Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 11 de 11
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Nat Mater ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38969782

RESUMO

Microorganisms typically used to produce food and pharmaceuticals are now being explored as medicines and agricultural supplements. However, maintaining high viability from manufacturing until use remains an important challenge, requiring sophisticated cold chains and packaging. Here we report synthetic extremophiles of industrially relevant gram-negative bacteria (Escherichia coli Nissle 1917, Ensifer meliloti), gram-positive bacteria (Lactobacillus plantarum) and yeast (Saccharomyces boulardii). We develop a high-throughput pipeline to define species-specific materials that enable survival through drying, elevated temperatures, organic solvents and ionizing radiation. Using this pipeline, we enhance the stability of E. coli Nissle 1917 by more than four orders of magnitude over commercial formulations and demonstrate its capacity to remain viable while undergoing tableting and pharmaceutical processing. We further show, in live animals and plants, that synthetic extremophiles remain functional against enteric pathogens and as nitrogen-fixing plant supplements even after exposure to elevated temperatures. This synthetic, material-based stabilization enhances our capacity to apply microorganisms in extreme environments on Earth and potentially during exploratory space travel.

2.
Ann Surg ; 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38482684

RESUMO

OBJECTIVE: To evaluate whether a machine learning algorithm (i.e. the "NightSignal" algorithm) can be used for the detection of postoperative complications prior to symptom onset after cardiothoracic surgery. SUMMARY BACKGROUND DATA: Methods that enable the early detection of postoperative complications after cardiothoracic surgery are needed. METHODS: This was a prospective observational cohort study conducted from July 2021 to February 2023 at a single academic tertiary care hospital. Patients aged 18 years or older scheduled to undergo cardiothoracic surgery were recruited. Study participants wore a Fitbit watch continuously for at least 1 week preoperatively and up to 90-days postoperatively. The ability of the NightSignal algorithm-which was previously developed for the early detection of Covid-19-to detect postoperative complications was evaluated. The primary outcomes were algorithm sensitivity and specificity for postoperative event detection. RESULTS: A total of 56 patients undergoing cardiothoracic surgery met inclusion criteria, of which 24 (42.9%) underwent thoracic operations and 32 (57.1%) underwent cardiac operations. The median age was 62 (IQR: 51-68) years and 30 (53.6%) patients were female. The NightSignal algorithm detected 17 of the 21 postoperative events a median of 2 (IQR: 1-3) days prior to symptom onset, representing a sensitivity of 81%. The specificity, negative predictive value, and positive predictive value of the algorithm for the detection of postoperative events were 75%, 97%, and 28%, respectively. CONCLUSIONS: Machine learning analysis of biometric data collected from wearable devices has the potential to detect postoperative complications-prior to symptom onset-after cardiothoracic surgery.

3.
Telemed J E Health ; 30(7): e1944-e1953, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38597957

RESUMO

Objective: We aimed to (1) describe telemedicine utilization and usability during the first 6 weeks of the pandemic and (2) determine if usability varied by individual- or visit-level characteristics. Methods: We conducted a retrospective cohort study of ambulatory pediatric telemedicine visits occurring between March 10, 2020, and April 18, 2020, across a large academic health system. We performed manual chart review to assess individual- and visit-level characteristics and invited caregivers to respond to an adapted Telehealth Usability Questionnaire (TUQ). We used multiple logistic regression to determine predictors of high usability. Results: There were 3,197 ambulatory pediatric telemedicine visits, representing 2,967 unique patients. Patients were racially/ethnically diverse (42.5% non-Hispanic White) and primarily English-speaking (89.2%). Surveys were completed by 441 (17%) of those invited. Every item of the TUQ had agreement or strong agreement from the majority of respondents. Compared with non-Hispanic White, non-Hispanic Asian identity was associated with lower usability in three domains and overall, and non-Hispanic Black identity was associated with higher satisfaction and future use. As compared with caregivers of infants younger than 1 year, caregivers of older patients reported lower usability in the three domains. Conclusions: Telemedicine was successfully implemented across 18 ambulatory pediatric specialties in the largest health system in New York State at the onset of COVID-19, and caregivers found it usable and acceptable. Usability scores did not vary by visit-level characteristics but did vary by race/ethnicity and age. Further research is necessary to identify modifiable drivers of the patient experience, particularly in non-Hispanic Asian communities and older adolescents.


Assuntos
COVID-19 , Medidas de Resultados Relatados pelo Paciente , SARS-CoV-2 , Telemedicina , Humanos , COVID-19/epidemiologia , Telemedicina/estatística & dados numéricos , Feminino , Masculino , Criança , New York , Estudos Retrospectivos , Pré-Escolar , Adolescente , Lactente , Pandemias , Pediatria , Assistência Ambulatorial/estatística & dados numéricos , Recém-Nascido
4.
Ann Surg ; 278(3): 417-425, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37334712

RESUMO

OBJECTIVES: We aimed to report efficacy, safety, and health-related quality of life (HRQoL) outcomes of a multidisciplinary treatment approach including supraclavicular thoracic outlet decompression among patients with thoracic outlet syndrome (TOS). BACKGROUND: TOS is a challenging condition where controversy remains in diagnosis and treatment, primarily given a lack of data exploring various treatment approaches and associated patient outcomes. METHODS: Patients who underwent unilateral, supraclavicular thoracic outlet decompression, or pectoralis minor tenotomy for neurogenic, venous, or arterial TOS were identified from a prospectively maintained database. Demography, use of preoperative botulinum toxin injection, and participation in multidisciplinary evaluation were measured. The primary endpoints were composite postoperative morbidity and symptomatic improvement compared with baseline. RESULTS: Among 2869 patients evaluated (2007-2021), 1032 underwent surgery, including 864 (83.7%) supraclavicular decompressions and 168 (16.3%) isolated pectoralis minor tenotomies. Predominant TOS subtypes among surgical patients were neurogenic (75.4%) and venous TOS (23.4%). Most patients (92.9%) with nTOS underwent preoperative botulinum toxin injection; 56.3% reported symptomatic improvement. Before surgical consultation, few patients reported participation in physical therapy (10.9%). The median time from first evaluation to surgery was 136 days (interquartile range: 55, 258). Among 864 patients who underwent supraclavicular thoracic outlet decompression, complications occurred in 19.8%; the most common complication was chyle leak (8.3%). Four patients (0.4%) required revisional thoracic outlet decompression. At a median follow-up of 420 days (interquartile range: 150, 937) 93.3% reported symptomatic improvement. CONCLUSION: Based on low composite morbidity, need for very few revisional operations, and high rates of symptomatic improvement, a multidisciplinary treatment approach including primarily supraclavicular thoracic outlet decompression is safe and effective for patients with TOS.


Assuntos
Toxinas Botulínicas , Síndrome do Desfiladeiro Torácico , Humanos , Resultado do Tratamento , Qualidade de Vida , Descompressão Cirúrgica/efeitos adversos , Síndrome do Desfiladeiro Torácico/cirurgia , Síndrome do Desfiladeiro Torácico/diagnóstico , Síndrome do Desfiladeiro Torácico/etiologia , Estudos Retrospectivos
5.
Am J Hum Genet ; 99(5): 1005-1014, 2016 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-27745832

RESUMO

Periodontal Ehlers-Danlos syndrome (pEDS) is an autosomal-dominant disorder characterized by early-onset periodontitis leading to premature loss of teeth, joint hypermobility, and mild skin findings. A locus was mapped to an approximately 5.8 Mb region at 12p13.1 but no candidate gene was identified. In an international consortium we recruited 19 independent families comprising 107 individuals with pEDS to identify the locus, characterize the clinical details in those with defined genetic causes, and try to understand the physiological basis of the condition. In 17 of these families, we identified heterozygous missense or in-frame insertion/deletion mutations in C1R (15 families) or C1S (2 families), contiguous genes in the mapped locus that encode subunits C1r and C1s of the first component of the classical complement pathway. These two proteins form a heterotetramer that then combines with six C1q subunits. Pathogenic variants involve the subunit interfaces or inter-domain hinges of C1r and C1s and are associated with intracellular retention and mild endoplasmic reticulum enlargement. Clinical features of affected individuals in these families include rapidly progressing periodontitis with onset in the teens or childhood, a previously unrecognized lack of attached gingiva, pretibial hyperpigmentation, skin and vascular fragility, easy bruising, and variable musculoskeletal symptoms. Our findings open a connection between the inflammatory classical complement pathway and connective tissue homeostasis.


Assuntos
Complemento C1r/genética , Complemento C1s/genética , Síndrome de Ehlers-Danlos/genética , Deleção de Genes , Mutação de Sentido Incorreto , Periodontite/genética , Adolescente , Adulto , Criança , Pré-Escolar , Mapeamento Cromossômico , Cromossomos Humanos Par 12/genética , Síndrome de Ehlers-Danlos/diagnóstico , Retículo Endoplasmático/genética , Retículo Endoplasmático/metabolismo , Exoma , Feminino , Loci Gênicos , Humanos , Masculino , Linhagem , Periodontite/diagnóstico , Conformação Proteica , Adulto Jovem
6.
Am J Med Genet A ; 164A(7): 1750-5, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24677762

RESUMO

Biallelic mutations in FKBP14 cause a recessive form of Ehlers-Danlos syndrome (EDS) characterized by progressive kyphoscoliosis, myopathy, and hearing loss. To date, four children and one adult with this condition have been reported. We recently identified a 42-year-old man with severe kyphoscoliosis, restrictive/obstructive lung disease, short stature, mild hearing loss, decreased muscle mass, and a dissection of the celiac artery at age 41. He also had complete occlusion of the superior mesenteric artery with compensatory flow through an enlarged and tortuous inferior mesenteric artery. He was homozygous for a previously identified FKBP14 mutation, c.362dupC, p.(Glu122Argfs*7). He had no mutations in COL3A1, ACTA2, TGFBR1, TGFBR2, or SMAD3. The FKBP14 mutations in our patient occurred on the same haplotype as others with this same mutation. Although one family member in a previous report was thought to have early vascular complications, it could not be confirmed that she had biallelic mutations in FKBP14. This report expands the phenotype of FKBP14-related EDS to include risk for vascular complications and also raises the question of whether the shared haplotype represents a risk allele or founder mutation.


Assuntos
Síndrome de Ehlers-Danlos/diagnóstico , Síndrome de Ehlers-Danlos/genética , Estudos de Associação Genética , Mutação , Peptidilprolil Isomerase/genética , Fenótipo , Adulto , Análise Mutacional de DNA , Fácies , Humanos , Angiografia por Ressonância Magnética , Masculino , Artéria Mesentérica Superior/patologia , Oclusão Vascular Mesentérica/diagnóstico , Linhagem
7.
ACS Synth Biol ; 13(4): 1225-1236, 2024 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-38551819

RESUMO

In recent decades, whole-cell biocatalysis has played an increasingly important role in the food, pharmaceutical, and energy sector. One promising application is the use of ethanologenic yeast displaying minicellulosomes on the cell surface to combine cellulose hydrolysis and fermentation into a single step for consolidated bioprocessing. However, cellulosic ethanol production using existing yeast whole-cell biocatalysts (yWCBs) has not reached industrial feasibility due to their inefficient cellulose hydrolysis. As prior studies have demonstrated enzyme density on the yWCB surface to be one of the most important parameters for enhancing cellulose hydrolysis, we sought to maximize this parameter at both the population and single-cell levels in yWCBs displaying tetrafunctional minicellulosomes. At the population level, enzyme density is limited by the presence of a nondisplay population constituting 25-50% of all cells. In this study, we identified the cause to be plasmid loss and successfully eliminated the nondisplay population to generate compositionally uniform yWCBs. At the single-cell level, we demonstrate that enzyme density is limited by molecular crowding, which hinders minicellulosome assembly. By adjusting the integrated gene copy number, we obtained yWCBs of tunable enzyme display levels. This tunability allowed us to avoid the crowding-limited regime and achieve a maximum enzyme density per cell. As a result, the best strain showed a cellulose-to-ethanol yield of 4.92 g/g, corresponding to 96% of the theoretical maximum and near-complete conversion (∼96%) of the starting cellulose (1% PASC). Our holistic engineering strategy that combines a population and single-cell level approach is broadly applicable to enhance the WCB performance in other biocatalytic cascade schemes.


Assuntos
Biocombustíveis , Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolismo , Membrana Celular/metabolismo , Fermentação , Celulose/metabolismo , Etanol/metabolismo
8.
Curr Oncol ; 31(3): 1529-1542, 2024 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-38534949

RESUMO

The objective of this study was to evaluate the overall survival of patients with ≤8 mm non-small cell lung cancer (NSCLC) who undergo wedge resection versus stereotactic body radiation therapy (SBRT). Kaplan-Meier analysis, multivariable Cox proportional hazards modeling, and propensity score-matched analysis were performed to evaluate the overall survival of patients with ≤8 mm NSCLC in the National Cancer Database (NCDB) from 2004 to 2017 who underwent wedge resection versus patients who underwent SBRT. The above-mentioned matched analyses were repeated for patients with no comorbidities. Patients who were coded in the NCDB as having undergone radiation because surgery was contraindicated due to patient risk factors (e.g., comorbid conditions, advance age, etc.) and those with a history of prior malignancy were excluded from analysis. Of the 1505 patients who had NSCLC ≤8 mm during the study period, 1339 (89%) patients underwent wedge resection, and 166 (11%) patients underwent SBRT. In the unadjusted analysis, multivariable Cox modeling and propensity score-matched analysis, wedge resection was associated with improved survival when compared to SBRT. These results were consistent in a sensitivity analysis limited to patients with no comorbidities.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radiocirurgia , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Radiocirurgia/métodos , Estimativa de Kaplan-Meier , Comorbidade
11.
Nat Genet ; 44(8): 922-7, 2012 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-22772368

RESUMO

Loeys-Dietz syndrome (LDS) associates with a tissue signature for high transforming growth factor (TGF)-ß signaling but is often caused by heterozygous mutations in genes encoding positive effectors of TGF-ß signaling, including either subunit of the TGF-ß receptor or SMAD3, thereby engendering controversy regarding the mechanism of disease. Here, we report heterozygous mutations or deletions in the gene encoding the TGF-ß2 ligand for a phenotype within the LDS spectrum and show upregulation of TGF-ß signaling in aortic tissue from affected individuals. Furthermore, haploinsufficient Tgfb2(+/-) mice have aortic root aneurysm and biochemical evidence of increased canonical and noncanonical TGF-ß signaling. Mice that harbor both a mutant Marfan syndrome (MFS) allele (Fbn1(C1039G/+)) and Tgfb2 haploinsufficiency show increased TGF-ß signaling and phenotypic worsening in association with normalization of TGF-ß2 expression and high expression of TGF-ß1. Taken together, these data support the hypothesis that compensatory autocrine and/or paracrine events contribute to the pathogenesis of TGF-ß-mediated vasculopathies.


Assuntos
Aneurisma da Aorta Torácica/genética , Mutação , Fator de Crescimento Transformador beta2/genética , Animais , Aneurisma da Aorta Torácica/patologia , Modelos Animais de Doenças , Feminino , Fibrilina-1 , Fibrilinas , Haploinsuficiência , Humanos , Síndrome de Loeys-Dietz/genética , Síndrome de Loeys-Dietz/patologia , Masculino , Síndrome de Marfan/genética , Síndrome de Marfan/patologia , Camundongos , Camundongos Knockout , Camundongos Mutantes , Proteínas dos Microfilamentos/genética , Linhagem , Fenótipo , Transdução de Sinais , Síndrome , Fator de Crescimento Transformador beta2/deficiência
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA