The evolution of autotrophy in relation to phosphorus requirement.

Abstract: The evolution of autotrophy is considered in relation to the availability of phosphorus (P), the ultimate elemental resource limiting biological productivity through Earth's history. Work on microbes and plants is emphasized, dealing in turn with the main uses for P in cells, namely nucleic acids, phospholipids, and water-soluble low molecular mass phosphate esters plus metabolically active inorganic orthophosphate. There is a greater minimum gene number and minimum DNA content in autotrophic than in osmochemoorganotrophic archaea and bacteria, as well as a lower rate of biomass increase per unit P (P-use efficiency) in autotrophs than in osmochemoorganotrophs, in eukaryotes as well as bacteria. This may be due to the diversion of rRNA from producing proteins common to all organisms to producing highly expressed proteins specific to autotrophs. The P requirement for phospholipids is decreased in oxygenic photolithotrophs, and some anoxygenic photolithotrophs, by substituting galactolipids and sulpholipids for phospholipids in the photosynthetic, and some other, membranes. The six different autotrophic inorganic carbon assimilation pathways have varying requirements for low molecular mass water-soluble phosphate esters. In oxygenic photolithotrophs, there is no clear evidence of a different P requirement for growth in the absence (diffusive CO2 entry) relative to the presence of CO2-concentrating mechanisms (CCMs). P limitation increases the expression of crassulacean acid metabolism (CAM) in facultative CAM plants, decreases the extent of inorganic carbon accumulation in algae with CCMs, and (usually) their inorganic carbon affinity and the water-use efficiency of growth of terrestrial plants, and the light-use efficiency of photolithotrophs.

phospholipids
rRNA
CO2-concentrating mechanisms
Anoxygenic photosynthesis
Rubisco.
chemolithotrophs
oxygenic photosynthesis


Microchannel-based regenerative scaffold for chronic peripheral nerve interfacing in amputees.

Abstract: Neurally controlled prosthetics that cosmetically and functionally mimic amputated limbs remain a clinical need because state of the art neural prosthetics only provide a fraction of a natural limb's functionality. Here, we report on the fabrication and capability of polydimethylsiloxane (PDMS) and epoxy-based SU-8 photoresist microchannel scaffolds to serve as viable constructs for peripheral nerve interfacing through in vitro and in vivo studies in a sciatic nerve amputee model where the nerve lacks distal reinnervation targets. These studies showed microchannels with 100 μm × 100 μm cross-sectional areas support and direct the regeneration/migration of axons, Schwann cells, and fibroblasts through the microchannels with space available for future maturation of the axons. Investigation of the nerve in the distal segment, past the scaffold, showed a high degree of organization, adoption of the microchannel architecture forming 'microchannel fascicles', reformation of endoneurial tubes and axon myelination, and a lack of aberrant and unorganized growth that might be characteristic of neuroma formation. Separate chronic terminal in vivo electrophysiology studies utilizing the microchannel scaffolds with permanently integrated microwire electrodes were conducted to evaluate interfacing capabilities. In all devices a variety of spontaneous, sensory evoked and electrically evoked single and multi-unit action potentials were recorded after five months of implantation. Together, these findings suggest that microchannel scaffolds are well suited for chronic implantation and peripheral nerve interfacing to promote organized nerve regeneration that lends itself well to stable interfaces. Thus this study establishes the basis for the advanced fabrication of large-electrode count, wireless microchannel devices that are an important step towards highly functional, bi-directional peripheral nerve interfaces.

Srinivasan|Akhil|A|
Tahilramani|Mayank|M|
Bentley|John T|JT|
Gore|Russell K|RK|
Millard|Daniel C|DC|
Mukhatyar|Vivek J|VJ|
Joseph|Anish|A|
Haque|Adel S|AS|
Stanley|Garrett B|GB|
English|Arthur W|AW|
Bellamkonda|Ravi V|RV|

D000200:Action Potentials
D000674:Amputees
D000818:Animals
D001369:Axons
D004195:Disease Models, Animal
D004558:Electric Stimulation
D004567:Electrodes, Implanted
D005071:Evoked Potentials
D005727:Ganglia, Spinal
D009416:Nerve Regeneration
D051381:Rats
D012584:Sciatic Nerve
D054457:Tissue Scaffolds

Peripheral nerve interfacing
Polydimethylsiloxane
Microchannel
Nerve regeneration
Nerve guide
Neural interfacing


All-Solution-Processed Organic Light-Emitting Diodes Based on Photostable Photo-cross-linkable Fluorescent Small Molecules.

Abstract: We demonstrate herein the fabrication of small molecule-based OLEDs where four organic layers from the hole- to the electron-transporting layers have successively been deposited by using an all-solution process. The key feature of the device relies on a novel photopolymerizable red-emitting material, made of small fluorophores substituted with two acrylate units, and displaying high-quality film-forming properties as well as high emission quantum yield as nondoped thin films. Insoluble emissive layers were obtained upon UV irradiation using low illumination doses, with no further need of postcuring. Very low photodegradation was noticed, giving rise to bright layers with a remarkable surface quality, characterized by a mean RMS roughness as low as 0.7 nm after development. Comparative experiments between solution-processed OLEDs and vacuum-processed OLEDs made of fluorophores with close architectures show external quantum efficiencies in the same range while displaying distinct behaviors in terms of current and power efficiencies. They validate the proof of concept of nondoped solution-processable emissive layers exclusively made of photopolymerized fluorophores, thereby reducing the amount of components and opening the way toward cost-effective fabrication of solution-processed OLED multilayer architectures.

Derue|Lionel|L| Olivier|Simon|S| Tondelier|Denis|D| Maindron|Tony|T| Geffroy|Bernard|B| Ishow|Eléna|E|

small fluorophores
solution-processed OLEDs
photopolymerization
acrylate monomers
cross-linking


Anti-Müllerian hormone (AMH), inhibin-α, growth differentiation factor 9 (GDF9), and bone morphogenic protein-15 (BMP15) mRNA and protein are influenced by photoperiod-induced ovarian regression and recrudescence in Siberian hamster ovaries.

Abstract: Exposure of Siberian hamsters to short photoperiod (SD) inhibits ovarian function, including folliculogenesis, whereas function is restored with their transfer to long photoperiods (LD). To investigate the mechanism of photo-stimulated recrudescence, we assessed key folliculogenic factors-anti-Müllerian hormone (AMH), inhibin-α, growth differentiation factor-9 (GDF9), and bone morphogenic protein-15 (BMP15)-across the estrus cycle and in photo-regressed and recrudescing ovaries. Adult hamsters were exposed to either LD or SD for 14 weeks, which respectively represent functional and regressed ovaries. Select regressed hamsters were transferred back to LD for 2 (post-transfer week 2; PTw2) or 8 weeks (PTw8). Ovaries were collected and fixed in formalin for immunohistochemistry or frozen in liquid nitrogen for real-time PCR. AMH, inhibin-α, GDF9, and BMP15 mRNA and protein were detected in all stages of the estrus cycle. Fourteen weeks of SD exposure increased (P < 0.05) ovarian AMH, GDF9, and BMP15, but not inhibin-α mRNA levels as compared to LD. Transfer of regressed hamsters to stimulatory long photoperiod for 8 weeks returned AMH and GDF9 mRNA levels to LD-treated levels, and further increased mRNA levels for inhibin-α and BMP15. Immunostaining for AMH, inhibin-α, GDF9, and BMP15 proteins was most intense in preantral/antral follicles and oocytes. The overall immunostaining extent for AMH and inhibin-α generally mirrored the mRNA data, though no changes were observed for GDF9 or BMP15 immunostaining. Shifts in mRNA and protein levels across photoperiod conditions suggest possible syncretic roles for these folliculogenic factors in photo-stimulated recrudescence via potential regulation of follicle recruitment, preservation, and development.

folliculogenesis
photostimulation
seasonal reproduction


The influence of psychological factors on postpartum weight retention 12 months post-birth.

Abstract: Background During the first postpartum year 20% of women retain excessive weight from pregnancy (postpartum weight retention; PPWR), which predicts long-term overweight/obesity. Objective The aim of this study was to explore the associations between psychological factors (depression, anxiety and stress symptoms and body attitudes) in late gestation and at 12-months postpartum with PPWR one-year post-birth. Methods Pregnant women (N = 176) completed questionnaires in early-mid pregnancy (Time 1; mean (SD) = 16.97 (1.35) weeks), late pregnancy (Time 2; mean (SD) = 33.33 (2.05) weeks), and one year postpartum (Time 3; mean (SD) = 53.12 (3.34) weeks). Women provided demographic characteristics, height and pre-pregnancy weight at Time 1. At Times 2 and 3, weight, depressive, anxiety and stress symptoms and body attitudes (salience of weight and shape, attractiveness, feeling fat, and strength and fitness) were assessed in addition to physiological, socio-contextual and lifestyle factors. Gestational weight gain and PPWR were calculated. Hierarchical linear regression models were conducted to explore variance in 12-month PPWR. Results Overall, models explained 26-39% variance in PPWR. Gestational weight gain in late pregnancy and low attractiveness at 12 months postpartum were the only variables associated significantly with 12-month PPWR. Conclusion While psychological factors did not appear to be important direct contributors to PPWR at 12 months, the overall contribution of all variables suggests that such factors may be implicated in a small and incremental way. Exploration of the interactions between variables will help unpack potential mechanisms of the development of PPWR at 12 months post-birth.

Postpartum weight retention
gestational weight gain
body dissatisfaction
depressive symptoms


An Amplified Fatty Acid-Binding Protein Gene Cluster in Prostate Cancer: Emerging Roles in Lipid Metabolism and Metastasis.

Abstract: Treatment for early stage and localized prostate cancer (PCa) is highly effective. Patient survival, however, drops dramatically upon metastasis due to drug resistance and cancer recurrence. The molecular mechanisms underlying PCa metastasis are complex and remain unclear. It is therefore crucial to decipher the key genetic alterations and relevant molecular pathways driving PCa metastatic progression so that predictive biomarkers and precise therapeutic targets can be developed. Through PCa cohort analysis, we found that a fatty acid-binding protein (FABP) gene cluster (containing five FABP family members) is preferentially amplified and overexpressed in metastatic PCa. All five FABP genes reside on chromosome 8 at 8q21.13, a chromosomal region frequently amplified in PCa. There is emerging evidence that these FABPs promote metastasis through distinct biological actions and molecular pathways. In this review, we discuss how these FABPs may serve as drivers/promoters for PCa metastatic transformation using patient cohort analysis combined with a review of the literature.

fatty acid-binding protein
prostate cancer
lipid metabolism
metastasis
gene amplification


Novel Peptides Targeting the β-Clamp Rapidly Kill Planktonic and Biofilm Staphylococcus epidermidis Both in vitro and in vivo.

Abstract: Antimicrobial resistance is an increasing threat to global health and challenges the way we treat infections. Peptides containing the PCNA interacting motif APIM (APIM-peptides) were recently shown to bind to the bacterial PCNA homolog, the beta (β)-clamp, and to have both antibacterial and anti-mutagenic activities. In this study we explore the antibacterial effects of these peptides on Staphylococcus epidermidis, a bacterial species commonly found in prosthetic joint infections (PJI). Drug-resistant bacterial isolates from PJIs often lead to difficult-to-treat chronic infections. We show that APIM-peptides have a rapid bactericidal effect which when used at sublethal levels also increase the efficacy of gentamicin. In addition, APIM-peptides reduce development and eliminate already existing S. epidermidis biofilm. To study the potential use of APIM-peptides to prevent PJI, we used an in vivo bone graft model in rats where APIM-peptide, gentamicin, or a combination of the two was added to cement. The bone grafts containing cement with the combination was more effective than cement containing only gentamicin, which is the current standard of care. In summary, these results suggest that APIM-peptides can be a promising new drug candidate for anti-infective implant materials to use in the fight against resistant bacteria and chronic PJI.

Raeder|Synnøve Brandt|SB|
Sandbakken|Erik Thorvaldsen|ET|
Nepal|Anala|A|
Løseth|Kirsti|K|
Bergh|Kåre|K|
Witsø|Eivind|E|
Otterlei|Marit|M|

antimicrobial resistance
APIM-peptide
prosthetic joint infections
antibiotic
antimicrobial peptides


Non-circadian aspects of BHLHE40 cellular function in cancer.

Abstract: While many genes specifically act as oncogenes or tumor suppressors, others are tumor promoters or suppressors in a context-dependent manner. Here we will review the basic-helix-loop-helix (BHLH) protein BHLHE40, (also known as BHLHB2, STRA13, DEC1, or SHARP2) which is overexpressed in gastric, breast, and brain tumors; and downregulated in colorectal, esophageal, pancreatic and lung cancer. As a transcription factor, BHLHE40 is expressed in the nucleus, where it binds to target gene promoters containing the E-box hexanucleotide sequence, but can also be expressed in the cytoplasm, where it stabilizes cyclin E, preventing cyclin E-mediated DNA replication and cell cycle progression. In different organs BHLHE40 regulates different targets; hence may have different impacts on tumorigenesis. BHLHE40 promotes PI3K/Akt/mTOR activation in breast cancer, activating tumor progression, but suppresses STAT1 expression in clear cell carcinoma, triggering tumor suppression. Target specificity likely depends on cooperation with other transcription factors. BHLHE40 is activated in lung and esophageal carcinoma by the tumor suppressor p53 inducing senescence and suppressing tumor growth, but is also activated under hypoxic conditions by HIF-1α in gastric cancer and hepatocellular carcinomas, stimulating tumor progression. Thus, BHLHE40 is a multi-functional protein that mediates the promotion or suppression of cancer in a context dependent manner.

Kiss|Zsofia|Z|
Mudryj|Maria|M|
Ghosh|Paramita M|PM|


Thoracolumbar interfascial plane block provides effective perioperative pain relief for patients undergoing lumbar spinal surgery; a prospective, randomized and double blinded trial.

Abstract:
STUDY OBJECTIVE
Background: Although bilateral ultrasound-guided thoracolumbar interfascial plane (TLIP) block provides effective analgesia to the lumbar spinal region, a few previous studies for the TLIP block have only been reported up to the present. We aimed to study whether the TLIP block in combination with general anesthesia would provide more effective pain relief compared to general anesthesia alone.

DESIGN
Prospective randomized controlled trial.

SETTING
Operation and recovery room, hospital ward.

PATIENTS
Seventy-two patients undergoing primary lumbar laminoplasty of less than three levels between May 2016 and April 2017.

INTERVENTIONS
Seventy-two patients undergoing primary lumbar laminoplasty of less than three levels were randomly allocated to receive either the TLIP block combined with general anesthesia (T group, n = 35) or general anesthesia alone (C group, n = 34).

MEASUREMENT
The primary outcome measured the cumulative amount of fentanyl delivered to the patients through PCA within 48 h after the end of surgery. Secondary outcomes measured the number of delivered and requested PCA doses and VAS pain scores at the surgical site obtained at rest as well as with movement at specific time points within 48 h after the surgery.

MAIN RESULTS
During the first 48 h after surgery, the cumulative amount of delivered fentanyl (mean [standard deviation]) (μg) was lower in the T group (198.3 [103.1]) (μg) than in the C group (452.9 [175.4]) (μg) (P < 0.001). The number of delivered and requested PCA doses and the VAS pain scores was also lower in the T group than in the C group at all time points (all data were less than P < 0.05).

CONCLUSIONS
Bilateral TLIP block combined with general anesthesia provides more effective perioperative pain relief than that provided by general anesthesia alone in patients who undergo lumbar spinal surgery.

Lumbar spine
Peripheral nerve block
Postoperative analgesia


Removal of micropollutants through a biological wastewater treatment plant in a subtropical climate, Queensland-Australia.

Abstract:
BACKGROUND
Municipal wastewaters contain a multitude of organic compounds derived from domestic and industrial sources including active components of pharmaceutical and personal care products and compounds used in agriculture, such as pesticides, or food processing such as artificial sweeteners often referred to as micropollutants. Some of these compounds or their degradation products may have detrimental effects on the environment, wildlife and humans. Acesuflame is one of the most popular artificial sweeteners to date used in foodstuffs. The main objectives of this descriptive study were to evaluate the presence of micropollutants in both the influent and effluent of a large-scale conventional biological wastewater treatment plant (WWTP) in South-East Queensland receiving wastewater from households, hospitals and various industries.

METHODS
Based on USEPA Method 1694: Filtered samples were spiked with mass-labelled chemical standards and then analysed for the micropollutants using liquid chromatography coupled with tandem mass spectrometry.

RESULTS
The presence of thirty-eight compounds were detected in the wastewater influent to the treatment plant while nine of the compounds in the categories of analgesic, anti-inflammatory, alkaloid and lipid/cholesterol lowering drugs were undetectable (100 % removed) in the effluent. They were: Analgesic: Paracetamol, Salicylic acid, Oxycodone; Anti-inflammatory: Naproxen + ve, Atorvastatin, Indomethacin, Naproxen; Alkaloid: Caffeine; Lipid/cholesterol lowering: Gemfibrozol.

CONCLUSIONS
The study results revealed that the micropollutants removal through this biological treatment process was similar to previous research reported from other countries including Europe the Americas and Asia, except for acesulfame, a highly persistent artificial sweetener. Surprisingly, acesulfame was diminished to a much greater extent (>90 %) than previously reported research for this type of WWTPs (45-65 %) that only include physical removal of objects and solids and a biodegradation step.

Cardenas|Miguel Antonio Reyes|MA|
Ali|Imtiaj|I|
Lai|Foon Yin|FY|
Dawes|Les|L|
Thier|Ricarda|R|
Rajapakse|Jay|J|

Biological wastewater treatment
Micropollutants removal
Sub-tropical climate


The use of chitosan as cationic coating or gel vehicle for polymeric nanocapsules: Increasing penetration and adhesion of imiquimod in vaginal tissue.

Abstract: The human papillomavirus (HPV) infection, which is strongly related to cervical cancer, can be reduced by the topical application of imiquimod. Some strategies have been used to increase the adhesion and penetration of drugs through the vaginal mucosa. Two of them are the development of mucoadhesive semisolid formulations and the development of polymeric nanocarriers. In this paper, we hypothesize that the combined use of these two strategies results in a better performance of the formulation to retain imiquimod into the vaginal tissue. Aiming this, two different systems are proposed: (a) chitosan-coated poly(ε-caprolactone)-nanocapsules incorporated into hydroxyethylcellulose gel (HEC-NCimiq-chit), and (b) poly(ε-caprolactone)-nanocapsules incorporated into chitosan hydrogel (CHIT-NCimiq). These formulations were submitted to three main tests: mucoadhesivity by interaction, permeation and washability test (or retention test). We developed an integrative index that allows comparing the global performance of the proposed formulations by considering jointly the results of these three tests. Thus, when considered the integrative indexes for the formulations, our results show that CHIT-NCimiq presents the best performance for the treatment of HPV.

Frank|Luiza A|LA|
Chaves|Paula S|PS|
D'Amore|Camilo M|CM|
Contri|Renata V|RV|
Frank|Alejandro G|AG|
Beck|Ruy C R|RC|
Pohlmann|Adriana R|AR|
Buffon|Andreia|A|
Guterres|Silvia S|SS|

Chitosan
Polymeric nanocapsules
Imiquimod
Vaginal mucosa
Mucoadhesion


The use of electrodessication in the treatment of cutaneous neurofibromatosis: A retrospective patient satisfaction outcome assessment.

Abstract:
INTRODUCTION
Neurofibromatosis I (NF-1) is an autosomal dominant disease giving rise to hundreds of cutaneous neurofibromas. In addition to localised symptoms such as pain and pruritus, these lesions can have a devastating psychosocial impact. To date, there is no consensus on the optimal management of these lesions. We present the clinical and patient-reported outcomes of a series of NF-1 patients treated with electrodessication by one surgeon.

METHODS
All patients treated by electrodessication for cutaneous neurofibromas between 2012 and 2015 by one clinician were retrospectively reviewed. Clinical and patient-reported outcomes were measured using a patient satisfaction questionnaire and review of the notes.

RESULTS
Six patients were operated on during the study period (five women and one man). Prior to this new technique, patients had on average eight episodes (range 4-20) of excisional procedures under local anaesthesia removing one to five lesions. With electrodessication, patients had on average three (range 1-5) electrodessication episodes under general anaesthesia, treating hundreds of lesions per session. All patients were treated as a day case. One patient experienced a minor wound infection and another minor bleeding. Five of six patients preferred electrodessication to surgical excision.

CONCLUSION
Electrodessication enables the treatment of hundreds of neurofibromas in a single operation. The procedure has low complication rates with high levels of clinical and patient-reported outcomes.

Lutterodt|C G|CG|
Mohan|A|A|
Kirkpatrick|N|N|

Electrodessication
Neurofibromatosis
Neurofibroma
Benign skin lesion
Cutaneous lesions
Neurofibromatosis type I


COVID-19 in patients with multiple sclerosis treated with cladribine tablets: An update.

Abstract:
BACKGROUND
We previously summarized outcomes for 46 cladribine tablets (CladT)-treated patients with multiple sclerosis (MS) and confirmed or suspected COVID-19, as reported to the Merck KGaA Global Patient Safety Database. This report updates on these findings, to 15 January 2021, for a total of 272 reported cases of COVID-19 among CladT recipients.

METHODS
Case definitions: confirmed (COVID-19 diagnostic test was positive); suspected (no confirmatory test performed/reported). Cases fulfilling the criteria of hospitalized, medically significant, or fatal were designated as serious and outcomes were classified per usual pharmacovigilance practice.

RESULTS
The evaluable cohort comprised 261 patients (confirmed COVID-19, n=160; suspected, n=101); an additional 11 patients had symptoms compatible with COVID-19 but were not evaluated further given their negative diagnostic tests. Median time to onset of COVID-19 from the most recent preceding CladT treatment course was 162 days (n=139). Outcomes were: recovered/recovering, n=133 (51%); not recovered/not resolved, n=19 (7%); died, n=1 (0.4%); and not reported/missing/pending, n=108 (41%). Of the total cohort, 40 (15%) experienced serious COVID-19.

CONCLUSION
Our results suggest that CladT-treated patients with MS are generally not at greater risk of serious disease and/or a severe outcome with COVID-19 compared with the general population and other patients with MS who acquired COVID-19.

Jack|Dominic|D| Damian|Doris|D| Nolting|Axel|A| Galazka|Andrew|A|

COVID-19
Multiple sclerosis
Cladribine tablets


Elongation factor eEF2 kinase and autophagy jointly promote survival of cancer cells.

Abstract: Cells within solid tumours can become deprived of nutrients; in order to survive, they need to invoke mechanisms to conserve these resources. Using cancer cells in culture in the absence of key nutrients, we have explored the roles of two potential survival mechanisms, autophagy and elongation factor 2 kinase (eEF2K), which, when activated, inhibits the resource-intensive elongation stage of protein synthesis. Both processes are regulated through the nutrient-sensitive AMP-activated protein kinase and mechanistic target of rapamycin complex 1 signalling pathways. We find that disabling both autophagy and eEF2K strongly compromises the survival of nutrient-deprived lung and breast cancer cells, whereas, for example, knocking out eEF2K alone has little effect. Contrary to some earlier reports, we find no evidence that eEF2K regulates autophagy. Unexpectedly, eEF2K does not facilitate survival of prostate cancer PC3 cells. Thus, eEF2K and autophagy enable survival of certain cell-types in a mutually complementary manner. To explore this further, we generated, by selection, cells which were able to survive nutrient starvation even when autophagy and eEF2K were disabled. Proteome profiling using mass spectrometry revealed that these 'resistant' cells showed lower levels of diverse proteins which are required for energy-consuming processes such as protein and fatty acid synthesis, although different clones of 'resistant cells' appear to adapt in dissimilar ways. Our data provide further information of the ways that human cells cope with nutrient limitation and to understanding of the utility of eEF2K as a potential target in oncology.

Lenchine|Roman V|RV|
Rao|Sushma R|SR|
Wang|Xuemin|X|
Fang|Danielle Meiwen|DM|
Proud|Christopher G|CG|

D015972:Gene Expression Regulation, Neoplastic

protein synthesis
alpha kinase
apoptosis
cancer therapy
translation


Comorbidity and cognitive overlap between developmental dyslexia and congenital amusia.

Abstract: This study investigated whether there is a co-occurrence between developmental dyslexia and congenital amusia in adults. First, a database of online musical tests on 18,000 participants was analysed. Self-reported dyslexic participants performed significantly lower on melodic skills than matched controls, suggesting a possible link between reading and musical disorders. In order to test this relationship more directly, we evaluated 20 participants diagnosed with dyslexia, 16 participants diagnosed with amusia, and their matched controls, with a whole battery of literacy (reading, fluency, spelling), phonological (verbal working memory, phonological awareness) and musical tests (melody, rhythm and metre perception, incidental memory). Amusia was diagnosed in six (30%) dyslexic participants and reading difficulties were found in four (25%) amusic participants. Thus, the results point to a moderate comorbidity between amusia and dyslexia. Further research will be needed to determine what factors at the neural and/or cognitive levels are responsible for this co-occurrence.

Developmental dyslexia
congenital amusia
literacy
phonology
music perception


Impact of structural relaxation on mechanical properties of amorphous polymers.

Abstract: Fusion based methods, such as hot-melt extrusion, are a common way of preparing amorphous solid dispersions. Since the amorphous glass, however, is not in a configurational equilibrium, the molecular arrangement of the obtained material can differ in dependence of the preparation conditions. Although the changes in the configuration of an amorphous material, which are commonly referred to as structural relaxation or physical aging, are well investigated, the impact on mechanical properties of amorphous solid dispersions have widely been neglected so far. The presented study investigated copovidone as a model polymer commonly used in amorphous solid dispersions and revealed that structural relaxation was already introduced into the polymer during hot-melt extrusion while its degree was cooling rate dependent. The degree of structural relaxation significantly affected the mechanical properties of copovidone as assessed by diametral compression tests, macroindentation and nanoindentation. An increase in Young's modulus and indentation hardness was observable with a higher degree of structural relaxation, which, during tablet compression, translated into tablets with significantly lower tensile strength. Furthermore, evaluation of the force-displacement curves during tablet compression revealed a decreased proportion of irreversible deformation with higher degree of structural relaxation correlating well with the increased indentation hardness during macroindentation. Thus, understanding structural relaxation and its impact on material properties is of utmost importance to assess the processability and compaction performance of amorphous solid dispersions in dependence of their preparation conditions and thermal history.

Structural relaxation
Amorphous polymer
Physical aging
Copovidone
Macroindentation
Nanoindentation
Tablet compression
Mechanical characterization
Relaxation enthalpy


Drought Drives Spatial Variation in the Millet Root Microbiome.

Abstract: Efforts to boost crop yield and meet global food demands while striving to reach sustainability goals are hindered by the increasingly severe impacts of abiotic stress, such as drought. One strategy for alleviating drought stress in crops is to utilize root-associated bacteria, yet knowledge concerning the relationship between plant hosts and their microbiomes during drought remain under-studied. One broad pattern that has recently been reported in a variety of monocot and dicot species from both native and agricultural environments, is the enrichment of Actinobacteria within the drought-stressed root microbiome. In order to better understand the causes of this phenomenon, we performed a series of experiments in millet plants to explore the roles of drought severity, drought localization, and root development in provoking Actinobacteria enrichment within the root endosphere. Through 16S rRNA amplicon-based sequencing, we demonstrate that the degree of drought is correlated with levels of Actinobacterial enrichment in four species of millet. Additionally, we demonstrate that the observed drought-induced enrichment of Actinobacteria occurs along the length of the root, but the response is localized to portions of the root experiencing drought. Finally, we demonstrate that Actinobacteria are depleted in the dead root tissue of Japanese millet, suggesting saprophytic activity is not the main cause of observed shifts in drought-treated root microbiome structure. Collectively, these results help narrow the list of potential causes of drought-induced Actinobacterial enrichment in plant roots by showing that enrichment is dependent upon localized drought responses but not root developmental stage or root death.

Simmons|Tuesday|T|
Styer|Alexander B|AB|
Pierroz|Grady|G|
Gonçalves|Antonio Pedro|AP|
Pasricha|Ramji|R|
Hazra|Amrita B|AB|
Bubner|Patricia|P|
Coleman-Derr|Devin|D|

drought
abiotic stress
root endosphere
plant microbe interaction
plant microbiome


Vascular effects of exercise training in CKD: current evidence and pathophysiological mechanisms.

Abstract: Cardiovascular disease remains the main cause of morbidity and mortality in patients with CKD, an observation that cannot be explained by the coexistence of traditional risk factors alone. Recently, other mechanisms, such as alterations in nitric oxide bioavailability, impaired endothelial repair mechanisms, inflammation, and oxidative stress (all characteristic in CKD), have gained much attention as mediators for the increased cardiovascular risk. Regular physical training is a valuable nonpharmacological intervention for primary and secondary prevention of cardiovascular disease. Likewise, the benefits of exercise training on exercise capacity and quality of life are increasingly recognized in patients with CKD. Furthermore, exercise training could also influence potential reversible mechanisms involved in atherosclerosis and arteriosclerosis. After discussing briefly the general concepts of vascular disease in CKD, this review provides an overview of the current evidence for the effects of exercise training at both clinical and preclinical levels. It concludes with some practical considerations on exercise training in this specific patient group.

Van Craenenbroeck|Amaryllis H|AH|
Van Craenenbroeck|Emeline M|EM|
Kouidi|Evangelia|E|
Vrints|Christiaan J|CJ|
Couttenye|Marie M|MM|
Conraads|Viviane M|VM|

glomerular filtration
glomerulus
renal physiology


Epidemiology of Taenia saginata taeniosis/cysticercosis in the Russian Federation.

Abstract:
BACKGROUND
Russia is traditionally an endemic area for Taenia saginata infection, where a programme for the prevention of infection has been implemented for sixty years. This paper aims, therefore, to review the recent epidemiology data of Taenia saginata infection in the Russian Federation.

METHODS
We undertook a systematic review of published and grey literature, and official data for information on the incidence, prevalence and distribution of Taenia saginata taeniosis and cysticercosis in the Russian Federation between 1st January 1991 and 31st December 2017.

RESULTS
From the 404 records returned by our search strategy, we identified 17 official county reports, 17 papers and one meeting abstract on the occurrence of taeniosis or cysticercosis from the Russian Federation, eligible for inclusion in this study. In the Russian Federation, Taenia saginata infection has been continuously present and notifiable in the study period between 1991-2016. In the same area, a continuous decrease in the incidence of human taeniosis cases was observed, from 1.4 to 0.04 cases per 100,000 inhabitants, as well as a reduction in the territory where the infection is reported. The prevalence of bovine cysticercosis, ranging between 0.1-19.0%, generally has a declining trend, especially after 2005.

CONCLUSIONS
Importance of Taenia saginata infection as a medical and veterinary problem has been decreasing in the 21st century but it is still an infection with health and economic impact in the Russian Federation.

Bobić|Branko|B|
Thomas|Lian F|LF|
Djaković|Olgica Djurković|OD|
Devleesschauwer|Brecht|B|
Dermauw|Veronique|V|
Dorny|Pierre|P|
Braae|Uffe Christian|UC|
Robertson|Lucy|L|
Saratsis|Anastasios|A|
Eichenberger|Ramon|R|
Torgerson|Paul R|PR|

Taenia saginata
Taeniosis
Russian Federation
Bovine cysticercosis
Beef tapeworm


Update in the Management of Myasthenia Gravis and Lambert-Eaton Myasthenic Syndrome.

Abstract: Myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) are the most common disorders of neuromuscular transmission in clinical practice. Disorders of the neuromuscular junction (NMJ) are characterized by fluctuating and fatigable weakness and include autoimmune, toxic, and genetic conditions. Adults with NMJ disorders are most often antibody mediated, with MG being the most common, having a prevalence of approximately 1 in 10,000, and with women being affected about twice as often as men. This article focuses on advances in management of autoimmune MG and LEMS.

Myasthenia gravis
Weakness
Complement inhibitor
Lambert Eaton myasthenic syndrome
Thymectomy


Influence of air pollution on renal activity in patients with childhood-onset systemic lupus erythematosus.

Abstract:
BACKGROUND
Childhood-onset systemic lupus erythematosus (cSLE) is an autoimmune and multifactorial disease that can affect the renal system. Exposure to air pollution can trigger systemic inflammation in cSLE patients and increase risk of disease activity. We evaluated effects of individual real-time exposure to air pollutants on renal activity in cSLE patients using the Systemic Lupus Erythematosus Disease Activity Index 2000.

METHODS
Longitudinal panel study of 108 repetitive measures from 9 pediatric lupus patients. Over three consecutive weeks, daily individual levels of fine particulate matter (PM2.5) and nitrogen dioxide (NO2) were measured, as well as weekly clinical evaluation and laboratory tests. This was repeated every 10 weeks over a 1-year period. Specific generalized estimating equation models were used to evaluate the impact of these pollutants on risk of nephritis and anti-dsDNA > 20 UI/mL and on 24-h urine protein and serum complement (C3) levels.

RESULTS
An interquartile range (IQR) increase of 18.12 μg/m3 in PM2.5 daily concentration was associated with increased risk of nephritis and positive results for anti-dsDNA. Moreover, increase in 24-h urine protein and decrease in C3 serum levels also associated with exposure to pollutants. An IQR increase in PM2.57-day moving average was associated with increased risks of leukocyturia (3.4; 95% CI 2.6:4.3), positive anti-dsDNA (3.1; 95% CI 2.1:4.0), and 36.3-mg increase (95% IC 20.2:52.3) in 24-h urine protein. An IQR increase (63.1 μg/m3) in 7-day cumulative NO2 levels was associated with decreased serum C3 levels.

CONCLUSIONS
This prospective study suggests exposure to air pollution can trigger renal activity in cSLE patients.

de Faria Coimbra Lichtenfels|Ana Julia|AJ|


Time-course effects of antioxidants and phase II enzymes on diesel exhaust particles-induced oxidative damage in the mouse lung.

Abstract: Mechanisms responsible for diesel exhaust particle (DEP)-induced toxicity in respiratory disorders are poorly understood, recent experimental and controlled exposure studies suggested that oxidative stress might be involved. To investigate the time-course effects DEP on nuclear factor erythroid 2-related factor 2 (Nrf2), a key regulator in cellular adaptive antioxidant response, mice were intratracheal instilled with 100 μg DEP/mouse and sacrificed after 30 min, 6 h, 12 h, 24 h, 48 h, and 72 h. We measured reactive oxygen species (ROS) as well as Nrf2 and antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and phase II enzymes including heme oxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase-1 (NQO1), glutamate-cysteine ligase catalytic subunit (GCLC), glutamate-cysteine ligase modifier subunit (GCLM) in the lungs. Additionally, histopathological changes were examined. At 6 h, ROS peaked, most of the enzymes were activated, and the histology showed the lungs were damaged. At 12 h, ROS returned to normal level and CAT activity decreased, while protein expression of Nrf2, HO-1, NQO1, GCLC, and GCLM increased, and the lungs were recovering from damage. After 24 h, ROS started to decrease and Nrf2 showed a decreasing trend at both gene and protein levels, while the lung damage had been entirely restored. These results suggested that a single exposure to DEP induce transient oxidative stress in the lungs, with time-dependent effects on Nrf2 and antioxidant enzymes and phase II enzymes.

Zheng|Xiaomei|X| Wang|Guanglei|G| Bin|Ping|P| Meng|Tao|T| Niu|Yong|Y| Yang|Mo|M| Zhang|Liping|L| Duan|Huawei|H| Yu|Tao|T| Dai|Yufei|Y| Zheng|Yuxin|Y|

D015971:Gene Expression Regulation, Enzymologic

D050217:Metabolic Detoxication, Phase II

Phase II enzymes
Diesel exhaust particles
Oxidative stress
Antioxidant enzymes
Time point


Cerebral coherence between communicators marks the emergence of meaning.

Abstract: How can we understand each other during communicative interactions? An influential suggestion holds that communicators are primed by each other's behaviors, with associative mechanisms automatically coordinating the production of communicative signals and the comprehension of their meanings. An alternative suggestion posits that mutual understanding requires shared conceptualizations of a signal's use, i.e., "conceptual pacts" that are abstracted away from specific experiences. Both accounts predict coherent neural dynamics across communicators, aligned either to the occurrence of a signal or to the dynamics of conceptual pacts. Using coherence spectral-density analysis of cerebral activity simultaneously measured in pairs of communicators, this study shows that establishing mutual understanding of novel signals synchronizes cerebral dynamics across communicators' right temporal lobes. This interpersonal cerebral coherence occurred only within pairs with a shared communicative history, and at temporal scales independent from signals' occurrences. These findings favor the notion that meaning emerges from shared conceptualizations of a signal's use.

Stolk|Arjen|A|
Noordzij|Matthijs L|ML|
Verhagen|Lennart|L|
Volman|Inge|I|
Schoffelen|Jan-Mathijs|JM|
Oostenveld|Robert|R|
Hagoort|Peter|P|
Toni|Ivan|I|

dual functional magnetic resonance imaging


Efficacy and safety of a non-mineral oil adjuvanted injectable vaccine for the protection of Atlantic salmon (Salmo salar L.) against Flavobacterium psychrophilum.

Abstract: Flavobacterium psychrophilum is the causative agent of Rainbow Trout Fry Syndrome which has had a major impact on global salmonid aquaculture. Recent outbreaks in Atlantic salmon in Scotland and Chile have added to the need for a vaccine to protect both salmon and trout. At present no licensed vaccines are available in Europe, leaving antibiotics as the only course of action to contain disease outbreaks. Outbreaks generally occur in fry at temperatures between 10 and 15 °C. Recently outbreaks in larger fish have given added impetus to the development of a vaccine which can provide long term protection from this highly heterogeneous pathogen. Most fish injectable vaccines are formulated with oil emulsion adjuvants to induce strong and long lasting immunity, but which are known to cause side effects. Alternative adjuvants are currently sought to minimise these adverse effects. The current study was performed to assess the efficacy of a polyvalent, whole cell vaccine containing formalin-inactivated F. psychrophilum to induce protective immunity in Atlantic salmon. The vaccine was formulated with an adjuvant containing squalene and aluminium hydroxide, and was compared to a vaccine formulated with a traditional oil adjuvant, Montanide ISA 760VG, and a non-adjuvanted vaccine. Duplicate groups of salmon (23.5 ± 6.8 g) were vaccinated with each of the vaccine formulations or phosphate buffered saline by intraperitoneal injection. Fish were challenged by intramuscular injection with F. psychrophilum six weeks post-vaccination to test the efficacy of the vaccines. Cumulative mortality reached 70% in the control salmon, while the groups of salmon that received vaccine had significantly lower mortality than the controls (p = 0.0001), with no significant difference in survival between vaccinated groups. The squalene/alum adjuvant was safe, more readily metabolised by the fish and induced less histopathological changes than the traditional oil adjuvant.

Hoare|R|R|
Jung|S-J|SJ|
Ngo|T P H|TPH|
Bartie|K|K|
Bailey|J|J|
Thompson|K D|KD|
Adams|A|A|

D000276:Adjuvants, Immunologic
D000536:Aluminum Hydroxide
D000818:Animals
D001428:Bacterial Vaccines
D005393:Fish Diseases
D045826:Flavobacteriaceae Infections
D005417:Flavobacterium
D011897:Random Allocation
D020317:Salmo salar
D013185:Squalene

Adjuvant
Vaccine
Salmon
Flavobacterium psychrophilum
RTFS


Architecture for interoperable software in biology.

Abstract: Understanding biological complexity demands a combination of high-throughput data and interdisciplinary skills. One way to bring to bear the necessary combination of data types and expertise is by encapsulating domain knowledge in software and composing that software to create a customized data analysis environment. To this end, simple flexible strategies are needed for interconnecting heterogeneous software tools and enabling data exchange between them. Drawing on our own work and that of others, we present several strategies for interoperability and their consequences, in particular, a set of simple data structures--list, matrix, network, table and tuple--that have proven sufficient to achieve a high degree of interoperability. We provide a few guidelines for the development of future software that will function as part of an interoperable community of software tools for biological data analysis and visualization.

Bare|James Christopher|JC|
Baliga|Nitin S|NS|

interoperability
data analysis
bioinformatics
integration
software engineering
systems biology


Novel Imaging Modalities Shedding Light on Plant Biology: Start Small and Grow Big.

Abstract: The acquisition of quantitative information on plant development across a range of temporal and spatial scales is essential to understand the mechanisms of plant growth. Recent years have shown the emergence of imaging methodologies that enable the capture and analysis of plant growth, from the dynamics of molecules within cells to the measurement of morphometricand physiological traits in field-grown plants. In some instances, these imaging methods can be parallelized across multiple samples to increase throughput. When high throughput is combined with high temporal and spatial resolution, the resulting image-derived data sets could be combined with molecular large-scale data sets to enable unprecedented systems-level computational modeling. Such image-driven functional genomics studies may be expected to appear at an accelerating rate in the near future given the early success of the foundational efforts reviewed here. We present new imaging modalities and review how they have enabled a better understanding of plant growth from the microscopic to the macroscopic scale.

Clark|Natalie M|NM|
Van den Broeck|Lisa|L|
Guichard|Marjorie|M|
Stager|Adam|A|
Tanner|Herbert G|HG|
Blilou|Ikram|I|
Grossmann|Guido|G|
Iyer-Pascuzzi|Anjali S|AS|
Maizel|Alexis|A|
Sparks|Erin E|EE|
Sozzani|Rosangela|R|

scanning fluorescent correlation spectroscopy


Automated oxygen titration and weaning with FreeO2 in patients with acute exacerbation of COPD: a pilot randomized trial.

Abstract:
INTRODUCTION
We developed a device (FreeO2) that automatically adjusts the oxygen flow rates based on patients' needs, in order to limit hyperoxia and hypoxemia and to automatically wean them from oxygen.

OBJECTIVE
The aim of this study was to evaluate the feasibility of using FreeO2 in patients hospitalized in the respiratory ward for an acute exacerbation of COPD.

METHODS
We conducted a randomized controlled trial comparing FreeO2 vs manual oxygen titration in the respiratory ward of a university hospital. We measured the perception of appropriateness of oxygen titration and monitoring in both groups by nurses and attending physicians using a Likert scale. We evaluated the time in the target range of oxygen saturation (SpO2) as defined for each patient by the attending physician, the time with severe desaturation (SpO2 <85%), and the time with hyperoxia (SpO2 >5% above the target). We also recorded length of stay, intensive care unit admissions, and readmission rate. Fifty patients were randomized (25 patients in both groups; mean age: 72±8 years; mean forced expiratory volume in 1 second: 1.00±0.49 L; and mean initial O2 flow 2.0±1.0 L/min).

RESULTS
Nurses and attending physicians felt that oxygen titration and monitoring were equally appropriate with both O2 administration systems. The percentage of time within the SpO2 target was significantly higher with FreeO2, and the time with severe desaturation and hyperoxia was significantly reduced with FreeO2. Time from study inclusion to hospital discharge was 5.8±4.4 days with FreeO2 and 8.4±6.0 days with usual oxygen administration (P=0.051).

CONCLUSION
FreeO2 was deemed as an appropriate oxygen administration system by nurses and physicians of a respiratory unit. This system maintained SpO2 at the target level better than did manual titration and reduced periods of desaturation and hyperoxia. Our results also suggest that FreeO2 has the potential to reduce the hospital length of stay.

Lellouche|François|F| Bouchard|Pierre-Alexandre|PA| Roberge|Maude|M| Simard|Serge|S| L'Her|Erwan|E| Maltais|François|F| Lacasse|Yves|Y|

D007722:Health Knowledge, Attitudes, Practice

D029424:Pulmonary Disease, Chronic Obstructive

hyperoxia
closed-loop
hypoxia
oxygen inhalation therapy
technological innovations


Metabolome Dynamics of Smutted Sugarcane Reveals Mechanisms Involved in Disease Progression and Whip Emission.

Abstract: Sugarcane smut disease, caused by the biotrophic fungus Sporisorium scitamineum, is characterized by the development of a whip-like structure from the plant meristem. The disease causes negative effects on sucrose accumulation, fiber content and juice quality. The aim of this study was to exam whether the transcriptomic changes already described during the infection of sugarcane by S. scitamineum result in changes at the metabolomic level. To address this question, an analysis was conducted during the initial stage of the interaction and through disease progression in a susceptible sugarcane genotype. GC-TOF-MS allowed the identification of 73 primary metabolites. A set of these compounds was quantitatively altered at each analyzed point as compared with healthy plants. The results revealed that energetic pathways and amino acid pools were affected throughout the interaction. Raffinose levels increased shortly after infection but decreased remarkably after whip emission. Changes related to cell wall biosynthesis were characteristic of disease progression and suggested a loosening of its structure to allow whip growth. Lignin biosynthesis related to whip formation may rely on Tyr metabolism through the overexpression of a bifunctional PTAL. The altered levels of Met residues along with overexpression of SAM synthetase and ACC synthase genes suggested a role for ethylene in whip emission. Moreover, unique secondary metabolites antifungal-related were identified using LC-ESI-MS approach, which may have potential biomarker applications. Lastly, a putative toxin was the most important fungal metabolite identified whose role during infection remains to be established.

Schaker|Patricia D C|PDC|
Peters|Leila P|LP|
Cataldi|Thais R|TR|
Labate|Carlos A|CA|
Caldana|Camila|C|
Monteiro-Vitorello|Claudia B|CB|

metabolomics
sugarcane smut
meristem
fungal pathogen
plant–microbe interactions


New phenolic glycosides from Anemone chinensis Bunge and their antioxidant activity.

Abstract: ABATRACTNine compounds, five phenolic glycosides (1, 2, 4-6), three phenylpropanoids (7-9), and a furanone glycoside (3), were isolated from aqueous soluble extract of the dried roots of Anemone chinensis Bunge. The structures of new compounds (1-4) were elucidated by comprehensive spectroscopic data analysis as well as chemical evidence. Pulsatillanin A (1) demonstrated significant antioxidant effects through scavenging free radical in DPPH assay, and relieved the oxidative stress in LPS-induced RAW 264.7 cells by reducing ROS production, enhancing antioxidant enzyme SOD activity, replenishing depleted GSH in a dose-dependent manner. Western blot analysis revealed that 1 showed antioxidant activity via activating Nrf2 signaling pathway.

Zhang|Zeng-Guang|ZG| Li|Yuan-Yuan|YY| Lin|Bin|B| Guan|Pei-Pei|PP| Mu|Yu|Y| Qiao|Wen-Jun|WJ| Zhang|Jing-Sheng|JS| Huang|Xue-Shi|XS| Han|Li|L|

phenolic glycosides
Anemone chinensis Bunge
antioxidant activity
Nrf2


Adherence to recommendations and clinical outcomes of patients hospitalized for stroke: the role of the admission ward-a real-life investigation from Italy.

Abstract:
OBJECTIVE
To determine whether out-of-hospital healthcare and adverse outcomes are better in stroke patients admitted to a neurology ward compared with those admitted to general wards.

METHODS
Beneficiaries of the National Health Service from the Italian Lombardy Region who were discharged alive after hospital admission during the year 2009 for ischemic stroke (9776 patients) or intracerebral or subarachnoid hemorrhage (1102 patients) entered into the cohort and were followed until 2012. Exposure of interest was the ward type where inpatients were admitted (neuro vs. general wards). Outcomes were out-of-hospital healthcare (i.e., drug prescriptions, diagnostic procedures, and laboratory clinical evaluations) and adverse clinical outcomes (i.e., all-cause death and hospital readmission). Exposure-outcome associations were investigated. High-dimensional propensity score methodology was used for taking into account confounders. Mediation analysis was used to verify whether the association between ward type and clinical outcomes is mediated by out-of-hospital adherence to healthcare.

RESULTS
Better adherence to out-of-hospital healthcare received from patients discharged from neuro, rather than general, wards was observed being the proportions of adherent patients 42.4% and 39.5%, respectively. Compared with general wards, discharge from neuro was associated with reduced 3-year emergency admissions (from 50.1 to 47.5% among ischemic stroke patients) and reduced 3-year mortality (from 37.5 to 27.0% among hemorrhagic stroke patients). From 10 to 15% of outcome risk, reductions were mediated by better adherence to out-of-hospital healthcare.

CONCLUSIONS
For patients with acute ischemic and hemorrhagic stroke, admission to neuro vs. general wards is associated with better out-of-hospital healthcare and long-term adverse outcomes.

Intracerebral or subarachnoid hemorrhage


Non-Melanoma Skin Cancer: news from microbiota research.

Abstract: Recently, research has been deeply focusing on the role of the microbiota in numerous diseases, either affecting the skin or other organs. What it is well established is that its dysregulation promotes several cutaneous disorders (i.e. psoriasis and atopic dermatitis). To date, little is known about its composition, mediators and role in the genesis, progression and response to therapy of Non-Melanoma Skin Cancer (NMSC). Starting from a bibliographic study, we classified the selected articles into four sections: i) normal skin microbiota; ii) in vitro study models; iii) microbiota and NMSC and iv) probiotics, antibiotics and NMSC. What has emerged is how skin microflora changes, mainly represented by increases of Staphylococcus aureus, Streptococcus pyogenes and Pseudomonas aeruginosa strains, modifications in the mutual quantity of β-Human papillomavirus genotypes, of Epstein Barr Virus and Malassezia or candidiasis, may contribute to the induction of a state of chronic self-maintaining inflammation, leading to cancer. In this context, the role of S. aureus and that of specific antimicrobial peptides look to be prominent. Moreover, although antibiotics may contribute to carcinogenesis, due to their ability to influence the microbiota balance, specific probiotics, such as Lacticaseibacillus rhamnosus GG, Lactobacillus johnsonii NCC 533 and Bifidobacteria spp., may be protective.

Squarzanti|Diletta Francesca|DF|
Zavattaro|Elisa|E|
Pizzimenti|Stefania|S|
Amoruso|Angela|A|
Savoia|Paola|P|
Azzimonti|Barbara|B|

Microbiota
Non-Melanoma Skin Cancer (NMSC)
in vitro 3D reconstructed skin
animal models
anti-/pro-biotics


Rapid generation of functional dopaminergic neurons from human induced pluripotent stem cells through a single-step procedure using cell lineage transcription factors.

Abstract: Current protocols for in vitro differentiation of human induced pluripotent stem cells (hiPSCs) to generate dopamine (DA) neurons are laborious and time-expensive. In order to accelerate the overall process, we have established a fast protocol by expressing the developmental transcription factors ASCL1, NURR1, and LMX1A. With this method, we were able to generate mature and functional dopaminergic neurons in as few as 21 days, skipping all the intermediate steps for inducting and selecting embryoid bodies and rosette-neural precursors. Strikingly, the resulting neuronal conversion process was very proficient, with an overall efficiency that was more than 93% of all the coinfected cells. hiPSC-derived DA neurons expressed all the critical molecular markers of the DA molecular machinery and exhibited sophisticated functional features including spontaneous electrical activity and dopamine release. This one-step protocol holds important implications for in vitro disease modeling and is particularly amenable for exploitation in high-throughput screening protocols.

Theka|Ilda|I|
Caiazzo|Massimiliano|M|
Dvoretskova|Elena|E|
Leo|Damiana|D|
Ungaro|Federica|F|
Curreli|Sebastiano|S|
Managò|Francesca|F|
Dell'Anno|Maria Teresa|MT|
Pezzoli|Gianni|G|
Gainetdinov|Raul R|RR|
Dityatev|Alexander|A|
Broccoli|Vania|V|

D051792:Basic Helix-Loop-Helix Transcription Factors

D018507:Gene Expression Regulation, Developmental

D057126:Nuclear Receptor Subfamily 4, Group A, Member 2

Neuron
Pluripotent stem cells
Dopamine
Direct cell conversion
Reprogramming


Recent progress in the development of recognition bioelements for polychlorinated biphenyls detection: Antibodies and aptamers.

Abstract: Polychlorinated biphenyls (PCBs) are persistent pollutants, which have expanded in foods and the environment. Detection of PCBs is considered essential due to recognized side-effects of PCBs on health and the public concerns in this regard. On the other hand, due to the trace levels of these organic chlorine compounds, reliable and sensitive assays must be developed. Recognition elements are essential parts of analytical detection assays and sensors of PCBs since these elements are involved in the selective identification of the analytes of interest. Understanding the fundamentals of the recognition elements of PCBs and the benefits of the sensor strategies result in the development of next-generation recognition devices. This review aimed to highlight the recent progress in the recognition elements as key parts of biosensors. We initially, focused on the developed antibody-based biosensors for the detection of PCBs, followed by discussing the aptamers as novel recognition elements. Furthermore, the recent advancement in the development of aptamer-based solid phase extractions has been evaluated. These findings could contribute to improving the design of commercial PCB-kits in the future.

Antibody
Aptamer
PCB
Recognition element
Biosensor


Sodium concentration measurement during hemodialysis through ion-exchange resin and conductivity measure approach: in vitro experiments.

Abstract: Sodium measurement during hemodialysis treatment is important to preserve the patient from clinical events related to hypo- or hyper-natremia Usually, sodium measurement is performed through laboratory equipment which is typically expensive, and requires manual intervention. We propose a new method, based on conductivity measurement after treatment of dialysate solution through ion-exchange resin. To test this method, we performed in vitro experiments. We prepared 40 ml sodium chloride (NaCl) samples at 280, 140, 70, 35, 17.5, 8.75, 4.375 mEq/l, and some "mixed samples", i.e., with added potassium chloride (KCl) at different concentrations (4.375-17.5 mEq/l), to simulate the confounding factors in a conductivity-based sodium measurement. We measured the conductivity of all samples. Afterwards, each sample was treated for 1 min with 1 g of Dowex G-26 resin, and conductivity was measured again. On average, the difference in the conductivity between mixed samples and corresponding pure NaCl samples (at the same NaCl concentration) was 20.9%. After treatment with the exchange resin, it was 14.7%, i.e., 42% lower. Similar experiments were performed with calcium chloride and magnesium chloride as confounding factors, with similar results. We also performed some experiments on actual dialysate solution during hemodialysis sessions in 15 patients, and found that the correlation between conductivity measures and sodium concentration improved after resin treatment (R=0.839 before treatment, R=0.924 after treatment, P<0.0001). We conclude that ion-exchange resin treatment coupled with conductivity measures may improve the measurement of sodium compared to conductivity measures alone, and may become a possible simple approach for continuous and automatic sodium measurement during hemodialysis.

Tura|Andrea|A| Sbrignadello|Stefano|S| Mambelli|Emanuele|E| Ravazzani|Paolo|P| Santoro|Antonio|A| Pacini|Giovanni|G|

sodium ion-exchange resin conductivity dialysis ultrafiltration


An Overview of Thrombophilia and Associated Laboratory Testing.

Abstract: Venous thromboembolism, usually entailing deep vein thrombosis, pulmonary embolism, or both, is a complex and multifactorial disorder, in which a number of putative conditions interplay and finally contribute to propel the individual risk over a certain degree, so ultimately culminating in the development of venous occlusive disorders. Thrombophilia is commonly defined as a propensity to develop venous thromboembolism on the basis of an underlying hypercoagulable state attributable to inherited or acquired disorders of blood coagulation or fibrinolysis. The thrombophilic conditions are conventionally classified as inherited (or genetically determined) and acquired. The former include deficiencies of natural anticoagulants such as antithrombin, protein C, protein S, increased values of clotting factors (especially factor VIII), as well as prothrombotic polymorphisms in genes encoding for factor V (i.e., factor V Leiden) and prothrombin. The latter conditions mainly entail antiphospholipid antibody syndrome, malignancy, acquired elevations of coagulation factors or acquired reduction of natural inhibitors, or hyperhomocysteinemia. Deepened knowledge of all potential risk factors, as well as the clear understanding of their role in the pathophysiology of venous thrombosis, are both essential to help achieve a faster and more efficient diagnosis of this condition as well as a more effective prophylaxis of patients at higher risk and treatment of those with manifest disease.

Thrombophilia
Factor V Leiden
Antiphospholipid antibody syndrome
Thrombophilic risk factors
VTE


Weighted Brain Network Metrics for Decoding Action Intention Understanding Based on EEG.

Abstract: Background: Understanding the action intentions of others is important for social and human-robot interactions. Recently, many state-of-the-art approaches have been proposed for decoding action intention understanding. Although these methods have some advantages, it is still necessary to design other tools that can more efficiently classify the action intention understanding signals. New Method: Based on EEG, we first applied phase lag index (PLI) and weighted phase lag index (WPLI) to construct functional connectivity matrices in five frequency bands and 63 micro-time windows, then calculated nine graph metrics from these matrices and subsequently used the network metrics as features to classify different brain signals related to action intention understanding. Results: Compared with the single methods (PLI or WPLI), the combination method (PLI+WPLI) demonstrates some overwhelming victories. Most of the average classification accuracies exceed 70%, and some of them approach 80%. In statistical tests of brain network, many significantly different edges appear in the frontal, occipital, parietal, and temporal regions. Conclusions: Weighted brain networks can effectively retain data information. The integrated method proposed in this study is extremely effective for investigating action intention understanding. Both the mirror neuron and mentalizing systems participate as collaborators in the process of action intention understanding.

Xiong|Xingliang|X| Yu|Zhenhua|Z| Ma|Tian|T| Luo|Ning|N| Wang|Haixian|H| Lu|Xuesong|X| Fan|Hui|H|

action intention understanding
phase lag index
classification accuracy
mentalizing system
mirror neuron system
weighted network metric


Extracorporeal membrane oxygenation and cytokine adsorption.

Abstract: Extracorporeal membrane oxygenation (ECMO) is an increasingly used technology for mechanical support of respiratory and cardio-circulatory failure. Excessive systemic inflammatory response is observed during sepsis and after cardiopulmonary bypass (CPB) with similar clinical features. The overwhelming inflammatory response is characterized by highly elevated pro- and anti-inflammatory cytokine levels. The excessive cytokine release during the overwhelming inflammatory response may result in multiple organ damage and failure. During ECMO therapy activation of complement and contact systems occur which may be followed by cytokine release. Controlling excessively increased cytokines may be considered as a valuable treatment option. Hemoadsorption therapy may be used to decrease cytokine levels in case of excessive inflammatory response and due to its unspecific adsorptive characteristics also substances like myoglobin, free hemoglobin or bilirubin. Controlling pro-inflammatory response with hemoadsorption may have positive impact on the endothelial glycocalix and also may be advantageous for maintenance of the vascular barrier function which plays a pivotal role in the development of tissue edema and oxygen mismatch. Hemoadsorption therapy seems to offer a promising new option for the treatment of patients with overwhelming inflammatory response leading to faster hemodynamic and metabolic stabilization finally resulting in preserved organ functions.

extracorporeal membrane oxygenation (ECMO)


Molecular Phylogeny of Trifolium L. Section Trifolium with Reference to Chromosome Number and Subsections Delimitation.

Abstract: The genus Trifolium is one of the largest genera of the legume family Fabaceae with ca. 255 species. The genus is divided into eight sections; the section Trifolium is a major section of the genus, comprising 73 species mainly distributed in the Mediterranean region. We used nuclear ribosomal DNA internal transcribed spacer (ITS) and morphological variation to reconsider the delimitation and phylogenetic relationships of species in the section Trifolium with reference to chromosomal variations. Bayesian analysis of ITS data delimited the species as three clades based on the analysis of ITS sequence and informative indels in combination with morphological variation. The phylogeny of the species by different analyses methods does not support their current delimitation in 17 subsections. The basic chromosome number x = 8 is the number for the genus Trifolium, from which x = 7, 6 and 5 were derived through successive aneuploidy events. With reference to the distribution of these numbers in the species of the section Trifolium, species in clade III and clade II are more evolved than species in clade I.

phylogeny
Trifolium
section Trifolium
chromosome number
ITS sequence


Intraarticular use of tranexamic acid reduces blood loss and transfusion rate after primary total knee arthroplasty.

Abstract:
BACKGROUND
Tranexamic acid (TXA) is effective in reduction of hemorrhage after major surgical procedures. In total joint replacement it is commonly administered intravenously. Despite various studies regarding the safety of its antifibrinolytic effect there are contraindications for systemic use. In total knee arthroplasty (TKA) TXA can also be administered intraarticular. However, there is a lack of studies focusing on dosage, effectiveness and complications of this local treatment. This study aimed to evaluate if blood loss and transfusion rate can be reduced in primary TKA by local application of TXA.

METHODS
We included a total of 202 consecutive primary, unilateral TKA patients, 101 without and 101 with intraartricular application of 2 g TXA. Surgery was conducted after a standardized protocol. Blood loss, transfusion and complication rates were evaluated until three months after surgery. Blood loss was estimated using the hematocrit-value (Hk) prior and five days after surgery by Rosenecher's and Mercuriali's formula.

RESULTS
By the use of TXA a significant reduction of blood loss (Rosencher average 1220 ml vs 1900 ml, Mercuriali average 430 ml vs 700 ml p < 0,001) and transfusion rate (0% vs 24.75% of patients, p < 0,001) was observed. There were no differences regarding complication rates. Due to the lower cost of TXA compared to applied erythrocyte concentrates a side effect of the treatment was a cost reduction of € 1.609 within this cohort.

CONCLUSIONS
The intraarticular application of 2 g TXA resulted in a significant reduction of blood loss and transfusion rate after primary TKA without increased complication rates. This method therefore seems to be a safe and cost effective instrument to reduce perioperative blood loss. However, it has to be considered that this is an off-label use.

Tranexamic acid
Blood loss
Transfusion rate
Primary total knee arthroplasty
TXA
TKA
Endoprosthetics
Risk reduction
Total joint arthroplasty


Percutaneous closure of an aortopulmonary window in a young adult patient: a case report of transcatheter closure with an occluder device.

Abstract:
Background
Aortopulmonary window is a congenital heart disease requiring a surgical approach to achieve a complete correction.

Case summary
We report on a case of a young female symptomatic adult patient with a significant aortopulmonary window. The patients refused surgical approach and since the defect was far enough from the pulmonary and aortic valve a percutaneous approach was proposed. The large aortopulmonary window was closed effectively with an Amplatzer Muscular Septal Occluder device (Abbott, Plymouth, MN, USA). At 1-year follow-up, the device was in a good position with no residual shunt.

Discussion
Transcatheter closure of an aortopulmonary window is an effective and safe procedure in specific anatomic defects.

Aortopulmonary window
Case report
Septal occluder device
Interventional cardiology


Glenoid component positioning and guidance techniques in anatomic and reverse total shoulder arthroplasty: A systematic review and meta-analysis.

Abstract:
Background
Positioning of the glenoid component is one of the most challenging steps in shoulder arthroplasty, and prosthesis longevity as well as functional outcomes is considered highly dependent on accurate positioning. This review considers the evidence supporting surgical navigation and patient-specific instruments for glenoid implant positioning in anatomic and reverse total shoulder arthroplasty.

Methods
A systematic literature search was performed for studies assessing glenoid implant positioning accuracy as measured by cross-sectional imaging on live subjects or cadaver models. Meta-analysis of controlled studies was performed to estimate the primary effects of navigation and patient-specific instruments on glenoid implant positioning error. Meta-analysis of absolute positioning outcomes was also performed for each group incorporating data from controlled and uncontrolled studies.

Results
Nine studies, four controlled and five uncontrolled, with 258 total subjects were included in the analysis. Meta-analysis of controlled studies supported that both navigation and patient-specific instruments had a moderate statistically significant effect on improving glenoid implant positioning outcomes. Meta-analysis of absolute positioning outcomes demonstrates glenoid implant positioning with standard instrumentation results in a high rate of malposition.

Discussion
Navigation and patient-specific instruments improve glenoid positioning outcomes. Whether the improvement in positioning outcomes achieved translate to better clinical outcomes is unknown.

glenoid
reverse total shoulder arthroplasty
total shoulder arthroplasty
surgical navigation
patient-specific instruments
image-guided surgery


Comparison of CE-MS/MS and LC-MS/MS sequencing demonstrates significant complementarity in natural peptide identification in human urine.

Abstract: Clinical proteomics has led to the identification of biomarkers specifically associated with a clinical condition that can serve for diagnostic or prognostic purposes. Learning more about the origin of these protein fragments would lead to a better insight in the pathology, and this requires improved identification of the peptide sequences. The aim of this study is to assess the complementarity of LC-MS/MS and CE-MS/MS as techniques in peptide sequence identification of the urinary low-molecular weight proteome. A male standard human urine sample was analyzed using LC- and CE-MS/MS (n = 10 per technique), identifying 905 unique peptide sequences with high confidence, 50% of those were identified only with LC, 20% only with CE and 30% with both techniques. Higher LC coverage might be due in part to the higher amount of sample that can be loaded onto an LC column. Peptides uniquely identified in CE are generally small and highly charged, likely unable to bind to the LC column In conclusion, we showed that LC-MS/MS and CE-MS/MS are highly complementary in identifying peptide sequences. The combination of both technologies results in significantly increased sequence coverage.

Klein|Julie|J| Papadopoulos|Theofilos|T| Mischak|Harald|H| Mullen|William|W|

MS
Clinical proteomics
Biomarkers
Peptide sequencing


The Role of Frozen Section in the Rapid Diagnosis of Severe Cutaneous Adverse Drug Reactions.

Abstract:
Context
Early diagnosis is the mainstay in the management of severe cutaneous adverse reactions (SCARs) to drugs.

Aims
To study the role of frozen section in the rapid diagnosis of SCARs and the impact on outcome of the affected patients.

Settings and Design
A single-blind, hospital-based study was conducted from December 2014-July 2016.

Methods and Material
We biopsied 32 adults with SCARs diagnosed by clinical features and standard criteria. The histopathological features seen on frozen sections were compared to that of paraffin blocks. The impact of rapid diagnosis on the clinical outcome was studied in toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP).

Statistical Analysis
Z test was used to compare two proportions. Kappa statistic, sensitivity, specificity, positive predictive value, and negative predictive value of the frozen section diagnosis were calculated in TEN/SJS and DRESS using MedCalc software.

Results
Frozen and paraffin sections were done in TEN/SJS spectrum (13), DRESS (17), and AGEP (2). The sensitivity, specificity and kappa values for frozen section diagnosis in SJS/TEN and DRESS were 91.7%, 95%, 0.867 and 94.4%, 100%, 0.937 respectively. The concordance between frozen and paraffin section diagnosis was 100% in TEN, SJS, DRESS and AGEP. All the 6 patients with TEN and 2 with AGEP survived. Taking the worst-case scenario, the mortality in SJS was 28.6%. The mortality among patients with DRESS was 11.8%.

Conclusions
Frozen section helps in the rapid diagnosis and early treatment of SCARs and differentiates it from diseases that mimic it.

Nicholas|Rajam|R|
Bindra|Mandeep Singh|MS|
Mathew|Lydia|L|
Sathishkumar|Dharshini|D|
Lakshmanan|Jeyaseelan|J|
George|Renu|R|

frozen section
rapid diagnosis
SCARs
outcome


Low plasma levels of calcitonin gene-related peptide in persistent post-traumatic headache attributed to mild traumatic brain injury.

Abstract:
OBJECTIVE
To investigate the role of calcitonin gene-related peptide (CGRP) in persistent post-traumatic headache (PTH) attributed to mild traumatic brain injury (TBI).

METHODS
A total of 100 individuals with persistent PTH attributed to mild TBI and 100 age- and gender-matched healthy controls were enrolled between July 2018 and June 2019. Blood was drawn from the antecubital vein and subsequently analyzed using a validated radioimmunoassay for human CGRP. Measurements were performed on coded samples by a board-certified laboratory technician who was blind to clinical information.

RESULTS
CGRP plasma levels were lower in subjects with persistent PTH (mean, 75.8 pmol/L; SD, 26.4 pmol/L), compared with age- and gender-matched healthy controls (mean, 88.0 pmol/L; SD, 34.1 pmol/L) (p = 0.04). No correlation was found of CGRP plasma levels with monthly headache days (r = -0.11; p = 0.27), monthly migraine-like days (r = 0.15; p = 0.13), headache quality (r = -0.14; p = 0.15), or a chronic migraine-like headache phenotype (r = -0.02; p = 0.85).

CONCLUSIONS
CGRP plasma measurements are unlikely a feasible blood-based biomarker of persistent PTH. Future studies should assess whether CGRP plasma measurements can be used to predict development of persistent PTH.

Ashina|Håkan|H|
Al-Khazali|Haidar Muhsen|HM|
Iljazi|Afrim|A|
Ashina|Sait|S|
Jørgensen|Niklas Rye|NR|
Amin|Faisal Mohammad|FM|
Ashina|Messoud|M|
Schytz|Henrik Winther|HW|

Biomarkers
concussion
head trauma
pathophysiology


Assessment of dosimetric and positioning accuracy of a magnetic resonance imaging-only solution for external beam radiotherapy of pelvic anatomy.

Abstract:
Background and purpose
The clinical feasibility of synthetic computed tomography (sCT) images derived from magnetic resonance imaging (MRI) images for external beam radiation therapy (EBRT) planning have been studied and adopted into clinical use recently. This paper evaluates the dosimetric and positioning performance of a sCT approach for different pelvic cancers.

Materials and methods
Seventy-five patients receiving EBRT at Turku University Hospital (Turku, Finland) were enrolled in the study. The sCT images were generated as part of a clinical MRI-simulation procedure. Dose calculation accuracy was assessed by comparing the sCT-based calculation with a CT-based calculation. In addition, we evaluated the patient position verification accuracy for both digitally reconstructed radiograph (DRR) and cone beam computed tomography (CBCT) -based image guidance using a subset of the cohort. Furthermore, the relevance of using continuous Hounsfield unit values was assessed.

Results
The mean (standard deviation) relative dose difference in the planning target volume mean dose computed over various cancer groups was less than 0.2 (0.4)% between sCT and CT. Among all groups, the average minimum gamma-index pass-rates were better than 95% with a 2%/2mm gamma-criteria. The difference between sCT- and CT-DRR-based patient positioning was less than 0.3 (1.4) mm in all directions. The registrations of sCT to CBCT produced similar results as compared with CT to CBCT registrations.

Conclusions
The use of sCT for clinical EBRT dose calculation and patient positioning in the investigated types of pelvic cancers was dosimetrically and geometrically accurate for clinical use.

Kemppainen|Reko|R| Suilamo|Sami|S| Ranta|Iiro|I| Pesola|Marko|M| Halkola|Aleksi|A| Eufemio|Alvin|A| Minn|Heikki|H| Keyriläinen|Jani|J|

Radiotherapy
Position verification
Image-guided radiotherapy
MRI-only


Exploration of the Prognostic and Immunotherapeutic Value of B and T Lymphocyte Attenuator in Skin Cutaneous Melanoma.

Abstract: B and T lymphocyte attenuator (BTLA) is a newly identified immune checkpoint molecular belonging to the CD28 immunoglobulin superfamily. However, the expression and clinical value of BTLA in skin cutaneous melanoma (SKCM) has not been widely characterized. We found that BTLA levels were upregulated in metastatic melanoma compared to normal skin tissues and primary melanoma. Higher BTLA was also correlated with improved prognosis in SKCM based on several datasets. The multivariate Cox regression model revealed that BTLA was an independent survival indicator in metastatic melanoma. Tumor microenvironment analysis indicated BTLA was positively associated with the infiltrating levels of different immune cells and the activity of the anti-cancer immunity cycle. Importantly, BTLA accurately predicted the outcome of melanoma patients treated with MAGE-A3 blocker or first-line anti-PD-1. The present findings disclose that BTLA is a reliable biomarker for prognosis and immunotherapeutic response and might contribute to developing novel SKCM immunological treatment strategies.

Dong|Xubin|X| Song|Jingjing|J| Chen|Buran|B| Qi|Yufeng|Y| Jiang|Wenjie|W| Li|Huihui|H| Zheng|Danni|D| Wang|Yinghao|Y| Zhang|Xiaohua|X| Liu|Haiguang|H|

skin cutaneous melanoma
B and T lymphocyte attenuator (BTLA)
prognosis
tumor microenvironment
immunotherapy
tumor-infiltration


Pyrolytic carbon-coated stainless steel felt as a high-performance anode for bioelectrochemical systems.

Abstract: Scale up of bioelectrochemical systems (BESs) requires highly conductive, biocompatible and stable electrodes. Here we present pyrolytic carbon-coated stainless steel felt (C-SS felt) as a high-performance and scalable anode. The electrode is created by generating a carbon layer on stainless steel felt (SS felt) via a multi-step deposition process involving α-d-glucose impregnation, caramelization, and pyrolysis. Physicochemical characterizations of the surface elucidate that a thin (20±5μm) and homogenous layer of polycrystalline graphitic carbon was obtained on SS felt surface after modification. The carbon coating significantly increases the biocompatibility, enabling robust electroactive biofilm formation. The C-SS felt electrodes reach current densities (jmax) of 3.65±0.14mA/cm(2) within 7days of operation, which is 11 times higher than plain SS felt electrodes (0.30±0.04mA/cm(2)). The excellent biocompatibility, high specific surface area, high conductivity, good mechanical strength, and low cost make C-SS felt a promising electrode for BESs.

Guo|Kun|K| Hidalgo|Diana|D| Tommasi|Tonia|T| Rabaey|Korneel|K|

Stainless steel felt
Bioelectrochemical systems
Microbial electrocatalysis
Pyrolytic carbon coating
Scalable electrode
Surface modification


Mitochondria and Coenzyme Q10 in the Pathogenesis of Preeclampsia.

Abstract: Hypertensive disorders during pregnancy constitute one of the main causes of maternal and perinatal morbidity and mortality across the world and particularly in developing countries such as Ecuador. However, despite its impact on public health, the primary pathophysiological processes involved are yet to be elucidated. It has been proposed, among other theories, that an abnormal placentation may induce an endothelial dysfunction, which is ultimately responsible for the final clinical manifestations. Mitochondria, particularly from trophoblastic cells, are responsible for the production of energy, which is extremely important for normal placentation. The malfunction in this supply of energy may produce higher levels of free radicals. In both production of energy and free radicals, coenzyme Q10 (CoQ10) plays a crucial role in electron transport. As such, the role of CoQ10 in the genesis and prevention of preeclampsia has become the focus of a number of research groups, including that of the authors. Developing an in-depth understanding of these mechanisms might allow us to design new and feasible strategies with which we can reduce preeclampsia, particularly in the Latin-American countries.

Teran|Enrique|E| Hernández|Isabel|I| Tana|Leandro|L| Teran|Santiago|S| Galaviz-Hernandez|Carlos|C| Sosa-Macías|Martha|M| Molina|Gustavo|G| Calle|Andrés|A|

mitochondria
coenzyme Q10
preeclampsia
pregnancy
placenta


Development of LC/MS/MS, high-throughput enzymatic and cellular assays for the characterization of compounds that inhibit kynurenine monooxygenase (KMO).

Abstract: Kynurenine monooxygenase (KMO) catalyzes the conversion of kynurenine to 3-hydroxykynurenine. Modulation of KMO activity has been implicated in several neurodegenerative diseases, including Huntington disease. Our goal is to develop potent and selective small-molecule KMO inhibitors with suitable pharmacokinetic characteristics for in vivo proof-of-concept studies and subsequent clinical development. We developed a comprehensive panel of biochemical and cell-based assays that use liquid chromatography/tandem mass spectrometry to quantify unlabeled kynurenine and 3-hydroxykynurenine. We describe assays to measure KMO inhibition in cell and tissue extracts, as well as cellular assays including heterologous cell lines and primary rat microglia and human peripheral blood mononuclear cells.

Winkler|Dirk|D|
Beconi|Maria|M|
Toledo-Sherman|Leticia M|LM|
Prime|Michael|M|
Ebneth|Andreas|A|
Dominguez|Celia|C|
Muñoz-Sanjuan|Ignacio|I|

LC/MS/MS
kynurenine
3-hydroxykynurenine
microglia
human PBMCs
kynurenine 3-monooxygenase


Keratopathy due to ophthalmic drug abuse with corneal melting and perforation presenting as Mooren-like ulcer: A case report.

Abstract: The present report describes the clinical course and treatment of a Mooren-like ulcer associated with abuse of topical anesthetics and dexamethasone. A 38-year-old male physician treated himself with lidocaine, tetracaine and dexamethasone (DEX) eye drops for severe pain and decline of vision in both eyes. After six months of treatment, his right cornea exhibited annular melting with full-thickness stromal infiltration at the limbus and central corneal haze. His left cornea was completely melted and exhibited iris prolapse. The patient was treated with topical antibiotics, lubricants and underwent a binocular keratoplasty. The surgery was successful and after eight months the postoperative best-corrected visual acuities were counting fingers in the right eye and light perception in the left eye. In summary, this report documents a severe case of keratopathy presenting as Mooren-like ulcer caused by topical anesthetics and DEX, which were treated via keratoplasty, resulting in useful vision being retained.

Wu|Hui|H| Hu|Yuan|Y| Shi|Xiao-Ru|XR| Xu|Feihong|F| Jiang|Chun-Ying|CY| Huang|Rong|R| Jia|Hui|H|

keratopathy
dexamethasone
keratoplasty
anesthetic abuse


Development of technologies applied to the biodegradation of warfare nerve agents: Theoretical evidence for asymmetric homogeneous catalysis.

Abstract: Organophosphorus compounds have been widely employed to the development of warfare nerve agents and pesticides, resulting in a huge number of people intoxicated annually, being a serious problem of public health. Efforts worldwide have been done in order to design new technologies that are capable of combating or even reversing the poisoning caused by these OP nerve agents. In this line, the bioremediation arises as a promising and efficient alternative for this purpose. As an example of degrading enzymes, there is the organophosphate-degrading (OpdA) enzyme from Agrobacterium radiobacter, which has been quite investigated experimentally due to its high performance in the degradation of neurotoxic nerve agents. This work aims to look into the structural and electronic details that govern the interaction modes of these compounds in the OpdA active site, with the posterior hydrolysis reaction prediction. Our findings have brought about data about the OpdA performance towards different nerve agents, and among them, we may realize that the degradation efficiency strongly depends on the nerve agent structure and its stereochemistry, being in this case the compound Tabun the one more effectively hydrolyzed. By means of the chemical bonds (AIM) and orbitals (FERMO) analysis, it is suggested that the initial reactivity of the OP nerve agents in the OpdA active site does not necessarily dictate the reactivity and interaction modes over the reaction coordinate.

Pereira|Ander Francisco|AF|
de Castro|Alexandre A|AA|
Soares|Flavia Villela|FV|
Soares Leal|Daniel Henriques|DH|
da Cunha|Elaine F F|EFF|
Mancini|Daiana Teixeira|DT|
Ramalho|Teodorico C|TC|

D016960:Agrobacterium tumefaciens
D001426:Bacterial Proteins
D001665:Binding Sites
D055162:Biocatalysis
D001673:Biodegradation, Environmental
D020134:Catalytic Domain
D006801:Humans
D062105:Molecular Docking Simulation
D000067397:Nerve Agents
D010744:Phosphoric Monoester Hydrolases
D011789:Quantum Theory
D012524:Sarin

Warfare nerve agents
AIM
FERMO
Docking
OpdA enzyme
QM/MM


Cavitation erosion mechanisms in Co-based coatings exposed to seawater.

Abstract: The cavitation erosion (CE) of most materials in seawater is more serious than in fresh water due to the onset of corrosion; however, in a previous study we reported results that contradict this widely accepted trend. In this research our objective is to provide fundamental insight into the mechanisms that may be responsible for these earlier results. To accomplish this objective, two types of Co-based coatings, prepared by high velocity oxygen fuel (HVOF) spraying system, were used to further investigate the underlying corrosion-mitigating CE mechanism in seawater. Accordingly, the influence of spraying parameters on microstructure, composition and mechanical properties of the coatings was analyzed on the basis of SEM, XRD, Raman spectroscopy, Vicker's hardness and nano-indentation results. Electrochemical corrosion tests were used to evaluate the corrosion behavior of the Co-based coatings. Their CE performances in seawater and deionized water were comparatively studied by a vibratory apparatus. Results demonstrated that a higher flame temperature facilitated the oxides formation with associated improvements in compactness, hardness and toughness of the coatings. The presence of alumina in combination with the oxides formed in-situ facilitated the formation of an oxidation film on surfaces, and effectively enhanced the charge transfer resistance of the coating, thereby significantly improving the corrosion resistance in seawater. Metallic Co was not only more easily oxidized but also more readily corroded than the alloyed Co. Compactness was identified as an important factor affecting CE resistance of coatings in deionized water, because defects facilitate the nucleation and eventual collapse of bubbles. Moreover, bubble collapse produced a transient high temperature spike in excess of 600 °C that also caused Co and Cr elements to oxidize. Because the CE tests were carried out in seawater, additional Co3O4 and Cr2O3 were generated owing to corrosion that more effectively increased the surface compactness and mechanical properties of the coatings. This behavior was particular notable for coatings with metallic Co and Cr, which should be why seawater corrosion could weaken the CE of Co-based coatings.

Hou|Guoliang|G| Ren|Yi|Y| Zhang|Xiaoliang|X| Dong|Fengxia|F| An|Yulong|Y| Zhao|Xiaoqin|X| Zhou|Huidi|H| Chen|Jianmin|J|

Cavitation erosion
Co-based coating
Corrosion
Mechanical properties
Oxidation


Ventral Tegmental Dopamine Neurons Participate in Reward Identity Predictions.

Abstract: Dopamine (DA) neurons in the ventral tegmental area (VTA) and substantia nigra (SNc) encode reward prediction errors (RPEs) and are proposed to mediate error-driven learning. However, the learning strategy engaged by DA-RPEs remains controversial. RPEs might imbue predictive cues with pure value, independently of representations of their associated outcome. Alternatively, RPEs might promote learning about the sensory features (the identity) of the rewarding outcome. Here, we show that, although both VTA and SNc DA neuron activation reinforces instrumental responding, only VTA DA neuron activation during consumption of expected sucrose reward restores error-driven learning and promotes formation of a new cue→sucrose association. Critically, expression of VTA DA-dependent Pavlovian associations is abolished following sucrose devaluation, a signature of identity-based learning. These findings reveal that activation of VTA- or SNc-DA neurons engages largely dissociable learning processes with VTA-DA neurons capable of participating in outcome-specific predictive learning, and the role of SNc-DA neurons appears limited to reinforcement of instrumental responses.

Keiflin|Ronald|R|
Pribut|Heather J|HJ|
Shah|Nisha B|NB|
Janak|Patricia H|PH|

dopamine
ventral tegmental area
substantia nigra
learning
blocking
conditioning
model-based
model-free
optogenetics
reward-prediction error


Cyanidin-3-O-β-glucoside ameliorates lipopolysaccharide-induced acute lung injury by reducing TLR4 recruitment into lipid rafts.

Abstract: Cyanidin-3-O-β-glucoside (C3G), a typical anthocyanin pigment that exists in the human diet, has been reported to have anti-inflammatory properties. The aim of this study was to detect the effect of C3G on LPS-induced acute lung injury and to investigate the molecular mechanisms. Acute lung injury was induced by intratracheal administration of LPS in mice. Alveolar macrophages from mice were stimulated with LPS and were treated with C3G. Our results showed that C3G attenuated lung histopathologic changes, myeloperoxidase (MPO) activity, TNF-α, IL-1β and IL-6 production in LPS-induced acute lung injury model. In vitro, C3G dose-dependently inhibited TNF-α, IL-1β, IL-6, IL-10 and IFN-β production, as well as NF-κB and IRF3 activation in LPS-stimulated alveolar macrophages. Furthermore, C3G disrupted the formation of lipid rafts by depleting cholesterol and inhibited TLR4 translocation into lipid rafts. Moreover, C3G activated LXRα-ABCG1-dependent cholesterol efflux. Knockout of LXRα abrogated the anti-inflammatory effects of C3G. In conclusion, C3G has a protective effect on LPS-induced acute lung injury. The promising anti-inflammatory mechanisms of C3G is associated with up-regulation of the LXRα-ABCG1 pathway which result in disrupting lipid rafts by depleting cholesterol and reducing translocation of TLR4 to lipid rafts, thereby suppressing TLR4 mediated inflammatory response.

Fu|Yunhe|Y| Zhou|Ershun|E| Wei|Zhengkai|Z| Wang|Wei|W| Wang|Tiancheng|T| Yang|Zhengtao|Z| Zhang|Naisheng|N|

D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1


Indications for pacemakers, implantable cardioverter-defibrillator and cardiac resynchronization devices.

Abstract: Implantable cardiac devices are important management tools for patients with heart rhythm disorders and heart failure. In this article, the current implantable cardiac rhythm devices are described in their evolution. The current indications and contraindications for these cardiac rhythm devices are reviewed.

Pacemaker
Implantable cardioverter-defibrillator
Cardiac rhythm devices
Arrhythmia
Cardiac resynchronization therapy
Systolic heart failure


Digital food environment during the coronavirus disease 2019 (COVID-19) pandemic in Brazil: an analysis of food advertising in an online food delivery platform.

Abstract: Online food delivery (OFD) platforms guarantee access to food during the coronavirus disease 2019 (COVID-19) pandemic when commercial food establishments are closed and access to food retail is controlled. The present study aimed to describe the advertisements published in an OFD platform in Brazilian capitals, during the 13th and 14th weeks of the pandemic. Data collection occurred on 1 d of the week and 1 d of the weekend and during lunch and dinner time. A random sample of 25 % of the advertisements (n 1754) published in this period was classified in accordance with the presence of food groups and to the use of marketing strategies. Sandwiches, ultra-processed beverages, traditional meals or pasta were the most common food groups shown in the advertisements. Free delivery prevailed in advertisements of ice cream, candies or salty packages snacks and pizza (P < 0·01). Combos were more frequently shown in the advertising of natural juices or smoothies, ultra-processed beverages, sandwiches and pizzas (P < 0·01). Messages about healthiness were more seen among natural juices or smoothies, vegetables and traditional meals and pasta advertisements (P < 0·01) and less seen in sandwiches (P = 0·02) and pizza advertisements (P < 0·01). Economy messages were rare in advertisements of traditional meals or pasta (P < 0·01) and more common in ultra-processed beverages (P = 0·03) and ice cream, candies or salty packages snacks (P < 0·01) advertisements. The OFD platform promoted unhealthy eating during the COVID-19 pandemic in Brazil due to the expressive presence of unhealthy foods advertising.

Food environment
COVID-19
Brazil
Digital media
Food marketing


Multi-functional self-assembled nanoparticles for pVEGF-shRNA loading and anti-tumor targeted therapy.

Abstract: Although RNA interference (RNAi) technology shows great potential in cancer treatment, the tumor target delivery and sufficient cytosolic transport of RNAi agents are still the main obstacles for its clinical applications. Herein, we report a functional supramolecular self-assembled nanoparticle vector for RNAi agent loading and tumor target therapy. Molecular block adamantane-grafted poly(ethylene glycol) (Ad-PEG) was modified with epidermal growth factor receptor (EGFR)-specific binding ligand GE11 or pH-sensitive fusogenic peptide GALA and then used for self-assembly with cyclodextrin-grafted branched polyethylenimine (CD-PEI), adamantane-grafted polyamidoamine dendrimer (Ad-PAMAM), and plasmid DNA containing a small hairpin RNA expression cassette against vascular endothelial growth factor (VEGF) into functional DNA-loaded supramolecular nanoparticles (GE11&GALA-pshVEGF@SNPs) based on molecular recognition and charge interaction. These functional peptides facilitated the target cell binding, internalization, and endosomal escape of GE11&GALA-pshVEGF@SNPs, resulting in increased reporter gene expression and efficient targeted gene silencing. The systemic delivery of the GE11&GALA-pshVEGF@SNPs can efficiently downregulate the intratumoral VEGF protein levels, reduce blood vessel formation, and significantly inhibit A549 xenograft tumor growth. These results reveal the potential of these multifunctional self-assembled nanoparticles as a nucleic acid drug delivery system for the treatment of lung cancer.

Lu|Sai|S| Bao|Xiao|X| Hai|Wangxi|W| Shi|Sanyuan|S| Chen|Yuetan|Y| Yu|Qianru|Q| Zhang|Maxin|M| Xu|Yuhong|Y| Peng|Jinliang|J|

D042461:Vascular Endothelial Growth Factor A