Publications by authors named "Sofia Martins"

45 Publications

A Pilot Randomized Clinical Trial: Oral Miltefosine and Pentavalent Antimonials Associated With Pentoxifylline for the Treatment of American Tegumentary Leishmaniasis.

Front Cell Infect Microbiol 2021 1;11:700323. Epub 2021 Jul 1.

Pós-Graduação de Ciências da Saúde da Faculdade de Ciências Saúde, Universidade de Brasília, Brasília, Brazil.

Introduction: American tegumentary leishmaniasis (ATL), which can present as either cutaneous (CL) or mucosal leishmaniasis (ML), is endemic in South America, and first-line antimonial treatments are known for their wide range of adverse effects (AEs). Growing reports of drug resistance increase the urgency of the need for better treatment options. The objective of this pilot clinical trial was to assess the efficacy of and AEs associated with the oral combination of miltefosine and pentoxifylline based on a analysis.

Methods: A pilot, randomized, open-label clinical trial was performed. The experimental group (M+P) received 50 mg twice a day (BID) miltefosine and 400 mg three times a day (TID) pentoxifylline, and the control group (A+P) received 20 mg Sb+V/kg/day intravenously and 400 mg TID pentoxifylline. Patients with ML received treatment for 28 days, and patients with CL received treatment for 20 days.

Results: Forty-three patients were included: 25 with ML and 18 with CL caused by . AEs were more frequent in the A+P group (p=0.322), and there was a need for treatment interruption due to severe AEs (p=0.027). Patients with CL had a higher chance of achieving a cure (p=0.042) and a higher risk of AEs (p=0.033). There was no difference in the chance of a cure based on the treatment (p=0.058).

Conclusion: In this pilot randomized clinical trial, M+P treatment and A+P treatment yielded similar cure rates, and the former was associated with a lower risk of AEs. Future studies with more patients and longer follow-up are recommended.
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http://dx.doi.org/10.3389/fcimb.2021.700323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281031PMC
July 2021

Successful treatment of diffuse cutaneous leishmaniasis caused by Leishmania amazonensis.

An Bras Dermatol 2021 Jul 14. Epub 2021 Jul 14.

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

Diffuse cutaneous leishmaniasis is a rare universal disease associated with an inadequate host cell immune response, caused by different species: infantum, aethiopica, major, mexicana, and others, which presents the challenge of a poor therapeutic response. In Brazil, it is caused by L. amazonensis. A case confirmed by histopathology with an abundance of vacuolated macrophages full of amastigotes and lymphocyte scarcity, identified by RFLP-ITS1PCR and in vitro decrease and exhaustion of the host cell immune response to L. amazonensis antigen, was treated early (3 months after the onset) with Glucantime (2 months) and allopurinol (29 months) with clinical cure, after a follow-up for 30 months after treatment.
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http://dx.doi.org/10.1016/j.abd.2021.03.003DOI Listing
July 2021

Monitoring Intracellular Calcium in Response to GPCR Activation: Comparison Between Microtiter Plates and Microfluidic Assays.

Methods Mol Biol 2021 ;2268:289-304

INESC Microsistemas e Nanotecnologias, Lisbon, Portugal.

Microfluidic strategies combined with transduction and electronic integration have the promise of enabling miniaturized, combinatorial assays at higher speeds and lower costs, while at the same time mimicking the local chemical concentrations and force fields of the cellular in vivo environment. In this chapter we introduce a microfluidic structure with hydrodynamic cell traps and a culture volume in the nanoliter range (50 nL), to quantitatively evaluate the transient calcium response of the endogenous Muscarinic type 1 receptor (M1) in HEK 293 T cells. The microfluidic fabrication protocol is described as well as a methodology to monitor the cell response in real time, after stimulation with M1 agonists (e.g., carbachol) and antagonists (e.g., Pirenzepine).
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http://dx.doi.org/10.1007/978-1-0716-1221-7_19DOI Listing
July 2021

Consumption of antidiabetic medicines in Portugal: results of a temporal data analysis of a thirteen-year study (2005-2017).

BMC Endocr Disord 2021 Feb 24;21(1):30. Epub 2021 Feb 24.

Nova Medical School, New University of Lisbon, Lisboa, Portugal.

Background: Studies of drug utilization in patients with diabetes, a chronic disease that can be treated with a wide range of available medicines, have attracted substantial social and clinical interest.

Objective: To characterize antidiabetic medicine consumption between 2005 and 2017, to evaluate the trends of these medicines in mainland Portugal, and to compare district consumption. An additional objective was to perform a statistical analysis on drug consumption in different regions of Portugal.

Methods: A descriptive, longitudinal observational study; the setting was mainland Portugal ( excluding Azores and Madeira). Each medicine has a respective defined daily dose (DDD). The sum of the DDD, provides the annual consumption in terms of the DDD for each district each year. When calculating the annual average for the resident district population and the number of days in a year, the denominator is expressed as 1000 inhabitants per day (TID).

Main Outcome Measure: The DDD/TID for mainland Portugal (for all districts) between 2005 and 2017 for antidiabetic medicines. Information was obtained from the official database of prescription medicine invoices with reimbursement in mainland Portugal.

Results: In mainland Portugal, the antidiabetic medicine consumption was 49.3 DDD/TID in 2005 and 88.2 DDD/TID in 2017. The consumption of insulins and their analogs increased from 10.8% to 17.4% compared to the total consumption of antidiabetic medicines. In 2017, the level of biguanide consumption was 23.1 DDD/TID, that of sulphonylurea consumption was 15.8 DDD/TID, that of DPP-4 inhibitor consumption was 6.8 DDD/TID, and that of SGLT2 inhibitor consumption was 3.0 DDD/TID. The oral consumption of fixed-dose combinations reached 21.4 DDD/TID. After employing a geographical division between north and south and between coastal and inland regions, the consumption of several different drugs showed statistically significant differences.

Conclusions: When comparing 2017 with 2005, the panorama was quite different, with higher levels of consumption of antidiabetic medicines, insulins and their analogs, noninsulin medicines, long-acting and fast-acting insulins and their analogs, metformin, DPP-4 inhibitors and, mainly, metformin combined with a DPP-4 inhibitor. The SGLT2 inhibitors achieved a representative consumption. Different consumption patterns may be related to sociodemographic factors or to clinical practices.
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http://dx.doi.org/10.1186/s12902-021-00686-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905618PMC
February 2021

Follow-up of infants born to mothers with Graves' disease.

Endocrinol Diabetes Nutr 2021 Aug-Sep;68(7):472-480. Epub 2020 Dec 30.

Pediatric Endrocrinology Unit of Pediatric Department, Hospital de Braga, Braga, Portugal.

Introduction: The prevalence of neonatal hyperthyroidism (HN) due to maternal Graves Disease (GD) ranges from 0.1 to 2.7%. It may occur in pregnant women with the following: active DG, after treatment with radioactive iodine, anti-thyroid or thyroidectomy or with a previous child with hyperthyroidism. The aim of our observational study was to evaluate the follow-up of infants born to mothers with GD at a Tertiary Hospital prior to the implementation of a follow-up protocol.

Methods: This was a retrospective observational study using data from the medical records of mothers with a diagnosis of GD and their newborns from January 2013 until May 2018. Newborns were divided into two groups: high and low risk for NH according to maternal TRAb, third trimester treatment and signs of fetal hyperthyroidism.

Results: We identified 31 newborns, 58% female; 87% high risk. In none of the newborns was umbilical cord blood collected. In the high risk group, 22% had thyroid function evaluation at day-1, one patient presented with hyperthyroidism and 82% were asymptomatic. Considering the cases with an insufficient blood sample for analysis, 9 consultations would have been spared. We found a significant delay in obtaining the high-risk group results which would have spared 10 appointments. A positive correlation was found between age at outpatient clinic discharge and the number of appointments and the maternal TRAb titer.

Conclusion: The correct surveillance of pregnancy and newborns with identification of those at high risk is essential to avoid unnecessary consultations and blood analyses that increase parental anxiety and hospital costs. Consequently, a multidisciplinary protocol was created to standardize the approach.
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http://dx.doi.org/10.1016/j.endinu.2020.09.005DOI Listing
December 2020

A retrospective cohort study of the effectiveness and adverse events of intralesional pentavalent antimonials in the treatment of cutaneous leishmaniasis.

Int J Parasitol Drugs Drug Resist 2020 12 19;14:257-263. Epub 2020 Nov 19.

University Hospital of Brasília, Dermatology Department, SGAN 605, Asa Norte, Brasília-DF, 70840-901, Brazil; Postgraduate in Medical Sciences, Medical College, University of Brasília, UnB - Darcy Ribeiro University Campus, Asa Norte, Brasília-DF, 70.910-900, Brazil; Dermatomycology Laboratory, Medical College, University of Brasília, UnB - Darcy Ribeiro University Campus, Asa Norte, Brasília-DF, 70.910-900, Brazil; Postgraduate in Health Sciences, Health Sciences College, University of Brasília, UnB - Darcy Ribeiro University Campus, Asa Norte, Brasília-DF, 70.910-900, Brazil.

Introduction: The standard therapy for American cutaneous leishmaniasis (ACL) is intravenous meglumine antimoniate (IV-MA). However, treatment interruptions due to adverse events (AEs) and non-adherence are frequent. Consequently, intralesional MA (IL-MA) was proposed.

Objective: This study examined the effectiveness of and AEs associated with IL-MA.

Methods: We performed a retrospective cohort study of 240 patients with ACL. We excluded patients with mucous lesions and disseminated leishmaniasis and those who received treatment in the previous 6 months. We considered protocol treatments as the main risk factors. IL-MA was performed using a subcutaneous injection of MA in a volume sufficient to elevate the lesion base (approximately 1 mL/cm of lesion area) once weekly for 1-8 weeks. IV-MA was performed via intravenous injections of MA at a dosage of 10-20 mg Sb/kg/day for 20 days. The primary outcome was defined as a lesion cure 3 months after treatment, and AEs were secondary outcomes.

Results: Seventy-three patients were included. The IL-MA group consisted of 21 patients, and the IV-MA group consisted of 52 patients. The IL-MA group was older, had more comorbidities and more previous unsuccessful treatment of ACL. The antimonial dose was significantly lower in this group. The cure rate for IL-MA was 66.7%, which was lower than that in the IV-MA group (relative risk (RR) = 0.68, 95% CI: 0.50-0.92, p < 0.001), while the rate of AEs was similar. Female sex (RR = 1.16, 95% CI: 1.02-1.33), lesion diameter ≤1 cm (RR = 1.25, 95% CI: 1.00-1.56) and treatment with IV-MA (RR = 1.43, 95% CI: 1.06-1.93) were independently associated with achieving a cure. Comorbidities (RR = 1.7, 95% CI: 1.06-2.98) were independently associated with AEs.

Conclusions: Patients of IL-MA group were older, had more comorbidities and more previous unsuccessful treatment of ACL. Nevertheless, IL-MA had a cure rate of 66.7%, and it was useful in this context. A prospective randomized trial is recommended.
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http://dx.doi.org/10.1016/j.ijpddr.2020.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723996PMC
December 2020

SPARC-p53: The double agents of cancer.

Adv Cancer Res 2020 21;148:171-199. Epub 2020 Jul 21.

Champalimaud Centre for the Unknown, Lisbon, Portugal. Electronic address:

Cancer is a complex disease with high incidence and mortality rates. The important role played by the tumor microenvironment in regulating oncogenesis, tumor growth, and metastasis is by now well accepted in the scientific community. SPARC is known to participate in tumor-stromal interactions and impact cancer growth in ambiguous ways, which either enhance or suppress cancer aggressiveness, in a context-dependent manner. p53 transcription factor, a well-established tumor suppressor, has been reported to promote tumor growth in certain situations, such as hypoxia, thus displaying a duality in its action. Although both proteins are being tested in clinical trials, the synergistic relation between them is yet to be explored in clinical practice. In this review, we address the controversial roles of SPARC and p53 as double agents in cancer, briefly summarizing the interaction found between these two molecules and its importance in cancer.
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http://dx.doi.org/10.1016/bs.acr.2020.05.004DOI Listing
September 2020

A statistical model to identify determinants of glycemic control in patients with type 2 diabetes with different pharmacotherapeutic profiles.

PLoS One 2020 6;15(7):e0235376. Epub 2020 Jul 6.

Department of Public Health, Nova Medical School, New University of Lisbon, Lisboa, Portugal.

Aim: To develop a statistical model to identify determinants of glycemic control.

Materials And Methods: A database was extracted from patients' records with at least one glycated hemoglobin (HbA1c) analysis and with antidiabetic therapy established and stabilized. A logistic regression model was designed to identify the statistical significance of factors associated with glycemic control.

Results: Higher probability of success (HbA1c ≤8% [64 mmol/mol]) was found for those who were older in age, those who were men, and those with higher education levels. Increased values for the following variables were associated with the poorest glycemic control: number of years of T2DM since diagnosis, number of antidiabetic medicines, body mass index, low-density lipoprotein cholesterol, triglycerides, systolic blood pressure and number of diabetes consultations in the last twelve months. The following pharmacotherapeutic treatments were associated with glycemic control (in decreasing order of the results): oral antidiabetic drugs; oral antidiabetic drugs and insulin; insulin. Patients using metformin and a dipeptidyl peptidase-4 inhibitors have a higher probability of success than do patients using metformin and a sulfonylurea, and patients using insulin and metformin have a higher probability of success than do patients using insulin alone.

Conclusions: Sociodemographic, clinical and therapeutic parameters can strongly affect glycemic control. Studies based on real-life patient data provide important information on the development of more effective glycemic control.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235376PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338077PMC
September 2020

Multiple Bacteria Identification in the Point-of-Care: an Old Method Serving a New Approach.

Sensors (Basel) 2020 Jun 12;20(12). Epub 2020 Jun 12.

INESC-MN- Microsystems and Nanotechnologies, 1000-029 Lisboa, Portugal.

The accurate diagnosis of bacterial infections is of critical importance for effective treatment decisions. Due to the multietiologic nature of most infectious diseases, multiplex assays are essential for diagnostics. However, multiplexability in nucleic acid amplification-based methods commonly resorts to multiple primers and/or multiple reaction chambers, which increases analysis cost and complexity. Herein, a polymerase chain reaction (PCR) offer method based on a universal pair of primers and an array of specific oligonucleotide probes was developed through the analysis of the bacterial 16S ribosomal RNA gene. The detection system consisted of DNA hybridization over an array of magnetoresistive sensors in a microfabricated biochip coupled to an electronic reader. Immobilized probes interrogated single-stranded biotinylated amplicons and were obtained using asymmetric PCR. Moreover, they were magnetically labelled with streptavidin-coated superparamagnetic nanoparticles. The benchmarking of the system was demonstrated to detect five major bovine mastitis-causing pathogens: , sp., , and . All selected probes proved to specifically detect their respective amplicon without significant cross reactivity. A calibration curve was performed for which demonstrates demonstrating a limit of detection below 30 fg/µL. Thus, a sensitive and specific multiplex detection assay was established, demonstrating its potential as a bioanalytical device for point-of-care applications.
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http://dx.doi.org/10.3390/s20123351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349726PMC
June 2020

A comprehensive systematic review of leishmaniasis in patients undergoing drug-induced immunosuppression for the treatment of dermatological, rheumatological and gastroenterological diseases.

Rev Inst Med Trop Sao Paulo 2020 11;62:e28. Epub 2020 May 11.

Universidade de Brasília, Faculdade de Medicina, Programa de Pós-Graduação em Ciências Médicas, Brasília, Brazil

Immunosuppression is an important risk factor for leishmaniasis. We assessed the clinical profile, geographic distribution and prevalence of leishmaniasis in patients undergoing immunosuppressive therapy for dermatological, rheumatological or gastroenterological autoimmune diseases. We identified relevant studies in PubMed, EMBASE, Scopus, Web of Science and LILACS on July 3rd, 2018. We included articles that reported at least one case of leishmaniasis in patients undergoing immunosuppressive treatment for dermatological, rheumatological or gastroenterological diseases. Our protocol was registered in PROSPERO (CRD42018103050). We assessed the quality of the included studies with the Joanna Briggs Institute Critical Appraisal Tool. After the removal of duplicates, 5,431 articles were collected and screened. We included 138 articles; the prevalence of leishmaniasis in six methodologically similar studies varied from three to 1,282 cases per 100,000 patients using anti-TNFα drugs, but the results were significantly heterogeneous . Leishmaniasis in patients treated with immunosuppressive drugs is a health problem mostly reported in European countries bordering the Mediterranean Sea; sporadic activities, such as travelling, seem not to be associated with a significant risk of leishmaniasis, although effective control measures must always be observed.
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http://dx.doi.org/10.1590/s1678-9946202062028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232954PMC
May 2020

Flucloxacillin-Induced Hepatotoxicity - Association with HLA-B*5701.

Rev Assoc Med Bras (1992) 2020 27;66(1):12-17. Epub 2020 Feb 27.

. Hospital Assistant Physician Graduated on Internal Medicine, Tondela-Viseu Hospital Center, Viseu, Portugal.

Drug-induced liver injury (DILI) to flucloxacillin is rare and is classified as idiosyncratic, as it is dependent on individual susceptibility, unpredictable, and dose-independent. The authors present the case of a 74 - year - old man with a history of monoclonal gammopathy under investigation and alcoholic habits of 24 g/day, with asthenia, anorexia, nausea, abdominal discomfort, and fever with three days of evolution. He was treated with two courses of antibiotic therapy with flucloxacillin to erysipelas previously (3 months and 2 weeks before admission). Lab tests showed serum AST levels of 349 U/L, ALT 646 U/L, alkaline phosphatase 302 U/L, GGT 652 U/L, total bilirubin 3.3 mg/dL and direct bilirubin 2.72 mg/dL. Infectious, autoimmune, and metabolic causes were ruled out. Magnetic resonance cholangiopancreatography showed normal results. Liver biopsy showed mild multifocal (predominantly microvesicular) steatosis; marked changes in the centrilobular areas (sinusoidal dilatation, marked congestion, hemorrhage, and multifocal hepatocyte collapse); expansion of the portal areas with the formation of bridges; proliferated bile ducts and inflammatory infiltrate of variable density, predominantly mononuclear type. The HLA-B*5701 screening test was positive. Hepatic biochemical tests remain abnormal with a significative increase in total bilirubin, which reached levels of 24.1 mg/dL, with the development of jaundice, pruritus, and choluria. DILI was assumed, and the patient was treated with ursodeoxycholic acid. There was favorable evolution, without evidence of blood coagulation dysfunction or encephalopathy. The analytic normalization was, however, slow, with evolution to chronicity. The authors present this case to remind the possibility of moderate/severe drug-induced liver injury to flucloxacillin, an antibiotic commonly used in clinical practice and association with the HLA-B * 5701 allele reported in the literature.
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http://dx.doi.org/10.1590/1806-9282.66.1.12DOI Listing
April 2020

Autoimmune Polyglandular Syndrome type 2.

Rev Assoc Med Bras (1992) 2019 Dec;65(12):1434-1437

. Hospital Assistant with a Degree on Internal Medicine, Tondela-Viseu Hospital Center, Portugal.

Autoimmune polyglandular syndrome type 2 (APS 2) is defined by the presence of Addison's disease (AD) associated with autoimmune thyroid disease and/or Type 1 diabetes mellitus (T1DM). It is a rare disease, affecting about 1.4-2 cases/100,000 inhabitants. Its less frequent clinical presentation is the combination of AD, Graves' disease, and T1DM. We present the case of a 42-year-old woman with a history of total thyroidectomy due to Graves' disease, type 2 diabetes mellitus, and hypertension, who sought the ED due to asthenia, dizziness, nausea, and vomiting. She reported having stopped antihypertensive therapy due to hypotension and presented a glycemic record with frequent hypoglycemia. On physical examination, she had cutaneous hyperpigmentation. She had no leukocytosis, anemia, hypoglycemia, hyponatremia or hyperkalemia, and a negative PCR. Serum cortisol <0.5 ug/dl (4,3-22,4), urine free cortisol 9 ug/24h (28-214), ACTH 1384 pg/mL (4,7-48,8), aldosterone and renin in erect position of 0 pg/ml (41-323) and 430.7 uUI/ml (4.4-46.1) respectively. Quantiferon TB was negative; computerized axial tomography of the adrenals showed no infiltrations, hemorrhage, or masses. The 21-hydroxylase antibody assay was positive. B12 vitamin was normal, anti-GAD antibodies were positive, anti-insulin, anti-IA2, and anti-transglutaminase antibodies were all negative. The patient started insulin therapy and treatment for AD with prednisolone and fludrocortisone with good clinical response. This case aims to alert to the need for high clinical suspicion in the diagnosis of AD. Since this is a rare autoimmune disease, it is important to screen for other autoimmune diseases in order to exclude APS.
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http://dx.doi.org/10.1590/1806-9282.65.12.1434DOI Listing
December 2019

Maturity-Onset Diabetes of the Young (MODY) in Portugal: Novel , and Mutations.

J Clin Med 2020 Jan 20;9(1). Epub 2020 Jan 20.

CICS-UBI, Health Sciences Research Centre, University of Beira Interior, 6200-506 Covilhã, Portugal.

Maturity-onset diabetes of the young (MODY) is a frequently misdiagnosed type of diabetes, which is characterized by early onset, autosomal dominant inheritance, and absence of insulin dependence. The most frequent subtypes are due to mutations of the (MODY 2), (MODY 3), and (MODY 1) genes. We undertook the first multicenter genetic study of MODY in the Portuguese population. The , and genes were sequenced in 46 unrelated patients that had at least two of the three classical clinical criteria for MODY (age at diagnosis, family history, and clinical presentation). The functional consequences of the mutations were predicted by bioinformatics analysis. Mutations were identified in 23 (50%) families. Twelve families had mutations in the gene, eight in the gene, and three in the gene. These included seven novel mutations ( c.494T>C, c.563C>G, c.1623G>A, c.1729C>G, c.68delG, c.422G>C, c.602A>C). Mutation-positive patients were younger at the time of diagnosis when compared to mutation-negative patients (14.3 vs. 23.0 years, = 0.011). This study further expands the spectrum of known mutations associated with MODY, and may contribute to a better understanding of this type of diabetes and a more personalized clinical management of affected individuals.
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http://dx.doi.org/10.3390/jcm9010288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019520PMC
January 2020

Panoramic dermoscopy.

J Am Acad Dermatol 2019 Oct 15. Epub 2019 Oct 15.

Instituto de Dermatologia Prof. Rubem David Azulay (IDPRDA), Rio de Janeiro-RJ.

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http://dx.doi.org/10.1016/j.jaad.2019.09.082DOI Listing
October 2019

Panoramic trichoscopy.

J Am Acad Dermatol 2021 Feb 24;84(2):e85-e86. Epub 2019 Sep 24.

Instituto de Dermatologia Prof Rubem David Azulay, Rio de Janeiro, Brazil.

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http://dx.doi.org/10.1016/j.jaad.2019.09.041DOI Listing
February 2021

Biosensors for On-Farm Diagnosis of Mastitis.

Front Bioeng Biotechnol 2019 31;7:186. Epub 2019 Jul 31.

INESC Microsistemas e Nanotecnologias Rua Alves Redol, Lisbon, Portugal.

Bovine mastitis is an inflammation of the mammary gland caused by a multitude of pathogens with devastating consequences for the dairy industry. Global annual losses are estimated to be around €30 bn and are caused by significant milk losses, poor milk quality, culling of chronically infected animals, and occasional deaths. Moreover, mastitis management routinely implies the administration of antibiotics to treat and prevent the disease which poses serious risks regarding the emergence of antibiotic resistance. Conventional diagnostic methods based on somatic cell counts (SCC) and plate-culture techniques are accurate in identifying the disease, the respective infectious agents and antibiotic resistant phenotypes. However, pressure exists to develop less lengthy approaches, capable of providing on-site information concerning the infection, and in this way, guide, and hasten the most adequate treatment. Biosensors are analytical tools that convert the presence of biological compounds into an electric signal. Benefitting from high signal-to-noise ratios and fast response times, when properly tuned, they can detect the presence of specific cells and cell markers with high sensitivity. In combination with microfluidics, they provide the means for development of automated and portable diagnostic devices. Still, while biosensors are growing at a fast pace in human diagnostics, applications for the veterinary market, and specifically, for the diagnosis of mastitis remain limited. This review highlights current approaches for mastitis diagnosis and describes the latest outcomes in biosensors and lab-on-chip devices with the potential to become real alternatives to standard practices. Focus is given to those technologies that, in a near future, will enable for an on-farm diagnosis of mastitis.
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http://dx.doi.org/10.3389/fbioe.2019.00186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6684749PMC
July 2019

A randomized, open-label clinical trial comparing the long-term effects of miltefosine and meglumine antimoniate for mucosal leishmaniasis.

Rev Soc Bras Med Trop 2019 Mar 28;52:e20180292. Epub 2019 Mar 28.

Laboratório de Dermatomicologia, Faculdade de Medicina, Universidade de Brasília, Brasília, DF, Brasil.

Introduction: The treatment of mucosal leishmaniasis (ML) is difficult due to the toxicity and route of administration of standard drugs. Miltefosine is an oral agent used for leishmaniasis treatment; however, no data exist regarding its use for ML in Brazil. In this study, we aimed to evaluate the efficacy of miltefosine for ML treatment compared to that of pentavalent antimonial in a pilot study.

Methods: We performed a randomized clinical trial with two parallel groups. The tested intervention consisted of miltefosine 1.3-2 mg/kg/day (two capsules) for 28 days or intravenous 20 mg SbV/kg/day of meglumine antimoniate (N-MA) for 30 days. The final endpoint was defined as complete healing of the lesion four years after treatment. We also analyzed an early endpoint at 90 days after treatment.

Results: Forty patients were included in this study: each experimental group comprised 20 patients. Applying a multivariate model in an intention-to-treat analysis, we observed that patients treated with miltefosine had a cure probability 2.08 times greater (95% confidence interval [CI] = 1.03-4.18) than those treated with N-MA at 90 days after treatment. At the final endpoint, we observed no differences in cure probability between miltefosine and N-MA (relative risk = 0.66; 95% CI = 0.33-1.32). With respect to adverse reactions, significant differences between groups were related to gastrointestinal effects, which were more frequent in the miltefosine group.

Conclusions: Miltefosine may be an interesting alternative for treating ML because of its oral administration and cure rate after long-term follow-up.
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http://dx.doi.org/10.1590/0037-8682-0292-2018DOI Listing
March 2019

Go with the flow: advances and trends in magnetic flow cytometry.

Anal Bioanal Chem 2019 Mar 19;411(9):1839-1862. Epub 2019 Feb 19.

INESC-Microsistemas e Nanotecnologias (INESC-MN) and IN, Rua Alves Redol 9, 1000-029, Lisbon, Portugal.

The growing need for biological information at the single cell level has driven the development of improved cytometry technologies. Flow cytometry is a particularly powerful method that has evolved over the past few decades. Flow cytometers have become essential instruments in biomedical research and routine clinical tests for disease diagnosis, prognosis, and treatment monitoring. However, the increasing number of cellular parameters unveiled by genomic, proteomic, and metabolomic data platforms demands an augmented multiplexability. Also, the need for identification and quantification of relevant biomarkers at low levels requires outstanding analytical sensitivity and reliability. In addition, growing awareness of the advantages associated with miniaturization of analytical devices is pushing forward the progress in integrated and compact, microfluidic-based devices at the point-of-care. In this context, novel types of flow cytometers are emerging during the search to tackle these challenges. Notwithstanding the relevance of other promising alternatives to standard optical flow cytometry (e.g., mass cytometry, various optical and electrical microcytometers), this report focuses on a recent microcytometric technology based on magnetic sensors and magnetic particles integrated into microfluidic structures for dynamic bioanalysis of fluid samples-magnetic flow cytometry. Its concept, main developments, targeted applications, as well as the challenges and trends behind this technology are presented and discussed. Graphical abstract ᅟ "Kindly advise whether there is online abstract figure for this paper. If so, kindly resupply.The graphical abstract is correctly supplied.
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http://dx.doi.org/10.1007/s00216-019-01593-9DOI Listing
March 2019

High frequency of CHD7 mutations in congenital hypogonadotropic hypogonadism.

Sci Rep 2019 02 7;9(1):1597. Epub 2019 Feb 7.

CICS-UBI, Health Sciences Research Centre, University of Beira Interior, 6200-506, Covilhã, Portugal.

Congenital hypogonadotropic hypogonadism (CHH) is characterized by lack of normal pubertal development due to deficient gonadotropin-releasing hormone (GnRH) secretion or action, and is caused by genetic defects in several genes. Mutations in the CHD7 gene cause CHARGE syndrome (Coloboma of the eye, Heart defects, Atresia of the choanae, Retardation of growth and development, Genital hypoplasia and Ear abnormalities), but have also been found in patients with isolated CHH. The aim of this study was to identify CHD7 mutations in patients with CHH. Fifty Portuguese patients with CHH were screened for mutations in the CHD7 gene by DNA sequencing. Eight (16%) patients had CHD7 rare sequence variants that consisted of six missense (p.Gly388Glu, p.His903Pro, p.Thr1082Ile, p.Val1452Leu, p.Asp1854Gly, and p.Arg2065His) and two synonymous (p.Ser559Ser, and p.Ala2785Ala) mutations. Five of these mutations have never been reported before. Three CHD7 mutations occurred in patients that had mutations in additional CHH-genes. This study uncovered novel genetic variants that expand the known spectrum of mutations associated with CHH. The frequency of CHD7 mutations in this cohort was higher than that of other major CHH-genes and confirms the importance of including CHD7 in the genetic testing of CHH, even in the absence of additional CHARGE features.
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http://dx.doi.org/10.1038/s41598-018-38178-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367338PMC
February 2019

Deep venous thrombosis of lower limbs in adolescents: a study in a tertiary hospital.

Int J Adolesc Med Health 2019 Feb 1;33(2). Epub 2019 Feb 1.

Unit of Adolescent Medicine, Department of Pediatrics, Hospital of Braga, Braga, Portugal.

Background: Venous thromboembolism (VTE) - which includes deep venous thrombosis (DVT) and pulmonary embolism (PE) - has been increasingly recognized in the pediatric population. The estimated incidence is 0.07-0.14 cases per 10,000 children. Most cases are associated with two or more risk factors. Medium and long-term complications include recurrence and post-thrombotic syndrome (PTS).

Objective: To characterize the adolescent population with the diagnosis of DVT of lower limbs in a tertiary hospital, regarding its clinical presentation, associated risk factors, treatment and outcome.

Methods: Retrospective analysis of adolescents with the diagnosis of DVT of lower limbs in our hospital for a period of 7 years.

Results: Eight patients were identified; seven were females; median age was 15 years. The main symptoms were local pain and edema. Left lower limb was affected in six patients. PE occurred in two cases. Positive family history of venous thromboembolism was found in five patients. Seven patients had at least two identifiable risk factors. Combined oral contraceptive pill use was the most common (seven patients). Factor V Leiden mutation was found in three patients and protein C deficiency in one. Iliac vein compression syndrome was diagnosed in one patient. The median time for discharge was 8 days. Election treatment was enoxaparin followed by warfarin, for a median period of 10.9 months. Three patients developed PTS.

Conclusions: Although uncommon, VTE is an emerging reality in adolescents, particularly in females using oral contraceptive pills. Appropriated prevention strategies and treatment are required as most orientations are extrapolated from adults.
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http://dx.doi.org/10.1515/ijamh-2018-0137DOI Listing
February 2019

Iatrogenic water intoxication in a female adolescent with hypopituitarism.

BMJ Case Rep 2018 Mar 9;2018. Epub 2018 Mar 9.

Pediatric Endocrinology Unit, Hospital de Braga, Braga, Portugal.

The authors report a case of a 15-year-old girl with hypopituitarism due to pituitary stalk interruption syndrome diagnosed in the neonatal period. The patient was admitted to the emergency room with impaired consciousness and hypoglycaemia. The day before, she increased her water intake to about 1.5 L to perform a pelvic ultrasound. In the following hours, she developed vomiting and food refusal. Blood analysis revealed hypoglycaemia, hyponatraemia, decreased serum osmolality and normal urinary density. Hyponatraemia and adrenal crisis were managed with a gradual but slow resolution of consciousness and electrolytic balance. This case describes an episode of iatrogenic water intoxication in a patient under desmopressin treatment. Although uncommon, dilutional hyponatraemia is the main complication of desmopressin treatment. We reinforce the importance of patients and caregivers' long-life education for the potential complications of an increase in fluid intake in patients treated with desmopressin.
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http://dx.doi.org/10.1136/bcr-2017-223021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5847927PMC
March 2018

American cutaneous leishmaniasis triggered by electrocoagulation.

Rev Soc Bras Med Trop 2018 Jan-Feb;51(1):108-110

Pós-graduação de Ciências da Saúde da Faculdade de Ciências da Saúde da Universidade de Brasília, Brasília, DF, Brasil .

Cutaneous leishmaniasis is usually transmitted by infected phlebotomine sand fly bites that initiate local cutaneous lesions. Few reports in the literature describe other modes of transmission. We report a case of a previously healthy 59-year-old woman who underwent electrocoagulation to remove seborrheic keratosis confirmed by dermatoscopy. Three months later, a skin fragment tested positive for Leishmania culture; the parasite was identified as L. (V.) braziliensis. Trauma may generate inflammatory cascades that favor Leishmania growth and lesion formation in previously infected patients. American cutaneous leishmaniasis is a dynamic disease with unclear pathophysiology because of continually changing environments, demographics, and human behaviors.
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http://dx.doi.org/10.1590/0037-8682-0306-2017DOI Listing
April 2018

Unilateral erythaema nodosum: atypical presentation in paediatrics.

BMJ Case Rep 2017 Nov 23;2017. Epub 2017 Nov 23.

Department of Pediatrics, Hospital de Braga, Braga, Portugal.

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http://dx.doi.org/10.1136/bcr-2017-222441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5720296PMC
November 2017

Lab-on-Chip Devices: Gaining Ground Losing Size.

ACS Nano 2017 11 27;11(11):10659-10664. Epub 2017 Oct 27.

INESC - Microsistemas e Nanotecnologias, Lisboa , Rua Alves Redol 9, 1000-049 Lisbon, Portugal.

Portable analytical devices are notably gaining relevance in the panorama of urgent testing. Such devices have the potential to play an important role as easy-to-handle tools in critical situations. Epidemic infectious disease agents (e.g., Ebola virus, Coronavirus, Zika virus) could be controlled more easily by testing travelers on-site at the country borders to prevent outbreaks from spreading. The increasing incidence of hospital-acquired infections caused by antibiotic resistant pathogens could be minimized by point-of-care microbial analysis as well as rapid screening tests of bacteria resistance. The threat of bioterrorism using novel unknown bioweapons has never been so high, thus, in-the-field early identification of the biological agent is crucial for triggering a coordinated response. Food allergies are a growing public health concern-allergic reactions can result in anaphylactic shock, which can prove fatal in minutes-thus, the ability to test foods for common allergens, rapidly and locally, before ingestion, would improve food safety for those with allergies. Lab-on-chip devices are becoming widely available for diverse applications and are becoming increasingly affordable. However, to shrink in price and size simultaneously, some trade-offs must be made. In this Perspective, we present considerations about product specifications, design concepts, and application scenarios.
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http://dx.doi.org/10.1021/acsnano.7b06703DOI Listing
November 2017

A Pediatric Case of Cowden Syndrome with Graves' Disease.

Case Rep Pediatr 2017 31;2017:2750523. Epub 2017 Jan 31.

Anatomic Pathology Department, Hospital de Braga, Sete Fontes, São Victor, 4710-243 Braga, Portugal.

Cowden syndrome (CS) is a rare dominantly inherited multisystem disorder, characterized by an extraordinary malignant potential. In 80% of cases, the human tumor suppressor gene phosphatase and tensin homolog (PTEN) is mutated. We present a case of a 17-year-old boy with genetically confirmed CS and Graves' disease (GD). At the age of 15, he presented with intention tremor, palpitations, and marked anxiety. On examination, he had macrocephaly, coarse facies, slight prognathism, facial trichilemmomas, abdominal keratoses, leg hemangioma, and a diffusely enlarged thyroid gland. He started antithyroid drug (ATD) therapy with methimazole and, after a 2-year treatment period without achieving a remission status, a total thyroidectomy was performed. Diagnosis and management of CS should be multidisciplinary. Thyroid disease is frequent, but its management has yet to be fully defined. The authors present a case report of a pediatric patient with CS and GD and discuss treatment options.
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http://dx.doi.org/10.1155/2017/2750523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5306985PMC
January 2017

Severe systemic type 1 pseudohypoaldosteronism: 5 years of evolution.

Endocrinol Nutr 2016 Nov 18;63(9):502-505. Epub 2016 Sep 18.

Department of Pediatrics, Hospital de Braga, Sete Fontes, São Victor, 4710-243 Braga, Portugal.

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http://dx.doi.org/10.1016/j.endonu.2016.08.002DOI Listing
November 2016

Assessment of nanofiltration and reverse osmosis potentialities to recover metals, sulfuric acid, and recycled water from acid gold mining effluent.

Water Sci Technol 2016;74(2):367-74

Department of Sanitary and Environmental Engineering, Federal University of Minas Gerais, PO Box 1294, Belo Horizonte, MG 30.270-901, Brazil E-mail:

This work assessed the potential of nanofiltration (NF) and reverse osmosis (RO) to treat acid streams contaminated with metals, such as effluent from the pressure oxidation process (POX) used in refractory gold ore processing. NF and RO were evaluated in terms of rejections of sulfuric acid and metals. Regarding NF, high sulfuric acid permeation (∼100%), was observed, while metals were retained with high efficiencies (∼90%), whereas RO led to high acid rejections (<88%) when conducted in pH values higher than 1. Thus, sequential use of NF and RO was proved to be a promising treatment for sulfuric acid solutions contaminated by metals, such as POX effluent. In this context, a purified acid stream could be recovered in NF permeate, which could be further concentrated in RO. Recovered acid stream could be reused in the gold ore processing or commercialized. A metal-enriched stream could be also recovered in NF retentate and transferred to a subsequent metal recovery stage. In addition, considering the high acid rejection obtained through the proposed system, RO permeate could be used as recycling water.
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http://dx.doi.org/10.2166/wst.2016.206DOI Listing
January 2017

The tadpoles of two species of the Bokermannohyla circumdata group (Hylidae, Cophomantini).

Zootaxa 2015 Nov 25;4048(2):151-73. Epub 2015 Nov 25.

División Herpetología, Museo Argentino de Ciencias Naturales-CONICET, Angel Gallardo 470, C1405DJR, Buenos Aires, Argentina; and Departamento de Biodiversidad y Biología Experimental, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires; Email: unknown.

We describe the external morphology and oral cavity of the tadpoles of Bokermannohyla caramaschii and B. diamantina respectively from the states of Espírito Santo and Bahia, Brazil. Larvae of both species are distinguished from each other by external characters such as body shape, labial tooth-row formula, number of marginal papillae, coloration and internal oral anatomy features. Some of the character states of the tadpoles of B. caramaschii and B. diamantina that are shared with all other described tadpoles of the Bokermannohyla circumdata group, such as the absence/reduction of small flaps with accessory labial teeth laterally in the oral disc, and the absence/reduction of submarginal papillae, may represent morphological synapomorphies of this species group, or at least of some internal clade. The general pattern of brownish coloration with longitudinal stripes on the caudal muscle is also common to most species of the group. We did not find character states of the oral cavity that are exclusively shared by species of the B. circumdata group, or by other groups of Bokermannohyla.
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http://dx.doi.org/10.11646/zootaxa.4048.2.1DOI Listing
November 2015

Detailed characterization of incretin cell distribution along the human small intestine.

Surg Obes Relat Dis 2015 Nov-Dec;11(6):1323-31. Epub 2015 Feb 17.

Department of Anatomy, Unit for Multidisciplinary Research in Biomedicine (UMIB), ICBAS, University of Porto, Portugal. Electronic address:

Background: Incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1), are physiologic stimulants of insulin release that have been implicated in diabetes remission after bariatric surgery. The detailed distribution of incretin cells along the human small gut, so far unknown, is of utmost importance for the understanding of the metabolic changes observed after bariatric surgery because diabetes remission rate varies according to the type of anatomic rearrangement.

Objective: To characterize the distribution of incretin producing cells along the human jejunum-ileum.

Setting: Academic public institution.

Methods: Small intestines (n = 30) from autopsies were sampled every 20 cm along their entire length and tissue microarrays were constructed. The percentage of immunohistochemistry-stained cell areas for GLP-1, GIP, and chromogranin A at each segment length was quantified using a computer-aided analysis tool.

Results: The percentage of stained area for GLP-1 immunoreactive cells was found to be significantly higher from 200 cm from Treitz ligament onward compared with the first 80 cm of the small intestine, whereas GIP immunoreactive cells were predominant expressed in the first 80 cm. In contrast, chromogranin A expression was constant along the entire jejunum-ileum.

Conclusion: The uneven distribution of GLP-1-expressing cells, with a higher density from 200 cm of the jejunum-ileum, could contribute to explain the improvement of glycemic profile of diabetic patients observed after anatomic rearrangement of the intestinal tract, in particular when subjected to gastric bypass with longer biliopancreatic limbs.
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http://dx.doi.org/10.1016/j.soard.2015.02.011DOI Listing
October 2016

[Kikuchi-Fujimoto disease prior to childhood-systemic lupus erythematosus diagnosis].

Rev Bras Reumatol 2014 Sep-Oct;54(5):400-3. Epub 2014 Jul 6.

Unidade de Reumatologia Pediátrica, Faculdade de Medicina, Universidade São Paulo, São Paulo, SP, Brasil; Divisão de Reumatologia, Faculdade de Medicina, Universidade São Paulo, São Paulo, SP, Brasil. Electronic address:

Kikuchi-Fujimoto disease (KFD) is a self-limiting histiocytic necrotizing lymphadenitis of unknown origin. Of note, KFD was infrequently reported in adult systemic lupus erythematosus (SLE), with rare occurrence in childhood-SLE (C-SLE) patients. To our knowledge, the prevalence of KFD in the paediatric lupus population was not studied. Therefore, in a period of 29 consecutive years, 5,682 patients were followed at our institution and 289 (5%) met the American College of Rheumatology classification criteria for SLE, one had isolated KFD (0.03) and only one had KFD associated to C-SLE diagnoses, which case was reported herein. A 12 year-old female patient had high fever, fatigue and cervical and axillary lymphadenopathy. The antinuclear antibodies (ANA) were negative, with positive IgM and IgG herpes simplex virus type 1 and type 2 serologies. Fluorine-18-fluoro-deoxy-glucose positron emission tomography/computed tomography (PET/CT) imaging demonstrated diffuse lymphadenopathy. The axillary lymph node biopsy showed necrotizing lymphadenitis with histiocytes, without lymphoproliferative disease, compatible with KFD. After 30 days, she presented spontaneous regression and no therapy was required. Nine months later, she developed malar rash, photosensitivity, oral ulcers, lymphopenia and ANA 1:320 (homogeneous nuclear pattern). At that moment the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score was 10 and she was treated with prednisone (1.0mg/kg/day) and hidroxychloroquine showing progressive improvement of hers signs and symptoms. In conclusion, KFD is a benign and rare disease in our paediatric lupus population. We also would like to reinforce the relevance of autoimmune diseases diagnosis during the follow-up of patients with KFD.
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http://dx.doi.org/10.1016/j.rbr.2013.03.003DOI Listing
December 2016