Publications by authors named "João Costa"

469 Publications

3DICE coding matrix multidirectional macro-architecture modulates cell organization, shape, and co-cultures endothelization network.

Biomaterials 2021 Aug 31;277:121112. Epub 2021 Aug 31.

3B's Research Group, I3Bs, Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Zona Industrial da Gandra, AvePark, Barco GMR, 4805-017, Portugal; ICVS/3B's, PT Government Associate Laboratory, Braga, Guimarães, Portugal. Electronic address:

Natural extracellular matrix governs cells providing biomechanical and biofunctional outstanding properties, despite being porous and mostly made of soft materials. Among organs, specific tissues present specialized macro-architectures. For instance, hepatic lobules present radial organization, while vascular sinusoids are branched from vertical veins, providing specific biofunctional features. Therefore, it is imperative to mimic such structures while modeling tissues. So far, there is limited capability of coupling oriented macro-structures with interconnected micro-channels in programmable long-range vertical and radial sequential orientations. Herein, a three-directional ice crystal elongation (3DICE) system is presented to code geometries in cryogels. Using 3DICE, guided ice crystals growth templates vertical and radial pores through bulky cryogels. Translucent isotropic and anisotropic architectures of radial or vertical pores are fabricated with tunable mechanical response. Furthermore, 3D combinations of vertical and radial pore orientations are coded at the centimeter scale. Cell morphological response to macro-architectures is demonstrated. The formation of endothelial segments, CYP450 activity, and osteopontin expression, as liver fibrosis biomarkers, present direct response and specific cellular organization within radial, linear, and random architectures. These results unlock the potential of ice-templating demonstrating the relevance of macro-architectures to model tissues, and broad possibilities for drug testing, tissue engineering, and regenerative medicine.
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http://dx.doi.org/10.1016/j.biomaterials.2021.121112DOI Listing
August 2021

A Narrative Review on the Unexplored Potential of Colostrum as a Preventative Treatment and Therapy for Diarrhea in Neonatal Dairy Calves.

Animals (Basel) 2021 Jul 28;11(8). Epub 2021 Jul 28.

Department of Animal and Food Sciences, University of Kentucky, Lexington, KY 40506, USA.

Diarrhea is the leading cause of morbidity and mortality in pre-weaned dairy calves and, as such, represents a significant animal health and welfare concern. Furthermore, digestive disease early in life is associated with several long-term consequences such as reduced growth rate and decreased milk yield during the first lactation, thus generating severe economic losses. The majority of diarrheic cases in young calves are treated with antimicrobials; however, it is necessary to develop alternative treatments, as excessive antimicrobial usage can lead to antimicrobial resistance and can negatively impact the gut microflora of a calf. Bovine colostrum is abundant in immune and bioactive factors that improve immune function and development. This rich and natural combination of immunoglobulins, natural antimicrobial factors, growth factors, anti-inflammatories and nutrients may be an attractive alternative to antimicrobials in the treatment of diarrhea in young dairy calves. There is evidence that supports the use of colostrum as an early treatment for diarrhea in young calves. Future research should investigate its therapeutic and economic effectiveness.
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http://dx.doi.org/10.3390/ani11082221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8388388PMC
July 2021

Risk of SARS-CoV-2 Infection and COVID-19 Severity Associated With Exposure to Nonsteroidal Anti-Inflammatory Drugs: Systematic Review and Meta-Analysis.

J Clin Pharmacol 2021 Aug 5. Epub 2021 Aug 5.

Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.

Nonsteroidal anti-inflammatory drugs (NSAIDs) were thought to increase the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus entrance into cells. Hence, it was suggested in the media that NSAIDs could lead to a higher risk of infection and/or disease severity. To determine the existence or absence of this association, we aimed to systematically evaluate the risk of SARS-CoV-2 infection and mortality and the risk of severe coronavirus disease 2019 (COVID-19) associated with previous exposure to NSAIDs. MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and EMBASE were searched in February 2021 for controlled studies. The results were calculated through random-effect meta-analyses and reported in terms of odds ratios (ORs) with 95% confidence intervals (CIs). Heterogeneity was assessed with I test. Eleven studies were included, comprising a total of 683 715 patients. NSAID exposure did not increase the risk of having a positive test for SARS-CoV-2 infection (OR, 0.97; 95%CI, 0.85-1.11, I = 24%; 5 studies). The exposure to NSAIDs did not increase the risk of severe/critical COVID-19 disease (OR, 0.92; 95%CI, 0.80-1.05; I = 0%; 5 studies) nor all-cause mortality among patients with COVID-19 (OR, 0.86; 95%CI, 0.75-0.99; I = 14%, 4 studies). Our data did not suggest that exposure to NSAIDs increases the risk of having SARS-CoV-2 infection or increases the severity of COVID-19 disease. Also, the fragility of the studies included precludes definite conclusions and highlights the need for further robust data.
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http://dx.doi.org/10.1002/jcph.1949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426976PMC
August 2021

Recurrent myocarditis in the context of Behçet's disease: a case report.

Eur Heart J Case Rep 2021 Jul 30;5(7):ytab212. Epub 2021 Jul 30.

Department of Cardiology, Hospital Distrital de Santarém, Av. Bernardo Santareno, 2005-177 Santarém, Portugal.

Background: Behçet's syndrome is a multisystemic vasculitis of unknown aetiology. Cardiac involvement is rare, with described prevalence between 1% and 46%, with pericarditis, valvular insufficiency, intracardiac thrombosis, and eventually sinus of Valsalva aneurysms being the most common findings. Although previously reported, myocarditis is a very rare complication of Behçet's syndrome.

Case Summary: A 26-year-old man, smoker but otherwise healthy, was admitted to the emergency department with atypical chest pain, with no radiation, relation to efforts, position or deep inspiration, and dyspnoea, since the day before. His physical examination was unremarkable, including no fever, tachycardia, or pericardial friction rub. Electrocardiogram (ECG) revealed an early repolarization pattern, with no changes noted in subsequent exams. He had elevation of inflammatory parameters and an increased high-sensitivity troponin level of 3300 ng/L. Transthoracic echocardiography (TTE) was unremarkable. Coronary angiography showed no coronary stenosis. A presumed diagnosis of non-complicated viral myocarditis was established. The patient's condition improved with acetylsalicylic acid as needed and colchicine and he was discharged after 3 days. Cardiac magnetic resonance was performed, showing late epicardial enhancement in the apical segment of the lateral wall, supporting the diagnosis of myocarditis. Four months later, the patient returned with recurrence of chest pain. Additionally, he also complained of fever, odynophagia, and otalgia since the previous week. Oropharyngeal examination revealed tonsillar pillars aphthosis. The ECG was similar to the previous and TTE was normal. Bloodwork revealed once again elevation of inflammatory parameters and elevation of troponin. Recurrent myocarditis was diagnosed. Treatment with ibuprofen, colchicine, and antibiotic therapy was started with no significant improvement. After a more thorough physical examination, an ulcerated scrotal lesion, a left buttock folliculitis, and an axillary hidradenitis were found, which, according to the patient, were recurrent in the last year. Accordingly, the diagnosis of Behçet's syndrome with mucocutaneous and cardiac involvement was established. The patient was kept on colchicine and was also started on immunosuppressive therapy with corticosteroids and azathioprine, with resolution of the symptoms in the following day. A positron emission tomography (PET) was performed 2 days after discharge and showed a higher myocardial uptake in the left ventricular basal segments and both papillary muscles. Prednisolone tapering was started after 2 months, while maintaining azathioprine. At 1-year follow-up, the patient remained asymptomatic. A re-evaluation PET was performed, showing no images suggestive of metabolically active disease in the myocardium.

Discussion: This case highlights the importance of awareness of this rare but potentially serious entity and reinforces the significance of aetiology investigation in cases of recurrent myocarditis. It also shows the success of immunosuppressive therapy in a context where the optimal management is still considerably uncertain.
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http://dx.doi.org/10.1093/ehjcr/ytab212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323063PMC
July 2021

Which are the demographic and clinical characteristics of patients who respond to subcutaneous esketamine?

J Psychopharmacol 2021 Aug 3:2698811211035392. Epub 2021 Aug 3.

Walter Cantídio Teaching Hospital, Federal University of Ceará, Fortaleza, Brazil.

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http://dx.doi.org/10.1177/02698811211035392DOI Listing
August 2021

Low Donor Site Morbidity Associated With Tricortical Calcaneal Bone Graft [Formula: see text].

Foot Ankle Int 2021 Jul 30:10711007211032665. Epub 2021 Jul 30.

Head of Foot and Ankle Surgery Group, Orthopaedics and Traumatology Unit, Prevent Senior, São Paulo, Brazil.

Background: Autologous grafting is widely used in orthopedic surgery because of its high osteogenic capacity, immunologic compatibility, for the absence of risk of disease transmission, and for not requiring a bone bank. The posterior-superior calcaneal tuberosity is an option for obtaining a cortical and cancellous structural bone. This study aims to describe the operative technique and complications observed at the donor site of the posterior-superior calcaneal tuberosity.

Methods: Patients who underwent graft harvesting from the posterior-superior calcaneal tuberosity were retrospectively evaluated by pain outcomes, imaging tests, and intra- and postoperative complications.

Results: Twenty patients with a median age of 69 years (range 48-77) and follow-up of 16 months (12-26) were assessed. Median postoperative pain at the donor site was 0 (0-6), with 2 patients reporting persistent local pain. No case of Achilles tendon rupture or intra- or postoperative calcaneal fracture were identified. One patient developed a superficial infection that was quickly resolved using oral antibiotic therapy.

Conclusion: The posterior-superior calcaneal tuberosity is an alternative source of autologous graft with low donor site morbidity.

Level Of Evidence: Level IV, case series.
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http://dx.doi.org/10.1177/10711007211032665DOI Listing
July 2021

A narrative review of the migration and invasion features of non-small cell lung cancer cells upon xenobiotic exposure: insights from studies.

Transl Lung Cancer Res 2021 Jun;10(6):2698-2714

Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisboa, Portugal.

Lung cancer (LC) is the leading cause of cancer deaths worldwide, being non-small lung cancer (NSCLC) sub-types the most prevalent. Since most LC cases are only detected during the last stage of the disease the high mortality rate is strongly associated with metastases. For this reason, the migratory and invasive capacity of these cancer cells as well as the mechanisms involved have long been studied to uncover novel strategies to prevent metastases and improve the patients' prognosis. This narrative review provides an overview of the main migration and invasion assays employed in NSCLC research. While several methods have been developed, experiments using conventional cell culture models prevailed, specifically the wound-healing and the transwell migration and invasion assays. Moreover, it is provided herewith a summary of the available information concerning chemical contaminants that may promote the migratory/invasive properties of NSCLC cells , shedding some light on possible LC risk factors. Most of the reported agents with pro-migration/invasion effects derive from cigarette smoking [e.g., Benzo(a)pyrene and cadmium] and air pollution. This review further presents several studies in which different dietary/plant-derived compounds demonstrated to impair migration/invasion processes in NSCLC cells . These chemicals that have been proposed as anti-migratory consisted mainly of natural bioactive substances, including polyphenols non-flavonoids, flavonoids, bibenzyls, terpenes, alkaloids, and steroids. Some of these compounds may eventually represent novel therapeutic strategies to be considered in the future to prevent metastasis formation in LC, which highlights the need for additional methodologies that more closely resemble the tumor microenvironment and cancer cell interactions. These studies along with adequate models should be further explored as proof of concept for the most promising compounds.
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http://dx.doi.org/10.21037/tlcr-21-121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264350PMC
June 2021

3D Bioprinted Highly Elastic Hybrid Constructs for Advanced Fibrocartilaginous Tissue Regeneration.

Chem Mater 2020 Oct 25;32(19):8733-8746. Epub 2020 Sep 25.

Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, United States.

Advanced strategies to bioengineer a fibrocartilaginous tissue to restore the function of the meniscus are necessary. Currently, 3D bioprinting technologies have been employed to fabricate clinically relevant patient-specific complex constructs to address unmet clinical needs. In this study, a highly elastic hybrid construct for fibrocartilaginous regeneration is produced by co-printing a cell-laden gellan gum/fibrinogen (GG/FB) composite bioink together with a silk fibroin methacrylate (Sil-MA) bioink in an interleaved crosshatch pattern. We characterize each bioink formulation by measuring the rheological properties, swelling ratio, and compressive mechanical behavior. For biological evaluations, porcine primary meniscus cells (pMCs) are isolated and suspended in the GG/FB bioink for the printing process. The results show that the GG/FB bioink provides a proper cellular microenvironment for maintaining the cell viability and proliferation capacity, as well as the maturation of the pMCs in the bioprinted constructs, while the Sil-MA bioink offers excellent biomechanical behavior and structural integrity. More importantly, this bioprinted hybrid system shows the fibrocartilaginous tissue formation without a dimensional change in a mouse subcutaneous implantation model during the 10-week postimplantation. Especially, the alignment of collagen fibers is achieved in the bioprinted hybrid constructs. The results demonstrate this bioprinted mechanically reinforced hybrid construct offers a versatile and promising alternative for the production of advanced fibrocartilaginous tissue.
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http://dx.doi.org/10.1021/acs.chemmater.0c03556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294671PMC
October 2020

Atherosclerosis: The cost of illness in Portugal.

Rev Port Cardiol (Engl Ed) 2021 Jun 6;40(6):409-419. Epub 2021 Feb 6.

Centro de Estudos de Medicina Baseada na Evidência, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal; Laboratório de Farmacologia Clínica e Terapêutica, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal; Unidade de Farmacologia Clínica, Centro Hospitalar Lisboa Central EPE, Lisboa, Portugal.

Introduction And Objectives: Cardiovascular disease is the leading cause of death in Portugal and atherosclerosis is the most common underlying pathophysiological process. The aim of this study was to quantify the economic impact of atherosclerosis in Portugal by estimating disease-related costs.

Methods: Costs were estimated based on a prevalence approach and following a societal perspective. Three national epidemiological sources were used to estimate the prevalence of the main clinical manifestations of atherosclerosis. The annual costs of atherosclerosis included both direct costs (resource consumption) and indirect costs (impact on population productivity). These costs were estimated for 2016, based on data from the Hospital Morbidity Database, the health care database (SIARS) of the Regional Health Administration of Lisbon and Tagus Valley including real-world data from primary care, the 2014 National Health Interview Survey, and expert opinion.

Results: The total cost of atherosclerosis in 2016 reached 1.9 billion euros (58% and 42% of which was direct and indirect costs, respectively). Most of the direct costs were associated with primary care (55%), followed by hospital outpatient care (27%) and hospitalizations (18%). Indirect costs were mainly driven by early exit from the labor force (91%).

Conclusions: Atherosclerosis has a major economic impact, being responsible for health expenditure equivalent to 1% of Portuguese gross domestic product and 11% of current health expenditure in 2016.
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http://dx.doi.org/10.1016/j.repce.2020.08.003DOI Listing
June 2021

Forward genetics in Wolbachia: Regulation of Wolbachia proliferation by the amplification and deletion of an addictive genomic island.

PLoS Genet 2021 Jun 18;17(6):e1009612. Epub 2021 Jun 18.

Instituto Gulbenkian de Ciência, Oeiras, Portugal.

Wolbachia is one of the most prevalent bacterial endosymbionts, infecting approximately 40% of terrestrial arthropod species. Wolbachia is often a reproductive parasite but can also provide fitness benefits to its host, as, for example, protection against viral pathogens. This protective effect is currently being applied to fight arboviruses transmission by releasing Wolbachia-transinfected mosquitoes. Titre regulation is a crucial aspect of Wolbachia biology. Higher titres can lead to stronger phenotypes and fidelity of transmission but can have a higher cost to the host. Since Wolbachia is maternally transmitted, its fitness depends on host fitness, and, therefore, its cost to the host may be under selection. Understanding how Wolbachia titres are regulated and other aspects of Wolbachia biology has been hampered by the lack of genetic tools. Here we developed a forward genetic screen to identify new Wolbachia over-proliferative mutant variants. We characterized in detail two new mutants, wMelPop2 and wMelOctoless, and show that the amplification or loss of the Octomom genomic region lead to over-proliferation. These results confirm previous data and expand on the complex role of this genomic region in the control of Wolbachia proliferation. Both new mutants shorten the host lifespan and increase antiviral protection. Moreover, we show that Wolbachia proliferation rate in Drosophila melanogaster depends on the interaction between Octomom copy number, the host developmental stage, and temperature. Our analysis also suggests that the life shortening and antiviral protection phenotypes of Wolbachia are dependent on different, but related, properties of the endosymbiont; the rate of proliferation and the titres near the time of infection, respectively. We also demonstrate the feasibility of a novel and unbiased experimental approach to study Wolbachia biology, which could be further adapted to characterize other genetically intractable bacterial endosymbionts.
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http://dx.doi.org/10.1371/journal.pgen.1009612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244876PMC
June 2021

Considerations when using microplates and Neubauer counting chamber in ecotoxicity tests on microplastics.

Mar Pollut Bull 2021 Sep 11;170:112615. Epub 2021 Jun 11.

Centre for Environmental and Marine Studies (CESAM), Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.

The ubiquity of microplastics raises issues regarding contamination control measures and laboratory practices. The objective was to adapt the use of counting chambers and plastic microplates on the ecotoxicity evaluation of microplastics. Counting chambers, originally used to quantify cells, can also be used to count high concentrations of microplastics (<100 μm) used in laboratory assays. By decontaminating the chamber and mixing the test solution with Nile Red (1:1), fluorescent particles can be easily counted under optical microscopy. Microplate wells, due to their composition, can be contaminated or release microplastics to the test medium, which can interfere with the results of ecotoxicity assays or spectroscopy readings. A cleaning method based on ethanol was developed, which effectively removed particles by 91% without interfering with microalgae yield. Besides providing practical applications that can improve ecotoxicity assays, this work intends to raise awareness on the need to adapt laboratory practices when working with microplastics.
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http://dx.doi.org/10.1016/j.marpolbul.2021.112615DOI Listing
September 2021

Preparation of biological samples for microplastic identification by Nile Red.

Sci Total Environ 2021 Aug 17;783:147065. Epub 2021 Apr 17.

Centre for Environmental and Marine Studies (CESAM) & Department of Chemistry, University of Aveiro, Aveiro, Portugal. Electronic address:

Many methods have been used to isolate and identify microplastics from biological matrices. In biological samples, Nile Red can stain undigested residues, such as fats, soaps, and gels formed during organic matter removal, hindering the identification of fluorescent microplastics (≥2 μm). Thus, adjustments on sample preparation (e.g., fat removal) are required for the accurate identification of Nile Red stained microplastics. Multiples tests allowed to identify that digestion with 10% KOH at 60 °C for 24 h, followed by treatments with boiling water, acetone, and staining, produced good results in fourteen biological samples, including vertebrates and invertebrates. Digestion efficiencies were 94-100%, except for feces, which were 87%. Recovery rates of spiked microplastics were 97-100%, and few effects were observed in the infrared spectra and carbonyl index of seven polymers, with only the occasional yellowing suggesting surface changes. Filtration rates were improved by reducing the amount of sample. Small fluorescent microplastics could be identified in all samples under the microscope. Overall, the proposed method was efficient in removing natural organic matter from biological samples for Nile Red staining, requiring minimal sample handling, improving sample throughput, and allowing quantification of fluorescent microplastics in biological samples.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147065DOI Listing
August 2021

Adolescents' Perspectives on the Barriers and Facilitators of Physical Activity: An Updated Systematic Review of Qualitative Studies.

Int J Environ Res Public Health 2021 05 6;18(9). Epub 2021 May 6.

Facultad de Ciencias del Deporte y la Educación Física, Universidad de A Coruña, 15001 A Coruña, Spain.

Listening to adolescents' voices has been important to promote meaningful physical activity (PA) opportunities. Therefore, an updated systematic review of the available qualitative literature on adolescents' perspectives on the barriers and facilitators of PA was conducted, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies published between 2014 (date of the last systematic review) and 2020 were searched in the Web of Science, EBSCO, and SCOPUS databases. Based on the inclusion criteria applied, 30 out of 8069 studies were included in the review. A thematic analysis was used to inductively and deductively analyze the perspectives of ~1250 adolescents (13-18 years). The studies took place in 13 countries from different continents. The main PA barriers and facilitators of PA were presented and discussed around five higher-order themes: (1) Individual factors (e.g., psychological-motivation, self-efficacy; cognitive-knowledge, understanding; physical-motor skills); (2) social and relational factors (family, friends, significant others); (3) PA nature factors (fun, school-based PA and physical education); (4) life factors (time and competing activities; life-course); and (5) sociocultural and environmental factors (e.g., availability/access to PA facilities, programs; urban/rural zones). By transnationally framing adolescents' voices, this study provides updated evidence and discusses innovative implications for developing tailored interventions and pedagogical strategies aimed at promoting active and healthy lifestyles.
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http://dx.doi.org/10.3390/ijerph18094954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125166PMC
May 2021

TLR4-Endothelin Axis Controls Syncytiotrophoblast Motility and Confers Fetal Protection in Placental Malaria.

Infect Immun 2021 07 15;89(8):e0080920. Epub 2021 Jul 15.

Instituto Gulbenkian de Ciência, Oeiras, Portugal.

Pregnancy-associated malaria is often associated with adverse pregnancy outcomes. Placental circulatory impairments are an intriguing and unsolved component of malaria pathophysiology. Here, we uncovered a Toll-like receptor 4 (TLR4)-TRIF-endothelin axis that controls trophoblast motility and is linked to fetal protection during infection. In a cohort of 401 pregnancies from northern Brazil, we found that infection during pregnancy reduced expression of endothelin receptor B in syncytiotrophoblasts, while endothelin expression was only affected during acute infection. We further show that quantitative expression of placental endothelin and endothelin receptor B proteins are differentially controlled by maternal and fetal TLR4 alleles. Using murine malaria models, we identified placental autonomous responses to malaria infection mediated by fetally encoded TLR4 that not only controlled placental endothelin gene expression but also correlated with fetal viability protection. assays showed that control of endothelin expression in fetal syncytiotrophoblasts exposed to -infected erythrocytes was dependent on TLR4 via the TRIF pathway but not MyD88 signaling. Time-lapse microscopy in syncytiotrophoblast primary cultures and cell invasion assays demonstrated that ablation of TLR4 or endothelin receptor blockade abrogates trophoblast collective motility and cell migration responses to infected erythrocytes. These results cohesively substantiate the hypothesis that fetal innate immune sensing, namely, the TRL4-TRIF pathway, exerts a fetal protective role during malaria infection by mediating syncytiotrophoblast vasoregulatory responses that counteract placental insufficiency.
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http://dx.doi.org/10.1128/IAI.00809-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281214PMC
July 2021

European List of Essential Medicines for Medical Education: a protocol for a modified Delphi study.

BMJ Open 2021 05 4;11(5):e045635. Epub 2021 May 4.

Department of Internal Medicine, Section Pharmacotherapy, Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands.

Introduction: Junior doctors are responsible for a substantial number of prescribing errors, and final-year medical students lack sufficient prescribing knowledge and skills just before they graduate. Various national and international projects have been initiated to reform the teaching of clinical pharmacology and therapeutics (CP&T) during undergraduate medical training. However, there is as yet no list of commonly prescribed and available medicines that European doctors should be able to independently prescribe safely and effectively without direct supervision. Such a list could form the basis for a European Prescribing Exam and would harmonise European CP&T education. Therefore, the aim of this study is to reach consensus on a list of widely prescribed medicines, available in most European countries, that European junior doctors should be able to independently prescribe safely and effectively without direct supervision: the European List of Essential Medicines for Medical Education.

Methods And Analysis: This modified Delphi study will recruit European CP&T teachers (expert group). Two Delphi rounds will be carried out to enable a list to be drawn up of medicines that are available in ≥80% of European countries, which are considered standard prescribing practice, and which junior doctors should be able to prescribe safely and effectively without supervision.

Ethics And Dissemination: The study has been approved by the Medical Ethics Review Committee of VU University Medical Center (no. 2020.335) and by the Ethical Review Board of the Netherlands Association for Medical Education (approved project no. NVMO-ERB 2020.4.8). The European List of Essential Medicines for Medical Education will be presented at national and international conferences and will be submitted to international peer-reviewed journals. It will also be used to develop and implement the European Prescribing Exam.
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http://dx.doi.org/10.1136/bmjopen-2020-045635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098946PMC
May 2021

Microfluidics for Peptidomics, Proteomics, and Cell Analysis.

Nanomaterials (Basel) 2021 Apr 26;11(5). Epub 2021 Apr 26.

Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemigovo n. 542/2, 166 10 Prague 6, Czech Republic.

Microfluidics is the advanced microtechnology of fluid manipulation in channels with at least one dimension in the range of 1-100 microns. Microfluidic technology offers a growing number of tools for manipulating small volumes of fluid to control chemical, biological, and physical processes relevant to separation, analysis, and detection. Currently, microfluidic devices play an important role in many biological, chemical, physical, biotechnological and engineering applications. There are numerous ways to fabricate the necessary microchannels and integrate them into microfluidic platforms. In peptidomics and proteomics, microfluidics is often used in combination with mass spectrometric (MS) analysis. This review provides an overview of using microfluidic systems for peptidomics, proteomics and cell analysis. The application of microfluidics in combination with MS detection and other novel techniques to answer clinical questions is also discussed in the context of disease diagnosis and therapy. Recent developments and applications of capillary and microchip (electro)separation methods in proteomic and peptidomic analysis are summarized. The state of the art of microchip platforms for cell sorting and single-cell analysis is also discussed. Advances in detection methods are reported, and new applications in proteomics and peptidomics, quality control of peptide and protein pharmaceuticals, analysis of proteins and peptides in biomatrices and determination of their physicochemical parameters are highlighted.
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http://dx.doi.org/10.3390/nano11051118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145566PMC
April 2021

Upgrading the Topical Delivery of Poorly Soluble Drugs Using Ionic Liquids as a Versatile Tool.

Int J Mol Sci 2021 Apr 21;22(9). Epub 2021 Apr 21.

CBIOS-Universidade Lusófona's Research Center for Biosciences & Health Technologies, Campo Grande 376, 1749-024 Lisboa, Portugal.

Numerous studies are continuously being carried out in pursuit of formulations with higher performance. Problems such as poor drug solubility, which hinders drug incorporation into delivery systems and bioavailability, or limitations concerning the stability and performance of the formulations may cause difficulties, since solving all these drawbacks at once is a huge challenge. Ionic liquids (ILs), due to their tunable nature, may hypothetically be synthesized for a particular application. Therefore, predicting the impact of a particular combination of ions within an IL in drug delivery could be a useful strategy. Eight ILs, two choline amino acid ILs, two imidazole halogenated ILs, and four imidazole amino acid ILs, were prepared. Their applicability at non-toxic concentrations, for improving solubility and the incorporation of the poorly soluble, ferulic, caffeic, and -coumaric acids, as well as rutin, into topical emulsions, was assessed. Next, the impact of the ILs on the performance of the formulations was investigated. Our study showed that choosing the appropriate IL leads to a clear upgrade of a topical emulsion, by optimizing multiple features of its performance, such as improving the delivery of poorly soluble drugs, altering the viscosity, which may lead to better sensorial features, and increasing the stability over time.
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http://dx.doi.org/10.3390/ijms22094338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122351PMC
April 2021

Antithrombotic Therapy Recommendations in the European Society of Cardiology Guidelines: How Robust Are the Randomized Controlled Trials Underpinning Them?

TH Open 2021 Apr 14;5(2):e125-e133. Epub 2021 Apr 14.

Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.

 Criticisms have been raised against the sole use of -value in interpreting results from randomized controlled trials (RCTs). Additional tools have been suggested, like the fragility index (FI), a measure of a trial's robustness/fragility, and derivative measures. The FI is the minimum number of patients who would have to be converted from nonevents to events, in the group with the least events, for a result to lose statistical significance.  This study aimed to evaluate RCT supporting European Society of Cardiology (ESC) guidelines regarding antithrombotics, using the FI and FI-related measures.  FI, fragility quotient (FQ), and FI minus LTF lost to follow-up (FI - LTF) were calculated for the RCT underpinning recommendations regarding antithrombotic therapy from the updated ESC guidelines. LTF was compared with FI. Results were calculated for the total group of studies, as per guideline and as per recommendation type.  Overall, 61 studies were included. The median FI was 24.5 (interquartile range [IQR]: 9.0-60.0) and median FQ was 0.0035 (IQR: 0.0019-0.0056). Median FI - LTF was 2.0 (IQR: 0.0-38.0). Twenty (32.8%) of the studies had one primary or main safety outcome with LTF exceeding FI. Peripheral arterial disease guideline and chronic coronary syndrome guideline had the lowest (2.5; IQR: 1.8-3.3) and the highest (48.5; IQR: 23.8-73.0) FI, respectively.  The median FI suggests robustness of clinical trials evaluating antithrombotic drugs cited in the guidelines, but about one-third of them had LTF larger than FI. This emphasizes the need for assessing trials' robustness when constructing guidelines.
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http://dx.doi.org/10.1055/s-0041-1725043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046518PMC
April 2021

Selection of microplastics by Nile Red staining increases environmental sample throughput by micro-Raman spectroscopy.

Sci Total Environ 2021 Aug 9;783:146979. Epub 2021 Apr 9.

Centre for Environmental and Marine Studies (CESAM), Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal. Electronic address:

Nile Red staining enables visual identification and quantification of fluorescent particles as a proxy to microplastics at low cost and high throughput, including those of small sizes (≥2 μm), when preceded by proper natural organic matter removal, but providing no chemical characterization. On the other hand, micro-spectroscopy methods allow chemical characterization of particles based on their spectra, essential for polymer identification, but are costly and time-consuming. This work addresses the combination of both Nile Red staining with micro-Raman spectroscopy for the identification of microplastics. Besides being useful for quantification, Nile Red staining can be advantageously used as an objective criterion for pre-selection of particles for micro-Raman spectroscopy, producing little interference. The use of the 442 nm laser in micro-Raman spectroscopy induces Nile Red luminescence thus allowing to target the specific suspected microplastics when using an orange filter, reducing the number of particles subjected to identification and improving sample throughput. Staining dyes could also be used for mapping suspected microplastics before targeted analysis by micro-Raman spectroscopy. Thus, coupling Nile Red with micro-Raman spectroscopy can be useful to improve time efficiency while using this equipment.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146979DOI Listing
August 2021

Botulinum toxin type A versus anticholinergics for cervical dystonia.

Cochrane Database Syst Rev 2021 04 14;4:CD004312. Epub 2021 Apr 14.

Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal.

Background: This is an update of a Cochrane Review first published in 2005. Cervical dystonia is the most common form of focal dystonia and is a highly disabling movement disorder, characterised by involuntary, usually painful, head posturing. Currently, botulinum toxin type A (BtA) is considered the first line therapy for this condition. Before BtA, anticholinergics were the most widely accepted treatment.

Objectives: To compare the efficacy, safety, and tolerability of BtA versus anticholinergic drugs in adults with cervical dystonia.

Search Methods: We searched the Cochrane Movement Disorders' Trials Register to June 2003, screened reference lists of articles and conference proceedings to September 2018, and searched CENTRAL, MEDLINE, and Embase, with no language restrictions, to July 2020.

Selection Criteria: Double-blind, parallel, randomised trials (RCTs) of BtA versus anticholinergic drugs in adults with cervical dystonia.

Data Collection And Analysis: Two review authors independently assessed records, selected included studies, extracted data using a paper pro forma, and evaluated the risk of bias and quality of the evidence. We resolved disagreements by consensus or by consulting a third review author. If enough data had been available, we were to perform meta-analyses using a random-effects model for the comparison of BtA versus anticholinergic drugs to estimate pooled effects and corresponding 95% confidence intervals (95% CI). The primary efficacy outcome was improvement in cervical dystonia-specific impairment. The primary safety outcome was the proportion of participants with any adverse event.

Main Results: We included one RCT of moderate overall risk of bias (as multiple domains were at unclear risk of bias), which included 66 BtA-naive participants with cervical dystonia. Two doses of BtA (Dysport; week 0 and 8; mean dose 262 to 292 U) were compared with daily trihexyphenidyl (up to 24 mg daily). The trial was sponsored by the BtA producer. BtA reduced cervical dystonia severity by an average of 2.5 points (95% CI 0.68 to 4.32) on the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) severity subscale 12 weeks after injection, compared to trihexyphenidyl. More participants reported adverse events in the trihexyphenidyl treatment group (76 events), compared with the BtA group (31 events); however, the difference in dropouts due to adverse events was inconclusive between groups. There was a decreased risk of dry mouth, and memory problems with BtA, but the differences were inconclusive between groups for the other reported side effects (blurred vision, dizziness, depression, fatigue, pain at injection site, dysphagia, and neck weakness).

Authors' Conclusions: We found very low-certainty evidence that BtA is more effective, better tolerated, and safer than trihexyphenidyl. We found no information on a dose-response relationship with BtA, differences between BtA formulations or different anticholinergics, the utility of electromyography-guided injections, or the duration of treatment effect.
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http://dx.doi.org/10.1002/14651858.CD004312.pub3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092669PMC
April 2021

Microplastics on Barra beach sediments in Aveiro, Portugal.

Mar Pollut Bull 2021 Jun 29;167:112264. Epub 2021 Mar 29.

Université de Sfax, Laboratoire de Génie de l'Environnement et Ecotechnologie, GEET-ENIS, Route de Soukra km 4, Po. Box 1173, Sfax 3038, Tunisia.

Microplastic (MPs) pollution has been recognized as a serious threat to marine environment with the growing use of plastics. There is no sufficient data on the extent and characteristics of MPs pollution in the beach sediments and sand in the Atlantic Ocean. The coastal area is one of the main tourist zones in Aveiro in Portugal, thus, impacted by both tourism and maritime traffic, which are major sources of MPs. Considering this issue, 33 sediment samples were collected from the Praia da Barra beach in Aveiro. This pilot study showed that large quantities of MPs are accumulated on this beach with a median concentration of 100 MP kg-1 (15-320 MP kg-1), that is dominated by polyethylene (30%), polypropylene (27%), polystyrene (18%), nylon (12%), and polyester (6%). Size <1 mm constituted 99.5% of particles, mostly of transparent or black colors, with highest concentrations closest to the water line.
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http://dx.doi.org/10.1016/j.marpolbul.2021.112264DOI Listing
June 2021

A sodium alginate bilayer coating incorporated with green propolis extract as a powerful tool to extend Colossoma macropomum fillet shelf-life.

Food Chem 2021 Sep 18;355:129610. Epub 2021 Mar 18.

Centro de Ciências Agrárias Ambientais e Biológicas-CCAAB, Núcleo de Estudos em Pesca e Aquicultura-NEPA, Universidade Federal do Recôncavo da Bahia - UFRB, Cruz das Almas, Bahia, Brazil. Electronic address:

Fish deterioration imposes great economic losses and serious human health hazards. The objective of this work was to evaluate the effect of a sodium alginate bilayer coating incorporated to the green propolis extract in shelf-life, physical-chemical properties, microbiological properties and sensory acceptance of Colossoma macropomum fillets. Additionally, the chemical composition, along with the antioxidant and antibacterial activities of Brazilian green propolis extract (GPE) were investigated. GPE showed promising antioxidant and antibacterial activities. Twenty-seven metabolites were identified by gas chromatography (GC-MS), which mainly comprised terpenoids (52.14%). Cyclolaudenol was the major constituent of the GPE and it is described for the first time in green propolis extracts. C. macropomum fillets treated with the sodium alginate bilayer coating showed high sensory acceptance, reduced microbial deterioration and extended shelf-life (up to 11 days) during cold storage. Taken together, these results show that GPE can be a great alternative of a natural preservative for fish coating.
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http://dx.doi.org/10.1016/j.foodchem.2021.129610DOI Listing
September 2021

XCM Biologic Tissue Matrix xenograft and autologous micromucosa graft for vaginal reconstruction in Mayer-Rokitansky-Küster-Hauser syndrome.

Arch Plast Surg 2021 Mar 15;48(2):185-188. Epub 2021 Mar 15.

Department of Plastic, Reconstructive and Maxillofacial Surgery, Hospital of Egas Moniz, CHLO, Lisbon, Portugal.

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome can be treated through numerous surgical and nonsurgical methods. We present a surgical technique in which a neovagina was reconstructed and shaped by a vaginal expander with acellular porcine dermal matrix (XCM Biologic Tissue Matrix) and mucosal interposition using microfragments harvested from the hymen. In our case, we found this procedure to be safe and effective, resulting in satisfactory sexual function and good cosmetic results, without donor site morbidity. To our best knowledge, this tissue-engineered biomaterial has never been used for vaginal reconstruction before.
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http://dx.doi.org/10.5999/aps.2020.00556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007459PMC
March 2021

Predicting morbidity and mortality using automated milk feeders: A scoping review.

J Dairy Sci 2021 Jun 23;104(6):7177-7194. Epub 2021 Mar 23.

Department of Population Medicine, University of Guelph, Guelph, ON, Canada N1G 2W1. Electronic address:

Automated milk feeders (AMF) are computerized systems that provide producers with a tool that can be used to more efficiently raise dairy calves and allow for easier implementation of a high plane of nutrition during the milk feeding phase. Automated milk feeders also have the ability to track individualized behavioral data, such as milk consumption, drinking speed, and the number of rewarded and unrewarded visits to the feeder, that could potentially be used to predict disease development. The objective of this scoping review was to characterize the body of literature investigating the use of AMF data to predict morbidity and mortality in dairy calves during the preweaning stage. This review lists the parameters that have been examined for associations with disease in calves and identify discrepancies found in the literature. Five databases and relevant conference proceedings were searched. Eligible studies focused on the use of behavioral parameters measured by AMF to predict morbidity or mortality in preweaned dairy calves. Two reviewers independently screened titles and abstracts from 6,675 records identified during the literature search. After title and abstract screening, 382 studies were included and then assessed at the full-text level. Of these, 56 studies fed calves using an AMF and provided some measure of morbidity or mortality. Thirteen examined AMF parameters for associations with morbidity or mortality. The studies were completed in North America (n = 6), Europe (n = 6), and New Zealand (n = 1). The studies varied in sample size, ranging from 30 to 1,052 calves with a median of 100 calves. All 13 studies included enteric disease as an outcome and 11 studies evaluated respiratory disease. Of the studies measuring enteric disease, 8 provided disease definitions (n = 8/13, 61.2%); however, for respiratory disease, only 5 provided a disease definition (n = 5/11, 45.5%). Disease definitions and thresholds varied greatly between studies, with 10 using some form of health scoring. When evaluating feeding metrics as indicators of disease, all 13 studies investigated milk consumption and 6 and 7 studies investigated drinking speed and number of rewarded and unrewarded visits, respectively. Overall, this scoping review identified that daily milk consumption, drinking speed, and rewarded and unrewarded visits may provide insight into early disease detection in preweaned dairy calves. However, the disparity in reporting of study designs and results between included studies made comparisons challenging. In addition, to aid with the interpretation of studies, standardized disease outcomes should be used to improve the utility of this primary research.
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http://dx.doi.org/10.3168/jds.2020-19645DOI Listing
June 2021

Eugenia piauhiensis Vellaff. essential oil and γ-elemene its major constituent exhibit antileishmanial activity, promoting cell membrane damage and in vitro immunomodulation.

Chem Biol Interact 2021 Apr 10;339:109429. Epub 2021 Mar 10.

Laboratório de Doenças Infecciosas, Campus Ministro Reis Velloso, Universidade Federal do Delta do Parnaíba, 64202-020, Parnaíba, PI, Brazil. Electronic address:

Leishmaniasis is considered as one of the most Neglected Tropical Diseases (NTDs) in the world, caused by protozoan parasites of the genus Leishmania. Treatment of leishmaniasis by chemotherapy remains a challenge because of limited efficacy, toxic side effects, and drug resistance. The search for new therapeutic agents from natural sources has been a constant for the treatment of diseases such as leishmaniasis. The objective of this study was to evaluate the biological activity of Eugenia piauhiensis Vellaff. essential oil (EpEO) and its major constituent γ-elemene on promastigote and amastigote forms of Leishmania (Leishmania) amazonensis, its cytotoxicity, and possible mechanisms of action. EpEO was more active (IC 6.43 ± 0.18 μg/mL) against promastigotes than γ-elemene [9.82 ± 0.15 μg/mL (48.05 ± 0.73 μM)] and the reference drug miltefosine [IC 17.25 ± 0.26 μg/mL (42.32 ± 0.64 μM)]. EpEO and γ-elemene exhibited low cytotoxicity against J774.A1 macrophages, with CC 225.8 ± 3.57 μg/mL and 213.21 ± 3.3 μg/mL (1043 ± 16.15 μM), respectively. Additionally, EpEO and γ-elemene present direct activity against the parasite, decreasing plasma membrane integrity. EpEO and γ-elemene also proved to be even more active against intracellular amastigotes of the parasite [IC 4.59 ± 0.07 μg/mL and 8.06 ± 0.12 μg/mL (39.44 ± 0.59 μM)], respectively), presenting indirect effects through macrophage activity modulation. Anti-amastigote activity was associated with increased TNF-α, IL-12, NO, and ROS levels. In conclusion, our results suggest EpEO and γ-elemene as promising candidates for new drug development against leishmaniasis.
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http://dx.doi.org/10.1016/j.cbi.2021.109429DOI Listing
April 2021

Corrigendum to "The importance of contamination control in airborne fibers and microplastic sampling: Experiences from indoor and outdoor air sampling in Aveiro, Portugal" [Mar. Pollut. Bull. 159 (2020) 111522].

Mar Pollut Bull 2021 May 8;166:111888. Epub 2021 Mar 8.

Centre for Environmental and Marine Studies (CESAM) & Department of Environment and Planning, University of Aveiro, 3810-193 Aveiro, Portugal.

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http://dx.doi.org/10.1016/j.marpolbul.2020.111888DOI Listing
May 2021

Effect of partial exchange of lactose with fat in milk replacer on ad libitum feed intake and performance in dairy calves.

J Dairy Sci 2021 May 6;104(5):5432-5444. Epub 2021 Mar 6.

Trouw Nutrition R&D, PO Box 299, 3800 AG, Amersfoort, the Netherlands.

Compared with Holstein whole milk, commercial milk replacers (MR) for calves deliver relatively high levels of lactose and low levels of fat, and protein levels are rather comparable, resulting in a lower energy density and energy-to-protein ratio of the diet. Thus, the objective of this study was to determine the effects of partially exchanging lactose with fat in MR on voluntary feed intake, growth performance, and feeding behavior. Thirty-two male Holstein calves (2.1 ± 0.16 d of age, 46.4 ± 0.77 kg of body weight; BW) were assigned to 16 blocks of 2 calves per block based on arrival date and serum IgG. Within each block, calves were randomly assigned to 2 treatments: a high-lactose MR (HL; 17% fat; 44% lactose), or a high-fat MR (HF; 23% fat; 37% lactose). Lactose was exchanged by fat on a weight per weight basis, resulting in a 6% difference in metabolizable energy density per kilogram of MR. The experiment was divided into 3 phases: preweaning (P1; 0-35 d), weaning (P2; 36-56 d), and postweaning (P3; 57-84 d). For the first 2 wk of P1, calves were individually housed, fed their respective MR ad libitum through teat buckets, and provided access to water. At 14.2 ± 0.5 d of age, calves were group-housed (4 blocks/pen, 8 calves) and housed in group pens for the remainder of the study. In the group pens, calves were fed ad libitum MR, starter feed, chopped wheat straw, and water via automated feeders. During P2, calves were gradually weaned until complete milk withdrawal by 57 d and then monitored until 84 d (P3). Measurements included daily intakes and feeding behavior (rewarded and unrewarded visits), weekly BW and body measurements, and biweekly blood samples. Increasing fat content at the expense of lactose decreased MR intake during P1 by 15% (HL = 1.32 ± 0.04; HF = 1.17 ± 0.04 kg of dry matter per day), whereas total starter intake was not affected by MR composition. Once MR was restricted during P2, HL calves were reported to have more unrewarded visits to the automatic milk feeder than HF calves (11.9 ± 0.95 vs. 8.4 ± 1.03 visits/d, respectively). Crude protein intake was higher for HL calves during P1 (352.1 ± 11.2 vs. 319.6 ± 11.6 g/d), which was attributed to the higher intake of MR during that period, and metabolizable energy intake and protein-to-energy ratio remained comparable between treatments. Plasma cholesterol and nonesterified fatty acids levels were higher in HF calves as a consequence of the diet. Nevertheless, final BW (84 d) did not differ between treatments. Overall, calves fed ad libitum seemed to regulate their intake of MR based on its energy density, without significant effects on solid feed intake and overall growth.
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http://dx.doi.org/10.3168/jds.2020-19485DOI Listing
May 2021

A One Health perspective of the impacts of microplastics on animal, human and environmental health.

Sci Total Environ 2021 Jul 27;777:146094. Epub 2021 Feb 27.

Centre for Environmental and Marine Studies (CESAM), Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal. Electronic address:

Microplastics contamination is widespread in the environment leading to the exposure of both humans and other biota. While most studies overemphasize direct toxicity of microplastics, particle concentrations, characteristics and exposure conditions being used in these assays needs to be taken into consideration. For instance, toxicity assays that use concentrations over 100,000 times higher than those expected in the environment have limited practical relevance. Thus, adverse effects on animal and human health of current environmental concentrations are identified as a knowledge gap. Conversely, this does not suggest the lack of any significant effects of microplastics on a global scale. The One Health approach provides a novel perspective focused on the intersection of different areas, namely animal, human, and environmental health. This review provides a One Health transdisciplinary approach to microplastics, addressing indirect effects beyond simple toxicological effects. Microplastics can, theoretically, change the abiotic properties of matrices (e.g., soil permeability) and interfere with essential ecosystem functions affecting ecosystem services (e.g., biogeochemical processes) that can in turn impact human health. The gathered information suggests that more research is needed to clarify direct and indirect effects of microplastics on One Health under environmentally relevant conditions, presenting detailed knowledge gaps.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146094DOI Listing
July 2021

Engineering bioinks for 3D bioprinting.

Biofabrication 2021 04 8;13(3). Epub 2021 Apr 8.

3B's Research Group, I3Bs-Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Zona Industrial da Gandra, 4805-017 Barco GMR, Portugal.

In recent years, three-dimensional (3D) bioprinting has attracted wide research interest in biomedical engineering and clinical applications. This technology allows for unparalleled architecture control, adaptability and repeatability that can overcome the limits of conventional biofabrication techniques. Along with the emergence of a variety of 3D bioprinting methods, bioinks have also come a long way. From their first developments to support bioprinting requirements, they are now engineered to specific injury sites requirements to mimic native tissue characteristics and to support biofunctionality. Current strategies involve the use of bioinks loaded with cells and biomolecules of interest, without altering their functions, to deliverthe elements required to enhance healing/regeneration. The current research and trends in bioink development for 3D bioprinting purposes is overviewed herein.
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http://dx.doi.org/10.1088/1758-5090/abec2cDOI Listing
April 2021
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