Publications by authors named "Luis Sousa"

56 Publications

Remote ischemic conditioning improves rat brain antioxidant defense in a time-dependent mechanism.

Acta Cir Bras 2021 3;36(7):e360707. Epub 2021 Sep 3.

PhD. Laboratory for Experimental Surgery - Department of Experimental Surgery - Universidade do Estado do Pará (UEPA) - Belém (PA), Brazil.

Purpose: To clarify the best protocol for performing remote ischemic conditioning and to minimize the consequences of ischemia and reperfusion syndrome in brain, the present study aimed to evaluate different time protocols and the relation of the organs and the antioxidant effects of this technique.

Methods: The rat's left femoral artery was clamped with a microvascular clamp in times that ranged from 1 to 5 minutes, according to the corresponding group. After the cycles of remote ischemic conditioning and a reperfusion of 20 minutes, the brain and the left gastrocnemius were collected. The samples were used to measure glutathione peroxidase, glutathione reductase and catalase levels.

Results: In the gastrocnemius, the 4-minute protocol increased the catalase concentration compared to the 1-minute protocol, but the latter increased both glutathione peroxidase and glutathione reductase compared to the former. On the other hand, the brain demonstrated higher catalase and glutathione peroxidase in 5-minute group, and the 3-minute group reached higher values of glutathione reductase.

Conclusions: Remote ischemic conditioning increases brain antioxidant capacity in a time-dependent way, while muscle presents higher protection on 1-minute cycles and tends to decrease its defence with longer cycles of intermittent occlusions of the femoral artery.
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http://dx.doi.org/10.1590/ACB360707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428670PMC
September 2021

Insulin-degrading enzyme: an ally against metabolic and neurodegenerative diseases.

J Pathol 2021 Aug 16. Epub 2021 Aug 16.

CEDOC, NOVA Medical School, NMS, Universidade Nova de Lisboa, Lisbon, Portugal.

Insulin-degrading enzyme (IDE) function goes far beyond its known proteolytic role as a regulator of insulin levels. IDE has a wide substrate promiscuity, degrading several proteins such as amyloid-β peptide, glucagon, islet amyloid polypeptide (IAPP), and insulin-like growth factors, which have diverse physiological and pathophysiological functions. Importantly, IDE plays other non-proteolytic functions such as: a chaperone/dead-end chaperone, an E1-ubiquitin activating enzyme, and a proteasome modulator. It also responds as a heat shock protein, regulating cellular proteostasis. Notably, amyloidogenic proteins such as IAPP, amyloid-β, and α-synuclein have been reported as substrates for IDE chaperone activity. This is of utmost importance as failure of IDE may result in increased protein aggregation, a key hallmark in the pathogenesis of beta cells in type 2 diabetes mellitus and of neurons in neurodegenerative diseases such as Alzheimer's and Parkinson's disease. In this review, we focus on the biochemical and biophysical properties of IDE and the regulation of its physiological functions. We further raise the hypothesis that IDE plays a central role in the pathological context of dysmetabolic and neurodegenerative diseases and discuss its potential as a therapeutic target. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/path.5777DOI Listing
August 2021

Self-concept and body image of people living with lupus: A systematic review.

Int J Rheum Dis 2021 Jul 27. Epub 2021 Jul 27.

Department Obstetrics and Gynecology, School of Medical Science, University of Campinas (UNICAMP), Campinas, Brazil.

Aim: To summarize existing evidence regarding body image in patients with systemic lupus erythematosus, with the following considerations: (a) the perceptions patients have of their body changes; (b) how patients cope with changes in their body; (c) and what their perceptions are of body changes.

Method: A systematic review of literature integrating quantitative and qualitative studies. We searched databases (PubMed, CINAHL, Embase, SCOPUS, the Web of Science, Medline, Medline Complete, and Academic Search Premier) and publications from 2010 to 2020 with "Systemic Lupus Erythematosus" AND "Self-Concept" OR "Body Image" AND "Woman" as medical subheading terms. The studies included were subjected to a thematic content analysis, which allowed subjective interpretation of data through a systematic classification process for coding themes or patterns.

Results: We identified 647 studies, of which 22 were analyzed in this study. Our results indicate that changes in the body image of people with lupus and their perception are issues that must be treated as characteristics of the disease; therefore, they need to receive the same attention as is given to physical disabilities and pain. The analysis identified 3 thematic categories: (a) depression and anxiety associated with body changes (hair loss, weight gain); (b) body image reflecting the disease; and (c) confrontations and interventions to promote acceptance and adaptation to the new image.

Conclusions: The dimensions of self-concept and body image are essential for assessing the quality of life of individuals with lupus. The formation of a adjusted self-concept can be managed by health professionals supporting these people.
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http://dx.doi.org/10.1111/1756-185X.14187DOI Listing
July 2021

The fear of falls in the caregivers of institutionalized elders.

Rev Gaucha Enferm 2021 16;42:e20200258. Epub 2021 Jul 16.

Universidade de Évora, Comprehensive Health Research Centre. Évora, Portugal.

Aims: To understand how the fear of falls emerges and manifests itself in caregivers of institutionalized elders.

Method: It is a qualitative study, based on the Grounded Theory and carried out with 24 informal caregivers, 5 nurses, 2 physicians and 2 directors of two Portuguese nursing homes. Data collection took place through interviews, participant observation, and documentation analysis, between October 2016 and January 2018. Data was collected and analyzed simultaneously, following the stages of open, axial, and selective coding.

Results: The comparative analysis of the findings identified the conceptual category "Fear of falls in the caregivers of institutionalized elders". The main category is associated with the categories: maintaining safety, hidden fear of falls, the perceived self-efficacy in the prevention of falls, falls and interpersonal relations, previous experiences, and team support.

Conclusions: The fear has an influence on the self-efficacy perceived in the prevention of falls; the quality of the teamwork, in turn, is affected by previous negative experiences and by the support of the team.
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http://dx.doi.org/10.1590/1983-1447.2021.20200258DOI Listing
July 2021

Evaluation of the effectiveness of an intervention in a health team to prevent falls in hospitalized elderly people.

Rev Esc Enferm USP 2021 31;55:e03695. Epub 2021 May 31.

Centro de Inovação em Tecnologias e Cuidados de Saúde (ciTechCare), Leiria, Portugal.

Objective: To evaluate the effectiveness of an intervention program in practices and behaviors of a health team to prevent falls in hos pitalized elderly people.

Method: This was an action, mixed-methods, and longitudinal study that applied an intervention based on TeamSTEPPS®, and organized into five domains: team training, communication, leadership, monitoring, and mutual support. The population was nurses and nursing aides who worked at the medical service of a Portuguese hospital center. Data were obtained by consulting process records and interviews, and by applying the Scale of Practices and Behaviors of Teams for Fall Prevention.

Results: There was improvement in all indicators of the scale, with evident progress in discussion of risk factors and preventive measures to be implemented.

Conclusion: This intervention promoted decision-making regarding the preventive measures to be applied to each elderly person and improved communication and the interest in identifying the causes of falls to prevent their recurrence.
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http://dx.doi.org/10.1590/S1980-220X2019031403695DOI Listing
August 2021

Self-Care in Heart Failure Inpatients: What Is the Role of Gender and Pathophysiological Characteristics? A Cross-Sectional Multicentre Study.

Healthcare (Basel) 2021 Apr 8;9(4). Epub 2021 Apr 8.

Center for Health Technology and Services Research (CINTESIS) NursID, Instituto Politécnico de Bragança, 5300-253 Bragança, Portugal.

Heart failure is often characterised by low exercise capacity and a great impairment of performance in the activities of daily living. The correct management of the disease can prevent the worsening of symptoms and promote a better quality of life. The aims of this study are to understand the relationship of gender and pathophysiological characteristics with self-care behaviour and to evaluate the self-care behaviour in a sample of Portuguese heart failure inpatients, using the Self-Care of Heart Failure Index (SCHFI). A cross-sectional multicentre study enrolling 225 heart failure inpatients from eight hospitals from Portugal was performed. At admission, each patient's functional capacity was evaluated as well as their self-care behaviour, using the SCHFI Portuguese v6.2. A comparison between self-care behaviour with gender was performed. The patients' mean age was 68.4 ± 10.7 years old, 68% were male and 82.3% had reduced ejection fraction. A mean value of 47.9, 35.6 and 38.8 points was found in the SCHFI score of the sections self-care maintenance, self-care management and self-care confidence, respectively. Heart failure inpatients present inadequate levels of self-care behaviour. The results do not suggest a relationship between gender and pathophysiological characteristics with self-care behaviour.
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http://dx.doi.org/10.3390/healthcare9040434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068008PMC
April 2021

The importance of a training program on active aging from the perspective of elderly individuals.

Rev Bras Enferm 2021 8;74Suppl 2(Suppl 2):e20190843. Epub 2021 Feb 8.

Universidade de Évora, Departamento de Enfermagem. Évora, Portugal.

Objective: to assess the results of a training program focused on the well-being of elderly individuals from the perspective of users, through the opinion on the program impact on their active aging.

Methods: a qualitative research, carried out from an intentional sample, consisting of 10 elderly women. Interview conducted by focus group, recorded and transcribed, which constituted the corpus of analysis. Lexical analysis of textual data was performed using the Alceste software.

Results: from the analysis, three classes emerged: 1) Health-Activity; 2) Activity-Expectation; 3) Mind-Body Unit. The Activity-Expectation class stands out.

Conclusions: the research revealed that elderly individuals consider it important to have expectation, which results in satisfaction and involvement with life as well as the ability to remain active in a perspective of mind-body unit. Future projects should focus on enhancing mental and physical functions to promote active and healthy aging.
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http://dx.doi.org/10.1590/0034-7167-2019-0843DOI Listing
June 2021

Sexual Competence in Higher Education: Global Perspective in a Multicentric Project in the Nursing Degree.

Healthcare (Basel) 2021 Feb 4;9(2). Epub 2021 Feb 4.

EdSex Project, Comprehensive Health Research Centre Integrated Researcher, Nursing Department, University of Evora, 7000-811 Evora, Portugal.

Sexuality is an important issue in the university careers of nursing students to ensure that they provide comprehensive care. It is necessary according to the recommendation of the World Health Organization. However, research reveals deficiencies and the need for further development. The aim of the study is to describe the perspective of teachers and students on the content of sexuality in nursing education. The project aims to analyze the attitudes and beliefs of the students about the sexuality of their patients. Furthermore, the experience and sexual lives of the future nurses, as well the teaching of sexuality content in the curriculum, will be analyzed. As for the educators, their level of knowledge about sexuality and vision of sexuality education in undergraduate nursing education will be analyzed. This study is an exploratory and descriptive study with a quantitative-qualitative approach in a multi-center context. The sample is composed of students and professors of nursing courses from five universities (Portugal, Spain, Italy and United States). Questionnaires and semistructured interviews will be used for data collection. The results of the study will allow the inclusion of sexual competence in the curriculum from the beginning in higher education. This article describes the research protocol.
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http://dx.doi.org/10.3390/healthcare9020166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915218PMC
February 2021

Comparison of remote and local postconditioning against hepatic ischemic-reperfusion injury in rats.

Acta Cir Bras 2021 1;36(1):e360101. Epub 2021 Feb 1.

Graduate student. Universidade do Estado do Pará - School of Medicine - Department of Experimental Surgery - Belém (PA), Brazil.

Purpose: The aim of this study is to compare the hepatic protective effect of both remote and local postconditioning (POS).

Methods: Twenty-eight Wistar rats were assigned into four groups: sham group(SHAM), ischemia-reperfusion group (IR), local ischemic POS group (lPOS) and remote ischemic POS group (rPOS). Animals were subjected to liver ischemia for 30 min. Local ischemic POS group consisted of four cycles of 5 min liver ischemia, followed by 5 min reperfusion (40 min). Remote ischemic POS group consisted of four cycles of 5 min hind limb ischemia, followed by 5 min hind limb perfusion after the main liver ischemia period. After 190 minutes median and left liver lobes were harvested for biochemical and histopathology analysis.

Results: All the conditioning techniques were able to increase the level of bothglutathione reductase and peroxidase, showing higher values in the rPOS group when compared to the lPOS. Also, thiobarbituric acid reactive substances were higher in all intervention groups when compared to SHAM, but rPOS had the lower rates of increase, showing the best result. The histopathology analysis showed that all groups had worst injury levels than SHAM, but rPOS had lower degrees of damage when compared to the lPOS, although it was not statistically significant.

Conclusion: Remote postconditioning is a promising technique to reduce liver ischemia-reperfusion injury, once it increased antioxidants substances and reduced the damage.
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http://dx.doi.org/10.1590/ACB360101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853697PMC
February 2021

The effects of diet composition and chronic obesity on muscle growth and function.

J Appl Physiol (1985) 2021 01 19;130(1):124-138. Epub 2020 Nov 19.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa.

Diet-induced obesity (DIO) is associated with glucose intolerance, insulin resistance (IR), and an increase in intramyocellular lipids (IMCL), which may lead to disturbances in glucose and protein metabolism. To this matter, it has been speculated that chronic obesity and elevated IMCL may contribute to skeletal muscle loss and deficits in muscle function and growth capacity. Thus, we hypothesized that diets with elevated fat content would induce obesity and insulin resistance, leading to a decrease in muscle mass and an attenuated growth response to increased external loading in adult male mice. Male C57BL/6 mice (8 wk of age) were subjected to five different diets, namely, chow, low-dat-diet (LFD), high-fat-diet (HFD), sucrose, or Western diet, for 28 wk. At 25 wk, HFD and Western diets induced a 60.4% and 35.9% increase in body weight, respectively. Interestingly, HFD, but not Western or sucrose, induced glucose intolerance and insulin resistance. Measurement of isometric torque (ankle plantar flexor and ankle dorsiflexor muscles) revealed no effect of DIO on muscle function. At 28 wk of intervention, muscle area and protein synthesis were similar across all diet groups, despite insulin resistance and increased IMCL being observed in HFD and Western diet groups. In response to 30 days of functional overload, an attenuated growth response was observed in only the HFD group. Nevertheless, our results show that DIO alone is not sufficient to induce muscle atrophy and contractile dysfunction in adult male C57BL/6 mice. However, diet composition does have an impact on muscle growth in response to increased external loading. The effects of diet-induced obesity on skeletal muscle mass are complex and dependent on diet composition and diet duration. The present study results show that chronic exposure to high levels of fatty acids does not affect muscle mass, contractile function, or protein synthesis in obese C57BL/6 mice compared with the consumption of chow. Obesity did result in a delay in load-induced growth; however, only a 45% HFD resulted in attenuated growth following 30 days of functional overload.
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http://dx.doi.org/10.1152/japplphysiol.00156.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944928PMC
January 2021

Mutant CFTR Drives TWIST1 mediated epithelial-mesenchymal transition.

Cell Death Dis 2020 10 26;11(10):920. Epub 2020 Oct 26.

University of Lisboa, Faculty of Sciences, BioISI - Biosystems & Integrative Sciences Institute, C8 bdg, 1749-016, Campo Grande, Lisboa, Portugal.

Cystic fibrosis (CF) is a monogenetic disease resulting from mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene encoding an anion channel. Recent evidence indicates that CFTR plays a role in other cellular processes, namely in development, cellular differentiation and wound healing. Accordingly, CFTR has been proposed to function as a tumour suppressor in a wide range of cancers. Along these lines, CF was recently suggested to be associated with epithelial-mesenchymal transition (EMT), a latent developmental process, which can be re-activated in fibrosis and cancer. However, it is unknown whether EMT is indeed active in CF and if EMT is triggered by dysfunctional CFTR itself or a consequence of secondary complications of CF. In this study, we investigated the occurrence of EMT in airways native tissue, primary cells and cell lines expressing mutant CFTR through the expression of epithelial and mesenchymal markers as well as EMT-associated transcription factors. Transepithelial electrical resistance, proliferation and regeneration rates, and cell resistance to TGF-β1induced EMT were also measured. CF tissues/cells expressing mutant CFTR displayed several signs of active EMT, namely: destructured epithelial proteins, defective cell junctions, increased levels of mesenchymal markers and EMT-associated transcription factors, hyper-proliferation and impaired wound healing. Importantly, we found evidence that the mutant CFTR triggered EMT was mediated by EMT-associated transcription factor TWIST1. Further, our data show that CF cells are over-sensitive to EMT but the CF EMT phenotype can be reversed by CFTR modulator drugs. Altogether, these results identify for the first time that EMT is intrinsically triggered by the absence of functional CFTR through a TWIST1 dependent mechanism and indicate that CFTR plays a direct role in EMT protection. This mechanistic link is a plausible explanation for the high incidence of fibrosis and cancer in CF, as well as for the role of CFTR as tumour suppressor protein.
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http://dx.doi.org/10.1038/s41419-020-03119-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588414PMC
October 2020

First report of straelensiosis in red foxes (Vulpes vulpes).

Vet Dermatol 2020 Dec 7;31(6):482-e127. Epub 2020 Oct 7.

Wildlife Rehabilitation Centre, Veterinary Hospital, University of Trás-os-Montes e Alto Douro, Vila Real, 5000-801, Portugal.

Background: Straelensia cynotis, a trombidioid larval mite, was identified as a cause of nodular dermatitis in dogs in Southern Europe. It has been suggested that red fox (Vulpes vulpes) is a natural host for S. cynotis. However, no case has been reported in this species.

Objective: To describe three suspected cases of straelensiosis in red foxes.

Animals: Three juvenile wild red foxes from Portugal.

Results: Erythematous papules and nodules were found in the head, neck and limbs of these foxes with no associated pruritus. In skin biopsies, well-preserved larval mites were found within dilated hair follicles. These follicular lesions were multifocal and consisted of a degenerative and necrotic area nearby the parasite's mouthparts with marked pseudoepitheliomatous hyperplasia and perifollicular mucinosis. These features are considered pathognomonic in S. cynotis infestations in dogs. Treatment and outcome are outlined.

Conclusions And Clinical Importance: To the best of the authors' knowledge, the present case series documents the first known occurrence of nodular dermatitis by Straelensia spp. in red foxes. This new evidence may corroborate participation of the red fox in the life cycle of S. cynotis.
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http://dx.doi.org/10.1111/vde.12896DOI Listing
December 2020

Impact of KLF4 on Cell Proliferation and Epithelial Differentiation in the Context of Cystic Fibrosis.

Int J Mol Sci 2020 Sep 14;21(18). Epub 2020 Sep 14.

BioISI-Biosystems & Integrative Sciences Institute, Faculty of Sciences, University of Lisboa, 1749-016 Lisbon, Portugal.

Cystic fibrosis (CF) cells display a more cancer-like phenotype vs. non-CF cells. KLF4 overexpression has been described in CF and this transcriptional factor acts as a negative regulator of wt-CFTR. KLF4 is described as exerting its effects in a cell-context-dependent fashion, but it is generally considered a major regulator of proliferation, differentiation, and wound healing, all the processes that are also altered in CF. Therefore, it is relevant to characterize the differential role of KLF4 in these processes in CF vs. non-CF cells. To this end, we used wt- and F508del-CFTR CFBE cells and their respective KLF4 knockout (KO) counterparts to evaluate processes like cell proliferation, polarization, and wound healing, as well as to compare the expression of several epithelial differentiation markers. Our data indicate no major impact of KLF4 KO in proliferation and a differential impact of KLF4 KO in transepithelial electrical resistance (TEER) acquisition and wound healing in wt- vs. F508del-CFTR cells. In parallel, we also observed a differential impact on the levels of some differentiation markers and epithelial-mesencymal transition (EMT)-associated transcription factors. In conclusion, KLF4 impacts TEER acquisition, wound healing, and the expression of differentiation markers in a way that is partially dependent on the CFTR-status of the cell.
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http://dx.doi.org/10.3390/ijms21186717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555189PMC
September 2020

Antibacterial and Antivirulence Activity of Manuka Honey against Genetically Diverse Staphylococcus pseudintermedius Strains.

Appl Environ Microbiol 2020 10 1;86(20). Epub 2020 Oct 1.

Department of Biomedical Sciences, Cardiff Metropolitan University, Cardiff, United Kingdom

causes opportunistic infections in dogs. It also has significant zoonotic potential, with the emergence of multidrug resistance leading to difficulty treating both animal and human infections. Manuka honey has previously been reported to inhibit many bacterial pathogens, including methicillin-resistant , and is successfully utilized in both clinical and veterinary practice. Here, we evaluated the ability of manuka honey to inhibit strains of grown alone and in combination with antibiotics, as well as its capacity to modulate virulence within multiple isolates. All 18 of the genetically diverse strains sequenced and tested were inhibited by ≤12% (wt/vol) medical-grade manuka honey, although tolerance to five clinically relevant antibiotics was observed. The susceptibility of the isolates to four of these antibiotics was significantly increased ( ≤ 0.05) when combined with sublethal concentrations of honey, although sensitivity to oxacillin was decreased. Virulence factor (DNase, protease, and hemolysin) activity was also significantly reduced ( ≤ 0.05) in over half of isolates when cultured with sublethal concentrations of honey (13, 9, and 10 isolates, respectively). These findings highlight the potential for manuka honey to be utilized against infections. is an important member of the skin microbial community in animals and can cause opportunistic infections in both pets and their owners. The high incidence of antimicrobial resistance in highlights that this opportunistic zoonotic pathogen can cause infections which require prolonged and intensive treatment to resolve. Manuka honey has proven efficacy against many bacterial pathogens and is an accepted topical treatment for infections in both veterinary and clinical practice, and so it is a particularly appropriate antimicrobial for use with zoonotic pathogens such as Here, we demonstrate that not only is manuka honey highly potent against novel multidrug-resistant isolates, it also acts synergistically with clinically relevant antibiotics. In addition, manuka honey modulates virulence activity, even at subinhibitory concentrations. In a clinical setting, these attributes may assist in controlling infection, allowing a more rapid resolution and reducing antibiotic use.
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http://dx.doi.org/10.1128/AEM.01768-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7531947PMC
October 2020

Outcomes, Mortality Causes, and Pathological Findings in European Hedgehogs (, Linnaeus 1758): A Seventeen Year Retrospective Analysis in the North of Portugal.

Animals (Basel) 2020 Jul 30;10(8). Epub 2020 Jul 30.

CECAV, University of Trás-os-Montes and Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal.

This study aimed to analyze the admission causes, outcomes, primary causes of death, and main lesions observed in the post mortem examinations of Western European hedgehogs, (Linnaeus, 1758), in the north of Portugal. The data were obtained by consulting the records from the two main wildlife rehabilitation centers located in the north of Portugal (Wildlife Rehabilitation Centre of Parque Biologico de Gaia and the Wildlife Rehabilitation Centre of the University of Trás-os-Montes and Alto Douro). Over 17 years (2002-2019) a total of 740 animals were admitted. Most of the animals were juveniles, with the highest number of admissions occurring during summer (36.8%) and spring (33.2%). The main reasons for admission were debilitation (30.7%) and random finds (28.4%). Of the total number of individuals admitted to these centers, 66.6% were successfully released back into the wild. The most relevant causes of death were trauma of unknown origin (32.7%), nontrauma causes of unknown origin (26.6%), and nutritional disorders (20.2%). The main lesions observed were related to trauma, including skeletal and skin lesions (fractures, hemorrhages, wounds) and organ damage, particularly to the lungs and liver. The hedgehog is a highly resilient and adaptable animal. The urban environment has many benefits for hedgehogs, yet the presence of humans can be harmful. In the future, the public needs to become even more involved in the activities of the wildlife centres, which will make a positive difference for these populations.
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http://dx.doi.org/10.3390/ani10081305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460247PMC
July 2020

KLF4 Acts as a wt-CFTR Suppressor through an AKT-Mediated Pathway.

Cells 2020 07 2;9(7). Epub 2020 Jul 2.

BioISI-Biosystems & Integrative Sciences Institute, Faculty of Sciences, University of Lisbon, 1749-016 Lisbon, Portugal.

Cystic Fibrosis (CF) is caused by >2000 mutations in the CF transmembrane conductance regulator (CFTR) gene, but one mutation-F508del-occurs in ~80% of patients worldwide. Besides its main function as an anion channel, the CFTR protein has been implicated in epithelial differentiation, tissue regeneration, and, when dysfunctional, cancer. However, the mechanisms that regulate such relationships are not fully elucidated. Krüppel-like factors (KLFs) are a family of transcription factors (TFs) playing central roles in development, stem cell differentiation, and proliferation. Herein, we hypothesized that these TFs might have an impact on CFTR expression and function, being its missing link to differentiation. Our results indicate that KLF4 (but not KLF2 nor KLF5) is upregulated in CF vs. non-CF cells and that it negatively regulates wt-CFTR expression and function. Of note, F508del-CFTR expressing cells are insensitive to KLF4 modulation. Next, we investigated which KLF4-related pathways have an effect on CFTR. Our data also show that KLF4 modulates wt-CFTR (but not F508del-CFTR) via both the serine/threonine kinase AKT1 (AKT) and glycogen synthase kinase 3 beta (GSK3β) signaling. While AKT acts positively, GSK3β is a negative regulator of CFTR. This crosstalk between wt-CFTR and KLF4 via AKT/ GSK3β signaling, which is disrupted in CF, constitutes a novel mechanism linking CFTR to the epithelial differentiation.
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http://dx.doi.org/10.3390/cells9071607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408019PMC
July 2020

Renal protective effect of pinitol in experimental diabetes.

Eur J Pharmacol 2020 Aug 30;880:173130. Epub 2020 Apr 30.

Instituto Superior de Ciências Biomédicas, Programa de Pós-Graduação em Ciências Fisiológicas, Universidade Estadual do Ceará, Fortaleza, Brazil. Electronic address:

Pinitol is a natural antidiabetic agent shown to prevent or ameliorate metabolic and overall vascular and neural function. In the present study we have evaluated the potential benefits of pinitol on renal function of streptozotocin (STZ)-induced diabetic rats. Both euglycemic or 8-week or 16-week diabetic rats were treated with either saline (1 ml/kg/12h; p.o) or pinitol (20 mg/kg/12h; p.o). The renal function was evaluated by using metabolic cages, renal hemodynamic and tubular parameters measurements. Histological examination and evaluation of the protein expression of renal markers such as nephrin, TGFβ and pERK were also performed. Pinitol decreased by 50% the increased urinary albumin/creatinine ratio in both 8-week and 16 week diabetic rats. In addition, the glomerular volume of 16-week rats increased by 55% and this increase was blunted by pinitol. Remarkably, pressure-natriuresis was completely blunted in both 8 and 16-week diabetic rats but this impairment was prevented by pinitol in both treatment regimens. Pinitol ameliorated renal lesions and also prevented the decrease in nephrin expression and the increase of pERK and TGFβ expression in both diabetic groups. Natriuresis due to high renal perfusion pressure increased 7-fold in control animals but was blocked in 16-week diabetic rats and remarkably pinitol partially restored pressure natriuresis (3-fold increase in sodium excretion during pressure natriuresis). Pinitol prevents and ameliorates albuminuria, glomerular expansion, impairment of pressure-natriuresis, renal structural alterations and changes of renal markers and has the potential to be tested for the prevention of diabetic kidney disease.
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http://dx.doi.org/10.1016/j.ejphar.2020.173130DOI Listing
August 2020

Effect of indole alkaloids from roots of Rauvolfia ligustrina in the noradrenergic neurotransmission.

Fitoterapia 2020 Jun 7;143:104545. Epub 2020 Mar 7.

Departamento de Química Orgânica e Inorgânica, Universidade Federal do Ceará, 60971-270 Fortaleza, CE, Brazil. Electronic address:

The new glucosyl sarpagan alkaloid designated as 21(R*)-(O-β-glucosyl)-hydroxy-sarpagan-17-oic acid, along with eleven known alkaloids were isolated from a soluble alkaloidal fraction from the ethanol extract of Rauvolfia ligustrina. Their structures were elucidated by interpretation of spectroscopic data (1D and 2D NMR), HRESIMS experiment, GIAO C NMR calculations, and comparison with literature data. All the isolated alkaloids were screened by their neuroinhibitory effects using the electrically stimulated mice vas deferens bioassay. Compounds 1, 2 and 9 presented a potent inhibitory effect in the neurotransmission while 3 and 11 showed an acute neuroexcitatory effect. Compound 10 exhibited a very effective post-synaptic inhibitory activity.
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http://dx.doi.org/10.1016/j.fitote.2020.104545DOI Listing
June 2020

Brucellosis: A rapid risk assessment by a regional outbreak team and its coordinated response with the Directorate-General for Food and Veterinary, North region of Portugal, 2019.

Zoonoses Public Health 2020 08 8;67(5):587-590. Epub 2020 Feb 8.

Public Health Department, North Region Health Administration, Porto, Portugal.

We report a Brucella outbreak with seven cases in the Northern Region of Portugal in 2018-2019, associated with the consumption of fresh cheese. This outbreak has implications for risk assessment in Portuguese migrants related to this area, and it is an example of cooperation between public institutions, in a One Health based approach.
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http://dx.doi.org/10.1111/zph.12692DOI Listing
August 2020

The 2019 Novel Coronavirus (2019-nCoV): Novel Virus, Old Challenges.

Acta Med Port 2020 Feb 5. Epub 2020 Feb 5.

Departamento de Saúde Pública. Administração Regional de Saúde do Norte. Porto. Unidade Multidisciplinar de Investigação Biomédica (UMIB). Instituto de Ciências Biomédicas Abel Salazar. Universidade do Porto. Porto. Portugal.

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http://dx.doi.org/10.20344/amp.13547DOI Listing
February 2020

Self-reported lipodystrophy, nutritional, lipemic profile and its impact on the body image of HIV-1-infected persons, with and without antiretroviral therapy.

AIDS Care 2020 10 11;32(10):1317-1322. Epub 2019 Nov 11.

Department of Pathology and Clinical Analysis, Campus Diadema, Universidade Federal de São Paulo, FMABC, Santo André, Brasil.

A cross-sectional study was conducted with 227 adults, 162 using antiretroviral therapy (ART), both sexes, in Secondary Immunodeficiency Outpatient Clinic of the Department of Dermatology of the Hospital das Clínicas of the Faculty of Medicine of University of São Paulo. The patients were grouped into 92 under ART and self-reported lipodystrophy (G1); 70 under ART and without self-reported lipodystrophy (G2); 65 without ART (G3). We evaluated: (1) self-reported lipodystrophy, self-perception and feeling about body image; (2) Anthropometric and lipemic profile. We included 67% ( = 152) male; 33% ( = 77) female. There was a negative impact of self-reported lipodystrophy on body image, where female was more critical, although it was significant for male ( = 0.014). BMI revealed excess weight in female ( = 0.058). Hip waist ratio was shown to be a better parameter than abdominal perimeter when measuring fat in central region of male and lipohypertrophy was characterized in both sexes. There was lipoatrophy in upper and lower limbs for individuals of the (G1) and the male of this group presented hypertriglyceridemia, ( = 0.012). There was a difference in sex, pattern of self - perceived morphologic alterations and feeling in relation to body image when associated with self - reported lipodystrophy, ART use, anthropometric and lipemic profile.
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http://dx.doi.org/10.1080/09540121.2019.1687832DOI Listing
October 2020

Novel approach for connecting real driving emissions to the European vehicle laboratorial certification test procedure.

Environ Sci Pollut Res Int 2019 Dec 4;26(34):35163-35182. Epub 2019 Nov 4.

IN+, Center for Innovation, Technology and Policy Research-Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1, 1049-001, Lisbon, Portugal.

Vehicle emission certification is evaluated under laboratorial conditions, where vehicles perform a standard driving cycle in controlled conditions leading to several critics, which have resulted in the implementation of the Worldwide harmonized Light Vehicle Test Procedure (WLTP) and the Real Driving Emissions (RDE) testing procedure, as a complementary certification procedure. RDE is still under debate since boundary conditions; evaluation and trip selection methods are still being studied to allow test reproducibility. Currently, the official data analysis method uses the moving average window (MAW_EC), based on the WLTP CO emissions for trip validity evaluation (RDE package 4) and emissions (RDE package 3). However, this does not consider the impact of vehicle dynamics. Consequently, this work focuses on developing a novel method to relate certification driving cycle dynamics and on-road test vehicle dynamics, to evaluate RDE tests fuel use and exhaust emissions in a comparable way to certification driving cycles, indicating how close, or far, real-world driving is from the laboratorial certification test. For this, a new method was developed called road vehicle evaluation method (ROVET), which relies on the cycle vehicle dynamic and on-road trip dynamics for assessing if both tests are comparable. Results from 5 measured vehicles with a portable emissions measurement system (PEMS) through reproducibility tests and 2 case studies, show that the ROVET provides results closer to the certification calculated reference than the most commonly used method in Europe (1% avg. difference for ROVET while 8% avg. difference for MAW_EC, regarding CO emission, for example). The use of vehicle dynamics on construction and references of a method could be used to incentivize the regulators to review the references used by the current used methods, which suffers several criticisms since their release. As the regulated methods are in constant update, this study could be useful for helping to improve or to be used as additional method for future vehicle certification procedures. Graphical abstract.
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http://dx.doi.org/10.1007/s11356-019-06484-1DOI Listing
December 2019

Humor intervention in the nurse-patient interaction.

Rev Bras Enferm 2019 Aug 19;72(4):1078-1085. Epub 2019 Aug 19.

Escola Superior de Saúde Atlântica. Barcarena, Portugal.

Objective: To describe the factors influencing the use of humor in nursing care, its applicability and benefits.

Method: A scoping review was performed using the Arksey and O'Mally methodology. A search for articles published between 2008 and 2018 was performed using the platforms EBSCO Host, Virtual Health Library and Google Scholar.

Results: From the initial 465 articles found, 17 were included for final revision. Data allowed to retrieve information on humor definition; its applicability as a nursing intervention; humor as a tool to improve nurse-patient communication and relationship; influence factors; type of humor interventions; humor benefits in health care context and; limitations and precautions of humor intervention.

Conclusion: The use of humor promotes both communication and human interaction; it promotes well-being; helps deal/cope with difficult and unpleasant situations, reduces tension, discomfort and stress; and strengthens the immune system. This intervention should be used with caution.
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http://dx.doi.org/10.1590/0034-7167-2018-0609DOI Listing
August 2019

ULK2 is essential for degradation of ubiquitinated protein aggregates and homeostasis in skeletal muscle.

FASEB J 2019 11 9;33(11):11735-11745. Epub 2019 Aug 9.

Department of Health and Human Physiology, The University of Iowa, Iowa City, Iowa, USA.

Basal protein turnover, which largely relies on the degradation of ubiquitinated substrates, is instrumental for maintenance of muscle mass and function. However, the regulation of ubiquitinated protein degradation in healthy, nonatrophying skeletal muscle is still evolving, and potential tissue-specific modulators remain unknown. Using an unbiased expression analysis of 34 putative autophagy genes across mouse tissues, we identified unc-51 like autophagy activating kinase (), a homolog of the yeast autophagy related protein 1, as particularly enriched in skeletal muscle. Subsequent experiments revealed accumulations of insoluble ubiquitinated protein aggregates associated with the adaptors sequestosome 1 (SQSTM1, also known as p62) and next to breast cancer type 1 susceptibility protein gene 1 protein (NBR1) in adult muscles with ULK2 deficiency. ULK2 deficiency also led to impaired muscle force and caused myofiber atrophy and degeneration. These features were not observed in muscles with deficiency of the ULK2 paralog, ULK1. Furthermore, short-term ULK2 deficiency did not impair autophagy initiation, autophagosome to lysosome fusion, or protease activities of the lysosome and proteasome. Altogether, our results indicate that skeletal muscle ULK2 has a unique role in basal selective protein degradation by stimulating the recognition and proteolytic sequestration of insoluble ubiquitinated protein aggregates associated with p62 and NBR1. These findings have potential implications for conditions of poor protein homeostasis in muscles as observed in several myopathies and aging.-Fuqua, J. D., Mere, C. P., Kronemberger, A., Blomme, J., Bae, D., Turner, K. D., Harris, M. P., Scudese, E., Edwards, M., Ebert, S. M., de Sousa, L. G. O., Bodine, S. C., Yang, L., Adams, C. M., Lira, V. A. ULK2 is essential for degradation of ubiquitinated protein aggregates and homeostasis in skeletal muscle.
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http://dx.doi.org/10.1096/fj.201900766RDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902739PMC
November 2019

Brachial plexus neuropathy by hibernoma compression: An unusual presentation of peripheral non-neural sheath nerve tumor and a systematic review of literature.

Neurol India 2019 Mar-Apr;67(2):481-484

Citopar Laboratory, Curitiba, Brazil.

Brachial plexus neuropathies are uncommon and are rarely caused by a tumor. The clinical presentation of a brachial plexus neuropathy caused by a tumor depends on the degree of malignancy of the tumor and its localization. We report an illustrative case of a 27-year old female subject with a progressively increasing mass lesion causing brachial plexus compression, ipsilateral shoulder pain, C8 dermatomal paresthesia, and impairment of motor power. The patient underwent surgical resection of the mass and neurolysis of the nerves in the vicinity. Following the surgical procedure, the patient had improvement in the pain and paresthesia that he was suffering from. The histopathological diagnosis revealed a hibernoma, an extremely rare tumor described only once previously in this location. A systematic review of the literature was performed utilizing the PubMed database to access articles published before March 2018, using: A - the term 'hibernoma' in the title/abstract associated with the following MeSH terms: brachial plexus neuropathies OR brachial plexus neuropathy OR nerve compression syndrome, OR brachial plexus; B - the MeSH term 'brachial plexus' associated with the term 'non neural sheath nerve tumor' or 'peripheral non-neural sheath nerve tumor'. The origin of the hibernoma, as well as its metabolic influence, pathology, and treatment have been discussed.
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http://dx.doi.org/10.4103/0028-3886.258049DOI Listing
July 2019

Musculoskeletal symptoms in nursing students: concept analysis.

Rev Bras Enferm 2019 Jan-Feb;72(1):287-292

Faculdade Motricidade Humana, Departamento Educação em Saúde. Dafundo, Portugal.

Objective: to analyze the musculoskeletal symptomatology concept in undergraduate nursing students through Rodgers' evolutionary method.

Method: An integrative review of the literature was performed for the identification and selection of ten articles. A concept analysis was performed according to Rodgers' evolutionary method. Article search was performed using the EBOSCO Host platform, Virtual Health Library and Google scholar for the years from 2004 to 2018.

Results: Based on the 3 elements of Rodgers model we found: 1) substitute terms and related concepts, where musculoskeletal disorders and musculoskeletal symptoms were highlighted; 2) as essential attributes of the concept we highlight pain and discomfort, as well as, measurement using the Nordic Musculoskeletal Questionnaire; and 3) risk factors were identified as antecedents, and the consequences were the impact on students' lives.

Conclusions: This study contributes to the knowledge and clarification of the concept of musculoskeletal symptomatology in nursing students.
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http://dx.doi.org/10.1590/0034-7167-2018-0612DOI Listing
May 2019

Fear of falling among Brazilian and Portuguese older adults.

Int J Older People Nurs 2019 Jun 12;14(2):e12230. Epub 2019 Mar 12.

Nursing Department, College of Applied Medical Sciences, Shaqra University, Al Dawadmi, Saudi Arabia.

Background: Falling is the leading cause of physical disability, mortality and social exclusion in older adults. In Brazil and Portugal, falls cause thousands of hospitalisations every year. Fear of falling (FOF) causes loss of confidence in accomplishing daily tasks, restriction in social activities and increased dependence.

Aim: To compare the prevalence of FOF between Brazilian and Portuguese community-dwelling older adults and the factors associated with FOF.

Methods: A secondary analysis of cross-sectional survey data collected from older adults residing in Brazil (n = 170; M age=70.44 years) and Portugal (n = 170; M age=73.56 years).

Results: The prevalence of FOF was significantly higher (p = 0.015) among Portuguese (n = 133, 54.1%) versus Brazilian (n = 113, 45.9%) older adults. FOF among Brazilian older adults was associated with being 76 + years of age and female. Among Portuguese older adults, factors associated with FOF were intake of daily medications, having fallen within the past year, and visual difficulties.

Conclusions: Fear of falling is linked with modifiable and non-modifiable factors. Timely assessments of FOF and factors associated with FOF are essential.

Implications For Practice: Primary care nurses should assess and address FOF in older people with interdisciplinary practitioners.
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http://dx.doi.org/10.1111/opn.12230DOI Listing
June 2019

Assessing the influence of boundary conditions, driving behavior and data analysis methods on real driving CO and NO emissions.

Sci Total Environ 2019 Mar 11;658:879-894. Epub 2018 Dec 11.

IN+, Center for Innovation, Technology and Policy Research, - Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1, - 1049-001 Lisboa, Portugal; ADEM, Mechanical Engineering Department, - Instituto Superior de Engenharia de Lisboa (ISEL), Rua Conselheiro Emídio Navarro, 1, - 1959-007 Lisboa, Portugal.

The need to verify vehicle emissions in real world operation led to the implementation of Real Driving Emissions (RDE) test procedures, effective since September 2017 for new Euro 6 cars following the Commission Regulation (EU) 2016/427, which defines the RDE test conditions and data analysis methods to allow representative results. Main factors addressed by the regulation include the share of driving operation, ambient temperature range, altitude and elevation difference. However, RDE is still debatable since not only boundary conditions but also the evaluation methods and trip selection are being discussed together with a carbon dioxide (CO) regulation, which is planned to be implemented in the short term. Thus, this work focuses on analyzing the effect of different data measurement and analysis methods (i.e. cold-operation, road grade, trip selection and driving style) on CO and nitrogen oxides (NO) emissions based on 13 RDE tests performed in the Lisbon Metropolitan Area, Portugal. The tests were conducted by 2 drivers using 5 vehicles. Each driver performed 2 trips per vehicle, one in normal driving and other in aggressive driving. A Portable Emissions Measurement System (PEMS) was used to collect 1 Hz data, which was compared and analyzed using the European Commission (EC) proposed method for RDE tests. Results show the effects of each parameter such as average difference between drivers (7% in CO and 55% in NO emissions) and between aggressive and normal driving. For road grade, big oscillations happen during the slope profile, which impacts emissions during all trips. Considering cold-operation, CO and NO emissions are, on average, ~25% and 55% higher, respectively, than in hot-operation. These results highlight the need for deeper studies on these factors to assure that RDE tests evolve to a more established certification procedure than laboratorial certifications.
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http://dx.doi.org/10.1016/j.scitotenv.2018.12.053DOI Listing
March 2019

Aerobic exercise, but not metformin, prevents reduction of muscular performance by AMPk activation in mice on doxorubicin chemotherapy.

J Cell Physiol 2018 12 28;233(12):9652-9662. Epub 2018 Jun 28.

Immunometabolism Research Group, Department of Cell and Developmental Biology, University of São Paulo, Butantã, São Paulo, Brazil.

Doxorubicin (DOX) is a chemotherapy agent widely used in clinical practice, and it is very efficient in tumor suppression, but the use of DOX is limited by a strong association with the development of severe muscle atrophy and cardiotoxicity effects. Reversion or neutralization of the muscular atrophy can lead to a better prognosis. Recent studies have proposed that the negative effect of DOX on skeletal muscle is linked to its inhibition of AMP-activated protein kinase (AMPk), a key mediator of cellular metabolism. On the basis of this, our goal was to evaluate if aerobic exercise or metformin treatment, activators of AMPk, would be able to attenuate the deleterious effects on skeletal muscle induced by the DOX treatment. C57BL6 mice received either saline (control) or DOX (2.5 mg/kg body weight) intraperitoneally, twice a week. The animals on DOX were further divided into groups that received adjuvant treatment in the form of moderate aerobic physical exercise (DOX+T) or metformin gavage (300 mg/body weight/day). Body weight, metabolism, distance run, muscle fiber cross-sectional area (CSA), and protein synthesis and degradation were assessed. We demonstrated that aerobic training, but not metformin, associated with DOX increased the maximal aerobic capacity without changing muscle mass or fiber CSA, rescuing the muscle fatigue observed with DOX treatment alone. This improvement was associated with AMPk activation, thus surpassing the negative effects of DOX on muscle performance and bioenergetics. In conclusion, aerobic exercise increases AMPk activation and improved the skeletal muscle function, reducing the side effects of DOX.
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http://dx.doi.org/10.1002/jcp.26880DOI Listing
December 2018

Validation of the Falls Efficacy Scale - International in a sample of Portuguese elderly.

Rev Bras Enferm 2018 ;71 Suppl 2:747-754

Centre for Interdisciplinary Health Research, Universidade Católica Portuguesa, Lisbon, Portugal.

Objective: to translate and adapt Falls Efficacy Scale - International (FES-I). To analyze the psychometric properties of the FES-I Portugal version.

Method: psychometric study. Sample consisting of 170 elderly people residing in the Autonomous Region of Madeira. A two- part form was used (sociodemographic characterization and FES-I Portugal). The cross-cultural adaptation was performed and the following psychometric properties were evaluated: validity (construct, predictive, and discriminant), reliability (Cronbach's alpha), and inter-rater reliability.

Results: the results allow us to verify a dimension of less demanding physical activities and another of more demanding physical activities. The inter-rater reliability study was 0.62, with an interclass correlation coefficient of 0.859, for a 95% confidence interval. The internal consistency of the Portuguese version was 0.962.

Conclusion: the validity and reliability of the FES-I Portugal are consistent with the original version and proved to be appropriate instruments for evaluating the "impaired walking" and "risk of falls" nursing diagnoses in the older people.
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http://dx.doi.org/10.1590/0034-7167-2017-0497DOI Listing
October 2018
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