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Cholesterol and oxysterol sulfates: Physiological roles and analytical challenges
Lorena  Diaz Sanchez
Lorenzo  Pontini

Lorena Diaz Sanchez

and 5 more

April 24, 2020
Cholesterol (Chol) and oxysterol sulfates are important regulators of lipid metabolism, inflammation, cell apoptosis, and cell survival. Among the sulfate-based lipids, cholesterol sulfate (CS) is the most studied lipid both quantitatively and functionally. Despite the importance, very few studies have analysed and linked the actions of oxysterol sulfates to their physiological roles. Over expression of sulfotransferases confirmed the formation of a range of oxysterol sulfates and their antagonistic effects on liver X receptors (LXRs). It is therefore important to understand how further changes to oxysterol/oxysterol sulfate homeostasis can contribute to LXR activity in the physiological milieu. Here, we aim to bring together evidences for novel roles of oxysterol sulfates, the available techniques and the challenges for analysing them. Understanding the oxysterol/oxysterol sulfate levels and their physiological mechanisms could lead to new therapeutic targets for metabolic diseases.
Anti-cancer Activity of Two Novel Heterocyclic Compounds through Modulation of VEGFR...
Reem Hazem
Anhar Ali

Reem Hazem

and 5 more

April 24, 2020
Background and Purpose: Metastasis in breast cancer is a leading cause of mortality among women in many countries. This study investigated the anti-cancer role of benzoimidazoquinazoline and benzimidazotriazin; two novel compounds that were designed, synthesized, structurally elucidated, and biologically evaluated as potent anti-angiogenic agents that act through inhibition of vascular endothelial growth factor receptor-2 (VEGFR2). A model of breast cancer was induced by inoculation of Ehrlich Ascites Carcinoma (EAC) cells. Experimental Approach: Seventy swiss albino mice were randomly divided into 7 groups, 10 animals each: (1) normal, (2) control EAC group, (3) cisplatin treated group, (4&5) benzoimidazoquinazoline treated (5mg/kg and 10mg/kg), (6&7) benzimidazotriazin treated (5mg/kg and 10 mg/kg). The expression of miRNA-122 was assessed in the tumor tissue by quantitative PCR, and the VEGF level was determined in serum by ELISA. VEGFR2 and cluster of differentiation (CD)34 were assessed by immunohistochemistry. Serum levels of ALT, AST, creatinine, and urea were measured. Key Results: Treatment with benzoimidazoquinazoline and benzimidazotriazin caused a decrease in tumor weight and a significant decrease in the serum levels of VEGF and the expression of VEGFR2 and CD34 in the tumor tissue. MiRNA-122 was significantly upregulated especially in the group treated by benzimidazotriazin (10mg/kg). Interestingly, the new compounds had less renal toxicity compared to cisplatin. Conclusion and Implication: The designed small molecules are promising anti-cancer candidates that act through inhibition of angiogenesis and can provide a new strategy for the advancement of chemotherapy through modulation of miRNA.
Microbiome Analysis Enables Non-invasive Monitoring of Rocky Mountain Elk Populations
Samuel Pannoni
Kelly Proffitt

Samuel Pannoni

and 2 more

April 24, 2020
Rocky Mountain elk (Cervus elaphus nelsoni) seasonal migration, body-condition and sex ratios are important parameters for characterizing elk populations but have thus far been outside the scope of non-invasive methods. Fecal microbiomes can be surveyed non-invasively from scat samples and are associated with changes in diet, stress, age, disease and physical condition of the host, as well as differences between sexes. With this in mind, we surveyed the fecal microbiome of Montana elk that varied geographically (i.e. populations), by body condition, age and by sex. Our goal was to explore an approach for evaluating linkages between the host animal and its microbiome composition, and to develop bioinformatic techniques useful for characterizing host categories and population parameters based on microbiome analysis. We built a supervised-machine learning classifier based on bacterial taxa with cross validation to predict each fecal microbiome’s affiliation to known host categories. The microbiome classifier predicted host population, sex, age and body-condition with promising cross validation results. Monitoring wildlife microbiomes represents a breakthrough for non-invasive conservation biology, and we provide proof of concept for obtaining low cost, fine scale, management-relevant information from scat samples.
The Real-life Experience of Developing and Commercializing TruGraf, a Validated Non-I...
Martin First
Steven Kleiboeker

Martin First

and 4 more

April 24, 2020
Despite improvement in short-term outcomes, long-term results for kidney transplant recipients remain suboptimal. Immunological rejection is a leading cause of graft failure and recent research points to undetected “silent” subclinical acute rejection as a key component of this problem. While biopsies remain the gold-standard method for detecting silent rejection, non-invasive methods offer significant advantages especially in terms of patient safety and for serial monitoring of stable patients. This manuscript details the real-life challenges involved in the ultimately successful development and commercialization of TruGraf, a clinically validated, blood-based gene expression assay that offers the potential to reduce the use of surveillance (protocol) biopsies in renal transplant recipients with stable renal function.
Lung transplant in a recipient with tracheal bronchus
Duvuru Ram
Mark O'Carroll

Duvuru Ram

and 3 more

April 24, 2020
We describe the intra-operative surgical management of tracheal bronchus encountered in a lung transplant recipient.
Isolation and characterization of the first porcine Getah virus strain HNJZ-S1 from a...
Feng Zhou
Aojie Wang

Feng Zhou

and 6 more

April 24, 2020
Severity of porcine reproductive and respiratory syndrome (PRRS) implicated co-infection with other pathogens in pig herd in China, which normally were found Japanese encephalitis virus (JEV), pseudorabies virus (PRV), porcine reproductive and respiratory syndrome virus (PRRSV), porcine circovirus, porcine parvovirus and classical swine fever virus (CSFV). Here we verified a specific fragment which was similar to Getah virus (GETV) by RT-PCR and sequencing from aborted fetuses in Henan province, China. Then we isolated and purified the stain virus. We named it as HNJZ-S1. Furthermore, we characterized HNJZ-S1 by passage and plaque titer, whole genome sequencing, Electron microscopy and animal infection experiments with mice and piglets. The data show that the full-length genome sequence of HNJZ-S1was 11689 bp with homologous 97.4%–99.3% identical to the GETV sequence available in GenBank. Phylogenetic tree analysis showed that HNJZ-S1 was closely related to mosquito isolate 12IH26 from Japan, horse isolates 14-I-605-C1 and 14- I-605-C2, and mosquito isolate HB0234 from China. Animal experiments showed that the isolate HNJZ-S1 caused abortion in pregnant mice and was lethal postnatal day 3 mice and piglets. This study provides important information on the tropism, infection, pathogenicity, environmental microbiology and public health implications of pig derived GETV and will also serve as a source of reliable research materials.
VALIDATION OF A WEB APP FOR AUTOMATION OF ROBSON DATA COLLECTION FOR OBSTETRIC AUDITS...
Chandana Jayasundara
Indu Jayawardane

Chandana Jayasundara

and 2 more

April 24, 2020
ABSTRACT (223) Objective Validation of a webApp developed to automate the Robson classification and the WHO audit on rising Caesarean section rates Materials and Methods RobsApp will classify all the mothers admitted prospectively. The program generates an audit report based on the WHO criteria. Results Frequency distribution of the Caesarean section rates among the Robson groups was similar to the multicountry survey report. The Pearson’s correlation coefficient between the RobsApp and Robsons’s study was 0.752 4, Senanyake et al.’s study 0.8705, Keisuke and Kassam et al.’s study 0.7314. All correlations were significant at < 0.05. Discussion The results prove the validity of the RobsApp. The results are also broadly in agreement with the trends found in other studies reported in the literature. Therefore RobsApp may be used to analyze the Caesarean section rates of a given obstetric unit. The ease of use and convenient integration into routine ward workflow also suggest the outcome studies based on continuous audits are feasible. The App can also be used to analyze the intra-unit trends in Caesarean section rates as well as inter-unit, regional or even the national Caesarean section rates . Conclusion The RobsApp can confidently be used in obstetric units anywhere for the audit and outcome follow ups of caesarean section rates.
Role of First-trimester 3D Power Doppler of Placental Blood Flow and 3D Placental Vol...
Ameer Abdallah
Mohamed  Tawfik

Ameer Abdallah

and 5 more

April 24, 2020
Objective: First-trimester uterine artery Doppler was declared as a useful tool for predicting preeclampsia. Placental volume and vascular indices were recently used to predict preeclampsia. The study aims to assess the role of the first-trimester 3D placental volume and power Doppler of placental vascular indices combined with the uterine artery Doppler indices in prediction of preeclampsia. Design: A prospective cohort study Sample: 2019 women with a singleton pregnancy in their first-trimester. Methods: At 11-13+ weeks of gestation, 3D trans-abdominal ultrasound with Doppler scan for all participants then they were followed up until delivery. Main Outcome Measures: 3D placental volume, 3D Power Doppler of placental blood flow and uterine artery Doppler in the first trimester. Results: 163 women developed preeclampsia while 1856 women were normotensive. In the preeclampsia group, the placental volume, placental vascular indices (VI, FI, and VFI) showed a significant decrease, while means uterine PI and RI showed a significant increase. The placental vascular indices (VI, FI, and VFI) showed higher sensitivity while the placental volume and the uterine artery Doppler indices (PI and RI) showed higher specificity for the prediction of preeclampsia. Conclusion: Combined early screening of uterine artery Doppler with placental volume and vascular indices could be beneficial to increase the accuracy of early prediction of preeclampsia. Funding: There is no specific grant from any funding agency. Keywords: 3D-Doppler ultrasonography; placental volume; placental vascular indices; uterine artery Doppler; preeclampsia
Intraoperative cell salvage during cesarean section: what are the indications?
Valentine Servan-Schreiber
Catherine Barre-Drouard

Valentine Servan-Schreiber

and 5 more

April 24, 2020
Table 1. Characteristics of population. Table 1. Characteristics of population. Table 1. Characteristics of population. Table 1. Characteristics of population. Table 1. Characteristics of population. Table 1. Characteristics of population. Table 1. Characteristics of population. Table 1. Characteristics of population. Table 1. Characteristics of population. Table 1. Characteristics of population. Table 1. Characteristics of population. Characteristicsa Characteristicsa Characteristicsa ICS with autotransfusion N = 97 ICS with autotransfusion N = 97 ICS with autotransfusion N = 97 ICS without autotransfusion N = 196 ICS without autotransfusion N = 196 P P P Age, years Age, years Age, years 33.1 ± 5.0 33.1 ± 5.0 33.1 ± 5.0 32.5 ± 5.2 32.5 ± 5.2 0.37 0.37 0.37 BMIb, kg/m2 BMIb, kg/m2 BMIb, kg/m2 25.6 (22.3; 29.3) 25.6 (22.3; 29.3) 25.6 (22.3; 29.3) 25.4 (22.6; 29.6) 25.4 (22.6; 29.6) 0.75 0.75 0.75 Pregnancy parity Pregnancy parity Pregnancy parity 2 (1; 3) 2 (1; 3) 2 (1; 3) 2 (1; 4) 2 (1; 4) 0.22 0.22 0.22 Birth date Birth date Birth date 37 (35; 39) 37 (35; 39) 37 (35; 39) 38 (36; 39) 38 (36; 39) 0.06 0.06 0.06 Multiple pregnancy Multiple pregnancy Multiple pregnancy 10 (10.3) 10 (10.3) 10 (10.3) 18 (9.2) 18 (9.2) 0.76 0.76 0.76 History of PPHc History of PPHc History of PPHc 18 (18.6) 18 (18.6) 18 (18.6) 30 (15.31) 30 (15.31) 0.48 0.48 0.48 Obstetric indication for Cesarean Obstetric indication for Cesarean Obstetric indication for Cesarean Uterine scar Uterine scar Uterine scar 13 (13.4) 13 (13.4) 13 (13.4) 54 (27.6) 54 (27.6) 0.007 0.007 0.007 Placenta abnormality Placenta abnormality Placenta abnormality 57 (58.8) 57 (58.8) 57 (58.8) 90 (45.9) 90 (45.9) 0.04 0.04 0.04 Multiple pregnancy Multiple pregnancy Multiple pregnancy 7 (7.2) 7 (7.2) 7 (7.2) 15 (7.7) 15 (7.7) 0.90 0.90 0.90 Fetal Distress Fetal Distress Fetal Distress 6 (6.2) 6 (6.2) 6 (6.2) 18 (9.2) 18 (9.2) 0.38 0.38 0.38 Dystocia of labor Dystocia of labor Dystocia of labor 4 (4.1) 4 (4.1) 4 (4.1) 6 (3.1) 6 (3.1) 0.73 0.73 0.73 Maternal disease Maternal disease Maternal disease 8 (8.3) 8 (8.3) 8 (8.3) 15 (7.7) 15 (7.7) 0.86 0.86 0.86 Uterine abnormality Uterine abnormality Uterine abnormality 11 (11.3) 11 (11.3) 11 (11.3) 16 (8.2) 16 (8.2) 0.38 0.38 0.38 Pregnancy-related vascular disorder Pregnancy-related vascular disorder Pregnancy-related vascular disorder 5 (5.2) 5 (5.2) 5 (5.2) 14 (7.1) 14 (7.1) 0.52 0.52 0.52 Vaginal bleeding Vaginal bleeding Vaginal bleeding 4 (4.1) 4 (4.1) 4 (4.1) 6 (3.1) 6 (3.1) 0.73 0.73 0.73 Breech presentation Breech presentation Breech presentation 3 (3.1) 3 (3.1) 3 (3.1) 10 (5.1) 10 (5.1) 0.55 0.55 0.55 Type of Anesthesia Type of Anesthesia Type of Anesthesia General anesthesia General anesthesia General anesthesia 31 (32.0) 31 (32.0) 31 (32.0) 43 (21.9) 43 (21.9) 0.06 0.06 0.06 Epidural anesthesia Epidural anesthesia Epidural anesthesia 9 (9.3) 9 (9.3) 9 (9.3) 11 (5.6) 11 (5.6) 0.24 0.24 0.24 Spinal anesthesia Spinal anesthesia Spinal anesthesia 32 (33.0) 32 (33.0) 32 (33.0) 68 (34.7) 68 (34.7) 0.77 0.77 0.77 Combined spinal anesthesia Combined spinal anesthesia Combined spinal anesthesia 34 (35.1) 34 (35.1) 34 (35.1) 82 (41.8) 82 (41.8) 0.26 0.26 0.26 Urgency of Cesarean section Urgency of Cesarean section Urgency of Cesarean section Scheduled Scheduled Scheduled 65 (67.0) 65 (67.0) 65 (67.0) 138 (70.4) 138 (70.4) 0.55 0.55 0.55 Green code Green code Green code 15 (15.5) 15 (15.5) 15 (15.5) 26 (13.3) 26 (13.3) 0.61 0.61 0.61 Orange code Orange code Orange code 4 (4.1) 4 (4.1) 4 (4.1) 16 (8.2) 16 (8.2) 0.20 0.20 0.20 Red code Red code Red code 13 (13.4) 13 (13.4) 13 (13.4) 16 (8.2) 16 (8.2) 0.16 0.16 0.16 a: Values are given in terms of average ± standard deviation, in terms of median (1st quartile; 3rd quartile) or in terms of frequency (percentage). b: BMI: Body mass index c: PPH: Post-partum Haemorrhage a: Values are given in terms of average ± standard deviation, in terms of median (1st quartile; 3rd quartile) or in terms of frequency (percentage). b: BMI: Body mass index c: PPH: Post-partum Haemorrhage a: Values are given in terms of average ± standard deviation, in terms of median (1st quartile; 3rd quartile) or in terms of frequency (percentage). b: BMI: Body mass index c: PPH: Post-partum Haemorrhage a: Values are given in terms of average ± standard deviation, in terms of median (1st quartile; 3rd quartile) or in terms of frequency (percentage). b: BMI: Body mass index c: PPH: Post-partum Haemorrhage a: Values are given in terms of average ± standard deviation, in terms of median (1st quartile; 3rd quartile) or in terms of frequency (percentage). b: BMI: Body mass index c: PPH: Post-partum Haemorrhage a: Values are given in terms of average ± standard deviation, in terms of median (1st quartile; 3rd quartile) or in terms of frequency (percentage). b: BMI: Body mass index c: PPH: Post-partum Haemorrhage a: Values are given in terms of average ± standard deviation, in terms of median (1st quartile; 3rd quartile) or in terms of frequency (percentage). b: BMI: Body mass index c: PPH: Post-partum Haemorrhage a: Values are given in terms of average ± standard deviation, in terms of median (1st quartile; 3rd quartile) or in terms of frequency (percentage). b: BMI: Body mass index c: PPH: Post-partum Haemorrhage a: Values are given in terms of average ± standard deviation, in terms of median (1st quartile; 3rd quartile) or in terms of frequency (percentage). b: BMI: Body mass index c: PPH: Post-partum Haemorrhage a: Values are given in terms of average ± standard deviation, in terms of median (1st quartile; 3rd quartile) or in terms of frequency (percentage). b: BMI: Body mass index c: PPH: Post-partum Haemorrhage a: Values are given in terms of average ± standard deviation, in terms of median (1st quartile; 3rd quartile) or in terms of frequency (percentage). b: BMI: Body mass index c: PPH: Post-partum Haemorrhage Table 2. Univariate analysis: autotransfusion according to the indications for Intraoperative cell salvage (ICS). Table 2. Univariate analysis: autotransfusion according to the indications for Intraoperative cell salvage (ICS). Table 2. Univariate analysis: autotransfusion according to the indications for Intraoperative cell salvage (ICS). Table 2. Univariate analysis: autotransfusion according to the indications for Intraoperative cell salvage (ICS). Table 2. Univariate analysis: autotransfusion according to the indications for Intraoperative cell salvage (ICS). Table 2. Univariate analysis: autotransfusion according to the indications for Intraoperative cell salvage (ICS). Table 2. Univariate analysis: autotransfusion according to the indications for Intraoperative cell salvage (ICS). Table 2. Univariate analysis: autotransfusion according to the indications for Intraoperative cell salvage (ICS). Table 2. Univariate analysis: autotransfusion according to the indications for Intraoperative cell salvage (ICS). Table 2. Univariate analysis: autotransfusion according to the indications for Intraoperative cell salvage (ICS). Table 2. Univariate analysis: autotransfusion according to the indications for Intraoperative cell salvage (ICS). Indication of ICS a ; b Indication of ICS a ; b Indication of ICS a ; b ICS with autotransfusion N=97 ICS with autotransfusion N=97 ICS with autotransfusion N=97 ICS without autotransfusion N =196 ICS without autotransfusion N =196 P P P Placenta abnormality Placenta abnormality Placenta abnormality 55 (56.7) 55 (56.7) 55 (56.7) 86 (43.9) 86 (43.9) 0.039 0.039 0.039 Placenta accreta Placenta accreta Placenta accreta 27 (27.8) 27 (27.8) 27 (27.8) 24 (12.2) 24 (12.2) < .001 < .001 < .001 Placenta previa Placenta previa Placenta previa 30 (30.9) 30 (30.9) 30 (30.9) 63 (32.1) 63 (32.1) 0.834 0.834 0.834 Risk factors for uterine atony Risk factors for uterine atony Risk factors for uterine atony 22 (22.7) 22 (22.7) 22 (22.7) 33 (16.8) 33 (16.8) 0.228 0.228 0.228 Uterine fibroids Uterine fibroids Uterine fibroids 13 (13.4) 13 (13.4) 13 (13.4) 10 (5.1) 10 (5.1) 0.013 0.013 0.013 Multiple pregnancy Multiple pregnancy Multiple pregnancy 10 (10.3) 10 (10.3) 10 (10.3) 18 (9.2) 18 (9.2) 0.758 0.758 0.758 Fetal macrosomia Fetal macrosomia Fetal macrosomia 1 (1.0) 1 (1.0) 1 (1.0) 5 (2.6) 5 (2.6) - - - Uterin scar Uterin scar Uterin scar 14 (14.4) 14 (14.4) 14 (14.4) 47 (24.0) 47 (24.0) 0.058 0.058 0.058 Postoperative bleeding Postoperative bleeding Postoperative bleeding 10 (10.3) 10 (10.3) 10 (10.3) 3 (1.5) 3 (1.5) 0.001 0.001 0.001 Maternal heart disease Maternal heart disease Maternal heart disease 3 (3.1) 3 (3.1) 3 (3.1) 5 (2.6) 5 (2.6) 0.723 0.723 0.723 Pregnancy-related vascular disorder Pregnancy-related vascular disorder Pregnancy-related vascular disorder 5 (5.2) 5 (5.2) 5 (5.2) 8 (4.1) 8 (4.1) 0.765 0.765 0.765 Preeclampsia Preeclampsia Preeclampsia 2 (2.1) 2 (2.1) 2 (2.1) 3 (1.5) 3 (1.5) - - - HELLP syndrome HELLP syndrome HELLP syndrome 1 (1.0) 1 (1.0) 1 (1.0) 2 (1.0) 2 (1.0) - - - Retroplacental hematoma Retroplacental hematoma Retroplacental hematoma 2 (2.1) 2 (2.1) 2 (2.1) 3 (1.5) 3 (1.5) - - - Transfusion difficulties Transfusion difficulties Transfusion difficulties 6 (6.2) 6 (6.2) 6 (6.2) 28 (14.3) 28 (14.3) 0.042 0.042 0.042 Rare blood group Rare blood group Rare blood group 0 (0) 0 (0) 0 (0) 24 (12.2) 24 (12.2) 0.001 0.001 0.001 Jehovah’s witness Jehovah’s witness Jehovah’s witness 1 (1.0) 1 (1.0) 1 (1.0) 1 (0.5) 1 (0.5) - - - Sickle cell disease Sickle cell disease Sickle cell disease 5 (5.2) 5 (5.2) 5 (5.2) 3 (1.5) 3 (1.5) 0.121 0.121 0.121 Haemostasis disorder Haemostasis disorder Haemostasis disorder 0 (0) 0 (0) 0 (0) 8 (4.1) 8 (4.1) 0.056 0.056 0.056 Prepartum anemia Prepartum anemia Prepartum anemia 3 (3.1) 3 (3.1) 3 (3.1) 4 (2.0) 4 (2.0) - - - History of severe PPH History of severe PPH History of severe PPH 5 (5.2) 5 (5.2) 5 (5.2) 15 (7.7) 15 (7.7) 0.425 0.425 0.425 Other indication Other indication Other indication 4 (4.1) 4 (4.1) 4 (4.1) 17 (8.7) 17 (8.7) 0.228 0.228 0.228 a Values are given in terms of frequency (percentage). b Patients could have one, two or three indications for ICS. a Values are given in terms of frequency (percentage). b Patients could have one, two or three indications for ICS. a Values are given in terms of frequency (percentage). b Patients could have one, two or three indications for ICS. a Values are given in terms of frequency (percentage). b Patients could have one, two or three indications for ICS. a Values are given in terms of frequency (percentage). b Patients could have one, two or three indications for ICS. a Values are given in terms of frequency (percentage). b Patients could have one, two or three indications for ICS. a Values are given in terms of frequency (percentage). b Patients could have one, two or three indications for ICS. a Values are given in terms of frequency (percentage). b Patients could have one, two or three indications for ICS. a Values are given in terms of frequency (percentage). b Patients could have one, two or three indications for ICS. a Values are given in terms of frequency (percentage). b Patients could have one, two or three indications for ICS. a Values are given in terms of frequency (percentage). b Patients could have one, two or three indications for ICS. Table 3. Multivariate analysis: autotransfusion according to the indications for Intraoperative cell salvage. Table 3. Multivariate analysis: autotransfusion according to the indications for Intraoperative cell salvage. Table 3. Multivariate analysis: autotransfusion according to the indications for Intraoperative cell salvage. Table 3. Multivariate analysis: autotransfusion according to the indications for Intraoperative cell salvage. Table 3. Multivariate analysis: autotransfusion according to the indications for Intraoperative cell salvage. Table 3. Multivariate analysis: autotransfusion according to the indications for Intraoperative cell salvage. Table 3. Multivariate analysis: autotransfusion according to the indications for Intraoperative cell salvage. Table 3. Multivariate analysis: autotransfusion according to the indications for Intraoperative cell salvage. Table 3. Multivariate analysis: autotransfusion according to the indications for Intraoperative cell salvage. Indication of ICS OR OR OR CI 95% CI 95% CI 95% P P Placenta accreta 3.42 3.42 3.42 [1.8 ; 6.54] [1.8 ; 6.54] [1.8 ; 6.54] < .001 < .001 Uterine fibroids 3.74 3.74 3.74 [1.49 ; 9.38] [1.49 ; 9.38] [1.49 ; 9.38] 0.005 0.005 Postoperative bleeding 10.15 10.15 10.15 [2.67 ; 38.53] [2.67 ; 38.53] [2.67 ; 38.53] < .001 < .001 Transfusion difficulties 0.11 0.11 0.11 [0.015 ; 0.85] [0.015 ; 0.85] [0.015 ; 0.85] 0.034 0.034 Uterine scar 0.80 0.80 0.80 [0.39 ; 1.63] [0.39 ; 1.63] [0.39 ; 1.63] 0.536 0.536 Other 0.70 0.70 0.70 [0.21 ; 2.18] [0.21 ; 2.18] [0.21 ; 2.18] 0.519 0.519
Trisomy 8 mosaicism in the placenta: a Danish cohort study of 37 cases and a literatu...
Simon Horsholt Thomsen
Ida Charlotte Bay Lund

Simon Horsholt Thomsen

and 5 more

April 24, 2020
Objective: To evaluate the risk of fetal involvement when trisomy 8 mosaicism (T8M) is detected in chorionic villus samples (CVS). Design: A retrospective descriptive study of registered cases in Denmark and a systematic literature review. Setting: Cases of T8M in CVS registered in Denmark between January 1983 and March 2019 and published literature until March 2019. Sample: A total of 37 registered pregnancies in Denmark and 60 published cases. Methods: Registered pregnancies with T8M in CVS were identified through a database search. Published cases of T8M were found through a systematic literature search and backward snowballing. Pregnancies with T8M in CVS and no additional numerical chromosomal aberrations were included. Main outcome measures: Fetal involvement defined as T8M in amniotic fluid (AF) or fetal tissue. Results: T8M detected in a CVS was associated with fetal involvement in 18 out of 97 pregnancies (18.6% [95%CI: 11.4-27.7]). Eight out of 70 (11.4% [95%CI: 5.1-21.3]) interpreted prenatally to be confined placental mosaicism (CPM) were found to be true fetal mosaicisms (TFM). Conclusion: T8M detected in CVS poses a significant risk of fetal involvement, and examination of AF and/or fetal tissue should be offered. However, a normal result of AF still has a considerable residual risk of fetal involvement. Genetic counselling at an early gestational age is essential, and follow-up ultrasonography should be performed to predict fetal involvement if possible. Funding: Ida Vogel is funded by a research grant from the Novo Nordic Foundation: NNF16OC0018772 Keyword: Trisomy, mosaicism, prenatal
Bio-specific immobilization of enzymes on electrospun PHB nanofibers
Sun Ah Jang
Ji Hyun Park

Sun Ah Jang

and 7 more

April 24, 2020
Phasins are proteins found on the surface of natural polyhydroxyalkanoate (PHA) granules. Due to their high affinity for PHA, they can potentially be used as a fusion partner to immobilize other proteins. In this study, we investigated the immobilization of a lipase onto electrospun polyhydroxybutyrate nanofibers. Due to a superior surface area-to-volume ratio, PHB nanofibers retained much larger amounts of enzyme than conventional immobilization supports. More importantly, when used in combination with a phasin tag, the enzyme immobilized on PHB nanofibers exhibited markedly higher activity and reusability. Our approach combines the advantageous features of nanofibrous materials and the regio-specificity of biomolecular interactions for the efficient use of enzymes.
The effect of the expression of the antiapoptotic BHRF1 gene on the metabolic behavio...
Iván Martínez-Monge
Pere Comas

Iván Martínez-Monge

and 7 more

April 24, 2020
One of the most important limitations of mammalian cells-based bioprocesses, and particularly hybridoma cell cultures, is the deregulated metabolism related to glucose and glutamine consumption. The high uptake rates of glucose and glutamine (being both the main nutrients used as a carbon, nitrogen and energy sources) yields to the production and accumulation of large amounts of lactate and ammonia in the culture broth. Lactate and/or ammonia accumulation, together with the depletion of the main nutrients are the major causes that triggers the apoptosis in hybridoma cell cultures. The KB26.5 hybridoma cell line producing an IgG3 (used in the ABO blood testing system) was engineered with BHRF1 protein (KB26.5-BHRF1), an Epstein–Barr virus-encoded early protein homologous to the anti-apoptotic protein Bcl-2, with the aim of protecting the cell line from apoptosis. Surprisingly, besides achieving an effective protection from apoptosis, the expression of BHRF1 modified significantly the metabolism of the hybridoma cell line. The comparison of cell physiology and metabolism analysis of the original KB26.5 and KB26.5-BHRF1 revealed an increase of cell growth rate, a reduction of glucose and glutamine consumption, as well as a decrease on lactate secretion in KB26.5-BHRF1 cells. The flux balance analysis allowed quantifying intracellular fluxes of both cell lines. The main metabolic differences were identified in the glucose consumption and, consequently, the lactate generation. The lactate production flux was reduced by 60% since the need for NADH regeneration in the cytoplasm decreased due to the glucose uptake reduction by more than 50%. In general terms, BHRF1 engineered cell line showed a more efficient metabolism yielding to an increase of the biomass volumetric productivity under identical culture conditions.
Techno-economic analysis of semicontinuous bioreactor production of biopharmaceutical...
Jasmine Corbin
Matthew McNulty

Jasmine Corbin

and 4 more

April 24, 2020
Biopharmaceutical protein production using transgenic plant cell bioreactor processes offers advantages over microbial and mammalian cell culture platforms due to the ability to produce complex biologics, use of simple chemically-defined, animal component-free media, robustness of host cells, and biosafety. A disadvantage of plant cells from a traditional batch bioprocessing perspective is their slow growth rate which has motivated us to develop semicontinuous and/or perfusion processes. Although the economic benefits of plant cell culture bioprocesses are often mentioned in the literature, to our knowledge no rigorous techno-economic models or analyses have been published. Here we present techno-economic models in SuperPro Designer® for the large-scale production of recombinant butyrylcholinesterase (BChE), a prophylactic/therapeutic bioscavenger against organophosphate nerve agent poisoning, in inducible transgenic rice cell suspension cultures. The base facility designed to produce 25 kg BChE per year utilizing two-stage semicontinuous bioreactor operation manufactures a single 400 mg dose of BChE for $263. Semicontinuous operation scenarios result in 4-11% reduction over traditional two-stage batch operation scenarios. In addition to providing a simulation tool that will be useful to the plant-made pharmaceutical community, the model also provides a computational framework that can be used for other semicontinuous or batch bioreactor-based processes.
Homology Modelling and in-silico analysis of 39bp Insertion-Deletion in Sahiwal Cattl...
P.B. Nandhini
D. Ravikumar

P.B. Nandhini

and 4 more

April 24, 2020
SERPINA14 proteins are progesterone induced and are secreted during pregnancy in large quantities by the endometrial epithelium. Serine proteinase inhibitor being represented only in a limited group of mammals has been associated with higher embryo survival rates, productive life, milk production and health traits and a minisatellite insertion has been reported in Bali cattle. The most variable exons (1 and 4) of SERPINA14 gene in Sahiwal cattle were sequenced to reveal the 39bp repeats in the coding region of the exon 4. In order to ascertain the changes in this gene that directly affects the protein structure, its structure was deduced using homology modelling with Bos taurus as reference, after imputing the missing coding sequence. The comparison of protein structure using SWISS-MODEL, I-TASSER and PHYRE2 showed that PHYRE2 predicted the best model for the proteinswith more than 90% of the residues lying in the most favoured regions in the Ramachandran plot.The impact of the indel with 5 repeats was assessed to be deleterious using PROVEANwith a score of -22.464 while indel with 4 repeats had a score of -10.676 against athreshold of -2.5 comparing with 130 sequences and 30 clusters.However, the association of the indel with reproduction data failed to reveal any significant effect which could be attributed to the data size. Phylogenetic study of the gene with its relatives showed that the sequence with 5 repeats was similar to Yak and Bison while the one with 4 repeats resembled all bovines alike.
Endopharyngeal Ultrasound
Taha Mur
Osamu Sakai

Taha Mur

and 4 more

April 24, 2020
Key Points: • We describe a novel procedure, Endopharyngeal Ultrasound (EPhUS) and EPhUS-guided FNA • EPhUS requires an operator and an assistant, can be performed transnasal or transoral, and utilizes a Endoscopic Ultrasonography Bronchoscope • EPhUS is a safe and effective method for biopsy of deep space neck masses inaccessible to transcutaneous FNA
Tinnitus severity correlated with zinc, copper, risk factors: a large-scale case-cont...
Jiangfeng Huang
Jing  He

Jiangfeng Huang

and 16 more

April 24, 2020
Objectives This large-scale case-control study aimed to explore the trace elements (Zn & Cu) and risk factors associated with tinnitus severity (mild and moderate-to-severe tinnitus). Methods The serum levels of Zn & Cu of participants were measured by inductively coupled plasma mass spectrometry (ICP-MS). The potential risk factors were analyzed by simple and multiple logistic regression analysis. Results Compared mild tinnitus with moderate-to-severe tinnitus, the serum Zn of participants had a significant difference (P=0.05), and only the age variable displayed an evident difference in main clinical characteristics analysis table (P<0.05). Under a multivariable-adjusted analysis, the potential risk factors included hearing loss (AOR: 1.704, 95% CI: 1.009-2.880), HADS-A (borderline abnormal, AOR: 2.876, 95% CI: 1.248-6.625; abnormal, AOR: 12.149, 95% CI: 2.722-54.218), AIS (slight sleep problems, AOR: 2.030, 95% CI: 1.061-3.885; probable/definite insomnia, AOR: 6.955, 95% CI: 3.669-13.185), ear-self-cleaning (<1 t/w, AOR: 2.117, 95% CI: 1.178-3.805; 3-6 t/w, AOR: 2.462, 95% CI: 1.081-5.607; ≥7 t/w, AOR: 2.472, 95% CI: 1.041-5.868), tea consumption (AOR: 1.138, 95% CI: 1.052-1.231) and sleep apnea (AOR: 1.805, 95% CI: 1.036-3.145). Next, a stratified analysis was made on these risk factors, and the results showed that the low levels of Zn were significantly associated with tinnitus severity in hearing loss group——both in “no” and “yes” subgroups (“no”, AOR: 2.588, 95% CI: 1.348-6.061; “yes”, AOR: 4.213, 95% CI: 1.106-8.430), and in HADS-A group——noly in “normal” subgroup (AOR: 2.928, 95% CI: 1.790-6.984). Conclusions Serum Zn deficiency and potential risk factors (including hearing loss, tea consumption, sleep apnea, anxiety, insomnia and ear-self-cleaning habit) were significantly correlated with tinnitus severity. Intervention with these risk factors could prevent the mild tinnitus from becoming moderate-to-severe tinnitus.
Xylitol-Gum Chewing for the Management of Otitis Media with Effusion
kanokrat suvarnsit
Jutamas  Techapanuwat

kanokrat suvarnsit

and 6 more

April 24, 2020
Introduction: Otitis media with effusion (OME) is the collection of fluid in the middle ear without signs or symptoms of an acute infection. It is cured by treating the cause and restoring normal eustachian tube function. By activating jaw movement and inducing frequent swallowing, chewing gum could be effective in the conservative management of OME. Objectives: To determine the recovery rate after chewing xylitol gum for the treatment of OME, and the factors associated with OME cures in adults. Materials and methods: A non-randomized, controlled trial was conducted on 30 OME patients May 2018–December 2019. The subjects chewed 2 tabs of gum for 5–10 minutes, 3 times daily, for up to 3 months. Physical and audiometric examinations were performed at 2, 6 and 12 weeks. Results: Thirty patients were enrolled. Their mean age was 55.0 ± 20.19 years. OME resolution was found in 23/43 ears (53.49%). Myringotomy was performed in 13/43 ears (30.23%). Two factors were associated with shorter resolution times. Firstly, a patient age of 40–60 years, compared with other ages (p-value = 0.030). Secondly, an initial average air-bone gap of ≤ 20 dB, compared with larger gaps (p-value = 0.027). Conclusions: Xylitol-gum chewing did not increase the overall OME resolution rate. Nonetheless, it is still a choice for OME management as it tends to shorten the resolution time, with only minor side effects being experienced by some patients. Keywords: Otitis media with effusion, otitis media, OME, xylitol chewing gum, gum chewing, xylitol gum, gum
Gully network expansion and spatial and temporal dynamics of catchment geomorphic cha...
Shiro Mukai
Paolo Billi

Shiro Mukai

and 4 more

April 24, 2020
To analyse the driving forces of gully erosion using a present dataset of geomorphic parameters and land use/cover involves limitations because past datasets at the time of gully incision may best explain the gully formation and evolution at that time. The recent development of photogrammetric techniques enabled to estimate temporal gully volume changes. This study conducted in semi-arid Ethiopian Rift Valley used field measurements and gully volume–length relation to analyse spatial and temporal dynamics of catchment geomorphology and topographical threshold of gully heads to explain the difference in the gully volumes and area-specific gully volumes between two study sub-areas. The topographic thresholds of the gully heads, expressed by the slope (= s) and drainage area (= a), (i) formed in each catchment and (ii) that had the same land use/cover items (forest, grassland, and farmland) in all the catchments of each sub-area were approximated by power functions (s = ka-b). Analysis of covariance found that these threshold lines had clear spatial and temporal patterns: the threshold lines maintained almost the same exponent b specific to each sub-area while the threshold coefficient k significantly decreased in the order of forest, grassland, and farmland. The spatial variability and its temporal changes in relief aspect of the catchment morphology can responsible for the difference in the area-specific volumes of gullies between the sub-areas, while the continuous reduction in vegetation cover over time can be the main driving force of the similar scale and changing patterns of the gully volumes between the sub-areas.
No population left behind: improving pediatric drug safety using informatics and syst...
Nicholas Giangreco
Jonathan Elias

Nicholas Giangreco

and 2 more

April 24, 2020
The current drug safety landscape inadequately serves the millions of children prescribed medications every year. Randomized clinical trials are limited in detecting pediatric adverse drug effects due to low participant enrollment, complicated study design, and short trial duration. While the biology of human development and the pathology of childhood diseases are well studied research topics, current pharmacoepidemiology approaches do not use this knowledge when investigating drug safety in children. Here, we describe how adverse drug effects manifest as children develop from birth through the teenage years. We discuss the benefits of an empirical approach for evaluating clinical relevance and biological causality of identified adverse drug effects in children. We argue that a data-driven strategy that leverages observational data and biomedical knowledge is an ethical and effective methodology to improve pediatric drug safety.
Ethical Framework for Head and Neck Endocrine Surgery in the COVID 19 pandemic
Head and Neck Editor

Amy Y. Chen, MD, MPH

April 24, 2020
Amy Y. Chen, MD, MPHEmory Universityachen@emory.eduMaisie Shindo, MDOregon Health Sciences Universityshindom@ohsu.eduCorresponding author:Amy Y. Chen, MD, MPHEmory Department of Otolaryngology Head and Neck Surgery550 Peachtree St. MOT 1135Atlanta, GA 30308404-778-2178achen@emory.eduShort title: Ethics Endocrine Surgery COVID 19Ethical Framework for Head and Neck Endocrine Surgery in the COVID 19 pandemicThe COVID-19 pandemic has halted all elective surgeries, allowing only emergent surgeries, and in some hospitals time-sensitive urgent surgeries to proceed. “Mr. X, This is Dr. I’m calling to discuss with you your previously planned surgery. “ I’ve been having many conversations like this with my patients over the past weeks. Surgeries may be delayed or the patient and his/ her family may need to make a heart wrenching decision whether to proceed with surgery in a hospital filling with COVID patients, risking infection themselves, and without any visitors. Endocrine surgery falls into this valley where it is neither life threatening nor totally benign either. The American Association of Endocrine Surgeons1 as well as the endocrine section of the American Head and Neck Surgery2 have put forth recommendations for thyroid and parathyroid conditions that would be considered urgent time-sensitive surgery. These include 1) high risk thyroid cancers such as those with bulky central and lateral neck disease, concern for tracheal or esophageal involvement, or short doubling time 2) Graves’ disease with thyrotoxicosis that cannot be controlled with anti-thyroid medications, 3) compressive large goiters with dyspnea or significant symptomatic vascular compression, 4) Primary hyperparathyroidism with life-threatening hypercalcemia that cannot be managed medically, 5) endocrine disorders in pregnant patient that are dangerous to the health of the mother or fetus that cannot be controlled medically.Certainly, there has been an international push to observe more well differentiated thyroid cancer; however, what about those “smallish” cancers that are near the isthmus, near the trachea/ esophagus, or with extracapsular extension? Despite their small size, these can become invasive to the degree that could result in the need to perform a more morbid procedure if surgery is delayed, and thus should be considered in the category of “time-sensitive surgery”. What about indeterminate thyroid nodules with adverse molecular markers? If such nodules present with ultrasound findings that are concerning for local invasion, even though the cytologic diagnosis is not “malignant”, such lesions should be treated as high risk cancer, and surgery should not be delayed.If proceeding with surgery, the surgeon has an ethical responsibility to discuss with the patient the potential risk of COVID-19 infection. We as surgeons have a responsibility to reduce risk of infection not only to the patient but the healthcare team who will be caring for the patient. At the minimum COVID-19 testing should be performed preoperatively within 2 days of surgery, and the patient should be educated on the importance of self-isolation and necessary precautions.If potential difficult airway is anticipated communication and planning with anesthesia pre-procedure is important. Despite that fact that the patient may test negative for COVID-19, the false negative rate is not zero, and as such, precautions need to be taken to minimize exposure. A difficult airway may result in manipulation of the airway that could potentially be aerosolizing. Having the appropriate protective gear and all necessary difficult airway equipment is essential in such a situation. If the patient needs fiberoptic laryngoscopy or tracheoscopy, nasal pledgets should be used in lieu of sprays. Surgery should certainly be postponed in Covid-19 positive patients.Scarcity of resources, surge planning, and public health mitigation efforts have all combined in a perfect storm to delay and in some situations, to deny treatment to head and neck surgery patients. Whereas some of our patients may afford a delay in their treatment, others do not have that luxury. It is incumbent upon us, as their clinicians, to integrate competing priorities into an acceptable plan.Justice, or to be just/ fair, must include a lens towards equity. One way to honor this ethical principle is to incorporate both clinical and non-clinical factors in risk assessment. Many papers have reported on the profound effect of sociodemographic factors on patient outcomes. An intersection between higher comorbidity burden and lower socioeconomic status can worsen disparities of who gets treatment. For example, algorithms that incorporate comorbidity are necessary so that resources can be allocated for the “greater good;” however, these guidelines risk heightening disparities and health inequity. Strategies to ameliorate these disparities include flexibility of treatment options, creative discharge planning, and thorough pre-operative conditioning. Flexibility of treatment options include consideration of definitive chemoradiation, induction chemotherapy prior to surgery (to buy time), and resection with delayed reconstruction.Beneficence, or to do good, is a guiding principle of ethics. With limited resources, the “good” of society supersedes the “good’ of the individual. Hence, the cancellation of elective, non-emergent cases is instituted. So is the prioritization of surgical cases that are not likely to need ICU care, blood products, extended inpatient stay, and extensive ancillary laboratory/ radiology testing.However, these cancellations/ delays in treatment/ changes in treatment can cause anxiety for both the clinician and his/ her patient. Many of our patients have been waiting for several weeks for their treatment to start, only to have it be delayed or altered. How do we reassure the patient that the new plan is the best plan, given the restrictions that the COVID 19 pandemic places on systems? How do we, as clinicians, resolve our inner turmoil in delaying/ denying/ altering treatment.Early data already demonstrate that COVID 19 is affecting vulnerable racial minorities at a higher disproportionate rate. To compound the adverse effects, this cohort has more access issues due to transportation, hourly job limitations, and lack of stable insurance. The delay in surgery may result in the patient’s loss of insurance status due to loss of income and/ or being furloughed. As we move into the next phase of easing up restrictions, such factors need to be taken into consideration in prioritizing whom we select for surgery.1. https://www.endocrinesurgery.org/assets/COVID-19/AAES-Elective-Endocrine-Surgery.pdf2. https://www.ahns.info/wp-content/uploads/2020/03/Endocrine-Surgery-during-the-Covid.pdf
Respiratory Sampling for SARS-CoV-2 – An Overview
Head and Neck Editor

Anna See, MMed

April 24, 2020
The novel coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was declared a pandemic in March 2020. A plethora of respiratory sampling methods for SARS-CoV-2 viral detection has been used and in the current evolving situation, there is no international consensus on the recommended method of respiratory sampling for diagnosis. Otolaryngologists deal intimately with the upper respiratory tract and a clear understanding of the respiratory sampling methods is of paramount importance. This article aims to provide an overview of the various methods and their evidence till date.
Quantitative automated assays in living cells to screen for inhibitors of hemichannel...
Emmanuelle Soleilhac
Marjorie Comte

Emmanuelle Soleilhac

and 8 more

April 23, 2020
In vertebrates, intercellular communication is largely mediated by connexins, a family of structurally related transmembrane proteins that assemble to form hemichannels (HCs) at the plasma membrane. HCs are upregulated in different brain disorders; hence represent innovative therapeutic targets and identifying modulators of Cx-based HCs is of great interest for better understanding their function and defining new treatments. In this study, we developed automated versions of two different cell-based assays to identify new pharmacological modulators of HCs. The first assay follows the incorporation of a fluorescent dye, Yo-Pro, by real-time imaging while the second is based on the quenching of a fluorescent protein, YFPQL, by iodide after iodide uptake. These assays were then used to screen a collection of 2,242 approved drugs and compounds under development. This study led to the identification of 11 new HC blockers, active in the two assays, with 5 drugs active on HC but not on gap junction (GJ) activities. To our knowledge, this is the first screening on HC activity and our results suggest the potential of a new use of already approved drugs in CNS disorders with HC impairments.
Genome analysis of Getah virus (GETV) isolated from and contaminated in a live swine...
Feng Zhou
Aojie Wang

Feng Zhou

and 6 more

April 23, 2020
GETV cause fetus death and reproductive disorders in pigs. In this study, a GETV strain, named GETV-V1, was isolated from a commercial modified live vaccine (MLV) against porcine reproductive and respiratory syndrome virus (PRRSV), which is widely used on pigs in China. Further results showed that nine batches of MLV vaccine (three batches per year) from the same manufacturer between 2015 and 2017 were all positive for GETV. We then further characterized the GETV-V1 strain and performed phylogenetic analysis, revealing that the GETV strains circulating in China are genetically diverse and providing a potential platform for evolution. Therefore, this research firstly reported the contamination of GETV in live attenuated PRRS vaccines in China, implying that monitoring of exogenous virus in live vaccines for pigs needs to be improved.
Detection and genetic characterization of porcine circovirus 4 (PCV4) in Guangxi, Chi...
chao sun
Qian  Du

chao sun

and 5 more

April 23, 2020
Porcine circovirus type 4 (PCV4), a novel circovirus, was first detected in pigs with porcine dermatitis and nephropathy syndrome (PDNS) in China. This study investigated the frequency of porcine circovirus 4 (PCV4) in pigs in Guangxi Province, China, from 2015 to 2019 and its genome diversity. Thirteen of 257 (5.1%) samples were positive for PCV4, 9 of 13 (69.2%) PCV4-positive samples were coinfected with PCV2 or PCV3, and one PCV4-positive sample was coinfected with both PCV2 and PCV3. Similar to other PCVs, PCV4 contains two major ORFs and a stem loop (TTCAGTATTAC). Multiple sequence alignments showed that the PCV4 genome shares 25.3-73.8% nucleotide similarity with other representative circovirus genomes. Interestingly, the PCV4 Cap protein shares relatively high homology (approximately 50%) with the PCV2 Cap protein and has multiple highly homologous peptides. Multiple amino acid sequence alignments of the Cap protein revealed that PCV2 and PCV4 have multiple highly homologous antigen sites and identical receptor binding sites. Therefore, PCV2 and PCV4 may have cross-protective immunogenicity. Phylogenetic analysis showed that PCV4 is closely related to mink circovirus and bat-associated circovirus. In summary, this was the first seroprevalence and genetic investigation of PCV4 in Guangxi Province, China. The results provide insights into the epidemiology and pathogenesis of this important virus.
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