Effectiveness and safety of CT-guided (125)I seed brachytherapy for postoperative locoregional recurrence in patients with non-small cell lung cancer.

Abstract:
PURPOSE
To retrospectively evaluate the effectiveness and safety of CT-guided (125)I seed brachytherapy (CTISB) in 38 non-small cell lung cancer (NSCLC) patients with locoregional recurrence (LRR).

METHODS AND MATERIALS
In total, we analyzed 38 NSCLC patients with LRR treated with percutaneous CTISB in our hospital between 2001 and 2008; among them, 15 also received combined chemotherapy: 1-6 cycles (median, 2) of platinum-based regimens. The change in tumor volume was evaluated based on followup contrast material-enhanced CT or positron emission tomography scans.

RESULTS
The median Day 0 dosimetry was as follows: The volume treated with the prescription dose (V100) was 96.3% (90.1-123.5%), and the minimum dose received by at least 90% of the tumor volume (D90) was 124.8 Gy (116.0-130.7 Gy). The median duration of the followup period calculated from the first CTISB treatment was 22.5 months (range, 8-98 months). Two months after CTISB, complete response, partial response, and progressive disease were observed in 50%, 37%, and 8% of patients, respectively. Median overall survival (OS) after CTISB was 21 months (95% confidence interval, 7.4-34.6), and the rates of 2-year OS, progression-free survival, and local control were 47.4%, 39.5%, and 83.5%, respectively. Both univariate and multivariate analysis indicated that D90 was significant prognostic factors for OS and progression-free survival.

CONCLUSION
For selected NSCLC patients with limited LRR, CTISB is effective and can provide a high rate of local cancer control with minimal trauma.

Huo|Xiaodong|X| Wang|Huixing|H| Yang|Jingkui|J| Li|Xiaodong|X| Yan|Weiliang|W| Huo|Bin|B| Zheng|Guangjun|G| Chai|Shude|S| Wang|Junjie|J| Guan|Zhiyu|Z| Yu|Zhengtao|Z|

D000971:Antineoplastic Combined Chemotherapy Protocols

Brachytherapy
Locoregional recurrence
Iodine-125 seed
Non–small cell lung cancer
Surgery


Postural sway, falls, and self-reported neuropathy in aging female cancer survivors.

Abstract:
BACKGROUND
Falls are a major public health concern in older adults, and the proportion of older adults that has been diagnosed with cancer is growing. Yet, while falls, peripheral neuropathy, and postural instability are more common in aging cancer survivors, it is unclear how these factors interact.

RESEARCH QUESTION
Our objective was to examine how components of sway related to self-reported neuropathy and falls.

METHODS
Postural sway during static stance was recorded with an inertial sensor (APDM Opal), placed on the lumbar spine region in 434 older female cancer survivors (mean age 63) and 49 healthy older female control subjects (mean age 63). Measures of sway were resolved into principal components that were compared between women with and women without self-reported falls in the previous 6 months and between those with and without self-reported symptoms of peripheral neuropathy.

RESULTS
Cancer survivors had worse sway than healthy control subjects in components related to sway magnitude and mediolateral frequency of sway, but no difference in the component related to resultant / AP sway jerk and frequency. Cancer survivors who reported neuropathy were more likely to have higher resultant / AP sway frequencies and jerk than asymptomatic survivors, while survivors who reported a fall were more likely to have lower frequencies of mediolateral sway than non-fallers. Falls were more strongly associated with mediolateral sway in survivors with more severe neuropathy; whereas falls were more strongly associated with resultant / AP sway frequency in survivors with less severe neuropathy SIGNIFICANCE: Postural stability, falls, and neuropathy have complex interactions that can vary across components of postural sway. While the frequency of mediolateral sway was associated with falls across our entire cohort, neuropathy influenced the associations between specific characteristics of sway and falls, which may have implications for fall prevention interventions.

Fino|Peter C|PC|
Horak|Fay B|FB|
El-Gohary|Mahmoud|M|
Guidarelli|Carolyn|C|
Medysky|Mary E|ME|
Nagle|Sarah J|SJ|
Winters-Stone|Kerri M|KM|

D010523:Peripheral Nervous System Diseases

Mediolateral
Postural stability
Balance
Chemotherapy


Distribution of genes encoding resistance to macrolides, lincosamides, and streptogramins among methicillin-resistant Staphylococcus aureus strains isolated from burn patients.

Abstract: The increasing resistance to macrolide, lincosamide, and streptogramin B agents among methicillin-resistant Staphylococcus aureus (MRSA) is a worldwide problem for the health community. This study aimed to investigate the prevalence of ermA, ermB, ermC, and msrA in MRSA strains isolated from burn patients in Ahvaz, southwest of Iran. A total of 76 isolates of S. aureus were collected from January to May 2017 from Taleghani Burn Hospital in Ahvaz. Among 76 S. aureus strains collected, 60 (78.9%) isolates were MRSA. The antimicrobial susceptibility testing for MRSA showed extreme high resistance rate to clarithromycin (100%) and azithromycin (100%), followed by erythromycin (98.3%). The PCR assay revealed that the frequency rates of msrA, ermA, and ermC genes were 23 (38.3%), 28 (46.7%), and 22 (36.7%), respectively. In addition, none of the MRSA isolates had the ermB gene. Because of the high prevalence of macrolide and lincosamide resistance found in MRSA isolates from infections of burn patients in Ahvaz, southwest of Iran, it is recommended that local periodic survey be performed for controlling the dissemination of antimicrobial resistance.

Khoshnood|Saeed|S|
Shahi|Fatemeh|F|
Jomehzadeh|Nabi|N|
Montazeri|Effat Abbasi|EA|
Saki|Morteza|M|
Mortazavi|Seyed Mojtaba|SM|
Maghsoumi-Norouzabad|Leila|L|


Robotic Tongue-Base Resection Combined With Tongue-Base Suspension for Obstructive Sleep Apnea.

Abstract:
OBJECTIVES/HYPOTHESIS
Our primary objective was to evaluate the feasibility, morbidity, and efficacy of transoral robotic surgery (TORS) tongue-base resection (TBR) combined with tongue-base suspension (TBS) for obstructive sleep apnea (OSA) with tongue-base collapse. Our secondary objective included evaluation of factors influencing treatment success.

STUDY DESIGN
Single-arm, prospective, observational cohort study.

METHODS
Patients were eligible if they had moderate-to-severe OSA (apnea hypopnea index [AHI] > 15) or positional OSA, had a tongue-base collapse and glossoptosis identified by drug-induced sleep endoscopy (DISE), and failed continuous positive airway pressure. All patients underwent TORS-TBR combined with TBS. Additionally, concomitant epiglottoplasty, uvulopalatopharyngoplasty, or expansion pharyngoplasty were performed based on DISE findings.

RESULTS
In total, 64 patients were enrolled in the trial. The mean age was 45.9 years, mean body mass index was 30.5 kg/m2 , and mean AHI was 41.7 events/hour. The mean robotic surgical time, total volume of tongue-base tissue removed, and the length of hospital stay were 21.4 minutes, 15.16 mL, and 6.5 days, respectively. Postoperatively, almost all polysomnographic metrics improved significantly (AHI = 41.72 vs. 18.82 events/hour, lowest oxygen saturation = 80.43% vs. 85.14%, Epworth Sleepiness Scale = 10.49 vs. 4.09). The procedure provided an overall success rate of 75%, with minor morbidity. All patients experienced varying degrees of temporary lingual edema postoperatively. Tracheotomy was not required for any patient. Although no independent predictor of treatment success was determined, patients with more severe disease tend to exhibit lower response to the treatment.

CONCLUSIONS
TORS-TBR combined with TBS is a feasible, safe, and efficient procedure for OSA with tongue-base collapse.

LEVEL OF EVIDENCE
4 Laryngoscope, 130:2285-2291, 2020.

tongue-base suspension
Obstructive sleep apnea
robotic surgery
tongue-base reduction


Roles of plant hormones in the regulation of host-virus interactions.

Abstract: Hormones are tuners of plant responses to biotic and abiotic stresses. They are involved in various complicated networks, through which they modulate responses to different stimuli. Four hormones primarily regulate plant defence to pathogens: salicylic acid (SA), jasmonic acid (JA), ethylene (Et) and abscisic acid (ABA). In susceptible plants, viral infections result in hormonal disruption, which manifests as the simultaneous induction of several antagonistic hormones. However, these antagonistic hormones may exhibit some sequential accumulation in resistant lines. Virus propagation is usually restricted by the activation of the small interfering RNA (siRNA) antiviral machinery and/or SA signalling pathway. Several studies have investigated these two systems, using different model viruses. However, the roles of hormones other than SA, especially those with antagonistic properties, such as ABA, have been neglected. Increasing evidence indicates that hormones control components of the small RNA system, which regulates many processes (including the siRNA antiviral machinery and the microRNA system) at the transcriptional or post-transcriptional level. Consequently, cross-talk between the antagonistic SA and ABA pathways modulates plant responses at multiple levels. In this review, we summarize recent findings on the different roles of hormones in the regulation of plant-virus interactions, which are helping us to elucidate the fine tuning of viral and plant systems by hormones.

D054884:Host-Pathogen Interactions
D010937:Plant Growth Regulators
D010944:Plants
D015398:Signal Transduction

plant hormones
host-virus interaction
defence pathways
plant virus


Fibrostenotic strictures in Crohn's disease.

Abstract: The use of biologic agents including anti-tumor necrosis factor monoclonal antibodies followed by anti-integrins and anti-interleukins has drastically changed the treatment paradigm of Crohn's disease (CD) by improving clinical symptoms and mucosal healing. However, up to 70% of CD patients still eventually undergo surgery mainly due to fibrostenotic strictures. There are no specific anti-fibrotic drugs yet. This review comprehensively addresses the mechanism, prediction, diagnosis and treatment of the fibrostenotic strictures in CD. We also introduce promising anti-fibrotic agents which may be available in the near future and summarize challenges in developing novel therapies to treat fibrostenotic strictures in CD.

Yoo|Jun Hwan|JH|
Holubar|Stefan|S|
Rieder|Florian|F|

Stricture
Crohn disease
Endoscopic balloon dilatation
Fibrostenosis
Intestinal fibrosis


The Effects of Using Partial or Uncorrected Correlation Matrices When Comparing Network and Latent Variable Models.

Abstract: Network models of the WAIS-IV based on regularized partial correlation matrices have been reported to outperform latent variable models based on uncorrected correlation matrices. The present study sought to compare network and latent variable models using both partial and uncorrected correlation matrices with both types of models. The results show that a network model provided better fit to matrices of partial correlations but latent variable models provided better fit to matrices of full correlations. This result is due to the fact that the use of partial correlations removes most of the covariance common to WAIS-IV tests. Modeling should be based on uncorrected correlations since these represent the majority of shared variance between WAIS-IV test scores.

latent variable modeling
intelligence
process overlap theory
psychometric network analysis


Multi-chemical analysis combined with chemometrics to characterize PDO and PGI Italian apples.

Abstract:
BACKGROUND
The use of PDO (protected designation of origin) and PGI (protected geographical indication) labels allows to protect and promote agricultural products characterized by unique features related to the place of origin and traditional know-how. However, the presence of non-authentic products in the market represents a fraud that can be tackled applying analytical techniques combined with chemometric analysis. In this study, we applied multi-element and multi-isotope analysis to characterize PDO and PGI apples cultivated in northern Italy, comparing them with Italian apples without labels of geographical indications.

RESULTS
The multi-element and multi-isotope approach allowed to characterize the apples cultivated in northern Italy. Despite a significant effect of the sampling sites on the apple composition, the comparison of the multi-chemical fingerprint of the apples significantly varied among cultivation areas. Results of this characterization were used to classify samples according to their cultivation area applying a linear discriminant analysis (LDA). Outputs of the LDA showed that correct sample classification can be successfully achieved (balanced accuracy > 96%). Moreover, using a selection of variables, it was possible to correctly classify samples also at regional level.

CONCLUSION
The presented evidences indicate that the multi-element and multi-isotope fingerprint can be successfully applied to traceability studies. The combination of this characterization with chemometric tools allows the classification of Italian apples based on their origin both on a national and regional scale. This approach represents an interesting tool to enhance and protect PDO and PGI Italian products. © 2021 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

linear discriminant analysis
PDO and PGI labels
geographical origin
isotope ratio
mass spectrometry
multi-element analysis


Dysregulated expression of ACTN4 contributes to endothelial cell injury via the activation of the p38-MAPK/p53 apoptosis pathway in preeclampsia.

Abstract: Preeclampsia (PE) is a hypertensive disease associated with increased endothelial cell dysfunction caused by systemic oxidative stress. Alpha-actinin-4 (ACTN4) is a member of the α-actinin family of actin crosslinking proteins that are upregulated in several types of cancer. However, its role in PE remains unclear. In this study, we found that ACTN4 was localized in placenta vascular endothelial cells (ECs), and its expression was downregulated in primary human umbilical vein endothelial cells (HUVECs) from severe preeclamptic patients compared to that in HUVECs from normotensive pregnant women. ACTN4 expression was also decreased in normotensive HUVECs treated with H2O2. Downregulation of ACTN4 by siRNA or H2O2 treatment promoted normotensive HUVEC apoptosis and increased p38-MAPK phosphorylation along with elevated levels of p53 phosphorylation, caspase cascade proteins, and bax and repressed expression of bcl-2. Conversely, upregulation of ACTN4 in PE HUVECs significantly inhibited apoptosis and decreased p38-MAPK phosphorylation compared to that of the PE HUVEC controls. In addition, overexpression of ACTN4 in normotensive HUVECs attenuated H2O2 treatment-induced apoptosis with decreased p53 phosphorylation, caspase cascade, and bax expression levels and increased expression of bcl-2 compared to that of only H2O2 treatment. Moreover, the suppression of ACTN4 induced apoptosis, which could be blocked by the p38-MAPK inhibitor SB202190. Collectively, these results demonstrate that dysregulated ACTN4 expression may be associated with PE due to its effects on endothelial cell apoptosis via the p38-MAPK/p53 apoptosis pathway.

Zhao|Jianlin|J| Peng|Wei|W| Ran|Yuxin|Y| Ge|Huisheng|H| Zhang|Chen|C| Zou|Hong|H| Ding|Yubin|Y| Qi|Hongbo|H|

D061307:Human Umbilical Vein Endothelial Cells

D048051:p38 Mitogen-Activated Protein Kinases

Apoptosis
Preeclampsia
Endothelial cell dysfunction
Oxidative stress
P38-MAPK/p53 pathway


A fluorometric assay for alkaline phosphatase activity based on β-cyclodextrin-modified carbon quantum dots through host-guest recognition.

Abstract: A convenient, reliable and highly sensitive assay for alkaline phosphatase (ALP) activity in the real-time manner is developed based on β-cyclodextrin-modified carbon quantum dots (β-CD-CQDs) nanoprobe through specific host-guest recognition. Carbon quantum dots were first functionalized with 3-aminophenyl boronic acid to produce boronic acid-functionalized CQDs, and then further modified with hydropropyl β-cyclodextrins (β-CD) through B-O bonds to form β-CD-CQDs nanoprobe. p-Nitrophenol phosphate disodium salt is used as the substrate of ALP, and can hydrolyze to p-nitrophenol under the catalysis of ALP. The resulting p-nitrophenol can enter the cavity of β-CD moiety in the nanoprobe due to their specific host-guest recognition, where photoinduced electron transfer process between p-nitrophenol and CQDs takes place to efficiently quench the fluorescence of the probe. The correlation between quenched fluorescence and ALP level can be used to establish quantitative evaluation of ALP activity in a broad range from 3.4 to 100.0U/L with the detection limit of 0.9U/L. This assay shows a high sensitivity to ALP even in the presence of a very high concentration of glucose. This study demonstrates a good electron donor/acceptor pair, which can be used to design general detection strategy through PET process, and also broadens the application of host-guest recognition for enzymes detection in clinical practice.

Tang|Cong|C| Qian|Zhaosheng|Z| Huang|Yuanyuan|Y| Xu|Jiamin|J| Ao|Hang|H| Zhao|Meizhi|M| Zhou|Jin|J| Chen|Jianrong|J| Feng|Hui|H|

Carbon quantum dots
Alkaline phosphatase (ALP) activity
Photoinduced electron transfer (PET)
Real-time fluorometric assay


The possible role of microcystin (D-Leu1 MC-LR) as an antioxidant on Microcystis aeruginosa (Cyanophyceae). In vitro and in vivo evidence.

Abstract: Microcystins constitute a serious threat to the quality of drinking water worldwide. However, the eco-physiological role of them is not completely known and it is suggested that toxins can play a role in the antioxidant protection. The objective of this study was to evaluate the microcystin antioxidant capacity in vitro by Electronic Paramagnetic Resonance, highly specific for the different reactive oxygen species and in vivo by 7 days exposure of Microcystis aeruginosa to high (29 °C) temperature in addition to a 26 °C control condition. An effective in vitro antioxidant activity was observed for [D-Leu1]MC-LR against hydrosoluble radicals. As far as we know, this is the first in vitro record of the role of MC as antioxidant. In addition, a significant increase in cellular biomass was observed under 26 °C in cultures with [D-Leu1]MC-LR supplementation in coincidence with a significant decrease of reactive species. For cultures at 29 °C, the antioxidant role of toxins was inconclusive probably due to the presence of different reactive species generated during the experiment. Thus, MC could scavenge certain reactive species associated with the antioxidant role of CAT or the OH content by SOD activity (not measured) and then CAT activity could be lower in the presence of MC. Reinforcing our hypothesis, the [D-Leu1]MC-LR consumption after 7 days was significantly higher in cells with [D-Leu1]MC-LR supplementation in both 26 °C and 29 °C.When the production of reactive species was controlled by the scavenger activity of antioxidants plus MC, cells avoided the potential oxidative damage and started with exponential growth.

Microcystins
Microcystis aeruginosa
Temperature
Catalase
ROS


Construction of Genetic Logic Gates Based on the T7 RNA Polymerase Expression System in Rhodococcus opacus PD630.

Abstract: Rhodococcus opacus PD630 (R. opacus) is a nonmodel, Gram-positive bacterium that holds promise as a biological catalyst for the conversion of lignocellulosic biomass to value-added products. In particular, it demonstrates both a high tolerance for and an ability to consume inhibitory lignin-derived aromatics, generates large quantities of lipids, exhibits a relatively rapid growth rate, and has a growing genetic toolbox for engineering. However, the availability of genetic parts for tunable, high-activity gene expression is still limited in R. opacus. Furthermore, genetic logic circuits for sophisticated gene regulation have never been demonstrated in Rhodococcus spp. To address these shortcomings, two inducible T7 RNA polymerase-based expression systems were implemented for the first time in R. opacus and applied to the construction of AND and NAND genetic logic gates. Additionally, three isopropyl β-d-1-thiogalactopyranoside (IPTG)-inducible promoters were created by inserting LacI binding sites into newly characterized constitutive promoters. Furthermore, four novel aromatic sensors for 4-hydroxybenzoic acid, vanillic acid, sodium benzoate, and guaiacol were developed, expanding the gene expression toolbox. Finally, the T7 RNA polymerase platform was combined with a synthetic IPTG-inducible promoter to create an IMPLY logic gate. Overall, this work represents the first demonstration of a heterologous RNA polymerase system and synthetic genetic logic in R. opacus, enabling complex and tunable gene regulation in this promising nonmodel host for bioproduction.

DeLorenzo|Drew M|DM|
Moon|Tae Seok|TS|0000-0001-8373-9051

D001426:Bacterial Proteins
D012321:DNA-Directed RNA Polymerases
D006139:Guaiacol
D007544:Isopropyl Thiogalactoside
D010226:Parabens
D011401:Promoter Regions, Genetic
D012240:Rhodococcus
D020160:Sodium Benzoate
D014641:Vanillic Acid

T7 RNA polymerase
aromatic sensors
Boolean logic
genetic circuit
nonmodel organism


Evaluation of Functional Filtering Bleb Using Optical Coherence Tomography Angiography.

Abstract:
Purpose
This study investigated whether filtering blebs can be evaluated using optical coherence tomography angiography (OCT-A) and compared vascularity parameters with conventional bleb grading systems.

Methods
A total of 92 patients with glaucoma, who underwent mitomycin C-augmented trabeculectomy, were enrolled in this study, and 92 eyes were assessed in total. The participants underwent OCT-A in external mode and anterior segment photography for bleb evaluation. For evaluation of bleb vascularity, a blinded observer carefully drew the bleb area on the original OCT-A image using a semiautomated program that calculated the color and brightness densities of the selected area. A blinded observer also classified the grades of the bleb vessels using the Indiana Bleb Appearance Grading Scale (IBAGS) and Moorfields Bleb Grading System (MBGS). The vascularity parameters using OCT-A were compared with the IBAGS and MBGS results. In addition, the correlation between intraocular pressure (IOP) and the bleb vascularity parameters was assessed.

Results
Vessel density measured by OCT-A demonstrated excellent inter- and intraobserver reproducibility. The color and brightness densities were positively correlated with the IBAGS and MBGS vascularity scores. There was no difference in accuracy when predicting IOP risk using vascularity scores from the IBAGS and MBGS or when estimating IOP risk using the color and brightness densities on the net reclassification index.

Conclusions
Bleb evaluation using OCT-A can evaluate vessel vascularity and showed correlation to the IBAGS and MBGS vascularity grading.

Translational Relevance
Bleb vascularity measurements using OCT-A could potentially provide objective and quantitative vessel parameters for bleb evaluation following trabeculectomy.

Seo|Je Hyun|JH|
Kim|Ye An|YA|
Park|Keun Heung|KH|
Lee|Young|Y|


Assessment of ochratoxin A occurrence in Argentine red wines using a novel sensitive quechers-solid phase extraction approach prior to ultra high performance liquid chromatography-tandem mass spectrometry methodology.

Abstract:
BACKGROUND
The assessment of ochratoxin A (OTA) in wine is relevant for food safety and its continuous control allows to reduce the risk of intake. Thus, a novel sensitive QuEChERS-SPE (Quick, Easy, Cheap, Effective, Rugged and Safe - Solid Phase Extraction) pretreatment prior to liquid chromatography coupled to tandem mass spectrometry was developed for the determination of OTA in red wine samples from different grape-growing regions in Argentine.

RESULTS
A sensitive methodology was achieved and thus the limits of detection and quantification were 0.02 and 0.05 µg L-1 , respectively. Recoveries ranged from 89.0% to 105.3%. The method was applied to 136 red wine samples (Argentina's flagship varieties: Malbec and Cabernet Sauvignon) from ten grape-growing regions, during vintages 2013-2015. Although all of the samples investigated were contaminated with OTA (concentrations ranged from 0.02 to 0.98 µg L-1 ), the levels detected were lower than the maximum allowable concentration limit of 2.0 µg L-1 established by international regulations.

CONCLUSION
The methodology proposed is suitable for reliable OTA analysis in red wines. Similarly, the values obtained from the samples analyzed were in accordance with the current regulations and, as a consequence, preventive actions to reduce this mycotoxin incidence can be undertaken. © 2016 Society of Chemical Industry.

Mariño-Repizo|Leonardo|L| Gargantini|Raquel|R| Manzano|Humberto|H| Raba|Julio|J| Cerutti|Soledad|S|

D002851:Chromatography, High Pressure Liquid

ochratoxin A
Argentinean red wines
QuEChERS
UHPLC-MS/MS


H2S-induced thiol-based redox switches: Biochemistry and functional relevance for inflammatory diseases.

Abstract: During the last decades, small inorganic molecules like reactive oxygen species (ROS), nitric oxide (NO), carbon monoxide (CO) and even the highly toxic hydrogen sulfide (H2S) have been evolved as important signaling molecules that trigger crucial cellular processes by regulating the activity of kinases, phosphatases and transcription factors. These redox molecules use similar target structures and therefore, the composition of the complex "redox environment" determines the final outcome of signaling processes and may subsequently also affect the behavior of a cell in an inflammatory environment. Here, we discuss the role of H2S in this complex interplay with a focus on the transcription factors Nrf2 and NFκB.

Thiol-based redox switches
Hydrogen sulfide
Hydropersulfide


Proteolytic extracts of three Bromeliaceae species as eco-compatible tools for leather industry.

Abstract: Most tanneries use high proportions of Na2S and CaO during the dehairing step, resulting in effluents of high alkalinity and large amounts of suspended solid, besides the risk of liberating the toxic H2S. Solid waste rich in protein is another environmental problem of tanneries. Enzymes are an interesting technological tool for industry due to their biodegradability, nontoxic nature, and nonpolluting effluent generation. In the leather industry, proteases have been chosen as a promising eco-friendly alternative to Na2S/CaO dehairing. Extracts with high proteolytic activity have been obtained from fruits of Bromeliaceae species: Bromelia balansae Mez (Bb), Bromelia hieronymi Mez (Bh), and Pseudananas macrodontes (Morr.) Harms (Pm). In this work, Bb, Bh, and Pm have been studied for application in the leather industry, focusing in their dehairing properties. Enzymatic activities were measured against collagen, keratin, elastin, and epidermis while a dehairing assay was performed by employing cowhide. All extracts showed similar activity on collagen and epidermis, while Bh and Pm were the most active against keratin at the same caseinolytic unit (CU) values; Bh was the only extract active against elastin. Bb (1 CU/ml), Bh (1.5 CU/ml), and Pm (0.5 CU/ml) were able to depilate cowhide. Desirable characteristics of dehairing were observed for all extracts since hair pores did not show residual hair, grain surface was clean and intact, and collagen fiber bundles of dermis were not damaged. In conclusion, results here presented show that proteolytic extracts of Bromeliaceae species are promising eco-compatible tools for leather industry.

Bromeliaceae
Leather
Enzymatic dehairing
Lime and sulfide-free dehairing
Plant proteases
Protein waste


Mobile-bearing total knee arthroplasty: More rotation is evident during more demanding tasks.

Abstract:
BACKGROUND
Some reports showed few but significant more axial femorotibial rotation in favor of mobile-bearing (MB) versus fixed-bearing (FB) total knee arthroplasty (TKA), mostly during knee bend fluoroscopic studies. The goal of the current study was to submit MB and FB groups of TKA patients to a turning activity, in which additional rotation was to be expected.

METHODS
Two consecutive cohorts of patients after TKA (10 FB and 11 MB knees in a total of 18 patients) were assessed using motion analysis five year postoperatively, while performing gait and sit-to-walk (STW) movements with and without turning steps.

RESULTS
Mean range of rotation in the FB group increased from 9.7° during gait, to 11.7° during STW straight, and to 14.3° during STW turning. Mean range of rotation in the MB group increased from 13.4° during gait to 21.0° during STW straight, and stayed at 21.1° during STW turning.

CONCLUSIONS
Too many uncontrolled variables in the current study hinder a meaningful discrimination of MB from FB TKA rotation. However, the study does illustrate how more demanding task loads could be helpful in exploring the geometric constraints of TKA variants.

LEVEL OF EVIDENCE
Level III, therapeutic study.

Zürcher|Arthur W|AW|
van Hutten|Kim|K|
Harlaar|Jaap|J|
Terwee|Caroline B|CB|
Rob Albers|G H|GH|
Pöll|Ruud G|RG|


EX-PRESS glaucoma filtration device: Review of clinical experience and comparison with trabeculectomy.

Abstract: Glaucoma filtration surgery is performed to reduce intraocular pressure (IOP) in patients for whom maximal tolerable pharmacologic IOP-lowering therapy and/or laser surgery fail to lower IOP sufficiently and/or fail to prevent optic nerve damage or visual field deterioration. For decades, the most widely utilized procedure for glaucoma filtration surgery has been trabeculectomy. Although this approach reliably provides long-term IOP reduction in many patients, the postoperative complication rate is high. This has driven the development of alternative approaches to reduce IOP surgically. The EX-PRESS glaucoma filtration device was developed to mimic IOP control by trabeculectomy and to have a better safety profile. This non-valved, medical-grade stainless steel device diverts aqueous humor from the anterior chamber to an intrascleral space. Despite the widespread use of the EX-PRESS device, only a few studies compare its efficacy and safety with that of trabeculectomy. We analyze available data regarding the safety and efficacy of the EX-PRESS device, particularly in comparison with trabeculectomy.

glaucoma
glaucoma filtration device
trabeculectomy
intraocular pressure
postoperative complications


A survey and evaluation of Web-based tools/databases for variant analysis of TCGA data.

Abstract: The Cancer Genome Atlas (TCGA) is a publicly funded project that aims to catalog and discover major cancer-causing genomic alterations with the goal of creating a comprehensive 'atlas' of cancer genomic profiles. The availability of this genome-wide information provides an unprecedented opportunity to expand our knowledge of tumourigenesis. Computational analytics and mining are frequently used as effective tools for exploring this byzantine series of biological and biomedical data. However, some of the more advanced computational tools are often difficult to understand or use, thereby limiting their application by scientists who do not have a strong computational background. Hence, it is of great importance to build user-friendly interfaces that allow both computational scientists and life scientists without a computational background to gain greater biological and medical insights. To that end, this survey was designed to systematically present available Web-based tools and facilitate the use TCGA data for cancer research.

Zhang|Zhuo|Z| Li|Hao|H| Jiang|Shuai|S| Li|Ruijiang|R| Li|Wanying|W| Chen|Hebing|H| Bo|Xiaochen|X|

survey
databases
The Cancer Genome Atlas
cancer
bioinformatics tools


A new species of Odontothrips Amyot amp; Serville (Thysanoptera, Thripidae) from Japan.

Abstract: Odontothrips kudoi sp. n. is described from Japan and details of Japanese distribution of O. biuncus John is recorded. Moreover, O. loti (Haliday) is excluded from the Japanese fauna.

Thysanoptera, Fabaceae, glandular opening, Megalurothrips genus-group, Odontothrips biuncus, Odontothrips loti, Hokkaido


The role of intestinal microbiota of the marine fish (Acanthopagrus latus) in mercury biotransformation.

Abstract: Both inorganic (IHg) and organic (MeHg) forms of Hg can be converted into each other by methylation or demethylation, leading to changes of Hg speciation and distribution in fish. However, Hg biotransformation in fish is not thoroughly understood and the key factors in this process are unclear. The present study investigated the in vivo Hg transformation in a marine fish (Acanthopagrus latus) and explored the roles of intestinal microbiota in Hg biotransformation. We first demonstrated that Hg methylation or demethylation occurred in the fish gut under dietary IHg or MeHg exposure, respectively. The demethylation was observed to be faster than methylation, suggesting that demethylation could significantly influence the Hg speciation in fish. This study also strongly suggested that intestinal microbiota played a predominant role in Hg biotransformation and thus significantly affected the overall Hg accumulation and distribution in fish body. The richness of Hg methylators or demethylators was elevated under IHg or MeHg treatment, respectively. Furthermore, the intestinal microbiota composition was also altered by Hg exposure. This study highlights the importance of intestinal microbiota in Hg biotransformation in fish body, and suggests that modulating the gut microbiome could be a possible solution to minimize Hg contamination in fish.

Yang|Tao-Tao|TT| Liu|Yong|Y| Tan|Sha|S| Wang|Wen-Xiong|WX| Wang|Xun|X|

Intestinal microbiota
Fish
Mercury
Methylation
Demethylation


A new generation of companion diagnostics: cobas BRAF, KRAS and EGFR mutation detection tests.

Abstract: The cobas(®) (Roche) portfolio of companion diagnostics in oncology currently has three assays CE-marked for in vitro diagnostics. Two of these (EGFR and BRAF) are also US FDA-approved. These assays detect clinically relevant mutations that are correlated with response (BRAF, EGFR) or lack of response (KRAS) to targeted therapies such as selective mutant BRAF inhibitors in malignant melanoma, tyrosine kinases inhibitor in non-small cell lung cancer and anti-EGFR monoclonal antibodies in colorectal cancer, respectively. All these assays are run on a single platform using DNA extracted from a single 5 µm section of a formalin-fixed paraffin-embedded tissue block. The assays provide an 'end-to-end' solution from extraction of DNA to automated analysis and report on the cobas z 480. The cobas tests have shown robust and reproducible performance, with high sensitivity and specificity and low limit of detection, making them suitable as companion diagnostics for clinical use.

companion diagnostics
EGFR mutations
malignant melanoma
colorectal cancer
BRAF mutations
KRAS mutations
cobas 480
molecular pathology
non-small-cell lung cancer


Visual hallucinations following a left-sided unilateral tuberothalamic artery infarction.

Abstract: A 20-year-old man presented with realistic visual hallucinations and no motor or sensory neurological findings. The absence of motor or sensory deficits on physical examination made for a diagnostic challenge, but an altered mental status with dysnomic word-finding difficulty was the clue to the existence of an encephalopathy that resulted in evaluation for structural pathology. Brain imaging revealed an infarction in the territory of the left tuberothalamic artery. A head magnetic resonance imaging scan identified the neuropathology that led to immediately starting treatment for stroke.

Lee|Sangsoo|S|
Kim|Dae Yoon|DY|
Kim|Jung Soo|JS|
Kaur|Gagandeep|G|
Lippmann|Steven|S|

visual hallucinations
absence of motor or sensory deficits
encephalopathy
left tuberothalamic artery
stroke
Cerebrovascular accident
anomia
brain infarction
central nervous system pathology
diagnostic accuracy
dysnomia


Dose to mass for evaluation and optimization of lung cancer radiation therapy.

Abstract:
PURPOSE
To evaluate potential organ at risk dose-sparing by using dose-mass-histogram (DMH) objective functions compared with dose-volume-histogram (DVH) objective functions.

METHODS
Treatment plans were retrospectively optimized for 10 locally advanced non-small cell lung cancer patients based on DVH and DMH objectives. DMH-objectives were the same as DVH objectives, but with mass replacing volume. Plans were normalized to dose to 95% of the PTV volume (PTV-D95v) or mass (PTV-D95m). For a given optimized dose, DVH and DMH were intercompared to ascertain dose-to-volume vs. dose-to-mass differences. Additionally, the optimized doses were intercompared using DVH and DMH metrics to ascertain differences in optimized plans. Mean dose to volume, Dv‾, mean dose to mass, DM‾, and fluence maps were intercompared.

RESULTS
For a given dose distribution, DVH and DMH differ by >5% in heterogeneous structures. In homogeneous structures including heart and spinal cord, DVH and DMH are nearly equivalent. At fixed PTV-D95v, DMH-optimization did not significantly reduce dose to OARs but reduced PTV-Dv‾ by 0.20±0.2Gy (p=0.02) and PTV-DM‾ by 0.23±0.3Gy (p=0.02). Plans normalized to PTV-D95m also result in minor PTV dose reductions and esophageal dose sparing (Dv‾ reduced 0.45±0.5Gy, p=0.02 and DM‾ reduced 0.44±0.5Gy, p=0.02) compared to DVH-optimized plans. Optimized fluence map comparisons indicate that DMH optimization reduces dose in the periphery of lung PTVs.

CONCLUSIONS
DVH- and DMH-dose indices differ by >5% in lung and lung target volumes for fixed dose distributions, but optimizing DMH did not reduce dose to OARs. The primary difference observed in DVH- and DMH-optimized plans were variations in fluence to the periphery of lung target PTVs, where low density lung surrounds tumor.

Tyler Watkins|William|W|
Moore|Joseph A|JA|
Hugo|Geoffrey D|GD|
Siebers|Jeffrey V|JV|

Lung cancer radiation therapy
DMH optimization
Mass optimization
Radiation therapy optimization


Pain in cervical dystonia: mechanisms, assessment and treatment.

Abstract:
INTRODUCTION
In patients with cervical dystonia (CD), pain is a major contributor to disability and social isolation and is often the main reason patients seek treatment. Surveys evaluating patient perceptions of their CD symptoms consistently highlight pain as a troublesome and disabling feature of their condition with significant impact on daily life and work.

AREAS COVERED
In this article, the authors review the epidemiology, assessment, possible mechanisms and treatment of pain in CD, including a meta-analysis of randomized controlled trial data with abobotulinumtoxinA.

EXPERT OPINION
Mechanisms of pain in CD may be muscle-based and non-muscle based. Accumulating evidence suggests that non-muscle-based mechanisms (such as abnormal transmission and processing of nociceptive stimuli, dysfunction of descending pain inhibitory pathways as well as structural and network changes in the basal ganglia, cortex and other areas) may also contribute to pain in CD alongside prolonged muscle contraction. Chemodenervation with botulinum toxin is considered the first-line treatment for CD. Treatment with botulinum toxin is usually effective, but optimization of the injection parameters should include consideration of pain as a core symptom in addition to the motor problems.

Rosales|Raymond L|RL|
Cuffe|Lorraine|L|
Regnault|Benjamin|B|
Trosch|Richard M|RM|

pain
cervical dystonia
botulinum toxin
AbobotulinumtoxinA
non-motor symptom


Organization of intensive cardiac care units in Europe: Results of a multinational survey.

Abstract:
BACKGROUND
The present survey aims to describe the intensive cardiac care unit organization and admission policies in Europe.

METHODS
A total of 228 hospitals (61% academic) from 27 countries participated in this survey. In addition to the organizational aspects of the intensive cardiac care units, including classification of the intensive cardiac care unit levels, data on the admission diagnoses were gathered from consecutive patients who were admitted during a two-day period. Admission policies were evaluated by comparing illness severity with the intensive cardiac care unit level. Gross national income was used to differentiate high-income countries (n=13) from middle-income countries (n=14).

RESULTS
A total of 98% of the hospitals had an intensive cardiac care unit: 70% had a level 1 intensive cardiac care unit, 76% had a level 2 intensive cardiac care unit, 51% had a level 3 intensive cardiac care unit, and 60% of the hospitals had more than one intensive cardiac care unit level. High-income countries tended to have more level 3 intensive cardiac care units than middle-income countries (55% versus 41%, p=0.07). A total of 5159 admissions were scored on illness severity: 63% were low severity, 24% were intermediate severity, and 12% were high severity. Patients with low illness severity were predominantly admitted to level 1 intensive cardiac care units, whereas patients with high illness severity were predominantly admitted to level 2 and 3 intensive cardiac care units. A policy mismatch was observed in 12% of the patients; some patients with high illness severity were admitted to level 1 intensive cardiac care units, which occurred more often in middle-income countries, whereas some patients with low illness severity were admitted to level 3 intensive cardiac care units, which occurred more frequently in high-income countries.

CONCLUSION
More than one-third of the admitted patients were considered intermediate or high risk. Although patients with higher illness severity were mostly admitted to high-level intensive cardiac care units, an admission policy mismatch was observed in 12% of the patients; this mismatch was partly related to insufficient logistic intensive cardiac care unit capacity.

Claeys|M J|MJ|
Roubille|F|F|
Casella|G|G|
Zukermann|R|R|
Nikolaou|N|N|
De Luca|L|L|
Gierlotka|M|M|
Iakobishvili|Z|Z|
Thiele|H|H|
Koutouzis|M|M|
Sionis|A|A|
Monteiro|S|S|
Beauloye|C|C|
Held|C|C|
Tint|D|D|
Zakke|I|I|
Serpytis|P|P|
Babic|Z|Z|
Belohlavev|J|J|
Magdy|A|A|
Sivagowry Rasalingam|M|M|
Daly|K|K|
Arroyo|D|D|
Vavlukis|M|M|
Radovanovic|N|N|
Trendafilova|E|E|
Marandi|T|T|
Hassenger|C|C|
Lettino|M|M|
Price|S|S|
Bonnefoy|E|E|

organization
Intensive cardiac care unit
admission policy
acute cardiovascular care


Poly(ortho ester) nanoparticles targeted for chronic intraocular diseases: ocular safety and localization after intravitreal injection.

Abstract: Treatment of posterior eye diseases is more challenging than the anterior segment ailments due to a series of anatomical barriers and physiological constraints confronted by drug delivery to the back of the eye. In recent years, concerted efforts in drug delivery have been made to prolong the residence time of drugs injected in the vitreous humor of the eye. Our previous studies demonstrated that poly(ortho ester) (POE) nanoparticles were biodegradable/biocompatible and were capable of long-term sustained release. The objective of the present study was to investigate the safety and localization of POE nanoparticles in New Zealand white rabbits and C57BL/6 mice after intravitreal administration for the treatment of chronic posterior ocular diseases. Two concentration levels of POE nanoparticles solution were chosen for intravitreal injection: 1.5 mg/ml and 10 mg/ml. Our results demonstrate that POE nanoparticles were distributed throughout the vitreous cavity by optical coherence tomography (OCT) examination 14 days post-intravitreal injection. Intraocular pressure was not changed from baseline. Inflammatory or adverse effects were undetectable by slit lamp biomicroscopy. Furthermore, we demonstrate that POE nanoparticles have negligible toxicity assessed at the cellular level evidenced by a lack of glia activation or apoptosis estimation after intravitreal injection. Collectively, POE nanoparticles are a novel and nontoxic as an ocular drug delivery system for the treatment of posterior ocular diseases.

Li|Huiling|H|
Palamoor|Mallika|M|
Jablonski|Monica M|MM|

poly(ortho ester) nanoparticles
Chronic intraocular diseases
safety
localization
intraocular delivery


The hepatitis C care cascade among people who inject drugs accessing harm reduction services in Catalonia: Major gaps for migrants.

Abstract:
BACKGROUND
This study aimed to describe the HCV cascade of care among people who inject drugs (PWID) in Catalonia, as well as to compare the observed gaps in care between Spanish-born and migrant PWID.

METHODS
A cross-sectional study of PWID (N = 410) attending four harm reduction services (HRS) was performed in 2016-17 (HepCdetect II Study). Participants were tested for both HCV antibodies (rapid testing) and RNA (from dried blood spot samples). The HCV care cascade was estimated from HCV testing results combined with self-reported data on previous testing, diagnosis and treatment collected through a questionnaire. Logistic regressions were used to test for an association between migration status and the proportions observed in each step of the HCV care cascade adjusting for age, sex, years of injection, homelessness, and treatment for drug dependence.

RESULTS
Overall, 85.4% were men and 28.0% were migrants. Among Spanish-born (n = 295) and migrant (n = 115) PWID participants in the study, 96.6% vs. 88.6% had previously been HCV screened (AOR=3.11; 95% CI: 1.11-8.65), 79.3% vs. 80.9% were antibody positive, and 70.7% vs. 67.6% were HCV-RNA positive or cured with treatment; among the latter, 36.6% vs. 18.2% had started treatment (AOR=2.41; 95% CI: 1.09-5.34), and 20.6% vs. 9.1% had been cured by treatment, respectively. Unawareness of having hepatitis C was more common among migrants than Spanish-born PWID (46.0% and 31.5%, respectively; p<0.05).

CONCLUSION
This study estimates the HCV care cascade among Spanish-born and migrant PWID in Catalonia for the very first time, and highlights a higher attrition of migrant PWID in all HCV care cascade stages. The observed limited linkage to care and treatment by PWID that attend the HRS network warrants future implementation of decentralized diagnosis and antiviral treatment. Strategies focusing on migrants by increasing HCV screening coverage and treatment access will be especially relevant in our setting.

Folch|Cinta|C| Saludes|Verónica|V| Reyes-Ureña|Juliana|J| Antuori|Adrián|A| Ibáñez|Nuria|N| Majó|Xavier|X| Colom|Joan|J| Matas|Lurdes|L| Casabona|Jordi|J| Martró|Elisa|E| |||

D003430:Cross-Sectional Studies
D040261:Harm Reduction
D006526:Hepatitis C
D006801:Humans
D008297:Male
D004364:Pharmaceutical Preparations
D013030:Spain
D015819:Substance Abuse, Intravenous
D014171:Transients and Migrants

migrants
Cascade of care
people who inject drugs (PWID)
Harm reduction services (HRS)
Hepatitis C virus (HCV)


Built to Last: Functional and Structural Mechanisms in the Moth Olfactory Network Mitigate Effects of Neural Injury.

Abstract: Most organisms suffer neuronal damage throughout their lives, which can impair performance of core behaviors. Their neural circuits need to maintain function despite injury, which in particular requires preserving key system outputs. In this work, we explore whether and how certain structural and functional neuronal network motifs act as injury mitigation mechanisms. Specifically, we examine how (i) Hebbian learning, (ii) high levels of noise, and (iii) parallel inhibitory and excitatory connections contribute to the robustness of the olfactory system in the Manduca sexta moth. We simulate injuries on a detailed computational model of the moth olfactory network calibrated to data. The injuries are modeled on focal axonal swellings, a ubiquitous form of axonal pathology observed in traumatic brain injuries and other brain disorders. Axonal swellings effectively compromise spike train propagation along the axon, reducing the effective neural firing rate delivered to downstream neurons. All three of the network motifs examined significantly mitigate the effects of injury on readout neurons, either by reducing injury's impact on readout neuron responses or by restoring these responses to pre-injury levels. These motifs may thus be partially explained by their value as adaptive mechanisms to minimize the functional effects of neural injury. More generally, robustness to injury is a vital design principle to consider when analyzing neural systems.

Delahunt|Charles B|CB|
Maia|Pedro D|PD|0000-0002-3335-4257
Kutz|J Nathan|JN|

moth olfactory network
injury mitigation
focal axonal swellings (FAS)
neuronal injury


A revision of the Australian cicada genus Punia Moulds, 2012 (Cicadidae: Cicadettinae: Cicadettini) with the description of four new species.

Abstract: Punia minima (Goding Froggatt, 1904) from the Northern Territory is redescribed and the female described for the first time. Four new species found across the monsoonal north of Australia are documented: P. hyas sp.n., P. limpida sp.n., P. kolos sp.n. and P. queenslandica sp.n. A key to all five species is provided and their phylogenetic relationships discussed.

Hemiptera, Cicadoidea, monsoonal cicadas, key to Punia species


Multilayer Mattress Stitches for Complicated Wounds in Spine Surgery.

Abstract:
Introduction
Local infection and prolonged fluid discharge account for most complications in lumbar spine surgery. This report is a brief description of a useful technique for revision of complicated, draining wounds with surprisingly positive results that otherwise frequently require multiple surgical interventions.

Technical Note
We describe the postoperative course of three patients, with prolonged and continuous serosanguineous discharge from the skin incision, who underwent wound revision with multilayered mattress stitches after open decompressive or instrumented spinal surgery. For this purpose, a thick monofilament suture is passed through the skin, subcutaneous fatty tissue, and paravertebral muscle in the fashion of a vertical mattress stitch while the loop above the skin level is augmented using a soft silicone capillary drainage to distribute tension along the wound margin.

Conclusions
None of the patients treated with the multilayered mattress stitches required further surgical intervention. In this small case series, the multilayered mattress stitches augmented with soft silicone tubing were a useful technique for treating complicated lumbar surgical wounds with prolonged serosanguineous discharge.

Bauer|David Ephraim|DE|
Laux|Christoph Johannes|CJ|
Farshad|Mazda|M|

mattress complication wound spine lumbar dermatotraction


Recognition and Management of Resistant Hypertension.

Abstract: Despite improvements in hypertension awareness and treatment, 30%-60% of hypertensive patients do not achieve BP targets and subsequently remain at risk for target organ damage. This therapeutic gap is particularly important to nephrologists, who frequently encounter treatment-resistant hypertension in patients with CKD. Data are limited on how best to treat patients with CKD and resistant hypertension, because patients with CKD have historically been excluded from hypertension treatment trials. First, we propose a consistent definition of resistant hypertension as BP levels confirmed by both in-office and out-of-office measurements that exceed appropriate targets while the patient is receiving treatment with at least three antihypertensive medications, including a diuretic, at dosages optimized to provide maximum benefit in the absence of intolerable side effects. Second, we recommend that each patient undergo a standardized, stepwise evaluation to assess adherence to dietary and lifestyle modifications and antihypertensive medications to identify and reduce barriers and discontinue use of substances that may exacerbate hypertension. Patients in whom there is high clinical suspicion should be evaluated for potential secondary causes of hypertension. Evidence-based management of resistant hypertension is discussed with special considerations of the differences in approach to patients with and without CKD, including the specific roles of diuretics and mineralocorticoid receptor antagonists and the current place of emerging therapies, such as renal denervation and baroreceptor stimulation. We endorse use of such a systematic approach to improve recognition and care for this vulnerable patient group that is at high risk for future kidney and cardiovascular events.

Braam|Branko|B|
Taler|Sandra J|SJ|
Rahman|Mahboob|M|
Fillaus|Jennifer A|JA|
Greco|Barbara A|BA|
Forman|John P|JP|
Reisin|Efrain|E|
Cohen|Debbie L|DL|
Saklayen|Mohammad G|MG|
Hedayati|S Susan|SS|

hypertension
diuretics
Mineralocorticoid Receptor
Antagonists
Denervation
kidney
Antihypertensive Agents
Humans
Life Style
Pressoreceptors
Renal Insufficiency, Chronic
blood pressure
cardiovascular disease
chronic kidney disease
renal denvervation
sodium intake


Neural adaptations in quadriceps muscle after 4 weeks of local vibration training in young versus older subjects.

Abstract: This study investigated the effects of a 4-week local vibration training (LVT) on the function of the knee extensors and corticospinal properties in healthy young and older subjects. Seventeen subjects (9 young and 8 older) performed 3 testing sessions: before (PRE1) and after (PRE2) a 4-week resting period to control the repeatability of the data as well as after the LVT (POST). Jump performance, maximal voluntary contraction (MVC) and electromyographic (EMG) activity on vastus lateralis and rectus femoris muscles were assessed. Single-pulse transcranial magnetic stimulation (TMS) allowed evaluation of cortical voluntary activation (VATMS), motor evoked potential (MEP) area, and silent period (SP) duration. All training adaptations were similar between young and older subjects (p > 0.05) and the following results reflect the pooled sample of subjects. MVC (+11.9% ± 8.0%, p < 0.001) and VATMS (+3.6% ± 5.2%, p = 0.004) were significantly increased at POST compared with PRE2. Maximal vastus lateralis EMG was significantly increased at POST (+21.9% ± 33.7%, p = 0.03). No changes were reported for MEPs on both muscles (p > 0.05). SPs recorded during maximal and submaximal contractions decreased in both muscles at POST (p < 0.05). Vertical jump performance was increased at POST (p < 0.05). LVT seems as effective in young as in older subjects to improve maximal functional capacities through neural modulations occurring at least partly at the supra-spinal level. Local vibration may be used as an efficient alternative training method to improve muscular performance in both healthy young and older subjects.

Souron|Robin|R|
Besson|Thibault|T|
Lapole|Thomas|T|
Millet|Guillaume Y|GY|

corticospinal excitability and inhibition

excitabilité et inhibition corticospinale


Pre-meal and postprandial lipaemia in subjects with the metabolic syndrome: effects of timing and protein quality (randomised crossover trial).

Abstract: Non-fasting TAG - postprandial lipaemia (PPL) - are to a higher degree associated with cardiovascular risk compared with fasting TAG. Dietary protein, especially whey proteins (WP), may lower PPL. We hypothesised that a WP pre-meal (17·6 g protein) consumed 15 v. 30 min before a fat-rich meal reduces the PPL response in subjects with the metabolic syndrome (MetS) and that a WP pre-meal has more potent effects than casein and gluten pre-meals. A total of sixteen subjects with the MetS completed an acute, randomised, crossover trial. WP pre-meals were consumed 15 and 30 min, and casein and gluten 15 min before a fat-rich meal. Blood samples were drawn 360 min postprandially to determine metabolite and hormone responses, S-paracetamol (for assessment of gastric emptying) and amino acids. Insulin and glucagon responses were affected by both timing and protein type (for all P <0·01), with significantly higher concentrations for WP given at -15 min than WP at -30 min and higher responses compared with gluten for the first 30 min after pre-meal consumption (for all P <0·05). The PPL responses changed neither by timing nor by protein type. Glucose-dependent insulinotropic peptide but not glucagon-like peptide 1 responses differed between the three protein types. S-paracetamol concentration was higher for WP (-30 min) than for WP (-15 min) 15 min after the main meal (P = 0·028), and higher for casein and gluten than for WP at time point 30 min (for all P <0·05). In conclusion, the PPL response was not changed by ingestion of a 17·6 g protein pre-meal, whereas both timing and protein quality affected hormone secretion (insulin and glucagon).

Postprandial lipaemia
Metabolic syndrome
Timing
Protein quality
Whey proteins
Pre-meal lipaemia


The effects of atorvastatin on emotional processing, reward learning, verbal memory and inflammation in healthy volunteers: An experimental medicine study.

Abstract:
BACKGROUND
Growing evidence from clinical trials and epidemiological studies suggests that statins can have clinically significant antidepressant effects, potentially related to anti-inflammatory action on several neurobiological structures. However, the underlying neuropsychological mechanisms of these effects remain unexplored.

AIMS
In this experimental medicine trial, we investigated the 7-day effects of the lipophilic statin, atorvastatin on a battery of neuropsychological tests and inflammation in healthy volunteers.

METHODS
Fifty healthy volunteers were randomised to either 7 days of atorvastatin 20 mg or placebo in a double-blind design. Participants were assessed with psychological questionnaires and a battery of well-validated behavioural tasks assessing emotional processing, which is sensitive to putative antidepressant effects, reward learning and verbal memory, as well as the inflammatory marker, C-reactive protein.

RESULTS
Compared to placebo, 7-day atorvastatin increased the recognition (p = 0.006), discriminability (p = 0.03) and misclassifications (p = 0.04) of fearful facial expression, independently from subjective states of mood and anxiety, and C-reactive protein levels. Otherwise, atorvastatin did not significantly affect any other psychological and behavioural measure, nor peripheral C-reactive protein.

CONCLUSIONS
Our results reveal for the first time the early influence of atorvastatin on emotional cognition by increasing the processing of anxiety-related stimuli (i.e. increased recognition, discriminability and misclassifications of fearful facial expression) in healthy volunteers, in the absence of more general effects on negative affective bias. Further studies exploring the effects of statins in depressed patients, especially with raised inflammatory markers, may clarify this finding and inform future clinical trials.

Atorvastatin
emotional processing
reward learning
verbal memory
inflammation
healthy volunteers
experimental medicine
depression


Hierarchical Microstructure of Tooth Enameloid in Two Lamniform Shark Species, Carcharias taurus and Isurus oxyrinchus.

Abstract: Shark tooth enameloid is a hard tissue made up of nanoscale fluorapatite crystallites arranged in a unique hierarchical pattern. This microstructural design results in a macroscopic material that is stiff, strong, and tough, despite consisting almost completely of brittle mineral. In this contribution, we characterize and compare the enameloid microstructure of two modern lamniform sharks, Isurus oxyrinchus (shortfin mako shark) and Carcharias taurus (spotted ragged-tooth shark), based on scanning electron microscopy images. The hierarchical microstructure of shark enameloid is discussed in comparison with amniote enamel. Striking similarities in the microstructures of the two hard tissues are found. Identical structural motifs have developed on different levels of the hierarchy in response to similar biomechanical requirements in enameloid and enamel. Analyzing these structural patterns allows the identification of general microstructural design principles and their biomechanical function, thus paving the way for the design of bioinspired composite materials with superior properties such as high strength combined with high fracture resistance.


Understanding the Chemical Reactivity of Phosphonium-Based Ionic Liquids with Tellurium.

Abstract: The chemical reactivity of phosphonium based ionic liquids (ILs) towards tellurium at temperatures above 220 °C was systematically investigated by a series of dissolution experiments, tracking the solute tellurium species by nuclear magnetic resonance, and characterizing the reaction products by X-ray diffraction and scanning electron microscopy. The initial step is the thermal elimination of an alkyl group of the phosphonium cation of the ILs, most probably via an SN 2 mechanism. The addition of tellurium follows to form trialkylphosphane tellurides as evidenced by 31 P and 125 Te NMR spectroscopic experiments. The trialkylphosphane tellurides can serve as a tellurium reservoir for the formation of metal tellurides, like Bi2 Te3 and Ag2 Te. It was observed that trihexyltetradecylphosphonium chloride ([P6 6 6 14 ]Cl) shows a very weak reactivity that is reflected by a low solubility of tellurium, while trihexyltetradecylphosphonium dicyanamide/decanoate ([P6 6 6 14 ][N(CN)2 ]/[P6 6 6 14 ][decanoate]) and tetrabutylphosphonium decanoate ([P4 4 4 4 ][decanoate]) dissolve tellurium to a much higher extent. We attribute these observations to the different Lewis basicity of the anions of the ILs as main influencing factor.

reactivity
ionic liquids
tellurium
phosphonium
trialkylphosphane tellurides


Temporal trend in the natural history of ulcerative colitis in a country with a low incidence of ulcerative colitis from 2000 through 2018.

Abstract:
BACKGROUND/AIMS
The incidence of ulcerative colitis (UC) in Thailand (crude incidence rate of 0.28 per 100,000 persons) is much lower than in the West. The burden of UC varies in different populations. The aim of this study was to evaluate the natural history of UC over the two decades in Bangkok, Thailand.

METHODS
This retrospective study included patients who were diagnosed with UC between 2000 and 2018 in 2 university hospitals. To evaluate changes in the disease course, we stratified patients into 2000-2009 cohort and 2010-2018 cohort. The cumulative probability of endoscopic healing, UC-related hospitalization and colectomy was estimated using the Kaplan-Meier method.

RESULTS
A total of 291 UC patients were followed for total of 2,228 person-years. Comparison between 2 cohorts, there were no differences in disease pattern and severity whereas an increase in the combination use of oral and topical mesalamine and the early use of thiopurine was observed. Only 1% of patients for each cohort required biologic agent at 5 years. The rate of achieving mucosal healing increased from 15% to 46% at 3 years (P< 0.01). The rate of UC-related hospitalization decreased from 30% to 21% at 5 years (P< 0.05). The rate of colectomy decreased from 6% to 2% at 5 years (P< 0.05).

CONCLUSIONS
The natural history of UC in a low incidence country was less aggressive than the West. Over the past two decades, the rates of UC-related hospitalization and colectomy have been decreasing which were similar to the West.

Aniwan|Satimai|S| Limsrivilai|Julajak|J| Pongprasobchai|Supot|S| Pausawasdi|Nonthalee|N| Prueksapanich|Piyapan|P| Kongtub|Natanong|N| Rerknimitr|Rungsun|R|

Natural history
Colitis, ulcerative
Epidemiology
Inflammatory bowel disease


Comparing the effect of sucrose gel and metronidazole gel in treatment of clinical symptoms of bacterial vaginosis: a randomized controlled trial.

Abstract:
BACKGROUND
Lactobacilli, as normal vaginal flora, have a central role in controlling body environment and preventing the growth of pathogens. Sucrose, by promoting the growth of Lactobacilli, accelerates the suppression of pathogenic bacteria. The aim of this research was to compare the effects of sucrose gel with those of metronidazole gel in treating women with bacterial vaginosis (BV).

METHODS
This triple-blind clinical trial (IRCT2016112631105N1) was conducted with 70 sexually active, premenopausal women diagnosed with bacterial vaginosis through meeting at least three out of four Amsel criteria. The subjects were randomly divided into two groups of 35 patients, one group treated with sucrose vaginal gel, and the other with metronidazole vaginal gel. The treatment period was 14 days for each group. At the end of the treatment period, the status of each woman's improvement was determined by elimination at least three out of four Amsel criteria (homogeneous vaginal discharge, presence of clue cells > 20%, positive whiff test and vaginal pH value > 4.5), and clinical complaints and reported side effects of medication were recorded for the patients. Data were analyzed using the t test, chi-squared test and McNemar's test).

RESULTS
The sucrose vaginal gel and metronidazole vaginal gel were not significantly different in reducing patients' clinical complaints or in elimination at least three out of four of the Amsel criteria that were positive before treatment. With an 85.7% improvement rate with sucrose gel and an 88.5% improvement rate with metronidazole gel, the differences in therapeutic response were not significant, and neither was statistically different in improving the disease (p = 0.389).

CONCLUSION
It seems that sucrose vaginal gel might be considered a possible alternative to metronidazole vaginal gel in the treatment of bacterial vaginosis.

TRIAL REGISTRATION
Iranian Registry of Clinical Trials, IRCT2016112631105N1 . Registered on 27 December 2016.

Bacterial vaginosis
Sucrose vaginal gel
Metronidazole vaginal gel


Differential Impact of Visuospatial Working Memory on Rule-based and Information-integration Category Learning.

Abstract: Previous studies have indicated that the category learning system is a mechanism with multiple processing systems, and that working memory has different effects on category learning. But how does visuospatial working memory affect perceptual category learning? As there is no definite answer to this question, we conducted three experiments. In Experiment 1, the dual-task paradigm with sequential presentation was adopted to investigate the influence of visuospatial working memory on rule-based and information-integration category learning. The results showed that visuospatial working memory interferes with rule-based but not information-integration category learning. In Experiment 2, the dual-task paradigm with simultaneous presentation was used, in which the categorization task was integrated into the visuospatial working memory task. The results indicated that visuospatial working memory affects information-integration category learning but not rule-based category learning. In Experiment 3, the dual-task paradigm with simultaneous presentation was employed, in which visuospatial working memory was integrated into the category learning task. The results revealed that visuospatial working memory interferes with both rule-based and information-integration category learning. Through these three experiments, we found that, regarding the rule-based category learning, working memory load is the main mechanism by which visuospatial working memory influences the discovery of the category rules. In addition, regarding the information-integration category learning, visual resources mainly operates on the category representation.


Absorption, distribution, metabolism, and excretion of 14C-MMB4 DMS administered intramuscularly to Sprague-Dawley rats and New Zealand White rabbits.

Abstract: 1,1'-Methylenebis[4-[(hydroxyimino)methyl]-pyridinium] dimethanesulfonate (MMB4 DMS) is currently under development for the treatment of chemical warfare organophosphorus nerve agent poisoning. The present study evaluates the absorption, distribution, metabolism, and excretion of (14)C-MMB4 DMS administered intramuscularly to rats and rabbits. The formulated mixture of radiolabeled and nonradiolabeled MMB4 DMS was administered as a single or 7-day repeated dose. Rat doses were 55 or 220 mg/kg (100 µCi/kg), and rabbit doses were 25 or 100 mg/kg (31.25 and 62.5 µCi/kg, respectively). Urine, bile (rats only), feces, blood, and tissues were collected for up to 72 hours. Metabolic profiling using high-performance liquid chromatography with radiodetection was performed on selected urine samples. For both animal species, the majority of the total radioactivity was excreted in the urine (74%-94%) by 72 hours after dosing with greater than 90% of the radioactivity measured in the urine within 8 to 12 hours after dosing. There were no apparent species or dose differences in the urine excretion pattern. The distribution of (14)C-MMB4 DMS-derived radioactivity was rapid and generally reached the highest concentration by the first collection time point (0.25 hours). The tissue-blood concentration ratios were highest at the injection sites and in the kidneys and gastrointestinal tract contents for both the species. Two metabolites of MMB4 DMS were detected in rat and rabbit urine; their structure was confirmed by liquid chromatography with tandem mass spectrometry as 4-pyridine aldoxime and isonicotinic acid (pyridine-4-carboxylic acid).

Lusiak|Bozena D|BD|
Kobs|Dean J|DJ|
Hong|S Peter|SP|
Burback|Brian L|BL|
Johnson|Jerry D|JD|

rat
rabbit
MMB4
MMB4 DMS
ADME
intramuscular


Network analysis based on low-rank method for mining information on integrated data of multi-cancers.

Abstract: The noise problem of cancer sequencing data has been a problem that can't be ignored. Utilizing considerable way to reduce noise of these cancer data is an important issue in the analysis of gene co-expression network. In this paper, we apply a sparse and low-rank method which is Robust Principal Component Analysis (RPCA) to solve the noise problem for integrated data of multi-cancers from The Cancer Genome Atlas (TCGA). And then we build the gene co-expression network based on the integrated data after noise reduction. Finally, we perform nodes and pathways mining on the denoising networks. Experiments in this paper show that after denoising by RPCA, the gene expression data tend to be orderly and neat than before, and the constructed networks contain more pathway enrichment information than unprocessed data. Moreover, learning from the betweenness centrality of the nodes in the network, we find some abnormally expressed genes and pathways proven that are associated with many cancers from the denoised network. The experimental results indicate that our method is reasonable and effective, and we also find some candidate suspicious genes that may be linked to multi-cancers.

Hou|Mi-Xiao|MX| Gao|Ying-Lian|YL| Liu|Jin-Xing|JX| Dai|Ling-Yun|LY| Kong|Xiang-Zhen|XZ| Shang|Junliang|J|

D057225:Data Mining
D030541:Databases, Genetic
D020869:Gene Expression Profiling
D053263:Gene Regulatory Networks
D006801:Humans
D009369:Neoplasms
D025341:Principal Component Analysis

Integrated data
Multi-cancers
Gene co-expression network
Noise reduction
Abnormally expressed genes


Production of Sustainable Construction Materials Using Agro-Wastes.

Abstract: The construction sector, in modern times, is faced by a myriad of challenges primarily due to the increase in the urban population and dwindling natural resources that facilitate the production of construction materials. Furthermore, higher awareness on climate change is forcing companies to rethink their strategies in developing more sustainable construction materials. Diverse types of agro-waste ranging from rice husk ash (RHA), sugarcane bagasse ash (SCBA), and bamboo leaves ash (BLA) among others have been identified as potent solutions in the development of sustainable construction materials. In this review paper, six different construction materials, made using agro-waste products, are examined. The materials include brick/masonry elements, green concrete, insulation materials for buildings, reinforcement materials for buildings, particleboards, and bio-based plastics. The main criterion adopted in selecting the materials regards their popularity and wide-scale use in modern construction applications. Additionally, as this research emphasizes identifying alternative approaches to develop sustainable construction materials, the focus is directed toward mainstream materials whose continued use has an adverse impact on the environment. The findings obtained from the review showed that the use of agro-waste to develop sustainable construction materials was effective, as the developed materials adhered to established building standards. Therefore, this indicates that agro-waste materials have the potential to replace conventional construction materials and hence achieve economic, environmental, and social sustainability in the long run.

sustainable
construction materials
agricultural by-products


Impact of the 'Seguro Médico Siglo XXI' medical insurance programme on neonatal and infant mortality in Mexico, 2006-14: an ecological approach to estimation.

Abstract: The 'Seguro Médico Siglo XXI' (SMSXXI), a universal coverage medical insurance programme for children under 5 years of age, started in 2006 to help avoid catastrophic health expenditures in poor families without social security in Mexico. The study used information from the National Health Information System for the 2006-14 period. An ecological approach was followed with a panel of the 2457 municipalities of Mexico as the units of analysis. The outcome variables were the municipality-level neonatal mortality and infant mortality rates in population without access to social security. The programme variable was the coverage of the SMSXXI programme at the municipality level, expressed as a proportion. Demographic and economic variables defined at the municipality level were included as covariates. Impact was estimated by fitting a fixed-effects negative binomial regression model. Results reveal that the SMSXXI significantly reduced both infant and neonatSal mortality in the target population, although in a non-linear fashion, with minimum mortality levels found around the 70% coverage range. The effect is mostly given by the transition from the first quintile to the fourth quintile of coverage (<13% vs 70.5-93.7% coverage), and it is attenuated significantly at coverage levels very close to or at 100%. The observed risk reduction amounted to an estimated total of 11 358 infant deaths being avoided due to the SMSXXI during the 2006-14 period, of which 48% were neonatal. In conclusion, we found a significant impact of the SMSXXI programme on both infant mortality and neonatal mortality. An attenuation of the effect of the insurance on mortality rates at levels close to 100% coverage may reflect the saturation of health units in detriment of the quality of care.

Urquieta-Salomón|José|J|
Lamadrid-Figueroa|Héctor|H|
Angeles|Gustavo|G|
Montoya|Alejandra|A|
Rojas-Martínez|Rosalba|R|
Martínez-Nolasco|Alejandro|A|
Torres-Pereda|Pilar|P|
O'Shea|Gabriel|G|
Villagrán|Victor M|VM|
Halley|Elizabeth|E|
Delgado-Sánchez|Verónica|V|
Lazcano-Ponce|Eduardo|E|

medical insurance
infant mortality
Mexico
Neonatal mortality
impact evaluation


Cancer and stress: NextGen strategies.

Abstract: Chronic stress is well-known to cause physiological distress that leads to body balance perturbations by altering signaling pathways in the neuroendocrine and sympathetic nervous systems. This increases allostatic load, which is the cost of physiological fluctuations that are required to cope with psychological challenges as well as changes in the physical environment. Recent studies have enriched our knowledge about the role of chronic stress in disease development, especially carcinogenesis. Stress stimulates the hypothalamic-pituitaryadrenal (HPA) axis and the sympathetic nervous system (SNS), resulting in an abnormal release of hormones. These activate signaling pathways that elevate expression of downstream oncogenes. This occurs by activation of specific receptors that promote numerous cancer biological processes, including proliferation, genomic instability, angiogenesis, metastasis, immune evasion and metabolic disorders. Moreover, accumulating evidence has revealed that β-adrenergic receptor (ADRB) antagonists and downstream target inhibitors exhibit remarkable anti-tumor effects. Psychosomatic behavioral interventions (PBI) and traditional Chinese medicine (TCM) also effectively relieve the impact of stress in cancer patients. In this review, we discuss recent advances in the underlying mechanisms that are responsible for stress in promoting malignancies. Collectively, these data provide approaches for NextGen pharmacological therapies, PBI and TCM to reduce the burden of tumorigenesis.

Cui|Bai|B|
Peng|Fei|F|
Lu|Jinxin|J|
He|Bin|B|
Su|Qitong|Q|
Luo|Huandong|H|
Deng|Ziqian|Z|
Jiang|Tonghui|T|
Su|Keyu|K|
Huang|Yanping|Y|
Ud Din|Zaheer|Z|
Lam|Eric W-F|EW|
Kelley|Keith W|KW|
Liu|Quentin|Q|

D052636:Allostasis
D006801:Humans
D007030:Hypothalamo-Hypophyseal System
D009369:Neoplasms
D009490:Neurosecretory Systems
D010913:Pituitary-Adrenal System
D013312:Stress, Physiological
D013315:Stress, Psychological
D013564:Sympathetic Nervous System


Impact of the Dynamic Change of Metabolic Health Status on the Incident Type 2 Diabetes: A Nationwide Population-Based Cohort Study.

Abstract:
BACKGROUND
Metabolically healthy obese (MHO) is regarded as a transient concept. We examined the effect of the dynamic change of metabolic health status on the incidence of type 2 diabetes mellitus (T2DM) both in obese and normal weight individuals.

METHODS
We analyzed 3,479,514 metabolically healthy subjects aged over 20 years from the Korean National Health Screening Program, who underwent health examination between 2009 and 2010, with a follow-up after 4 years. The relative risk for T2DM incidence until the December 2017 was compared among the four groups: stable metabolically healthy normal weight (MHNW), unstable MHNW, stable MHO, and unstable MHO.

RESULTS
During the 4 years, 11.1% of subjects in the MHNW group, and 31.5% in the MHO group converted to a metabolically unhealthy phenotype. In the multivariate adjusted model, the unstable MHO group showed the highest risk of T2DM (hazard ratio [HR], 4.67; 95% confidence interval [CI], 4.58 to 4.77). The unstable MHNW group had a higher risk of T2DM than stable MHO group ([HR, 3.23; 95% CI, 3.16 to 3.30] vs. [HR, 1.81; 95% CI, 1.76 to 1.85]). The stable MHO group showed a higher risk of T2DM than the stable MHNW group. The influence of the transition into a metabolically unhealthy phenotype on T2DM incidence was greater in subjects with aged <65 years, women, and those with weight gain.

CONCLUSION
Metabolically healthy phenotype was transient both in normal weight and obese individuals. Maintaining metabolic health was critical for the prevention of T2DM, irrespective of their baseline body mass index.

Kim|Jung A|JA|0000-0002-6595-6551
Kim|Da Hye|DH|
Kim|Seon Mee|SM|
Park|Yong Gyu|YG|
Kim|Nan Hee|NH|
Baik|Sei Hyun|SH|
Choi|Kyung Mook|KM|
Han|Kyungdo|K|0000-0002-6096-1263
Yoo|Hye Jin|HJ|0000-0003-0600-0266

Obesity
Diabetes mellitus, type 2
Metabolic syndrome


Disease-modifying effects of ranibizumab for central retinal vein occlusion.

Abstract:
PURPOSE
To identify anatomic endpoints altered by intravitreal ranibizumab in central retinal vein occlusion (CRVO) to determine any potential underlying disease modification that occurs with anti-vascular endothelial growth factor (anti-VEGF) therapy beyond best-corrected visual acuity and central optical coherence tomography outcomes.

METHODS
A post hoc analysis of a double-masked, multicenter, randomized clinical trial was performed. A total of 392 patients with macular edema after CRVO were randomized 1:1:1 to receive monthly intraocular injections of 0.3 or 0.5 mg of ranibizumab or sham injections. Central reading center-read data were reviewed to explore potential anatomic endpoints altered by therapy.

RESULTS
At 6 months, there was a reduction in the ranibizumab groups compared with sham groups with respect to total area of retinal hemorrhage (median change from baseline in disc areas: - 1.17 [sham], - 2.37 [ranibizumab 0.3 mg], - 1.64 [ranibizumab 0.5 mg]), development of disc neovascularization (prevalence: 3% [sham], 0% [ranibizumab 0.3 mg], 0% [ranibizumab 0.5 mg]), and presence of papillary swelling (prevalence: 22.9% [sham], 8.0% [ranibizumab 0.3 mg], 8.3% [ranibizumab 0.5 mg], p < 0.01). There was no difference between groups in collateral vessel formation. Analysis of vitreous and preretinal hemorrhage could not be performed due to low frequency of events in both treated and sham groups.

CONCLUSIONS
Ranibizumab for CRVO resulted in beneficial disease-modifying effects through a reduction in retinal hemorrhage, neovascularization, and papillary swelling. These findings may form the basis for future work in the development of a treatment response or severity scale for eyes with CRVO.

Huang|Jason M|JM|
Khurana|Rahul N|RN|
Ghanekar|Avanti|A|
Wang|Pin-Wen|PW|
Day|Bann-Mo|BM|
Blodi|Barbara A|BA|
Domalpally|Amitha|A|
Quezada-Ruiz|Carlos|C|
Ip|Michael S|MS|

Neovascularization
Drugs
Retina
Treatment medical


Stage IA Patients With Pancreatic Ductal Adenocarcinoma Cannot Benefit From Chemotherapy: A Propensity Score Matching Study.

Abstract: Purpose: Adjuvant chemotherapy following resection is recommended by clinical practice guidelines for all patients with pancreatic ductal adenocarcinoma (PDAC). This study aimed to evaluate the efficacy of adjuvant chemotherapy among the staging groups of the American Joint Committee on Cancer (AJCC) for PDAC. Patients and Methods: This retrospective cohort analysis was performed by the Surveillance Epidemiology and End Results (SEER) (2004-2015) database and multi-institutional dataset (2010-2018). Baseline clinicopathologic characteristics of PDAC patients, including age, gender, ethnicity, marital status, education level, county income level, county unemployed rate, insurance status, grade, stage, chemotherapy, and radiotherapy, were collected. Overall survival (OS) was analyzed using the Kaplan-Meier method. The SEER and multi-institutional data were adjusted with 1:1 ratio propensity score matching (PSM). Results: In total, 6,274 and 1,361 PDAC patients were included from the SEER database and multi-institutional dataset, respectively. Regardless of the count of resected lymph nodes, adjuvant chemotherapy prolonged the long-term OS time for stage IB, IIA, IIB, and III patients in both SEER and multi-institutional cohorts. Nevertheless, adjuvant chemotherapy did not provide additional clinical benefits even after a PSM adjustment for stage IA patients in both SEER and multi-institutional cohorts. Conclusion: Adjuvant chemotherapy improved the long-term survival of stage IB, IIA, IIB, and III PDAC patients; however, it demonstrated no survival benefit in stage IA PDAC patients. Thus, adjuvant chemotherapy should not be recommended for stage IA PDAC patients. These would significantly reduce the economic burden of society and improve the life quality of stage IA PDAC patients.

Zhang|Yuchao|Y| Xu|Gang|G| Chen|Maozhen|M| Wei|Qian|Q| Zhou|Tengteng|T| Chen|Ziliang|Z| Shen|Mingyang|M| Wang|Ping|P|

pancreatic ductal adenocarcinoma
chemotherapy
Surveillance
Epidemiology
End Results (SEER)
overall survival
prognosis


Supratentorial extraventricular anaplastic ependymoma presenting with repeated intratumoral hemorrhage.

Abstract: Supratentorial extraventricular anaplastic ependymomas are extremely rare. We report the case of a 23-year-old male with a supratentorial extraventricular anaplastic ependymoma that presented with repeated intratumoral hemorrhage. The patient was diagnosed with an intracerebral hematoma in the left occipital lobe and underwent operation. The hematoma did not reveal tumor cells, but a new tumor grew in the same location 5 years later. Magnetic resonance imaging showed a tumor with intratumoral hemorrhage. The patient underwent the tumor resection. Intraoperative findings showed that the tumor had no continuity with the ventricle. Histopathological examinations confirmed an anaplastic ependymoma. The spinal evaluation was unremarkable, and radiotherapy was administered to the left occipital lobe. Four years later, the tumor recurred at the cervicomedullary junction and T8-T9 levels. This case demonstrates that anaplastic ependymomas should be included in the differential diagnoses of supratentorial extraventricular tumors presenting with repeated intratumoral hemorrhage.

Han|Min-Hee|MH| Park|Ki-Su|KS| Park|Seong-Hyun|SH| Hwang|Jeong-Hyun|JH|

Supratentorial extraventricular
Anaplastic ependymoma
Intratumoral hemorrhage
Magnetic resonance imaging


Inflammatory myofibroblastic tumor of the small intestine mimicking acute appendicitis: a case report and review of the literature.

Abstract:
BACKGROUND
Inflammatory myofibroblastic tumor is a rare tumor of a borderline malignancy. Although it is commonly seen in children, the number of childhood cases in the current literature is limited. The lung is the most commonly affected location. However, cases that have been documented in the mesentery-omentum have mostly been located in the mesentery of the small bowel and not in the antimesenteric edge as in our patient.

CASE PRESENTATION
A 6-year-old Greek boy was referred to our hospital with acute abdominal pain mimicking appendicitis. Ultrasound and computed tomography revealed a solid mass in the abdomen. The patient underwent laparoscopic resection of the tumor, and histopathology and immunohistochemical analysis favored an omental-mesenteric myxoid hamartoma, which is a variant of an inflammatory myofibroblastic tumor. The patient's postoperative course was uneventful, and he has been asymptomatic during follow-up.

CONCLUSIONS
Inflammatory myofibroblastic tumor of the small intestine is a rare, benign neoplasm in children that should be considered as a possible cause of acute abdomen. A precise diagnosis can be made on the basis of histologic findings. Surgical excision is the treatment of choice.

Oeconomopoulou|Alexandra|A|
de Verney|Yvelise|Y|
Kanavaki|Katerina|K|
Stefanaki|Kalliopi|K|
Pavlakis|Kitty|K|
Salakos|Christos|C|

D018204:Neoplasms, Connective and Soft Tissue

Inflammatory myofibroblastic tumor (IMT)

Omental-mesenteric myxoid hamartoma (OMMH)


Identification and characterization of the 285L and K145R proteins of African swine fever virus.

Abstract: African swine fever (ASF) is a lethal disease of domestic pigs and wild boar, against which no vaccines are available to date. The large dsDNA genome of African swine fever virus (ASFV) contains up to 167 ORFs predicted to encode proteins. The functions and antigenic properties of many of these proteins are still unknown, which impedes vaccine development. Based on the results of mass spectrometry-based proteome analyses of ASFV-infected cells, two highly abundant but previously uncharacterized viral proteins, p285L and pK145R, were investigated in detail. To this end, monospecific rabbit antisera and corresponding gene deletion mutants of ASFV were prepared. RNA and immunoblot analyses revealed that p285L is an early gene product expressed prior to viral DNA replication, whereas pK145R is a true late protein. The predicted membrane protein p285L could be localized in purified ASFV particles. In contrast, pK145R was not detectable in virions, but accumulated diffusely in the cytoplasm of infected cells. Deletion of 285L or K145R from the genome of a virulent ASFV strain from Armenia did not significantly affect spread and productive growth in a permissive wild boar lung cell line, nor in primary macrophage cultures. Future studies must elucidate, whether p285L and pK145R, although non-essential for in vitro propagation of ASFV, are relevant for replication or virulence in swine. Furthermore, it remains to be investigated whether deletion of the abundant ASFV proteins p285L or pK145R might support serological differentiation from wild-type-infected animals.

Hübner|Alexandra|A|
Keßler|Catharina|C|
Pannhorst|Katrin|K|
Forth|Jan Hendrik|JH|
Kabuuka|Tonny|T|
Karger|Axel|A|
Mettenleiter|Thomas C|TC|
Fuchs|Walter|W|

D015967:Gene Expression Regulation, Viral


Navafenterol (AZD8871) in patients with COPD: a randomized, double-blind, phase I study evaluating safety and pharmacodynamics of single doses of this novel, inhaled, long-acting, dual-pharmacology bronchodilator.

Abstract:
BACKGROUND
Navafenterol (AZD8871) is a dual-pharmacology muscarinic antagonist β2-agonist (MABA) molecule in development for the treatment of chronic obstructive pulmonary disease (COPD). The pharmacodynamics, safety and tolerability of single doses of navafenterol were investigated in patients with moderate to severe COPD.

METHODS
This was a randomized, five-way complete cross-over study. Patients received single doses of navafenterol 400 μg, navafenterol 1800 μg and placebo (all double-blind) and indacaterol 150 μg and tiotropium 18 μg (both open-label active comparators). The primary pharmacodynamic endpoint was change from baseline in trough forced expiratory volume in 1 s (FEV1) on day 2. Safety and tolerability were monitored throughout.

RESULTS
Thirty-eight patients were randomized and 28 (73.7%) completed the study. Navafenterol 400 μg and 1800 μg demonstrated statistically significant improvements vs placebo in change from baseline in trough FEV1 (least squares mean [95% confidence interval]: 0.111 [0.059, 0.163] L and 0.210 [0.156, 0.264] L, respectively, both P < .0001). The changes were significantly greater with navafenterol 1800 μg vs the active comparators (least squares mean treatment difference: 0.065-0.069 L, both P < .05). The frequency of treatment-emergent adverse events was similar for placebo and the active comparators (range 34.4-37.5%), slightly higher for navafenterol 400 μg (52.9%), and lowest for navafenterol 1800 μg (22.6%).

CONCLUSIONS
Both doses of navafenterol demonstrated sustained bronchodilation over 24 h. Navafenterol was well tolerated and no safety concerns were raised.

TRIAL REGISTRY
ClinicalTrials.gov ; No.: NCT02573155 ; URL: www.clinicaltrials.gov . Registered 9th October, 2015.

Singh|Dave|D| Balaguer|Victor|V| Astbury|Carol|C| Wählby-Hamrén|Ulrika|U| Jimenez|Eulalia|E| Seoane|Beatriz|B| Villarroel|Cristina|C| Lei|Alejhandra|A| Aggarwal|Ajay|A| Psallidas|Ioannis|I|

D058666:Adrenergic beta-2 Receptor Agonists

D029424:Pulmonary Disease, Chronic Obstructive

Dual-pharmacology muscarinic receptor antagonist β2-adrenoceptor agonist


Enhanced active extracellular polysaccharide production from Ganoderma formosanum using computational modeling.

Abstract: Extracellular polysaccharide (EPS) is one of the major bioactive ingredients contributing to the health benefits of Ganoderma spp. In this study, response surface methodology was applied to determine the optimal culture conditions for EPS production of Ganoderma formosanum. The optimum medium composition was found to be at initial pH 5.3, 49.2 g/L of glucose, and 4.9 g/L of yeast extract by implementing a three-factor-three-level Box-Behnken design. Under this condition, the predicted yield of EPS was up to 830.2 mg/L, which was 1.4-fold higher than the one from basic medium (604.5 mg/L). Furthermore, validating the experimental value of EPS production depicted a high correlation (100.4%) with the computational prediction response model. In addition, the percentage of β-glucan, a well-recognized bioactive polysaccharide, in EPS was 53±5.5%, which was higher than that from Ganoderma lucidum in a previous study. Moreover, results of monosaccharide composition analysis indicated that glucose was the major component of G. formosanum EPS, supporting a high β-glucan percentage in EPS. Taken together, this is the first study to investigate the influence of medium composition for G. formosanum EPS production as well as its β-glucan composition.

Hsu|Kai-Di|KD| Wu|Shu-Pei|SP| Lin|Shin-Ping|SP| Lum|Chi-Chin|CC| Cheng|Kuan-Chen|KC|

extracellular polysaccharide
Ganoderma formosanum
response surface methodology
medium composition
β-glucan


Are three-dimensional airway evaluations obtained through computed and cone-beam computed tomography scans predictable from lateral cephalograms? A systematic review of evidence.

Abstract:
OBJECTIVE
To systematically review the literature correlating upper airway parameters between lateral cephalograms (LC) and cone-beam computed tomography (CBCT) or computed tomography (CT) scans to determine the utility of using LC to predict three-dimensional airway parameters.

MATERIALS AND METHODS
Both electronic and manual searches of the included studies were performed by two reviewers, and the quality of the studies that met selection criteria were assessed.

RESULTS
A total of 11 studies from the literature met the selection criteria. Assessed outcome variables showed correlation r < .7 between the LC and CT scans. The correlation between the LC and CBCT ranged from weak to strong with -.78 ≤ r and r ≤ .93 reported in the nasopharyngeal segment. In the oropharyngeal segment, a weak to strong correlation was reported with a range of -37 ≤ r and r ≤ .83 between the CBCT and LC. All associations in the hypopharyngeal segment showed a weak correlation. Four of studies were of weak quality, five were of moderate quality, and two were rated to be of strong quality.

CONCLUSION
No strong correlations were reported between the LC and CT scans. However, the LC-derived adenoid-nasopharyngeal ratio and the linear measurement (posterior nasal spine, PNS, to posterior pharyngeal wall) had a strong correlation with upright nasopharyngeal area and volume in the CBCTs. The area measurement in conventional LC can be also used as an initial screening tool to predict the upright three-dimensional oropharyngeal volumetric data. The variability of the hypopharyngeal segment cannot be predicted by LCs. However, more well-designed studies are needed to determine the clinical utility of using LC to predict airway size.

Eslami|Ehsan|E|
Katz|Eliot S|ES|
Baghdady|Mariam|M|
Abramovitch|Kenneth|K|
Masoud|Mohamed I|MI|

Lateral cephalograms
Systematic review
Upper airway
Cone beam computed tomography


Cardiac iron load and function in transfused patients treated with deferasirox (the MILE study).

Abstract:
OBJECTIVES
To assess the effect of iron chelation therapy with deferasirox on cardiac iron and function in patients with transfusion-dependent thalassemia major, sickle cell disease (SCD), and myelodysplastic syndromes (MDS).

METHODS
This phase IV, single-arm, open-label study over 53 wk evaluated the change in cardiac and liver iron load with deferasirox (up to 40 mg/kg/d), measured by magnetic resonance imaging (MRI).

RESULTS
Cardiac iron load (myocardial T2*) significantly improved (P = 0.002) overall (n = 46; n = 36 thalassemia major, n = 4 SCD, n = 6 MDS). Results were significant for patients with normal and moderate baseline cardiac iron (P = 0.017 and P = 0.015, respectively), but not in the five patients with severe cardiac iron load. Liver iron concentration (LIC) significantly decreased overall [mean LIC 10.4 to 8.2 mg Fe/g dry tissue (dw); P = 0.024], particularly in those with baseline LIC >7 mg Fe/g dw (19.9 to 15.6 mg Fe/g dw; P = 0.002). Furthermore, myocardial T2* significantly increased in patients with LIC <7 mg Fe/g dw, but not in those with a higher LIC. Safety was consistent with previous reports.

CONCLUSIONS
Once-daily deferasirox over 1 yr significantly increased myocardial T2* and reduced LIC. This confirms that single-agent deferasirox is effective in the management of cardiac iron, especially for patients with myocardial T2* >10 ms (Clinicaltrials.gov identifier: NCT00673608).

magnetic resonance imaging iron assessment


High-dose 8% capsaicin patch in treatment of chemotherapy-induced peripheral neuropathy: single-center experience.

Abstract: High-dose capsaicin patch is effective in treatment of neuropathic pain in HIV-associated neuropathy and diabetic neuropathy. There are no studies assessing effectiveness of high-dose capsaicin patch in treatment of chemotherapy-induced peripheral neuropathy. We sought to determine the effectiveness of treatment of pain associated with chemotherapy-induced peripheral neuropathy with high-dose capsaicin patch. Our study group consisted of 18 patients with clinically confirmed oxaliplatin-induced neuropathy. Baseline characteristic including underling disease, received cumulative dose of neurotoxic agent, neuropathic symptoms, prior treatment and initial pain level were recorded. Pain was evaluated with Numeric Rating Scale prior to treatment with high-dose capsaicin and after 1.8 day and after 8 and 12 weeks after introducing treatment. Patients were divided into two groups accordingly to the amount of neurotoxic agent that caused neuropathy (high sensitivity and low sensitivity group). Most frequent symptoms of chemotherapy-induced neuropathy were: pain (88.89%), paresthesis (100%), sock and gloves sensation (100%) and hypoesthesis (100%). Initial pain level was 7.45 ± 1.14. Mean cumulative dose of oxaliplatin after which patients developed symptoms was 648.07 mg/m2. Mean pain level after 12 weeks of treatment was 0.20 ± 0.41. When examined according to high and low sensitivity to neurotoxic agent patients with low sensitivity had higher pain reduction, especially after 8 days after introducing treatment (69.55 ± 12.09 vs. 49.40 ± 20.34%; p = 0.02) and after 12 weeks (96.96 ± 5.56 vs. 83.93 ± 18.59%; p = 0.04). High-dose capsaicin patch is an effective treatment for pain associated with chemotherapy-induced neuropathy in patients treated with oxaliplatin. Patients with lower sensitivity to neurotoxic agents have better response to treatment and pain reduction.