Plastic yearly production has surpassed the 300milliontons mark and recycling has all but failed in constituting a viable solution for the disposal of plastic waste. As these materials continue to ...accumulate in the environment, namely, in rivers and oceans, in the form of macro-, meso-, micro- and nanoplastics, it becomes of the utmost urgency to find new ways to curtail this environmental threat. Multiple efforts have been made to identify and isolate microorganisms capable of utilizing synthetic polymers and recent results point towards the viability of a solution for this problem based on the biodegradation of plastics resorting to selected microbial strains.
Herein, the response of the fungus Zalerion maritimum to different times of exposition to polyethylene (PE) pellets, in a minimum growth medium, was evaluated, based on the quantified mass differences in both the fungus and the microplastic pellets used. Additionally, molecular changes were assessed through attenuated total reflectance Fourier transform Infrared Spectroscopy (FTIR-ATR) and Nuclear Magnetic Resonance (NMR).
Results showed that, under the tested conditions, Z. maritimum is capable of utilizing PE, resulting in the decrease, in both mass and size, of the pellets. These results indicate that this naturally occurring fungus may actively contribute to the biodegradation of microplastics, requiring minimum nutrients.
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•Plastic pollution is of growing concern as it accumulates in the environment.•Multiple microorganisms have been described as potential bioremediation solutions.•The potential of Zalerion maritimum in the biodegradation of polyethylene was tested.•Z. maritimum used polyethylene as evidenced by FTIR, NMR and SEM results.•The results highlight the prospective use of Z. maritimum as a bioremediation tool.
Photodynamic Therapy (PDT) relies on the use of non-toxic photosensitizers that are locally and selectively activated by light to induce cell death or apoptosis through reactive oxygen species ...generation. The conjugation of porphyrinoids with sugars that target cancer is increasingly viewed as an effective way to increase the selectivity of PDT. To date, in vitro PDT efficacy is mostly screened using two-dimensional monolayer cultures. Compared to monolayer cultures, three-dimensional spheroid cultures have unique spatial distributions of nutrients, metabolites, oxygen and signalling molecules; therefore better mimic in vivo conditions. We obtained 0.05 mm3 spheroids with four different human tumor cell lines (HCT-116, MCF-7, UM-UC-3 and HeLa) with appropriate sizes for screening PDT agents. We observed that detachment from monolayer culture and growth as tumor spheroids was accompanied by changes in glucose metabolism, endogenous ROS levels, galectin-1 and glucose transporter GLUT1 protein levels. We compared the phototoxic responses of a porphyrin conjugated with four glucose molecules (PorGlu4) in monolayer and spheroid cultures. The uptake and phototoxicity of PorGlu4 is highly dependent on the monolayer versus spheroid model used and on the different levels of GLUT1 protein expressed by these in vitro platforms. This study demonstrates that HCT-116, MCF-7, UM-UC-3 and HeLa spheroids afford a more rational platform for the screening of new glycosylated-photosensitizers compared to monolayer cultures of these cancer cells.
Introduction
Rheumatoid arthritis (RA) is a common systemic autoimmune disease of unknown cause, characterized by a chronic, symmetric, and progressive inflammatory polyarthritis. One of the most ...deleterious effects induced by the chronic inflammation of RA is bone loss. During the last 15 years, the better knowledge of the cytokine network involved in RA allowed the development of potent inhibitors of the inflammatory process classified as biological DMARDs. These new drugs are very effective in the inhibition of inflammation, but there are only few studies regarding their role in bone protection. The principal aim of this review was to show the evidence of the principal biologic therapies and bone loss in RA, focusing on their effects on bone mineral density, bone turnover markers, and fragility fractures.
Methods
Using the PICOST methodology, two coauthors (PC, LM-S) conducted the search using the following MESH terms: rheumatoid arthritis, osteoporosis, clinical trials, TNF- antagonists, infliximab, adalimumab, etanercept, certolizumab, golimumab, IL-6 antagonists, IL-1 antagonists, abatacept, tocilizumab, rituximab, bone mineral density, bone markers, and fractures. The search was conducted electronically and manually from the following databases: Medline and Science Direct. The search period included articles from 2003 to 2015. The selection included only original adult human research written in English. Titles were retrieved and the same two authors independently selected the relevant studies for a full text. The retrieved selected studies were also reviewed completing the search for relevant articles. The first search included 904 titles from which 253 titles were selected. The agreement on the selection among researchers resulted in a Kappa statistic of 0.95 (p < 0.000). Only 248 abstracts evaluated were included in the acronym PICOST. The final selection included only 28 studies, derived from the systematic search. Additionally, a manual search in the bibliography of the selected articles was made and included into the text and into the section of “small molecules of new agents.”
Conclusion
Treatment with biologic drugs is associated with the decrease in bone loss. Studies with anti-TNF blocking agents show preservation or increase in spine and hip BMD and also a better profile of bone markers. Most of these studies were performed with infliximab. Only three epidemiological studies analyzed the effect on fractures after anti-TNF blocking agent’s treatment. IL-6 blocking agents also showed improvement in localized bone loss not seen with anti-TNF agents. There are a few studies with rituximab and abatacept. Although several studies reported favorable actions of biologic therapies on bone protection, there are still unmet needs for studies regarding their actions on the risk of bone fractures.
Despite the actual therapeutic approaches for inflammatory bowel disease (IBD), efficient and secure alternative options remain a research focus. In this context, anthocyanins seem promising natural ...anti-inflammatory agents, but their action mechanisms and efficacy as compared with established drugs still require more clarification. The main aim of this study was to compare the anti-inflammatory action of a chemically characterized anthocyanin-rich fraction (ARF), obtained from Portuguese blueberries (Vaccinium corymbosum L.), with that of 5-aminosalicylic acid (5-ASA), a first-line drug in IBD, in a 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis rat model. Such fraction showed a high content and great molecular diversity of anthocyanins, with malvidin-3-galactoside and petunidin-3-arabinoside in the highest concentrations. After daily administration by intragastric infusion for 8 days, ARF, at a molar anthocyanin concentration about 30 times lower than 5-ASA, showed a higher effectiveness in counteracting the intestinal inflammation, as assessed by i) body weight variation and colon damage score, ii) reduction in leukocyte infiltration, iii) increase in antioxidant defenses and iv) by downregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in colon tissue homogenates. The strong inhibition of COX-2 expression seems to be a crucial anti-inflammatory mechanism common to both ARF and 5-ASA, but the additional higher abilities of anthocyanins to downregulate iNOS and to decrease leukocytes infiltration and to increase antioxidant defenses in colon may account for the much higher anti-inflammatory action of anthocyanins. These data may contribute to the development of a promising natural approach in IBD management.
In 2017, the Australian Government funded the update of the National Physical Activity Recommendations for Children 0-5 years, with the intention that they be an integration of movement behaviours ...across the 24-h period. The benefit for Australia was that it could leverage research in Canada in the development of their 24-h guidelines for the early years. Concurrently, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group published a model to produce guidelines based on adoption, adaption and/or de novo development using the GRADE evidence-to-decision framework. Referred to as the GRADE-ADOLOPMENT approach, it allows guideline developers to follow a structured and transparent process in a more efficient manner, potentially avoiding the need to unnecessarily repeat costly tasks such as conducting systematic reviews. The purpose of this paper is to outline the process and outcomes for adapting the Canadian 24-Hour Movement Guidelines for the Early Years to develop the Australian 24-Hour Movement Guidelines for the Early Years guided by the GRADE-ADOLOPMENT framework.
The development process was guided by the GRADE-ADOLOPMENT approach. A Leadership Group and Consensus Panel were formed and existing credible guidelines identified. The draft Canadian 24-h integrated movement guidelines for the early years best met the criteria established by the Panel. These were evaluated based on the evidence in the GRADE tables, summaries of findings tables and draft recommendations from the Canadian Draft Guidelines. Updates to each of the Canadian systematic reviews were conducted and the Consensus Panel reviewed the evidence for each behaviour separately and made a decision to adopt or adapt the Canadian recommendations for each behaviour or create de novo recommendations. An online survey was then conducted (n = 302) along with five focus groups (n = 30) and five key informant interviews (n = 5) to obtain feedback from stakeholders on the draft guidelines.
Based on the evidence from the Canadian systematic reviews and the updated systematic reviews in Australia, the Consensus Panel agreed to adopt the Canadian recommendations and, apart from some minor changes to the wording of good practice statements, keep the wording of the guidelines, preamble and title of the Canadian Guidelines. The Australian Guidelines provide evidence-informed recommendations for a healthy day (24-h), integrating physical activity, sedentary behaviour (including limits to screen time), and sleep for infants (<1 year), toddlers (1-2 years) and preschoolers (3-5 years).
To our knowledge, this is only the second time the GRADE-ADOLOPMENT approach has been used. Following this approach, the judgments of the Australian Consensus Panel did not differ sufficiently to change the directions and strength of the recommendations and as such, the Canadian recommendations were adopted with very minor alterations. This allowed the Guidelines to be developed much faster and at lower cost. As such, we would recommend the GRADE-ADOLOPMENT approach, especially if a credible set of guidelines, with all supporting materials and developed using a transparent process, is available. Other countries may consider using this approach when developing and/or revising national movement guidelines.
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, Maryland; and Salt Lake City-Veterans Affairs Geriatrics, Research, Education, and ...Clinical Center (GRECC) and University of Utah School of Medicine, Salt Lake City, Utah
The classical studies of nicotine by Langley at the turn of the 20th century introduced the concept of a "receptive substance," from which the idea of a "receptor" came to light. Subsequent studies aided by the Torpedo electric organ, a rich source of muscle-type nicotinic receptors (nAChRs), and the discovery of -bungarotoxin, a snake toxin that binds pseudo-irreversibly to the muscle nAChR, resulted in the muscle nAChR being the best characterized ligand-gated ion channel hitherto. With the advancement of functional and genetic studies in the late 1980s, the existence of nAChRs in the mammalian brain was confirmed and the realization that the numerous nAChR subtypes contribute to the psychoactive properties of nicotine and other drugs of abuse and to the neuropathology of various diseases, including Alzheimer's, Parkinson's, and schizophrenia, has since emerged. This review provides a comprehensive overview of these findings and the more recent revelations of the impact that the rich diversity in function and expression of this receptor family has on neuronal and nonneuronal cells throughout the body. Despite these numerous developments, our understanding of the contributions of specific neuronal nAChR subtypes to the many facets of physiology throughout the body remains in its infancy.
•A deep learning approach to cope with Parkinson's disease (PD) diagnosis.•Handwritten dynamics to assess PD diagnosis.•Promising and accurate results.•An extensive experimental evaluation is ...conducted.•New insights about future research concerning automatic PD identification.
Parkinson's disease (PD) is considered a degenerative disorder that affects the motor system, which may cause tremors, micrography, and the freezing of gait. Although PD is related to the lack of dopamine, the triggering process of its development is not fully understood yet.
In this work, we introduce convolutional neural networks to learn features from images produced by handwritten dynamics, which capture different information during the individual's assessment. Additionally, we make available a dataset composed of images and signal-based data to foster the research related to computer-aided PD diagnosis.
The proposed approach was compared against raw data and texture-based descriptors, showing suitable results, mainly in the context of early stage detection, with results nearly to 95%.
The analysis of handwritten dynamics using deep learning techniques showed to be useful for automatic Parkinson's disease identification, as well as it can outperform handcrafted features.
The polymicrobial nature of ventilator-associated pneumonia (VAP) is now evident, with mixed bacterial-fungal biofilms colonizing the VAP endotracheal tube (ETT) surface. The microbial interplay ...within this infection may contribute for enhanced pathogenesis and exert impact towards antimicrobial therapy. Consequently, the high mortality/morbidity rates associated to VAP and the worldwide increase in antibiotic resistance has promoted the search for novel therapeutic strategies to fight VAP polymicrobial infections. Under this scope, this work aimed to assess the activity of mono- vs combinational antimicrobial therapy using one antibiotic (Polymyxin B; PolyB) and one antifungal (Amphotericin B; AmB) agent against polymicrobial biofilms of Pseudomonas aeruginosa and Candida albicans. The action of isolated antimicrobials was firstly evaluated in single- and polymicrobial cultures, with AmB being more effective against C. albicans and PolyB against P. aeruginosa. Mixed planktonic cultures required equal or higher antimicrobial concentrations. In biofilms, only PolyB at relatively high concentrations could reduce P. aeruginosa in both monospecies and polymicrobial populations, with C. albicans displaying only punctual disturbances. PolyB and AmB exhibited a synergistic effect against P. aeruginosa and C. albicans mixed planktonic cultures, but only high doses (256 mg L-1) of PolyB were able to eradicate polymicrobial biofilms, with P. aeruginosa showing loss of cultivability (but not viability) at 2 h post-treatment, whilst C. albicans only started to be inhibited after 14 h. In conclusion, combination therapy involving an antibiotic and an antifungal agent holds an attractive therapeutic option to treat severe bacterial-fungal polymicrobial infections. Nevertheless, optimization of antimicrobial doses and further clinical pharmacokinetics/pharmacodynamics and toxicodynamics studies underpinning the optimal use of these drugs are urgently required to improve therapy effectiveness and avoid reinfection.
The surface chemistry of a commercial AC (AC
0) was selectively modified, without changing significantly its textural properties, by chemical oxidation with HNO
3
(
AC
HNO
3
)
and O
2
(
AC
O
2
)
, ...and thermal treatments under H
2
(
AC
H
2
)
or N
2
(
AC
N
2
)
flow. The effect of modified AC on anaerobic chemical dye reduction was assayed with sulphide at different pH values 5, 7 and 9. Four dyes were tested: Acid Orange 7, Reactive Red 2, Mordant Yellow 10 and Direct Blue 71. Batch experiments with low amounts of AC (0.1
g
L
−1) demonstrated an increase of the first-order reduction rate constants, up to 9-fold, as compared with assays without AC. Optimum rates were obtained at pH 5 except for MY10, higher at pH 7. In general, rates increased with increasing the pH of point zero charge (pH
pzc), following the trend
AC
HNO
3
<
AC
O
2
<
AC
0
<
AC
N
2
<
AC
H
2
. The highest reduction rate was obtained for MY10 with
AC
H
2
at pH 7, which corresponded to the double, as compared with non-modified AC. In a biological system using granular biomass,
AC
H
2
also duplicated and increase 4.5-fold the decolourisation rates of MY10 and RR2, respectively. In this last experiment, reaction rate was independent of AC concentration in the tested range 0.1–0.6
g
L
−1.
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