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1.
Commun Biol ; 7(1): 786, 2024 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-38951579

RESUMEN

Fibroins' transition from liquid to solid is fundamental to spinning and underpins the impressive native properties of silk. Herein, we establish a fibroin heavy chain fold for the Silk-I polymorph, which could be relevant for other similar proteins, and explains mechanistically the liquid-to-solid transition of this silk, driven by pH reduction and flow stress. Combining spectroscopy and modelling we propose that the liquid Silk-I fibroin heavy chain (FibH) from the silkworm, Bombyx mori, adopts a newly reported ß-solenoid structure. Similarly, using rheology we propose that FibH N-terminal domain (NTD) templates reversible higher-order oligomerization driven by pH reduction. Our integrated approach bridges the gap in understanding FibH structure and provides insight into the spatial and temporal hierarchical self-assembly across length scales. Our findings elucidate the complex rheological behaviour of Silk-I, solutions and gels, and the observed liquid crystalline textures within the silk gland. We also find that the NTD undergoes hydrolysis during standard regeneration, explaining key differences between native and regenerated silk feedstocks. In general, in this study we emphasize the unique characteristics of native and native-like silks, offering a fresh perspective on our fundamental understanding of silk-fibre production and applications.


Asunto(s)
Bombyx , Fibroínas , Bombyx/metabolismo , Bombyx/química , Animales , Fibroínas/química , Fibroínas/metabolismo , Reología , Seda/química , Seda/metabolismo , Concentración de Iones de Hidrógeno
2.
Int J Surg Case Rep ; 121: 110033, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39018727

RESUMEN

INTRODUCTION: While prognosis in metastatic melanoma has traditionally been poor, novel systemic therapies such as immunotherapy and targeted agents have improved overall survival (Steininger et al., 2021). These medications are generally well tolerated but can be associated with immune related adverse events (Remash et al., 2021). Hepatic metastatectomy is an important component of management, conferring a survival benefit over systemic therapy alone in appropriately selected patients (Medina et al., 2020). Gadoxetic acid-enhanced magnetic resonance imaging (GA-MRI) has been demonstrated to have enhanced diagnostic accuracy compared with other imaging modalities for hepatic metastases (Freitas et al., 2021). The risk of tumour seeding associated fine-needle aspiration biopsy (FNAB) of hepatic lesions varies, with most studies reporting a low incidence (Maturen et al., 2006). PRESENTATION OF CASE: In February 2020, a 75-year-old male underwent wide local excision and sentinel lymph node biopsy for stage IIA (T2B, N0, M0) melanoma. Routine surveillance without adjuvant systemic treatment was commenced. In July 2022, he presented with haemoptysis and was subsequently diagnosed with widespread metastatic disease on positive emission tomography (PET). After combination ipilimumab and nivolumab, PET scans in August 2023 revealed new liver lesions with disease response at all other metastatic sites. Following a multi-disciplinary team (MDT) discussion, the patient proceeded to hepatic metastatectomy. Histopathology demonstrated chronic necrotising granulomatous hepatitis. DISCUSSION: This case reflects the challenges involved in investigation and management of hepatic metastases in melanoma. CONCLUSION: Despite the accuracy of modern imaging, this case demonstrates the need for MDT consideration of liver biopsy in patients on anti-CTL4 treatment or with response to systemic treatment at extrahepatic sites.

3.
Res Sq ; 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38798429

RESUMEN

Advancements in sequencing technologies and the development of new data collection methods produce large volumes of biological data. The Genomic Data Science Analysis, Visualization, and Informatics Lab-space (AnVIL) provides a cloud-based platform for democratizing access to large-scale genomics data and analysis tools. However, utilizing the full capabilities of AnVIL can be challenging for researchers without extensive bioinformatics expertise, especially for executing complex workflows. Here we present the AnVILWorkflow R package, which enables the convenient execution of bioinformatics workflows hosted on AnVIL directly from an R environment. AnVILWorkflowsimplifies the setup of the cloud computing environment, input data formatting, workflow submission, and retrieval of results through intuitive functions. We demonstrate the utility of AnVILWorkflowfor three use cases: bulk RNA-seq analysis with Salmon, metagenomics analysis with bioBakery, and digital pathology image processing with PathML. The key features of AnVILWorkflow include user-friendly browsing of available data and workflows, seamless integration of R and non-R tools within a reproducible analysis pipeline, and accessibility to scalable computing resources without direct management overhead. While some limitations exist around workflow customization, AnVILWorkflowlowers the barrier to taking advantage of AnVIL's resources, especially for exploratory analyses or bulk processing with established workflows. This empowers a broader community of researchers to leverage the latest genomics tools and datasets using familiar R syntax. This package is distributed through the Bioconductor project (https://bioconductor.org/packages/AnVILWorkflow), and the source code is available through GitHub (https://github.com/shbrief/AnVILWorkflow).

4.
J Marital Fam Ther ; 50(2): 390-406, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38426704

RESUMEN

Research has shown that children of undocumented Latinx parents in the United States are at greater risk for negative long-term effects on their mental health and overall well-being. Chief among these concerns are the negative effects of disrupted attachment processes, as deported parents are often taken from their families by force and required to parent from afar, if they can continue parenting at all. Despite the ubiquity of deported families, little is known about the effects of deportation on the attachment of left-behind children and the subsequent potential disruptive effect of deportation on their adult relationships. This phenomenological study aims to understand how adults who have experienced parental deportation in their childhood describe the effects of that event on their adult intimate relationships. Themes of (1) ambiguous loss; (2) inability to trust others; (3) fear of separation from loved ones; and (4) shame emerged and are discussed considering existing literature on attachment theory, immigration, and the Latinx population. Treatment implications are also discussed.


Asunto(s)
Deportación , Emigración e Inmigración , Adulto , Niño , Humanos , Estados Unidos , Padres/psicología , Responsabilidad Parental , Salud Mental
5.
J Vasc Surg Cases Innov Tech ; 10(1): 101381, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38130366

RESUMEN

Objective: Duplex ultrasound (US) of the lower extremities is commonly used to assess patients with lower extremity atherosclerosis. Arterial calcification can often be visualized in these images; however, efforts to quantify its extent have been limited. We, thus, sought to develop a new scoring system to measure calcification on duplex US studies of the femoral artery and correlate it with standard computed tomography (CT)-based methods. We then made preliminary attempts to correlate US-based femoral artery calcification scores with limb-specific outcomes in patients with peripheral arterial disease. Methods: Patients who underwent CT evaluation of the lower extremities and arterial duplex US of either lower extremity within 6 months of each examination were included in the study. CT-based calcium scores of the femoral artery were generated using calcium scoring software. To determine the US score, five standard arterial segments (ie, common femoral artery, proximal superficial femoral artery [SFA], mid-SFA, distal SFA, and above the knee popliteal artery) were scored using a scale of 0 to 2 (0, a completely normal vessel segment; 1, a vessel with hyperechoic irregularities of the vessel wall; and 2, clear anechoic shadowing). The available scores were then averaged to yield a single femoral calcium score for each leg. Predictors of femoral calcification scores were then assessed and compared with the CT-based methods. The correlation between the US- and CT-based femoral calcification was assessed, and then the association between the US-based femoral calcification score and limb outcomes was evaluated. Results: A total of 113 patients met the inclusion criteria and were included in the final analysis. US-based calcification scores were increased in patients with diabetes, renal failure, and the presence of chronic limb threatening ischemia similar to CT-based femoral calcification. The US- and CT-based calcification scores showed a moderate to strong correlation (r = 0.64). An elevated US-based femoral artery calcification score was associated with decreased amputation-free survival. Conclusions: A novel US-based method shows promise as a simple method for quantifying the extent of femoral artery calcification in patients with peripheral arterial disease. The US-based method correlates with standard CT-based methods. Preliminary studies show that it could be useful for predicating outcomes for patients with peripheral arterial disease.

6.
Proc Natl Acad Sci U S A ; 120(46): e2219547120, 2023 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-37903246

RESUMEN

The Hunga Tonga-Hunga Ha'apai (HT-HH) volcanic eruptions on January 13 and 15, 2022, produced a plume with the highest signal in stratospheric aerosol optical depth observed since the eruption of Mt. Pinatubo in 1991. Suites of balloon-borne instruments on a series of launches from Réunion Island intercepted the HT-HH plume between 7 and 10 d of the eruptions, yielding observations of the aerosol number and size distribution and sulfur dioxide (SO2) and water vapor (H2O) concentrations. The measurements reveal an unexpected abundance of large particles in the plume, constrain the total sulfur injected to approximately 0.2 Tg, provide information on the altitude of the injection, and indicate that the formation of sulfuric acid aerosol was complete within 3 wk. Large H2O enhancements contributed as much as ~30% to ambient aerosol surface area and likely accelerated SO2 oxidation and aerosol formation rates in the plume to approximately three times faster than under normal stratospheric conditions.

7.
Science ; 382(6668): eadg2551, 2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37856589

RESUMEN

The eruption of the Hunga Tonga-Hunga Ha'apai volcano on 15 January 2022 offered a good opportunity to explore the early impacts of tropical volcanic eruptions on stratospheric composition. Balloon-borne observations near Réunion Island revealed the unprecedented amount of water vapor injected by the volcano. The enhanced stratospheric humidity, radiative cooling, and expanded aerosol surface area in the volcanic plume created the ideal conditions for swift ozone depletion of 5% in the tropical stratosphere in just 1 week. The decrease in hydrogen chloride by 0.4 parts per million by volume (ppbv) and the increase in chlorine monoxide by 0.4 ppbv provided compelling evidence for chlorine activation within the volcanic plume. This study enhances our understanding of the effect of this unusual volcanic eruption on stratospheric chemistry and provides insights into possible chemistry changes that may occur in a changing climate.

8.
bioRxiv ; 2023 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-37873416

RESUMEN

Understanding the factors that shape variation in the human microbiome is a major goal of research in biology. While other genomics fields have used large, pre-compiled compendia to extract systematic insights requiring otherwise impractical sample sizes, there has been no comparable resource for the 16S rRNA sequencing data commonly used to quantify microbiome composition. To help close this gap, we have assembled a set of 168,484 publicly available human gut microbiome samples, processed with a single pipeline and combined into the largest unified microbiome dataset to date. We use this resource, which is freely available at microbiomap.org, to shed light on global variation in the human gut microbiome. We find that Firmicutes, particularly Bacilli and Clostridia, are almost universally present in the human gut. At the same time, the relative abundance of the 65 most common microbial genera differ between at least two world regions. We also show that gut microbiomes in undersampled world regions, such as Central and Southern Asia, differ significantly from the more thoroughly characterized microbiomes of Europe and Northern America. Moreover, humans in these overlooked regions likely harbor hundreds of taxa that have not yet been discovered due to this undersampling, highlighting the need for diversity in microbiome studies. We anticipate that this new compendium can serve the community and enable advanced applied and methodological research.

9.
bioRxiv ; 2023 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-37745420

RESUMEN

Rare diseases and conditions create unique challenges for genetic epidemiologists precisely because cases and samples are scarce. In recent years, whole-genome and whole-transcriptome sequencing (WGS/WTS) have eased the study of rare genetic variants. Paired WGS and WTS data are ideal, but logistical and financial constraints often preclude generating paired WGS and WTS data. Thus, many databases contain a patchwork of specimens with either WGS or WTS data, but only a minority of samples have both. The NCI Genomic Data Commons facilitates controlled access to genomic and transcriptomic data for thousands of subjects, many with unpaired sequencing results. Local reanalysis of expressed variants across whole transcriptomes requires significant data storage, compute, and expertise. We developed the bamSliceR package to facilitate swift transition from aligned sequence reads to expressed variant characterization. bamSliceR leverages the NCI Genomic Data Commons API to query genomic sub-regions of aligned sequence reads from specimens identified through the robust Bioconductor ecosystem. We demonstrate how population-scale targeted genomic analysis can be completed using orders of magnitude fewer resources in this fashion, with minimal compute burden. We demonstrate pilot results from bamSliceR for the TARGET pediatric AML and BEAT-AML projects, where identification of rare but recurrent somatic variants directly yields biologically testable hypotheses. bamSliceR and its documentation are freely available on GitHub at https://github.com/trichelab/bamSliceR.

10.
Nat Biotechnol ; 2023 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-37697152

RESUMEN

The literature of human and other host-associated microbiome studies is expanding rapidly, but systematic comparisons among published results of host-associated microbiome signatures of differential abundance remain difficult. We present BugSigDB, a community-editable database of manually curated microbial signatures from published differential abundance studies accompanied by information on study geography, health outcomes, host body site and experimental, epidemiological and statistical methods using controlled vocabulary. The initial release of the database contains >2,500 manually curated signatures from >600 published studies on three host species, enabling high-throughput analysis of signature similarity, taxon enrichment, co-occurrence and coexclusion and consensus signatures. These data allow assessment of microbiome differential abundance within and across experimental conditions, environments or body sites. Database-wide analysis reveals experimental conditions with the highest level of consistency in signatures reported by independent studies and identifies commonalities among disease-associated signatures, including frequent introgression of oral pathobionts into the gut.

11.
ACS Appl Mater Interfaces ; 15(38): 44711-44721, 2023 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-37715711

RESUMEN

Dual-emission fluorescence probes that provide high sensitivity are key for biomedical diagnostic applications. Nontoxic carbon dots (CDs) are an emerging alternative to traditional fluorescent probes; however, robust and reproducible synthetic strategies are still needed to access materials with controlled emission profiles and improved fluorescence quantum yields (FQYs). Herein, we report a practical and general synthetic strategy to access dual-emission CDs with FQYs as high as 0.67 and green/blue, yellow/blue, or red/blue excitation-dependent emission profiles using common starting materials such as citric acid, cysteine, and co-dopants to bias the synthetic pathway. Structural and physicochemical analysis using nuclear magnetic resonance, absorbance and fluorescence spectroscopy, Fourier-transform infrared spectroscopy, and X-ray photoelectron spectroscopy in addition to transmission electron and atomic force microscopy (TEM and AFM) is used to elucidate the material's composition which is responsible for the unique observed photoluminescence properties. Moreover, the utility of the probes is demonstrated in the clinical setting by the synthesis of green/blue emitting antibody-CD conjugates which are used for the immunohistochemical staining of human brain tissues of glioblastoma patients, showing detection under two different emission channels.


Asunto(s)
Puntos Cuánticos , Humanos , Puntos Cuánticos/química , Carbono/química , Espectroscopía de Fotoelectrones , Colorantes Fluorescentes/química , Espectroscopía Infrarroja por Transformada de Fourier
12.
J Funct Biomater ; 14(8)2023 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-37623638

RESUMEN

One of the most ambitious goals for bone implants is to improve bioactivity, incapability, and mechanical properties; to reduce the need for further surgery; and increase efficiency. Hydroxyapatite (HA), the main inorganic component of bones and teeth, has high biocompatibility but is weak and brittle material. Cortical bone is composed of 70% calcium phosphate (CaP) and 30% collagen and forms a complex hierarchical structure with anisotropic and lamellar microstructure (osteons) which makes bone a light, strong, tough, and durable material that can support large loads. However, imitation of concentric lamellar structure of osteons is difficult to achieve in fabrication. Nacre from mollusk shells with layered structures has now become the archetype of the natural "model" for bio-inspired materials. Incorporating a nacre-like layered structure into bone implants can enhance their mechanical strength, toughness, and durability, reducing the risk of implant catastrophic failure or fracture. The layered structure of nacre-like HA/polymer composites possess high strength, toughness, and tunable stiffness which matches that of bone. The nacre-like HA/polymer composites should also possess excellent biocompatibility and bioactivity which facilitate the bonding of the implant with the surrounding bone, leading to improved implant stability and long-term success. To achieve this, a bi-directional freeze-casting technique was used to produce elongated lamellar HA were further densified and infiltrated with polymer to produce nacre-like HA/polymer composites with high strength and fracture toughness. Mechanical characterization shows that increasing the ceramic fractions in the composite increases the density of the mineral bridges, resulting in higher flexural and compressive strength. The nacre-like HA/(methyl methacrylate (MMA) + 5 wt.% acrylic acid (AA)) composites with a ceramic fraction of 80 vol.% showed a flexural strength of 158 ± 7.02 MPa and a Young's modulus of 24 ± 4.34 GPa, compared with 130 ± 5.82 MPa and 19.75 ± 2.38 GPa, in the composite of HA/PMMA, due to the higher strength of the polymer and the interface of the composite. The fracture toughness in the composition of 5 wt.% PAA to PMMA improves from 3.023 ± 0.98 MPa·m1/2 to 5.27 ± 1.033 MPa·m1/2 by increasing the ceramic fraction from 70 vol.% to 80 vol.%, respectively.

13.
Nat Geosci ; 16(7): 577-583, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37441270

RESUMEN

Future increases in stratospheric water vapour risk amplifying climate change and slowing down the recovery of the ozone layer. However, state-of-the-art climate models strongly disagree on the magnitude of these increases under global warming. Uncertainty primarily arises from the complex processes leading to dehydration of air during its tropical ascent into the stratosphere. Here we derive an observational constraint on this longstanding uncertainty. We use a statistical-learning approach to infer historical co-variations between the atmospheric temperature structure and tropical lower stratospheric water vapour concentrations. For climate models, we demonstrate that these historically constrained relationships are highly predictive of the water vapour response to increased atmospheric carbon dioxide. We obtain an observationally constrained range for stratospheric water vapour changes per degree of global warming of 0.31 ± 0.39 ppmv K-1. Across 61 climate models, we find that a large fraction of future model projections are inconsistent with observational evidence. In particular, frequently projected strong increases (>1 ppmv K-1) are highly unlikely. Our constraint represents a 50% decrease in the 95th percentile of the climate model uncertainty distribution, which has implications for surface warming, ozone recovery and the tropospheric circulation response under climate change.

14.
Fam Process ; 62(4): 1459-1477, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37312637

RESUMEN

Through the application of a discovery-oriented task analysis, this research delineated specific therapist behaviors that resulted in a successful caregiver openness event in emotionally focused family therapy (EFFT). EFFT experts were recruited via email and asked to submit family therapy recordings where they believed a caregiver openness event occurred. Ten family therapy recordings were submitted by three experts. Within these recordings, 12 caregiver openness events were discovered and critically analyzed. Nine themes were identified and interventions therapists applied to accomplish these themes were delineated using the emotionally focused therapy-coding scheme (EFT-CS). These themes included: (1) validating and reframing the child's protected stance, (2) processing the impact of the child's unmet attachment longings, (3) validating the caregiver's blocked relational stance, (4) expanding caregiving intentions, (5) enacting the caregiver's intentions to meet the child's attachment longings, (6) processing the enactment, (7) processing and promoting caregiver accessibility to the child's response, (8) heightening the caregiver's accessible stance, and (9) enhancing shifting family dynamics. Additional findings, implications for clinical practice, training, and future research are discussed.


Asunto(s)
Cuidadores , Terapia Centrada en la Emoción , Niño , Humanos , Cuidadores/psicología , Terapia Familiar , Relaciones Familiares
15.
ANZ J Surg ; 93(10): 2297-2302, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37296520

RESUMEN

BACKGROUND: Emergency general surgery (EGS) patients have an increased risk of mortality and morbidity compared to other surgical patients. Limited risk assessment tools exist for use in both operative and non-operative EGS patients. We assessed the accuracy of a modified Emergency Surgical Acuity Score (mESAS) in EGS patients at our institution. METHODS: A retrospective cohort study from an acute surgical unit at a tertiary referral hospital was performed. Primary endpoints assessed included death before discharge, length of stay (LOS) >5 days and unplanned readmission within 28 days. Operative and non-operative patients were analysed separately. Validation was performed using the area under the receiver operating characteristic (AUROC), Brier score and Hosmer-Lemeshow test. RESULTS: A total of 1763 admissions between March 2018 and June 2021 were included for analysis. The mESAS was an accurate predictor of both death before discharge (AUROC 0.979, Brier score 0.007, Hosmer-Lemeshow P = 0.981) and LOS >5 days (0.787, 0.104, and 0.253, respectively). The mESAS was less accurate in predicting readmission within 28 days (0.639, 0.040, and 0.887, respectively). The mESAS retained its predictive ability for death before discharge and LOS >5 days in the split cohort analysis. CONCLUSION: This study is the first to validate a modified ESAS in a non-operatively managed EGS population internationally and the first to validate the mESAS in Australia. The mESAS accurately predicts death before discharge and prolonged LOS for all EGS patients, providing a highly useful tool for surgeons and EGS units worldwide.


Asunto(s)
Hospitalización , Procedimientos Quirúrgicos Operativos , Humanos , Estudios Retrospectivos , Tiempo de Internación , Readmisión del Paciente , Medición de Riesgo , Morbilidad , Complicaciones Posoperatorias/etiología
16.
Arthrosc Tech ; 11(9): e1547-e1550, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36185124

RESUMEN

A bony Bankart lesion is an avulsion of the labroligamentous complex associated with an anterior glenoid rim fracture. Bony Bankart lesions can be seen in up to 70% of traumatic shoulder dislocations. With such a high prevalence, the development of an optimal repair technique is important. Selection of the most appropriate repair method depends heavily on the individual hard- and soft-tissue characteristics of the presenting lesion, as well as surgeon experience with the various repair options. We describe 3 arthroscopic Bankart fixation techniques (labrum alone, transosseous, and double row) to address a range of presenting Bankart pathologies.

17.
Microbiology (Reading) ; 168(8)2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35920810

RESUMEN

Neisseria gonorrhoeae, the causative agent of gonorrhoea, is a major burden on global healthcare systems, with an estimated ~80-90 million new global cases annually. This burden is exacerbated by increasing levels of antimicrobial resistance, which has greatly limited viable antimicrobial therapies. Decreasing gonococcal drug susceptibility has been driven largely by accumulation of chromosomal resistance determinants, which can be acquired through natural transformation, whereby DNA in the extracellular milieu is imported into cells and incorporated into the genome by homologous recombination. N. gonorrhoeae possesses a specialized system for DNA uptake, which strongly biases transformation in favour of DNA from closely related bacteria by recognizing a 10-12 bp DNA uptake sequence (DUS) motif, which is highly overrepresented in their chromosomal DNA. This process relies on numerous proteins, including the DUS-specific receptor ComP, which assemble retractile protein filaments termed type IV pili (T4P) extending from the cell surface, and one model for neisserial DNA uptake proposes that these filaments bind DNA in a DUS-dependent manner before retracting to transport DNA into the periplasm. However, conflicting evidence indicates that elongated pilus filaments may not have such a direct role in DNA binding uptake as this model suggests. Here, we quantitatively measured DNA binding to gonococcal T4P fibres by directly visualizing binding complexes with confocal fluorescence microscopy in order to confirm the sequence-specific, comP-dependent DNA binding capacity of elongated T4P fibres. This supports the idea that pilus filaments could be responsible for initially capturing DNA in the first step of sequence-specific DNA uptake.


Asunto(s)
Gonorrea , Transformación Bacteriana , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , ADN Bacteriano/genética , ADN Bacteriano/metabolismo , Proteínas Fimbrias/genética , Proteínas Fimbrias/metabolismo , Fimbrias Bacterianas/genética , Fimbrias Bacterianas/metabolismo , Gonorrea/metabolismo , Humanos , Neisseria gonorrhoeae/genética , Neisseria gonorrhoeae/metabolismo
18.
Front Cell Infect Microbiol ; 12: 920447, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35873173

RESUMEN

The rapid spread of antimicrobial resistant Neisseria gonorrhoeae continues to pose a serious threat to global health. To successfully treat and control gonococcal infections, rapid diagnosis is critical. Currently, nucleic acid amplification tests are the recommended diagnostic, however, these are both technically demanding and time consuming, making them unsuitable for resource-poor clinics. Consequently, there is a substantial need for an affordable, point-of-care diagnostic to use in these settings. In this study, DNA-functionalised gold nanoparticles (gold nanoprobes), with the ability to specifically detect the DNA Uptake Sequence (DUS) of Neisseria gonorrhoeae, were prepared. Using complementary annealing, the gold nanoprobes were shown to hybridise to genomic gonococcal DNA, causing a significant shift in their salt stability. By exploiting the shift in nanoprobe stability under the presence of target DNA, a solution-based colorimetric diagnostic for gonococcal DNA was prepared. Detection of purified genomic DNA was achieved in under 30 minutes, with a detection limit of 15.0 ng. Significantly, testing with DNA extracted from an off-target control organism suggested specificity for Neisseria. These results highlight the potential of DUS-specific gold nanoprobes in the rapid point-of-care diagnosis of gonococcal infections.


Asunto(s)
Gonorrea , Nanopartículas del Metal , Antibacterianos/farmacología , ADN , Farmacorresistencia Bacteriana , Genómica , Oro , Gonorrea/diagnóstico , Humanos , Pruebas de Sensibilidad Microbiana , Neisseria gonorrhoeae/genética
19.
Nat Commun ; 13(1): 3695, 2022 06 27.
Artículo en Inglés | MEDLINE | ID: mdl-35760813

RESUMEN

Millions of transcriptomic profiles have been deposited in public archives, yet remain underused for the interpretation of new experiments. We present a method for interpreting new transcriptomic datasets through instant comparison to public datasets without high-performance computing requirements. We apply Principal Component Analysis on 536 studies comprising 44,890 human RNA sequencing profiles and aggregate sufficiently similar loading vectors to form Replicable Axes of Variation (RAV). RAVs are annotated with metadata of originating studies and by gene set enrichment analysis. Functionality to associate new datasets with RAVs, extract interpretable annotations, and provide intuitive visualization are implemented as the GenomicSuperSignature R/Bioconductor package. We demonstrate the efficient and coherent database search, robustness to batch effects and heterogeneous training data, and transfer learning capacity of our method using TCGA and rare diseases datasets. GenomicSuperSignature aids in analyzing new gene expression data in the context of existing databases using minimal computing resources.


Asunto(s)
Bases de Datos Genéticas , Programas Informáticos , Humanos , RNA-Seq , Transcriptoma/genética
20.
ANZ J Surg ; 92(10): 2511-2516, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35437895

RESUMEN

BACKGROUND: Several recent reports have identified significant variations in discharge practices following umbilical hernia repair (UHR). The primary aim of this paper is to determine Australian UHR same day discharge (SDD) rates over the past two decades. Secondary aims are to analyse factors which may contribute to variation in discharge practices, compare Australian UHR SDD rates internationally and determine LOS trends. METHODS: A retrospective, population-based cohort study was conducted using de-identified data from the Australian Institute of Health and Welfare (1 July 1998 to 30 June 2019). SDD rates and LOS were calculated for age, gender and complexity. Negative binomial models were used to investigate associations between characteristics. RESULTS: The overall mean UHR SDD rate was 41.2% with a modest improvement over the study period (36.5% to 44.4%, P < 0.0001). The mean LOS was 3.4 days, and this decreased over the study period (P = 0.01). Males had a higher rate of SDD (42.1% vs. 39.4%, P < 0.0001) and shorter LOS (3.0 vs. 3.7 days, P < 0.0001) compared with females. Increased age was associated with decreased SDD (P < 0.0001) and increased LOS (P < 0.0001). Australia's SDD rate was lower than in both New Zealand and the United Kingdom. CONCLUSION: While SDD and LOS following UHR improved across the study period, SDD rates remain below the RACS recommendation and compare unfavourably internationally. Advancing age and female gender were associated with decreased SDD and increased LOS demonstrating potential areas for improvement. Multiple strategies are discussed to address the persistently low rates of SDD after UHR.


Asunto(s)
Hernia Umbilical , Australia/epidemiología , Estudios de Cohortes , Femenino , Hernia Umbilical/cirugía , Humanos , Tiempo de Internación , Masculino , Alta del Paciente , Estudios Retrospectivos , Resultado del Tratamiento
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