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1.
Nat Immunol ; 25(8): 1411-1421, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38997431

RESUMO

A subset of individuals exposed to Mycobacterium tuberculosis (Mtb) that we refer to as 'resisters' (RSTR) show evidence of IFN-γ- T cell responses to Mtb-specific antigens despite serially negative results on clinical testing. Here we found that Mtb-specific T cells in RSTR were clonally expanded, confirming the priming of adaptive immune responses following Mtb exposure. RSTR CD4+ T cells showed enrichment of TH17 and regulatory T cell-like functional programs compared to Mtb-specific T cells from individuals with latent Mtb infection. Using public datasets, we showed that these TH17 cell-like functional programs were associated with lack of progression to active tuberculosis among South African adolescents with latent Mtb infection and with bacterial control in nonhuman primates. Our findings suggested that RSTR may successfully control Mtb following exposure and immune priming and established a set of T cell biomarkers to facilitate further study of this clinical phenotype.


Assuntos
Linfócitos T CD4-Positivos , Mycobacterium tuberculosis , Tuberculose , Mycobacterium tuberculosis/imunologia , Humanos , Animais , Adolescente , Tuberculose/imunologia , Tuberculose/microbiologia , Linfócitos T CD4-Positivos/imunologia , Células Th17/imunologia , Feminino , Macaca mulatta , Masculino , Fenótipo , Interferon gama/metabolismo , Interferon gama/imunologia , Antígenos de Bactérias/imunologia , Tuberculose Latente/imunologia , Tuberculose Latente/microbiologia , África do Sul , Adulto Jovem , Linfócitos T Reguladores/imunologia , Adulto
2.
Cell ; 177(2): 478-491.e20, 2019 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-30929901

RESUMO

Genomic studies have identified hundreds of candidate genes near loci associated with risk for schizophrenia. To define candidates and their functions, we mutated zebrafish orthologs of 132 human schizophrenia-associated genes. We created a phenotype atlas consisting of whole-brain activity maps, brain structural differences, and profiles of behavioral abnormalities. Phenotypes were diverse but specific, including altered forebrain development and decreased prepulse inhibition. Exploration of these datasets identified promising candidates in more than 10 gene-rich regions, including the magnesium transporter cnnm2 and the translational repressor gigyf2, and revealed shared anatomical sites of activity differences, including the pallium, hypothalamus, and tectum. Single-cell RNA sequencing uncovered an essential role for the understudied transcription factor znf536 in the development of forebrain neurons implicated in social behavior and stress. This phenotypic landscape of schizophrenia-associated genes prioritizes more than 30 candidates for further study and provides hypotheses to bridge the divide between genetic association and biological mechanism.


Assuntos
Esquizofrenia/genética , Esquizofrenia/fisiopatologia , Animais , Encéfalo , Córtex Cerebral , Modelos Animais de Doenças , Regulação da Expressão Gênica/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Peixe-Zebra/genética
4.
PLoS Biol ; 22(7): e3002658, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38991106

RESUMO

Tetrapods (amphibians, reptiles, birds, and mammals) are model systems for global biodiversity science, but continuing data gaps, limited data standardisation, and ongoing flux in taxonomic nomenclature constrain integrative research on this group and potentially cause biased inference. We combined and harmonised taxonomic, spatial, phylogenetic, and attribute data with phylogeny-based multiple imputation to provide a comprehensive data resource (TetrapodTraits 1.0.0) that includes values, predictions, and sources for body size, activity time, micro- and macrohabitat, ecosystem, threat status, biogeography, insularity, environmental preferences, and human influence, for all 33,281 tetrapod species covered in recent fully sampled phylogenies. We assess gaps and biases across taxa and space, finding that shared data missing in attribute values increased with taxon-level completeness and richness across clades. Prediction of missing attribute values using multiple imputation revealed substantial changes in estimated macroecological patterns. These results highlight biases incurred by nonrandom missingness and strategies to best address them. While there is an obvious need for further data collection and updates, our phylogeny-informed database of tetrapod traits can support a more comprehensive representation of tetrapod species and their attributes in ecology, evolution, and conservation research.


Assuntos
Biodiversidade , Aves , Mamíferos , Filogenia , Répteis , Animais , Répteis/classificação , Anfíbios , Ecossistema , Viés , Humanos , Tamanho Corporal
5.
EMBO Rep ; 25(3): 1570-1588, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38263329

RESUMO

5'-end modifications play key roles in determining RNA fates. Phospho-methylation is a noncanonical cap occurring on either 5'-PPP or 5'-P ends. We used ChemRAP, in which affinity purification of cellular proteins with chemically synthesized modified RNAs is coupled to quantitative proteomics, to identify 5'-Pme "readers". We show that 5'-Pme is directly recognized by EPRS, the central subunit of the multisynthetase complex (MSC), through its linker domain, which has previously been involved in key noncanonical EPRS and MSC functions. We further determine that the 5'-Pme writer BCDIN3D regulates the binding of EPRS to specific mRNAs, either at coding regions rich in MSC codons, or around start codons. In the case of LRPPRC (leucine-rich pentatricopeptide repeat containing), a nuclear-encoded mitochondrial protein associated with the French Canadian Leigh syndrome, BCDIN3D deficiency abolishes binding of EPRS around its mRNA start codon, increases its translation but ultimately results in LRPPRC mislocalization. Overall, our results suggest that BCDIN3D may regulate the translation of specific mRNA via RNA-5'-Pme.


Assuntos
Proteínas de Neoplasias , Biossíntese de Proteínas , Proteínas de Neoplasias/genética , Canadá , Metilação , RNA Mensageiro/genética , RNA/metabolismo
6.
Proc Natl Acad Sci U S A ; 120(11): e2208120120, 2023 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-36877837

RESUMO

Increasing fire severity and warmer, drier postfire conditions are making forests in the western United States (West) vulnerable to ecological transformation. Yet, the relative importance of and interactions between these drivers of forest change remain unresolved, particularly over upcoming decades. Here, we assess how the interactive impacts of changing climate and wildfire activity influenced conifer regeneration after 334 wildfires, using a dataset of postfire conifer regeneration from 10,230 field plots. Our findings highlight declining regeneration capacity across the West over the past four decades for the eight dominant conifer species studied. Postfire regeneration is sensitive to high-severity fire, which limits seed availability, and postfire climate, which influences seedling establishment. In the near-term, projected differences in recruitment probability between low- and high-severity fire scenarios were larger than projected climate change impacts for most species, suggesting that reductions in fire severity, and resultant impacts on seed availability, could partially offset expected climate-driven declines in postfire regeneration. Across 40 to 42% of the study area, we project postfire conifer regeneration to be likely following low-severity but not high-severity fire under future climate scenarios (2031 to 2050). However, increasingly warm, dry climate conditions are projected to eventually outweigh the influence of fire severity and seed availability. The percent of the study area considered unlikely to experience conifer regeneration, regardless of fire severity, increased from 5% in 1981 to 2000 to 26 to 31% by mid-century, highlighting a limited time window over which management actions that reduce fire severity may effectively support postfire conifer regeneration.


Assuntos
Incêndios , Traqueófitas , Incêndios Florestais , Clima , Mudança Climática
7.
PLoS Comput Biol ; 20(2): e1011870, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38335225

RESUMO

Chloroplasts are photosynthetic organelles in algal and plant cells that contain their own genome. Chloroplast genomes are commonly used in evolutionary studies and taxonomic identification and are increasingly becoming a target for crop improvement studies. As DNA sequencing becomes more affordable, researchers are collecting vast swathes of high-quality whole-genome sequence data from laboratory and field settings alike. Whole tissue read libraries sequenced with the primary goal of understanding the nuclear genome will inadvertently contain many reads derived from the chloroplast genome. These whole-genome, whole-tissue read libraries can additionally be used to assemble chloroplast genomes with little to no extra cost. While several tools exist that make use of short-read second generation and third-generation long-read sequencing data for chloroplast genome assembly, these tools may have complex installation steps, inadequate error reporting, poor expandability, and/or lack scalability. Here, we present CLAW (Chloroplast Long-read Assembly Workflow), an easy to install, customise, and use Snakemake tool to assemble chloroplast genomes from chloroplast long-reads found in whole-genome read libraries (https://github.com/aaronphillips7493/CLAW). Using 19 publicly available reference chloroplast genome assemblies and long-read libraries from algal, monocot and eudicot species, we show that CLAW can rapidly produce chloroplast genome assemblies with high similarity to the reference assemblies. CLAW was designed such that users have complete control over parameterisation, allowing individuals to optimise CLAW to their specific use cases. We expect that CLAW will provide researchers (with varying levels of bioinformatics expertise) with an additional resource useful for contributing to the growing number of publicly available chloroplast genome assemblies.


Assuntos
Genoma de Cloroplastos , Humanos , Genoma de Cloroplastos/genética , Fluxo de Trabalho , Análise de Sequência de DNA , Biologia Computacional , Cloroplastos/genética , Sequenciamento de Nucleotídeos em Larga Escala
8.
Ann Surg ; 279(3): 528-535, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37264925

RESUMO

OBJECTIVE: The purpose of this study was to describe management and outcomes from a contemporary cohort of children with Wilms tumor complicated by inferior vena caval thrombus. BACKGROUND: The largest series of these patients was published almost 2 decades ago. Since then, neoadjuvant chemotherapy has been commonly used to manage these patients, and outcomes have not been reported. METHODS: Retrospective review of 19 North American centers between 2009 and 2019. Patient and disease characteristics, management, and outcomes were investigated and analyzed. RESULTS: Of 124 patients, 81% had favorable histology (FH), and 52% were stage IV. IVC thrombus level was infrahepatic in 53 (43%), intrahepatic in 32 (26%), suprahepatic in 14 (11%), and cardiac in 24 (19%). Neoadjuvant chemotherapy using a 3-drug regimen was administered in 82% and postresection radiation in 90%. Thrombus level regression was 45% overall, with suprahepatic level showing the best response (62%). Cardiopulmonary bypass (CPB) was potentially avoided in 67%. The perioperative complication rate was significantly lower after neoadjuvant chemotherapy [(25%) vs upfront surgery (55%); P =0.005]. CPB was not associated with higher complications [CPB (50%) vs no CPB (27%); P =0.08]. Two-year event-free survival was 93% and overall survival was 96%, higher in FH cases (FH 98% vs unfavorable histology/anaplastic 82%; P =0.73). Neither incomplete resection nor viable thrombus cells affected event-free survival or overall survival. CONCLUSIONS: Multimodal therapy resulted in excellent outcomes, even with advanced-stage disease and cardiac extension. Neoadjuvant chemotherapy decreased the need for CPB to facilitate resection. Complete thrombectomy may not always be necessary.


Assuntos
Neoplasias Renais , Oncologia Cirúrgica , Trombose Venosa , Tumor de Wilms , Humanos , Criança , Neoplasias Renais/cirurgia , Veia Cava Inferior/cirurgia , Tumor de Wilms/cirurgia , Tumor de Wilms/tratamento farmacológico , Trombose Venosa/patologia , Trombectomia/métodos , Estudos Retrospectivos , Nefrectomia/métodos
9.
Am J Physiol Heart Circ Physiol ; 327(4): H947-H955, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39178028

RESUMO

Exaggerated blood pressure (BP) responses during exercise are independently associated with future development of hypertension. Partial sleep deprivation (PSD) can increase 24-h ambulatory BP, but the effects on exercise BP are unclear. We hypothesized that acute PSD would augment the BP response to constant load cycling exercise and a 20-min time trial. Twenty-two healthy adults (22 ± 3 yr old; 13 males; V̇o2peak, 43.6 ± 8.2 mL·kg-1·min-1) completed a randomized crossover trial in which they either slept normally (normal sleep-wake schedule for each participant) or sleep was partially deprived (early awakening, 40% of normal sleep duration). Each participant completed a 12-min warm-up consisting of two 6-min steps (step 1, 62 ± 25 W; step 2, 137 ± 60 W) followed by a 20-min time trial on a cycle ergometer. PSD did not alter power output during the 20-min time trial [(control vs. PSD) 170 ± 68 vs. 168 ± 68 W, P = 0.65]. Systolic BP did not differ during step 1 of the warm-up (141 ± 15 vs. 137 ± 12 mmHg, P = 0.39) but was lower following PSD during step 2 (165 ± 21 vs. 159 ± 22 mmHg, P = 0.004) and the 20-min time trial (171 ± 20 vs. 164 ± 23 mmHg, P < 0.001). These results were maintained when peak oxygen uptake (V̇o2peak) was included as a covariate. Systolic BP responses were modulated by sex (time × visit × sex interaction P = 0.03), with attenuated systolic BP during the warm-up and the 20-min time trial in males but not in females. In contrast to our hypothesis, acute PSD attenuates systolic BP responses during constant load and 20-min time trial cycling exercise; however, these observations appear to be primarily driven by changes in males.NEW & NOTEWORTHY A single night of partial sleep deprivation (PSD) can increase ambulatory blood pressure (BP) the following day. Despite this phenomenon, the present study found that acute PSD attenuates systolic BP responses to both constant load cycling and a 20-min cycling time trial in young healthy adults. Interestingly, the attenuated systolic BP responses following PSD appeared to be modulated by sex such that attenuations were observed in males but not in females.


Assuntos
Ciclismo , Pressão Sanguínea , Estudos Cross-Over , Exercício Físico , Privação do Sono , Humanos , Masculino , Privação do Sono/fisiopatologia , Feminino , Adulto Jovem , Adulto , Fatores de Tempo , Sono , Consumo de Oxigênio
10.
Radiology ; 311(2): e230750, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38713024

RESUMO

Background Multiparametric MRI (mpMRI) improves prostate cancer (PCa) detection compared with systematic biopsy, but its interpretation is prone to interreader variation, which results in performance inconsistency. Artificial intelligence (AI) models can assist in mpMRI interpretation, but large training data sets and extensive model testing are required. Purpose To evaluate a biparametric MRI AI algorithm for intraprostatic lesion detection and segmentation and to compare its performance with radiologist readings and biopsy results. Materials and Methods This secondary analysis of a prospective registry included consecutive patients with suspected or known PCa who underwent mpMRI, US-guided systematic biopsy, or combined systematic and MRI/US fusion-guided biopsy between April 2019 and September 2022. All lesions were prospectively evaluated using Prostate Imaging Reporting and Data System version 2.1. The lesion- and participant-level performance of a previously developed cascaded deep learning algorithm was compared with histopathologic outcomes and radiologist readings using sensitivity, positive predictive value (PPV), and Dice similarity coefficient (DSC). Results A total of 658 male participants (median age, 67 years [IQR, 61-71 years]) with 1029 MRI-visible lesions were included. At histopathologic analysis, 45% (294 of 658) of participants had lesions of International Society of Urological Pathology (ISUP) grade group (GG) 2 or higher. The algorithm identified 96% (282 of 294; 95% CI: 94%, 98%) of all participants with clinically significant PCa, whereas the radiologist identified 98% (287 of 294; 95% CI: 96%, 99%; P = .23). The algorithm identified 84% (103 of 122), 96% (152 of 159), 96% (47 of 49), 95% (38 of 40), and 98% (45 of 46) of participants with ISUP GG 1, 2, 3, 4, and 5 lesions, respectively. In the lesion-level analysis using radiologist ground truth, the detection sensitivity was 55% (569 of 1029; 95% CI: 52%, 58%), and the PPV was 57% (535 of 934; 95% CI: 54%, 61%). The mean number of false-positive lesions per participant was 0.61 (range, 0-3). The lesion segmentation DSC was 0.29. Conclusion The AI algorithm detected cancer-suspicious lesions on biparametric MRI scans with a performance comparable to that of an experienced radiologist. Moreover, the algorithm reliably predicted clinically significant lesions at histopathologic examination. ClinicalTrials.gov Identifier: NCT03354416 © RSNA, 2024 Supplemental material is available for this article.


Assuntos
Aprendizado Profundo , Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Idoso , Estudos Prospectivos , Imageamento por Ressonância Magnética Multiparamétrica/métodos , Pessoa de Meia-Idade , Algoritmos , Próstata/diagnóstico por imagem , Próstata/patologia , Biópsia Guiada por Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos
11.
Mol Phylogenet Evol ; 201: 108197, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39270765

RESUMO

Phylogenomics has enriched our understanding that the Tree of Life can have network-like or reticulate structures among some taxa and genes. Two non-vertical modes of evolution - hybridization/introgression and horizontal gene transfer - deviate from a strictly bifurcating tree model, causing non-treelike patterns. However, these reticulate processes can produce similar patterns to incomplete lineage sorting or recombination, potentially leading to ambiguity. Here, we present a brief overview of a phylogenomic workflow for inferring organismal histories and compare methods for distinguishing modes of reticulate evolution. We discuss how the timing of coalescent events can help disentangle introgression from incomplete lineage sorting and how horizontal gene transfer events can help determine the relative timing of speciation events. In doing so, we identify pitfalls of certain methods and discuss how to extend their utility across the Tree of Life. Workflows, methods, and future directions discussed herein underscore the need to embrace reticulate evolutionary patterns for understanding the timing and rates of evolutionary events, providing a clearer view of life's history.

12.
Opt Lett ; 49(19): 5447-5450, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39352978

RESUMO

Symmetry breaking has been shown to reveal interesting phenomena in physical systems. A notable example is the fundamental work of Otto Stern and Walther Gerlach [Stern and Zerlach, Z. Physik9, 349 (1922)10.1007/BF01326983] nearly 100 years ago demonstrating a spin angular momentum (SAM) deflection that differed from classical theory. Here we use non-separable states of SAM and orbital angular momentum (OAM), known as vector vortex modes, to demonstrate how a classical optics analogy can be used to reveal this non-separability, reminiscent of the work carried out by Stern and Gerlach. We show that by implementing a polarization insensitive device to measure the OAM, the SAM states can be deflected to spatially resolved positions.

13.
Rapid Commun Mass Spectrom ; 38(14): e9744, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-38741576

RESUMO

RATIONALE: Knudsen effusion mass spectrometry (KEMS) has been a powerful tool in physical chemistry since 1954. There are many excellent reviews of the basic principles of KEMS in the literature. In this review, we focus on the current status and potential growth areas for this instrumental technique. METHODS: We discuss (1) instrumentation, (2) measurement techniques, and (3) selected novel applications of the technique. Improved heating methods and temperature measurement allow for better control of the Knudsen cell effusive source. Accurate computer models of the effusive beam and its introduction to the ionizer allow optimization of such parameters as sensitivity and removal of background signals. Computer models of the ionizer allow for optimized sensitivity and resolution. Additionally, data acquisition systems specifically tailored to a KEMS system permit improved quantity and quality of data. RESULTS: KEMS is traditionally utilized for thermodynamic measurements of pure compounds and solutions. These measurements can now be strengthened using first principles and model-based computational thermochemistry. First principles can be used to calculate accurate Gibbs energy functions (gefs) for improving third law calculations. Calculated enthalpies of formation and dissociation energies from ab initio methods can be compared to those measured using KEMS. For model-based thermochemistry, solution parameters can be derived from measured thermochemical data on metallic and nonmetallic solutions. Beyond thermodynamic measurements, KEMS has been used for many specific applications. We select examples for discussion: measurements of phase changes, measurement/control of low-oxygen potential systems, thermochemistry of ultrahigh-temperature ceramics, geological applications, nuclear applications, applications to organic and organometallic compounds, and thermochemistry of functional room temperature materials, such as lithium ion batteries. CONCLUSIONS: We present an overview of the current status of KEMS and discuss ideas for improving KEMS instrumentation and measurements. We discuss selected KEMS studies to illustrate future directions of KEMS.

14.
AJR Am J Roentgenol ; 222(1): e2329964, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37729551

RESUMO

BACKGROUND. Precise risk stratification through MRI/ultrasound (US) fusion-guided targeted biopsy (TBx) can guide optimal prostate cancer (PCa) management. OBJECTIVE. The purpose of this study was to compare PI-RADS version 2.0 (v2.0) and PI-RADS version 2.1 (v2.1) in terms of the rates of International Society of Urological Pathology (ISUP) grade group (GG) upgrade and downgrade from TBx to radical prostatectomy (RP). METHODS. This study entailed a retrospective post hoc analysis of patients who underwent 3-T prostate MRI at a single institution from May 2015 to March 2023 as part of three prospective clinical trials. Trial participants who underwent MRI followed by MRI/US fusion-guided TBx and RP within a 1-year interval were identified. A single genitourinary radiologist performed clinical interpretations of the MRI examinations using PI-RADS v2.0 from May 2015 to March 2019 and PI-RADS v2.1 from April 2019 to March 2023. Upgrade and downgrade rates from TBx to RP were compared using chi-square tests. Clinically significant cancer was defined as ISUP GG2 or greater. RESULTS. The final analysis included 308 patients (median age, 65 years; median PSA density, 0.16 ng/mL2). The v2.0 group (n = 177) and v2.1 group (n = 131) showed no significant difference in terms of upgrade rate (29% vs 22%, respectively; p = .15), downgrade rate (19% vs 21%, p = .76), clinically significant upgrade rate (14% vs 10%, p = .27), or clinically significant downgrade rate (1% vs 1%, p > .99). The upgrade rate and downgrade rate were also not significantly different between the v2.0 and v2.1 groups when stratifying by index lesion PI-RADS category or index lesion zone, as well as when assessed only in patients without a prior PCa diagnosis (all p > .01). Among patients with GG2 or GG3 at RP (n = 121 for v2.0; n = 103 for v2.1), the concordance rate between TBx and RP was not significantly different between the v2.0 and v2.1 groups (53% vs 57%, p = .51). CONCLUSION. Upgrade and downgrade rates from TBx to RP were not significantly different between patients whose MRI examinations were clinically interpreted using v2.0 or v2.1. CLINICAL IMPACT. Implementation of the most recent PI-RADS update did not improve the incongruence in PCa grade assessment between TBx and surgery.


Assuntos
Neoplasias da Próstata , Masculino , Humanos , Idoso , Neoplasias da Próstata/patologia , Imageamento por Ressonância Magnética/métodos , Próstata/patologia , Estudos Retrospectivos , Estudos Prospectivos , Biópsia , Prostatectomia/métodos , Biópsia Guiada por Imagem/métodos
15.
Environ Sci Technol ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39007544

RESUMO

A stylized macro-scale energy model of least-cost electricity systems relying only on wind and solar generation was used to assess the value of different storage technologies, individually and combined, for the contiguous U.S. as well as for four geographically diverse U.S. load-balancing regions. For the contiguous U.S. system, at current costs, when only one storage technology was deployed, hydrogen energy storage produced the lowest system costs, due to its energy-capacity costs being the lowest of all storage technologies modeled. Additional hypothetical storage technologies were more cost-competitive than hydrogen (long-duration storage) only at very low energy-capacity costs, but they were more cost-competitive than Li-ion batteries (short-duration storage) at relatively high energy- and power-capacity costs. In all load-balancing regions investigated, the least-cost systems that included long-duration storage had sufficient energy and power capacity to also meet short-duration energy and power storage needs, so that the addition of short-duration storage as a second storage technology did not markedly reduce total system costs. Thus, in electricity systems that rely on wind and solar generation, contingent on social and geographic constraints, long-duration storage may cost-effectively provide the services that would otherwise be provided by shorter-duration storage technologies.

16.
Macromol Rapid Commun ; : e2400460, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39047164

RESUMO

Catalyst-free, radical-based reactive processing is used to transform low-density polyethylene (LDPE) into polyethylene covalent adaptable networks (PE CANs) using a dialkylamino disulfide crosslinker, BiTEMPS methacrylate (BTMA). Two versions of BTMA are used, BTMA-S2, with nearly exclusively disulfide bridges, and BTMA-Sn, with a mixture of oligosulfide bridges, to produce S2 PE CAN and Sn PE CAN, respectively. The two PE CANs exhibit identical crosslink densities, but the S2 PE CAN manifests faster stress relaxation, with average relaxation times ∼4.5 times shorter than those of Sn PE CAN over a 130 to 160 °C temperature range. The more rapid dynamics of the S2 PE CAN translate into a shorter compression-molding reprocessing time at 160 °C of only 5 min (vs 30 min for the Sn PE CAN) to achieve full recovery of crosslink density. Both PE CANs are melt-extrudable and exhibit full recovery within experimental uncertainty of crosslink density after extrusion. Both PE CANs are self-healable, with a crack fully repaired and the original tensile properties restored after 30 min for the S2 PE CAN or 60 min for the Sn PE CAN at a temperature slightly above the LDPE melting point and without the assistance of external forces.

17.
J Pediatr Gastroenterol Nutr ; 78(1): 36-42, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38291694

RESUMO

OBJECTIVES: Inflammation on diagnostic rectal biopsy for children with suspected Hirschsprung disease (HSCR) is reported on pathology, and its significance is unknown. We describe the management and outcomes of a cohort with inflammation on rectal biopsy compared to those without. Specifically, to address the hypothesis that inflammation on diagnostic biopsy is associated with increased complication rates irrespective of intervention type and timing. METHODS: A single institution retrospective review of children with HSCR who underwent biopsy and endorectal pull-through (ERPT) from 2010 to 2020 was performed. The primary outcome was overall complications at 30-days following ERPT. Secondary outcomes included timing and type of operative intervention as well as postoperative enterocolitis diagnosed within 6-months of ERPT. RESULTS: Forty-nine children were identified; inflammation was present on diagnostic biopsy for 17 children. Those with inflammation were more likely to have clinical evidence of enterocolitis at the time of biopsy (p = 0.001) and were more likely to undergo leveling colostomy before ERPT (p = 0.01). Children with inflammation had a higher anastomotic leak rate (p = 0.04). Subgroup analysis of patients with inflammation undergoing primary ERPT versus leveling colostomy demonstrated no significant difference in outcomes following definitive ERPT. CONCLUSIONS: Our study suggests inflammation on diagnostic rectal biopsy for HSCR is associated with increased anastomotic leak rates. While additional prospective studies are indicated, attention to methods of mitigating inflammation and confirming its resolution before definitive pull-through may be of benefit for improving clinical outcomes in patients found with inflammation on diagnostic rectal biopsy.


Assuntos
Enterocolite , Doença de Hirschsprung , Criança , Humanos , Lactente , Doença de Hirschsprung/complicações , Doença de Hirschsprung/diagnóstico , Doença de Hirschsprung/cirurgia , Reto/cirurgia , Estudos Prospectivos , Fístula Anastomótica , Relevância Clínica , Inflamação/complicações , Enterocolite/diagnóstico , Enterocolite/etiologia , Biópsia/efeitos adversos , Estudos Retrospectivos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia
18.
J Pediatr Gastroenterol Nutr ; 79(2): 278-289, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38828781

RESUMO

OBJECTIVES: To review recent evaluations of pediatric patients with intestinal failure (IF) for intestinal transplantation (ITx), waiting list decisions, and outcomes of patients listed and not listed for ITx at our center. METHODS: Retrospective chart review of 97 patients evaluated for ITx from January 2014 to December 2021 including data from referring institutions and protocol laboratory testing, body imaging, endoscopy, and liver biopsy in selected cases. Survival analysis used Kaplan-Meier estimates and Cox proportional hazards regression. RESULTS: Patients were referred almost entirely from outside institutions, one-third because of intestinal failure-associated liver disease (IFALD), two-thirds because of repeated infective and non-IFALD complications under minimally successful intestinal rehabilitation, and a single patient because of lost central vein access. The majority had short bowel syndrome (SBS). Waiting list placement was offered to 67 (69%) patients, 40 of whom for IFALD. The IFALD group was generally younger and more likely to have SBS, have received more parenteral nutrition, have demonstrated more evidence of chronic inflammation and have inferior kidney function compared to those offered ITx for non-IFALD complications and those not listed. ITx was performed in 53 patients. Superior postevaluation survival was independently associated with higher serum creatinine (hazard ratio [HR] 15.410, p = 014), whereas inferior postevaluation survival was associated with ITx (HR 0.515, p = 0.035) and higher serum fibrinogen (HR 0.994, p = 0.005). CONCLUSIONS: Despite recent improvements in IF management, IFALD remains a prominent reason for ITx referral. Complications of IF inherent to ITx candidacy influence postevaluation and post-ITx survival.


Assuntos
Intestinos , Listas de Espera , Humanos , Estudos Retrospectivos , Masculino , Feminino , Criança , Pré-Escolar , Lactente , Intestinos/transplante , Adolescente , Insuficiência Intestinal , Síndrome do Intestino Curto/cirurgia , Hepatopatias/cirurgia
19.
Int J Eat Disord ; 57(3): 727-739, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38379127

RESUMO

OBJECTIVE: Intuitive eating (IE) is an emerging health promotion framework which has shown promise in the prevention and early intervention of disordered eating (DE) behavior in adults. This study sought to extend this work by assessing the feasibility and preliminary efficacy of a 5-week IE intervention, "Your Body is Your Home," delivered in school classrooms for early adolescents aged 11-13. METHODS: The present study utilized a quasi-experimental design. Eligibility criteria were defined a priori and published in a registered protocol. Four classrooms (n = 128 student participants) were recruited into two streams, and self-report questionnaires were administered at pre-test, post-test, and 4-week follow-up. The questionnaires included the Intuitive Eating Scale for Early Adolescents (IES-2-EA), the Body Appreciation Scale (BAS-2), and the WHO Wellbeing Index (WHO-5). Linear mixed models were used to conduct preliminary efficacy testing. RESULTS: The results indicate that a brief classroom-based IE intervention is feasible and acceptable for both students and teaching staff; retention, fidelity, and attendance targets were achieved. Students and teachers rated all five sessions of the intervention as a highly feasible method of health promotion. Further, preliminary efficacy data suggest IE interventions aimed at early adolescents may be a feasible way of improving certain aspects of IE (p < .001) in male and female participants, and body appreciation (p < .001) in male participants. DISCUSSION: The study provides preliminary support for the implementation and evaluation of an IE intervention as part of school-based health promotion and offers preliminary effect size estimates for a larger-scale randomized trial. PUBLIC SIGNIFICANCE: Existing evidence suggests that IE may be a useful framework through which relationships with food and the body can be improved. The present study seeks to extend this work by adapting the framework for early adolescents (among whom the framework is not well understood) and examining feasibility, acceptability, and preliminary changes to several health and well-being metrics following a 5-week school-based intervention.


Assuntos
Transtornos da Alimentação e da Ingestão de Alimentos , Promoção da Saúde , Adulto , Humanos , Masculino , Feminino , Adolescente , Estudos de Viabilidade , Promoção da Saúde/métodos , Transtornos da Alimentação e da Ingestão de Alimentos/prevenção & controle , Inquéritos e Questionários , Estudantes
20.
Retina ; 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39325779

RESUMO

PURPOSE: To evaluate the effectiveness of anterior subtenon triamcinolone (AST) injections in the management of refractory macular edema. METHODS: This is a retrospective case series of consecutive eyes with refractory macular edema treated with AST at a single vitreoretinal surgeon's practice at Toronto Western Hospital, University of Toronto, Canada in 2018-2023. Refractory was defined as persistent macular edema with a central subfield thickness of 250µm or greater over a 24-week period, receiving at least four intravitreal anti-VEGF injections. Vision outcomes and optical coherence tomography features for all eyes were compared for three visits pre-AST treatment and two visits post-AST treatment. RESULTS: Ninety-three patients (119 eyes; diabetic macular edema (26%), and pseudophakic CME (74%), with a mean follow-up duration of 161 days were included. The presence of subretinal fluid (p=0.0013), central subfield macular thickness (p<0.0001), cube average thickness (p=0.0024) and macular cube volume (p= 0.0017) significantly improved from pre-AST to post-AST treatment. Visual acuity also significantly improved from pre-AST treatment to post-AST treatment (p<0.0001). There was no significant change in the intraocular pressures from pre-AST to post-AST (p=0.7920) and no complications were noted throughout the follow-up period. CONCLUSION: The findings from this study suggest that AST injections show modest improvement in anatomical and functional outcomes, and are safe for the treatment and management of refractory macular edema.

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