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1.
J Bacteriol ; 206(7): e0017524, 2024 07 25.
Artículo en Inglés | MEDLINE | ID: mdl-38953644

RESUMEN

Clostridioides difficile causes a serious diarrheal disease and is a common healthcare-associated bacterial pathogen. Although it has a major impact on human health, the mechanistic details of C. difficile intestinal colonization remain undefined. C. difficile is highly sensitive to oxygen and requires anaerobic conditions for in vitro growth. However, the mammalian gut is not devoid of oxygen, and C. difficile tolerates moderate oxidative stress in vivo. The C. difficile genome encodes several antioxidant proteins, including a predicted superoxide reductase (SOR) that is upregulated upon exposure to antimicrobial peptides. The goal of this study was to establish SOR enzymatic activity and assess its role in protecting C. difficile against oxygen exposure. Insertional inactivation of sor rendered C. difficile more sensitive to superoxide, indicating that SOR contributes to antioxidant defense. Heterologous C. difficile sor expression in Escherichia coli conferred protection against superoxide-dependent growth inhibition, and the corresponding cell lysates showed superoxide scavenging activity. Finally, a C. difficile SOR mutant exhibited global proteome changes under oxygen stress when compared to the parent strain. Collectively, our data establish the enzymatic activity of C. difficile SOR, confirm its role in protection against oxidative stress, and demonstrate SOR's broader impacts on the C. difficile vegetative cell proteome.IMPORTANCEClostridioides difficile is an important pathogen strongly associated with healthcare settings and capable of causing severe diarrheal disease. While considered a strict anaerobe in vitro, C. difficile has been shown to tolerate low levels of oxygen in the mammalian host. Among other well-characterized antioxidant proteins, the C. difficile genome encodes a predicted superoxide reductase (SOR), an understudied component of antioxidant defense in pathogens. The significance of the research reported herein is the characterization of SOR's enzymatic activity, including confirmation of its role in protecting C. difficile against oxidative stress. This furthers our understanding of C. difficile pathogenesis and presents a potential new avenue for targeted therapies.


Asunto(s)
Clostridioides difficile , Estrés Oxidativo , Oxígeno , Superóxidos , Clostridioides difficile/genética , Clostridioides difficile/enzimología , Clostridioides difficile/metabolismo , Oxígeno/metabolismo , Superóxidos/metabolismo , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Oxidorreductasas/metabolismo , Oxidorreductasas/genética , Regulación Bacteriana de la Expresión Génica
2.
Am J Physiol Lung Cell Mol Physiol ; 327(1): L40-L53, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38712443

RESUMEN

Chorioamnionitis is a common antecedent of preterm birth and induces inflammation and oxidative stress in the fetal lungs. Reducing inflammation and oxidative stress in the fetal lungs may improve respiratory outcomes in preterm infants. Creatine is an organic acid with known anti-inflammatory and antioxidant properties. The objective of the study was to evaluate the efficacy of direct fetal creatine supplementation to reduce inflammation and oxidative stress in fetal lungs arising from an in utero proinflammatory stimulus. Fetal lambs (n = 51) were instrumented at 90 days gestation to receive a continuous infusion of creatine monohydrate (6 mg·kg-1·h-1) or saline for 17 days. Maternal chorioamnionitis was induced with intra-amniotic lipopolysaccharide (LPS; 1 mg, O55:H6) or saline 7 days before delivery at 110 days gestation. Tissue creatine content was assessed with capillary electrophoresis, and inflammatory markers were analyzed with Luminex Magpix and immunohistochemistry. Oxidative stress was measured as the level of protein thiol oxidation. The effects of LPS and creatine were analyzed using a two-way ANOVA. Fetal creatine supplementation increased lung creatine content by 149% (PCr < 0.0001) and had no adverse effects on lung morphology. LPS-exposed groups showed increased levels of interleukin-8 in the bronchoalveolar lavage (PLPS < 0.0001) and increased levels of CD45+ leukocytes (PLPS < 0.0001) and MPO+ (PLPS < 0.0001) cells in the lung parenchyma. Creatine supplementation significantly reduced the levels of CD45+ (PCr = 0.045) and MPO+ cells (PCr = 0.012) in the lungs and reduced thiol oxidation in plasma (PCr < 0.01) and lung tissue (PCr = 0.02). In conclusion, fetal creatine supplementation reduced markers of inflammation and oxidative stress in the fetal lungs arising from chorioamnionitis.NEW & NOTEWORTHY We evaluated the effect of antenatal creatine supplementation to reduce pulmonary inflammation and oxidative stress in the fetal lamb lungs arising from lipopolysaccharide (LPS)-induced chorioamnionitis. Fetal creatine supplementation increased lung creatine content and had no adverse effects on systemic fetal physiology and overall lung architecture. Importantly, fetuses that received creatine had significantly lower levels of inflammation and oxidative stress in the lungs, suggesting an anti-inflammatory and antioxidant benefit of creatine.


Asunto(s)
Corioamnionitis , Creatina , Suplementos Dietéticos , Lipopolisacáridos , Pulmón , Estrés Oxidativo , Animales , Corioamnionitis/tratamiento farmacológico , Corioamnionitis/metabolismo , Corioamnionitis/patología , Creatina/farmacología , Femenino , Estrés Oxidativo/efectos de los fármacos , Embarazo , Ovinos , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Pulmón/patología , Neumonía/metabolismo , Neumonía/prevención & control , Neumonía/tratamiento farmacológico , Neumonía/patología , Modelos Animales de Enfermedad , Feto/metabolismo , Feto/efectos de los fármacos
3.
Appl Environ Microbiol ; 90(2): e0084223, 2024 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-38259077

RESUMEN

Diverse influenza A viruses (IAVs) circulate in wild birds, including highly pathogenic strains that infect poultry and humans. Consequently, surveillance of IAVs in wild birds is a cornerstone of agricultural biosecurity and pandemic preparedness. Surveillance is traditionally done by testing wild birds directly, but obtaining these specimens is labor intensive, detection rates can be low, and sampling is often biased toward certain avian species. As a result, local incursions of dangerous IAVs are rarely detected before outbreaks begin. Testing environmental specimens from wild bird habitats has been proposed as an alternative surveillance strategy. These specimens are thought to contain diverse IAVs deposited by a broad range of avian hosts, including species that are not typically sampled by surveillance programs. To enable this surveillance strategy, we developed a targeted genomic sequencing method for characterizing IAVs in these challenging environmental specimens. It combines custom hybridization probes, unique molecular index-based library construction, and purpose-built bioinformatic tools, allowing IAV genomic material to be enriched and analyzed with single-fragment resolution. We demonstrated our method on 90 sediment specimens from wetlands around Vancouver, Canada. We recovered 2,312 IAV genome fragments originating from all eight IAV genome segments. Eleven hemagglutinin subtypes and nine neuraminidase subtypes were detected, including H5, the current global surveillance priority. Our results demonstrate that targeted genomic sequencing of environmental specimens from wild bird habitats could become a valuable complement to avian influenza surveillance programs.IMPORTANCEIn this study, we developed genome sequencing tools for characterizing avian influenza viruses in sediment from wild bird habitats. These tools enable an environment-based approach to avian influenza surveillance. This could improve early detection of dangerous strains in local wild birds, allowing poultry producers to better protect their flocks and prevent human exposures to potential pandemic threats. Furthermore, we purposefully developed these methods to contend with viral genomic material that is diluted, fragmented, incomplete, and derived from multiple strains and hosts. These challenges are common to many environmental specimens, making these methods broadly applicable for genomic pathogen surveillance in diverse contexts.


Asunto(s)
Virus de la Influenza A , Gripe Aviar , Animales , Animales Salvajes , Aves , Genómica , Virus de la Influenza A/genética , Gripe Aviar/epidemiología , Filogenia , Aves de Corral , Humedales
4.
J Biomed Sci ; 31(1): 89, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39256822

RESUMEN

Realizing the immense clinical potential of mRNA-based drugs will require continued development of methods to safely deliver the bioactive agents with high efficiency and without triggering side effects. In this regard, lipid nanoparticles have been successfully utilized to improve mRNA delivery and protect the cargo from extracellular degradation. Encapsulation in lipid nanoparticles was an essential factor in the successful clinical application of mRNA vaccines, which conclusively demonstrated the technology's potential to yield approved medicines. In this review, we begin by describing current advances in mRNA modifications, design of novel lipids and development of lipid nanoparticle components for mRNA-based drugs. Then, we summarize key points pertaining to preclinical and clinical development of mRNA therapeutics. Finally, we cover topics related to targeted delivery systems, including endosomal escape and targeting of immune cells, tumors and organs for use with mRNA vaccines and new treatment modalities for human diseases.


Asunto(s)
Sistemas de Liberación de Medicamentos , Nanopartículas , ARN Mensajero , Humanos , ARN Mensajero/genética , ARN Mensajero/administración & dosificación , Nanopartículas/química , Sistemas de Liberación de Medicamentos/métodos , Vacunas de ARNm , Lípidos/química , Liposomas
5.
Nitric Oxide ; 150: 37-46, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39038732

RESUMEN

The combination of nitric oxide (NO) donors with nanomaterials has emerged as a promising approach to reduce postharvest losses. The encapsulation of NO donors provides protection from rapid degradation and controlled release, enhancing the NO effectiveness in postharvest treatments. Moreover, the application method can also influence postharvest responses. In this study, two application methods were evaluated, spraying and immersion, using S-nitrosoglutathione (GSNO, a NO donor) in free and encapsulated forms on papaya fruit. Our hypothesis was that GSNO encapsulated in chitosan nanoparticles would outperform the free form in delaying fruit senescence. In addition, this study marks the pioneering characterization of chitosan nanoparticles containing GSNO within the framework of a postharvest investigation. Overall, our findings indicate that applying encapsulated GSNO (GSNO-NP-S) through spraying preserves the quality of papaya fruit during storage. This method not only minimizes weight loss, ethylene production, and softening, but also stimulates antioxidant responses, thereby mitigating oxidative damage. Consequently, it stands out as the promising technique for delaying papaya fruit senescence. This innovative approach holds the potential to enhance postharvest practices and advance sustainable agriculture.


Asunto(s)
Carica , Quitosano , Frutas , Donantes de Óxido Nítrico , S-Nitrosoglutatión , Carica/química , Donantes de Óxido Nítrico/farmacología , Donantes de Óxido Nítrico/química , Frutas/química , S-Nitrosoglutatión/farmacología , S-Nitrosoglutatión/química , Quitosano/química , Quitosano/farmacología , Estrés Oxidativo/efectos de los fármacos , Nanopartículas/química , Conservación de Alimentos/métodos
6.
J Eur Acad Dermatol Venereol ; 38(9): 1694-1703, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38619384

RESUMEN

Current drug development strategies present many challenges that can impede drug approval by regulatory agencies. Alternative study models, such as adaptive trial designs, have recently sparked interest, as they provide a flexible and more efficient approach in conducting clinical trials. Adaptive trial designs offer several potential benefits over traditional randomized controlled trials, which include decrease in costs, reduced clinical development time and limiting exposure of patients to potentially ineffective treatments allowing completion of studies with fewer patients. This article explores the current use of adaptive trial designs in non-oncologic skin diseases and highlights the most common types of adaptive designs used in the field. We also review the operational challenges and statistical considerations associated with such designs and propose clinical development strategies to successfully implement adaptive designs. The article also proposes instances where adaptive trial designs are particularly beneficial, and other situations where they may not be very useful.


Asunto(s)
Dermatología , Proyectos de Investigación , Humanos , Dermatología/métodos , Enfermedades de la Piel/terapia , Ensayos Clínicos como Asunto , Ensayos Clínicos Adaptativos como Asunto/métodos
7.
Am J Epidemiol ; 192(8): 1249-1263, 2023 08 04.
Artículo en Inglés | MEDLINE | ID: mdl-36963379

RESUMEN

The Environmental Influences on Child Health Outcomes (ECHO)-Wide Cohort Study (EWC), a collaborative research design comprising 69 cohorts in 31 consortia, was funded by the National Institutes of Health (NIH) in 2016 to improve children's health in the United States. The EWC harmonizes extant data and collects new data using a standardized protocol, the ECHO-Wide Cohort Data Collection Protocol (EWCP). EWCP visits occur at least once per life stage, but the frequency and timing of the visits vary across cohorts. As of March 4, 2022, the EWC cohorts contributed data from 60,553 children and consented 29,622 children for new EWCP data and biospecimen collection. The median (interquartile range) age of EWCP-enrolled children was 7.5 years (3.7-11.1). Surveys, interviews, standardized examinations, laboratory analyses, and medical record abstraction are used to obtain information in 5 main outcome areas: pre-, peri-, and postnatal outcomes; neurodevelopment; obesity; airways; and positive health. Exposures include factors at the level of place (e.g., air pollution, neighborhood socioeconomic status), family (e.g., parental mental health), and individuals (e.g., diet, genomics).


Asunto(s)
Contaminación del Aire , Exposición a Riesgos Ambientales , Niño , Humanos , Estados Unidos/epidemiología , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisis , Estudios de Cohortes , Salud Infantil , Contaminación del Aire/análisis , Evaluación de Resultado en la Atención de Salud
8.
Nature ; 543(7643): 65-71, 2017 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-28199314

RESUMEN

The diagnosis of pancreatic neuroendocrine tumours (PanNETs) is increasing owing to more sensitive detection methods, and this increase is creating challenges for clinical management. We performed whole-genome sequencing of 102 primary PanNETs and defined the genomic events that characterize their pathogenesis. Here we describe the mutational signatures they harbour, including a deficiency in G:C > T:A base excision repair due to inactivation of MUTYH, which encodes a DNA glycosylase. Clinically sporadic PanNETs contain a larger-than-expected proportion of germline mutations, including previously unreported mutations in the DNA repair genes MUTYH, CHEK2 and BRCA2. Together with mutations in MEN1 and VHL, these mutations occur in 17% of patients. Somatic mutations, including point mutations and gene fusions, were commonly found in genes involved in four main pathways: chromatin remodelling, DNA damage repair, activation of mTOR signalling (including previously undescribed EWSR1 gene fusions), and telomere maintenance. In addition, our gene expression analyses identified a subgroup of tumours associated with hypoxia and HIF signalling.


Asunto(s)
Carcinoma Neuroendocrino/genética , Genoma Humano/genética , Genómica , Neoplasias Pancreáticas/genética , Secuencia de Bases , Proteínas de Unión a Calmodulina/genética , Ensamble y Desensamble de Cromatina/genética , Aberraciones Cromosómicas , Variaciones en el Número de Copia de ADN/genética , ADN Glicosilasas/genética , Análisis Mutacional de ADN , Reparación del ADN/genética , Femenino , Mutación de Línea Germinal/genética , Humanos , Masculino , Proteína EWS de Unión a ARN , Proteínas de Unión al ARN/genética , Serina-Treonina Quinasas TOR/metabolismo , Telómero/genética , Telómero/metabolismo
10.
J Eur Acad Dermatol Venereol ; 37(5): 976-983, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36652273

RESUMEN

Despite the emergence of novel targeted treatments for atopic dermatitis (AD), there is a lack of guidelines on standardizing analysis of clinical trial data. To define and estimate meaningful treatment comparisons, several factors, including intercurrent events, must be taken into account. Intercurrent events are defined as events occurring after treatment initiation that affect either the interpretation or existence of the measurements associated with clinical questions of interest. Due to the relapsing, unpredictable nature of AD, intercurrent events frequently occur in AD trials, such as use of rescue therapy for intense itch and sleep deprivation. Despite the impact of intercurrent events in AD, they are often handled in an inconsistent manner across trials, which limits results interpretation. The estimand framework is increasingly used to estimate treatment effects while accounting for intercurrent events. This review explores how guidance from the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) on the use of estimands can be applied to support AD clinical trial design and analysis. We propose that estimands are used in AD trials and defined early during trial design. The use of estimands can provide clinicians with interventional trial results that are more reflective of clinical practice, help facilitate comparisons across clinical trials, and are more informative to enable improved treatment selection for patients.


Asunto(s)
Dermatitis Atópica , Modelos Estadísticos , Humanos , Dermatitis Atópica/tratamiento farmacológico , Testimonio de Experto , Interpretación Estadística de Datos , Proyectos de Investigación
11.
Ophthalmology ; 129(2): 161-170, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34474070

RESUMEN

PURPOSE: To investigate the effect of systemic arterial blood pressure (BP) on rates of progressive structural damage over time in glaucoma. DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 7501 eyes of 3976 subjects with glaucoma or suspected of glaucoma followed over time from the Duke Glaucoma Registry. METHODS: Linear mixed models were used to investigate the effects of BP on the rates of retinal nerve fiber layer (RNFL) loss from spectral-domain OCT (SD-OCT) over time. Models were adjusted for intraocular pressure (IOP), gender, race, diagnosis, central corneal thickness (CCT), follow-up time, and baseline disease severity. MAIN OUTCOME MEASURE: Effect of mean arterial pressure (MAP), systolic arterial pressure (SAP), and diastolic arterial pressure (DAP) on rates of RNFL loss over time. RESULTS: A total of 157 291 BP visits, 45 408 IOP visits, and 30 238 SD-OCT visits were included. Mean rate of RNFL change was -0.70 µm/year (95% confidence interval, -0.72 to -0.67 µm/year). In univariable models, MAP, SAP, and DAP during follow-up were not significantly associated with rates of RNFL loss. However, when adjusted for mean IOP during follow-up, each 10 mmHg reduction in mean MAP (-0.06 µm/year; P = 0.007) and mean DAP (-0.08 µm/year; P < 0.001) but not SAP (-0.01 µm/year; P = 0.355) was associated with significantly faster rates of RNFL thickness change over time. The effect of the arterial pressure metrics remained significant after additional adjustment for baseline age, diagnosis, sex, race, follow-up time, disease severity, and corneal thickness. CONCLUSIONS: When adjusted for IOP, lower MAP and DAP during follow-up were significantly associated with faster rates of RNFL loss, suggesting that levels of systemic BP may be a significant factor in glaucoma progression.


Asunto(s)
Presión Sanguínea/fisiología , Glaucoma/diagnóstico , Glaucoma/fisiopatología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Presión Arterial/fisiología , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Presión Intraocular/fisiología , Masculino , Persona de Mediana Edad , Fibras Nerviosas/patología , Hipertensión Ocular/fisiopatología , Sistema de Registros , Células Ganglionares de la Retina/patología , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Tonometría Ocular
12.
Med Microbiol Immunol ; 211(5-6): 249-260, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35960328

RESUMEN

Human cytomegalovirus (HCMV) shedding has been extensively investigated in newborns and in young children, however, much less is known about it in immunocompetent adults. Shedding of HCMV was investigated in saliva, vaginal secretions and urine of pregnant women experiencing primary infection along with the development of the HCMV-specific immune response. Thirty-three pregnant women shed HCMV DNA in peripheral biological fluids at least until one year after onset of infection, while in blood HCMV DNA was cleared earlier. Significantly higher levels of viral load were found in vaginal secretions compared to saliva and urine. All subjects examined two years after the onset of infection showed a high avidity index, with IgM persisting in 36% of women. Viral load in blood was directly correlated with levels of HCMV-specific IgM and inversely correlated with levels of IgG specific for the pentameric complex gH/gL/pUL128L; in addition, viral load in blood was inversely correlated with percentage of HCMV-specific CD4+ and CD8+ expressing IL-7R (long-term memory, LTM) while viral load in biological fluids was inversely correlated with percentage of HCMV-specific CD4+ and CD8+ effector memory RA+(TEMRA). In conclusion, viral shedding during primary infection in pregnancy persists in peripheral biological fluids for at least one year and the development of both antibodies (including those directed toward the pentameric complex) and memory T cells are associated with viral clearance.


Asunto(s)
Infecciones por Citomegalovirus , Citomegalovirus , Adulto , Niño , Humanos , Femenino , Recién Nacido , Embarazo , Preescolar , Mujeres Embarazadas , Anticuerpos Antivirales , Inmunidad , Inmunoglobulina M
13.
Appl Microbiol Biotechnol ; 106(18): 6263-6276, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35972515

RESUMEN

Peridinin is a light-harvesting carotenoid present in phototrophic dinoflagellates and has great potential for new drug applications and cosmetics development. Herein, the effects of irradiance mediated by light-emitting diodes on growth performance, carotenoid and fatty acid profiles, and antioxidant activity of the endosymbiotic dinoflagellate Durusdinium glynnii were investigated. The results demonstrate that D. glynnii is particularly well adapted to low-light conditions; however, it can be high-light-tolerant. In contrast to other light-harvesting carotenoids, the peridinin accumulation in D. glynnii occurred during high-light exposure. The peridinin to chlorophyll-a ratio varied as a function of irradiance, while the peridinin to total carotenoids ratio remained stable. Under optimal irradiance for growth, there was a peak in docosahexaenoic acid (DHA) bioaccumulation. This study contributes to the understanding of the photoprotective role of peridinin in endosymbiont dinoflagellates and highlights the antioxidant activity of peridinin-rich extracts. KEY POINTS: • Peridinin has a protective role against chlorophyll photo-oxidation • High light conditions induce cellular peridinin accumulation • D. glynnii accumulates high amounts of DHA under optimal light supply.


Asunto(s)
Dinoflagelados , Antioxidantes , Carotenoides , Clorofila , Ácidos Docosahexaenoicos
14.
BMC Health Serv Res ; 22(1): 1252, 2022 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-36253852

RESUMEN

BACKGROUND: To positively impact the social determinants of health, disabled people need to contribute to policy planning and programme development. However, they report barriers to engaging meaningfully in consultation processes. Additionally, their recommendations may not be articulated in ways that policy planners can readily use. This gap contributes to health outcome inequities. Participatory co-production methods have the potential to improve policy responsiveness. This research will use innovative methods to generate tools for co-producing knowledge in health-related policy areas, empowering disabled people to articulate experience, expertise and insights promoting equitable health policy and programme development within Aotearoa New Zealand. To develop these methods, as an exemplar, we will partner with both tangata whaikaha Maori and disabled people to co-produce policy recommendations around housing and home (kainga)-developing a nuanced understanding of the contexts in which disabled people can access and maintain kainga meeting their needs and aspirations. METHODS: Participatory co-production methods with disabled people, embedded within a realist methodological approach, will develop theories on how best to co-produce and effectively articulate knowledge to address equitable health-related policy and programme development-considering what works for whom under what conditions. Theory-building workshops (Phase 1) and qualitative surveys (Phase 2) will explore contexts and resources (i.e., at individual, social and environmental levels) supporting them to access and maintain kainga that best meets their needs and aspirations. In Phase 3, a realist review with embedded co-production workshops will synthesise evidence and co-produce knowledge from published literature and non-published reports. Finally, in Phase 4, co-produced knowledge from all phases will be synthesised to develop two key research outputs: housing policy recommendations and innovative co-production methods and tools empowering disabled people to create, synthesise and articulate knowledge to planners of health-related policy. DISCUSSION: This research will develop participatory co-production methods and tools to support future creation, synthesis and articulation of the knowledge and experiences of disabled people, contributing to policies that positively impact their social determinants of health.


Asunto(s)
Personas con Discapacidad , Política de Salud , Humanos , Nativos de Hawái y Otras Islas del Pacífico , Nueva Zelanda , Formulación de Políticas
15.
J Environ Manage ; 320: 115897, 2022 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-35947909

RESUMEN

The increased demands and dependence on depleted oil reserves, accompanied by global warming and climate change have driven the world to explore and develop new strategies for global sustainable development. Among sustainable biomass sources, microalgae represent a promising alternative to fossil fuel and can contribute to the achievement of important Sustainable Development Goals (SDGs). This article has reviewed the various applications of microalgal biomass that includes (i) the use in aquaculture and its sustainability; (ii) commercial value and emerging extraction strategies of carotenoids; (iii) biofuels from microalgae and their application in internal combustion engines; (iv) the use and reuse of water in microalgae cultivation; and (v) microalgae biotechnology as a key factor to assist SDGs. The future prospects and challenges on the microalgae circular bio economy, issues with regard to the scale-up and water demand in microalgae cultivation are also highlighted.


Asunto(s)
Microalgas , Biocombustibles , Biomasa , Desarrollo Sostenible , Agua
16.
Cancer ; 127(4): 569-576, 2021 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-33107985

RESUMEN

BACKGROUND: The objective of this study was to report on a retrospective series of patients with epithelioid hemangioendothelioma (EHE) who received treatment with sirolimus within the Italian Rare Cancer Network. METHODS: From January 2005, 38 adult patients with advanced EHE received continuous-dosing sirolimus, 5 mg daily, until they developed either toxicity or disease progression. Disease progression in the 6 months before the start of treatment was required. Each pathologic diagnosis was reviewed. The daily dose of sirolimus was adjusted based on plasma levels. Response was retrospectively assessed by local investigators using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST). Survival was estimated using the Kaplan-Meier method. RESULTS: All 38 patients (WW Domain Containing Transcription Regulator 1 [WWTR1]-positive, n = 37; transcription factor E3 [TFE3]-positive, n = 1) had disease progression before starting sirolimus (at baseline, 13 of 38 patients had the presence of serosal effusions and systemic symptoms). Thirty-seven patients were evaluable for response (there was 1 early interruption). The best RECIST responses were a partial response in 4 patients (10.8%), stable disease in 28 patients (75.7%), and disease progression in 5 patients (13.5%). At a 41.5-month median follow-up (interquartile range [IQR], 23.9-56.8 months), the median PFS was 13 months (95% CI, 3.7 months to not estimated [NE]), and the median OS was 18.8 months (95% CI, 10.6 months to NE). In patients who had serosal effusions at baseline, the median PFS was 4.8 months (IQR, 3.5-11.7 months), and the median OS was 10.6 months (IQR, 5.1-13.0 months), compared with 47.8 months (IQR, 11.4 months to NE) and 47.8 months (IQR, 15.7 months to NE), respectively, in patients without serosal effusions. Overall, sirolimus was fairly well tolerated, with 10 patients reporting irregular menstruation/ovary disfunction. CONCLUSIONS: The current results confirm that sirolimus is active in EHE, leading to prolonged stabilization in most patients who present without serosal effusions. Serosal effusions are confirmed as an unfavorable prognostic sign associated with short survival, and sirolimus displays limited activity in this subgroup.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Hemangioendotelioma Epitelioide/tratamiento farmacológico , Péptidos y Proteínas de Señalización Intracelular/genética , Sirolimus/administración & dosificación , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Niño , Progresión de la Enfermedad , Femenino , Hemangioendotelioma Epitelioide/epidemiología , Hemangioendotelioma Epitelioide/genética , Hemangioendotelioma Epitelioide/patología , Humanos , Italia/epidemiología , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pronóstico , Criterios de Evaluación de Respuesta en Tumores Sólidos , Sirolimus/efectos adversos , Proteínas Coactivadoras Transcripcionales con Motivo de Unión a PDZ
17.
Histopathology ; 78(7): 976-986, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33428796

RESUMEN

AIMS: To present our experience on spinal sclerosing epithelioid fibrosarcoma (SEF) and review the existing literature pertaining to SEF of the spine. METHODS AND RESULTS: Six cases of spinal SEF were reviewed, and a literature search of all primary SEFs of the spine was performed. All tumours occurred in adults (median age, 41 years) and were located all along the spine, the lumbar vertebrae being the most commonly involved. All patients presented with pain that they had experienced for months. The mean tumour size at diagnosis was 52 mm. Five tumours showed a spectrum of microscopic features consistent with pure SEF, and one showed a hybrid morphology with areas of low-grade fibromyxoid sarcoma. All were diffusely and strongly positive for mucin 4. Two cases were initially misdiagnosed as epithelioid haemangioendothelioma and aggressive chondroblastoma. Fluorescence in-situ hybridisation showed rearrangements of either FUS or EWSR1 in four cases. Reverse transcription polymerase chain reaction showed the presence of FUS-CREB3L1 and EWSR1-CREB3L1 fusion transcripts in two cases and one case, respectively. Of five patients with follow-up data available, two developed one or more local recurrences and three patients had metastatic disease. Distant metastases were mainly to other osseous locations, followed by lungs and lymph nodes. At last follow-up, three patients had died of disease and one was alive with multiple metastases. CONCLUSIONS: SEF is an aggressive sarcoma that can involve the spine. It is important to recognise the spine as the primary location of SEF, in order to avoid misdiagnosis as more common primary spinal neoplasms, which can impact on therapeutic approaches.


Asunto(s)
Células Epitelioides/patología , Fibrosarcoma , Adulto , Diagnóstico Diferencial , Femenino , Fibrosarcoma/diagnóstico , Fibrosarcoma/genética , Fibrosarcoma/patología , Reordenamiento Génico , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Mucina 4/genética , Proteína EWS de Unión a ARN/genética , Proteína FUS de Unión a ARN/genética , Neoplasias de los Tejidos Blandos/diagnóstico , Neoplasias de los Tejidos Blandos/genética , Neoplasias de los Tejidos Blandos/patología , Columna Vertebral/patología
18.
Conserv Biol ; 35(2): 654-665, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-32537779

RESUMEN

Collisions with buildings cause up to 1 billion bird fatalities annually in the United States and Canada. However, efforts to reduce collisions would benefit from studies conducted at large spatial scales across multiple study sites with standardized methods and consideration of species- and life-history-related variation and correlates of collisions. We addressed these research needs through coordinated collection of data on bird collisions with buildings at sites in the United States (35), Canada (3), and Mexico (2). We collected all carcasses and identified species. After removing records for unidentified carcasses, species lacking distribution-wide population estimates, and species with distributions overlapping fewer than 10 sites, we retained 269 carcasses of 64 species for analysis. We estimated collision vulnerability for 40 bird species with ≥2 fatalities based on their North American population abundance, distribution overlap in study sites, and sampling effort. Of 10 species we identified as most vulnerable to collisions, some have been identified previously (e.g., Black-throated Blue Warbler [Setophaga caerulescens]), whereas others emerged for the first time (e.g., White-breasted Nuthatch [Sitta carolinensis]), possibly because we used a more standardized sampling approach than past studies. Building size and glass area were positively associated with number of collisions for 5 of 8 species with enough observations to analyze independently. Vegetation around buildings influenced collisions for only 1 of those 8 species (Swainson's Thrush [Catharus ustulatus]). Life history predicted collisions; numbers of collisions were greatest for migratory, insectivorous, and woodland-inhabiting species. Our results provide new insight into the species most vulnerable to building collisions, making them potentially in greatest need of conservation attention to reduce collisions and into species- and life-history-related variation and correlates of building collisions, information that can help refine collision management.


Correlaciones de las Colisiones de Aves contra Edificios en Tres Países de América del Norte Resumen Las colisiones contra los edificios causan hasta mil millones de fatalidades de aves al año en los Estados Unidos y en Canadá. Sin embargo, los esfuerzos por reducir estas colisiones se beneficiarían con estudios realizados a grandes escalas espaciales en varios sitios de estudio con métodos estandarizados y considerando las variaciones relacionadas a la historia de vida y a la especie y las correlaciones de las colisiones. Abordamos estas necesidades de investigación por medio de una recolección coordinada de datos sobre las colisiones de aves contra edificios en los Estados Unidos (35), Canadá (3) y México (2). Recolectamos todos los cadáveres y los identificamos hasta especie. Después de retirar los registros de cadáveres no identificados, las especies sin estimaciones poblacionales a nivel distribución y las especies con distribuciones traslapadas en menos de diez sitios, nos quedamos con 269 cadáveres de 64 especies para el análisis. Estimamos la vulnerabilidad a colisiones para 40 especies con ≥2 fatalidades con base en la abundancia poblacional para América del Norte, el traslape de su distribución entre los sitios de estudio y el esfuerzo de muestreo. De las diez especies que identificamos como las más vulnerables a las colisiones, algunas han sido identificadas previamente (Setophaga caerulescens), y otras aparecieron por primera vez (Sitta carolinensis), posiblemente debido a que usamos una estrategia de muestreo más estandarizada que en los estudios previos. El tamaño del edificio y el área del vidrio estuvieron asociados positivamente con el número de colisiones para cinco de ocho especies con suficientes observaciones para ser analizadas independientemente. La vegetación alrededor de los edificios influyó sobre las colisiones solamente para una de esas ocho especies Catharus ustulatus). Las historias de vida pronosticaron las colisiones; el número de colisiones fue mayor para las especies migratorias, insectívoras y aquellas que habitan en las zonas boscosas. Nuestros resultados proporcionan una nueva perspectiva hacia las especies más vulnerables a las colisiones contra edificios, lo que las pone en una necesidad potencialmente mayor de atención conservacionista para reducir estas colisiones y de estudio de las variaciones relacionadas con la especie y la historia de vida y las correlaciones de las colisiones contra edificios, información que puede ayudar a refinar el manejo de colisiones.


Asunto(s)
Conservación de los Recursos Naturales , Pájaros Cantores , Animales , Canadá , México , América del Norte , Estados Unidos
19.
Curr Opin Ophthalmol ; 32(2): 92-97, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33443958

RESUMEN

PURPOSE OF REVIEW: Perimetry remains important for the diagnosis and management of glaucoma despite advances in imaging technology. The purpose of this review is to describe advances in the acquisition and analysis of visual field data and highlight novel techniques for performing perimetry. RECENT FINDINGS: Studies have focused on improving the detection of patients at highest risk of severe vision loss and the development of innovative testing strategies that allow for more frequent testing. Artificial intelligence has been utilized in research settings to improve detection and characterization of glaucomatous field damage. Furthermore, tablet-based strategies and virtual reality headsets show promise for glaucoma screening and remote monitoring of patients with glaucoma. SUMMARY: New testing strategies and research findings have improved our ability to identify patients with both paracentral and mid-peripheral visual field progression. New strategies have the potential to make visual field testing more efficient, reliable and accessible for patients with glaucoma.


Asunto(s)
Glaucoma/diagnóstico , Trastornos de la Visión/diagnóstico , Pruebas del Campo Visual/métodos , Campos Visuales/fisiología , Inteligencia Artificial , Progresión de la Enfermedad , Humanos , Trastornos de la Visión/fisiopatología
20.
Pathologica ; 113(2): 70-84, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33179614

RESUMEN

Mesenchymal tumours represent one of the most challenging field of diagnostic pathology and refinement of classification schemes plays a key role in improving the quality of pathologic diagnosis and, as a consequence, of therapeutic options. The recent publication of the new WHO classification of Soft Tissue Tumours and Bone represents a major step toward improved standardization of diagnosis. Importantly, the 2020 WHO classification has been opened to expert clinicians that have further contributed to underline the key value of pathologic diagnosis as a rationale for proper treatment. Several relevant advances have been introduced. In the attempt to improve the prediction of clinical behaviour of solitary fibrous tumour, a risk assessment scheme has been implemented. NTRK-rearranged soft tissue tumours are now listed as an "emerging entity" also in consideration of the recent therapeutic developments in terms of NTRK inhibition. This decision has been source of a passionate debate regarding the definition of "tumour entity" as well as the consequences of a "pathology agnostic" approach to precision oncology. In consideration of their distinct clinicopathologic features, undifferentiated round cell sarcomas are now kept separate from Ewing sarcoma and subclassified, according to the underlying gene rearrangements, into three main subgroups (CIC, BCLR and not ETS fused sarcomas) Importantly, In order to avoid potential confusion, tumour entities such as gastrointestinal stroma tumours are addressed homogenously across the different WHO fascicles. Pathologic diagnosis represents the integration of morphologic, immunohistochemical and molecular characteristics and is a key element of clinical decision making. The WHO classification is as a key instrument to promote multidisciplinarity, stimulating pathologists, geneticists and clinicians to join efforts aimed to translate novel pathologic findings into more effective treatments.


Asunto(s)
Sarcoma de Ewing , Sarcoma , Neoplasias de los Tejidos Blandos , Biomarcadores de Tumor/genética , Humanos , Medicina de Precisión , Sarcoma/diagnóstico , Sarcoma/genética , Neoplasias de los Tejidos Blandos/diagnóstico , Neoplasias de los Tejidos Blandos/genética , Organización Mundial de la Salud
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