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1.
Chem Rev ; 123(7): 3761-3789, 2023 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-36250763

RESUMO

Anisotropic heterostructures of colloidal nanocrystals embed size-, shape-, and composition-dependent electronic structure within variable three-dimensional morphology, enabling intricate design of solution-processable materials with high performance and programmable functionality. The key to designing and synthesizing such complex materials lies in understanding the fundamental thermodynamic and kinetic factors that govern nanocrystal growth. In this review, nanorod heterostructures, the simplest of anisotropic nanocrystal heterostructures, are discussed with respect to their growth mechanisms. The effects of crystal structure, surface faceting/energies, lattice strain, ligand sterics, precursor reactivity, and reaction temperature on the growth of nanorod heterostructures through heteroepitaxy and cation exchange reactions are explored with currently known examples. Understanding the role of various thermodynamic and kinetic parameters enables the controlled synthesis of complex nanorod heterostructures that can exhibit unique tailored properties. Selected application prospects arising from such capabilities are then discussed.

2.
J Am Chem Soc ; 146(13): 9074-9083, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38517010

RESUMO

Colloidal nanorod heterostructures consisting of multiple quantum dots within a nanorod (n-DNRs, where n is the number of quantum dots within a nanorod) are synthesized with alternating segments of CdSe "dot" and CdS "rod" via solution heteroepitaxy. The reaction temperature, time dependent ripening, and asymmetry of the wurtzite lattice and the resulting anisotropy of surface ligand steric hindrance are exploited to vary the morphology of the growing quantum dot segments. The alternating CdSe and CdS growth steps can be easily repeated to increment the dot number in unidirectional or bidirectional growth regimes. As an initial exploration of electron occupation effects on their optical properties, asymmetric 2-DNRs consisting of two dots of different lengths and diameters are synthesized and are shown to exhibit a change in color and an unusual photoluminescence quantum yield increase upon photochemical doping.

3.
Skeletal Radiol ; 53(6): 1119-1124, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38062171

RESUMO

OBJECTIVE: To determine the preferred ankle, knee, and elbow arthrography injection techniques for Society of Skeletal Radiology (SSR) members and whether more recently described techniques are gaining acceptance. We also sought to determine whether the concept of knowledge translation might explain differences between the preferred technique, year of fellowship graduation, and year the newer technique was described. MATERIALS AND METHODS: A 29-question survey was created in Qualtrics and submitted to current SSR members to determine if they perform knee, elbow, and ankle arthrography, and if so, the year of fellowship completion and preferred approaches. Survey respondents indicated the starting and ending needle tip positions for three knee, two elbow, and three ankle arthrography approaches using grids placed over provided frontal and lateral radiographs. RESULTS: Two hundred seventy-four SSR members (mean post-fellowship 13 years; range 0-38) completed the survey and performed fluoroscopic-guided knee (93%), elbow (95%), and ankle (75%) arthrography. Preferred approaches included the following: knee lateral subpatellar (43%), anterior (40%); elbow radiocapitellar (74%); ankle anterior/peritendon (70%), lateral mortise (24%). Preference of newer technique was related to fellowship graduation year and publication year for the ankle mortise (26% before, 42% after; p = 0.03) and posterior trans-triceps elbow articles (19% before, 33% after; p < 0.01). The anterior knee approach preference increased from 11% in 2008 to 40% (p ≤ 0.001). CONCLUSION: Nearly twice as many SSR members who graduated after the posterior trans-triceps and ankle mortise techniques were published prefer them for performing arthrography, possibly due to knowledge translation. The preference of the anterior knee arthrography approach has increased nearly fourfold since 2008.


Assuntos
Artrografia , Radiologia , Humanos , Artrografia/métodos , Tornozelo , Cotovelo , Injeções Intra-Articulares/métodos
4.
Small ; 19(49): e2303317, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37612820

RESUMO

Patients with viral myocarditis are at risk of sudden death and may progress to dilated cardiomyopathy (DCM). Currently, no disease-specific therapies exist to treat viral myocarditis. Here it is examined whether reconstituted, lyophilized extracellular vesicles (EVs) from platelets from healthy men and women reduce acute or chronic myocarditis in male mice. Human-platelet-derived EVs (PEV) do not cause toxicity, damage, or inflammation in naïve mice. PEV administered during the innate immune response significantly reduces myocarditis with fewer epidermal growth factor (EGF)-like module-containing mucin-like hormone receptor-like 1 (F4/80) macrophages, T cells (cluster of differentiation molecules 4 and 8, CD4 and CD8), and mast cells, and improved cardiac function. Innate immune mediators known to increase myocarditis are decreased by innate PEV treatment including Toll-like receptor (TLR)4 and complement. PEV also significantly reduces perivascular fibrosis and remodeling including interleukin 1 beta (IL-1ß), transforming growth factor-beta 1, matrix metalloproteinase, collagen genes, and mast cell degranulation. PEV given at days 7-9 after infection reduces myocarditis and improves cardiac function. MicroRNA (miR) sequencing reveals that PEV contains miRs that decrease viral replication, TLR4 signaling, and T-cell activation. These data show that EVs from the platelets of healthy individuals can significantly reduce myocarditis and improve cardiac function.


Assuntos
Cardiomiopatia Dilatada , Miocardite , Humanos , Camundongos , Masculino , Feminino , Animais , Miocárdio/metabolismo , Cardiomiopatia Dilatada/metabolismo , Imunidade Inata , Macrófagos/metabolismo
5.
J Chem Phys ; 158(24)2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37347136

RESUMO

Double heterojunction nanorods enable both electroluminescence and light harvesting capabilities within the same device structure, providing a promising platform for energy-scavenging displays and related applications. However, the efficiency of the photovoltaic mode remains modest for useful power conversion and may be challenging to improve without sacrificing performance in electroluminescence. Through a facile on-film partial ligand exchange with benzenethiol integrated into the device fabrication step, we achieve an average of more than threefold increase in power conversion efficiency while maintaining the maximum external quantum efficiency and the maximum luminance in the LED mode. The improved photovoltaic performance is mainly due to the increase in the short circuit current, which we attribute to the enhanced charge separation afforded by the partial ligand exchange. The recovery of the photoluminescence lifetime under the forward bias suggests that the hole traps introduced by benzenethiols are filled prior to reaching the voltage at which light emission begins, allowing LED performance to be maintained and possibly improved.


Assuntos
Nanotubos , Ligantes , Fenóis , Compostos de Sulfidrila
6.
Semin Musculoskelet Radiol ; 27(3): 269-282, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37230127

RESUMO

Osteochondral lesions (OCLs) in the ankle are more common than OCLs of the foot, but both share a similar imaging appearance. Knowledge of the various imaging modalities, as well as available surgical techniques, is important for radiologists. We discuss radiographs, ultrasonography, computed tomography, single-photon emission computed tomography/computed tomography, and magnetic resonance imaging to evaluate OCLs. In addition, various surgical techniques used to treat OCLs-debridement, retrograde drilling, microfracture, micronized cartilage-augmented microfracture, autografts, and allografts-are described with an emphasis on postoperative appearance following these techniques.


Assuntos
Cartilagem Articular , Fraturas de Estresse , Tálus , Humanos , Tornozelo/diagnóstico por imagem , Tornozelo/cirurgia , Cartilagem Articular/cirurgia , Tálus/patologia , Tálus/cirurgia , Artroscopia/métodos , Imageamento por Ressonância Magnética , Resultado do Tratamento
7.
Adv Health Sci Educ Theory Pract ; 28(4): 1115-1130, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-36729194

RESUMO

Researchers have long been interested in understanding how different learning approaches impact learning outcomes. Learning approaches are often conceptualized as a dichotomy of superficial and deep, and learning outcomes are typically viewed on a cognitive scale that ranges from lower- to higher-order. While there appears to be an inherent relationship between learning approach and outcomes where superficial approaches lead to lower-order learning and deep approaches result in higher-order learning, this concept is not well documented. The purpose of this study is to better understand this relationship by evaluating whether student performance on higher- and lower-order examination questions is influenced by the approach a student takes when studying. To investigate this, survey and examination data were collected from an upper-level undergraduate Human Anatomy course at the University of Cincinnati. Results indicate that, on average, students in the course favored a deep approach to learning. The impact that learning approach had on examination performance was investigated using a series of analytical approaches, which revealed that students who took a deep approach to learning performed marginally better on both higher- and lower-order examination questions in lecture and practical examination settings. These results are contextualized within the literature, which highlights the need for more research surrounding the interrelatedness and dependency of categories within both learning approaches and cognitive levels.


Assuntos
Anatomia , Avaliação Educacional , Humanos , Avaliação Educacional/métodos , Aprendizagem , Estudantes , Currículo , Anatomia/educação
8.
J Ultrasound Med ; 42(2): 409-415, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35670273

RESUMO

OBJECTIVE: We evaluated the performance of ACR TI-RADS when points for lobulated margins are applied only when the margins meet a quantified measure of margin microlobulation and not applied when nodules only demonstrate macrolobulation. METHODS: We retrospectively reviewed ultrasound and pathology records (May 01, 2018 to July 31, 2020) to find all thyroid nodules at one institution characterized as having lobulated margins using the ACR TI-RADS lexicon and subsequently undergoing fine needle aspiration (FNA). Nodule margins were evaluated to note the presence or absence of microlobulation, quantitatively defined as a protrusion with a base <2.5 mm in length. The impact to detection of malignant nodules and avoidance of benign FNA when margin points for lobulation were added only when microlobulated was analyzed. RESULTS: 58 of 516 thyroid nodules undergoing US-guided FNA were classified as lobulated, comprising the study population. 21 (36.2%) had microlobulated margins, with 12 of the 21 (57.1%) being malignant. Comparatively, of the 37 nodules showing only macrolobulated margins without microlobulation, only 2 (5.4%) were malignant (P < .0001). For 53 nodules ≥10 mm, 15 (28.3%) benign nodules would not have met size criteria for FNA had points for margins not been applied when only showing macrolobulation, whereas all 10 malignant nodules would still have been sampled. CONCLUSION: Adding two points to the ACR TI-RADS score for lobulated thyroid nodules should only apply when microlobulations are present.


Assuntos
Nódulo da Glândula Tireoide , Humanos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/patologia , Estudos Retrospectivos , Biópsia por Agulha Fina , Ultrassonografia
9.
Nano Lett ; 22(23): 9500-9506, 2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36459088

RESUMO

Despite recent rapid advances in improving quantum dot light-emitting diodes, many fundamental aspects of the device operating mechanism remain unresolved. Through transient electroluminescence and time-resolved photoluminescence measurements, the effects of offset voltage on charging and charge transport are examined. First, capacitive charging occurs with a time constant of ∼500 ns, followed by electron transport through quantum dots with a mobility of ∼10-5 cm2 V-1 s-1. Hole injection then initiates an electroluminescence rise that is independent of offset voltage. The photoluminescence lifetime is also unaffected by the offset voltage, indicating no injection of charges into the quantum dots or on their surfaces prior to the voltage pulse. A slower equilibration to steady-state electroluminescence is dependent on the offset voltage, indicative of another charging process. Elemental mapping shows that ZnO deposition from solution can lead to the diffusion of charged species into the quantum dot layer, which may cause the slower process.

10.
Fungal Genet Biol ; 160: 103697, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35472450

RESUMO

Cryptococcus neoformans, a basidiomycete yeast, causes lethal meningitis in immunocompromised individuals. The ability of C. neoformans to proliferate at 37°C is essential for virulence. We identified anillin-like protein, CnBud4, as essential for proliferation of C. neoformans at 37°C and for virulence in a heterologous host Galleria mellonella at 25°C. C. neoformans cells lacking CnBud4 were inviable at 25°C in the absence of active calcineurin and were hypersensitive to membrane stress and an anti-fungal agent fluconazole, phenotypes previously described for C. neoformans mutants lacking septins. CnBud4 localized to the mother-bud neck during cytokinesis in a septin-dependent manner. In the absence of CnBud4, septin complex failed to transition from a collar-like single ring to the double ring during cytokinesis. In an ascomycete yeast, Saccharomyces cerevisiae, the anillin-like homologue ScBud4 participates in the organization of the septin ring at the mother-bud neck and plays an important role in specifying location for new bud emergence, known as axial budding pattern. In contrast to their role in S. cerevisiae, neither septins nor CnBud4 were needed to direct the position of the new bud in C. neoformans, suggesting that this function is not conserved in basidiomycetous yeasts. Our data suggest that the requirement of CnBud4 for growth at 37°C and pathogenicity in C. neoformans is based on its conserved role in septin complex organization.


Assuntos
Temperatura Corporal , Proteínas Contráteis , Cryptococcus neoformans , Criptococose/microbiologia , Cryptococcus neoformans/crescimento & desenvolvimento , Cryptococcus neoformans/patogenicidade , Interações entre Hospedeiro e Microrganismos , Humanos , Saccharomyces cerevisiae , Proteínas de Saccharomyces cerevisiae , Septinas/metabolismo
11.
Cell Mol Life Sci ; 78(8): 3817-3851, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33580835

RESUMO

Cells use mitophagy to remove dysfunctional or excess mitochondria, frequently in response to imposed stresses, such as hypoxia and nutrient deprivation. Mitochondrial cargo receptors (MCR) induced by these stresses target mitochondria to autophagosomes through interaction with members of the LC3/GABARAP family. There are a growing number of these MCRs, including BNIP3, BNIP3L, FUNDC1, Bcl2-L-13, FKBP8, Prohibitin-2, and others, in addition to mitochondrial protein targets of PINK1/Parkin phospho-ubiquitination. There is also an emerging link between mitochondrial lipid signaling and mitophagy where ceramide, sphingosine-1-phosphate, and cardiolipin have all been shown to promote mitophagy. Here, we review the upstream signaling mechanisms that regulate mitophagy, including components of the mitochondrial fission machinery, AMPK, ATF4, FoxOs, Sirtuins, and mtDNA release, and address the significance of these pathways for stress responses in tumorigenesis and metastasis. In particular, we focus on how mitophagy modulators intersect with cell cycle control and survival pathways in cancer, including following ECM detachment and during cell migration and metastasis. Finally, we interrogate how mitophagy affects tissue atrophy during cancer cachexia and therapy responses in the clinic.


Assuntos
Carcinogênese/metabolismo , Mitocôndrias/metabolismo , Mitofagia , Neoplasias/metabolismo , Animais , Carcinogênese/patologia , Humanos , Mitocôndrias/patologia , Dinâmica Mitocondrial , Metástase Neoplásica/patologia , Neoplasias/patologia
12.
Semin Musculoskelet Radiol ; 26(3): 203-215, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35654090

RESUMO

Postoperative ankle imaging requires knowledge of the underlying surgical techniques, the usefulness of various imaging modalities, as well as an appreciation for the desired clinical outcomes. Surgical procedures discussed in this article are tibiotalar fracture fixation, tibiotalar, subtalar, and tibiotalocalcaneal arthrodesis, total ankle arthroplasty, talar osteochondral lesion repair and grafting, lateral ligamentous repair and reconstruction, and peroneal and Achilles tendon repair and reconstruction. Imaging can play a vital role in determining if the expected outcome has been achieved and identifying complications, with particular emphasis placed on the use of radiographs, computed tomography (including weight-bearing), magnetic resonance imaging, and ultrasonography.


Assuntos
Tornozelo , Artroplastia de Substituição do Tornozelo , Articulação do Tornozelo/diagnóstico por imagem , Articulação do Tornozelo/cirurgia , Artrodese/métodos , Humanos , Radiografia
13.
Langenbecks Arch Surg ; 407(8): 3311-3314, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35927523

RESUMO

PURPOSE: The purpose of this paper is to showcase a fully stapled approach to creating a gastrojejunostomy during a robot-assisted Roux-en-Y gastric bypass. METHODS: We utilize two robotic 12-mm ports, two robotic 8-mm ports, and one 8-mm assistant port. The tools used are a fenestrated bipolar forceps, vessel sealer, cadiere grasper, needle driver, and a robotic stapler. After the partial gastrectomy, the roux limb is brought up to the gastric pouch where monopolar scissors are used to create a gastrotomy and enterotomy. The gastrotomy is made just above the staple line of the gastric pouch. The enterotomy is created 2 cm distal to the roux limb's staple line. The stapler is inserted into both the gastrotomy and enterotomy to create the common channel. A 2-0 vicryl suture is used to place four interrupted sutures across the remaining enterotomy in full thickness bites. An endoscope or Visigi bougie is advanced across the anastomosis into the roux limb before the final suture. The tails of the most lateral and medial sutures are grasped and lifted towards the abdominal wall. The stapler is advanced over the approximated enterostomy while holding tension with the suture tails. The stapler is fired transversely across the suture line to seal the gastrojejunostomy. The staple line may be oversewn with silk sutures. A leak test is performed prior to completing the reconstruction with the jejunojejunostomy. CONCLUSIONS: A fully stapled technique of anastomosis creation may reduce operative time, standardizes the process for reproducibility, and increases consistency across operators and patients.


Assuntos
Derivação Gástrica , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Derivação Gástrica/métodos , Reprodutibilidade dos Testes , Laparoscopia/métodos
14.
Biochem Soc Trans ; 49(1): 29-39, 2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33439256

RESUMO

Kinetoplastid parasites have essential organelles called glycosomes that are analogous to peroxisomes present in other eukaryotes. While many of the processes that regulate glycosomes are conserved, there are several unique aspects of their biology that are divergent from other systems and may be leveraged as therapeutic targets for the treatment of kinetoplastid diseases. Glycosomes are heterogeneous organelles that likely exist as sub-populations with different protein composition and function in a given cell, between individual cells, and between species. However, the limitations posed by the small size of these organelles makes the study of this heterogeneity difficult. Recent advances in the analysis of small vesicles by flow-cytometry provide an opportunity to overcome these limitations. In this review, we describe studies that document the diverse nature of glycosomes and propose an approach to using flow cytometry and organelle sorting to study the diverse composition and function of these organelles. Because the cellular machinery that regulates glycosome protein import and biogenesis is likely to contribute, at least in part, to glycosome heterogeneity we highlight some ways in which the glycosome protein import machinery differs from that of peroxisomes in other eukaryotes.


Assuntos
Kinetoplastida/citologia , Microcorpos/fisiologia , Animais , Kinetoplastida/genética , Kinetoplastida/metabolismo , Kinetoplastida/ultraestrutura , Microcorpos/metabolismo , Peroxissomos/metabolismo , Transporte Proteico , Proteínas de Protozoários/metabolismo
15.
BMC Geriatr ; 21(1): 165, 2021 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-33676401

RESUMO

BACKGROUND: Rehabilitation interventions are frequently cited as key in supporting frail older people's recovery following periods of decompensation and acute ill-health. Clinicians are required to make decisions about a patient's potential to respond to rehabilitation. 'Rehabilitation potential' decisions can determine access to services. In acute settings clinicians have limited time to assess and work with patients, families and carers. The complexities of ageing, recovery, rehabilitation and frailty may not be fully appreciated. This study aimed to explore multiple perspectives of the concept of rehabilitation potential and how it is assessed in older people living with frailty in the acute healthcare setting. METHODS: Five focus groups with a purposive sample of 28 participants which included clinicians and members of the public were conducted. Analysis comprised a thematic approach using the Framework method. RESULTS: Rehabilitation potential was found to encapsulate a complex decision-making process where clinicians judged an individual's ability to benefit from and participate in targeted rehabilitation. They asked, "Will it work?", "Is it wanted?" and "Is it available?" In order to predict who would benefit from rehabilitation interventions, clinicians assessed a range of holistic clinical and non-clinical factors. An iterative approach to assessment delivered by a multi-disciplinary team, centred around patient and carer needs and wants was needed to accommodate complexity. Participants believed that everyone had some form of potential but this was dependent on availability of rehabilitation resources and conceptualisations of frailty and rehabilitation. Tensions between iterative approaches to rehabilitation potential assessment and the realities of rapid decision making in the acute hospital setting were found. CONCLUSION: Rehabilitation potential decisions involve a complex process of multidisciplinary decision-making and prognostication on the likely outcome and benefit from rehabilitation programmes. These findings lay the foundation for developing structured approaches to rehabilitation potential decision making tools and guidance.


Assuntos
Fragilidade , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Cuidadores , Grupos Focais , Fragilidade/diagnóstico , Humanos , Pesquisa Qualitativa
16.
Public Health ; 197: 11-18, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34271270

RESUMO

OBJECTIVES: Falls in older adults cause significant morbidity and mortality and incur cost to health and care services. The Falls Management Exercise (FaME) programme is a 24-week intervention for older adults that, in clinical trials, improves balance and functional strength and leads to fewer falls. Similar but more modest outcomes have been found when FaME is delivered in routine practice. Understanding the degree to which the programme is delivered with fidelity is important if 'real-world' delivery of FaME is to achieve the same magnitude of outcome as in clinical trials. The objective of this study was to examine the implementation fidelity of FaME when delivered in the community to inform quality improvement strategies that maximise programme effectiveness. STUDY DESIGN: A mixed methods implementation study of FaME programme delivery. METHODS: Data from programme registers, expert observations of FaME classes, and semistructured interviews with FaME instructors were triangulated using a conceptual framework for implementation fidelity. Quantitative data were analysed using descriptive statistics. Interviews were transcribed verbatim and analysed using thematic analysis. RESULTS: In total, 356 participants enrolled on 29 FaME programmes, and 143 (40%) participants completed at least 75% of the classes within a programme. Observations showed that 72%-78% of programme content was delivered, and 80%-84% quality criteria were met. Important content that was most often left out included home exercises, Tai Chi moves, and floor work, whereas quality items most frequently missed out included asking about falls in the previous week, following up attendance absence and explaining the purpose of exercises. Only 24% of class participants made the expected strength training progression. Interviews with FaME instructors helped explain why elements of programme content and quality were not delivered. Strategies for improving FaME delivery were established and helped to maintain quality and fidelity. CONCLUSIONS: FaME programmes delivered in the 'real world' can be implemented with a high degree of fidelity, although important deviations were found. Facilitation strategies could be used to further improve programme fidelity and maximise participant outcomes.


Assuntos
Exercício Físico , Treinamento Resistido , Idoso , Terapia por Exercício , Humanos , Avaliação de Programas e Projetos de Saúde
17.
Int J Mol Sci ; 22(16)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34445539

RESUMO

BACKGROUND: Myocarditis is an inflammatory heart disease caused by viral infections that can lead to heart failure, and occurs more often in men than women. Since animal studies have shown that myocarditis is influenced by sex hormones, we hypothesized that endocrine disruptors, which interfere with natural hormones, may play a role in the progression of the disease. The human population is exposed to the endocrine disruptor bisphenol A (BPA) from plastics, such as water bottles and plastic food containers. METHODS: Male and female adult BALB/c mice were housed in plastic versus glass caging, or exposed to BPA in drinking water versus control water. Myocarditis was induced with coxsackievirus B3 on day 0, and the endpoints were assessed on day 10 post infection. RESULTS: We found that male BALB/c mice that were exposed to plastic caging had increased myocarditis due to complement activation and elevated numbers of macrophages and neutrophils, whereas females had elevated mast cell activation and fibrosis. CONCLUSIONS: These findings show that housing mice in traditional plastic caging increases viral myocarditis in males and females, but using sex-specific immune mechanisms.


Assuntos
Infecções por Coxsackievirus/complicações , Enterovirus Humano B/patogenicidade , Abrigo para Animais/estatística & dados numéricos , Miocardite/patologia , Plásticos/efeitos adversos , Animais , Infecções por Coxsackievirus/virologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Miocardite/etiologia , Miocardite/virologia , Fatores Sexuais
18.
BMC Med Res Methodol ; 20(1): 46, 2020 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-32106827

RESUMO

BACKGROUND: Trials are at risk of contamination bias which can occur when participants in the control group are inadvertently exposed to the intervention. This is a particular risk in rehabilitation studies where it is easy for trial interventions to be either intentionally or inadvertently adopted in control settings. The Falls in Care Homes (FinCH) trial is used in this paper as an example of a large randomised controlled trial of a complex intervention to explore the potential risks of contamination bias. We outline the FinCH trial design, present the potential risks from contamination bias, and the strategies used in the design of the trial to minimise or mitigate against this. The FinCH trial was a multi-centre randomised controlled trial, with embedded process evaluation, which evaluated whether systematic training in the use of the Guide to Action Tool for Care Homes reduced falls in care home residents. Data were collected from a number of sources to explore contamination in the FinCH trial. Where specific procedures were adopted to reduce risk of, or mitigate against, contamination, this was recorded. Data were collected from study e-mails, meetings with clinicians, research assistant and clinician network communications, and an embedded process evaluation in six intervention care homes. During the FinCH trial, there were six new falls prevention initiatives implemented outside the study which could have contaminated our intervention and findings. Methods used to minimise contamination were: cluster randomisation at the level of care home; engagement with the clinical community to highlight the risks of early adoption; establishing local collaborators in each site familiar with the local context; signing agreements with NHS falls specialists that they would maintain confidentiality regarding details of the intervention; opening additional research sites; and by raising awareness about the importance of contamination in research among participants. CONCLUSION: Complex rehabilitation trials are at risk of contamination bias. The potential for contamination bias in studies can be minimized by strengthening collaboration and dialogue with the clinical community. Researchers should recognise that clinicians may contaminate a study through lack of research expertise.


Assuntos
Prevenção de Acidentes/métodos , Acidentes por Quedas/prevenção & controle , Terapia por Exercício/métodos , Instituição de Longa Permanência para Idosos/estatística & dados numéricos , Casas de Saúde/estatística & dados numéricos , Idoso , Humanos , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco
19.
J Neurooncol ; 144(3): 591-601, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31407129

RESUMO

BACKGROUND: National guidelines recommend maximal safe resection of low-grade and high-grade oligodendrogliomas. However, there is no level 1 evidence to support these guidelines, and recent retrospective studies on the topic have yielded mixed results. OBJECTIVE: To assess the association between extent of resection (EOR) and survival for oligodendrogliomas in the general U.S. METHODS: Cases diagnosed between 2004 and 2013 were selected from the Surveillance, Epidemiology, and End-Results (SEER) Program and retrospectively analyzed for treatment, prognostic factors, and survival times. Cases that did not undergo tumor de-bulking surgery (e.g. no surgery or biopsy alone) were compared to subtotal resection (resection) and gross-total resection (GTR). The primary end-points were overall survival (OS) and cause-specific survival (CSS). An external validation cohort with 1p/19q-codeleted tumors was creating using the TCGA and GSE16011 datasets. RESULTS: 3135 Cases were included in the final analysis. The 75% survival time (75ST) and 5-year survival rates were 47 months and 70.8%, respectively. Subtotal resection (STR, 75ST = 50 months) and GTR (75ST = 61 months) were associated with improved survival times compared to cases that did not undergo surgical debulking (75ST = 20 months, P < 0.001 for both), with reduced hazard ratios (HRs) after controlling for other factors (HR 0.81 [0.68-0.97] and HR 0.65 [0.54-0.79], respectively). GTR was associated with improved OS in both low-grade and anaplastic oligodendroglioma subgroups (HR 0.74 [0.58-0.95], HR 0.60 [0.44-0.82], respectively) while STR fell short of significance in the subgroup analysis. All findings were corroborated by multivariable analysis of CSS and externally validated in a cohort of patients with 1p19q-codeleted tumors. CONCLUSION: Greater EOR is associated with improved survival in oligodendrogliomas. Our findings in this U.S. population-based cohort support national guidelines.


Assuntos
Neoplasias Encefálicas/mortalidade , Procedimentos Neurocirúrgicos/mortalidade , Oligodendroglioma/mortalidade , Adolescente , Adulto , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/métodos , Oligodendroglioma/epidemiologia , Oligodendroglioma/patologia , Oligodendroglioma/cirurgia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Estados Unidos/epidemiologia , Adulto Jovem
20.
Semin Cancer Biol ; 47: 110-124, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28450176

RESUMO

Mitophagy is a selective mode of autophagy in which mitochondria are specifically targeted for degradation at the autophagolysosome. Mitophagy is activated by stresses such as hypoxia, nutrient deprivation, DNA damage, inflammation and mitochondrial membrane depolarization and plays a role in maintaining mitochondrial integrity and function. Defects in mitophagy lead to mitochondrial dysfunction that can affect metabolic reprogramming in response to stress, alter cell fate determination and differentiation, which in turn affects disease incidence and etiology, including cancer. Here, we discuss how different mitophagy adaptors and modulators, including Parkin, BNIP3, BNIP3L, p62/SQSTM1 and OPTN, are regulated in response to physiological stresses and deregulated in cancers. Additionally, we explore how these different mitophagy control pathways coordinate with each other. Finally, we review new developments in understanding how mitophagy affects stemness, cell fate determination, inflammation and DNA damage responses that are relevant to understanding the role of mitophagy in cancer.


Assuntos
Mitocôndrias/genética , Mitocôndrias/metabolismo , Mitofagia , Neoplasias/genética , Neoplasias/metabolismo , Adaptação Biológica , Animais , Autofagia , Dano ao DNA , Metabolismo Energético , Humanos , Inflamação/genética , Inflamação/metabolismo , Transdução de Sinais , Estresse Fisiológico
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