Publications by authors named "Maria João Oliveira"

51 Publications

High-intensity infrasound effects on glucose metabolism in rats.

Sci Rep 2021 Aug 26;11(1):17273. Epub 2021 Aug 26.

Center for Interdisciplinary Research Egas Moniz (CiiEM), Quinta da Granja, Monte da Caparica, 2829-511, Caparica, Portugal.

Recent focus has been given on the effects of high-intensity infrasound (HII) exposure, and whether it induces changes in pancreatic morphology and glucose metabolism is still unknown. As such, we have studied the impact of HII exposure on glucose tolerance, insulin sensitivity, pancreatic islet morphology, muscle GLUT4 and plasma insulin and corticosterone levels. Normal and glucose intolerant wild-type Wistar rats were randomly divided in two groups: one group not exposed to HII and the other continuously exposed to HII. Animals were sacrificed at three timepoints of exposure (1, 6 or 12 weeks). An intraperitoneal glucose tolerance test was performed, blood samples were collected and the pancreas and the quadriceps femoris muscle were excised. Circulating insulin and corticosterone levels were determined and pancreatic and muscular tissue were routinely processed for histochemistry and immunohistochemistry with an anti-GLUT4 antibody. Animals exposed to HII had higher corticosterone levels than animals not exposed. No differences were found on insulin concerning HII exposure or glucose intolerance. Glucose intolerant animals had pancreatic islet fibrosis and no differences were found in GLUT4 ratio concerning HII exposure. In conclusion, we found that continuous exposure to HII increases stress hormone levels without inducing glucose intolerance in rats.
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http://dx.doi.org/10.1038/s41598-021-96796-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390459PMC
August 2021

20 years of Portuguese drug policy - developments, challenges and the quest for human rights.

Subst Abuse Treat Prev Policy 2021 Jul 17;16(1):59. Epub 2021 Jul 17.

University Institute of Maia (ISMAI), Research Unit in Criminology and Behavioral Sciences (UICCC/ISMAI) and Research Centre for Justice and Governance, University of Minho (JusGov/UM), ISMAI - Avenida Carlos de Oliveira Campos, 4475-690, Maia, Portugal.

Portugal decriminalized the public and private use, acquisition, and possession of all drugs in 2000; adopting an approach focused on public health rather than public-order priorities. Arguing that the Portuguese Drug Policy Model has not proven influential enough to emancipate drug use from the stigma that associates it either with crime or pathology, this article critically discusses the developments and current challenges the Portuguese drug policy confronts, namely the growing diversity of drug use patterns observed in Portugal as well as in Europe. To this end, international and national legal instruments concerning drugs and official local data were analysed. Despite encouraging results, conclusions indicate that these policies are marked by contradictions and ambiguities that have permeated its history since the very beginning, and modest ambitions, particularly regarding the implementation of harm reduction measures. Moreover, the polemical Supreme Court judgment that reestablished, in 2008, drug use as a crime when the quantities at play exceeded those required for an average individual's use for 10 days, might have impacted the landscape of drug use penalization. The last decade saw an increase of punitiveness targeted at drug users, including criminal sentences of jail terms. We finish with some suggestions that could be employed in the practical application of drug policy.
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http://dx.doi.org/10.1186/s13011-021-00394-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285857PMC
July 2021

High UV and Sunlight Photocatalytic Performance of Porous ZnO Nanostructures Synthesized by a Facile and Fast Microwave Hydrothermal Method.

Materials (Basel) 2021 May 4;14(9). Epub 2021 May 4.

i3N/CENIMAT, Department of Materials Science, Faculty of Science and Technology, Universidade NOVA de Lisboa and CEMOP/UNINOVA, Campus de Caparica, 2829-516 Caparica, Portugal.

The degradation of organic pollutants in wastewaters assisted by oxide semiconductor nanostructures has been the focus of many research groups over the last decades, along with the synthesis of these nanomaterials by simple, eco-friendly, fast, and cost-effective processes. In this work, porous zinc oxide (ZnO) nanostructures were successfully synthesized via a microwave hydrothermal process. A layered zinc hydroxide carbonate (LZHC) precursor was obtained after 15 min of synthesis and submitted to different calcination temperatures to convert it into porous ZnO nanostructures. The influence of the calcination temperature (300, 500, and 700 °C) on the morphological, structural, and optical properties of the ZnO nanostructureswas investigated. All ZnO samples were tested as photocatalysts in the degradation of rhodamine B (RhB) under UV irradiation and natural sunlight. All samples showed enhanced photocatalytic activity under both light sources, with RhB being practically degraded within 60 min in both situations. The porous ZnO obtained at 700 °C showed the greatest photocatalytic activity due to its high crystallinity, with a degradation rate of 0.091 and 0.084 min for UV light and sunlight, respectively. These results are a very important step towards the use of oxide semiconductors in the degradation of water pollutants mediated by natural sunlight.
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http://dx.doi.org/10.3390/ma14092385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125317PMC
May 2021

Asymptomatic pituitary apoplexy induced by corticotropin-releasing hormone in a 14 year-old girl with Cushing's disease.

J Pediatr Endocrinol Metab 2021 Jun 5;34(6):799-803. Epub 2021 Apr 5.

Paediatric Endocrinology Unit, Centro Hospitalar e Universitário do Porto, Porto, Portugal.

Objectives: Pituitary apoplexy is a rare complication of Cushing's disease (CD), especially in the paediatric age and even more rarely it can occur following anterior pituitary stimulation tests.

Case Presentation: We report a case of a 14-year-old girl who was admitted to our Hospital for evaluation of a possible Cushing's syndrome (CS). Her symptoms and initial laboratory tests were suggestive of CD. Magnetic resonance imaging (MRI) revealed a microadenoma of the pituitary gland. As part of her evaluation she was submitted to a corticotropin-releasing hormone (CRH) stimulation test. Two and a half months later the patient was re-evaluated and presented with both clinical improvement of CS, biochemical resolution of hypercortisolism and tumour size reduction in the MRI, also evidencing a haemorrhagic component favouring the diagnosis of pituitary apoplexy after CRH stimulation test. The patient denied any episodes of severe headache, nausea, vomiting or visual changes.

Conclusions: To our knowledge, the authors report the first case of a pituitary apoplexy after a CRH stimulation test in the paediatric age.
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http://dx.doi.org/10.1515/jpem-2020-0499DOI Listing
June 2021

Proof of Concept (PoC) 1.0-Implementing a Bioshading System Design Method.

Biomimetics (Basel) 2021 Jan 19;6(1). Epub 2021 Jan 19.

Rensselaer Polytechnic Institute, Troy, NY 12180, USA.

Nature provides a remarkable database of possible adaptation strategies that can be implemented in biomimetic design of shading systems. However, at this moment, successful design methods are conditioned to a limited knowledge and ability to emulate nature's strategies to meet corresponding functional needs. The implementation of biomimetic processes has some major challenges: (1) the search and selection among several databases of appropriate strategies adopted by nature; (2) difficulties in reading, interpreting and translating at different scales; (3) connection problems between concepts and material premises. The selection of nature models is a very common situation among architectural projects. Proof of Concept (PoC) 1.0 was the first experience of application of the Bioshading System Design Method (BSDM). BSDM is a problem-based method that guides its users since the initial architectural challenge definition, improving users' capabilities to interpret and translate nature strategies into architecture design, until its final state of creation, it's physical condition. This experience enabled us to validate and evolve initial decisions, based on users experience and evaluation. At the end, PoC 1.0 revealed to be a fundamental step into the final version of BSDM.
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http://dx.doi.org/10.3390/biomimetics6010008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839005PMC
January 2021

An intricate case of sporadic pseudohypoparathyroidism type 1B with a review of literature.

Arch Endocrinol Metab 2020 Dec 15. Epub 2020 Dec 15.

Departamento de Endocrinologia e Nutrição, Centro Hospitalar de Vila Nova de Gaia/Espinho (CHVNG/E), Vila Nova de Gaia, Portugal.

Pseudohypoparathyroidism comprehends an assorted group of genetically rare disorders that share end-organ resistance to parathyroid hormone. Genetic and epigenetic modifications on guanine nucleotide-binding protein alpha-stimulating gene locus are the most common underlying mechanisms associated with pseudohypoparathyroidism. Biochemical and molecular analysis stratify pseudohypoparathyroidism into types 1A, 1B, 1C, and 2. We describe an unusual case of sporadic pseudohypoparathyroidism type 1B. A 34-year-old Caucasian woman was admitted to the emergency department, with persistent asthenia, limb paresthesias, and tactile hyposensitivity. Her physical examination, previous personal and family histories were unsuspicious, except for mild, intermittent and self-limited complaints of paresthesia during her two pregnancies, but no detailed workup was done. No typical features of Albright hereditary osteodystrophy were observed. The initial laboratory investigation showed elevated parathyroid hormone level (311.2 pg/mL), hypocalcemia (albumin-corrected serum calcium 4.3 mg/dL), hypocalciuria, hyperphosphatemia, hypophosphaturia, and vitamin D deficiency. Combined calcium, vitamin D, and magnesium supplementation was commenced, with symptomatic and analytical improvement. Albeit resolution of vitamin D deficiency, the patient relapsed with mild and intermittent lower limb paresthesias. Pseudohypoparathyroidism was confirmed by molecular identification of the 3-kb STX16 deletion. The treatment was readjusted, and one year later, symptomatic remission was attained. Clinical and biochemical features, and their respective course, along with lack of distinctive features of Albright hereditary osteodystrophy pointed to pseudohypoparathyroidism type 1B. A careful follow-up is needed to avoid complications and recurrence. Once correction of hypocalcemia and hyperphosphatemia is achieved, with no reported complications and recurrence, a good prognosis is anticipated, comparable to the general population.
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http://dx.doi.org/10.20945/2359-3997000000316DOI Listing
December 2020

Clinicopathological Features as Prognostic Predictors of Poor Outcome in Papillary Thyroid Carcinoma.

Cancers (Basel) 2020 Oct 29;12(11). Epub 2020 Oct 29.

IPATIMUP-Instituto de Patologia e Imunologia Molecular, Universidade do Porto, 4200-135 Porto, Portugal.

Papillary thyroid cancer (PTC) has an indolent nature and usually excellent prognosis. Some PTC clinicopathological features may contribute to the development of aggressive metastatic disease. In this work, we want to evaluate PTC clinicopathological features that are presurgical prognostic predictors of patients' outcomes and find which indicators are more adequate for tailoring surgical procedures and follow-up. We studied a series of 241 PTC patients submitted to surgery. All patients' files and histological tumor samples were reviewed. The 8th edition AJCC/UICC (American Joint Committee on Cancer/Union for International Cancer) Controlstaging system and the 2015 American Thyroid Association risk stratification system were used. Total thyroidectomy was performed in 228 patients, lymphadenectomy in 28 patients. Gross extrathyroidal extension (ETE) was present in 10 patients and 31 tumor resection margins were incomplete. Cervical lymph node metastases (LNMs) were present in 34 patients and distant metastases at diagnosis in four patients. In multivariate analysis, male gender (OR = 15.4, = 0.015), venous invasion (OR = 16.7, = 0.022), and lateral compartment LNM (OR = 26.7, = 0.004) were predictors of mortality; psammoma bodies (PBs) (OR = 4.5, = 0.008), lymph vessel invasion (OR = 6.9, < 0.001), and gross ETE (OR = 16.1, = 0.001) were predictors of structural disease status; male gender (OR = 2.9, = 0.011), lymph vessel invasion (OR = 2.8, = 0.006), and incomplete resection margins (OR = 4.6, < 0.001) were predictors of recurrent/persistent disease. Our study supports that the factors helping to tailor patient's surgery are male gender, presence of PBs, gross ETE, and lateral compartment LNM. Together with pathological factors, lymph vessel invasion, venous invasion, necrosis, and incomplete surgical resection, should be taken into consideration regarding treatment and follow-up of patients.
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http://dx.doi.org/10.3390/cancers12113186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693726PMC
October 2020

Periodontal status, perceived stress, diabetes mellitus and oral hygiene care on quality of life: a structural equation modelling analysis.

BMC Oral Health 2020 08 20;20(1):229. Epub 2020 Aug 20.

Clinical Research Unit (CRU), CiiEM, IUEM, Almada, Portugal.

Background: To determine if periodontal risk assessment (PRA), the number of missing teeth, diabetes mellitus (DM), perceived stress and interproximal cleaning are associated with oral health-related quality of life (OHRQoL), using Andersen's behavioral modelling (ABM).

Material And Methods: Data derived from 472 adults derived from a representative population of the Study of Periodontal Health in Almada-Seixal (SoPHiAS) was used. Socioeconomic status, perceived stress scale (PSS-10), oral health behaviors and oral health impact profile (OHIP-14) were collected through questionnaire. Periodontal conditions were assessed with a full-mouth periodontal examination. PRA was computed through behavioral and clinical information. Variables were grouped into Predisposing Factors, Enabling, Need, Oral Health Behaviors and Perceived Health Outcome latent variables. Confirmatory factor analysis, structural ABM and model fitness were conducted.

Results: ABM applied to OHIP-14 showed acceptable model fit (χ = 2.75, CFI = 0.92, TLI = 0.90, RMSEA = 0.05, CI 90% [0.04-0.07]). The average of OHRQoL was 9.5 ± 11.3. Patient with periodontitis and with a high number of missing teeth experienced worse OHRQoL. Uncontrolled DM participants had more periodontal treatment necessity and poorer OHRQoL. Characteristic like aging and lower levels of education were directly associated with better OHRQoL, but in indirect path the OHRQoL was diminishes. Good oral hygiene and preventative measures were associated to lower periodontal treatment necessity. Lower periodontal treatment necessity was associated to higher OHRQoL. Age, tooth loss and interproximal cleaning were the most associated items to Predisposing, Need and Oral Health Behaviors, respectively.

Conclusion: ABM confirmed age, number of missing teeth, DM, interproximal cleaning and perceived stress as associated factors for OHRQoL. Uncontrolled DM was associated to higher Need and poorer OHRQoL. Good oral hygiene habits promote a healthy periodontium and, consequently, increases OHRQoL.
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http://dx.doi.org/10.1186/s12903-020-01219-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441730PMC
August 2020

Effects of high-intensity infrasound on liver lipid content of rats.

Heliyon 2020 Jul 4;6(7):e04383. Epub 2020 Jul 4.

Center for Interdisciplinary Research Egas Moniz (CiiEM), Monte da Caparica, Portugal.

Previous experimental studies show that exposure to noise with high and audible frequencies causes multiple metabolic alterations, such as increased liver glycogen and triglycerides. However, the effect of exposure to sound with lower frequencies, such as high-intensity infrasound (frequency <20 Hz and sound pressure level >90 dB), on the liver lipid content is still unclear. As such, we aimed to study the effect of exposure to high-intensity infrasound of both normal and glucose intolerant rats on the liver lipid content. For this study, 79 wild-type male Wistar rats were randomly divided into two groups: G1, no treatment, and G2, induced glucose intolerance. Each of these two groups was randomly divided in two subgroups: s (animals kept in silence) and i (animals continuously exposed to high-intensity infrasound noise). At three noise-exposure time-points (1, 6 and 12 weeks) the rats were sacrificed, the liver was excised and hepatic lipids extracted. Data analysis was performed using a two-way ANOVA (p = 0.05). No significant effects due to interactions between the several factors exist on the liver lipid content (p=0.077). Moreover, no significant effects due to infrasound exposure (p=0.407) or glucose tolerance status (p=0.938) were observed. Our study shows that continuous exposure to high-intensity infrasound has no influence on the lipid content of the liver of both normal and glucose intolerant animals. This finding reinforces the need for further experimental studies on the physiological effects of infrasound due to its possible hazardous effects on human health.
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http://dx.doi.org/10.1016/j.heliyon.2020.e04383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338782PMC
July 2020

Perceived xerostomia, stress and periodontal status impact on elderly oral health-related quality of life: findings from a cross-sectional survey.

BMC Oral Health 2020 07 10;20(1):199. Epub 2020 Jul 10.

Clinical Research Unit (CRU), Centro de Investigação Interdisciplinar Egas Moniz (CiiEM), Egas Moniz, CRL, Quinta da Granja, Almada, 2829 - 511, Portugal.

Background: To investigate if self-perceived xerostomia and stress are significant variables on the Oral-Health Related Quality of Life (OHRQoL) of elderly patients, considering the periodontal status, oral hygiene habits and sociodemographic characteristics simultaneously.

Methods: The study cohort included 592 participants (320 females/272 Males), aged 65 years or older, representing the elder inhabitants of the Study of Periodontal Health in Almada-Seixal (SoPHiAS). Patients answered a socio-demographic and oral hygiene habits questionnaire. The Oral Health Impact Profile-14 (OHIP-14), Summated Xerostomia Inventory-5 (SXI-5) and Perceived Stress Scale-10 (PSS-10) were used. Full-mouth circumferential periodontal inspection was carried out. Multivariable regression analyses were used considering the level of periodontitis, clinical characteristics, the number of teeth, SXI, PSS-10, age, gender and oral hygiene habits.

Results: Self-perceived xerostomia and stress showed a positive significant correlation with OHRQoL and each of its domains. Multiple linear regression analysis demonstrated the significant impact of SXI-5 (B = 1.20, p <  0.001) and PSS-10 (B = 0.35, p <  0.001) on the OHRQoL. SXI-5 (Odds Ratio (OR) = 1.28, p <  0.001) and PSS-10 (OR = 1.03, p = 0.022) were associated with a more frequently affected OHRQoL. The number of missing teeth, being male, mean probing depth and mean clinical attachment loss were also significant towards a frequently affected OHRQoL. Conversely, age was negatively associated with a lower OHRQoL.

Conclusion: Self-perceived xerostomia and stress are significant variables towards OHRQoL in elderly patients. Future studies should consider these self-perceived xerostomia and stress when investigating the impact of periodontitis and missing teeth on quality of life of older adults.
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http://dx.doi.org/10.1186/s12903-020-01183-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350690PMC
July 2020

Hyperinsulinaemic Hypoglycaemia and Polycystic Kidney Disease - A Rare Case Concerning Gene Pleiotropy.

Eur Endocrinol 2020 Apr 4;16(1):66-68. Epub 2020 Feb 4.

Paediatric Endocrinology Unit, Northern Maternal and Child Centre, Porto University Hospital Centre, Porto, Portugal.

Co-occurrence of hyperinsulinaemic hypoglycaemia and polycystic kidney disease (HIPKD) has been recently described. It is caused by a non-coding variant in the promoter region for phosphomannomutase 2 (), c.-167G>T, both in homozygous or compound heterozygous variants with deleterious coding. Although has been associated with congenital disorder of glycosylation, patients do not present with this phenotype and have normal carbohydrate-deficient transferring testing. The authors present a rare case where specific study was performed as a result of clinical suspicions. The patient was a 6-year-old female followed at our clinic due to congenital hyperinsulinism since she was 1 month old. She also presented with bilateral polycystic kidneys, detected in prenatal set, and simple hepatic cysts, for which she was treated with diazoxide and captopril. Initial metabolic and genetic studies were normal. gene sequence study revealed the promotor variant c.-167G>T in compound heterozygosity with the previously described pathogenic variant c.422G>A (p.Arg141His), confirming the diagnosis of HIPKD. This is a notable case as it highlights the importance of keeping this diagnostic hypothesis in mind and serves as a reminder to perform proper clinical and genetic investigation. A correct, and early, diagnosis will avoid unnecessary additional investigations and will allow appropriate genetic counselling for this autosomal recessive disorder.
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http://dx.doi.org/10.17925/EE.2020.16.1.66DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308104PMC
April 2020

Design and Simple Assembly of Gold Nanostar Bioconjugates for Surface-Enhanced Raman Spectroscopy Immunoassays.

Nanomaterials (Basel) 2019 Nov 4;9(11). Epub 2019 Nov 4.

UCIBIO, REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal.

Immunoassays using Surface-Enhanced Raman Spectroscopy are especially interesting on account not only of their increased sensitivity, but also due to its easy translation to point-of-care formats. The bases for these assays are bioconjugates of polyclonal antibodies and anisotropic gold nanoparticles functionalized with a Raman reporter. These bioconjugates, once loaded with the antigen analyte, can react on a sandwich format with the same antibodies immobilized on a surface. This surface can then be used for detection, on a microfluidics or immunochromatographic platform. Here, we have assembled bioconjugates of gold nanostars functionalized with 4-mercaptobenzoic acid, and anti-horseradish peroxidase antibodies. The assembly was by simple incubation, and agarose gel electrophoresis determined a high gold nanostar to antibody binding constant. The functionality of the bioconjugates is easy to determine since the respective antigen presents peroxidase enzymatic activity. Furthermore, the chosen antibody is a generic immunoglobulin G (IgG) antibody, opening the application of these principles to other antibody-antigen systems. Surface-Enhanced Raman Spectroscopy analysis of these bioconjugates indicated antigen detection down to 50 µU of peroxidase activity. All steps of conjugation were fully characterized by ultraviolet-visible spectroscopy, dynamic light scattering, ζ -Potential, scanning electron microscopy, and agarose gel electrophoresis. Based on the latter technique, a proof-of-concept was established for the proposed immunoassay.
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http://dx.doi.org/10.3390/nano9111561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6915668PMC
November 2019

Impact of overweight and obesity on pregnancy outcomes in women with gestational diabetes - results from a retrospective multicenter study.

Arch Endocrinol Metab 2020 Feb 30;64(1):45-51. Epub 2019 Sep 30.

Departamento de Endocrinologia, Centro Hospitalar de Vila Nova de Gaia, Espinho, Porto, Portugal.

Objective The aim of this study was to evaluate the impact of pre-pregnancy body mass index (BMI) on pregnancy outcomes in women with gestational diabetes (GD). Subjects and methods Retrospective multicenter study using data from the Portuguese National Register. We included women with GD with a singleton pregnancy. GD diagnosis was according to the International Association of the Diabetes and Pregnancy Study Group criteria. Women were divided into groups according to their pre-pregnancy BMI: < 18.5 kg/m2 (underweight), ≥ 18.5 and < 25.0 kg/m2 (normal weight), ≥ 25 and < 30 kg/m2 (overweight) and ≥ 30 kg/m2 (obese). Results We included 3,103 pregnant women with GD, 29.6% (n = 918) were overweight and 27.3% (n = 846) were obese. Compared to normal weight, the overweight and obese groups had a higher percentage of gestational hypertension (4.0% and 8.5% vs. 2.1%), cesarean delivery (32.8% and 41.3% vs. 27.9%), macrosomia (3.9% and 6.7% vs. 2.4%), and large for gestational age (LGA) newborns (8.3% and 13.5% vs. 6.0%). Obesity increased the risk of gestational hypertension (OR 4.5, p < 0.001), preeclampsia (OR 1.9, p = 0.034), cesarean delivery (OR 2.0, p < 0.001), macrosomia (OR 3.1, p < 0.001) and LGA (OR 2.3, p < 0.001). Conclusion In pregnant women with GD, pregnancy complications increase with pre-pregnancy BMI. In obese women, appropriate diet and counseling prior to gestation and more aggressive medical intervention during pregnancy are needed in order to prevent macrosomic and LGA newborns and to reduce maternal complications.
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http://dx.doi.org/10.20945/2359-3997000000178DOI Listing
February 2020

Nivolumab-induced hypothyroidism followed by isolated ACTH deficiency.

BMJ Case Rep 2019 Aug 28;12(8). Epub 2019 Aug 28.

Department of Endocrinology, Centro Hospitalar de Vila Nova de Gaia Espinho EPE, Vila Nova de Gaia, Portugal.

Cancer immunotherapy has been used in several malignancies with clinical benefit. Despite the clinical success, immune-related adverse events are frequent and endocrinopathies can be particularly severe. We report a 55-year-old male patient with stage IV pulmonary carcinoma treated with nivolumab who presented with thyroid dysfunction after the sixth administration of the drug. One year after thyroid dysfunction, the patient complained of severe fatigue, asthenia and weight loss. Laboratory testing showed low morning cortisol with undetected adrenocorticotropic hormone; other pituitary hormones were normal and MRI showed homogeneous enhancement of the pituitary gland and no space-occupying lesions. The diagnosis of nivolumab-induced hypophysitis was made and replacement treatment with hydrocortisone was started with clinical improvement. This case demonstrates that patients under immunotherapy are at risk for a large spectrum of endocrine dysfunctions that may worsen their prognosis. Close monitoring of these patients is warranted.
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http://dx.doi.org/10.1136/bcr-2019-231236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6720681PMC
August 2019

Graves' disease complicated by fetal goitrous hypothyroidism treated with intra-amniotic administration of levothyroxine.

BMJ Case Rep 2019 Aug 15;12(8). Epub 2019 Aug 15.

Endocrinology, Centro Hospitalar de Vila Nova de Gaia Espinho EPE, Vila Nova de Gaia, Portugal.

Fetal goitrous hypothyroidism is a rare entity and is caused mainly by maternal treatment of Graves' disease (GD). We report a case of a 22-year-old woman referred at 12 weeks of gestation due to hyperthyroidism subsequent to recently diagnosed GD. She started treatment with propylthiouracil and, at 21 weeks of gestation, fetal goitre was detected. A cordocentesis confirmed the diagnosis of fetal goitrous hypothyroidism, and intra-amniotic administration of levothyroxine (LT4) was performed and repeated through the pregnancy due to maintenance of fetal goitre. The pregnancy proceeded without further complications and a healthy female infant was born at 37 weeks of gestation, with visible goitre and thyroid function within the normal range at birth. Although there is no consensus on the optimal dose, the number of injections and the interval between them, intra-amniotic LT4 administration is recommended once fetal goitrous hypothyroidism is suspected, in order to prevent long-term complications of fetal hypothyroidism.
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http://dx.doi.org/10.1136/bcr-2019-230457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700595PMC
August 2019

CYP21A2 Gene Pathogenic Variants: A Multicenter Study on Genotype-Phenotype Correlation from a Portuguese Pediatric Cohort.

Horm Res Paediatr 2019 19;91(1):33-45. Epub 2019 Mar 19.

Department of Pediatric Endocrinology, Centro Materno-infantil do Norte, Porto, Portugal.

Background: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) is an autosomal recessive disorder characterized by 3 overlapping phenotypes: salt-wasting (SW), simple virilizing (SV), and non-classic (NC). We aimed at conducting a nationwide genotype description of the CAH pediatric patients and to establish their genotype-phenotype correlation.

Methods: CAH patients were recruited from Portuguese pediatric endocrinology centers and classified as SW, SV, or NC. Genetic analysis was performed by polymerase chain reaction (sequence specific primer, restriction fragment length polymorphism) or direct Sanger sequencing. Genotypes were categorized into 4 groups (0, A, B, and C), according to their predicted enzymatic activity. In each group, the expected phenotype was compared to the observed phenotype to assess the genotype-phenotype correlation.

Results: Our cohort comprises 212 unrelated pediatric CAH patients (29% SW, 11% SV, 60% NC). The most common pathogenic variant was p.(Val282Leu; 41.3% of the 424 alleles analyzed). The p.(Val282Leu) variant, together with c.293-13A/C>G, p.(Ile173Asn), p.(Leu308Thr), p.(Gln319*), and large deletions/conversions were responsible for 86.4% of the mutated alleles. Patients' stratification by disease subtype revealed that the most frequent pathogenic variants were c.293-13A/C>G in SW (31.1%), p.(Ile173Asn) in SV (46.9%), and p.(Val282Leu) in NC (69.5%). The most common genotype was homozygosity for p.(Val282Leu; 33.0%). Moreover, we found 2 novel variants: p.(Ile161Thr) and p.(Trp202Arg), in exons 4 and 5, respectively. The global genotype-phenotype correlation was 92.4%. Group B (associated with the SV form) showed the lowest genotype-phenotype correlation (80%).

Conclusion: Our cohort has one of the largest NC CAH pediatric populations described. We emphasize the high frequency of the p.(Val282Leu) variant and the very high genotype-phenotype correlation observed.
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http://dx.doi.org/10.1159/000497485DOI Listing
November 2019

Sociedade Portuguesa de Cuidados Intensivos guidelines for stress ulcer prophylaxis in the intensive care unit.

Rev Bras Ter Intensiva 2019 28;31(1):5-14. Epub 2019 Feb 28.

Sociedade Portuguesa de Cuidados Intensivos - Lisboa, Portugal.

Critically ill patients are at risk of developing stress ulcers in the upper digestive tract. Agents that suppress gastric acid are commonly prescribed to reduce the incidence of clinically important stress ulcer-related gastrointestinal bleeding. However, the indiscriminate use of stress ulcer prophylaxis in all patients admitted to the intensive care unit is not warranted and can have potential adverse clinical effects and cost implications. The present guidelines from the Sociedade Portuguesa de Cuidados Intensivos summarizes the current evidence and gives six clinical statements and an algorithm aiming to provide a standardized prescribing policy for the use of stress ulcer prophylaxis in the intensive care unit.
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http://dx.doi.org/10.5935/0103-507X.20190002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443317PMC
August 2019

Prenatal Diagnosis and Management of a Fetal Goiter Hypothyroidism due to Dyshormonogenesis.

Case Rep Endocrinol 2018 19;2018:9564737. Epub 2018 Dec 19.

Pediatric Endocrinology Unit, Department of Pediatrics, Centro Materno Infantil do Norte-Centro Hospitalar Universitário do Porto, Oporto, Portugal.

Fetal goiter is a rare disorder not expected to be found during a healthy woman's pregnancy. It can be a prenatal manifestation of congenital hypothyroidism due to thyroid dyshormonogenesis and it can lead to serious perinatal complications. A vascularized fetal neck mass was detected at 29 weeks' gestation of a healthy primigravida. Magnetic resonance was suggestive of goiter causing airway deviation without polyhydramnios. Maternal thyroid function was normal and thyroid antibodies were negative. Two intra-amniotic levothyroxine infusions were performed at 32 and 33 weeks. Serial imaging control showed no progression of the mass. Elective caesarean section was performed at 38 weeks. The male newborn was admitted to the intensive care unit due to cardiorespiratory insufficiency with pulmonary hypertension. Hormonal assays revealed primary congenital hypothyroidism and ultrasonography confirmed diffuse goiter. Levothyroxine was started. Currently, he is 6 years old with adequate growth and normal psychomotor development. Genetic study found a heterozygous mutation in the TPO gene.
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http://dx.doi.org/10.1155/2018/9564737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6313984PMC
December 2018

Seed-Layer Free Zinc Tin Oxide Tailored Nanostructures for Nanoelectronic Applications: Effect of Chemical Parameters.

ACS Appl Nano Mater 2018 Aug 20;1(8):3986-3997. Epub 2018 Jul 20.

i3N/CENIMAT, Department of Materials Science, Faculty of Science and Technology, Universidade NOVA de Lisboa and CEMOP/UNINOVA, Campus de Caparica, 2829-516 Caparica, Portugal.

Semiconductor nanowires are mostly processed by complex, expensive, and high temperature methods. In this work, with the intent of developing zinc tin oxide nanowires (ZTO NWs) by low-cost and low-complexity processes, we show a detailed study on the influence of chemical parameters in the hydrothermal synthesis of ZTO nanostructures at temperatures of only 200 °C. Two different zinc precursors, the ratio between zinc and tin precursors, and the concentration of the surfactant agent and of the mineralizer were studied. The type and the crystallinity of the nanostructures were found to be highly dependent on the used precursors and on the concentration of each reagent. Conditions for obtaining different ZTO nanostructures were achieved, namely, ZnSnO nanoparticles and ZnSnO nanowires with length ∼600 nm, with the latter being reported for the first time ever by hydrothermal methods without the use of seed layers. Optical and electrical properties were analyzed, obtaining band gaps of 3.60 and 3.46 eV for ZnSnO and ZnSnO, respectively, and a resistivity of 1.42 kΩ·cm for single ZnSnO nanowires, measured using nanomanipulators after localized deposition of Pt electrodes by e-beam assisted gas decomposition. The low-temperature hydrothermal methods explored here proved to be a low-cost, reproducible, and highly flexible route to obtain multicomponent oxide nanostructures, particularly ZTO NWs. The diversity of the synthesized ZTO structures has potential application in next-generation nanoscale devices such as field effect nanotransistors, nanogenerators, resistive switching memories, gas sensors, and photocatalysis.
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http://dx.doi.org/10.1021/acsanm.8b00743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6166637PMC
August 2018

Assessment of Respiratory Muscle Weakness in Subjects With Neuromuscular Disease.

Respir Care 2018 Oct 31;63(10):1223-1230. Epub 2018 Jul 31.

Department of Pulmonology, Centro Hospitalar de Vila Nova de Gaia e Espinho, Entidade Pública Empresarial (EPE), Vila Nova de Gaia, Portugal.

Introduction: Neuromuscular diseases (NMD) are a group of rare heterogeneous disorders that may be accompanied by respiratory muscle weakness. The simplest measurements of respiratory muscle strength are maximum inspiratory pressure (P) and maximum expiratory pressure (P) of the mouth. Inspiratory muscle weakness can also be evaluated by the sniff test (sniff nasal inspiratory pressure method). This study tested the agreements in P and P (measured by using a plethysmograph and portable equipment) as well as the correlations of P and P by using the sniff nasal inspiratory pressure method, lung function, and arterial blood gas parameters in subjects with NMD.

Methods: This prospective, noninterventional study measured respiratory parameters in all the subjects with NMD who underwent measurement of maximum respiratory pressures.

Results: A total of 55 subjects with NMD were included. There were no statistically significant differences in P and P measured by using a plethysmograph and portable equipment. Moreover, P showed a good correlation with the sniff nasal inspiratory pressure method.

Conclusions: Measurements of P and P by using portable equipment were equivalent to those performed by using the accepted standard, plethysmography, in the subjects with NMD. Noninvasive evaluation of the sniff test with the portable equipment correlates with P, which makes this approach a good method for measuring the maximum strength of inspiratory muscles in patients with NMD.
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http://dx.doi.org/10.4187/respcare.06136DOI Listing
October 2018

Treatment of Graves' disease in children: The Portuguese experience.

Endocrinol Diabetes Nutr (Engl Ed) 2018 Mar 9;65(3):143-149. Epub 2018 Jan 9.

Division of Endocrinology, Centro Hospitalar Vila Nova de Gaia/Espinho, Portugal; Portuguese Society of Pediatric Endocrinology and Diabetology, Portugal.

Introduction: Graves' disease (GD) is an autoimmune thyroid disease, common in adults but rare in children. The best therapeutic approach remains controversial.

Objectives: To ascertain the current treatment of pediatric GD in Portugal and to assess the clinical and biochemical factors that determine definitive/long-term remission after treatment with antithyroid drugs (ATDs).

Patients And Methods: A retrospective analysis of data about pediatric GD treatment collected from a nationwide survey conducted by the Portuguese Society of Pediatric Endocrinology and Diabetology from May to August 2013. Population was categorized based on sex, age, use of ATDs, dosage, treatment duration, adverse reactions, thyrotropin receptor-stimulating antibody (TRAB) titer, remission and remission/relapse rates, and definitive treatment, and divided into group A (with ongoing treatment) and group B (with treatment stopped). Group B was subdivided into 'Remission', 'Remission+relapse' and 'No remission' subgroups based on the course of disease. The same parameters were compared between both groups.

Results: Survey response rate was 77%; 152 subjects, 116 female, mean age at diagnosis 11.23±3.46 years. They all started treatment with ATDs, 70.4% with thiamazole, with a mean treatment duration of 32.38±28.29 months, and 5.9% had adverse effects. Remission rate was 32.6%. Lower age at diagnosis correlated with higher remission rates. Treatment duration was longer when propylthiouracil was used. Initial TRAB titer was significantly higher in the 'No remission' group. Surgery and radioiodine were used as second-line treatments.

Conclusion: Our study results were similar to those reported in the literature. Age and TRAB titer were identified as potential clinical and laboratory determinants of remission. Based on risk/benefit analysis, it was concluded that treatment should be individualized based on age, accessibility to treatments, and physician's experience.
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http://dx.doi.org/10.1016/j.endinu.2017.11.014DOI Listing
March 2018

Office paper decorated with silver nanostars - an alternative cost effective platform for trace analyte detection by SERS.

Sci Rep 2017 05 30;7(1):2480. Epub 2017 May 30.

i3n/CENIMAT, Departamento de Ciência dos Materiais, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa and CEMOP/UNINOVA, Campus de Caparica, 2829-516, Caparica, Portugal.

For analytical applications in portable sensors to be used in the point-of-need, low-cost SERS substrates using paper as a base, are an alternative. In this work, SERS substrates were produced on two different types of paper: a high porosity paper (Whatman no. 1); and a low porosity paper (commercially available office paper, Portucel Soporcel). Solutions containing spherical silver nanoparticles (AgNPs) and silver nanostars (AgNSs) were separately drop-casted on hydrophilic wells patterned on the papers. The porosity of the paper was found to play a determinant role on the AgNP and AgNS distribution along the paper fibres, with most of the nanoparticles being retained at the illuminated surface of the office paper substrate. The highest SERS enhancements were obtained for the office paper substrate, with deposited AgNSs. A limit of detection for rhodamine-6G as low as 11.4 ± 0.2 pg could be achieved, with an analytical enhancement factor of ≈10 for this specific analyte. The well patterning technique allowed good signal uniformity (RSD of 1.7%). Besides, these SERS substrates remained stable after 5 weeks of storage (RSD of 7.3%). Paper-induced aggregation of AgNPs was found to be a viable alternative to the classical salt-induced aggregation, to obtain a highly sensitive SERS substrates.
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http://dx.doi.org/10.1038/s41598-017-02484-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5449394PMC
May 2017

Use of Thoracic Ultrasound in the Detection of Pneumothorax Resolution after Drainage.

Arch Bronconeumol 2017 05 22;53(5):288. Epub 2016 Dec 22.

Pulmonology Department, Centro Hospitalar de Vila Nova de Gaia e Espinho, Vila Nova de Gaia, Portugal.

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http://dx.doi.org/10.1016/j.arbres.2016.10.017DOI Listing
May 2017

Alpha-1-antitrypsin (SERPINA1) mutation spectrum: Three novel variants and haplotype characterization of rare deficiency alleles identified in Portugal.

Respir Med 2016 07 3;116:8-18. Epub 2016 May 3.

Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal; Instituto de Investigação e Inovação em Saúde, Universidade do Porto (I3S), Porto, Portugal. Electronic address:

Background: Alpha-1-antitrypsin deficiency (AATD) is a genetic condition caused by SERPINA1 mutations, which culminates into lower protease inhibitor activity in the serum and predisposes affected individuals to emphysema. Clinical manifestations of AATD are often associated to ZZ (p.Glu342Lys) and SZ (p.Glu264Val) genotypes and less frequently to rare deficiency or null alleles in heterozygous and homozygous states.

Methods: We sequenced SERPINA1 (approximately 8 kb) and genotyped two microsatellites located upstream and downstream of the gene (195 and 5.6 kb, respectively) in a cohort of 51 AATD patients found to carry different rare alleles. A meta-analysis of SERPINA1 mutation spectrum was also performed.

Results: We detected a total of 14 rare alleles including 3 defined by novel mutations (p.Glu162Gly, p.Arg281Lysfs*17 and p.Met374Leufs*19) and 11 characterized by previously described variants (c.-5+2dupT, p.Arg39Cys, p.Phe52del, p.Thr68Ile, p.Asp256Val, p.Leu263Pro, p.Glu264Val, p.Leu353Phefs*24, p.Pro369Ser and p.Pro369Leu) but in several instances differing in their molecular backgrounds. So far, SERPINA1 has 132 low-frequency variants (<1%), where AATD mutations are not evenly distributed across the three-dimensional structure and tend to cluster in functional domains like the gate or the shutter.

Conclusion: The contribution of rare SERPINA1 alleles into AATD should not be neglected in the diagnosis practice given there is a wide spectrum of variants originated by mutation and sometimes shuffled between chromosomes by recombination. Even though many of the rare variants are likely to be recent and population specific others seems to be as old as the Z allele and dispersed across European populations.
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http://dx.doi.org/10.1016/j.rmed.2016.05.002DOI Listing
July 2016

[Thirdhand Smoke: A Concept to Remember!].

Acta Med Port 2015 Sep-Oct;28(5):676-7. Epub 2015 Oct 30.

Serviço de Pneumologia. Centro Hospitalar de Vila Nova de Gaia e Espinho. Vila Nova de Gaia. Portugal.

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February 2018

BCGitis: A rare complication after intravesical BCG therapy.

J Bras Pneumol 2015 Sep-Oct;41(5):480-1

Centro Hospitalar de Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal.

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http://dx.doi.org/10.1590/S1806-37132015000000126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4635097PMC
July 2016

A misleading tumor. Benign metastatic leiomyoma.

Arch Bronconeumol 2016 Jul 30;52(7):391. Epub 2015 Jul 30.

Servicio de Cirugía Cardiotorácica, Centro Hospitalario de Vila Nova de Gaia e Espinho, Vila Nova de Gaia, Portugal.

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http://dx.doi.org/10.1016/j.arbres.2015.06.009DOI Listing
July 2016

Histomorphometric evaluation of the small coronary arteries in rats exposed to industrial noise.

Int J Mol Sci 2015 May 4;16(5):10095-104. Epub 2015 May 4.

Center for Interdisciplinary Research Egas Moniz (CIIEM), Health Sciences Institute, 2829-511 Monte de Caparica, Portugal.

Unlabelled: Morphological changes induced by industrial noise (IN) have been experimentally observed in several organs. Histological observations of the coronary arteries showed prominent perivascular tissue and fibrosis among IN-exposed rats. The effects on the small arteries are unknown.

Objective: To evaluate the histomorphometric changes induced by IN on rat heart small arteries.

Methods: Twenty Wistar rats exposed to IN during a maximum period of seven months and 20 age-matched controls were studied. Hearts were transversely sectioned from ventricular apex to atria and a mid-ventricular fragment was selected for analysis. The histological images were obtained with an optical microscope using 400× magnifications. A total of 634 arterial vessels (298 IN-exposed and 336 controls) were selected. The mean lumen-to-vessel wall (L/W) and mean vessel wall-to-perivascular tissue (W/P) ratios were calculated using image J software.

Results: There were no differences between exposed and control animals in their L/W ratios (p=0.687) and time variations in this ratio were non-significant (p=0.110). In contrast, exposed animals showed lower W/P ratios than control animals (p<0.001), with significant time variations (p=0.004).

Conclusions: Industrial noise induced an increase in the perivascular tissue of rat small coronary arteries, with significant development of periarterial fibrosis.
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http://dx.doi.org/10.3390/ijms160510095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4463634PMC
May 2015

High concentration of phosphorus is a distinctive feature of myelin. An X-ray elemental microanalysis study using freeze-fracture scanning electron microscopy of rat sciatic nerve.

Microsc Res Tech 2015 Jul 14;78(7):537-9. Epub 2015 Apr 14.

Department of Anatomy and UMIB, ICBAS, University of Porto, Porto, Portugal.

We have used rat sciatic nerves submitted to freezing and freeze-fracture to determine the elemental composition of small domains of the peripheral nerve studied at high resolution by scanning electron microscopy. We found that myelin of Schwann cells is unique in its high content in phosphorus (P) that was more than 10 times higher than P measured in any other cells. This high concentration in P makes myelin chemistry suitable of monitoring at the subcellular level using the herein described methodology.
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http://dx.doi.org/10.1002/jemt.22506DOI Listing
July 2015

[Congenital adrenal hyperplasia due to 21-hydroxylase deficiency: genotype-phenotype correlation].

Acta Med Port 2015 Jan-Feb;28(1):56-62. Epub 2015 Feb 27.

Departamento da Criança e do Adolescente. Unidade de Endocrinologia Pediátrica. Centro Hospitalar do Porto. Porto. Portugal.

Introduction: Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is one of the most frequent inborn conditions. It is caused by distinct mutations in the CYP21A2 gene and in the majority of cases the disease's severity correlates with CYP21A2 allelic variation Our aim was to describe the mutational spectrum of CYP21A2 and evaluate genotype-phenotype correlation in a cohort of portuguese patients with 21-hydroxylase deficiency.

Material And Methods: Retrospective study of 22 patients with clinical diagnosis of 21-hydroxylase deficiency. Molecular analysis of CYP21A2 was performed and genotype-phenotype correlation was then established.

Results: Genotyping was performed in 22 unrelated patients: 5 with classic salt-wasting (average age of diagnosis 10,2 days; minimum 1, maximum 20 days), 7 with classic simple virilizing (average age of diagnosis 3,5 years; minimum 0 days, maximum 7 years) and 10 with nonclassical form (average age of diagnosis 5,7 years; minimum 4 years, maximum 8 years). The most frequent genetic defects in the classic forms were I2 splice (24%) and I172N (24%), followed by Q318X (16%) and gene deletions (16%) and in the nonclassical form, the V281L (80%). The overall concordance between genotype and phenotype was 81,8%. Genotype accurately predicted phenotype in 83,3%, 100% and 90% of patients with classic salt-wasting, classic simple virilizing and nonclassical mutations, respectively.

Discussion: The frequency of genetic defects in our patients was comparable to similar studies. In most cases there was a good correlation between genotype and phenotype.

Conclusions: Molecular analysis of CYP21A2 provides useful information in terms of prediction of disease severity, genetic and prenatal counseling.
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January 2017
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