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Pulmonary arterial hypertension (PAH) is a form of precapillary pulmonary hypertension caused by a complex process of endothelial dysfunction and vascular remodeling. If left untreated, this progressive disease presents with symptoms of incapacitating fatigue causing marked loss of quality of life, eventually culminating in right ventricular failure and death. Patient management is complex and based on accurate diagnosis, risk stratification, and treatment initiation, with close monitoring of response and disease progression. Understanding the underlying pathophysiology has enabled the development of multiple drugs directed at different targets in the pathological chain. Vasodilator therapy has been the mainstay approach for the last few years, significantly improving quality of life, functional status, and survival. Recent advances in therapies targeting dysfunctional pathways beyond endothelial dysfunction may address the fundamental processes underlying the disease, raising the prospect of increasingly effective options for this high-risk group of patients with a historically poor prognosis. Resumo: A hipertensão arterial pulmonar (HAP) é um tipo de hipertensão pulmonar pré-capilar causada por um processo complexo de disfunção endotelial e remodelação vascular desfavorável. A história natural desta doença progressiva inclui sintomatologia de insuficiência cardíaca e perda de qualidade de vida, culminando em falência ventricular direita e morte. A gestão dos doentes é complexa, baseando-se num diagnóstico preciso, estratificação de risco e início de terapêutica adequada, sendo essencial a monitoração apertada da resposta e progressão da doença.A compreensão da fisiopatologia subjacente permitiu o desenvolvimento de múltiplos fármacos dirigidos a diferentes alvos na cadeia patológica. A terapêutica vasodilatadora destaca-se como a abordagem de base nas últimas décadas, tendo permitido melhoria significativa da qualidade de vida, estado funcional e sobrevida dos doentes. Os avanços terapêuticos recentes, com o advento da utilização de fármacos dirigido aos mecanismos subjacentes à doença, trazem a promessa de opções terapêuticas cada vez mais eficazes para este grupo de doentes de alto risco, com um prognóstico historicamente reservado.

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Alzheimer’s disease (AD) is the most common form of dementia worldwide, characterized by progressive memory impairment, behavioral changes, and, ultimately, loss of consciousness and death. Recently, microRNA (miRNA) dysfunction has been associated with increased production and impaired clearance of amyloid-β (Aβ) peptides, whose accumulation is one of the most well-known pathophysiological markers of this disease. In this study, we identified several miRNAs capable of targeting key proteins of the amyloidogenic pathway. The expression of one of these miRNAs, miR-31, previously found to be decreased in AD patients, was able to simultaneously reduce the levels of APP and Bace1 mRNA in the hippocampus of 17-month-old AD triple-transgenic (3xTg-AD) female mice, leading to a significant improvement of memory deficits and a reduction in anxiety and cognitive inflexibility. In addition, lentiviral-mediated miR-31 expression significantly ameliorated AD neuropathology in this model, drastically reducing Aβ deposition in both the hippocampus and subiculum. Furthermore, the increase of miR-31 levels was enough to reduce the accumulation of glutamate vesicles in the hippocampus to levels found in non-transgenic age-matched animals. Overall, our results suggest that miR-31-mediated modulation of APP and BACE1 can become a therapeutic option in the treatment of AD. Keywords: Alzheimer’s disease, miR-31, gene therapy, lentiviral vector, APP, BACE1, amyloid-β peptide, cognitive function, memory

Introducción: La longevidad se ha convertido en uno los mayores logros de la segunda mitad del siglo XX. Objetivo: Comparar la calidad de vida de los adultos mayores de Brasil y Portugal que reciben atención primaria de salud. Materiales y métodos: Se realizó un estudio cuantitativo transversal comparativo con una muestra probabilística de 294 adultos mayores que fueron acompañados por la estrategia de Salud Familiar y divididos en dos grupos: 130 adultos mayores ubicados en Benevides, Brasil y 164 en Coímbra, Portugal durante 2015 y 2017. La caracterización sociodemográfica y la evaluación de la calidad de vida se obtuvieron mediante el Cuestionario de Calidad de Vida de la Organización Mundial de la Salud (WHOQOL-BREF), que consta de 26 preguntas divididas en cuatro áreas: salud física, salud psicológica, relaciones sociales y ambiente. Se aplicó la prueba U de Mann-Whitney para el análisis estadístico comparativo. Resultados: En los grupos se observó el predominio de las mujeres casadas, jubiladas y con baja escolaridad (entre 1 y 4 años). La edad media fue de 70 años en Brasil y 76 años en Portugal. En cuanto a la calidad de vida, los adultos mayores brasileños obtuvieron mejores puntuaciones en el área de salud psicológica (79.1%) mientras que los adultos mayores portugueses tuvieron la mejor puntuación en el área ambiental (65.6%). Las puntuaciones más bajas se presentaron en el área ambiental en Benevides (56.3%) y en la salud física (60.7%) en Coímbra. Discusión: La calidad de vida en el proceso de envejecimiento es un importante predictor para la preservación de la autonomía de los adultos mayores. Conclusiones: Estos resultados amplían la concepción de la importancia de la atención integral en el proceso de envejecimiento para brindar una mejor calidad de vida, lo que contribuye a satisfacer las necesidades específicas de la población de edad avanzada. Como citar este artículo: Sousa, Fabianne de Jesus Dias de; Oliveira, Catarina Resende de; Pinto, Anabela Mota; Rodrigues, Victor; Gonçalves, Lucia Hisako Takase; Gamba, Mônica Antar. Qualidade de vida de idosos brasileiros e portugueses: uma análise comparativa. Revista Cuidarte. 2021;12(1):e1230. http://dx.doi.org/10.15649/cuidarte.1230

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Objectives: To describe our experience with a coronavirus disease 2019 (COVID-19) outbreak within a large rheumatology department early in the pandemic.Methods: Symptomatic and asymptomatic healthcare workers (HCWs) had a naso-oropharyngeal swab for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and were followed clinically. Reverse transcription polymerase-chain reaction (RT-PCR) was repeated to document cure, and serological response was assessed. Patients with risk contacts within the department in the 14 days preceding the outbreak were screened for COVID-19 symptoms.Results: 14/34 HCWs (41%; 40 ± 14 years, 71% female) tested positive for SARS-CoV-2, and 11/34 (32%) developed symptoms but were RT-PCR-negative. Half of RT-PCR-positive HCWs did not report fever, cough, or dyspnea before testing, which were absent in 3/14 cases (21%). Mild disease prevailed (79%), but 3 HCWs had moderate disease requiring further assessment, which excluded severe complications. Nevertheless, symptom duration (28 ± 18 days), viral shedding (31 ± 10 days post-symptom onset, range 15–51), and work absence (29 ± 28 days) were prolonged. 13/14 (93%) of RT-PCR-positive and none of the RT-PCR-negative HCWs had a positive humoral response Higher IgG indexes were observed in individuals over 50 years of age (14.5 ± 7.7 vs. 5.0 ± 4.4, p = 0.012). Of 617 rheumatic patients, 8 (1.3%) developed COVID-19 symptoms (1/8 hospitalization, 8/8 complete recovery), following a consultation/procedure with an asymptomatic (7/8) or mildly symptomatic (1/8) HCW.Conclusions: A COVID-19 outbreak can occur among HCWs and rheumatic patients, swiftly spreading over the presymptomatic stage. Mild disease without typical symptoms should be recognized and may evolve with delayed viral shedding, prolonged recovery, and adequate immune response in most individuals.

Introdução: O tromboembolismo pulmonar e trombose venosa profunda ocorrem em idade pediátrica com incidência, morbilidade e mortalidade desconhecidas. O objetivo foi rever epidemiologia, apresentação clínica, exames complementares de diagnóstico e prognóstico de doentes com tromboembolismo pulmonar e trombose venosa profunda. Material e Métodos: Estudo retrospetivo, descritivo e analítico de doentes pediátricos internados num hospital de nível II por tromboembolismo pulmonar e trombose venosa profunda, entre 2000 e 2014. Estudaram-se características demográficas, história clínica, comorbilidades e fatores de risco. Resultados: Foram internados 11 doentes (sete com tromboembolismo pulmonar, cinco com trombose venosa profunda e um com ambos), 64% do género feminino e idade média de 16 anos. Todos os doentes com tromboembolismo pulmonar referiam toracalgia/dispneia, 25% síncope/palpitações e 25% febre. Todos os doentes com trombose venosa profunda referiam dor no local da obstrução, 83% edema/cianose do membro afetado e 17% febre. O estudo da trombofilia positivo foi o fator de risco mais frequente nas duas entidades. O valor médio dos D-dímeros foi 3252 ug/L e 2660 ug/L no tromboembolismo pulmonar e trombose venosa profunda, respetivamente. Todos os doentes iniciaram anticoagulação, três necessitaram de cuidados intensivos, três apresentaram sequelas e houve um óbito. Discussão: Todos os doentes tinham pelo menos um fator de risco associado e as condições de hipercoagulabilidade herdadas foram o fator de risco mais frequentemente encontrado nos nossos adolescentes. Conclusão: O aumento da incidência na população pediátrica descrito na literatura pode ser atribuído à crescente sensibilização para esta patologia, aos avanços médicos e aumento da sobrevida de doenças crónicas. Escasseiam recomendações baseadas na evidência que identifiquem os doentes com risco de trombose, para que as decisões possam ser tomadas de forma cuidadosa, equilibrando o risco e benefício em cada caso.

Abstract Background Cerebrospinal fluid (CSF) biomarkers have been used to increase the evidence of underlying Alzheimer’s disease (AD) pathology in mild cognitive impairment (MCI). However, CSF biomarker-based classification often results in conflicting profiles with controversial prognostic value. Normalization of the CSF Aβ42 concentration to the level of total amyloid beta (Aβ), using the Aβ42/40 ratio, has been shown to improve the distinction between AD and non-AD dementia. Therefore, we evaluated whether the Aβ42/40 ratio would improve MCI categorization and more accurately predict progression to AD. Methods Our baseline population consisted of 197 MCI patients, of which 144 had a follow-up ≥ 2 years, and comprised the longitudinal study group. To establish our own CSF Aβ42/40 ratio reference value, a group of 168 AD-dementia patients and 66 neurological controls was also included. CSF biomarker-based classification was operationalized according to the framework of the National Institute of Aging–Alzheimer Association criteria for MCI. Results When using the core CSF biomarkers (Aβ42, total Tau and phosphorylated Tau), 30% of the patients fell into the high-AD-likelihood (HL) group (both amyloid and neurodegeneration markers positive), 30% into the low-AD-likelihood group (all biomarkers negative), 28% into the suspected non-Alzheimer pathophysiology (SNAP) group (only neurodegeneration markers positive) and 12% into the isolated amyloid pathology group (only amyloid-positive). Replacing Aβ42 by the Aβ42/40 ratio resulted in a significant increase in the percentage of patients with amyloidosis (42–59%) and in the proportion of interpretable biological profiles (61–75%), due to a reduction by half in the number of SNAP cases and an increase in the proportion of the HL subgroup. Survival analysis showed that risk of progression to AD was highest in the HL group, and increased when the Aβ42/40 ratio, instead of Aβ42, combined with total Tau and phosphorylated Tau was used for biomarker-based categorization. Conclusions Our results confirm the usefulness of the CSF Aβ42/40 ratio in the interpretation of CSF biomarker profiles in MCI patients, by increasing the proportion of conclusive profiles and enhancing their predictive value for underlying AD.

Introduction: Aging is an inevitable process that has a social impact in the forecoming decades, and it will present a great challenge regarding public health. An efficient health system requires a reflection on the preventive measures to be implemented. Material and Methods: The study population comprised a total number of 2672 individuals of both genders, aged 55 years and over, residents in continental Portugal, to whom a questionnaire was applied that included the following sections: Social network; Locomotion; Physical autonomy; Instrumental autonomy; Cognitive assessment; Physical activity. Results: The study of aging in the Portuguese population found that physical autonomy for tasks related to daily life are associated with better cognitive evaluation. A statistically significant association was found between performance in cognitive assessment and gender, age, schooling, the fact of living alone, the number of hours being alone, autonomy to walk in the street, washing, dressing, eating, preparing meals, doing shopping, managing money and taking medications and washer / treat clothing. Discussion: Cognitive evaluation is negatively influenced by the number of hours that an individual is alone. Conclusion: Activities of daily life must be valued, since they require the ability to plan and carry out tasks and their preservation is a key component in successful aging.

A partir da leitura dos estudos de Foucault sobre o cuidado de si e de Deleuze e Guattari sobre o corpo sem órgãos (CsO), tivemos o objetivo de traçar as possíveis aproximações entre a escrita de si e o diário de CsO. Esse exercício de escrita de si constitui um exercício de constituição de corpos que além de um voltar-se sobre si, oferece um cuidado de si para cuidar dos outros. Concebemos o diário de CsO enquanto uma prática de si que oferece um movimento etopoiético na direção de uma dimensão ética e estética, mas também política da vida.

Core cerebrospinal fluid (CSF) biomarkers-Aβ42, Tau and pTau–have been recently incorporated in the revised criteria for Alzheimer’s disease (AD). However, their widespread clinical application lacks standardization. Pre-analytical sample handling and storage play an important role in the reliable measurement of these biomarkers across laboratories. In this study, we aim to surpass the efforts from previous studies, by employing a multicentre approach to assess the impact of less studied CSF pre-analytical confounders in AD-biomarkers quantification. Four different centres participated in this study and followed the same established protocol. CSF samples were analysed for three biomarkers (Aβ42, Tau and pTau) and tested for different spinning conditions (temperature: Room temperature (RT) vs. 4oC; speed: 500g vs. 2000g vs. 3000g), storage volume variations (25%, 50% and 75% of tube total volume) as well as freezing-thaw cycles (up to 5 cyles). The influence of sample routine parameters, inter-centre variability and relative value of each biomarker (reported as normal/abnormal), was analysed. Centrifugation conditions did not influence biomarkers levels, except for samples with a high CSF total protein content, where either non centrifugation or centrifugation at RT, compared to 4ºC, led to higher Aβ42 levels. Reducing CSF storage volume from 75% to 50% of total tube capacity, decreased Aβ42 concentration (within analytical CV of the assay), whereas no change in Tau or pTau was observed. Moreover, the concentration of Tau and pTau appears to be stable up to 5 freeze-thaw cycles, whereas Aβ42 levels decrease if CSF is freeze-thawed more than 3 times. This systematic study reinforces the need for CSF centrifugation at 4ºC prior to storage and highlights the influence of storage conditions in Aβ42 levels. This study contributes to the establishment of harmonized standard operating procedures that will help reducing inter-lab variability of CSF-AD biomarkers evaluation.

Type one diabetes mellitus is the second most frequent disease in childhood, presenting with serious complications when inadequately controlled. The most useful measure of metabolic control is hemoglobin A1c (HbA1c), being essential the awareness of the causes of its variability.to evaluate the effect of age and time of disease on HbA1c; to evaluate the relationship between HbA1c and serum lipid and microalbuminuria values.Observational, transversal and analytic study, based on data obtained in the files of all patients that attain the Pediatric Diabetic Consult. The studied variables were: sex, actual age, diagnostic age, metabolic control and chronic complications. Statistical analysis was made with Excel2003® and SPSS 15.0®. A significance level of 5% was adopted. Results: a 96 diabetic population was obtained. Last year HbA1c average was 8,3% and was less than 7,5% in one third of the cases. Adolescent's HbA1c (8,4%) was significantly higher than in children (7,8%) (p=0,03). Diabetics with a disease longer than five years presented higher HbA1c values (9% vs. 7,8%; p

BACKGROUND: Glioblastoma multiforme (GBM) displays multiple amplicons and homozygous deletions that involve relevant pathogenic genes and other genes whose role remains unknown. METHODOLOGY: Single-nucleotide polymorphism (SNP)-arrays were used to determine the frequency of recurrent amplicons and homozygous deletions in GBM (n = 46), and to evaluate the impact of copy number alterations (CNA) on mRNA levels of the genes involved. PRINCIPAL FINDINGS: Recurrent amplicons were detected for chromosomes 7 (50%), 12 (22%), 1 (11%), 4 (9%), 11 (4%), and 17 (4%), whereas homozygous deletions involved chromosomes 9p21 (52%) and 10q (22%). Most genes that displayed a high correlation between DNA CNA and mRNA levels were coded in the amplified chromosomes. For some amplicons the impact of DNA CNA on mRNA expression was restricted to a single gene (e.g., EGFR at 7p11.2), while for others it involved multiple genes (e.g., 11 and 5 genes at 12q14.1-q15 and 4q12, respectively). Despite homozygous del(9p21) and del(10q23.31) included multiple genes, association between these DNA CNA and RNA expression was restricted to the MTAP gene. CONCLUSIONS: Overall, our results showed a high frequency of amplicons and homozygous deletions in GBM with variable impact on the expression of the genes involved, and they contributed to the identification of other potentially relevant genes.

BACKGROUND: Large-scale gene expression profiling of peripheral blood mononuclear cells from Rheumatoid Arthritis (RA) patients could provide a molecular description that reflects the contribution of diverse cellular responses associated with this disease. The aim of our study was to identify peripheral blood gene expression profiles for RA patients, using Illumina technology, to gain insights into RA molecular mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: The Illumina Human-6v2 Expression BeadChips were used for a complete genome-wide transcript profiling of peripheral blood mononuclear cells (PBMCs) from 18 RA patients and 15 controls. Differential analysis per gene was performed with one-way analysis of variance (ANOVA) and P values were adjusted to control the False Discovery Rate (FDR

Resumo O presente artigo realizado por pesquisadores do Laboratório de Corporeidade e Subjetividade (CORPOREILABS - Universidade Federal Fluminense [UFF], Faculdade Angel Vianna [FAV], Universidade Federal do Rio de Janeiro [UFRJ], Universidade Federal do Ceará [UFC]) surge da necessidade de explicitar o tema da corporeidade nos saberes e práticas psis na contemporaneidade. O sujeito moderno emerge de uma radical experiência de separação eu-mundo e a subjetividade, entendida por uma perspectiva representacional, sofre uma cisão dos processos sensíveis do corpo. No intuito de afirmar uma outra política de percepção a respeito da subjetividade, afirma-se nesse artigo a necessidade de incluir nos estudos da subjetividade sua relação intrínseca com os processos de corporeidade. Desde esta perspectiva se abre uma clínica e um modo de pesquisar como processualidades, em que a dimensão sensorial, ética, estética e política são convocadas.

ImportanceCerebral amyloid-β aggregation is an early event in Alzheimer disease (AD). Understanding the association between amyloid aggregation and cognitive manifestation in persons without dementia is important for a better understanding of the course of AD and for the design of prevention trials.ObjectiveTo investigate whether amyloid-β aggregation is associated with cognitive functioning in persons without dementia.Design, setting, and participantsThis cross-sectional study included 2908 participants with normal cognition and 4133 with mild cognitive impairment (MCI) from 53 studies in the multicenter Amyloid Biomarker Study. Normal cognition was defined as having no cognitive concerns for which medical help was sought and scores within the normal range on cognitive tests. Mild cognitive impairment was diagnosed according to published criteria. Study inclusion began in 2013 and is ongoing. Data analysis was performed in January 2017.Main outcomes and measuresGlobal cognitive performance as assessed by the Mini-Mental State Examination (MMSE) and episodic memory performance as assessed by a verbal word learning test. Amyloid aggregation was measured with positron emission tomography or cerebrospinal fluid biomarkers and dichotomized as negative (normal) or positive (abnormal) according to study-specific cutoffs. Generalized estimating equations were used to examine the association between amyloid aggregation and low cognitive scores (MMSE score ≤27 or memory z score≤-1.28) and to assess whether this association was moderated by age, sex, educational level, or apolipoprotein E genotype.ResultsAmong 2908 persons with normal cognition (mean [SD] age, 67.4 [12.8] years), amyloid positivity was associated with low memory scores after age 70 years (mean difference in amyloid positive vs negative, 4% [95% CI, 0%-7%] at 72 years and 21% [95% CI, 10%-33%] at 90 years) but was not associated with low MMSE scores (mean difference, 3% [95% CI, -1% to 6%], P = .16). Among 4133 patients with MCI (mean [SD] age, 70.2 [8.5] years), amyloid positivity was associated with low memory (mean difference, 16% [95% CI, 12%-20%], P

Biomarkers that accurately identify mild cognitive impairment (MCI) are of greater importance for Alzheimer's disease (AD) management and treatment. On the other hand, blood-based biomarkers are not only more practical but also less invasive than the common cerebrospinal fluid biomarkers. In their report in the Journal of Alzheimer's Disease, Wang and collaborators identified 67 upregulated and 220 downregulated long noncoding RNAs (lncRNAs). They further demonstrated that 4 of these lncRNAs could discriminate MCI from cognitively healthy individuals. Apart from their significance as potential biomarkers for MCI diagnosis, these lncRNAs can offer additional information on the cellular mechanisms of AD pathology. [ABSTRACT FROM AUTHOR]

ImportanceCerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies.ObjectiveTo use individual participant data meta-analysis to estimate the prevalence of amyloid pathology as measured with biomarkers in participants with normal cognition, subjective cognitive impairment (SCI), or mild cognitive impairment (MCI).Data sourcesRelevant biomarker studies identified by searching studies published before April 2015 using the MEDLINE and Web of Science databases and through personal communication with investigators.Study selectionStudies were included if they provided individual participant data for participants without dementia and used an a priori defined cutoff for amyloid positivity.Data extraction and synthesisIndividual records were provided for 2914 participants with normal cognition, 697 with SCI, and 3972 with MCI aged 18 to 100 years from 55 studies.Main outcomes and measuresPrevalence of amyloid pathology on positron emission tomography or in cerebrospinal fluid according to AD risk factors (age, apolipoprotein E [APOE] genotype, sex, and education) estimated by generalized estimating equations.ResultsThe prevalence of amyloid pathology increased from age 50 to 90 years from 10% (95% CI, 8%-13%) to 44% (95% CI, 37%-51%) among participants with normal cognition; from 12% (95% CI, 8%-18%) to 43% (95% CI, 32%-55%) among patients with SCI; and from 27% (95% CI, 23%-32%) to 71% (95% CI, 66%-76%) among patients with MCI. APOE-ε4 carriers had 2 to 3 times higher prevalence estimates than noncarriers. The age at which 15% of the participants with normal cognition were amyloid positive was approximately 40 years for APOE ε4ε4 carriers, 50 years for ε2ε4 carriers, 55 years for ε3ε4 carriers, 65 years for ε3ε3 carriers, and 95 years for ε2ε3 carriers. Amyloid positivity was more common in highly educated participants but not associated with sex or biomarker modality.Conclusions and relevanceAmong persons without dementia, the prevalence of cerebral amyloid pathology as determined by positron emission tomography or cerebrospinal fluid findings was associated with age, APOE genotype, and presence of cognitive impairment. These findings suggest a 20- to 30-year interval between first development of amyloid positivity and onset of dementia.