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1.
BMC Infect Dis ; 20(1): 880, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33228580

RESUMO

BACKGROUND: Following infection with Mycobacterium tuberculosis (M.tb), individuals may rapidly develop tuberculosis (TB) disease or enter a "latent" infection state with a low risk of progression to disease. Mathematical models use a variety of structures and parameterisations to represent this process. The effect of these different assumptions on the predicted impact of TB interventions has not been assessed. METHODS: We explored how the assumptions made about progression from infection to disease affect the predicted impact of TB preventive therapy. We compared the predictions using three commonly used model structures, and parameters derived from two different data sources. RESULTS: The predicted impact of preventive therapy depended on both the model structure and parameterisation. At a baseline annual TB incidence of 500/100,000, there was a greater than 2.5-fold difference in the predicted reduction in incidence due to preventive therapy (ranging from 6 to 16%), and the number needed to treat to avert one TB case varied between 67 and 157. The relative importance of structure and parameters depended on baseline TB incidence and assumptions about the efficacy of preventive therapy, with the choice of structure becoming more important at higher incidence. CONCLUSIONS: The assumptions use to represent progression to disease in models are likely to influence the predicted impact of preventive therapy and other TB interventions. Modelling estimates of TB preventive therapy should consider routinely incorporating structural uncertainty, particularly in higher burden settings. Not doing so may lead to inaccurate and over confident conclusions, and sub-optimal evidence for decision making.

2.
Acad Med ; 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33003036

RESUMO

PROBLEM: American Indian/Alaska Native (AI/AN) populations are facing multiple health crises, including limited access to care, high rates of chronic disease, and early mortality that is far worse than other underrepresented minorities in the U.S. According to the Association of American Indian Physicians, AI/AN people represent 2.0% of the U.S. population but only 0.2% of medical students and 0.1% of full-time faculty at MD-granting institutions. Increasing the number of AI/AN clinicians and scientists is one strategy to improve health outcomes in the AI/AN population and address these crises. APPROACH: In 2010, the University of Utah partnered with research, cultural, and professional mentors to create a 10-week summer Native American Research Internship (NARI) program for AI/AN college students across the U.S. who are interested in pursuing biomedical careers. NARI attracts and supports AI/AN students by offering mentored summer research internships in an innovative, culturally-aware framework that adapts to observed challenges to optimize educational experiences and support biomedical career aspirations. OUTCOMES: During the first decade of the NARI program, 128 students from 22 U.S. states, representing 46 tribal nations and 57 colleges and universities, have participated. Of those 128 students, 113 (88%) have completed a bachelor's degree and the remaining 15 (12%) are currently working towards a bachelor's degree. No NARI student has dropped out of college. Twenty-six (20%) NARI alumni have matriculated to medical school and 30 (23%) to graduate school. Eight (6%) participants have completed medical school and 3 (2%) participants are pursuing a PhD in science. An additional 36 (28%) have gained employment in biomedical research fields. NEXT STEPS: The NARI program has increased the participation of AI/AN students in medicine and the biomedical sciences. The innovative, culturally-aware, and adaptive framework is a model for other programs for AI/AN students and students in other underrepresented communities.

3.
Sci Transl Med ; 12(564)2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028708

RESUMO

More effective tuberculosis vaccines are needed to help reach World Health Organization tuberculosis elimination goals. Insufficient evidence exists on the potential impact of future tuberculosis vaccines with varying characteristics and in different epidemiological settings. To inform vaccine development decision making, we modeled the impact of hypothetical tuberculosis vaccines in three high-burden countries. We calibrated Mycobacterium tuberculosis (M.tb) transmission models to age-stratified demographic and epidemiological data from China, South Africa, and India. We varied vaccine efficacy to prevent infection or disease, effective in persons M.tb uninfected or infected, and duration of protection. We modeled routine early-adolescent vaccination and 10-yearly mass campaigns from 2025. We estimated median percentage population-level tuberculosis incidence rate reduction (IRR) in 2050 compared to a no new vaccine scenario. In all settings, results suggested vaccines preventing disease in M.tb-infected populations would have greatest impact by 2050 (10-year, 70% efficacy against disease, IRR 51%, 52%, and 54% in China, South Africa, and India, respectively). Vaccines preventing reinfection delivered lower potential impact (IRR 1, 12, and 17%). Intermediate impact was predicted for vaccines effective only in uninfected populations, if preventing infection (IRR 21, 37, and 50%) or disease (IRR 19, 36, and 51%), with greater impact in higher-transmission settings. Tuberculosis vaccines have the potential to deliver substantial population-level impact. For prioritizing impact by 2050, vaccine development should focus on preventing disease in M.tb-infected populations. Preventing infection or disease in uninfected populations may be useful in higher transmission settings. As vaccine impact depended on epidemiology, different development strategies may be required.

4.
NMR Biomed ; : e4420, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33021342

RESUMO

INTRODUCTION: Magnetic resonance elastography (MRE)-derived aortic stiffness is a potential biomarker for multiple cardiovascular diseases. Currently, gradient-recalled echo (GRE) MRE is a widely accepted technique to estimate aortic stiffness. However, multi-slice GRE MRE requires multiple breath-holds (BHs), which can be challenging for patients who cannot consistently hold their breath. The aim of this study was to investigate the feasibility of a multi-slice spin-echo echo-planar imaging (SE-EPI) MRE sequence for quantifying in vivo aortic stiffness using a free-breathing (FB) protocol and a single-BH protocol. METHOD: On Scanner 1, 25 healthy subjects participated in the validation of FB SE-EPI against FB GRE. On Scanner 2, another 15 healthy subjects were recruited to compare FB SE-EPI with single-BH SE-EPI. Among all volunteers, five participants were studied on both scanners to investigate the inter-scanner reproducibility of FB SE-EPI aortic MRE. Bland-Altman analysis, Lin's concordance correlation coefficient (LCCC) and coefficient of variation (COV) were evaluated. The phase-difference signal-to-noise ratios (PD SNR) were compared. RESULTS: Aortic MRE using FB SE-EPI and FB GRE yielded similar stiffnesses (paired t-test, P = 0.19), with LCCC = 0.97. The FB SE-EPI measurements were reproducible (intra-scanner LCCC = 0.96) and highly repeatable (LCCC = 0.99). The FB SE-EPI MRE was also reproducible across different scanners (inter-scanner LCCC = 0.96). Single-BH SE-EPI scans yielded similar stiffness to FB SE-EPI scans (LCCC = 0.99) and demonstrated a low COV of 2.67% across five repeated measurements. CONCLUSION: Multi-slice SE-EPI aortic MRE using an FB protocol or a single-BH protocol is reproducible and repeatable with advantage over multi-slice FB GRE in reducing acquisition time. Additionally, FB SE-EPI MRE provides a potential alternative to BH scans for patients who have challenges in holding their breath.

5.
Value Health ; 23(11): 1462-1469, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33127017

RESUMO

OBJECTIVES: Health systems face nonfinancial constraints that can influence the opportunity cost of interventions. Empirical methods to explore their impact, however, are underdeveloped. We develop a conceptual framework for defining health system constraints and empirical estimation methods that rely on routine data. We then present an empirical approach for incorporating nonfinancial constraints in cost-effectiveness models of health benefit packages for the health sector. METHODS: We illustrate the application of this approach through a case study of defining a package of services for tuberculosis case-finding in South Africa. An economic model combining transmission model outputs with unit costs was developed to examine the cost-effectiveness of alternative screening and diagnostic algorithms. Constraints were operationalized as restrictions on achievable coverage based on: (1) financial resources; (2) human resources; and (3) policy constraints around diagnostics purchasing. Cost-effectiveness of the interventions was assessed under one "unconstrained" and several "constrained" scenarios. For the unconstrained scenario, incremental cost-effectiveness ratios were estimated with and without the costs of "relaxing" constraints. RESULTS: We find substantial differences in incremental cost-effectiveness ratios across scenarios, leading to variations in the decision rules for prioritizing interventions. In constrained scenarios, the limiting factor for most interventions was not financial, but rather the availability of human resources. CONCLUSIONS: We find that optimal prioritization among different tuberculosis control strategies in South Africa is influenced by whether and how constraints are taken into consideration. We thus demonstrate both the importance and feasibility of considering nonfinancial constraints in health sector resource allocation models.

6.
PLoS One ; 15(10): e0240184, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33057454

RESUMO

Consistency and duplicability in Computed Tomography (CT) output is essential to quantitative imaging for lung cancer detection and monitoring. This study of CT-detected lung nodules investigated the reproducibility of volume-, density-, and texture-based features (outcome variables) over routine ranges of radiation dose, reconstruction kernel, and slice thickness. CT raw data of 23 nodules were reconstructed using 320 acquisition/reconstruction conditions (combinations of 4 doses, 10 kernels, and 8 thicknesses). Scans at 12.5%, 25%, and 50% of protocol dose were simulated; reduced-dose and full-dose data were reconstructed using conventional filtered back-projection and iterative-reconstruction kernels at a range of thicknesses (0.6-5.0 mm). Full-dose/B50f kernel reconstructions underwent expert segmentation for reference Region-Of-Interest (ROI) and nodule volume per thickness; each ROI was applied to 40 corresponding images (combinations of 4 doses and 10 kernels). Typical texture analysis metrics (including 5 histogram features, 13 Gray Level Co-occurrence Matrix, 5 Run Length Matrix, 2 Neighboring Gray-Level Dependence Matrix, and 3 Neighborhood Gray-Tone Difference Matrix) were computed per ROI. Reconstruction conditions resulting in no significant change in volume, density, or texture metrics were identified as "compatible pairs" for a given outcome variable. Our results indicate that as thickness increases, volumetric reproducibility decreases, while reproducibility of histogram- and texture-based features across different acquisition and reconstruction parameters improves. To achieve concomitant reproducibility of volumetric and radiomic results across studies, balanced standardization of the imaging acquisition parameters is required.

7.
Microbiome ; 8(1): 135, 2020 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-32938503

RESUMO

BACKGROUND: Shark Bay, Australia, harbours one of the most extensive and diverse systems of living microbial mats that are proposed to be analogs of some of the earliest ecosystems on Earth. These ecosystems have been shown to possess a substantial abundance of uncultivable microorganisms. These enigmatic microbes, jointly coined as 'microbial dark matter' (MDM), are hypothesised to play key roles in modern microbial mats. RESULTS: We reconstructed 115 metagenome-assembled genomes (MAGs) affiliated to MDM, spanning 42 phyla. This study reports for the first time novel microorganisms (Zixibacterial order GN15) putatively taking part in dissimilatory sulfate reduction in surface hypersaline settings, as well as novel eukaryote signature proteins in the Asgard archaea. Despite possessing reduced-size genomes, the MDM MAGs are capable of fermenting and degrading organic carbon, suggesting a role in recycling organic carbon. Several forms of RuBisCo were identified, allowing putative CO2 incorporation into nucleotide salvaging pathways, which may act as an alternative carbon and phosphorus source. High capacity of hydrogen production was found among Shark Bay MDM. Putative schizorhodopsins were also identified in Parcubacteria, Asgard archaea, DPANN archaea, and Bathyarchaeota, allowing these members to potentially capture light energy. Diversity-generating retroelements were prominent in DPANN archaea that likely facilitate the adaptation to a dynamic, host-dependent lifestyle. CONCLUSIONS: This is the first study to reconstruct and describe in detail metagenome-assembled genomes (MAGs) affiliated with microbial dark matter in hypersaline microbial mats. Our data suggests that these microbial groups are major players in these systems. In light of our findings, we propose H2, ribose and CO/CO2 as the main energy currencies of the MDM community in these mat systems. Video Abstract.

8.
Cell Syst ; 11(5): 536-546.e7, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-32910905

RESUMO

Transcriptional profiling of tumors has revealed a stress-like state among the cancer cells with the concerted expression of genes such as fos, jun, and heat-shock proteins, though this has been controversial given possible dissociation-effects associated with single-cell RNA sequencing. Here, we validate the existence of this state using a combination of zebrafish melanoma modeling, spatial transcriptomics, and human samples. We found that the stress-like subpopulation of cancer cells is present from the early stages of tumorigenesis. Comparing with previously reported single-cell RNA sequencing datasets from diverse cancer types, including triple-negative breast cancer, oligodendroglioma, and pancreatic adenocarcinoma, indicated the conservation of this state during tumorigenesis. We also provide evidence that this state has higher tumor-seeding capabilities and that its induction leads to increased growth under both MEK and BRAF inhibitors. Collectively, our study supports the stress-like cells as a cancer cell state expressing a coherent set of genes and exhibiting drug-resistance properties.

9.
Cancer Discov ; 10(9): 1255-1257, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32873617

RESUMO

Alicea and colleagues demonstrate that aged fibroblasts secrete lipids into the tumor microenvironment, allowing for nutrient exchange with melanoma cells. This supportive function of fibroblasts results in increased resistance to BRAF/MEKi therapy in the context of an aged microenvironment, providing crucial mechanistic insight into age-related drug resistance.See related article by Alicea et al., p. 1282.

10.
ANZ J Surg ; 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32902084

RESUMO

BACKGROUND: Open surgery for abdominal aortic aneurysms in the UK is usually performed via a midline transperitoneal incision. However, the left retroperitoneal (RP) approach may be beneficial for juxtarenal abdominal aortic aneurysms and certain physiological reasons. One potential disadvantage is that the left kidney usually requires mobilization anteromedially risking injury to the renal tract and possibly the ureter. METHODS: In this retrospective study, the time of onset, clinical presentation and treatment of left renal tract complications are scrutinized and discussed. Reasons for open aortic surgery as opposed to endovascular repair being undertaken were documented. Also, the aortic cross-clamp positions and type of reconstruction were examined. RESULTS: A total of 208 patients underwent RP aortic surgery for aneurysmal disease. The aortic cross-clamp positions were infrarenal in 115 (55%), suprarenal in 78 (38%) and supra-superior mesenteric artery or supracoeliac in 15 (7%). Two percent (4/208) sustained ureteric complications and all occurred in the upper third of the left ureter. The time of onset of symptoms ranged from 2 to 14 days post-operatively with a median of 3.5. Clinical signs were non-specific including pyrexia, tachycardia and flank pain. CONCLUSION: Ureteric complications following left RP aortic surgery is uncommon and usually occurs in the upper third of the renal tract. Trauma appears to be the most common cause, although ureteric ischaemia can occur but presents later particularly in those with comorbidities.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32925201

RESUMO

PURPOSE: In mild cognitive impairment (MCI), identifying individuals at high risk for progressive cognitive deterioration can be useful for prognostication and intervention. This study quantitatively characterizes cognitive decline rates in MCI and tests whether volumetric data from baseline magnetic resonance imaging (MRI) can predict accelerated cognitive decline. METHODS: The authors retrospectively examined Alzheimer Disease Neuroimaging Initiative data to obtain serial Mini-Mental Status Exam (MMSE) scores, diagnoses, and the following baseline MRI volumes: total intracranial volume, whole-brain and ventricular volumes, and volumes of the hippocampus, entorhinal cortex, fusiform gyrus, and medial temporal lobe. Subjects with <24 months or <4 measurements of MMSE data were excluded. Predictive modeling of fast cognitive decline (defined as >0.6/year) from baseline volumetric data was performed on subjects with MCI using a single hidden layer neural network. RESULTS: Among 698 baseline MCI subjects, the median annual decline in the MMSE score was 1.3 for converters to dementia versus 0.11 for stable MCI (P<0.001). A 0.6/year threshold captured dementia conversion with 82% accuracy (sensitivity 79%, specificity 85%, area under the receiver operating characteristic curve 0.88). Regional volumes on baseline MRI predicted fast cognitive decline with a test accuracy of 71%. DISCUSSION: An MMSE score decrease of >0.6/year is associated with MCI-to-dementia conversion and can be predicted from baseline MRI.

12.
J Med Imaging (Bellingham) ; 7(4): 044501, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32832577

RESUMO

Purpose: Our study investigates whether a machine-learning-based system can predict the rate of cognitive decline in mildly cognitively impaired patients by processing only the clinical and imaging data collected at the initial visit. Approach: We built a predictive model based on a supervised hybrid neural network utilizing a three-dimensional convolutional neural network to perform volume analysis of magnetic resonance imaging (MRI) and integration of nonimaging clinical data at the fully connected layer of the architecture. The experiments are conducted on the Alzheimer's Disease Neuroimaging Initiative dataset. Results: Experimental results confirm that there is a correlation between cognitive decline and the data obtained at the first visit. The system achieved an area under the receiver operator curve of 0.70 for cognitive decline class prediction. Conclusion: To our knowledge, this is the first study that predicts "slowly deteriorating/stable" or "rapidly deteriorating" classes by processing routinely collected baseline clinical and demographic data [baseline MRI, baseline mini-mental state examination (MMSE), scalar volumetric data, age, gender, education, ethnicity, and race]. The training data are built based on MMSE-rate values. Unlike the studies in the literature that focus on predicting mild cognitive impairment (MCI)-to-Alzheimer's disease conversion and disease classification, we approach the problem as an early prediction of cognitive decline rate in MCI patients.

14.
Int Wound J ; 2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32744430

RESUMO

Wound complications following arterial surgery in the groin are relatively common and can result in significant morbidity and mortality. Vascularised muscle flaps (VMF) may be used as an adjunct to aid healing, either to manage complications or prophylactically. This series describes 46 patients who received sartorius or gracilis muscle flaps, of which 70% were performed as a salvage procedure to treat complications ranging from wound breakdown to vascular graft infection. The remaining 30% were performed at the time of the arterial surgery in patients with risk factors such as re-do surgery or immunosuppression. The peri-operative mortality rate was 9% and the major amputation rate was 26%, reflecting the complexity of patients that require intervention. Overall, 85% achieved successful healing in the groin without the need for further treatment following VMF. Only one case of flap necrosis occurred. Wound healing complications occurred more commonly after sartorius muscle flaps. The gracilis muscle offers a bulkier mass and greater mobility and so may be preferable, particularly for larger groin defects. This series has shown that VMF offer a safe and reliable option for selected cases to achieve wound healing in the groin in patients with often significant co-morbidities.

15.
Eur Respir J ; 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32855219

RESUMO

Previous analyses suggest children with tuberculosis (TB) are no more or no less likely to have multidrug- or rifampicin-resistant TB (MDR/RR-TB) than adults. However, the availability of new data, particularly for high MDR/RR-TB burden countries, suggest updates of country-specific estimates are warranted.We used data from population-representative surveys and surveillance collected between 2000 and 2018 to compare the odds ratio (OR) of MDR/RR-TB among children (<15 years) with TB, compared to the odds of MDR/RR-TB among adults (≥15 years) with TB.In most settings (45/55 countries), and globally as a whole, there is no evidence that age is associated with odds of MDR/RR-TB. However, in some settings such as former Soviet Union countries in general, and Georgia, Kazakhstan, Lithuania, Tajikistan and Uzbekistan in particular, as well as Peru, MDR/RR-TB is positively associated with age ≥15. Meanwhile, in Western Europe in general, and the UK, Poland, Finland and Luxembourg in particular, MDR/RR-TB is positively associated with age <15. Sixteen countries had sufficient data to compare over time between 2000-2011 and 2012-2018, with evidence for decreases in the OR in children compared to adults in Germany, Kazakhstan and the USA.Our results support findings that in most settings a child with TB is as likely as an adult with TB to have MDR/RR-TB. However, setting-specific heterogeneity requires further investigation. Further, the OR for MDR/RR-TB in children compared to adults is generally either stable or decreasing. There are important gaps in detection, recording and reporting of drug resistance among paediatric TB cases, limiting our understanding of transmission risks and measures needed to combat the global TB epidemic.

16.
PLoS Genet ; 16(8): e1008941, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32760060

RESUMO

Apolipoprotein B-containing lipoproteins (B-lps) are essential for the transport of hydrophobic dietary and endogenous lipids through the circulation in vertebrates. Zebrafish embryos produce large numbers of B-lps in the yolk syncytial layer (YSL) to move lipids from yolk to growing tissues. Disruptions in B-lp production perturb yolk morphology, readily allowing for visual identification of mutants with altered B-lp metabolism. Here we report the discovery of a missense mutation in microsomal triglyceride transfer protein (Mtp), a protein that is essential for B-lp production. This mutation of a conserved glycine residue to valine (zebrafish G863V, human G865V) reduces B-lp production and results in yolk opacity due to aberrant accumulation of cytoplasmic lipid droplets in the YSL. However, this phenotype is milder than that of the previously reported L475P stalactite (stl) mutation. MTP transfers lipids, including triglycerides and phospholipids, to apolipoprotein B in the ER for B-lp assembly. In vitro lipid transfer assays reveal that while both MTP mutations eliminate triglyceride transfer activity, the G863V mutant protein unexpectedly retains ~80% of phospholipid transfer activity. This residual phospholipid transfer activity of the G863V mttp mutant protein is sufficient to support the secretion of small B-lps, which prevents intestinal fat malabsorption and growth defects observed in the mttpstl/stl mutant zebrafish. Modeling based on the recent crystal structure of the heterodimeric human MTP complex suggests the G865V mutation may block triglyceride entry into the lipid-binding cavity. Together, these data argue that selective inhibition of MTP triglyceride transfer activity may be a feasible therapeutic approach to treat dyslipidemia and provide structural insight for drug design. These data also highlight the power of yolk transport studies to identify proteins critical for B-lp biology.


Assuntos
Proteínas de Transporte/genética , Lipídeos/genética , Lipoproteínas/genética , Triglicerídeos/genética , Animais , Fígado Gorduroso/genética , Fígado Gorduroso/patologia , Trato Gastrointestinal/metabolismo , Humanos , Imunoprecipitação , Gotículas Lipídicas/metabolismo , Lipoproteínas/metabolismo , Mutação de Sentido Incorreto/genética , Mutação Puntual/genética , Transporte Proteico/genética , Triglicerídeos/metabolismo , Peixe-Zebra/genética
17.
Surgery ; 168(3): 518-526, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32669204

RESUMO

BACKGROUND: It is unknown whether all thick melanomas share the same prognostic features. We present a large, multi-institutional study on thick melanoma, evaluating for factors prognostic of survival. METHODS: We queried the database of the Sentinel Lymph Node Working Group for patients with thick melanoma (>4 mm) who had a sentinel lymph node biopsy from 1993 to 2018. Clinicopathologic characteristics were correlated with overall survival. RESULTS: There were 1,235 patients with a median follow-up of 28 months. Median thickness was 5.9 mm, with 713, 356, and 166 cases having a thickness of >4 to 6, >6 to 10, and >10 mm, respectively. Ulceration was seen in 51.2% of cases, while sentinel lymph node metastases were seen in 439 of 1,235 (35.5%) cases. For melanomas >4 to 6 mm, age, thickness, ulceration, lymphovascular invasion, and sentinel lymph node metastasis were correlated with overall survival (all P < .05), but for melanomas >6 to 10 mm, only sex and sentinel lymph node metastasis were prognostic of overall survival (both P < .05). For melanomas >10 mm, only sentinel lymph node metastasis predicted overall survival on multivariable analyses (P < .05). CONCLUSION: Prognostic markers of overall survival for thick melanoma include thickness, ulceration, and sentinel lymph node metastasis, but also include other unique factors such as lymphovascular invasion. Moreover, certain prognostic markers for survival are associated with different subgroups of thick melanoma, which vary based on thickness group.


Assuntos
Procedimentos Cirúrgicos Dermatológicos , Melanoma/mortalidade , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Cutâneas/mortalidade , Pele/patologia , Idoso , Vasos Sanguíneos/patologia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática/patologia , Vasos Linfáticos/patologia , Masculino , Melanoma/patologia , Melanoma/cirurgia , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Linfonodo Sentinela/patologia , Biópsia de Linfonodo Sentinela/estatística & dados numéricos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Carga Tumoral
18.
Trends Microbiol ; 2020 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-32654857

RESUMO

Stromatolites are geobiological systems formed by complex microbial communities, and fossilized stromatolites provide a record of some of the oldest life on Earth. Microbial mats are precursors of extant stromatolites; however, the mechanisms of transition from mat to stromatolite are controversial and are still not well understood. To fully recognize the profound impact that these ecosystems have had on the evolution of the biosphere requires an understanding of modern lithification mechanisms and how they relate to the geological record. We propose here viral mechanisms in carbonate precipitation, leading to stromatolite formation, whereby viruses directly or indirectly impact microbial metabolisms that govern the transition from microbial mat to stromatolite. Finding a tangible link between host-virus interactions and changes in biogeochemical processes will provide tools to interpret mineral biosignatures through geologic time, including those on Earth and beyond.

19.
J Antimicrob Chemother ; 75(10): 2760-2768, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32681170

RESUMO

OBJECTIVES: To investigate the genomic context of a novel resistance island (RI) in multiply antibiotic-resistant Acinetobacter baumannii clinical isolates and global isolates. METHODS: Using a combination of long and short reads generated from the Oxford Nanopore and Illumina platforms, contiguous chromosomes and plasmid sequences were determined. BLAST-based analysis was used to identify the RI insertion target. RESULTS: Genomes of four multiply antibiotic-resistant A. baumannii clinical strains, from a US hospital system, belonging to prevalent MLST ST2 (Pasteur scheme) and ST281 (Oxford scheme) clade F isolates were sequenced to completion. A class 1 integron carrying aadB (tobramycin resistance) and aadA2 (streptomycin/spectinomycin resistance) was identified. The class 1 integron was 6.8 kb, bounded by IS26 at both ends, and embedded in a new target location between an α/ß-hydrolase and a reductase. Due to its novel insertion site and unique RI composition, we suggest naming this novel RI AbGRI4. Molecular analysis of global A. baumannii isolates identified multiple AbGRI4 RI variants in non-ST2 clonal lineages, including variations in the resistance gene cassettes, integron backbone and insertion breakpoints at the hydrolase gene. CONCLUSIONS: A novel RI insertion target harbouring a class 1 integron was identified in a subgroup of ST2/ST281 clinical isolates. Variants of the RI suggested evolution and horizontal transfer of the RI across clonal lineages. Long- and short-read hybrid assembly technology completely resolved the genomic context of IS-bounded RIs, which was not possible using short reads alone.

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