Publications by authors named "Marta Alves"

130 Publications

The Impact of Ischemia Assessed by Magnetic Resonance on Functional, Arrhythmic, and Imaging Features of Hypertrophic Cardiomyopathy.

Front Cardiovasc Med 2021 17;8:761860. Epub 2021 Dec 17.

Inherited Cardiac Disease Unit, Bart's Heart Centre, St Bartholomew's Hospital, London, United Kingdom.

The aim of the study is to investigate the association between the degree of ischemia due to coronary microvascular dysfunction (CMD) and the left ventricular (LV) tissue characteristics, systolic performance, and clinical manifestations in hypertrophic cardiomyopathy (HCM). This prospective study enrolled 75 patients with HCM without obstructive epicardial coronary artery disease. Each patient underwent cardiovascular magnetic resonance (CMR) including parametric mapping, perfusion imaging during regadenoson-induced hyperemia, late gadolinium enhancement (LGE) and three-dimensional longitudinal, circumferential, and radial strains analysis. Electrocardiogram, 24-h Holter recording, and cardiopulmonary exercise testing (CPET) were performed to assess arrhythmias and functional capacity. In total, 47 (63%) patients were men with the mean age of 54.6 (14.8) years, 51 (68%) patients had non-obstructive HCM, maximum wall thickness (MWT) was 20.2 (4.6) mm, LV ejection fraction (LVEF) was 71.6 (8.3%), and ischemic burden was 22.5 (16.9%) of LV. Greater MWT was associated with the severity of ischemia (β-estimate:1.353, 95% CI:0.182; 2.523, = 0.024). Ischemic burden was strongly associated with higher values of native T1 (β-estimate:9.018, 95% CI:4.721; 13.315, < 0.001). The association between ischemia and LGE was significant in following subgroup analyses: MWT 15-20 mm (β-estimate:1.941, 95% CI:0.738; 3.143, = 0.002), non-obstructive HCM (β-estimate:1.471, 95% CI:0.258; 2.683, = 0.019), women (β-estimate:1.957, 95% CI:0.423; 3.492, = 0.015) and age <40 years (β-estimate:4.874, 95% CI:1.155; 8.594, = 0.016). Ischemia in ≥21% of LV was associated with LGE >15% (AUC 0.766, sensitivity 0.724, specificity 0.659). Ischemia was also associated with atrial fibrillation or flutter (AF/AFL) (OR-estimate:1.481, 95% CI:1.020; 2.152, = 0.039), but no association was seen for non-sustained ventricular tachycardia. Ischemia was associated with shorter time to anaerobic threshold (β-estimate: -0.442, 95% CI: -0.860; -0.023, = 0.039). In HCM, ischemia associates with morphological markers of severity of disease, fibrosis, arrhythmia, and functional capacity.
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http://dx.doi.org/10.3389/fcvm.2021.761860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8718511PMC
December 2021

Green-Synthesized Magnesium Hydroxide Nanoparticles Induced Osteoblastic Differentiation in Bone Co-Cultured Cells.

Pharmaceuticals (Basel) 2021 Dec 8;14(12). Epub 2021 Dec 8.

EST Setúbal, CDP2T, Instituto Politécnico de Setúbal, Campus IPS, 2910-761 Setúbal, Portugal.

In this work, magnesium hydroxide NPs were synthesized using water (Mg(OH) NPs) or a rose hip (RH) extract (Mg(OH)RH NPs) and tested for the bone cells' effects in co-cultured osteoblastic and osteoclastic cells, using a Transwell insert system, allowing reciprocal cell paracrine interactions. Behavior of each cell population was characterized for typical phenotype markers, at days 1 and 6. Cell cultures treated with osteogenic/osteoclastogenic inducers were used as positive control of cell differentiation. The NPs presented a round shape morphology with an average diameter ~90 nm (Mg(OH) NPs) and below 10 nm (Mg(OH)RH NPs. Both NPs induced osteoblastic and osteoclastic behavior similarly to that observed in induced osteoblastic and osteoclastic cultures (positive controls). Differences between the two types of particles were evident at the gene expression level. Compared to Mg(OH) NPs, the green-synthesized NPs greatly increased the expression of osteoblastic genes coding for the early markers ALP and collagen type 1 and the later transcription factor osterix, while decreasing the expression of osteoclastogenic genes, namely the essential transcription factor NFATC1, TRAP and the genes coding for the functional markers CA2 and CTSK. Overall, a positive added effect could be hypothesized for Mg(OH)RH NPs with potential usefulness to promote bone formation in regenerative applications.
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http://dx.doi.org/10.3390/ph14121281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704631PMC
December 2021

Acute Treatment of Isolated Posterior Cerebral Artery Occlusion: Single Center Experience.

J Stroke Cerebrovasc Dis 2021 Dec 12;31(2):106239. Epub 2021 Dec 12.

Neuroradiology Department, Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal; NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal.

Background And Objectives: Randomized trials for mechanical thrombectomy (MT) excluded patients with ischemic strokes due to isolated posterior cerebral artery occlusion (IPCAO), and there is no evidence for best acute treatment strategy in these patients. We aimed to assess the effectiveness and safety of MT in acute IPCAO.

Methods: We retrospectively analyzed consecutive patients with acute stroke due to IPCAO submitted to MT and/or intravenous thrombolysis (IVT), between 2015-2019. Effectiveness outcomes (recanalization rate, first-pass effect, NIHSS 24h improvement and 3-month Modified Ranking Scale - mRS) and safety outcomes (complications, symptomatic intracranial hemorrhage (SICH) and 3-month mortality) were described and compared between groups.

Results: A total of 38 patients were included, 25 underwent MT and 13 had IVT alone. Successful and complete recanalization were achieved in 68% and 52% of MT patients, respectively. NIHSS improvement at 24h was found in 56% of MT patients versus 30.8% of patients submitted to IVT alone (OR [95% CI]=2.86 [0.69-11.82]) and excellent functional outcome at 3 months (mRS≤1) was achieved in 54.2% of MT patients versus 38.5% in the IVT group (OR [95% CI]=1.60 [0.41-6.32]). Complications occurred in 3 (12%) procedures and there were no SICH. Mortality at 3 months was 20% in the MT group and 15.4% in patients submitted to IVT alone.

Conclusions: Our results reflect a real-world scenario in a single center and seem to support the recently growing literature showing that MT is a feasible and safe treatment in IPCAO, with favorable effectiveness.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.106239DOI Listing
December 2021

Author Correction: Flexible ZnO-mAb nanoplatforms for selective peripheral blood mononuclear cell immobilization.

Sci Rep 2021 Dec 7;11(1):23900. Epub 2021 Dec 7.

Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001, Lisboa, Portugal.

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http://dx.doi.org/10.1038/s41598-021-03382-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651715PMC
December 2021

Biocompatibility and Antimicrobial Activity of Nanostructured Lipid Carriers for Topical Applications Are Affected by Type of Oils Used in Their Composition.

Pharmaceutics 2021 Nov 17;13(11). Epub 2021 Nov 17.

Instituto de Tecnologia Química e Biológica António Xavier, NOVA University Lisbon, 2780-157 Oeiras, Portugal.

Nanostructured lipid carriers (NLCs) have gained significant attention as tools for the dermal delivery of therapeutics due to their stability, biocompatibility, and ability to improve drug bioavailability. The use of natural plant oils (NPO) in NLC formulations has numerous benefits for the skin due to their therapeutic potential. This work shows the effect of NLC composition on bioavailability in epidermal cells and antimicrobial activity against . Sixteen systems containing fixed (sunflower, olive, corn, peanut, coconut, castor, and sweet almond) and essential (eucalyptus) oils, with different solid lipid (SL): liquid lipid (LL) ratios, were engineered. The structural properties, bioavailability, and antimicrobial action of the particles was studied. The choice of NPO influenced the physicochemical stability by changing the diameter of NLC formulations (between 160 nm and 185 nm) and Z-potential (between -46 mV and -61 mV). All of the systems were characterized by concentration-dependent cytocompatibility with human epidermal keratinocytes (HaCaT) and human dermal fibroblasts (HDFn). The SL:LL ratio in some NLC systems impacted cell cytotoxicity differently. Antimicrobial properties were observed in all 16 systems; however, the type of oil and SL:LL ratio affected the activity of the formulations. Two NLC-NPO systems were found to be non-cytotoxic to human cells lines at concentrations that completely inhibited bacterial growth. These results present a strong argument that the use of natural oils in NLC formulations presents a promising tool for the treatment of skin infections.
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http://dx.doi.org/10.3390/pharmaceutics13111950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8618763PMC
November 2021

Building Innovative Teams: Exploring the Positive Contribute of Emotions Expression and Affective Commitment.

Front Psychol 2021 3;12:732171. Epub 2021 Nov 3.

Research Center in Business Sciences (NECE-UBI), University of Beira Interior, Covilhã, Portugal.

The current challenging organizational context demands that organizations adapt quickly and continuously in order to survive and maintain their competitive advantage. Considering this need, one of the responses given by companies has been the valorization of work teams and their capacity for innovation, as well as fostering positive skills and emergent states in employees, such as emotional carrying capacity and affective commitment, respectively. The aim of this research is thus to study the relationship between emotional carrying capacity and group innovation, considering affective commitment as the mediating variable. To test these relationships, an empirical cross-sectional study was conducted including 138 Portuguese work teams belonging to different sectors of activity, composed of 625 members and their respective leaders. The results were analyzed through structural equation modeling (SEM) and showed positive relationships between emotional carrying capacity and affective commitment, as well as between affective commitment and group innovation. In addition, the mediating role of affective commitment in the relationship between emotional carrying capacity and group innovation was also supported. Therefore, the results suggest that a work context in which members openly express their emotions contributes to reinforcing their affective attachment to the group, making them feel more involved and available to test and implement new ideas and procedures. The findings reinforce the benefits of promoting the expression of emotions and the development of healthy bonds between team members.
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http://dx.doi.org/10.3389/fpsyg.2021.732171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8595118PMC
November 2021

Previous Disability and Benefit of Acute Phase Therapy in Functional Prognosis of Selected Patients with Ischemic Stroke.

J Stroke Cerebrovasc Dis 2022 Jan 28;31(1):106183. Epub 2021 Oct 28.

Stroke Unit, Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal.

Objectives: Patients' previous disability (PD) is a key factor when considering acute stroke therapy. PD's exact impact on functional prognosis of patients with acute ischemic stroke remains not entirely clarified. We aimed to analyze PD's influence on functional outcome three months after ischemic stroke.

Materials And Methods: Retrospective analysis of prospectively collected data concerning patients with acute ischemic stroke admitted to Stroke Unit of a tertiary center who underwent acute phase therapy between 2017 and 2019. Modified Rankin Scale (mRS) was used to define PD (with previous mRS≥3). Patients with PD were selected for treatment based on similar baseline characteristics to patients without PD. Patients were classified into two groups according to previous mRS: mRS<3 and mRS≥3. We defined bad outcome at three months after stroke as mRS≥3 for patients with previous mRS<3, and as a higher score than baseline mRS for patients with previous mRS≥3.

Results: We identified 1169 eligible patients - 1016 patients with previous mRS<3 and 153 patients with previous mRS≥3. Most baseline characteristics did not differ significantly between them. For patients ≤75 years old, PD was associated with worse outcome (odds ratio estimate [OR] 4.50, p < 0.001). For patients >75 years old, PD was protective against worse outcome (OR 0.42, p < 0.001). In patients with previous mRS≥3 and >75 years old, there was a higher proportion of women (p = 0.005).

Conclusions: PD might not be a relevant factor when considering acute stroke therapy in selected patients >75 years old, especially women. Further studies are needed to clarify these findings.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.106183DOI Listing
January 2022

An Open Access Standardised Voice Evaluation Protocol.

J Voice 2021 Oct 21. Epub 2021 Oct 21.

Center for Research and Development in Mathematics and Applications (CIDMA) and Department of Mathematics (DMat), University of Aveiro, Aveiro, Portugal.

Purpose: A comprehensive protocol to evaluate voice quality can support a full characterisation of voice disorders and be used to plan voice interventions. The purpose of this study was to develop and validate a standardised protocol for voice assessment, contributing with a comprehensive and valuable tool for clinician practice and research.

Method: The initial structure and content of the protocol was based on an extensive literature review of existing voice assessment tools. The content validity was then assessed by a panel of voice specialist, using a modified Bland and Altman graphical method and the intraclass correlation coefficient (ICC). A group of participants with vocal pathology was finally assessed by two voice specialists on the same day (inter-rater reliability), and, on a second day, by a single evaluator (intra-rater reliability). Inter and intra-reliability were evaluated through Cohen's kappa (k) for nominal variables, and Spearman's Correlation Coefficient (ρ) for quantitative and ordinal variables.

Results: The Bland and Altman analysis, revealed a reasonable agreement between the experts and the ICC values were lower than expected, but the confidence intervals were very wide. The intra-rater reliability of the protocol's nominal variables was almost perfect, with a mean k of 0.977; inter-rater reliability of nominal variables was also almost perfect, with a mean k of 0.893. The ordinal and quantitative variables revealed a very good to excellent relationship, with a mean ρ of 0.912.

Conclusions: Evidence of content validity, high intra and inter-rater reliability of a standardised protocol for voice assessment, have been shown. This protocol can be used to assess and collect data from patients, to train voice specialists and to develop reference voice databases. It has been designed to serve voice experts with diverse backgrounds and assessment needs.
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http://dx.doi.org/10.1016/j.jvoice.2021.09.010DOI Listing
October 2021

Self-Assembly Nanoparticles of Natural Bioactive Abietane Diterpenes.

Int J Mol Sci 2021 Sep 22;22(19). Epub 2021 Sep 22.

CBIOS-Universidade Lusófona's Research Center for Biosciences & Health Technologies, Campo Grande 376, 1749-024 Lisbon, Portugal.

Different approaches have been reported to enhance penetration of small drugs through physiological barriers; among them is the self-assembly drug conjugates preparation that shows to be a promising approach to improve activity and penetration, as well as to reduce side effects. In recent years, the use of drug-conjugates, usually obtained by covalent coupling of a drug with biocompatible lipid moieties to form nanoparticles, has gained considerable attention. Natural products isolated from plants have been a successful source of potential drug leads with unique structural diversity. In the present work three molecules derived from natural products were employed as lead molecules for the synthesis of self-assembled nanoparticles. The first molecule is the cytotoxic royleanone 7α-acetoxy-6β-hydroxyroyleanone (Roy, ) that has been isolated from hairy coleus ( (Forssk.) Schweinf). ex Sprenger leaves in a large amount. This royleanone, its hemisynthetic derivative 7α-acetoxy-6β-hydroxy-12-benzoyloxyroyleanone (12BzRoy, ) and 6,7-dehydroroyleanone (DHR, ), isolated from the essential oil of thicket coleus ( (Pers.) Benth.) were employed in this study. The royleanones were conjugated with squalene (sq), oleic acid (OA), and/or 1-bromododecane (BD) self-assembly inducers. Roy-OA, DHR-sq, and 12BzRoy-sq conjugates were successfully synthesized and characterized. The cytotoxic effect of DHR-sq was previously assessed on three human cell lines: NCI-H460 (IC 74.0 ± 2.2 µM), NCI-H460/R (IC 147.3 ± 3.7 µM), and MRC-5 (IC 127.3 ± 7.3 µM), and in this work Roy-OA NPs was assayed against Vero-E6 cells at different concentrations (0.05, 0.1, and 0.2 mg/mL). The cytotoxicity of DHR-sq NPs was lower when compared with DHR alone in these cell lines: NCI-H460 (IC 10.3 ± 0.5 µM), NCI-H460/R (IC 10.6 ± 0.4 µM), and MRC-5 (IC16.9 ± 0.5 µM). The same results were observed with Roy-OA NPs against Vero-E6 cells as was found to be less cytotoxic than Roy alone in all the concentrations tested. From the obtained DLS results, 12BzRoy-sq assemblies were not in the nano range, although Roy-OA NP assemblies show a promising size (509.33 nm), Pdl (0.249), zeta potential (-46.2 mV), and spherical morphology from SEM. In addition, these NPs had a low release of Roy at physiological pH 7.4 after 24 h. These results suggest the nano assemblies can act as prodrugs for the release of cytotoxic lead molecules.
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http://dx.doi.org/10.3390/ijms221910210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508833PMC
September 2021

A Rare Cause of Abdominal Pain: Intestinal Angioedema.

J Med Cases 2021 Apr 8;12(4):138-140. Epub 2021 Feb 8.

Internal Medicine Department, Porto University Hospital Center (Centro Hospitalar Universitario do Porto), Porto, Portugal.

Angioedema with evidence of mucosal swelling is a rare condition that can be caused by angiotensin-converting enzyme inhibitors. The authors describe a case of a 28-year-old woman medicated with lisinopril 2 months before, with abdominal pain associated with nausea, vomiting and a onetime watery stool. A small volume of ascites was found in the abdominal ultrasound and the parietal thickening of the middle ileum in the abdominal computed tomography (CT). The complementary study was negative. The symptoms stopped after drug withdrawal. The authors intend to warn to this diagnosis, which has non-specific symptoms and if not suspected, can lead to a great morbidity for patients. The authors also intend to identify various signs that can be clues for its correct diagnosis.
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http://dx.doi.org/10.14740/jmc3651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383657PMC
April 2021

Rosehip Extract-Functionalized Magnesium Hydroxide Nanoparticles and Its Effect on Osteoblastic and Osteoclastic Cells.

Materials (Basel) 2021 Jul 27;14(15). Epub 2021 Jul 27.

Department of Animal Science, University of Trás-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal.

Considering the role of magnesium in bone metabolism and the increasing relevance of plant-mediated green-synthesis, this work compares the bone cytocompatibility of magnesium hydroxide nanoparticles (NPs) produced by using pure water, Mg(OH), or a rosehip (RH) aqueous extract, Mg(OH)RH. The NPs were evaluated for dose- and time-dependent effects on human osteoblastic and osteoclastic response, due to the direct involvement of the two cell types in bone metabolism. Mg(OH) NPs presented nanoplatelet-like morphology (mean diameter ~90 nm) and a crystalline structure (XRD analysis); the RH-mediated synthesis yielded smaller rounded particles (mean diameter <10 nm) with decreased crystallinity. On the ATR-FTIR spectra, both NPs presented the characteristic Mg-OH peaks; Mg(OH)RH exhibited additional vibration bands associated with the presence of phytochemicals. On osteoblastic cells, NPs did not affect cell growth and morphology but significantly increased alkaline phosphatase (ALP) activity; on osteoclastic cells, particles had little effect in protein content, tartrate-resistant acid phosphatase (TRAP) activity, percentage of multinucleated cells, and cell area. However, compared with Mg(OH), Mg(OH)RH increased osteoblastic differentiation by inducing ALP activity and promoting the expression of Runx2, SP7, Col1a1, and ALP, and had a negative effect on the expression of the osteoclastic genes NFATC1, CA2, and CTSK. These observations suggest the potential usefulness of Mg(OH)RH NPs in bone regeneration.
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http://dx.doi.org/10.3390/ma14154172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348532PMC
July 2021

Bioactive Coatings with Ag-Camphorimine Complexes to Prevent Surface Colonization by the Pathogenic Yeast .

Antibiotics (Basel) 2021 May 26;10(6). Epub 2021 May 26.

Centro de Química Estrutural (CQE), Departamento de Engenharia Química, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.

Currently there is a gap between the rate of new antifungal development and the emergence of resistance among clinical strains, particularly threatened by the extreme adhesiveness of to indwelling medical devices. Two silver camphorimine complexes, [Ag(OH){OCHN(CH)NCHO}] (compound P) and [{Ag(OCHNCHCH-p)}(μ-O)] (compound Q), are herein demonstrated as having high inhibiting activity towards the growth of and clinical strains resistant to azoles, the frontline antifungals used in clinical practice. Compounds P and Q were also explored as bioactive coatings to prevent colonization by and colonize the surface of indwelling medical devices, resulting in persistent infections. Functionalization of stainless steel with polycaprolactone (PCL) matrix embedded with compounds P or Q was reported for the first time to inhibit the colonization of by 82% and 75%, respectively. The coating of PCL loaded with Q or P did not cause cytotoxic effects in mammalian cells, demonstrating the biocompatibility of the explored approach. The identification and further exploration of new approaches for surface engineering based on new molecules that can sensitize resistant strains, as herein demonstrated for complexes P and Q, is a significant step forward to improve the successful treatment of candidiasis.
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http://dx.doi.org/10.3390/antibiotics10060638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227220PMC
May 2021

Concomitant allergic contact dermatitis and aquagenic urticaria caused by personal protective equipment in a healthcare worker during the COVID-19 pandemic.

Contact Dermatitis 2021 10 27;85(4):471-472. Epub 2021 May 27.

Allergy and Clinical Immunology Unit, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.

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http://dx.doi.org/10.1111/cod.13897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239518PMC
October 2021

Trabeculectomy with mitomycin C alone or coupled with intracamerular bevacizumab? A 2-year comparative study.

Br J Ophthalmol 2021 Apr 30. Epub 2021 Apr 30.

Ophthalmology, Centro Hospitalar Lisboa Norte, Lisboa, Portugal.

Purpose: To compare outcomes of primary trabeculectomy using either mitomycin C (MMC) alone versus MMC augmented with intracamerular bevacizumab in patients with open-angle glaucoma.

Methods: Retrospective, cohort, two-centre, comparative study. Patients' data were screened between October 2015 and March 2019, with inclusion requiring a minimum follow-up of 24 months. Primary outcome was intraocular pressure (IOP) lowering at 24 months, with surgical success defined with different maximum IOP targets (≤18, ≤16 and ≤14 mm Hg) and at least 30% reduction and higher than 5 mm Hg. Absolute success was achieved if no IOP-lowering medication was needed and a qualified success if otherwise. Safety outcomes were analysed.

Results: A total of 110 eyes underwent trabeculectomy with MMC, 51 of these combined with intracamerular bevacizumab. Both strategies were effective in terms of IOP lowering (baseline vs 2 years postoperatively: 24.4 (8.0) mm Hg vs 12.1 (5.3) mm Hg in the MMC group; 25.1 (8.7) vs 10.8 (3.8) mm Hg in the MMC+bevacizumab group; p<0.001 in both comparisons). The MMC+bevacizumab group had a significant difference towards higher efficacy on absolute success rates at all targets (IOP≤14 or ≤16 or ≤18 mm Hg; p=0.010, p=0.039 and p=0.007, respectively). The large majority (93%) of the MMC+bevacizumab group was drop-free at 24 months, and 41% had IOP below 10 mm Hg. Complication rates were low and similar between groups, with no systemic adverse events.

Conclusions: Intracamerular bevacizumab in MMC-augmented primary trabeculectomy increases the chances of obtaining low IOP outcomes. This strategy may be useful when planning for surgeries aiming at target pressures in the low teens.

Trial Registration Number: ISRCTN93098069.
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http://dx.doi.org/10.1136/bjophthalmol-2021-319039DOI Listing
April 2021

Patch test-proven delayed-type hypersensitivity from naltrexone/bupropion possibly eliciting psoriasis.

Contact Dermatitis 2021 Oct 11;85(4):456-458. Epub 2021 May 11.

Department of Dermatology and Venereology, Hospital de Braga, Braga, Portugal.

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http://dx.doi.org/10.1111/cod.13875DOI Listing
October 2021

Does Fetal Growth Adequacy Affect the Nutritional Composition of Mothers' Milk?: A Historical Cohort Study.

Am J Perinatol 2021 Apr 20. Epub 2021 Apr 20.

Neonatal Intensive Care Unit, Hospital Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal.

Objective:  The study aimed to assess the association between intrauterine growth of preterm infants and energy and macronutrient contents in their mothers' milk.

Study Design:  A historical cohort of mothers of preterm infants was assessed according to offspring's intrauterine growth. Fetal growth restriction (FGR) was defined as small-for-gestational age or appropriate for gestational age with fetal growth deceleration. During the first 4 weeks after delivery, the composition of daily pool samples of mothers' milk was measured by using a mid-infrared human milk analyzer. Explanatory models for milk energy, true protein, total carbohydrate, and fat contents were obtained by generalized additive mixed effects regression models.

Results:  In total, 127 milk samples were analyzed from 73 mothers who delivered 92 neonates. Energy content was significantly higher in mothers with chronic hypertension (average: +6.28 kcal/dL; 95% confidence interval [CI]: 0.54-12.01;  = 0.034) and for extremely preterm compared with very preterm infants (average: +5.95 kcal/dL; 95% CI: 2.16-9.73;  = 0.003), and weakly associated with single pregnancies (average: +3.38 kcal/dL; 95% CI: 0.07-6.83;  = 0.057). True protein content was significantly higher in mothers with chronic hypertension (average: +0.91 g/dL; 95% CI: 0.63-1.19;  < 0.001) and with hypertension induced by pregnancy (average: +0.25 g/dL, 95% CI: 0.07-0.44;  = 0.007), and for extremely preterm compared with very and moderate preterm infants (average: +0.19; 95% CI: 0.01-0.38;  = 0.043 and +0.28 g/dL; 95% CI: 0.05-0.51;  = 0.017, respectively). Fat content was weakly and negatively associated with FGR, both in SGA infants and AGA infants with fetal growth deceleration (average: -0.44 g/dL; 95% CI: -0.92 to -0.05;  = 0.079 and average: -0.36 g/dL; 95% CI: -0.74 to -0.02;  = 0.066, respectively).

Conclusion:  Energy and macronutrient contents in mothers' milk of preterm infants was significantly and positively associated with the degree of prematurity and hypertension. The hypothesis that the composition of milk is associated with FGR was not demonstrated.

Key Points: · Energy and protein are higher for more immature infants.. · Energy and/or protein is higher in hypertension.. · Fat may be lower for infants with intrauterine growth restriction..
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http://dx.doi.org/10.1055/s-0041-1727278DOI Listing
April 2021

Corneal Subbasal Nerve Plexus Evaluation by Confocal Microscopy in Multiple Sclerosis: A Potential New Biomarker.

Curr Eye Res 2021 10 6;46(10):1452-1459. Epub 2021 Apr 6.

Department of Ophthalmology, Hospital CUF Cascais, Cascais, Portugal.

: Our study aims to evaluate corneal subbasal nerve plexus morphology by corneal confocal microscopy (CCM) in Multiple Sclerosis (MS) patients and to explore its potential ability to distinguish between MS patients and healthy subjects.: Cross-sectional study, including 60 MS patients and 22 healthy subjects. Expanded Disability Status Scale (EDSS) was used to assess neurological disability. All participants underwent full ophthalmology evaluation, CCM and optical coherence tomography (OCT). Corneal nerve fibre density (CNFD), branch density (CNBD), fibre length (CNFL) and fibre tortuosity (CNFT) were analysed. Generalized additive regression models were used to analyse the data.: Compared to controls, MS patients had lower CNFD, CNBD and CNFL ( < .001) and higher CNFT ( = .002). The area under the ROC curve to distinguish MS patients from healthy controls with CNFD and CNBD was 0.84 (95%CI: 0.75 to 0.93; 95%CI: 0.75 to 0.92, respectively). A nonlinear association between EDSS and CNFD was found, with an initial density increase followed by a significant decrease until more severe disability status. EDSS was associated with CNFL and CNBD, with values being significantly lower for patients with an EDSS > 2.5 (-2.06 mm/mm2; 95%CI: -3.84 to -0.28; = .027 and -8.70 branches/mm2; 95%CI: -14.69 to -2.71; = .006, respectively). An optic neuritis (ON) history did not influence CCM parameters.: Our results confirm CCM parameters' potential to differentiate MS patients from healthy subjects, not being influenced by a previous ON history. A significant relationship between patient's disability and corneal nerve morphology was also found.
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http://dx.doi.org/10.1080/02713683.2021.1904509DOI Listing
October 2021

Burkholderia cenocepacia transcriptome during the early contacts with giant plasma membrane vesicles derived from live bronchial epithelial cells.

Sci Rep 2021 03 11;11(1):5624. Epub 2021 Mar 11.

iBB-Institute for Bioengineering and Biosciences, Biological Sciences Research Group, Av. Rovisco Pais 1, 1049-001, Lisbon, Portugal.

Burkholderia cenocepacia is known for its capacity of adherence and interaction with the host, causing severe opportunistic lung infections in cystic fibrosis patients. In this work we produced Giant Plasma Membrane Vesicles (GPMVs) from a bronchial epithelial cell line and validated their use as a cell-like alternative to investigate the steps involved in the adhesion process of B. cenocepacia. RNA-sequencing was performed and the analysis of the B. cenocepacia K56-2 transcriptome after the first contacts with the surface of host cells allowed the recognition of genes implicated in bacterial adaptation and virulence-associated functions. The sensing of host membranes led to a transcriptional shift that caused a cascade of metabolic and physiological adaptations to the host specific environment. Many of the differentially expressed genes encode proteins related with central metabolic pathways, transport systems, cellular processes, and virulence traits. The understanding of the changes in gene expression that occur in the early steps of infection can uncover new proteins implicated in B. cenocepacia-host cell adhesion, against which new blocking agents could be designed to control the progression of the infectious process.
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http://dx.doi.org/10.1038/s41598-021-85222-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970998PMC
March 2021

Functional Outcome After Mechanical Thrombectomy with or without Previous Thrombolysis.

J Stroke Cerebrovasc Dis 2021 Feb 10;30(2):105495. Epub 2020 Dec 10.

Unidade Cerebrovascular, Departamento de Neurociências do Centro Hospitalar Universitário Lisboa Central Portugal. Electronic address:

Introduction: Combined intravenous therapy (IVT) and mechanical thrombectomy (MT) is the standard treatment for acute ischemic stroke (AIS) with large vessel occlusion (LVO). However, the use of  IVT before MT is recently being questioned.

Objectives: To compare patients treated with IVT before MT with those treated with MT alone, in a real-world scenario.

Methods: Retrospective analysis of AIS patients with LVO of the anterior circulation who underwent MT, with or without previous IVT, between 2016 and 2018.

Results: A total of 524 patients were included (347 submitted to IVT+MT; 177 to MT alone). No differences between groups were found except for a higher time from stroke onset to CT and to groin puncture in the MT group (297.5 min vs 115.0 min and 394.0 min vs 250.0 min respectively, p < 0.001). Multivariable analysis showed that age<75 years (OR 2.65, 95% CI 1.71-4.07, p < 0.001), not using antiplatelet therapy (OR 1.93, 95% CI 1.21-3.08, p = 0.006), low prestroke mRS (OR 4.33, 95% CI 1.89-9.89, p < 0.001), initial NIHSS (OR 0.89, 95% CI 0.86-0.93, p < 0.001), absent cerebral edema (OR 7.83, 95% CI 3.31-18.51, p < 0.001), and mTICI 2b/3 (OR 4.56, 95% CI 2.17-9.59, p < 0.001) were independently associated with good outcome (mRS 0-2).

Conclusions: Our findings support the idea that IVT before MT does not influence prognosis, in a real-world setting.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105495DOI Listing
February 2021

Exploring antibiotic resistance in environmental integron-cassettes through intI-attC amplicons deep sequencing.

Braz J Microbiol 2021 Mar 27;52(1):363-372. Epub 2020 Nov 27.

Departamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Antônio Carlos 6627, Belo Horizonte, MG, 31270-901, Brazil.

Introduction: Freshwater ecosystems provide propitious conditions for the acquisition and spread of antibiotic resistance genes (ARGs), and integrons play an important role in this process.

Material And Methods: In the present study, the diversity of putative environmental integron-cassettes, as well as their potential bacterial hosts in the Velhas River (Brazil), was explored through intI-attC and 16S rRNA amplicons deep sequencing. RESULTS AND DISCUSSION: ORFs related to different biological processes were observed, from DNA integration to oxidation-reduction. ARGs-cassettes were mainly associated with class 1 mobile integrons carried by pathogenic Gammaproteobacteria, and possibly sedentary chromosomal integrons hosted by Proteobacteria and Actinobacteria. Two putative novel ARG-cassettes homologs to fosB3 and novA were detected. Regarding 16SrRNA gene analysis, taxonomic and functional profiles unveiled Proteobacteria, Bacteroidetes, Firmicutes, and Actinobacteria as dominant phyla. Betaproteobacteria, Alphaproteobacteria, and Actinobacteria classes were the main contributors for KEGG orthologs associated with resistance.

Conclusions: Overall, these results provide new information about environmental integrons as a source of resistance determinants outside clinical settings and the bacterial community in the Velhas River.
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http://dx.doi.org/10.1007/s42770-020-00409-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966681PMC
March 2021

Retinal and choroidal thickness changes in systemic lupus erythematosus patients: a longitudinal study.

Eye (Lond) 2021 10 24;35(10):2771-2780. Epub 2020 Nov 24.

Department of Ophthalmology, Centro Hospitalar Universitário de Coimbra, Coimbra, Portugal.

Background/objectives: To prospectively evaluate changes in peripapillary retinal nerve fibre layer (pRNFL), in all macular layers and in choroidal thickness (CT) in a cohort of systemic lupus erythematosus (SLE) patients without ophthalmologic manifestations. To associate those changes with ophthalmic characteristics, disease activity state, medication and systemic comorbidities.

Subjects/methods: Prospective cohort study of 68 previously diagnosed SLE patients. In two study visits (V1 and V2) at least 12 months apart, patients underwent a complete ophthalmologic examination including spectral domain-optical coherence tomography (SD-OCT) and an autoimmune disease specialist assessment. Automatic retinal segmentation was performed. pRNFL was determined globally and in the six peripapillary sectors and each macular layer thickness was determined in the nine early treatment diabetic retinopathy study (ETDRS) subfields. CT was manually measured at 13 locations in the posterior pole. Only one eye per patient was randomly selected for inclusion. Generalised linear mixed effects models were employed.

Results: Sixty-five patients completed the study. The median follow-up time was twelve months. At V2, pRNFL was significantly thinner globally (p = 0.006) and in the temporal inferior sector (p = 0.017). Patients under chronic medication with anticoagulants or antihypertensives had significantly thinner pRNFL in some locations. No significant changes were observed in macular layers or choroidal thickness between study visits.

Conclusions: SLE patients presented early SD-OCT signs of neurodegeneration, evidenced by a progressive reduction in pRNFL thickness. Regardless of study visit, baseline chronic medication with anticoagulants or antihypertensives was associated with lower pRNFL thickness, accounting for a deleterious effect of cardiovascular risk factors.
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http://dx.doi.org/10.1038/s41433-020-01292-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452661PMC
October 2021

Retinal structural changes in preterm children without retinopathy of prematurity.

Graefes Arch Clin Exp Ophthalmol 2021 Apr 4;259(4):1025-1033. Epub 2020 Nov 4.

Departamento Oftalmologia, Hospital CUF Cascais, R. Fernão Lopes 60, 2750-663 Cobre, Cascais, Lisbon, Portugal.

Purpose: The aim of this study was to compare all retinal layers' thickness in full-term and preterm children without retinopathy of prematurity (ROP).

Methods: Cross-sectional study including two groups of patients: group 1 children with history of preterm gestation without ROP (gestational age < 37 weeks) and group 2 healthy children with history of full-term gestation. All subjects underwent an ophthalmic examination including spectral domain-optical coherence tomography. After automatic retinal segmentation, each retinal layer thickness (eight separate layers and overall thickness) was calculated in all nine Early Treatment Diabetic Retinopathy Study areas. Demographic, systemic, gestational, and birth data were collected. Generalized additive regression models were used to analyze the data.

Results: Fifty-one children (51 eyes) were recruited, 19 full-term and 32 preterm children, mean age at ophthalmic examination of 10.58 (4.21) and 14.13 (3.16), respectively. In multivariable analysis, the preterm group's retinal thickness was significantly decreased in total retina nasal outer sector, ganglion cell layer (GCL), and inner plexiform layer (IPL), specifically GCL temporal outer (p = 0.010), GCL superior outer (p = 0.009), IPL temporal outer (p = 0.022), and IPL superior outer (p = 0.004), when compared with full-term group. From the variables compared only with birth head circumference that influenced the models, a non-linear association was identified and consequently modeled with splines through a generalized additive model.

Conclusion: This study suggests that preterm children without ROP have structural retinal alterations, mostly in GCL and IPL in outer areas of the macula. Therefore, it is crucial to question gestational history since these retinal changes may be found later in life leading to useless investigation.
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http://dx.doi.org/10.1007/s00417-020-04986-0DOI Listing
April 2021

How does the Leader's Centrality affect Team Performance Assessment? Testing the Role of Leader's Satisfaction.

Span J Psychol 2020 Oct 15;23:e38. Epub 2020 Oct 15.

CeBER, Universidade de Coimbra, Portugal.

The study aims to test how the association between leader's centrality (outdegree and betweenness) in the group network, considering both workflow and friendship ties between leader and members, and the perception of team performance is mediated by the leader's satisfaction with the team. The research included a total of 74 formal leaders of organizational teams from several organizations. Total, direct and indirect effects were calculated through the estimation of an OLS regression-based mediation model, controlling for team size. Results revealed that only leader's outdegree and betweenness centrality in the team friendship network positively predicted the leader's perception of team performance. In contrast to the predictions, a significant negative indirect effect of outdegree centrality of the leader within the team workflow network on the evaluation of group performance through leader's satisfaction was observed. Also, both leader´s outdegree and betweenness centrality levels in the friendship network were shown to have a positive effect on leader's assessment of team performance through leader's satisfaction with the team. Overall, findings point to the negative effects of leader's centrality in the workflow team network and the positive effects of leader's centrality in the friendship team network on his/her attitudes toward the team. The effects of the more or less central position of the leader within each of the group networks are discussed.
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http://dx.doi.org/10.1017/SJP.2020.42DOI Listing
October 2020

Evolution of Resting Energy Expenditure, Respiratory Quotient, and Adiposity in Infants Recovering from Corrective Surgery of Major Congenital Gastrointestinal Tract Anomalies: A Cohort Study.

Nutrients 2020 Oct 11;12(10). Epub 2020 Oct 11.

NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Campo dos Mártires da Pátria, Number 130, 1169-056 Lisbon, Portugal.

This cohort study describes the evolution of resting energy expenditure (REE), respiratory quotient (RQ), and adiposity in infants recovering from corrective surgery of major congenital gastrointestinal tract anomalies. Energy and macronutrient intakes were assessed. The REE and RQ were assessed by indirect calorimetry, and fat mass index (FMI) was assessed by air displacement plethysmography. Longitudinal variations over time are described. Explanatory models for REE, RQ, and adiposity were obtained by multiple linear regression analysis. Twenty-nine infants were included, 15 born preterm and 14 at term, with median gestational age of 35.3 and 38.1 weeks and birth weight of 2304 g and 2935 g, respectively. In preterm infants, median REE varied between 55.7 and 67.4 Kcal/kg/d and median RQ increased from 0.70 to 0.86-0.92. In term infants, median REE varied between 57.3 and 67.9 Kcal/kg/d and median RQ increased from 0.63 to 0.84-0.88. Weight gain velocity was slower in term than preterm infants. FMI, assessed in a subset of 15 infants, varied between a median of 1.7 and 1.8 kg/m at term age. This low adiposity may be related to poor energy balance, low fat intakes, and low RQ¸ that were frequently recorded in several follow-up periods.
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http://dx.doi.org/10.3390/nu12103093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599456PMC
October 2020

Prostate cancer with cribriform pattern: Exclusion criterion for active surveillance?

Arch Ital Urol Androl 2020 Oct 2;92(3). Epub 2020 Oct 2.

Urology Department, Central Lisbon Hospital Center, Lisbon.

Introduction: Following the 2014 International Society of Urological Pathology meeting, a rapidly growing body of evidence by several researchers has been demonstrating a poor prognosis in association with cribriform morphology. The aim of our study was to describe the presence of cribriform foci in specimens of radical prostatectomies and to evaluate whether demographic and clinical characteristics are associated with the presence of cribriform pattern.

Materials And Methods: This cohort study was based on 70 radical retropubic prostatectomies specimens collected between 2012 and 2016 and evaluated for the association of the cribriform pattern with age, prostate-specific antigen at surgery day, Gleason on biopsy, Gleason after radical prostatectomy, extracapsular extension, vesicles invasion, margins, multiparametric magnetic resonance imaging, and post-operative radiotherapy. Results; From the univariable analysis, biochemical prostatespecific antigen recurrence (p = 0.001), extracapsular extension (p = 0.003), pre-operative prostate-specific antigen (p = 0.017), vesicles invasion, (p = 0.038) and post-operative radiotherapy (p < 0.001) showed an association with the presence of cribriform pattern. There was also a significant difference of cribriform pattern and Gleason 7 in needle biopsy (p = 0.020) and cribriform pattern and Gleason 8 or 9 in radical prostatectomy specimen (p = 0.036).

Conclusions: In our study, the increase in preoperative prostate-specific antigen had a high association with cribriform pattern. Further evidence is needed to discriminate preoperative prostate specific antigen values that might potentially be associated with the presence of cribriform pattern. Raising our knowledge about the cribriform pattern can be an excellent opportunity to correctly identify and treat patients who will eventually die from prostate cancer, sparing treatment in those who will not.
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http://dx.doi.org/10.4081/aiua.2020.3.235DOI Listing
October 2020

Flexible ZnO-mAb nanoplatforms for selective peripheral blood mononuclear cell immobilization.

Sci Rep 2020 09 14;10(1):15018. Epub 2020 Sep 14.

Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001, Lisboa, Portugal.

Cancer is the second cause of death worldwide. This devastating disease requires specific, fast, and affordable solutions to mitigate and reverse this trend. A step towards cancer-fighting lies in the isolation of natural killer (NK) cells, a set of innate immune cells, that can either be used as biomarkers of tumorigenesis or, after autologous transplantation, to fight aggressive metastatic cells. In order to specifically isolate NK cells (which express the surface NKp30 receptor) from peripheral blood mononuclear cells, a ZnO immunoaffinity-based platform was developed by electrodeposition of the metal oxide on a flexible indium tin oxide (ITO)-coated polyethylene terephthalate (PET) substrate. The resulting crystalline and well-aligned ZnO nanorods (NRs) proved their efficiency in immobilizing monoclonal anti-human NKp30 antibodies (mAb), obviating the need for additional procedures for mAb immobilization. The presence of NK cells on the peripheral blood mononuclear cell (PBMCs) fraction was evaluated by the response to their natural ligand (B7-H6) using an acridine orange (AO)-based assay. The successful selection of NK cells from PBMCs by our nanoplatform was assessed by the photoluminescent properties of AO. This easy and straightforward ZnO-mAb nanoplatform paves the way for the design of biosensors for clinic diagnosis, and, due to its inherent biocompatibility, for the initial selection of NK cells for autotransplantation immunotherapies.
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http://dx.doi.org/10.1038/s41598-020-72133-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490409PMC
September 2020

Better balance: a randomised controlled trial of oculomotor and gaze stability exercises to reduce risk of falling after stroke.

Clin Rehabil 2021 Feb 9;35(2):213-221. Epub 2020 Sep 9.

Epidemiology and Statistics Office of the Research Unit, Centro Hospitalar Universitário Lisboa Central, Lisboa, Portugal.

Objective: To assess the effect of a domiciliary program of oculomotor and gaze stability exercises on the incidence of falls and risk of fall in stroke survivors.

Design: Two-arm, non-blinded parallel randomized controlled trial.

Subjects: Stroke survivors older than 60 years, with positive Romberg test and autonomous gait after the stroke.

Setting: Physiotherapy outpatient clinic of a tertiary care hospital.

Interventions: Every participant accomplished the current rehabilitation program; the intervention group was randomly allocated into an additional three weeks intervention with a domiciliary program of oculomotor and gaze stability exercises.

Main Measures: Primary outcome was the incidence of falls through the three weeks after the intervention started; in addition, the variation of the estimated risk for falling assessed by both Berg Balance Scale (four points) and Timed Up and Go Test (four seconds) was the secondary outcome.

Results: 79 patients were recruited and 68 completed the protocol (control group 35; intervention group 33). During the follow up, falls were registered in 4/35 participants in the control group and no event occurred in the intervention group ( = 0.064). The estimated risk for falling decreased in 11/35 control group participants and in 28/33 intervention group participants (RR 0.37; 95%CI 0.22-0.62; < 0.001).

Conclusion: After three weeks of a domiciliary program of oculomotor and gaze stability exercises, the estimated risk of falling significantly diminished and no falls occurred among the intervention group. These findings encourage further exploration of this promising intervention.

Trial Registration: ClinicalTrials.gov Identifier: NCT02280980.
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http://dx.doi.org/10.1177/0269215520956338DOI Listing
February 2021

Mechanical thrombectomy in stroke in nonagenarians: useful or futile?

J Stroke Cerebrovasc Dis 2020 Sep 16;29(9):105015. Epub 2020 Jun 16.

Neuroradiology Department - Hospital de São Jose, Centro Hospitalar Universitário de Lisboa Central; Faculdade de Ciências Médicas/NOVA Medical School, Universidade Nova de Lisboa. Electronic address:

Background: Mechanical thrombectomy is the standard treatment in acute ischemic stroke due to large vessel occlusion, but there is limited evidence about its efficacy in very old patients. We sought to analyse safety and effectiveness of mechanical thrombectomy in nonagenarian versus octagenarian patients.

Methods: We included consecutive patients with acute ischemic stroke due to large vessel occlusion subjected to mechanical thrombectomy, during 29 months in a tertiary center. Patients were divided into two sub-groups, according to age: 80-89 and >90 years old. Recanalization, complications, functional outcome and mortality at discharge and at 3 months were compared. Multivariable analysis was performed to identify independent predictors of functional outcome at 3 months of follow-up, assessed by the modified Rankin Scale.

Results: A total of 128 octogenarians (88.9%) and 16 nonagenarians (11.1%) met the inclusion criteria. Successful revascularization was achieved in 87.5% of octagenarians and in 81.3% of nonagenarians (p = 0.486). Symptomatic hemorrhage occurred in 3.1% and 6.3% of younger and older patients, respectively (p = 0.520). Cerebral edema occured in 35.2% of octagenarians versus 25.0% of nonagenarians (p = 0.419). Functional independence (mRS ≤ 2) at 3 months was achieved in 28 (22.6%) and 5 (31.3%) of octagenarians and nonagenarians, respectively (p = 0.445). Mortality at 3 months was not significantly higher in nonagenarians (37.5%) versus octagenarians (33.9%, p = 0.773).

Conclusions: No significant diferences were found in functional outcome, mortality, recanalization and complication rates between octagenarians and nonagenarians submitted to mechanical thrombectomy, underlining that patients should not be excluded from mechanical thrombectomy based on age alone.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105015DOI Listing
September 2020

Citrate zinc hydroxyapatite nanorods with enhanced cytocompatibility and osteogenesis for bone regeneration.

Mater Sci Eng C Mater Biol Appl 2020 Oct 2;115:111147. Epub 2020 Jun 2.

Centro Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal; EST Setúbal, CDP2T, Instituto Politécnico de Setúbal, Campus IPS, 2910 Setúbal, Portugal. Electronic address:

The development of biomaterials that mimicking the hydroxyapatite nanoparticles existent in the immature bone tissue is crucial, especially to accelerate the bone remodeling and regeneration. In this work, it was developed for the first time, hydroxyapatite nanoparticles (NPs) incorporating citrate and zinc (cit-Zn-Hap) in their composition towards a one-step hydrothermal procedure. For comparison purposes, hydroxyapatite NPs incorporating only zinc (Zn-Hap) or citrate (cit-Hap), as well as hydroxyapatite without any of these elements (Hap) were synthesised. The physicochemical characterization was carried out reveling that, the presence of zinc on hydroxyapatite (cit-Zn-Hap), reduced the size of nanoparticles, changed the phosphate environment and decreased the surface charge when compared with cit-Hap nanoparticles. The osteogenic potential of cit-Zn-Hap NPs was analysed in human bone marrow-derived stromal cells (BMSCs), in the absence of osteoinductive factors. NPs were internalized by endocytosis appearing trapped in endosomes and lysosomes scattered through the cytoplasm. Exposure to these NPs resulted in a significant induction of ALP activity, extracellular matrix mineralization, and gene expression of early and later osteogenic transcription factors, as well as of osteoblastic markers. The osteoinductive effect might be regulated, at least in part, by the increased signalling through the canonical WNT pathway. Evaluation of the cell behaviour following exposure to Zn-Hap and cit-Hap strongly suggested a synergistic effect of citrate and Zn in cit-Zn-Hap NPs towards the induction of the osteogenic commitment and functionality of BMSCs. These findings will allow the design of new biomimetic hydroxyapatite nanoparticles with great potential for bone regeneration.
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http://dx.doi.org/10.1016/j.msec.2020.111147DOI Listing
October 2020

Pheochromocytoma Due to Mutation - The Importance of Genetic Testing for Clinical Decision.

Eur Endocrinol 2020 Apr 1;16(1):72-74. Epub 2020 Apr 1.

Braga Public Hospital, Braga, Portugal.

Apreviously healthy 53-year-old woman presented with new onset arterial hypertension diagnosed during workup for daily pulsatile bilateral frontal headaches and paroxysmal episodes of fatigue, palpitations and sweating. High urinary metanephrines were detected and an abdominal magnetic resonance image evidenced two nodular bilateral adrenal lesions and a left iliac focal lesion. F-FDG-PET/CT (fluorodeoxyglucose-positron emission tomography/computed tomography) scanning revealed mild-to-moderate uptake in both adrenal lesions and mild uptake in the iliac bone, whereas I-metaiodobenzylguanide scintigraphy revealed uptake only in the right adrenal. CT-scan confirmed the heterogeneous nodular lesion on the right adrenal gland as suspicious for pheochromocytoma and a non-specific sclerotic lesion in the iliac. A right adrenalectomy was performed with posterior resolution of symptoms and normalisation of urinary metanephrines. Histology confirmed a pheochromocytoma and later a mutation of the gene was detected. The present case highlights the importance of genetic testing for pheochromocytoma in order to better guide the management of these patients.
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http://dx.doi.org/10.17925/EE.2020.16.1.72DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308108PMC
April 2020
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