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1.
Nucleic Acids Res ; 52(16): e74, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39011878

RESUMO

Genome search and/or classification typically involves finding the best-match database (reference) genomes and has become increasingly challenging due to the growing number of available database genomes and the fact that traditional methods do not scale well with large databases. By combining k-mer hashing-based probabilistic data structures (i.e. ProbMinHash, SuperMinHash, Densified MinHash and SetSketch) to estimate genomic distance, with a graph based nearest neighbor search algorithm (Hierarchical Navigable Small World Graphs, or HNSW), we created a new data structure and developed an associated computer program, GSearch, that is orders of magnitude faster than alternative tools while maintaining high accuracy and low memory usage. For example, GSearch can search 8000 query genomes against all available microbial or viral genomes for their best matches (n = ∼318 000 or ∼3 000 000, respectively) within a few minutes on a personal laptop, using ∼6 GB of memory (2.5 GB via SetSketch). Notably, GSearch has an O(log(N)) time complexity and will scale well with billions of genomes based on a database splitting strategy. Further, GSearch implements a three-step search strategy depending on the degree of novelty of the query genomes to maximize specificity and sensitivity. Therefore, GSearch solves a major bottleneck of microbiome studies that require genome search and/or classification.


Assuntos
Algoritmos , Genômica , Software , Genômica/métodos , Genoma Viral , Bases de Dados Genéticas
2.
Brain Behav Immun ; 122: 353-367, 2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39187049

RESUMO

Chronic stress increases activity of the brain's innate immune system and impairs function of the medial prefrontal cortex (mPFC). However, whether acute stress triggers similar neuroimmune mechanisms is poorly understood. Across four studies, we used a Syrian hamster model to investigate whether acute stress drives changes in mPFC microglia in a time-, subregion-, and social status-dependent manner. We found that acute social defeat increased expression of ionized calcium binding adapter molecule 1 (Iba1) in the infralimbic (IL) and prelimbic (PL) and altered the morphology Iba1+ cells 1, 2, and 7 days after social defeat. We also investigated whether acute defeat induced tissue degeneration and reductions of synaptic plasticity 2 days post-defeat. We found that while social defeat increased deposition of cellular debris and reduced synaptophysin immunoreactivity in the PL and IL, treatment with minocycline protected against these cellular changes. Finally, we tested whether a reduced conditioned defeat response in dominant compared to subordinate hamsters was associated with changes in microglia reactivity in the IL and PL. We found that while subordinate hamsters and those without an established dominance relationships showed defeat-induced changes in morphology of Iba1+ cells and cellular degeneration, dominant hamsters showed resistance to these effects of social defeat. Taken together, these findings indicate that acute social defeat alters microglial morphology, increases markers of tissue degradation, and impairs structural integrity in the IL and PL, and that experience winning competitive interactions can specifically protect the IL and reduce stress vulnerability.

3.
Horm Behav ; 164: 105577, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38878493

RESUMO

Social stress is a negative emotional experience that can increase fear and anxiety. Dominance status can alter the way individuals react to and cope with stressful events. The underlying neurobiology of how social dominance produces stress resistance remains elusive, although experience-dependent changes in androgen receptor (AR) expression is thought to play an essential role. Using a Syrian hamster (Mesocricetus auratus) model, we investigated whether dominant individuals activate more AR-expressing neurons in the posterior dorsal and posterior ventral regions of the medial amygdala (MePD, MePV), and display less social anxiety-like behavior following social defeat stress compared to subordinate counterparts. We allowed male hamsters to form and maintain a dyadic dominance relationship for 12 days, exposed them to social defeat stress, and then tested their approach-avoidance behavior using a social avoidance test. During social defeat stress, dominant subjects showed a longer latency to submit and greater c-Fos expression in AR+ cells in the MePD/MePV compared to subordinates. We found that social defeat exposure reduced the amount of time animals spent interacting with a novel conspecific 24 h later, although there was no effect of dominance status. The amount of social vigilance shown by dominants during social avoidance testing was positively correlated with c-Fos expression in AR+ cells in the MePV. These findings indicate that dominant hamsters show greater neural activity in AR+ cells in the MePV during social defeat compared to their subordinate counterparts, and this pattern of neural activity correlates with their proactive coping response. Consistent with the central role of androgens in experience-dependent changes in aggression, activation of AR+ cells in the MePD/MePV contributes to experience-dependent changes in stress-related behavior.


Assuntos
Mesocricetus , Neurônios , Receptores Androgênicos , Predomínio Social , Estresse Psicológico , Animais , Masculino , Receptores Androgênicos/metabolismo , Estresse Psicológico/metabolismo , Neurônios/metabolismo , Neurônios/fisiologia , Cricetinae , Complexo Nuclear Corticomedial/metabolismo , Complexo Nuclear Corticomedial/fisiologia , Tonsila do Cerebelo/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ansiedade/metabolismo , Dominação-Subordinação
4.
Phytopathology ; 113(8): 1387-1393, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37081724

RESUMO

Strains of Xanthomonas citri pv. malvacearum cause bacterial blight of cotton, a potentially serious threat to cotton production worldwide, including in sub-Saharan countries. Development of disease symptoms, such as water soaking, has been linked to the activity of a class of type 3 effectors, called transcription activator-like (TAL) effectors, which induce susceptibility genes in the host's cells. To gain further insight into the global diversity of the pathogen, to elucidate their repertoires of TAL effector genes, and to better understand the evolution of these genes in the cotton-pathogenic xanthomonads, we sequenced the genomes of three African strains of X. citri pv. malvacearum using nanopore technology. We show that the cotton-pathogenic pathovar of X. citri is a monophyletic lineage containing at least three distinct genetic subclades, which appear to be mirrored by their repertoires of TAL effectors. We observed an atypical level of TAL effector gene pseudogenization, which might be related to resistance genes that are deployed to control the disease. Our work thus contributes to a better understanding of the conservation and importance of TAL effectors in the interaction with the host plant, which can inform strategies for improving resistance against bacterial blight in cotton.

5.
J Helminthol ; 97: e5, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36635102

RESUMO

This study describes changes in oxidative stress (OS) parameters in mice experimentally infected with Angiostrongylus costaricensis, which causes abdominal angiostrongyliasis. For this, 28 Swiss mice were used, divided into two groups (G1 and G2), with 14 animals each. Of these, eight were infected with ten infective larvae each, by gavage, and six were used as a control group. Mice from G1 and G2 were euthanized at 14 days and 24 days post-infection, respectively. Tissue samples were used for histopathological analysis and blood (serum) samples were taken to assess the levels of proteins, non-protein thiols (NPTs) and nitric oxide (NO), from centrifugation and subsequent collection of aliquots of the supernatant. Among OS parameters, infected mice in both groups had higher NO levels than the control group, due to the presence of: eosinophil infiltrate in the liver and intestine; pancreatitis; and intestinal granuloma. However, the infected mice of both groups showed a reduction in the levels of NPTs, in relation to the control group, due to the presence of: eosinophilic infiltrate in the liver and intestine; and intestinal granuloma. Our results suggest that A. costaricensis infection has important effects on the intestine, liver and pancreas, and the analyses were performed from the tissue of these organs. The mechanisms for these changes are related to the decrease in the body's main antioxidant defences, as demonstrated by the reduction of NPTs, thus contributing to the development of more severe tissue damage. Thus, the objective of the present study was to evaluate the relationship between histopathological lesions and markers for OS.


Assuntos
Angiostrongylus , Infecções por Strongylida , Camundongos , Animais , Granuloma , Estresse Oxidativo
6.
Rev Med Chil ; 151(7): 830-840, 2023 Jul.
Artigo em Espanhol | MEDLINE | ID: mdl-39093172

RESUMO

INTRODUCTION: Several factors intervene in the evolution of the characteristics of Coronary artery bypass grafting (CABG), such as demographic changes, surgical technique, and perioperative care. Our objective was to analyze the evolution of the characteristics of coronary artery disease in patients treated with CABG and its immediate results. METHODS: In an analytical study, we analyzed a cohort of patients with isolated CABG from January 2006 to December 2008 and from January 2016 to December 2018 in Hospital Clínico Regional Concepción, Chile. After the ethics committee's approval, we reviewed the database and surgical protocols. We used Chi-square and U Mann Whitney tests for statistical analysis (SPSSv25®), considering significant p < 0,05. RESULTS: We analyzed 1,400 isolated CABG, 658 from the first period and 742 from the second, with a mean age of 62.0 ± 8.7 and 64.6 ± 9.3 respectively (p < 0.001). The subgroup with ventricular dysfunction in the second period showed a significant increase in diabetes mellitus, chronic obstructive pulmonary disease, acute myocardial infarction (AMI), and severe ventricular dysfunction. The second group decreased off-pump surgery and increased the use of ≥ 2 arterial grafts (p < 0.05). The Additive EuroSCORE I increased from 3.6 ± 2.5 to 4.4 ± 2.7 (p = 0.001). High-risk subgroup: 137 (20.8%) to 236 (31.8%), p < 0.001. Mortality of 13 (1.98%) and 16 (2.2%) in the first and second group respectively, p = 0.813. CONCLUSION: There was a significant increase in the estimated surgical risk; however, mortality remained unchanged. The increase in surgical risk is consistent with the increase in mean age and prevalence of comorbidities, as well as the increase in severe ventricular dysfunction in the group ofpatients with ventricular dysfunction and recent AMI in the second period.


Assuntos
Ponte de Artéria Coronária , Doença da Artéria Coronariana , Humanos , Ponte de Artéria Coronária/estatística & dados numéricos , Pessoa de Meia-Idade , Masculino , Feminino , Idoso , Doença da Artéria Coronariana/cirurgia , Chile/epidemiologia , Resultado do Tratamento , Fatores de Risco , Fatores de Tempo , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia
7.
Trends Immunol ; 40(1): 66-80, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30595189

RESUMO

Infiltrating and tissue-resident myeloid cells are essential regulators of innate and adaptive immunity. During inflammation, and in response to microbial products, these cells can adapt to microenvironmental conditions and acquire specialized functions, including phagocytosis and the production of proinflammatory cytokines. Such myeloid plasticity is driven, in part, by epigenetic dynamics that can sustain stable phenotypes after activation, and which may lead to maladaptive cell polarization states associated with inflammation and autoimmunity. Here, we review recent reports describing epigenetic mechanisms linked to such polarization states and innate immune memory (tolerance and training) in monocyte and macrophage lineages. We discuss how these mechanisms might be targeted to develop putative immunomodulatory tools that might be used to treat a variety of immune-mediated diseases.


Assuntos
Epigênese Genética/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Fatores Imunológicos/uso terapêutico , Memória Imunológica/efeitos dos fármacos , Células Mieloides/efeitos dos fármacos , Animais , Epigênese Genética/genética , Epigênese Genética/imunologia , Humanos , Imunidade Inata/imunologia , Fatores Imunológicos/imunologia , Memória Imunológica/imunologia , Células Mieloides/imunologia
8.
Artigo em Inglês | MEDLINE | ID: mdl-36125864

RESUMO

Thousands of new bacterial and archaeal species and higher-level taxa are discovered each year through the analysis of genomes and metagenomes. The Genome Taxonomy Database (GTDB) provides hierarchical sequence-based descriptions and classifications for new and as-yet-unnamed taxa. However, bacterial nomenclature, as currently configured, cannot keep up with the need for new well-formed names. Instead, microbiologists have been forced to use hard-to-remember alphanumeric placeholder labels. Here, we exploit an approach to the generation of well-formed arbitrary Latinate names at a scale sufficient to name tens of thousands of unnamed taxa within GTDB. These newly created names represent an important resource for the microbiology community, facilitating communication between bioinformaticians, microbiologists and taxonomists, while populating the emerging landscape of microbial taxonomic and functional discovery with accessible and memorable linguistic labels.


Assuntos
Archaea , Ácidos Graxos , Archaea/genética , Bactérias/genética , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
9.
Nature ; 536(7615): 179-83, 2016 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-27487207

RESUMO

Bacteria of the SAR11 clade constitute up to one half of all microbial cells in the oxygen-rich surface ocean. SAR11 bacteria are also abundant in oxygen minimum zones (OMZs), where oxygen falls below detection and anaerobic microbes have vital roles in converting bioavailable nitrogen to N2 gas. Anaerobic metabolism has not yet been observed in SAR11, and it remains unknown how these bacteria contribute to OMZ biogeochemical cycling. Here, genomic analysis of single cells from the world's largest OMZ revealed previously uncharacterized SAR11 lineages with adaptations for life without oxygen, including genes for respiratory nitrate reductases (Nar). SAR11 nar genes were experimentally verified to encode proteins catalysing the nitrite-producing first step of denitrification and constituted ~40% of OMZ nar transcripts, with transcription peaking in the anoxic zone of maximum nitrate reduction activity. These results link SAR11 to pathways of ocean nitrogen loss, redefining the ecological niche of Earth's most abundant organismal group.


Assuntos
Alphaproteobacteria/classificação , Alphaproteobacteria/metabolismo , Organismos Aquáticos/metabolismo , Nitrogênio/análise , Oceanos e Mares , Oxigênio/análise , Água do Mar/química , Adaptação Fisiológica/genética , Alphaproteobacteria/genética , Alphaproteobacteria/isolamento & purificação , Anaerobiose/genética , Organismos Aquáticos/enzimologia , Organismos Aquáticos/genética , Organismos Aquáticos/isolamento & purificação , Desnitrificação , Perfilação da Expressão Gênica , Genes Bacterianos , Genoma Bacteriano/genética , Nitrato Redutases/genética , Nitrato Redutases/metabolismo , Nitratos/metabolismo , Nitritos/metabolismo , Nitrogênio/metabolismo , Oxirredução , Oxigênio/metabolismo , Filogenia , Análise de Célula Única , Transcrição Gênica
10.
J Eur Acad Dermatol Venereol ; 36(1): 108-112, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34549834

RESUMO

BACKGROUND: Many patients with chronic itch and atopic dermatitis (AD) or psoriasis do not receive/use available medical and psychosocial treatments properly due to system, provider and/or patient factors. OBJECTIVE: An educational website (ITCH-RELIEF) to improve itch-related quality of life (QoL) for adults with AD or psoriasis and chronic itch was developed and assessed. ITCH RELIEF stands for Interactive Toolbox of Comprehensive Health Resources to Enhance Living with Itch - Educational Facilitation (for Adults). METHODS: Single-arm pre- and post-test design with 1-month follow-up (N = 137 at baseline). RESULTS: There was statistically and clinically significant improvement in the primary outcome of itch-related QoL impairment as assessed by the ItchyQoL from baseline [M = 78.9, 95% confidence interval (CI) = 75.9, 81.9] to follow up (M = 75.4, CI = 72.4, 78.5), P = 0.007, as well as statistically significant improvement in several itch-related secondary outcomes (all Ps < 0.05). CONCLUSIONS: This study demonstrated initial effectiveness of an online intervention to improve itch-related QoL among individuals with AD or psoriasis and chronic itch. Future studies should address limitations by randomizing more heterogeneous participants, utilizing a longer follow-up and assessing medication use.


Assuntos
Dermatite Atópica , Intervenção Baseada em Internet , Psoríase , Adulto , Dermatite Atópica/complicações , Dermatite Atópica/terapia , Humanos , Prurido/etiologia , Prurido/terapia , Psoríase/complicações , Psoríase/terapia , Qualidade de Vida
11.
Rev Clin Esp ; 222(4): 205-211, 2022 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-34305157

RESUMO

Background: Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 infection, spreads swiftly in nursing homes and assisted living facilities, leading to a high degree of lethality. The data generated by an epidemiological surveillance program allow for obtaining valid information on the diseases' epidemiology and possible prevention methods. Objective: This work aims to analyze COVID-19 epidemiology among healthcare staff based in the Seville healthcare district (Spain) and evaluate its role in outbreaks in nursing homes. Methods: This is an observational, descriptive study of 88 assisted living facilities located in the city of Seville from March 1 to May 23, 2020. Data were obtained via epidemiological surveys on staff at centers where there were outbreaks (n = 732 in 14 nursing homes). The cumulative incidence, epidemic curves, sociodemographic and clinical characteristics, and delays in isolation and notification of cases were calculated. For the statistical analysis, measures of central tendency and dispersion were used as well as confidence intervals and statistical hypothesis tests. Results: There were 124 cases in staff members (cumulative incidence 16.9%), 79.0% of which were in women. The majority presented with mild symptoms (87.1%). The most common symptoms were fever (31.5%) and cough (49.2%). The median number of days from onset of symptoms to isolation was three. Conclusions: A high incidence in nursing home staff along with delays in isolation were observed, which could affect the dynamics of transmission in outbreaks. It is necessary to review disease identification and isolation practices among staff as well as emphasize rapid implementation of prevention measures.

12.
Hum Genet ; 140(12): 1665-1678, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34448047

RESUMO

Syndromic retinal diseases (SRDs) are a group of complex inherited systemic disorders, with challenging molecular underpinnings and clinical management. Our main goal is to improve clinical and molecular SRDs diagnosis, by applying a structured phenotypic ontology and next-generation sequencing (NGS)-based pipelines. A prospective and retrospective cohort study was performed on 100 probands with an a priori diagnosis of non-Usher SRDs, using available clinical data, including Human Phenotype Ontology annotation, and further classification into seven clinical categories (ciliopathies, specific syndromes and five others). Retrospective molecular diagnosis was assessed using different molecular and bioinformatic methods depending on availability. Subsequently, uncharacterized probands were prospectively screened using other NGS approaches to extend the number of analyzed genes. After phenotypic classification, ciliopathies were the most common SRD (35%). A global characterization rate of 52% was obtained, with six cases incompletely characterized for a gene that partially explained the phenotype. An improved characterization rate was achieved addressing prospective cases (83%) and well-recognizable syndrome (62%) subgroups. The 27% of the fully characterized cases were reclassified into a different clinical category after identification of the disease-causing gene. Clinical-exome sequencing is the most appropriate first-tier approach for prospective cases, whereas whole-exome sequencing and bioinformatic reanalysis increases the diagnosis of uncharacterized retrospective cases to 45%, mostly those with unspecific symptoms. Our study describes a comprehensive approach to SRDs in daily clinical practice and the importance of thorough clinical assessment and selection of the most appropriate molecular test to be used to solve these complex cases and elucidate novel associations.


Assuntos
Oftalmopatias Hereditárias/diagnóstico , Ontologia Genética , Sequenciamento de Nucleotídeos em Larga Escala , Doenças Retinianas/diagnóstico , Ciliopatias/genética , Estudos de Coortes , Oftalmopatias Hereditárias/genética , Feminino , Estudos de Associação Genética , Testes Genéticos , Humanos , Masculino , Técnicas de Diagnóstico Molecular , Mutação , Fenótipo , Estudos Prospectivos , Doenças Retinianas/genética , Estudos Retrospectivos , Síndrome
13.
J Intern Med ; 289(6): 906-920, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33274479

RESUMO

BACKGROUND: COVID-19 pandemic causes high global morbidity and mortality and better medical treatments to reduce mortality are needed. OBJECTIVE: To determine the added benefit of cyclosporine A (CsA), to low-dose steroid treatment, in patients with COVID-19. METHODS: Open-label, non randomized pilot study of patients with confirmed infection of SARS-CoV-2 hospitalized from April to May 2020 at a single centre in Puebla, Mexico. Patients were assigned to receive either steroids or CsA plus steroids. Pneumonia severity was assessed by clinical, laboratory, and lung tomography. The death rate was evaluated at 28 days. RESULTS: A total of 209 adult patients were studied, 105 received CsA plus steroids (age 55.3 ± 13.3; 69% men), and 104 steroids alone (age 54.06 ± 13.8; 61% men). All patients received clarithromycin, enoxaparin and methylprednisolone or prednisone up to 10 days. Patient's death was associated with hypertension (RR = 3.5) and diabetes (RR = 2.3). Mortality was 22 and 35% for CsA and control groups (P = 0.02), respectively, for all patients, and 24 and 48.5% for patients with moderate to severe disease (P = 0.001). Higher cumulative clinical improvement was seen for the CsA group (Nelson Aalen curve, P = 0.001, log-rank test) in moderate to severe patients. The Cox proportional hazard analysis showed the highest HR improvement value of 2.15 (1.39-3.34, 95%CI, P = 0.0005) for CsA treatment in moderate to severe patients, and HR = 1.95 (1.35-2.83, 95%CI, P = 0.0003) for all patients. CONCLUSION: CsA used as an adjuvant to steroid treatment for COVID-19 patients showed to improve outcomes and reduce mortality, mainly in those with moderate to severe disease. Further investigation through controlled clinical trials is warranted.


Assuntos
Tratamento Farmacológico da COVID-19 , Ciclosporina/uso terapêutico , Glucocorticoides/uso terapêutico , Metilprednisolona/uso terapêutico , Prednisona/uso terapêutico , COVID-19/mortalidade , COVID-19/patologia , Ciclosporina/efeitos adversos , Quimioterapia Combinada , Feminino , Glucocorticoides/administração & dosagem , Humanos , Pulmão/patologia , Masculino , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Projetos Piloto , Prednisona/administração & dosagem , Resultado do Tratamento
14.
Appl Environ Microbiol ; 87(6)2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33452027

RESUMO

The recovery of metagenome-assembled genomes (MAGs) from metagenomic data has recently become a common task for microbial studies. The strengths and limitations of the underlying bioinformatics algorithms are well appreciated by now based on performance tests with mock data sets of known composition. However, these mock data sets do not capture the complexity and diversity often observed within natural populations, since their construction typically relies on only a single genome of a given organism. Further, it remains unclear if MAGs can recover population-variable genes (those shared by >10% but <90% of the members of the population) as efficiently as core genes (those shared by >90% of the members). To address these issues, we compared the gene variabilities of pathogenic Escherichia coli isolates from eight diarrheal samples, for which the isolate was the causative agent, against their corresponding MAGs recovered from the companion metagenomic data set. Our analysis revealed that MAGs with completeness estimates near 95% captured only 77% of the population core genes and 50% of the variable genes, on average. Further, about 5% of the genes of these MAGs were conservatively identified as missing in the isolate and were of different (non-Enterobacteriaceae) taxonomic origin, suggesting errors at the genome-binning step, even though contamination estimates based on commonly used pipelines were only 1.5%. Therefore, the quality of MAGs may often be worse than estimated, and we offer examples of how to recognize and improve such MAGs to sufficient quality by (for instance) employing only contigs longer than 1,000 bp for binning.IMPORTANCE Metagenome assembly and the recovery of metagenome-assembled genomes (MAGs) have recently become common tasks for microbiome studies across environmental and clinical settings. However, the extent to which MAGs can capture the genes of the population they represent remains speculative. Current approaches to evaluating MAG quality are limited to the recovery and copy number of universal housekeeping genes, which represent a small fraction of the total genome, leaving the majority of the genome essentially inaccessible. If MAG quality in reality is lower than these approaches would estimate, this could have dramatic consequences for all downstream analyses and interpretations. In this study, we evaluated this issue using an approach that employed comparisons of the gene contents of MAGs to the gene contents of isolate genomes derived from the same sample. Further, our samples originated from a diarrhea case-control study, and thus, our results are relevant for recovering the virulence factors of pathogens from metagenomic data sets.


Assuntos
Escherichia coli/genética , Fezes/microbiologia , Genoma Bacteriano , Escherichia coli/isolamento & purificação , Humanos , Metagenoma
15.
BMC Microbiol ; 21(1): 14, 2021 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407123

RESUMO

BACKGROUND: The type VI protein secretion system (T6SS) is important in diverse cellular processes in Gram-negative bacteria, including interactions with other bacteria and with eukaryotic hosts. In this study we analyze the evolution of the T6SS in the genus Xanthomonas and evaluate its importance of the T6SS for virulence and in vitro motility in Xanthomonas phaseoli pv. manihotis (Xpm), the causal agent of bacterial blight in cassava (Manihot esculenta). We delineate the organization of the T6SS gene clusters in Xanthomonas and then characterize proteins of this secretion system in Xpm strain CIO151. RESULTS: We describe the presence of three different clusters in the genus Xanthomonas that vary in their organization and degree of synteny between species. Using a gene knockout strategy, we also found that vgrG and hcp are required for maximal aggressiveness of Xpm on cassava plants while clpV is important for both motility and maximal aggressiveness. CONCLUSION: We characterized the T6SS in 15 different strains in Xanthomonas and our phylogenetic analyses suggest that the T6SS might have been acquired by a very ancient event of horizontal gene transfer and maintained through evolution, hinting at their importance for the adaptation of Xanthomonas to their hosts. Finally, we demonstrated that the T6SS of Xpm is functional, and significantly contributes to virulence and motility. This is the first experimental study that demonstrates the role of the T6SS in the Xpm-cassava interaction and the T6SS organization in the genus Xanthomonas.


Assuntos
Biologia Computacional/métodos , Sistemas de Secreção Tipo VI/genética , Xanthomonas/patogenicidade , Técnicas de Inativação de Genes , Transferência Genética Horizontal , Mutação , Filogenia , Análise de Sequência de DNA , Virulência , Xanthomonas/classificação , Xanthomonas/genética , Xanthomonas/fisiologia
16.
Br J Surg ; 108(5): 484-498, 2021 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-34043773

RESUMO

BACKGROUND: Lynch syndrome is the most common genetic predisposition for hereditary cancer but remains underdiagnosed. Large prospective observational studies have recently increased understanding of the effectiveness of colonoscopic surveillance and the heterogeneity of cancer risk between genotypes. The need for gene- and gender-specific guidelines has been acknowledged. METHODS: The European Hereditary Tumour Group (EHTG) and European Society of Coloproctology (ESCP) developed a multidisciplinary working group consisting of surgeons, clinical and molecular geneticists, pathologists, epidemiologists, gastroenterologists, and patient representation to conduct a graded evidence review. The previous Mallorca guideline format was used to revise the clinical guidance. Consensus for the guidance statements was acquired by three Delphi voting rounds. RESULTS: Recommendations for clinical and molecular identification of Lynch syndrome, surgical and endoscopic management of Lynch syndrome-associated colorectal cancer, and preventive measures for cancer were produced. The emphasis was on surgical and gastroenterological aspects of the cancer spectrum. Manchester consensus guidelines for gynaecological management were endorsed. Executive and layperson summaries were provided. CONCLUSION: The recommendations from the EHTG and ESCP for identification of patients with Lynch syndrome, colorectal surveillance, surgical management of colorectal cancer, lifestyle and chemoprevention in Lynch syndrome that reached a consensus (at least 80 per cent) are presented.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/terapia , Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Quimioprevenção , Colonoscopia , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Técnica Delphi , Procedimentos Cirúrgicos do Sistema Digestório , Detecção Precoce de Câncer , Feminino , Triagem de Portadores Genéticos , Testes Genéticos , Neoplasias dos Genitais Femininos/diagnóstico , Neoplasias dos Genitais Femininos/genética , Humanos , Estilo de Vida , Procedimentos Cirúrgicos Profiláticos
17.
Br J Surg ; 108(11): 1315-1322, 2021 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-34467970

RESUMO

BACKGROUND: There is a lack of information regarding the provision of parental leave for surgical careers. This survey study aims to evaluate the experience of maternity/paternity leave and views on work-life balance globally. METHODS: A 55-item online survey in 24 languages was distributed via social media as per CHERRIES guideline from February to March 2020. It explored parental leave entitlements, attitude towards leave taking, financial impact, time spent with children and compatibility of parenthood with surgical career. RESULTS: Of the 1393 (male : female, 514 : 829) respondents from 65 countries, there were 479 medical students, 349 surgical trainees and 513 consultants. Consultants had less than the recommended duration of maternity leave (43.8 versus 29.1 per cent), no paid maternity (8.3 versus 3.2 per cent) or paternity leave (19.3 versus 11.0 per cent) compared with trainees. Females were less likely to have children than males (36.8 versus 45.6 per cent, P = 0.010) and were more often told surgery is incompatible with parenthood (80.2 versus 59.5 per cent, P < 0.001). Males spent less than 20 per cent of their salary on childcare and fewer than 30 hours/week with their children. More than half (59.2 per cent) of medical students did not believe a surgical career allowed work-life balance. CONCLUSION: Surgeons across the globe had inadequate parental leave. Significant gender disparity was seen in multiple aspects.


Assuntos
Escolha da Profissão , Internato e Residência/estatística & dados numéricos , Licença Parental/estatística & dados numéricos , Estudantes de Medicina/estatística & dados numéricos , Cirurgiões/estatística & dados numéricos , Inquéritos e Questionários , Adulto , Atitude do Pessoal de Saúde , Feminino , Humanos , Masculino , Fatores Sexuais , Adulto Jovem
18.
Ultrasound Obstet Gynecol ; 58(6): 864-874, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33942916

RESUMO

OBJECTIVES: To describe the prenatal neuroimaging spectrum of rhombencephalosynapsis (RES) and criteria for its classification according to the severity of vermian anomaly. METHODS: In this multicenter retrospective study of fetuses with RES between 2002 and 2020, the medical records and brain ultrasound and magnetic resonance images were evaluated comprehensively to determine the severity of the vermian anomaly and the presence of associated brain findings. RES was classified, according to the pattern of vermian agenesis and the extent of the fusion of the hemispheres, as complete RES (complete absence of the vermis) or partial RES (further classified according to the part of the vermis that was missing and, consequently, the region of hemispheric fusion, as anterior, posterior, severe or mixed RES). Findings were compared between cases with complete and those with partial RES. RESULTS: Included in the study were 62 fetuses with a gestational age ranging between 12 and 37 weeks. Most had complete absence of the vermis (complete RES, 77.4% of cases), a 'round-shaped' cerebellum on axial views (72.6%) and a transverse cerebellar diameter (TCD) < 3rd centile (87.1%). Among the 22.6% of cases with partial RES, 6.5% were classified as severe partial, 6.5% as partial anterior, 8.1% as partial mixed and 1.6% as partial posterior. Half of these cases presented with normal or nearly normal cerebellar morphology and 28.5% had a TCD within the normal limits. Infratentorially, the fourth ventricle was abnormal in 88.7% of cases overall, and anomalies of the midbrain and pons were frequent (93.5% and 77.4%, respectively). Ventriculomegaly was observed in 80.6% of all cases, being more severe in cases with complete RES than in those with partial RES, with high rates of parenchymal and septal disruption. CONCLUSIONS: This study provides prenatal neuroimaging criteria for the diagnosis and classification of RES, and identification of related features, using ultrasound and magnetic resonance imaging. According to our findings, a diagnosis of RES should be considered in fetuses with a small TCD (severe cerebellar hypoplasia) and/or a round-shaped cerebellum on axial views, during the second or third trimester, especially when associated with ventriculomegaly. Partial RES is more common than previously thought, but presents an extreme diagnostic challenge, especially in cases with normal or nearly-normal cerebellar morphobiometric features. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.


Assuntos
Anormalidades Múltiplas/diagnóstico por imagem , Vermis Cerebelar/anormalidades , Cerebelo/anormalidades , Anormalidades do Olho/diagnóstico por imagem , Doenças Renais Císticas/diagnóstico por imagem , Malformações do Sistema Nervoso/diagnóstico por imagem , Neuroimagem , Diagnóstico Pré-Natal/métodos , Retina/anormalidades , Rombencéfalo/anormalidades , Anormalidades Múltiplas/embriologia , Adulto , Vermis Cerebelar/diagnóstico por imagem , Vermis Cerebelar/embriologia , Cerebelo/diagnóstico por imagem , Cerebelo/embriologia , Anormalidades do Olho/embriologia , Feminino , Idade Gestacional , Humanos , Doenças Renais Císticas/embriologia , Imageamento por Ressonância Magnética , Imagem Multimodal , Malformações do Sistema Nervoso/embriologia , Gravidez , Retina/diagnóstico por imagem , Retina/embriologia , Estudos Retrospectivos , Rombencéfalo/diagnóstico por imagem , Rombencéfalo/embriologia , Índice de Gravidade de Doença , Ultrassonografia Pré-Natal
19.
J Helminthol ; 95: e40, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34353407

RESUMO

This study describes changes in haematological parameters, cytokine profile, histopathology and cortisol levels in Swiss mice experimentally infected with Angiostrongylus costaricensis. Twenty-eight Swiss mice were divided into two groups (G1 and G2) of 14 animals each. In each group, eight animals were infected orally with ten third-stage larvae of A. costaricensis and six were used as a control group. The mice of groups G1 and G2 were sacrificed 14 and 24 days after infection, respectively. Samples were collected for histopathological and haematological analyses and determination of the cytokine profile and cortisol levels. Granulomatous reaction, eosinophilic infiltrate and vasculitis in the intestinal tract, pancreas, liver and spleen were observed with varying intensity in infected animals. Our results showed that the mice developed normocytic and hypochromic anaemia, and that the histopathological lesions caused by the experimental infection influenced increases in cortisol, neutrophil and monocyte levels. In addition to this, we detected increased interleukin-6 and tumour necrosis factor alpha levels in the infected animals.


Assuntos
Angiostrongylus , Infecções por Strongylida , Animais , Hidrocortisona , Intestinos , Larva , Camundongos
20.
Clin Invest Ginecol Obstet ; 48(1): 3-13, 2021.
Artigo em Espanhol | MEDLINE | ID: mdl-32836610

RESUMO

During a pandemic, the three basic principles are. to prioritize medical resources, ensure patients' lockdown in order to avoid community transmission and prevent healthcare collapse, and keep the number of visits to an absolute minimum to avoid patient exposure and safeguard healthcare workers. Antenatal care must be maintained during a health crisis, regardless of the COVID-19 state of alert. Routine and specialist obstetric ultrasound scans are essential for clinical decision-making during pregnancy, as it has a direct impact on the management of mothers and fetuses and on the perinatal outcome. In an attempt to minimize in-person visits, these will be organized according to the established ultrasound schedule. Based on scientific evidence, and on existing main national and international guidelines, this document has been prepared, in which proposals and options are provided for managing pregnant women in the context of the SARS-CoV-2 pandemic. It includes how a Fetal Medicine Unit facing this health crisis should be restructured, what safety measures should be followed in the performance of obstetric scans and invasive procedures, and how ultrasound rooms, equipment and transducers should be cleaned and disinfected. These recommendations should be adapted to different units based on their resources and infrastructure.

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