Development of a calibration methodology for large-volume, solid ⁶⁸Ge phantoms for traceable measurements in positron emission tomography.

Abstract: We have developed a methodology to calibrate the (68)Ge activity concentration in large (9L) cylindrical epoxy phantoms in a way that is traceable to national standards. The method was tested on two prototype cylindrical phantoms that are being used in a clinical trial and gave (68)Ge activity concentration values with combined standard uncertainties of about 1.1%. Imaging data from the phantoms using a calibrated PET-CT scanner gave values consistent with the calibrated activity concentrations within experimental uncertainties.

Zimmerman|B E|BE|
Pibida|L|L|
King|L E|LE|
Bergeron|D E|DE|
Cessna|J T|JT|
Mille|M M|MM|

Traceability
Positron emission tomography
Standards
Germanium-68
PET


Recent progresses in the exploration of machine learning methods as in-silico ADME prediction tools.

Abstract: In-silico methods have been explored as potential tools for assessing ADME and ADME regulatory properties particularly in early drug discovery stages. Machine learning methods, with their ability in classifying diverse structures and complex mechanisms, are well suited for predicting ADME and ADME regulatory properties. Recent efforts have been directed at the broadening of application scopes and the improvement of predictive performance with particular focuses on the coverage of ADME properties, and exploration of more diversified training data, appropriate molecular features, and consensus modeling. Moreover, several online machine learning ADME prediction servers have emerged. Here we review these progresses and discuss the performances, application prospects and challenges of exploring machine learning methods as useful tools in predicting ADME and ADME regulatory properties.

Tao|L|L|
Zhang|P|P|
Qin|C|C|
Chen|S Y|SY|
Zhang|C|C|
Chen|Z|Z|
Zhu|F|F|
Yang|S Y|SY|
Wei|Y Q|YQ|
Chen|Y Z|YZ|

D003198:Computer Simulation
D006801:Humans
D000069550:Machine Learning
D008954:Models, Biological
D004364:Pharmaceutical Preparations
D010599:Pharmacokinetics

Machine learning
ADME
Drug discovery
Absorption
Distribution
Excretion
Metabolism
Molecular descriptors
QSAR


Understanding human resource management practices in Botswana's public health sector.

Abstract: Purpose The purpose of this paper is to assess the management of the public sector health workforce in Botswana. Using institutional frameworks it aims to document and analyse human resource management (HRM) practices, and make recommendations to improve employee and health system outcomes. Design/methodology/approach The paper draws from a large study that used a mixed methods approach to assess performance of Botswana's Ministry of Health (MOH). It uses data collected through document analysis and in-depth interviews of 54 key informants comprising policy makers, senior staff of the MOH and its stakeholder organizations. Findings Public health sector HRM in Botswana has experienced inadequate planning, poor deployment and underutilization of staff. Lack of comprehensive retention strategies and poor working conditions contributed to the failure to attract and retain skilled personnel. Relationships with both formal and informal environments affected HRM performance. Research limitations/implications While document review was a major source of data for this paper, the weaknesses in the human resource information system limited availability of data. Practical implications This paper presents an argument for the need for consideration of formal and informal environments in developing effective HRM strategies. Originality/value This research provides a rare system-wide approach to health HRM in a Sub-Saharan African country. It contributes to the literature and evidence needed to guide HRM policy decisions and practices.

Seitio-Kgokgwe|Onalenna Stannie|OS|
Gauld|Robin|R|
Hill|Philip C|PC|
Barnett|Pauline|P|

D000288:Administrative Personnel
D001902:Botswana
D006280:Health Workforce
D006801:Humans
D007407:Interviews as Topic
D011634:Public Health
D017150:Public Sector
D036301:Qualitative Research
D040841:Resource Allocation

Human resource management
Botswana
Public health sector
Institutional theory


Video Game Addiction and Life Style Changes: Implications for Caregivers Burden.

Abstract: Limitation of available information on caregiver perspective on managing the users excessive use of technology. The present case series explore the caregiver burden related to users addictive use of video game. The users and caregivers approached the service of healthy use of technology (SHUT clinic) for management. They were assessed using Griffith criteria for video game; General Health questionnaire and family burden interview schedule. It demonstrate the addictive use of video game and its impact on users life style and the presence of psychiatric distress/family burden in the caregivers. Caregivers also reported presence of disturbance in psychosocial domains and helplessness to manage the excessive use. It has implications for building support group and service to handle parents' distress and enabling them to handle the dysfunction in users.


Excess stroke incidence in young Aboriginal people in South Australia: Pooled results from two population-based studies.

Abstract: Background Retrospective data indicate increased stroke incidence in Aboriginal/Torres Strait Islander (Indigenous) Australians, possibly with poorer outcomes. We present the first prospective population-based stroke incidence study in Indigenous Australians. Methods We pooled data from ASCEND and SEARCH, two prospective "ideal" South Australian stroke incidence studies, ASCEND conducted in urban Northwestern Adelaide (2009-2010) and SEARCH in five South Australian rural centers (2009-2011). We calculated age-standardized incidence for Aboriginal and non-Aboriginal people. Results The study population comprised 261,403 inhabitants. Among 432 first-ever strokes, 13 were in Aboriginal people (median age 51 vs. 78 years for non-Aboriginal people, p < 0.001). Age-standardized stroke incidence per 100,000 in Aboriginal patients (116, 95% CI: 95-137) was nearly two-fold that of non-Aboriginal patients (67, 95% CI: 51-84). Age-stratified excess incidence in Aboriginal people was restricted to those aged < 55 years (incidence rate ratio (IRR) 3.5, 95% CI: 2-7), particularly for intracerebral hemorrhage (IRR: 16, 95% CI: 4-61). Conclusion The excess stroke incidence in Aboriginal South Australians appears substantial, especially in those aged <55 years. Further work is required to delineate and address disparities.

Balabanski|Anna H|AH|
Newbury|Jonathan|J|
Leyden|James M|JM|
Arima|Hisatomi|H|
Anderson|Craig S|CS|
Castle|Sally|S|
Cranefield|Jennifer|J|
Paterson|Tracey|T|
Thrift|Amanda G|AG|0000-0001-8533-4170
Katzenellenbogen|Judith|J|
Brown|Alex|A|
Kleinig|Timothy J|TJ|

Stroke
Aboriginal
epidemiology
hemorrhagic stroke
ischemic stroke


Dynamic Susceptibility Contrast Magnetic Resonance Imaging Protocol of the Normal Canine Brain.

Abstract: Perfusion magnetic resonance imaging (MRI), specifically dynamic susceptibility MRI (DSC-MRI) is routinely performed as a supplement to conventional MRI in human medicine for patients with intracranial neoplasia and cerebrovascular events. There is minimal data on the use of DSC-MRI in veterinary patients and a DSC-MRI protocol in the veterinary patient has not been described. Sixteen normal dogs, 6 years or older were recruited for this study. The sample population included 11 large dogs (>11 kg) and 5 small dogs (<11 kg). DSC-MRI was performed on a 1.5-T MRI using an adjusted protocol inherent to the MRI. Contrast media was injected using an automatic power injector. Injections were made after five MR measurements were obtained. Following image acquisition, an arterial input function (AIF) graph mapping the transit time of contrast within the cerebral arteries was generated. The manually selected time points along this graph were used to compute perfusion maps. A dose and rate of 0.1 mmol/kg gadolinium-based contrast media at 3 ml/s followed by 10 ml saline flush at 3 ml/s was used in all dogs greater than 11 kg. In all dogs >11 kg, a useable AIF and perfusion map was generated. One dog less than 11 kg received the same contrast dose and rate. In this patient, the protocol did not generate a useable AIF. The remainder of the dogs less than 11 kg followed a protocol of 0.2 mmol/kg gadolinium-based contrast media at 1.5 ml/s with a 10 ml saline flush at 1.5 ml/s. A useable AIF and perfusion map was generated in the remaining dogs <11 kg using the higher contrast dose and slower rate protocol. This study establishes a contrast dose and administration rate for canine DSC-MRI imaging that is different in dogs greater than 11 kg compared to dogs less than 11 kg. These protocols may be used for future applications to evaluate hemodynamic disturbances in canine intracranial pathology.

Stadler|Krystina L|KL|
Pease|Anthony P|AP|
Ballegeer|Elizabeth A|EA|

dynamic susceptibility contrast
magnetic resonance imaging
canine
perfusion
neuroimaging


Effect of saikosaponins and extracts of vinegar-baked Bupleuri Radix on the activity of β-glucuronidase.

Abstract: In Traditional Chinese Medicine, liver targeting is usually achieved by coadministration with Vinegar-baked Radix Bupleuri (VBRB), but the mechanism is unclear. In this paper, the influence of VBRB on the activity of β-glucuronidase was investigated and compared with that of saikosaponins. The activity of β-glucuronidase was measured by microplate reader using a 4-nitrophenyl-β-d-glucuronide substrate. The change of 4-nitrophenol content was used to characterize the activity of β-glucuronidase. Bupleurum chinenes were found to be the inhibitor of β-glucuronidase. The inhibition rate of Bupleurum chinenes extracts BC1 (high molecular weight polysaccharides), BC2 (ethanol soluble/water insoluble component), BC3 (extracted by n-butanol, soluble in water), and BC4 (low molecular weight water soluble parts) on the activity of β-glucuronidase was found to be 45.15%, 33.94%, 24.94%, and 34.54%, respectively, after 1 h incubation, with BC1 showing the highest inhibition rate. In contrast, the saikosaponins were demonstrated to be the promoter of β-glucuronidase, with promotion rates of 333.56%, 217.04%, 247.87%, 149.75%, and 92.50% for saikosaponin standard samples A, B, B2, C, and D, respectively, (p<0.05). In conclusion, inhibiting the activity of β-glucuronidase might be one of the reasons why VBRB could influence drug distribution upon its coadministration with other drugs. Since saikosaponins and VBRB extracts have opposite effect, more attention should be paid to the content of saikosaponins in the extracts upon its application.

Chen|Xianzhi|X| Yu|Tongya|T| Chen|Zhenxing|Z| Zhao|Ruizhi|R| Mao|Shirui|S|

saikosaponins
β-glucuronidase
vinegar-baked Radix Bupleuri (VBRB)
4-Nitrophenyl-β-d-glucuronide


Reversible Mechanical Regulation and Splicing Ability of Alginate-Based Gel Based on Photo-Responsiveness of Molecular-Level Conformation.

Abstract: In this study, benefiting from the sensitive molecular conformation transversion in azobenzene, a new strategy for fabricating alginate gels with the abilities of splicing and photo-responsive mechanical adjustment is reported. Firstly, a 4,4'-azobis(benzoylhydrazide) (Azo-hydrazide) linker was used to crosslink alginate physically via the electrostatic interaction between hydrazide groups and carboxyl groups. It was then shaped and transferred in situ to a chemically crosslinked gel via 450 nm light irradiation. Under the irradiation, the molecular conformation change of azobenzene in the linker was able to form covalent bonds at the crosslinking points of the gels. Furthermore, the reversible conformation transformation of azobenzene was able to induce the increase and decrease of the storage modulus under irradiation with 365 nm light and 450 nm light, respectively, while also providing gel-like mechanical properties, depending upon the irradiation time and given wavelength. Meanwhile, the results also indicated that active groups could contribute to the splicing ability of the gel and construct a hollow cavity structure. It is believed that this work could provide a versatile strategy for preparing photo-responsive gels with reversibly tunable mechanical properties.

Ma|Xiaozhou|X| He|Linhai|L| Wan|Xingjie|X| Xiang|Shunyu|S| Fan|Yu|Y| Xiong|Xia|X| Gan|Lin|L| Huang|Jin|J|

azobenzene
alginate gel
mechanical adjustment
photo-responsive gel
gel splicing


Reduced CSF leak in complete calvarial reconstructions of microvascular decompression craniectomies using calcium phosphate cement.

Abstract:
OBJECT
Calcium phosphate cement provides a biomaterial that can be used for calvarial reconstruction in a retrosigmoid craniectomy for microvascular decompression (MVD). This study evaluates the outcomes of postoperative CSF leak and wound infection for patients undergoing a complete cranioplasty using calcium phosphate cement versus incomplete cranioplasty using polyethylene titanium mesh following a retrosigmoid craniectomy for MVD.

METHODS
The authors evaluated 211 cases involving patients who underwent first-time retrosigmoid craniectomies performed by a single attending surgeon fortrigeminal neuralgia from October 2008 to June 2014. From this patient population, 111 patients underwent calvarial reconstruction after retrosigmoid craniectomy using polyethylene titanium mesh, and 100 patients had reconstructions using calcium phosphate cement. A Pearson's chi-square test was used to compare postoperative complications of CSF leak and wound infection in these 2 types of cranioplasties.

RESULTS
The polyethylene titanium mesh group included 5 patients (4.5%) with postoperative CSF leak or pseudomeningocele and 3 patients (2.7%) with wound infections. In the calcium phosphate cement group, no patients had a CSF leak, and 2 patients (2%) had wound infections. This represented a statistically significant reduction of postoperative CSF leak in patients who underwent calcium phosphate reconstructions of their calvarial defect compared with those who underwent polyethylene titanium mesh reconstructions (p = 0.03). No significant difference was seen between the 2 groups in the number of patients with postoperative wound infections.

CONCLUSIONS
Calcium phosphate cement provides a viable alternative biomaterial for calvarial reconstruction of retrosigmoid craniectomy defects in patients who have an MVD. The application of this material provides a biocompatible barrier that reduces the incidence of postoperative CSF leaks.

Eseonu|Chikezie I|CI|
Goodwin|C Rory|CR|
Zhou|Xin|X|
Theodros|Debebe|D|
Bender|Matthew T|MT|
Mathios|Dimitrios|D|
Bettegowda|Chetan|C|
Lim|Michael|M|

microvascular decompression
calcium phosphate
retrosigmoid craniectomy
infection
cranioplasty
titanium mesh
MMA = methyl methacrylate
MVD = microvascular decompression
cerebrospinal fluid leak
diagnostic and operative techniques


Silica Nanoparticles as a Probable Anti-Oomycete Compound Against Downy Mildew, and Yield and Quality Enhancer in Grapevines: Field Evaluation, Molecular, Physiological, Ultrastructural, and Toxicity Investigations.

Abstract: Downy mildew is the most destructive disease of grapevines in the regions of relatively warm and humid climate causing up to 50% yield losses. Application of silicon- (Si-) based products have been extensively studied against various oomycete, fungal, bacterial, and viral plant diseases, but studies on Si application in their nanosize are limited. In this study, the field application of silica nanoparticles (SiNPs) on Thompson Seedless grapevines (H4 strain) infected with downy mildew was evaluated. In addition, molecular, physiological, ultrastructural, and toxicity investigations were also conducted. The obtained results revealed that spraying of grapevines with SiNPs at 150 ppm significantly overexpressed the transcription factor jasmonate and ethylene-responsive factor 3 recording 8.7-fold, and the defense-related genes β-1,3-glucanase (11-fold), peroxidase (10.7-fold) pathogenesis-related-protein 1 (10.6-fold), and chitinase (6.5-fold). Moreover, a reduction up to 81.5% in the disease severity was achieved in response to this treatment. Shoot length and yield per grapevine were considerably enhanced recording up to 26.3 and 23.7% increase, respectively. The berries quality was also improved. Furthermore, this treatment led to an enhancement in the photosynthetic pigments, induction of phenolic and ascorbic acid contents, an increase in the activity of peroxidase and polyphenol oxidase enzymes, and a reduction in the cellular electrolyte leakage, lipid peroxidation, and H2O2 content. Scanning electron microscopy observations showed an increase up to 86.6% in the number of closed stomata and a reduction up to 55% in the average stomatal pore area in response to this treatment. Observations of the transmission electron microscopy showed ultrastructural alterations in the cells of a grapevine leaf due to the infection with downy mildew, including plasmolysis and disruption of the cellular components, abnormal chloroplasts, and thickening of the cell wall and cell membrane. These abnormal alterations were reduced in response to SiNPs spray. In contrast, this study also showed that this treatment had considerable cytotoxic and genotoxic effects at this direct dose/concentration. So, additional investigations to determine the SiNPs residue in the produced edible plant parts are urgently needed. In addition, the pre-harvest interval, toxicity index, and risk assessment should be evaluated before any recommendation for use.

Rashad|Younes M|YM|
El-Sharkawy|Hany H A|HHA|
Belal|Bassam E A|BEA|
Abdel Razik|Elsayed S|ES|
Galilah|Doaa A|DA|

downy mildew
grapevine
SiNPs
Plasmopara viticola
plant resistance


Increased serum levels of adhesion molecules ICAM-1 and VCAM-1 in systemic sclerosis are not specific for pulmonary manifestations.

Abstract: Studies suggest elevated serum intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) levels may be markers of pulmonary arterial hypertension in systemic sclerosis (SSc-PAH). We sought to evaluate whether ICAM-1 and VCAM-1 levels are useful screening biomarkers for incident SSc-PAH. In this cross-sectional study, four groups were selected from the Australian Scleroderma Cohort Study: group 1 (n = 15) had definite PAH; group 2 (n = 19) had interstitial lung disease (ILD); group 3 (n = 30) were SSc-controls; and group 4 (n = 34) were healthy controls. Serum ICAM-1 and VCAM-1 levels were measured using the Millipore Milliplex MAP Human 2-Plex Panel. There were no differences in ICAM-1 levels in the PAH versus ILD group (263.0 ± 85.4 vs 380.4 ± 168.3 ng/mL, p = 0.136), SSc-controls (263.0 ± 85.4 vs 253.1 ± 98.0 ng/mL, p = 1.00), or healthy controls (263.0 ± 85.4 vs 201.8 ± 57.2 ng/mL, p = 0.093). Similarly, there were no differences in VCAM-1 level in PAH versus ILD groups (1476.2 ± 434.9 vs 1424.8 ± 527.6 ng/mL, p = 1.00) and SSc-controls (1476.2 ± 434.9 vs 1409.5 ± 341.1 ng/mL, p = 1.00). SSc subjects had significantly higher levels of ICAM-1 (297.4 ± 134.0 vs 201.8 ± 57.2 ng/mL, p < 0.0001) and VCAM-1 compared to healthy controls (1432.7 ± 427.4 vs 1125.6 ± 273.4 ng/mL, p < 0.0001). Neither ICAM-1 nor VCAM-1 is a specific screening biomarker of SSc-PAH. Instead, increased levels of these adhesion molecules in SSc, irrespective of pulmonary complications, suggest that they may play a role in SSc pathogenesis.

Thakkar|Vivek|V|
Patterson|Karen A|KA|
Stevens|Wendy|W|
Wilson|Michelle|M|
Roddy|Janet|J|
Sahhar|Joanne|J|
Proudman|Susanna|S|
Hissaria|Pravin|P|
Nikpour|Mandana|M|

D019010:Vascular Cell Adhesion Molecule-1

Intercellular adhesion molecule-1 (ICAM-1)

Vascular cell adhesion molecule-1 (VCAM-1)


Causal information quantification of prominent dynamical features of biological neurons.

Abstract: Neurons tend to fire a spike when they are near a bifurcation from the resting state to spiking activity. It is a delicate balance between noise, dynamic currents and initial condition that determines the phase diagram of neural activity. Many possible ionic mechanisms can be accounted for as the source of spike generation. Moreover, the biophysics and the dynamics behind it can usually be described through a phase diagram that involves membrane voltage versus the activation variable of the ionic channel. In this paper, we present a novel methodology to characterize the dynamics of this system, which takes into account the fine temporal 'structures' of the complex neuronal signals. This allows us to accurately distinguish the most fundamental properties of neurophysiological neurons that were previously described by Izhikevich considering the phase-space trajectory, using a time causal space: statistical complexity versus Fisher information versus Shannon entropy.

Montani|Fernando|F|
Baravalle|Roman|R|
Montangie|Lisandro|L|
Rosso|Osvaldo A|OA|

neurons
statistical complexity
entropy
Fisher information measure


Diagnostic performance of the urinary canine calgranulins in dogs with lower urinary or urogenital tract carcinoma.

Abstract:
BACKGROUND
Onset of canine transitional cell carcinoma (TCC) and prostatic carcinoma (PCA) is usually insidious with dogs presenting at an advanced stage of the disease. A biomarker that can facilitate early detection of TCC/PCA and improve patient survival would be useful. S100A8/A9 (calgranulin A/B or calprotectin) and S100A12 (calgranulin C) are expressed by cells of the innate immune system and are associated with several inflammatory disorders. S100A8/A9 is also expressed by epithelial cells after malignant transformation and is involved in the regulation of cell proliferation and metastasis. S100A8/A9 is up-regulated in human PCA and TCC, whereas the results for S100A12 have been ambiguous. Also, the urine S100A8/A9-to-S100A12 ratio (uCalR) may have potential as a marker for canine TCC/PCA. Aim of the study was to evaluate the diagnostic accuracy of the urinary S100/calgranulins to detect TCC/PCA in dogs by using data and urine samples from 164 dogs with TCC/PCA, non-neoplastic urinary tract disease, other neoplasms, or urinary tract infections, and 75 healthy controls (nested case-control study). Urine S100A8/A9 and S100A12 (measured by species-specific radioimmunoassays and normalized against urine specific gravity [S100A8/A9USG; S100A12USG], urine creatinine concentration, and urine protein concentration and the uCalR were compared among the groups of dogs.

RESULTS
S100A8/A9USG had the highest sensitivity (96%) and specificity (66%) to detect TCC/PCA, with specificity reaching 75% after excluding dogs with a urinary tract infection. The uCalR best distinguished dogs with TCC/PCA from dogs with a urinary tract infection (sensitivity: 91%, specificity: 60%). Using a S100A8/A9USG ≥ 109.9 to screen dogs ≥6 years of age for TCC/PCA yielded a negative predictive value of 100%.

CONCLUSIONS
S100A8/A9USG and uCalR may have utility for diagnosing TCC/PCA in dogs, and S100A8/A9USG may be a good screening test for canine TCC/PCA.

Heilmann|Romy M|RM|
McNiel|Elizabeth A|EA|
Grützner|Niels|N|
Lanerie|David J|DJ|
Suchodolski|Jan S|JS|
Steiner|Jörg M|JM|

Transitional cell carcinoma
Biomarker
S100A8/A9
Calprotectin
S100A12
Diagnostic accuracy


HPV-FRAME: A consensus statement and quality framework for modelled evaluations of HPV-related cancer control.

Abstract: Intense research activity in HPV modelling over this decade has prompted the development of additional guidelines to those for general modelling. A specific framework is required to address different policy questions and unique complexities of HPV modelling. HPV-FRAME is an initiative to develop a consensus statement and quality-based framework for epidemiologic and economic HPV models. Its development involved an established process. Reporting standards have been structured according to seven domains reflecting distinct policy questions in HPV and cancer prevention and categorised by relevance to a population or evaluation. Population-relevant domains are: 1) HPV vaccination in pre-adolescent and young adolescent individuals; 2) HPV vaccination in older individuals; 3) targeted vaccination in men who have sex with men; 4) considerations for individuals living with HIV and 5) considerations for low- and middle-income countries. Additional considerations applicable to specific evaluations are: 6) cervical screening or integrated cervical screening and HPV vaccination approaches and 7) alternative vaccine types and alternative dosing schedules. HPV-FRAME aims to promote the development of models in accordance with an explicit framework, to better enable target audiences to understand a model's strength and weaknesses in relation to a specific policy question and ultimately improve the model's contribution to informed decision-making.

Canfell|Karen|K|
Kim|Jane J|JJ|
Kulasingam|Shalini|S|
Berkhof|Johannes|J|
Barnabas|Ruanne|R|
Bogaards|Johannes A|JA|
Campos|Nicole|N|
Jennett|Chloe|C|
Sharma|Monisha|M|
Simms|Kate T|KT|
Smith|Megan A|MA|
Velentzis|Louiza S|LS|
Brisson|Marc|M|
Jit|Mark|M|

Modelling
Guidelines
Prevention
Vaccination
Cervical screening
Human papillomavirus


Enrichment of circulating trophoblasts from maternal blood using laminar microscale vortices.

Abstract:
OBJECTIVE
Enrichment of circulating trophoblasts (CTs) from maternal blood at week 11-13 of gestation, using laminar microscale vortices, and evaluation of the performance of the VTX-1 Liquid Biopsy System in terms of CT recovery and purity.

METHOD
Eight mililiter of blood was collected from 15 pregnant women and processed with the VTX-1 Liquid Biopsy System. Y-chromosome specific quantitative PCR was performed to estimate the number of enriched male CTs. To evaluate the VTX-1 performance, the target cell recovery was characterized by spiking experiments with a trophoblast cell line. Furthermore, the total quantity of DNA after enrichment was used to calculate the number of retained maternal cells.

RESULTS
Successful recovery of male CTs was established in 7 out of 10 first trimester samples from pregnant women carrying a male fetus. The number of CTs, recovered from 8 ml of blood, was estimated between two and six. Spiking experiments resulted in a CT recovery of ±35 % with ±1524 retained maternal blood cells.

CONCLUSION
CTs can be enriched from maternal blood with high purity, using laminar microscale vortices, starting from 8 ml of blood.

noninvasive prenatal testing < fetal cells, nucleic acids & proteins

prenatal diagnosis, fetal cells < fetal cells, nucleic acids & proteins


Association between diabetes complications and leukocyte counts in Iranian patients.

Abstract:
BACKGROUND
The long term complications of diabetes can be fatal. They are also renowned for being an economic burden. Previous studies have demonstrated a relationship between inflammatory markers and complications of diabetes. The objective of this study was to evaluate the relationship between leukocyte counts and these complications.

METHODS
The study included 184 patients diagnosed with type 2 diabetes. The study was carried out in Iran during 2007 and 2008. Data collected on the subjects were as follows: age, gender, weight, height, blood pressure, smoking history, lipid profile including low density lipoprotein (LDL), high density lipoprotein (HDL), total cholesterol, triglycerides, and leukocyte count, albuminuria, and retinopathy. Furthermore, information on cardiac history for 100 patients was collected. The subjects were split into two groups according to their leukocyte levels: low (≤7000/mm(3)) and high (>7000/mm(3)); and then analyzed by Student's t-test or Mann-Whitney U-test as appropriate.

RESULTS
The average leukocyte count in these patients was 7594 ± 1965/mm(3). Leukocyte count was significantly different in patients with and without retinopathy and albuminuria (P < 0.0001). According to this analysis, a leukocyte count of 6750/mm(3) with a sensitivity of 80.2% and a specificity of 56.4%, and a count of 7550/mm(3) with a sensitivity of 63.2% and a specificity of 74.6% indicated at least one diabetes complication.

CONCLUSION
An elevated leukocyte count even within the normal range was associated with chronic complications in type 2 diabetes.

Moradi|Sedigheh|S|
Kerman|Scott Reza Jafarian|SR|
Rohani|Farzaneh|F|
Salari|Fereshteh|F|

diabetes complications
leukocytes
inflammation


Nitrogen release from urea with different coatings.

Abstract:
BACKGROUND
Coatings or urease inhibitors are designed to reduce losses of ammonia [NH3(g) ] from urea fertilizers. However, nitrogen (N) release and its effects on soil solution have not previously been evaluated under standardized conditions in soils. In this study, the urea fertilizers were incubated in chambers filled with sandy loam soil, adapted for the collection of NH3(g) and soil solution by centrifugation.

RESULTS
In the fast-release N fertilizers, around 93% and 100% of urea-N applied was recovered within the first hours of incubation. In contrast, in the slow-release N fertilizers, less than 40% of urea-N applied, was recovered at 19 days of incubation. The maximum N release from the fertilizers followed the order: UP1 (106%) ≈ UNBPT (102%) ≈ urea (93%) > USP2 (57%) ≈ USP3 (57%) > USP4 (31%) ≈ USP5 (18%). NH3(g) volatilization accounted for only 3% of the applied N in the slow-release fertilizers, which corresponded to about 88% less than the NH3(g) loss from prilled urea.

CONCLUSION
This study demonstrated distinct N release patterns, which changed the N dynamics in the soil. Some coatings effectively delayed urea release from granules and reduced NH3(g) gas losses, while other were not efficient. © 2017 Society of Chemical Industry.

volatilization
slow-release fertilize
N-(n-butyl) thiophosphoric triamide
hydrolysis


Synthesis and Catalytic Activity of Atrane-type Hard and Soft Lewis Superacids with a Silyl, Germyl, or Stannyl Cationic Center.

Abstract: The synthesis and isolation of atrane-type molecules 1E+ (E=Si, Ge, or Sn) having a cationic group 14 elemental center are reported. The cations 1E+ act as hard and soft Lewis superacids, which readily interact with various hard and soft Lewis basic substrates. The rigid atrane framework stabilizes the localized positive charge on the elemental center and assists the formation of the well-defined highly coordinated states of 1E+ . The cations were applied to the hydrodefluorination, Friedel-Crafts reaction, alkyne cyclization, and carbonyl reduction as Lewis acid catalysts. Most notably, [1Si][ClO4 ] exhibits unique chemoselectivity that depends on a solvent in the competitive reaction of silyl enol ether with a mixture of benzaldehyde dimethyl acetal and benzaldehyde. Our findings indicate the potential of hard and soft Lewis superacids in organic synthesis.

hard and soft Lewis superacid
group 14 element
Lewis acid catalyst
chemoselectivity
cationic metal center


A Self-Supported λ-MnO2 Film Electrode used for Electrochemical Lithium Recovery from Brines.

Abstract: Lithium recovery from an aqueous resource was accelerated by electrochemically driving the transformation of MnIV /MnIII with a spinel λ-MnO2 film electrode. A λ-MnO2 electrode without binders or conductive additives is preferred for achieving a large capacity at high current density and long-term cycling capability. In this study, a film of Mn(OH)2 was first deposited on the surface of Pt or graphite substrates owing to alkalization near the cathode, then it was oxidized to a Mn3 O4 film by air, followed by being hydrothermally lithiated to LiMn2 O4 spinel and, finally, it was turned into the λ-MnO2 film electrode through potentiostatic delithiation. The results show that the charging/discharging electric capacity of the fabricated λ-MnO2 film electrode was up to ≈100 mAh g-1 at a current density of 50 mA g-1 in 30 mm Li+ aqueous solution, twice that of the λ-MnO2 powder electrode. Also, 82.3 % lithium capacity remained after 100 cycles of an electrochemically assisted lithium recovery process, indicating high availability and good stability of the λ-MnO2 spinel on the electrode. The energy consumption for each cycle is estimated to be approximately 1.55±0.09 J, implying that only 4.14 Wh is required for recovery of one mole of lithium ions by this method.

λ-MnO2
electrodes
lithium recovery
polypyrroles
spinel LiMn2O4


Gut microorganisms and their metabolites modulate the severity of acute colitis in a tryptophan metabolism-dependent manner.

Abstract:
PURPOSE
Growing evidence shows that nutrient metabolism affects inflammatory bowel diseases (IBD) development. Previously, we showed that deficiency of indoleamine 2,3-dioxygenase 1 (Ido1), a tryptophan-catabolizing enzyme, reduced the severity of dextran sulfate sodium (DSS)-induced colitis in mice. However, the roles played by intestinal microbiota in generating the differences in disease progression between Ido1+/+ and Ido1-/- mice are unknown. Therefore, we aimed to investigate the interactions between the intestinal microbiome and host IDO1 in governing intestinal inflammatory responses.

METHODS
Microbial 16s rRNA sequencing was conducted in Ido1+/+ and Ido1-/- mice after DSS treatment. Bacteria-derived tryptophan metabolites were measured in urine. Transcriptome analysis revealed the effects of the metabolite and IDO1 expression in HCT116 cells. Colitis severity of Ido1+/+ was compared to Ido1-/- mice following fecal microbiota transplantation (FMT).

RESULTS
Microbiome analysis through 16S-rRNA gene sequencing showed that IDO1 deficiency increased intestinal bacteria that use tryptophan preferentially to produce indolic compounds. Urinary excretion of 3-indoxyl sulfate, a metabolized form of gut bacteria-derived indole, was significantly higher in Ido1-/- than in Ido1+/+ mice. Transcriptome analysis showed that tight junction transcripts were significantly increased by indole treatment in HCT116 cells; however, the effects were diminished by IDO1 overexpression. Using FMT experiments, we demonstrated that bacteria from Ido1-/- mice could directly attenuate the severity of DSS-induced colitis.

CONCLUSIONS
Our results provide evidence that a genetic defect in utilizing tryptophan affects intestinal microbiota profiles, altering microbial metabolites, and colitis development. This suggests that the host and intestinal microbiota communicate through shared nutrient metabolic networks.

Shin|Ji-Hee|JH|
Lee|Young-Kwan|YK|
Shon|Woo-Jeong|WJ|
Kim|Bora|B|
Jeon|Che Ok|CO|
Cho|Joo-Youn|JY|
Morse|Herbert C|HC|
Choi|Eun Young|EY|
Shin|Dong-Mi|DM|

Colitis
Tryptophan
Indoleamine 2,3-dioxygenase 1
Indole
Gut microbiota


Surface Interactions between Bacterial Nanocellulose and B-Complex Vitamins.

Abstract: The interactions between films of bacterial nanocellulose (BNC) and B complex vitamins were studied using a Quartz Crystal Microbalance with Dissipation monitoring (QCM-D). Thin films of BNC were generated in situ by QCM-D, followed by real-time measurements of the vitamin adsorption. The desorption of vitamins was induced by rinsing the system using phosphate buffers at a pH of 2 and 6.5, emulating gastric conditions. Changes in frequency (which are proportional to changes in adsorbed mass, ∆m) detected by QCM-D were used to determine the amounts of vitamin adsorbed and released from the BNC film. Additionally, changes in dissipation (∆D) were proven to be useful in identifying the effects of the pH in both pristine cellulose films and films with vitamin pre-adsorbed, following its changes during release. The effects of pH on the morphology of the vitamin-BNC surfaces were also monitored by changes in rugosity from images obtained by atomic force microscopy (AFM). Based on this data, we propose a model for the binding phenomena, with the contraction on the relaxation of the cellulose film depending on pH, resulting in an efficient vitamin delivery process.

Sánchez-Osorno|Diego Mauricio|DM|
Gomez-Maldonado|Diego|D|
Castro|Cristina|C|0000-0002-8994-597X
Peresin|María Soledad|MS|

D058525:Quartz Crystal Microbalance Techniques

bacterial nanocellulose
vitamins
QCM-D
adsorption
release


Cross-infection of virulent Dichelobacter nodosus between sheep and co-grazing cattle.

Abstract: Dichelobacter nodosus is the main aetiological agent of ovine footrot and the bacterium has also been associated with interdigital dermatitis is cattle. The aim of this study was to investigate possible cross-infection of virulent D. nodosus between sheep and co-grazing cattle. Five farms, where sheep previously diagnosed with virulent D. nodosus were co-grazing with cattle for different periods of time, were included. The study sample consisted of 200 cows and 50 sheep. All cows were examined for the presence of interdigital dermatitis, and ten ewes, preferably with symptoms of footrot, had the footrot scores recorded. On each farm, the same ten ewes and ten cows were chosen for bacterial analyses. Swabs were analysed for D. nodosus by PCR and culturing. D. nodosus isolates were virulence-tested and assigned to serogroups by fimA variant determination. Biopsies were evaluated histopathologically and analysed by fluorescent in situ hybridization for D. nodosus, Treponema spp. and Fusobacterium necrophorum. D. nodosus defined as virulent by the gelatin gel test were isolated from 16 sheep from four farms and from five cows from two of the same farms. All five cows had interdigital dermatitis. Two of the cows stayed infected for at least eight months. By pulsed-field gel electrophoresis (PFGE), the isolates from the five cows were found to be genetically indistinguishable or closely related to isolates from sheep from the same farm. This indicates that cross-infection between sheep and cows have occurred.

Knappe-Poindecker|Maren|M|
Gilhuus|Marianne|M|
Jensen|Tim K|TK|
Vatn|Synnøve|S|
Jørgensen|Hannah J|HJ|
Fjeldaas|Terje|T|

Cross-infection
Dichelobacter nodosus
Sheep
Cattle


NKILA inhibits NF-κB signaling and suppresses tumor metastasis.

Abstract: The long non-coding RNA (lncRNA) NKILA (nuclear transcription factor NF-κB interacting lncRNA) functions as a suppressor in human breast cancer and tongue cancer. However, the clinical significance and biological roles of NKILA in esophageal squamous cell carcinoma (ESCC) remain unknown. In this study, we showed that NKILA was downregulated in ESCC tissues and cancer cells compared with their normal counterparts. Low NKILA expression correlated with large tumor size and advanced TNM stage, and predicted poor overall and disease-free survival of ESCC patients. Further loss- and gain-of-function assays indicated that NKILA inhibited proliferation and migration of ESCC cells in vitro, suppressed tumor growth and lung metastasis in vivo. Mechanistically, NKILA could inhibit phosphorylation of IκBα, suppress p65 nuclear translocation and downregulate the expression of NF-κB target genes in ESCC cells. These results suggest NKILA could suppress malignant development of ESCC via abrogation of the NF-κB signaling and may potentially serve as a prognostic marker for ESCC.

Ke|Shun|S| Li|Rui-Chao|RC| Meng|Fan-Kai|FK| Fang|Ming-Hao|MH|

D000077277:Esophageal Squamous Cell Carcinoma

D060888:Real-Time Polymerase Chain Reaction

NKILA
NF-κB
metastasis
long non-coding RNA
esophageal squamous cell carcinoma


Life satisfaction and positive and negative feelings of workers: a systematic review protocol.

Abstract:
BACKGROUND
In this article, conceptualization of well-being is a starting point. According to Diener, subjective well-being refers to all kinds of evaluation, both positive and negative, people make about their own lives. It includes cognitive assessments, such as satisfaction with life and satisfaction with work, as well as affective reactions to life events, such as sadness and contentment. Low levels of health and well-being in workers lead to many consequences. Sick leave, low productivity, and absenteeism are some examples. In this systematic review, the main objective is to assess workers' subjective well-being.

METHODS
The studies should include workers, whether they are paid or volunteers. Also, they must assess workers' subjective well-being. Observational peer-reviewed studies will be included. Qualitative studies will be excluded. The primary outcomes to be considered are the subjective well-being indicators described. Only studies that used six (6) instruments, developed by Diener, will be included. The instruments are Satisfaction With Life Scale (SWLS), Scale of Positive and Negative Experience (SPANE), Positive Thinking Scale (PTS), Flourishing Scale (FS), Comprehensive Inventory of Thriving (CIT), and Brief Inventory of Thriving (BIT). The studies will come from Scientific Electronic Library Online (SciELO), Biblioteca Virtual em Saúde (BVS), Portal da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), MEDLINE, Embase, Web of Science, and Global Index Medicus databases. The studies must be written in Portuguese, English, or Spanish.

DISCUSSION
As far as we know, this is the first systematic review related specially to workers' subjective well-being. We hope that this study contributes to the "well-being at work" discussion and also to the development of effective interventions, used outside and inside organizations, that could improve well-being scores and increase correlate variables scores such as general health, social relations, and quality of life.

SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42016039520.

Worker
Systematic review
Protocol
Subjective well-being


Leveraging an Implementation- Research Partnership to Improve Effectiveness of Nutrition-Sensitive Programs at the World Food Programme.

Abstract:
BACKGROUND
Nutrition-sensitive programs can accelerate progress in addressing malnutrition. However, evidence gaps exist related to their effectiveness and how to optimize program design and implementation.

OBJECTIVE
We present the process the International Food Policy Research Institute and the World Food Programme (WFP) used to develop nutrition-sensitive program guidance and plans for improving program effectiveness and contributing to the evidence base through rigorous evaluations.

METHODS
A 5-step process, using principles of design thinking (a systematic, iterative analytical approach to problem solving), was used to develop, test, and refine WFP's nutrition-sensitive guidance. The guidance focuses on improving nutrition outcomes for nutritionally vulnerable groups across the life cycle: women and children in the first 1000 days, preschoolers, schoolchildren, and adolescents.

RESULTS
Through iterative consultations, we created WFP's nutrition-sensitive guidance that includes harmonized theories of change across WFP's programs; 7 opportunities to enhance the programs' nutrition-sensitivity; and mapping of these opportunities to WFP programs and key evidence gaps. This guidance has been rolled out to WFP's offices worldwide to support improved nutrition outcomes. Finally, several evaluation designs have been proposed to fill identified evidence gaps.

CONCLUSIONS
By leveraging our implementation-research partnership, we expect that WFP's programs will be more effective and cost effective for improving nutrition. This can be assessed through coupling newly designed nutrition-sensitive programs with rigorous evaluations. Evaluation results will be used to refine WFP's nutrition-sensitive guidance and improve their programs globally. This guidance, and creation process, could be useful for others interested in designing nutrition-sensitive programs and increasing program effectiveness for nutrition.

Olney|Deanna K|DK|0000-0002-2420-8565
Marshall|Quinn|Q|
Honton|Geraldine|G|
Ogden|Kathryn|K|
Hambayi|Mutinta|M|
Piccini|Sarah|S|
Go|Ara|A|
Gelli|Aulo|A|
Bliznashka|Lilia|L|

program effectiveness
implementation science
implementation–research partnership
nutrition sensitive


Managing reversal of direct oral anticoagulants in emergency situations. Anticoagulation Education Task Force White Paper.

Abstract: Anticoagulation is the cornerstone of prevention and treatment of venous thromboembolism (VTE) and stroke prevention in patients with atrial fibrillation (AF). However, the mechanisms by which anticoagulants confer therapeutic benefit also increase the risk of bleeding. As such, reversal strategies are critical. Until recently, the direct oral anticoagulants (DOACs) dabigatran, rivaroxaban, apixaban, and edoxaban lacked a specific reversal agent. This report is based on findings from the Anticoagulation Education Task Force, which brought together patient groups and professionals representing different medical specialties with an interest in patient safety and expertise in AF, VTE, stroke, anticoagulation, and reversal agents, to discuss the current status of anticoagulation reversal and fundamental changes in management of bleeding associated with DOACs occasioned by the approval of idarucizumab, a specific reversal agent for dabigatran, as well as recent clinical data on specific reversal agents for factor Xa inhibitors. Recommendations are given for when there is a definite need for a reversal agent (e.g. in cases of life-threatening bleeding, bleeding into a closed space or organ, persistent bleeding despite local haemostatic measures, and need for urgent interventions and/or interventions that carry a high risk for bleeding), when reversal agents may be helpful, and when a reversal agent is generally not needed. Key stakeholders who require 24-7/around-the-clock access to these agents vary among hospitals; however, from a practical perspective the emergency department is recommended as an appropriate location for these agents. Clearly, the advent of new agents requires standardised protocols for treating bleeding on an institutional level.

Ageno|Walter|W|
Büller|Harry R|HR|
Falanga|Anna|A|
Hacke|Werner|W|
Hendriks|Jeroen|J|
Lobban|Trudie|T|
Merino|Jose|J|
Milojevic|Ivan S|IS|
Moya|Francisco|F|
van der Worp|H Bart|HB|
Randall|Gary|G|
Tsioufis|Konstantinos|K|
Verhamme|Peter|P|
Camm|A John|AJ|

Anticoagulation
venous thromboembolism
stroke prevention
atrial fibrillation
reversal agents


Immunoglobulin gene analysis as a tool for investigating human immune responses.

Abstract: The human immunoglobulin repertoire is a hugely diverse set of sequences that are formed by processes of gene rearrangement, heavy and light chain gene assortment, class switching and somatic hypermutation. Early B cell development produces diverse IgM and IgD B cell receptors on the B cell surface, resulting in a repertoire that can bind many foreign antigens but which has had self-reactive B cells removed. Later antigen-dependent development processes adjust the antigen affinity of the receptor by somatic hypermutation. The effector mechanism of the antibody is also adjusted, by switching the class of the antibody from IgM to one of seven other classes depending on the required function. There are many instances in human biology where positive and negative selection forces can act to shape the immunoglobulin repertoire and therefore repertoire analysis can provide useful information on infection control, vaccination efficacy, autoimmune diseases, and cancer. It can also be used to identify antigen-specific sequences that may be of use in therapeutics. The juxtaposition of lymphocyte development and numerical evaluation of immune repertoires has resulted in the growth of a new sub-speciality in immunology where immunologists and computer scientists/physicists collaborate to assess immune repertoires and develop models of immune action.


Epidemiology, Pathophysiology, and Management of Hepatorenal Syndrome.

Abstract: Acute kidney injury (AKI) is a common presentation in patients with advanced cirrhosis hospitalized with acute decompensation. A new revised classification now divides AKI in cirrhotic patients into two broad subgroups: hepatorenal syndrome AKI (HRS AKI) and non-hepatorenal syndrome AKI (non-HRS AKI). HRS AKI represents the end-stage complication of decompensated cirrhosis with severe portal hypertension and is characterized by worsening of renal function in the absence of prerenal azotemia, nephrotoxicity, and intrinsic renal disease. Non-HRS AKI may be caused by prerenal hypoperfusion, bile acid nephropathy, nephrotoxicity, or acute parenchymal insult. There have been several mechanisms proposed to explain the pathophysiology of HRS AKI and non-HRS AKI, and a number of biomarkers have been suggested to aid in differentiation between these types of AKI and to act as prognostic indicators. The standard of care clinical management for patients with HRS AKI is to exclude other etiologies of AKI, followed by volume expansion with human albumin solution and then the introduction of vasopressors. However, some 40% of patients treated for HRS AKI fail to respond. In this review, we discuss the current and recent data about classification, pathophysiology, and management of AKI in general, with specific insight about the treatment of HRS AKI.

Amin|Ahmed Adel|AA|
Alabsawy|Eman Ibrahim|EI|
Jalan|Rajiv|R|
Davenport|Andrew|A|

hepatorenal syndrome
acute kidney injury
Cirrhosis
acute-on-chronic liver failure (ACLF)


Rare case of acral calcified angioleiomyoma with macroscopic calcium extrusion.

Abstract: Acral calcified angioleiomyoma is an uncommon tumor that presents as a non-descript papule or subcutaneous nodule, classically on the foot. Biopsy or excision is typically the diagnostic method of choice as well as the treatment for these sometimes painful tumors. We report an uncommon clinical presentation of acral calcified angioleiomyoma with considerable extrusion of calcium perforating through the skin.

Blalock|Travis W|TW|
Kerr|Christy|C|
DeRienzo|Damian P|DP|
Greenway|Hubert T|HT|


The influence of personality traits on smokers' affect, withdrawal and cessation intervention outcome.

Abstract: The personality traits of harm avoidance (HA), novelty seeking (NS), and reward dependence (RD), as measured by the Tridimensional Personality Questionnaire (TPQ), have been linked to smoking behavior. The extent to which these traits are associated with smoking withdrawal and cessation outcome is unclear. We sought to address this question among 131 treatment-seeking smokers who were randomly assigned to either a smoking cessation treatment (four 30-min behavioral counseling sessions) or a control condition. We found that HA was positively associated with baseline depressive symptoms, baseline negative affect, and post-quit withdrawal, and negatively associated with positive affect at both baseline and post-quit. Additionally, we found that smokers with higher HA scores were more likely to be abstinent. NS was negatively associated with post-quit positive affect and positively associated with post-quit negative affect and withdrawal. RD was not found to be related to any outcome measures. Our findings suggest that, despite experiencing greater baseline and post-quit negative affect, smokers higher in trait harm avoidance are more likely to quit smoking. The treatment and theoretical ramifications of these findings are discussed.

Cui|Yong|Y|
Tang|Rui|R|
Lam|Cho Y|CY|
Cinciripini|Paul M|PM|
Robinson|Jason D|JD|


Recognition-Mediated Hydrogel Swelling Controlled by Interaction with a Negative Thermoresponsive LCST Polymer.

Abstract: Most polymeric thermoresponsive hydrogels contract upon heating beyond the lower critical solution temperature (LCST) of the polymers used. Herein, we report a supramolecular hydrogel system that shows the opposite temperature dependence. When the non-thermosesponsive hydrogel NaphtGel, containing dialkoxynaphthalene guest molecules, becomes complexed with the tetra cationic macrocyclic host CBPQT4+ , swelling occurred as a result of host-guest complex formation leading to charge repulsion between the host units, as well as an osmotic contribution of chloride counter-ions embedded in the network. The immersion of NaphtGel in a solution of poly(N-isopropylacrylamide) with tetrathiafulvalene (TTF) end groups complexed with CBPQT4+ induced positive thermoresponsive behaviour. The LCST-induced dethreading of the polymer-based pseudorotaxane upon heating led to transfer of the CBPQT4+ host and a concomitant swelling of NaphtGel. Subsequent cooling led to reformation of the TTF-based host-guest complexes in solution and contraction of the hydrogel.

hydrogels
swelling
host-guest compounds
supramolecular chemistry
thermoresponsive polymers


Linking susceptibility genes and pathogenesis mechanisms using mouse models of systemic lupus erythematosus.

Abstract: Systemic lupus erythematosus (SLE) represents a challenging autoimmune disease from a clinical perspective because of its varied forms of presentation. Although broad-spectrum steroids remain the standard treatment for SLE, they have many side effects and only provide temporary relief from the symptoms of the disease. Thus, gaining a deeper understanding of the genetic traits and biological pathways that confer susceptibility to SLE will help in the design of more targeted and effective therapeutics. Both human genome-wide association studies (GWAS) and investigations using a variety of mouse models of SLE have been valuable for the identification of the genes and pathways involved in pathogenesis. In this Review, we link human susceptibility genes for SLE with biological pathways characterized in mouse models of lupus, and discuss how the mechanistic insights gained could advance drug discovery for the disease.

Crampton|Steve P|SP|
Morawski|Peter A|PA|
Bolland|Silvia|S|

D020022:Genetic Predisposition to Disease

Susceptibility genes
Mouse models
Lupus
SLE
Human genetics


Visual impairment and depressive symptoms in an older Australian cohort: longitudinal findings from the Blue Mountains Eye Study.

Abstract:
AIMS
To assess the association between visual impairment (VI) and subsequent presence of depressive symptoms among older persons.

METHODS
Of the 3654 baseline participants (aged over 49 years) of the Blue Mountains Eye Study, 2334, 1952 and 1149 were re-examined after 5, 10 and 15 years, respectively. VI was defined as best-corrected visual acuity <6/12 in either or both eyes. Presence of depressive symptoms was defined if mental health index (MHI) scores <59 or incident use of antidepressant medications. Persons with VI detected at the 5-year or 10-year follow-up visits were assessed for depressive symptoms in 5 years. Persons with VI detected at baseline or the 5-year follow-up were assessed for depressive symptoms over 10 years. Controls were persons without VI over the corresponding period. Discrete logistic regression models with time-dependent study and outcome variables were used, adjusting for potential confounders.

RESULTS
Of 1568 participants who had the MHI assessed at two consecutive visits, 226 had bilateral or unilateral VI detected 5 years earlier and 120 had VI detected over 10 years earlier. Depressive symptoms were reported in 27% and 31.6% of cases with VI detected 5 and over 10 years earlier, respectively, compared with 10.8%-11.5% of controls. There was a significantly greater odds of presenting depressive symptoms among VI cases detected 5 years earlier (OR, 3.06, 95% CI 1.72 to 5.44), but this was non-significant for cases detected over 10 years earlier (OR 1.29, 95% CI 0.84 to 1.98).

CONCLUSIONS
VI was associated with subsequently presenting depressive symptoms over 5 years among older persons.

Hong|Thomas|T|
Mitchell|Paul|P|
Burlutsky|George|G|
Gopinath|Bamini|B|
Liew|Gerald|G|
Wang|Jie Jin|JJ|

D000368:Aged
D003430:Cross-Sectional Studies
D003866:Depressive Disorder
D005260:Female
D005500:Follow-Up Studies
D006801:Humans
D015994:Incidence
D007361:Intelligence Tests
D008297:Male
D008875:Middle Aged
D015233:Models, Statistical
D009517:New South Wales
D016017:Odds Ratio
D018434:Sickness Impact Profile
D011795:Surveys and Questionnaires
D014786:Vision Disorders
D014792:Visual Acuity
D019987:Visually Impaired Persons


Implanted vagus nerve stimulation in 126 patients: surgical technique and complications.

Abstract:
INTRODUCTION
Vagus nerve stimulation is a palliative treatment for patients with refractory epilepsy to reduce the frequency and intensity of seizures. A bipolar helical electrode is placed around the left vagus nerve at the cervical level and is connected to the pulse generator placed in a subcutaneous pocket, most commonly in the subclavian region.

METHODS
Between March 1998 and October 2019, we performed 196 procedures related to the vagal nerve stimulation at the Neurosurgery Department in Motol University Hospital. Of these, 126 patients were vagal nerve stimulator implantation surgeries for intractable epilepsy. The cases included 69 female and 57 male patients with mean age at the time of the implantation surgery 22±12.4 years (range 2.158.4 years).

RESULTS
Nine patients (7.1%) were afflicted by complications related to implantation. Surgical complications included postoperative infection in 1.6%, VNS-associated arrhythmias in 1.6%, jugular vein bleeding in 0.8% and vocal cord paresis in 2.4%. One patient with vocal cord palsy also suffered from severe dysphagia. One patient (0.8%) did not tolerate extra stimulation with magnet due to a prolonged spasm in his throat. The extra added benefit of vagus stimulation in one patient was a significant reduction of previously regular severe headaches.

CONCLUSION
Vagus nerve stimulation is an appropriate treatment for patients with drug-resistant epilepsy who are not candidates for focal resective surgery. Implantation of the vagus nerve stimulator is a relatively safe operative procedure.

epilepsy − epilepsy surgery − vagus nerve stimulation


Pregnancies in women with Turner Syndrome: A retrospective multicentre UK study.

Abstract:
OBJECTIVE
To determine the characteristics and outcomes of pregnancy in women with Turner Syndrome DESIGN: Retrospective 20-year cohort study (2000-2020) SETTING: 16 tertiary referral maternity units in the UK POPULATION OR SAMPLE: 81 women with Turner syndrome who became pregnant METHODS: Retrospective chart analysis MAIN OUTCOME MEASURES: Mode of conception, pregnancy outcomes RESULTS: We obtained data on 127 pregnancies in 81 women with a Turner phenotype. All non-spontaneous pregnancies (54/127 (42.5%)) were by egg donation. Only 9/31 (29%) of pregnancies in women with karyotype 45,X were spontaneous, compared with 53/66 (80.3%) with mosaic karyotype 45,X/46,XX (p<0.0001). Women with mosaic 45,X/46,XX were younger at first pregnancy by 5.5-8.5 years compared to other TS-karyotype groups (p<0.001), and more likely to have a spontaneous menarche (75.8% vs 50% or less, p=0.008). There were 17 miscarriages, 3 terminations of pregnancy, 2 stillbirths and 105 livebirths. Two women had aortic dissection (2.5%); both were 45,X karyotype, with bicuspid aortic valves and ovum donation pregnancies, one died. Another woman had an aortic root replacement within six months of delivery. 10/106 (9.4%) births with gestational age data were preterm and 22/96 (22.9%) with singleton birthweight/gestational age data weighed <10th centile. The caesarean section rate was 72/107 (67.3%). In only 73/127 (57.4%) of pregnancies was there documentation of cardiovascular imaging within 24 months prior to conceiving.

CONCLUSIONS
Pregnancy in women with TS is associated with major maternal cardiovascular risks and deserve thorough cardiovascular assessment and counselling prior to assisted or spontaneous pregnancy managed by a specialist team.

pregnancy
Turner syndrome
aortic dissection


Effects of an Injury Prevention Program on Anterior Cruciate Ligament Injury Risk Factors in Adolescent Females at Different Stages of Maturation.

Abstract: The ideal timing to implement anterior cruciate ligament injury prevention programs with respect to maturation is unclear. The purpose of this study was to investigate the effects of an injury prevention program on knee mechanics in early-, late-, and post-pubertal females. In the study, 178 adolescent female basketball players were assigned to six groups: early-pubertal training, early-pubertal control, late-pubertal training, and late-pubertal control, post-pubertal training, and post-pubertal control. The training groups performed an injury prevention program for six months. Medial knee displacement, knee flexion range of motion, and the probability of high knee abduction moment were assessed before and after the training period. After the six-month training period, medial knee displacement was significantly increased in the early-pubertal control group whereas it was unchanged in the early-pubertal training group. Knee flexion range of motion was significantly decreased in the early-pubertal control group whereas it did not change in the early-pubertal training group. The probability of high knee abduction moment was increased in the early-pubertal control group whereas it was unchanged in the earl-pubertal training group. The probability of high knee abduction moment was also decreased in the post-pubertal training group whereas it did not change in the post-pubertal control group. The program limited the development of high-risk movement patterns associated with maturation in early puberty while improving the knee mechanics in post-pubertal adolescents. Therefore, an injury prevention program should be initiated in early puberty and continue through the post-puberty years.

Otsuki|Reiko|R| Benoit|Daniel|D| Hirose|Norikazu|N| Fukubayashi|Toru|T|

D000070598:Anterior Cruciate Ligament Injuries

puberty
Knee injuries
landing
neuromuscular control


An assessment of hand volumetric and temperature changes during office related repetitive activities.

Abstract:
BACKGROUND
Hand usage and movement is routinely performed by all individuals daily irrespective of age. These movements can vary and can be repetitive in nature. Exposure of the hard and soft tissues of the hand to prolonged repetitive activities could contribute to the development of work related upper limb disorders (WRULD).

OBJECTIVE
Within the work setting, work related upper limb disorders (WRULDs) rank high in the United Kingdom (UK), second only to back complaints. This paper reports the amount of tendon travel and swelling that occurs in the hand during repetitive office activities associated with WRULDs.

PARTICIPANTS
Nine healthy adults (five males; four females) participated in the study.

METHODS
A 30-minute laboratory-based simulated office activity that consisted of data entry, mouse clicking and dragging, and mouse scrolling tasks was performed. Participants wore a custom-made cost effective flexible electrogoniometric glove (FEG) as two experimental conditions were tested; namely, FEG - only, and FEG using a Splint (FEG - Splint).

RESULTS
The FEG - only condition produced a higher overall tendon travel compared to the FEG - Splint condition. Both hands presented no statistically significant differences in hand temperature (p > 0.05) and hand volume increments (p > 0.05) with respect to the FEG - only and FEG - Splint office activity experiments. All participants that showed a decrease in hand volumetric measurement produced final temperature measurements lower than initial temperature measurements taken at the commencement of the experiment. Based on participants' perception, the mouse scrolling task was deemed as most strenuous.

CONCLUSION
The findings can help to advise patients on biomechanical 'risks' associated with repetitive activities.

Ugbolue|U Chris|UC|
Nicol|Alexander C|AC|

tendon travel
office activity
flexible electrogoniometric glove
Carpal tunnel syndrome


Association study of functional polymorphisms in interleukins and interleukin receptors genes: IL1A, IL1B, IL1RN, IL6, IL6R, IL10, IL10RA and TGFB1 in schizophrenia in Polish population.

Abstract: Schizophrenia has been associated with a large range of autoimmune diseases, with a history of any autoimmune disease being associated with a 45% increase in risk for the illness. The inflammatory system may trigger or modulate the course of schizophrenia through complex mechanisms influencing neurodevelopment, neuroplasticity and neurotransmission. In particular, increases or imbalance in cytokine before birth or during the early stages of life may affect neurodevelopment and produce vulnerability to the disease. A total of 27 polymorphisms of IL1N gene: rs1800587, rs17561; IL1B gene: rs1143634, rs1143643, rs16944, rs4848306, rs1143623, rs1143633, rs1143627; IL1RN gene: rs419598, rs315952, rs9005, rs4251961; IL6 gene: rs1800795, rs1800797; IL6R gene: rs4537545, rs4845617, rs2228145, IL10 gene: rs1800896, rs1800871, rs1800872, rs1800890, rs6676671; IL10RA gene: rs2229113, rs3135932; TGF1B gene: rs1800469, rs1800470; each selected on the basis of molecular evidence for functionality, were investigated in this study. Analysis was performed on a group of 621 patients with diagnosis of schizophrenia and 531 healthy controls in Polish population. An association of rs4848306 in IL1B gene, rs4251961 in IL1RN gene, rs2228145 and rs4537545 in IL6R with schizophrenia have been observed. rs6676671 in IL10 was associated with early age of onset. Strong linkage disequilibrium was observed between analyzed polymorphisms in each gene, except of IL10RA. We observed that haplotypes composed of rs4537545 and rs2228145 in IL6R gene were associated with schizophrenia. Analyses with family history of schizophrenia, other psychiatric disorders and alcohol abuse/dependence did not show any positive findings. Further studies on larger groups along with correlation with circulating protein levels are needed.

Kapelski|Pawel|P| Skibinska|Maria|M| Maciukiewicz|Malgorzata|M| Wilkosc|Monika|M| Frydecka|Dorota|D| Groszewska|Agata|A| Narozna|Beata|B| Dmitrzak-Weglarz|Monika|M| Czerski|Piotr|P| Pawlak|Joanna|J| Rajewska-Rager|Aleksandra|A| Leszczynska-Rodziewicz|Anna|A| Slopien|Agnieszka|A| Zaremba|Dorota|D| Twarowska-Hauser|Joanna|J|

D053590:Interleukin 1 Receptor Antagonist Protein

D053773:Transforming Growth Factor beta1

Association
Functional polymorphism
Interleukin
Interleukin receptor


The Prevalence and Risk Factors for S2 Alar-Iliac Screw Loosening with a Minimum 2-Year Follow-up.

Abstract:
STUDY DESIGN
A retrospective cohort study.

PURPOSE
The purpose of this study was to investigate the prevalence and risk factors for S2 alar-iliac (SAI) screw loosening following lumbosacral fixation, with a minimum 2-year follow-up.

OVERVIEW OF LITERATURE
Although SAI screws allow surgeons to perform lumbosacral fixation with a low profile and enhanced biomechanical strength, screw loosening following surgery can occur in some cases. However, few studies have investigated the prevalence and risk factors for SAI screw loosening.

METHODS
This retrospective study included 35 patients (mean age, 72.8±8.0 years; male, 10; female, 25) who underwent lumbosacral fixation using SAI screws with at least 2 years of follow-up. SAI screw loosening and L5-S bony fusion were assessed using computed tomography. The period for which the screws appeared loose and the risk factors for SAI screw loosening were investigated 2 years after surgery.

RESULTS
A total of 70 SAI screws and 70 S1 pedicle screws were inserted. Loosening was observed 0.5, 1, and 2 years after surgery in 17 (24.3%), 35 (50.0%), and 35 (50.0%) SAI screws, respectively. Bony fusion rate at L5-S was significantly lower in patients with SAI screw loosening than in those without screw loosening (65.0% vs. 93.3%, p =0.048). The score for SAI screw contact with the iliac cortical bone and the bony fusion rate at L5-S were significantly lower in the loosening group than in the non-loosening group (1.8±0.5 vs. 2.2±0.3, p <0.001, respectively). Postoperative pelvic incidence-lumbar lordosis was significantly higher in the loosening group than in the non-loosening group (7.9°±15.4° vs. 0.5°±8.7°, p =0.02, respectively).

CONCLUSIONS
SAI screw loosening is closely correlated with pseudoarthrosis at L5-S. Appropriate screw insertion and optimal lumbar lordosis restoration are important to prevent postoperative complications related to SAI screws.

Nakashima|Hiroaki|H| Kanemura|Tokumi|T| Satake|Kotaro|K| Ito|Kenyu|K| Ishikawa|Yoshimoto|Y| Ouchida|Jun|J| Segi|Naoki|N| Yamaguchi|Hidetoshi|H| Imagama|Shiro|S|

Risk factors
S2 alar-iliac screw
Screw loosening
Bony fusion


The Synergistic Effects of Matrix Stiffness and Composition on the Response of Chondroprogenitor Cells in a 3D Precondensation Microenvironment.

Abstract: Improve functional quality of cartilage tissue engineered from stem cells requires a better understanding of the functional evolution of native cartilage tissue. Therefore, a biosynthetic hydrogel was developed containing RGD, hyaluronic acid and/or type-I collagen conjugated to poly(ethylene glycol) acrylate to recapitulate the precondensation microenvironment of the developing limb. Conjugation of any combination of the three ligands did not alter the shear moduli or diffusion properties of the PEG hydrogels; thus, the influence of ligand composition on chondrogenesis could be investigated in the context of varying matrix stiffness. Gene expression of ligand receptors (CD44 and the b1-integrin) as well as markers of condensation (cell clustering and N-cadherin gene expression) and chondrogenesis (Col2a1 gene expression and sGAG production) by chondroprogenitor cells in this system were modulated by both matrix stiffness and ligand composition, with the highest gene expression occurring in softer hydrogels containing all three ligands. Cell proliferation in these 3D matrices for 7 d prior to chondrogenic induction increased the rate of sGAG production in a stiffness-dependent manner. This biosynthetic hydrogel supports the features of early limb-bud condensation and chondrogenesis and is a novel platform in which the influence of the matrix physicochemical properties on these processes can be elucidated.

Carrion|Bita|B|
Souzanchi|Mohammad F|MF|
Wang|Victor T|VT|
Tiruchinapally|Gopinath|G|
Shikanov|Ariella|A|
Putnam|Andrew J|AJ|
Coleman|Rhima M|RM|

matrix stiffness
3D
chondrogenesis
condensation
engineered microenvironment
polyethylene glycol


The Role of Multimodality Imaging in Athlete's Heart Diagnosis: Current Status and Future Directions.

Abstract: "Athlete's heart" is a spectrum of morphological and functional changes which occur in the heart of people who practice physical activity. When athlete's heart occurs with its most marked expression, it may overlap with a differential diagnosis with certain structural cardiac diseases, including cardiomyopathies, valvular diseases, aortopathies, myocarditis, and coronary artery anomalies. Identifying the underlying cardiac is essential to reduce the potential for sudden cardiac death. For this purpose, a spectrum of imaging modalities, including rest and exercise stress echocardiography, speckle tracking echocardiography, cardiac magnetic resonance, computed tomography, and nuclear scintigraphy, can be undertaken. The objective of this review article is to provide to the clinician a practical step-by-step approach, aiming at distinguishing between extreme physiology and structural cardiac disease during the athlete's cardiovascular evaluation.

multimodality imaging
cardiomyopathies
sudden cardiac death
stress echocardiography
echocardiography
cardiac magnetic resonance
athlete’s heart
cardiac computed tomography
strain


Role of DNA profiling in forensic odontology.

Abstract: The recent advances in DNA profiling have made DNA evidence to be more widely accepted in courts. This has revolutionized the aspect of forensic odontology. DNA profiling/DNA fingerprinting has come a long way from the conventional fingerprints. DNA that is responsible for all the cell's activities, yields valuable information both in the healthy and diseased individuals. When other means of traditional identification become impossible following mass calamities or fire explosions, teeth provide a rich source of DNA as they have a high chemical as well as physical resistance. The recent evolution in the isolation of DNA and the ways of running a DNA fingerprint are highlighted in this literature review.

Sakari|S Leena|SL|
Jimson|Sudha|S|
Masthan|K M K|KM|
Jacobina|Jenita|J|

DNA profiling
forensic odontology
DNA isolation


Frontal white matter injuries predestine gait difficulties in Parkinson's disease.

Abstract:
OBJECTIVES
This study applies diffusion tensor imaging (DTI) to determine differences in neuronal integrity between motor phenotypes in Parkinson's disease.

MATERIAL AND METHODS
One hundred and twenty-two patients (47 females, mean age = 70.3 years) were included at baseline. Forty patients were tremor dominant (TD), 64 had postural imbalance and gait difficulty (PIGD), and 18 patients were indeterminate. The DTI was repeated after one, three and 5 years, including reassessment of phenotype. DTI was quantified using fractional anisotropy (FA), and mean, radial and axial diffusion. Targeted white matter involved six regions of interests (ROIs) in prefrontal cortex (PFC), the entrance to the external capsule (EEC) and lateral to the horn of the anterior ventricle (LVAH). Grey matter involved the basal ganglia. Data were analysed using mixed linear models with P < 0.05 (Bonferroni corrected) as significance threshold.

RESULTS
PIGD and Indeterminate had reduced FA and axial diffusion in PFC, EEC and LVAH compared to Tremor dominant (P < 0.05). Basal ganglia showed no differences. Post hoc analysis showed that FA correlated negatively, and mean and radial diffusion positively, to PIGD symptoms in EEC, LVAH and four ROIs in PFC (P < 0.05). Tremor symptoms showed no correlations. Patients converting to PIGD and Indeterminate had lower FA, and higher mean and radial diffusion, at baseline in EEC, LVAH and four areas in PFC compared to non-converting patients (P < 0.05).

CONCLUSION
Degeneration in frontal white matter is connected to PIGD symptoms in Parkinson's disease and if present at an early stage, the risk for conversion to the PIGD phenotype increases.

Lenfeldt|N|N| Holmlund|H|H| Larsson|A|A| Birgander|R|R| Forsgren|L|L|

gait
parkinsonism
diffusion tensor imaging
tremor
anisotropy


Meat quality and intramuscular fatty acid composition of Catria Horse.

Abstract: In order to extend scientific knowledge on autochthonous Italian equine meat, the physical-chemical parameters of Catria Horse Longissimus thoracis (LT) muscle and its nutritional characteristics have been investigated. Ten steaks of Catria foal raised at pasture and fattened indoors for 2 months were dissected, and LT muscle was analyzed for chemical composition, total iron, drip loss, colorimetric characteristics, intramuscular fat, fatty acid profile and nutritional indexes. Steak dissection showed that LT muscle accounted for 36.78% and fat accounted for 9.19% of weight of steak. Regarding chemical composition, protein and fat content was 20.31% and 2.83%, respectively. Total iron content (1.95 mg/100 g) was lower than data reported in the literature. Color parameters showed a luminous and intense red hue muscle. The sum of unsaturated fatty acid composition (50.3%) was higher than the sum of saturated fatty acids (46.64 %). The fatty acid profile and nutritional values of Catria Horse meat could be modified adopting extensive rearing systems and grazing. The data suggests that further investigation on the composition of Catria Horse meat should be carried out to valorize this autochthonous breed, reared in sustainable livestock systems, and its meat in local short-chain systems.

Trombetta|Maria Federica|MF|
Nocelli|Francesco|F|
Pasquini|Marina|M|

fatty acids
Longissimus thoracis
Catria Horse foal
meat proximate analysis


Impact of Perioperative Hypnosedation on Postmastectomy Chronic Pain: Preliminary Results.

Abstract: Objectives: The main aim of this prospective nonrandomized study was to evaluate if mastectomy performed with perioperative hypnosedation led to a lower incidence of chronic pain compared with mastectomy under general anesthesia. Methods: Forty-two breast cancer patients who underwent mastectomy either under GA (GA group, n = 21) or HYP (HYP group, n = 21) associated with local and/or regional anesthesia were included. The type of adjuvant therapy as well as the number of reconstructive surgical procedures were well balanced between the 2 groups. The average age of the patients and the type of axillary surgery were also equivalent. Incidence of postmastectomy chronic pain, lymphedema, and shoulder range of motion (ROM) were evaluated after a mean 4-year follow-up. Results: The study shows a statistically significant lower incidence of postmastectomy chronic pain in HYP group (1/21, 1 patient out of 21 experiencing pain) compared with GA group (9/21) with 9 patients out of 21 experiencing pain (P = .008). ROM for shoulder was also less frequently affected in the hypnosedation group, as only 1 patient had decreased ROM, instead of 7 in the other group (P = .04). Conclusions: Our study is the first to hint at the potential benefits of hypnosedation on postmastectomy chronic pain. Despite the limitations of this study (nonrandomized, small sample), preliminary results merit further study of hypnosedation.

Lacroix|Camille|C|
Duhoux|Francois P|FP|
Bettendorff|Julie|J|
Watremez|Christine|C|
Roelants|Fabienne|F|
Docquier|Marie-Agnes|MA|
Potié|Arnaud|A|
Coyette|Maude|M|
Gerday|Amandine|A|
Samartzi|Vasiliki|V|
Piette|Philippe|P|
Piette|Nathan|N|
Berliere|Martine|M|0000-0002-6472-9867

D000768:Anesthesia, General
D001943:Breast Neoplasms
D016022:Case-Control Studies
D059350:Chronic Pain
D003131:Combined Modality Therapy
D005260:Female
D006801:Humans
D006991:Hypnosis, Anesthetic
D008408:Mastectomy
D008875:Middle Aged
D010149:Pain, Postoperative
D011446:Prospective Studies

mastectomy
breast cancer
benefits of hypnosis
hypnoanalgesia
postmastectomy pain syndrome


Extending import detection algorithms for concept import from two to three biomedical terminologies.

Abstract:
BACKGROUND
While enrichment of terminologies can be achieved in different ways, filling gaps in the IS-A hierarchy backbone of a terminology appears especially promising. To avoid difficult manual inspection, we started a research program in 2014, investigating terminology densities, where the comparison of terminologies leads to the algorithmic discovery of potentially missing concepts in a target terminology. While candidate concepts have to be approved for import by an expert, the human effort is greatly reduced by algorithmic generation of candidates. In previous studies, a single source terminology was used with one target terminology.

METHODS
In this paper, we are extending the algorithmic detection of "candidate concepts for import" from one source terminology to two source terminologies used in tandem. We show that the combination of two source terminologies relative to one target terminology leads to the discovery of candidate concepts for import that could not be found with the same "reliability" when comparing one source terminology alone to the target terminology. We investigate which triples of UMLS terminologies can be gainfully used for the described purpose and how many candidate concepts can be found for each individual triple of terminologies.

RESULTS
The analysis revealed a specific configuration of concepts, overlapping two source and one target terminology, for which we coined the name "fire ladder" pattern. The three terminologies in this pattern are tied together by a kind of "transitivity." We provide a quantitative analysis of the discovered fire ladder patterns and we report on the inter-rater agreement concerning the decision of importing candidate concepts from source terminologies into the target terminology. We algorithmically identified 55 instances of the fire ladder pattern and two domain experts agreed on import for 39 instances. In total, 48 concepts were approved by at least one expert. In addition, 105 import candidate concepts from a single source terminology into the target terminology were also detected, as a "beneficial side-effect" of this method, increasing the cardinality of the result.

CONCLUSION
We showed that pairs of biomedical source terminologies can be transitively chained to suggest possible imports of concepts into a target terminology.

Keloth|Vipina K|VK|0000-0001-6919-1122
Geller|James|J|
Chen|Yan|Y|
Xu|Julia|J|

D039061:Systematized Nomenclature of Medicine

Concept import
Terminologies
UMLS
Density differences
National cancer institute thesaurus
SNOMED CT


Nitrogen isotopes in the soil-to-tree continuum - Tree rings express the soil biogeochemistry of boreal forests exposed to moderate airborne emissions.

Abstract: Anthropogenic N emissions represent a potential threat for forest ecosystems, and environmental indicators that provide insight into the changing forest N cycle are needed. Tree ring N isotopic ratios (δ15N) appear as a contentious choice for this role as the exact mechanisms behind tree-ring δ15N changes seldom benefit from a scrutiny of the soil-to-tree N continuum. This study integrates the results from the analysis of soil chemistry, soil microbiome genomics, and δ15N values of soil N compounds, roots, ectomycorrhizal (EcM) fungi and recent tree rings of thirteen white spruce trees sampled in five stands, from two regions exposed to moderate anthropogenic N emissions (3.9 to 8.1 kg/ha/y) with distinctive δ15N signals. Our results reveal that airborne anthropogenic N with distinct δ15N signals may directly modify the NO3- δ15N values in surface soils, but not the ones of NH4+, the preferred N form of the studied trees. Hence, the tree-ring δ15N values reflect specific soil N conditions and assimilation modes by trees. Along with a wide tree-ring δ15N range, we report differences in: soil nutrient content and N transformation rates; δ15N values of NH4+, total dissolved N (TDN) and EcM mantle enveloping the root tips; and bacterial and fungal community structures. We combine EcM mantle and root δ15N values with fungal identification to infer that hydrophobic EcM fungi transfer N from the dissolved organic N (DON) pool to roots under acidic conditions, and hydrophilic EcM fungi transfer various N forms to roots, which also assimilate N directly under less acidic conditions. Despite the complexities of soil biogeochemical properties and processes identified in the studied sites, in the end, the tree-ring δ15N averages inversely correlate with soil pH and anthropogenic N inputs, confirming white spruce tree-ring δ15N values as a suitable indicator for environmental research on forest N cycling.

Savard|Martine M|MM|
Martineau|Christine|C|
Laganière|Jérôme|J|
Bégin|Christian|C|
Marion|Joëlle|J|
Smirnoff|Anna|A|
Stefani|Franck|F|
Bergeron|Jade|J|
Rheault|Karelle|K|
Paré|David|D|
Séguin|Armand|A|

Soil microbiome
N transformation
pH
Airborne pollutants
Ectomycorrhizal fungi
Reactive N


Molecular Imaging of Brain Tumor-Associated Epilepsy.

Abstract: Epilepsy is a common clinical manifestation and a source of significant morbidity in patients with brain tumors. Neuroimaging has a pivotal role in neuro-oncology practice, including tumor detection, differentiation, grading, treatment guidance, and posttreatment monitoring. In this review, we highlight studies demonstrating that imaging can also provide information about brain tumor-associated epileptogenicity and assist delineation of the peritumoral epileptic cortex to optimize postsurgical seizure outcome. Most studies focused on gliomas and glioneuronal tumors where positron emission tomography (PET) and advanced magnetic resonance imaging (MRI) techniques can detect metabolic and biochemical changes associated with altered amino acid transport and metabolism, neuroinflammation, and neurotransmitter abnormalities in and around epileptogenic tumors. PET imaging of amino acid uptake and metabolism as well as activated microglia can detect interictal or peri-ictal cortical increased uptake (as compared to non-epileptic cortex) associated with tumor-associated epilepsy. Metabolic tumor volumes may predict seizure outcome based on objective treatment response during glioma chemotherapy. Advanced MRI, especially glutamate imaging, can detect neurotransmitter changes around epileptogenic brain tumors. Recently, developed PET radiotracers targeting specific glutamate receptor types may also identify therapeutic targets for pharmacologic seizure control. Further studies with advanced multimodal imaging approaches may facilitate development of precision treatment strategies to control brain tumor-associated epilepsy.

epilepsy
brain tumors
seizures
glioma
positron emission tomography
magnetic resonance imaging
amino acid
neuroinflammation
glutamate
peritumoral cortex


The complete mitochondrial genome of Pidorus atratus (Lepidoptera: Zygaenoidea: Zygaenidae).

Abstract: The complete mitochondrial genome (mitogenome) of Pidorus atratus (Lepidoptera: Zygaenoidea: Zygaenidae) is described in this study. The circular molecule is 15,383 bp in length and contains 37 typical mitochondrial genes and one non-coding AT-rich region. All protein-coding genes (PCGs) start with ATN, except for cox1 gene with CGA; 10 of the 13 PCGs harbour the typical stop codon TAA, whereas cox1, cox2, and nad4 end with a single T. Two ribosomal RNA genes (rRNAs) are 1366 bp and 544 bp in length, respectively. The AT-rich region is 658 bp in size and harbours several features characteristic of the lepidopterans, including the motif ATAGA followed by a 20 bp poly-T stretch and a microsatellite-like (TA)9 element. The complete mitogenome data would be useful for further understanding the taxonomy and phylogeny of Zygaenoidea.

Wang|Zihui|Z| Yao|Shun|S| Zhu|Xiaoyue|X| Hao|Jiasheng|J|

Mitochondrial genome
Pidorus atratus
Zygaenoidea
Zygaenidae


Polyunsaturated fatty acid supplementation reverses cystic fibrosis-related fatty acid abnormalities in CFTR-/- mice by suppressing fatty acid desaturases.

Abstract: Cystic fibrosis patients and model systems exhibit consistent abnormalities in metabolism of polyunsaturated fatty acids that appear to play a role in disease pathophysiology. Recent in vitro studies have suggested that these changes are due to overexpression of fatty acid desaturases that can be reversed by supplementation with the long-chain polyunsaturated fatty acids docosahexaenoate and eicosapentaenoate. However, these findings have not been tested in vivo. The current study aimed to test these results in an in vivo model system, the CFTR(-/-) knockout mouse. When compared with wild-type mice, the knockout mice exhibited fatty acid abnormalities similar to those seen in cystic fibrosis patients and other model systems. The abnormalities were confined to lung, ileum and pancreas, tissues that are affected by the disease. Similar to in vitro models, these fatty acid changes correlated with increased expression of Δ5- and Δ6-desaturases and elongase 5. Dietary supplementation with high-dose free docosahexaenoate or a combination of lower-dose docosahexaenoate and eicosapentaenoate in triglyceride form corrected the fatty acid abnormalities and reduced expression of the desaturase and elongase genes in the ileum and liver of knockout mice. Only the high-dose docosahexaenoate reduced histologic evidence of disease, reducing mucus accumulation in ileal sections. These results provide in vivo support for the hypothesis that fatty acid abnormalities in cystic fibrosis result from abnormal expression and activity of metabolic enzymes in affected cell types. They further demonstrate that these changes can be reversed by dietary n-3 fatty acid supplementation, highlighting the potential therapeutic benefit for cystic fibrosis patients.

Njoroge|Sarah W|SW|
Laposata|Michael|M|
Boyd|Kelli L|KL|
Seegmiller|Adam C|AC|

Fatty acid
Desaturase
Cystic fibrosis
Docosahexaenoate
Eicosapentaenoate
Arachidonate


Balloon-occluded chemoembolization for hepatocellular carcinoma: a prospective study of safety, feasibility and outcomes.

Abstract:
Aim
Evaluation of safety and efficacy of selective balloon-occluded transarterial chemoembolization using polyethylene glycol embolizing microspheres in patients with hepatocellular carcinoma.

Materials & methods
Twenty-four consecutive patients were included in this monocentric prospective trial. Adverse events were evaluated at 24 h and 1 month. Imaging response according to modified response evaluation criteria in solid tumors was assessed at 1, 3 and 6 months.

Results
The median time of follow-up was of 22.8 months (interquartile range (IQR) 17.38-26.22). Clinical grade 1/2 toxicities (0% >grade 2) were reported in 25.7% of patients, with abdominal pain being the most frequent complication (17.1%). No 30-days mortalities or liver decompensation were observed. The 1-month follow-up MRI showed an overall response rate of 74.3%.

Conclusion
Balloon-occluded transarterial chemoembolization was shown to be safe and effective.

balloon-occluded transarterial chemoembolization using drug-eluting microspheres


Optical Quantification of Harmonic Acoustic Radiation Force Excitation in a Tissue-Mimicking Phantom.

Abstract: Optical tracking was used to characterize acoustic radiation force-induced displacements in a tissue-mimicking phantom. Amplitude-modulated 3.3-MHz ultrasound was used to induce acoustic radiation force in the phantom, which was embedded with 10-μm microspheres that were tracked using a microscope objective and high-speed camera. For sine and square amplitude modulation, the harmonic components of the fundamental and second and third harmonic frequencies were measured. The displacement amplitudes were found to increase linearly with acoustic radiation force up to 10 μm, with sine modulation having 19.5% lower peak-to-peak amplitude values than square modulation. Square modulation produced almost no second harmonic, but energy was present in the third harmonic. For the sine modulation, energy was present in the second harmonic and low energy in the third harmonic. A finite-element model was used to simulate the deformation and was both qualitatively and quantitatively in agreement with the measurements.

D054459:Elasticity Imaging Techniques
D008863:Microspheres
D019047:Phantoms, Imaging

Acoustic radiation force
Tissue-mimicking phantom
Optical tracking
Amplitude modulation
Finite-element analysis
Harmonic displacement
Tissue deformation


A three-degree-of-freedom thin-film PZT-actuated microactuator with large out-of-plane displacement.

Abstract: A novel three degree-of-freedom microactuator based on thin-film lead-zirconate-titanate (PZT) is described with its detailed structural model. Its central rectangular-shaped mirror platform, also referred to as the stage, is actuated by four symmetric PZT bending legs such that each leg provides vertical translation for one corner of the stage. It has been developed to support real-time in vivo vertical cross-sectional imaging with a dual axes confocal endomicroscope for early cancer detection, having large displacements in three axes (z, θx, θy) and a relatively high bandwidth in the z-axis direction. Prototype microactuators closely meet the performance requirements for this application; in the out-of-plane (z-axis) direction, it has shown more than 177 μm of displacement and about 84 Hz of structural natural frequency, when two diagonal legs are actuated at 14V. With all four legs, another prototype of the same design with lighter stage mass has achieved more than 430 μm of out-of-plane displacement at 15V and about 200 Hz of bandwidth. The former design has shown approximately 6.4° and 2.9° of stage tilting about the x-axis and y-axis, respectively, at 14V. This paper also presents a modeling technique that uses experimental data to account for the effects of fabrication uncertainties in residual stress and structural dimensions. The presented model predicts the static motion of the stage within an average absolute error of 14.6 μm, which approaches the desired imaging resolution, 5 μm, and also reasonably anticipates the structural dynamic behavior of the stage. The refined model will support development of a future trajectory tracking controller for the system.

Choi|Jongsoo|J| Qiu|Zhen|Z| Rhee|Choong-Ho|CH| Wang|Thomas|T| Oldham|Kenn|K|

PZT
endomicroscopy
microactuator modeling
multi-axis microactuator
piezoelectric actuator


Genetic risk factors for pediatric-onset multiple sclerosis.

Abstract:
BACKGROUND
Strong evidence supports the role of both genetic and environmental factors in pediatric-onset multiple sclerosis (POMS) etiology.

OBJECTIVE
We comprehensively investigated the association between established major histocompatibility complex (MHC) and non-MHC adult multiple sclerosis (MS)-associated variants and susceptibility to POMS.

METHODS
Cases with onset <18 years (n = 569) and controls (n = 16,251) were included from the United States and Sweden. Adjusted logistic regression and meta-analyses were performed for individual risk variants and a weighted genetic risk score (wGRS) for non-MHC variants. Results were compared to adult MS cases (n = 7588).

RESULTS
HLA-DRB1*15:01 was strongly associated with POMS (odds ratio (OR)meta = 2.95, p < 2.0 × 10-16). Furthermore, 28 of 104 non-MHC variants studied (23%) were associated (p < 0.05); POMS cases carried, on average, a higher burden of these 28 variants compared to adults (ORavg = 1.24 vs 1.13, respectively), though the difference was not significant. The wGRS was strongly associated with POMS (ORmeta = 2.77, 95% confidence interval: 2.33, 3.32, p < 2.0 × 10-16) and higher, on average, when compared to adult cases. Additional class III risk variants in the MHC region associated with POMS were revealed after accounting for HLA-DRB1*15:01 and HLA-A*02.

CONCLUSION
Pediatric and adult MS share many genetic variants suggesting similar biological processes are present. MHC variants beyond HLA-DRB1*15:01 and HLA-A*02 are also associated with POMS.

Gianfrancesco|Milena A|MA|
Stridh|Pernilla|P|
Shao|Xiaorong|X|
Rhead|Brooke|B|
Graves|Jennifer S|JS|
Chitnis|Tanuja|T|
Waldman|Amy|A|
Lotze|Timothy|T|
Schreiner|Teri|T|
Belman|Anita|A|
Greenberg|Benjamin|B|
Weinstock-Guttman|Bianca|B|
Aaen|Gregory|G|
Tillema|Jan M|JM|
Hart|Janace|J|
Caillier|Stacy|S|
Ness|Jayne|J|
Harris|Yolanda|Y|
Rubin|Jennifer|J|
Candee|Meghan|M|
Krupp|Lauren|L|
Gorman|Mark|M|
Benson|Leslie|L|
Rodriguez|Moses|M|
Mar|Soe|S|
Kahn|Ilana|I|
Rose|John|J|
Roalstad|Shelly|S|
Casper|T Charles|TC|
Shen|Ling|L|
Quach|Hong|H|
Quach|Diana|D|
Hillert|Jan|J|
Hedstrom|Anna|A|
Olsson|Tomas|T|
Kockum|Ingrid|I|
Alfredsson|Lars|L|
Schaefer|Catherine|C|
Barcellos|Lisa F|LF|
Waubant|Emmanuelle|E|
|||

genetics
Multiple sclerosis
pediatrics
epidemiology


Organic mineral supplementation on differential protein profile of Osmanabadi bucks (Capra hircus).

Abstract: The present study aimed to determine the differential protein profile of seminal plasma proteins of bucks supplemented with trace minerals. Forty bucks of uniform size and body weight were assigned as ten groups (n = 4). The control group (T1) was fed with the control diet (concentration mixture and roughages) whereas the remaining groups were supplemented the control diet with Zn20 mg (T2), Zn40 mg (T3), Zn60 mg (T4), Cu12.5 mg (T5), Cu25 mg (T6), Cu37.5 mg (T7), Zn20 mg + Cu12.5 mg (T8), Zn40 mg + Cu25 mg (T9), and Zn60 mg + Cu37.5 mg (T10) for eight months. Seminal plasma proteins from each group were subjected to two-dimensional electrophoresis and fifteen differential proteins were selected based on differential expression, subjected to identification using Nano-LC-MS/MS (LTQ-Qrbitrap-MS). The identified proteins were Triacylglycerol lipase, EGF like repeats and discoidin domains 3, Lipocalin, Iodothyronine deiodinase, Transcription factor AP2-delta, 60S ribosomal protein L13, IST1 factor associated with ESCRT-III, Lysozyme, Uncharacterized protein (BRI3-binding protein), Uncharacterized protein, Histone deacetylase 11, General transcription factor IIF subunit 2, Nudix hydrolase 6, Protein kinase cAMP-activated catalytic subunit beta and Elongin C. The organic Cu supplemented group is the better than the organic Zn and organic Zn + Cu supplemented groups.

Sekar|Backialakshmi|B|
Arangasamy|Arunachalam|A|
Naidu|Sharanya Jeevendra|SJ|
Reddy|Ippala Janardhan|IJ|
Bhatta|Raghavendra|R|

Organic mineral
Differential protein
Bucks
Seminal plasma
Fecundity


Combination of Anterior Acetabular Coverage and Femoral Head Shape Predicts Femoroacetabular Impingement After Periacetabular Osteotomy.

Abstract:
BACKGROUND
Femoroacetabular impingement (FAI) after periacetabular osteotomy (PAO) may be affected by both anterior acetabular coverage and femoral head shape. This study aimed to radiographically evaluate the relationship of the combination of acetabular coverage and femoral head shape with the occurrence of FAI after curved PAO.

METHODS
In this study, 76 hip joints from patients with symptomatic developmental dysplasia of the hip underwent curved PAO. The relationship between the combined postoperative anterior center-edge and alpha angles (ie, the combination angle) and the occurrence of postoperative FAI was evaluated. Clinical factors and the preoperative and postoperative 3-dimensional center-edge angles, acetabular versions, femoral versions, radiographic alpha angles of the femoral head, and the combination angle were measured and compared to clinical outcomes.

RESULTS
The modified Harris Hip Scores, University of California, Los Angeles activity scores, and acetabular coverage angles were significantly improved following curved PAO. Receiver operator characteristic curve analysis demonstrated that the combination angle over 108° may be a predictive factor for the occurrence of FAI after curved PAO. Multivariate analysis demonstrated that an age <40 years (odds ratio 6.6, 95% confidence interval 1.2-36.4, P = .037) and a combination angle <108° (odds ratio 9.2, 95% confidence interval 1.7-50.0, P = .010) were significantly associated with modified Harris Hip Scores ≧90 points.

CONCLUSION
A combination angle >108° may be a predictive factor for the occurrence of FAI after curved PAO and impaired clinical outcomes. To avoid postoperative FAI, we propose that osteochondroplasty of the femoral head should be performed for patients with preoperative combination angles >90°.

Hayashi|Shinya|S| Hashimoto|Shingo|S| Kuroda|Yuichi|Y| Matsumoto|Tomoyuki|T| Kamenaga|Tomoyuki|T| Kuroda|Ryosuke|R|

anterior acetabular coverage
femoroacetabular impingement
periacetabular osteotomy
alpha angle
combination angle