Mechanisms of Mitochondrial Iron-Sulfur Protein Biogenesis.

Abstract: Mitochondria are essential in most eukaryotes and are involved in numerous biological functions including ATP production, cofactor biosyntheses, apoptosis, lipid synthesis, and steroid metabolism. Work over the past two decades has uncovered the biogenesis of cellular iron-sulfur (Fe/S) proteins as the essential and minimal function of mitochondria. This process is catalyzed by the bacteria-derived iron-sulfur cluster assembly (ISC) machinery and has been dissected into three major steps: de novo synthesis of a [2Fe-2S] cluster on a scaffold protein; Hsp70 chaperone-mediated trafficking of the cluster and insertion into [2Fe-2S] target apoproteins; and catalytic conversion of the [2Fe-2S] into a [4Fe-4S] cluster and subsequent insertion into recipient apoproteins. ISC components of the first two steps are also required for biogenesis of numerous essential cytosolic and nuclear Fe/S proteins, explaining the essentiality of mitochondria. This review summarizes the molecular mechanisms underlying the ISC protein-mediated maturation of mitochondrial Fe/S proteins and the importance for human disease.

cytosolic iron-sulfur protein assembly machinery

multiple mitochondrial dysfunction syndromes


Maximisation of oil recovery from an oil-water separator sludge: Influence of type, concentration, and application ratio of surfactants.

Abstract: Worldwide the generation of oil sludges is approximately 160 million metric tonnes per annum. The washing of oil sludge with surfactant solutions can be used to recover the oil and reused as a feedstock for fuel production. There is a need to establish the influence of the surfactant type, concentration, and application (surfactant to oil sludge, S/OS) ratio to oil sludge for the maximisation of oil recovery. This study presented the oil recovery rates from the washing of an oil-water separator sludge using surfactants, Triton X-100, sodium dodecyl sulphate (SDS), Tween 80, rhamnolipid, and Triton X-114. The surfactants were characterised by critical micelle concentration (CMC), micelle size, and surface activity. A Taguchi experimental design was applied to reduce the number of experimental runs. In general, Triton X-100 and X-114, and rhamnolipid had higher micelle sizes and surfactant activities which resulted in higher oil recoveries. The key role of the surfactants in the washing was evidenced because the ORR values with the surfactants were significantly higher than the value with the control with no surfactant solution. The S/OS ratio was the factor with the largest effect on the Taguchi signal-to-noise ratio (an indicator of variation) of the oil recovery rate. The levels with the maximum recovery rate were 1:1 S/OS, 2CMC of surfactant concentration and Triton X-100 (32% ± 5), Triton X-114 (30% ± 7), and rhamnolipid (29% ± 8). In conclusion, less surfactant solution (1:1 S/OS) and low surfactant concentration (≤2CMC) provided the maximum oil recovery from this type of oil sludge. To our knowledge, no previous study with surfactants has reported low oil recovery values at high S/OS ratios in the oil sludge washing.

Oil recovery
Surfactants
Oil sludge
Taguchi experimental design
Oil sludge washing (OSW)


Application of enzymatic calcification for dust control and rainfall erosion resistance improvement.

Abstract: Globally, most cities are facing severe challenges associated with dust pollution and it is of great significance to propose an effective and environmentally friendly dust control method. This study used enzymatically induced calcite precipitation (EICP) technology for dust control. Moreover, polyvinyl acetate (PVAc) was added to the cementation solution to improve its rainfall erosion resistance. The results showed that the optimum ratio of urease solution to cementation solution differed according to the concentrations of reactants in the cementation solution. Under combined EICP and PVAc (50 g/L) treatment, the stability of the dust-slope significantly improved. Moreover, little dust soil loss was washed out by simulated rainfall because of the more stable spatial structure of CaCO3 precipitation. Furthermore, PVAc addition increased the surface strength of slopes, while the cemented layer became thinner. With this combined EICP and PVAc (50 g/L) treatment, in a field test, the treated area of the slope had higher surface strengths and stronger erosion resistance than untreated areas. These higher surface strengths were attributed to the smaller particle size, and the stronger cementing effect of grass seeds. These results demonstrated that EICP-PVAc treatment significantly controlled dust and mitigated surface erosion of dust-slopes. This represents promising potential for the prevention of dust pollution.

Sun|Xiaohao|X| Miao|Linchang|L| Yuan|Junhao|J| Wang|Hengxing|H| Wu|Linyu|L|

Enzymatically induced carbonate precipitation


Chlorogenic Acid Inhibits Human Glioma U373 Cell Progression via Regulating the SRC/MAPKs Signal Pathway: Based on Network Pharmacology Analysis.

Abstract:
Introduction
Chlorogenic acid (CGA) is a type of polyphenolic substance that is widely extracted from many traditional Chinese medicines (eg, Lonicera japonica Thunb, Eucommia ulmoides Oliver) and exhibits a wide range of anti-tumor effects. However, the potential molecular mechanisms of CGA in glioma U373 cells remain unclear.

Methods
Network pharmacology analysis was used to explore the potential therapeutic targets of CGA in glioma. Human glioma U373 cells were treated with different concentrations of CGA for 24 h. CCK-8 assays were used to detect the inhibitory rate of cell growth. Annexin V-FITC/PI staining and Hoechst 33342 staining were used to detect apoptosis. PI staining was used to investigate cell-cycle progression. Wound healing assays and transwell assays were used to detect the cell migration and invasion, respectively. Western blotting and immunohistochemistry were used to measure protein levels in vitro and in vivo.

Results
The proliferation of U373 cells was significantly inhibited by CGA in a dose- and time-dependent manner. CGA significantly arrested the cell cycle of U373 cells in the G2/M phase and induced apoptosis. Moreover, CGA significantly suppressed the migration and invasion of U373 cells. Additionally, we found that CGA inhibited the growth of U373 cells in vivo. Furthermore, network pharmacology analysis suggested that the anti-tumor effects of CGA on U373 cells were associated with the down-regulation of the SRC/MAPKs signaling pathway.

Discussion
The present study indicated that CGA had anti-glioma effects on U373 cells by down-regulating SRC/MAPKs signal pathway.

Zhou|Jiabin|J| Zhang|Fengqi|F| Chen|Jun|J| Zhang|Shilin|S| Wang|Haijun|H|

D004354:Drug Screening Assays, Antitumor

chlorogenic acid
SRC/MAPKs signal pathway
network pharmacology
apoptosis
migration and invasion


Classification of thyroid nodules using ultrasound images.

Abstract: Medical imaging using image sensors play an essential role in effective diagnosis. Therefore, it is of interest to use medical imaging techniques for the diagnosis of thyroid-linked dysfunction. Ultrasound is the low-cost image processing technique to study internal organs and blood flow in blood vessels. Digital processed images help to distinguish between normal, benign and malignant tissue stages in organs.Hence, it is of importance to discuss the design and development of a computer-aided image-processing model for thyroid nodule identification, classification and diagnosis.

thyroid nodules
Computer Aided Diagnosis (CAD)
Ultrasonography
feature extraction


SARS-CoV-2, myocardial injury and inflammation: insights from a large clinical and autopsy study.

Abstract:
OBJECTIVE
Despite growing evidence about myocardial injury in hospitalized COronaVIrus Disease 2019 (COVID-19) patients, the mechanism behind this injury is only poorly understood and little is known about its association with SARS-CoV-2-mediated myocarditis. Furthermore, definite evidence of the presence and role of SARS-CoV-2 in cardiomyocytes in the clinical scenario is still lacking.

METHODS
We histologically characterized myocardial tissue of 40 patients deceased with severe SARS-CoV-2 infection during the first wave of the pandemic. Clinical data were also recorded and analyzed. In case of findings supportive of myocardial inflammation, histological analysis was complemented by RT-PCR and immunohistochemistry for SARS-CoV-2 viral antigens and in situ RNA hybridization for the detection of viral genomes.

RESULTS
Both chronic and acute myocardial damage was invariably present, correlating with the age and comorbidities of our population. Myocarditis of overt entity was found in one case (2.5%). SARS-CoV-2 genome was not found in the cardiomyocytes of the patient with myocarditis, while it was focally and negligibly present in cardiomyocytes of patients with known viral persistence in the lungs and no signs of myocardial inflammation. The presence of myocardial injury was not associated with myocardial inflammatory infiltrates.

CONCLUSIONS
In this autopsy cohort of COVID-19 patients, myocarditis is rarely found and not associated with SARS-CoV-2 presence in cardiomyocytes. Chronic and acute forms of myocardial damage are constantly found and correlate with the severity of COVID-19 disease and pre-existing comorbidities.

Dal Ferro|Matteo|M|
Bussani|Rossana|R|
Paldino|Alessia|A|
Nuzzi|Vincenzo|V|
Collesi|Chiara|C|
Zentilin|Lorena|L|
Schneider|Edoardo|E|
Correa|Ricardo|R|
Silvestri|Furio|F|
Zacchigna|Serena|S|
Giacca|Mauro|M|
Metra|Marco|M|
Merlo|Marco|M|
Sinagra|Gianfranco|G|

Myocardial injury
COVID-19
Myocarditis
Cardiac autopsy study
Necrosis


Atopic dermatitis or eczema? Consequences of ambiguity in disease name for biomedical literature mining.

Abstract:
BACKGROUND
Biomedical research increasingly relies on computational approaches to extract relevant information from large corpora of publications.

OBJECTIVE
To investigate the consequence of the ambiguity between the use of terms "Eczema" and "Atopic Dermatitis" (AD) from the Information Retrieval perspective, and its impact on meta-analyses, systematic reviews and text mining.

METHODS
Articles were retrieved by querying the PubMed using terms 'eczema' (D003876) and "dermatitis, atopic" (D004485). We used machine learning to investigate the differences between the contexts in which each term is used. We used a decision tree approach and trained model to predict if an article would be indexed with eczema or AD tags. We used text-mining tools to extract biological entities associated with eczema and AD, and investigated the discrepancy regarding the retrieval of key findings according to the terminology used.

RESULTS
Atopic dermatitis query yielded more articles related to veterinary science, biochemistry, cellular and molecular biology; the eczema query linked to public health, infectious disease and respiratory system. Medical Subject Headings terms associated with "AD" or "Eczema" differed, with an agreement between the top 40 lists of 52%. The presence of terms related to cellular mechanisms, especially allergies and inflammation, characterized AD literature. The metabolites mentioned more frequently than expected in articles with AD tag differed from those indexed with eczema. Fewer enriched genes were retrieved when using eczema compared to AD query.

CONCLUSIONS AND CLINICAL RELEVANCE
There is a considerable discrepancy when using text mining to extract bio-entities related to eczema or AD. Our results suggest that any systematic approach (particularly when looking for metabolites or genes related to the condition) should be performed using both terms jointly. We propose to use decision tree learning as a tool to spot and characterize ambiguity, and provide the source code for disambiguation at https://github.com/cfrainay/ResearchCodeBase.

atopic dermatitis
eczema
information retrieval
text mining
medical terminology


Spelling Errors in French-speaking Children with Dyslexia: Phonology May Not Provide the Best Evidence.

Abstract: For children with dyslexia, learning to write constitutes a great challenge. There has been consensus that the explanation for these learners' delay is related to a phonological deficit. Results from studies designed to describe dyslexic children's spelling errors are not always as clear concerning the role of phonological processes as those found in reading studies. In irregular languages like French, spelling abilities involve other processes than phonological processes. The main goal of this study was to describe the relative contribution of these other processes in dyslexic children's spelling ability. In total, 32 francophone dyslexic children with a mean age of 11.4 years were compared with 24 reading-age matched controls (RA) and 24 chronological-age matched controls (CA). All had to write a text that was analysed at the graphemic level. All errors were classified as either phonological, morphological, visual-orthographic or lexical. Results indicated that dyslexic children's spelling ability lagged behind not only that of the CA group but also of the RA group. Because the majority of errors, in all groups, could not be explained by inefficiency of phonological processing, the importance of visual knowledge/processes will be discussed as a complementary explanation of dyslexic children's delay in writing. Copyright © 2016 John Wiley & Sons, Ltd.

Daigle|Daniel|D| Costerg|Agnès|A| Plisson|Anne|A| Ruberto|Noémia|N| Varin|Joëlle|J|

dyslexia
spelling ability
phonological errors
visual-orthographic errors


Mental Health Recovery Narratives and Their Impact on Recipients: Systematic Review and Narrative Synthesis.

Abstract:
OBJECTIVE
Mental health recovery narratives are often shared in peer support work and antistigma campaigns. Internet technology provides access to an almost unlimited number of narratives, and yet little is known about how they affect recipients. The aim of this study was to develop a conceptual framework characterizing the impact of recovery narratives on recipients.

METHOD
A systematic review of evidence about the impact of mental health recovery narratives was conducted. Searches used electronic databases (n = 9), reference tracking, hand-searching of selected journals (n = 2), grey literature searching, and expert consultation (n = 7). A conceptual framework was generated through a thematic analysis of included articles, augmented by consultation with a Lived Experience Advisory Panel.

RESULTS
In total, 8137 articles were screened. Five articles were included. Forms of impact were connectedness, understanding of recovery, reduction in stigma, validation of personal experience, affective responses, and behavioural responses. Impact was moderated by characteristics of the recipient, context, and narrative. Increases in eating disorder behaviours were identified as a harmful response specific to recipients with eating disorders.

CONCLUSIONS
Mental health recovery narratives can promote recovery. Recovery narratives might be useful for clients with limited access to peers and in online interventions targeted at reducing social isolation in rural or remote locations, but support is needed for the processing of the strong emotions that can arise. Caution is needed for use with specific clinical populations. Protocol registration: Prospero-CRD42018090923.

D006801:Humans
D000073038:Mental Health Recovery
D063545:Personal Narratives as Topic

mental health
recovery narratives
impact
memoirs
recovery stories


Species distribution modelling for conservation of an endangered endemic orchid.

Abstract: Concerns regarding the long-term viability of threatened and endangered plant species are increasingly warranted given the potential impacts of climate change and habitat fragmentation on unstable and isolated populations. Orchidaceae is the largest and most diverse family of flowering plants, but it is currently facing unprecedented risks of extinction. Despite substantial conservation emphasis on rare orchids, populations continue to decline. Spiranthes parksii (Navasota ladies' tresses) is a federally and state-listed endangered terrestrial orchid endemic to central Texas. Hence, we aimed to identify potential factors influencing the distribution of the species, quantify the relative importance of each factor and determine suitable habitat for future surveys and targeted conservation efforts. We analysed several geo-referenced variables describing climatic conditions and landscape features to identify potential factors influencing the likelihood of occurrence of S. parksii using boosted regression trees. Our model classified 97 % of the cells correctly with regard to species presence and absence, and indicated that probability of existence was correlated with climatic conditions and landscape features. The most influential variables were mean annual precipitation, mean elevation, mean annual minimum temperature and mean annual maximum temperature. The most likely suitable range for S. parksii was the eastern portions of Leon and Madison Counties, the southern portion of Brazos County, a portion of northern Grimes County and along the borders between Burleson and Washington Counties. Our model can assist in the development of an integrated conservation strategy through: (i) focussing future survey and research efforts on areas with a high likelihood of occurrence, (ii) aiding in selection of areas for conservation and restoration and (iii) framing future research questions including those necessary for predicting responses to climate change. Our model could also incorporate new information on S. parksii as it becomes available to improve prediction accuracy, and our methodology could be adapted to develop distribution maps for other rare species of conservation concern.

Wang|Hsiao-Hsuan|HH|
Wonkka|Carissa L|CL|
Treglia|Michael L|ML|
Grant|William E|WE|
Smeins|Fred E|FE|
Rogers|William E|WE|

species distribution models
conservation
Boosted regression trees
Navasota ladies’ tresses
endangered species
reintroduction


Pilot study shows right ventricular diastolic function impairment in young children with obstructive respiratory disease.

Abstract:
AIM
This study determined cardiovascular impairment in young children with obstructive respiratory disease who were assessed using the opening interrupter technique (RINT).

METHODS
This pilot study enrolled 41 children who had been referred to pulmonology and allergology specialists at the University of Catania, Italy, from March to July 2017: 23 (mean age 4.13 ± 0.62 years) had chronic coughs and wheezing and 18 controls (mean age 4.27 ± 0.66 years) had obstructive chest disease, but were otherwise healthy. Airway resistance was evaluated using RINT and cardiac function by studying the ejection fraction, pulmonary artery systolic pressure (PASP), tricuspid annular plane systolic excursion and tricuspid flow propagation velocity (TFPV).

RESULTS
The RINT and PASP values were significantly higher in the patient group when compared to the controls, but the TFPV values were lower. A direct and significant Spearman's correlation coefficient (r) between RINT and PASP values was observed (r = 0.81). We found a significant inverse correlation between RINT and TFPV (r = -0.83), as well as TFPV and PASP (r = -0.78).

CONCLUSION
This study showed that children with obstructive respiratory diseases had a major risk of cardiovascular impairment. Impaired diastolic function of the right ventricle occurred very early when airway resistance was abnormally increased.

Manti|S|S|
Parisi|G F|GF|0000-0003-4291-0195
Giacchi|V|V|
Sciacca|P|P|0000-0003-2642-316X
Tardino|L|L|
Cuppari|C|C|
Salpietro|C|C|
Chikermane|A|A|
Leonardi|S|S|

Obstructive respiratory disease
Cardiovascular impairment
Opening interrupter technique
Pulmonary function
Right cardiac function


Anterior regeneration after fission in the holothurian Cladolabes schmeltzii (Dendrochirotida: Holothuroidea).

Abstract: The regeneration of the anterior portion of the body after fission was studied in the holothurian Cladolabes schmeltzii using electron microscopy methods. Following fission, the posterior portion of the digestive tube, cloaca, and respiratory trees remain in the posterior fragment of the body. The regeneration comprises five stages. In the first stage, connective-tissue thickening (an anlage of the aquapharyngeal bulb) occurs on the anterior end between the torn-off ends of the ambulacra. Most of the lost anterior organs developed in the second and third stages. The structures of water-vascular system and nerve ring form through dedifferentiation, proliferation, and migration of cells of the radial water-vascular canals and the radial nerve cords, correspondently. The lost digestive system portion is restored through the formation and merging of two anlagen. The digestive epithelium of the esophagus and pharynx develops from lining cells of microcavities near the central portion of the connective-tissue thickening, which probably migrate from the epidermis. The second gut anlage develops through transformation of the anterior gut remnant portion. The enterocytes partly dedifferentiate, but the epithelium retains integrity. The gut anlage grows down the mesentery and joins the regenerating aquapharyngeal bulb. In the fourth and fifth stages, all lost organs are formed and have nearly normal structure. The regeneration was concluded to occur through morphallactic rearrangements of the remaining parts of organs. Epithelial morphogenesis is the key development mechanism of the digestive, water-vascular, and nervous systems.

Kamenev|Yaroslav O|YO|
Dolmatov|Igor Y|IY|

D009424:Nervous System Physiological Phenomena

regeneration
fission
Cladolabes schmeltzii
Holothuroidea
asexual reproduction


Abstract: Adiponectin (APN), an adipocyte-derived adipokine, has been shown to limit lung injury originating from endothelial cell (EC) damage. Previously we reported that obese mice with low circulatory APN levels exhibited pulmonary vascular endothelial dysfunction. This study was designed to investigate the cellular and molecular mechanisms underlying the pulmonary endothelium-dependent protective effects of APN. Our results demonstrated that in APN-/- mice, there was an inherent state of endothelium mitochondrial dysfunction that could contribute to endothelial activation and increased susceptibility to LPS-induced acute lung injury (ALI). We noted that APN-/- mice showed decreased expression of mitochondrial biogenesis regulatory protein peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) and its downstream proteins nuclear respiratory factor 1, transcription factor A, mitochondrial, and Sirtuin (Sirt)3 and Sirt1 expression in whole lungs and in freshly isolated lung ECs from these mice at baseline and subjected to LPS-induced ALI. We further showed that treating APN-/- mice with PGC-1α activator pyrroloquinoline quinone enhances mitochondrial biogenesis and function in lung endothelium and attenuation of ALI. These results suggest that the pulmonary endothelium-protective properties of APN are mediated, at least in part, by an enhancement of mitochondrial biogenesis through a mechanism involving PGC-1α activation.-Shah, D., Torres, C., Bhandari, V. Adiponectin deficiency induces mitochondrial dysfunction and promotes endothelial activation and pulmonary vascular injury.

D000071199:NLR Family, Pyrin Domain-Containing 3 Protein

adipokine
endothelial dysfunction
acute lung injury
PGC-1α mitochondria biogenesis


Mechanical properties of fibroblasts depend on level of cancer transformation.

Abstract: Recently, it was revealed that tumor cells are significantly softer than normal cells. Although this phenomenon is well known, it is connected with many questions which are still unanswered. Among these questions are the molecular mechanisms which cause the change in stiffness and the correlation between cell mechanical properties and their metastatic potential. We studied mechanical properties of cells with different levels of cancer transformation. Transformed cells in three systems with different transformation types (monooncogenic N-RAS, viral and cells of tumor origin) were characterized according to their morphology, actin cytoskeleton and focal adhesion organization. Transformation led to reduction of cell spreading and thus decreasing the cell area, disorganization of actin cytoskeleton, lack of actin stress fibers and decline in the number and size of focal adhesions. These alterations manifested in a varying degree depending on type of transformation. Force spectroscopy by atomic force microscopy with spherical probes was carried out to measure the Young's modulus of cells. In all cases the Young's moduli were fitted well by log-normal distribution. All the transformed cell lines were found to be 40-80% softer than the corresponding normal ones. For the cell system with a low level of transformation the difference in stiffness was less pronounced than for the two other systems. This suggests that cell mechanical properties change upon transformation, and acquisition of invasive capabilities is accompanied by significant softening.

Efremov|Yu M|YM|
Lomakina|M E|ME|
Bagrov|D V|DV|
Makhnovskiy|P I|PI|
Alexandrova|A Y|AY|
Kirpichnikov|M P|MP|
Shaitan|K V|KV|

D002471:Cell Transformation, Neoplastic
D005347:Fibroblasts
D022001:Focal Adhesions
D006801:Humans
D018625:Microscopy, Atomic Force
D008856:Microscopy, Fluorescence

Fibroblast
Transformed cell
Force spectroscopy
Young's modulus
AFM


Migration of CXCR4 gene-modified bone marrow-derived mesenchymal stem cells to the acute injured kidney.

Abstract: Bone marrow-derived mesenchymal stem cells (BMSCs) can migrate to the injured kidney after acute kidney injury (AKI) with limited efficiency. This study investigated the effect of CXCR4 overexpression on BMSC migration to the AKI kidney and the possible mechanisms. CXCR4 gene-modified BMSCs (CXCR4-BMSCs) and null-BMSCs were prepared and transplanted into the AKI mice. Blood indicators, histology, expression of stromal cell-derived factor 1 (SDF-1), and BMSC migration were investigated. Hypoxia/re-oxygenation-pretreated renal tubular epithelial cells (HR-RTECs) were prepared to generate AKI in vitro. The chemotaxis experiment was performed using the transwell chamber. The phosphorylation of AKT and MAPK in the BMSCs was also investigated. The CXCR4-BMSCs showed a remarkable expression of CXCR4. The SDF-1 expression in the AKI renal tissue was increased. CXCR4-BMSCs transplantation sharply increased the accumulation of BMSCs in the renal tissue, which was consistent with a greater improvement of renal function. The in vitro experiments showed that the migration of BMSCs to the HR-RTEC culturing chamber was CXCR4-dependent, and could be fully inhibited by AMD3100, a CXCR4-specific antagonist. The migration could also be partly blocked by either LY294002 (PI3K inhibitor) or PD98059 (MAPK inhibitor). Phosphorylated Akt and MAPK were increased in the BMSCs co-cultured with HR-RTECs and their expression was the highest in the CXCR4-BMSCs, which could be recovered by AMD3100. Overexpression of CXCR4 gene could enhance BMSC migration to the kidney area after AKI. The SDF-1/CXCR4 axis via its activation of PI3K/AKT and MAPK in BMSCs could be the possible mechanisms underlying this function.

Liu|Nanmei|N| Tian|Jun|J| Cheng|Jin|J| Zhang|Jinyuan|J|

D045164:Mesenchymal Stem Cell Transplantation

D020929:Mitogen-Activated Protein Kinase Kinases

BONE MARROW-DERIVED MESENCHYMAL STEM CELLS


Managing the female patient with hereditary angioedema.

Abstract: Hereditary angioedema (HAE) is a rare disorder resulting from decreased functional levels of C1-inhibitor (C1-INH), which manifests as periodic episodes of localized edema which can be extremely painful, debilitating and even fatal if the swelling affects the larynx. HAE can complicate many aspects of obstetric/gynecologic care, and an awareness of the disease is critical for clinicians involved in the care of women because of potential HAE-related complications pertaining to pregnancy, labor and delivery, and other women's health issues. This article provides a review of published literature specific to HAE and its management in female patients, including important concerns regarding obstetric/gynecologic care. A growing body of relevant experience is presented to help guide the care of women with HAE.

D003174:Complement C1 Inactivator Proteins

hereditary angioedema
C1-inhibitor
women
ecallantide
icatibant


Alkaloids from Piper nigrum Exhibit Antiinflammatory Activity via Activating the Nrf2/HO-1 Pathway.

Abstract: In the present study, ten alkaloids, namely chabamide (1), pellitorine (2), retrofractamide A (3), pyrroperine (4), isopiperolein B (5), piperamide C9:1 (8E) (6), 6,7-dehydrobrachyamide B (7), 4,5-dihydropiperine (8), dehydropipernonaline (9), and piperine (10), were isolated from the fruits of Piper nigrum. Among these, chabamide (1), pellitorine (2), retrofractamide A (3), isopiperolein B (5), and 6,7-dehydrobrachyamide B (7) exhibited significant inhibitory activity on lipopolysaccharide-induced nitric oxide (NO) production in RAW264.7 cells, with IC50 values of 6.8, 14.5, 30.2, 23.7, and 38.5 μM, respectively. Furthermore, compound 1 inhibited lipopolysaccharide-induced NO production in bone marrow-derived macrophages with IC50 value of 9.5 μM. Consistent with NO inhibition, treatment of RAW264.7 cells with chabamide (1), pellitorine (2), and 6,7-dehydrobrachyamide B (7) suppressed expression of inducible NO synthase and cyclooxygenase-2. Chabamide (1), pellitorine (2), and 6,7-dehydrobrachyamide B (7) induced heme-oxygenase-1 expression at the transcriptional level. In addition, compound 1 induced the nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) and upregulated the expression of Nrf2 target genes, NAD(P)H:quinone oxidoreductase 1 and γ-glutamyl cysteine synthetase catalytic subunit, in a concentration-dependent manner in RAW264.7 cells. These findings suggest that chabamide (1) from P. nigrum exert antiinflammatory effects via the activation of the Nrf2/heme-oxygenase-1 pathway; hence, it might be a promising candidate for the treatment of inflammatory diseases. Copyright © 2017 John Wiley & Sons, Ltd.

alkaloid
Piper nigrum
Nrf2
chabamide
antiinflammation
heme oxygenase-1


The association between high risk of sleep apnea, comorbidities, and risk of COVID-19: a population-based international harmonized study.

Abstract:
PURPOSE
Obstructive sleep apnea (OSA) may increase the risk of severe COVID-19; however, the level of potential modulation has not yet been established. The objective of the study was to determine the association between high risk of OSA, comorbidities, and increased risk for COVID-19, hospitalization, and intensive care unit (ICU) treatment.

METHODS
We conducted a cross-sectional population-based web survey in adults in 14 countries/regions. The survey included sociodemographic variables and comorbidities. Participants were asked questions about COVID-19, hospitalization, and ICU treatment. Standardized questionnaire (STOP questionnaire for high risk of OSA) was included. Multivariable logistic regression was conducted adjusting for various factors.

RESULTS
Out of 26,539 respondents, 20,598 (35.4% male) completed the survey. Mean age and BMI of participants were 41.5 ± 16.0 years and 24.0 ± 5.0 kg/m2, respectively. The prevalence of physician-diagnosed OSA was 4.1% and high risk of OSA was 9.5%. We found that high risk of OSA (adjusted odds ratio (aOR) 1.72, 95% confidence interval (CI): 1.20, 2.47) and diabetes (aOR 2.07, 95% CI: 1.23, 3.48) were associated with reporting of a COVID-19 diagnosis. High risk for OSA (aOR 2.11, 95% CI: 1.10-4.01), being male (aOR: 2.82, 95% CI: 1.55-5.12), having diabetes (aOR: 3.93, 95% CI: 1.70-9.12), and having depression (aOR: 2.33, 95% CI: 1.15-4.77) were associated with increased risk of hospitalization or ICU treatment.

CONCLUSIONS
Participants at high risk of OSA had increased odds of having COVID-19 and were two times more likely to be hospitalized or treated in ICU.

COVID-19
Obstructive sleep apnea
STOP questionnaire
Diabetes
Depression


Confidential machine learning on untrusted platforms: a survey.

Abstract: With the ever-growing data and the need for developing powerful machine learning models, data owners increasingly depend on various untrusted platforms (e.g., public clouds, edges, and machine learning service providers) for scalable processing or collaborative learning. Thus, sensitive data and models are in danger of unauthorized access, misuse, and privacy compromises. A relatively new body of research confidentially trains machine learning models on protected data to address these concerns. In this survey, we summarize notable studies in this emerging area of research. With a unified framework, we highlight the critical challenges and innovations in outsourcing machine learning confidentially. We focus on the cryptographic approaches for confidential machine learning (CML), primarily on model training, while also covering other directions such as perturbation-based approaches and CML in the hardware-assisted computing environment. The discussion will take a holistic way to consider a rich context of the related threat models, security assumptions, design principles, and associated trade-offs amongst data utility, cost, and confidentiality.

Machine learning
Confidential computing
Cryptographic protocols


Efficacy of the nicotine vaccine 3'-AmNic-rEPA (NicVAX) co-administered with varenicline and counselling for smoking cessation: a randomized placebo-controlled trial.

Abstract:
BACKGROUND AND AIMS
Nicotine vaccination has been proposed as a possible treatment to aid smoking cessation. First efficacy results of the nicotine vaccine 3'-AmNic-rEPA (NicVAX) showed that only a subgroup of the top 30% antibody responders achieved higher abstinence rates than placebo. The present study examined the efficacy of adding NicVAX versus placebo to varenicline and behavioural support as an aid in smoking cessation and relapse prevention.

DESIGN
Randomized placebo-controlled trial.

SETTING
Two research centres (Maastricht University Medical Centre and Slotervaart Hospital) in the Netherlands.

PARTICIPANTS
A total of 558 smokers were assigned randomly to six injections with NicVAX (n = 278) or placebo (n = 280) both co-administered with open label varenicline and behavioural support.

MEASURES
Outcomes were prolonged carbon monoxide-validated abstinence from weeks 9 to 52 (primary) and weeks 37 to 52 (secondary). We also performed a pre-planned subgroup analysis in the top 30% antibody responders.

FINDINGS
There was no difference in abstinence rates between NicVAX and placebo from weeks 9 to 52 [27.7 versus 30.0%, odds ratio (OR) = 0.89, 95% confidence interval (CI) = 0.62-1.29] or weeks 37 to 52 (33.8 versus 33.2%, OR = 1.03, 95% CI = 0.73-1.46). The top 30% antibody responders, compared to the placebo group, showed a non-significant tendency towards higher abstinence rates from weeks 37 to 52 (42.2 versus 33.2%, OR = 1.47, 95% CI = 0.89-2.42).

CONCLUSION
The nicotine vaccine, NicVAX, does not appear to improve the chances of stopping smoking when given in addition to varenicline and behavioural support.

Hoogsteder|Philippe H J|PH|
Kotz|Daniel|D|
van Spiegel|Paul I|PI|
Viechtbauer|Wolfgang|W|
van Schayck|Onno C P|OC|

Efficacy
nicotine vaccine
randomized
trial
placebo
immunogenicity
safety


Did the Affordable Care Act's Dependent Coverage Expansion Affect Race/Ethnic Disparities in Health Insurance Coverage?

Abstract:
OBJECTIVE
To test the impact of the dependent coverage expansion (DCE) on insurance disparities across race/ethnic groups.

DATA SOURCES/STUDY SETTING
Survey data from the National Survey of Drug Use and Health (NSDUH).

STUDY DESIGN
Triple-difference (DDD) models were applied to repeated cross-sectional surveys of the U.S. adult population.

DATA COLLECTION/EXTRACTION METHODS
Data from 6 years (2008-2013) of the NSDUH were combined.

PRINCIPAL FINDINGS
Following the DCE, the relative odds of insurance increased 1.5 times (95 percent CI 1.1, 1.9) among whites compared to blacks and 1.4 times (95 percent CI 1.1, 1.8) among whites compared to Hispanics.

CONCLUSIONS
Health reform efforts, such as the DCE, can have negative effects on race/ethnic disparities, despite positive impacts in the general population.

Breslau|Joshua|J|0000-0002-1194-4643
Han|Bing|B|
Stein|Bradley D|BD|
Burns|Rachel M|RM|
Yu|Hao|H|

D058991:Patient Protection and Affordable Care Act

Health insurance coverage
health disparities
young adults


Gambling Participation, Expenditure and Risk of Harm in Australia, 1997-1998 and 2010-2011.

Abstract: Gambling-related harm results primarily from financial losses. Internationally Australia continues to rank as the largest spending nation per capita on gambling products. This would suggest that Australian gamblers are at disproportionately high risk of harm despite almost two decades of industry scrutiny and regulation, and investment in research, treatment and education programs. However, declines in participation rates, per capita expenditure, household expenditure, national disposable income spent on gambling and problem gambling rates have been cited as evidence that fewer people are gambling, that gamblers are spending less, and that gambling safety in Australia has improved. The current study investigated these propositions using national population and accounts data, and statistics from Australia's two population-representative gambling surveys conducted in 1997-1998 and 2010-2011. Despite a falling participation rate the study found no real change in the number of people gambling overall, and increasing numbers consuming casino table games, race wagering and sports betting. Further found were increases rather than decreases in average gambler expenditure, overall, and across most products, particularly electronic gaming machines (EGMs). Potentially risky levels of average expenditure were observed in both periods, overall and for race wagering, casino table gaming, and EGMs. Changes in the proportion of income spent on gambling suggest risks declined overall and for race wagering and casino table gaming, but increased for EGMs. Finally, while problem gambling statistics were not comparable between periods, the study found double the number of moderate risk gamblers previously estimated for 2010-2011 amongst the 2 million Australians found to have experienced one or more gambling-related problems. The findings have implications for public health policy and resourcing, and the way in which prevalence and expenditure statistics have been interpreted by researchers, government and industry in Australia and elsewhere.

Armstrong|Andrew Richard|AR|
Thomas|Anna|A|
Abbott|Max|M|

Participation
Expenditure
Australia
Problem gambling
Casino
Sports betting
Gaming machine
EGM
Public health
Policy
Prevalence
Government
Adaptation
Harm minimisation
Horse racing
PGSI


Fabrication and characterization of strontium incorporated 3-D bioactive glass scaffolds for bone tissue from biosilica.

Abstract: Bioactive glass scaffolds that contain silica are high viable biomaterials as bone supporters for bone tissue engineering due to their bioactive behaviour in simulated body fluid (SBF). In the human body, these materials help inorganic bone structure formation due to a combination of the particular ratio of elements such as silicon (Si), calcium (Ca), sodium (Na) and phosphorus (P), and the doping of strontium (Sr) into the scaffold structure increases their bioactive behaviour. In this study, bioactive glass scaffolds were produced by using rice hull ash (RHA) silica and commercial silica based bioactive glasses. The structural properties of scaffolds such as pore size, porosity and also the bioactive behaviour were investigated. The results showed that undoped and Sr-doped RHA silica-based bioactive glass scaffolds have better bioactivity than that of commercial silica based bioactive glass scaffolds. Moreover, undoped and Sr-doped RHA silica-based bioactive glass scaffolds will be able to be used instead of undoped and Sr-doped commercial silica based bioactive glass scaffolds for bone regeneration applications. Scaffolds that are produced from undoped or Sr-doped RHA silica have high potential to form new bone for bone defects in tissue engineering.

Strontium
Bioactive glass
Scaffold
Silica
Rice hull ash


Validity of an Athletic Skills Track among 6- to 12-year-old children.

Abstract: The purpose of this study was to examine the feasibility and validity of an Athletic Skills Track (AST) to assess fundamental movement skills among 6- to 12-year-old children in a physical education setting. Four hundred sixty-three Dutch children (211 girls, 252 boys) completed three tests: the Körperkoordinationstest für Kinder (KTK) and two Athletic Skills Tracks (AST-1, AST-2). The validity of AST-1 and AST-2 was examined by correlating the time (s) needed to complete the tracks and the KTK Motor Quotient (MQ). Overall, there was a low correlation between AST-1 and the KTK MQ (r = -0.474 (P < 0.01)) and a moderate correlation between AST-2 and the KTK MQ (r = -0.502 (P < 0.01)). When split up by age group the associations were much higher and ranged between r = -0.469 and r = -0.767), with the exception of the low correlation coefficient of the AST-2 in 7-year-olds. The results indicate that fundamental movement skills of 6- to 12-year-old children can be assessed with a quick, convenient and low-cost motor competence test in a physical education setting, i.e., an Athletic Skills Track. Future studies should further assess the reliability, discriminative ability and validity of age-specific versions of the AST.

Hoeboer|Joris|J|
De Vries|Sanne|S|
Krijger-Hombergen|Michiel|M|
Wormhoudt|René|R|
Drent|Annelies|A|
Krabben|Kay|K|
Savelsbergh|Geert|G|

validity
Physical education
motor competence
child
health
paediatrics


Stress Prevention@Work: a study protocol for the evaluation of a multifaceted integral stress prevention strategy to prevent employee stress in a healthcare organization: a cluster controlled trial.

Abstract:
BACKGROUND
Adequate implementation of work-related stress management interventions can reduce or prevent work-related stress and sick leave in organizations. We developed a multifaceted integral stress-prevention strategy for organizations from several sectors that includes a digital platform and collaborative learning network. The digital platform contains a stepwise protocol to implement work-related stress-management interventions. It includes stress screeners, interventions and intervention providers to facilitate access to and the selection of matching work-related stress-management interventions. The collaborative learning network, including stakeholders from various organizations, plans meetings focussing on an exchange of experiences and good practices among organizations for the implementation of stress prevention measures. This paper describes the design of an integral stress-prevention strategy, Stress Prevention@Work, and the protocol for the evaluation of: 1) the effects of the strategy on perceived stress and work-related outcomes, and 2) the barriers and facilitators for implementation of the strategy.

METHODS
The effectiveness of Stress Prevention@Work will be evaluated in a cluster controlled trial, in a large healthcare organization in the Netherlands, at six and 12 months. An independent researcher will match teams on working conditions and size and allocate the teams to the intervention or control group. Teams in the intervention group will be offered Stress Prevention@Work. For each intervention team, one employee is responsible for applying the strategy within his/her team using the digital platform and visiting the collaborative learning network. Using a waiting list design, the control group will be given access to the strategy after 12 months. The primary outcome is the employees' perceived stress measured by the stress subscale of the Depression, Anxiety, and Stress Scale (DASS-21). Secondary outcome measures are job demands, job resources and the number of preventive stress measures implemented at the team level. Alongside the trial, a process evaluation, including barriers and facilitators of the implementation of Stress Prevention@Work, will be conducted in one healthcare organisation.

DISCUSSION
If Stress Prevention@Work is found to be effective in one healthcare organisation, further implementation on a broader scale might lead to increased productivity and decreased stress and sick leave in other organizations. Results are expected in 2018.

TRIAL REGISTRATION
NTR5527 . Registered 7 Dec 2015.

Hoek|Rianne J A|RJA|
Havermans|Bo M|BM|
Houtman|Irene L D|ILD|
Brouwers|Evelien P M|EPM|
Heerkens|Yvonne F|YF|
Zijlstra-Vlasveld|Moniek C|MC|
Anema|Johannes R|JR|
van der Beek|Allard J|AJ|
Boot|Cécile R L|CRL|

Work-related stress management interventions


Research Progress on the Anti-Disproportionation of the ZrCo Alloy by Element Substitution.

Abstract: Hydrogen-induced disproportionation (HID) during the cycles of absorption and desorption leads to a serious decline in the storage capacity of the ZrCo alloy, which has been recognized as the biggest obstacle to its application. Therefore, the prerequisite of a ZrCo application is to solve its anti-disproportionation problem in the field of rapid hydrogen isotope storage. Beyond surface modification and nanoball milling, this work systematically reviews the method of element substitution, which can obviously improve the anti-disproportionation. From a micro angle, as hydrogen atoms that occupy the 8e site in the ZrCoH3 lattice are instable and are considered to be the driving force of disproportionation, researchers believe that element substitution by changing the occupation of hydrogen atoms at the 8e site can improve the anti-disproportionation of the alloy. At present, Ti/Nb substitutions for the Zr terminal among substitute elements have an excellent anti-disproportionation performance. In this work, up-to-date research studies on anti-disproportionation and its disproportionation mechanism of the ZrCo alloy are introduced by combining experiments and simulations. Moreover, the optimization of the alloy based on the occupation mechanism of 8e sites is expected to improve the anti-disproportionation of the ZrCo alloy.

anti-disproportionation
ZrCo alloy
element substitution
hydrogen storage performance
storage and delivery system


CA IX Stabilizes Intracellular pH to Maintain Metabolic Reprogramming and Proliferation in Hypoxia.

Abstract: Tumor hypoxia represents a severe microenvironmental stress that is frequently associated with acidosis. Cancer cells respond to these stresses with changes in gene expression that promote survival at least in part through pH regulation and metabolic reprogramming. Hypoxia-induced carbonic anhydrase IX (CA IX) plays a critical adaptive role in response to hypoxic and acidic environments by catalytically hydrating extracellular CO2 to produce bicarbonate for buffering intracellular pH (pHi). We used proteome-wide profiling to study the cellular response to transient CA IX knockdown in hypoxia and found a decrease in the levels of key glycolytic enzymes and lactate dehydrogenase A (LDHA). Interestingly, the activity of LDH was also decreased as demonstrated by native in-gel activity assay. These changes led to a significant reduction in glycolytic flux and extracellular lactate levels in cancer cells in vitro, contributing to a decrease in proliferation. Interestingly, addition of the alternative LDH substrate alpha-ketobutyrate restored LDHA activity, extracellular acidification, pHi, and cellular proliferation. These results indicate that in the absence of CA IX, reduction of pHi disrupts LDHA activity and hinders the cellular capacity to regenerate NAD+ and secrete protons to the extracellular space. Hypoxia-induced CA IX therefore mediates adaptation to microenvironmental hypoxia and acidosis directly, by enzymatically converting extracellular CO2 to bicarbonate, and indirectly, by maintaining glycolysis-permissive intracellular milieu.

Benej|Martin|M|
Svastova|Eliska|E|
Banova|Radivojka|R|
Kopacek|Juraj|J|
Gibadulinova|Adriana|A|
Kery|Martin|M|
Arena|Simona|S|
Scaloni|Andrea|A|
Vitale|Monica|M|
Zambrano|Nicola|N|
Papandreou|Ioanna|I|
Denko|Nicholas C|NC|
Pastorekova|Silvia|S|

metabolism
hypoxia
pH regulation
carbonic anhydrase IX
glycolysis


Assembly of Dynamic Supramolecular Polymers on a DNA Origami Platform.

Abstract: Biological processes rely on transient interactions that govern assembly of biomolecules into higher order, multi-component systems. A synthetic platform for the dynamic assembly of multicomponent complexes would provide novel entries to study and modulate the assembly of artificial systems into higher order topologies. Here, we establish a hybrid DNA origami-based approach as an assembly platform that enables dynamic templating of supramolecular architectures. It entails the site-selective recruitment of supramolecular polymers to the platform with preservation of the intrinsic dynamics and reversibility of the assembly process. The composition of the supramolecular assembly on the platform can be tuned dynamically, allowing for monomer rearrangement and inclusion of molecular cargo. This work should aid the study of supramolecular structures in their native environment in real-time and incites new strategies for controlled multicomponent self-assembly of synthetic building blocks.

polymers
self-assembly
multicomponent assembly
supramolecular synthesis


FDG-PET/CT in intensive care patients with bloodstream infection.

Abstract:
BACKGROUND
2-Deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) is an advanced imaging technique that can be used to examine the whole body for an infection focus in a single examination in patients with bloodstream infection (BSI) of unknown origin. However, literature on the use of this technique in intensive care patients is scarce. The purpose of this study was to evaluate the diagnostic yield of FDG-PET/CT in intensive care patients with BSI.

METHODS
In this retrospective cohort study, all intensive care patients from our Dutch university medical center who had culture-proven BSI between 2010 and 2020 and underwent FDG-PET/CT to find the focus of infection were included. Diagnostic performance was calculated and logistic regression analysis was performed to evaluate the association between FDG-PET/CT outcome and C-reactive protein level (CRP), leukocyte count, duration of antibiotic treatment, duration of ICU stay, quality of FDG-PET/CT, and dependency on mechanical ventilation. In addition, the impact of FDG-PET/CT on clinical treatment was evaluated.

RESULTS
30 intensive care patients with BSI were included. In 21 patients, an infection focus was found on FDG-PET/CT which led to changes in clinical management in 14 patients. FDG-PET/CT achieved a sensitivity of 90.9% and specificity of 87.5% for identifying the focus of infection. Poor quality of the FDG-PET images significantly decreased the likelihood of finding an infection focus as compared to reasonable or good image quality (OR 0.16, P = 0.034). No other variables were significantly associated with FDG-PET/CT outcome. No adverse events during the FDG-PET/CT procedure were reported.

CONCLUSION
FDG-PET/CT has a high diagnostic yield for detecting the infection focus in patients with BSI admitted to intensive care. Poor PET image quality was significantly associated with a decreased likelihood of finding the infection focus in patients with BSI. This could be improved by adequate dietary preparation and cessation of intravenous glucose and glucose-regulating drugs. Recent advances in PET/CT technology enable higher image quality with shorter imaging time and may contribute to routinely performing FDG-PET/CT in intensive care patients with BSI of unknown origin.

Pijl|Jordy P|JP|0000-0001-6361-8068
Londema|Mark|M|
Kwee|Thomas C|TC|
Nijsten|Maarten W N|MWN|
Slart|Riemer H J A|RHJA|
Dierckx|Rudi A J O|RAJO|
van der Voort|Peter H J|PHJ|
Glaudemans|Andor W J M|AWJM|
Pillay|Janesh|J|

D000072078:Positron Emission Tomography Computed Tomography

Bloodstream infection
PET/CT
Bacteremia
Candidemia
Fungemia
Sepsis


Placental weight centiles adjusted for age, parity and fetal sex.

Abstract:
INTRODUCTION
The weight of the placenta can be indicative of efficacy in nutrient and oxygen supply. Furthermore, it has been suggested that a measure of the placenta's ability to adequately supply nutrients to the fetus can be found in the relationship between birth weight and placental weight expressed as a ratio. Our aim was to develop age adjusted placenta weight and birth weight to placenta weight ratio reference curves that are stratified by maternal parity and fetal sex.

METHODS
We included singleton, non-anomalous births with a gestational age inclusive of 28 + 0 weeks to 42 + 6 weeks. Excluded were pregnancies of multiplicity, fetuses with congenital abnormalities, stillbirths and pregnancies that had placental complications (ie placenta previa or abruption). Generalised additive model for location, shape and scale (GAMLSS) was used to fit reference curves.

RESULTS
We stratified 97,882 pregnancies by maternal nulliparity status and fetal sex. Extensive assessment model goodness-of-fit showed appropriate modeling and accurate fit to the four parameters of distribution. Our results show accurate model fit of the reference curves to the data. We demonstrated that the influence that parity has on the placenta weight is far greater than that exerted by fetal sex, and that the difference is dependent on gestational age.

DISCUSSION
This is the largest presentation of age and parity adjusted placenta weight and feto-placental weight ratio reference ranges to date. The difference observed between nulliparous and multiparous pregnancies could be explained by biological memory and the remnants of maternal endo-myometrial vascularity after the first pregnancy.

Flatley|Christopher|C| Sole-Navais|Pol|P| Vaudel|Marc|M| Helgeland|Øyvind|Ø| Modzelewska|Dominika|D| Johansson|Stefan|S| Jacobsson|Bo|B| Njølstad|Pål|P|

Parity
Placenta
Placenta weight
Reference curves
Father and Child cohort study
Feto-placenta ratio
Norwegian Mother


Music meets robotics: a prospective randomized study on motivation during robot aided therapy.

Abstract:
BACKGROUND
Robots have been successfully applied in motor training during neurorehabilitation. As music is known to improve motor function and motivation in neurorehabilitation training, we aimed at integrating music creation into robotic-assisted motor therapy. We developed a virtual game-like environment with music for the arm therapy robot ARMin, containing four different motion training conditions: a condition promoting creativity (C+) and one not promoting creativity (C-), each in a condition with (V+) and without (V-) a visual display (i.e., a monitor). The visual display was presenting the game workspace but not contributing to the creative process itself. In all four conditions the therapy robot haptically displayed the game workspace. Our aim was to asses the effects of creativity and visual display on motivation.

METHODS
In a prospective randomized single-center study, healthy participants were randomly assigned to play two of the four training conditions, either with (V+) or without visual display (V-). In the third round, the participants played a repetition of the preferred condition of the two first rounds, this time with a new V condition (i.e., with or without visual display). For each of the three rounds, motivation was measured with the Intrinsic Motivation Inventory (IMI) in the subscales interest/enjoyment, perceived choice, value/usefulness, and man-machine-relation. We recorded the actual training time, the time of free movement, and the velocity profile and administered a questionnaire to measure perceived training time and perceived effort. All measures were analysed using linear mixed models. Furthermore, we asked if the participants would like to receive the created music piece.

RESULTS
Sixteen healthy subjects (ten males, six females, mean age: 27.2 years, standard deviation: 4.1 years) with no known motor or cognitive deficit participated. Promotion of creativity (i.e., C+ instead of C-) significantly increased the IMI-item interest/enjoyment (p=0.001) and the IMI-item perceived choice (p=0.010). We found no significant effects in the IMI-items man-machine relation and value/usefulness. Conditions promoting creativity (with or without visual display) were preferred compared to the ones not promoting creativity. An interaction effect of promotion of creativity and omission of visual display was present for training time (p=0.013) and training intensity (p<0.001). No differences in relative perceived training time, perceived effort, and perceived value among the four training conditions were found.

CONCLUSIONS
Promoting creativity in a visuo-audio-haptic or audio-haptic environment increases motivation in robot-assisted therapy. We demonstrated the feasibility of performing an audio-haptic music creation task and recommend to try the system on patients with neuromuscular disorders.

TRIAL REGISTRATION
ClinicalTrials.gov, NCT02720341. Registered 25 March 2016, https://clinicaltrials.gov/ct2/show/NCT02720341.

Baur|Kilian|K|0000-0002-3106-3050 Speth|Florina|F| Nagle|Aniket|A| Riener|Robert|R| Klamroth-Marganska|Verena|V|

Creativity
Intrinsic motivation
Audio-haptic display
Music therapy
Robotic arm rehabilitation
Serious games
Stroke
User interface


Bioinformatics analysis and identification of genes and molecular pathways in steroid-induced osteonecrosis of the femoral head.

Abstract:
BACKGROUND
Steroid-induced osteonecrosis of the femoral head (ONFH) is a common hip joint disease and is difficult to be diagnosed early. At present, the pathogenesis of steroid-induced ONFH remains unclear, and recognized and effective diagnostic biomarkers are deficient. The present study aimed to identify potentially important genes and signaling pathways involved in steroid-induced ONFH and investigate their molecular mechanisms.

METHODS
Microarray data sets GSE123568 (peripheral blood) and GSE74089 (cartilage) were obtained from the Gene Expression Omnibus database, including 34 ONFH samples and 14 control samples. Morpheus software and Venn diagram were used to identify DEGs and co-expressed DEGs, respectively. Besides, we conducted Kyoto Encyclopedia of Genome (KEGG) and gene ontology (GO) pathway enrichment analysis. We construct a protein-protein interaction (PPI) network through GEO2R and used cytoHubba to divide the PPI network into multiple sub-networks. Additionally, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to verify the bioinformatics analysis results.

RESULTS
A total of 118 intersecting DEGs were obtained between the peripheral blood and cartilage samples, including 40 upregulated genes and 78 downregulated genes. Then, GO and KEGG pathway enrichment analysis revealed that upregulated DEGs focused on the signaling pathways related to staphylococcus aureus infection, leishmaniasis, antigen processing, and presentation, as well as asthma and graft-versus-host disease. Downregulated genes were concentrated in the FoxO signaling pathway, AMPK signaling pathway, signaling pathway regulating stem cell pluripotency, and mTOR signaling pathway. Some hub genes with high interactions such as CXCR1, FPR1, MAPK1, FOXO3, FPR2, CXCR2, and TYROBP were identified in the PPI network. The results of qRT-PCR demonstrated that CXCR1, FPR1, and TYROBP were upregulated while MAPK1 was downregulated in peripheral blood of steroid-induced ONFH patients. This was consistent with the bioinformatics analysis.

CONCLUSIONS
The present study would provide novel insight into the genes and associated pathways involved in steroid-induced ONFH. CXCR1, FPR1, TYROBP, and MAPK1 may be used as potential drug targets and biomarkers for the diagnosis and prognosis of steroid-induced ONFH.

Lin|Tianye|T| Chen|Weijian|W| Yang|Peng|P| Li|Ziqi|Z| Wei|Qiushi|Q| Liang|Du|D| Wang|Haibin|H| He|Wei|W| Zhang|Qingwen|Q|

D048868:Adaptor Proteins, Signal Transducing

D019950:Mitogen-Activated Protein Kinase 1

Osteonecrosis of the femoral head
Peripheral blood
Cartilage
Enrichment analysis
Differentially expressed gene


Subthalamic deep brain stimulation affects heading perception in Parkinson's disease.

Abstract: Parkinson's disease (PD) presents with visuospatial impairment and falls. It is critical to understand how subthalamic deep brain stimulation (STN DBS) modulates visuospatial perception. We hypothesized that DBS has different effects on visual and vestibular perception of linear motion (heading), a critical aspect of visuospatial navigation; and such effects are specific to modulated STN location. Two-alternative forced-choice experiments were performed in 14 PD patients with bilateral STN DBS and 19 age-matched healthy controls (HC) during passive en bloc linear motion and 3D optic-flow in immersive virtual reality measured vestibular and visual heading. Objective measure of perception with Weibull psychometric function revealed that PD has significantly lower accuracy [L: 60.71 (17.86)%, R: 74.82 (17.44)%] and higher thresholds [L: 16.68 (12.83), R: 10.09 (7.35)] during vestibular task in both directions compared to HC (p < 0.05). DBS significantly improved vestibular discrimination accuracy [81.40 (14.36)%] and threshold [4.12 (5.87), p < 0.05] in the rightward direction. There were no DBS effects on the slopes of vestibular psychometric curves. Visual heading perception was better than vestibular and it was comparable to HC. There was no significant effect of DBS on visual heading response accuracy or discrimination threshold (p > 0.05). Patient-specific DBS models revealed an association between change in vestibular heading perception and the modulation of the dorsal STN. In summary, DBS may have different effects on vestibular and visual heading perception in PD. These effects may manifest via dorsal STN putatively by its effects on the cerebellum.

Visual
Vestibular
Cerebellum
Basal ganglia
Motion perception
Optic flow


Dibutyl phthalate aggravated asthma-like symptoms through oxidative stress and increasing calcitonin gene-related peptide release.

Abstract: Dibutyl phthalate (DBP) is one of the most ubiquitous phthalate esters found in everyday products, and is receiving increased attention as an immunologic adjuvant. However, information regarding DBP-aggravated allergic asthma is still limited. This study used a mouse model sensitized with ovalbumin (OVA) to determine any adverse effects of DBP on allergic asthma. Our results reveal that allergic asthmatic mice exposed to DBP for an extended period had a significant increase in inflammatory cell infiltration; a significant increase in levels of serum immunoglobulin and T helper 2 cell (Th2) and T helper 17 cell (Th17) cytokines in lung tissue; and significant changes in lung histology and AHR, all of which are typical asthmatic symptoms. The levels of oxidative stress and levels of the neuropeptide, calcitonin gene related peptide (CGRP), were also elevated after DBP exposure. Interestingly, blocking oxidative stress by administering melatonin (MT) not only reduced oxidative stress and CGRP levels, but also ameliorated the asthmatic symptoms. Collectively, these results show that DBP exacerbates asthma-like pathologies by increasing the expression of CGRP mediated by oxidative stress.

Zhou|Sangyu|S| Han|Man|M| Ren|Yaolin|Y| Yang|Xu|X| Duan|Liju|L| Zeng|Yan|Y| Li|Jinquan|J|

Dibutyl phthalate
Oxidative stress
Calcitonin gene-related peptide
Allergic asthma
Melatonin


An expanded framework for biomolecular visualization in the classroom: Learning goals and competencies.

Abstract: A thorough understanding of the molecular biosciences requires the ability to visualize and manipulate molecules in order to interpret results or to generate hypotheses. While many instructors in biochemistry and molecular biology use visual representations, few indicate that they explicitly teach visual literacy. One reason is the need for a list of core content and competencies to guide a more deliberate instruction in visual literacy. We offer here the second stage in the development of one such resource for biomolecular three-dimensional visual literacy. We present this work with the goal of building a community for online resource development and use. In the first stage, overarching themes were identified and submitted to the biosciences community for comment: atomic geometry; alternate renderings; construction/annotation; het group recognition; molecular dynamics; molecular interactions; monomer recognition; symmetry/asymmetry recognition; structure-function relationships; structural model skepticism; and topology and connectivity. Herein, the overarching themes have been expanded to include a 12th theme (macromolecular assemblies), 27 learning goals, and more than 200 corresponding objectives, many of which cut across multiple overarching themes. The learning goals and objectives offered here provide educators with a framework on which to map the use of molecular visualization in their classrooms. In addition, the framework may also be used by biochemistry and molecular biology educators to identify gaps in coverage and drive the creation of new activities to improve visual literacy. This work represents the first attempt, to our knowledge, to catalog a comprehensive list of explicit learning goals and objectives in visual literacy. © 2016 by The International Union of Biochemistry and Molecular Biology, 45(1):69-75, 2017.

curriculum design development and implementation

judging quality of macromolecular models

skill development including cognitive skills

teaching and learning techniques methods and approaches

using modeling as a research tool for investigating teaching


Recognition and Differential Diagnosis of Hereditary Angioedema in the Emergency Department.

Abstract:
BACKGROUND
Angioedema (AE) is a clinical syndrome marked by localized swelling of the subcutaneous layer of the skin or the submucosal layer of the respiratory or gastrointestinal tracts. While AE is commonly mediated by histamine (allergic AE), some types result from excessive bradykinin activity, including hereditary AE (HAE), acquired AE, and angiotensin-converting enzyme inhibitor-induced AE. These are less common but important to consider given different treatment requirements and potentially serious outcomes, including death from laryngeal swelling.

OBJECTIVE
This review describes the pathophysiology and clinical features of AE as well as the diagnosis and treatment of AE in the emergency department (ED).

DISCUSSION
Bradykinin-mediated AE does not respond to antihistamines and corticosteroids. By contrast, several targeted, effective therapies are available, including C1-inhibitor (C1-INH) concentrates, which replace the missing protein activity underlying some bradykinin-mediated AE, and medications that directly lessen bradykinin activity (eg, ecallantide and icatibant). Urticaria is generally absent in bradykinin-mediated AE and serves as a primary differentiating factor in the clinical diagnosis. Relevant laboratory assessments may include C1-INH levels, C1-INH function, and C4 complement. Patients with HAE or a family member can communicate their known diagnosis when presenting to the ED, and some may even bring their own medication(s) with them. Patients newly diagnosed with HAE in the ED should be referred for specialized outpatient care upon ED discharge.

CONCLUSIONS
There is a great need for ED clinicians to be aware of HAE, its differential diagnosis, and appropriate treatment to ensure that patients receive optimal and timely treatment.

Pines|Jesse M|JM|
Poarch|Kimberly|K|
Hughes|Sandra|S|

diagnosis
hereditary angioedema
angioedema
treatment
pathophysiology
bradykinin-mediated
histamine-mediated


Modeling an auditory stimulated brain under altered states of consciousness using the generalized Ising model.

Abstract: Propofol is a short-acting medication that results in decreased levels of consciousness and is used for general anesthesia. Although it is the most commonly used anesthetic in the world, much remains unknown about the mechanisms by which it induces a loss of consciousness. Characterizing anesthesia-induced alterations to brain network activity might provide a powerful framework for understanding the neural mechanisms of unconsciousness. The aim of this work was to model brain activity in healthy brains during various stages of consciousness, as induced by propofol, in the auditory paradigm. We used the generalized Ising model (GIM) to fit the empirical fMRI data of healthy subjects while they listened to an audio clip from a movie. The external stimulus (audio clip) is believed to be at least partially driving a synchronization process of the brain activity and provides a similar conscious experience in different subjects. In order to observe the common synchronization among the subjects, a novel technique called the inter subject correlation (ISC) was implemented. We showed that the GIM-modified to incorporate the naturalistic external field-was able to fit the empirical task fMRI data in the awake state, in mild sedation, in deep sedation, and in recovery, at a temperature T* which is well above the critical temperature. To our knowledge this is the first study that captures human brain activity in response to real-life external stimuli at different levels of conscious awareness using mathematical modeling. This study might be helpful in the future to assess the level of consciousness of patients with disorders of consciousness and help in regaining their consciousness.

Kandeepan|Sivayini|S|
Rudas|Jorge|J|
Gomez|Francisco|F|
Stojanoski|Bobby|B|
Valluri|Sreeram|S|
Owen|Adrian Mark|AM|
Naci|Lorina|L|
Nichols|Emily Sophia|ES|
Soddu|Andrea|A|

Consciousness
The generalized Ising model
Inter-subject correlation
Naturalistic stimuli


Evaluating the roles of biotransformation, spatial concentration differences, organism home range, and field sampling design on trophic magnification factors.

Abstract: Trophic magnification factors (TMFs) are field-based measurements of the bioaccumulation behavior of chemicals in food-webs. TMFs can provide valuable insights into the bioaccumulation behavior of chemicals. However, bioaccumulation metrics such as TMF may be subject to considerable uncertainty as a consequence of systematic bias and the influence of confounding variables. This study seeks to investigate the role of systematic bias resulting from spatially-variable concentrations in water and sediments and biotransformation rates on the determination of TMF. For this purpose, a multibox food-web bioaccumulation model was developed to account for spatial concentration differences and movement of organisms on chemical concentrations in aquatic biota and TMFs. Model calculated and reported field TMFs showed good agreement for persistent polychlorinated biphenyl (PCB) congeners and biotransformable phthalate esters (PEs) in a marine aquatic food-web. Model testing showed no systematic bias and good precision in the estimation of the TMF for PCB congeners but an apparent underestimation of model calculated TMFs, relative to reported field TMFs, for PEs. A model sensitivity analysis showed that sampling designs that ignore the presence of concentration gradients may cause systematically biased and misleading TMF values. The model demonstrates that field TMFs are most sensitive to concentration gradients and species migration patterns for substances that are subject to a low degree of biomagnification or trophic dilution. The model is useful in anticipating the effect of spatial concentration gradients on the determination of the TMF; guiding species collection strategies in TMF studies; and interpretation of the results of field bioaccumulation studies in study locations where spatial differences in chemical concentration exist.

Kim|Jaeshin|J|
Gobas|Frank A P C|FA|
Arnot|Jon A|JA|
Powell|David E|DE|
Seston|Rita M|RM|
Woodburn|Kent B|KB|

D000818:Animals
D001711:Biotransformation
D004784:Environmental Monitoring
D004785:Environmental Pollutants
D020387:Food Chain
D008956:Models, Chemical
D011078:Polychlorinated Biphenyls

Biotransformation
Home range
Trophic magnification factor (TMF)
Bioaccumulation
Concentration gradient
Sediment-water fugacity ratio


Laccase as an efficacious approach to remove anticancer drugs: A study of doxorubicin degradation, kinetic parameters, and toxicity assessment.

Abstract: The degradation of an anticancer drug by laccase was investigated for the first time, bringing a new approach to treat these hazardous substances through the direct enzymatic application. Degradations of doxorubicin by laccase were performed in different enzymatic concentrations, pH values and temperatures through kinetic studies. The highest enzymatic degradation of doxorubicin was achieved at pH 7 and 30 ºC, which resembles effluent characteristics from wastewater treatment plants. Assays were carried out in different doxorubicin concentrations to comprehend the enzymatic kinetics of degradation. Michaelis-Menten kinetic parameters obtained were maximum velocity obtained (Vmax) of 702.8 µgDOX h-1 L-1 and Michaelis-Menten constant (KM) of 4.05 µM, which showed a good affinity for the substrate. The toxicity was evaluated against L-929 cell line, and the degraded doxorubicin solution did not show a reduction in cell viability in the concentration of 250 µg L-1. In contrast, the doxorubicin shows a reduction of 27% in cell viability. Furthermore, in the highest tested concentration (1000 µg L-1), enzymatic degradation reduced in up 41.4% the toxicity of doxorubicin, which indicates laccase degrades doxorubicin to non-toxic compounds. In conclusion, this study provides a new application to laccase since the results showed great potential to remove anticancer drugs from effluents.

Kelbert|Maikon|M|
Pereira|Camila Senna|CS|
Daronch|Naionara Ariete|NA|
Cesca|Karina|K|
Michels|Camila|C|
de Oliveira|Débora|D|
Soares|Hugo Moreira|HM|

Anticancer drugs
Enzymatic degradation
Antineoplastic drugs
Oxidoreductases


European Society of Contact Dermatitis guideline for diagnostic patch testing - recommendations on best practice.

Abstract: The present guideline summarizes all aspects of patch testing for the diagnosis of contact allergy in patients suspected of suffering, or having been suffering, from allergic contact dermatitis or other delayed-type hypersensitivity skin and mucosal conditions. Sections with brief descriptions and discussions of different pertinent topics are followed by a highlighted short practical recommendation. Topics comprise, after an introduction with important definitions, materials, technique, modifications of epicutaneous testing, individual factors influencing the patch test outcome or necessitating special considerations, children, patients with occupational contact dermatitis and drug eruptions as special groups, patch testing of materials brought in by the patient, adverse effects of patch testing, and the final evaluation and patient counselling based on this judgement. Finally, short reference is made to aspects of (continuing) medical education and to electronic collection of data for epidemiological surveillance.

guideline
patch testing
contact allergy
review


The impact of economic recessions on depression and individual and social well-being: the case of Spain (2006-2013).

Abstract:
PURPOSE
Although there is abundant evidence about the impact of economic crises on depression and other mental health problems, little is known about the protective role of variables linked to positive functioning (i.e., psychological well-being).

METHODS
We analyzed data from Spain, one of the European countries most affected by the 2008-2013 economic recession, collected in Round 3 (R3, 2006) and Round 6 (R6, 2013) of the European Social Survey interviews. Both surveys included measures of psychological well-being, social well-being and depression. Both samples were nationally representative of the general population (R3: 1877 participants, 49.2% men; R6: 1889 participants, 48.9% men).

RESULTS
Data from the R6 survey showed that, compared to data gathered in R3 (i.e., before the onset of the recession) Spanish citizens showed significantly less life satisfaction (95% CIs 0.37-0.63), less personal optimism (95% CIs 0.03-0.15), less social optimism (95% CIs 0.75-0.85), and higher levels of depressive symptoms (95% CIs - 0.74 to - 0.19). Structural equation modeling revealed that protective factors for depression changed in both rounds. In R3 (2006), close relationships, social optimism and social trust were significant mediators between well-being and depression. However, social optimism and social trust were no longer significant in R6 (2013), whereas close relationships remained a partial mediator of the effects of psychological well-being on depression.

CONCLUSIONS
Economic crises are associated with a significant increase in depressive symptoms. Furthermore, financial crises seem to have a corrosive impact on mental health by reducing the mediating effects of positive beliefs regarding the good nature of society.

Depression
Mental health
Economic issues
Population survey
Social factors
Stressful life events


Spray-Deposited Large-Area Copper Nanowire Transparent Conductive Electrodes and Their Uses for Touch Screen Applications.

Abstract: Large-area conducting transparent conducting electrodes (TCEs) were prepared by a fast, scalable, and low-cost spray deposition of copper nanowire (CuNW) dispersions. Thin, long, and pure copper nanowires were obtained via the seed-mediated growth in an organic solvent-based synthesis. The mean length and diameter of nanowires are, respectively, 37.7 μm and 46 nm, corresponding to a high-mean-aspect ratio of 790. These wires were spray-deposited onto a glass substrate to form a nanowire conducting network which function as a TCE. CuNW TCEs exhibit high-transparency and high-conductivity since their relatively long lengths are advantageous in lowering in the sheet resistance. For example, a 2 × 2 cm(2) transparent nanowire electrode exhibits transmittance of T = 90% with a sheet resistance as low as 52.7 Ω sq(-1). Large-area sizes (>50 cm(2)) of CuNW TCEs were also prepared by the spray coating method and assembled as resistive touch screens that can be integrated with a variety of devices, including LED lighting array, a computer, electric motors, and audio electronic devices, showing the capability to make diverse sizes and functionalities of CuNW TCEs by the reported method.

Chu|Hsun-Chen|HC| Chang|Yen-Chen|YC| Lin|Yow|Y| Chang|Shu-Hao|SH| Chang|Wei-Chung|WC| Li|Guo-An|GA| Tuan|Hsing-Yu|HY|

large-area
copper
nanowire
transparent conductive electrode
touch screen
spray deposition


Assessment of the effect of grape seed cake inclusion in the diet of healthy fattening-finishing pigs.

Abstract: Modulatory capacity of bioactive compounds from different wastes has been scarcely investigated in pigs. This study aimed to evaluate the effects of dietary inclusion of grape seed cakes (GS diet) on performance and plasma biochemistry parameters as health indicators, as well as on several markers related to inflammation and antioxidant defence in the liver of fattening-finishing pigs. Twelve cross-bred pigs (TOPIG) were randomly assigned to one of two experimental diets: control and 5% grape seed cake diet during finishing period (24 days). No effect of GS diet on pig performance and blood biochemistry was observed. However, GS diet decreased significantly (-9.05%, p < .05) the cholesterol concentration (85.71 ± 0.94 mg/dl vs 94.24 ± 2.16 mg/dl) and increased IgA level (+49.90%, p < .05) in plasma (5.04 ± 0.5 mg/ml vs 3.36 ± 0.7 mg/ml). GS cakes decreased the inflammatory response in the liver of pigs fed with GS diet by lowering the Gene expression and protein concentration of pro-inflammatory cytokines (IL-1β, IL-8, TNF-α and IFN-γ) as well as the mRNA abundances of NF-κB signalling molecules. The antioxidant status was not increased by GS diet. The gene expression and activity of catalase decreased significantly. The gene expression of Nrf2, superoxide dismutase, glutathione peroxidase and heat-shock protein decreased, and no effect on their activity was observed with the exception of catalase activity which decreased. However, TBARS was reduced significantly. GS diet showed a modulatory effect on antioxidative status as well as anti-inflammatory and hypocholesterolic properties without effect on pig performance.

D000824:Animal Nutritional Physiological Phenomena

diet
inflammation
antioxidant status
fattening pigs
grape waste


Electrosprayed Soft Capsules of Millimeter Size for Specifically Delivering Fish Oil/Nutrients to the Stomach and Intestines.

Abstract: Contrasting to the traditional centimeter-sized soft capsules that are difficult to swallow or micro/nanometer-sized soft capsules that suffer from limited loading capacity for fish oil/nutrients and lowered stability, the millimeter-sized soft capsules with good enough stability could be a potential solution in solving these problems. Herein, we report millimeter-sized soft core-shell capsules of 0.42-1.85 mm with an inner diameter of 0.36-1.75 mm, for fish oil/nutrients, obtained through an electrospray approach upon optimization of different fabrication parameters such as applied voltage, sodium alginate concentration, shell/core feeding rate ratio, times of feeding rate, and types of coaxial needles. Further in vitro and in vivo studies reveal that the resulting soft capsules were apparently weakened and became mechanically destructive in the simulated small intestine solution and were totally destroyed in the simulated small intestine solution if they were first treated in the simulated stomach solution but not in the simulated stomach solution, which makes the millimeter-sized capsules useful as containers for specific delivery of fish oils and lipophilic nutrients to the stomach and intestines with excellent in vivo bioavailability (>90%). The whole fabrication approach is very facile with no complicated polymer modification and formulations involved, which endows the resulting soft capsules with broad application prospect in food and drug industries.

electrospray
soft capsules
fish oil
alginate
targeting
β-carotene


The Current Status of Intervention for Intermediate Coronary Stenosis in the Korean Percutaneous Coronary Intervention (K-PCI) Registry.

Abstract:
BACKGROUND AND OBJECTIVES
Intermediate coronary lesion that can be under- or over-estimated by visual estimation frequently results in stenting of functionally nonsignificant lesions or deferral of percutaneous coronary intervention (PCI) of significant lesions inappropriately. We evaluated current status of PCI for intermediate lesions from a standardized database in Korea.

METHODS
We analyzed the Korean percutaneous coronary intervention (K-PCI) registry data which collected a standardized PCI database of the participating hospitals throughout the country from January 1, 2014, through December 31, 2014. Intermediate lesion was defined as a luminal narrowing between 50% and 70% by visual estimation and then compared whether the invasive physiologic or imaging study was performed or not.

RESULTS
Physiology-guided PCI for intermediate lesions was performed in 16.8% for left anterior descending artery (LAD), 9.8% for left circumflex artery (LCX), 13.2% for right coronary artery (RCA). PCI was more frequently performed using intravascular ultrasound (IVUS) than using fractional flow reserve (FFR) for coronary artery segments (27.7% vs. 13.9% for LAD, 32.9% vs. 8.1% for LCX, and 33.8% vs. 10.8% for RCA). In accordance with or without FFR, PCI for intermediate lesions was more frequently performed in the hospitals with available FFR device than without FFR, especially in left main artery (LM), proximal LAD lesion (40.9% vs. 5.9% for LM, 24.6% vs 7.6% for proximal LAD).

CONCLUSIONS
These data provide the current PCI practice pattern with the use of FFR and IVUS in intermediate lesion. More common use of FFR for intermediate lesion should be encouraged.

Percutaneous coronary intervention
Coronary artery disease
Fractional flow reserve, myocardial


Biogenic C-doped titania templated by cyanobacteria for visible-light photocatalytic degradation of Rhodamine B.

Abstract: Cyanobacteria, which occurred in eutrophic water harvest solar light to carry out photosynthesis with high efficiency. In this work, cyanobacteria (Microcystis sp.) were used as biotemplate to synthesize titania structure. The synthesized titania sample had similar morphology to that of the original template in spite of the fragile unicellular structures and extremely high water content of cyanobacterial cells. Incorporation of biogenic C, as well as the morphology inherited from biotemplate improved visible-light absorbance of the titania structure. The sample exhibited higher visible-light photocatalytic activity than commercial titania photocatalyst Degussa P25 for Rhodamine B (RhB) degradation. Compared with those C-doped titania photocatalysts prepared by other methods, cyanobacteria templated titania photocatalyst offer some potential for competitive advantages. The reported strategy opened up a new use for the cyanobacteria. It could also be used for titania in applications such as treatment of polluted water, dye-sensitized solar cells, or other regions.

He|Jiao|J| Zi|Guoli|G| Yan|Zhiying|Z| Li|Yongli|Y| Xie|Jiao|J| Duan|Deliang|D| Chen|Yongjuan|Y| Wang|Jiaqiang|J|

C-doped titania cyanobacteria visible-light photocatalysis


Lipophilicity predicts the ability of nonsulphonylurea drugs to block pancreatic beta-cell KATP channels and stimulate insulin secretion; statins as a test case.

Abstract:
Aims
KATP ion channels play a key role in glucose-stimulated insulin secretion. However, many drugs block KATP as "off targets" leading to hyperinsulinaemia and hypoglycaemia. As such drugs are often lipophilic, the aim was to examine the relationship between drug lipophilicity (P) and IC 50 for KATP block and explore if the IC 50's of statins could be predicted from their lipophilicity and whether this would allow one to forecast their acute action on insulin secretion.

Materials and methods
A meta-analysis of 26 lipophilic, nonsulphonylurea, blockers of KATP was performed. From this, the IC 50's for pravastatin and simvastatin were predicted and then tested experimentally by exploring their effects on KATP channel activity via patch-clamp measurement, calcium imaging and insulin secretion in murine beta cells and islets.

Results
Nonsulphonylurea drugs inhibited KATP channels with a Log IC 50 linearly related to their logP. Simvastatin blocked KATP with an IC 50 of 25 nmol/L, a value independent of cytosolic factors, and within the range predicted by its lipophilicity (21-690 nmol/L). 10 μmol/L pravastatin, predicted IC 50 0.2-12 mmol/L, was without effect on the KATP channel. At 10-fold therapeutic levels, 100 nmol/L simvastatin depolarized the beta-cell membrane potential and stimulated Ca2+ influx but did not affect insulin secretion; the latter could be explained by serum binding.

Conclusions
The logP of a drug can aid prediction for its ability to block beta-cell KATP ion channels. However, although the IC 50 for the block of KATP by simvastatin was predicted, the difference between this and therapeutic levels, as well as serum sequestration, explains why hypoglycaemia is unlikely to be observed with acute use of this statin.

Real|Joana|J|
Miranda|Caroline|C|
Olofsson|Charlotta S|CS|
Smith|Paul A|PA|0000-0002-8710-6830

KATP channel
insulin
simvastatin
beta‐cell


Risk of recurrence of sigmoid volvulus: a single-centre cohort study.

Abstract:
AIM
Sigmoid volvulus is a condition with a tendency to recur if treated conservatively. Little is known about the best type of treatment or when to perform definitive surgery. The aim of this study was to review treatment, and assess the outcome, of sigmoid volvulus in adult patients treated at a Swedish university hospital.

METHOD
The medical records of patients treated for sigmoid volvulus at Sahlgrenska University Hospital, Sweden from January 2000 to September 2016 were reviewed retrospectively. Median follow-up time was 8.3 years.

RESULTS
One hundred and sixty-eight patients were included with a total of 453 admissions for sigmoid volvulus. Nonoperative decompression was attempted as the initial treatment in 438/453 (97%), with a success rate of 92% (403/438), which was not influenced by whether it was the first episode or a recurrence. Without planned surgery, recurrence occurred after 84% of successful nonoperative decompressions with a median of two recurrences (1-16). Recurrence was less common after the first episode compared with subsequent episodes. Median time until recurrence was 58 days. Mortality after planned surgery following successful decompression was 3.3% (2/61) compared with 13% (6/46) following emergency surgery.

CONCLUSION
In our cohort, the recurrence rate of sigmoid volvulus following successful nonoperative decompression was high. Still, more than 20% of patients did not experience a recurrence after their first episode. Nonoperative decompression could thus be suggested as the sole treatment for the first episode of volvulus. However, after the second episode it is probable that early planned surgery would improve outcome and reduce health-care consumption.

D013505:Digestive System Surgical Procedures

recurrence
Sigmoid volvulus
surgery
nonoperative
decompression


Extracellular Protein Kinase A Modulates Intracellular Calcium/Calmodulin-Dependent Protein Kinase II, Nitric Oxide Synthase, and the Glutamate-Nitric Oxide-cGMP Pathway in Cerebellum. Differential Effects in Hyperammonemia.

Abstract: Extracellular protein kinases, including cAMP-dependent protein kinase (PKA), modulate neuronal functions including N-methyl-d-aspartate (NMDA) receptor-dependent long-term potentiation. NMDA receptor activation increases calcium, which binds to calmodulin and activates nitric oxide synthase (NOS), increasing nitric oxide (NO), which activates guanylate cyclase, increasing cGMP, which is released to the extracellular fluid, allowing analysis of this glutamate-NO-cGMP pathway in vivo by microdialysis. The function of this pathway is impaired in hyperammonemic rats. The aims of this work were to assess (1) whether the glutamate-NO-cGMP pathway is modulated in cerebellum in vivo by an extracellular PKA, (2) the role of phosphorylation and activity of calcium/calmodulin-dependent protein kinase II (CaMKII) and NOS in the pathway modulation by extracellular PKA, and (3) whether the effects are different in hyperammonemic and control rats. The pathway was analyzed by in vivo microdialysis. The role of extracellular PKA was analyzed by inhibiting it with a membrane-impermeable inhibitor. The mechanisms involved were analyzed in freshly isolated cerebellar slices from control and hyperammonemic rats. In control rats, inhibiting extracellular PKA reduces the glutamate-NO-cGMP pathway function in vivo. This is due to reduction of CaMKII phosphorylation and activity, which reduces NOS phosphorylation at Ser1417 and NOS activity, resulting in reduced guanylate cyclase activation and cGMP formation. In hyperammonemic rats, under basal conditions, CaMKII phosphorylation and activity are increased, increasing NOS phosphorylation at Ser847, which reduces NOS activity, guanylate cyclase activation, and cGMP. Inhibiting extracellular PKA in hyperammonemic rats normalizes CaMKII phosphorylation and activity, NOS phosphorylation, NOS activity, and cGMP, restoring normal function of the pathway.

D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2

D017868:Cyclic AMP-Dependent Protein Kinases


In Vitro Synthesis, Structure elucidation and its antioxidant properties of Platinum(IV)-hydrazide complexes: Molecular modeling of free-hydrazides suggested as potent lipoxygenase inhibitor.

Abstract:
BACKGROUND
Combination of biologically active ligand and metal in one molecule may increase the activity and reduce the toxicity.

OBJECTIVES
In this study synthesis and characterization of platinum(IV) complexes with bioactive hydrazide ligands is discussed.

METHOD
Elemental analysis, conductivity measurements and spectroscopic studies were used to elucidate the structure of complexes.

RESULTS
Our study suggests that hydrazide ligands coordinate with Pt(IV) in bidenate fashion. The platinum(IV) complexes have octahedral geometry with metal to ligand ratio of 1:2. Hydrazide ligands coordinated with central metal platinum(IV) by oxygen of carbonyl group and nitrogen of primary amine. Synthesized complexes exhibited variable DPPH radical scavenging and lipoxygenase inhibition activity. Furthermore, it is also found that Pt(IV)-hydrazide complexes are more potent superoxide and nitric oxide radical scavengers than their uncoordinated hydrazide ligands while in case of lipoxygenase enzyme inhibition, some of the free hydrazide ligands are more active than their respective Pt(IV) complexes. In silico docking technique explores molecular interactions of synthesized ligands in the active site of lipoxygenase enzyme. Predicted docking energies are in good agreement with experimental data suggesting that in silico studies might be useful for discovery of therapeutic candidates.

CONCLUSION
Structure function relationship demonstrates that the radical scavenging and enzyme inhibition activities of the Pt(IV) compounds are effected by nature of ligand, position of substituent, electronic and steric effects. However, electronic factor seem to play more important role than other factors.

Badar|Rooma|R|
Ashiq|Uzma|U|
Jamal|Rifat Ara|RA|
Akhter|Parveen|P|
Mahroof-Tahir|Mohammad|M|
Gul|Sana|S|
Ali|Syed Tahir|ST|

Lipoxygenase
Platinum(IV)
Hydrazide
DPPH radical
Superoxide
Nitric oxide
In silico docking.


Ultrasound-Based Molecular Imaging of Tumors with PTPmu Biomarker-Targeted Nanobubble Contrast Agents.

Abstract: Ultrasound imaging is a widely used, readily accessible and safe imaging modality. Molecularly-targeted microbubble- and nanobubble-based contrast agents used in conjunction with ultrasound imaging expand the utility of this modality by specifically targeting and detecting biomarkers associated with different pathologies including cancer. In this study, nanobubbles directed to a cancer biomarker derived from the Receptor Protein Tyrosine Phosphatase mu, PTPmu, were evaluated alongside non-targeted nanobubbles using contrast enhanced ultrasound both in vitro and in vivo in mice. In vitro resonant mass and clinical ultrasound measurements showed gas-core, lipid-shelled nanobubbles conjugated to either a PTPmu-directed peptide or a Scrambled control peptide were equivalent. Mice with heterotopic human tumors expressing the PTPmu-biomarker were injected with PTPmu-targeted or control nanobubbles and dynamic contrast-enhanced ultrasound was performed. Tumor enhancement was more rapid and greater with PTPmu-targeted nanobubbles compared to the non-targeted control nanobubbles. Peak tumor enhancement by the PTPmu-targeted nanobubbles occurred within five minutes of contrast injection and was more than 35% higher than the Scrambled nanobubble signal for the subsequent two minutes. At later time points, the signal in tumors remained higher with PTPmu-targeted nanobubbles demonstrating that PTPmu-targeted nanobubbles recognize tumors using molecular ultrasound imaging and may be useful for diagnostic and therapeutic purposes.

D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2

molecular imaging
PTPmu
nanobubbles
receptor protein tyrosine phosphatase
dynamic contrast enhanced ultrasound
time intensity curve
ultrasound contrast agents


Hyperacute peripheral neuropathy is a predictor of oxaliplatin-induced persistent peripheral neuropathy.

Abstract:
PURPOSE
Chronic peripheral neuropathy is a major adverse response to oxaliplatin-containing chemotherapy regimens, but there are no established risk factors pertaining to it. We investigated the efficacy of hyperacute peripheral neuropathy (HAPN) as a predictor of oxaliplatin-induced persistent peripheral neuropathy (PPN).

METHODS
Forty-seven cases of stage III colorectal cancer who received adjuvant chemotherapy with oxaliplatin after curative surgery between January 2010 and August 2014 were retrospectively reviewed. HAPN was defined as acute peripheral neuropathy (APN) occurring on day 1 (≤24 h after oxaliplatin infusion) of the first cycle. PPN was defined as neuropathy lasting >1 year after oxaliplatin discontinuation.

RESULTS
The average total dose of oxaliplatin was 625.8 mg/m2, and the average relative dose intensity was 66.7%. Twenty-two of the 47 patients (46.8%) had PPN and 13 (27.7%) had HAPN. Male sex, treatment for neuropathy, HAPN, and APN were significantly more frequent in patients with PPN (p = 0.013, 0.02, <0.001, and 0.023, respectively). There was no significant difference in the total oxaliplatin dose between patients with and without PPN (p = 0.061). Multivariate analyses revealed total dose of oxaliplatin and HAPN as independent predictors of PPN [p = 0.015; odds ratio (OR) = 1.005, 95% confidence interval (CI), 1.001-1.009 and p = 0.001; OR = 75.307, 5.3-1070.123, respectively]. The total dose of oxaliplatin was relatively lower in patients with HAPN than that in those without HAPN in the PPN-positive group (not significant, p = 0.068).

CONCLUSION
HAPN was found to be a predictor of oxaliplatin-induced PPN.

Tanishima|Hiroyuki|H| Tominaga|Toshiji|T| Kimura|Masamichi|M| Maeda|Tsunehiro|T| Shirai|Yasutsugu|Y| Horiuchi|Tetsuya|T|

D000971:Antineoplastic Combined Chemotherapy Protocols

D010523:Peripheral Nervous System Diseases

Predictor of persistent peripheral neuropathy