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1.
Artigo em Inglês | MEDLINE | ID: mdl-39235911

RESUMO

OBJECTIVE: Research has not often delved into the experiences of the Moroccan-heritage community in Western societies. We followed a mixed-methods approach, combining qualitative with quantitative methods, applying an intersectionality perspective to analyze the feelings and perceptions of Moroccan-heritage people about their situation in Spain, interaction with Spaniards, perceived discrimination, and metaperceptions to understand their affective reactions to injustice (Studies 1 and 2), and willingness to mobilize (Study 2). METHOD: In Study 1, we conducted four discussion groups with Moroccan-heritage women (n = 12) and men (n = 13) separately. In Study 2, we analyzed with a quantitative survey (n = 147) participants' identity fusion with Morocco and Spain, perceived metaprejudice and discrimination, metadehumanization, the evaluation of the ingroup situation, affective reactions to their situation, and support of collective actions for their rights. RESULTS: The analysis of Study 1 revealed experiences of discrimination and spontaneous positive but also negative metaperceptions, especially among women, including an alarming metadehumanization. Quantitative analyses in Study 2 confirmed gender differences, with women reporting worse feelings and perceptions, and confirmed that metadehumanization was crucial to predict indignation and anger of Moroccan-heritage people, while perceived discrimination was significant for mobilization. CONCLUSIONS: Although gender differences need additional clarification, these findings advance our theoretical knowledge about the sources of shared grievances among disadvantaged group members and the role of metadehumanization in their affective reactions to injustice. Interventions are urgent to address metadehumanization and canalize its affective consequences to promote social change. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

2.
Foods ; 13(17)2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39272485

RESUMO

This study investigates the effect of daily consumption of a concentrated garlic and onion extract on COVID-19 symptoms among elderly nursing home residents. Volunteers consumed a daily capsule of the concentrated powder rich in organosulfur compounds over 36 weeks during lunch. The incidence and severity of COVID-19 symptoms between the treatment and control groups were compared, along with monitoring the safety of consumption, incidence of other diseases, and medicine usage. The treatment group showed a significant reduction in both the number and severity of COVID-19 symptoms compared to the control group, with no significant adverse effects observed. No significant reduction in symptom duration was detected. This study provides preliminary evidence that concentrated garlic and onion extract may aid in the treatment of COVID-19 among older adults. These findings suggest potential public health benefits, emphasizing the need for further research to explore the immunomodulatory properties of these natural compounds.

3.
bioRxiv ; 2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39257766

RESUMO

Antibody discovery is crucial for developing therapeutics and vaccines as well as understanding adaptive immunity. However, the lack of approaches to synthesize antibodies with defined sequences in a high-throughput manner represents a major bottleneck in antibody discovery. Here, we presented oPool+ display, which combines oligo pool synthesis and mRNA display to construct and characterize many natively paired antibodies in parallel. As a proof-of-concept, we applied oPool+ display to rapidly screen the binding activity of >300 natively paired influenza hemagglutinin (HA) antibodies against the conserved HA stem domain. Structural analysis of 16.ND.92, one of the identified HA stem antibodies, revealed a unique binding mode distinct from other known broadly neutralizing HA stem antibodies with convergent sequence features. Yet, despite such differences, 16.ND.92 remained broadly reactive and conferred in vivo protection. Overall, this study not only established an experimental platform that can be applied in both research and therapeutics to accelerate antibody discovery, but also provides molecular insights into antibody responses to the influenza HA stem, which is a major target for universal influenza vaccine development.

4.
bioRxiv ; 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39131281

RESUMO

Prior reward is a potent cue for attentional capture, but the underlying neurobiology is largely unknown. In a novel whisker touch detection task, we show that mice flexibly shift attention between specific whiskers on a trial-by-trial timescale, guided by the recent history of stimulus-reward association. Two-photon calcium imaging and spike recordings revealed a robust neurobiological correlate of attention in the somatosensory cortex (S1), boosting sensory responses to the attended whisker in L2/3 and L5, but not L4. Attentional boosting in L2/3 pyramidal cells was topographically precise and whisker-specific, and shifted receptive fields toward the attended whisker. L2/3 VIP interneurons were broadly activated by whisker stimuli, motion, and arousal but did not carry a whisker-specific attentional signal, and thus did not mediate spatially focused tactile attention. Together, these findings establish a new model of focal attention in the mouse whisker tactile system, showing that the history of stimuli and rewards in the recent past can dynamically engage local modulation in cortical sensory maps to guide flexible shifts in ongoing behavior.

5.
Elife ; 122024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39102289

RESUMO

Like other volume electron microscopy approaches, automated tape-collecting ultramicrotomy (ATUM) enables imaging of serial sections deposited on thick plastic tapes by scanning electron microscopy (SEM). ATUM is unique in enabling hierarchical imaging and thus efficient screening for target structures, as needed for correlative light and electron microscopy. However, SEM of sections on tape can only access the section surface, thereby limiting the axial resolution to the typical size of cellular vesicles with an order of magnitude lower than the acquired xy resolution. In contrast, serial-section electron tomography (ET), a transmission electron microscopy-based approach, yields isotropic voxels at full EM resolution, but requires deposition of sections on electron-stable thin and fragile films, thus making screening of large section libraries difficult and prone to section loss. To combine the strength of both approaches, we developed 'ATUM-Tomo, a hybrid method, where sections are first reversibly attached to plastic tape via a dissolvable coating, and after screening detached and transferred to the ET-compatible thin films. As a proof-of-principle, we applied correlative ATUM-Tomo to study ultrastructural features of blood-brain barrier (BBB) leakiness around microthrombi in a mouse model of traumatic brain injury. Microthrombi and associated sites of BBB leakiness were identified by confocal imaging of injected fluorescent and electron-dense nanoparticles, then relocalized by ATUM-SEM, and finally interrogated by correlative ATUM-Tomo. Overall, our new ATUM-Tomo approach will substantially advance ultrastructural analysis of biological phenomena that require cell- and tissue-level contextualization of the finest subcellular textures.


Assuntos
Barreira Hematoencefálica , Tomografia com Microscopia Eletrônica , Animais , Camundongos , Tomografia com Microscopia Eletrônica/métodos , Barreira Hematoencefálica/ultraestrutura , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/ultraestrutura , Camundongos Endogâmicos C57BL , Masculino , Microscopia Eletrônica de Varredura/métodos , Microtomia
6.
Nutr Hosp ; 41(4): 758-765, 2024 Aug 29.
Artigo em Espanhol | MEDLINE | ID: mdl-38967309

RESUMO

Introduction: Introduction: malnutrition is a very frequent problem in oncology patients and may have serious repercussions. Adequate nutritional management is cost-effective in terms of health and survival in this population, but it requires multidisciplinary coordination, specific training, and continuous follow-up. Objective: to validate the applicability and efficacy of a multidisciplinary nutritional support protocol in oncology patients. Methods: a multidisciplinary nutritional protocol was developed for oncology patients, with guidelines for screening and assessment of malnutrition, treatment, re-evaluation, and management of side effects, as well as guidance on supplementation and eating patterns. The protocol would be implemented in various clinical centers, collecting data through a structured questionnaire, registering variables before and after implementation. Results: the protocol and its impact were implemented and evaluated in 39 centers. An improvement in nutritional care was observed, evidenced by an earlier initiation of nutritional assessment and an increase in the number of patients receiving adequate care following the protocol implementation. Problems related to inadequate malnutrition coding in the centers, limited resources, and the need for greater interdepartmental collaboration were identified. Conclusions: the conduct of this study provides insights into how the implementation of a multidisciplinary nutritional support protocol can improve the nutritional care received by patients and informs about the main obstacles to adequate implementation.


Introducción: Introducción: la desnutrición es un problema muy frecuente en el paciente oncológico y puede tener graves repercusiones. Un manejo nutricional adecuado es coste-efectivo en términos de salud y supervivencia en esta población, pero requiere de coordinación multidisciplinar, formación específica y seguimiento continuo. Objetivo: validar la aplicabilidad y eficacia de un protocolo multidisciplinar de soporte nutricional en pacientes oncológicos. Métodos: se desarrolló un protocolo nutricional multidisciplinar para pacientes oncológicos, con pautas para el cribado y valoración de la desnutrición, el tratamiento, la reevaluación y la gestión de los efectos secundarios, además de orientaciones sobre suplementación y patrones de alimentación. Se implementaría el protocolo en diversos centros clínicos, recogiendo datos a través de un cuestionario estructurado, registrando variables antes y después de la implementación. Resultados: se implementó y se valoraron el protocolo y su impacto en 39 centros. Se observó una mejoría en la atención nutricional, evidenciada por un inicio más precoz de la valoración nutricional y un aumento en el número de pacientes que recibían atención adecuada tras la implementación del protocolo. Se identificaron problemas relacionados con una inadecuada codificación de la desnutrición en los centros, recursos limitados y la necesidad de mayor colaboración interdepartamental. Conclusiones: la realización de este estudio ofrece información de cómo la implementación de un protocolo multidisciplinar de soporte nutricional puede contribuir a mejorar la atención nutricional que reciben los pacientes e informa de cuáles son los principales obstáculos para una implementación adecuada.


Assuntos
Desnutrição , Neoplasias , Avaliação Nutricional , Apoio Nutricional , Humanos , Espanha , Desnutrição/terapia , Desnutrição/diagnóstico , Desnutrição/etiologia , Apoio Nutricional/métodos , Apoio Nutricional/normas , Neoplasias/complicações , Masculino , Feminino , Protocolos Clínicos , Equipe de Assistência ao Paciente , Pessoa de Meia-Idade , Inquéritos e Questionários , Idoso
7.
Nat Commun ; 15(1): 5175, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890325

RESUMO

The receptor-binding site of influenza A virus hemagglutinin partially overlaps with major antigenic sites and constantly evolves. In this study, we observe that mutations G186D and D190N in the hemagglutinin receptor-binding site have coevolved in two recent human H3N2 clades. X-ray crystallography results show that these mutations coordinately drive the evolution of the hemagglutinin receptor binding mode. Epistasis between G186D and D190N is further demonstrated by glycan binding and thermostability analyses. Immunization and neutralization experiments using mouse and human samples indicate that the evolution of receptor binding mode is accompanied by a change in antigenicity. Besides, combinatorial mutagenesis reveals that G186D and D190N, along with other natural mutations in recent H3N2 strains, alter the compatibility with a common egg-adaptive mutation in seasonal influenza vaccines. Overall, our findings elucidate the role of epistasis in shaping the recent evolution of human H3N2 hemagglutinin and substantiate the high evolvability of its receptor-binding mode.


Assuntos
Epistasia Genética , Evolução Molecular , Glicoproteínas de Hemaglutininação de Vírus da Influenza , Vírus da Influenza A Subtipo H3N2 , Influenza Humana , Humanos , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H3N2/metabolismo , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/química , Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Animais , Camundongos , Sítios de Ligação , Influenza Humana/virologia , Mutação , Cristalografia por Raios X , Vacinas contra Influenza , Ligação Proteica , Receptores Virais/metabolismo , Receptores Virais/genética , Receptores Virais/química , Feminino
8.
Eur J Pharm Biopharm ; 201: 114385, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38945408

RESUMO

In the current "era of lipid carriers," numerous strategies have been developed to manufacture lipid nanoparticles (LNPs). Nevertheless, the potential impact of various preparation methods on the characteristics, use, and/or stability of these LNPs remains unclear. In this work, we attempted to compare the effects of three different preparation methods: microfluidics (MF), reverse phase evaporation (RV), and ouzo (OZ) on lipid-peptide NPs (LPNPs) as plasmid DNA delivery carriers. These LPNPs had the same components, namely DOTMA cationic lipid, DSPC, cholesterol, and protamine. Subsequently, we compared the LPNPs in terms of their physicochemical features, functionality as gene delivery vehicles in two distinct cell lines (NT2 and D1-MSCs), and finally, their storage stability over a six-month period. It was clear that all three LPNP formulations worked to deliver EGFP-pDNA while keeping cells alive, and their physicochemical stability was high for 6 months. However, the preparation technique had a significant impact on their physicochemical characteristics. The MF produced LPNPs with a lesser size, polydispersity index, and zeta potential than the other synthesis methods. Additionally, their DNA entrapment efficiency, cell viability, and functional stability profiles were generally superior. These findings provide new insights for comparing different manufacturing methods to create LPNPs with the desired characteristics for effective and safe gene delivery.


Assuntos
DNA , Técnicas de Transferência de Genes , Lipídeos , Microfluídica , Nanopartículas , Peptídeos , Plasmídeos , Nanopartículas/química , Plasmídeos/administração & dosagem , Humanos , Lipídeos/química , DNA/administração & dosagem , DNA/química , Microfluídica/métodos , Peptídeos/química , Linhagem Celular , Transfecção/métodos , Tamanho da Partícula , Sobrevivência Celular/efeitos dos fármacos
9.
J Soc Psychol ; : 1-19, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38635592

RESUMO

A mixed-methods approach was used to analyze the social representations of four ethnic minorities in southern Spain. Following a between-subjects design, Spanish participants (n = 532) were assigned to evaluate either Romanian Roma, Spanish Roma, Moroccan, or Romanian non-Roma people, with a free-association task and scales of stereotypes, emotions, and behavioral tendencies. Results showed that Romanian Roma was the most devalued target, eliciting the worst representation and attitudes. The content analysis revealed that participants described minorities mainly in terms of social exclusion, culture, appearance, personality, opportunity seeking, stigmatization, and personalization/equality, with social exclusion being a key category associated with worst attitudes.

10.
Front Plant Sci ; 15: 1323087, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38455727

RESUMO

Olive (Olea europaea L. subsp. europaea) is one of the most important crops of the Mediterranean Basin and temperate areas worldwide. Obtaining new olive varieties adapted to climatic changing conditions and to modern agricultural practices, as well as other traits such as biotic and abiotic stress resistance and increased oil quality, is currently required; however, the long juvenile phase, as in most woody plants, is the bottleneck in olive breeding programs. Overexpression of genes encoding the 'florigen' Flowering Locus T (FT), can cause the loss of the juvenile phase in many perennials including olives. In this investigation, further characterization of three transgenic olive lines containing an FT encoding gene from Medicago truncatula, MtFTa1, under the 35S CaMV promoter, was carried out. While all three lines flowered under in vitro conditions, one of the lines stopped flowering after acclimatisation. In soil, all three lines exhibited a modified plant architecture; e.g., a continuous branching behaviour and a dwarfing growth habit. Gene expression and hormone content in shoot tips, containing the meristems from which this phenotype emerged, were examined. Higher levels of OeTFL1, a gene encoding the flowering repressor TERMINAL FLOWER 1, correlated with lack of flowering. The branching phenotype correlated with higher content of salicylic acid, indole-3-acetic acid and isopentenyl adenosine, and lower content of abscisic acid. The results obtained confirm that heterologous expression of MtFTa1 in olive induced continuous flowering independently of environmental factors, but also modified plant architecture. These phenotypical changes could be related to the altered hormonal content in transgenic plants.

11.
PLoS One ; 19(3): e0300304, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38470897

RESUMO

Diarrheagenic E. coli (DEC) strains are one of the most important etiology factors causing diarrhea in children worldwide, especially in developing countries. DEC strains have characteristic virulence factors; however, other supplemental virulence genes (SVG) may contribute to the development of diarrhea in children. Therefore, this study aimed to determine the prevalence of DEC in children with diarrhea in southwestern Mexico and to associate childhood symptoms, SVG, and pathotypes with diarrhea-causing DEC strains. DEC strains were isolated from 230 children with diarrhea aged 0-60 months from the state of Oaxaca, southwestern Mexico; clinical data were collected, and PCR was used to identify SVG and pathotypes. Antibiotic resistance profiling was performed on DEC strains. 63% of samples were DEC positive, single or combined infections (two (21%) or three strains (1.3%)) of aEPEC (51%), EAEC (10.2%), tEPEC (5.4%), DAEC (4.8%), ETEC (4.1%), EIEC (1.4%), or EHEC (0.7%) were found. Children aged ≤ 12 and 49-60 months and symptoms (e.g., fever and blood) were associated with DEC strains. SVG related to colonization (nleB-EHEC), cytotoxicity (sat-DAEC and espC-tEPEC), and proteolysis (pic-aEPEC) were associated with DECs strains. E. coli phylogroup A was the most frequent, and some pathotypes (aEPEC-A, DAEC-B), and SVG (espC-B2, and sat-D) were associated with the phylogroups. Over 79% of the DEC strains were resistant to antibiotics, and 40% were MDR and XDR, respectively. In conclusion aEPEC was the most prevalent pathotype in children with diarrhea in this region. SVG related to colonization, cytotoxicity, and proteolysis were associated with diarrhea-producing DEC strains, which may play an essential role in the development of diarrhea in children in southwestern Mexico.


Assuntos
Infecções por Escherichia coli , Escherichia coli , Criança , Humanos , Escherichia coli/genética , Infecções por Escherichia coli/epidemiologia , Antibacterianos/farmacologia , Virulência , México , Farmacorresistência Bacteriana , Diarreia/epidemiologia
12.
Biotechnol Adv ; 72: 108350, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38537878

RESUMO

The extraordinary success that chimeric antigen receptor (CAR) T cell therapies have shown over the years on fighting hematological malignancies is evidenced by the six FDA-approved products present on the market. CAR T treatments have forever changed the way we understand cellular immunotherapies, as current research in the topic is expanding even outside the field of cancer with very promising results. Until now, virus-based strategies have been used for CAR T cell manufacturing. However, this methodology presents relevant limitations that need to be addressed prior to wide spreading this technology to other pathologies and in order to optimize current cancer treatments. Several approaches are being explored to overcome these challenges such as virus-free alternatives that additionally offer the possibility of developing transient CAR expression or in vivo T cell modification. In this review, we aim to spotlight a pivotal juncture in the history of medicine where a significant change in perspective is occurring. We review the current progress made on viral-based CAR T therapies as well as their limitations and we discuss the future outlook of virus-free CAR T strategies to overcome current challenges and achieve affordable immunotherapies for a wide variety of pathologies, including cancer.


Assuntos
Neoplasias , Receptores de Antígenos Quiméricos , Humanos , Receptores de Antígenos Quiméricos/genética , Imunoterapia Adotiva , Neoplasias/terapia , Linfócitos T , Tecnologia
13.
Genes (Basel) ; 15(2)2024 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-38397163

RESUMO

Extra virgin olive oil phenolic compounds have been identified as possible biostimulant agents against different pathological processes, including alterations in healing processes. However, there is little evidence on the molecular mechanisms involved in this process. The aim was to analyse the effect of hydroxytyrosol, tyrosol, and oleocanthal on fibroblast gene expression. PCR was used to determine the expression of different differentiation markers, extracellular matrix elements, and growth factors in cultured human fibroblasts CCD-1064Sk treated with different doses of hydroxytyrosol (10-5 M and 10-6 M), tyrosol (10-5 M and 10-6 M), and oleocanthal (10-6 M and 10-7 M). After 24 h of hydroxytyrosol treatment, increased expression of connective tissue growth factor, fibroblast growth factor (FGF), platelet-derived growth factor, vascular endothelial growth factor, transforming growth factor ß1 (TGF-ß1), and their receptors was observed. Tyrosol and olecanthal modulated the expression of FGF and TGFßR1. All phytochemicals tested modified the expression of differentiation markers and extracellular matrix elements, increasing gene expression of actin, fibronectin, decorin, collagen I, and III. Phenolic compounds present in extra virgin olive could have a beneficial effect on tissue regeneration by modulating fibroblast physiology.


Assuntos
Aldeídos , Monoterpenos Ciclopentânicos , Fenóis , Álcool Feniletílico/análogos & derivados , Óleos de Plantas , Fator A de Crescimento do Endotélio Vascular , Humanos , Azeite de Oliva/farmacologia , Óleos de Plantas/análise , Biomarcadores , Antígenos de Diferenciação , Proliferação de Células , Fibroblastos , Expressão Gênica
14.
Cyberpsychol Behav Soc Netw ; 27(4): 261-267, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38377604

RESUMO

This study aimed at exploring the association of nomophobia with alcohol, tobacco, and/or cannabis consumption among high school students. We carried out a cross-sectional study among high school and vocational training students in Galicia, Northwest Spain (N = 3,100). Collected data included nomophobia, sociodemographic variables, and alcohol, tobacco, and cannabis consumption. Nomophobia was measured using the validated Nomophobia Questionnaire. Adjusted odds ratios (ORs) and their 95 percent confidence intervals (CIs) were estimated using generalized linear mixed models. More than a quarter of the adolescents (27.7 percent) had nomophobia. We found an association between nomophobia and a high level of tobacco smoking in the last month in boys (OR = 2.16; 95 percent CI: 1.55-3.03). Nomophobia was also associated with higher odds of binge drinking in both genders (girls: OR = 1.86; 95 percent CI: 1.61-3.52; boys: OR = 2.29; 95 percent CI: 1.68-3.13) and with cannabis consumption in boys (OR = 1.74; 95 percent CI: 1.07-2.81). Our findings highlight the importance of a comprehensive investigation of the factors underlying alcohol, tobacco, and cannabis consumption in the adolescent population.


Assuntos
Consumo de Bebidas Alcoólicas , Humanos , Masculino , Adolescente , Feminino , Espanha/epidemiologia , Estudos Transversais , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/psicologia , Uso da Maconha/epidemiologia , Uso da Maconha/psicologia , Uso de Tabaco/epidemiologia , Uso de Tabaco/psicologia , Estudantes/estatística & dados numéricos , Estudantes/psicologia , Transtornos Fóbicos/epidemiologia , Transtornos Fóbicos/psicologia , Inquéritos e Questionários , Comportamento do Adolescente/psicologia
15.
Rev. méd. Urug ; 40(2): e703, 2024.
Artigo em Espanhol | LILACS, BNUY | ID: biblio-1565720

RESUMO

Introducción: el hidrops fetal es grave, de mal pronóstico y alta morbimortalidad, a pesar de mejoras diagnósticas y terapéuticas desarrolladas en los últimos tiempos. El pronóstico estará determinado por la etiología y posibilidades terapéuticas asociadas a mejores resultados, a la edad gestacional, al diagnóstico y al nacimiento, si bien cabe destacar que no existen suficientes estudios de seguimiento a largo plazo. El diagnóstico ecográfico es confirmatorio, siendo la principal complejidad identificar la etiología y plantear la estrategia terapéutica adecuada. Descripción del caso: presentamos una paciente con diagnóstico de hidrops fetal de tipo no inmune y su abordaje terapéutico. La causa del hidrops correspondió a anemia fetal severa, requiriendo la realización de tres procedimientos con exanguinotransfusión parcial intrauterina mediante cordocentesis. A las 33 semanas, se decidió la finalización del embarazo, con buena evolución neonatal. Conclusión: el hidrops fetal aumenta la morbimortalidad fetal y neonatal, siendo un enorme desafío para el equipo tratante, que requiere de un equipo asistencial interdisciplinario. El conocimiento de esta patología permite realizar un abordaje completo, orientar a la etiología, realizando un diagnóstico oportuno y la selección adecuada del tratamiento. Como en este caso, al identificar la anemia severa como causa del hidrops, es mandatorio definir el manejo para los fetos candidatos a terapia intrauterina.


Introduction: fetal hydrops is a serious condition with a poor prognosis and high morbidity and mortality, despite improvements in diagnostics and therapeutics in recent years. Prognosis is determined by the etiology and therapeutic options associated with better outcomes, gestational age, diagnosis, and birth, although it should be noted that there are not enough long-term follow-up studies. Ultrasound diagnosis is confirmatory, with the main challenge being to identify the etiology and propose the appropriate therapeutic strategy. Description of the case: we present a patient diagnosed with non-immune fetal hydrops and its therapeutic approach. The cause of hydrops was severe fetal anemia, requiring 3 procedures with intrauterine partial exsanguination transfusion through Cordocentesis. At 33 weeks, the decision was made to terminate the pregnancy, with good neonatal outcomes. Conclusions: fetal hydrops increases fetal and neonatal morbidity and mortality, posing a significant challenge for the treating team and requiring an interdisciplinary healthcare team. Understanding this condition allows for a comprehensive approach, guiding the etiology, providing timely diagnosis, and selecting appropriate treatment. As in this case, identifying severe anemia as the cause of hydrops mandates defining the management for fetuses eligible for intrauterine therapy.


Introdução: a hidropisia fetal é grave, com mau prognóstico e elevada morbimortalidade, apesar das melhorias diagnósticas e terapêuticas desenvolvidas nos últimos tempos. O prognóstico será determinado pela etiologia e possibilidades terapêuticas associadas a melhores resultados, idade gestacional, diagnóstico e nascimento, embora se deva salientar que não existem estudos suficientes de seguimento a longo prazo. O diagnóstico ultrassonográfico é confirmatório, sendo a principal complexidade identificar a etiologia e propor a estratégia terapêutica adequada. Descrição do caso: apresentamos uma paciente com diagnóstico de hidropisia fetal não imune e sua abordagem terapêutica. A causa da hidropisia correspondeu a anemia fetal grave, sendo necessária a realização de 3 procedimentos com exsanguineotransfusão intrauterina parcial por meio de cordocentese. Às 33 semanas foi decidida a interrupção da gravidez, com boa evolução neonatal. Conclusão: a hidropisia fetal aumenta a morbimortalidade fetal e neonatal, sendo um enorme desafio para a equipe responsável pelo tratamento, necessitando de uma equipe de atendimento interdisciplinar. O conhecimento desta patologia permite uma abordagem completa, orientação sobre a etiologia, diagnóstico atempado e seleção do tratamento adequado. Assim como neste caso, quando se identifica anemia grave como causa da hidropisia, é obrigatória a definição do manejo para os fetos candidatos à terapia intrauterina.


Assuntos
Transfusão de Sangue Intrauterina , Hidropisia Fetal , Hidropisia Fetal/terapia , Cordocentese , Anemia
16.
Neurol Int ; 15(4): 1253-1272, 2023 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37873836

RESUMO

Type 2 diabetes mellitus (T2D) is a metabolic disease reaching pandemic levels worldwide. In parallel, Alzheimer's disease (AD) and vascular dementia (VaD) are the two leading causes of dementia in an increasingly long-living Western society. Numerous epidemiological studies support the role of T2D as a risk factor for the development of dementia. However, few basic science studies have focused on the possible mechanisms involved in this relationship. On the other hand, this review of the literature also aims to explore the relationship between T2D, AD and VaD. The data found show that there are several alterations in the central nervous system that may be promoting the development of T2D. In addition, there are some mechanisms by which T2D may contribute to the development of neurodegenerative diseases such as AD or VaD.

17.
Int J Infect Dis ; 136: 100-106, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37726066

RESUMO

OBJECTIVES: We aimed to determine if starting antiretroviral therapy (ART) in the first 30 days after acquiring HIV infection has an impact on immunovirological response. METHODS: Observational, ambispective study including 147 patients with confirmed acute HIV infection (January/1995-August/2022). ART was defined as very early (≤30 days after the estimated date of infection), early (31-180 days), and late (>180 days). We compared time to viral suppression (viral load [VL] <50 copies/ml) and immune recovery (IR) (CD4+/CD8+ ratio ≥1) according to the timing and type of ART using survival analysis. RESULTS: ART was started in 140 (95.2%) patients. ART was very early in 24 (17.1%), early in 77 (55.0%), and late in 39 (27.9%) cases. Integrase strand transfer inhibitor (INSTI)-based regimens were the most used in both the overall population (65%) and the very early ART group (23/24, 95.8%). Median HIV VL and CD4+/CD8+ ratio pre-ART were higher in the very early ART group (P <0.05). Patients in the very early and early ART groups and treated with INSTI-based regimens achieved IR earlier (P <0.05). Factors associated with faster IR were the CD4+/CD8+ ratio pre-ART (hazard ratio: 9.3, 95% CI: 3.1-27.8, P <0.001) and INSTI-based regimens (hazard ratio: 2.4, 95% CI: 1.3-4.2, P = 0.003). CONCLUSIONS: The strongest predictors of IR in patients who start ART during AHI are the CD4+/CD8+ ratio pre-ART and INSTI-based ART regimens.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Humanos , Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/uso terapêutico , Carga Viral
18.
Methods Cell Biol ; 177: 125-170, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37451765

RESUMO

In this chapter, we review Automated Tape Collecting Ultramicrotomy (ATUM), which, among other array tomography methods, substantially simplified large-scale volume electron microscopy (vEM) projects. vEM reveals biological structures at nanometer resolution in three dimensions and resolves ambiguities of two-dimensional representations. However, as the structures of interest-like disease hallmarks emerging from neuropathology-are often rare but the field of view is small, this can easily turn a vEM project into a needle in a haystack problem. One solution for this is correlated light and electron microscopy (CLEM), providing tissue context, dynamic and molecular features before switching to targeted vEM to hone in on the object's ultrastructure. This requires precise coordinate transfer between the two imaging modalities (e.g., by micro computed tomography), especially for block face vEM which relies on physical destruction of sections. With array tomography methods, serial ultrathin sections are collected into a tissue library, thus allowing storage of precious samples like human biopsies and enabling repetitive imaging at different resolution levels for an SEM-based search strategy. For this, ATUM has been developed to reliably collect serial ultrathin sections via a conveyor belt onto a plastic tape that is later mounted onto silicon wafers for serial scanning EM (SEM). The ATUM-SEM procedure is highly modular and can be divided into sample preparation, serial ultramicrotomy onto tape, mounting, serial image acquisition-after which the acquired image stacks can be used for analysis. Here, we describe the steps of this workflow and how ATUM-SEM enables targeting and high resolution imaging of specific structures. ATUM-SEM is widely applicable. To illustrate this, we exemplify the approach by reconstructions of focal pathology in an Alzheimer mouse model and CLEM of a specific cortical synapse.


Assuntos
Microtomia , Microscopia Eletrônica de Volume , Camundongos , Animais , Humanos , Microscopia Eletrônica de Varredura , Microtomografia por Raio-X , Microtomia/métodos , Neurônios , Imageamento Tridimensional/métodos
19.
Sci Rep ; 13(1): 10985, 2023 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-37415069

RESUMO

The electrocardiogram (ECG) represents an essential tool to determine cardiac electrical abnormalities in COVID-19 patients, the effects of anti-SARS-CoV-2 drugs, and potential drug interactions. Smartphone-based heart monitors have increased the spectrum of ECG monitoring however, we are not aware of its reliability in critically ill COVID-19 patients. We aim to evaluate the feasibility and reliability of nurse-performed smartphone electrocardiography for QT interval monitoring in critically ill COVID-19 patients using KardiaMobile-6L compared with the standard 12-lead ECG. An observational comparative study was conducted comparing consecutive KardiaMobile-6L and 12-lead ECG recordings obtained from 20 patients admitted to the intensive care unit with SARS-CoV-2 infection and on invasive mechanical ventilation. The heart rate-corrected QT (QTc) intervals measured by KardiaMobile-6L and 12-lead ECG were compared. In 60 percent of the recordings, QTc intervals measured by KardiaMobile-6L matched those by 12-lead ECG. The QTc intervals measured by KardiaMobile-6 and 12-lead ECG were 428 ± 45 ms and 425 ± 35 ms (p = 0.82), respectively. The former demonstrated good agreement (bias = 2.9 ms; standard deviation of bias = 29.6 ms) with the latter, using the Bland-Altman method of measurement agreement. In all but one recording, KardiaMobile-6L demonstrated QTc prolongation. QTc interval monitoring with KardiaMobile-6L in critically ill COVID-19 patients was feasible and demonstrated reliability comparable to the standard 12-lead ECG.


Assuntos
COVID-19 , Síndrome do QT Longo , Humanos , Cuidados Críticos , Estado Terminal , Eletrocardiografia/métodos , Estudos de Viabilidade , Síndrome do QT Longo/diagnóstico , Pandemias , Reprodutibilidade dos Testes , SARS-CoV-2
20.
J Occup Environ Hyg ; 20(10): 427-438, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37405865

RESUMO

Asbestos is a mineral that is carcinogenic to humans. Its use has been banned in many occidental countries yet it is still produced in the United States, and materials that contain asbestos remain in many occupational settings and indoor environments. Even though asbestos carcinogenicity is well known, there is scant literature on its specific effects regarding small cell lung cancer (SCLC). We therefore conducted a systematic review and meta-analysis to determine SCLC risk among workers exposed to asbestos. A systematic search of the literature was conducted to identify studies which reported occupational exposure to asbestos and SCLC-related deaths and/or incidence. We identified seven case-control studies that included 3,231 SCLC cases; four studies reported smoking-adjusted risks. A significantly increased risk of SCLC (pooled OR 1.89; 95% CI, 1.25-2.86) was observed on pooling studies on men (six studies) that displayed moderate heterogeneity (I2 = 46.0%). Overall, our synthesis suggests that occupational exposure to asbestos significantly increases the risk of SCLC on men.


Assuntos
Amianto , Neoplasias Pulmonares , Doenças Profissionais , Exposição Ocupacional , Carcinoma de Pequenas Células do Pulmão , Masculino , Humanos , Estados Unidos/epidemiologia , Carcinoma de Pequenas Células do Pulmão/etiologia , Carcinoma de Pequenas Células do Pulmão/induzido quimicamente , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/epidemiologia , Amianto/efeitos adversos , Exposição Ocupacional/efeitos adversos , Carcinógenos , Doenças Profissionais/epidemiologia
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