Numerical Transcoding Proficiency in 10-Year-Old Schoolchildren is Associated with Gray Matter Inter-Individual Differences: A Voxel-Based Morphometry Study.

Abstract: Are individual differences in numerical performance sustained by variations in gray matter volume in schoolchildren? To our knowledge, this challenging question for neuroeducation has not yet been investigated in typical development. We used the Voxel-Based Morphometry method to search for possible structural brain differences between two groups of 10-year-old schoolchildren (N = 22) whose performance differed only in numerical transcoding between analog and symbolic systems. The results indicated that children with low numerical proficiency have less gray matter volume in the parietal (particularly in the left intraparietal sulcus and the bilateral angular gyri) and occipito-temporal areas. All the identified regions have previously been shown to be functionally involved in transcoding between analog and symbolic numerical systems. Our data contribute to a better understanding of the intertwined relationships between mathematics learning and brain structure in healthy schoolchildren.

Lubin|Amélie|A| Rossi|Sandrine|S| Simon|Grégory|G| Lanoë|Céline|C| Leroux|Gaëlle|G| Poirel|Nicolas|N| Pineau|Arlette|A| Houdé|Olivier|O|

schoolchildren
gray matter
voxel-based morphometry
neuroeducation
mathematics learning
educational neuroscience
number processing


Risk Factors for Middle East Respiratory Syndrome Coronavirus Infection among Camel Populations, Southern Jordan, 2014-2018.

Abstract: After the first detection of Middle East respiratory syndrome coronavirus (MERS-CoV) in camels in Jordan in 2013, we conducted 2 consecutive surveys in 2014-2015 and 2017-2018 investigating risk factors for MERS-CoV infection among camel populations in southern Jordan. Multivariate analysis to control for confounding demonstrated that borrowing of camels, particularly males, for breeding purposes was associated with increased MERS-CoV seroprevalence among receiving herds, suggesting a potential route of viral transmission between herds. Increasing age, herd size, and use of water troughs within herds were also associated with increased seroprevalence. Closed herd management practices were found to be protective. Future vaccination strategies among camel populations in Jordan could potentially prioritize breeding males, which are likely to be shared between herds. In addition, targeted management interventions with the potential to reduce transmission between herds should be considered; voluntary closed herd schemes offer a possible route to achieving disease-free herds.

Holloway|Peter|P|
Gibson|Matthew|M|
van Doremalen|Neeltje|N|
Nash|Stephen|S|
Holloway|Tanja|T|
Letko|Michael|M|
Cardwell|Jacqueline M|JM|
Al Omari|Bilal|B|
Al-Majali|Ahmad|A|
Abu-Basha|Ehab|E|
Mangtani|Punam|P|
Munster|Vincent J|VJ|
Guitian|Javier|J|

D065207:Middle East Respiratory Syndrome Coronavirus


The Role of the Ventromedial Prefrontal Cortex in Purchase Intent Among Older Adults.

Abstract: Older adults are frequently the targets of scams and deception, with millions of individuals being affected each year in the United States alone. Previous research has shown that the ventromedial prefrontal cortex (vmPFC) may play a role in vulnerability to fraud. The current study examined brain activation patterns in relation to susceptibility to scams and fraud using functional magnetic resonance imaging (fMRI). Twenty-eight healthy, community-dwelling older adults were subdivided into groups of impaired and unimpaired decision makers as determined by their performance on the Iowa Gambling Task (IGT). While in the scanner, the participants viewed advertisements that were created directly from cases deemed deceptive by the Federal Trade Commission (FTC). We then obtained behavioral measures involving comprehension of claims and purchase intention of the product in each advertisement. Contrasts show brain activity in the vmPFC was less correlated with purchase intention in impaired vs. unimpaired older adult decision makers. Our results have important implications for both future research and recognizing the possible causes of fraud susceptibility among older adults.

Koestner|Bryan P|BP|
Hedgcock|William|W|
Halfmann|Kameko|K|
Denburg|Natalie L|NL|

fraud
MRI
aging
decision making
frontal lobe


Liquid chromatography-tandem mass spectrometry and passive sampling: powerful tools for the determination of emerging pollutants in water for human consumption.

Abstract: Among the wide range of emerging pollutants, perfluorinated compounds and various pharmaceuticals, such as nonsteroidal anti-inflammatory drugs, are showing growing concern. These contaminants can be found in freshwater ecosystems because of their incomplete removal during wastewater treatments so, their water solubility and poor degradability result in their continuous discharge and pseudo-persistent contamination. Usually, expected levels of these analytes are particularly low; therefore, sensitive and selective analytical techniques are required for their determination. Moreover, sampling and preconcentration are fundamental steps to reach the low detection limits required. The polar organic chemical integrative sampler (POCIS) represents a modern sampling approach that allows the in-situ preconcentration of ultra-trace pollutants. In this work, a fast liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method was developed for the determination of diclofenac, ketoprofen, mefenamic acid, naproxen, ibuprofen, perfluorooctanoic acid, perfluorooctanesulfonate and caffeine in water for human consumption. The chromatographic separation of analytes was achieved in less than 6 min. Quantitative analysis was performed in multiple reaction monitoring mode using ketoprofen-d3 as internal standard. Two different sites of Northern Italy were studied deploying POCIS for four weeks in both inlet and outlet of two drinking water treatment plants. The evaluation of time-weighted average concentration of contaminants was accomplished after the calibration of POCIS; to this aim, the sampling rate values for each compound were obtained by means of a simple calibration system developed in our laboratory. Ketoprofen, perfluorooctane sulfonate, perfluorooctanoate and caffeine were measured in both sites at the ng l(-1) level. Copyright © 2016 John Wiley & Sons, Ltd.

Mirasole|Cristiana|C|
Di Carro|Marina|M|
Tanwar|Shivani|S|
Magi|Emanuele|E|

D002853:Chromatography, Liquid
D060766:Drinking Water
D004784:Environmental Monitoring
D006801:Humans
D007558:Italy
D057230:Limit of Detection
D016014:Linear Models
D015203:Reproducibility of Results
D053719:Tandem Mass Spectrometry
D014874:Water Pollutants, Chemical
D014881:Water Supply

passive sampling
emerging pollutants
anti-inflammatory drugs
POCIS
ground water
liquid chromatography
tandem mass spectrometry
water analysis


Reducing the Emotionality of Auditory Hallucination Memories in Patients Suffering From Auditory Hallucinations.

Abstract: Eye movement desensitization and reprocessing (EMDR) therapy targets emotionally disturbing visual memories of traumatic life events, and may be deployed as an efficacious treatment for posttraumatic stress disorder. A key element of EMDR therapy is recalling an emotionally disturbing visual memory while simultaneously performing a dual task. Previous studies have shown that auditory emotional memories may also become less emotional as a consequence of dual tasking. This is potentially beneficial for psychotic patients suffering from disturbing emotional auditory memories of auditory hallucinations. The present study examined whether and to what extent emotionality of auditory hallucination memories could be reduced by dual tasking. The study also assessed whether a modality matching dual task (recall + auditory taxation) could be more effective than a cross modal dual task (recall + visual taxation). Thirty-six patients suffering from auditory hallucinations were asked to recall an emotionally disturbing auditory memory related to an auditory hallucination, to rate emotionality of the memory, and to recall it under three conditions: two active conditions, i.e., visual taxation (making eye-movements) or auditory taxation (counting aloud), and one control condition (staring at a non-moving dot) counterbalanced in order. Patients re-rated emotionality of the memory after each condition. Results show the memory emotionality of auditory hallucinations was reduced and the active conditions showed stronger effects than the control condition. No modality-specific effect was found: the active conditions had an equal effect.

Matthijssen|Suzy Johanna Martina Adriana|SJMA|

eye movement desensitization and reprocessing


KBG syndrome.

Abstract:
CLINICAL DESCRIPTION
KBG syndrome is characterized by macrodontia of upper central incisors, distinctive craniofacial features such as triangular face, prominent nasal bridge, thin upper lip and synophrys; skeletal findings including short stature, delayed bone age, and costovertebral anomalies; and developmental delay/intellectual disability sometimes associated with seizures and EEG abnormalities. The condition was named KBG syndrome after the initials of the last names of three original families reported in 1975.

EPIDEMIOLOGY
The prevalence of KBG syndrome is not established. There are over 100 patients reported in the literature. It is likely that KBG syndrome is underreported due to incomplete recognition and very mild presentations of the disorder in some individuals. KBG syndrome is typically milder in females.

ETIOLOGY
Causative variants in ANKRD11 have been identified in affected individuals. The vast majority of identified variants are loss of function, which include nonsense and frameshift variants and larger deletions at 16q24.3. Haploinsufficiency appears to be the mechanism of pathogenicity.

GENETIC COUNSELING
Familial and de novo cases have been reported. Causative de novo variants occur approximately one third of the time. Transmission follows an autosomal dominant pattern. The syndrome displays inter- and intra-familial variability.

Morel Swols|Dayna|D|
Foster|Joseph|J|
Tekin|Mustafa|M|

KBG syndrome
Macrodontia
Short stature
ANKRD11
Review


Detection of the Adamkiewicz artery in computed tomography of the thorax and abdomen.

Abstract:
BACKGROUND
The great anterior radiculomedullary artery, also known as the artery of Adamkiewicz (AKA), is a small-caliber vessel which arises from the intercostal or lumbar arteries branching out from the aorta.

OBJECTIVES
The aim of this study was to evaluate detection of the AKA, as well as its level and side of origin, with multi-slice contrast enhanced computed tomography (MSCT) of the abdomen and thorax performed during everyday clinical practice, and to compare the results with the literature.

MATERIAL AND METHODS
The study retrospectively evaluated 200 consecutive MSCT images of the thoracic and thoracoabdominal aorta performed at Wroclaw Medical University's Department of General and Interventional Radiology and Neuroradiology as part of normal clinical work-ups. The CT examinations were performed with a 64-slice CT scanner. Arterial-phase images were analyzed for detection of the AKA and for anatomical variants of the AKA.

RESULTS
Recognition of the AKA was achieved in 43 of 200 patients (21.5%). Out of these 43 cases, the AKA originated on the left side in 36 instances (83.7%) - a significantly higher number than on the right side (only in 6 cases, 14%); in one case (2.3%) it arose from both sides (p < 0.05, T-test). Most of the AKAs (24 cases, 55.8%) originated on the left side at level T11 or T12. In 13 patients (30.2%) the AKA arose from T11 or from T12 intercostal arteries. The origin of the AKA varied greatly and ranged from T5 (2.3%) to L2 (2.3%).

CONCLUSIONS
The AKA is characterized by left-side lateralization and is associated with a wide range of origin, from T5 to L2. Detection of the AKA is, relatively speaking, rarely possible in routine clinical CT in the arterial phase - only in 1/5 of the patients. Therefore it is necessary to perform dedicated, individual arterial phase bolus tracking enhancement CT scans from the T5 to L3 level.

Guziński|Maciej|M|
Bryl|Maciej|M|
Ziemińska|Katarzyna|K|
Wolny|Kamila|K|
Sąsiadek|Marek|M|
Garcarek|Jerzy S|JS|

great anterior radiculomedullary artery
Adamkiewicz artery (AKA)
computed tomograpy (CT)


Loss of core fucosylation reduces low-density lipoprotein receptor expression in hepatocytes by inducing PCSK9 production.

Abstract: Fucosylation is a type of glycosylation, a form of post-transcriptional regulation of proteins, involved in cancer and inflammation. It involves the attachment of a fucose residue to N-glycans, O-glycans, and glycolipids, which is catalyzed by a family of enzymes called fucosyltransferases (Futs). Among the many Futs, α-1,6-fucosyltransferase (Fut8) is the only enzyme that produces α-1,6-fucosylated oligosaccharides (core fucose). In the human liver, the expression and activity of Fut8 are frequently elevated during progression of chronic liver diseases. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a well-known negative regulator of the low-density lipoprotein receptor (LDLR). Here, we found that loss of core fucose in immortalized hepatocytes led to LDLR downregulation through a dramatic induction of PCSK9. We used the immortalized hepatocytes derived from Fut8 knockout mice or a Fut8 knockdown AML12 hepatocyte cell line. Using these cells, we investigated the effects of Fut8 on hepatocyte cholesterol influx. Both cell lines had reduced LDLR protein levels, resulting from marked increases in PCSK9 expression. Intracellular cholesterol levels were significantly lower and LDL cholesterol uptake was suppressed in Fut8-KO cells. Hepatocyte nuclear factor 1α accumulated in nuclei of Fut8-KO hepatocytes, which mediated increases in PCSK9 mRNA expression. Our findings demonstrated that loss of core fucosylation promoted degradation of LDLR and impaired cholesterol uptake, which is a novel mechanism that regulates cholesterol influx, suggesting that Fut8 might be a novel causative gene for familial hypercholesterolemia.

Kamada|Yoshihiro|Y| Yamamoto|Akiko|A| Fujiyoshi|Anna|A| Koseki|Masahiro|M| Morishita|Koichi|K| Asuka|Tatsuya|T| Takamatsu|Shinji|S| Sakata|Yasushi|Y| Takehara|Tetsuo|T| Taniguchi|Naoyuki|N| Miyoshi|Eiji|E|


Outcomes of osseointegrated implants in patients with benign and malignant pathologies of the head and neck: a 10-year single-centre study.

Abstract: The surgical management of head and neck pathologies involving the maxilla and mandible results in significant functional and aesthetic deficits, and ultimately reduced quality of life. Composite free flaps used for reconstruction address many of these deficits and create a foundation for the use of osseointegrated implants to support prosthetic replacement of the dentition. There are few comparative studies examining outcomes of implants in native and reconstructed bone in head and neck cancer patients. The aim of this retrospective cohort study was to compare survival rates and the effects of risk factors between implants placed in native and reconstructed bone. The Kaplan-Meier method estimated cumulative 1- and 5-year implant survival rates of 99.5% and 95% for native bone and 96% and 88% for reconstructed bone. Multivariate Cox regression found an increased risk of implant failure in reconstructed bone (hazard ratio (HR) 9.9, 95% confidence interval (CI) 3.4-29.7, P<0.001). Subgroup analysis of the cohorts found an increased risk of failure in the reconstructed group associated with radiotherapy (HR 6.4, 95% CI 1.8-22.3, P=0.004), current smoking (HR 23.2, 95% CI 2.7-198.6, P=0.004), and previous smoking (HR 9.0, 95% CI 1.1-71.9, P=0.038). There was no effect in the native bone group. Implants placed into reconstructed bone had higher rates of failure, and smoking status and radiotherapy increased the risk of implant failure.

Khadembaschi|D|D|
Borgna|S C|SC|
Beech|N|N|
Batstone|M D|MD|

bone transplantation
endosseous dental implantation
free tissue flaps
head and neck neoplasms
reconstructive surgical procedures


Synthesis and characterization of a polyurethane carrier used for a prolonged transmembrane transfer of a chili pepper extract.

Abstract:
Purpose
Red chili peppers have been highly valued in gastronomy and traditional medicine since ancient times; it seems that it is not just an ingredient for food but also a good remedy for various medical conditions such as increased blood pressure and high levels of serum triglycerides and cholesterol, myocardial infarction, arthritis, and migraines. The objective of this study is the characterization of a new carrier used for encapsulated extract.

Methods
Chili pepper extract was obtained and was physically entrapped inside polyurethane microparticles in order to diminish the irritative potential of this extract. The particles were evaluated by Zetasizer measurements, small-angle neutron scattering and thermal analysis, scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy; the encapsulation efficacy and the drug release profile were assessed by UV-Vis spectroscopy. Bioevaluations on mice skin were performed to predict the irritative potential of the samples.

Results
Two different types of samples were compared: hollow polyurethane microparticles vs polyurethane particles containing the natural extract. The sizes of the particles were very similar, but the sample containing the extract presents three particle populations (the polydispersity index increases from 0.3 to 0.6 from one sample to another). The zeta-potential measurements and SEM images indicate a medium tendency to form clusters, while the UV-Vis study revealed an almost 70% encapsulation efficacy.

Conclusion
The results suggest that encapsulation of a chili pepper extract inside polyurethane microparticles leads to a non-irritative product with a prolonged release: ~30% of encapsulated extract is released within the first 8 days and a maximum 45% is reached in 2 weeks.

Borcan|Livia-Cristina|LC|
Dudas|Zoltan|Z|
Len|Adel|A|
Fuzi|Janos|J|
Borcan|Florin|F|
Tomescu|Mirela Cleopatra|MC|

D017550:Spectroscopy, Fourier Transform Infrared

UV-Vis
zeta-potential
FTIR
SANS
corneometry
drug delivery system
erythema


Extracellular Vesicles as Mediators of Cellular Crosstalk Between Immune System and Kidney Graft.

Abstract: Extracellular vesicles (EVs) are known immune-modulators exerting a critical role in kidney transplantation (KT). EV bioactive cargo includes graft antigens, costimulatory/inhibitory molecules, cytokines, growth factors, and functional microRNAs (miRNAs) that may modulate expression of recipient cell genes. As paracrine factors, neutrophil- and macrophage-derived EVs exert immunosuppressive and immune-stimulating effects on dendritic cells, respectively. Dendritic cell-derived EVs mediate alloantigen spreading and modulate antigen presentation to T lymphocytes. At systemic level, EVs exert pleiotropic effects on complement and coagulation. Depending on their biogenesis, they can amplify complement activation or shed complement inhibitors and prevent cell lysis. Likewise, endothelial- and platelet-derived EVs can exert procoagulant/prothrombotic effects and also promote endothelial survival and angiogenesis after ischemic injury. Kidney endothelial- and tubular-derived EVs play a key role in ischemia-reperfusion injury (IRI) and during the healing process; additionally, they can trigger rejection by inducing both alloimmune and autoimmune responses. Endothelial EVs have procoagulant/pro-inflammatory effects and can release sequestered self-antigens, generating a tissue-specific autoimmunity. Renal tubule-derived EVs shuttle pro-fibrotic mediators (TGF-β and miR-21) to interstitial fibroblasts and modulate neutrophil and T-lymphocyte influx. These processes can lead to peritubular capillary rarefaction and interstitial fibrosis-tubular atrophy. Different EVs, including those from mesenchymal stromal cells (MSCs), have been employed as a therapeutic tool in experimental models of rejection and IRI. These particles protect tubular and endothelial cells (by inhibition of apoptosis and inflammation-fibrogenesis or by inducing autophagy) and stimulate tissue regeneration (by triggering angiogenesis, cell proliferation, and migration). Finally, urinary and serum EVs represent potential biomarkers for delayed graft function (DGF) and acute rejection. In conclusion, EVs sustain an intricate crosstalk between graft tissue and innate/adaptive immune systems. EVs play a major role in allorecognition, IRI, autoimmunity, and alloimmunity and are promising as biomarkers and therapeutic tools in KT.

Quaglia|Marco|M| Dellepiane|Sergio|S| Guglielmetti|Gabriele|G| Merlotti|Guido|G| Castellano|Giuseppe|G| Cantaluppi|Vincenzo|V|

extracellular vesicles
miRNA
autoimmunity
biomarker
acute rejection
ischemia-reperfusion syndrome
renal transplant


Maternal butalbital use and selected defects in the national birth defects prevention study.

Abstract:
BACKGROUND
Butalbital is a barbiturate contained in combination products with caffeine and an analgesic prescribed for the treatment of migraine and tension-type headaches. Controversy exists as to whether butalbital should continue to be prescribed in the United States because of the potential for abuse, overuse headache, and withdrawal syndromes. Butalbital crosses the placenta but there is limited information about potential teratogenicity.

OBJECTIVE
To evaluate associations between butalbital and a wide range of specific birth defects.

METHODS
The National Birth Defects Prevention Study is an ongoing, case-control study of nonsyndromic, major birth defects conducted in 10 states. The detailed case classification and large number of cases in the National Birth Defects Prevention Study allowed us to examine the association between maternal self-reported butalbital use and specific birth defects. We conducted an analysis of 8373 unaffected controls and 21,090 case infants with estimated dates of delivery between 1997 and 2007; included were birth defects with 250 or more cases. An exploratory analysis examined groups with 100 to 249 cases.

RESULTS
Seventy-three case mothers and 15 control mothers reported periconceptional butalbital use. Of 30 specific defect groups evaluated, adjusted odds ratios for maternal periconceptional butalbital use were statistically significant for 3 congenital heart defects: tetralogy of Fallot (adjusted odds ratio = 3.04; 95% confidence interval = 1.07-8.62), pulmonary valve stenosis (adjusted odds ratio = 5.73; 95% confidence interval = 2.25-14.62), and secundum-type atrial septal defect (adjusted odds ratio = 3.06; 95% confidence interval = 1.07-8.79). In the exploratory analysis, an elevated odds ratio was detected for 1 congenital heart defect, single ventricle.

CONCLUSIONS
We observed relationships between maternal periconceptional butalbital use and certain congenital heart defects. These associations have not been reported before, and some may be spurious. Butalbital use was rare and despite the large size of the National Birth Defects Prevention Study, the number of exposed case and control infants was small. However, if confirmed in additional studies, our findings will be useful in weighing the risks and benefits of butalbital for the treatment of migraine and tension-type headaches.

Browne|Marilyn L|ML|
Van Zutphen|Alissa R|AR|
Botto|Lorenzo D|LD|
Louik|Carol|C|
Richardson|Sandra|S|
Druschel|Charlotte M|CM|

D011297:Prenatal Exposure Delayed Effects

butalbital
birth defect
migraine
headache


Nationwide Twin Birth Weight Percentiles by Gestational Age in Taiwan.

Abstract:
BACKGROUND
Nationwide birth weight norms for twins have been reported in several countries across different ethnicities, but such data have not been established in Taiwan. The purpose of this study was to develop reference growth charts that are population-based and contain the information of birth weight percentiles by gestational age for twin neonates in Taiwan.

METHODS
In this study, we collected nationwide birth weight data for twins by sex and gestational age through the Taiwan Birth Registry. Percentiles, means, and standard deviations of birth weight for each 1-week increment of gestational age from 21 weeks of gestation were estimated and smoothed using weighted polynomial models.

RESULTS
The 10(th), 50(th), and 90(th) percentiles of birth weight born at the 37(th) gestational week were 2174 g, 2580 g, and 3125 g for male twins, respectively, and they were 2100 g, 2500 g, and 3000 g for female twins, respectively. The 10(th), 50(th), and 90(th) percentiles of birth weight born at the 40(th) gestational week were 2326, 3285, and 3790 g for male twins, respectively, and they were 2200 g, 2770 g, and 3690 g for female twins, respectively.

CONCLUSION
This is the first nationwide birth weight norm for twins in Taiwan, which is particularly useful for investigation into the predictors and outcomes of altered fetal growth through twin studies in the Taiwanese population.

Hu|I-Jan|IJ| Hsieh|Chia-Jung|CJ| Jeng|Suh-Fang|SF| Wu|Hui-Chen|HC| Chen|Chien-Yi|CY| Chou|Hung-Chieh|HC| Tsao|Po-Nien|PN| Lin|Shio-Jean|SJ| Chen|Pau-Chung|PC| Hsieh|Wu-Shiun|WS|

twin
birth weight
percentile
gestational age
intrauterine growth


Polygonum cuspidatum extract attenuates fructose-induced liver lipid accumulation through inhibiting Keap1 and activating Nrf2 antioxidant pathway.

Abstract:
BACKGROUND
Polygonum cuspidatum has been used in traditional Chinese medicine to treat liver disorders associated with oxidative stress, inflammation and lipid accumulation for centuries in patients.

PURPOSE
The aim of this study was to examine whether P. cuspidatum extract (PCE) prevented against fructose-induced liver lipid accumulation via regulating Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway.

METHOD
PCE was administered orally to male Sprague-Dawley rats given 10% fructose drinking water for 6 weeks at 80 and 160 mg/kg once daily for 11 weeks.

RESULTS
PCE significantly alleviated liver lipid accumulation in fructose-fed rats with metabolic syndrome. It also inhibited Keap1, activated Nrf2 antioxidant pathway, resulting in the suppression of oxidative stress, evidenced by reducing hydrogen peroxide (H2O2), malondialdehyde (MDA) and hydroxy radical (OH•) levels, and increasing glutathione (GSH)/oxidized glutathione (GSSG) ratio as well as superoxidase dismutase (SOD) and catalase (CAT) activity in the liver of fructose-fed rats. Additionally, PCE up-regulated peroxisome proliferator activated receptor-α (PPAR-α), and down-regulated sterol regulatory element binging protein 1 (SREBP-1), fatty acid synthetase (FAS) and stearoyl-CoA desaturase-1 (SCD-1) in this animal model, being consistent with its reduction of triglyceride (TG) levels.

CONCLUSION
These results demonstrate that PCE reduces oxidative stress, and prevent lipid accumulation in the liver of fructose-fed rats possibly by targeting the Keap1/Nrf2 pathway. PCE may be a promising therapeutic strategy for fructose-associated liver lipid accumulation.

Zhao|Xiao-Juan|XJ| Chen|Li|L| Zhao|Yue|Y| Pan|Ying|Y| Yang|Yan-Zi|YZ| Sun|Yang|Y| Jiao|Rui-Qing|RQ| Kong|Ling-Dong|LD|

D000072019:Kelch-Like ECH-Associated Protein 1

D051780:Sterol Regulatory Element Binding Protein 1

Polygonum cuspidatum extract
Liver lipid accumulation
Fructose
Keap1/Nrf2 pathway


The Clinicopathological features and survival outcomes of patients with different metastatic sites in stage IV breast cancer.

Abstract:
BACKGROUND
The features and survival of stage IV breast cancer patients with different metastatic sites are poorly understood. This study aims to examine the clinicopathological features and survival of stage IV breast cancer patients according to different metastatic sites.

METHODS
Using the Surveillance, Epidemiology, and End Results database, we restricted our study population to stage IV breast cancer patients diagnosed between 2010 to 2015. The clinicopathological features were examined by chi-square tests. Breast cancer-specific survival (BCSS) and overall survival (OS) were compared among patients with different metastatic sites by the Kaplan-Meier method with log-rank test. Univariable and multivariable analyses were also performed using the Cox proportional hazard model to identify statistically significant prognostic factors.

RESULTS
A total of 18,322 patients were identified for survival analysis. Bone-only metastasis accounted for 39.80% of patients, followed by multiple metastasis (33.07%), lung metastasis (10.94%), liver metastasis (7.34%), other metastasis (7.34%), and brain metastasis (1.51%). The Kaplan-Meier plots showed that patients with bone metastasis had the best survival, while patients with brain metastasis had the worst survival in both BCSS and OS (p < 0.001, for both). Multivariable analyses showed that age, race, marital status, grade, tumor subtype, tumor size, surgery of primary cancer, and a history of radiotherapy or chemotherapy were independent prognostic factors.

CONCLUSION
Stage IV breast cancer patients have different clinicopathological characteristics and survival outcomes according to different metastatic sites. Patients with bone metastasis have the best prognosis, and brain metastasis is the most aggressive subgroup.

D000328:Adult
D000368:Aged
D000369:Aged, 80 and over
D001943:Breast Neoplasms
D005260:Female
D006801:Humans
D053208:Kaplan-Meier Estimate
D008875:Middle Aged
D009362:Neoplasm Metastasis
D009367:Neoplasm Staging
D063868:Patient Outcome Assessment
D011379:Prognosis
D016016:Proportional Hazards Models
D018426:SEER Program
D016019:Survival Analysis
D055815:Young Adult

Survival outcomes
Metastatic sites
Breast cancer
SEER


Rational molecular design for improving digestive enzyme resistance of beta-glucosidase from Trichoderma viride based on inhibition of bound state formation.

Abstract: Beta-glucosidase (BGL1) is widely used in animal feed industries. However, degradation caused by digestive enzymes in the intestine hampers its application. Improving the resistance of feed enzymes against proteases is crucial in livestock farming. To improve the resistance of beta-glucosidase against pepsin and trypsin, a rational molecular design based on the inhibition of bound-state formation and secondary design was developed. The strategy includes: (1) prediction of the interaction surface of the pepsin-BGL1 complex structure, (2) prediction of key amino acids affecting the formation of the complex, (3) optimization of pepsin-resistant mutants by structural evaluation, (4) secondary molecular design based on pepsin-resistant mutants, and optimization of pepsin and trypsin-resistant mutants. Two BGL1 protein mutants (BGL1Q627C and BGL1Q627C/R543H/R646W) were constructed, and then mutated and wild-type BGL1s were expressed in Pichia pastoris. The half-life of BGL1Q627C and BGL1Q627C/R543H/R646W were 1.36 and 1.51 times that of the wild type upon pepsin exposure, respectively. For trypsin resistance, the half-life were 0.93 and 1.53 times that of the wild type, respectively. Compare to those of the wild type, most of the basic enzymatic properties of both mutants were not significantly changed except for increased Michaelis constants. The rational design method can be used as a guide for modifying other feed enzymes.

Wang|Hao|H| Lin|Xiangna|X| Li|Shuang|S| Lin|Jianlin|J| Xie|Chunfang|C| Liu|Daling|D| Yao|Dongsheng|D|

Secondary design
Trypsin resistance
Beta-glucosidase 1
Pepsin resistance
molecular simulation


Impact of atrial fibrillation on stroke-related healthcare costs.

Abstract:
BACKGROUND
Limited data exist on the economic implications of stroke among patients with atrial fibrillation (AF). This study assesses the impact of AF on healthcare costs associated with ischemic stroke (IS), hemorrhagic stroke (HS), or transient ischemic attack (TIA).

METHODS AND RESULTS
A retrospective analysis of MarketScan claims data (2005-2011) for AF patients ≥18 years old with ≥1 inpatient claim for stroke, or ≥1 ED or inpatient claim for TIA as identified by ICD-9-CM codes who had ≥12 months continuous enrollment prior to initial stroke. Initial event- and stroke-related costs 12 months post-index were compared among patients with AF and without AF. Adjusted costs were estimated, controlling for demographics, comorbidities, anticoagulant use, and baseline resource use. Data from 23,807 AF patients and 136,649 patients without AF were analyzed. Unadjusted mean cost of the index event was $20,933 for IS, $59,054 for HS, $8616 for TIA hospitalization, and $3395 for TIA ED visit. After controlling for potential confounders, adjusted mean incremental costs (index plus 12-month post-index) for AF patients were higher than those for non-AF patients by: $4726, $7824, and $1890 for index IS, HS, TIA (identified by hospitalization), respectively, and $1700 for TIA (identified by ED) (all P<0.01). In multivariate regression analysis, AF was associated with a 20% (IS), 13% (HS), and 18% (TIA) increase in total stroke-related costs.

CONCLUSION
Stroke-related care for IS, HS, and TIA is costly, especially among individuals with AF. Reducing the risk of AF-related stroke is important from both clinical and economic standpoints.

Sussman|Matthew|M|
Menzin|Joseph|J|
Lin|Iris|I|
Kwong|Winghan J|WJ|
Munsell|Michael|M|
Friedman|Mark|M|
Selim|Magdy|M|

D000368:Aged
D000369:Aged, 80 and over
D000925:Anticoagulants
D001281:Atrial Fibrillation
D002545:Brain Ischemia
D017046:Cost Savings
D003362:Cost-Benefit Analysis
D016527:Drug Costs
D005260:Female
D017048:Health Care Costs
D017721:Hospital Costs
D006801:Humans
D020300:Intracranial Hemorrhages
D002546:Ischemic Attack, Transient
D008297:Male
D008875:Middle Aged
D018803:Models, Economic
D011379:Prognosis
D012189:Retrospective Studies
D020521:Stroke
D013997:Time Factors
D014481:United States

economics
ischemic stroke
hemorrhage
transient ischemic attack
outcomes research


Annotation of snoRNA abundance across human tissues reveals complex snoRNA-host gene relationships.

Abstract:
BACKGROUND
Small nucleolar RNAs (snoRNAs) are mid-size non-coding RNAs required for ribosomal RNA modification, implying a ubiquitous tissue distribution linked to ribosome synthesis. However, increasing numbers of studies identify extra-ribosomal roles of snoRNAs in modulating gene expression, suggesting more complex snoRNA abundance patterns. Therefore, there is a great need for mapping the snoRNome in different human tissues as the blueprint for snoRNA functions.

RESULTS
We used a low structure bias RNA-Seq approach to accurately quantify snoRNAs and compare them to the entire transcriptome in seven healthy human tissues (breast, ovary, prostate, testis, skeletal muscle, liver, and brain). We identify 475 expressed snoRNAs categorized in two abundance classes that differ significantly in their function, conservation level, and correlation with their host gene: 390 snoRNAs are uniformly expressed and 85 are enriched in the brain or reproductive tissues. Most tissue-enriched snoRNAs are embedded in lncRNAs and display strong correlation of abundance with them, whereas uniformly expressed snoRNAs are mostly embedded in protein-coding host genes and are mainly non- or anticorrelated with them. Fifty-nine percent of the non-correlated or anticorrelated protein-coding host gene/snoRNA pairs feature dual-initiation promoters, compared to only 16% of the correlated non-coding host gene/snoRNA pairs.

CONCLUSIONS
Our results demonstrate that snoRNAs are not a single homogeneous group of housekeeping genes but include highly regulated tissue-enriched RNAs. Indeed, our work indicates that the architecture of snoRNA host genes varies to uncouple the host and snoRNA expressions in order to meet the different snoRNA abundance levels and functional needs of human tissues.

Fafard-Couture|Étienne|É|
Bergeron|Danny|D|
Couture|Sonia|S|
Abou-Elela|Sherif|S|
Scott|Michelle S|MS|0000-0001-6231-7714

SnoRNA
Human tissues
RNA-Seq
Transcriptome
Dual-initiation promoters
Nonsense-mediated decay
SnoRNA/host gene relationship
TGIRT-Seq


Neonatal morbidity after spontaneous labor onset prior to intended cesarean delivery at term: a cohort study.

Abstract:
INTRODUCTION
We aimed to investigate if labor onset before planned cesarean delivery (CD) affects the risk of neonatal admission, respiratory distress, or neonatal infectious morbidity.

MATERIAL AND METHODS
Our cohort included singleton term pregnant women with intended CD who delivered at Aarhus University Hospital from 1990 to 2012. Two groups of women were identified: women with intended CD performed before labor (nonlabor CD) and women with intended CD performed after spontaneous labor onset (labor-onset CD); in both groups there was no other maternal or fetal medical indication for an immediate CD or for early-term CD scheduling. Data were stratified in early-term (37-38 weeks) and full-term (39-40 weeks) deliveries. The main outcome measures were neonatal admission, respiratory distress and neonatal infectious morbidity.

RESULTS
Among 103 919 live births, 5071 deliveries were nonlabor CDs and 731 were labor-onset CDs. Compared to nonlabor CD, labor-onset CD was associated with similar risks of neonatal admission and respiratory distress, both at early and full term, but with a two- to three-fold increased risk of newborn septicemia or antibiotic treatment at early term. Labor onset at early term was associated with a lower risk of maternal blood loss of more than 500 mL, but with a higher risk of postoperative antibiotic treatment and endometritis.

CONCLUSIONS
Labor onset before planned CD was not associated with a decrease in neonatal respiratory morbidity, but may be associated with increased risks of neonatal infection.

Glavind|Julie|J|
Milidou|Ioanna|I|
Uldbjerg|Niels|N|
Maimburg|Rikke|R|
Henriksen|Tine B|TB|

labor onset
Cesarean
infections
neonatology
rupture of membranes


Effects of Rebamipide on Differences in Power and Axis of Corneal Astigmatism Between Two Intra-patient Keratometric Measurements in Dry Eyes.

Abstract:
INTRODUCTION
This study investigated the effect of rebamipide on discrepancies in the power and axis of astigmatism between two intra-patient keratometric measurements in patients with dry eyes.

METHODS
Fifty-eight dry eyes (with a short tear breakup time [TBUT] of less than 5 s) were analyzed. Patients with dry eye were treated with 2% rebamipide ophthalmic suspension (group R) or Mytear® artificial tear ophthalmic solution (group M) for 4 weeks. TBUT and corneal higher-order aberrations (HOAs) were evaluated at baseline and 4 weeks after treatment. Astigmatism power and axis were measured twice during both evaluations, at 5-min intervals. Baseline and post-treatment measurements were compared. Changes in TBUT and HOAs, and intra-patient discrepancies in astigmatism power and axis measurements were evaluated.

RESULTS
HOAs showed significant positive correlations with intra-patient differences in astigmatism power and axis (P < 0.001). At the 4-week post-treatment follow-up, TBUT increased, and HOAs and astigmatism power and axis discrepancies decreased in a significant number of patients in group R (P < 0.001). In group M, only differences in astigmatism power decreased in a significant number of cases (P = 0.005). The degree of change in the intra-patient difference in astigmatism power between the two post-treatment keratometric measurements was significantly greater in group R than in group M (P < 0.001). In group R, baseline HOAs exhibited a significant positive correlation with changes in HOAs and intra-patient differences in astigmatism power (both P < 0.001). In group M, baseline HOAs were only significantly correlated with changes in intra-patient differences in astigmatism power (P = 0.030).

CONCLUSION
In dry eyes with short TBUTs, rebamipide significantly improved the corneal surface condition and significantly reduced intra-patient discrepancies in astigmatism power and axis measurements. Rebamipide may improve the accuracy of intraocular lens (IOL) power calculations in dry eyes, particularly when toric IOLs are implanted.

Rebamipide
Keratometric measurement
Dry eye
Astigmatic power
Astigmatism axis


In vivo evidence that the cannabinoid receptor 2-63 RR variant is associated with the acquisition and/or expansion of HIV infection.

Abstract:
OBJECTIVES
The aim of the study was to investigate whether the rs35761398 variants of the cannabinoid receptor 2 (CB2) gene may influence the acquisition of HIV infection and the clinical presentation of HIV/hepatitis C virus (HCV) coinfection.

METHODS
We compared 166 HIV/HCV-coinfected patients with 186 HCV-monoinfected patients, all with biopsy-proven chronic hepatitis (using the Ishak scoring system), naïve for anti-HCV treatment and tested for the CB2 rs35761398 polymorphism (using the TaqMan assay).

RESULTS
The HIV/HCV-coinfected patients were more frequently male (P < 0.002), were younger (P < 0.001), and had lower median BMI (P < 0.001) and HCV RNA (P < 0.05) and higher median aspartate aminotransferase (AST; P < 0.001), alanine aminotransferase (ALT; P < 0.001) and gamma glutamyl transferase (GGT; P < 0.001) levels than the HCV-monoinfected patients. The CB2 RR variant predominated in HIV/HCV-coinfected patients (45.8% vs. 31.2% in HCV-monoinfected patients; P < 0.001) and the CB2 QR variant in HCV-monoinfected patients (57.5% vs. 38.6% in HIV/HCV-coinfected patients; P < 0.00001), and the CB2 QQ variant was equally distributed. Focusing on patients with the CB2 QQ variant, the 26 HIV/HCV-coinfected patients, compared with the 21 HCV-monoinfected patients, showed less severe liver necroinflammation [lower histological activity index (HAI)] (P < 0.05). Of the patients with the CB2 RR variant, the 76 HIV/HCV-coinfected patients, compared with the 58 HCV-monoinfected patients, were more frequently male (P < 0.05), were younger (P < 0.001), and had a lower median body mass index (BMI; P < 0.001), a higher median AST level (P < 0.001), a higher mean HAI score (P < 0.05) and a higher rate of cases with severe steatosis (P = 0.05). In an analysis of variance (anova) of HCV/HIV-coinfected and HCV-monoinfected patient data, those with the CB2 RR variant (P = 0.003) and of male sex (P = 0.002) were more prevalent in the HCV/HIV-coinfected group.

CONCLUSIONS
There is the suggestion of a positive effect of the CB2 RR variant on HIV acquisition and/or spread, which is in accordance with previous in vitro observations.

Sagnelli|C|C|0000-0002-6413-7810 Uberti-Foppa|C|C| Hasson|H|H| Bellini|G|G| Minichini|C|C| Salpietro|S|S| Messina|E|E| Barbanotti|D|D| Merli|M|M| Punzo|F|F| Coppola|N|N| Lazzarin|A|A| Sagnelli|E|E|0000-0003-2817-8436 Rossi|F|F|

D020022:Genetic Predisposition to Disease

cannabinoid receptor
cannabinoid receptor 2
HIV/hepatitis C virus coinfection
endocannabinoids
liver biopsy
liver histology
liver steatosis


Amorphous InGaMgO Ultraviolet Photo-TFT with Ultrahigh Photosensitivity and Extremely Large Responsivity.

Abstract: Recently, amorphous InGaZnO ultraviolet photo thin-film transistors have exhibited great potential for application in future display technologies. Nevertheless, the transmittance of amorphous InGaZnO (~80%) is still not high enough, resulting in the relatively large sacrifice of aperture ratio for each sensor pixel. In this work, the ultraviolet photo thin-film transistor based on amorphous InGaMgO, which processes a larger bandgap and higher transmission compared to amorphous InGaZnO, was proposed and investigated. Furthermore, the effects of post-deposition annealing in oxygen on both the material and ultraviolet detection characteristics of amorphous InGaMgO were also comprehensively studied. It was found that oxygen post-deposition annealing can effectively reduce oxygen vacancies, leading to an optimized device performance, including lower dark current, higher sensitivity, and larger responsivity. We attributed it to the combined effect of the reduction in donor states and recombination centers, both of which are related to oxygen vacancies. As a result, the 240-min annealed device exhibited the lowest dark current of 1.7 × 10-10 A, the highest photosensitivity of 3.9 × 10⁶, and the largest responsivity of 1.5 × 10⁴ A/W. Therefore, our findings have revealed that amorphous InGaMgO photo thin-film transistors are a very promising alternative for UV detection, especially for application in touch-free interactive displays.

Zhang|Yiyu|Y| Qian|Ling-Xuan|LX| Wu|Zehan|Z| Liu|Xingzhao|X|

InGaMgO
ultraviolet photo-TFT
photosensitivity
responsivity
post-deposition annealing
oxygen vacancy


Design, synthesis and biological evaluation of selective hybrid coumarin-thiazolidinedione aldose reductase-II inhibitors as potential antidiabetics.

Abstract: Thiazolidinediones (TZD), benzopyrans are the proven scaffolds for inhibiting Aldose reductase (ALR2) activity and their structural confluence with the retention of necessary fragments helped in designing a series of hybrid compounds 2-(5-cycloalkylidene-2,4-dioxothiazolidin-3-yl)-N-(2-oxo-2H-chromen-3-yl)acetamide (10a-n) for better ALR2 inhibition. The compounds were synthesized by treating substituted 3-(N-bromoacetyl amino)coumarins (9a-d) with potassium salt of 5-cyclo alkylidene-1,3-thiazolidine-2,4-diones (4a-d). The inhibition activity against ALR2 with IC50 values range from 0.012 ± 0.001 to 0.056 ± 0.007 μM. N-[(6-Bromo-3-coumarinyl)-2-(5-cyclopentylidene-2,4-dioxothiazolidin-3-yl)] acetamide (10c) with cyclopentylidene group on one end and the 6-bromo group on the other end showed better inhibitory property (IC50 = 0.012 μM) and selectivity index (324.166) against the ALR2, a forty fold superiority over sorbinil, a better molecule over epalrestat and rest of the analogues exhibited a far superior response over sorbinil and slightly better as compared with epalrestat. It was further confirmed by the insilico studies that compound 10c showed best inhibition activity among the synthesized compounds with a high selectivity index against the ALR2. In invivo experiments, supplementation of compound 10c to STZ induced rats delayed the progression of cataract in a dose-dependent manner warranting its further development as a potential agent to treat thediabetic secondary complications especially cataract.

Kumar Pasala|Vijay|V|
Gudipudi|Gopinath|G|
Sankeshi|Venu|V|
Basude|Manohar|M|
Gundla|Rambabu|R|
Singh Jadav|Surendar|S|
Srinivas|Burra|B|
Yadaiah Goud|E|E|
Nareshkumar|Devasani|D|

Benzopyrans
1,3-Thiazolidine-2,4-diones
Aldose reductase inhibitors
Diabetic complications
Molecular modeling


Survival after complete cytoreductive surgery and HIPEC for extensive pseudomyxoma peritonei.

Abstract:
INTRODUCTION
The optimal treatment for pseudomyxoma peritonei (PMP) combines complete cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Yet, achieving CRS is challenging in the case of extensive involvement of the peritoneal cavity and the survival benefit in this setting remains uncertain. The present study evaluated the surgical outcomes according to the peritoneal extent.

METHODS
Between 1992 and 2014, 245 patients underwent CRS and HIPEC for PMP in our institution. Their characteristics were reviewed using a prospective database. Extensive PMP was defined as a peritoneal cancer index (PCI) ≥ 28. Sixty-one patients with extensive PMP were compared to 184 with non-extensive PMP.

RESULTS
Severe complications were more frequent in the extensive group (46% vs. 23%, p < 0.001) but the post-operative mortality was not significantly different (8% vs. 3%, p = 0.1). The 5-year disease-free survival reached 45% in the extensive and 78% in the non-extensive group (p < 0.0001). The 5-year overall survival was 70% and 90% in the extensive and non-extensive group respectively (p < 0.021).

CONCLUSION
CRS with HIPEC offers prolonged survival even in the case of extensive PMP. Because of the high rate of surgical morbidity in the extensive group, patients should be carefully selected.

Benhaim|Léonor|L| Faron|Matthieu|M| Gelli|Maximiliano|M| Sourrouille|Isabelle|I| Honoré|Charles|C| Delhorme|Jean-Baptiste|JB| Elias|Dominique|D| Goere|Diane|D|

D010478:Chemotherapy, Cancer, Regional Perfusion

Surgery
HIPEC
PMP
Peritoneal carcinomatosis
Prognostic factors


Real-Time Measurement of Melanoma Cell-Mediated Human Brain Endothelial Barrier Disruption Using Electric Cell-Substrate Impedance Sensing Technology.

Abstract: Electric cell-substrate impedance sensing (ECIS) is an impedance-based method for monitoring changes in cell behaviour in real-time. In this paper, we highlight the importance of ECIS in measuring the kinetics of human melanoma cell invasion across human brain endothelium. ECIS data can be mathematically modelled to assess which component of the endothelial paracellular and basolateral barriers is being affected and when. Our results reveal that a range of human melanoma cells can mediate disruption of human brain endothelium, primarily involving the paracellular route, as demonstrated by ECIS. The sensitivity of ECIS also reveals that the paracellular barrier weakens within 30-60 min of the melanoma cells being added to the apical face of the endothelial cells. Imaging reveals pronounced localisation of the melanoma cells at the paracellular junctions consistent with paracellular migration. Time-lapse imaging further reveals junctional opening and disruption of the endothelial monolayer by the invasive melanoma cells all within several hours. We suggest that the ability of ECIS to resolve changes to barrier integrity in real time, and to determine the route of migration, provides a powerful tool for future studies investigating the key molecules involved in the invasive process of cancer cells.

D015374:Biosensing Techniques
D001812:Blood-Brain Barrier
D001921:Brain
D017097:Electric Impedance
D042783:Endothelial Cells
D006801:Humans
D008545:Melanoma
D012878:Skin Neoplasms
D013997:Time Factors

impedance
ECIS
endothelium
barrier function
blood–brain barrier


Quantitative analysis of autophagic flux by confocal pH-imaging of autophagic intermediates.

Abstract: Although numerous techniques have been developed to monitor autophagy and to probe its cellular functions, these methods cannot evaluate in sufficient detail the autophagy process, and suffer limitations from complex experimental setups and/or systematic errors. Here we developed a method to image, contextually, the number and pH of autophagic intermediates by using the probe mRFP-GFP-LC3B as a ratiometric pH sensor. This information is expressed functionally by AIPD, the pH distribution of the number of autophagic intermediates per cell. AIPD analysis reveals how intermediates are characterized by a continuous pH distribution, in the range 4.5-6.5, and therefore can be described by a more complex set of states rather than the usual biphasic one (autophagosomes and autolysosomes). AIPD shape and amplitude are sensitive to alterations in the autophagy pathway induced by drugs or environmental states, and allow a quantitative estimation of autophagic flux by retrieving the concentrations of autophagic intermediates.

Maulucci|Giuseppe|G|
Chiarpotto|Michela|M|
Papi|Massimiliano|M|
Samengo|Daniela|D|
Pani|Giovambattista|G|
De Spirito|Marco|M|

mechanistic target of rapamycin (serine/threonine kinase)

microtubule-associated protein 1 light chain 3

phosphatidylinositol 3-kinase catalytic subunit type 3


Long-term outcomes of tissue-based ACTH-antibody assay-guided transsphenoidal resection of pituitary adenomas in Cushing disease.

Abstract: OBJECTIVE Cushing disease is caused by a pituitary micro- or macroadenoma that hypersecretes adrenocorticotropic hormone (ACTH), resulting in hypercortisolemia. For decades, transsphenoidal resection (TSR) has been an efficacious treatment but with certain limitations, namely precise tumor localization and complete excision. The authors evaluated the novel use of a double-antibody sandwich assay for the real-time quantitation of ACTH in resected pituitary specimens with the goals of augmenting pathological diagnosis and ultimately improving long-term patient outcome. METHODS This study involved a retrospective review of records and an analysis of assay values, pathology slides, and MRI studies of patients with Cushing disease who had undergone TSR in the period from 2009 to 2014 and had at least 1 year of follow-up in coordination with an endocrinologist. In the operating room, biopsy specimens from the patients had been analyzed for tissue ACTH concentration. Additional samples were simultaneously sent for frozen-section pathological analysis. The ACTH assay performance was compared against pathology assessments of surgical tumor samples using receiver operating characteristic (ROC) analysis and against pre- and postoperative MRI studies. RESULTS Fourteen patients underwent TSR with guidance by ACTH-antibody assay and pathological assessment of 127 biopsy samples and were followed up for an average of 3 years. The ACTH threshold for discriminating adenomatous from normal tissue was 290,000 pg/mg of tissue, based on jointly maximized sensitivity (95.0%) and specificity (71.3%). Lateralization discordance between preoperative MRI studies and surgical visualization was noted in 3 patients, confirming the impression that MRI alone may not achieve optimal localization. A majority of the patients (85.7%) attained long-term disease remission based on urinary free cortisol levels, plasma cortisol levels, and long-term corticosteroid therapy. Comparisons of patient-months of remission and treatment failure showed that the remission rate in the study sample statistically exceeds the rate in historical controls (71.9%; p = 0.0007, Fisher's exact test). Long-term unexpected hormonal deficiencies were statistically similar between study patients (29%) and those in a meta-analysis (25%; p = 0.7596, Fisher's exact test). CONCLUSIONS These preliminary findings reflect the promising potential of tissue-based ACTH-antibody-guided assay for improving the cure rates of Cushing disease patients undergoing TSR. Further studies with larger sample sizes, further refinements of assay interpretation, and longer-term follow-ups are needed.

Erfe|J Mark|JM|
Perry|Avital|A|
McClaskey|John|J|
Inzucchi|Silvio E|SE|
James|Whitney Sheen|WS|
Eid|Tore|T|
Bronen|Richard A|RA|
Mahajan|Amit|A|
Huttner|Anita|A|
Santos|Florecita|F|
Spencer|Dennis|D|

BIPSS = bilateral inferior petrosal sinus sampling


Biosorption of chromium by alginate extraction products from Sargassum filipendula: investigation of adsorption mechanisms using X-ray photoelectron spectroscopy analysis.

Abstract: The alginate extraction products from Brazilian brown seaweed Sargassum filipendula were studied for chromium biosorption. Batch experiments were conducted at pH 2 and 3 and 20°C to determine the sorption capacity of this biosorbents for chromium (VI) and (III). The biomass was characterized before and after metal binding by X-ray photoelectron spectroscopy (XPS) in order to determine the mechanisms of chromium biosorption. The residue has a high adsorption capacity, close the value obtained with seaweed and higher than that of alginate for both Cr(III) and Cr(VI). XPS analysis of the biosorbents revealed that carboxyl, amino and sulfonate groups are responsible for the binding of the metal ions. The analysis also indicated that the Cr(VI) bound to the biomass was reduced to Cr(III).

Bertagnolli|Caroline|C|
Uhart|Arnaud|A|
Dupin|Jean-Charles|JC|
da Silva|Meuris Gurgel Carlos|MG|
Guibal|Eric|E|
Desbrieres|Jacques|J|

Biosorption Chromium Seaweed XPS Alginate-extraction


CircZNF609/miR-134-5p/BTG-2 axis regulates proliferation and migration of glioma cell.

Abstract:
OBJECTIVES
MicroRNAs are abundant in eukaryotic cells and play key roles in cancers. Circular RNAs (CircRNAs) served as the competing endogenous RNAs (ceRNAs) in mediating multiple cell processes. This study aims to define the role of CircRNA CircZNF609/miR-134-5p in glioma as well as the underlying regulating mechanism.

METHODS
Relative expression of miR-134-5p, CircZNF609 and BTG-2 mRNA was determined by quantitative real-time PCR. Cell proliferation was analysed by CCK-8 assay. Cell migration was assessed by cell wound scratch assay. The direct regulatory of miR-134-5p on BTG-2 and CircZNF609 was verified by luciferase report gene assay.

KEY FINDINGS
MiR-134-5p was significantly upregulated in glioma cells. The overexpression of miR-134-5p inhibited cell proliferation and migration of glioma cell U251 and U87. Reversely, knock-down of miR-134-5p enhanced cell proliferation and migration. Both BTG-2 and CircZNF609 are the direct targets of miR-134-5p, and their expression could be negatively regulated by miR-134-5p. CircZNF609 was significantly upregulated in U251 and U87 cells and acted as an oncogene to promote cell proliferation and cell migration of glioma cell U251 and U87.

CONCLUSIONS
These data proved that CircZNF609 served as a competing RNA to bind miR-134-5p that promoted BTG-2 expression leading to reduced proliferation and migration of glioma cell.

D015972:Gene Expression Regulation, Neoplastic


A Literature Review and Gap Analysis of Emerging Technologies and New Trends in Gambling.

Abstract: There have been significant changes in the gambling landscape particularly relating to gambling in the digital age. As the gambling landscape changes, regulation of gambling also needs to change. In 2018, the Office of Responsible Gambling in New South Wales, Australia, commissioned a gap analysis to inform their research objectives and priority focus areas. This included an identification of gaps in our understanding of emerging technologies and new trends in gambling. A gap analysis of the peer-reviewed literature published since 2015 was undertaken, identifying 116 articles. The main area of focus was Internet gambling, followed by articles exploring the relationship between video gaming and gambling, the expansion of the sports betting market, Electronic Gambling Machines characteristics and articles exploring new technologies and trends in advertising and inducements. Key gaps related to the need for more research in general, as well as research focusing on subpopulations such as those using different gambling formats, those with varying levels of problem gambling, and vulnerable populations. From a methods perspective, researchers saw the need for longitudinal studies, more qualitative research and improved outcome measures. The development and testing of a public health approach to addressing the harms associated with gambling in these areas is needed.

Lawn|Sharon|S| Oster|Candice|C| Riley|Ben|B| Smith|David|D| Baigent|Michael|M| Rahamathulla|Mubarak|M|

internet gambling
sports betting
advertising
electronic gaming machines
simulated gambling


Transnasal Endoscopy in Unsedated Children With Eosinophilic Esophagitis Using Virtual Reality Video Goggles.

Abstract:
BACKGROUND & AIMS
Evaluation and treatment of children with eosinophilic esophagitis (EoE) requires serial endoscopic, visual, and histologic assessment by sedated esophagogastroduodenoscopy (EGD). Unsedated transnasal endoscopy (TNE) was reported to be successful in a pilot study of children. We evaluated video goggle and virtual reality-based unsedated TNE in children with EoE, collecting data on rates of completion, adverse events, and adequacy of visual and histologic findings.

METHODS
We performed a retrospective study of 190 children and young adults (age, 3-22 y) who underwent video goggle or virtual reality-based unsedated TNE from January 2015 through February 2018. We analyzed data on patient demographics, procedure completion, endoscope type, adverse events, visual and histologic findings, estimated costs, and duration in the facility. Esophageal biopsies from the first 173 subjects who underwent TNE were compared with those from previous EGD evaluations.

RESULTS
During 300 attempts, 294 TNEs were performed (98% rate of success). Fifty-four patients (age, 6-18 y) underwent multiple TNEs for dietary or medical management of EoE. There were no significant adverse events. Visual and histologic findings were adequate for assessment of EoE. TNE reduced costs by 53.4% compared with EGD (TNE $4393.00 vs EGD $9444.33). TNE was used increasingly from 2015 through 2017, comprising 31.8% of endoscopies performed for EoE. The total time spent in the clinic (front desk check-in to check-out) in 2018 was 71 minutes.

CONCLUSIONS
In a retrospective study of 190 children and young adults (age, 3-22 y) who underwent video goggle or virtual reality-based unsedated TNE, TNE was safe and effective and reduced costs of EoE monitoring. Advantages of TNE include reduced risk and cost associated with anesthesia as well as decreased in-office time, which is of particular relevance for patients with EoE, who require serial EGDs.

Nguyen|Nathalie|N|
Lavery|William J|WJ|
Capocelli|Kelley E|KE|
Smith|Clinton|C|
DeBoer|Emily M|EM|
Deterding|Robin|R|
Prager|Jeremy D|JD|
Leinwand|Kristina|K|
Kobak|Greg E|GE|
Kramer|Robert E|RE|
Menard-Katcher|Calies|C|
Furuta|Glenn T|GT|
Atkins|Dan|D|
Fleischer|David|D|
Greenhawt|Matthew|M|
Friedlander|Joel A|JA|

Endoscopy
Adverse Events
Anesthesia
Eosinophilic Oesophagitis
Transnasal Esophagogastroduodenoscopy
Transnasal Esophagoscopy


Microfluidic Designing Microgels Containing Highly Concentrated Gold Nanoparticles for SERS Analysis of Complex Fluids.

Abstract: Surface-enhanced Raman scattering (SERS) is one of the most promising methods to detect small molecules for point-of-care analysis as it is rapid, nondestructive, label-free, and applicable for aqueous samples. Here, microgels containing highly concentrated yet evenly dispersed gold nanoparticles are designed to provide SERS substrates that simultaneously achieve contamination-free metal surfaces and high signal enhancement and reproducibility. With capillary microfluidic devices, water-in-oil-in-water (W/O/W) double-emulsion drops are prepared to contain gold nanoparticles and hydrogel precursors in innermost drop. Under hypertonic condition, water is selectively pumped out from the innermost drops. Therefore, gold nanoparticles are gently concentrated without forming aggregates, which are then captured by hydrogel matrix. The resulting microgels have a concentration of gold nanoparticles ≈30 times higher and show Raman intensity two orders of magnitude higher than those with no enrichment. In addition, even distribution of gold nanoparticles results in uniform Raman intensity, providing high signal reproducibility. Moreover, as the matrix of the microgel serves as a molecular filter, large adhesive proteins are rejected, which enables the direct detection of small molecules dissolved in the protein solution. It is believed that this advanced SERS platform is useful for in situ detection of toxic molecules in complex mixtures such as biological fluids, foods, and cosmetics.

Kim|Yeong Hwa|YH|
Kim|Dong Jae|DJ|
Lee|Sangmin|S|
Kim|Dong-Ho|DH|
Park|Sung-Gyu|SG|
Kim|Shin-Hyun|SH|0000-0003-4095-5779

microfluidics
microgels
surface-enhanced Raman scattering
double-emulsion drops
metal nanoparticles


Atopic dermatitis microbiomes stratify into ecologic dermotypes enabling microbial virulence and disease severity.

Abstract:
BACKGROUND
Atopic dermatitis (AD) is a common skin disease affecting up to 20% of the global population, with significant clinical heterogeneity and limited information about molecular subtypes and actionable biomarkers. Although alterations in the skin microbiome have been described in subjects with AD during progression to flare state, the prognostic value of baseline microbiome configurations has not been explored.

OBJECTIVE
Our aim was to identify microbial signatures on AD skin that are predictive of disease fate.

METHODS
Nonlesional skin of patients with AD and healthy control subjects were sampled at 2 time points separated by at least 4 weeks. Using whole metagenome analysis of skin microbiomes of patients with AD and control subjects (n = 49 and 189 samples), we identified distinct microbiome configurations (dermotypes A and B). Blood was collected for immunophenotyping, and skin surface samples were analyzed for correlations with natural moisturizing factors and antimicrobial peptides.

RESULTS
Dermotypes were robust and validated across 2 additional cohorts (63 individuals), with strong enrichment of subjects with AD in dermotype B. Dermotype B was characterized by reduced microbial richness, depletion of Cutibacterium acnes, Dermacoccus and Methylobacterium species, individual-specific outlier abundance of Staphylococcus species (eg, S epidermidis, S capitis, S aureus), and enrichment in metabolic pathways (eg, branched chain amino acids and arginine biosynthesis) and virulence genes (eg, β-toxin, δ-toxin) that defined a pathogenic ecology. Skin surface and circulating host biomarkers exhibited a distinct microbial-associated signature that was further reflected in more severe itching, frequent flares, and increased disease severity in patients harboring the dermotype B microbiome.

CONCLUSION
We report distinct clusters of microbial profiles that delineate the role of microbiome configurations in AD heterogeneity, highlight a mechanism for ongoing inflammation, and provide prognostic utility toward microbiome-based disease stratification.

Tay|Angeline S L|ASL|
Li|Chenhao|C|
Nandi|Tannistha|T|
Chng|Kern Rei|KR|
Andiappan|Anand Kumar|AK|
Mettu|Vijaya Saradhi|VS|
de Cevins|Camille|C|
Ravikrishnan|Aarthi|A|
Dutertre|Charles-Antoine|CA|
Wong|X F Colin C|XFCC|
Ng|Amanda Hui Qi|AHQ|
Matta|Sri Anusha|SA|
Ginhoux|Florent|F|
Rötzschke|Olaf|O|
Chew|Fook Tim|FT|
Tang|Mark B Y|MBY|
Yew|Yik Weng|YW|
Nagarajan|Niranjan|N|
Common|John E A|JEA|

Atopic dermatitis
microbiome
skin
biomarkers
nonlesional
stratification


Ex-vivo delivery of monoclonal antibody (Rituximab) to treat human donor lungs prior to transplantation.

Abstract:
BACKGROUND
Ex-vivo lung perfusion (EVLP) is an innovative platform for assessing donor lungs in the pre-transplant window. In this study, we demonstrate an extension of its utility by administering the anti-CD20 monoclonal antibody, Rituximab, during EVLP. We hypothesized that this would lead to targeted depletion of allograft B-cells which may provide significant clinical benefit, including the potential to reduce latent Epstein-Barr virus (EBV) and decrease the incidence of post-transplant lymphoproliferative malignancies.

METHODS
Twenty human donor lungs rejected for transplantation were placed on EVLP with (n = 10) or without (n = 10) 500 mg of Rituximab. Safety parameters such as lung physiology and inflammatory cytokines were evaluated. We measured the delivery efficacy through flow cytometry, immunohistochemistry and ELISA. An in-vitro culture assay, in the presence of complement, was further conducted to monitor whether B-cell depletion would occur in Rituximab-perfused samples.

FINDINGS
Rituximab was successfully delivered to human lungs during EVLP as evidenced by flow cytometric binding assays where lung tissue and lymph node biopsies demonstrated occupied CD20 epitopes after perfusion with the antibody. Lymph nodes from Rituximab perfusions demonstrated a 10.9 fold-reduction in CD20+ staining compared to controls (p = 0.0003). In lung tissue, Rituximab resulted in an 8.75 fold-reduction in CD20+ staining relative to controls (p = 0.0002). This decrease in CD20+ binding illustrates the successful delivery and occupation of epitopes after perfusion with the Rituximab. No apparent safety concerns were seen as exhibited by markers associated with acute cell injury (e.g., proinflammatory cytokines), cell death (e.g., TUNEL staining), or pulmonary physiology. In a post-perfusion tissue culture model, the addition of complement (human serum) resulted in evidence of B-cell depletion consistent with what would be expected with posttransplant activation of bound Rituximab.

INTERPRETATION
Our experiments illustrate the potential of EVLP as a platform to deliver monoclonal antibody therapies to treat donor lungs pretransplant with the goal of eliminating a latent virus responsible for considerable morbidity after lung transplantation.

FUNDING
Supported by the University Health Network Transplant Center.

Ku|Terrance J Y|TJY|
Ribeiro|Rafaela V P|RVP|
Ferreira|Victor H|VH|
Galasso|Marcos|M|
Keshavjee|Shaf|S|
Kumar|Deepali|D|
Cypel|Marcelo|M|
Humar|Atul|A|

Rituximab
Ex-vivo lung perfusion
Epstein-Barr virus
Monoclonal therapy
PTLD


Factors influencing mothers' decisions on whether to provide seafood during early years' feeding: A qualitative study.

Abstract: The first year of a child's life is a key period of transition from an exclusive milk diet to solid foods to meet growing nutritional demands. An increased requirement for nutrients includes the introduction of protein-rich solid foods, such as seafood, which additionally provides valuable omega-3 fatty acids. However, consumption of seafood is low in the British child population. The aim of this study was to identify maternal perceptions of the factors that can influence the decision on whether to provide seafood during early years' feeding using a multi-method qualitative study design. A total of 26 discussions posted by mothers on parenting websites; Mumknowsbest, Mumsnet and Netmums, accessed July 2013, together with discussions from six focus groups (February-July 2014) in the North East of Scotland were included for thematic qualitative analysis. Discussions on the inclusion of seafood during the early years were centred across four interrelating themes; - food-related attributes, mother-centred aspects, family-centred aspects, and external information sources. Concerns regarding safety and mothers' limited knowledge and skills on seafood were apparent from discussions; however, the practicalities of providing a cost effective family meal were also issues raised by mothers. An understanding of the numerous and sometimes contradictory influences on mothers' decisions to include seafood during early years' period could be used to develop strategies to help increase regular seafood consumption. In particular, ensuring formal information and guidance clearly addresses the safety concerns of mothers and the development of practical education schemes to encourage and teach cooking skills should be considered.

Carstairs|Sharon A|SA|
Craig|Leone C A|LCA|
Marais|Debbi|D|
Kiezebrink|Kirsty|K|

D002664:Child Nutritional Physiological Phenomena

D007722:Health Knowledge, Attitudes, Practice

Mothers
Seafood
Early years
Concerns
Infant feeding
Online forums


Characteristics and outcome of patients with acute myeloid leukaemia and t(8;16)(p11;p13): results from an International Collaborative Study.

Abstract: In acute myeloid leukaemia (AML) t(8;16)(p11;p13)/MYST3-CREBBP is a very rare abnormality. Previous small series suggested poor outcome. We report on 59 patients with t(8;16) within an international, collaborative study. Median age was 52 (range: 16-75) years. AML was de novo in 58%, therapy-related (t-AML) in 37% and secondary after myelodysplastic syndrome (s-AML) in 5%. Cytogenetics revealed a complex karyotype in 43%. Besides MYST3-CREBBP, whole-genome sequencing on a subset of 10 patients revealed recurrent mutations in ASXL1, BRD3, FLT3, MLH1, POLG, TP53, SAMD4B (n = 3, each), EYS, KRTAP9-1 SPTBN5 (n = 4, each), RUNX1 and TET2 (n = 2, each). Complete remission after intensive chemotherapy was achieved in 84%. Median follow-up was 5·48 years; five-year survival rate was 17%. Patients with s-/t-AML (P = 0·01) and those with complex karyotype (P = 0·04) had an inferior prognosis. Allogeneic haematopoietic cell transplantation (allo-HCT) was performed in 21 (36%) patients, including 15 in first complete remission (CR1). Allo-HCT in CR1 significantly improved survival (P = 0·04); multivariable analysis revealed that allo-HCT in CR1 was effective in de novo AML but not in patients with s-AML/t-AML and less in patients exhibiting a complex karyotype. In summary, outcomes of patients with t(8;16) are dismal with chemotherapy, and may be substantially improved with allo-HCT performed in CR1.

Kayser|Sabine|S|0000-0003-3796-8843
Hills|Robert K|RK|0000-0003-0166-0062
Langova|Ralitsa|R|
Kramer|Michael|M|
Guijarro|Francesca|F|
Sustkova|Zuzana|Z|
Estey|Elihu H|EH|
Shaw|Carole M|CM|
Ráčil|Zdeněk|Z|0000-0003-3511-4596
Mayer|Jiri|J|
Zak|Pavel|P|
Baer|Maria R|MR|
Brunner|Andrew M|AM|
Szotkowski|Tomas|T|
Cetkovsky|Petr|P|
Grimwade|David|D|
Walter|Roland B|RB|0000-0002-9268-3341
Burnett|Alan K|AK|
Ho|Anthony D|AD|
Ehninger|Gerhard|G|
Müller-Tidow|Carsten|C|
Platzbecker|Uwe|U|
Thiede|Christian|C|
Röllig|Christoph|C|
Schulz|Angela|A|
Warsow|Gregor|G|
Brors|Benedikt|B|
Esteve|Jordi|J|
Russell|Nigel H|NH|
Schlenk|Richard F|RF|
Levis|Mark J|MJ|0000-0003-0473-6982

D000971:Antineoplastic Combined Chemotherapy Protocols

D018380:Hematopoietic Stem Cell Transplantation

allogeneic haematopoietic cell transplantation


Colloidal Bismuth Nanocrystals as a Model Anode Material for Rechargeable Mg-Ion Batteries: Atomistic and Mesoscale Insights.

Abstract: At present, the technical progress of secondary batteries employing metallic magnesium as the anode material has been severely hindered due to the low oxidation stability of state-of-the-art Mg electrolytes, which cannot be used to explore high-voltage (>3 V versus Mg2+/Mg) cathode materials. All known electrolytes based on oxidatively stable solvents and salts, such as Mg(ClO4)2 and Mg bis(trifluoromethanesulfonimide), react with the metallic magnesium anode, forming a passivating layer at its surface and preventing the reversible plating and stripping of Mg. Therefore, in a near-term effort to extend the upper voltage limit in the exploration of future candidate Mg-ion battery cathode materials, bismuth anodes have attracted considerable attention due to their efficient magnesiation and demagnesiation alloying reaction in such electrolytes. In this context, we present colloidal Bi nanocrystals (NCs) as a model anode material for the exploration of cathode materials for rechargeable Mg-ion batteries. Bi NCs demonstrate a stable capacity of 325 mAh g-1 over at least 150 cycles at a current density of 770 mA g-1, which is among the most-stable performance of Mg-ion battery anode materials. First-principles crystal structure prediction methodologies and ex situ X-ray diffraction measurements reveal that the magnesiation of Bi NCs leads to the simultaneous formation of the low-temperature trigonal structure, α-Mg3Bi2, and the high-temperature cubic structure, β-Mg3Bi2, which sheds insight into the high stability of this reversible alloying reaction. Furthermore, small-angle X-ray scattering measurements indicate that although the monodispersed, crystalline nature of the Bi NCs is indeed disturbed during the first discharge step, no notable morphological or structural changes occur in the following electrochemical cycles. The cost-effective and facile synthesis of colloidal Bi NCs and their remarkably high electrochemical stability upon magnesiation make them an excellent model anode material with which to accelerate progress in the field of Mg-ion secondary batteries.

nanocrystal
Mg-ion battery
magnesium
synthesis
energy storage


In vitro comparison of bradykinin degradation by aliskiren, a renin inhibitor, and an inhibitor of angiotensin-converting enzyme.

Abstract:
INTRODUCTION
Angiotensin-converting enzyme (ACE) inhibitors cause angioedema due to diminished degradation of bradykinin. Angiotensin receptor blockers may occasionally cause angioedema but the mechanism is unknown, and are generally considered safe, even in those who have reacted to ACE inhibitors. We determined whether aliskiren, a renin inhibitor, has an effect on the rate of bradykinin degradation.

METHODS
The ability of renin to metabolize bradykinin was studied and the rate of bradykinin degradation compared in the presence or absence of aliskiren. Enalapril, a known ACE inhibitor that causes angioedema served as positive control.

RESULTS
Renin was unable to digest bradykinin, indicating that a renin inhibitor is unlikely to affect the rate of bradykinin degradation. In a plasma system, aliskiren had no effect on the rate of bradykinin degradation while enalapril inhibited it appreciably. An inhibitory effect of aliskiren on the rate of bradykinin degradation by human pulmonary endothelial cells was observed, estimated to be about 5% of that of enalapril.

CONCLUSION
Aliskiren has no effect upon the rate of bradykinin degradation in plasma and a minimal effect employing vascular endothelial cells. The latter suggests inhibition of a non-renin enzyme that is a minor contributor to bradykinin degradation.

Joseph|Kusumam|K|
Tholanikunnel|Tracy E|TE|
Kaplan|Allen P|AP|

bradykinin
aliskiren
Angioedema
ACE inhibitor
enalapril


Spatial and temporal analysis of hospitalized dengue patients in Bandung: demographics and risk.

Abstract:
BACKGROUND
Bandung, the fourth largest city in Indonesia and capital of West Java province, has been considered a major endemic area of dengue, and studies show that the incidence in this city could increase and spread rapidly. At the same time, estimation of incidence could be inaccurate due to a lack of reliable surveillance systems. To provide strategic information for the dengue control program in the face of limited capacity, this study used spatial pattern analysis of a possible outbreak of dengue cases, through the Geographic Information System (GIS). To further enhance the information needed for effective policymaking, we also analyzed the demographic pattern of dengue cases.

METHODS
Monthly reports of dengue cases from January 2014 to December 2016 from 16 hospitals in Bandung were collected as the database, which consisted of address, sex, age, and code to anonymize the patients. The address was then transformed into geocoding and used to estimate the relative risk of a particular area's developing a cluster of dengue cases. We used the kernel density estimation method to analyze the dynamics of change of dengue cases.

RESULTS
The model showed that the spatial cluster of the relative risk of dengue incidence was relatively unchanged for 3 years. Dengue high-risk areas predominated in the southern and southeastern parts of Bandung, while low-risk areas were found mostly in its western and northeastern regions. The kernel density estimation showed strong cluster groups of dengue cases in the city.

CONCLUSIONS
This study demonstrated a strong pattern of reported cases related to specific demographic groups (males and children). Furthermore, spatial analysis using GIS also visualized the dynamic development of the aggregation of disease incidence (hotspots) for dengue cases in Bandung. These data may provide strategic information for the planning and design of dengue control programs.

Bandung
Spatial pattern
Dengue infection


Whole genome global insight of antibiotic resistance gene repertoire and virulome of high - risk multidrug-resistant Uropathogenic Escherichiacoli.

Abstract: Elucidation of genetic determinants via whole genome sequence (WGS) analyses can help understand the high risk multidrug-resistant (MDR) Uropathogenic Escherichia coli (UPEC) associated with urinary tract infections (UTI) and its evasion strategies from treatment. We investigated the WGS of 30 UPEC strains from UTI samples across the world (2016-2019) and found 25 UPEC strains carrying 2-23 antibiotic resistance genes (ARGs) scattered across 1-3 plasmids per strain. Different ARGs (blaTEM, blaCTXM, blaNDM, blaOXA, blaCMY) encoding extended-spectrum beta-lactamases (TEM, CTXM, CMY) and carbapenemases (NDM, OXA) were found in 24/30, ARGs encoding aminoglycoside modifying enzymes (AAC, APH, AAD) variants in 23/30, trimethoprim ARGs (dfrA17, dfrA12, dfrA5, dfrB4 variants) encoding dihydrofolate reductase in 19/30 and sulfonamide ARGs (sul1, sul2, sul3) encoding dihydropteroate synthase and macrolide ARGs (mph1) encoding macrolide 2' phosphotransferase in 15/30 UPEC strains. Collectively the ARGs were distributed in different combinations in 40 plasmids across UPEC strains with 20 plasmids displaying co-occurrence of multiple ARGs conferring resistance to beta lactam, aminoglycoside, sulfonamide, trimethoprim and macrolide antibiotics. These resistance plasmids belonged to seven incompatibility groups (IncF, IncI, IncC, IncH, IncN, IncB and Col), with IncFI and IncFII being the predominant resistance plasmids. Additionally, we observed co-occurrence of specific mutation pattern in quinolone resistance determining region (QRDR) viz., DNA gyrase (gyrA: S83L, D87N), and topoisomerase IV (parC: S80I, E84V; parE: I529L) in 18/30 strains. The strains also harbored diverse virulence genes, such as fimH, gad, iss, iha, ireA, iroN, cnf1 and san. Multilocus sequence typing (MLST) reconfirmed ST131(n = 10) as the predominant global high-risk clonal strain causing UTI. In summary, our findings contribute to better understand the plasmid mediated ARGs and its encoded enzymes that may contribute in antibiotic inactivation/modification or alteration in the antibiotic target site in high risk MDR hypervirulent UPEC strains causing UTI. The study reinforces the need to characterize and design appropriate inhibitors to counterattack different enzymes and devise strategies to curtail resistance plasmid.

Mitra|Susweta Das|SD|
Irshad|Pir|P|
Anusree|M|M|
Rekha|Injeti|I|
Shailaja|S|S|
Suresh|Janshi|J|
Aishwarya|G|G|
Shrestha|Smeeta|S|
Shome|Bibek Ranjan|BR|

Whole genome sequence (WGS)
Antibiotic resistance gene (ARG)
Virulence gene
Multidrug resistance (MDR) plasmid
ST131
Uropathogenic E. coli (UPEC)


HEV-LFS : A novel scoring model for patients with hepatitis E virus-related liver failure.

Abstract: A noninvasive assessment method for acute or acute-on-chronic liver failure in patients with hepatitis E virus (HEV) infection is urgently needed. We aimed to develop a scoring model for diagnosing HEV patients who developed liver failure (HEV-LF) at different stages. A cross-sectional set of 350 HEV-LF patients were identified and enrolled, and the Guidelines for Diagnosis and Treatment of Liver Failure in China and the Asian Pacific Association for the Study of the Liver were adopted as references. HEV-LFS , a novel scoring model that incorporates data on cholinesterase (CHE), urea nitrogen (UREA), platelets and international normalized ratio was developed using a derived dataset. For diagnosing HEV-LF stages F1 to F3, the HEV-LFS scoring model (F1: 0.87; F2: 0.90; F3: 0.92) had a significantly higher AUROC than did the CLIF-C-ACLFs (F1: 0.65; F2: 0.56; F3: 0.51) and iMELD (F1: 0.70; F2: 0.57; F3: 0.51) scoring models, of which the HEV-LFS scoring model had the best sensitivity and specificity. In addition, the HEV-LFS scoring model was correlated with mortality, length of hospitalization and ICU stay. As the GDTLF score increased, the CHE level decreased and the UREA increased gradually. Encouragingly, a calibration curve showed good agreement between the derivation and validation sets. Notably, we also established a nomogram to facilitate the practical operability of the HEV-LFS scoring model in clinical settings. In conclusion, both CHE and UREA may be indicators for HEV-LF patients. The HEV-LFS scoring model is an efficient and accessible model for classifying HEV-LF at different stages.

Wu|Jian|J| Guo|Naizhou|N| Zhang|Xueyan|X| Xiong|Cunquan|C| Liu|Jun|J| Xu|Yanping|Y| Fan|Jun|J| Yu|Jiong|J| Zhao|Xinguo|X| Liu|Bin|B| Wang|Wei|W| Zhang|Jinrong|J| Cao|Hongcui|H|0000-0002-6604-6867 Li|Lanjuan|L|0000-0001-6945-0593

hepatitis E
liver failure
cholinesterase
international normalized ratio
HEV-LFS scoring model


Use of antibiotics among non-medical students in a Nigerian university.

Abstract:
BACKGROUND
Antibiotic misuse is a major contributory factor to treatment failure, antibiotic resistance and high healthcare costs.

OBJECTIVES
To evaluate level of self-reported antibiotic misuse among non-medical undergraduate students of a Nigerian university.

METHODS
Respondents' knowledge of antibiotics and disposal system for left-over antibiotics were explored using a structured questionnaire. Data were summarized with descriptive statistics. Chi square was used to evaluate relationship between specific categorical variables and respondents' opinions with p<0.05.

RESULTS
More than half the respondents obtained their antibiotics through doctor's prescriptions (273; 68.3%). The study revealed gross antibiotic misuse with majority, (298;74.5%) either by keeping left-over antibiotics for future use or throwing it away with refuse. Respondents (289; 72.3%) sometimes forgot to take the antibiotics. Financial constraints (73; 18.3%), long duration of treatment (70; 17.5%), side effects experienced (60;15.0%), polypharmacy (56;14.0%), tablet size (45;11.3%), and perceived low level of confidence in the prescriber (11; 2.8%) were major reasons for non-adherence. Course of study of respondents had no significant effect on respondents' knowledge or adherence (p>0.05).

CONCLUSION
Misuse of antibiotics among non-medical undergraduate students in a Nigerian university setting is pervasive suggesting an urgent need for enlightenment on rational use and disposal of antibiotics.

Sanya|T E|TE|
Titilayo|O F|OF|
Adisa|R|R|
Segun|J S|JS|

Antibiotic misuse
Nigeria
University Students


Coculture of dorsal root ganglion neurons and differentiated human corneal stromal stem cells on silk-based scaffolds.

Abstract: Corneal tissue displays the highest peripheral nerve density in the human body. Engineering of biomaterials to promote interactions between neurons and corneal tissue could provide tissue models for nerve/cornea development, platforms for drug screening, as well as innovative opportunities to regenerate cornea tissue. The focus of this study was to develop a coculture system for differentiated human corneal stromal stem cells (dhCSSCs) and dorsal root ganglion neurons (DRG) to mimic the human cornea tissue interactions. Axon extension, connectivity, and neuron cell viability were studied. DRG neurons developed longer axons when cocultured with dhCSSCs in comparison to neuron cultures alone. To assess the mechanism involved in the coculture response, nerve growth factors (NGF) secreted by dhCSSCs including NGF, brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), and neurotrophin-3 were characterized with greater focus on BDNF secretion. DhCSSCs also secreted collagen type I, an extracellular matrix molecule favorable for neuronal outgrowth. This coculture system provides a slowly degrading silk matrix to study neuronal responses in concert with hCSSCs related to innervation of corneal tissue with utility toward human corneal nerve regeneration and associated diseases.

Wang|Siran|S|
Ghezzi|Chiara E|CE|
White|James D|JD|
Kaplan|David L|DL|


A Comparison of the Performance between the 60- and 120-Second Conditions of the Korean-Color Word Stroop Test: Color Reading (K-CWST: CR).

Abstract:
Background and Purpose
The Korean-Color Word Stroop Test: Color Reading (K-CWST: CR) included in the Seoul Neuropsychological Screening Battery, 2nd Edition (SNSB-II) examines inhibitory control deficit. It provides normative data for both 60- and 120-second conditions, but the validity of the 60-second condition has not yet been proven. This study examined the validity of the 60-second condition by observing concordance between the performances in cognitively normal, MCI, and mild dementia groups.

Methods
There were 1,336 patients performed the SNSB-II, including the K-CWST: CR. Based on the cognitive test results, activities of daily living, and clinical interview, the patients were assigned to normal cognition (n=104), MCI (n=884), or mild dementia (n=348) groups. Abnormal performance on the K-CWST: CR was operationally defined as 1SD below the normative mean. The receiver operating characteristic curve analyses were conducted to compare the discriminability between the 60- and 120-second conditions.

Results
The percentages of abnormal performance in the MCI group were 41.5% and 42.3%, and those in the mild dementia group were 82.7% and 82.4% for the 60- and 120-second conditions, respectively. The areas under the curve for the 60- and 120-seconds were as follows; 0.80 and 0.81 in differentiating normal from MCI; 0.95 and 0.96 in normal from mild dementia; and 0.77 and 0.77 in MCI from mild dementia.

Conclusions
The 60-second condition of the K-CWST showed very similar results, not statistically different from the 120-second condition. Therefore, the 60-second condition could be used interchangeably with the 120-second condition in a clinical setting.

Stroop Test
Dementia
Mild Cognitive Impairment


Evaluation of phytoremediation potential of native dominant plants and spatial distribution of heavy metals in abandoned mining area in Southwest China.

Abstract: A field investigation on the content of heavy metals in soils and dominant plants was conducted in three sites (A<0.5 km, B<1.0 km, C<1.5 km) with different distances of mine tailings. The spatial distribution of heavy metals and the accumulation in plants were compared, and the candidate species for ecosystem restoration were selected. The results indicated that the soil was polluted by chromium (Cr), Cadmium (Cd), copper (Cu), nickel (Ni) in varying degrees, which is 2.07, 2.60, 1.79, and 4.49 times higher than the Class-Ⅱ standard in China. The concentrate of Ni, Cd, and Zinc (Zn) increased, while Cr, Lead (Pb), and Cu decreased with the distance from the mine tailings. 73 species (34 families) were found and mainly herbaceous plants. The concentrate of Cd, Cu, Cr, and Ni in 29 dominant plants were measured and 66.67%, 21.43%, 100%, 47.62% plants exceeded the normal concentration range. Based on the comparative analysis of heavy metal content, bioconcentration factor, and translocation factor in plants, Polygonum capitatum has good phytoextraction ability, Boehmeria nivea, Chrysanthemum indicum, Miscanthus floridulus, Conyza canadensis, Rubus setchuenensis, Senecio scandens, and Arthraxon hispidus showed remarkable phytostabilization abilities of Cr, Cd, Ni, and Cu, which can be used as potential phytoremediation candidate.

Wu|Bohan|B| Peng|He|H| Sheng|Mingping|M| Luo|Huanyan|H| Wang|Xitong|X| Zhang|Rong|R| Xu|Fei|F| Xu|Heng|H|

Phytoremediation
Dominant plants
Heavy metals
Mine
Accumulation


Development of a goosegrass (Eleusine indica) draft genome and application to weed science research.

Abstract:
BACKGROUND
Genomes are vital to the study of genomics, population genetics, and evolution of species. To date, only one genome (Echinochloa crus-galli) for C4 annual weedy grass species has been sequenced. Research was conducted to develop a draft genome of goosegrass (Eleusine indica; 2n = 2x = 18), one of the most common and troublesome weeds in the world.

RESULTS
A draft assembly of an approximately 492 Mb whole-genome sequence of goosegrass was obtained by de novo assembly of paired-end and mate-paired reads generated by Illumina sequencing of total genomic DNA. The genome was assembled into 24,072 scaffolds with N50 = 233,459 bp. More than 99% of transcriptome sequences were mapped to the goosegrass draft genome, and 95% of the commonly conserved plant genes were present. The assembled genome contains 25,467 unique protein-coding genes. Genes associated with herbicide resistance were obtained and variant calling allowed the detection of 754,409 single nucleotide polymorphisms. In addition, we also report 115,417 simple sequence repeats which can be deployed in population genetics and phylogenetic analysis.

CONCLUSION
This is the first report of genome sequence of goosegrass. Our assembly was able to identify all major herbicide-resistance related genes and develop a useful tool for other genomic and evolutionary analysis. © 2019 Society of Chemical Industry.

D031748:Eleusine
D018745:Genome, Plant
D053209:Herbicide Resistance
D057685:Plant Weeds
D058728:Weed Control

goosegrass
herbicide resistance
weed evolution
weed genome


Rapid-sequence intubation and cricoid pressure.

Abstract: Airway management is the most important clinical skill for anesthesiologist, emergency physician, and other providers who are involved in oxygenation and ventilation of the lungs. Rapid-sequence intubation is the preferred method to secure airway in patients who are at risk for aspiration because it results in rapid unconsciousness (induction) and neuromuscular blockade (paralysis). Application of cricoid pressure (CP) for patients undergoing rapid-sequence intubation is controversial. Multiple specialty societies have recommended that CP is not effective in preventing aspiration; rather it may worsen laryngoscopic view and impair bag-valve mask ventilation. Some experts think that CP should be applied in trauma and patients at risk for aspiration; however CP, if necessary, should be altered or removed to facilitate intubation.

Stewart|Joshua C|JC|
Bhananker|Sanjay|S|
Ramaiah|Ramesh|R|

rapid-sequence intubation
cricoid pressure
Aspiration


SGLT-2 inhibitors reduce the risk of cerebrovascular/cardiovascular outcomes and mortality: A systematic review and meta-analysis of retrospective cohort studies.

Abstract: Despite Sodium-glucose co-transporter-2 (SGLT2) inhibitors have been associated with a reduced risk of heart failure in patients with type 2 diabetes mellitus (T2DM), the effect observed for other cardiovascular (CV) and cerebrovascular outcomes differed among clinical trials. Different observational studies have investigated the effects of SGLT2 inhibitors on these outcomes and mortality. The present meta-analysis aimed to assess the effects of SGLT2 inhibitors on the risk of CV (major adverse CV event - MACE, non-fatal myocardial infarction, or hospitalization for heart failure) and cerebrovascular (stroke) outcomes. A systematic review was conducted in Pubmed from January 1, 2012 to November 31, 2020. Only retrospective cohort studies including as control group users of dipeptidyl peptidase-4 (DPP-4) inhibitors or non-SGLT2 inhibitors were retained and analysed separately. A random effect meta-analysis approach was used. This study followed the PRISMA statement. Of the 158 references identified, 20 articles were selected for meta-analysis, of which 13 considered the comparison with DPP-4 inhibitors and 7 the comparison with non-SGLT2 inhibitors. The pooled intention-to-treat analysis showed a reduced risk of stroke with SGLT2 inhibitors compared to DPP-4 inhibitors (Hazard ratio HR, 0.89; 95%CI, 0.82-0.96; I2 = 25%; p = 0.25) and non-SGLT2 inhibitors (HR, 0.83; 95%CI, 0.77-0.91; I2 = 11%; p = 0.34). Finally, SGLT2 inhibitors were also associated with a reduced risk of CV outcomes and mortality in all comparisons. Our data support contemporary society recommendations to prioritise the use of SGLT2 inhibitors in patients with T2DM and at high risk for CV complications.

Mascolo|Annamaria|A| Scavone|Cristina|C| Scisciola|Lucia|L| Chiodini|Paolo|P| Capuano|Annalisa|A| Paolisso|Giuseppe|G|

Risk
Cardiovascular outcome
Mortality
Type 2 diabetes mellitus
Cerebrovascular outcome
SGLT2 inhibitors


Applications of linking PBPK and PD models to predict the impact of genotypic variability, formulation differences, differences in target binding capacity and target site drug concentrations on drug responses and variability.

Abstract: This study aimed to demonstrate the added value of integrating prior in vitro data and knowledge-rich physiologically based pharmacokinetic (PBPK) models with pharmacodynamics (PDs) models. Four distinct applications that were developed and tested are presented here. PBPK models were developed for metoprolol using different CYP2D6 genotypes based on in vitro data. Application of the models for prediction of phenotypic differences in the pharmacokinetics (PKs) and PD compared favorably with clinical data, demonstrating that these differences can be predicted prior to the availability of such data from clinical trials. In the second case, PK and PD data for an immediate release formulation of nifedipine together with in vitro dissolution data for a controlled release (CR) formulation were used to predict the PK and PD of the CR. This approach can be useful to pharmaceutical scientists during formulation development. The operational model of agonism was used in the third application to describe the hypnotic effects of triazolam, and this was successfully extrapolated to zolpidem by changing only the drug related parameters from in vitro experiments. This PBPK modeling approach can be useful to developmental scientists who which to compare several drug candidates in the same therapeutic class. Finally, differences in QTc prolongation due to quinidine in Caucasian and Korean females were successfully predicted by the model using free heart concentrations as an input to the PD models. This PBPK linked PD model was used to demonstrate a higher sensitivity to free heart concentrations of quinidine in Caucasian females, thereby providing a mechanistic understanding of a clinical observation. In general, permutations of certain conditions which potentially change PK and hence PD may not be amenable to the conduct of clinical studies but linking PBPK with PD provides an alternative method of investigating the potential impact of PK changes on PD.

Chetty|Manoranjenni|M|
Rose|Rachel H|RH|
Abduljalil|Khaled|K|
Patel|Nikunjkumar|N|
Lu|Gaohua|G|
Cain|Theresa|T|
Jamei|Masoud|M|
Rostami-Hodjegan|Amin|A|

PBPK linked PD models
CYP P450 genotypes and response
formulation effects on drug response
heart drug concentration and QTc
target site concentrations and response