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2.
Cureus ; 16(7): e63814, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39099950

RESUMEN

Fluoropyrimidines are metabolized mainly by the enzyme dihydropyrimidine dehydrogenase (DPD). Some variants in the coding gene, DPYD, have already been associated with increased toxicity, and their testing is recommended in patients proposed for treatment with these drugs. In this clinical case, a patient without the four variants recommended for testing showed toxicity from the second cycle of capecitabine onwards, requiring hospitalization in the third cycle. Sequencing of the DPYD gene showed the presence of three heterozygous variants which the laboratory interpreted as deleterious to the expression or function of DPD. In the absence of phenotypic testing, the patient stopped treatment, which is also the usual procedure in the case of compound heterozygosity of the variants usually tested. The literature review shows data for and against the role of each variant found in fluoropyrimidine toxicity, but there may be more concrete data in the study of haplotypes with multiple variants and the need to research alterations in other genes to better understand their relationship with toxicity.

3.
Int J Cardiovasc Imaging ; 40(8): 1745-1753, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38940965

RESUMEN

Right ventricle-pulmonary artery (RV-PA) coupling has been linked to clinical outcomes in patients with severe aortic stenosis (AS) undergoing transcatheter valve implantation (TAVI). However, the best timing for prognostic assessment remains uncertain. Our aim was to determine the impact of RV longitudinal function parameters and RV-PA coupling on mortality in patients undergoing TAVI.  Retrospective, single center, analysis including patients with AS who underwent TAVI between 2007 and 2021. Echocardiographic evaluation was performed before, shortly after the procedure, and during follow-up. RV-PA uncoupling was defined as a TAPSE/PASP ratio<0.55 (severe RV uncoupling was defined as TAPSE/PASP ratio<0.32. The effect of RV parameters on all-cause mortality up to 12 months was assessed.  Among the 577 patients included, pre-procedural TAPSE/PASP ratio data were available for 205. RV-PA uncoupling was present in 113 patients (55.1%), with severe uncoupling observed in 31 (15.1%). Within the first 12 months after TAVI, 51 patients (9%) died. Severe RV-PA uncoupling was associated with mortality in univariable Cox regression; however, this association was lost after adjusting for EuroSCORE II. A significant association was found between the TAPSE/PASP ratio (per 0.1-unit increase) after the procedure and the primary endpoint (HR: 0.73; 95% CI: 0.56, 0.97; p=0.029). Higher postprocedural PASP (HR: 1.04; 95% CI: 1.02, 1.06; p<0.001 was also associated with all-cause mortality.  V-PA uncoupling and PASP after TAVI are associated with all-cause mortality in patients and may be valuable for patient selection and for planning post-procedural care.


Asunto(s)
Estenosis de la Válvula Aórtica , Válvula Aórtica , Arteria Pulmonar , Índice de Severidad de la Enfermedad , Reemplazo de la Válvula Aórtica Transcatéter , Función Ventricular Derecha , Humanos , Masculino , Estudios Retrospectivos , Femenino , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Reemplazo de la Válvula Aórtica Transcatéter/mortalidad , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/fisiopatología , Estenosis de la Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/mortalidad , Arteria Pulmonar/fisiopatología , Arteria Pulmonar/diagnóstico por imagen , Anciano , Resultado del Tratamiento , Anciano de 80 o más Años , Factores de Tiempo , Factores de Riesgo , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/fisiopatología , Válvula Aórtica/cirugía , Medición de Riesgo , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología
4.
Schizophr Res ; 270: 260-272, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38944972

RESUMEN

BACKGROUND: It is known that the immune system is dysregulated in schizophrenia, having a state similar to chronic neuroinflammation. The origin of this process is unknown, but it is known that T and B lymphocytes, which are components of the adaptive immune system, play an important role in the pathogenic mechanisms of schizophrenia. METHODS: We analysed the membrane of PBMCs from patients diagnosed with schizophrenia through proteomic analysis (n = 5 schizophrenia and n = 5 control). We found the presence of the Kv1.3 voltage-gated potassium channel and its auxiliary subunit ß1 (KCNAB1) and ß2 (KCNAB2). From a sample of 90 participants, we carried out a study on lymphocytes with whole-cell patch-clamp experiments (n = 7 schizophrenia and n = 5 control), western blot (n = 40 schizophrenia and n = 40 control) and confocal microscopy to evaluate the presence and function of different channels. Kv in both cells. RESULTS: We demonstrated the overexpression of Kv1.1, Kv1.2, Kv1.3, Kv1.6, Kv4.2, Kv4.3 and Kv7.2 channels in PBMCs from patients with schizophrenia. This study represents a groundbreaking exploration, as it involves an electrophysiological analysis performed on T and B lymphocytes from patients diagnosed of schizophrenia compared to healthy participants. We observed that B lymphocytes exhibited an increase in output current along with greater peak current amplitude and voltage conductance curves among patients with schizophrenia compared with healthy controls. CONCLUSIONS: This study showed the importance of the B lymphocyte in schizophrenia. We know that the immune system is altered in schizophrenia, but the physiological mechanisms of this system are not very well known. We suggest that the B lymphocyte may be relevant in the pathophysiology of schizophrenia and that it should be investigated in more depth, opening a new field of knowledge and possibilities for new treatments combining antipsychotics and immunomodulators. The limitation is that all participants received antipsychotic medication, which may have influenced the differences observed between patients and controls. This implies that more studies need to be done where the groups can be separated according to the antipsychotic drug.


Asunto(s)
Canales de Potasio con Entrada de Voltaje , Esquizofrenia , Humanos , Esquizofrenia/metabolismo , Esquizofrenia/inmunología , Esquizofrenia/fisiopatología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Canales de Potasio con Entrada de Voltaje/metabolismo , Técnicas de Placa-Clamp , Linfocitos/metabolismo , Potenciales de la Membrana/fisiología , Potenciales de la Membrana/efectos de los fármacos , Proteómica
5.
Cureus ; 16(2): e54154, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38496108

RESUMEN

Background and objective Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL Ph+) is quite rare among pediatric patients. Its management has undergone significant changes in the past few years, leading to some variability in how it is approached. At the Portuguese Oncology Institute of Porto (IPOP), a tertiary oncological center, the standard of care has been aligned with the guidelines proposed by the European intergroup study of post-induction treatment of ALL Ph+ (EsPhALL). In this study, we aimed to examine the experience and outcomes related to the treatment of pediatric patients with ALL Ph+ at IPOP. Methods This retrospective cohort study involved pediatric patients diagnosed with ALL Ph+ at IPOP between January 2008 and December 2022 and analyzed their outcomes. Results A total of 14 patients were included. IKFZ1 was altered in five patients (out of nine in whom it was searched). Five patients were treated according to EsPhALL 2004, which involved starting imatinib later in a discontinuous manner [resulting in both five-year overall survival (OS) and progression-free survival (PFS) of 60%]. The EsPhALL 2010 (preconizing a continuous imatinib regimen instead) was employed in three patients, with a five-year OS and PFS of 66.7%. All children mentioned above received cranial irradiation therapy (CRT). Finally, six were treated according to the EsPhALL 2015, which stopped including CRT in its backbone. The five-year OS was 100%, whereas every patient progressed with an increase in BCR::ABL1 levels greater than 1-log. Moreover, until 2015, all patients had been recommended to undergo allogeneic hematopoietic stem cell transplantation (alloHSCT). However, since 2015, alloHSCT has been exclusively reserved for relapsed/refractory (R/R) disease or poor responders with positive measurable residual disease (MRD). In total, alloHSCT was performed in nine patients. Conclusions Although initially associated with a poor prognosis, the ALL Ph+ paradigm is drastically shifting. Further studies will hopefully clarify the outcomes in this population and help understand the role of central nervous system (CNS) prophylaxis, alloHSCT, and MRD quantification.

6.
Sleep Med ; 115: 122-130, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38359591

RESUMEN

STUDY OBJECTIVES: to characterize possible differences in the function of the ANS in patients with chronic insomnia compared to a control group, using a wearable device, in order to determine whether those findings allow diagnosing this medical entity. METHODS: Thirty-two patients with chronic insomnia and nineteen patients without any sleep disorder, as a control group, were recruited prospectively. Both groups of patients underwent an in-patient night with simultaneous polysomnography and wearable device recording Empatica E4 a diverse array of physiological signals, including electrodermal activity, temperature, accelerometry, and photoplethysmography, providing a comprehensive resource for in-depth sleep analysis. RESULTS: In polysomnography, patients suffering from insomnia showed a significant decrease in sleep efficiency and total sleep time, prolonged sleep latency, and increased wakefulness after sleep onset. Accelerometry results were statistically significant differences in the three axis (x, y, z) just in stage N3, no differences were observed between both groups in REM sleep. The lowest temperature was reached in REM sleep in both groups. Peripheral temperature did not decrease during the different sleep phases compared to wakefulness in insomnia, unlike in the control group. Heart rate was higher in patients with insomnia than in controls during wakefulness and sleep stage. Heart rate variability was lower in stage N3 and higher in REM sleep compared to wakefulness in both groups. Sweating was significantly higher in patients with insomnia compared to the control group, as indicated by Skin Conductance Variability values and Sudomotor Nerve. CONCLUSIONS: Our study suggests that patients with insomnia have increased sympathetic activity during sleep, showing a higher heart rate. Temperature and sweating significantly influence the different sleep phases.


Asunto(s)
Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Sistema Nervioso Autónomo , Sueño/fisiología , Vigilia/fisiología , Sueño REM/fisiología , Frecuencia Cardíaca/fisiología
7.
Cureus ; 16(1): e53099, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38283775

RESUMEN

Turnpenny-Fry Syndrome (TPFS) is a rare genetic disorder characterized by a severe developmental delay and a distinctive facial gestalt. It is caused by mutations in the Polycomb Group Ring Finger Protein 2 (PCGF2) gene, which is also known to play a role in numerous tumor types. Up to date, there have been no published case reports of patients with TPFS and concomitant malignancies. The present case describes the clinical evaluation and follow-up of a male infant with severe global developmental delay (GDD) and a distinctive phenotype. At 4 years of age, clinical exome sequencing confirmed the diagnosis of TPFS. Posteriorly, at 5 years of age, the patient was also diagnosed with T-cell acute lymphoblastic leukemia (ALL). Given the scarce literature regarding this syndrome, the authors expect that this case report will provide valuable information that could improve the follow-up of patients with TPFS. Furthermore, this case highlights the necessity for the appropriate diagnosis of developmental disorders, to ensure adequate care, surveillance of comorbidities and proper genetic counselling.

8.
Anal Methods ; 15(37): 4905-4917, 2023 09 28.
Artículo en Inglés | MEDLINE | ID: mdl-37718950

RESUMEN

The growth and development of the human brain is a long and complex process that requires a precise sequence of genetic and molecular events. This begins in the third week of gestation with the differentiation of neural progenitor cells and extends at least until late adolescence, possibly for life. One of the defects of this development is that we know very little about the signals that modulate this sequence of events. The first 3 years of life, during breastfeeding, is one of the critical periods in brain development. In these first years of life, it is believed that neurodevelopmental problems may be the molecular causes of mental disorders. Therefore, we herein propose a new hypothesis, according to which the chemical signals that could modulate this entire complex sequence of events appear in this early period, and the molecular level study of human breast milk and colostrum of mothers who give birth to children in different gestation periods could give us information on proteins influencing this process. In this work, we collected milk and colostrum samples (term, late preterm and moderate/very preterm) and exosomes were isolated. The samples of exosomes and complete milk from each fraction were analyzed by LC-ESI-MS/MS. In this work, we describe proteins in the different fractions of mature milk and colostrum of mothers with term, late preterm, or very preterm delivery, which could be involved in the regulation of the nervous system by their functions. We describe how they differ in different types of milk, paving the way for the investigation of possible new neuroregulatory pathways as possible candidates to modulate the nervous system.


Asunto(s)
Exosomas , Nacimiento Prematuro , Recién Nacido , Femenino , Embarazo , Adolescente , Niño , Humanos , Leche Humana/química , Leche Humana/metabolismo , Calostro/química , Calostro/metabolismo , Nacimiento Prematuro/metabolismo , Lactancia/fisiología , Exosomas/metabolismo , Proteómica , Espectrometría de Masas en Tándem
9.
Nutrients ; 15(14)2023 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-37513702

RESUMEN

Human milk is the biological fluid with the highest exosome amount and is rich in microRNAs (miRNAs). These are key regulators of gene expression networks in both normal physiologic and disease contexts, miRNAs can influence many biological processes and have also shown promise as biomarkers for disease. One of the key aspects in the regeneration of the nervous system is that there are practically no molecules that can be used as potential drugs. In the first weeks of lactation, we know that human breast milk must contain the mechanisms to transmit molecular and biological information for brain development. For this reason, our objective is to identify new modulators of the nervous system that can be used to investigate neurodevelopmental functions based on miRNAs. To do this, we collected human breast milk samples according to the time of delivery and milk states: mature milk and colostrum at term; moderate and very preterm mature milk and colostrum; and late preterm mature milk. We extracted exosomes and miRNAs and realized the miRNA functional assays and target prediction. Our results demonstrate that miRNAs are abundant in human milk and likely play significant roles in neurodevelopment and normal function. We found 132 different miRNAs were identified across all samples. Sixty-nine miRNAs had significant differential expression after paired group comparison. These miRNAs are implicated in gene regulation of dopaminergic/glutamatergic synapses and neurotransmitter secretion and are related to the biological process that regulates neuron projection morphogenesis and synaptic vesicle transport. We observed differences according to the delivery time and with less clarity according to the milk type. Our data demonstrate that miRNAs are abundant in human milk and likely play significant roles in neurodevelopment and normal function.


Asunto(s)
MicroARNs , Embarazo , Recién Nacido , Femenino , Humanos , Animales , MicroARNs/genética , MicroARNs/metabolismo , Leche Humana/metabolismo , Leche/metabolismo , Calostro/metabolismo , Lactancia/genética , Sinapsis/metabolismo
10.
Cad. Bras. Ter. Ocup ; 31(spe): e3389, 2023. tab
Artículo en Portugués | LILACS-Express | LILACS, Index Psicología - Revistas | ID: biblio-1447747

RESUMEN

Resumo Com o crescente número de terapeutas ocupacionais atuantes no Sistema Único de Assistência Social (SUAS), amplia-se a necessidade por processos formativos que desenvolvam criticamente a atuação profissional neste campo. A partir desta demanda formativa foi criado, em outubro de 2020, um projeto de extensão intitulado "Comunidade de práticas em terapia ocupacional no SUAS: articulação profissional e construção de estratégias", com o intuito de promover trocas de conhecimento e experiências entre terapeutas ocupacionais trabalhadoras em unidades socioassistenciais. Neste artigo se apresentam as possibilidades e os limites do trabalho no SUAS sob o ponto de vista de terapeutas ocupacionais que nele atuam e que foram participantes da Comunidade de Práticas, analisando se e como suas ações profissionais têm se relacionado com a fundamentação teórico-metodológica da terapia ocupacional social. Para isso, foi revisitado todo o material de registro produzido nos dois ciclos do projeto, efetivados de outubro de 2020 a julho de 2021. As informações extraídas das atas foram organizadas em um quadro que agrupou as temáticas encontradas. A análise dos dados revelou dois principais aspectos que possibilitam a correlação das ações das profissionais com a fundamentação teórico-metodológica da terapia ocupacional social, sendo: a necessária leitura acerca da indissociabilidade entre os fatores micro e macrossociais para o desenvolvimento do trabalho e a dimensão técnico-política da atuação terapêutico-ocupacional. Em ambos os debates a fundamentação teórico-metodológica da terapia ocupacional social foi e tem sido o fio condutor do processo, possibilitando uma leitura social e maior apropriação das finalidades técnico-profissionais no âmbito da assistência social.


Abstract With the growing number of occupational therapists working at the Unified Social Assistance System (SUAS) in Brazil, there has been an increasing need for education processes focusing on the critical development of professional practice in this field. From this education demand, a project was created in October 2020: "Communities of Practice in Occupational Therapy at SUAS: professional planning and construction of strategies" aiming to promote the exchange of knowledge and experiences between occupational therapists working in social assistance. This study aims to present the work possibilities and limits at SUAS from the point of view of occupational therapists who work at its units and who participated in the Community of Practice, analyzing whether and how their professional actions have been related to the social occupational therapy theoretical-methodological framework. To this end, all the recording material produced in the two project cycles from October 2020 to July 2021 was revisited. The collected information was organized in a table that grouped the themes found. Data analysis revealed two main aspects that allow the correlation of the professionals' actions with the social occupational therapy theoretical-methodological framework, namely, the necessary interpretation of the inseparability between micro- and macro-social factors for the development of work and the professional and political dimensions of the occupational-therapeutic actions. In both debates, the social occupational therapy theoretical-methodological framework has been the guiding thread of the process, enabling a social reading and a greater understanding of technical-professional purposes within the scope of social assistance.

11.
Cad. Bras. Ter. Ocup ; 31(spe): e2302, 2023.
Artículo en Portugués | LILACS-Express | LILACS, Index Psicología - Revistas | ID: biblio-1447757
12.
Front Pharmacol ; 13: 850583, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35496309

RESUMEN

At the beginning of the pandemic, we observed that lithium carbonate had a positive effect on the recovery of severely ill patients with COVID-19. Lithium is able to inhibit the replication of several types of viruses, some of which are similar to the SARS-CoV-2 virus, increase the immune response and reduce inflammation by preventing or reducing the cytokine storm. Previously, we published an article with data from six patients with severe COVID-19 infection, where we proposed that lithium carbonate could be used as a potential treatment for COVID-19. Now, we set out to conduct a randomized clinical trial number EudraCT 2020-002008-37 to evaluate the efficacy and safety of lithium treatment in patients infected with severe SARS-CoV-2. We showed that lithium was able to reduce the number of days of hospital and intensive care unit admission as well as the risk of death, reduces inflammatory cytokine levels by preventing cytokine storms, and also reduced the long COVID syndromes. We propose that lithium carbonate can be used to reduce the severity of COVID-19.

13.
Cell Mol Neurobiol ; 42(6): 1921-1932, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33712885

RESUMEN

The brain extracellular matrix (ECM) is involved in crucial processes of neural support, neuronal and synaptic plasticity, extrasynaptic transmission, and neurotransmission. ECM is a tridimensional fibrillary meshwork composed of macromolecules that determine its bioactivity and give it unique characteristics. The characterization of the brain ECM is critical to understand its dynamic in SZ. Thus, a comparative study was developed with 71 patients with schizophrenia (SZ) and 70 healthy controls. Plasma of participants was analysed by label-free liquid chromatography-tandem mass spectrometry, and the results were validated using the classical western blot method. Lastly, immunostaining of post-mortem human brain tissue was performed to analyse the distribution of the brain ECM proteins by confocal microscopy. The analysis identified four proteins: fibronectin, lumican, nidogen-1, and secreted protein acidic and rich in cysteine (SPARC) as components of the brain ECM. Statistical significance was found for fibronectin (P = 0.0166), SPARC (P = 0.0003), lumican (P = 0.0012), and nidogen-1 (P < 0.0001) that were decreased in the SZ group. Fluorescence imaging of prefrontal cortex (PFC) sections revealed a lower expression of ECM proteins in SZ. Our study proposes a pathophysiological dysregulation of proteins of the brain ECM, whose abnormal composition leads to a progressive neuronal impairment and consequently to neurodegenerative processes due to lack of neurophysiological support and dysregulation of neuronal homeostasis. Moreover, the brain ECM and its components are potential pharmacological targets to develop new therapeutic approaches to treat SZ.


Asunto(s)
Fibronectinas , Esquizofrenia , Encéfalo/metabolismo , Matriz Extracelular/metabolismo , Proteínas de la Matriz Extracelular/metabolismo , Fibronectinas/metabolismo , Humanos , Lumican/metabolismo , Osteonectina/metabolismo , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/metabolismo
14.
Cad. Bras. Ter. Ocup ; 30: e2984, 2022. tab
Artículo en Portugués | LILACS-Express | LILACS, Index Psicología - Revistas | ID: biblio-1360271

RESUMEN

Resumo Introdução Estudos feministas contribuíram para o entendimento dos papéis de gênero atribuídos à mulher e ao homem enquanto processos socialmente construídos e não biologicamente determinados. No trabalho em saúde no Brasil, marcado pela predominância numérica de mulheres, a divisão sexual do trabalho é influenciada pela naturalização do cuidado como atributo feminino. Na terapia ocupacional, segundo o Conselho Regional da categoria, apenas 3,7% dos profissionais do Estado de São Paulo são homens, o que confere singularidade às relações entre gêneros na profissão. Objetivo Busca-se identificar e analisar experiências e percepções relacionadas ao gênero entre terapeutas ocupacionais autodeclarados homens. Método Estudo qualitativo de tipo exploratório, realizado por meio de entrevistas em profundidade com cinco terapeutas ocupacionais no município de São Paulo, SP, Brasil, posteriormente analisadas por meio de análise temática. Resultados Os entrevistados identificaram experiências que consideram ser privilégios de gênero não dissimulados, principalmente no que tange ao acesso ao emprego e à valorização profissional. Percebem que, no ambiente profissional, atuam estereótipos ligados ao padrão de comportamento atribuído ao gênero masculino, associando-o à força, autoridade e poder. Em se tratando de relações de cuidado com usuários, alguns participantes não percebem a presença de normas de gênero, o que parece convergente com a invisibilidade social desses processos. Conclusão Questões de gênero estão presentes nas vivências profissionais dos entrevistados, os quais, de modo geral, percebem-nas sob uma perspectiva crítica. Mostra-se relevante para a terapia ocupacional brasileira que novos estudos adensem reflexões e abordem distintas faces das relações de gênero na prática profissional.


Abstract Introduction Feminist studies have contributed to the understanding of the gender roles assigned to women and men as socially constructed and not biologically determined processes. In health work in Brazil, marked by the numerical predominance of women, the sexual division of labor is influenced by the naturalization of care as a female attribute. In occupational therapy, according to the Regional Council of the category, only 3.7% of professionals in the State of São Paulo are male, which gives uniqueness to gender relations in the profession. Objective We seek to identify and analyze gender-related experiences and perceptions among self-declared male occupational therapists. Method Qualitative exploratory study, carried out through in-depth interviews with five occupational therapists in the city of São Paulo, SP, Brazil, later analyzed through thematic analysis. Results Respondents identified experiences that they consider to be undisguised gender privileges, especially regarding access to employment and professional development. They perceive that, in the professional environment, there are stereotypes linked to the pattern of behavior attributed to the male gender, associating it with strength, authority and power. When it comes to care relationships with users, some participants do not perceive the presence of gender norms, which seems to converge with the social invisibility of these processes. Conclusion Gender issues are present in the professional experiences of the respondents, who, in general, perceive them from a critical perspective. It is relevant for Brazilian occupational therapy that new studies increase reflections and address different aspects of gender relations in professional practice.

15.
Int J Mol Sci ; 22(16)2021 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-34445205

RESUMEN

The neurobiology of schizophrenia is multifactorial, comprising the dysregulation of several biochemical pathways and molecules. This research proposes a peripheral biomarker for schizophrenia that involves the second extracellular loop of norepinephrine transporter (NEText), the tropomyosin receptor kinase C (TrkC), and the neurotrophin-3 (NT-3) in T cells. The study of NEText, NT-3, and TrkC was performed in T cells and plasma extracted from peripheral blood of 54 patients with schizophrenia and 54 healthy controls. Levels of NT-3, TrkC, and NET were significantly lower in plasma and T cells of patients compared to healthy controls. Co-immunoprecipitation (co-IPs) showed protein interactions with Co-IP NEText-NT-3 and Co-IP NEText-TrkC. Computational modelling of protein-peptide docking by CABS-dock provided a medium-high accuracy model for NT-3-NEText (4.6935 Å) and TrkC-NEText (2.1365 Å). In summary, immunocomplexes reached statistical relevance in the T cells of the control group contrary to the results obtained with schizophrenia. The reduced expression of NT-3, TrkC, and NET, and the lack of molecular complexes in T cells of patients with schizophrenia may lead to a peripheral dysregulation of intracellular signaling pathways and an abnormal reuptake of norepinephrine (NE) by NET. This peripheral molecular biomarker underlying schizophrenia reinforces the role of neurotrophins, and noradrenergic and immune systems in the pathophysiology of schizophrenia.


Asunto(s)
Simulación del Acoplamiento Molecular , Neurotrofina 3/química , Proteínas de Transporte de Noradrenalina a través de la Membrana Plasmática/química , Receptor trkC/química , Esquizofrenia/etiología , Adulto , Biomarcadores/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neurotrofina 3/genética , Neurotrofina 3/metabolismo , Proteínas de Transporte de Noradrenalina a través de la Membrana Plasmática/genética , Proteínas de Transporte de Noradrenalina a través de la Membrana Plasmática/metabolismo , Estructura Secundaria de Proteína , Receptor trkC/genética , Receptor trkC/metabolismo , Esquizofrenia/genética , Esquizofrenia/metabolismo
16.
Microb Pathog ; 157: 105000, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34048888

RESUMEN

Infections caused by Staphylococcus aureus are increasingly prevalent, and treatment has become more difficult due to the emergence of strains that are resistant to multiple drugs, such as methicillin-resistant Staphylococcus aureus (MRSA). Penicillin-binding proteins (PBPs) are essential enzymes in peptidoglycan biosynthesis. Only found in bacteria, they are an excellent target for the development of bacterial control strategies. S. aureus has 4 PBPs, and only PBP2 has transglycosylation activity, making it a good model to evaluate whether the inactivation of the transglycosylase domain (PBP2t) could lead to bacterial death. (His6)-tagged PBP2t was purified from the E. coli cell lysate using Ni-charged resin, and ELISA and immunoblotting assays demonstrated that PBP2t is immunogenic. Flow cytometry analysis was performed to verify the binding of polyclonal antibodies to the bacterial cell surface. In order to verify the ability to provide protection, immunized mice were challenged with a sublethal dose of MRSA, and the bacterial loads in kidneys and spleen were evaluated. A reduction of 2-2.5 logs was seen in organs from immunized mice compared with the negative controls in two independent assays (p < 0.01). Our results demonstrate that the PBP2t is a promising target for the development of novel antimicrobial strategies, but further testing should be performed to validate the protection conferred by immunization with this protein.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Staphylococcus aureus , Animales , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Proteínas Bacterianas , Escherichia coli , Inmunoterapia , Ratones , Proteínas de Unión a las Penicilinas/genética
17.
Comput Biol Med ; 133: 104387, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33872966

RESUMEN

KnowSeq R/Bioc package is designed as a powerful, scalable and modular software focused on automatizing and assembling renowned bioinformatic tools with new features and functionalities. It comprises a unified environment to perform complex gene expression analyses, covering all the needed processing steps to identify a gene signature for a specific disease to gather understandable knowledge. This process may be initiated from raw files either available at well-known platforms or provided by the users themselves, and in either case coming from different information sources and different Transcriptomic technologies. The pipeline makes use of a set of advanced algorithms, including the adaptation of a novel procedure for the selection of the most representative genes in a given multiclass problem. Similarly, an intelligent system able to classify new patients, providing the user the opportunity to choose one among a number of well-known and widespread classification and feature selection methods in Bioinformatics, is embedded. Furthermore, KnowSeq is engineered to automatically develop a complete and detailed HTML report of the whole process which is also modular and scalable. Biclass breast cancer and multiclass lung cancer study cases were addressed to rigorously assess the usability and efficiency of KnowSeq. The models built by using the Differential Expressed Genes achieved from both experiments reach high classification rates. Furthermore, biological knowledge was extracted in terms of Gene Ontologies, Pathways and related diseases with the aim of helping the expert in the decision-making process. KnowSeq is available at Bioconductor (https://bioconductor.org/packages/KnowSeq), GitHub (https://github.com/CasedUgr/KnowSeq) and Docker (https://hub.docker.com/r/casedugr/knowseq).


Asunto(s)
Biología Computacional , Programas Informáticos , Algoritmos , Humanos , Transcriptoma
18.
Referência ; serV(6): e20111, abr. 2021. tab
Artículo en Portugués | LILACS-Express | BDENF - Enfermería | ID: biblio-1346880

RESUMEN

Resumo Enquadramento: As vivências pessoais e em ensino clínico influenciam o modo como os estudantes de enfermagem lidam com a morte. Objetivo: Avaliar as atitudes dos estudantes de enfermagem perante a morte e os cuidados em fim de vida. Metodologia: Estudo descritivo. Os dados foram recolhidos através de um questionário online. Participaram 158 estudantes do curso de licenciatura em Enfermagem. Os dados quantitativos foram analisados com recurso ao programa IBM SPSS Statistics. Foram realizadas análises estatísticas descritivas e exploratórias dos dados através de testes paramétricos e não paramétricos. Resultados: Os estudantes evidenciam maior proximidade com atitudes de neutralidade, medo e aproximação perante a morte e menos proximidade com atitudes de evitamento e escape. Relativamente aos cuidados em fim de vida, os estudantes que já realizaram ensino clínico apresentam atitudes positivas. Conclusão: É importante utilizar metodologias de ensino/aprendizagem que permitam ao estudante expor as suas experiências com a morte e com os cuidados em fim de vida em ensino clínico.


Abstract Background: Personal and clinical experiences influence how nursing students cope with death. Objective: To assess nursing students' attitudes towards death and end-of-life care. Methods: Descriptive study. Data were collected through an online questionnaire. The sample consisted of 158 undergraduate nursing students. Quantitative data were analyzed using IBM SPSS Statistics software. Descriptive statistics and exploratory data analysis were performed through parametric and non-parametric tests. Results: Students tend more to attitudes of neutral acceptance, fear of death, and approach acceptance and less to attitudes of avoidance and escape. Regarding end-of-life care, students who had already completed clinical training showed positive attitudes. Conclusion: Teaching and learning methodologies should be used to allow students to expose their experiences with death and end-of-life care in clinical training.


Resumen Marco contextual: Las experiencias personales y en la enseñanza clínica influyen en el modo en que los estudiantes de enfermería se enfrentan a la muerte. Objetivo: Evaluar las actitudes de los estudiantes de Enfermería hacia la muerte y los cuidados al final de la vida. Metodología: Estudio descriptivo. Los datos se recogieron mediante un cuestionario en línea. Participaron un total de 158 estudiantes de la licenciatura de Enfermería. Los datos cuantitativos se analizaron con el programa IBM SPSS Statistics. Se realizaron análisis estadísticos descriptivos y exploratorios de los datos mediante pruebas paramétricas y no paramétricas. Resultados: Los estudiantes mostraron una mayor proximidad a las actitudes de neutralidad, miedo y cercanía hacia la muerte, y una menor proximidad a las actitudes de evitación y huida. Con respecto a los cuidados al final de la vida, los estudiantes que ya han realizado la enseñanza clínica tienen actitudes positivas. Conclusión: Es importante utilizar metodologías de enseñanza/aprendizaje que permitan a los estudiantes exponer sus experiencias con la muerte y los cuidados al final de la vida en la enseñanza clínica.

19.
Rev. ter. ocup ; 32(1-3): e204894, jan.-dez. 2021-2022.
Artículo en Inglés, Portugués | LILACS-Express | LILACS | ID: biblio-1418581

RESUMEN

In Brazil, a large part of adopted children and adolescents were sheltered after a protective court order. In the adoption process, after the steps of gradual contact, children and parents start to live together permanently, when they experience the process of building a new daily life, in which activities and interactions already known undergo transformations. The study aimed to understand the deinstitutionalization process by adoption from the point of view of fathers and mothers who adopted children over two years. It was support by references that constitute the understanding of everyday life in the scope of occupational therapy, from a perspective that denaturalizes it, putting into view its complexity in the constellation of human interactions. It took place through the collection and analysis of interviews with adopting fathers and mothers. The results composed thematic axes gathering the perspectives of the parents, indicating that: a) their projections about future daily life were relevant in defining the profile of the children to be adopted; b) children's daily experiences in SAI were not properly presented to them prior to the phase of definitive coexistence; c) the process of building parenthood was essentially linked to the constitution of a common daily life, in family. It is essential to pay attention to the centrality of everyday life to build bonds and a stable socio-relational environments It is essential to pay attention to the centrality of everyday life to build bonds and stable socio-relational environments that are conducive to the development of children and adolescents

20.
Rev. ter. ocup ; 32(1-3): e204941, jan.-dez. 2021-2022.
Artículo en Inglés, Portugués | LILACS-Express | LILACS | ID: biblio-1418625

RESUMEN

Introdução: Coletivos juvenis de periferias urbanas têm se constituído em torno de linguagens artísticas diversas e adquirido importância central na mediação das juventudes com a sociedade. Alguns se reúnem em torno dos Sound Systems de música reggae, que com a ocupação sonora de espaços públicos com caixas de som empilhadas e discos de vinil criam eventos culturais de rua. Objetivos: Conhecer os Sound Systems como atividade cultural, bem como suas repercussões no cotidiano de jovens que participam de coletivos que os promovem. Metodologia: Observações em eventos de Sound System e entrevistas com seletores de coletivos, interpretadas por análise temática. Resultados e discussão: Os coletivos se organizam na conjunção entre sonoridade, celebração e difusão de valores ligados à cultura negra. Para os seletores, o Sound System deve oferecer oportunidades de aprendizagem sobre a opressão histórica dos povos negros, bem como de fortalecimento da identidade e cultura negra. O pertencimento social, a elevação da autoestima e as oportunidades de aprendizagem pessoal foram mudanças associadas por eles à participação na cultura Sound System. Considerações finais: Os coletivos buscam ativamente produzir pontes entre o universo reggae jamaicano e as realidades dos jovens negros das periferias pobres da cidade de São Paulo, investindo no resgate da história e dos poderes agregadores da memória, da sonoridade, e de símbolos e mensagens da cultura reggae.


Introduction: Youth groups from urban peripheries have been constituted around diverse artistic languages and have acquired central importance in the mediation of youths with society. Some gather around the reggae music Sound Systems, which with the sound occupation of public spaces through stacked speakers and vinyl records create cultural street events. Objectives: To learn about the Sound Systems as a cultural activity as well as its repercussions on the daily lives of young people who participate in groups that promote them. Methodology: Observation in Sound System events and interviews with young people who work as selectors of these groups, interpreted by thematic analysis. Results and discussion: Sound System groups have been organized around the conjunction between sonority, celebration and dissemination of values linked to black culture. The selectors interviewed argue that the Sound System should provide opportunities to learn about the historical oppression of black people, as well as to strengthen of black identity and culture. Social belonging, increased self-esteem and opportunities for personal learning were changes they associated with participation in the Sound System culture. Final considerations: The groups actively seek to build bridges between the Jamaican reggae universe and the realities experienced by young black people from the disadvantaged peripheral areas of São Paulo city, investing in the rescue of history and the aggregating powers of memory, sound, symbols and messages from reggae culture.

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