Evaluation of biologically mediated changes in oil sands naphthenic acid composition by Chlamydomonas reinhardtii using negative-ion electrospray orbitrap mass spectrometry.

Abstract: Industrial activity associated with oil-sands extraction in Canada's Athabasca region produces a variety of contaminants of concern, including naphthenic acid fraction components (NAFCs). NAFCs are a complex mixture of organic compounds that are poorly understood both in terms of their chemical composition and effects on the environment. NAFC toxicity in the unicellular green algae Chlamydomonas reinhardtii P.A.Dangeard was correlated with the presence of the algal cell wall. It was suggested that the toxicity of NAFCs in C. reinhardtii was due to surfactant effects. Surfactant-cell wall interactions are specific and governed by the compound class and structure, and by the nature of the biological material. Here, we investigate the effects of wildtype (WT) C. reinhardtii and two cell-wall mutants on specific classes of NAFCs when growing cultures were treated with a 100 mg · L(-1) solution of NAFCs. Changes in the NAFC composition in the media were examined using high resolution mass spectrometry over a period of 4 d. Algal mediated changes in the NAFCs were limited to specific classes of NAFCs. In particular, the removal of large, classical naphthenic acids, with a double bond equivalent of 8, was observed in WT C. reinhardtii cultures. The observed algal mediated changes in NAFC composition would have been masked by low resolution mass spectrometry and highlight the importance of this tool in examining bioremediation of complex mixtures of NAFCs.

Goff|Kira L|KL|
Peru|Kerry|K|
Wilson|Kenneth E|KE|
Headley|John V|JV|

oil sands
naphthenic acids
algae
high resolution mass spectrometry
bioremediation
cell-wall proteins


Effect of mediterranean diet in diabetes control and cardiovascular risk modification: a systematic review.

Abstract:
BACKGROUND
Over the past few years, there has been a worldwide significant increase in the incidence of type II diabetes mellitus with both increase in morbidity and mortality. Controlling diabetes through life style modifications, including diet and exercise has always been the cornerstone in diabetes management. Increasing evidence suggests that the Mediterranean diet could be of benefit in diseases associated with chronic inflammation, including metabolic syndrome, diabetes, obesity as well as atherosclerosis, cancer, pulmonary diseases, and cognition disorders As a matter of fact, a number of studies addressed the relationship between Mediterranean diet and diabetes control. The result of these studies was conflicting. Some were able to elicit a protective role, while others showed no added benefit. As a result; we decided to conduct a systematic review to have a better understanding of the relationship between adherence to Mediterranean diet and diabetes control.

METHODS
A systematic review was conducted on the effect of Mediterranean diet in diabetes control and cardiovascular risk modification as well as the possible mechanism through which this diet might exhibit its beneficial role. We did a comprehensive search of multiple electronic databases such as Medline, Google Scholars, PubMed, and the Cochrane central register data until May 2014. We included cross-sectional, prospective, and controlled clinical trials that looked at the associations between Mediterranean diet and indices of diabetes control such HbA1c, fasting glucose, and homeostasis model assessment, in addition to cardiovascular and peripheral vascular outcomes.

OUTCOME/CONCLUSION
Most of the studies showed favorable effects of Mediterranean diet on glycemic control and CVD, although a certain degree of controversy remains regarding some issues, such as obesity. Important methodological differences and limitations in the studies make it difficult to compare results, thus further longer term studies are needed to evaluate the long-term efficacy of the Mediterranean diet along with the possibility of explaining its mechanism.

Sleiman|Dana|D|
Al-Badri|Marwa R|MR|
Azar|Sami T|ST|

Mediterranean diet
cardiovascular risk
type II diabetes
HbA1c
glycemic control
dietary pattern
insulin resistance


Synaptic Plasticity in Cortical Inhibitory Neurons: What Mechanisms May Help to Balance Synaptic Weight Changes?

Abstract: Inhibitory neurons play a fundamental role in the normal operation of neuronal networks. Diverse types of inhibitory neurons serve vital functions in cortical networks, such as balancing excitation and taming excessive activity, organizing neuronal activity in spatial and temporal patterns, and shaping response selectivity. Serving these, and a multitude of other functions effectively requires fine-tuning of inhibition, mediated by synaptic plasticity. Plasticity of inhibitory systems can be mediated by changes at inhibitory synapses and/or by changes at excitatory synapses at inhibitory neurons. In this review, we consider that latter locus: plasticity at excitatory synapses to inhibitory neurons. Despite the fact that plasticity of excitatory synaptic transmission to interneurons has been studied in much less detail than in pyramids and other excitatory cells, an abundance of forms and mechanisms of plasticity have been observed in interneurons. Specific requirements and rules for induction, while exhibiting a broad diversity, could correlate with distinct sources of excitatory inputs and distinct types of inhibitory neurons. One common requirement for the induction of plasticity is the rise of intracellular calcium, which could be mediated by a variety of ligand-gated, voltage-dependent, and intrinsic mechanisms. The majority of the investigated forms of plasticity can be classified as Hebbian-type associative plasticity. Hebbian-type learning rules mediate adaptive changes of synaptic transmission. However, these rules also introduce intrinsic positive feedback on synaptic weight changes, making plastic synapses and learning networks prone to runaway dynamics. Because real inhibitory neurons do not express runaway dynamics, additional plasticity mechanisms that counteract imbalances introduced by Hebbian-type rules must exist. We argue that weight-dependent heterosynaptic plasticity has a number of characteristics that make it an ideal candidate mechanism to achieve homeostatic regulation of synaptic weight changes at excitatory synapses to inhibitory neurons.

Bannon|Nicholas M|NM|
Chistiakova|Marina|M|
Volgushev|Maxim|M|

synaptic plasticity
inhibitory neurons
heterosynaptic plasticity
hippocampus
homeostasis
homosynaptic plasticity
neocortex


CT and MR imaging findings of sinonasal angiomatous polyps.

Abstract:
OBJECTIVE
To characterize the CT and MR imaging findings of patients with sinonasal angiomatous polyps (SAPs) and evaluate their respective clinical value in the diagnosis of SAP.

METHODS
CT and MR imaging findings of 15 patients with pathologically proven SAP were examined. Assessed image features included location, size, margin, attenuation, and change of the bony walls of the sinonasal cavity on CT, and signal intensity and enhancement pattern on MR.

RESULTS
On CT, the SAP was mostly isoattenuated with patches of slight hyperattenuation. Most lesions caused changes in the adjacent bone, including expansile remodeling (n=8), defect or destruction (n=7), and hyperostosis (n=6). All lesions examined by MR showed heterogeneous isointense signal intensity on T1-weighted images and mixed obvious hyperintense and hypointense signal intensity with linear hypointense septum internally (n=10), and hypointense peripheral rim on T2-weighted images (n=10). Postcontrast MR images demonstrated areas of heterogeneous and marked enhancement with an unenhanced hypointense rim and septa (n=7).

CONCLUSIONS
CT and MR imaging have respective advantages in the diagnosis of SAP. Combined application of CT and MR examinations is necessary for patients with suspected SAP.

Zou|Jing|J| Man|Fengyuan|F| Deng|Kai|K| Zheng|Yuanyuan|Y| Hao|Dapeng|D| Xu|Wenjian|W|

Hemangioma
Magnetic resonance imaging
Nasal polyps
Paranasal sinus diseases
Tomography, X-ray computed


Preferred Formation of Minority Concomitant Polymorphs in 2D Self-Assembly under Lateral Nanoconfinement.

Abstract: Control over polymorph formation in the crystallization of organic molecules remains a huge scientific challenge. Now, preferential formation is presented of one polymorph, formed by chiral molecules, in controlled two-dimensional (2D) nanoconfinement conditions at a liquid-solid interface. So-called nanocorrals to control concomitant polymorph formation were created in situ via a nanoshaving protocol at the interface between 1-phenyloctane and covalently modified highly-oriented pyrolytic graphite (HOPG). The preferentially formed polymorphs, which were less stable in the large-scale monolayers, could be selected simply by varying the orientation of the square nanocorrals with respect to the HOPG lattice.

polymorphism
nanoconfinement
2D crystallization
scanning tunneling microscopy
supramolecular chemistry


In vivo Characterization of Amorphous Silicon Carbide As a Biomaterial for Chronic Neural Interfaces.

Abstract: Implantable microelectrode arrays (MEAs) offer clinical promise for prosthetic devices by enabling restoration of communication and control of artificial limbs. While proof-of-concept recordings from MEAs have been promising, work in animal models demonstrates that the obtained signals degrade over time. Both material robustness and tissue response are acknowledged to have a role in device lifetime. Amorphous Silicon carbide (a-SiC), a robust material that is corrosion resistant, has emerged as an alternative encapsulation layer for implantable devices. We systematically examined the impact of a-SiC coating on Si probes by immunohistochemical characterization of key markers implicated in tissue-device response. After implantation, we performed device capture immunohistochemical labeling of neurons, astrocytes, and activated microglia/macrophages after 4 and 8 weeks of implantation. Neuron loss and microglia activation were similar between Si and a-SiC coated probes, while tissue implanted with a-SiC displayed a reduction in astrocytes adjacent to the probe. These results suggest that a-SiC has a similar biocompatibility profile as Si, and may be suitable for implantable MEA applications as a hermetic coating to prevent material degradation.

Knaack|Gretchen L|GL|
McHail|Daniel G|DG|
Borda|German|G|
Koo|Beomseo|B|
Peixoto|Nathalia|N|
Cogan|Stuart F|SF|
Dumas|Theodore C|TC|
Pancrazio|Joseph J|JJ|

amorphous silicon carbide
foreign body response
in vivo models
neural electrode
neuroinflammatory response
neuroprosthetic device


The epidemiology of multiple sclerosis in the Isle of Man: 2006-2011.

Abstract:
BACKGROUND
We sought to determine the prevalence of MS on the Isle of Man in 2006 and 2011, and the incidence and mortality rates over this interval.

METHODS
Cases were identified by hospital medical record review, General Practitioners and the local MS Society. The significance of the change in prevalence over time and the significance of differences in frequencies by sex and place of birth were assessed by Poisson regression.

RESULTS
The 2006 prevalence was 153.64 per 100,000 persons and the 2011 prevalence was 179.89. The prevalence was higher among females and persons born in the Isle of Man at both time points. The 2006-2011 incidence rate was 6.86 per 100,000 person-years, much higher among females and persons born in the Isle of Man. The prevalence sex ratios in 2006 and 2011, 2.77 and 2.59, respectively, and the incidence sex ratio, 2.19, are similar to others found in the region. The mortality rate over the study period was 2.84 per 100,000 person-years, this solely among persons born overseas.

CONCLUSIONS
This is the first study of MS epidemiology in the Isle of Man, finding this area to be of high prevalence and to have one of the highest incidence rates in the UK region.

epidemiology
Isle of Man
prevalence
mortality
incidence rate


Maintenance immunosuppression in heart transplantation: insights from network meta-analysis of various immunosuppression regimens.

Abstract: Previous studies have reported superiority of mechanistic target-of-rapamycin (mTOR) antagonists (mTA) over calcineurin inhibitors (CNI) as part of maintenance immunosuppression (IS) in mitigating cardiac allograft vasculopathy (CAV) after heart transplantation (HT). MEDLINE and EMBASE were searched through October 2019 for studies comparing maintenance IS with mTA + antimetabolites (AM), CNI + mTA or CNI + AM post HT. The main outcomes were all-cause mortality, CAV, acute rejection, CMV infections, and change in eGFR. To compare different IS antagonists, a random-effects network meta-analysis was performed. We used p-scores to rank best treatments per outcome. Our search identified fifteen eligible studies (5 studies comparing mTA + AM vs. CNI + AM, 9 comparing CNI + mTA vs. CNI + AM, 1 comparing mTA + AM vs. CNI + mTA, 8 using everolimus and 7 sirolimus as mTA) reporting the selected outcomes. We did not identify any statistical difference in all-cause mortality among the three IS regimens without heterogeneity among studies. CAV rates were significantly lower with CNI + mTA (odds ratio [OR] 0.53, 95% confidence interval [CI] 0.3-0.92). Acute rejection rates were significantly lower with CNI + AM (OR 0.26, 95% CI 0.12-0.56) and with CNI + mTA (OR 0.16, 95% CI 0.07-0.33) compared with mTA + AM without significant heterogeneity (I2 = 43%, p = 0.9). CMV infections were significantly lower with mTA + AM (OR 0.13, 95% CI 0.03-0.46) and with CNI + mTA (OR 0.27, 95% CI 0.2-0.38) compared with CNI + AM without heterogeneity. mTA + AM led to higher eGFR compared with CNI + AM (9.06 ml/min/1.73 m2, 95% CI 3.15-14.97) and CNI + Mta (9.64 ml/min/1.73 m2, 95% CI 0.91-18.36), but the heterogeneity among studies was significant. CNI + mTA ranked better for CAV (p = 0.78), and acute rejection (p = 0.99) while mTA + AM for CMV infection (p = 0.94) and improvement in renal function (p = 0.93) than other regimens. Different IS regimens have similar effects on survival post HT, but CNI + mTA was associated with lower CAV rates, and acute rejection, while mTA + AM with less CMV infection post HT.

Maintenance immunosuppression
Heart transplantation
Allograft vasculopathy


General retrospective mega-analysis framework for rare variant association tests.

Abstract: Here, we describe a retrospective mega-analysis framework for gene- or region-based multimarker rare variant association tests. Our proposed mega-analysis association tests allow investigators to combine longitudinal and cross-sectional family- and/or population-based studies. This framework can be applied to a continuous, categorical, or survival trait. In addition to autosomal variants, the tests can be applied to conduct mega-analyses on X-chromosome variants. Tests were built on study-specific region- or gene-level quasiscore statistics and, therefore, do not require estimates of effects of individual rare variants. We used the generalized estimating equation approach to account for complex multiple correlation structures between family members, repeated measurements, and genetic markers. While accounting for multilevel correlations and heterogeneity across studies, the test statistics were computationally efficient and feasible for large-scale sequencing studies. The retrospective aspect of association tests helps alleviate bias due to phenotype-related sampling and type I errors due to misspecification of phenotypic distribution. We evaluated our developed mega-analysis methods through comprehensive simulations with varying sample sizes, covariates, population stratification structures, and study designs across multiple studies. To illustrate application of the proposed framework, we conducted a mega-association analysis combining a longitudinal family study and a cross-sectional case-control study from Genetic Analysis Workshop 19.

family study
mixed study design
pedigree data
retrospective association tests


Clinical Development of Sphingosine as Anti-Bacterial Drug: Inhalation of Sphingosine in Mini Pigs has no Adverse Side Effects.

Abstract:
BACKGROUND/AIMS
Pulmonary infections with Pseudomonas aeruginosa (P. aeruginosa) or Staphylococcus aureus (S. aureus) are of utmost clinical relevance in patients with cystic fibrosis, chronic obstructive pulmonary disease, after trauma and burn, upon ventilation or in immuno-compromised patients. Many P. aeruginosa and S. aureus strains are resistant to many known antibiotics and it is very difficult or often impossible to eradicate the pathogens in patient´s lungs. We have recently shown that the sphingoid base sphingosine very efficiently kills many pathogens, including for instance P. aeruginosa, S. aureus or Acinetobacter baumannii, in vitro. In vivo experiments of our group on cystic fibrosis mice indicated that inhalation of sphingosine prevents or eliminates existing acute or chronic pneumonia with P. aeruginosa or S. aureus in these mice. We also demonstrated that sphingosine is safe to use for inhalation up to high doses, at least in mice. To facilitate development of sphingosine to an anti-bactericidal drug that can be used in humans for inhalation, safety data on non-rodents, larger animals are absolutely required.

METHODS
Here, we inhaled mini pigs with increasing doses of sphingosine for 10 days and analyzed the uptake of sphingosine into epithelial cells of bronchi as well as into the trachea and lung and the systemic circulation. Moreover, we measured the generation of ceramide and sphingosine 1-phosphate that potentially mediate inflammation, the influx of leukocytes, epithelial cell death and disruption of the epithelial cell barrier.

RESULTS
We demonstrate that inhalation of sphingosine results in increased levels of sphingosine in the luminal membrane of bronchi and the trachea, but not in systemic accumulation. Inhaled sphingosine had no side effects up to very high doses.

CONCLUSION
In summary, we demonstrate that inhalation of sphingosine results in an increase of sphingosine concentrations in the luminal plasma membrane of tracheal and bronchial epithelial cells. The inhalation has no systemic or local side effects.

Carstens|Henning|H|
Schumacher|Fabian|F|
Keitsch|Simone|S|
Kramer|Melanie|M|
Kühn|Claudine|C|
Sehl|Carolin|C|
Soddemann|Matthias|M|
Wilker|Barbara|B|
Herrmann|Daniel|D|
Swaidan|Ashraf|A|
Kleuser|Burkhard|B|
Verhaegh|Rabea|R|
Hilken|Gero|G|
Edwards|Michael J|MJ|
Dubicanac|Marko|M|
Carpinteiro|Alexander|A|
Wissmann|Andreas|A|
Becker|Katrin Anne|KA|
Kamler|Markus|M|
Gulbins|Erich|E|

Sphingosine
Inhalation
Side effects
Lung
Inflammation
Cell death


The Angiotensin Converting Enzyme 2 (ACE2), Gut Microbiota, and Cardiovascular Health.

Abstract:
BACKGROUND
The renin-angiotensin system (RAS) is an important enzymatic system responsible for the regulation of biological functions, such as the arterial pressure, hydroelectrolytic control, vascular vasodilatation/vasoconstriction and more recently metabolic functions.

OBJECTIVES
The aim of the present review is to discuss the associations between the gut microbiome and the renin-angiotensin system and the influence of their intimate relationship on the cardiovascular health.

METHODS
A literature review of the main studies published regarding the relationship among the renin-angiotensin system, gut microbiota and cardiovascular health was performed.

RESULTS
The association between the ACE2 and gut microbiota has been discussed. It is shown that the ACE2/Ang 1-7 axis modulates the immune response, influencing the microbiota composition, and thus being one of the causes for some diseases physiophatologies, such as diarrhea and intestinal inflammatory disease.

CONCLUSION
The association between RAS and gut microbiota seems to have a strong influence on the genesis of cardiovascular diseases, through direct mechanisms, such as nerve stimulation, or indirectly on metabolic parameters, such as weight, adiposity and lipid profile.

Oliveira Andrade|Joao Marcus|JM|
de Farias Lelis|Deborah|D|
Mafra|Valeria|V|
Cota|Junio|J|


Why do we itch?

Abstract: Why do we have the sensation of itch and the associated scratching response? The conventional explanation is that arthropods and other environmental irritants elicit the sensation of itch that then leads to scratching and removal of the stimulus. This explanation is reasonable yet is too limiting for this fascinating sensory phenomenon and the associated somatic (voluntary) response of scratching. We delve into other explanations here. Some of these explanations fit within current areas of basic and clinical knowledge while others are speculative and may help to frame future discussions and study.

itch barrier grooming neuroimmune pleasure


Oncogenic signaling in uveal melanoma.

Abstract: Uveal melanoma is the most common primary cancer of the eye, and despite rapidly emerging insights into the molecular profile of this disease, prognosis of patients with metastatic uveal melanoma remains poor with mortality rates unchanged in over 35 years. Early genetic events activate G protein-coupled receptor signaling in nearly all uveal tumors via mutually exclusive mutations in the GNAQ, GNA11, CYSLTR2, or PLCB4 genes. A multitude of signaling cascades downstream of G protein activation, including protein kinase C and mitogen-activated protein kinase activity, are actionable, and many ongoing clinical trials are targeting these pathways. Additional cytogenetic and genetic changes, however, including chromosome 3 monosomy, mutations in the BAP1 tumor suppressor gene, alterations in the splicing factors SRSF2/SF3B1, and mutations in the translation initiation factor EIF1AX, modulate signaling output in uveal tumors and modify the risk of metastases. Here, we review the complex interactions between genetic, molecular signaling, and prognostic profiles in uveal melanoma; the clinical implications of these interactions; and the latest potential targets for rational therapy.


Symptom burden and functional performance in patients with chronic obstructive pulmonary disease.

Abstract:
BACKGROUND
The burden of COPD is growing, and it is one of the leading disease burdens worldwide. Studies on symptom burden as a multidimensional concept in COPD and functional performance are lacking, and little is known about the effect of multiple symptoms and symptom burden on functional performance.

METHODS
A descriptive, cross-sectional correlational survey design was used. The Memorial Symptom Assessment Scale (MSAS) and the Functional Performance Inventory-Short Form (FPI-SF) were used to measure the symptom burden and functional performance. Data were analyzed using descriptive and inferential statistics. Participants (n = 214) were recruited from the respiratory outpatient clinic in one of the teaching hospitals in Ireland.

RESULTS
Patients with COPD, regardless of classification, experienced significant physical and psychological symptom burden. A total of 20 symptoms were negatively correlated with overall functional performance, indicating a high symptom burden for those symptoms was associated with low overall functional performance. A statistically significant negative correlation between physical symptom burden, psychological symptom burden, total symptom burden, and functional performance was found.

CONCLUSION
Patients with COPD experience a significant symptom burden and low functional performance. Decreased functional performance was not related only to a single burdensome symptom, but may also be related to the contribution of several physical/psychological burdensome symptoms, or both. Assessment and management of these symptoms are essential and imply that alleviating these symptoms' burden may promote improved functional performance. This study supported the growing body of evidence of the need for patients with advanced COPD to receive palliative care.

Melhem|Omar|O|
Savage|Eileen|E|
Al Hmaimat|Nathira|N|
Lehane|Elaine|E|
Fattah|Hadya Abdel|HA|

D029424:Pulmonary Disease, Chronic Obstructive

Chronic Obstructive Pulmonary Disease (COPD)


Pyogenic sacroiliitis: A rare complication of inflammatory bowel disease.

Abstract: Although sacroiliitis is not uncommon in patients with inflammatory bowel diseases (IBD), bacterial infection of the sacroiliac joint is rare. The diagnosis is often delayed because of low clinical suspicion, a vague clinical picture and poorly defined localization of symptoms. We report a case of pyogenic sacroiliitis in a patient with Crohn's disease caused by Clostridia spp. and discuss key clinical components and protocol for the successful evaluation, diagnosis, and treatment of this uncommon illness.


Fast track triage for COVID-19 based on a population study: The soda score.

Abstract:
Background
Healthcare systems are under prominent stress due to the COVID-19 pandemic. A fast and simple triage is mandatory to screen patients who will benefit from early hospitalization, from those that can be managed as outpatients. There is a lack of all-comers scores, and no score has been proposed for western-world population.

Aims
To develop a fast-track risk score valid for every COVID-19 patient at diagnosis.

Methods
Single-center, retrospective study based on all the inhabitants of a healthcare area. Logistic regression was used to identify simple and wide-available risk factors for adverse events (death, intensive care admission, invasive mechanical ventilation, bleeding > BARC3, acute renal injury, respiratory insufficiency, myocardial infarction, acute heart failure, pulmonary emboli, or stroke).

Results
Of the total healthcare area population, 447.979 inhabitants, 965 patients (0.22%), were diagnosed with COVID-19. A total of 124 patients (12.85%) experienced adverse events. The novel SODA score (based on sex, peripheral O2 saturation, presence of diabetes, and age) demonstrated good accuracy for adverse events prediction (area under ROC curve 0.858, CI: 0.82-0.98). A cut-off value of ≤2 points identifies patients with low risk (positive predictive value [PPV] for absence of events: 98.9%) and a cut-off of ≥5 points, high-risk patients (PPV 58.8% for adverse events).

Conclusions
This quick and easy score allows fast-track triage at the moment of diagnosis for COVID-19 using four simple variables: age, sex, SpO2, and diabetes. SODA score could improve preventive measures taken at diagnosis in high-risk patients and also relieve resources by identifying very low-risk patients.

Lopez-Pais|Javier|J|
Otero|Diego López|DL|
Ferreiro|Teba Gonzalez|TG|
Antonio|Carla Eugenia Cacho|CEC|
Muiños|Pablo José Antúnez|PJA|
Perez-Poza|Marta|M|
García|Óscar Otero|ÓO|
Ramos|Victor Jimenez|VJ|
Fernández|Manuela Sestayo|MS|
Fernandez|María Bastos|MB|
Pena|Xoan Carlos Sanmartin|XCS|
Roman|Alfonso Varela|AV|
Romero|Manuel Portela|MP|
Lago|Ana López|AL|
Escudero|Julián Álvarez|JÁ|
Román|Alberto San|AS|
Gonzalez-Juanatey|Jose Ramón|JR|
|||

Triage
COVID-19
Score
Fast-track
COVID-19, Coronavirus Disease 2019
ICU, Intensive Care Unit
IMV, Invasive Mechanical Ventilation
Prognosis
ROC, Receiver Operating Characteristic
SARS, Severe Acute Respiratory Syndrome
SARS-COV-2, SARS Coronavirus 2
SpO2, Peripheral O2 Saturation


Predictive value of serum VEGF, IL-1 and TNF-α in the treatment of thromboangiitis obliterans by revascularization.

Abstract: Effect of revascularization in the treatment of thromboangiitis obliterans (TAO) and the predictive value of serum vascular endothelial growth factor (VEGF), interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) of risk factors of amputation were investigated. From April 2012 to August 2015, a total of 117 patients with TAO admitted to the First Hospital of Lanzhou University were selected. Patients treated with revascularization combined with prostaglandin sodium and cilostazol were enrolled in group A (67 patients), and patients treated with sodium and cilostazol were enrolled in group B (50 patients). The clinical efficacy was evaluated by calculating the intermittent claudication distance and the ankle brachial index (ABI) of patients. The occurrence probability of nausea and vomiting, skin pruritus, abdominal pain, coagulation abnormalities and amputation were recorded. The concentration of serum VEGF, IL-1 and TNF-α were measured using enzyme-linked immunosorbent assay (ELISA). After treatment, the intermittent claudication distance, ABI and efficiency of group A was markedly higher than that of group B (P<0.05). After treatment, serum VEGF concentration in group A was clearly higher than that in group B (P<0.05), and IL-1 and TNF-α levels were much lower than those in group B (P<0.05). The amputation rate in group A was significantly lower than that in group B (P<0.05). Patients with amputation in both groups were enrolled in the study group (24 cases), and those without amputation were included in the control group (93 cases). The serum VEGF concentration in the study group before treatment was significantly lower than that in the control group (P<0.05), while IL-1 and TNF-α levels were significantly higher than those of the control group (P<0.05). In conclusion, pretreatment serum VEGF, IL-1 and TNF-α had a positive diagnostic value for poor prognosis of patients with amputation, and low concentration of VEGF and higher concentration of IL-1 and TNF-α are the risk factors for amputations in patients with TAO.

Li|Zheng-Fei|ZF| Shu|Xiao-Jun|XJ| Wang|Wen-Hui|WH| Liu|Sheng-Ye|SY| Dang|Lei|L| Shi|Yan-Qiang|YQ| Bai|Yan-Wen|YW|

thromboangiitis obliterans
revascularization
clinical efficacy
prognosis


Characterisation of sputter deposited niobium and boron interlayer in the copper-diamond system.

Abstract: In most metal matrix composites (MMCs) interfaces are decisive but hard to manipulate. Especially copper-carbon composites can exhibit excellent mechanical and thermal properties only if the Cu/C interface is modified by an optimised interlayer. Due to the excellent thermal conductivity and mechanical stability of diamond this form of carbon is preferred as reinforcement in heat sink materials (copper-diamond composite) which are often subjected to severe thermal and mechanical loads. In the present case niobium and boron interlayers of various thicknesses were deposited on diamond and vitreous carbon substrates by magnetron sputter deposition. After the coverage of all samples by a copper film, a part of the samples was subjected to heat treatment for 30 min at 800 °C under high vacuum (HV) to simulate the thermal conditions during the production of the composite material by uniaxial hot pressing. De-wetting during heat treatment leads to the formation of holes or humps in the Cu coating. This effect was investigated by scanning electron microscopy (SEM) and atomic force microscopy (AFM). A comparison of time-of-flight secondary ion mass spectroscopy (TOF SIMS) profiles of heat treated samples with those of as deposited ones showed the influence of interdiffusion during the heating process. Diffusion behaviour and chemical composition of the interface were also studied by cross sectional transmission electron microscopy (X-TEM) investigations using focused ion beam (FIB) cut samples. The thermal contact resistance (TCR) of the interface was calculated from results obtained from modulated infrared radiometry (IR). Thin interlayers suppressed de-wetting most effectively and consequently the TCR at the Cu-diamond interface was found to decrease. Therefore they are promising candidates for optimising the Cu-diamond interface.

Hell|J|J| Chirtoc|M|M| Eisenmenger-Sittner|C|C| Hutter|H|H| Kornfeind|N|N| Kijamnajsuk|P|P| Kitzmantel|M|M| Neubauer|E|E| Zellhofer|K|K|

Sputter deposition
Niobium
Interlayer
Heat sink materials
Interdiffusion
Copper–diamond composite


Synthesis of Tungsten-Doped Vanadium Dioxide Using a Modified Polyol Method Involving 1-Dodecanol.

Abstract: The doping of tungsten into VO2 (M) via a polyol process that is based on oligomerization of ammonium metavanadate and ethylene glycol (EG) to synthesize a vanadyl ethylene glycolate (VEG) followed by postcalcination was carried out by simply adding 1-dodecanol and the tungsten source tungstenoxytetrachloride (WOCl4). Tungsten-doped VEGs (W-VEGs) and their calcinated compounds (WxVO2) were prepared with varying mixing ratios of EG to 1-dodecanol and WOCl4 concentrations. Characterizations of W-VEGs by powder X-ray diffraction, differential scanning calorimetry, scanning electron microscopy, and infrared and transmittance spectroscopy showed that tungsten elements were successfully doped into WxVO2, thereby decreasing the metal-insulator transition temperature from 68 down to 51 °C. Our results suggested that WOCl4 variously combined with 1-dodecanol might interrupt the linear growth of W-VEGs, but that such an interruption might be alleviated at the optimal 1:1 mixing ratio of EG to 1-dodecanol, resulting in the successful W doping. The difference in the solar modulations of a W0.0207VO2 dispersion measured at 20 and 70 °C was increased to 21.8% while that of a pure VO2 dispersion was 2.5%. It was suggested that WOCl4 coupled with both EG and 1-dodecanol at an optimal mixing ratio could improve the formation of W-VEG and WxVO2 and that the bulky dodecyl chains might act as defects to decrease crystallinity.

Lee|Yonghyun|Y|
Jung|Sang Won|SW|
Park|Sang Hwi|SH|
Yoo|Jung Whan|JW|
Park|Juhyun|J|0000-0003-1300-5743

nanoparticles
smart windows
thermochromic
tungsten doping
vanadium oxide


Prevention Strategies of Alcohol and Substance Use Disorders in Older Adults.

Abstract: Older adults are increasingly engaging in unhealthy substance use. Owing to aging and comorbid medical conditions, older adults are at increased risk of adverse effects from alcohol, tobacco, and illicit drug use. Preventative measures, regular screening, and appropriate intervention can protect older adults from the negative outcomes of substance use and potentially improve their quality of life. This article reviews the latest trends of substance use in older adults, impact on health, and the best practice approaches for the clinical assessment of substance use disorders in this age group.

El Hayek|Samer|S|
Geagea|Luna|L|
El Bourji|Hussein|H|
Kadi|Tamara|T|
Talih|Farid|F|

Prevention
Substance use disorder
Older adults
Screening
Assessment
Addiction


Utility of Bayesian Single-Arm Design in New Drug Application for Rare Cancers in Japan: A Case Study of Phase 2 Trial for Sarcoma.

Abstract: Investigational drugs for rare cancers are often approved based solely on a single-arm phase II trial that primarily evaluates response rate in Japan. Such trials typically use a fixed sample size determined on the basis of the frequentist manner. However, since predicting the speed of patient enrollment is challenging because of the disease rarity, the time needed to complete the enrollment of the fixed number of patients is prolonged in some cases. A Bayesian design without fixing the sample size is useful for single-arm phase II trials of rare cancers. However, the arbitrariness of prior distribution specifications and the frequentist operating characteristics are regulatory issues. We recently started a Bayesian single-arm phase II trial of nivolumab in patients with sarcoma for new drug application in Japan and examined the statistical rationale and design consideration. In the Bayesian design, we specify the minimum and maximum numbers of enrolled patients during the enrollment period and the prior distributions of response rates. Considering these parameters, we obtain the minimum number of responders needed for the positive conclusion of the efficacy of nivolumab for each sample size. Simulation studies demonstrated that the operating characteristics of this design would be acceptable from the frequentist view. The Bayesian design provided an adaptive decision rule for efficacy conclusion for the drug without fixing the sample size. We hope our trial's success will provide a new drug development option for rare cancers in Japan.

Hirakawa|Akihiro|A| Nishikawa|Tadaaki|T| Yonemori|Kan|K| Shibata|Taro|T| Nakamura|Kenichi|K| Ando|Masashi|M| Ueda|Takafumi|T| Ozaki|Toshifumi|T| Tamura|Kenji|K| Kawai|Akira|A| Fujiwara|Yasuhiro|Y|

D001499:Bayes Theorem
D000066491:Clinical Decision-Making
D015507:Drugs, Investigational
D006801:Humans
D007564:Japan
D015233:Models, Statistical
D000077594:Nivolumab
D035583:Rare Diseases
D012107:Research Design
D018401:Sample Size
D012509:Sarcoma
D016019:Survival Analysis
D016896:Treatment Outcome

rare cancer
Bayesian design
single-arm trial


Ecological risk assessment of trace metals in the surface sediments of the Persian Gulf and Gulf of Oman: Evidence from subtropical estuaries of the Iranian coastal waters.

Abstract: This study aimed to investigate the ecological risk assessment of Khamir, Tiyab, and Jagin estuaries and the impact of anthropogenic activities on these ecosystems during a one-year study period (April 2015 to March 2016) using trace metals as pollution indices. The sediment samples were collected from nine sampling stations, following a gradient of contamination from the industrial wastewater and shrimp farming effluents to the less impacted stations. Pollution indices (i.e. PERI and PLI) were applied to ascertain the sediment quality. Based on pollution indices, the overall pattern of environmental quality status demonstrated that industrial sewage and shrimp farming effluents are major sources of pollution in the Khamir and Tiyab estuaries, respectively. The sediments in the most stations in studied coastal ecosystems of Iran posed moderate or considerable ecological risk. Results from this study showed that Zn, Pb, Cu, and Cd were mostly derived from anthropogenic activities such as domestic sewage and industrial effluents. Also, the findings of this study revealed that the pollution indices are suitable for evaluating the environmental situation of coastal ecosystems and the separation of areas with less impacted by human activities from areas affected by these activities and could be used as a robust management tool for monitoring programs in coastal areas. Altogether, these findings could be useful in providing more effective and targeted strategies of development better management practices for coastal areas.

Sharifinia|Moslem|M|
Taherizadeh|Mohammadreza|M|
Namin|Javid Imanpour|JI|
Kamrani|Ehsan|E|

Ecological risk assessment
Trace metals
Pollution indices
Organic matter
Shrimp farms impact


Fetal and neonatal genistein exposure aggravates to interfere with ovarian follicle development of obese female mice induced by high-fat diet.

Abstract: With epidemic of obesity, it affects aspects of female reproduction. Genistein could ameliorate obesity in people and animals, but might exert adverse effects on the female reproductive system. To evaluate the effects of fetal and neonatal genistein exposure on the ovarian health of F1 obese female mice with obesity induced by high-fat diet after weaning, we simulated a diet-induced obesity model to observe and determine biological effects of genistein exposure on the ovarian follicle of overfed female mice. Results showed that F1 female mice with obesity induced by high-fat diet significantly prolonged the estrus cycle, disrupted sex hormonal balance and ovarian follicle development after they were exposed to 25 mg/kg b.w./day of genistein during the fetal and neonatal stages. Genistein significantly up-regulated the ovarian mRNA expression of estrogen receptor beta in F1 obese female mice, and high-fat diet influenced the ovarian mRNA expression of estrogen receptor alpha, luteinizing hormone receptor and follicle-stimulating hormone receptor. Hence, genistein exposure from the fetal stage might increase the risk of reproductive diseases in obese females in later life. Thus, the long-term risks of genistein to obese females should be thoroughly assessed.

Liu|Xin|X| Li|Fenfen|F| Xie|Jianhua|J| Huang|Danfei|D| Xie|Mingyong|M|

Genistein
Ovarian follicle
Obesity
Fetal and neonatal exposure
Reproductive development


Patients with pacemaker or implantable cardioverter-defibrillator.

Abstract: The preparation of patients with a cardiac implantable electronic device (CIED) for the perioperative period necessitates familiarity with recommendations from the American Society of Anesthesiologists and Heart Rhythm Society. Even clinicians who are not CIED experts should understand the indications for implantation, as well as the basic functions, operations, and limitations of these devices. Before any scheduled procedure, proper CIED function should be verified and a specific CIED prescription obtained. Acquiring the requisite knowledge base and developing the systems to competently manage the CIED patient ensures safe and efficient perioperative care.

Schulman|Peter M|PM|
Rozner|Marc A|MA|
Sera|Valerie|V|
Stecker|Eric C|EC|

D058409:Cardiac Resynchronization Therapy Devices

Pacemaker Cardioverter-Defibrillator Perioperative Management Preoperative


Are low birth weight children predisposed to renal loss of carnitine?

Abstract: Aim: The plasma homeostasis of both free and esterified carnitines is mostly regulated by renal tubular reabsorption, which may be disturbed in low birth weight children. The aim of study was to check whether disturbances in excretion of l-carnitine (LC) and its main ester, acetyl-carnitine (ALC), may be the result of renal dysfunction in low birth weight children (LBW).Methods: This study included 59 LBW children (2165 g [1490-2440]) and 22 children with normal birth weight as a reference group (3500 g [3275-3650]). Subjects were divided into three groups: 0-3 months, 4-12 months and over 1 year at the time of testing. Urinary levels of carnitine were measured spectrophotometrically.Results: The urine excretion of Free LC, Free LC/cr, Total LC and Total LC/cr. Were significantly higher in 0-3 and 4-12-month old LBW infants study groups when compared to the reference groups. We found statistically significant higher urine excretion of ALC and ALC/cr. in all age groups of LBW infants compared to the reference group. There was a negative correlation between birth weight and free LC/cr. (r= -0.3, p < .05), Total LC/cr. (r= -0.34, p < .05), and ALC/cr. (r= -39, p < .05), and in the children >12-month-old strong negative correlation between eGFR and free LC/cr. (r= -0.6, p < .05), Total LC/cr. (r= -0.61, p < .05), ALC/cr. (r= -0.61, p < .05.)Conclusion: Higher urine excretion of both LC and ALC and its negative correlation with birth weight and eGFR may reflect some degree of renal dysfunction in LBW infants.

Protas|Piotr Tomasz|PT|
Kępka|Alina|A|
Rybi-Szuminska|Agnieszka|A|
Storonowicz|Justyna|J|
Klukowski|Mark|M|
Wasilewska|Anna|A|


Using likelihood ratios to detect invalid performance with performance validity measures.

Abstract: Larrabee (2008) applied chained likelihood ratios to selected performance validity measures (PVMs) to identify non-valid performances on neuropsychological tests. He presented a method of combining different PVMs with different sensitivities and specificities into an overall probability of non-validity. We applied his methodology to a set of 11 PVMs using a sample of 255 subjects. The results of the study show that in various combinations of two or three PVMs, a high reliability of invalidity can be determined using the chained likelihood ratio method. This study advances the ability of clinicians to chain various PVMs together and calculate the probability that a set of data is invalid.

Meyers|John E|JE|
Miller|Ronald M|RM|
Thompson|Lisa M|LM|
Scalese|Adam M|AM|
Allred|Bonnie C|BC|
Rupp|Zachary W|ZW|
Dupaix|Zacharias P|ZP|
Junghyun Lee|Amy|A|

Assessment
Impairment
Malingering/symptom validity testing
Mild cognitive
Test construction


Airborne polybrominated diphenyl ethers (PBDEs), polybrominated dibenzo-p-dioxins/furans (PBDD/Fs), and dechlorane plus (DP) in concentrated vehicle parking areas.

Abstract: This study investigated polybrominated diphenyl ethers (PBDEs), polybrominated dibenzo-p-dioxins/furans (PBDD/Fs), and dechlorane plus (DP) in air around three concentrated vehicle parking areas (underground, indoor, and outdoor) in a metropolitan of South China. The parking areas showed higher concentrations of PBDEs, PBDD/Fs, and DP than their adjacent urban area or distinct congener/isomer profiles, which indicate their local emission sources. The highest PBDE and DP concentrations were found in the outdoor parking lot, which might be related to the heating effect of direct sunlight exposure. Multi-linear regression analysis results suggest that deca-BDEs without noticeable transformation contributed most to airborne PBDEs in all studied areas, followed by penta-BDEs. The statistically lower anti-DP fractions in the urban area than that of commercial product signified its degradation/transformation during transportation. Neither PBDEs nor vehicle exhaust contributed much to airborne PBDD/Fs in the parking areas. There were 68.1-100 % of PBDEs, PBDD/Fs, and DP associated with particles. Logarithms of gas-particle distribution coefficients (K ps) of PBDEs were significantly linear-correlated with those of their sub-cooled vapor pressures (p Ls) and octanol-air partition coefficients (K OAs) in all studied areas. The daily inhalation doses of PBDEs, DP, and PBDD/Fs were individually estimated as 89.7-10,741, 2.05-39.4, and 0.12-4.17 pg kg(-1) day(-1) for employees in the parking areas via Monte Carlo simulation.

Li|Huiru|H| Liu|Hehuan|H| Mo|Ligui|L| Sheng|Guoying|G| Fu|Jiamo|J| Peng|Ping'an|P|

D000393:Air Pollutants
D002681:China
D004147:Dioxins
D004784:Environmental Monitoring
D005663:Furans
D055768:Halogenated Diphenyl Ethers
D006801:Humans
D006843:Hydrocarbons, Chlorinated
D019570:Inhalation Exposure
D018986:Motor Vehicles
D016273:Occupational Exposure
D011083:Polycyclic Compounds

Automobile
Brominated dioxins and furans
Brominated flame retardant
Chlorinated flame retardant
Fireproof plastics
Persistent organic pollutants (POPs)


In Vitro Metabolic Studies of REV-ERB Agonists SR9009 and SR9011.

Abstract: SR9009 and SR9011 are attractive as performance-enhancing substances due to their REV-ERB agonist effects and thus circadian rhythm modulation activity. Although no pharmaceutical preparations are available yet, illicit use of SR9009 and SR9011 for doping purposes can be anticipated, especially since SR9009 is marketed in illicit products. Therefore, the aim was to identify potential diagnostic metabolites via in vitro metabolic studies to ensure effective (doping) control. The presence of SR9009 could be demonstrated in a black market product purchased over the Internet. Via human liver microsomal metabolic assays, eight metabolites were detected for SR9009 and fourteen metabolites for SR9011 by liquid chromatography-high resolution mass spectrometry (LC-HRMS). Structure elucidation was performed for all metabolites by LC-HRMS product ion scans in both positive and negative ionization mode. Retrospective data analysis was applied to 1511 doping control samples previously analyzed by a full-scan LC-HRMS screening method to verify the presence of SR9009, SR9011 and their metabolites. So far, the presence of neither the parent compound nor the metabolites could be detected in routine urine samples. However, to further discourage use of these potentially harmful compounds, incorporation of SR9009 and SR9011 into screening methods is highly recommended.

Geldof|Lore|L|
Deventer|Koen|K|
Roels|Kris|K|
Tudela|Eva|E|
Van Eeno|Peter|P|

D002851:Chromatography, High Pressure Liquid

D056953:Nuclear Receptor Subfamily 1, Group D, Member 1

liquid chromatography–high resolution mass spectrometry (LC–HRMS)


Pattern formation in a 2-population homogenized neuronal network model.

Abstract: We study pattern formation in a 2-population homogenized neural field model of the Hopfield type in one spatial dimension with periodic microstructure. The connectivity functions are periodically modulated in both the synaptic footprint and in the spatial scale. It is shown that the nonlocal synaptic interactions promote a finite band width instability. The stability method relies on a sequence of wave-number dependent invariants of [Formula: see text]-stability matrices representing the sequence of Fourier-transformed linearized evolution equations for the perturbation imposed on the homogeneous background. The generic picture of the instability structure consists of a finite set of well-separated gain bands. In the shallow firing rate regime the nonlinear development of the instability is determined by means of the translational invariant model with connectivity kernels replaced with the corresponding period averaged connectivity functions. In the steep firing rate regime the pattern formation process depends sensitively on the spatial localization of the connectivity kernels: For strongly localized kernels this process is determined by the translational invariant model with period averaged connectivity kernels, whereas in the complementary regime of weak and moderate localization requires the homogenized model as a starting point for the analysis. We follow the development of the instability numerically into the nonlinear regime for both steep and shallow firing rate functions when the connectivity kernels are modeled by means of an exponentially decaying function. We also study the pattern forming process numerically as a function of the heterogeneity parameters in four different regimes ranging from the weakly modulated case to the strongly heterogeneous case. For the weakly modulated regime, we observe that stable spatial oscillations are formed in the steep firing rate regime, whereas we get spatiotemporal oscillations in the shallow regime of the firing rate functions.

Pattern formation
Neural field models
Homogenization theory
Turing type of instability


The left anterior right temporal (LART) placement for electroconvulsive therapy: A computational modelling study.

Abstract: Electrode placement in electroconvulsive therapy (ECT) has a major impact on treatment efficacy and cognitive side effects. Left Anterior Right Temporal (LART) is a lesser utilised bilateral montage which may produce more optimal clinical outcomes relative to standard bitemporal ECT. In this study we used computational modelling to explore how stimulation effects from LART and two novel variants (LART - F3 and LART - Frontal) compared to the more common bilateral placements of bitemporal and bifrontal ECT. High resolution finite element human head models were generated from MRI scans of three subjects with Major Depressive Disorder. Differences in regional stimulation were examined through parametric tests for regions of interest and subtraction maps. Compared to bitemporal ECT, LART - Original resulted in significantly greater stimulation of the left cingulate gyrus (hypothesised to be associated with treatment efficacy), and relatively reduced stimulation of the bilateral hippocampi (potentially associated with cognitive side effects). No additional clinical benefit was suggested with the novel LART placements compared to the original LART. The original LART placement is a promising montage for further clinical investigation.

Steward|Ben|B|
Bakir|Azam Ahmad|AA|
Martin|Donel|D|
Dokos|Socrates|S|
Loo|Colleen K|CK|

Computational modelling
Electroconvulsive therapy (ECT)
Efficacy
Cognition
Depression


Suicidal Ideation Profiles in Patients with Fibromyalgia Using Transdiagnostic Psychological and Fibromyalgia-Associated Variables.

Abstract: Several studies have emphasized the heterogeneity of fibromyalgia patients. Furthermore, fibromyalgia patients are considered a high-risk suicide group. The ideation-to-action framework proposes a set of transdiagnostic psychological factors involved in the development of suicidal ideation. The present study aims to explore the existence of different subgroups according to their vulnerability to suicidal ideation through these transdiagnostic psychological variables and a set of variables typically associated with fibromyalgia. In this cross-sectional study, 151 fibromyalgia patients were assessed through the Revised Fibromyalgia Impact Questionnaire, Beck Depression Inventory-II, Plutchik Suicide Risk Scale, Interpersonal Needs Questionnaire, Defeat Scale, Entrapment Scale, Psychache Scale, and Beck Hopelessness Scale. A K-means cluster analysis identified two clusters, one (45.70%) according to a low vulnerability, and a second (54.30%) with a high vulnerability to suicidal ideation. These clusters showed statistically significant differences in suicidal ideation and suicide risk. However, no differences were observed in most socio-demographic variables. In conclusion, fibromyalgia patients who present a clinical condition characterized by a moderate-high degree of physical dysfunction, overall disease impact and intensity of fibromyalgia-associated symptoms, along with a high degree of perceived burdensomeness, thwarted belongingness, defeat, entrapment, psychological pain and hopelessness, form a homogeneous group at high risk for suicidal ideation.

suicidal ideation
suicide
profiles
fibromyalgia
transdiagnostic psychological factors


Knockout of Murine Mamld1 Impairs Testicular Growth and Daily Sperm Production but Permits Normal Postnatal Androgen Production and Fertility.

Abstract: MAMLD1 has been implicated in testicular function in both human and mouse fetuses. Although three patients with MAMLD1 mutations were reported to have hypergonadotropic hypogonadism in their teens, the functional significance of MAMLD1 in the postnatal testis remains unclear. Here, we analyzed the phenotype of Mamld1 knockout (KO) male mice at reproductive ages. The reproductive organs of KO male mice were morphologically unremarkable, except for relatively small testes. Seminiferous tubule size and number of proliferating spermatogonia/spermatocytes were reduced in the KO testis. Daily sperm production of KO mice was mildly attenuated, whereas total sperm counts in epididymal semen remained normal. Sperm motility and morphology, as well as androgen levels in serum and testicular tissues and the number of pups born from cross-mated wildtype (WT) female mice, were comparable between WT and KO male mice. These results indicate that MAMLD1 contributes to the maintenance of postnatal testicular growth and daily sperm production but is dispensable for androgen biosynthesis and fertility. MAMLD1 likely plays supporting roles in multiple and continuous steps of male reproduction.

Miyado|Mami|M| Yoshida|Kaoru|K| Miyado|Kenji|K| Katsumi|Momori|M| Saito|Kazuki|K| Nakamura|Shigeru|S| Ogata|Tsutomu|T| Fukami|Maki|M|

D018507:Gene Expression Regulation, Developmental

androgen
mutation
testis
reproduction
knockout mouse


Three-dimensional pattern of extraretinal neovascular development in retinopathy of prematurity.

Abstract:
BACKGROUND
The application of three-dimensional (3D) visualization techniques to evaluate the earliest visible onset of abnormal retinal vascular development in preterm infants with retinopathy of prematurity (ROP), using bedside non-contact optical coherence tomography (OCT) imaging to characterize morphology and sequential structural changes of abnormal extraretinal neovascularization.

METHODS
Thirty-one preterm infants undergoing routine ROP screening with written informed consent for research imaging were enrolled in this prospective observational study. We imaged the macula and temporal periphery of preterm infants using a handheld OCT system (Envisu 2300 or handheld swept-source research system). The scans obtained were segmented and, using enhanced ray casting, were converted to 3D volumes to which color filter was applied.

RESULTS
Using colorized 3D visualization, we defined extraretinal neovascular structures as buds, bridging networks, and placoid lesions. We could longitudinally follow progression and regression of extraretinal neovascularization in stage 3 ROP after treatment in one infant over 12 weeks and document the appearance of early buds, and formation of florid neovascularization. From stages 2 to 3 ROP, we observed progression from sessile buds to a complex plaque that corresponded to stage 3 ROP on clinical examination. We demonstrated regression of neovascular complexes to small pre-retinal tufts after treatment with anti-VEGF.

CONCLUSIONS
The extension of OCT processing to include surface flattening and colorization that further improved structural analysis rendered better understanding of extraretinal tissue. Our ability to image similar areas in the same infant over multiple visits enabled us to study the evolution of these structural components and follow pathological vascular events longitudinally in development and regression after treatment. These methods can be applied to further study which are likely contribute to our understanding of the pathophysiology of neovascularization in ROP.

D042461:Vascular Endothelial Growth Factor A

Retinopathy of prematurity
3D
Visualization
ROP
Optical coherence tomography
OCT


Positive Psychological Constructs and Health Outcomes in Hematopoietic Stem Cell Transplantation Patients: A Systematic Review.

Abstract: Positive psychological constructs (eg, optimism, positive affect) have been independently associated with superior health outcomes across many medical populations. However, there has been little synthesis of the literature examining these associations among patients with hematologic malignancies receiving hematopoietic stem cell transplantation (HSCT). To address this gap we completed a systematic review, using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, of studies examining relationships between positive psychological constructs and health-related outcomes (eg, psychiatric symptoms, function, health-related quality of life [HRQoL], or treatment compliance) after HSCT. Eighteen eligible studies (N = 4201; 47% women; mean age, 47.1) were identified. Optimism (n = 12 studies) was the most frequently studied positive construct and HRQoL (examined in n = 11 studies) the most common outcome. All 17 studies with quantitative analyses found a significant (P < .05) association between a positive psychological construct and a health outcome; most but not all controlled for 1 or more relevant covariates. Among patients with hematologic malignancies who receive HSCT, positive psychological constructs appear to be associated with improved HRQoL and other health outcomes. Further work is warranted to more comprehensively understand the independent effects of positive psychological constructs on a variety of health outcomes and to develop interventions to promote well-being that are adapted to the needs of this population.

Amonoo|Hermioni L|HL|
Barclay|Margot E|ME|
El-Jawahri|Areej|A|
Traeger|Lara N|LN|
Lee|Stephanie J|SJ|
Huffman|Jeff C|JC|

D018380:Hematopoietic Stem Cell Transplantation

Positive psychology
Health outcomes
Hematopoietic stem cell transplant
Optimism
Health-related quality of life
Positive constructs
Positive psychological well-being


Subcutaneous immunoglobulin for maintenance therapy in stiff-person syndrome: One-year follow-up in two patients.

Abstract: Stiff person syndrome is a rare condition characterised by prolonged stiffness with superimposed muscle spasms. Immunotherapy relies mainly on intravenous immunoglobulin, steroids and plasma exchange. Azathioprine or rituximab are other possible options. We describe two patients who showed a good clinical response with intravenous immunoglobulin and persistence of the clinical improvement after shifting to equivalent dosage of subcutaneous immunoglobulin. Both patients received a diagnosis of stiff person syndrome based on their clinical symptoms (episodes of stiffness and spasms) and presence of antiglutamic acid decarboxylase. Treatment with intravenous immunoglobulin was started with improvement of symptoms as reported by patients and confirmed also by the spasm frequency scale and modified Ashworth scale. After clinical stabilisation in order to avoid the hospitalisation required for intravenous immunoglobulin treatment a switch to subcutaneous immunoglobulins was made. After one year of follow-up from the switch, the patients show clinical stability. Their scores on the modified Ashworth scale, spasm frequency scale and on the 10 Meter Walking Test were also stable. Subcutaneous formulation of immunoglobulin could be as effective as intravenous immunoglobulin in the maintenance treatment of Stiff person syndrome, although studies involving a larger cohort of patients are needed in order to confirm our anecdotal experience.

Fileccia|E|E|
Rinaldi|R|R|
Minicuci|G M|GM|
D'Angelo|R|R|
Bartolomei|L|L|
Liguori|R|R|
Donadio|V|V|

Subcutaneous immunoglobulin
Stiff persons syndrome
Intravenous immunoglobulin
Immuno-modulation


Switchable Plasmonic Film Using Nanoconfined Liquid Crystals.

Abstract: Structural coloration using plasmonic particles has received substantial attention due to its robust, permanent, and scalable characteristics across the full color range. In this study, a plasmonic structure based on a porous anodic aluminum oxide (AAO) film coated with a metallic film was fabricated. Colors were varied by changing the refractive index, which was achieved with a convolution with nanopores of AAO film and an infiltrated liquid crystal (LC) material. LC molecules confined in the porous AAO film were uniformly aligned, and they exhibited pore-size-dependent colors because of the specific refractive index. The thermal phase transition of the LC material in the nanopores changed the effective refractive index, switching the reflected colors, and the LC-infiltrated AAO remained stable over a month. We believe LC materials can extend the use of rigid conventional plasmonic structures from simple sensor applications to multifunctional uses such as color printing, writing pens, and displays.

switchable
plasmonic
liquid crystals
anodic aluminum oxide (AAO)
confinement


Risk factors for lymph node metastasis (LNM) in patients with papillary thyroid microcarcinoma (PTMC): role of preoperative ultrasound.

Abstract: Objective This study aimed to investigate the risk factors and clinical value of lymph node metastasis (LNM) and missed central lymph node metastasis (CLNM) using preoperative ultrasound (US) in patients with papillary thyroid microcarcinoma (PTMC). Methods This retrospective study included 521 patients who underwent thyroidectomy for confirmed PTMC based on a final histological examination between January 2014 and June 2015. Based on the presence of LNM, 521 cases were divided into two groups: metastasis (218) and non-metastasis (303). Univariate and multivariate logistic regression analyses were used to analyse the US and clinical characteristics of the primary tumour. Results We defined LNM based on the tumour diameter with an optimal critical value of 0.55 cm using ROC analysis with a sensitivity of 65.6% and specificity of 59.6%. We defined US-missed CLNM based on the optimal critical value of 0.65 cm using diagnostic ROC analysis with a sensitivity of 66.0% and specificity of 73.0%. The odds ratios of significant factors with LNM by US were 10.3 (95% confidence interval [95% CI], 6.2-17.0), 5.3 (95% CI, 3.3-8.7), 2.7 (95% CI, 1.1-6.5), 4.3 (95% CI, 1.7-10.5), 2.5 (95% CI, 1.5-4.1), and 2.7 (95% CI, 1.7-4.4) for extrathyroidal invasion, blood flow, multifocality, tumour diameter greater than 0.55 cm, male sex, and age younger than 47 years, respectively. Conclusions US characteristics, such as extrathyroidal invasion, blood flow, tumour diameter, sex, and age, may improve the efficacy of predicting LNM and facilitating diagnosis of PTMC. Furthermore, tumour invasion to the extracapsular thyroid and a diameter greater than 0.65 cm indicate CLNM.

Zhao|Cheng|C| Jiang|Wenbin|W| Gao|Yuxiu|Y| Niu|Weidong|W| Zhang|Xiaojuan|X| Xin|Lei|L|

lymph node metastasis
Papillary thyroid microcarcinoma
ultrasound
central lymph node metastasis


Quantitative Analysis of ¹⁸F-(E)-N-(3-Iodoprop-2-Enyl)-2β-Carbofluoroethoxy-3β-(4'-Methyl-Phenyl) Nortropane Binding to the Dopamine Transporter in Parkinson Disease.

Abstract:
UNLABELLED
(18)F-(E)-N-(3-iodoprop-2-enyl)-2β-carbofluoroethoxy-3β-(4'-methyl-phenyl) nortropane ((18)F-FE-PE2I) is a recently developed radioligand for the in vivo quantification of the dopamine transporter (DAT) in the striatum and substantia nigra (SN). The aim of this study was to examine the suitability of (18)F-FE-PE2I as a tool for imaging the nigrostriatal pathway in Parkinson disease (PD) with PET.

METHODS
Ten PD patients (9 men and 1 woman; mean age ± SD, 60 ± 9 y; Hoehn and Yahr, 1-2; Unified Parkinson Disease Rating Scale motor, 18.9 ± 6.7) and 10 controls (9 men and 1 woman; mean age ± SD, 60 ± 7 y) were included. PET measurements with (18)F-FE-PE2I were conducted for 93 min using the High-Resolution Research Tomograph. Venous blood was drawn to compare protein binding, parent fraction, and radiometabolite composition in PD patients and controls. Regions of interest for the caudate, putamen, ventral striatum, SN, and cerebellum were drawn on coregistered MR images. The outcome measure was the binding potential (BP(ND)) estimated with the simplified reference tissue model and the Logan graphical analysis, using the cerebellum as a reference region. Time stability of BP(ND) was examined to define the shortest acquisition protocol for quantitative studies. The wavelet-aided parametric imaging method was used to obtain high-resolution BP(ND) images to compare DAT availability in the striatum and SN in PD patients and control subjects. Group differences were assessed with the unpaired t test (P < 0.05).

RESULTS
Parent, radiometabolite fractions, plasma concentration, and cerebellar uptake of (18)F-FE-PE2I did not differ significantly between PD patients and controls. Stable estimates of BP(ND) (<8% of the 93-min value) were obtained with the simplified reference tissue model using approximately 66 min of data. BP(ND) values in PD patients were significantly lower than those in controls (P < 0.05) in the caudate (2.54 ± 0.79 vs. 3.68 ± 0.56), putamen (1.39 ± 1.04 vs. 4.41 ± 0.54), ventral striatum (2.26 ± 0.93 vs. 3.30 ± 0.46), and SN (0.46 ± 0.20 vs. 0.68 ± 0.15).

CONCLUSION
(18)F-FE-PE2I is clearly a suitable radioligand for DAT quantification and imaging of the nigrostriatal pathway in PD. Similar metabolism in controls and PD patients, suitability of the cerebellum as a reference region, and accuracy of quantification using approximately 66 min of PET data are advantages for noninvasive and simplified imaging protocols for PD studies. Finally, DAT loss in PD can be measured in both the striatum and the SN, supporting the utility of (18)F-FE-PE2I as an imaging tool of the nigrostriatal pathway.

Fazio|Patrik|P|
Svenningsson|Per|P|
Forsberg|Anton|A|
Jönsson|Erik G|EG|
Amini|Nahid|N|
Nakao|Ryuji|R|
Nag|Sangram|S|
Halldin|Christer|C|
Farde|Lars|L|
Varrone|Andrea|A|

D050483:Dopamine Plasma Membrane Transport Proteins

dopamine transporter
Parkinson disease
substantia nigra
PET


Staying hot to fight the heat-high body temperatures accompany a diurnal endothermic lifestyle in the tropics.

Abstract: Much of our knowledge of the thermoregulation of endotherms has been obtained from species inhabiting cold and temperate climates, our knowledge of the thermoregulatory physiology of tropical endotherms is scarce. We studied the thermoregulatory physiology of a small, tropical mammal, the large treeshrew (Tupaia tana, Order Scandentia) by recording the body temperatures of free-ranging individuals, and by measuring the resting metabolic rates of wild individuals held temporarily in captivity. The amplitude of daily body temperature (~ 4 °C) was higher in treeshrews than in many homeothermic eutherian mammals; a consequence of high active-phase body temperatures (~ 40 °C), and relatively low rest-phase body temperatures (~ 36 °C). We hypothesized that high body temperatures enable T. tana to maintain a suitable gradient between ambient and body temperature to allow for passive heat dissipation, important in high-humidity environments where opportunities for evaporative cooling are rare. Whether this thermoregulatory phenotype is unique to Scandentians, or whether other warm-climate diurnal small mammals share similar thermoregulatory characteristics, is currently unknown.

Body temperature
Tropics
Thermoregulation
Scandentia
Endothermy
Heterothermy


The Many Facets of the Small Non-coding RNA RsaE (RoxS) in Metabolic Niche Adaptation of Gram-Positive Bacteria.

Abstract: Small regulatory RNAs (sRNAs) are increasingly recognized as players in the complex regulatory networks governing bacterial gene expression. RsaE (synonym RoxS) is an sRNA that is highly conserved in bacteria of the Bacillales order. Recent analyses in Bacillus subtilis, Staphylococcus aureus and Staphylococcus epidermidis identified RsaE/RoxS as a potent riboregulator of central carbon metabolism and energy balance with many molecular RsaE/RoxS functions and targets being shared across species. Similarities and species-specific differences in cellular processes modulated by RsaE/RoxS suggest that this sRNA plays a prominent role in the adaptation of Gram-positive bacteria to niches with varying nutrient availabilities and environmental cues. This review summarizes recent findings on the molecular function of RsaE/RoxS and its interaction with mRNA targets. Special emphasis will be on the integration of RsaE/RoxS into metabolic regulatory circuits and, derived from this, the role of RsaE/RoxS as a putative driver to generate phenotypic heterogeneity in bacterial populations. In this respect, we will particularly discuss heterogeneous RsaE expression in S. epidermidis biofilms and its possible contribution to metabolic niche diversification, programmed bacterial lysis and biofilm matrix production.

Marincola|Gabriella|G|
Wencker|Freya D R|FDR|
Ziebuhr|Wilma|W|

D015964:Gene Expression Regulation, Bacterial

sRNA
RsaE/RoxS
biofilm
bacterial metabolism
population heterogeneity


Transdermal System Based on Solid Cilostazol Nanoparticles Attenuates Ischemia/Reperfusion-Induced Brain Injury in Mice.

Abstract: Cilostazol (CIL) exerted a protective effect by promoting blood-brain barrier integrity as well as improving the status of neurological dysfunctions following cerebral ischemia/reperfusion (I/R) injury. We attempted to design a 0.5% CIL carbopol gel using solid nanoparticles (CIL-Ngel), and then investigated the relationships between energy-dependent endocytosis and the skin penetration of CIL-Ngel in this study. In addition, we evaluated whether the CIL-Ngel attenuated I/R-induced brain injury in a middle cerebral artery occlusion (MCAO)/reperfusion model mouse. The particle size of CIL was decreased using a bead mill, and the CIL particles (14.9 × 1014 particles/0.3 g) in the CIL-Ngel were approximately 50-180 nm. The release of CIL in the CIL-Ngel was higher than that in gel containing CIL powder (CIL-Mgel), and the CIL particles were released from the CIL-Ngel as nanoparticles. In addition, the percutaneous absorption of CIL from the CIL-Ngel was higher in comparison with that from CIL-Mgel, and clathrin-dependent endocytosis and caveolae-dependent endocytosis were related to the enhanced skin penetration of CIL-NPs. In the traditional (oral administration of CIL powder, 3 mg/kg) and transdermal administration (CIL-Ngel, 0.3 g) for 3 days (once a day), the area under the plasma CIL concentration-time curves (AUC) was similar, although the CIL supplied to the blood by the CIL-Ngel was more sustained than that via oral administration of CIL powder. Furthermore, the CIL-Ngel attenuated the ischemic stroke. In conclusion, we designed a gel using solid CIL-NPs, and we showed that the sustained release of CIL by CIL-Ngel provided an effective treatment for ischemic stroke in MCAO/reperfusion model mice. These findings induce the possibilities of developing novel applications of CIL solid nanoparticles.

cilostazol
nanoparticle
endocytosis
ischemic stroke
transdermal delivery system


Clinical findings of acute acquired comitant esotropia in young patients.

Abstract:
PURPOSE
This study aimed to identify the characteristics of acute acquired comitant esotropia (AACE) in young patients from a single institution; and clarify their relationship with the excess use of digital devices.

STUDY DESIGN
Retrospective, observational.

METHODS
We extracted the clinical charts of patients aged between 5 and 35 years who presented at the Hamamatsu University Hospital with AACE symptoms from January 1, 2015 to December 31, 2018. The age of onset, angle of deviation, refractive errors, history of near work, including excess smartphone use, and treatment modality were retrieved. Patients were divided into three groups: CHILD (aged 5-12 years), JUNIOR (aged 13-17 years), and ADULT (aged 18-35 years) and statistically analyzed with Kruskal-Wallis test.

RESULTS
Forty-one patients were retrieved, with a mean age at onset of 15.8 (5-28) years; eight in the CHILD group, 23 in the JUNIOR group, and 10 in the ADULT group. Refractive errors and age of patients were correlated, but were not significantly different among groups. The mean angle of deviation at distance was 28.0 ± 12.8 prism diopters (PD) and 28.6 ± 17.2 PD at near. The CHILD group showed the largest near-distant dissociation. History of excessive near work was found in all groups.

CONCLUSION
AACE was most commonly found in the JUNIOR group, especially those aged 15-16 years. AACE may encompass multiple diseases; using common diagnostic criteria and asking common questions regarding digital device usage is necessary to clarify the influence of digital device usage, and a multicenter prospective study is recommended.

Esotropia
Digital device
Diplopia
Strabismus


TOTAL MANDIBULAR DEFECT RECONSTRUCTION BY TOTAL TITANIUM PATIENT-SPECIFIC IMPLANT: CLINICAL EFFICACY AND LONG TERM FOLLOW UP. CLINICAL CASE.

Abstract: The aim of this clinical case in demonstrating the possibility of replacing total defect of the mandible with a patient specific implant and the result of long-term follow up. Literature data on the replacement of total mandibular defects are extremely limited and they are presented by only several clinical cases where various surgical approaches were used. In the available literature, there are two approaches to solving this problem, including the replacement of the jaw with vascularised bone grafts, of which the fibula flap is the most promising, and the implantation of endoprostheses of the jaws, of which patient-specific anatomical endoprostheses made using additive technologies are the most advanced. The concept of using patient-specific endoprostheses of the whole mandible is considered revolutionary because it has a number of significant benefits, including the greatest accuracy in restoring the anatomical shape of the mandible. One of the unresolved problems associated with the installation of total mandibular endoprostheses is the prosthetic rehabilitation of patients using fixed structures. The analysis of the presented case can be a good tool for the clinician and bioengineer while making the final decision on the treatment method and modality in patients who need an identical option for the repair of a mandibular defect. Based on CT data, we can conclude that the employed approach, methodology of design and manufacture of patient-specific titanium mandibular endoprosthesis for the total defect demonstrated the sufficient efficacy, which suggest the need for further systematic studies to address this issue.

Chernohorskyi|Denis M|DM|
Chepurnyi|Yuriy V|YV|
Kanyura|Oleksandr A|OA|
Kopchak|Andriy V|AV|

total mandibular defect
Patient specific implant
mandible reconstruction
mandible segmentation


Effective Connectivity between Major Nodes of the Limbic System, Salience and Frontoparietal Networks Differentiates Schizophrenia and Mood Disorders from Healthy Controls.

Abstract: This study was conducted to examine whether there are quantitative or qualitative differences in the connectome between psychiatric patients and healthy controls and to delineate the connectome features of major depressive disorder (MDD), schizophrenia (SCZ) and bipolar disorder (BD), as well as the severity of these disorders. Toward this end, we performed an effective connectivity analysis of resting state functional MRI data in these three patient groups and healthy controls. We used spectral Dynamic Causal Modeling (spDCM), and the derived connectome features were further subjected to machine learning. The results outlined a model of five connections, which discriminated patients from controls, comprising major nodes of the limbic system (amygdala (AMY), hippocampus (HPC) and anterior cingulate cortex (ACC)), the salience network (anterior insula (AI), and the frontoparietal and dorsal attention network (middle frontal gyrus (MFG), corresponding to the dorsolateral prefrontal cortex, and frontal eye field (FEF)). Notably, the alterations in the self-inhibitory connection of the anterior insula emerged as a feature of both mood disorders and SCZ. Moreover, four out of the five connectome features that discriminate mental illness from controls are features of mood disorders (both MDD and BD), namely the MFG→FEF, HPC→FEF, AI→AMY, and MFG→AMY connections, whereas one connection is a feature of SCZ, namely the AMY→SPL connectivity. A large part of the variance in the severity of depression (31.6%) and SCZ (40.6%) was explained by connectivity features. In conclusion, dysfunctions in the self-regulation of the salience network may underpin major mental disorders, while other key connectome features shape differences between mood disorders and SCZ, and can be used as potential imaging biomarkers.

effective connectivity
schizophrenia
mood disorders
depression
salience network
psychiatry


Use of medical services and medicines attributable to type 2 diabetes care in Yaoundé, Cameroon: a cross-sectional study.

Abstract:
BACKGROUND
The increasing numbers of people with type 2 diabetes (T2D) is a global concern and especially in sub-Saharan Africa, where diabetes must compete for resources with communicable diseases. Diabetes intensifies health care utilisation and leads to an increase in medical care costs. However, In Cameroon like in most developing countries, data on the impact of diabetes on the medical health system are scarce. We aimed to analyse the use of medical services and medicines attributable to T2D care in Yaoundé, Cameroon.

METHODS
We conducted a cross-sectional study comparing the use of medical services and medicines on 500 people with T2D attending the diabetic outpatient units of three hospitals in Yaoundé and 500 people without diabetes matched for age, sex and residence. We performed multivariate logistic and quantile regressions to assess the effect of diabetes on the use of medical services and medicines and the presence of other chronic health problems. Models were adjusted for age, educational level, marital status, occupation and family income.

RESULTS
Overall, the rate of use of health services was found to be greater in people with T2D than those without diabetes. People with T2D had greater odds of having an outpatient visit to any clinician (OR 97.1 [95% CI: 41.6-226.2]), to be hospitalised (OR 11.9 [95% CI: 1.6-87.9]), to take at least one medicine (OR 83.1 [37.1-185.8]) compared with people without diabetes. We also observed an association between diabetes and some chronic diseases/diabetes complications including hypertension (OR 9.2 [95% CI: 5.0-16.9]), cardiovascular diseases (OR 1.9 [95% CI: 0.8-4.9]), peripheral neuropathy (OR 6.2 [95% CI: 3.4-11.2]), and erectile dysfunction (OR 5.8 [95% CI: 2.7-12.1]).

CONCLUSIONS
This study showed that the presence of diabetes is associated with an increased use of health care services and medicines as well as with some chronic diseases/diabetes complications.

D010342:Patient Acceptance of Health Care

Medical services
Medicines
Type 2 diabetes
Cameroon
Africa
Complications


Three-dimensional virtual bronchoscopy using a tablet computer to guide real-time transbronchial needle aspiration.

Abstract:
Objectives
We proposed a new virtual bronchoscopy tool to improve the accuracy of traditional transbronchial needle aspiration for mediastinal staging.

Methods
Chest-computed tomographic images (1 mm thickness) were reconstructed with Osirix software to produce a virtual bronchoscopic simulation. The target adenopathy was identified by measuring its distance from the carina on multiplanar reconstruction images. The static images were uploaded in iMovie Software, which produced a virtual bronchoscopic movie from the images; the movie was then transferred to a tablet computer to provide real-time guidance during a biopsy. To test the validity of our tool, we divided all consecutive patients undergoing transbronchial needle aspiration retrospectively in two groups based on whether the biopsy was guided by virtual bronchoscopy (virtual bronchoscopy group) or not (traditional group). The intergroup diagnostic yields were statistically compared.

Results
Our analysis included 53 patients in the traditional and 53 in the virtual bronchoscopy group. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy for the traditional group were 66.6%, 100%, 100%, 10.53% and 67.92%, respectively, and for the virtual bronchoscopy group were 84.31%, 100%, 100%, 20% and 84.91%, respectively. The sensitivity ( P  = 0.011) and diagnostic accuracy ( P  = 0.011) of sampling the paratracheal station were better for the virtual bronchoscopy group than for the traditional group; no significant differences were found for the subcarinal lymph node.

Conclusions
Our tool is simple, economic and available in all centres. It guided in real time the needle insertion, thereby improving the accuracy of traditional transbronchial needle aspiration, especially when target lesions are located in a difficult site like the paratracheal station.

Fiorelli|Alfonso|A|
Raucci|Antonio|A|
Cascone|Roberto|R|
Reginelli|Alfonso|A|
Di Natale|Davide|D|
Santoriello|Carlo|C|
Capuozzo|Antonio|A|
Grassi|Roberto|R|
Serra|Nicola|N|
Polverino|Mario|M|
Santini|Mario|M|

Virtual bronchoscopy
Transbronchial needle aspiration
Mediastinal staging


A phase I, open-label, two-stage study to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of the oral AKT inhibitor GSK2141795 in patients with solid tumors.

Abstract: Background We sought to determine the recommended phase II dose (RP2D) and schedule of GSK2141795, an oral pan-AKT kinase inhibitor. Patients and Methods Patients with solid tumors were enrolled in the dose-escalation phase. Pharmacokinetic (PK) analysis after a single dose (Cycle 0) informed dose escalation using accelerated dose titration. Once one grade 2 toxicity or dose-limiting toxicity was observed in Cycle 1, the accelerated dose titration was terminated and a 3 + 3 dose escalation was started. Continuous daily dosing was evaluated along with two intermittent regimens (7 days on/7 days off and 3 times per week). In the expansion phase at RP2D, patients with endometrial or prostate cancer, as well as those with select tumor types with a PIK3CA mutation, AKT mutation or PTEN loss, were enrolled. Patients were evaluated for adverse events (AEs), PK parameters, blood glucose and insulin levels, and tumor response. Results The RP2D of GSK2141795 for once-daily dosing is 75 mg. The most common (>10%) treatment-related AEs included diarrhea, fatigue, vomiting, and decreased appetite. Most AEs were low grade. The frequency of hyperglycemia increased with dose; however, at the RP2D, grade 3 hyperglycemia was only reported in 4% of patients and no grade 4 events were observed. PK characteristics were favorable, with a prolonged half-life and low peak-to-trough ratio. There were two partial responses at the RP2D in patients with either a PIK3CA mutation or PTEN loss. Conclusion GSK2141795 was safe and well-tolerated, with clinical activity seen as monotherapy at the RP2D of 75 mg daily. NCT00920257.

Aghajanian|Carol|C|
Bell-McGuinn|Katherine M|KM|
Burris|Howard A|HA|
Siu|Lillian L|LL|
Stayner|Lee-Ann|LA|
Wheler|Jennifer J|JJ|
Hong|David S|DS|
Kurkjian|Carla|C|
Pant|Shubham|S|
Santiago-Walker|Ademi|A|
Gauvin|Jennifer L|JL|
Antal|Joyce M|JM|
Opalinska|Joanna B|JB|
Morris|Shannon R|SR|
Infante|Jeffrey R|JR|


QEVO® - A new digital endoscopic microinspection tool - A cadaveric study and first clinical experiences (case series).

Abstract:
Background
The use of endoscopes in neurosurgery is well established, but the integration of a full high definition signaling, 45° angled endoscopic tool into a digital surgical microscope, is new. We report our first experiences in a cadaveric study and a clinical case series using the new microinspection tool QEVO® that serves as a plug-in feature for the recently launched KINEVO 900 digital visualization platform (CARL ZEISS MEDITEC, Oberkochen, Germany). For illustration purposes, we offer video footage.

Methods
The handling, workflow, and visualization patterns of the QEVO® microinspection tool were critically evaluated in cadaver specimens by simulating four standardized neurosurgical approaches: (1) pterional, (2) retrosigmoidal, (3) transsphenoidal, (4) and transcallosal. Similarly, we evaluated the QEVO® tool in corresponding clinical cases of (1) aneurysm clipping, (2) removal of cerebellar cavernoma, (3) and pituitary adenomectomy.

Results
In both the cadaveric study and clinical case series, the QEVO® tool was found to be beneficial in terms of high-quality visualization of fine structures and for displaying hidden anatomical details ("looking around the corner"). The handling was good, and the workflow was easy. However, the use of this tool was restricted by the lack of an external fixation and a working channel, the shortness of the tool, and the impossibility to switch to a 0° or 30° optic.

Conclusion
Despite some restrictions, the QEVO® microinspection tool is an innovative, handheld, endoscopic tool that allows excellent additional visualization of the surgical field. In our opinion, this tool effectively enhances the modern neurosurgical armamentarium.

Schebesch|Karl-Michael|KM|
Brawanski|Alexander|A|
Tamm|Ernst R|ER|
Kühnel|Thomas S|TS|
Höhne|Julius|J|

QEVO
microinspection tool
surgical microscope
KINEVO
Endoscopy


Case Report: 18F-FDG PET-CT for Diagnosing Prosthetic Device-Related Infection in an Infant With CHD.

Abstract: Patients who have undergone cardiac surgery using prosthetic devices have an increased risk of developing prosthetic device-related infection and mediastinitis. However, accurate diagnosis of prosthetic device-related infection can be difficult to evaluate and treat with antibiotic therapy alone. In recent years, 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) has made promising contributions to detect infective endocarditis, pacemaker infections, or other inflammations. Nevertheless, 18F-FDG PET-CT for congenital heart disease (CHD) with device infection has been sparsely reported. We present an infantile girl diagnosed with pulmonary atresia with a ventricular septal defect who underwent replacement of the right ventricle-to-pulmonary artery (RV-PA) conduit for improvement cyanosis. She developed high fever and was diagnosed with mediastinitis and bacteremia by Pseudomonas aeruginosa (P. aeruginosa) on postoperative day 4. Mediastinal drainage and 6 weeks of antibiotic therapy improved her condition, but bacteremia flared up on postoperative day 56. Despite a long course of antibiotic therapy, she had two more recurrences of bacteremia with the detection of P. aeruginosa. Echocardiography and chest contrast CT showed no evidence of vegetation and mediastinitis. On postoperative day 115, 18F-FDG PET-CT revealed an accumulation on the RV-PA conduit (SUV max 3.4). Finally, she developed an infectious ventricular pseudo-aneurysm on postoperative day 129 and underwent aneurysm removal and RV-PA conduit replacement on postoperative day 136. Our case showed the importance of 18F-FDG PET-CT for diagnosing specific localization of prosthetic device-related infection which is hard to detect using other imaging techniques. It can be a useful diagnostic tool for infantile patients with CHD with cardiac prosthetic devices and improve subsequent clinical treatments.

Kawamura|Junpei|J| Ueno|Kentaro|K| Taimura|Eri|E| Matsuba|Tomoyuki|T| Imoto|Yutaka|Y| Jinguji|Megumi|M| Kawano|Yoshifumi|Y|

infant
congenital heart disease
device infection
Pseudomonas aeruginosa
SUV max
PET
pediatric
pseudoaneurysm


Development and psychometric testing of the nursing student mentors' competence instrument (MCI): A cross-sectional study.

Abstract:
BACKGROUND
Mentors require competence at a diverse array of skills to mentor students during clinical practice. According to the latest evidence, competence at mentoring includes: knowledge, skills and attributes of individual students' learning objectives, core elements of nursing, learning processes, a reciprocal and trustful relationship, feedback, evaluation, cooperation with stakeholders, and the mentor's personal qualities.

OBJECTIVE
The purpose of the study was to test psychometric properties of a mentor's competence instrument developed to self-evaluate mentors' competence at mentoring nursing students in clinical practice.

DESIGN
A cross-sectional, descriptive, explorative study design was used.

SETTINGS
Data were collected from mentors at five university hospitals in Finland in 2016.

PARTICIPANTS
A total of 576 mentors participated in this study.

METHODS
The instrument was developed through systematic review, experts' evaluations, and pilot versions of the instrument tested in previous studies. The construct validity and reliability of the instrument were tested using exploratory factor analysis (EFA) with promax rotation and Cronbach's alpha.

RESULTS
A 10-factor model showed that the instrument has acceptable construct validity. Cronbach's alpha values for the subscales observed ranged from 0.76 to 0.90.

CONCLUSIONS
The instrument exhibited acceptable psychometric properties, thereby proving itself a valuable tool for evaluating mentors' competence at mentoring students. Further assessments of its reliability, validity and generality for measuring mentor's competence for mentoring students in different contexts and cultures are recommended.

Tuomikoski|Anna-Maria|AM| Ruotsalainen|Heidi|H| Mikkonen|Kristina|K| Miettunen|Jouko|J| Kääriäinen|Maria|M|

Psychometric testing
Nursing
Students
Mentoring
Clinical practice
Instrument development
Validation


Colorectal Carcinogenesis, Radiation Quality, and the Ubiquitin-Proteasome Pathway.

Abstract: Adult colorectal epithelium undergoes continuous renewal and maintains homeostatic balance through regulated cellular proliferation, differentiation, and migration. The canonical Wnt signaling pathway involving the transcriptional co-activator β-catenin is important for colorectal development and normal epithelial maintenance, and deregulated Wnt/β-catenin signaling has been implicated in colorectal carcinogenesis. Colorectal carcinogenesis has been linked to radiation exposure, and radiation has been demonstrated to alter Wnt/β-catenin signaling, as well as the proteasomal pathway involved in the degradation of the signaling components and thus regulation of β-catenin. The current review discusses recent progresses in our understanding of colorectal carcinogenesis in relation to different types of radiation and roles that radiation quality plays in deregulating β-catenin and ubiquitin-proteasome pathway (UPP) for colorectal cancer initiation and progression.

Datta|Kamal|K|
Suman|Shubhankar|S|
Kumar|Santosh|S|
Fornace|Albert J|AJ|

β-catenin
Proteasome
APCMin/+
HZE-particles
High-LET radiation
Intestinal tumor
Space radiation
Tumorigenesis


Discrete-time sliding mode controller based on backstepping disturbance compensation for robust current control of PMSM drives.

Abstract: A robust current control approach with disturbance cross-coupling compensation for permanent magnet synchronous motor drives (PMSM) is proposed in this paper. The proposed approach can enhance the reference tracking and provides a robust option for current control of PMSM drives. A discrete-time sliding mode current controller is proposed. The PMSM model includes the digital implementation delay, present due to the discrete-time algorithm execution. A discrete-time backstepping disturbance observer is developed, being combined to the sliding mode controller as a means to improve the robustness and tracking capability. The effects of coupling, parametric uncertainties and load disturbances are compensated by the backstepping disturbance observer. The stability analysis of the combined system is presented and the limits for overall system stability are discussed. Simulations and experimental results validate the combined scheme and demonstrate the good performance of the proposal.

Gabbi|Thieli S|TS|
de Araujo|Marcelo B|MB|
Rocha|Lucas R|LR|
Scalcon|Filipe P|FP|
Gründling|Hilton A|HA|
Vieira|Rodrigo P|RP|

Discrete-time sliding mode
Backstepping
PMSM


Associations between plasma concentrations of PCB 28 and possible indoor exposure sources in Danish school children and mothers.

Abstract:
BACKGROUND
Polychlorinated biphenyls (PCBs) are ubiquitously present in the environment and are suspected of carcinogenic, neurotoxic and immunotoxic effects. Significantly higher plasma concentrations of the congener PCB 28 occur in children compared to adults. Exposure in schools may contribute to this difference.

OBJECTIVE
To determine whether increased blood plasma concentrations of PCB 28 in Danish school children and mothers are associated with living in homes or attending schools constructed in the PCB period (1959-1977).

METHODS
PCB 28 was analyzed in plasma samples from 116 children aged 6-11years and 143 mothers living in an urban and a rural area in Denmark and participating in the European pilot project DEMOCOPHES (Demonstration of a study to COordinate and Perform Human Biomonitoring on a European Scale). In Denmark, PCBs were used in construction in the period 1950-1977, and year of construction or renovation of the homes and schools was used as a proxy for indoor PCB exposure. Linear regression models were used to assess the association between potential PCB exposure from building materials and lipid adjusted concentrations of PCB 28 in plasma, with and without adjustment for potential confounders.

RESULTS
Among the 116 children and 143 mothers, we were able to specify home construction period in all but 4 children and 5 mothers leaving 111 children and 138 mothers for our analyses. The median lipid adjusted plasma PCB 28 concentration was 3 (range: 1-28) ng/g lipid in the children and 2 (range: 1-8) ng/g lipid in the mothers. Children living in homes built in the PCB period had significantly higher lipid adjusted plasma PCB 28 concentrations compared to children living in homes built before or after the PCB period. Following adjustment for covariates, PCB 28 concentrations in children were 40 (95% CI: 13; 68) percent higher than concentrations of children living in homes constructed at other times. Furthermore, children attending schools built or substantially refurbished in the PCB period also had significantly higher (46%, 95% CI: 22; 70) PCB 28 concentrations compared to children attending schools constructed before or after the PCB period, while their mothers had similar concentrations. Adjustment for the most prevalent congener, PCB 153, did not change this effect of home or school construction. When both home and school construction year were included in the models, the increase in lipid adjusted plasma PCB 28 for children living in or attending schools from the PCB period was no longer statistically significant. The individual effect of home and school construction periods could not be evaluated further with the available data.

CONCLUSION
Our results suggest that PCB exposure in the indoor environment in schools and homes constructed during the PCB period may contribute significantly to children's plasma PCB 28 concentration. Efforts to minimize PCB exposure in indoor environments should be considered.

Egsmose|Emilie Lund|EL|
Bräuner|Elvira Vaclavik|EV|
Frederiksen|Marie|M|
Mørck|Thit Aarøe|TA|
Siersma|Volkert Dirk|VD|
Hansen|Pernille Winton|PW|
Nielsen|Flemming|F|
Grandjean|Philippe|P|
Knudsen|Lisbeth E|LE|

Polychlorinated biphenyl
Homes
Year of construction
Environmental exposure
PCB-exposed population
Residents


Thoracoscopic Localization of Small Peripheral Pulmonary Lesions Using Percutaneous Computed Tomography-guided Pleural Dye Marking: A Retrospective Analysis.

Abstract: Small pulmonary lesions are often difficult to localize during thoracoscopic surgery. We describe a new com-puted tomography (CT)-guided pleural dye-marking method for small peripheral pulmonary lesions that does not involve a visceral pleural puncture. We used this technique for 23 lesions (22 patients) who underwent tho-racoscopic partial lung resection (Nov. 2016-Jan. 2018). With the patient in the lateral decubitus position, pre-operative CT-guided marking on the skin over the lesion was performed. During the surgery, we marked the visceral pleura with a skin marker directly or with an infant-size nutrition catheter with crystal violet at the tip through a venous indwelling needle inserted perpendicular to the skin marking. We localized and resected the lesions in all cases, without complications. The median nodule size measured histopathologically was 8 (4-20) mm overall, and 7 (0-20) mm of the solid part; the median distance from the visceral pleura to the nodule was 9 (1-33) mm. The median operation time was 67 (37-180) min. The median postoperative hospital stay was 3 (3-11) days. Our CT-guided pleural dye-marking method is useful and safe for the localization of small periph-eral pulmonary lesions in thoracoscopic partial lung resections.

Kubo|Yujiro|Y| Watanabe|Mototsugu|M| Choshi|Haruki|H| Matsubara|Kei|K| Shiotani|Toshio|T| Kataoka|Kazuhiko|K|

localization
marking
Small pulmonary lesion
ground glass nodule
thoracocentesis