus-infected gallinaceous birds.

Abstract: Using eye samples of nine 9-week-old experimentally West Nile virus (WNV)-infected red-legged partridges (Alectoris rufa), time course of lesions and WNV antigen appearance in ocular structures were examined. In addition, eye samples of 6 red-legged partridges and 3 common pheasants (Phasianus colchicus) naturally infected with Bagaza virus (BAGV) were used to study lesions and flavivirus antigen distribution in relation to apparent blindness in the former. The rapid onset of microscopic lesions and early presence of viral antigen in the eye of experimentally WNV-infected partridges, prior to the central nervous system involvement, suggested hematogenous spread of the virus into the eye. BAGV-infected partridges had a more pronunced inflammatory reaction and more widespread flavivirus antigen distribution in the retina compared with pheasants and experimentally fatally WNV-infected partridges. Our results suggest that flavivirus replication and development of lesions in ocular structures of gallinaceous game birds vary with the specific virus and host species involved.

Gamino|V|V|
Escribano-Romero|E|E|
Gutiérrez-Guzmán|A V|AV|
Blázquez|A B|AB|
Saiz|J C|JC|
Höfle|U|U|

eye
Bagaza virus
flavivirus
West Nile virus.
common pheasant Phasianus colchicus
histology
immunohistochemistry
red-legged partridge Alectoris rufa


Identification of Novel Antiviral Compounds Targeting Entry of Hantaviruses.

Abstract: Hemorrhagic fever viruses, among them orthohantaviruses, arenaviruses and filoviruses, are responsible for some of the most severe human diseases and represent a serious challenge for public health. The current limited therapeutic options and available vaccines make the development of novel efficacious antiviral agents an urgent need. Inhibiting viral attachment and entry is a promising strategy for the development of new treatments and to prevent all subsequent steps in virus infection. Here, we developed a fluorescence-based screening assay for the identification of new antivirals against hemorrhagic fever virus entry. We screened a phytochemical library containing 320 natural compounds using a validated VSV pseudotype platform bearing the glycoprotein of the virus of interest and encoding enhanced green fluorescent protein (EGFP). EGFP expression allows the quantitative detection of infection and the identification of compounds affecting viral entry. We identified several hits against four pseudoviruses for the orthohantaviruses Hantaan (HTNV) and Andes (ANDV), the filovirus Ebola (EBOV) and the arenavirus Lassa (LASV). Two selected inhibitors, emetine dihydrochloride and tetrandrine, were validated with infectious pathogenic HTNV in a BSL-3 laboratory. This study provides potential therapeutics against emerging virus infection, and highlights the importance of drug repurposing.

Mayor|Jennifer|J| Torriani|Giulia|G| Engler|Olivier|O| Rothenberger|Sylvia|S|

D000998:Antiviral Agents
D004353:Drug Evaluation, Preclinical
D006476:Hantavirus
D018778:Hantavirus Infections
D006801:Humans
D053586:Virus Internalization

orthohantaviruses
arenavirus
GFP
antiviral screening
ebolavirus
entry inhibitors
viral hemorrhagic fever