Publications by authors named "Marta Pereira"

131 Publications

Dermatologists' attitude towards psoriasis treatment during the COVID-19 pandemic.

Drugs Context 2021 9;10. Epub 2021 Jun 9.

Department of Dermatology, Hospital Lusíadas, Lisbon, Portugal.

Background: The COVID-19 pandemic introduced new challenges in several dimensions in healthcare services. Herein, we describe the real-life strategies and therapeutic options adopted by dermatologists regarding their patients with psoriasis being treated with or with an indication for systemic therapy during the first COVID-19 lockdown period in Portugal.

Methods: The study involves a web-based survey on the clinical management of systemic therapy for psoriasis during the COVID-19 pandemic administered to Portuguese dermatologists. The survey consisted of 55 questions (4 open-ended questions; 51 closed-ended questions), grouped into 6 sections.

Results: A total of 60 dermatologists voluntarily participated in this survey. Nearly 63% of the participants opted for suspending biologics during the COVID-19 lockdown period and 23.3% increased the time between drug administrations. Eighty percent of the participants agreed that biologics did not change the probability of acquiring COVID-19 and 58.4% believed that these drugs decreased or did not change the severity of the disease. Approximately one-third of the participants opted not to prescribe a biological agent in patients despite clinical indication over the duration of the pandemic. Nearly 25% of the participants opted for suspending traditional immunosuppressant administration. Virtual appointments were an option for 93.3% of the participants.

Conclusion: The COVID-19 pandemic has significantly affected the management of patients with psoriasis being treated with or with an indication for systemic therapy. Some of the decisions made during the first lockdown period were contrary to what we know today. These decisions might have had a significant impact on patients' quality of life and on future therapeutic success. An adequate interpretation and analysis of the available data will be extremely important to an insightful adaptation of the clinical practice in future confinement or restrictive scenarios.
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http://dx.doi.org/10.7573/dic.2021-4-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195567PMC
June 2021

A CHALLENGING CASE OF SPORADIC MELANOCYTOMA OF THE JUGULAR FORAMEN.

Neurochirurgie 2021 Jun 19. Epub 2021 Jun 19.

Department of Neurosurgery, Manchester Centre for Clinical Neurosciences, Salford Royal Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.

Background: The jugular foramen (JF) can be the site of several tumours. Paragangliomas, schwannomas and meningiomas are the most commonly reported. We describe a case of melanocytoma originating from the JF and presenting with an accessory nerve palsy. Illustrative case: A 48-year-old woman presented with a 6-month history of cervical and left shoulder pain with wasting and weakness of the left trapezius. A Magnetic Resonance Imaging (MRI) showed a T1-hyperintense, T2-isointense, heterogeneously enhancing lesion involving the left JF and extending into the cerebello-medullary and cerebello-pontine cisterns. A retrosigmoid craniotomy was performed and a near total removal achieved. The accessory nerve was involved by tumour and could not be preserved. Given the diagnostic uncertainty between melanotic schwannoma, metastatic melanoma and meningeal melanocytoma, next generation sequencing and genome-wide DNA methylation arrays were performed, documenting a mutation in GNA11 (c.6226A>T, p. Gln209Leu) and a methylation profile consistent with melanocytoma. The patient underwent adjuvant fractionated radiotherapy of the tumour remnant. A follow-up MRI 4 years after surgery did not show any tumour recurrence.

Conclusions: The differential diagnosis of skull base pigmented tumours can be challenging, particularly when they occur in unusual locations such as the JF. They can be misdiagnosed given their similar clinical, neuroradiological and pathological features if anatomy of the site of origin is not carefully considered and molecular tests are not performed, leading to erroneous treatment and follow up planning.
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http://dx.doi.org/10.1016/j.neuchi.2021.06.001DOI Listing
June 2021

Useful Ultrasonographic Parameters to Predict Difficult Laryngoscopy and Difficult Tracheal Intubation-A Systematic Review and Meta-Analysis.

Front Med (Lausanne) 2021 28;8:671658. Epub 2021 May 28.

School of Medicine, Life and Health Sciences Research Institute (ICVS), University of Minho, Braga, Portugal.

Unexpected difficult airway management can cause significant morbidity and mortality in patients admitted for elective procedures. Ultrasonography is a promising tool for perioperative airway assessment, nevertheless it is still unclear which sonographic parameters are useful predictors of difficult laryngoscopy and tracheal intubation. To determine the ultrasonographic predictors of a difficult airway that could be applied for routine practice, a systematic review and meta-analysis was conducted. Literature search was performed on PubMED, Web of Science and Embase using the selected keywords. Human primary studies, published in English with the use of ultrasonography to prediction of difficult laryngoscopy or tracheal intubation were included. A total of 19 articles (4,570 patients) were analyzed for the systematic review and 12 articles (1,141 patients) for the meta-analysis. Standardized mean differences between easy and difficult laryngoscopy groups were calculated and the parameter effect size quantified. A PRISMA methodology was used and the critical appraisal tool from Joanna Briggs Institute was applied. Twenty-six sonographic parameters were studied. The overall effect of the distance from skin to hyoid bone ( = 0.02); skin to epiglottis ( = 0.02); skin to the anterior commissure of vocal cords ( = 0.02), pre-epiglottis space to distance between epiglottis and midpoint between vocal cords ( = 0.01), hyomental distance in neutral ( < 0.0001), and extended ( = 0.0002) positions and ratio of hyomental distance in neutral to extended ( = 0.001) was significant. This study shows that hyomental distance in the neutral position is the most reliable parameter for pre-operative airway ultrasound assessment. The main limitations of the study are the small sample size, heterogeneity of studies, and absence of a standardized ultrasonographic evaluation method [Registered at International prospective register of systematic reviews (PROSPERO): number 167931].
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http://dx.doi.org/10.3389/fmed.2021.671658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193063PMC
May 2021

Anesthetic management of child with Gitelman Syndrome: case report.

Braz J Anesthesiol 2021 Jun 6. Epub 2021 Jun 6.

Hospital Senhora da Oliveira, Guimarães, Portugal.

Gitelman syndrome is a rare autosomal recessive inherited disease that affects the thiazidesensitive sodium-chloride cotransport channels and the magnesium channels in the distal convoluted tubule, leading to hypokalemic metabolic alkalosis, hypomagnesemia and hypocalciuria. There is no cure for this condition and supportive treatment relies on ionic supplementation and symptom management. Literature regarding the anesthetic approach is scarce. This case report presents the anesthetic management of a child with Gitelman syndrome and its difficult electrolyte optimization.
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http://dx.doi.org/10.1016/j.bjane.2021.05.003DOI Listing
June 2021

Generation of mitochondrial reactive oxygen species is controlled by ATPase inhibitory factor 1 and regulates cognition.

PLoS Biol 2021 May 13;19(5):e3001252. Epub 2021 May 13.

Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid (CSIC-UAM), Madrid, Spain.

The mitochondrial ATP synthase emerges as key hub of cellular functions controlling the production of ATP, cellular signaling, and fate. It is regulated by the ATPase inhibitory factor 1 (IF1), which is highly abundant in neurons. Herein, we ablated or overexpressed IF1 in mouse neurons to show that IF1 dose defines the fraction of active/inactive enzyme in vivo, thereby controlling mitochondrial function and the production of mitochondrial reactive oxygen species (mtROS). Transcriptomic, proteomic, and metabolomic analyses indicate that IF1 dose regulates mitochondrial metabolism, synaptic function, and cognition. Ablation of IF1 impairs memory, whereas synaptic transmission and learning are enhanced by IF1 overexpression. Mechanistically, quenching the IF1-mediated increase in mtROS production in mice overexpressing IF1 reduces the increased synaptic transmission and obliterates the learning advantage afforded by the higher IF1 content. Overall, IF1 plays a key role in neuronal function by regulating the fraction of ATP synthase responsible for mitohormetic mtROS signaling.
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http://dx.doi.org/10.1371/journal.pbio.3001252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148373PMC
May 2021

Acute kidney disease and long-term outcomes in critically ill acute kidney injury patients with sepsis: a cohort analysis.

Clin Kidney J 2021 May 27;14(5):1379-1387. Epub 2020 Sep 27.

Division of Nephrology and Renal Transplantation, Department of Medicine, Centro Hospitalar Lisboa Norte, EPE, Lisboa, Portugal.

Background: Acute kidney injury (AKI) is frequent during hospitalization and may contribute to adverse short- and long-term consequences. Acute kidney disease (AKD) reflects the continuing pathological processes and adverse events developing after AKI. We aimed to evaluate the association of AKD, long-term adverse renal function and mortality in a cohort of patients with sepsis.

Methods: We performed a retrospective analysis of adult patients with septic AKI admitted to the Division of Intensive Medicine of the Centro Hospitalar Lisboa Norte (Lisbon, Portugal) between January 2008 and December 2014. Patients were categorized according to the development of AKI using the Kidney Disease: Improving Global Outcomes (KDIGO) classification. AKI was defined as an increase in absolute serum creatinine (SCr) ≥0.3 mg/dL or by a percentage increase in SCr ≥50% and/or by a decrease in urine output to <0.5 mL/kg/h for >6 h. AKD was defined as presenting at least KDIGO Stage 1 criteria for >7 days after an AKI initiating event. Adverse renal outcomes (need for long-term dialysis and/or a 25% decrease in estimated glomerular filtration rate after hospital discharge) and mortality after discharge were evaluated.

Results: From 256 selected patients with septic AKI, 53.9% developed AKD. The 30-day mortality rate was 24.5% ( = 55). The mean long-term follow-up was 45.9 ± 43.3 months. The majority of patients experience an adverse renal outcome [ = 158 (61.7%)] and 44.1% ( = 113) of patients died during follow-up. Adverse renal outcomes, 30-day mortality and long-term mortality after hospital discharge were more frequent among AKD patients [77.5 versus 43.2% (P < 0.001), 34.1 versus 6.8% (P < 0.001) and 64.8 versus 49.1% (P = 0.025), respectively]. The 5-year cumulative probability of survival was 23.2% for AKD patients, while it was 47.5% for patients with no AKD (log-rank test, P < 0.0001). In multivariate analysis, AKD was independently associated with adverse renal outcomes {adjusted hazard ratio [HR] 2.87 [95% confidence interval (CI) 2.0-4.1]; P < 0.001} and long-term mortality [adjusted HR 1.51 (95% CI 1.0-2.2); P = 0.040].

Conclusions: AKD after septic AKI was independently associated with the risk of long-term need for dialysis and/or renal function decline and with the risk of death after hospital discharge.
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http://dx.doi.org/10.1093/ckj/sfaa130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087131PMC
May 2021

Validation of the Brief Version of the Cancer Behavior Inventory in Breast Cancer Portuguese Patients.

J Clin Psychol Med Settings 2021 Apr 3. Epub 2021 Apr 3.

School of Psychology, University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal.

Self-efficacy is a coping resource with a positive impact on well-being, quality of life, anxiety, and depression in cancer patients, even after treatment. This study focused on the validation of the Cancer Behavior Inventory-Brief Version (CBI-B) in Portuguese patients with breast cancer. The study included 115 patients with breast cancer receiving outpatient chemotherapy in four hospitals located in Portugal. Participants (N = 115) completed the translated version of the CBI-B in Portuguese and measures of quality of life (QLQ- C30), psychological distress (HADS), and illness perceptions (IPQ-B). Confirmatory factor analysis supported the four-factor original structure of the CBI-B. The Portuguese version of the CBI-B showed good psychometric properties as shown by measures of internal consistency (Cronbach's alpha = .88), test-retest reliability (intraclass correlation coefficient = .59), convergent validity with the QLQ-C30 (r = .43, p < .001), and divergent validity with the HADS (r = -.60, p < .001) and the IPQ-B (r = -.51, p < .001). The Portuguese version of the CBI-B is a valid and reliable instrument to evaluate the self-efficacy for coping in Portuguese breast cancer patients. Future studies should validate the CBI-B in patients with other types of cancer.
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http://dx.doi.org/10.1007/s10880-021-09773-5DOI Listing
April 2021

High likelihood of actionable pathogenic variant detection in breast cancer genes in women with very early onset breast cancer.

J Med Genet 2021 Mar 23. Epub 2021 Mar 23.

Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.

Background: While the likelihood of identifying constitutional breast cancer-associated , and pathogenic variants (PVs) increases with earlier diagnosis age, little is known about the correlation with age at diagnosis in other predisposition genes. Here, we assessed the contribution of known breast cancer-associated genes to very early onset disease.

Methods: Sequencing of , and c.1100delC was undertaken in women with breast cancer diagnosed ≤30 years. Those testing negative were screened for PVs in a minimum of eight additional breast cancer-associated genes. Rates of PVs were compared with cases ≤30 years from the Prospective study of Outcomes in Sporadic vs Hereditary breast cancer (POSH) study.

Results: Testing 379 women with breast cancer aged ≤30 years identified 75 PVs (19.7%) in , 35 (9.2%) in , 22 (5.8%) in and 2 (0.5%) c.1100delC. Extended screening of 184 PV negative women only identified eight additional actionable PVs. PVs were more common in women aged 26-30 years than in younger women (p=0.0083) although the younger age group had rates more similar to those in the POSH cohort. Out of 26 women with ductal carcinoma (DCIS) alone, most were high-grade and 11/26 (42.3%) had a PV (=6, =2, =2, =1). This PV yield is similar to the 61 (48.8%) PVs identified in 125 women with triple-negative breast cancer. The POSH cohort specifically excluded pure DCIS which may explain lower PV rates in this group (1.7%).

Conclusion: The rates of , and PVs are high in very early onset breast cancer, with limited benefit from testing of additional breast cancer-associated genes.
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http://dx.doi.org/10.1136/jmedgenet-2020-107347DOI Listing
March 2021

Next generation human brain models: engineered flat brain organoids featuring gyrification.

Biofabrication 2021 03 16;13(1):011001. Epub 2021 Mar 16.

Department of Molecular Biology, Autonomous University of Madrid, Center of Molecular Biology Severo Ochoa (CBMSO, UAM-CSIC), Madrid, Spain.

Brain organoids are considered to be a highly promising in vitro model for the study of the human brain and, despite their various shortcomings, have already been used widely in neurobiological studies. Especially for drug screening applications, a highly reproducible protocol with simple tissue culture steps and consistent output, is required. Here we present an engineering approach that addresses several existing shortcomings of brain organoids. By culturing brain organoids with a polycaprolactone scaffold, we were able to modify their shape into a flat morphology. Engineered flat brain organoids (efBOs) possess advantageous diffusion conditions and thus their tissue is better supplied with oxygen and nutrients, preventing the formation of a necrotic tissue core. Moreover, the efBO protocol is highly simplified and allows to customize the organoid size directly from the start. By seeding cells onto 12 by 12 mm scaffolds, the brain organoid size can be significantly increased. In addition, we were able to observe folding reminiscent of gyrification around day 20, which was self-generated by the tissue. To our knowledge, this is the first study that reports intrinsically caused gyrification of neuronal tissue in vitro. We consider our efBO protocol as a next step towards the generation of a stable and reliable human brain model for drug screening applications and spatial patterning experiments.
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http://dx.doi.org/10.1088/1758-5090/abc95eDOI Listing
March 2021

Factors associated with length of stay and death in tube-fed patients: A cross-sectional multicentre study.

Nurs Open 2021 Jan 27. Epub 2021 Jan 27.

University of São Paulo at Ribeirão Preto College of Nursing, São Paulo, Brazil.

Objectives: To analyse the factors associated with length of stay (LOS) and death in nasogastric/nasoenteric tube (NG/NET)-fed patients.

Design: A cross-sectional multicentre study.

Method: Data collection took place from October 2017-April 2019, and the sample consisted of 365 participants from seven Brazilian hospitals. Demographic, clinical and therapeutic data were collected from the patients' medical records. Data analysis was performed using bivariate and multivariate tests, considering a significance level of p<.05.

Results: Most patients were male, older adults, with high risk of death and highly dependent on nursing care. The LOS was associated with age, patient care complexity and length of NG/NET use. Death was associated with patient age. In the multivariate analysis, patients highly dependent on nursing care, and intensive and semi-intensive care had a greater chance of dying when compared with patients receiving minimal care. Screening for factors affecting LOS and death is important to plan effective nursing care.
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http://dx.doi.org/10.1002/nop2.774DOI Listing
January 2021

Validation of the Short-Form Survivor Unmet Needs Survey in older patients with myeloma.

Psychogeriatrics 2021 Mar 19;21(2):185-192. Epub 2021 Jan 19.

Portuguese Institute of Oncology Francisco Gentil, Lisbon, Portugal.

Background: Multiple myeloma (MM) affects mainly the older population and is the second most prevalent haematologic cancer. MM patients' unmet needs are diverse, arise at different stages, and are associated with greater psychological distress. This study examined the psychometric properties of the Short-Form Survivor Unmet Needs Survey (SF-SUNS) in Portuguese MM patients.

Methods: This cross-sectional study included 213 MM patients. The internal consistency of the scale was analyzed with Cronbach's α. Principal component analysis and confirmatory factor analysis were used to assess construct validity. Convergent validity was examined by using correlations with quality of life, satisfaction with social support, and psychological morbidity. Multiple regression analyses were conducted to explore the contribution of sociodemographic and clinical variables to unmet needs.

Results: The Portuguese SF-SUNS's factor structure follows the original's structure, although it includes fewer items. For each domain, Cronbach's α was ≤0.70, the minimum acceptable criterion. For construct validity, only unmet relationship and emotional needs had significant correlations (r ≥ 0.40)-specifically negative associations with quality of life and social support and positive associations with psychological morbidity. Regarding patient variables and SF-SUNS results, only cancer stage contributed significantly to unmet information needs, with patients at stage I reporting more needs than patients at stage III.

Conclusions: The SF-SUNS represents a valid and reliable tool to assess unmet needs among Portuguese MM patients. It may be useful in designing and monitoring interventions to improve well-being in cancer survivors.
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http://dx.doi.org/10.1111/psyg.12653DOI Listing
March 2021

Correction to: Infantile fibrosarcoma with TPN3-NTRK3 fusion in a boy with Bloom Syndrome.

Fam Cancer 2021 Jan 6. Epub 2021 Jan 6.

Stem Cell and Leukaemia Proteomics Laboratory, School of Cancer and Imaging Sciences, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.

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http://dx.doi.org/10.1007/s10689-020-00223-zDOI Listing
January 2021

Portuguese recommendations for the treatment of psoriasis with biologic therapy.

Eur J Dermatol 2020 Dec;30(6):645-654

Department of Dermatology, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, LisboaPortugal, Faculty of Medicine, University of Lisboa, LisboaPortugal, Dermatology Research Unit, iMM João Lobo Antunes, University of Lisboa, LisboaPortugal.

Psoriasis is a highly prevalent chronic, inflammatory multisystem disease with a considerable impact on patients' quality of life and the healthcare system. This report presents the recommendations developed by the Portuguese Psoriasis Group of the Portuguese Society of Dermatology and Venereology that address several clinical questions arising during the management and care of psoriasis with biologic therapy, based on the available evidence. The recommendations were generated following thorough evaluation of existing guidelines on the treatment of psoriasis, publications concerning new biologic treatments that have not yet been considered in existing guidelines, as well as expert-based recommendations. Considerations regarding the severity of psoriasis, indications for initiating biologic therapy, parameters to be considered in treatment choice (in particular, treatment goals), as well as recommendations for using and monitoring therapy and screening programmes are also included.
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http://dx.doi.org/10.1684/ejd.2020.3945DOI Listing
December 2020

Infantile fibrosarcoma with TPM3-NTRK1 fusion in a boy with Bloom syndrome.

Fam Cancer 2020 Nov 21. Epub 2020 Nov 21.

Stem Cell and Leukaemia Proteomics Laboratory, School of Cancer and Imaging Sciences, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.

Bloom syndrome (BS) is a genomic and chromosomal instability disorder with prodigious cancer predisposition caused by pathogenic variants in BLM. We report the clinical and genetic details of a boy who first presented with infantile fibrosarcoma (IFS) at the age of 6 months and subsequently was diagnosed with BS at the age of 9 years. Molecular analysis identified the pathogenic germline BLM sequence variants (c.1642C>T and c.2207_2212delinsTAGATTC). This is the first report of IFS related to BS, for which we show that both BLM alleles are maintained in the tumor and demonstrate a TPM3-NTKR1 fusion transcript in the IFS. Our communication emphasizes the importance of long-term follow up after treatment for pediatric neoplastic conditions, as clues to important genetic entities might manifest later, and the identification of a heritable tumor predisposition often leads to changes in patient surveillance and management.
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http://dx.doi.org/10.1007/s10689-020-00221-1DOI Listing
November 2020

Factors associated with mechanical device-related complications in tube fed patients: A multicenter prospective cohort study.

PLoS One 2020 19;15(11):e0241849. Epub 2020 Nov 19.

University of São Paulo at Ribeirão Preto College of Nursing, Ribeirão Preto, São Paulo, Brazil.

Aims: To identify the types of nasogastric/nasoenteric tube (NGT/NET)-related adverse events and to analyze the degree of harm and the factors associated with mechanical device-related complications.

Materials And Methods: A prospective cohort study was conducted from October 2017 to April 2019 in seven Brazilian hospitals. Data from 447 adult patients with NGT/NET were collected through electronic forms. Three methods were used to assess the NGT/NET-related adverse events: (1) encouraging spontaneous reports; (2) regular visits to the wards; and (3) review of medical records. The events were classified as mechanical device-related complications and other events. The degree of harm was classified according to the World Health Organization's International Classification for Patient Safety. Data were analyzed using the R program, version 3.5.3. The following tests were applied to identify associations between the explanatory and response variables: Cochran-Armitage Chi-Square test, Fisher's exact test, and Linear-by-linear Chi-Square test. Logistic regression analysis was performed to verify the predictors of mechanical device-related complications. All analyses were performed considering a 5% significance level.

Results: 191 NGT/NET-related adverse events were identified in 116 patients; the majority were mechanical device-related complications and resulted in mild harm to the patient. At the moment of the event, patients had a mean of 3.27 comorbidities, were highly dependent on nursing care, with high risk of death and altered level of consciousness. There was no association between the degree of harm and the care complexity, disease severity or level of consciousness. Intensive care was the strongest predictor for mechanical device-related complications and critical patients had a four times greater likelihood of presenting this type of event when compared to patients receiving minimal care.

Conclusion: Intensive care patients should receive special attention as the complexity of care is an important predictor for mechanical device-related complications in tube fed patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241849PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676660PMC
January 2021

Breast cancer post-surgical impact on women´s quality of life during chemotherapy treatment: A structural equation modelling approach.

Eur J Cancer Care (Engl) 2021 Jan 6;30(1):e13349. Epub 2020 Nov 6.

School of Psychology, University of Minho, Psychology Research Center (CIPsi), Braga, Portugal.

Objective: Breast cancer is an important public health problem that is increasing in incidence, being a stressor with a negative impact on women's quality of life. This study is focused on the evaluation of temporal precursors (one month before) of women's quality of life undergoing chemotherapy, considering post-surgical personal, clinical, cognitive and neuropsychophysiological factors, according to the Transactional Stress and Coping Model.

Methods: This longitudinal study included 112 patients with breast cancer. Data were collected in two different moments: before and during the adjuvant chemotherapy. Structural equation modelling was used to support a theoretically based model in which some antecedent factors impact patients' long-term quality of life through a set of mediators.

Results: The associations of breast symptoms, body image and sexual functioning with psychological distress and quality of life were totally mediated by illness perceptions, while the associations of working memory with psychological distress and quality of life were totally mediated by self-efficacy for coping. Patients with greater psychological distress showed higher levels of nadir cortisol.

Conclusions: Results showed the importance of assessing patients' perceptions of their illness, prior to chemotherapy, as well as promoting more self-efficacy for coping, in order to improve women's emotional state and quality of life.
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http://dx.doi.org/10.1111/ecc.13349DOI Listing
January 2021

Artery of Percheron and Endoscopic Endonasal Surgery: Case Report and Review of the Literature.

Asian J Neurosurg 2020 Jul-Sep;15(3):777-780. Epub 2020 Aug 28.

Department of Neurosurgery, Sant Pau Hospital, Barcelona, Spain.

Artery of Percheron (AOP) is a rare anatomical variant in which a single perforating artery arising from the P1 segment of the posterior cerebral artery supplies paramedian thalami and rostral midbrain. The occlusion of AOP produces bilateral thalamic ischemia and may be a rare complication in relation to an extended endoscopic endonasal approach. We report the case of a patient who developed AOP damage during endoscopic endonasal surgery (EES); to our knowledge, this complication has been previously reported only in one case, in relation to a second surgery. We also review the anatomical variants in thalamic vascularization and the factors that may be involved in this complication. A 52-year-old female underwent an extended endoscopic endonasal approach with intraoperative neurophysiological monitoring. In the postoperative period, she presented with a decreased level of consciousness and bilateral mydriasis. Magnetic resonance imaging showed rostral midbrain and paramedian thalami ischemia congruent with AOP infarction. AOP infarction may be associated with extended EES when treating lesions with retrosellar extension. Every effort should be made to preserve the small perforating arteries. Intraoperative neurophysiological monitoring of the motor and sensory pathways may not detect damage to the AOP.
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http://dx.doi.org/10.4103/ajns.AJNS_370_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591203PMC
August 2020

Calcium Modulation, Anti-Oxidant and Anti-Inflammatory Effect of Skin Allergens Targeting the Nrf2 Signaling Pathway in Alzheimer's Disease Cellular Models.

Int J Mol Sci 2020 Oct 21;21(20). Epub 2020 Oct 21.

Center for Neuroscience and Cell Biology and Institute for Biomedical Imaging and Life Sciences, University of Coimbra, 3000-548 Coimbra, Portugal.

Experimental evidence highlights nuclear factor (erythroid-derived 2)-like 2 (Nrf2) as a molecular target in Alzheimer's disease (AD). The well-known effect of electrophilic cysteine-reactive skin allergens on Nrf2-activation led to the hypothesis that these compounds could have a therapeutic role in AD. This was further supported by the neuroprotective activity of the skin allergen dimethyl fumarate (DMF), demonstrated in in vivo models of neurodegenerative diseases. We evaluated the effect of the cysteine-reactive allergens 1,4-phenylenediamine (PPD) and methyl heptine carbonate (MHC) on (1) neuronal redox imbalance and calcium dyshomeostasis using N2a wild-type (N2a-wt) and human APP-overexpressing neuronal cells (wild-type, N2a-APPwt) and (2) on neuroinflammation, using microglia BV-2 cells exposed to LPS (lipopolysaccharide). Phthalic anhydride (PA, mainly lysine-reactive), was used as a negative control. DMF, PPD and MHC increased Hmox1 gene and HMOX1 protein levels in N2a-APPwt cells suggesting Nrf2-dependent antioxidant activity. MHC, but also PA, rescued N2a-APPwt mitochondrial membrane potential and calcium levels in a Nrf2-independent pathway. All the chemicals showed anti-inflammatory activity by decreasing iNOS protein in microglia. This work highlights the potential neuroprotective and anti-inflammatory role of the selected skin allergens in in vitro models of AD, and supports further studies envisaging the validation of the results using in vivo AD models.
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http://dx.doi.org/10.3390/ijms21207791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594024PMC
October 2020

Absence of R-Ras1 and R-Ras2 causes mitochondrial alterations that trigger axonal degeneration in a hypomyelinating disease model.

Glia 2021 Mar 3;69(3):619-637. Epub 2020 Oct 3.

Departamento de Biología Molecular and Centro Biología Molecular "Severo Ochoa", Universidad Autónoma de Madrid - Consejo Superior de Investigaciones Científicas, Madrid, Spain.

Fast synaptic transmission in vertebrates is critically dependent on myelin for insulation and metabolic support. Myelin is produced by oligodendrocytes (OLs) that maintain multilayered membrane compartments that wrap around axonal fibers. Alterations in myelination can therefore lead to severe pathologies such as multiple sclerosis. Given that hypomyelination disorders have complex etiologies, reproducing clinical symptoms of myelin diseases from a neurological perspective in animal models has been difficult. We recently reported that R-Ras1 and/or R-Ras2 mice, which lack GTPases essential for OL survival and differentiation processes, present different degrees of hypomyelination in the central nervous system with a compounded hypomyelination in double knockout (DKO) mice. Here, we discovered that the loss of R-Ras1 and/or R-Ras2 function is associated with aberrant myelinated axons with increased numbers of mitochondria, and a disrupted mitochondrial respiration that leads to increased reactive oxygen species levels. Consequently, aberrant myelinated axons are thinner with cytoskeletal phosphorylation patterns typical of axonal degeneration processes, characteristic of myelin diseases. Although we observed different levels of hypomyelination in a single mutant mouse, the combined loss of function in DKO mice lead to a compromised axonal integrity, triggering the loss of visual function. Our findings demonstrate that the loss of R-Ras function reproduces several characteristics of hypomyelinating diseases, and we therefore propose that R-Ras1 and R-Ras2 neurological models are valuable approaches for the study of these myelin pathologies.
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http://dx.doi.org/10.1002/glia.23917DOI Listing
March 2021

Primary glomus tumour of the pituitary gland: diagnostic challenges of a rare and potentially aggressive neoplasm.

Virchows Arch 2021 May 12;478(5):977-984. Epub 2020 Sep 12.

Department of Neurosurgery, Manchester Centre for Clinical Neurosciences, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.

Primary non-neuroendocrine tumours of the pituitary gland and sella are rare lesions often challenging to diagnose. We describe two cases of clinically aggressive primary glomus tumour of the pituitary gland. The lesions occurred in a 63-year-old male and a 30-year-old female who presented with headache, blurred vision and hypopituitarism. Neuroimaging demonstrated large sellar and suprasellar tumours invading the surrounding structures. Histologically, the lesions were characterised by angiocentric sheets and nests of atypical cells that expressed vimentin, smooth muscle actin and CD34. Perivascular deposition of collagen IV was also a feature. Case 2 expressed synaptophysin. INI-1 (SMARCB1) expression was preserved. Both lesions were mitotically active and demonstrated a Ki-67 labelling index of 30%. Next-generation sequencing performed in case 1 showed no mutations in the reading frame of 37 commonly mutated oncogenes, including BRAF and KRAS. Four pituitary glomus tumours have previously been reported, none of which showed features of malignant glomus tumour. Similar to our two patients, three previous examples displayed aggressive behaviour.
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http://dx.doi.org/10.1007/s00428-020-02923-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099815PMC
May 2021

Pyrolytic Carbon Nanograss Enhances Neurogenesis and Dopaminergic Differentiation of Human Midbrain Neural Stem Cells.

Adv Healthc Mater 2020 10 9;9(20):e2001108. Epub 2020 Sep 9.

Department of Biotechnology and Biomedicine (DTU Bioengineering), Produktionstorvet, Building 423, Room 122, Kgs. Lyngby, 2800, Denmark.

Advancements in research on the interaction of human neural stem cells (hNSCs) with nanotopographies and biomaterials are enhancing the ability to influence cell migration, proliferation, gene expression, and tailored differentiation toward desired phenotypes. Here, the fabrication of pyrolytic carbon nanograss (CNG) nanotopographies is reported and demonstrated that these can be employed as cell substrates boosting hNSCs differentiation into dopaminergic neurons (DAn), a long-time pursued goal in regenerative medicine based on cell replacement. In the near future, such structures can play a crucial role in the near future for stem-cell based cell replacement therapy (CRT) and bio-implants for Parkinson's disease (PD). The unique combination of randomly distributed nanograss topographies and biocompatible pyrolytic carbon material is optimized to provide suitable mechano-material cues for hNSCs adhesion, division, and DAn differentiation of midbrain hNSCs. The results show that in the presence of the biocoating poly-L-lysine (PLL), the CNG enhances hNSCs neurogenesis up to 2.3-fold and DAn differentiation up to 3.5-fold. Moreover, for the first time, consistent evidence is provided, that CNGs without any PLL coating are not only supporting cell survival but also lead to significantly enhanced neurogenesis and promote hNSCs to acquire dopaminergic phenotype compared to PLL coated topographies.
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http://dx.doi.org/10.1002/adhm.202001108DOI Listing
October 2020

Early recognition of surgical patients with sepsis: Contribution of nursing records.

Appl Nurs Res 2021 02 25;57:151352. Epub 2020 Aug 25.

Department of General and Specialized Nursing, University of São Paulo at Ribeirão Preto College of Nursing, Ribeirão Preto, SP, Brazil. Electronic address:

Objective: This study aimed to analyze the contribution of nursing records to the early identification and management of sepsis in surgical patients at a university hospital.

Method: This is a study with a quantitative, retrospective, descriptive, and correlational design. Data collection was performed through hospital information systems in the first semester of 2017 with the approval of the research ethics committee. We included 28 patients who met the inclusion criteria of the study.

Results: The analysis of the content of the records evidenced the development of the first signs of systemic inflammatory response syndrome (SIRS) and organ dysfunction until the fifth day of hospitalization in 19 patients (67.8%). Confirmation or hypothesis of sepsis diagnosis occurred until the 10th day of hospitalization in 15 patients (53.5%). The analysis of the content of the records showed that the first signs of SIRS were predominantly identified in the electronic patient monitoring system in 26 cases (92.9%), whereas the first signs of organ dysfunction were described in the nursing staff records in 24 patients (85.7%).

Conclusion: The results confirm the importance of the quality of nursing records for risk identification, early recognition, and proper management of sepsis in surgical patients, aiming at achieving greater effectiveness in the management of healthcare processes.
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http://dx.doi.org/10.1016/j.apnr.2020.151352DOI Listing
February 2021

Subjective suffering in patients with low back pain.

Int J Rheum Dis 2020 Oct 31;23(10):1379-1387. Epub 2020 Aug 31.

School of Psychology, Psychology Research Center (CIPsi), University of Minho, Braga, Portugal.

Aim: Low back pain (LPB) is a prevalent rheumatic and musculoskeletal disease and patients often experience physical discomfort and functional limitations. This study aimed to evaluate how subjective suffering relates to illness perceptions, pain intensity and psychological morbidity as well as to understand the mediator (direct and indirect) effects on functional disability.

Methods: A cross-sectional study with 125 patients who received physiotherapy and answered the following instruments: Illness Perception Questionnaire-Revised; Illness Subjective Suffering Inventory; Hospital Anxiety and Depression Scale and the Oswestry LBP Incapacity Questionnaire.

Results: In the structural equation modeling analysis, subjective suffering totally mediated the relationship between both emotional response (estimate = 0.068, 95% highest posterior density interval [HPDI] = [0.017, 0.133]), consequences (estimate = 0.118, 95% HPDI = [0.035, 0.211]) and functional disability. The relationship between coherence and disability was partially mediated by subjective suffering (estimate = -0.067, 95% HPDI = [-0.134, -0.016]). Only identity and pain intensity showed direct effects on functional disability.

Conclusion: Intervention in patients with LBP should focus on subjective suffering to reduce functional disability, providing information and promoting the acceptance of disease and pain.
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http://dx.doi.org/10.1111/1756-185X.13936DOI Listing
October 2020

Paper-Based Platform with an In Situ Molecularly Imprinted Polymer for β-Amyloid.

ACS Omega 2020 Jun 15;5(21):12057-12066. Epub 2020 May 15.

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

Alzheimer's disease (AD) is one of the most common forms of dementia affecting millions of people worldwide. Currently, an easy and effective form of diagnosis is missing, which significantly hinders a possible improvement of the patient's quality of life. In this context, biosensors emerge as a future solution, opening the doors for preventive medicine and allowing the premature diagnosis of numerous pathologies. This work presents a pioneering biosensor that combines a bottom-up design approach using paper as a platform for the electrochemical recognition of peptide amyloid β-42 (Aβ-42), a biomarker for AD present in blood, associated with visible differences in the brain tissue and responsible for the formation of senile plaques. The sensor layer relies on a molecularly imprinted polymer as a biorecognition element, created on the carbon ink electrode's surface by electropolymerizing a mixture of the target analyte (Aβ-42) and a monomer (-phenylenediamine) at neutral pH 7.2. Next, the template molecule was removed from the polymeric network by enzymatic and acidic treatments. The vacant sites so obtained preserved the shape of the imprinted protein and were able to rebind the target analyte. Morphological and chemical analyses were performed in order to control the surface modification of the materials. The analytical performance of the biosensor was evaluated by an electroanalytical technique, namely, square wave voltammetry. For this purpose, the analytical response of the biosensor was tested with standard solutions ranging from 0.1 ng/mL to 1 μg/mL of Aβ-42. The linear response of the biosensor went down to 0.1 ng/mL. Overall, the developed biosensor offered numerous benefits, such as simplicity, low cost, reproducibility, fast response, and repeatability less than 10%. All together, these features may have a strong impact in the early detection of AD.
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http://dx.doi.org/10.1021/acsomega.0c00062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271027PMC
June 2020

Chemical composition of essential oils from four species, differentiation using multivariate analysis and antioxidant activity.

Nat Prod Res 2020 Jun 4:1-4. Epub 2020 Jun 4.

Department of Biodiversity, National Institute for Amazonian Research, Manaus, Brazil.

Essential oils from the leaves of four species of obtained through hydrodistillation were analyzed using GC-MS andmultivariate data analysis. The chemical analysis enabled the identification of qualitative and quantitative differences among the oils. -selinene (32.44 ± 1.14%), ()-nerolidol (44.23 ± 2.23%), -caryophyllene (19.11 ± 0.40%) and caryophyllene oxide (16.92 ± 0.21%) were identified as the major constituents of the and oils, respectively. The differences in the chemical profiles of the oils were confirmed by principal component analysis. All four species exhibited antioxidant activity. The oil from achieved the best results on the DPPH test (EC = 64.8 µg/ml) and with the ABTS radical (EC = 159.7 µg/ml).
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http://dx.doi.org/10.1080/14786419.2020.1774761DOI Listing
June 2020

Dysfunctional oxidative phosphorylation shunts branched-chain amino acid catabolism onto lipogenesis in skeletal muscle.

EMBO J 2020 07 3;39(14):e103812. Epub 2020 Jun 3.

Departamento de Biología Molecular, Centro de Biología Molecular "Severo Ochoa" (CBMSO), Universidad Autónoma de Madrid, Madrid, Spain.

It is controversial whether mitochondrial dysfunction in skeletal muscle is the cause or consequence of metabolic disorders. Herein, we demonstrate that in vivo inhibition of mitochondrial ATP synthase in muscle alters whole-body lipid homeostasis. Mice with restrained mitochondrial ATP synthase activity presented intrafiber lipid droplets, dysregulation of acyl-glycerides, and higher visceral adipose tissue deposits, poising these animals to insulin resistance. This mitochondrial energy crisis increases lactate production, prevents fatty acid β-oxidation, and forces the catabolism of branched-chain amino acids (BCAA) to provide acetyl-CoA for de novo lipid synthesis. In turn, muscle accumulation of acetyl-CoA leads to acetylation-dependent inhibition of mitochondrial respiratory complex II enhancing oxidative phosphorylation dysfunction which results in augmented ROS production. By screening 702 FDA-approved drugs, we identified edaravone as a potent mitochondrial antioxidant and enhancer. Edaravone administration restored ROS and lipid homeostasis in skeletal muscle and reinstated insulin sensitivity. Our results suggest that muscular mitochondrial perturbations are causative of metabolic disorders and that edaravone is a potential treatment for these diseases.
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http://dx.doi.org/10.15252/embj.2019103812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360968PMC
July 2020

Real-world evidence in antiretroviral therapy: drug safety data.

Braz J Infect Dis 2020 May - Jun;24(3):271-272. Epub 2020 May 15.

University of Porto, Faculty of Medicine, Health Information and Decision (MEDCIDS), Porto, Portugal; University of Porto, Faculty of Medicine, Center for Health Technology and Service Research (CINTESIS), Porto, Portugal.

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http://dx.doi.org/10.1016/j.bjid.2020.04.013DOI Listing
August 2020

Uptake of pre-symptomatic testing for and is age, gender, offspring and time-dependent.

J Med Genet 2020 Apr 30. Epub 2020 Apr 30.

Clinical Genetics Service, Manchester Centre for Genomic Medicine, Manchester University Hospitals NHS Foundation Trust, Manchester, UK

Background: Genetic testing for pathogenic variants (PVs) has been available in North West England since 1995. We assessed uptake of pre-symptomatic testing in 1564 families with PVs over a 24.5year follow-up (FU) period.

Methods: First-degree relatives (FDRs) in families with or PVs were eligible from date of index family report if unaffected by a relevant cancer and alive at report date. FDRs were censored as not having undergone a pre-symptomatic test at diagnosis of a relevant cancer, date of death, age 93 or 30/03/2019. Time to uptake of pre-symptomatic testing was assessed by Kaplan-Meier curves, by gender and children.

Results: 2554 male and 3115 female FDRs were eligible. Overall uptake was 775 (30.3%) in men and 1935 (62.1%) in women. This increased at 15 years to 33.6% and 67.9%, and continued to rise until 24 years (p<0.001). For women, the 29-year to 39-year age group had the highest uptake at 10 years FU (72.5%; p<0.01), whereas the 50-year to 59-year age group was highest in men (37.2%; p<0.01). Women <18 years at the time of familial variant identification had lower initial uptake, but this rose to >80% by 15 years. Uptake was higher in parous women (p<0.001) and in men with daughters (p<0.0001).

Conclusion: Uptake of / pre-symptomatic testing is age, gender and time-dependent, and higher in women with children and men with daughters.
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http://dx.doi.org/10.1136/jmedgenet-2019-106544DOI Listing
April 2020

Visual Search Efficiency in Mild Cognitive Impairment and Alzheimer's Disease: An Eye Movement Study.

J Alzheimers Dis 2020 ;75(1):261-275

Laboratório de Neurociências (LIM-27), Departamento e Instituto de Psiquiatria HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil.

Background: Visual search abilities are essential to everyday life activities and are known to be affected in Alzheimer's disease (AD). However, little is known about visual search efficiency in mild cognitive impairment (MCI), a transitive state between normal aging and dementia. Eye movement studies and machine learning methods have been recently used to detect oculomotor impairments in individuals with dementia.

Objective: The aim of the present study is to investigate the association between eye movement metrics and visual search impairment in MCI and AD.

Methods: 127 participants were tested: 43 healthy controls, 51 with MCI, and 33 with AD. They completed an eyetracking visual search task where they had to find a previously seen target stimulus among distractors.

Results: Both patient groups made more fixations on the screen when searching for a target, with longer duration than controls. MCI and AD fixated the distractors more often and for a longer period of time than the target. Healthy controls were quicker and made less fixations when scanning the stimuli for the first time. Machine-learning methods were able to distinguish between controls and AD subjects and to identify MCI subjects with a similar oculomotor profile to AD with a good accuracy.

Conclusion: Results showed that eye movement metrics are useful for identifying visual search impairments in MCI and AD, with possible implications in the early identification of individuals with high-risk of developing AD.
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http://dx.doi.org/10.3233/JAD-190690DOI Listing
May 2021

[Nevus Sebaceous of Jadassohn in the Newborn].

Acta Med Port 2020 Apr 1;33(4):288. Epub 2020 Apr 1.

Serviço de Neonatologia. Hospital Pedro Hispano. Porto. Portugal.

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http://dx.doi.org/10.20344/amp.12164DOI Listing
April 2020
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