Publications by authors named "Joana Monteiro"

29 Publications

  • Page 1 of 1

Techniques for effective local anaesthetic administration for the paediatric patient.

Br Dent J 2020 Dec 18;229(12):779-785. Epub 2020 Dec 18.

Paediatric Dentistry, UCL, 256 Grays Inn Road, London, WC1 X8LD, UK.

Local anaesthesia forms the backbone of pain control techniques in dentistry and has a major role in dentistry for children and adults alike. Dental anxiety is still prevalent among children, causing delays in seeking dental care and leading to increased rates in childhood caries, resulting in increased hospital admissions for dental care under general anaesthesia. There is a constant search for more comfortable means of achieving local anaesthesia to provide a more positive experience for paediatric patients when seeking dental treatment. This article aims to provide an overview of local anaesthetic techniques used in paediatric dentistry, as well as methods utilised to make local anaesthetic administration more comfortable and how to increase acceptability.
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http://dx.doi.org/10.1038/s41415-020-2453-2DOI Listing
December 2020

[Differences between Patients Undergoing Laparoscopic Cholecystectomy with Discharge at the End of the Day Versus Overnight Stay: A Retrospective Study].

Acta Med Port 2020 Sep 1;33(9):552-558. Epub 2020 Sep 1.

Serviço de Cirurgia Geral. Hospital Pedro Hispano. Unidade Local de Saúde de Matosinhos. Senhora da Hora. Portugal.

Introduction: Although laparoscopic cholecystectomy is an increasingly performed technique in the outpatient setting, it is not done in some Units due to lack of overnight stay. The objectives of this study are to identify the differences between patients with discharge at the end of the day versus overnight stay and the factors predicting overnight stay.

Material And Methods: A retrospective analysis of the pre, peri and postoperative data of patients operated between January/2014 and December/2017 was performed, and a statistical analysis of the variables.

Results: A total of 311 patients were included, 33.4% of whom stayed overnight. Of these, 81.7% were operated after 2pm. As predictors factors of overnight stay, the age (p = 0.001) was identified in the morning group, with a greater possibility of overnight stay (15.3%) from 61.50 years (Younden index = 0.396) and the surgery start time (p < 0.0001) in the afternoon group, with a greater possibility of overnight stay (77.1%) from 4:30 pm (Younden index = 0.492).

Discussion: Most patients stayed overnight due to the time at which recovery was completed, since no cause was identified (84.7%). If our unit would not have an overnight stay we would have an overall hospitalization rate of 8.4%, which corresponds to patients with an identified cause for overnight stay, and to admitted patients.

Conclusion: Ambulatory cholecystectomy can be performed in units that cannot cater for an overnight stay, provided that surgeries are performed during the morning period, patients are carefully selected and there is the possibility of admission.
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http://dx.doi.org/10.20344/amp.12420DOI Listing
September 2020

Impact of Navigated Task-specific fMRI on Direct Cortical Stimulation.

J Neurol Surg A Cent Eur Neurosurg 2020 Nov 1;81(6):555-564. Epub 2020 Jul 1.

Faculdade de Ciências da Universidade de Lisboa, Instituto de Biofísica e Engenharia Biomédica, Lisboa, Portugal.

Background And Study Aims:  Cortical mapping (CM) with direct cortical stimulation (DCS) in awake craniotomy is used to preserve cognitive functions such as language. Nevertheless, patient collaboration during this procedure is influenced by previous neurological symptoms and growing discomfort with DCS duration. Our study aimed to evaluate the impact of navigated task-specific functional magnetic resonance imaging (nfMRI) on the practical aspects of DCS.

Material And Methods:  We recruited glioma patients scheduled for awake craniotomy for prior fMRI-based CM, acquired during motor and language tasks (i.e., verb generation, semantic and syntactic decision tasks). Language data was combined to generate a probabilistic map indicating brain regions activated with more than one paradigm. Presurgical neurophysiological language tests (i.e., verb generation, picture naming, and semantic tasks) were also performed. We considered for subsequent study only the patients with a minimum rate of correct responses of 50% in all tests. These patients were then randomized to perform intraoperative language CM either using the multimodal approach (mCM), using nfMRI and DCS combined, or electrical CM (eCM), with DCS alone. DCS was done while the patient performed picture naming and nonverbal semantic decision tasks. Methodological features such as DCS duration, number of stimuli, total delivered stimulus duration per task, and frequency of seizures were analyzed and compared between groups. The correspondence between positive responses obtained with DCS and nfMRI was also evaluated.

Results:  Twenty-one surgeries were included, thirteen of which using mCM (i.e., test group). Patients with lower presurgical neuropsychological performance (correct response rate between 50 and 80% in language tests) showed a decreased DCS duration in comparison with the control group. None of the compared methodological features showed differences between groups. Correspondence between DCS and nfMRI was 100/84% in the identification of the precentral gyrus for motor function/opercular frontal inferior gyrus for language function, respectively.

Conclusion:  Navigated fMRI data did not influence DCS in practice. Presurgical language disturbances limited the applicability of DCS mapping in awake surgery.
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http://dx.doi.org/10.1055/s-0040-1712496DOI Listing
November 2020

[Hamman's Syndrome (Spontaneous Pneumomediastinum)].

Rev Port Cir Cardiotorac Vasc 2020 Jan-Mar;27(1):43-45

Serviço de Medicina Interna 2, Centro Hospital de Leiria, Leiria, Portugal.

The authors present the case of a previously healthy, 22-year-old male nonsmoker who sought emergency room treatment complaining of retrosternal pain. He reported a history of odynophagia two days before, followed by produc- tive cough, fever and dyspnea. On chest radiography, a line could be observed surrounding the heart and the continuous diaphragm sign. The chest computed tomography scan confirmed the presence of pneumomediastinum and soft tissue emphysema. The case was discussed in a multidisciplinary team, and the possibility of surgical intervention was rejected. Conservative treatment was decided with complete resolution of the pneumomediastinum.
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October 2020

Interventions for increasing acceptance of local anaesthetic in children and adolescents having dental treatment.

Cochrane Database Syst Rev 2020 02 27;2:CD011024. Epub 2020 Feb 27.

The University of Manchester, PhD student at School of Medical Sciences, Division of Dentistry, Manchester, UK.

Background: Delivery of pain-free dentistry is crucial for reducing fear and anxiety, completion of treatment, and increasing acceptance of future dental treatment in children. Local anaesthetic (LA) facilitates this pain-free approach but it remains challenging. A number of interventions to help children cope with delivery of LA have been described, with no consensus on the best method to increase its acceptance.

Objectives: To evaluate the effects of methods for acceptance of LA in children and adolescents during dental treatment.

Search Methods: Cochrane Oral Health's Information Specialist searched the Cochrane Oral Health's Trials Register (to 24 May 2019); the Cochrane Central Register of Controlled Trials (CENTRAL; 2019 Issue 4) in the Cochrane Library (searched 24 May 2019); MEDLINE Ovid (1946 to 24 of May 2019); Embase Ovid (1980 to 24 May 2019); and Web of Science (1900 to 24 May 2019). The US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and World Health Organization International Clinical Trials Registry Platform were also searched to 24 May 2019. There were no restrictions on language or date of publications.

Selection Criteria: Parallel randomised controlled trials (RCTs) of interventions used to increase acceptance of dental LA in children and adolescents under the age of 18 years.

Data Collection And Analysis: We used standard methodological procedures expected by Cochrane. We performed data extraction and assessment of risk of bias independently and in duplicate. We contacted authors for missing information. We assessed the certainty of the body of evidence using GRADE.

Main Results: We included 26 trials with 2435 randomised participants aged between 2 and 16 years. Studies were carried out between 2002 and 2019 in dental clinics in the UK, USA, the Netherlands, Iran, India, France, Egypt, Saudi Arabia, Syria, Mexico, and Korea. Studies included equipment interventions (using several LA delivery devices for injection or audiovisual aids used immediately prior to or during LA delivery or both) and dentist interventions (psychological behaviour interventions delivered in advance of LA (video modelling), or immediately prior to or during delivery of LA or both (hypnosis, counter-stimulation). We judged one study to be at low risk and the rest at high risk of bias. Clinical heterogeneity of the included studies rendered it impossible to pool data into meta-analyses. None of the studies reported on our primary outcome of acceptance of LA. No studies reported on the following secondary outcomes: completion of dental treatment, successful LA/painless treatment, patient satisfaction, parent satisfaction, and adverse events. Audiovisual distraction compared to conventional treatment: the evidence was uncertain for the outcome pain-related behaviour during delivery of LA with a reduction in negative behaviour when 3D video glasses where used in the audiovisual distraction group (risk ratio (RR) 0.13, 95% confidence interval (CI) 0.03 to 0.50; 1 trial, 60 participants; very low-certainty evidence). The wand versus conventional treatment: the evidence was uncertain regarding the effect of the wand on pain-related behaviour during delivery of LA. Four studies reported a benefit in using the wand while the remaining studies results suggested no difference between the two methods of delivering LA (six trials, 704 participants; very low-certainty evidence). Counter-stimulation/distraction versus conventional treatment: the evidence was uncertain for the outcome pain experience during delivery of LA with children experiencing less pain when counter-stimulation was used (RR 0.12, 95% CI 0.04 to 0.34; 1 trial, 134 participants; very low-certainty evidence). Hypnosis versus conventional treatment: the evidence was uncertain for the outcome pain experience during delivery of LA with participants in the hypnosis group experiencing less pain (mean difference (MD) -1.79, 95% CI -3.01 to -0.57; 1 trial, 29 participants; very low-certainty evidence). Other comparisons considered included pre-cooling of the injection site, the wand versus Sleeper One, the use of a camouflage syringe, use of an electrical counter-stimulation device, and video modelling acclimatisation, and had a single study each. The findings from these other comparisons were insufficient to draw any affirmative conclusions about their effectiveness, and were considered to be very low-certainty evidence.

Authors' Conclusions: We did not find sufficient evidence to draw firm conclusions as to the best interventions to increase acceptance of LA in children due to variation in methodology and nature/timing of outcome measures. We recommend further parallel RCTs, reported in line with the CONSORT Statement. Care should be taken when choosing outcome measures.
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http://dx.doi.org/10.1002/14651858.CD011024.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7045283PMC
February 2020

The Impact of Infection on Body Condition of Zebrafish.

Zebrafish 2020 04 22;17(2):139-146. Epub 2020 Jan 22.

Department of Biomedical Sciences, Oregon State University, Corvallis, Oregon.

The zebrafish is a widely used animal model in biomedical research. Despite this, pathogens continue to be common in laboratory zebrafish. It is important to determine and describe the pathophysiology of cryptic infections on zebrafish to elucidate the impacts on experimental endpoints. Body condition is a basic measurement used experimentally and in health monitoring of animals. We exposed three wild-type zebrafish strains: AB, WIK, and 5D to . After 8 weeks postexposure, we individually imaged and processed fish for histology. Morphometric analysis was performed on images and an index of body condition was calculated based on the ratio of length/width from the dorsal aspect. Histological sections from each fish were examined to establish sex, severity of infection, and tissue distribution. We observed a significant decrease in body condition in female fish that was not observed in males. In addition, we observed a negative correlation between the total gonadal area of exposed females and unexposed controls. These results illustrate the sex-specific impacts of a common chronic pathogen on zebrafish health and a commonly used experimental endpoint, further supporting the establishment of rigorous health monitoring programs in laboratory zebrafish colonies that include screening for chronic infectious diseases.
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http://dx.doi.org/10.1089/zeb.2019.1812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153649PMC
April 2020

Adult Atypical Teratoid/Rhabdoid Tumor in the Pineal Region: Case Report and Literature Review.

World Neurosurg 2020 Feb 20;134:428-433. Epub 2019 Nov 20.

Department of Neurosurgery, Hospital Garcia de Orta, Almada, Portugal.

Background: Atypical teratoid/rhabdoid tumor (AT/RT) is a malignant embryonal central nervous system tumor with a poor prognosis. Its occurrence in the pineal region is extremely rare, with only 6 cases in adults reported so far.

Case Description: We report on a puerperal woman with an AT/RT in the pineal region. Total tumor resection was performed. Definitive diagnosis was confirmed by the loss of nuclear INI1/SMARCB1 staining. The patient underwent radiotherapy and chemotherapy with no evidence of recurrence at 31 months after surgery.

Conclusions: This case highlights the importance of immunohistochemistry in the diagnosis of the disease and the importance of an aggressive treatment.
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http://dx.doi.org/10.1016/j.wneu.2019.11.075DOI Listing
February 2020

European Portuguese version of the functional disability inventory: translation and cultural adaptation, validity, and reliability in adolescents with chronic spinal pain.

Disabil Rehabil 2019 Oct 10:1-8. Epub 2019 Oct 10.

School of Health Sciences (ESSUA), University of Aveiro, Campus Universitário de Santiago , Aveiro , Portugal.

Functional disability affects a large percentage of adolescents with chronic pain. The functional disability inventory (FDI) has been widely described in the literature to assess functional disability, with good psychometric properties. To translate and adapt the FDI to European Portuguese language and assess the validity, reliability, and measurement error of this version in adolescents with chronic musculoskeletal pain and, specifically, with neck and low back pain. The translation and cross-cultural adaptation of the FDI was conducted according to international guidelines. After that, 1730 adolescents completed the following scales and questionnaires: FDI, Nordic Musculoskeletal Questionnaire, Numeric Pain Rating Scale, Pain Catastrophizing Scale, Depression, Anxiety and Stress Scale, Tampa Scale of Kinesiophobia, and Basic Scale on Insomnia complaints and Quality of Sleep. Sixty-three of these adolescents, with at least one painful body site, completed the questionnaire twice to assess reliability and measurement error. Exploratory factor analysis and hypothesis testing was used to assess construct validity. Cronbach's alpha ranged from 0.81 and 0.88, ICC was 0.86 (95%CI:0.77; 0.92), the SEM and the SDC were 2.50 and 6.93 (total score of 60 points), respectively. Fair to moderate correlations were obtained between FDI and pain intensity ( = 0.33 to 0.43), catastrophizing ( = 0.41 to 0.44) depression, anxiety, and stress ( = 0.48 to 0.53), fear of movement ( = 0.32 to 0.42), and sleep impairments ( = 0.34 to 0.38). The factor analysis suggested a two-factor solution. The European Portuguese version of the FDI has very good internal consistency, good test-retest reliability, and construct validity when used in a sample of community adolescents with chronic pain. Implications for rehabilitation One of the most widely instruments used to assess functional disability is the Functional Disability Inventory (FDI), which in its original version has good psychometric properties and is recommended by the Pediatric Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials; However, the FDI has not been translated yet into European Portuguese language and its psychometric properties have not been assessed in adolescents with chronic spinal pain; This study suggests that the European Portuguese version of the FDI has very good internal consistency, good test-retest reliability as well as construct validity when used in a sample of community adolescents with chronic spinal pain; Therefore, these findings suggest the use of the European Portuguese version of the FDI to assess the functional disability in adolescents with chronic spinal pain.
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http://dx.doi.org/10.1080/09638288.2019.1672110DOI Listing
October 2019

UK dental professionals' knowledge, experience and confidence when treating patients on the autism spectrum.

Br Dent J 2019 Sep;227(6):504-510

Centre for Research in Autism and Education, Department of Psychology and Human Development, UCL Institute of Education, University College London, UK.

Background Over 1% of the UK population have a diagnosis of autism, and yet there is minimal information regarding the experiences of dental professionals working with people on the autistic spectrum. The current study is the first to investigate UK dental professionals' knowledge of autism, their perceived confidence when treating autistic patients, and the factors that affect this.Methods An online, self-report survey was completed by 482 UK dental professionals and included questions on participants' training, prior experiences and knowledge of autism, and confidence when treating autistic patients.Results Over half the respondents reported having no formal autism training but average knowledge levels across the whole sample were good. Conversely, levels of confidence were only moderate. Respondents often cited conflict between understanding the additional needs for successful treatment of autistic patients and a lack of resources to implement support strategies. Despite this, the vast majority were positive about making the necessary modifications to support autistic patients.Conclusion This study highlights ways in which UK dental professionals adapt their practices to meet the needs of their autistic patients, yet report only moderate confidence levels when doing so. Implications for future training initiatives are discussed.
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http://dx.doi.org/10.1038/s41415-019-0786-5DOI Listing
September 2019

A Contribution for the Valorisation of Sheep and Goat Cheese Whey through Nanofiltration.

Membranes (Basel) 2018 Nov 20;8(4). Epub 2018 Nov 20.

LEAF-Linking Landscape, Environment, Agriculture and Food, Instituto Superior de Agronomia, University of Lisbon, Tapada da Ajuda, 1349-017 Lisboa, Portugal.

The amount of cheese whey generated from the production of speciality sheep and goat cheese is significantly growing due to the acclaimed nutritional and medicinal benefits of the milk from these species. However, most of the cheese whey generated has no applications, thus giving rise to environmental problems. This work focuses on the study of the performance of the nanofiltration process for recovering the permeates of ultrafiltration from sheep and goat cheese whey. Nanofiltration experiments were carried out with membranes of nanofiltration (NF) in total recirculation and concentration modes, at 25 °C. Nanofiltration of the ultrafiltration permeates from sheep cheese whey was done at a pressure of 3.0 × 10⁶ Pa and a circulation velocity of 1.42 m·s, until a volume concentration factor (VCF) of 2.5. Nanofiltration of the permeates from ultrafiltration of goat cheese whey was performed at a pressure of 2.0 × 10⁶ Pa and a circulation velocity of 0.94 m·s, until a VCF of 2.0. From the results, it was concluded that osmotic pressure was the most important factor affecting the performance of the process. In both cases, the final permeates had a much lower organic load and its future use in the process of cheese making should be evaluated.
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http://dx.doi.org/10.3390/membranes8040114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315593PMC
November 2018

SRC inhibition prevents P-cadherin mediated signaling and function in basal-like breast cancer cells.

Cell Commun Signal 2018 11 7;16(1):75. Epub 2018 Nov 7.

Epithelial Interactions in Cancer (EPIC), i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135, Porto, Portugal.

Background: Basal-like breast cancer (BLBC) is a poor prognosis subgroup of triple-negative carcinomas that still lack specific target therapies and accurate biomarkers for treatment selection. P-cadherin is frequently overexpressed in these tumors, promoting cell invasion, stem cell activity and tumorigenesis by the activation of Src-Family kinase (SRC) signaling. Therefore, our aim was to evaluate if the treatment of BLBC cells with dasatinib, the FDA approved SRC inhibitor, would impact on P-cadherin induced tumor aggressive behavior.

Methods: P-cadherin and SRC expression was evaluated in a series of invasive Breast Cancer and contingency tables and chi-square tests were performed. Cell-cell adhesion measurements were performed by Atomic Force Microscopy, where frequency histograms and Gaussian curves were applied. 2D and 3D cell migration and invasion, proteases secretion and self-renew potential were evaluated in vitro. Student's t-tests were used to determine statistically significant differences. The cadherin/catenin complex interactions were evaluated by in situ proximity-ligation assay, and statistically significant results were determined by using Mann-Whitney test with a Bonferroni correction. In vivo xenograft mouse models were used to evaluate the impact of dasatinib on tumor growth and survival. ANOVA test was used to evaluate the differences in tumor size, considering a confidence interval of 95%. Survival curves were estimated by the Kaplan-Meier's method, using the log-rank test to assess significant differences for mice overall survival.

Results: Our data demonstrated that P-cadherin overexpression is significantly associated with SRC activation in breast cancer cells, which was also validated in a large series of primary tumor samples. SRC activity suppression with dasatinib significantly prevented the in vitro functional effects of P-cadherin overexpressing cells, as well as their in vivo tumorigenic and metastatic ability, by increasing mice overall survival. Mechanistically, SRC inhibition affects P-cadherin downstream signaling, rescues the E-cadherin/p120-catenin complex to the cell membrane, recovering cell-cell adhesion function.

Conclusions: In conclusion our findings show that targeting P-cadherin/SRC signaling and functional activity may open novel therapeutic opportunities for highly aggressive and poor prognostic basal-like breast cancer.
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http://dx.doi.org/10.1186/s12964-018-0286-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6223051PMC
November 2018

Late preterms: are they all the same?

J Matern Fetal Neonatal Med 2020 May 29;33(10):1780-1785. Epub 2018 Oct 29.

São Sebastião Hospital, Santa Maria Feira, Portugal.

Very preterm infants (VPT) and, especially extreme low gestational age (ELGA) preterms, often on the threshold of viability, make the headlines of both, the scientific as well as the popular press. However, all together they represent between 1 and 2% of all livebirths. Late preterms (LPT) those born between 34/07 and 36/06 weeks, on the other hand, may account for up to 80% of all preterms and for some 5-8% of all births. Although mortality is low they are prone to increasing neonatal morbidities posing a considerable medical, financial and psychosocial burden. In the last years, for many reasons, LPT appear to have increased considerably throughout the western world. But are LPT neonates all the same? In spite of overlapping gestational ages (GA) LPT may behave quite differently depending on circumstances surrounding their pre- and postnatal events. We can identify three different classes of LPT neonates: spontaneous late preterms (SpLPT) born in the absence of previous maternal illnesses and/or pregnancy related disorders; Induced LPT (IdLPT) due to maternal/fetal complications and those babies being born after 34-week gestation from postponed delivery at an earlier GA (PtLPT) - and they are quite different babies, with different behavior, despite a common and same gestational age.
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http://dx.doi.org/10.1080/14767058.2018.1527897DOI Listing
May 2020

The Impact of Two Different Cold-Extruded Feeds and Feeding Regimens on Zebrafish Survival, Growth and Reproductive Performance.

J Dev Biol 2018 Jun 21;6(3). Epub 2018 Jun 21.

Fish Platform, Champalimaud Center for the Unknown, 1400-038 Lisbon, Portugal.

Zebrafish () is one of the top model organisms used in biomedical research. Therefore, it is fundamental that zebrafish facilities continuously improve husbandry methods to provide fish with the best physiological and welfare conditions that suit each experimental purpose. Nutrition is a husbandry aspect that needs further optimization, as it greatly affects growth, reproduction, health and behaviour. Here, we have compared the impact of different feeding regimens on zebrafish survival, growth and reproductive performance. Mutant and wild-type zebrafish were raised using several combinations of two cold-extruded processed feeds—SkrettingGemmaMicro and SparosZebrafeed—and one live feed (rotifers). Zebrafeed outperformed GemmaMicro in terms of survival rate, and embryo viability was also higher when the spawners were fed with Zebrafeed either from larval stage or upon sexual maturation. In contrast, GemmaMicro favoured growth, both in size and weight. The use of rotifers until 60 days post-fertilization improved survival of fish co-fed with GemmaMicro, while delaying their growth. Zebrafeed performance was not affected by co-feeding rotifers. Overall, we showed that different nutritional formulas affect physiological parameters, allowing for the establishment of feeding protocols adapted to the objectives of each facility. At the same time, we validated SkrettingGemmaMicro and SparosZebrafeed as two commercially available feeds that are well suited for zebrafish nutrition in a laboratory environment.
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http://dx.doi.org/10.3390/jdb6030015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6162542PMC
June 2018

Biological and Molecular Characterization of Strains from Four States of Brazil.

Am J Trop Med Hyg 2018 02 4;98(2):453-463. Epub 2018 Jan 4.

Department of Biological Sciences, Faculdade de Ciências Farmacêuticas da Universidade Estadual Paulista Júlio de Mesquita Filho, Araraquara, Brazil.

Chagas disease affects between six and seven million people. Its etiological agent, , is classified into six discrete typing units (DTUs). The biological study of 11 strains presented here included four parameters: growth kinetics, parasitemia curves, rate of macrophage infection, and serology to evaluate IgM, total IgG, IgG1, IgG2a, and IgG3. Sequencing of small subunit of ribosomal RNA (SSU rRNA)was performed and the strains were classified into three DTUs. When their growth in liver infusion tryptose medium was represented in curves, differences among the strains could be noted. The parasitemia profile varied among the strains from the TcI, TcII, and TcIII groups, and the 11 strains produced distinct parasitemia levels in infected BALB/c. The TcI group presented the highest rate of macrophage infection by amastigotes, followed by TcII and TcIII. Reactivity to immunoglobulins was observed in the TcI, TcII, and TcIII; all the animals infected with the different strains of showed anti- antibodies. The molecular study presented here resulted in the classification of the strains into the TcI (Bolivia, T lenti, Tm, SC90); TcII (Famema, SC96, SI8, Y); and TcIII (QMM3, QMM5, SI5) groups. These biological and molecular results from 11 strains clarified the factors involved in the biology of the parasite and its hosts. The collection of triatomine (vector) species, and the study of geographic distribution, as well as biological and molecular characterization of the parasite, will contribute to the reporting and surveillance measures in Brazilian states.
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http://dx.doi.org/10.4269/ajtmh.16-0200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5929169PMC
February 2018

Foxj1a is expressed in ependymal precursors, controls central canal position and is activated in new ependymal cells during regeneration in zebrafish.

Open Biol 2017 11;7(11)

Instituto de Medicina Molecular e Instituto de Histologia e Biologia do Desenvolvimento, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal

Zebrafish are able to regenerate the spinal cord and recover motor and sensory functions upon severe injury, through the activation of cells located at the ependymal canal. Here, we show that cells surrounding the ependymal canal in the adult zebrafish spinal cord express Foxj1a. We demonstrate that ependymal cells express Foxj1a from their birth in the embryonic neural tube and that Foxj1a activity is required for the final positioning of the ependymal canal. We also show that in response to spinal cord injury, Foxj1a ependymal cells actively proliferate and contribute to the restoration of the spinal cord structure. Finally, this study reveals that Foxj1a expression in the injured spinal cord is regulated by regulatory elements activated during regeneration. These data establish Foxj1a as a pan-ependymal marker in development, homeostasis and regeneration and may help identify the signals that enable this progenitor population to replace lost cells after spinal cord injury.
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http://dx.doi.org/10.1098/rsob.170139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5717339PMC
November 2017

Use of Zymography in Trypanosomiasis Studies.

Methods Mol Biol 2017 ;1626:213-220

Programa de Pós-graduação em Bioquímica, Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal, Brazil.

Zymography assay is a semiquantitative technique, very sensitive, and commonly used to determine metalloproteinase levels in different types of biological samples, including tissues, cells, and extracts of protein. Samples containing metalloproteinases are loaded onto a polyacrylamide gel containing sodium dodecyl sulphate (SDS) and a specific substrate (gelatin, casein, collagen, etc.). Then proteins are allowed to migrate under an electric current and the distance of migration is inversely correlated with the molecular weight. After migration, the gel is placed in a renaturing buffer to allow proteins to regain their tertiary structure, necessary for enzymatic activity (metalloproteinase activity). In the context of infections caused by trypanosomatids (Leishmania spp., Trypanosoma cruzi, and Trypanosoma brucei), the characterization of metalloproteinase by zymography can contribute to the comprehension of the pathogenesis mechanisms and host-parasite interaction.
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http://dx.doi.org/10.1007/978-1-4939-7111-4_20DOI Listing
March 2018

Clarifying changes in student empathy throughout medical school: a scoping review.

Adv Health Sci Educ Theory Pract 2017 Dec 27;22(5):1293-1313. Epub 2016 Jul 27.

Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus de Gualtar, Gualtar, 4710-057, Braga, Portugal.

Despite the increasing awareness of the relevance of empathy in patient care, some findings suggest that medical schools may be contributing to the deterioration of students' empathy. Therefore, it is important to clarify the magnitude and direction of changes in empathy during medical school. We employed a scoping review to elucidate trends in students' empathy changes/differences throughout medical school and examine potential bias associated with research design. The literature published in English, Spanish, Portuguese and French from 2009 to 2016 was searched. Two-hundred and nine potentially relevant citations were identified. Twenty articles met the inclusion criteria. Effect sizes of empathy scores variations were calculated to assess the practical significance of results. Our results demonstrate that scoped studies differed considerably in their design, measures used, sample sizes and results. Most studies (12 out of 20 studies) reported either positive or non-statistically significant changes/differences in empathy regardless of the measure used. The predominant trend in cross-sectional studies (ten out of 13 studies) was of significantly higher empathy scores in later years or of similar empathy scores across years, while most longitudinal studies presented either mixed-results or empathy declines. There was not a generalized international trend in changes in students' empathy throughout medical school. Although statistically significant changes/differences were detected in 13 out of 20 studies, the calculated effect sizes were small in all but two studies, suggesting little practical significance. At the present moment, the literature does not offer clear conclusions relative to changes in student empathy throughout medical school.
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http://dx.doi.org/10.1007/s10459-016-9704-7DOI Listing
December 2017

Toward an Integrated Zebrafish Health Management Program Supporting Cancer and Neuroscience Research.

Zebrafish 2016 07 9;13 Suppl 1:S47-55. Epub 2016 Mar 9.

1 Champalimaud Centre for the Unknown , Lisbon, Portugal .

Zebrafish is already one of the most used model organisms in biomedical sciences and other research fields. It is therefore becoming increasingly important to assure that zebrafish maintained in laboratory aquaculture conditions are raised and housed under rigorous standards that promote health and welfare to guarantee the required quality and reproducibility of research data. Specifying the programs each facility is adopting would be the first step to achieve this by allowing other facilities to compare, improve, and discuss their protocols and fish performance. We provide in this article a detailed description of an integrated facility health management program, with protocols and readouts, fully designed and aimed at maximizing fish health, welfare, and performance for research.
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http://dx.doi.org/10.1089/zeb.2015.1198DOI Listing
July 2016

V-ATPase proton pumping activity is required for adult zebrafish appendage regeneration.

PLoS One 2014 26;9(3):e92594. Epub 2014 Mar 26.

Instituto Gulbenkian de Ciência, Oeiras, Portugal; Department de Anatomía Humana, Biología Celular y Zoología, Facultad de Medicina, Universidad de Extremadura, Badajoz, Spain.

The activity of ion channels and transporters generates ion-specific fluxes that encode electrical and/or chemical signals with biological significance. Even though it is long known that some of those signals are crucial for regeneration, only in recent years the corresponding molecular sources started to be identified using mainly invertebrate or larval vertebrate models. We used adult zebrafish caudal fin as a model to investigate which and how ion transporters affect regeneration in an adult vertebrate model. Through the combined use of biophysical and molecular approaches, we show that V-ATPase activity contributes to a regeneration-specific H+ ef`flux. The onset and intensity of both V-ATPase expression and H+ efflux correlate with the different regeneration rate along the proximal-distal axis. Moreover, we show that V-ATPase inhibition impairs regeneration in adult vertebrate. Notably, the activity of this H+ pump is necessary for aldh1a2 and mkp3 expression, blastema cell proliferation and fin innervation. To the best of our knowledge, this is the first report on the role of V-ATPase during adult vertebrate regeneration.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0092594PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3966808PMC
December 2015

Cancer stemness in Wnt-driven mammary tumorigenesis.

Carcinogenesis 2014 Jan 16;35(1):2-13. Epub 2013 Aug 16.

Department of Pathology, Josephine Nefkens Institute, Erasmus MC 3000 CA Rotterdam, The Netherlands and.

Wnt signaling plays a central role in mammary stem cell (MaSC) homeostasis and in breast cancer. In particular, epigenetic alterations at different members of the Wnt pathway have been identified among triple-negative, basal-like breast cancers. Previously, we developed a mouse model for metaplastic breast adenocarcinoma, a subtype of triple-negative breast cancer, by targeting a hypomorphic mutations in the endogenous Apc gene (Apc (1572T/+)). Here, by employing the CD24 and CD29 cell surface antigens, we have identified a subpopulation of mammary cancer stem cells (MaCSCs) from Apc (1572T/+) capable of self-renewal and differentiation both in vivo and in vitro. Moreover, immunohistochemical analysis of micro- and macrolung metastases and preliminary intravenous transplantation assays suggest that the MaCSCs underlie metastasis at distant organ sites. Expression profiling of the normal and tumor cell subpopulations encompassing MaSCs and CSCs revealed that the normal stem cell compartment is more similar to tumor cells than to their own differentiated progenies. Accordingly, Wnt signaling appears to be active in both the normal and cancer stem cell compartments, although at different levels. By comparing normal with cancer mouse mammary compartments, we identified a MaCSC gene signature able to predict outcome in breast cancer in man. Overall, our data indicate that constitutive Wnt signaling activation affects self-renewal and differentiation of MaSCs leading to metaplasia and basal-like adenocarcinomas.
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http://dx.doi.org/10.1093/carcin/bgt279DOI Listing
January 2014

Partial genetic deficiency in tissue kallikrein impairs adaptation to high potassium intake in humans.

Kidney Int 2013 Dec 12;84(6):1271-7. Epub 2013 Jun 12.

Faculty of Medicine, Porto University, Porto, Portugal.

Inactivation of the tissue kallikrein gene in mice impairs renal handling of potassium due to enhanced H, K-ATPase activity, and induces hyperkalemia. We investigated whether the R53H loss-of-function polymorphism of the human tissue kallikrein gene affects renal potassium handling. In a crossover study, 30 R53R homozygous and 10 R53H heterozygous healthy males were randomly assigned to a low-sodium/high-potassium or a high-sodium/low-potassium diet to modulate tissue kallikrein synthesis. On the seventh day of each diet, participants were studied before and during a 2-h infusion of furosemide to stimulate distal potassium secretion. Urinary kallikrein activity was significantly lower in R53H than in R53R subjects on the low-sodium/high-potassium diet and was similarly reduced in both genotypes on high-sodium/low-potassium. Plasma potassium and renal potassium reabsorption were similar in both genotypes on an ad libitum sodium/potassium diet or after 7 days of a high-sodium/low-potassium diet. However, the median plasma potassium was significantly higher after 7 days of low-sodium/high-potassium diet in R53H than in R53R individuals. Urine potassium excretion and plasma aldosterone concentrations were similar. On the low-sodium/high-potassium diet, furosemide-induced decrease in plasma potassium was significantly larger in R53H than in R53R subjects. Thus, impaired tissue kallikrein stimulation by a low-sodium/high-potassium diet in R53H subjects with partial tissue kallikrein deficiency highlights an inappropriate renal adaptation to potassium load, consistent with experimental data in mice.
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http://dx.doi.org/10.1038/ki.2013.224DOI Listing
December 2013

Cardiac venous arterialization in acute myocardial infarction: how great is the benefit?

Interact Cardiovasc Thorac Surg 2013 Mar 30;16(3):307-13. Epub 2012 Nov 30.

ICBAS (Abel Salazar Institute for Biomedical Sciences), University of Porto, Porto, Portugal.

Objectives: Cardiac venous arterialization has been proposed as an alternative approach for myocardial revascularization in ischaemic heart disease. It is based on using the cardiac venous system to transport arterial blood from a systemic artery to infarcted myocardial areas. Our goal was to evaluate its benefit in reducing acute myocardial infarct size and its effects on cardiac performance.

Methods: In a group of pigs, the left internal mammary artery was anastomosed to the left anterior descending vein; this vein was ligated proximally. The left anterior descending coronary artery was also occluded. Over 5 days, several diagnostic procedures were used to characterize and measure the extent of myocardial infarct, namely ECG, echocardiography, cardiac biomarkers and histopathology. Data were compared with those from a control group of pigs, which were submitted to ligation of only the left anterior descending coronary artery.

Results: In the experimental group, echocardiography revealed that the ejection fraction and thickness of the ventricular walls remained unchanged 4 days after surgery, in contrast to the major alterations in the control group. In fact, the ejection fraction in the control group decreased by 21% (P < 0.001), with a reduction of 31% (P < 0.004) in the thickness of the interventricular septum at end systole and enlargement of the left ventricular lumen by 28% (P < 0.001). In the experimental group, the sum for ST segment shift was 50% lower (P = 0.038) and the total ventricular histological lesion size was 50% smaller (P < 0.001). Within this lesion, the area of necrotic tissue was 70% smaller (P < 0.001). Cardiac biomarkers were not different between the two groups (P > 0.2).

Conclusions: This study reveals that selective cardiac venous arterialization can nourish the myocardium and is able to reduce infarct size by more than 50%, while protecting cardiac performance. We believe, therefore, that further investigation should be carried out into this technique in order for it to be considered as an option in coronary surgery.
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http://dx.doi.org/10.1093/icvts/ivs471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3568797PMC
March 2013

Surgical porcine myocardial infarction model through permanent coronary occlusion.

Comp Med 2011 Oct;61(5):445-52

Department of Anatomy, University of Porto, Porto, Portugal.

Using domestic pigs as an animal model, we here validated a reproducible and standardized myocardial infarction (MI) surgical model, to achieve the largest possible infarct extent with the lowest morbidity and mortality. To this end, we included several anesthetic and perisurgical precautions to minimize surgical complications. Mortality and morbidity rates were compared among groups of pigs that underwent permanent occlusion at different locations of either the left circumflex or left anterior descending artery. In addition, to compare the resulting MI between groups, data were collected by using cardiac biomarkers (including troponin I), electrocardiography, and echocardiography. These data were correlated to the final mean infarct size calculated by microscopic studies. Proximal occlusions lead to high mortality rates, whereas distal occlusions induced rather small MI areas. The optimal occlusion site in terms of morbidity, mortality, and lesion extent was the midpoint of the left anterior descending artery. In this group, only one pig died, and group cardiac data showed a rise in biomarker levels, marked left ventricular dysfunction on electrocardiography and echocardiography, and well-defined transmural MI in both ventricles. Infarct size quantitated through histologic studies revealed an average 15% ventricular lesion. Because interanimal variability in results from this group was negligible, we consider that the induced myocardial injury of this model is reliable.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3193068PMC
October 2011

Cancer stemness and metastasis: therapeutic consequences and perspectives.

Eur J Cancer 2010 May 18;46(7):1198-203. Epub 2010 Mar 18.

Department of Pathology, Josephine Nefkens Institute, Erasmus MC, Rotterdam, The Netherlands.

The transient and dynamic nature of cancer cells that underlie metastasis cannot only be explained by the progressive accumulation of irreversible genetic changes occurring in the primary tumour. The capacity of cells to switch between different cellular identities, as in epithelial to mesenchymal (EMT) and mesenchymal to epithelial transitions (MET), allows them to respond to different cellular environments, thus efficiently disseminating from the primary mass to eventually colonise distant organs. These more dynamic stem-like cancer cells are earmarked by the ability to self-renew and de-/re-differentiate, and eventually recapitulate the heterogeneous composition of the primary tumour in a distant organ site. This dynamic concept of metastasis has profound consequences and implications for cancer diagnostics, prognostics and therapy. Many of the characteristics that define stem cells, like dormancy, active DNA repair, the expression of several drug transporters, and resistance to apoptosis may underlie the capacity of migrating cancer cells to survive conventional therapeutic protocols based on genotoxic agents targeting active proliferating cells. Accordingly, signal transduction pathways that regulate the balance between self-renewal and differentiation are likely to represent future targets in the development of tailor-made intervention strategies. Also, specific stem cell features, such as the capacity to migrate to diseased areas (pathotropism), open novel avenues towards the development of cell vehicles capable of tracking and delivering anti-cancer compounds to disseminated metastatic lesions.
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http://dx.doi.org/10.1016/j.ejca.2010.02.030DOI Listing
May 2010

Genetic variability of human immunodeficiency virus-1 in Bahia state, Northeast, Brazil: high diversity of HIV genotypes.

J Med Virol 2009 Mar;81(3):391-9

Laboratório Avançado de Saúde Pública, CPqGM/FIOCRUZ, Salvador, Bahia, Brazil.

The HIV-1 genetic variability in Bahia state, Brazil, was investigated. DNA samples from 229 and 213 HIV-1-infected individuals were analyzed using the heteroduplex mobility assay (HMA) in gag and env fragments, respectively. One hundred seventy-five samples were characterized in both genes. Thirty-two subtype F and BF recombinant viruses were sequenced and analyzed by phylogenetic methods. The combination of HMA and sequencing results showed that seven different HIV-1 genotypes comprised this sample: 147 (84%) B/B, 4 (2.3%) F/F, 3 (1.7%) B/F, 1 (0.6%) F/B, 1 (0.6%) F/D, 1 (0.6%) BF/F, and 18 (10.3%) BF/B. A significant divergence was observed between these two techniques results (84.4%). This is explained by the low accuracy of the HMA for detecting recombinant viruses. These recombinants were unrelated to CRF12, while two sequences were related to CRF28 and CRF29. Nineteen BF mosaics shared the same gag breakpoint. In conclusion, the use of HMA may be inappropriate in regions where different subtypes are co-circulating. Subtype B is the most common genotype, however, an increased prevalence (13.1%) of different BF variants and a potentially new CRF suggest that recombination is occurring frequently in Bahia. These viruses were associated with women infected heterosexually. Finally, this study identified the presence of an F/D recombinant HIV-1 in Brazil.
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http://dx.doi.org/10.1002/jmv.21414DOI Listing
March 2009

Pulpal status of human primary teeth with physiological root resorption.

Int J Paediatr Dent 2009 Jan;19(1):16-25

Department of Paediatric Dentistry, Leeds Dental Institute, Leeds, UK.

Objective: The overall aim of this study was to determine whether any changes occur in the pulpal structure of human primary teeth in association with physiological root resorption.

Methods: The experimental material comprised 64 sound primary molars, obtained from children requiring routine dental extractions under general anaesthesia. Pulp sections were processed for indirect immunofluorescence using combinations of: (i) protein gene product 9.5 (a general neuronal marker); (ii) leucocyte common antigen CD45 (a general immune cell marker); and (iii) Ulex europaeus I lectin (a marker of vascular endothelium). Image analysis was then used to determine the percentage area of staining for each label within both the pulp horn and mid-coronal region. Following measurement of the greatest degree of root resorption in each sample, teeth were subdivided into three groups: those with physiological resorption involving less than one-third, one-third to two-thirds, and more than two-thirds of their root length.

Results: Wide variation was evident between different tooth samples with some resorbed teeth showing marked changes in pulpal histology. Decreased innervation density, increased immune cell accumulation, and increased vascularity were evident in some teeth with advanced root resorption. Analysis of pooled data, however, did not reveal any significant differences in mean percentage area of staining for any of these variables according to the three root resorption subgroups (P > 0.05, analysis of variance on transformed data).

Conclusions: This investigation has revealed some changes in pulpal status of human primary teeth with physiological root resorption. These were not, however, as profound as one may have anticipated. It is therefore speculated that teeth could retain the potential for sensation, healing, and repair until advanced stages of root resorption.
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http://dx.doi.org/10.1111/j.1365-263X.2008.00963.xDOI Listing
January 2009

Tyrosine polysulfation of human salivary histatin 1. A post-translational modification specific of the submandibular gland.

J Proteome Res 2007 Jul 16;6(7):2472-80. Epub 2007 May 16.

Department of Sciences Applied to Biosystems, Cagliari University, Cagliari, Italy.

Histatin 1 (His-1) derivatives showing serial mass increases of 80.0 +/- 0.1 Da were detected in human saliva by HPLC-ESI-MS. The same derivatives were also found in granules of submandibular glands and secretions of submandibular/sublingual glands, but not in granules and secretions of parotid glands. Only one phosphate group was present in His-1 and its derivatives, since treatment with alkaline phosphatase provided an 80.0 Da mass decrease. His-1 derivatives were almost completely transformed into His-1 by treatment with 1 M HCl at 100 degrees C, suggesting the presence of O-sulfotyrosine, which is more labile than phospho-Tyr to acidic hydrolysis. CE-MS analysis of pronase extensive digestion of derivatives confirmed the presence of sulfotyrosine. Derivatives were digested by trypsin, proteinase K, and protease V-8 and analyzed by different MS strategies. The results allowed locating sulfation on the last four tyrosines (Tyr 27, 30, 34, and 36). This study is the first report of the gland-specific sulfation of a salivary phosphopeptide in vivo.
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http://dx.doi.org/10.1021/pr0700706DOI Listing
July 2007

Genetic and biologic characterization of HIV type 1 subtype C isolates from south Brazil.

AIDS Res Hum Retroviruses 2007 Jan;23(1):135-43

Laboratório Avançado de Saúde Pública, Centro de Pesquisa Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Bahia, Brazil.

The molecular and biological properties of HIV-1 subtype C strains from South Brazil were investigated. We sequenced gag and env fragments of viruses from 22 HIV-1-infected individuals from Porto Alegre City, which has the highest frequency of subtype C in the country. The sequences were then compared with other subtype B, C, and F strains isolated in Brazil and other countries using phylogenetic methods. Amino acid signatures were identified and correlated with phenotypic characteristics. We identified six strains with subtype C (27.3%), eight subtype B (36.4%), one subtype F (4.5%), six C/B recombinants (27.3%), and one B/F recombinant (4.5%). The Brazilian subtype C sequences formed a unique phylogenetic group and presented 6 and 18 specific amino acid signatures in gag and env, respectively. Three distinct patterns of C/B recombinants presented characteristic Brazilian amino acid substitutions. Subtype C viruses were predominantly R5 and non-syncytium-inducing, while C/B recombinants were R5/X4 and syncytium-inducing viruses. These findings suggest that subtype C viruses circulating in Brazil are the result of a unique introduction into the country. Recombination events between subtypes B and C have been occurring frequently for more than 10 years in South Brazil. Biological characterization confirms the hypothesis that subtype C is distinct from the others in the evolution of coreceptor utilization.
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http://dx.doi.org/10.1089/aid.2006.0064DOI Listing
January 2007