Publications by authors named "Isabel Santos"

213 Publications

Reproduction-related cognitive processing and distress among young adult women: the role of personal breast cancer history.

Cogn Process 2021 Apr 2. Epub 2021 Apr 2.

Center for Health Technology and Services Research (CINTESIS), Department of Education and Psychology, University of Aveiro, Campus Universitário de Santiago, 3810-193, Aveiro, Portugal.

Breast cancer diagnosis can threaten fertility and biological motherhood in women of reproductive age due to the gonadotoxic effects of treatments. Much evidence documents these women fertility-related concerns and distress, but no study has attempted to understand how implicit cognitive processes can contribute to this maladjustment. In this research, we explored whether reproduction-related stimuli interfere with cognition among cancer survivors with infertility risk using an emotional Stroop task. Furthermore, we investigated the relationship between reproduction-related cognitive processing and psychological morbidity. Young cancer survivors aged 18-40 years who received anticancer treatments and an age-matched non-cancer control group without known fertility problems were compared. Color-naming times and error rates were assessed. Participants in both groups were slower naming the color of reproduction-related words in comparison to unrelated negative valence words. Although in the same direction, this difference did not reach statistical significance for positive and neutral unrelated word lists. Further analysis suggested that biased attention toward reproduction-related information was associated with higher depression levels in young women with personal breast cancer history, but not in healthy women. These findings suggest that biased processing of reproduction-related cues might be a vulnerability factor after a breast cancer diagnosis. Additionally, this study puts in evidence the potential usefulness of using experimental tasks to investigate attentional bias in a context where fertility is at risk.
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http://dx.doi.org/10.1007/s10339-021-01026-5DOI Listing
April 2021

[Autism Spectrum Disorder in Infancy and Early Childhood: The Model of the Centro de Estudos do Bebé e da Criança for Diagnosis and Therapeutic Intervention].

Acta Med Port 2021 Jan 27. Epub 2021 Jan 27.

Centro de Estudos do Bebé e da Criança. Unidade de Desenvolvimento. Hospital Dona Estefânia. Centro Hospitalar Universitário de Lisboa Central. Lisboa. Portugal.

Introduction: The Centro de Estudos do Bebé e da Criança in Hospital Dona Estefânia has organized a multidisciplinary model for children under three with suspected autism spectrum disorder, thus implementing the recent guidelines established by the Directorate General for Health. The aim of this study is to describe this model and case series.

Material And Methods: A retrospective descriptive study of observed children with suspected ASD. They were observed according to the model of the Centro de Estudos do Bebé e da Criança and DC:0-5TM classification, between January 2018 and September 2019.

Results: The study included 178 children. The average age at the initial assessment was 27 months. From the total sample, 116 children concluded the diagnostic sessions (axis I): Autism Spectrum Disorder/Early Atypical (36%), Developmental Language Disorder (18%), Other (19%). Factors of axes II, III, IV and V of DC:0-5TM were determinant for clinical diagnosis in 26%.

Discussion: Of 116 children, 36% were diagnosed with Autism Spectrum Disorder. This highlights the diagnostic challenge posed by neurodevelopmental disorders in early infancy. The sample shows that the characteristics of the relationship with the caregiver (axis II), presence of physical conditions (axis III), psycho-social stressors (axis IV) and developmental trajectory (axis V) have a significant clinical impact. In the future, the initial assessment should take place well before the age of 27 months because of the impact on prognosis.

Conclusion: This model is a pioneering approach in Portugal. It promotes a common approach of Child and Adolescent Psychiatry and Neuropediatrics/Developmental Pediatrics in early infancy. Moreover, it increases the diagnostic acuity of Autism Spectrum Disorders and early therapeutic intervention.
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http://dx.doi.org/10.20344/amp.13397DOI Listing
January 2021

Gallium and indium complexes with new hexadentate bis(semicarbazone) and bis(thiosemicarbazone) chelators.

Dalton Trans 2021 Feb;50(5):1631-1640

Instituto de Química de São Carlos, Universidade de São Paulo, CEP 13566-590 São Carlos, SP, Brazil.

The synthesis of two new hexadentate potentially tetra-anionic acyclic chelators, an N2O4-donor bis(semicarbazone) (H4bsc) and an N2O2S2-donor bis(thiosemicarbazone) (H4btsc), is described. Coordination reactions of the ligands with gallium and indium precursors were investigated and yielded the complexes [Ga(Hbsc)] (1) and [In(Hbtsc)] (2), respectively. Ligands and complexes structures were confirmed by several techniques, including FTIR, NMR (1H, 13C, COSY, HSQC), ESI(+)-MS and single crystal X-ray diffraction analysis. The radioactive congeners [67Ga(Hbsc)] (1*) and [111In(Hbtsc)] (2*) were also synthesized and their radiolabeling yield and radiochemical purity were certified by HPLC and ITLC analyses. Biodistribution assays in groups of CD-1 mice showed a high uptake of both radiocomplexes in liver and intestine where 1* presented higher retention. In vitro and in vivo assays revealed higher stability of 1* compared with 2*, namely in the blood. The results suggest that radiocomplex 1* is a candidate for further investigation as it could be prepared in high yields (>95%), at low temperature (20-25 °C) and at fast reaction time (15 min), which are very desirable synthesis conditions for potential new radiopharmaceuticals.
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http://dx.doi.org/10.1039/d0dt04028bDOI Listing
February 2021

What happens in Brazil? A pandemic of misinformation that culminates in an endless disease burden.

Rev Soc Bras Med Trop 2020 21;54:e07132020. Epub 2020 Dec 21.

Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Bioquímica e Imunologia, Ribeirão Preto, SP, Brasil.

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http://dx.doi.org/10.1590/0037-8682-0713-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7747809PMC
January 2021

Corrigendum: Impact of Hydroxychloroquine on Antibody Responses to the SARS-CoV-2 Coronavirus.

Front Immunol 2020 2;11:615628. Epub 2020 Nov 2.

Nathan Portela Institute of Tropical Medicine, Federal University of Piauí, Teresina, Brazil.

[This corrects the article DOI: 10.3389/fimmu.2020.01739.].
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http://dx.doi.org/10.3389/fimmu.2020.615628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667991PMC
November 2020

Conducting neutral gold bisdithiolene complex [Au(dspdt)]˙.

Dalton Trans 2020 Oct;49(39):13737-13743

Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, E.N. 10, P-2695-066 Bobadela LRS, Portugal. and Departamento de Engenharia e Ciências Nucleares, Instituto Superior Técnico, Universidade de Lisboa, E.N. 10, P-2695-066 Bobadela LRS, Portugal.

[Au(dspdt)2] (dspdt = 2,3-dihydro-5,6-selenophenedithiolate) is an unprecedented example of a neutral gold bisdithiolene complex with a unique structure composed of interacting dimer and trimer chains displaying relatively high electrical conductivity (0.1 S cm-1 at room temperature).
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http://dx.doi.org/10.1039/d0dt02931aDOI Listing
October 2020

Fertility under uncertainty: exploring differences in fertility-related concerns and psychosocial aspects between breast cancer survivors and non-cancer infertile women.

Breast Cancer 2020 Nov 24;27(6):1177-1186. Epub 2020 Jun 24.

Center for Health Technology and Services Research (CINTESIS), Department of Education and Psychology, University of Aveiro, Campus Universitário de Santiago, 3810-193, Aveiro, Portugal.

Background: The threat to fertility due to anticancer treatments can be distressing to women who wish to complete their family. The current study assessed the fertility-related concerns, psychological distress and health-related quality of life (HRQoL) of breast cancer survivors in comparison to non-cancer women with infertility history and to healthy controls from the general population.

Methods: We surveyed young adult women aged 18 to 40 who wished to have a (or another) biological child. Participants completed self-report measures assessing fertility concerns, anxiety, depression and physical, emotional, role and social functioning. Group differences were assessed using multivariate comparisons as well as univariate tests and discriminant analysis for individual measures.

Results: A total of 136 women were recruited, of whom 43 were breast cancer survivors, 56 non-cancer infertile women and 37 healthy controls. Considering the female cancer survivors as the focus of the analysis, data suggested that these women presented identical concerns to the non-cancer infertile group and higher than the healthy women with regard to fertility potential (p < 0.01). However, women diagnosed with cancer reported worse HRQoL than their counterparts, showing lower scores in physical functioning (p < 0.05) than infertile women and lower role (p < 0.05) and social HRQoL (p < 0.01) than the controls. Anxiety and depressive symptoms did not differ between the three groups.

Conclusions: The results suggest that living with uncertainty about reproductive potential after cancer can be a disruptive experience. Breast cancer survivors and infertile women are at risk of future emotional maladjustments, given the reported level of fertility concern.
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http://dx.doi.org/10.1007/s12282-020-01124-wDOI Listing
November 2020

The European Portuguese version of the Reproductive Concerns After Cancer Scale (RCACS): A psychometric validation for young adult female cancer survivors.

Eur J Oncol Nurs 2020 Aug 12;47:101781. Epub 2020 Jun 12.

Center for Health Technology and Services Research (CINTESIS), Department of Education and Psychology, University of Aveiro, Aveiro, Portugal. Electronic address:

Purpose: The purpose of this study was to evaluate the psychometric properties of the Portuguese version of the 18-item Reproductive Concerns After Cancer Scale (RCACS) among young adult female cancer survivors.

Methods: The psychometric validation was conducted based on a convenience sample of 192 cancer survivors aged between 18 and 40 years. An exploratory factor analysis (EFA) was used to test the factor structure of the Portuguese version of RCACS and reliabilities were examined. Convergent and discriminant validity was also used to assess the construct validity. The Hospital Anxiety and Depression Scale (HADS), the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORT QLQ-C30) and the need for parenthood and rejection of child-free lifestyle subscales of the Fertility Problem Inventory (FPI) were used as convergent measures.

Results: A five-factor model was obtained with acceptable fit indexes and internal consistencies (.72<α<.89): (1) fertility potential, (2) children's health risk and future life, (3) partner disclosure, (4) barriers to getting pregnant/having children and (5) acceptance. Overall, convergent and discriminant validities were confirmed. Levels of anxiety and depression symptoms as well as health-related quality of life (QoL) had weak-to-moderate associations with reproductive concerns. Women who had a child or did not want a biological child were less concerned.

Conclusion: This scale proved to be a reliable and valid measure of reproductive concerns for the Portuguese population with potential relevance for application in clinical practice.
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http://dx.doi.org/10.1016/j.ejon.2020.101781DOI Listing
August 2020

[Co/Fe(α-Alkyl-tpdt)]: Alkyl-Substituted Cobalt and Iron Bis-dithiolenethiophenic Complexes.

Inorg Chem 2020 Jul 16;59(13):9261-9269. Epub 2020 Jun 16.

Departament de Quı́mica Inorgànica i Orgànica, Institut de Quı́mica Teòrica i Computacional, Diagonal 645, 08028 Barcelona, Spain.

Tetraphenylphosphonium salts of Co and Fe complexes with alkyl-substituted, -butyl (), and isopropyl () 2,3-thiophenedithiolate (α-tpdt) ligands, namely, TPP[Co(α--tpdt)] (), TPP[Fe(α--tpdt)] (-), TPP[Co(α--tpdt)] (), and TPP[Fe(α--tpdt)] () were prepared and characterized by cyclic voltammetry, single crystal X-ray diffraction, magnetic susceptibility measurements, and Fe Mössbauer spectroscopy. Compound and are isostructural with their Au and Ni analogues with a square-planar coordination geometry. Compound presents two polymorphs (-) both showing a Fe(III) bisdithiolene dimerization. The magnetic susceptibility of and exhibits behavior dominated by antiferromagnetic interactions, with room-temperature magnetic moments of 3.40 and 3.36 μB, respectively, indicating that these square-planar Co(III) complexes assume an intermediate spin electronic configuration ( = 1) as supported by multiconfigurational and DFT calculations.
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http://dx.doi.org/10.1021/acs.inorgchem.0c01154DOI Listing
July 2020

Toward an Understanding of the Factors Associated With Reproductive Concerns in Younger Female Cancer Patients: Evidence From the Literature.

Cancer Nurs 2020 May 11. Epub 2020 May 11.

Author Affiliations: Center for Health Technology and Services Research (CINTESIS), Department of Education and Psychology, University of Aveiro (Drs Bártolo and Monteiro); William James Center for Research, Department of Education and Psychology, University of Aveiro, Aveiro, Portugal (Dr Santos).

Background: Cancer treatments may compromise fertility and family building in reproductive-age women. Previous research has shown that younger women with cancer experienced several reproductive health concerns.

Objective: The aim of this study was to conduct a focused review of existing research about the subjective perceptions of reproductive concerns among young women with cancer (aged 15-49 years) and identify their potential predictors and outcomes.

Methods: A systematic synthesis of mixed-methods research was conducted including peer-reviewed articles in English. Relevant studies were identified through the electronic databases Scopus, Web of Science, PubMed, ProQuest, and Psychology & Behavioral Sciences Collection (through EBSCOhost).

Results: A total of 22 reports met the eligibility criteria (8 qualitative and 14 quantitative). Research showed that younger women reported concerns related to their fertility status and/or own health after conception, their children's health, and their dyadic relationships. Redefinition of the motherhood role and the family future were also a source of concern. However, there is variance among women in concerns and experiences based on life stages and expectations.

Conclusions: Reproductive concerns seem to be affected by personal circumstances and previous therapeutics. These concerns constitute a potential risk factor, simultaneously, for psychosocial maladjustment and adherence to endocrine therapy and fertility care.

Implications For Practice: This article proposes a conceptual framework to understand the dimensions and potential predictors and outcomes of perceived concerns among reproductive-age cancer patients. Our data allow us to look at these concerns from a multifactorial perspective, identifying areas to be addressed in providing clinical care, namely, by nurses accompanying patients over an extended period.
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http://dx.doi.org/10.1097/NCC.0000000000000822DOI Listing
May 2020

Depression and Health-Related Quality of Life Among Young Adult Breast Cancer Patients: The Mediating Role of Reproductive Concerns.

J Adolesc Young Adult Oncol 2020 06 24;9(3):431-435. Epub 2020 Mar 24.

Center for Health Technology and Services Research (CINTESIS), Department of Education and Psychology, University of Aveiro, Aveiro, Portugal.

Biological motherhood plays an important role in the lives of many young women facing breast cancer and threats to reproduction may be disruptive. In this study, we explored the indirect effects of the importance of parenthood and childlessness on depression and health-related quality of life (HRQoL) among cancer patients 18-40 years of age ( = 104) through reported reproductive concerns. These specific concerns fully mediated the relationship between the importance of parenthood in women's lives and HRQoL. Greater importance of parenthood was directly associated with higher depression symptoms. Interventions should address the reproductive needs and concerns of patients to improve their HRQoL.
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http://dx.doi.org/10.1089/jayao.2019.0144DOI Listing
June 2020

CO conversion to phenyl isocyanates by uranium(vi) bis(imido) complexes.

Chem Commun (Camb) 2020 Jan;56(3):431-434

Centro de Ciências e Tecnologias Nucleares (C2TN), Instituto Superior Técnico, Universidade de Lisboa, 2695-066 Bobadela, Portugal.

Uranium(vi) trans-bis(imido) complexes [U(κ4-{(tBu2ArO)2Me2-cyclam})(NPh)(NPhR)] react with CO2 to eliminate phenyl isocyanates and afford uranium(vi) trans-[O[double bond, length as m-dash]U[double bond, length as m-dash]NR]2+ complexes, including [U(κ4-{(tBu2ArO)2Me2-cyclam})(NPh)(O)] that was crystallographically characterized. DFT studies indicate that the reaction proceeds by endergonic formation of a cycloaddition intermediate; the secondary reaction to form a dioxo uranyl complex is both thermodynamically and kinetically hindered.
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http://dx.doi.org/10.1039/c9cc07411bDOI Listing
January 2020

On the path to gold: Monoanionic Au bisdithiolate complexes with antimicrobial and antitumor activities.

J Inorg Biochem 2020 01 22;202:110904. Epub 2019 Oct 22.

Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10, km 139.7, 2695-066 Bobadela LRS, Portugal. Electronic address:

The emergence of resistance to antimicrobial and anticancer drugs poses severe threats to public health worldwide, highlighting the need for more efficient treatments. Here, four monoanionic Au bisdithiolate complexes [Au(mnt)] (where mnt = 1,1-dicyanoethylene-2,2-dithiolate)(1), [Au(i-mnt)] (where i-mnt = 2,2-dicyanoethylene-1,1-dithiolate)(2), [Au(cdc)] (where cdc = cyanodithioimido carbonate)(3), and [Au(qdt)] (where qdt = quinoxaline-2,3-dithiolate)(4) were screened for their antimicrobial and antitumor activities. Complexes 3 and 4 showed antibacterial activity against Staphylococcus aureus [minimal inhibitory concentration (MIC) = 15.3 and 14.7 μg/mL, respectively]. Complex 3 also caused significant growth inhibition of Candida glabrata (MIC = 7.0 μg/mL). Concentrations of complexes 1-4 up to 125 μg/mL had no growth inhibition activity against Escherichia coli. The cytotoxic activity of complexes 1-4 was evaluated against the ovarian cancer cells A2780 and A2780cisR, sensitive and resistant to cisplatin, respectively. All compounds showed high cytotoxic activities against both tumoral cell lines, exhibiting IC values in the low micromolar range (0.9-5.5 μM) upon 48 h incubation. In contrast to complex 1, the complexes 2-4 induced a dose-dependent formation of reactive oxygen species (ROS), similar to the observed for the reference drugs auranofin and cisplatin. Opposite to 4, complexes 1-3 were able to activate caspase 3/7, suggesting the involvement of apoptosis in the mechanism of cell death. Contrasting with cisplatin, complexes 3, 4 and auranofin did not cause DNA damage. Combined, these data provide evidence that these monoanionic gold bisdithiolates, particularly complex 3, are potential lead compounds to further explore as therapeutic drugs.
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http://dx.doi.org/10.1016/j.jinorgbio.2019.110904DOI Listing
January 2020

Translation, cross-cultural adaptation and validation of the underactive bladder questionnaire to portuguese.

Int Urol Nephrol 2019 Aug 27;51(8):1329-1334. Epub 2019 May 27.

Universidade de Pernambuco, Recife, Pernambuco, Brazil.

Objective: The aim of the current study was to perform the translation, cross-cultural adaptation and validation of the Underactive Bladder Questionnaire (UAB-q).

Methods: The study design included the Portuguese translation, cross-cultural adaptation and validation of the UAB-q in 90 patients from a urology outpatient clinic following international methodology. The psychometric properties tested were the validity, reliability, internal consistency and stability of the instrument.

Results: The content validity index at the item (I-CVI) and scale level (S-CVI) were above 0.80 and did not require changes. Regarding the reliability analysis, Cronbach's alpha was 0.79. The internal consistency and the base time stability (test-retest) had excellent indexes; all were above 0.90.

Conclusions: These results indicate that the UAB-q is a valid, reproducible and reliable instrument for screening underactive bladders and is a potentially useful tool to guide health actions and improve the care of underactive patients.
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http://dx.doi.org/10.1007/s11255-019-02176-4DOI Listing
August 2019

Lay Perspectives of Quality of Life in Rheumatoid Arthritis Patients: The Relevance of Autonomy and Psychological Distress.

Community Ment Health J 2019 11 29;55(8):1395-1401. Epub 2019 Mar 29.

Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Rua Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal.

The aim of this study is to increase the understanding of Quality of Life (QoL) in rheumatoid arthritis (RA) patients and explore the personal features of living with the disease. Sixty-two RA patients (M = 56.7; SD = 11.2; female = 83.9%) were interviewed. Assessment included topics on medical condition, functional status (HAQ-DI), and on their perceived difficulties and worries in having RA. Patients' overall definition of QoL was also inquired. Most patients lived with RA for a long period of time (M = 16.5 years; SD = 11.6) and presented moderate HAQ-DI scores (M = 1.37; SD = 0.75). Main features of QoL in RA highlight the importance given to physical health, particularly to independence and autonomy. Psychological distress emerged also as an important feature of living with RA, constraining a good QoL. Medical staff should consider the RA patients' emotional needs, expectations, and main perceived determinants of their QoL to better help them.
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http://dx.doi.org/10.1007/s10597-019-00377-wDOI Listing
November 2019

Nutritional status of iodine in children: When appropriateness relies on milk consumption and not adequate coverage of iodized salt in households.

Clin Nutr ESPEN 2019 04 4;30:52-58. Epub 2019 Mar 4.

Servicio de Neonatología, Hospital Universitario La Paz, Madrid, Spain.

Background & Aims: Iodine deficiency inhibits the normal development of human beings and is the leading cause of preventable mental retardation. Our study aims to update the urinary iodine concentrations and the intake of iodized salt in children in Madrid (Spain).

Methods: A cross-sectional study was designed where 217 children aged 3-14 years old were studied. A nutritional survey including the intake of iodized salt and other iodine-rich foods was performed. In addition, the urinary concentration of iodine was determined in each patient.

Results: Near 60% of the surveyed households routinely used iodized salt. Significant differences in age, sex, country of birth, or country of birth and parents educational levels and iodized salt consumption were not found. The median of the urinary iodine level (120 μg/L; interquartile range 80-184) was significantly higher in boys than girls and more elevated in younger children. Iodized salt and milk consumption significantly increased the concentration of urinary iodine. Children who drank less than two glasses of milk per day and did not consume iodized salt have four times the risk of iodine deficiency compared to children who daily drank at least two glasses of milk and consumed iodized salt (P < 0.001).

Conclusions: The nutritional level of iodine in the children studied is appropriate despite the low consumption of iodized salt. This is due to the consumption of dairy products and milk. The younger the child, the better his/her iodine nutritional level. Teenagers studied are at higher risk of iodine deficiency.
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http://dx.doi.org/10.1016/j.clnesp.2019.02.007DOI Listing
April 2019

Constitutive heterochromatin heteromorphism in the Neotropical armored catfish (Ihering, 1905) (Loricariidae, Hypostominae) from the Paraguay River basin (Mato Grosso do Sul, Brazil).

Comp Cytogenet 2019 11;13(1):27-39. Epub 2019 Feb 11.

Universidade Estadual de Maringá, Departamento de Biotecnologia, Genética e Biologia Celular, 87020-900 Maringá, Paraná, Brazil.

A cytogenetic analysis based on the integration of a number of different chromosomal methodologies, including chromosome microdissection was carried out to characterize the chromosomally polymorphic population from the Paraguay River basin, state of Mato Grosso do Sul in Brazil. All specimens had 2n=72 (FN=116) but two distinct karyotype formulas: karyomorph A (12m+14sm+18s+28a) and karyomorph B (13m+14sm+17st+28a). Karyomorph A and B differed only for pair 19 that consisted of two subtelocentrics in karyomorph A and a large metacentric and a subtelocentric in karyomorph B. This heteromorphism was due to extensive heterochromatinization of the short arm of the large metacentric, as highlighted by C-banding. The microdissection of the large metacentric of pair 19 allowed the production of a probe, named HrV ( Variant), that hybridized to the whole arm of the large metacentric and the pericentromeric region of the short arm of its (subtelocentric) homologue (karyomorph B) and of both homologs of pair 19 in karyomorph A. Additional cytogenetic techniques (FISH with 18S and 5S rDNA probes, CMA and DAPI staining) allowed a finer distinction of the two karyomorphs. These results reinforced the hypothesis that the novel large metacentric of (karyomorph B) was the result of the amplification of heterochromatin segments, which contributed to karyotypic diversification in this species.
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http://dx.doi.org/10.3897/CompCytogen.v13i1.30134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379321PMC
February 2019

Unravelling the antitumoral potential of novel bis(thiosemicarbazonato) Zn(II) complexes: structural and cellular studies.

J Biol Inorg Chem 2019 02 24;24(1):71-89. Epub 2018 Nov 24.

Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10 (km 139,7), 2695-066, Bobadela LRS, Portugal.

The development of pharmacologically active compounds based on bis(thiosemicarbazones) (BTSC) and on their coordination to metal centers constitutes a promising field of research. We have recently explored this class of ligands and their Cu(II) complexes for the design of cancer theranostics agents with enhanced uptake by tumoral cells. In the present work, we expand our focus to aliphatic and aromatic BTSC Zn(II) complexes bearing piperidine/morpholine pendant arms. The new complexes ZnL-ZnL were characterized by a variety of analytical techniques, which included single-crystal X-ray crystallography for ZnL and ZnL. Taking advantage of the fluorescent properties of the aromatic complexes, we investigated their cellular uptake kinetics and subcellular localization. Furthermore, we tried to elucidate the mechanism of action of the cytotoxic effect observed in human cancer cell line models. The results show that the aliphatic complexes (ZnL and ZnL) have a symmetrical structure, while the aromatic counterparts (ZnL and ZnL) have an asymmetrical nature. The cytotoxic activity was higher for the aromatic BTSC complexes, as well as the cellular uptake, evaluated by measurement of intracellular Zn accumulation. Among the most active complexes, ZnL presented the fastest uptake kinetics and lysosomal localization assessed by live-cell microscopy. Detailed studies of its impact on cellular production of reactive oxygen species and impairment of lysosomal membrane integrity reinforced the influence of the pendant piperidine in the biological performance of aromatic BTSC Zn(II) complexes.
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http://dx.doi.org/10.1007/s00775-018-1629-6DOI Listing
February 2019

Odor evaluation scales for odor in neoplastic wounds: an integrative review.

Rev Bras Enferm 2018 Sep-Oct;71(5):2552-2560

Universidade de Pernambuco, Nossa Senhora das Graças Nursing School. Recife, Pernambuco, Brazil.

Objective: Checking for the existence of assessment instruments for odor in neoplastic wounds.

Method: Integrative review performed in the databases Lilacs, SCiELO, Ibecs and MedLine, including national and international publications.

Results: 15 articles were analyzed, in its majority performed by nurses and being of the revision type. Nine scales were found, of which the majority assesses only the odor intensity. The scale most used to evaluate products and/or bandage covers for neoplastic injuries was the Odor Evaluation Guideline, of qualitative-quantitative nature, that establishes the symptom within four levels; only one of which being validated (Teler scale).

Conclusion: The results of this study showed that, currently, there is only one scale that is validated for assessing odor in neoplastic wounds, pointing towards the need to develop new instruments that incorporate validated and reliable instruments in clinical practice.
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http://dx.doi.org/10.1590/0034-7167-2017-0428DOI Listing
January 2019

Effectiveness of educational outreach visits compared with usual guideline dissemination to improve family physician prescribing-an 18-month open cluster-randomized trial.

Implement Sci 2018 09 5;13(1):120. Epub 2018 Sep 5.

Grupo de Investigação Académica Independente - Chronic Diseases Research Center, NOVA Medical School | Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal.

Background: Educational outreach visits are meant to improve the practice of health professionals by promoting face-to-face visits to deliver educational contents. They have been shown to change prescription behavior, but long-term effects are still uncertain. This trial aimed to determine if they improve family physician prescribing compared with passive guideline dissemination.

Methods: Parallel, open, superiority, and cluster-randomized trial. National Health Service primary care practices (clusters) were recruited in the Lisbon region-Portugal between March 2013 and January 2014. They could enter if they had at least four family physicians willing to participate and not planning to retire in the follow-up period. Three national guidelines were chosen for dissemination: acid secretion modifiers, non-steroidal anti-inflammatory drugs, and antiplatelets. Physicians in the intervention group received one 15 to 20 min educational outreach visit at their workplace for each guideline. Physicians in the control group had access to guidelines through the Directorate-General for Health's website (passive dissemination). Primary outcomes were the proportion of COX-2 inhibitors prescribed within the NSAID class and the proportion of omeprazole within the PPI class at 18 months after the intervention. A cost-benefit analysis was performed. Practices were randomized by minimization. Data analyses were done at individual physician level using generalized mixed-effects regression models. Participants could not be blinded.

Results: Thirty-eight practices with 239 physicians were randomized (120 to intervention and 119 to control). Of 360 planned visits, 322 were delivered. No differences were found between physicians in the intervention and control groups regarding the proportion of omeprazole prescribed among PPIs 18 months after the visit (46.28 vs 47.15%, p = 0.971) or the proportion of COX-2 inhibitors among NSAIDs (12.07 vs 13.08%, p = 0.085). All secondary outcome comparisons showed no effect. There was no difference in cumulative drug costs at 18 months (3223.50€/1000 patients in the intervention group and 3143.92€/1000 patients in the control group, p = 0.848).

Conclusions: Educational outreach visits were unsuccessful in improving compliance with guideline recommendations among Portuguese family physicians. No effects were observed at 1, 6, and 18 months after the intervention, and there were no associated cost savings.

Trial Registration: ClinicalTrials.gov NCT01984034 . Registered 7 November 2013.
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http://dx.doi.org/10.1186/s13012-018-0810-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6126017PMC
September 2018

Effect of European Medicines Agency's restrictions on trimetazidine utilization in Portugal.

Pharmacoepidemiol Drug Saf 2018 09 10;27(9):962-968. Epub 2018 Jul 10.

Group for Independent Academic Information, Chronic Diseases Research Center, NOVA Medical School, Lisbon, Portugal.

Purpose: Following safety concerns regarding trimetazidine, the European Medicines Agency (EMA) recommended restrictions on its use. Our objective was to determine the impact of regulatory actions on trimetazidine utilization in Portugal.

Methods: Retrospective interrupted time-series analysis of monthly ambulatory pharmacy reimbursement records for the Portuguese National Health Service between January 2006 and December 2015. Regulatory actions were identified by searching the EMA, Portuguese Medicines Authority, and European Commission's websites. Concurrent factors in the same period were also identified. The main outcome was the dispensing of trimetazidine-containing products per month in Portugal.

Results: Two interruption periods were defined in the series: May 2011, when EMA announced it would review trimetazidine safety, and June 2012 to January 2013, when EMA announced it had reached a final opinion recommending restrictions; the European Commission approved EMA's recommendation; the Portuguese Medicines Authority issued safety alerts, changed the summary of product characteristics, and approved a direct health-care professional letter; and a regional bulletin was issued. Interruption 1 had no effect on trimetazidine use, but interruption 2 resulted in decreases in level and trend-from 8.3 million defined daily doses in 2010 to 2.8 million in 2015. After interruption 2, trimetazidine use tended towards a lower steady state.

Conclusions: There was a significant decrease in trimetazidine use in Portugal following a complex intervention that included safety alerts, changes to the summary of product characteristics, a direct health-care professional letter, and a regional drug bulletin. No effect was seen when EMA announced its review of trimetazidine safety.
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http://dx.doi.org/10.1002/pds.4585DOI Listing
September 2018

Uranium(iii) complexes supported by hydrobis(mercaptoimidazolyl)borates: synthesis and oxidation chemistry.

Dalton Trans 2018 Aug;47(31):10601-10612

Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10, 2695-066 Bobadela LRS, Portugal.

The reaction of [UI3(thf)4] with the sodium or lithium salts of hydrobis(2-mercapto-1-methylimidazolyl)borate ligands ([H(R)B(timMe)2]-) in a 1 : 2 ratio, in tetrahydrofuran, gave the U(iii) complexes [UI{κ3-H,S,S'-H(R)B(timMe)2}2(thf)2] (R = H (1), Ph (2)) in good yields. Crystals of [UI{κ3-H,S,S'-H(Ph)B(timMe)2}2(thf)2] (2) were obtained by recrystallization from a tetrahydrofuran/acetonitrile solution, and the ion-separated uranium complex [U{κ3-H,S,S'-H(Ph)B(timMe)2}2(CH3CN)3][I] (3-I) was obtained by dissolution of 2 in acetonitrile followed by recrystallization. One-electron oxidation of 2 with AgBPh4 or I2 resulted in the formation of the cationic U(iv) complexes [U{κ3-H,S,S'-H(Ph)B(timMe)2}3][X] (X = BPh4 (6-BPh4), I (6-I)), due to a ligand redistribution process. These complexes are the first examples of homoleptic poly(azolyl)borate U(iv) complexes. Treatment of complex 2 with azobenzene led to the isolation of crystals of the U(iv) compound [UI{κ3-H(Ph)B(timMe)2}2(κ2-timMe)] (7). Treatment of 2 with pyridine-N oxide (pyNO) led to the formation of the uranyl complex [UO2{κ2-S,S'-H(Ph)B(timMe)2}2] (8) and of complex 6-I, while from the reaction of [U{κ3-H(Ph)B(timMe)2}2(thf)3][BPh4] (5) with pyNO, the oxo-bridged U(iv) complex [{U{κ3-H(Ph)B(timMe)2}2(pyNO)}2(μ-O)][BPh4]2 (9) was also obtained. In the U(iii) and U(iv) complexes, the bis(azolyl)borate ligands bind to the uranium center in a κ3-H,S,S' coordination mode, while in the U(vi) complex the ligands bind to the metal in a κ2-S,S' mode. The presence of UH-B interactions in the solid-state, for the nine-coordinate complexes 1, 2, 3, 6 and 7 and for the eight-coordinate complex 9, was supported by IR spectroscopy and/or X-ray diffraction analysis.
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http://dx.doi.org/10.1039/c8dt01149dDOI Listing
August 2018

Effect of European Medicines Agency's regulatory measures on nimesulide utilization in Portugal.

Pharmacoepidemiol Drug Saf 2018 06 30;27(6):630-637. Epub 2018 Mar 30.

Former member Group for Independent Academic Information, Chronic Diseases Research Center, NOVA Medical School, Lisbon, Portugal.

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http://dx.doi.org/10.1002/pds.4424DOI Listing
June 2018

Food insecurity and social support in families of children with sickle-cell disease.

J Pediatr (Rio J) 2019 May - Jun;95(3):306-313. Epub 2018 Mar 15.

Universidade do Estado do Rio de Janeiro (UERJ), Instituto de Nutrição, Departamento de Nutrição Aplicada, Rio de Janeiro, RJ, Brazil. Electronic address:

Objective: To examine the associations between food insecurity (IA) and social support in families of children with sickle-cell disease (DF).

Methods: This cross-sectional study in families of 190 children from five to nine years old in follow-up at a hematology referral hospital in Rio de Janeiro State. IA was measured using the Brazilian food insecurity scale and social support was measured using the Brazilian version of the MOS social support survey instrument. The relation between IA and social support was analyzed by way of a multinomial logistic model.

Results: There was IA in 62.2% of the families, in moderate and severe form in, respectively, 11.1% and 7.9% of cases. In families of children with DF, levels of mild and severe food insecurity (IALe and IAGr) were found to relate inversely to levels of social support in the following dimensions: informational support (IALe OR=0.98; 95% CI 0.96-0.99 and IAGr OR=0.95; 95% CI 0.92-0.98); social interaction (IALe OR=0.98; 95% CI 0.96-0.99 and IAGr OR=0.96; 95% CI 0.93-0.99) and tangible social support (IALe OR=0.97; 95% CI 0.96-0.99 and IAGr OR=0.97; 95% CI 0.94-0.99).

Conclusion: Considering the positive effects of social support on IA, public policies should be encouraged to assure food and nutritional security and social assistance for care for people with DF. Also, social support groups for people with DF should be strengthened.
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http://dx.doi.org/10.1016/j.jped.2018.01.005DOI Listing
October 2019

Gold and Nickel Extended Thiophenic-TTF Bisdithiolene Complexes.

Molecules 2018 Feb 14;23(2). Epub 2018 Feb 14.

C²TN, Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, E.N. 10 ao km 139.7, 2695-066 Bobadela LRS, Portugal.

Gold and nickel bisdithiolene complexes with methyl and -butyl substituted thiophenetetrathiafulavalenedithiolate ligands (α-mtdt and α-tbtdt) were prepared and characterized. These complexes were obtained, under anaerobic conditions, as tetrabutylammonium salts. The diamagnetic gold monoanion (-Bu₄N)[Au(α-mtdt)₂] () and nickel dianionic species (-Bu₄N)[Ni(α-mtdt)₂] (x = 1,2) () were similar to the related non-substituted extended thiophenic-TTF (TTF = tetrathiafulvalene) bisdithiolenes. However the introduction of the large, bulky substituent -butyl, led to the formation of a Au (I) dinuclear complex, (-Bu₄N)₂[Au₂(α-tbtdt)₂] (). The neutral methyl substituted gold and nickel complexes were easily obtained through air or iodine exposure as polycrystalline or amorphous fine powder. [Au(α-mtdt)₂] () and [Ni(α-mtdt)₂] () polycrystalline samples display properties of a metallic system with a room temperature electrical conductivity of 0.32 S/cm and ≈4 S/cm and a thermoelectric power of ≈5 µV/K and ≈32 µV/K, respectively. While [Au(α-mtdt)₂] () presented a Pauli-like magnetic susceptibility typical of conducting systems, in [Ni(α-mtdt)₂] () large magnetic susceptibilities indicative of high spin states were observed. Both electric transport properties and magnetic properties for gold and nickel [M(α-mtdt)₂] are indicative that these compounds are single component molecular conductors.
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http://dx.doi.org/10.3390/molecules23020424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6017561PMC
February 2018

Effectiveness of psycho-educational interventions with telecommunication technologies on emotional distress and quality of life of adult cancer patients: a systematic review.

Disabil Rehabil 2019 04 7;41(8):870-878. Epub 2017 Dec 7.

a Department of Education and Psychology , Center for Health Technology and Services Research (CINTESIS), University of Aveiro , Aveiro , Portugal.

Purpose: To provide a comprehensive review of psycho-educational interventions using telecommunication technologies developed for adult cancer patients, assessing their effectiveness in reducing emotional distress and improving quality of life (QoL).

Materials And Methods: A narrative approach was used for extraction and synthesis of the data. Relevant studies were identified through the electronic databases PubMed, Scopus, Web of Science, ProQuest, Psychology & Behavioral Sciences Collection (through EBSCOhost), and CENTRAL.

Results: Eight studies involving 1016 participants met inclusion criteria. The majority of the studies included (n = 6) used a randomized design and were published between 2007 and 2016. Interventions used a variety of delivery resources, such as telephone, e-mail and websites, but all were aiming to respond to information needs and develop stress control skills. A trend toward reducing distress and improving QoL was found, but estimated effect sizes were typically small (d < 0.5). Telephonically delivered psycho-educational interventions presented the highest between-group effects on these outcomes during survival, but were limited by sample size.

Conclusions: The efficacy of interventions using distance approaches in the cancer setting is still not well-established. Further research should be conducted through well-designed studies with more interactive features that minimize the lack of face-to-face interaction. Implications for rehabilitation Rehabilitation professionals working in the field of oncology should invest in the development of psycho-educational interventions responding the patients' educational needs and promoting their stress control skills. Programs using telecommunications technologies may reduce disparities in service delivery within this setting, minimizing geographic and socio-economic barriers to engagement in the interventions. With the current technological development, it is possible to perform more interactive interventions that stimulate therapist-patient interactions. However, available protocols in this field still employ basic resources (e.g., websites, e-mail, and videos). Young adult cancer patients are exposed to additional requirements related to fertility and parenthood. New intervention approaches should consider their informational needs.
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http://dx.doi.org/10.1080/09638288.2017.1411534DOI Listing
April 2019

Intensive Follow-Up After Curative Surgery for Colorectal Cancer.

Acta Med Port 2017 Sep 29;30(9):633-641. Epub 2017 Sep 29.

Department of Gastroenterology. Instituto Português de Oncologia de Lisboa Francisco Gentil. Lisboa. Portugal.

Introduction: The purpose of postoperative surveillance programs after curative treatment for colorectal cancer is to detect asymptomatic recurrences with the premise that an important rate will be eligible for curative resection, improving overall survival. We have implemented a surveillance program for patients with colorectal cancer, stages II-III, with periodic clinical, carcinoembryonic antigen and cancer antigen-19-9 assessment, computed tomography and colonoscopy. The aim of this study was to assess the rate of curative treatment of recurrence, colorectal cancer mortality and clinical characteristics associated with non-resectable recurrence.

Material And Methods: Open cohort study, single center. All patients on the intensive surveillance program between March 2008 and January 2015 were included.

Statistics: chi-square, Wilcoxon rank sum test, logistic regression, Kaplan-Meier log-rank test (SPSS20®).

Results: We had a total 404 patients evaluated; 59.6% male; mean age of 65 ± 10 years; 50.7% rectal tumor; 56.2% stage III. The average time of follow-up was 37 months and the recurrence rate was 12.9% (n = 52), mostly detected in the first three years (88.4%). The pattern of recurrence was associated with the site of the primary tumor (p < 0.001). Twenty-one patients underwent curative resection. Factors associated with non-resectable recurrence were aged ≥ 70 years (p = 0.022), disease location in the colon (p = 0.033) and cancer antigen-19-9-9 elevation (p = 0.024). The overall rate of cancer-specific mortality was 2.2% (n = 9).

Discussion: The association between colon cancer and non-resectable recurrence is explained by the higher rate of disseminated disease in these patients. Cancer antigen-19-9 added no benefit to the surveillance program.

Conclusion: This intensive real-world postoperative surveillance program allowed performing curative surgery to 40.3% of patients with recurrence.
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http://dx.doi.org/10.20344/amp.7889DOI Listing
September 2017

A Multifunctional Radiotheranostic Agent for Dual Targeting of Breast Cancer Cells.

ChemMedChem 2017 07 30;12(14):1103-1107. Epub 2017 Jun 30.

Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10, km 139.7, 2695-066, Bobadela, LRS, Portugal.

A straightforward synthetic route for a new multifunctional 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) derivative is described. To demonstrate the versatility of this pro-chelator for the preparation of radiolabeled hybrid compounds containing two different biological targeting moieties, an antitumor agent (e.g., a DNA-intercalating agent) and an estrogen receptor (ER) ligand (e.g., LXXLL-based peptide) were regiospecifically conjugated to the DOTA derivative. The bifunctional probe was radiolabeled with the auger electron emitter indium-111, and the resulting radioconjugate was demonstrated to induce DNA damage in vitro, which, along with the nuclear internalization exhibited in breast cancer cells, might enhance its therapeutic activity. This favorable in vitro performance suggests that these hybrid compounds could be attractive probes for theranostic applications.
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http://dx.doi.org/10.1002/cmdc.201700287DOI Listing
July 2017

Technetium-99m complexes of l-arginine derivatives for targeting amino acid transporters.

Dalton Trans 2017 Oct;46(42):14537-14547

Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10 (km 139.7), 2695-066 Bobadela LRS, Portugal.

Although relevant from the clinical point of view, radiotracers targeting cationic amino acid transporters are relatively unexplored and, in particular, no metal-based radiotracers are known. The rare examples of complexes recognized by amino acid transporters, namely by the Na-independent neutral l-type amino acid transporter 1 (LAT1), are Tc(i)/Re(i) compounds. Herein, we describe conjugates comprising a pyrazolyl-diamine chelating unit and the cationic amino acid l-arginine (l-Arg) linked by a propyl (L1) or hexyl linker (L2), which allowed the preparation of stable complexes of the type fac-[Tc(CO)(k-L)] (Tc1, L = L1; Tc2, L = L2) and of the respective surrogates Re1 and Re2. Interestingly, complex Tc2 exhibited moderate levels of time-dependent internalization in three human tumoural cell lines, with approximately 3% of total applied activity internalized, corresponding to 21% of the cell-associated activity. A putative mechanism of retention in the cytoplasm of cells could be the interaction of the complex with inducible nitric oxide synthase (iNOS), which is the enzyme responsible for the catalytic oxidation of l-Arg to citrulline and nitric oxide. However, the surrogate complex Re2 does not recognize iNOS, as demonstrated by the in vitro assays with purified iNOS and in studies with lipopolysaccharide(LPS)-activated macrophages. Preliminary mechanistic studies suggest that the internalization of Tc2 is linked to the cationic amino acid transporters, namely system y. This finding might open the way towards the development of novel families of metal-based radiotracers for probing metabolically active cancer cells.
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http://dx.doi.org/10.1039/c7dt01146fDOI Listing
October 2017

Enhanced Cytotoxicity and Reactivity of a Novel Platinum(IV) Family with DNA-Targeting Naphthalimide Ligands.

Inorg Chem 2017 Jun 10;56(11):6175-6183. Epub 2017 May 10.

Departamento de Química Inorgánica, Universidad Autónoma de Madrid , ES-28049 Madrid, Spain.

Pt(IV) complexes are known as prodrugs that can potentially overcome cisplatin limitations by slowing down its reactivity and, once reduced, act as the corresponding Pt(II) drugs. We report a new approach toward trans Pt(IV) complexes, conceived to afford nonconventional active trans Pt(II) complexes with dual-targeting properties. The reduction of the complexes has been studied in the presence of ascorbic acid and glutathione, showing that different species are formed in the process. The interaction with DNA after reduction has been also studied and correlated to the formation of Pt(II) species. The cytotoxicity profile of the Pt(IV) complexes corroborated the rationale behind this approach.
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http://dx.doi.org/10.1021/acs.inorgchem.7b00136DOI Listing
June 2017