Publications by authors named "M F Pinheiro"

842 Publications

Perceptions of senior nursing students regarding clinical decision-making.

Rev Bras Enferm 2021 9;74(1):e20200921. Epub 2021 Apr 9.

Escola Superior de Enfermagem de Lisboa. Lisboa, Portugal.

Objectives: to understand the perceptions of senior students in an undergraduate nursing course at a nursing college in Lisbon regarding skills related to clinical decision-making learned during their initial training.

Methods: qualitative study, of an exploratory and descriptive nature. Data collection occurred by carrying out a focus group with eight senior students in an undergraduate nursing course. Data treatment applied content analysis, performed with twebQDA® software.

Results: data were analyzed according to the four dimensions of Tanner's model of clinical judgment, and noticing and interpreting stood out as the most influential in clinical decision-making. Theoretical and clinical knowledge, validation of care planning, prioritization, and capacity to discuss and debate about situations emerged as the most representative skills.

Final Considerations: students make decisions by means of a complex process by using the knowledge and skills learned during their training.
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http://dx.doi.org/10.1590/0034-7167-2020-0921DOI Listing
April 2021

Vegetation patterns and the influence of rainfall after long-term fire suppression on a woody community of a Brazilian savanna.

An Acad Bras Cienc 2021 16;93(1):e20191405. Epub 2021 Apr 16.

Universidade Estadual Paulista, Departamento de Botânica, campus de Rio Claro, Av. 24-A, 1515, 13506-900 Rio Claro, SP, Brazil.

We evaluated the structural and floristic characteristics of a Brazilian savanna fragment occupied by cerradão (CD) and cerrado sensu stricto (CS) in response to the influence of rainfall and long-term fire suppression. We carried out floristic, phytosociological and remote sensing studies in a cerrado fragment located in Corumbataí (SP, Brazil) after 43 years of complete fire suppression. We surveyed 43 plots of 200 m2 each (17 plots in CS and 26 plots in CD) and all individuals ≥ 0.32 cm diameter measured at 30 cm from the ground were included in the sample. We calculated phytosociological parameters for each species and classified them in three ecological groups, namely savanna, generalist and forest species. The remote sensing analysis used aerial photographs and satellite images from 1962 to 2019 (i.e. 59 years). The structural study of community revealed high predominance of forest and generalist species when compared to savanna species. Non-linear correlation between CD expansion rates and total rainfall within the study period indicated a positive influence of the rainfall (R2 = 0.42). Thus, our analysis indicated a tendency of a continuous and fast expansion of CD over areas of CS in the long-term absence of fire combined with periods of heavy rain.
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http://dx.doi.org/10.1590/0001-3765202120191405DOI Listing
April 2021

Speech in implant-supported and removable complete denture wearers: A systematic review.

J Prosthet Dent 2021 Apr 14. Epub 2021 Apr 14.

Professor, Department of Prosthodontics and Periodontology, Piracicaba Dental School, University of Campinas, Piracicaba, São Paulo, Brazil. Electronic address:

Statement Of Problem: Prosthetic rehabilitation, especially with removable complete dentures (CDs), can contribute to speech problems, although the prevalence of the problem is unclear.

Purpose: The purpose of this systematic review was to examine the influence of implant-supported fixed complete dentures (FCDs), implant-supported overdentures, and removable CDs on speech articulation disorders in patients with at least 1 completely edentulous jaw.

Material And Methods: This study was prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered in the International Prospective Register of Systematic Reviews (CRD42020182705). The PubMed/Medline, Embase, Web of Science, Scopus, Latin American and Caribbean Health Sciences, Brazilian Clinical Trials Registry, and Cochrane Library databases were searched through April 2020 to identify clinical trials comparing maxillary and/or mandibular implant-supported dentures with removable CD use in terms of speech articulation in participants with at least 1 completely edentulous jaw. The risk of bias of selected studies was assessed with the Joanna Briggs Institute critical appraisal tools, and the quality of evidence was tested by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Results: Initially, 2586 articles were identified, and their titles and abstracts were read. Sixteen articles were read in full, and 8 studies (4 paired clinical trials and 4 cross-sectional studies) were included in this review. In total, 290 prosthesis users aged 29 to 90 years, approximately 44 of whom had hearing difficulties, were included. Four studies had a low risk of bias, and 4 studies had a high risk of bias. Distortions of the /s/ phoneme were observed more often in the first 6 months of maxillary FCD use than with removable CD use. Speech articulation did not differ between mandibular FCD and removable CD users. The quality of evidence for speech articulation disorders was low.

Conclusions: Given the low quality of evidence on speech articulation disorders, further research on speech articulation disorders in prosthesis wearers is needed.
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http://dx.doi.org/10.1016/j.prosdent.2021.03.006DOI Listing
April 2021

Are Endocan Plasma Levels Altered in Preeclampsia?

Rev Bras Ginecol Obstet 2021 Mar 15;43(3):232-234. Epub 2021 Apr 15.

Department of Clinical and Toxicological Analysis, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.

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http://dx.doi.org/10.1055/s-0041-1728661DOI Listing
March 2021

A Protocol for the Diagnosis of Autism Spectrum Disorder Structured in Machine Learning and Verbal Decision Analysis.

Comput Math Methods Med 2021 30;2021:1628959. Epub 2021 Mar 30.

University of Fortaleza (UNIFOR)-Graduate Program in Applied Informatics, Av. Washington Soares, 1321-Bl J Sl 30-60.811-905 Fortaleza, Brazil.

Autism Spectrum Disorder is a mental disorder that afflicts millions of people worldwide. It is estimated that one in 160 children has traces of autism, with five times the higher prevalence in boys. The protocols for detecting symptoms are diverse. However, the following are among the most used: the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5), of the American Psychiatric Association; the Revised Autistic Diagnostic Observation Schedule (ADOS-R); the Autistic Diagnostic Interview (ADI); and the International Classification of Diseases, 10th edition (ICD-10), published by the World Health Organization (WHO) and adopted in Brazil by the Unified Health System (SUS). The application of machine learning models helps make the diagnostic process of Autism Spectrum Disorder more precise, reducing, in many cases, the number of criteria necessary for evaluation, denoting a form of attribute engineering (feature engineering) efficiency. This work proposes a hybrid approach based on machine learning algorithms' composition to discover knowledge and concepts associated with the multicriteria method of decision support based on Verbal Decision Analysis to refine the results. Therefore, the study has the general objective of evaluating how the mentioned hybrid methodology proposal can make the protocol derived from ICD-10 more efficient, providing agility to diagnosing Autism Spectrum Disorder by observing a minor symptom. The study database covers thousands of cases of people who, once diagnosed, obtained government assistance in Brazil.
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http://dx.doi.org/10.1155/2021/1628959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026297PMC
March 2021

Why do patients leave the Pediatric Emergency Department and what happens to them?

Minerva Pediatr (Torino) 2021 Apr 2. Epub 2021 Apr 2.

Serviço de Pediatria, Unidade Autónoma de Gestão da Mulher e da Criança, Centro Hospitalar Universitário de São João, Porto, Portugal.

Background: The dropout rate is an important indicator of the quality of emergency services. The authors intent to evaluate factors that influence abandonments in the Pediatric Emergency Department (PED) and to assess outcome and destination of the highest triage leveled patients.

Methods: Retrospective analysis of the abandonment cases occurring between 2014 and 2016 in a tertiary hospital, including sociodemographic characterization, temporal factors, triage level, referral from other health services, waiting time and patient attendance. The outcome of the highest triage level was also accessed.

Results: In the three years analyzed, there were 240171 PED visits, with an abandonment rate of 2.57%. PED abandonment was influenced by higher patient attendance and waiting time, a younger age, and less urgent triage level. Only 1.78% of the urgent or emergent patients (level three or two) abandoned the PED. Of these, 44% sought medical care in the next five days, 41% of which in private institutions, 40% in public hospitals and 19% in primary care. Only 0.81% of those were hospitalized.

Conclusions: The majority of patients who leave the PED do not correspond to urgent cases. Health education awareness campaigns, clinical counseling platforms (online or phone services) and the improved accessibility of primary health care may optimize the usage of health resources. The reinforcement of the teams in times of greater affluence may contribute to decrease the rate of abandonment.
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http://dx.doi.org/10.23736/S2724-5276.21.05883-7DOI Listing
April 2021

mU54 tRNA Hypomodification by Lack of TRMT2A Drives the Generation of tRNA-Derived Small RNAs.

Int J Mol Sci 2021 Mar 14;22(6). Epub 2021 Mar 14.

Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, 3810 Aveiro, Portugal.

Transfer RNA (tRNA) molecules contain various post-transcriptional modifications that are crucial for tRNA stability, translation efficiency, and fidelity. Besides their canonical roles in translation, tRNAs also originate tRNA-derived small RNAs (tsRNAs), a class of small non-coding RNAs with regulatory functions ranging from translation regulation to gene expression control and cellular stress response. Recent evidence indicates that tsRNAs are also modified, however, the impact of tRNA epitranscriptome deregulation on tsRNAs generation is only now beginning to be uncovered. The 5-methyluridine (mU) modification at position 54 of cytosolic tRNAs is one of the most common and conserved tRNA modifications among species. The tRNA methyltransferase TRMT2A catalyzes this modification, but its biological role remains mostly unexplored. Here, we show that TRMT2A knockdown in human cells induces mU54 tRNA hypomodification and tsRNA formation. More specifically, mU54 hypomodification is followed by overexpression of the ribonuclease angiogenin (ANG) that cleaves tRNAs near the anticodon, resulting in accumulation of 5'tRNA-derived stress-induced RNAs (5'tiRNAs), namely 5'tiRNA-Gly and 5'tiRNA-Glu, among others. Additionally, transcriptomic analysis confirms that down-regulation of TRMT2A and consequently mU54 hypomodification impacts the cellular stress response and RNA stability, which is often correlated with tiRNA generation. Accordingly, exposure to oxidative stress conditions induces TRMT2A down-regulation and tiRNA formation in mammalian cells. These results establish a link between tRNA hypomethylation and ANG-dependent tsRNAs formation and unravel mU54 as a tRNA cleavage protective mark.
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http://dx.doi.org/10.3390/ijms22062941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001983PMC
March 2021

Oropharyngeal Squamous Cell Carcinoma Morphology and Subtypes by Human Papillomavirus Type and by 16 Lineages and Sublineages.

Head Neck Pathol 2021 Apr 2. Epub 2021 Apr 2.

Department of Otolaryngology - Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.

Oropharyngeal squamous cell carcinoma (SCC) is increasing in incidence and, in Western countries, strongly associated with transcriptionally-active high-risk human papillomavirus (HPV). Within HPV-positive tumors, there is wide morphologic diversity with numerous histologic subtypes of SCC. There are also variable degrees of keratinization, anaplasia, stromal fibrosis, and maturing squamous differentiation. Unlike in the uterine cervix, where associations between HPV types and lineages/sublineages within types have been investigated with some clear correlations identified, little to no data exists for oropharyngeal SCC. In this study, for a large cohort of oropharyngeal SCC patients, we performed RTPCR for high-risk HPV. For the HPV positive patients, we sequenced the DNA of the entire HPV16 genome and determined lineages and sublineages, correlating HPV status, genotype, and HPV16 lineages/sublineages with SCC subtype and various histologic features. Of the 259 patients, 224 (86.5%) were high-risk HPV positive, of which 210/224 (93.8%) were HPV type 16 and 6/224 (2.7%) HPV type 33. Of the four HPV16 lineages, A was the most frequent (192/214 or 89.8%) and of the HPV16 A sublineages, A1 was the most frequent (112/210 or 53.3%). Patients with HPV negative tumors were more often keratinizing vs other types (23/35 or 65.7%) and thus more likely to have more maturing squamous differentiation and stromal desmoplasia. There was no significant correlation between HPV type (16 versus other), between HPV16 lineage (A versus others), or HPV16 A sublineages (A1 or A2 versus others) and morphologic type of SCC nor the various morphologic features of anaplasia/multinucleation, degree of keratinization, nor amount of stromal desmoplasia. In summary, in our cohort, there was no correlation between the type of HPV, the HPV 16 lineage or sublineage, and any of the histologic features or morphologic SCC subtypes.
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http://dx.doi.org/10.1007/s12105-021-01318-4DOI Listing
April 2021

Health promotion actions in the School Health Program in Ceará: nursing contributions.

Rev Bras Enferm 2021 24;74(1):e20190769. Epub 2021 Mar 24.

Universidade Federal do Ceará. Fortaleza, Ceará, Brazil.

Objectives: to compare health promotion actions carried out by Family Health teams in Ceará, linked to the School Health Program.

Methods: a cross-sectional study involving the first and second cycles of an external assessment of 910 and 1,626 teams from 184 municipalities, which joined the Brazilian National Program for Improvement of Access and Quality of Primary Care. Eight clinical assessment and seven health promotion indicators were assessed, together with health professionals working in schools.

Results: the interviewees were nurses (95.6% and 98.3%). Between the cycles, there was an increase in clinical assessment (78.7% and 91.3%), health promotion and disease prevention (82.5% and 89.3%) and survey of students for follow-up (41.4% and 66.4%) in schools.

Conclusions: health actions at school advanced between cycles, with nurses as protagonists in school health, which can reduce vulnerabilities in children and adolescents and qualify Primary Care.
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http://dx.doi.org/10.1590/0034-7167-2019-0769DOI Listing
March 2021

Comparative Effectiveness of the Homeopathic Preparation Traumeel S in Third Molar Extraction Surgery: A Preliminary Triple-Blind Clinical Trial.

Homeopathy 2021 Mar 25. Epub 2021 Mar 25.

Division of Oral and Maxillofacial Surgery, Department of Dentistry, Federal University of Vales Jequitinhonha and Mucuri, Diamantina, Minas Gerais, Brazil.

Background And Aim:  This preliminary study aimed to evaluate whether a homeopathic preparation () might be a good option to control post-operative outcomes (pain, edema and trismus) associated with surgical removal of mandibular third molar teeth. The null hypothesis was that is not different from dexamethasone (gold standard) in controlling these post-operative inflammatory complications.

Methods:  A randomized, "split-mouth", triple-blind clinical trial was conducted. Seventeen healthy patients with a mean age of 20.94 ( ± 5.83) years had their lower asymptomatic bilateral third molars removed. Patients were randomized to receive or dexamethasone pre-operatively by injection into the masseter muscle; each patient acted as his/her own control. At 24, 48, 72 hours and 7 days after the surgery, the pain was evaluated according to a visual analog scale, edema through linear measurements of the face, and trismus through the maximum buccal opening. Wilcoxon statistics or paired -test were used, and a significance level of 95% was adopted.

Results:  For pain, the results for were not different ( > 0.05) from those of dexamethasone after 24 hours, 72 hours, and 7 days. For edema, the results for were not different ( > 0.05) from those of dexamethasone at all post-operative evaluations. For mouth opening, the results for were not different ( > 0.05) from those of dexamethasone at 72 hours and 7 days after third molar extraction.

Conclusion:  With the exception of some early post-operative findings, the null hypothesis is not rejected. might be a good alternative approach to dexamethasone for controlling pain, edema and trismus after third molar removal.
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http://dx.doi.org/10.1055/s-0041-1725038DOI Listing
March 2021

Brief Symptoms Inventory psychometric properties supports the hypothesis of a general psychopathological factor.

Trends Psychiatry Psychother 2021 Mar 23. Epub 2021 Mar 23.

Mental Health Department, Medical School, Federal University of Minas Gerais. Universidade FUMEC.

Introduction: The existence of a general factor related to psychiatric symptoms is supported by studies using a variety of methods in both clinical and non-clinical samples.

Objective: This study aims to evaluate the replicability of the internal structure of the Brief Symptom Inventory of a large Brazilian sample.

Methods: Participants were 6,427 Brazilian subjects (81% female). The mean age was 42.1 years old (SD = 13.6, Min = 13, Max = 80). All participants completed the online version of the Brief Symptom Inventory. This scale presents a general score (GSI) and nine specific clusters of symptoms (depression, anxiety, phobic anxiety, interpersonal sensibility, psychoticism, paranoid ideation, obsessive-compulsive behavior, hostility, and somatization symptoms).

Results: Confirmatory factorial analysis was performed to assess the factorial BSI structure. Results support that the bifactorial solution was the best-fitting model and the general factor showed itself to be the main dimension explaining most of the reliable variability in the data.

Conclusions: Findings suggest that BSI internal structure was replicated in a non-clinical sample and the general factor is the most reliable score. However, it is necessary to have a better understanding of the meaning of the general factor scores in a non-clinical sample to increase the interpretability of its scores.
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http://dx.doi.org/10.47626/2237-6089-2021-0207DOI Listing
March 2021

Combination of vitamin D and dipeptidyl peptidase-4 inhibitors (VIDPP-4i) as an immunomodulation therapy for autoimmune diabetes.

Int Immunopharmacol 2021 Mar 20;95:107518. Epub 2021 Mar 20.

Diabetes Research Institute Federation (DRIF), Division of Endocrinology and Diabetes, CTO Andrea Alesini Hospital, ASL Roma 2, Department of Systems Medicine, University of Rome Tor Vergata, Via San Nemesio 21, 00145 Rome, Italy; UniCamillus, Saint Camillus International University of Health Sciences, Via di Sant'Alessandro, 8, 00131 Rome, Italy; Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Via San Nemesio 21, 00145 Rome, Italy. Electronic address:

Type 1 diabetes (T1D) and latent autoimmune diabetes in adults (LADA) represent the most common types of autoimmune diabetes and are characterized by different age of onset, degrees of immune-mediated destruction of pancreatic beta cells and rates of disease progression towards insulin dependence. Several immunotherapies aimed to counteract autoimmune responses against beta cells and preserve beta-cell function are currently being investigated, particularly in T1D. Preliminary findings suggest a potential role of combination therapy with vitamin D and dipeptidyl peptidase-4 (DPP-4) inhibitors (VIDPP-4i) in preserving beta-cell function in autoimmune diabetes. This manuscript aims to provide a comprehensive overview of the immunomodulatory properties of vitamin D and DPP-4 inhibitors, as well as the rationale for investigation of their combined use as an immunomodulation therapy for autoimmune diabetes.
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http://dx.doi.org/10.1016/j.intimp.2021.107518DOI Listing
March 2021

Effects of Participating in a Research Project During the COVID-19 Pandemic on Medical Students' Educational Routines and Mental Health: Protocol for a Web-Based Survey Study.

JMIR Res Protoc 2021 04 9;10(4):e24617. Epub 2021 Apr 9.

see Acknowledgments, .

Background: The COVID-19 pandemic has resulted in social isolation, which has a potential negative impact on the educational routines (eg, the suspension of face-to-face appointments) and mental health of medical students. The Mario Pinotti II (MPII) study is a 24-week observational study that conducted scheduled telephone calls every 2 weeks to verify the occurrence of COVID-19 in patients with rheumatic diseases on chronic hydroxychloroquine therapy (from March 29, 2020, to September 30, 2020). The effects of voluntarily participating in a research project (ie, one that involves interactions via telephone contact with patients, professors, rheumatologists, and colleagues) on the daily lives and mental health of medical students requires evaluation.

Objective: As medical students are professionals in training and have a high level of responsibility in terms of handling the emotional and physical aspects of several diseases, this study aims to evaluate the impacts of the COVID-19 pandemic and participation in the MPII study on the educational routines and mental health of medical students.

Methods: A web-based survey was carried out to perform a cross-sectional comparative assessment of medical students who participated in the MPII study and their colleagues who were not involved in the MPII study. Participants from both groups were matched based on sex, age, and medical school. The web questionnaire was developed by a panel composed of graduate medical students, rheumatologists, medical school professors, and a psychology professor. The questionnaire included details on demographic and life habits data and evaluated participants' impressions of the MPII study and the impact of the COVID-19 pandemic on their educational routines and medical training. In addition, depression, anxiety, and stress were evaluated using the Brazilian version of the Depression, Anxiety, and Stress Scale (DASS)-21, and currently, the DASS-21 scores are grouped as those that indicate a low, moderate, or high risk of mental distress. This project was approved by the Federal University of São Paulo Ethics Committee (CAAE: 34034620.0.0000.5505).

Results: Data were collected from both medical student groups from July 20 to August 31, 2020. Data extraction was completed in September 2020. The data analysis is ongoing. We expect the results to be published in the first semester of 2021.

Conclusions: This study will provide insight into the effects of participating in a research project on depression, anxiety, and stress, which will be determined by applying the DASS-21 to a large sample of Brazilian undergraduate medical students. We will also evaluate the impact of the COVID-19 pandemic on medical students' educational routines and medical training.

International Registered Report Identifier (irrid): DERR1-10.2196/24617.
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http://dx.doi.org/10.2196/24617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041051PMC
April 2021

Transferrin-functionalized lipid nanoparticles for curcumin brain delivery.

J Biotechnol 2021 Apr 13;331:108-117. Epub 2021 Mar 13.

LAQV, REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, 4050-313, Porto, Portugal.

Curcumin is an anti-inflammatory and antioxidant compound with potent neuroprotective activity. Due to its poor water solubility, low bioavailability, rapid elimination and the challenges for crossing and transposing the blood-brain barrier (BBB), solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) loaded with curcumin were successfully produced and functionalized with transferrin, in order to mediate the transport of these particles through the BBB endothelium to the brain. The nanosystems revealed Z-averages under 200 nm, polydispersity index below 0.2 and zeta potential around -30 mV. Curcumin encapsulation around 65 % for SLNs and 80 % for NLCs was accomplished, while the functionalized nanoparticles presented a value around 70-75 %. A stability study revealed these characteristics remained unchanged for at least 3 months. hCMEC/D3 cells viability was firstly analysed by MTT and LDH assays, respectively, and a concentration of 10 μM of curcumin-loaded nanoparticles were then selected for the subsequent permeability assay. The permeability study was conducted using transwell devices with hCMEC/D3 cells monolayers and a 1.5-fold higher permeation of curcumin through the BBB was verified. Both SLNs and NLCs are promising for curcumin brain delivery, protecting the incorporated curcumin and targeting to the brain by the addition of transferrin to the nanoparticles surface.
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http://dx.doi.org/10.1016/j.jbiotec.2021.03.010DOI Listing
April 2021

Plant cell wall architecture guided design of CBM3-GH11 chimeras with enhanced xylanase activity using a tandem repeat left-handed β-3-prism scaffold.

Comput Struct Biotechnol J 2021 16;19:1108-1118. Epub 2021 Jan 16.

Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP CEP 14040-901, Brazil.

Effective use of plant biomass as an abundant and renewable feedstock for biofuel production and biorefinery requires efficient enzymatic mobilization of cell wall polymers. Knowledge of plant cell wall composition and architecture has been exploited to develop novel multifunctional enzymes with improved activity against lignocellulose, where a left-handed β-3-prism synthetic scaffold (BeSS) was designed for insertion of multiple protein domains at the prism vertices. This allowed construction of a series of chimeras fusing variable numbers of a GH11 β-endo-1,4-xylanase and the CipA-CBM3 with defined distances and constrained relative orientations between catalytic domains. The cellulose binding and endoxylanase activities of all chimeras were maintained. Activity against lignocellulose substrates revealed a rapid 1.6- to 3-fold increase in total reducing saccharide release and increased levels of all major oligosaccharides as measured by polysaccharide analysis using carbohydrate gel electrophoresis (PACE). A construct with CBM3 and GH11 domains inserted in the same prism vertex showed highest activity, demonstrating interdomain geometry rather than number of catalytic sites is important for optimized chimera design. These results confirm that the BeSS concept is robust and can be successfully applied to the construction of multifunctional chimeras, which expands the possibilities for knowledge-based protein design.
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http://dx.doi.org/10.1016/j.csbj.2021.01.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890094PMC
January 2021

Anti-inflammatory and antioxidant effects of the nanocomposite Fullerol decrease the severity of intestinal inflammation induced by gut ischemia and reperfusion.

Eur J Pharmacol 2021 May 26;898:173984. Epub 2021 Feb 26.

Laboratório de Interação Microrganismo Hospedeiro, Departamento de Microbiologia, Belo Horizonte, MG, Brazil. Electronic address:

Intestinal ischemia is a vascular emergency that arises when blood flow to the intestine is compromised. Reperfusion is necessary to restore intestinal function but might lead to local and systemic inflammatory responses and bacterial translocation, with consequent multiple organ dysfunction syndrome (MODS). During reperfusion occurs production of reactive oxygen species. These species contribute to intestinal injury through direct toxicity or activation of inflammatory pathways. Fullerol is a nanacomposite which has been shown to act as reactive oxygen species and reactive nitrogen species (RNS) scavengers. Thus, our aim was to evaluate whether Fullerol confer anti-inflammatory activity during intestinal ischemia and reperfusion (IIR). Intestinal ischemia was induced by total occlusion of the superior mesenteric artery. Groups were treated with vehicle or Fullerol 10 min before reperfusion. Mice were euthanized after 6 h of reperfusion, and small intestines were collected for evaluation of plasma extravasation, leukocyte influx, cytokine production and histological damage. Bacterial translocation to the peritoneal cavity and reactive oxygen and nitrogen species production by lamina propria cells were also evaluated. Our results showed that treatment with Fullerol inhibited bacterial translocation to the peritoneal cavity, delayed and decreased the lethality rates and diminished neutrophil influx and intestinal injury induced by IIR. Reduced severity of reperfusion injury in Fullerol-treated mice was associated with blunted reactive oxygen and nitrogen species production in leukocytes isolated from gut lamina propria and decreased production of pro-inflammatory mediators. Thus, the present study shows that Fullerol is a potential therapy to treat inflammatory bowel disorders associated with bacterial translocation, such as IIR.
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http://dx.doi.org/10.1016/j.ejphar.2021.173984DOI Listing
May 2021

Is skin temperature associated with muscle recovery status following a single bout of leg press?

Physiol Meas 2021 Apr 9;42(3). Epub 2021 Apr 9.

Federal Institute of Sudeste of Minas Gerais, Campus Rio Pomba, MG, Brazil.

. The measurement of skin temperature using infrared thermography has gained a lot of attention in sport and science since it might be related to the recovery process following high intensity, potentially damaging exercise. This study investigated the time course of the skin temperature response and the muscle recovery status following a resistance training session involving leg press exercise.. Fourteen young male college students (19.9 ± 1.7 years, 176 ± 6 cm, 66.1 ± 7.6 kg, 21.1 ± 1.8 kg.m) performed one session involving 10 sets, of 10 repetition maximum each (RM), of unilateral leg press 45° exercise, performed to momentary muscle failure, with 2 min rest between sets. Perceived recovery, mean and maximum thigh skin temperatures, thigh muscle thickness, maximal isometric strength, muscle soreness, and horizontal jump performance were measured pre, 24, 48, and 72 h following exercise.. The exercise protocol resulted in significant reduction in isometric strength, horizontal jump performance, and perceived recovery ( < 0.05). There was also a significant ( < 0.05) increase in muscle thickness and muscle soreness. With exception of jump performance, that recovered at 48 ( > 0.05), recovery parameters did not recover up to 72 h post-exercise ( > 0.05). Surprisingly, skin temperatures were not altered throughout the entire 72 h post-exercise period ( > 0.05). No significant positive correlation was found between skin temperatures and muscle thickness. Additionally, only one out of 16 correlation coefficients showed significant ( = -0.56, = 0.036) inverse association between skin temperature and isometric strength.. In conclusion, thigh skin temperature remains unaffected up to 72 h following a leg press exercise, and the time course response of thigh skin temperature was not associated with recovery status.
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http://dx.doi.org/10.1088/1361-6579/abe9feDOI Listing
April 2021

The One21 Technique: An Individualized Treatment for Glabellar Lines Based on Clinical and Anatomical Landmarks.

Clin Cosmet Investig Dermatol 2021 2;14:97-105. Epub 2021 Feb 2.

Departamento de Dermatologia da FMB-Unesp, Botucatu, SP, Brazil.

Purpose: Botulinum toxin type A is an effective treatment for glabellar dynamic wrinkles. As the muscular group involved in the contraction of the glabella varies among people, individualized treatment can achieve optimal results. This study evaluates a customized assessment for the treatment of glabellar lines with Incobotulinumtoxin-A, leading to an individualized points distribution and dosage.

Patients And Methods: A single-center, evaluator-blinded, therapeutic cohort study enrolled 130 women with moderate or severe glabellar wrinkles. They underwent Incobotulinumtoxin-A injection following the standard 5-point injection at the glabellar muscles (n = 65) or an individualized assessment and scheme treatment based on anatomical references of contraction, the One21 technique (n = 65). All the patients were photographed under maximum contraction before treatment (T0) and after 4 weeks (T28). The photos were randomly assessed by two blinded, experienced raters to consensually grade the severity according to the Merz Aesthetics Scales (MAS). The primary clinical efficacy was defined as a 2-point reduction in the MAS score, on Day 28.

Results: The groups were homogeneous regarding age, phototype, and baseline MAS scores. On Day 28 (T28), 64 (98.5%) patients from the One21 group and 52 (80%) from the 5-point group reduced the MAS score by at least two points ( < 0.01). When adjusted by age and phototype, both groups reduced the MAS score at T28 ( < 0.01); nevertheless, patients from the One21 group significantly performed better ( < 0.01), with a much higher rate response rate at T28, in comparison to the 5-point group. Of patients enrolled in the 5-point group, 83.1% utilized muscle groups other than the procerus and corrugator in glabellar wrinkle formation, and 17 (24.6%) presented asymmetrical contraction. Patients from the 5-point group with glabellar asymmetry and those who utilized the frontalis and orbicularis presented inferior performance ( < 0.05), reinforcing the importance of an individualized assessment and treatment plan.

Conclusion: The One21 technique yielded better results than the standard 5-point treatment in reducing glabellar dynamic lines with Incobotulinumtoxin-A, especially for asymmetric lines of the glabella or the involvement of muscle groups other than the procerus and corrugator.
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http://dx.doi.org/10.2147/CCID.S281901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866909PMC
February 2021

Dynamic sex chromosome expression in Drosophila male germ cells.

Nat Commun 2021 02 9;12(1):892. Epub 2021 Feb 9.

Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Kidney and Digestive Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.

Given their copy number differences and unique modes of inheritance, the evolved gene content and expression of sex chromosomes is unusual. In many organisms the X and Y chromosomes are inactivated in spermatocytes, possibly as a defense mechanism against insertions into unpaired chromatin. In addition to current sex chromosomes, Drosophila has a small gene-poor X-chromosome relic (4) that re-acquired autosomal status. Here we use single cell RNA-Seq on fly larvae to demonstrate that the single X and pair of 4 chromosomes are specifically inactivated in primary spermatocytes, based on measuring all genes or a set of broadly expressed genes in testis we identified. In contrast, genes on the single Y chromosome become maximally active in primary spermatocytes. Reduced X transcript levels are due to failed activation of RNA-Polymerase-II by phosphorylation of Serine 2 and 5.
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http://dx.doi.org/10.1038/s41467-021-20897-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873209PMC
February 2021

Chromosomal painting of the sandpiper (Actitis macularius) detects several fissions for the Scolopacidae family (Charadriiformes).

BMC Ecol Evol 2021 01 22;21(1). Epub 2021 Jan 22.

Laboratório de Citogenética, Centro de Estudos Avançados da Biodiversidade, ICB, Universidade Federal do Pará, PCT-Guamá, Terreno 11, Belém, Pará, 66075-750, Brazil.

Background: The Scolopacidae family (Suborder Scolopaci, Charadriiformes) is composed of sandpipers and snipes; these birds are long-distance migrants that show great diversity in their behavior and habitat use. Cytogenetic studies in the Scolopacidae family show the highest diploid numbers for order Charadriiformes. This work analyzes for the first time the karyotype of Actitis macularius by classic cytogenetics and chromosome painting.

Results: The species has a diploid number of 92, composed mostly of telocentric pairs. This high 2n is greater than the proposed 80 for the avian ancestral putative karyotype (a common feature among Scolopaci), suggesting that fission rearrangements have formed smaller macrochromosomes and microchromosomes. Fluorescence in situ hybridization using Burhinus oedicnemus whole chromosome probes confirmed the fissions in pairs 1, 2, 3, 4 and 6 of macrochromosomes.

Conclusion: Comparative analysis with other species of Charadriiformes studied by chromosome painting together with the molecular phylogenies for the order allowed us to raise hypotheses about the chromosomal evolution in suborder Scolopaci. From this, we can establish a clear idea of how chromosomal evolution occurred in this suborder.
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http://dx.doi.org/10.1186/s12862-020-01737-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853317PMC
January 2021

High levels of immunosuppression are related to unfavourable outcomes in hospitalised patients with rheumatic diseases and COVID-19: first results of ReumaCoV Brasil registry.

RMD Open 2021 01;7(1)

Hospital Universitário de Brasilia, Universidade de Brasília, Brasilia, Brazil.

Objectives: To evaluate risk factors associated with unfavourable outcomes: emergency care, hospitalisation, admission to intensive care unit (ICU), mechanical ventilation and death in patients with immune-mediated rheumatic disease (IMRD) and COVID-19.

Methods: Analysis of the first 8 weeks of observational multicentre prospective cohort study (ReumaCoV Brasil register). Patients with IMRD and COVID-19 according to the Ministry of Health criteria were classified as eligible for the study.

Results: 334 participants were enrolled, a majority of them women, with a median age of 45 years; systemic lupus erythematosus (32.9%) was the most frequent IMRD. Emergency care was required in 160 patients, 33.0% were hospitalised, 15.0% were admitted to the ICU and 10.5% underwent mechanical ventilation; 28 patients (8.4%) died. In the multivariate adjustment model for emergency care, diabetes (prevalence ratio, PR 1.38; 95% CI 1.11 to 1.73; p=0.004), kidney disease (PR 1.36; 95% CI 1.05 to 1.77; p=0.020), oral glucocorticoids (GC) (PR 1.49; 95% CI 1.21 to 1.85; p<0.001) and pulse therapy with methylprednisolone (PR 1.38; 95% CI 1.14 to 1.67; p=0.001) remained significant; for hospitalisation, age >50 years (PR 1.89; 95% CI 1.26 to 2.85; p=0.002), no use of tumour necrosis factor inhibitor (TNFi) (PR 2.51;95% CI 1.16 to 5.45; p=0.004) and methylprednisolone pulse therapy (PR 2.50; 95% CI 1.59 to 3.92; p<0.001); for ICU admission, oral GC (PR 2.24; 95% CI 1.36 to 3.71; p<0.001) and pulse therapy with methylprednisolone (PR 1.65; 95% CI 1.00 to 2.68; p<0.043); the two variables associated with death were pulse therapy with methylprednisolone or cyclophosphamide (PR 2.86; 95% CI 1.59 to 5.14; p<0.018).

Conclusions: Age >50 years and immunosuppression with GC and cyclophosphamide were associated with unfavourable outcomes of COVID-19. Treatment with TNFi may have been protective, perhaps leading to the COVID-19 inflammatory process.
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http://dx.doi.org/10.1136/rmdopen-2020-001461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844930PMC
January 2021

Effects of environmentally relevant levels of polyethylene microplastic on Mytilus galloprovincialis (Mollusca: Bivalvia): filtration rate and oxidative stress.

Environ Sci Pollut Res Int 2021 Jan 25. Epub 2021 Jan 25.

Faculty of Sciences of Bizerte, Laboratory of Environment Bio-monitoring, University of Carthage, 7021 Zarzouna, Bizerte, Tunisia.

The objective of the present study was to evaluate the potential toxic effects of polyethylene microplastics (PE-MPs) (40-48 μm) on the Mediterranean mussel Mytilus galloprovincialis in controlled laboratory conditions. The exposure was carried out for 14 days with three environmentally relevant PE-MPs concentrations of 1, 10, and 100 and a high concentration of 1000 μg/L. Effects of PE-MPs were assessed by evaluating the filtration rate (FR) after 7 and 14 days of exposure and by analyzing biochemical biomarkers of oxidative stress (catalase - CAT, glutathione S-transferase - GST, and the levels of lipid peroxidation - LPO) in the M. galloprovincialis digestive gland after 14 days of exposure. Results showed that M. galloprovincialis does not accumulate PE-MPs of 40-48 μm size in its whole tissues. The filtration rate was significantly reduced with the increase of PE-MPs concentrations. The biochemical biomarkers indicated that PE-MPs induced oxidative damage (LPO) at low concentrations (1 and 10 μg/L) with a significant reduction in females of 1000 μg/L treated group and inactivate antioxidative system (CAT and GST) in the digestive gland of both sexes at high concentrations (100 and 1000 μg/L). This study demonstrates that PE-MPs have biological effects on M. galloprovincialis at environmentally relevant concentrations thus brings new insights on the potential impacts of PE-MPs in marine bivalves.
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http://dx.doi.org/10.1007/s11356-021-12506-8DOI Listing
January 2021

Functional, biochemical and molecular impact of sediment plumes from deep-sea mining on Mytilus galloprovincialis under hyperbaric conditions.

Environ Res 2021 04 22;195:110753. Epub 2021 Jan 22.

CIIMAR - Interdisciplinary Centre of Marine and Environmental Research, Avenida General Norton de Matos S/N, 4450-208, Matosinhos, Portugal; FCUP - Faculty of Sciences, University of Porto, Rua do Campo Alegre S/N, 4169-007, Porto, Portugal. Electronic address:

The deep-sea is the biggest ecosystem in the world and despite the extreme conditions that characterize it, is highly biodiverse and complex. Deep-sea mining has been foreseen as a potential and concerning new stressor, and among the deep-sea mining associated stressors, sediment plumes, likely to be released into the water column as a side effect of mining, can reach habitats within a radius of more than a hundred kilometers. The present study examined the effects of suspended sediments of different grain sizes (63-125 μm, 125-250 μm and 250-500 μm) in the model species Mytilus galloprovincialis, at 4 bar, as a proxy to address the potential effects of sediment plumes, in the water column, with different grain sizes under high pressure conditions. Functional (filtration rate - FR), biochemical (catalase - CAT, glutathione s-transferase - GST, lipid peroxidation - LPO) and molecular (gene expression of [actin (ACTN), glutathione S-transferase alpha (GSTA), superoxide dismutase 2 (SOD2), catalase (CAT), heat shock protein 60 (HSP60), cytochrome c oxidase (COI) and DNA mismatch repair protein (MSH6)]) endpoints were studied in juvenile organisms. The FR decreased significantly for all tested grain size ranges, with a more severe effect for the particles with a diameter between 63 and 125 μm. In addition to the FR, significant changes were also observed for all tested biomarkers. Gene expression was significantly downregulated for CAT and ACTN. Overall, this study demonstrated that the smaller sized particles are the ones leading to more severe effects. Given their high dispersion potential and longer suspension periods under mining operation scenarios, particular attention should be given to the release of sediment plumes that may affect deep-sea environments and the water column. It is, therefore, vital to create standards and guidelines for sustainable mining practices.
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http://dx.doi.org/10.1016/j.envres.2021.110753DOI Listing
April 2021

Factors associated with seeking medical care for low back pain in a twin adult sample.

Eur J Pain 2021 May 16;25(5):1091-1106. Epub 2021 Feb 16.

School of Health Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.

Background: Previous studies have only investigated how symptom presentation and socio-demographic factors influence care-seeking for low back pain (LBP). However, the influence of health and lifestyle factors remains unclear, and the potential confounding effects of aggregated familial factors (including genetics and the early shared environment) has not been considered extensively.

Methods: A cross-sectional analysis was performed on 1605 twins enrolled in the Murcia Twin Registry (Spain). The outcome was seeking medical care for LBP and various self-reported demographic, health and lifestyle factors were considered predictors. All variables except sleep quality and diabetes were collected in 2013, which were cross-referenced from 2009 to 2010. A multivariate logistic regression model was performed on the total sample, followed by a co-twin case-control analysis.

Results: The only significant factor found to increase the odds of seeking medical care for LBP without being affected by familial factors was poor sleep quality (total sample OR = 1.58, 95%CI 1.24-2.01; case-control OR = 1.75, 95%CI 1.14-2.69). The factors that were associated with reduced odds of seeking medical care for LBP and not confounded by familial factors were male sex (case-control OR = 0.55, 95%CI 0.33-0.93), alcohol intake (case-control OR = 0.90, 95%CI 0.82-0.99) and a history of diabetes (case-control OR = 0.50, 95%CI 0.25-0.97). No other factors significantly influenced medical care-seeking for LBP.

Conclusions: People reporting poor sleep quality are more likely to seek medical care for LBP in the long term, with this relationship being independent from aggregated familial factors. Conversely, males, people reporting higher alcohol intake, and people with a history of diabetes are less likely to seek medical care for LBP.

Significance: This is the first study investigating the factors that influence seeking medical care for LBP, while adjusting for the influence of familial factors using a co-twin control design. Poor sleep quality is associated with seeking medical care for LBP in the long term and does not appear to be confounded by familial factors. Early screening for indicators of poor sleep quality and appropriate referral to interventions for improving sleep quality or reducing pain in sleep may improve LBP management.
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http://dx.doi.org/10.1002/ejp.1731DOI Listing
May 2021

Why Are Men More Likely to Endorse Myths About Child Sexual Abuse Than Women? Evidence From Disposition and Situation-Based Approaches.

Child Maltreat 2021 Jan 20:1077559520988353. Epub 2021 Jan 20.

Instituto Universitário de Lisboa (ISCTE-IUL), Cis-IUL, Lisbon, Portugal.

Research on attitudes toward Child Sexual Abuse (CSA) consistently shows that men are more likely to endorse myths about CSA events, victims and perpetrators, compared to women. Here we present two studies that examine these gender differences occur. Study one (N = 439) followed a dispositional approach to test the mediating role of empathy, social dominance orientation (SDO) and propensity for moral disengagement in the association between gender and the endorsement of CSA myths. Male participants showed higher levels of SDO and propensity for moral disengagement, and lower empathy, which in turn were associated with greater CSA myths acceptance. Study two (N = 360) followed a situational approach to test these processes using a specific case of CSA. Male participants showed higher levels of SDO and lower empathy, which in turn were associated with lower scores of perceived assault seriousness, victim credibility, perpetrator culpability, and greater victim culpability. Overall, the results suggest that men and women may appraise CSA differently, which can be partly explained by differences in SDO, propensity to morally disengage, and empathy. Furthermore, different cognitive mechanisms may be activated with regard to general appraisals of CSA compared to specific cases of CSA.
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http://dx.doi.org/10.1177/1077559520988353DOI Listing
January 2021

Potential vectors of Leishmania spp. in an Atlantic Forest conservation unit in northeastern Brazil under anthropic pressure.

Parasit Vectors 2021 Jan 11;14(1):38. Epub 2021 Jan 11.

Laboratório de Pesquisas em Entomologia, Departamento de Microbiologia e Parasitologia, Centro de Biociências, Universidade Federal do Rio Grande do Norte, Avenida Senador Salgado Filho, 3000, Natal, Rio Grande do Norte, Brazil.

Background: Phlebotomines are a group of insects which include vectors of the Leishmania parasites that cause visceral leishmaniasis (VL) and cutaneous leishmaniasis (CL), diseases primarily affecting populations of low socioeconomic status. VL in Brazil is caused by Leishmania infantum, with transmission mainly attributed to Lutzomyia longipalpis, a species complex of sand fly, and is concentrated mainly in the northeastern part of the country. CL is distributed worldwide and occurs in five regions of Brazil, at a higher incidence in the north and northeast regions, with etiological agents, vectors, reservoirs and epidemiological patterns that differ from VL. The aim of this study was to determine the composition, distribution and ecological relationships of phlebotomine species in an Atlantic Forest conservation unit and nearby residential area in northeastern Brazil.

Methods: Centers for Disease Control and Shannon traps were used for collections, the former at six points inside the forest and in the peridomestic environment of surrounding residences, three times per month for 36 months, and the latter in a forest area, once a month for 3 months. The phlebotomines identified were compared with climate data using simple linear correlation, Pearson's correlation coefficient and cross-correlation. The estimate of ecological parameters was calculated according to the Shannon-Wiener diversity index, standardized index of species abundance and the dominance index.

Results: A total of 75,499 phlebotomines belonging to 11 species were captured in the CDC traps, the most abundant being Evandromyia walkeri, Psychodopygus wellcomei and Lu. longipalpis. Evandromyia walkeri abundance was most influenced by temperature at collection time and during the months preceding collection and rainfall during the months preceding collection. Psychodopygus wellcomei abundance was most affected by rainfall and relative humidity during the collection month and the month immediately preceding collection time. Lutzomyia longipalpis abundance showed a correlation with temperature and the rainfall during the months preceding collection time. The Shannon trap contained a total of 3914 phlebotomines from these different species. Psychodopygus wellcomei, accounting for 91.93% of the total, was anthropophilic and active mainly at night.

Conclusions: Most of the species collected in the traps were seasonal and exhibited changes in their composition and population dynamics associated with local adaptions. The presence of vectors Ps. wellcomei and Lu. longipalpis underscore the epidemiological importance of these phlebotomines in the conservation unit and surrounding anthropized areas. Neighboring residential areas should be permanently monitored to prevent VL or CL transmission and outbreaks.
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http://dx.doi.org/10.1186/s13071-020-04523-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798338PMC
January 2021

Ambiguity and Ambivalence: an Issue for the Subjective Dynamics in the Relation between Language and Affection.

Integr Psychol Behav Sci 2021 Jan 7. Epub 2021 Jan 7.

Department of Psychology, Federal University of Pernambuco (UFPE), Av. da Arquitetura, s/n, Centro de Filosofia e Ciências Humanas - CFCH, 8° Andar, Recife, PE, 50740-550, Brazil.

This article stems from an interest taken in discussing the usage of the terms ambivalence and ambiguity, which are very present in Psychology's publications and savoir faire. It is important to reiterate that in common sense and even in scientific publications these terms are often used as synonyms or notions of little conceptual delimitation. The relevance of such differentiation is proposed once these notions participates of the emergence of the new in human subjective experience, and, in a methodological approach, ambiguity and ambivalence are dimensions that leads the researcher goes beyond a repetitive sterile description of the subject's speech, moving towards new perspectives of the psychological data. This paper aims to retrieve the qualifying power of such notions by making a broader reflection on the functions of language in the production of interpretive realities. We also propose to bring up a reflection about ambiguity in the construction of meaning and to reiterate ambivalences as inherent to human nature, its affective record and the process of human becoming. As a way to explain the proposed themes, we will analyse an excerpt from the documentary "Últimas Conversas", produced by the Brazilian filmmaker Eduardo Coutinho, in which high school students from public state schools in Rio de Janeiro tell their stories, speaking of dreams and shared challenges. The character Rafaela was selected for this article because of the emergence of unspeakable emotions from her narrative about an expected future as a promise of reconciliation with the alterity of her life story.
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http://dx.doi.org/10.1007/s12124-020-09593-6DOI Listing
January 2021

Insights into the Membranolytic Activity of Antimalarial Drug-Cell Penetrating Peptide Conjugates.

Membranes (Basel) 2020 Dec 22;11(1). Epub 2020 Dec 22.

LAQV-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre 687, P-4169-007 Porto, Portugal.

Conjugation of TP10, a cell-penetrating peptide with intrinsic antimalarial activity, to the well-known antimalarial drugs chloroquine and primaquine has been previously shown to enhance the peptide's action against, respectively, blood- and liver-stage malaria parasites. Yet, this was achieved at the cost of a significant increase in haemolytic activity, as fluorescence microscopy and flow cytometry studies showed the conjugates to be more haemolytic for non-infected than for -infected red blood cells. To gain further insight into how these conjugates distinctively bind, and likely disrupt, membranes of both -infected and non-infected erythrocytes, we used dynamic light scattering and surface plasmon resonance to study the interactions of two representative conjugates and their parent compounds with lipid model membranes. Results obtained are herein reported and confirm that a strong membrane-disruptive character underlies the haemolytic properties of these conjugates, thus hampering their ability to exert selective antimalarial action.
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http://dx.doi.org/10.3390/membranes11010004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822033PMC
December 2020

Antileishmanial activity of fullerol and its liposomal formulation in experimental models of visceral leishmaniasis.

Biomed Pharmacother 2021 Feb 17;134:111120. Epub 2020 Dec 17.

Departamento de Fisiologia e Biofísica, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Avenida Antônio Carlos 6627, Pampulha, 31270-901, Belo Horizonte, Minas Gerais, Brazil. Electronic address:

Visceral leishmaniasis (VL) is a systemic parasitic disease that leads to high rates of morbidity and mortality in humans worldwide. There is a great need to develop new drugs and novel strategies to make chemotherapy for this disease more efficacious and well tolerated. Recent reports on the immunomodulatory effects and the low toxicity of the spherical carbon nanostructure fullerol led us to investigate in vitro and in vivo antileishmanial activity in free and encapsulated forms in liposomes. When assayed against intramacrophagic Leishmania amastigotes, fullerol showed a dose-dependent reduction of the infection index with IC of 0.042 mg/mL. When given daily by i.p. route for 20 days (0.05 mg/kg/d) in a murine model of acute VL, fullerol promoted significant reduction in the liver parasite load. To improve the delivery of fullerol to the infection sites, liposomal formulations were prepared by the dehydration-rehydration method. When evaluated in the acute VL model, liposomal fullerol (Lip-Ful) formulations given i.p. at 0.05 and 0.2 mg/kg with 4-days intervals were more effective than the free form, with significant parasite reductions in both liver and spleen. Lip-Ful at 0.2 mg/kg promoted complete parasite elimination in the liver. The antileishmanial activity of Lip-Ful was further confirmed in a chronic model of VL. Lip-Ful was also found to induce secretion of pro-inflammatory TNF-α, IFN-γ and IL-1β cytokines. In conclusion, this work reports for the first time the antileishmanial activity of fullerol and introduces an innovative approach for treatment of VL based on the association of this nanostructure with liposomes.
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http://dx.doi.org/10.1016/j.biopha.2020.111120DOI Listing
February 2021