Uniportal video-assisted thoracoscopic surgery (VATS) technique is associated with decreased narcotic usage over traditional VATS lobectomy.

Abstract:
BACKGROUND
Uniportal video-assisted thoracoscopic surgery (VATS) is gaining popularity internationally, but remains an uncommon practice in the United States. One proposed benefit is a decrease in narcotic usage and peri-operative pain when compared to traditional multiple incision VATS. The purpose of this study was to determine the post-operative narcotic usage between patients undergoing anatomic lobectomy via traditional VATS as compared to patients undergoing uniportal VATS.

METHODS
All consecutive patients undergoing anatomic lobectomy for presumed malignancy by a single surgeon at an academic medical institution were recorded between July 2013 and September 2015. Patients were excluded if they were narcotic dependent prior to the operation, if they had an epidural catheter placed, or if they were under 18 years of age. All narcotics were converted to oral morphine equivalents (OMEq) using standard formulas.

RESULTS
Data were collected on 84 patients. There was no difference between groups with regard to age, gender, tumor size, length of stay, or duration of post-operative thoracostomy. The groups had a similar rate of complications including post-operative atrial fibrillation and need for prolonged thoracostomy. Patients undergoing uniportal VATS had significantly lower narcotic usage in the recovery room, and on post-operative days 1 and 2. In addition, the total narcotic usage during their inpatient stay was significantly lower for patients undergoing uniportal VATS.

CONCLUSIONS
Uniportal VATS is a safe and effective strategy for the surgical management of benign and malignant lung disease. In patients undergoing anatomic lobectomy, there was an association with significantly less post-operative narcotic usage in patients undergoing uniportal VATS when compared to traditional VATS. This emerging technology may benefit patients by allowing less narcotic usage during their post-operative hospitalization.

Louis|Scott Gregory|SG|
Gibson|William James|WJ|
King|Chase Lynn|CL|
Veeramachaneni|Nirmal Kumar|NK|

Video-assisted thoracoscopic surgery (VATS)


Conservative treatment of caustic oesophageal injuries in children: 15 years of experience in a tertiary care paediatric centre.

Abstract:
Introduction
Endoscopic dilatation is good choice of conservative treatment for caustic digestive tract injuries in children.

Aim
To set up a strategy of management of caustic digestive tract injury based on our experience and literature review.

Material and methods
We retrospectively analysed medical records of 34 paediatric patients who were admitted to the Centre of Paediatric Surgery of the Children's Hospital between 2000 and 2017. Age at presentation, gender, anatomic location, circumstances and distribution of injury, early and late complications, clinical signs, and the first aid were analysed. Upper gastrointestinal (GI) endoscopy was performed within 12-24 h after ingestion in all cases. The Zargar classification system was used to grade the severity of the injury. Fisher's exact test was used for statistical analysis, with p < 0.05 considered as the limit of statistical significance.

Results
The upper GI endoscopy revealed caustic injuries in 5 (15%) and 8 (23%) patients were classified as grade IIa and IIb, respectively. Oesophageal and ventricle caustic injuries in 3 (9%) and 2 (6%) patients were classified as grade IIIa and IIIb, respectively. Thirteen patients with grade IIa and IIIb injuries suffered permanent damage and required repeated dilatation. All patients underwent stricture treatment using late or early endoscopic dilatation of the oesophagus. An average of 15 dilatation procedures were required to achieve a satisfactory lumen.

Conclusions
Our experience of 34 children revealed that endoscopic dilatation may be required as a primary treatment for oesophageal strictures.

Povilavičius|Jonas|J|
Samalavičius|Narimantas Evaldas|NE|
Verkauskas|Gilvydas|G|
Trainavičius|Kęstutis|K|
Povilavičienė|Milda|M|

conservative treatment
endoscopic dilatation
caustic injury


Chemical Composition and Allelopathic, Antibacterial, Antifungal, and Antiacetylcholinesterase Activity of Fish-mint (Houttuynia cordataThunb.) from India.

Abstract: Fish-mint (Houttuynia cordataThunb.), belonging to family Saururaceae, has long been used as food and traditional herbal medicine. The present study was framed to assess the changes occurring in the essential-oil composition of H. cordata during annual growth and to evaluate allelopathic, antibacterial, antifungal, and antiacetylcholinesterase activities. The essential-oil content ranged from 0.06 - 0.14% and 0.08 - 0.16% in aerial parts and underground stem, respectively. The essential oils were analysed by GC-FID, GC/MS, and NMR (1 H and 13 C). Major constituents of aerial-parts oil was 2-undecanone (19.4 - 56.3%), myrcene (2.6 - 44.3%), ethyl decanoate (0.0 - 10.6%), ethyl dodecanoate (1.1 - 8.6%), 2-tridecanone (0.5 - 8.3%), and decanal (1.1 - 6.9%). However, major constituents of underground-stem oil were 2-undecanone (29.5 - 42.3%), myrcene (14.4 - 20.8%), sabinene (6.0 - 11.1%), 2-tridecanone (1.8 - 10.5%), β-pinene (5.3 - 10.0%), and ethyl dodecanoate (0.8 - 7.3%). Cluster analysis revealed that essential-oil composition varied substantially due to the plant parts and season of collection. The oils exhibited significant allelopathic (inhibition: 77.8 - 88.8%; LD50 : 2.45 - 3.05 μl/plate), antibacterial (MIC: 0.52 - 2.08 μl/ml; MBC: bacteriostatic) and antifungal (MIC: 2.08 - 33.33 μl/ml; MFC: 4.16 - 33.33 μl/ml) activities. The results indicate that the essential oil from H. cordata has a significant potential to allow future exploration and exploitation as a natural antimicrobial and allelopathic agent.

Verma|Ram S|RS|
Joshi|Neeta|N|
Padalia|Rajendra C|RC|
Singh|Ved R|VR|
Goswami|Prakash|P|
Kumar|Ajay|A|
Iqbal|Hina|H|
Verma|Rajesh K|RK|
Chanda|Debabrata|D|
Chauhan|Amit|A|
Saikia|Dharmendra|D|

Essential-oil composition
Plant parts
Season
Houttuynia cordata
Antimicrobial activity
Phytotoxic activity


Risk factors for reoperation after lumbar total disc replacement at short-, mid-, and long-term follow-up.

Abstract:
BACKGROUND CONTEXT
The reoperation rate following TDR (Total Disc replacement) has been established at short- and mid-term time points through the Food and Drug Administration Investigational Device Exemption (FDA IDE) trials. However, these trials include highly selected centers and surgeons with strict governance of indications. The utilization of TDR throughout the community needs further analysis.

PURPOSE
To identify the risk factors for lumbar spine reoperation in patients undergoing lumbar total disc replacement (TDR) at short-, mid-, and long-term follow-up.

STUDY DESIGN/SETTING
This study is a multi-center retrospective cohort study utilizing the New York Statewide Planning and Research Cooperative System database.

PATIENT SAMPLE
We identified 1,368 patients who underwent an elective primary lumbar TDR in New York State between January 1, 2005 and September 30, 2013.

OUTCOME MEASURES
The primary functional outcome of interest was lumbar reoperation, specifically the evaluation of independent risk factors for lumbar reoperation at a minimum of 2 years, with sub-analyses performed at 5 and ten years.

METHODS
International Classification of Diseases, Ninth revision codes were utilized to identify patients undergoing a primary lumbar TDR. We excluded patients with primary/revision lumbar fusion procedures and revision disc replacement procedures. Hospital academic status was determined by the Accreditation Council for Graduate Medical Education. Unique encrypted patient identifiers allowed for longitudinal follow-up for reoperation. Logistic regression models compared reoperation and no-reoperation cohorts, and were performed on sub-analyses for significant univariate predictors of reoperation.

RESULTS
Between January 2005 and September 2013, 1368 patients underwent a primary lumbar TDR. Reoperation occurred in 8.8% by 2 years, 15.8% by 5 years, and 19.5% by ten years. Diabetics were more likely to have reoperations (7.5% vs 3.8%, p=.013). Teaching hospitals experienced a decreased reoperation rate compared to nonteaching hospitals at 2-year (5.0% vs 10.5%, p=.002), 5-year (10.7% vs 17.9%, p=.002) and 10-year (11.7% vs 21.9%, p=.045) follow-up. Lumbar fusion was the most common reoperation (14.2%).

CONCLUSION
We identified an 8.8% reoperation rate after inpatient lumbar TDR at 2-years, 15.8% at 5-years, and 19.5% at 10-years. When stratifying by teaching status, reoperation rates at teaching centers align with those reported in FDA IDE studies. Diabetes was the only patient factor influencing reoperation rate. There is a growing consensus that lumbar TDR is a durable and appropriate surgical option for lumbar degenerative disc disease. Proper indications are crucial to obtaining good outcomes with lumbar TDR.

Perfetti|Dean C|DC|
Galina|Jesse M|JM|
Derman|Peter B|PB|
Guyer|Richard D|RD|
Ohnmeiss|Donna D|DD|
Satin|Alexander M|AM|

Risk factors
Reoperation
Lumbar Total disc replacement
Revision
Academic teaching status
Epidemiology


ZhiJingSan Inhibits Osteoclastogenesis via Regulating RANKL/NF-κB Signaling Pathway and Ameliorates Bone Erosion in Collagen-Induced Mouse Arthritis.

Abstract: Bone erosion is the most evident pathological condition of rheumatoid arthritis (RA), which is the main cause of joint deformities and disability in RA patients. At present, the conventional RA drugs have not achieved satisfactory effect in improving bone erosion. ZhiJingSan (ZJS), which is a traditional Chinese prescription composed of scolopendra (dried body of Scolopendra subspinipes mutilans L. Koch, scolopendridae) and scorpion (dried body of Buthus martensii Karsch, Buthus), exhibits anti-rheumatism, analgesic and joint deformities improvement effects. This study aimed to assess the therapeutic effect of ZJS on RA bone erosion and to elucidate the underlying mechanism. The effect of ZJS on RA bone erosion was investigated in a murine model of bovine collagen-induced arthritis (CIA), and the underlying mechanism was investigated in vitro in an osteoclast differentiation cell model. Administration of ZJS delayed the onset of arthritis, alleviated joint inflammation, and attenuated bone erosion in the CIA mice. Meanwhile, ZJS decreased the serum levels of TNF-α, IL-6, and anti-bovine collagen II-specific antibodies. Furthermore, ZJS treatment reduced the number of osteoclasts and the expression of cathepsin K in the ankle joints of CIA mice. ZJS also inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation and the expression of MMP9 and cathepsin K in vitro. Mechanistically, ZJS blocked RANKL-induced p65 phosphorylation, nucleation, and inhibited the expression of downstream NFATc1 and c-Fos in bone marrow-derived macrophages (BMMs). Taken together, ZJS exerts a therapeutic effect on bone erosion in CIA mice by inhibiting RANKL/NF-κB-mediated osteoclast differentiation, which suggested that ZJS is a promising prescription for treating RA bone erosion.

Ling|Yuanyuan|Y| Yang|Jie|J| Hua|Di|D| Wang|Dawei|D| Zhao|Chenglei|C| Weng|Ling|L| Yue|Dandan|D| Cai|Xueting|X| Meng|Qinghai|Q| Chen|Jiao|J| Sun|Xiaoyan|X| Kong|Weikang|W| Zhu|Lizhong|L| Cao|Peng|P| Hu|Chunping|C|

ZhiJingSan
RANKL
NF-κB
bone erosion
rheumatoid arthritis
osteoclasts


Screening for coeliac disease in 1624 mainly asymptomatic children with type 1 diabetes: is genotyping for coeliac-specific human leucocyte antigen the right approach?

Abstract:
OBJECTIVES
To investigate the frequency of coeliac disease (CD)-specific human leucocyte antigen (HLA) genotypes in paediatric patients with type 1 diabetes (T1D), who are known to have a higher prevalence of CD than the general population, and to evaluate whether HLA genotyping is a suitable first-line screening method for CD.

STUDY DESIGN
The study was a multicentre observational analysis of patients with T1D aged <20 years of whom a subgroup had undergone HLA genotyping. Patient data were retrieved from the Diabetes Prospective Follow-up database, a large diabetes follow-up registry. The present analysis included data from 439 centres throughout Germany, Austria, Switzerland and Luxembourg.

RESULTS
In March 2017, the database contained 75 202 patients with T1D (53% male, mean age (SD) 14.6 (4.1) years, mean age at diagnosis 8.8 (4.3) years and mean diabetes duration 5.8 (4.3) years). 1624 patients had undergone coeliac-specific HLA genotyping, of whom 1344 (82.8%) were positive for HLA-DQ2, HLA-DQ8 or both, while 17.2% had no coeliac-specific HLA-markers. 26.6% of at-risk patients had a clinical suspected diagnosis of CD, and 3.6% had biopsy-proven CD.

CONCLUSIONS
Genotyping for HLA-DQ2, HLA-DQ8 or both is positive in the vast majority (>80%) of patients with T1D. Therefore, screening for coeliac-specific HLA genotypes as a first-line test is not a suitable method to exclude CD in T1D. Regular screening for coeliac-specific antibodies in T1D is still recommended.

Binder|Elisabeth|E|
Rohrer|Tilmann|T|
Denzer|Christian|C|
Marg|Wolfgang|W|
Ohlenschläger|Ute|U|
Schenk-Huber|Heike|H|
Schierloh|Ulrike|U|
Skopnik|Heino|H|
Fröhlich-Reiterer|Elke Elisabeth|EE|
Holl|Reinhard W|RW|
Prinz|Nicole|N|

screening
diabetes
gastroenterology
immunology
paediatric practice


Silencing NKD2 by promoter region hypermethylation promotes gastric cancer invasion and metastasis by up-regulating SOX18 in human gastric cancer.

Abstract: Naked cuticle homolog2 (NKD2) is located in chromosome 5p15.3, which is frequently loss of heterozygosity in human colorectal and gastric cancers. In order to understand the mechanism of NKD2 in gastric cancer development, 6 gastric cancer cell lines and 196 cases of human primary gastric cancer samples were involved. Methylation specific PCR (MSP), gene expression array, flow cytometry, transwell assay and xenograft mice model were employed in this study. The expression of NKD1 and NKD2 was silenced by promoter region hypermethylation. NKD1 and NKD2 were methylated in 11.7% (23/196) and 53.1% (104/196) in human primary gastric cancer samples. NKD2 methylation is associated with cell differentiation, TNM stage and distant metastasis significantly (all P < 0.05), and the overall survival time is longer in NKD2 unmethylated group compared to NKD2 methylated group (P < 0.05). Restoration of NKD2 expression suppressed cell proliferation, colony formation, cell invasion and migration, induced G2/M phase arrest, and sensitized cancer cells to docetaxel. NKD2 inhibits SOX18 and MMP-2,7,9 expression and suppresses BGC823 cell xenograft growth. In conclusion, NKD2 methylation may serve as a poor prognostic and chemo-sensitive marker in human gastric cancer. NKD2 impedes gastric cancer metastasis by inhibiting SOX18.

Jia|Yan|Y|
Cao|Baoping|B|
Yang|Yunsheng|Y|
Linghu|Enqiang|E|
Zhan|Qimin|Q|
Lu|Youyong|Y|
Yu|Yingyan|Y|
Herman|James G|JG|
Guo|Mingzhou|M|

D048868:Adaptor Proteins, Signal Transducing


Rhein inhibits malignant phenotypes of human renal cell carcinoma by impacting on MAPK/NF-κB signaling pathways.

Abstract:
Background
Rhein, an anthraquinone derivative of rhubarb, is traditionally used in Chinese herbal medicine. Now emerging studies suggest its antitumor properties in many human cancers. The present study aims to investigate the antitumor role of Rhein and its possible mechanism in human renal cell carcinoma (RCC).

Materials and methods
Three RCC cell lines (A489, 786-O and ACHN) were used as the cell models. We applied CCK-8, cell counting, colony formation, wound healing and Transwell assays to assess the antitumor roles of Rhein in RCC cells in vitro. The therapeutic efficacy of Rhein was further evaluated by intraperitoneal administrations in tumor formation of mice. Western blot was used to investigate the underlying mechanisms of action of Rhein.

Results
Rhein inhibited RCC cell proliferation in a dose- and time-dependent manner. It also suppressed RCC cell migration and invasion in vitro. Moreover, Rhein was able to inhibit tumor growth in nude mice by intraperitoneal administration in vivo. Mechanistically, the protein levels of phosphorylated MAPK (mitogen-activated protein kinase, extracellular signal-regulated kinase and c-Jun N-terminal kinase), phosphorylated Akt and two targets of NF-κB (nuclear factor kappa-light-chain enhancer of activated B cells) pathway, matrix metalloproteinase 9 and CCND1 were all markedly reduced by Rhein treatment.

Conclusion
Rhein processed the antitumor effects in RCC cells by inhibiting cell proliferation, migration and invasion, and these tumor-suppressing functions might be mediated by MAPK/NF-κB signaling pathways.

Rhein
renal cell carcinoma
MAPK
NF-κB
antitumor effects


The caval index: an adequate non-invasive ultrasound parameter to predict fluid responsiveness in the emergency department?

Abstract:
BACKGROUND
Fluid therapy is the first important step in patients with signs of shock but assessment of the volume status is difficult and invasive measurements are not readily available in the emergency department. We have investigated whether the respiratory variation in diameter of the inferior vena cava is a reliable parameter to predict fluid responsiveness in spontaneous breathing emergency department patients with signs of shock.

METHODS
All patients admitted to the emergency department during a 15 week period were screened for signs of shock. If the attending physician planned to give a fluid challenge, the caval index was determined by transabdominal ultrasonography in supine position. Immediately afterwards 500 ml NaCl 0.9% was administered in 15 minutes and the clinical response was observed. An adequate response was defined as an increase in systolic blood pressure of at least 10 mm Hg. Based on this definition patients were divided into responders and non-responders.

RESULTS
After selection a total number of 45 patients was included. A low caval index (< 36.5%) in patients with signs of shock reliably predicted the absence of an adequate response to fluid therapy (negative predictive value 92%). The positive predictive value of a high caval index was much lower (48%) despite the fact that responders had a significantly higher pre-infusion caval index than non-responders (48.7% vs 31.8%, p 0.014).

CONCLUSIONS
In spontaneously breathing patients with signs of shock in the emergency department, a high caval index (>36.5%) does not reliably predict fluid responsiveness in our study, while a low caval index (<36.5%) makes fluid responsiveness unlikely. An explanation for the absence of a blood pressure response in the group of patients with a low high caval index might be that these patients represent a group requiring more volume therapy than 500 ml.

de Valk|Silke|S|
Olgers|Tycho Joan|TJ|
Holman|Mirjam|M|
Ismael|Farouq|F|
Ligtenberg|Jack Johannes Maria|JJ|
Ter Maaten|Jan Cornelis|JC|

Ultrasound
Fluid responsiveness
Emergency department
Shock
Inferior vena cava


Bone age in children with obstetrical brachial plexus palsy: effect of peripheral nerve injury on skeletal maturation.

Abstract: The purpose of this retrospective study was to analyze the effect of peripheral nerve injury on the skeletal maturation process. The bone ages of the affected and unaffected hand-wrists of 42 children with obstetrical brachial palsy were determined according to the Greulich and Pyle atlas. In 23 patients, the bone ages of the both sides were identical (bone-age-symmetrical group), in 19 patients the bone age of the affected side was delayed (bone-age-delayed group). The mean bone age of the affected side was delayed 0.48 ± 0.25 years that of the unaffected side (P = .000), and the delay of bone age was inversely correlated with chronological age (R (2) = .45, P < .02) in the bone-age-delayed group. Skeletal retardation can be recognized after appearance of ossification centers by plain radiography, dating from the third month of life, in early infancy. Thus, bone age determination method might be helpful for predicting potential future limb shortness.

Oktay|Fügen|F|
Cömert|Didem|D|
Gökkaya|Nilüfer Kutay Ordu|NK|
Ozbudak|Sibel Demir|SD|
Uysal|Hilmi|H|

bone age
peripheral nerve injury
skeletal maturation
neuroplasticity
obstetrical brachial plexus injury


Prescribing of long-term antibiotics to adolescents in primary care: a retrospective cohort study.

Abstract:
BACKGROUND
Antibiotic overuse is linked to increased risk of antimicrobial resistance. Long-term antibiotics are commonly used for treating acne and prophylaxis of urinary tract infection. Their contribution to the overall burden of antibiotic use is relatively unknown.

AIM
To describe the volume of commonly prescribed long-term (≥28 days) antibiotic prescriptions in adolescents and young adults, trends over time, and comparisons with acute prescriptions.

DESIGN AND SETTING
A retrospective cohort study using UK electronic primary care records.

METHOD
Patients born between 1979 and 1996 and with data in the Care and Health Information Analytics database were included. The main outcome measures were antibiotic prescription rates per 1000 person-years and antibiotic prescription days per person-year between the ages of 11 and 21.

RESULTS
In total, 320 722 participants received 710 803 antibiotic prescriptions between the ages of 11 and 21 years from 1998 to 2017. Of these 710 803 prescriptions, 191 443 (26.93%) were for long-term antibiotics (≥28 days and ≤6 months in duration). Long-term antibiotics accounted for more than two-thirds (72.48%) of total antibiotic exposure (days per person-year). Total long-term antibiotic prescribing peaked in 2013 at just under 6 days per person-year and declined to around 4 days in 2017.

CONCLUSION
Among adolescents and young adults, exposure to long-term antibiotics (primarily lymecycline used for acne) was much greater than for acute antibiotics and is likely to make an important contribution to antimicrobial resistance. Urgent action is needed to reduce unnecessary exposure to long-term antibiotics in this group. Increasing the use of, and adherence to, effective non-antibiotic treatments for acne is key to achieving this.

Lown|Mark|M| McKeown|Sam|S| Stuart|Beth|B| Francis|Nick|N| Santer|Miriam|M| Lewith|George|G| Su|Fangzhong|F| Moore|Michael|M| Little|Paul|P|

antibiotics
antibiotic prescriptions
antimicrobial drug resistance
general practice


Interactive effects of pH and metals on mitochondrial functions of intertidal bivalves Crassostrea virginica and Mercenaria mercenaria.

Abstract: Intertidal bivalves experience broad fluctuations of environmental temperature, pH and oxygen content which could change their intracellular pH. They are also exposed to trace metals such as cadmium (Cd) and copper (Cu) that accumulate in their tissues and may negatively affect mitochondrial functions and bioenergetics. We determined the interactive effects of pH and trace metals (25 μM Cd or Cu) on mitochondrial functions (including respiration and membrane potentials in both ADP-stimulated (state 3) and resting (state 4) states) of two common marine bivalves, the hard clams (Mercenaria mercenaria) and eastern oysters (Crassostrea virginica). In the absence of the trace metals, mitochondrial functions of C. virginica and M. mercenaria were insensitive to pH in a broad physiologically relevant range (6.6-7.8). Mitochondrial respiration was generally suppressed by 25 μM Cd or Cu (with the stronger effects observed for ADP-stimulated compared to the resting respiration) while the mitochondrial membrane potential was unaffected. pH modulated the effects of Cu and Cd on mitochondrial respiration of the bivalves. In oysters, Cu suppressed ADP-stimulated mitochondrial respiration at high and low pH values (6.6 and 7.8, respectively), but had no effect in the intermediate pH range (7.0-7.4). In clams, the negative effect of Cu on ADP-stimulated respiration was only observed at extremely high pH (7.8). A decrease in pH was also protective against Cd in mitochondria of clams and oysters. In clams, 25 μM Cd suppressed ADP-stimulated respiration at all pH; however, at low pH (6.6-7.0) this suppression was paralleled by a decrease in the rates of proton leak thereby effectively restoring mitochondrial coupling. In oysters, the inhibitory effects of Cd on ADP-stimulated respiration were fully abolished at low pH (6.6-7.0). This indicates that moderate acidosis (such as occurs during exposure to air, extreme salinities or elevated CO2 levels in the intertidal zone) may have a beneficial side-effect of protecting mitochondria of clams and oysters against the toxic effects of trace metals in polluted estuaries.

Cadmium
Copper
Bioenergetics
Mitochondrial respiration
Mitochondrial membrane potential
Proton leak
Mollusks


The Aonia-Solis-Valles dust storm track in the southern hemisphere of Mars.

Abstract: Dust storm activity in the Aonia-Solis-Valles Marineris (ASV) region is analyzed using data collected from 8 Mars years of Mars Daily Global Maps. During L  = 120°-180°, dust storms within the ASV region tend to organize into dust storm sequences, making ASV an important storm track in the southern hemisphere outside the conventional dust storm season. In late southern winter, the ASV region is influenced by a combination of strong time-mean winds, synoptic eddies, and tidal winds. The ASV dust storm sequences can increase the background dust opacity and sometimes significantly influence the large-scale atmospheric thermal structure and planetary waves. They can be divided into two groups - one with large size and long duration; the other with small size and mostly short duration. The time series of storm area exhibits a pseudo-periodicity near 20 sols. This periodicity is similar to that found in eddy kinetic energy and traveling waves and to the Baroclinic Annular Mode of the terrestrial atmosphere.

Atmospheres
atmosphere Mars
climate
dynamics Mars


Quantification accuracy for dynamic contrast enhanced (DCE) CT imaging: phantom and quality assurance framework.

Abstract:
PURPOSE
Standardization and protocol optimization is essential for quantification of Dynamic Contrast Enhanced CT as an imaging biomarker. Currently, no commercially available quality assurance (QA) phantoms can provide for testing a complete set of imaging parameters pertaining to routine quality control for contrast-enhanced (CE) CT, as well as spatiotemporal accuracy. The purpose of this work was, therefore: (a) developing a solid calibration phantom for routine CE CT quality assurance; (b) investigating the sensitivity of CECT to organ motion, and (c) characterizing a volumetric CT scanner for CECT.

METHODS
CECT calibration phantom consisting of an acrylic uniform cylinder containing multiple capsules of varying diameters and orientations was designed and built. The capsules contain different solid density materials mimicking iodine contrast enhancement. Sensitivity and accuracy of CECT measurements on all capsules was performed using a 320-slice CT scanner for a range of scan parameters both with and without phantom motion along the transaxial axis of the scanner.

RESULTS
Routine commissioning tests such as uniformity, spatial resolution and image noise were successfully determined using the CECT phantom. Partial volume effect and motion blurring both contribute to a general decrease in contrast enhancement and this was further dependent on capsule orientation (least pronounced for the transaxial orientation). Scanning with a rotation time of less than 0.5 s, the effect of blurring is less than 3% for all orientations and phantom speeds.

CONCLUSION
A new robust contrast calibration phantom was developed and used to evaluate the performance of a 320-slice volumetric CT scanner for DCE-CT.

Coolens|C|C|
Mohseni|H|H|
Dhodi|S|S|
Ma|S|S|
Keller|H|H|
Jaffray|D A|DA|

D003287:Contrast Media
D019047:Phantoms, Imaging
D011786:Quality Control
D011856:Radiographic Image Enhancement
D015203:Reproducibility of Results
D012680:Sensitivity and Specificity
D014057:Tomography, X-Ray Computed

CT
Quality assurance
Biomarker
DCE CT
Perfusion
Quantitative imaging


Improves in external and internal egg quality of Japanese quail (Coturnix coturnix japonica) by giving lactic acid bacteria as alternative antibiotic growth promoter.

Abstract:
Background and Objectives
An experiment was designed to determine the effect of using lactic acid bacteria as alternative antibiotic growth promoters on external and internal quality of egg's Coturnix coturnix japonica.

Materials and Methods
Coturnix coturnix japonica (n=240, 14 weeks of age) were randomly distributed into six treatment groups. The treatments were P0 (free antibiotic feed), P1 (free antibiotic feed with 1 gram antibiotic growth promoters (AGP)/100kg feed), P2 (free antibiotic feed with 5 gram probiotic/100kg feed), P3 (free antibiotic feed with 10 grams probiotic/100kg feed), P4 (free antibiotic feed with 5 gram probiotic/200L drinking water), and P5 (free antibiotic feed with 10 gram probiotic/200L drinking water). Probiotic contained Lactobacillus casei (L. casei) and Lactobacillus rhamnosus (L. rhamnosus) culture (1.2 × 108 CFU/gram). To assess the quality parameters, twenty eggs were randomly collected from each treatment at the end of the experimental period, and the data were analysed using one way Anova.

Results
Results of the external quality indicated that egg's weight, length, and width, along with the shell weight and thickness were significantly different (P<0.05) after treatment. Likewise, the results of internal egg quality indicated that yolk color, height, width, and length, together with the albumen height, width, length, index and haugh unit were significantly different (P <0.05) after treatment.

Conclusion
It was concluded from this research that dietary supplementation with probiotic which contains L. casei and L. rhamnosus could be used in laying Japanese quail with benefit on external and internal egg quality.

Lokapirnasari|Widya Paramita|WP|
Al Arif|Anam|A|
Soeharsono|Soeharsono|S|
Fathinah|Anisah|A|
Najwan|Rifqi|R|
Wardhani|Hana Cipka Pramuda|HCP|
Noorrahman|Nabil Fariz|NF|
Huda|Khoirul|K|
Ulfah|Nuria|N|
Yulianto|Andreas Berny|AB|

External and internal egg quality
Japanese quail
Lactobacillus casei
Lacrobacillus rhamnosus


Simultaneous detection of fumonisin B1 and ochratoxin A using dual-color, time-resolved luminescent nanoparticles (NaYF4: Ce, Tb and NH2-Eu/DPA@SiO2) as labels.

Abstract: A rapid and highly sensitive time-resolved fluorescence (TRF)-based aptasensor for simultaneous recognition of mycotoxins ochratoxin A (OTA) and fumonisin B1 (FB1) was developed using multi-color, Ln3+-doped time-resolved fluorescence nanoparticles (TRF-NPs) (NaYF4: Ce, Tb and NH2-Eu/DPA@SiO2 NPs) coupled with complementary strand DNA (cDNA) as luminescence probe and aptamers-conjugated amine-functionalized Fe3O4 magnetic nanoparticles (MNPs) act as a capture probe. Under the optimized conditions, the time-resolved fluorescence intensities at 544 and 618 nm corresponded with Tb3+ and Eu3+, respectively, were used to measure FB1 (Y = 19,177.1 + (- 12,054.4)x, R2 = 0.9917) and OTA (Y = 4138.8 + (- 11,182.6)x, R2 = 0.9924), respectively. The limits of detection (LODs) for FB1 and OTA were 0.019 pg mL-1 and 0.015 pg mL-1, respectively, which were much lower than previously described methods for simultaneous recognition of mycotoxins OTA and FB1 while detection range varied from 0.0001-0.5 ng mL-1. This aptasensor was effectively applied to quantity FB1 and OTA in maize samples and results were compared with ELISA method. This is the first reported time-resolved fluorescence (TRF)-based aptasensor to detect two agriculturally important toxins in the maize. The developed aptasensor has potential to be used for detection of toxins in food safety fields. Graphical abstract.

Niazi|Sobia|S|
Khan|Imran Mahmood|IM|
Yan|Lv|L|
Khan|Muhammad Issa|MI|
Mohsin|Ali|A|
Duan|Nuo|N|
Wu|Shijia|S|
Wang|Zhouping|Z|


Community dental health coordinators' role in community-based pediatric dental education.

Abstract:
PURPOSE
The University of Alabama at Birmingham (UAB) School of Dentistry utilized a Community Dental Health Coordinator (CDHC) to transform a community-based dental education rotation into a positive learning experience for senior dental students. Based in a county health department's Women, Infant, and Children's (WIC) clinic and dental clinic, the initial rotation before implementation of the CDHC was received poorly by students and community partners. This paper reports how CDHC involvement improved student experiences with pediatric patients.

METHODS
In 2018, the CDHC embedded in the WIC clinic where student rotations occur and developed relationships with the community partners to identify key issues. The CDHC then implemented qualitative improvements, including a restructured workflow, preparatory educational modules, and assessment systems to address the issues. Student performance reports, focus group discussions, and a postgraduation questionnaire provided data for evaluation of performance.

RESULTS
By year 3, dental appointments for patients under age 6 increased, resulting in 95% of UAB students seeing this age patient; 74% completed four or more. Three-quarters of students reported performing restorative procedures on children. Student and community partner acceptance of the rotation also improved. Postgraduation questionnaires (32% response rate) indicate 35% of graduates continue to treat Medicaid patients after graduation.

CONCLUSION
The CDHC's unique skills in community relationship-building, community-based dental screenings, and pediatric dental care coordination produced measurable improvements in community participation and student clinical experiences. The CDHC can be a vital part of dental education, especially in community education settings. Community-based dental education generated measurable improvements in students' clinical experiences.

Mitchell|Stephen C|SC|
West|Cherri A|CA|
Lockwood|Stuart A|SA|

community dental health coordinator
dental education
community-based dental education
dental faculty shortage
pediatric dentistry


COVID-19 and delivery of difficult asthma services.

Abstract: The COVID-19 pandemic necessitated an urgent reconfiguration of our difficult asthma (DA) service. We rapidly switched to virtual clinics and rolled out home spirometry based on clinical need. From March to August 2020, 110 patients with DA (68% virtually) were seen in clinic, compared with March-August 2019 when 88 patients were seen face-to-face. There was DA clinic cancellation/non-attendance (16% vs 43%; p<0.0003). In patients with home spirometers, acute hospital admissions (6 vs 26; p<0.01) from March to August 2020 were significantly lower compared with the same period in 2019. There was no difference in the number of courses of oral corticosteroids or antibiotics prescribed (47 vs 53; p=0.81). From April to August 2020, 50 patients with DA performed 253 home spirometry measurements, of which 39 demonstrated >20% decrease in forced expiratory volume in 1 s, resulting in new action plans in 87% of these episodes. In our DA cohort, we demonstrate better attendance rates at virtual multidisciplinary team consultations and reduced hospital admission rates when augmented with home spirometry monitoring.

COVID-19
paediatrics
respiratory medicine
technology


Parallel imaging compressed sensing for accelerated imaging and improved signal-to-noise ratio in MRI-based postimplant dosimetry of prostate brachytherapy.

Abstract:
PURPOSE
To investigate the feasibility of using parallel imaging compressed sensing (PICS) to reduce scan time and improve signal-to-noise ratio (SNR) in MRI-based postimplant dosimetry of prostate brachytherapy.

METHODS AND MATERIALS
Ten patients underwent low-dose-rate prostate brachytherapy with radioactive seeds stranded with positive magnetic resonance-signal seed markers and were scanned on a Siemens 1.5T Aera. MRI comprised a fully balanced steady-state free precession sequence with two 18-channel external pelvic array coils with and without a rigid two-channel endorectal coil. The fully sampled data sets were retrospectively subsampled with increasing acceleration factors and reconstructed with parallel imaging and compressed sensing algorithms. The images were assessed in a blinded reader study by board-certified care providers. Rating scores were compared for statistically significant differences between reconstruction types.

RESULTS
Images reconstructed from subsampling up to an acceleration factor of 4 with PICS demonstrated consistently sufficient quality for dosimetry with no apparent loss of SNR, anatomy depiction, or seed/marker conspicuity when compared to the fully sampled images. Images obtained with acceleration factors of 5 or 6 revealed reduced spatial resolution and seed marker contrast. Nevertheless, the reader study revealed that images obtained with an acceleration factor of up to 5 and reconstructed with PICS were adequate-to-good for postimplant dosimetry.

CONCLUSIONS
Combined parallel imaging and compressed sensing can substantially reduce scan time in fully balanced steady-state free precession imaging of the prostate while maintaining adequate-to-good image quality for postimplant dosimetry. The saved scan time can be used for multiple signal averages and improved SNR, potentially obviating the need for an endorectal coil in MRI-based postimplant dosimetry.

Sanders|Jeremiah W|JW|
Song|Hao|H|
Frank|Steven J|SJ|
Bathala|Tharakeswara|T|
Venkatesan|Aradhana M|AM|
Anscher|Mitchell|M|
Tang|Chad|C|
Bruno|Teresa L|TL|
Wei|Wei|W|
Ma|Jingfei|J|

Compressed sensing
Prostate brachytherapy
SNR
MRI
Endorectal coil


Dynamic Functional Connectivity as a complex random walk: Definitions and the dFCwalk toolbox.

Abstract: •We have developed a framework to describe the dynamics of Functional Connectivity (dFC) estimated from brain activity time-series as a complex random walk in the space of possible functional networks. This conceptual and methodological framework considers dFC as a smooth reconfiguration process, combining "liquid" and "coordinated" aspects. Unlike other previous approaches, our method does not require the explicit extraction of discrete connectivity states.•In our previous work, we introduced several metrics for the quantitative characterization of the dFC random walk. First, dFC speed analyses extract the distribution of the time-resolved rate of reconfiguration of FC along time. These distributions have a clear peak (typical dFC speed, that can already serve as a biomarker) and fat tails (denoting deviations from Gaussianity that can be detected by suitable scaling analyses of FC network streams). Second, meta-connectivity (MC) analyses identify groups of functional links whose fluctuations co-vary in time and that define veritable dFC modules organized along specific dFC meta-hub controllers (differing from conventional FC modules and hubs). The decomposition of whole-brain dFC by MC allows performing dFC speed analyses separately for each of the detected dFC modules.•We present here blocks and pipelines for dFC random walk analyses that are made easily available through a dedicated MATLABⓇ toolbox (dFCwalk), openly downloadable. Although we applied such analyses mostly to fMRI resting state data, in principle our methods can be extended to any type of neural activity (from Local Field Potentials to EEG, MEG, fNIRS, etc.) or even non-neural time-series.

Arbabyazd|Lucas M|LM|
Lombardo|Diego|D|
Blin|Olivier|O|
Didic|Mira|M|
Battaglia|Demian|D|
Jirsa|Viktor|V|

Functional Connectivity
fMRI
Chronnectome
Neuroimaging


A trio of infectious diseases and pulmonary embolism: A developing world's reality.

Abstract:
Introduction
Human immunodeficiency virus (HIV), Tuberculosis (TB) and coronavirus disease (COVID-19) infections independently possess the ability to trigger formation of venous thromboembolism (VTE) and pulmonary embolism (PE). To the authors' knowledge, this is the first case report describing the presence of PE in a patient with all three aforementioned infectious co-morbidities.

Presentation
A patient living with HIV with virological failure secondary to defaulting antiretroviral therapy (ART) presented with hypoxia, clinical and radiological features suggestive of community-acquired pneumonia (CAP) with raised inflammatory markers and D-dimer levels.

Management
She was commenced on prophylactic anticoagulation, supplemental oxygen and empirical antibiotics targeting CAP and pneumocystis jiroveci pneumonia, swabbed for COVID-19 infection and had sputa sent for Gene Xpert® TB testing. A day later, COVID-19 results returned positive and the patient was transferred to isolation and added onto dexamethasone and therapeutic anticoagulation. Sputa returned positive for mycobacterium TB a day later, and anti-tuberculosis therapy was added. She remained persistently hypoxic, with a Well's score of 3 placing her at moderate risk for PE, which prompted for a computed tomography pulmonary angiogram (CTPA) being ordered, which demonstrated left lower lobe subsegmental PE. Warfarin was added to her regimen. She was discharged on day 18 with a therapeutic international normalised ratio (INR) and not requiring oxygen therapy.

Conclusion
This scenario is relevant in low to middle-income countries. The utilisation of a raised D-Dimer in the setting of all four coexisting conditions in arriving at a definite diagnosis remains uncertain. We noted that despite our index patient being on thrombo-prophylaxis, she developed PE highlighting the need for increased vigilance in all COVID-19 patients, even those on prophylactic anticoagulation.

pulmonary embolism
HIV
tuberculosis
COVID-19
middle-income countries


Immediate effects of myofascial release on neuromechanical characteristics in female and male patients with low back pain and healthy controls as assessed by tensiomyography. A controlled matched-pair study.

Abstract:
BACKGROUND
Low back pain (LBP) is a major health issue in most industrialised countries. Lumbodorsal fascia has been advocated as a potential source of pain in the lumbopelvic region. Myofascial release constitutes a manual therapeutic approach focussing on the restoration of altered soft tissue function. No previous study has focused on quantifying neuromechanical effects of myofascial release on LBP patients through tensiomyography. The purpose of this study was to quantify immediate neuromechanical alterations of myofascial release on patients with LBP and healthy controls through tensiomyography parameters.

METHODS
The participants' (n = 30) bilateral lumbar erector spinae muscles were assessed via tensiomyography before and after a 6-min myofascial release treatment of the lumbodorsal fascia to evaluate the muscles' mechanical characteristics. Subjects with LBP (n = 15) were eligible to partake if they reported having had LBP for most days in the past 12 weeks. Muscle displacement (Dm [mm]), velocity of contraction (Vc [mm/s]), and lateral symmetry (Ls [%]) were assessed through tensiomyography testing.

FINDINGS
Statistical analyses revealed a significant increase for velocity of contraction in the right (p = .021) and left (p = .041) lumbar erector spinae for the subjects with LBP but not for the healthy controls (both p > .14).

INTERPRETATION
We suggested that myofascial release alters neuromechanical characteristics in subjects with LBP. Tensiomyography may be implemented in clinical settings to monitor intervention effects of the myofascial system, especially the tensiomyography parameter velocity of contraction.

Back pain
Fascia
Fascia thoracolumbalis
Mechanomyography
Muscle contraction
Myofascial induction


Clinical Characteristics and Management of Methamphetamine-Associated Cardiomyopathy: State-of-the-Art Review.

Abstract: Methamphetamine-associated cardiomyopathy (MACM) is an increasingly recognized disease entity in the context of a rapidly spreading methamphetamine epidemic. MACM may afflict individuals with a wide range of ages and socioeconomic backgrounds. Presentations can vary greatly and may involve several complications unique to the disease. Given the public health significance of this disease, there is a relative dearth of consensus material to guide clinicians in understanding, diagnosing, and managing MACM. This review therefore aims to: (1) describe pathologic mechanisms of methamphetamine as they pertain to the development, progression, and prognosis of MACM, and the potential to recover cardiac function; (2) summarize existing data from epidemiologic studies and case series in an effort to improve recognition and diagnosis of the disease; (3) guide short- and long-term management of MACM with special attention to expected or potential sequelae of the disease; and (4) highlight pivotal unanswered questions in need of urgent investigation from a public health perspective.

Reddy|Pavan K V|PKV|
Ng|Tien M H|TMH|
Oh|Esther E|EE|
Moady|Gassan|G|
Elkayam|Uri|U|

D000697:Central Nervous System Stimulants

management
cardiomyopathy
methamphetamine
diagnosis
heart failure


Coronary CT Angiography with Knowledge-Based Iterative Model Reconstruction for Assessing Coronary Arteries and Non-Calcified Predominant Plaques.

Abstract:
OBJECTIVE
To assess the effects of iterative model reconstruction (IMR) on image quality for demonstrating non-calcific high-risk plaque characteristics of coronary arteries.

MATERIALS AND METHODS
This study included 66 patients (53 men and 13 women; aged 39-76 years; mean age, 55 ± 13 years) having single-vessel disease with predominantly non-calcified plaques evaluated using prospective electrocardiogram-gated 256-slice CT angiography. Paired image sets were created using two types of reconstruction: hybrid iterative reconstruction (HIR) and IMR. Plaque characteristics were compared using the two algorithms. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the images and the CNR between the plaque and adjacent adipose tissue were also compared between the two reformatted methods.

RESULTS
Seventy-seven predominantly non-calcified plaques were detected. Forty plaques showed napkin-ring sign with the IMR reformatted method, while nineteen plaques demonstrated napkin-ring sign with HIR. There was no statistically significant difference in the presentation of positive remodeling, low attenuation plaque, and spotty calcification between the HIR and IMR reconstructed methods (all p > 0.5); however, there was a statistically significant difference in the ability to discern the napkin-ring sign between the two algorithms (χ² = 12.12, p < 0.001). The image noise of IMR was lower than that of HIR (10 ± 2 HU versus 12 ± 2 HU; p < 0.01), and the SNR and CNR of the images and the CNR between plaques and surrounding adipose tissues on IMR were better than those on HIR (p < 0.01).

CONCLUSION
IMR can significantly improve image quality compared with HIR for the demonstration of coronary artery and atherosclerotic plaques using a 256-slice CT.

D011857:Radiographic Image Interpretation, Computer-Assisted

Atherosclerosis
Computed tomography angiography
Coronary artery disease
Image reconstruction
Multidetector computed tomography


Guidance on diagnosis, prevention and treatment of thromboembolic complications in COVID-19: a position paper of the Brazilian Society of Thrombosis and Hemostasis and the Thrombosis and Hemostasis Committee of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy.

Abstract: Hemostatic abnormalities and thrombotic risk associated with coronavirus disease 2019 (COVID-19) are among the most discussed topics in the management of this disease. The aim of this position paper is to provide the opinion of Brazilian experts on the thromboprophylaxis and management of thrombotic events in patients with suspected COVID-19, in the sphere of healthcare in Brazil. To do so, the Brazilian Society of Thrombosis and Hemostasis (BSTH) and the Thrombosis and Hemostasis Committee of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy (ABHH) have constituted a panel of experts to carefully review and discuss the available evidence about this topic. The data discussed in this document was reviewed by May 9, 2020. Recommendations and suggestions reflect the opinion of the panel and should be reviewed periodically as new evidence emerges.

Orsi|Fernanda Andrade|FA|
De Paula|Erich V|EV|
Santos|Fernanda de Oliveira|FO|
Teruchkin|Marcelo Melzer|MM|
Campêlo|Dirceu Hamilton Cordeiro|DHC|
Mello|Tayana Teixeira|TT|
Chindamo|Maria Chiara|MC|
Macedo|Ariane Vieira Scarlatelli|AVS|
Rocha|Ana Thereza|AT|
Ramacciotti|Eduardo|E|
Nascimento|Ana Clara Kneese|ACK|
Annichino-Bizzacchi|Joyce|J|
Lourenco|Dayse Maria|DM|
Guerra|João Carlos de Campos|JCC|
Rezende|Suely Meireles|SM|
Cavalheiro Filho|Cyrillo|C|

Prevention
Treatment
Coronavirus disease 2019
Coagulopathy
Venous thromboembolism


Lysine, methionine, phenylalanine, arginine, valine, isoleucine, leucine, and threonine maintenance requirements of broiler breeders.

Abstract: Five hundred and sixty Cobb-Vantress broiler breeders were used to determine the maintenance requirement of dietary Arg, His, Ile, Leu, Lys, Met, Phe, Thr, and Val in 10 21-d assays using the comparative slaughter technique. Fifty sexually immature broiler breeder pullets per assay were given crystalline amino acid diets containing graded levels of Arg, His, Ile, Leu, Lys, Met, Phe, Thr, or Val, respectively, representing 0, 10, 20, 30, 40% of their suggested requirement level (NRC, 1994) with all other amino acids maintained at 40% of their suggested requirement level. Sixty hens were slaughtered prior to the beginning of the study to assess initial body composition at 3 weight groups. Linear regression lines (protein accretion vs. amino acid intake) were determined and the maintenance requirements were calculated based on zero protein accretion. The maintenance requirements expressed on a metabolic weight basis were determined to be 174, 94, 52, 81, 60, 126, 133, and 155 mg/kg(0.75)/d for Arg, Ile, Leu, Lys, Met, Phe, Thr, and Val, respectively. Additionally, the maintenance requirements, expressed on metabolic protein weight basis, were determined to be 651, 329, 172, 295, 223, 523, 478, and 546 mg/kgCP/d for Arg, Ile, Leu, Lys, Met, Phe, Thr, and Val, respectively. The requirement for His could not be established as the results obtained were outside of assay range.

Sakomura|N K|NK|
Ekmay|R D|RD|
Mei|S J|SJ|
Coon|C N|CN|

D000824:Animal Nutritional Physiological Phenomena

maintenance
requirements
broiler breeders
amino acids


Antimicrobial Activity of Gallium Compounds on ESKAPE Pathogens.

Abstract: ESKAPE bacteria are a major cause of multidrug-resistant infections, and new drugs are urgently needed to combat these pathogens. Given the importance of iron in bacterial physiology and pathogenicity, iron uptake and metabolism have become attractive targets for the development of new antibacterial drugs. In this scenario, the FDA-approved iron mimetic metal Gallium [Ga(III)] has been successfully repurposed as an antimicrobial drug. Ga(III) disrupts ferric iron-dependent metabolic pathways, thereby inhibiting microbial growth. This work provides the first comparative assessment of the antibacterial activity of Ga(NO3)3 (GaN), Ga(III)-maltolate (GaM), and Ga(III)-protoporphyrin IX (GaPPIX), belonging to the first-, second- and third-generation of Ga(III) formulations, respectively, on ESKAPE species, including reference strains and multidrug-resistant (MDR) clinical isolates. In addition to the standard culture medium Mueller Hinton broth (MHB), iron-depleted MHB (DMHB) and RPMI-1640 supplemented with 10% human serum (HS) (RPMI-HS) were also included in Ga(III)-susceptibility tests, because of their different nutrient and iron contents. All ESKAPE species were resistant to all Ga(III) compounds in MHB and DMHB (MIC > 32 μM), except Staphylococcus aureus and Acinetobacter baumannii, which were susceptible to GaPPIX. Conversely, the antibacterial activity of GaN and GaM was very evident in RPMI-HS, in which the low iron content and the presence of HS better mimic the in vivo environment. In RPMI-HS about 50% of the strains were sensitive (MIC < 32) to GaN and GaM, both compounds showing a similar spectrum of activity, although GaM was more effective than GaN. In contrast, GaPPIX lost its antibacterial activity in RPMI-HS likely due to the presence of albumin, which binds GaPPIX and counteracts its inhibitory effect. We also demonstrated that the presence of multiple heme-uptake systems strongly influences GaPPIX susceptibility in A. baumannii. Interestingly, GaN and GaM showed only a bacteriostatic effect, whereas GaPPIX exerted a bactericidal activity on susceptible strains. Altogether, our findings raise hope for the future development of Ga(III)-based compounds in the treatment of infections caused by multidrug-resistant ESKAPE pathogens.

Hijazi|Sarah|S| Visaggio|Daniela|D| Pirolo|Mattia|M| Frangipani|Emanuela|E| Bernstein|Lawrence|L| Visca|Paolo|P|

D000900:Anti-Bacterial Agents
D003470:Culture Media
D005708:Gallium
D006090:Gram-Negative Bacteria
D006094:Gram-Positive Bacteria
D006801:Humans
D008826:Microbial Sensitivity Tests

ESKAPE
iron uptake
antibacterial
gallium maltolate
gallium nitrate
gallium protoporphyrin IX


Polymer Micelles Composed of Molecular-Bottlebrush-Based Surfactants: Precisely Controlling Aggregation Number Corresponding to Polyhedral Structures.

Abstract: Over the past few decades, there has been remarkable progress in the construction of self-assemblies in the field of supramolecular chemistry, such as micelles with precisely controlled and refined structures. One promising approach represents the previously proposed concept of Platonic micelles, in which the aggregation number (Nagg ) is discretized in accordance with vertexes of regular polyhedra (i.e., Platonic solids), i.e., 4, 6, 8, 12, and 20 units. Herein, attempt is made to construct Platonic polymer micelles using rigid and persistent architecture of molecular-bottlebrush-based surfactant (MBS). The structure of MBS micelles is carefully elucidated using small-angle X-ray and light scattering and analytical centrifugation measurements. This study shows that the Nagg of MBS micelles is consistent with one of the Platonic numbers when Nagg is intentionally set in the range of 4-20. In addition, some of the MBS micelles demonstrate a discontinuous change in Nagg , when the salt concentration is changed, which is an important factor in controlling micellar Nagg . This is one of the characteristic aggregation behaviors of Platonic micelles in surfactant systems, which strongly indicates the formation of Platonic micelles from macromolecular surfactants.

polymer micelles
platonic micelles
X-ray scattering
molecular bottlebrushes


Retinal blood vessel-origin yes-associated protein (YAP) governs astrocytic maturation via leukaemia inhibitory factor (LIF).

Abstract:
OBJECTIVES
To testify that endothelial cells (ECs) induce astrocyte maturation by leukaemia inhibitory factor (LIF) secretion.

MATERIALS AND METHODS
In vivo experiments, mice bearing floxed alleles of YAP were crossed with mice expressing a Cre recombinase driven by the endothelial Tek promoter (Tek-Cre) to finally obtain the following three genotypes: YAPf/f , Tek-Cre; YAPf/w , Tek-Cre; and YAPf/f . Retinal vascularization and astrocyte network were evaluated by whole-mount fluorescence and Western blotting. In vitro, experiments were performed in an astrocyte and human microvascular endothelial cell (HMEC-1) coculture model to analyse the mechanisms underlying the effect of endothelial YAP on astrocytes.

RESULTS
In vivo, YAPf/f ;Tek-Cre mice showed delayed angiogenesis, sparse vessels and decreased glial fibrillary acidic protein (GFAP)+ astrocytes but aberrant growth of endothelial networks and immature astrocytes (platelet-derived growth factor A, PDGFRA+ astrocytes) overgrowth. In vitro, Yap deletion attenuated the LIF release that delayed the maturation of retinal astrocyte which was consistent with the results of HMEC-1-astrocyte coculture. The effect of YAP overexpression on LIF-LIFR axis in HMEC-1 interferes the GFAP expression of astrocyte. In contrast, LIF protein rescues the astrocytic GFAP expression when EC YAP was inhibited by siRNAs.

CONCLUSIONS
We show that EC yes-associated protein (YAP) is not only a critical coactivator of Hippo signalling in retinal vessel development but also plays an essential role in retinal astrocyte maturation by regulating LIF production.

yes-associated protein
leukaemia inhibitory factor
retinal vessel development
astrocyte premature


Measurement properties of the Nepali version of the Quick-DASH in patients with shoulder pain.

Abstract:
PURPOSE
To examine the measurement properties of the Nepali version of the Quick-Disabilities of the Arm, Shoulder and Hand (QuickDASH-NP).

MATERIALS AND METHODS
The Nepali DASH and Shoulder Pain and Disability Index (SPADI) were completed at baseline assessment, and again at follow-up with the Nepali Global Rating of Change (GROC-NP) score. The 11 items of the QuickDASH-NP were extracted from the DASH and tested for confirmatory factory analysis (CFA), exploratory factor analysis (EFA), internal consistency (α), item-total correlation (ITC), test-retest reliability (ICC), measurement errors, hypothesis testing (correlation with DASH and SPADI) and responsiveness (effect size-ES, standardised response mean-SRM).

RESULTS
A total of 156 participants completed questionnaires at baseline and 121 at follow-up with all questionnaires valid (no participant leaving more than one question blank). CFA suggested a poor fit for the single-factor model. The EFA demonstrated two factors with acceptable internal consistency (α = 0.79 and 0.75) for each factor. The test-retest reliability was excellent (ICC = 0.94; 95%CI:0.92-0.98), correlation was positive and very strong with the DASH-NP (r = 0.96) and strong with the SPADI-NP (r = 0.81). The Standard Error of Measurement was 2.83 and Smallest Detectable Change 7.84/100. The ES and SRM were moderate to high.

CONCLUSIONS
The QuickDASH-NP is reliable, valid, and able to detect change in shoulder symptoms among Nepali participants. It offers a short, easy to complete self-reporting tool for clinical use and research.

Kc|Sudarshan|S| Sharma|Saurab|S| Ginn|Karen|K| Reed|Darren|D|

Measurement property
Quick-DASH
Shoulder pain
DASH
Clinimetrics


Cross-Talk between Mitochondrial Dysfunction-Provoked Oxidative Stress and Aberrant Noncoding RNA Expression in the Pathogenesis and Pathophysiology of SLE.

Abstract: Systemic lupus erythematosus (SLE) is a prototype of systemic autoimmune disease involving almost every organ. Polygenic predisposition and complicated epigenetic regulations are the upstream factors to elicit its development. Mitochondrial dysfunction-provoked oxidative stress may also play a crucial role in it. Classical epigenetic regulations of gene expression may include DNA methylation/acetylation and histone modification. Recent investigations have revealed that intracellular and extracellular (exosomal) noncoding RNAs (ncRNAs), including microRNAs (miRs), and long noncoding RNAs (lncRNAs), are the key molecules for post-transcriptional regulation of messenger (m)RNA expression. Oxidative and nitrosative stresses originating from mitochondrial dysfunctions could become the pathological biosignatures for increased cell apoptosis/necrosis, nonhyperglycemic metabolic syndrome, multiple neoantigen formation, and immune dysregulation in patients with SLE. Recently, many authors noted that the cross-talk between oxidative stress and ncRNAs can trigger and perpetuate autoimmune reactions in patients with SLE. Intracellular interactions between miR and lncRNAs as well as extracellular exosomal ncRNA communication to and fro between remote cells/tissues via plasma or other body fluids also occur in the body. The urinary exosomal ncRNAs can now represent biosignatures for lupus nephritis. Herein, we'll briefly review and discuss the cross-talk between excessive oxidative/nitrosative stress induced by mitochondrial dysfunction in tissues/cells and ncRNAs, as well as the prospect of antioxidant therapy in patients with SLE.

Tsai|Chang-Youh|CY|0000-0002-4154-4018 Hsieh|Song-Chou|SC| Lu|Cheng-Shiun|CS|0000-0002-4794-9438 Wu|Tsai-Hung|TH| Liao|Hsien-Tzung|HT| Wu|Cheng-Han|CH| Li|Ko-Jen|KJ| Kuo|Yu-Min|YM| Lee|Hui-Ting|HT| Shen|Chieh-Yu|CY| Yu|Chia-Li|CL|

D020022:Genetic Predisposition to Disease

cross-talk
oxidative stress
noncoding RNA
systemic lupus erythematosus
microRNA
long noncoding RNA
mitochondrial dysfunction
nitrosative stress. exosome


Synthesis and antiproliferative activity of aromatic and aliphatic bis[aminomethylidene(bisphosphonic)] acids.

Abstract: A series of aromatic and aliphatic bis[aminomethylidene(bisphosphonic)] acids was synthesized in the reaction of triethylphosphite with isonitriles followed by hydrolysis or dealkylation. The in vitro anti-proliferative effect of all synthesized tetraphosphonic acids against MCF-7 breast cancer cells, J774E macrophages and HL-60 promyelocytic leukemia cells was determined. Three aromatic derivatives (5a, 5f and 5j) showed a similar or higher anti-proliferative activity than zoledronic acid.

D004354:Drug Screening Assays, Antitumor

Isonitrile
Tetraphosphonate
Anti-proliferative activity
Bisphosphonate
Bisphosphonic acid
Isocyanide
Osteoclasts
Tumor cells


Evolutionary characterization of the emerging porcine epidemic diarrhea virus worldwide and 2014 epidemic in Taiwan.

Abstract: Since 2010, a new variant of PEDV belonging to Genogroup 2 has been transmitting in China and further spreading to the Unites States and other Asian countries including Taiwan. In order to characterize in detail the temporal and geographic relationships among PEDV strains, the present study systematically evaluated the evolutionary patterns and phylogenetic resolution in each gene of the whole PEDV genome in order to determine which regions provided the maximal interpretative power. The result was further applied to identify the origin of PEDV that caused the 2014 epidemic in Taiwan. Thirty-four full genome sequences were downloaded from GenBank and divided into three non-mutually exclusive groups, namely, worldwide, Genogroup 2 and China, to cover different ranges of secular and spatial trends. Each dataset was then divided into different alignments by different genes for likelihood mapping and phylogenetic analysis. Our study suggested that both nsp3 and S genes contained the highest phylogenetic signal with substitution rate and phylogenetic topology similar to those obtained from the complete genome. Furthermore, the proportion of nodes with high posterior support (posterior probability >0.8) was similar between nsp3 and S genes. The nsp3 gene sequences from three clinical samples of swine with PEDV infections were aligned with other strains available from GenBank and the results suggested that the virus responsible for the 2014 PEDV outbreak in Taiwan clustered together with Clade I from the US within Genogroup 2. In conclusion, the current study identified the nsp3 gene as an alternative marker for a rapid and unequivocal classification of the circulating PEDV strains which provides complementary information to the S gene in identifying the emergence of epidemic strain resulting from recombination.

Sung|Ming-Hua|MH| Deng|Ming-Chung|MC| Chung|Yi-Hsuan|YH| Huang|Yu-Liang|YL| Chang|Chia-Yi|CY| Lan|Yu-Ching|YC| Chou|Hsin-Lin|HL| Chao|Day-Yu|DY|

D000818:Animals
D001499:Bayes Theorem
D018352:Coronavirus Infections
D004196:Disease Outbreaks
D019143:Evolution, Molecular
D005814:Genes, Viral
D005838:Genotype
D014943:Global Health
D049674:History, 21st Century
D010802:Phylogeny
D053485:Porcine epidemic diarrhea virus
D064370:Spike Glycoprotein, Coronavirus
D013552:Swine
D013553:Swine Diseases
D013624:Taiwan

Porcine epidemic diarrhea virus
Taiwan
Likelihood mapping
Nsp3
Phylogenetic signal
Evolutionary rate
Spike


Influence of Surgeon Volume on Inpatient Complications, Cost, and Length of Stay Following Total Ankle Arthroplasty.

Abstract:
BACKGROUND
Increased surgeon volume may be associated with improved outcomes following operative procedures. However, there is a lack of information on the effect of surgeon volume on inpatient adverse events and resource utilization following total ankle arthroplasty (TAA).

METHODS
A retrospective cohort study of TAA patients was performed using the Nationwide Inpatient Sample (NIS) from 2003 to 2009. High-volume surgeons were considered as those with volume ≥90th percentile of surgeons performing TAA. Multivariate regression was used to compare the rates of adverse events, hospital length of stay, and total hospital charges between surgeon volume categories.

RESULTS
A total of 4800 TAA patients were identified. The 90th percentile for surgeon volume was 21 cases per year. Mean length of stay was 2.8 ± 2.3 days and mean hospital charges were $45 963 ± $43 983. On multivariate analysis, high-volume surgeons had decreased overall complications (OR 0.5, P = .034) and rate of medial malleolus fracture (OR 0.1, P = .043), decreased length of stay (-0.9 days, P < .001), and decreased hospital charges (-$20 904, P < .001).

CONCLUSIONS
Surgeons with volume ≥90th percentile had a decreased rate of complications, decreased length of stay, and reduced hospital charges compared to other surgeons.

LEVEL OF EVIDENCE
Level III, comparative study.

Basques|Bryce A|BA|
Bitterman|Adam|A|
Campbell|Kevin J|KJ|
Haughom|Bryan D|BD|
Lin|Johnny|J|
Lee|Simon|S|

volume
inpatient complications
cost
length of stay
total ankle arthroplasty
total ankle replacement


A multicentre randomized pilot trial on the effectiveness of different levels of cooling in comatose survivors of out-of-hospital cardiac arrest: the FROST-I trial.

Abstract:
PURPOSE
To obtain initial data on the effect of different levels of targeted temperature management (TTM) in out-of-hospital cardiac arrest (OHCA).

METHODS
We designed a multicentre pilot trial with 1:1:1 randomization to either 32 °C (n = 52), 33 °C (n = 49) or 34 °C (n = 49), via endovascular cooling devices during a 24-h period in comatose survivors of witnessed OHCA and initial shockable rhythm. The primary endpoint was the percentage of subjects surviving with good neurologic outcome defined by a modified Rankin Scale (mRS) score of ≤ 3, blindly assessed at 90 days.

RESULTS
At baseline, different proportions of patients who had received defibrillation administered by a bystander were assigned to groups of 32 °C (13.5%), 33 °C (34.7%) and 34 °C (28.6%; p = 0.03). The percentage of patients with an mRS ≤ 3 at 90 days (primary endpoint) was 65.3, 65.9 and 65.9% in patients assigned to 32, 33 and 34 °C, respectively, non-significant (NS). The multivariate Cox proportional hazards model identified two variables significantly related to the primary outcome: male gender and defibrillation by a bystander. Among the 43 patients who died before 90 days, 28 died following withdrawal of life-sustaining therapy, as follows: 7/16 (43.8%), 10/13 (76.9%) and 11/14 (78.6%) of patients assigned to 32, 33 and 34 °C, respectively (trend test p = 0.04). All levels of cooling were well tolerated.

CONCLUSIONS
There were no statistically significant differences in neurological outcomes among the different levels of TTM. However, future research should explore the efficacy of TTM at 32 °C.

CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov unique identifier: NCT02035839 ( http://clinicaltrials.gov ).

Cardiac arrest
Targeted temperature management
Brain injury
Post-cardiac arrest syndrome
Resuscitation
Sudden death


Effectiveness of Allograft Reconstruction vs Tenodesis for Irreparable Peroneus Brevis Tears: A Cadaveric Model.

Abstract:
BACKGROUND
Irreparable peroneus brevis tendon tears are uncommon, and there is scant evidence on which to base operative treatment. Options include tendon transfer, segmental resection with tenodesis to the peroneus longus tendon, and allograft reconstruction. However, the relative effectiveness of the latter 2 procedures in restoring peroneus brevis function has not been established.

METHODS
Custom-made strain gage-based tension transducers were implanted into the peroneus longus and brevis tendons near their distal insertions in 10 fresh-frozen cadaver feet. Axial load was applied to the foot, and the peroneal tendons and antagonistic tibialis anterior and posterior tendons were tensioned to 50% and 100% of physiologic load. Distal tendon tension was recorded in this normal condition and after sequential peroneus brevis-to-longus tenodesis and peroneus brevis allograft reconstruction. Measurements were made in 5 foot inversion/eversion and plantarflexion/dorsiflexion positions.

RESULTS
Distal peroneus brevis tendon tension after allograft reconstruction significantly exceeded that measured after tenodesis in all tested loading conditions (P ≤ 0.022). With 50% of physiologic load applied, peroneus brevis tension was 1% to 28% of normal (depending on foot position) after tenodesis and 73% to 101% of normal after allograft reconstruction. Under the 100% loading condition, peroneus brevis tension was 6% to 43% of normal after tenodesis and 88% to 99% of normal after reconstruction with allograft. Distal peroneus longus tension remained within 20% of normal under all operative and loading conditions.

CONCLUSION
Allograft reconstruction of a peroneus brevis tendon tear in this model substantially restored distal tension when the peroneal tendons and their antagonists were loaded to 50% and 100% of physiologic load. Tenodesis to the peroneus longus tendon did not effectively restore peroneus brevis tension under the tested conditions.

CLINICAL RELEVANCE
Because tenodesis was demonstrated to be ineffective for restoration of peroneus brevis function, this procedure may result in an imbalanced foot clinically.

Pellegrini|Manuel J|MJ|
Glisson|Richard R|RR|
Matsumoto|Takumi|T|
Schiff|Adam|A|
Laver|Lior|L|
Easley|Mark E|ME|
Nunley|James A|JA|

tenodesis
peroneus brevis
peroneus longus


Catalytic Pyrolysis Kinetic Behavior and TG-FTIR-GC-MS Analysis of Metallized Food Packaging Plastics with Different Concentrations of ZSM-5 Zeolite Catalyst.

Abstract: Recently, the pyrolysis process has been adapted as a sustainable strategy to convert metallized food packaging plastics waste (MFPW) into energy products (paraffin wax, biogas, and carbon black particles) and to recover aluminum. Usually, catalysts are used in pyrolysis treatment to refine pyrolysis products and to increase their yield. In order to study the effect of a catalyst on the formulated volatile products, this work aims to study the pyrolysis behavior of MFPW in presence of catalyst, using TG-FTIR-GC-MS system. The pyrolysis experiments were conducted with ZSM-5 Zeolite catalyst with different concentrations (10, 30, and 50 wt.%) at different heating rates (5, 10, 15, 20, 25, and 30 °C/min). In addition, TG-FTIR system and GC-MS unit were used to observe and analyze the thermal and chemical degradation of the obtained volatile compounds at maximum decomposition peaks. In addition, the kinetic results of catalytic pyrolysis of ZSM-5/MFPW samples matched when model-free methods, a distributed activation energy model (DAEM), and an independent parallel reaction kinetic model (IPR) were used. The TGA-DTG results showed that addition of a catalyst did not have a significant effect on the features of the TGA-DTG curves with similar weight loss of 87-90 wt.% (without taking the weight of the catalyst into account). Meanwhile, FTIR results manifested strong presence of methane and high-intensity functional group of carboxylic acid residues, especially at high concentration of ZSM-5 and high heating rates. Likewise, GC-MS measurements showed that Benzene, Toluene, Hexane, p-Xylene, etc. compounds (main flammable liquid compounds in petroleum oil) generated catalysts exceeding 50%. Finally, pyrolysis kinetics showed that the whole activation energies of catalytic pyrolysis process of MFPW were estimated at 289 kJ/mol and 110, 350, and 174 kJ/mol for ZSM-5/MFPW samples (10, 30, and 50 wt.%, respectively), whereas DAEM and IPR approaches succeeded to simulate TGA and DTG profiles with deviations below <1.

Eimontas|Justas|J|
Striūgas|Nerijus|N|
Abdelnaby|Mohammed Ali|MA|
Yousef|Samy|S|0000-0002-4846-3202


Analysis of patients' request to switch from a generic drug to the original drug in external prescriptions.

Abstract:
BACKGROUND
Generic drugs are heavily promoted in Japan. The aim of this retrospective single-center study was to clarify whether the frequency and reason that patients request a switch from a generic drug to the original drug differ according to therapeutic category and dosage form.

METHODS
This study was performed at Chiba University Hospital. Prescription inquiries about 121 generic drugs from community pharmacies over a 3-year period (from July 2014 to June 2017) were analyzed.

RESULTS
Approximately 30% of the requests were related to the efficacy, safety, and comfort of the generic drug. The most cited motive was "patient's desire with no reason given" at 44.5%. According to multiple logistic regression analysis, therapeutic categories and dosage forms were associated with the requests. The median request frequency differed according to therapeutic category and dosage form. The frequency was highest for "agents affecting the central nervous system" and "tablets and capsules", respectively. Among the therapeutic categories, "agents affecting the central nervous system" had the highest median number of requests related to "decreased effectiveness"; "cardiovascular agents" had the highest median number of requests related to "physician's instruction"; and "agents for the epidermis" had the highest median number of requests related to "uncomfortable to use". Among dosage forms, the odds ratio for patients' original drug request for "liniment and patch" was about 1.5 times that for "tablets and capsules". "Liniment and patch" had the highest median frequency of requests related to "decreased effectiveness", "uncomfortable to use", and "patient's desire with no reason given".

CONCLUSIONS
The request frequency and reason differed according to therapeutic category and dosage form. Pharmacists should advise each patient properly about the choice and switching of drug brands, taking into account the therapeutic category and dosage form, especially liniments and patches.

Hamada|Yuhei|Y| Uchida|Masashi|M| Arai|Sayaka|S| Yamazaki|Kaori|K| Takeda|Mariko|M| Arai|Kenichi|K| Nakamura|Takako|T| Suzuki|Takaaki|T| Ishii|Itsuko|I|

Generic drug
Original drug
External prescription
Inquiries


SENP Proteases as Potential Targets for Cancer Therapy.

Abstract: SUMOylation is a reversible post-translational modification (PTM) involving a covalent attachment of small ubiquitin-related modifier (SUMO) proteins to substrate proteins. SUMO-specific proteases (SENPs) are cysteine proteases with isopeptidase activity facilitating the de-conjugation of SUMO proteins and thus participating in maintaining the balance between the pools of SUMOylated and unSUMOylated proteins and in SUMO recycling. Several studies have reported that SENPs' aberrant expression is associated with the development and progression of cancer. In this review, we will discuss the role of SENPs in the pathogenesis of cancer, focusing on DNA repair and the cell cycle-cellular pathways malfunctioning in most cancer cells. The plausible role of SENPs in carcinogenesis resulted in the design and development of their inhibitors, including synthetic protein-based, peptide-based, and small molecular weight inhibitors, as well as naturally occurring compounds. Computational methods including virtual screening have been implemented to identify a number of lead structures in recent years. Some inhibitors suppressed the proliferation of prostate cancer cells in vitro and in vivo, confirming that SENPs are suitable targets for anti-cancer treatment. Further advances in the development of SENP-oriented inhibitors are anticipated toward SENP isoform-specific molecules with therapeutic potential.

SENP proteases
SUMOylation
DNA repair
SENP inhibitors
cancer progression
cell cycle
deSUMOylation


Esophageal metastasis to the iris effectively palliated using stereotactic body radiation therapy and adjuvant intravitreal chemotherapy: case report and literature review.

Abstract: We report a case of isolated iris metastasis from esophageal adenocarcinoma that was successfully managed with local application of stereotactic body radiation therapy (SBRT) and adjunctive intravitreal therapy. A 53-year-old man with locally advanced esophageal adenocarcinoma achieved a complete clinical and radiographic response after surgery and chemotherapy. Four months later, he developed headache and decreased vision and was diagnosed with metastasis to the iris by slit-lamp examination. The decrease in vision was secondary to cystoid macular edema. The metastatic tumor and the patient's symptoms resolved after treatment with SBRT and intravitreal injections of bevacizumab and triamcinolone. We conclude that SBRT combined with intravitreal chemotherapy is an effective and well-tolerated palliative treatment for metastasis of esophageal adenocarcinoma to the iris.

Dhakal|Sughosh|S|
Lema|Gareth M C|GM|
Diloreto|David A|DA|
Katz|Alan W|AW|

Stereotactic body radiation therapy
Iris metastasis
Intravitreal injection
Bevacizumab
Esophageal carcinoma


Management of acute postoperative hypertension for reducing cardiovascular complications in cancer patients: when and how aggressively?

Abstract:
BACKGROUND/AIM
We sought to determine what factors cardiovascular complications (CVCs) correlate with in cancer patients with acute postoperative hypertension (APH) and to define when and how aggressively to treat this disorder in the present study.

MATERIALS AND METHODS
A retrospective observational study of cancer patients with postoperative hypertension at a single intensive care unit between July 2007 and June 2013 was conducted. The outcome of interest was the incidence of a CVC.

RESULTS
There were 1162 patients enrolled, of which 92 (7.9%) experienced one or more CVCs. Preexisting hypertension (OR 38.3, 95% CI 3.2-457.4, P = 0.004) and choice of vasodilator (OR 6.5, 95% CI 2.3-18.6, P = 0.000) were predictors of a CVC. Cardiovascular complications were less likely to occur if pain was relieved efficiently during the postoperative period (OR 15.9, 95% CI 1.9-130.1, P = 0.01). Furthermore, there were increased CVCs among patients with postoperative hypertensive crises compared to those with stage 1 or stage 2 hypertension with the treatment threshold for systolic blood pressure (OR 5.7, 95% CI 2.0-16.5, P = 0.001) or diastolic blood pressure (OR 6.0, 95% CI 1.8-20.3, P = 0.004).

CONCLUSION
To reduce CVCs, APH may be defined and managed as a hypertensive crisis in cancer patients.

Lou|Ning|N| Wang|Daofeng|D| Wang|Zhi|Z| Ye|Wenfeng|W| Liu|Xiao|X|

Acute postoperative hypertension
cardiovascular complication
cancer
surgery


Effect of whole-body vibration therapy on lower extremity function in subacute stroke patients.

Abstract: This study aimed to investigate the effect of whole-body vibration therapy on lower extremity function in subacute stroke patients. Subacute stroke patients who were able to undergo gait training were randomly divided into a vibration therapy group and a control group. All patients attended 20-min training sessions twice daily, 5 times a week for 2 weeks. Each session included 45 squats. The vibration group trained on a vibration platform and the control group trained on the ground. The degree of maximal isokinetic voluntary contraction torque was evaluated, and manual muscle tests of hip and knee flexion and extension were performed. The Berg Balance Scale, 10-m walk test, Timed Up and Go Test, and Functional Ambulation Category were used. A total of 38 patients, 20 in the vibration group and 18 in the control group, were included in the analysis. After the 2-week therapy, the vibration group showed significant improvements in lower extremity strength, balance, and gait performance. The vibration group showed significantly better performance on the Berg Balance Scale, 10-m walk test, and Functional Ambulation Category than the control group. There were no significant differences in maximal isokinetic voluntary contraction torque or manual muscle tests between the groups. Our results suggest that additional training with whole-body vibration may effectively improve the balance and gait performance of subacute stroke patients. Further studies on large populations are required to determine the therapy's clinical efficacy.

Kim|Jin Wan|JW|
Lee|Jong Hwa|JH|0000-0003-2489-358X

Whole-body vibration therapy
Lower extremity function
Subacute stroke


Serotonin excites hippocampal CA1 GABAergic interneurons at the stratum radiatum-stratum lacunosum moleculare border.

Abstract: The hippocampus receives robust serotonergic innervation that is thought to control the excitability of both pyramidal cells and GABAergic interneurons. Previous work has addressed serotonergic regulation of pyramidal cells but considerable gaps remain in our understanding of how serotonin regulates different interneuron subclasses. 5-HT2A receptors (5-HT2A Rs) appear to localize predominantly, if not solely, on interneurons in the hippocampus and have been implicated in the regulation of hippocampal function including mnemonic and novelty recognition processes. Interneurons are functionally diverse. Therefore in the current work, we have used a BAC transgenic mouse line expressing EGFP under the control of the 5-HT2A R promoter to identify the interneuron subtype(s) regulated by serotonin via 5-HT2A Rs. We find that EGFP expression in this mouse identifies a group of interneurons that resides predominantly along the border of the stratum radiatum (SR) and stratum lacunosum moleculare (SLM) of the CA1 region. We then show that these cells are depolarized and excited by serotonin acting through 5-HT2A Rs and appear to belong predominantly to the perforant pathway-associated and Schaffer collateral/commissural pathway-associated subtypes. These results indicate that serotonin interneurons expressing 5-HT2A Rs are localized primarily along the SR-SLM border of the CA1 region and represent a newly identified target for serotonin regulation in the hippocampus. © 2016 Wiley Periodicals, Inc.

D000818:Animals
D056547:CA1 Region, Hippocampal
D059330:GABAergic Neurons
D049452:Green Fluorescent Proteins
D007150:Immunohistochemistry
D007395:Interneurons
D008564:Membrane Potentials
D008822:Mice, Transgenic
D018408:Patch-Clamp Techniques
D019580:Perforant Pathway
D011401:Promoter Regions, Genetic
D044402:Receptor, Serotonin, 5-HT2A
D012701:Serotonin
D018490:Serotonin Agents
D046509:Tissue Culture Techniques
D005680:gamma-Aminobutyric Acid

GABAergic interneuron
hippocampus
5-HT2A receptors
SR-SLM border
5-HT


Type 2 innate lymphoid cell suppression by regulatory T cells attenuates airway hyperreactivity and requires inducible T-cell costimulator-inducible T-cell costimulator ligand interaction.

Abstract:
BACKGROUND
Atopic diseases, including asthma, exacerbate type 2 immune responses and involve a number of immune cell types, including regulatory T (Treg) cells and the emerging type 2 innate lymphoid cells (ILC2s). Although ILC2s are potent producers of type 2 cytokines, the regulation of ILC2 activation and function is not well understood.

OBJECTIVE
In the present study, for the first time, we evaluate how Treg cells interact with pulmonary ILC2s and control their function.

METHODS
ILC2s and Treg cells were evaluated by using in vitro suppression assays, cell-contact assays, and gene expression panels. Also, human ILC2s and Treg cells were adoptively transferred into NOD SCID γC-deficient mice, which were given isotype or anti-inducible T-cell costimulator ligand (ICOSL) antibodies and then challenged with IL-33 and assessed for airway hyperreactivity.

RESULTS
We show that induced Treg cells, but not natural Treg cells, effectively suppress the production of the ILC2-driven proinflammatory cytokines IL-5 and IL-13 both in vitro and in vivo. Mechanistically, our data reveal the necessity of inducible T-cell costimulator (ICOS)-ICOS ligand cell contact for Treg cell-mediated ILC2 suppression alongside the suppressive cytokines TGF-β and IL-10. Using a translational approach, we then demonstrate that human induced Treg cells suppress syngeneic human ILC2s through ICOSL to control airway inflammation in a humanized ILC2 mouse model.

CONCLUSION
These findings suggest that peripheral expansion of induced Treg cells can serve as a promising therapeutic target against ILC2-dependent asthma.

Rigas|Diamanda|D|
Lewis|Gavin|G|
Aron|Jennifer L|JL|
Wang|Bowen|B|
Banie|Homayon|H|
Sankaranarayanan|Ishwarya|I|
Galle-Treger|Lauriane|L|
Maazi|Hadi|H|
Lo|Richard|R|
Freeman|Gordon J|GJ|
Sharpe|Arlene H|AH|
Soroosh|Pejman|P|
Akbari|Omid|O|

Type 2 innate lymphoid cells
regulatory T cells
airway hyperreactivity
asthma
IL-5
IL-13
inducible T-cell costimulator
inducible T-cell costimulator ligand


A novel screening system based on gene targeting to enrich the modified mammalian cells: without leaving selection marker and additional sequence.

Abstract: Gene targeting by homologous recombination (HR) has some disadvantages in screening modified cells that limits their use in targeting gene fragments in long exons. These disadvantages include retention of remaining selection marker after targeting, not removing cells with vector random integration, and leaving loxP sequences after removal of selection markers. Therefore, to overcome these disadvantages, we decided to design a eukaryotic two-step screening system to isolate the favorable, edited cells from undesirable cells in a gene targeting project. This system included two targeting plasmids containing one positive marker and two inducible negative markers. It was designed in such a way that, during the two-step HR and subsequent selection, only the well-edited cells survive and cells with vector random integration, and untargeted and episomal targeting plasmids are eliminated. The percentage of GFP-positive cells in two-step screening method (76.10 ± 3.50) was significantly higher than in the one-step screening method (0.90 ± 0.37) (p < 0.0001). GFP noise caused by the presence of the GFP-episomal expression plasmid had no significant effect on our results. We developed an efficient system to screen and enrich the HR-modified cells from undesired-HR and untargeted cells, without leaving the selection markers in mammalian cells. This method may be a promising method in ex vivo gene therapy approaches, especially when the target is a gene fragment within a large exon.

Screening
Gene targeting
Selection marker
Homologous recombination


Corrigendum: FGF23 in Cardiovascular Disease: Innocent Bystander or Active Mediator?

Abstract: [This corrects the article DOI: 10.3389/fendo.2018.00351.].

Stöhr|Robert|R|
Schuh|Alexander|A|
Heine|Gunnar H|GH|
Brandenburg|Vincent|V|

FGF23
cardiovascular diseases
heart failure
hypertrophy
left ventricular
myocardial infarction


The advantages of carbon dioxide laser applications in paediatric oral surgery. A prospective cohort study.

Abstract: The aim of this study is to evaluate and demonstrate the advantages of the carbon dioxide laser in paediatric oral surgery patients in terms of less post-operative complications, healing without scaring, functional benefits, positive patient perception and acceptance of the treatment. One hundred fit and healthy paediatric patients (aged 4-15 years) were recruited to undergo laser surgery for different soft tissue conditions. The outcome of these laser treatments was examined. The Wong-Baker Faces Pain Rating Scale was employed to evaluate the pain before, immediately after laser treatment in the clinic and 1 day after post-operatively at home. Post-operative complications and patients' perception and satisfaction were self-reported during a review telephone call the day after treatment. The patients were reviewed 2 weeks after surgery. Laser parameter was 1.62 W, measured by power meter, continuous wave mode with 50 % emission cycle. The beam spot size at the target tissue was 0.8 mm. The pain score pre-operative, during and immediately after laser treatment was rated 0. Whilst the pain score 1 day after surgery was rated between 0 and 2, the healing time was measured over 2 weeks. None of the patients reported post-operative complications after surgery. Patients' perception and acceptance were rated very good. Laser dentistry is a promising field in modern minimally invasive dentistry, which enables provision of better care for children and adolescents. In this cohort study, the use of the carbon dioxide laser therapy offers a desirable, acceptable and minimally invasive technique in the surgical management of soft tissues in paediatric oral surgery with minimal post-operative complications.

Advantages
Laser applications
Lasers
CO2 laser
Paediatric dentistry
Patients’ pain scoring
Patients’ perception
Soft tissue healing


Complementary and alternative medicine for gastroparesis.

Abstract: Complementary and alternative medicine is of great interest to patients with gastrointestinal disorders and some will choose to ask their health care providers about those therapies for which some scientific evidence exists. This review focuses on those therapies most commonly used by patients, namely acupuncture/electroacupuncture and various herbal formulations that have been the focus of clinical and laboratory investigation. A discussion of their possible mechanisms of action and the results of clinical studies are summarized.

Lee|Linda A|LA|
Chen|Jiande|J|
Yin|Jieyun|J|

Acupuncture
Gastrointestinal motility
Marijuana
Rikkunshito
STW 5


Randomized Phase 2 Study of Trebananib (AMG 386) with or without Continued Anti-Vascular Endothelial Growth Factor Therapy in Patients with Renal Cell Carcinoma Who Have Progressed on Bevacizumab, Pazopanib, Sorafenib, or Sunitinib - Results of NCI/CTEP Protocol 9048.

Abstract:
Background
In renal cell carcinoma (RCC), angiopoietin (Ang) 2 is elevated at the time of progression on anti-vascular endothelial growth factor (VEGF) therapy and may contribute to resistance.

Objective
We tested trebananib, an Ang 1 and 2 neutralizing peptibody in patients with RCC progressing on anti-VEGF treatment.

Methods
Patients with measurable RCC progressing despite an anti-VEGF agent within 12 weeks, any number of prior treatments, and good PS were randomized to trebananib 15 mg/kg IV weekly without (Arm A) or with (Arm B) continuation of the prior anti-VEGF agent. The primary endpoint for each arm was tumor response (RECIST 1.1). Secondary endpoints included progression free survival and adverse events.

Results
Of 41 enrolled patients, 35 were eligible and started treatment (17 Arm A, 18 Arm B) with median age 60 (46-76) and 3 prior treatments (1-8). Four died prior to documented progression and 27 progressed as their first event. Both arms were stopped after interim analysis, 2 responses (11%; 95% C.I. 1-35%) were observed in Arm B. Median PFS of 2.7 (95% C.I. 2.3-4.7) months in Arm A and 5.2 (95% C.I. 2.7-10.8) months in Arm B did not support continued study. Common adverse events including fatigue, nausea, and increased creatinine were generally grade 1-2 and numerically higher in Arm B. The most common grade 3 or higher adverse events were hypertension and dyspnea.

Conclusions
While tolerable, trebananib either without or with continued anti-VEGF therapy did not show promising activity in RCC patients who recently progressed on anti-VEGF therapy alone.

Semrad|Thomas J|TJ|
Groshen|Susan|S|
Luo|Chunqiao|C|
Pal|Sumanta|S|
Vaishampayan|Ulka|U|
Joshi|Monika|M|
Quinn|David I|DI|
Mack|Philip C|PC|
Gandara|David R|DR|
Lara|Primo N|PN|

trebananib
Renal cell carcinoma
angiopoietin
vascular endothelial growth factor


The Study of Physico-Mechanical Properties of Polylactide Composites with Different Level of Infill Produced by the FDM Method.

Abstract: The aim of this study was to evaluate the changes in physical-mechanical properties of the samples manufactured by 3D printing technology with the addition of varying degrees of polylactide (PLA) infill (50, 70, 85 and 100%). Half of the samples were soaked in physiological saline. The material used for the study was neat PLA, which was examined in terms of hydrolytic degradation, crystallization, mechanical strength, variability of properties at elevated temperatures, and dissipation of mechanical energy depending on the performed treatment. A significant impact of the amount of infill on changeable mechanical properties, such as hydrolytic degradation and crystallization was observed. The FDM printing method allows for waste-free production of light weight unit products with constant specyfic strength.

FDM method
3D printing
hydrolytic degradation
crystallization
Vicat temperature
different degrees of infill
hysteresis loops
polylactic acid


Antibody persistence after a single dose of quadrivalent HPV vaccine and the effect of a dose of nonavalent vaccine given 3-8 years later - an exploratory study.

Abstract: The objective of this study was to assess the persistence of antibodies after a single dose of quadrivalent HPV vaccine (4vHPV) and the effect of a dose of nonavalent HPV vaccine (9vHPV) given 3-8 years later. Such data might be of interest in the decision-making process regarding the 2-dose course completion in non-compliant vaccinees in jurisdictions which switched from 4vHPV to 9vHPV. Girls who previously received a single dose of 4vHPV were eligible to participate. Blood specimens were collected just before and one month post-9vHPV administration. The specimens were tested by ELISA for the presence of antibodies to 9 HPV types included in the 9vHPV. Thirty-one girls aged 13-18 years (mean 15.5 years) participated in the study. Pre-9vHPV administration, all participants were seropositive to 4 HPV types included in 4vHPV and 58%-87% were seropositive to the five other HPV types included in the 9vHPV. GMTs were 6.1 AU/ml, 7.7 AU/ml, 20.1 IU/ml and 6.3 IU/ml to HPV6, HPV11, HPV16 and HPV18, respectively. The GMTs for the other five HPV types varied from 1.0 to 2.9 AU/ml. One month post-9vHPV administration all 31 participants were seropositive to all 9 HPV types with a 36.1 to 89.1-fold increase of GMTs. High seropositivity rates observed several years after a single dose of 4vHPV and 100% seropositivity after a dose of 9vHPV suggest that this schedule might be used in non-compliant vaccinees or when switching immunization programs from 4vHPV to 9vHPV.

Gilca|Vladimir|V|
Sauvageau|Chantal|C|
Panicker|Gitika|G|
De Serres|Gaston|G|
Ouakki|Manale|M|
Unger|Elizabeth R|ER|

D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18

vaccination
human papillomavirus
mixed schedule


Preliminary study of perineural invasion in patients with hilar cholangiocarcinoma by computed tomography imaging.

Abstract:
OBJECTIVES
To explore the characteristics of hepatic plexuses and celiac ganglia, and their relationships with hilar cholangiocarcinoma (HCCA) perineural invasion (PNI) by computed tomography (CT) imaging preliminarily.

MATERIALS AND METHODS
Sixty-five HCCA patients (55 with PNI) between December 2014 and February 2019 were included in this retrospective study. The CT values of hepatic plexuses in Region 1 (the fat tissue around proper hepatic artery), in Region 2 (the fat tissue around common hepatic artery), and in Region 3 (the fat tissue around celiac trunk), and the CT values and diameters of celiac ganglia were measured on the preoperative CT images. Mann-Whitney U test was used to compare the measurements between PNI group and Non-PNI group. ROC curve was performed to analyze the sensitivity, specificity and optimal threshold of the measurements in discriminating HCCA PNI.

RESULTS
The CT values of hepatic plexuses in PNI group were significantly higher than those in Non-PNI group (all P < 0.05). The CT values of right celiac ganglia were significantly higher in PNI group than those in Non-PNI group (P = 0.007). There were no significant differences between two groups in other measurements (all P > 0.05). The CT values of hepatic plexuses in Region 1 showed the highest sensitivity (90.9%) and the CT values of right celiac ganglia demonstrated the highest specificity (80.0%).

CONCLUSIONS
The increases of CT values of hepatic plexuses around proper hepatic artery may be used as an indicator of PNI in patients with HCCA and may facilitate treatment planning in considering its early recurrence after surgery and poor prognosis.

Li|Jie|J| Wang|Lixue|L| Li|Li|L| Qiao|Jian|J| Zheng|Zhuozhao|Z|

Cholangiocarcinoma
Ganglia
Celiac plexus
Klatskin tumor
Tomography, X-ray computed


Social decisions affect neural activity to perceived dynamic gaze.

Abstract: Gaze direction, a cue of both social and spatial attention, is known to modulate early neural responses to faces e.g. N170. However, findings in the literature have been inconsistent, likely reflecting differences in stimulus characteristics and task requirements. Here, we investigated the effect of task on neural responses to dynamic gaze changes: away and toward transitions (resulting or not in eye contact). Subjects performed, in random order, social (away/toward them) and non-social (left/right) judgment tasks on these stimuli. Overall, in the non-social task, results showed a larger N170 to gaze aversion than gaze motion toward the observer. In the social task, however, this difference was no longer present in the right hemisphere, likely reflecting an enhanced N170 to gaze motion toward the observer. Our behavioral and event-related potential data indicate that performing social judgments enhances saliency of gaze motion toward the observer, even those that did not result in gaze contact. These data and that of previous studies suggest two modes of processing visual information: a 'default mode' that may focus on spatial information; a 'socially aware mode' that might be activated when subjects are required to make social judgments. The exact mechanism that allows switching from one mode to the other remains to be clarified.

Latinus|Marianne|M|
Love|Scott A|SA|
Rossi|Alejandra|A|
Parada|Francisco J|FJ|
Huang|Lisa|L|
Conty|Laurence|L|
George|Nathalie|N|
James|Karin|K|
Puce|Aina|A|

N170
averted gaze
direct gaze
social and non-social context
task modulation