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1.
JMIR Pediatr Parent ; 7: e52540, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38602309

RESUMO

Background: The use of a smartphone built-in microphone for auscultation is a feasible alternative to the use of a stethoscope, when applied by physicians. Objective: This cross-sectional study aims to assess the feasibility of this technology when used by parents-the real intended end users. Methods: Physicians recruited 46 children (male: n=33, 72%; age: mean 11.3, SD 3.1 y; children with asthma: n=24, 52%) during medical visits in a pediatric department of a tertiary hospital. Smartphone auscultation using an app was performed at 4 locations (trachea, right anterior chest, and right and left lung bases), first by a physician (recordings: n=297) and later by a parent (recordings: n=344). All recordings (N=641) were classified by 3 annotators for quality and the presence of adventitious sounds. Parents completed a questionnaire to provide feedback on the app, using a Likert scale ranging from 1 ("totally disagree") to 5 ("totally agree"). Results: Most recordings had quality (physicians' recordings: 253/297, 85.2%; parents' recordings: 266/346, 76.9%). The proportions of physicians' recordings (34/253, 13.4%) and parents' recordings (31/266, 11.7%) with adventitious sounds were similar. Parents found the app easy to use (questionnaire: median 5, IQR 5-5) and were willing to use it (questionnaire: median 5, IQR 5-5). Conclusions: Our results show that smartphone auscultation is feasible when performed by parents in the clinical context, but further investigation is needed to test its feasibility in real life.

2.
J Hazard Mater ; 471: 134243, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38657506

RESUMO

Iron-magnetic nanoparticles (Fe-NMPs) are widely used in environmental remediation, while porphyrin-based hybrid materials anchored to silica-coated Fe3O4-nanoparticles (Fe3O4-NPs) have been used for water disinfection purposes. To assess their safety on plants, especially concerning potential environmental release, it was investigated for the first time, the impact on plants of a silica-coated Fe3O4-NPs bearing a porphyrinic formulation (FORM) - FORM@NMP. Additionally, FORM alone and the magnetic nanoparticles without FORM anchored (NH2@NMP) were used for comparison. Wheat (Triticum aestivum L.) was chosen as a model species and was subjected to three environmentally relevant doses during germination and tiller development through root application. Morphological, physiological, and metabolic parameters were assessed. Despite a modest biomass decrease and alterations in membrane properties, no major impairments in germination or seedling development were observed. During tiller phase, both Fe3O4-NPs increased leaf length, and photosynthesis exhibited varied impacts: both Fe3O4-NPs and FORM alone increased pigments; only Fe3O4-NPs promoted gas exchange; all treatments improved the photochemical phase. Regarding oxidative stress, lipid peroxidation decreased in FORM and FORM@NMP, yet with increased O2-• in FORM@NMP; total flavonoids decreased in NH2@NMP and antioxidant enzymes declined across all materials. Phenolic profiling revealed a generalized trend towards a decrease in flavones. In conclusion, these nanoparticles can modulate wheat physiology/metabolism without apparently inducing phytotoxicity at low doses and during short-time exposure. ENVIRONMENTAL IMPLICATION: Iron-magnetic nanoparticles are widely used in environmental remediation and fertilization, besides of new applications continuously being developed, making them emerging contaminants. Soil is a major sink for these nanoparticles and their fate and potential environmental risks in ecosystems must be addressed to achieve more sustainable environmental applications. Furthermore, as the reuse of treated wastewater for agricultural irrigation is being claimed, it is of major importance to disclose the impact on crops of the nanoparticles used for wastewater decontamination, such as those proposed in this work.

3.
Vet Microbiol ; 292: 110056, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38537400

RESUMO

Klebsiella spp. are important pathogens of humans and companion animals such as cats and dogs, capable of causing severe life-threatening diseases. The aim of this study was to characterize the molecular and phenotypic properties of Klebsiella pneumoniae and Klebsiella oxytoca isolated from ill companion animals by whole genome sequencing, followed by in vitro assessment of biofilm formation and in vivo pathogenicity using the Galleria mellonella model. Two LPS O-types were identified for all the K. pneumoniae isolates tested (O3B and O1/O2v2) and only one for K. oxytoca isolates (OL104), and the most common STs found were ST11 and ST266. Furthermore, a high diversity of K-locus types was found for K. pneumoniae (KL102; KL105; KL31, and KL13). Within K. pneumoniae, one specific O/K/ST-types combination (i.e., KL105-ST11-O1/O2v2) showed results that were of concern, as it exhibited a high inflammatory response at 12 h post-infection in G. mellonella with 80% of the larvae dead at 72 h post-infection. This virulence potential, on the other hand, did not appear to be directly related to the biofilm-forming capacity. Also, virulence and resistance scores obtained for this set of strains did surpass score 1. The present study demonstrated that Klebsiella spp. isolated from companion animals belonging to STs that can cause human infections and present virulence on an invertebrate model. Thus, this study underscores the role of dogs and cats as reservoirs of resistant Klebsiella spp. that could potentially be transmitted to humans.


Assuntos
Doenças do Gato , Doenças do Cão , Infecções por Klebsiella , Gatos , Cães , Humanos , Animais , Virulência , Klebsiella pneumoniae , Klebsiella oxytoca/genética , Portugal/epidemiologia , Doenças do Gato/epidemiologia , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/veterinária , Doenças do Cão/epidemiologia , Antibacterianos , beta-Lactamases
4.
Pharmaceutics ; 16(2)2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38399315

RESUMO

Type 2 diabetes mellitus (DM) continues to escalate, necessitating innovative therapeutic approaches that target distinct pathways and address DM complications. Flavonoids have been shown to possess several pharmacological activities that are important for DM. This study aimed to evaluate the in vivo effects of the flavonoid melanoxetin using Goto-Kakizaki rats. Over a period of 14 days, melanoxetin was administered subcutaneously to investigate its antioxidant, anti-inflammatory, and antidiabetic properties. The results show that melanoxetin reduced insulin resistance in adipose tissue by targeting protein tyrosine phosphatase 1B. Additionally, melanoxetin counteracted oxidative stress by reducing nitrotyrosine levels and modulating superoxide dismutase 1 and hemeoxygenase in adipose tissue and decreasing methylglyoxal-derived hydroimidazolone (MG-H1), a key advanced glycation end product (AGE) implicated in DM-related complications. Moreover, the glyoxalase 1 expression decreased in both the liver and the heart, correlating with reduced AGE levels, particularly MG-H1 in the heart. Melanoxetin also demonstrated anti-inflammatory effects by reducing serum prostaglandin E2 levels, and increasing the antioxidant status of the aorta wall through enhanced acetylcholine-dependent relaxation in the presence of ascorbic acid. These findings provide valuable insights into melanoxetin's therapeutic potential in targeting multiple pathways involved in type 2 DM, particularly in mitigating oxidative stress and glycation.

5.
Front Cell Infect Microbiol ; 14: 1257586, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38318163

RESUMO

During the recent avian influenza epizootics that occurred in France in 2020/21 and 2021/22, the virus was so contagiousness that it was impossible to control its spread between farms. The preventive slaughter of millions of birds consequently was the only solution available. In an effort to better understand the spread of avian influenza viruses (AIVs) in a rapid and innovative manner, we established an amplicon-based MinION sequencing workflow for the rapid genetic typing of circulating AIV strains. An amplicon-based MinION sequencing workflow based on a set of PCR primers targeting primarily the hemagglutinin gene but also the entire influenza virus genome was developed. Thirty field samples from H5 HPAIV outbreaks in France, including environmental samples, were sequenced using the MinION MK1C. A real-time alignment of the sequences with MinKNOW software allowed the sequencing run to be stopped as soon as enough data were generated. The consensus sequences were then generated and a phylogenetic analysis was conducted to establish links between the outbreaks. The whole sequence of the hemagglutinin gene was obtained for the 30 clinical samples of H5Nx HPAIV belonging to clade 2.3.4.4b. The consensus sequences comparison and the phylogenetic analysis demonstrated links between some outbreaks. While several studies have shown the advantages of MinION for avian influenza virus sequencing, this workflow has been applied exclusively to clinical field samples, without any amplification step on cell cultures or embryonated eggs. As this type of testing pipeline requires only a short amount of time to link outbreaks or demonstrate a new introduction, it could be applied to the real-time management of viral epizootics.


Assuntos
Vírus da Influenza A , Influenza Aviária , Sequenciamento por Nanoporos , Animais , Influenza Aviária/epidemiologia , Filogenia , Hemaglutininas , Fluxo de Trabalho , Surtos de Doenças , Vírus da Influenza A/genética
6.
Clin Neurophysiol ; 159: 1-12, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38232654

RESUMO

OBJECTIVE: The aim of this study was to explore differences in brain activity and connectivity using simultaneous electroencephalography and near-infrared spectroscopy in patients with focal dystonia during handwriting and finger-tapping tasks. METHODS: Patients with idiopathic right upper limb focal dystonia and controls were assessed by simultaneous near-infrared spectroscopy and electroencephalography during the writing and finger-tapping tasks in terms of the mu-alpha, mu-beta, beta and low gamma power and effective connectivity, as well as relative changes in oxyhemoglobin (oxy-Hb) and deoxyhemoglobin using a channel-wise approach with a mixed-effect model. RESULTS: Patients exhibited higher oxy-Hb levels in the right and left motor cortex and supplementary motor area during writing, but lower oxy-Hb levels in the left sensorimotor and bilateral somatosensory area during finger-tapping compared to controls. During writing, patients showed increased low gamma power in the bilateral sensorimotor cortex and less mu-beta and beta attenuation compared to controls. Additionally, patients had reduced connectivity between the supplementary motor area and the left sensorimotor cortex during writing. No differences were observed in terms of effective connectivity in either task. Finally, patients failed to attenuate the mu-alpha, mu-beta, and beta rhythms during the finger-tapping task. CONCLUSIONS: Cortical blood flow and EEG spectral power differ between controls and dystonia patients, depending on the task. Writing increased blood flow and altered connectivity in dystonia patients, and it also decreased slow-band attenuation. Finger-tapping decreased blood flow and slow-band attenuation. SIGNIFICANCE: Simultaneous fNIRS and EEG may show relevant information regarding brain dynamics in movement disorders patients in unconstrained environments.


Assuntos
Distonia , Distúrbios Distônicos , Córtex Motor , Córtex Sensório-Motor , Humanos , Eletroencefalografia
8.
Ann Surg Oncol ; 31(2): 847-859, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37934383

RESUMO

BACKGROUND: Preoperative exercise training is recommended for improvement of clinical outcomes after lung cancer (LC) surgery. However, its effectiveness in preventing postoperative decline in quality of life (QoL) remains unknown. This study investigated the effect of preoperative home-based exercise training (PHET) on QoL after LC surgery. METHODS: Patients awaiting LC resection were randomized to PHET or a control group (CG). The PHET program combined aerobic and resistance exercise, with weekly telephone supervision. Primary outcome was QoL-assessed with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) at baseline, before surgery, and 1 month after surgery. The secondary outcomes were hospital length of stay and physical performance. The main analysis included a factorial repeated-measures analysis of variance. Additionally, the proportion of patients experiencing clinical deterioration from baseline to post-surgery was assessed. RESULTS: The study included 41 patients (68.1 ± 9.3 years; 68.3% male) in the intention-to-treat analysis (20 PHET patients, 21 CG patients). A significant group × time interaction was observed for global QoL (p = 0.004). Between-group differences in global QoL were statistically and clinically significant before surgery (mean difference [MD], 13.5 points; 95% confidence interval [CI], 2.4-24.6; p = 0.019) and after surgery (MD, 12.4 points; 95% CI, 1.3-23.4; p = 0.029), favoring PHET. Clinical deterioration of global QoL was reported by 71.4% of the CG patients compared with 30 % of the PHET patients (p = 0.003). Between-group differences in favor of PHET were found in pain and appetite loss as well as in physical, emotional and role functions after surgery (p < 0.05). Compared with CG, PHET was superior in improving preoperative five-times sit-to-stand and postoperative exercise capacity (p < 0.05). No between-group differences in other secondary outcomes were observed. CONCLUSION: The study showed that PHET can effectively prevent the decline in QoL after LC surgery.


Assuntos
Deterioração Clínica , Neoplasias Pulmonares , Humanos , Masculino , Feminino , Qualidade de Vida , Neoplasias Pulmonares/cirurgia , Exercício Pré-Operatório , Exercício Físico
9.
Saúde Soc ; 33(1): e220584pt, 2024. tab, graf
Artigo em Português | LILACS-Express | LILACS | ID: biblio-1536866

RESUMO

Resumo Centrando-se no impacto que a comunicação de risco emitida pelas organizações de saúde pública tem na mudança dos comportamentos da sociedade, esta investigação pretende analisar as mensagens-chave que a Organização Mundial de Saúde (OMS) definiu para promover o programa de vacinação contra a covid-19. Para cumprir este objetivo, enveredou-se por uma metodologia de estudo qualitativa, que privilegiou o uso da análise do conteúdo publicado nas páginas de Facebook e de Instagram da OMS, no período de 1 de abril a 31 de agosto de 2021. No total, foram analisadas 62 publicações. Os resultados mostraram que a OMS utilizou quatro eixo de comunicação para promover a importância da vacinação na sociedade: garantir a credibilidade e a transparência da informação transmitida; certificar a segurança e a eficácia da vacina; apelar ao sentido de responsabilidade coletiva; e associar a vacina à solução para pôr fim à pandemia. As conclusões do estudo mostram que, embora a equidade no acesso à vacina ainda seja uma realidade em construção, os quase 70% da população mundial vacinada sugerem que as mensagens enviadas pela OMS no contexto de comunicação de risco podem ter contribuído para a construção de uma imagem positiva do programa de vacinação.


Abstract Focusing on the impact that risk communication issued by public health organizations brings to changing societal behaviors, this research aimed to analyze the key messages that the World Health Organization (WHO) has defined to promote the COVID-19 vaccination program. In order to achieve this goal, a qualitative study methodology was used to analyze the content published on the WHO's Facebook and Instagram pages from April 1 to August 31, 2021. In total, 62 publications were analyzed. The results showed that the WHO used four key communication messages to promote the importance of vaccination in society: ensuring the credibility and transparency of the information transmitted; certifying the safety and efficacy of the vaccine; appealing to a sense of collective responsibility; and associating the vaccine with the solution to end the pandemic were the chosen communication axes. The conclusions of this study show that, although fair access to the vaccine is still a reality in the making, the fact that almost 70% of the world's population has been vaccinated suggests that the messages sent by the WHO in the context of risk communication may have contributed to building a positive image of the vaccination program.

10.
Int J Mol Sci ; 24(20)2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37895081

RESUMO

The Mycobacterium abscessus complex (MABC) is an emerging, difficult to treat, multidrug-resistant nontuberculous mycobacteria responsible for a wide spectrum of infections and associated with an increasing number of cases worldwide. Dominant circulating clones (DCCs) of MABC have been genetically identified as groups of strains associated with higher prevalence, higher levels of antimicrobial resistance, and worse clinical outcomes. To date, little is known about the genomic characteristics of MABC species circulating in Portugal. Here, we examined the genetic diversity and antimicrobial resistance profiles of 30 MABC strains isolated between 2014 and 2022 in Portugal. The genetic diversity of circulating MABC strains was assessed through a gene-by-gene approach (wgMLST), allowing their subspecies differentiation and the classification of isolates into DCCs. Antimicrobial resistance profiles were defined using phenotypic, molecular, and genomic approaches. The majority of isolates were resistant to at least two antimicrobials, although a poor correlation between phenotype and genotype data was observed. Portuguese genomes were highly diverse, and data suggest the existence of MABC lineages with potential international circulation or cross-border transmission. This study highlights the genetic diversity and antimicrobial resistance profile of circulating MABC isolates in Portugal while representing the first step towards the implementation of a genomic-based surveillance system for MABC at the Portuguese NIH.


Assuntos
Anti-Infecciosos , Infecções por Mycobacterium não Tuberculosas , Mycobacterium abscessus , Humanos , Mycobacterium abscessus/genética , Portugal , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Micobactérias não Tuberculosas , Anti-Infecciosos/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Testes de Sensibilidade Microbiana
11.
Healthcare (Basel) ; 11(19)2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37830726

RESUMO

Cancer patients may experience significant distress. The "Emotion Thermometers" (ETs) are a short visual analogue scale used to screen patients for psychosocial risk. This study aimed to assess emotional distress in a large sample of cancer patients attending psychological services at an non-governmental organization (NGO), and to explore factors that may contribute to it. The ETs were answered by 899 cancer patients. They were, on average, 59.9 years old, the majority were female, had breast cancer, were under treatment or were disease-free survivors, and reported high levels of emotional distress, above the cut-off (≥5). A Generalized Linear Model was used to measure the association between the level of distress, age, gender, disease phase and 33 items of the problem list. Four items-sadness, depression, sleep and breathing-were found to be significantly related to a higher level of distress. Additionally, women and patients who were in the palliative phase also had significantly higher levels of distress. The results confirm the need for early emotional screening in cancer patients, as well as attending to the characteristics of each patient. Additionally, they highlight the utility of the ETs for the clinical practice, allowing to optimize the referral to specialized psychosocial services.

12.
J Cancer Policy ; 38: 100437, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37625468

RESUMO

BACKGROUND: This study aims to provide an academic medical overview of the framework and key outcomes of two mammography quality certification programs in Brazil. METHODS: These programs assess radiation dose and phantom image quality in mammography units through a postal system. Each unit that passes this initial assessment is required to submit a sample of copies of five complete examinations. The quality of the patient images and reports is then reviewed by radiologists and medical physicist experts. Additionally, the number of mammography units and mammography coverage in the target population, were assessed. RESULTS: During the study period, 1007 units applied to the certification programs, and 934 (92.8%) successfully passed the assessment of radiation dose and phantom image quality. Out of these, 556 (59.5%) also passed the review of clinical image quality and reports, earning certification. The main issues related to mammogram and report quality were associated with the performance of radiographers (in terms of positioning) and radiologists (in terms of interpretation). On average, there are more than two mammography units/10,000 women in the target group. The screening mammography coverage in this group is 26.3% for women relying exclusively on the public healthcare and 58.1% for women with private healthcare plans. CONCLUSION: This study demonstrates the suitability of the framework adopted by national mammography quality certification programs in a middle-income country. These programs are carried out by relatively small workforce and at reasonable costs, utilizing postal resources to cover the large number of existing mammographic units and the vast distances within the country. POLICY STATEMENT: All mammography services in Brazil must adhere to the quality requirements for examinations and reference values for radiation dose to women established by the Ministry of Health. This ensures standardized conditions for early detection of breast cancer and minimizes the risk associated with x-rays.


Assuntos
Neoplasias da Mama , Mamografia , Feminino , Humanos , Brasil , Neoplasias da Mama/diagnóstico , Detecção Precoce de Câncer , Mamografia/métodos , Recursos Humanos
15.
Sleep Sci ; 16(1): 38-43, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37151762

RESUMO

Background Blepharospasm is a focal dystonia that affects the orbicularis oculi muscles. The interest in nonmotor symptoms is due to their impact on quality of life. Objective We evaluated the frequency of sleep disorders and circadian rhythm in a sample of Brazilian blepharospasm patients. Methods A total of 51 patients, who met the clinical criteria for blepharospasm, evaluated by 2 specialists in movement disorders, were recruited from the outpatient clinic for movement disorders of two reference centers in the city of São Paulo: Universidade Federal de São Paulo and Hospital do Servidor Público do Estado de São Paulo. The selected 13 patients were evaluated from 13 days before to 13 days after using botulinum toxin. They were interviewed, underwent physical examination and actigraphy, and completed sleep diaries. Results After using botulinum toxin, the group that reported sleep improvement exhibited a 50% decrease in sleep latency. There was no change in restless leg syndrome or circadian rhythm. Patients who reported no sleep improvement after using botulinum toxin presented poorer synchronization of the light-dark cycle. Conclusion Blepharospasm patients have poor sleep quality. About 50% of the patients had sleep improvement after using botulinum toxin. The synchronization of the light-dark cycle should be influenced by this finding.

16.
Antibiotics (Basel) ; 12(4)2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-37107044

RESUMO

Swine pathogenic infection caused by Escherichia coli, known as swine colibacillosis, represents an epidemiological challenge not only for animal husbandry but also for health authorities. To note, virulent E. coli strains might be transmitted, and also cause disease, in humans. In the last decades, diverse successful multidrug-resistant strains have been detected, mainly due to the growing selective pressure of antibiotic use, in which animal practices have played a relevant role. In fact, according to the different features and particular virulence factor combination, there are four different pathotypes of E. coli that can cause illness in swine: enterotoxigenic E. coli (ETEC), Shiga toxin-producing E. coli (STEC) that comprises edema disease E. coli (EDEC) and enterohemorrhagic E. coli (EHEC), enteropathogenic E. coli (EPEC), and extraintestinal pathogenic E. coli (ExPEC). Nevertheless, the most relevant pathotype in a colibacillosis scenario is ETEC, responsible for neonatal and postweaning diarrhea (PWD), in which some ETEC strains present enhanced fitness and pathogenicity. To explore the distribution of pathogenic ETEC in swine farms and their diversity, resistance, and virulence profiles, this review summarizes the most relevant works on these subjects over the past 10 years and discusses the importance of these bacteria as zoonotic agents.

17.
Infect Genet Evol ; 112: 105437, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37100339

RESUMO

Mycobacteroides abscessus complex (MAB), a fast-growing nontuberculous mycobacterium, is emerging as a significant infectious disease threat, due to both intrinsic and acquired resistance mechanisms to antibiotics and disinfectants and the need for extensive and multidrug regimens for treatment. Despite the prolonged regimens, outcomes are poor and persistence cases have been reported. Here, we describe clinical, microbiologic and genomic features of a M. abscessus subsp. bolletii (M. bolletii) strain consecutively isolated from a patient within an eight-year infection period. From April 2014 to September 2021, the National Reference Laboratory for Mycobacteria received eight strains isolated from a male patient. Species identification, molecular resistance profile and phenotypic drug susceptibility were determined. Five of these isolates were recovered for further in-depth genomic analysis. Genomic analysis confirmed the multidrug resistant pattern of the strain and also other genetic changes associated with adaptation to environment and defence mechanisms. We highlight the identification of new mutations in locus MAB_1881c and in locus MAB_4099c (mps1 gene), already described as associated with macrolides resistance and morphotype switching, respectively. Additionally, we also observed the emergence and fixation of a mutation in locus MAB_0364c that appeared at a frequency of 36% for the 2014 isolate, 57% for the 2015 isolate and 100% for the 2017 and 2021 isolates, clearly illustrating a fixation process underlying a microevolution of the MAB strain within the patient. Altogether these results suggest that the observed genetic alterations are a reflection of the bacterial population's continuous adaptation and survival to the host environment during infection, contributing to persistence and treatment failure.


Assuntos
Doenças Transmissíveis , Infecções por Mycobacterium não Tuberculosas , Mycobacterium abscessus , Mycobacterium , Masculino , Humanos , Mycobacterium abscessus/genética , Infecção Persistente , Micobactérias não Tuberculosas , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Testes de Sensibilidade Microbiana
18.
J Cell Biol ; 222(5)2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-37017932

RESUMO

Enduring chromosome segregation errors represent potential threats to genomic stability due to eventual chromosome copy number alterations (aneuploidy) and formation of micronuclei-key intermediates of a rapid mutational process known as chromothripsis that is found in cancer and congenital disorders. The spindle assembly checkpoint (SAC) has been viewed as the sole surveillance mechanism that prevents chromosome segregation errors during mitosis and meiosis. However, different types of chromosome segregation errors stemming from incorrect kinetochore-microtubule attachments satisfy the SAC and are more frequent than previously anticipated. Remarkably, recent works have unveiled that most of these errors are corrected during anaphase and only rarely result in aneuploidy or formation of micronuclei. Here, we discuss recent progress in our understanding of the origin and fate of chromosome segregation errors that satisfy the SAC and shed light on the surveillance, correction, and clearance mechanisms that prevent their transmission, to preserve genomic stability.


Assuntos
Aneuploidia , Segregação de Cromossomos , Instabilidade Genômica , Humanos , Anáfase , Cinetocoros , Microtúbulos , Mitose , Fuso Acromático
19.
Pediatr Blood Cancer ; 70(7): e30352, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37057832

RESUMO

Local therapies are increasingly used for ocular preservation in retinoblastoma. In middle-income countries, these techniques pose specific challenges mostly related to more advanced disease at diagnosis. The Grupo de America Latina de Oncología Pediátrica (GALOP) developed a consensus document for the management of conservative therapy for retinoblastoma. Intra-arterial chemotherapy (OAC) is the preferred therapy, except for those with less advanced disease or age younger than 6 months. OAC allowed for a reduction in the use of external beam radiotherapy in our setting. Intravitreal chemotherapy is the preferred treatment for vitreous seeding. Enucleation is the treatment of choice for eyes with advanced disease.


Assuntos
Neoplasias da Retina , Retinoblastoma , Humanos , Lactente , Retinoblastoma/tratamento farmacológico , Neoplasias da Retina/tratamento farmacológico , Tratamento Conservador , Consenso , América do Sul , Estudos Retrospectivos
20.
Arq Neuropsiquiatr ; 81(3): 296-307, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-37059439

RESUMO

Plasma exchange (PLEX) is a therapeutic apheresis modality in which the plasma is separated from inflammatory factors such as circulating autoreactive immunoglobulins, the complement system, and cytokines, and its therapeutic effect is based on the removal of these mediators of pathological processes. Plasma exchange is well established for various neurological disorders, and it is applied successfully in central nervous system inflammatory demyelinating diseases (CNS-IDD). It mainly modulates the humoral immune system; thus, it has a greater theoretical effect in diseases with prominent humoral mechanisms, such as neuromyelitis optica (NMO). However, it also has a proven therapeutic effect in multiple sclerosis (MS) attacks. Several studies have suggested that patients with severe attacks of CNS-IDD have poor response to steroid therapy but show clinical improvement after the PLEX treatment. Currently, PLEX is generally established only as a rescue therapy for steroid unresponsive relapses. However, there are still research gaps in the literature regarding plasma volume, number of sessions, and how early the apheresis treatment needs to started. Thus, in the present article, we summarize the clinical studies and meta-analyses, especially about MS and NMO, outlining clinical data regarding the experience with therapeutic PLEX in severe attacks of CNS-IDD, the clinical improvement rates, the prognostic factors of a favorable response, and highlighting the likely role of the early apheresis treatment. Further, we have gathered this evidence and suggested a protocol for the treatment of CNS-IDD with PLEX in the routine clinical practice.


Plasmaférese (PLEX) é um procedimento em que o plasma é separado de fatores inflamatórios como imunoglobulinas autorreativas circulantes, sistema complemento e citocinas, e seu efeito terapêutico se baseia na remoção desses mediadores de processos patológicos. A PLEX está bem estabelecida no tratamento de diversos distúrbios neurológicos, e é utilizada com sucesso em surtos de doenças desmielinizantes inflamatórias do sistema nervoso central (CNS-IDD). A PLEX modula principalmente o sistema imunológico humoral; assim, tem efeito teórico maior em doenças com mecanismos patológicos humorais proeminentes, como a neuromielite óptica (NMO). No entanto tem também efeito terapêutico comprovado em surtos de esclerose múltipla (EM). Estudos sugerem que a corticoterapia é pouco eficaz em pacientes com surtos graves de CNS-IDD, e que estes apresentam melhora clínica após o tratamento com PLEX. Atualmente, a PLEX está geralmente estabelecida apenas como terapia de resgate para surtos não responsivos a corticosteroides. No entanto, há lacunas na literatura sobre a quantidade de troca de volume plasmático, o número de sessões, e o tempo de início da aférese terapêutica. Dessa forma, resumimos neste artigo estudos clínicos e metanálises, especialmente sobre EM e NMO, e delineamos os dados clínicos sobre a experiência com o uso de PLEX em surtos graves de CNS-IDD, as taxas de melhora clínica, os fatores prognósticos para uma resposta favorável, e destacamos o provável papel do tratamento precoce nestes casos. Em um segundo momento, reunimos essas evidências em uma sugestão de protocolo de tratamento de CNS-IDD com PLEX na prática clínica rotineira.


Assuntos
Doenças do Sistema Nervoso Central , Esclerose Múltipla , Neuromielite Óptica , Humanos , Sistema Nervoso Central/patologia , Doenças do Sistema Nervoso Central/terapia , Esclerose Múltipla/terapia , Neuromielite Óptica/terapia , Troca Plasmática/métodos
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