Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 31
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Util Policy ; 82: 101550, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37041882

RESUMO

The outbreak of COVID-19 led to restrictions on movements and activities, which presented a serious challenge to the resilience of the water sector. It is essential to understand how successfully water companies responded to this unprecedented event so effective plans can be built for future disruptive events. This study aimed to evaluate how the water sectors in the UK and Ireland were affected from a holistic sustainability and resilience-based perspective. Using pre-COVID data for 18 indicators of company performance and comparing them to the first year of the pandemic, the direction and magnitudes of change varied across companies. Financial indicators were significantly negatively affected, with interest cover ratio, post-tax return on regulated equity, and operating profit, exhibiting the greatest average declines of 21%, 21%, and 18%, respectively, a trend that would be dangerous to provisions and company operations if continued. Despite this, service and environmental indicators improved during the first year of the pandemic, exemplified by unplanned outage, risk of sewer storm flooding, and water quality compliance risk decreasing by a mean average of 37%, 32%, and 27%, respectively. Analysis using the Hicks-Moorsteen Productivity Index concluded that average productivity increased by 35%. The results suggest that the water sector was relatively resilient to the COVID-19 pandemic in terms of services, but adverse effects may have manifested in a deteriorated financial position that could exacerbate future challenges arising from exogenous pressures such as climate change. Specific advice for the UK water sector is to scrutinize non-critical spending, such as shareholder payments, during periods of economic downturn to ensure essential capital projects can be carried out. Although results are temporal and indicator selection sensitive, we recommend that policy, regulation, and corporate culture embrace frameworks that support long-term resilience to since the relative success in response to COVID-19 does not guarantee future success against differing challenges. This study generates a timely yet tentative insight into the diverse performance of the water sector during the pandemic, pertinent to the water industry, regulators, academia, and the public.

2.
J Clin Sleep Med ; 18(9): 2273-2279, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35499278

RESUMO

STUDY OBJECTIVES: Continuous positive airway pressure (CPAP) improves sleepiness in patients with obstructive sleep apnea, but some patients remain sleepy. The objective of this study was to identify determinants that are associated with improvements in self-reported sleepiness in patients with obstructive sleep apnea on CPAP therapy. METHODS: A retrospective cohort study was performed in a clinic-based population to determine which variables contributed to the improvement in the Epworth Sleepiness Scale (ESS) in patients on CPAP therapy for OSA, stratified by baseline ESS score (< 11 or ≥ 11). Variables associated with ESS scores normalizing with CPAP were also assessed. RESULTS: Patients with a baseline high ESS score showed greater improvements in the ESS with CPAP. When looking at interactions between baseline ESS classification and changes in ESS, we found that a higher apnea-hypopnea index was only associated with improvement in the ESS among patients with a high baseline ESS. Other assessed factors or covariates were not significantly different. When looking at ESS normalization, we found that female sex and lower body mass index were associated with a lower likelihood of ESS normalization. The difference in the rate of ESS normalization between females and males was higher with more days on CPAP. CONCLUSIONS: Of all the assessed factors and covariates, only the apnea-hypopnea index was associated with the change in the ESS differently in patients with a high or normal baseline ESS score. ESS normalization rates were lower in females than in males, and this disparity was amplified by more days on CPAP. CITATION: Scharf MT, Zhang P, Walker NA, et al. Sex differences in Epworth Sleepiness Scale normalization with continuous positive airway pressure. J Clin Sleep Med. 2022;18(9):2273-2279.


Assuntos
Pressão Positiva Contínua nas Vias Aéreas , Apneia Obstrutiva do Sono , Feminino , Humanos , Masculino , Estudos Retrospectivos , Caracteres Sexuais , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/terapia , Sonolência , Resultado do Tratamento
3.
Primates ; 62(6): 887-896, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34541622

RESUMO

Habitat fragmentation is one of the major types of anthropogenic change, though fragmented landscapes predate human intervention. At present, the Central Highlands of Madagascar are covered by extensive grasslands interspersed with small discrete forest patches of unknown antiquity. Ankafobe, an actively protected site, comprises two such fragments of 12 and 30 ha, respectively, known to harbor three lemur species and other endemic wildlife. At this location, we conducted a survey of resident Goodman's mouse lemurs, Microcebus lehilahytsara, to determine baseline behavioral and ecological conditions for this isolated population. By studying primates in forest fragments, investigators can characterize the effects of shrinking habitats and decreasing connectivity on species diversity and survival, thus providing a glimpse into the potential resilience of species in the face of anthropogenic disturbance. Investigating the behavioral ecology of Goodman's mouse lemurs across their geographic range could help us understand their metabolic and ecological flexibility and predict species long-term survival prospects. We conducted night transect walks, using capture techniques and telemetry, to track eight radio-collared individuals. Preliminary density estimates based on a limited number of sightings (n = 18) were 2.19 ind/ha, and home range assessments ranged between 0.22 and 3.67 ha. Mouse lemurs traveled an average of 425 m nightly during the 5-h tracking periods and primarily fed on fruits of the mistletoe Bakerella clavata. The finding that Goodman's mouse lemurs apparently thrive in the seasonally cold and arid forest fragments in the Central Highlands indicates that they may be among the most tolerant and adaptable lemur species in Madagascar. These results point towards an exciting research program that focuses on ecological tolerance as a mechanism for long-term species survival.


Assuntos
Cheirogaleidae , Lemur , Animais , Ecossistema , Florestas , Madagáscar
4.
J Environ Manage ; 300: 113613, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34560465

RESUMO

The collection, treatment and disposal of wastewater is estimated to consume more than 2% of the world's electrical energy, whilst some wastewater treatment plants (WWTPs) can account for over 20% of electrical consumption within municipalities. To investigate areas to improve wastewater treatment, international benchmarking on energy (electrical) intensity was conducted with the indicator kWh/m3 and a quality control of secondary treatment or better for ≥95% of treated volume. The core sample included 321 companies from 31 countries, however, to analyse regional differences, 11 countries from an external sample made up of various studies of WWTPs was also used in places. The sample displayed a weak-negative size effect with energy intensity, although Kruskal-Wallace analyses showed there was a significant difference between the size of groups (p-value of 0.015), suggesting that as companies get larger; they consume less electricity per cubic metre of wastewater treated. This relationship was not completely linear, as mid to large companies (10,001-100,000 customers) had the largest average consumption of 0.99 kWh/m3. In the regional analysis, EU states had the largest average kWh/m3 with 1.18, which appeared a result of the higher wastewater effluent standards of the region. This was supported by Denmark being the second largest average consuming country (1.35 kWh/m3), since it has some of strictest effluent standards in the world. Along with energy intensity, the associated greenhouse gas (GHG) emissions were calculated enabling the targeting of regions for improvement in response to climate change. Poland had the highest carbon footprint (0.91 kgCO2e/m3) arising from an energy intensity of 0.89 kWh/m3; conversely, a clean electricity grid can affectively mitigate wastewater treatment inefficiencies, exemplified by Norway who emit just 0.013 kgCO2e per cubic meter treated, despite consuming 0.60 kWh/m3. Finally, limitations to available data and the analysis were highlighted from which, it is advised that influent vs. effluent and net energy, as opposed to gross, data be used in future analyses. The large international sample size, energy data with a quality control, GHG analysis, and specific benchmarking recommendations give this study a novelty which could be of use to water industry operators, benchmarking organisations, and regulators.


Assuntos
Eliminação de Resíduos Líquidos , Purificação da Água , Benchmarking , Pegada de Carbono , Águas Residuárias
5.
J Environ Manage ; 287: 112317, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33714737

RESUMO

The provision of fundamental services by water and sewage companies (WaSCs) requires substantial energy and material inputs. A sustainability assessment of these companies requires a holistic evaluation of both performance and efficiency. The Hicks-Moorsteen productivity index was applied to 12 WaSCs in the United Kingdom (UK) over a 6-year period to benchmark their sustainability, based on eight approaches using different input and output variables for efficiency assessment. The choice of variables had a major influence on the ranking and perceived operational efficiency among WaSCs. Capital expenditure (utilised as part of total expenditure) for example, is an important input for tracking company operations however, potential associated efficiency benefits can lag investment, leading to apparent poor short-term performance following capital expenditure. Furthermore, water supplied and wastewater treated was deemed an unconstructive output from a sustainability perspective since it contradicts efforts to improve sustainability through reduced leakage and consumption per capita. Customer satisfaction and water quality measures are potential suitable alternatives. Despite these limitations, total expenditure and water supplied and wastewater treated were used alongside customer satisfaction and self-generated renewable energy for a holistic sustainability assessment within a small sample. They indicated the UK water sector has improved in productivity by 1.8% on average for 2014-18 and still had room for improvement, as a technical decline was evident for both the best and worst performers. Collectively the sample's production frontier was unchanged but on average companies moved 2.1% closer to it, and further decomposition of productivity revealed this was due to improvements in economies of scale and scope. Careful selection of appropriate input and output variables for efficiency benchmarking across water companies is critical to align with sustainability objectives and to target future investment and regulation within the water sector.


Assuntos
Benchmarking , Água , Eficiência , Reino Unido , Águas Residuárias
6.
JRSM Open ; 11(7): 2054270420921066, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32685179

RESUMO

Head and neck carcinoma of unknown primary accounts for approximately 1-5% of all head and neck cancers and presents a genuine diagnostic and therapeutic dilemma. Despite advanced investigations, the primary tumour location remains unknown in up to 40% of these cases. Transoral robotic surgery presents a viable diagnostic and therapeutic option in these patients. This surgical innovation alongside advances in the understanding of head and neck cancer biology means that a multidisciplinary approach in the management of these complex patients is of utmost importance to ensure optimal therapeutic outcomes.

7.
J Environ Manage ; 269: 110810, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32561014

RESUMO

Water companies consume up to 8% of global energy demand, at billions of dollars' cost. Benchmarking of performance between utilities can facilitate improvements in efficiency; however, inconsistencies in benchmarking practices may obscure pathways to improvement. The aspiration was to conduct an unbiased efficiency comparison within a sample of 17 water only companies and water and sewerage companies in England and Wales, accounting for exogenous factors, whilst evaluating the accuracy of common proxies. Proxies were tested, and bias-corrected energy and economic efficiency scores with explanatory factors were analysed using a double-bootstrap data envelopment method. Bias correction altered the rankings of two companies for energy efficiency only. Results imply that on average, companies could reduce energy inputs by 91.7%, and economic inputs by 92.3%, which was symptomatic of the companies specialising in drinking water supply considerably out-performing combined water and sewerage companies. As exogenous influences were likely to be a factor in the disparity between the companies, five indicators were evaluated. The results varied but of note were average pumping head height, which displayed a significant negative effect for energy efficiency, and proportion of water passing through the largest four treatment works, that exhibited a significant negative effect on economic efficiency. Within proxy performance, population served for drinking water was an adequate replacement for volume of water produced, with results matching the core variable apart from two companies changing rank in the economic analysis. Conversely, length of water mains performed poorly when replacing capital expenditure, implying companies were on average 12.6% more efficient, resulting in ten companies changing their rank and causing explanatory variables to contradict direction of influence and significance. The findings contribute new insights for benchmarking, including how different types of water companies perform under bias-correcting methods, the degree to which factors affect efficiency and how appropriate some proxies are.


Assuntos
Eficiência , Água , Inglaterra , País de Gales , Abastecimento de Água
8.
Sleep Breath ; 24(4): 1759-1765, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31938991

RESUMO

PURPOSE: The Epworth sleepiness scale (ESS) is a widely used tool which has been validated as a measure of sleepiness. However, the scores within individual patients referred for clinical sleep services vary considerably which may limit the clinical use of the ESS. We sought to determine the test-retest reliability of the ESS if scores were classified as either normal or sleepy. METHODS: We measured the ESS in patients presenting to our sleep center at a clinical visit and again when a sleep study was done. Demographic and clinical information was extracted from the electronic medical record. RESULTS: Average ESS scores were similar on 2 administrations, mean (SD) of 9.8 (5.4) and 10.2 (6.2). Bland-Altman analysis showed upper and lower limits of agreement of 7.5 and - 6.7, respectively. No demographic or clinical variables were identified which contributed to the intra-individual variability. Of the patients who presented with an initial ESS < 11, 80% had a second ESS < 11. Of the patients who presented with an initial ESS ≥ 11, 89% had a second ESS ≥ 11. Cohen's kappa for the two administrations of the ESS was 0.67 (95% CI of 0.51-0.83). Using previously published reports, we calculated Cohen's kappa for polysomnographic determination of the apnea-hypopnea index (AHI) with values ranging from 0.26 to 0.69. CONCLUSIONS: Individual ESS scores varied considerably within individual patients, but with classification into either normal or sleepy, the test-retest reliability was substantial and in line with other clinical measures including polysomnographic determination of the AHI.


Assuntos
Sonolência , Inquéritos e Questionários/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos
9.
Plant Dis ; 103(8): 2010-2014, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31140925

RESUMO

A multiplex end-point polymerase chain reaction (PCR) assay was developed for identifying the three-fungal species in the genus Ophiosphaerella that cause spring dead spot (SDS), a devastating disease of bermudagrass. These fungi are difficult to identify by morphology because they seldom produce pseudothecia. To achieve species-specific diagnosis, three pairs of primers were designed to identify fungal isolates and detect the pathogen in infected roots. The internal transcribed spacer region, the translation elongation factor 1-α, and the RNA polymerase II second-largest subunit were selected as targets and served as templates for the design of each primer pair. To achieve uniform melting temperatures, three to five random nucleotide extensions (flaps) were added to the 5' terminus of some of the designed specific primers. Temperature cycling conditions and PCR components were standardized to optimize specificity and sensitivity of the multiplex reaction. Primers were tested in multiplex on DNA extracted from axenic fungal cultures and from field-collected infected and uninfected roots. A distinct amplicon was produced for each Ophiosphaerella sp. tested. The DNA from Ophiosphaerella close relatives and other common bermudagrass pathogens did not amplify during the multiplex assay. Metagenomic DNA from infected bermudagrass produced species-specific amplicons while DNA extracted from noninfected roots did not. This multiplex end-point PCR approach is a sensitive and specific molecular technique that allows for correct identification of SDS-associated Ophiosphaerella spp. from field-collected roots.


Assuntos
Ascomicetos , Cynodon , Reação em Cadeia da Polimerase Multiplex , Ascomicetos/genética , Cynodon/microbiologia , Estações do Ano , Especificidade da Espécie
10.
J Environ Manage ; 241: 363-373, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31026725

RESUMO

For water companies, benchmarking their performance relative to other companies can be an effective way to identify the scope for efficiency gains to be made through infrastructure investment and operational improvements. However, a key limitation to benchmarking is the confounding effect of exogenous factors, which may not be factored in to benchmarking methodologies. The purpose of this study was to provide an unbiased comparison of efficiency across a sample of water and sewage companies, accounting for important exogenous factors. Bias-corrected economic and environmental efficiency estimates with explanatory factors were evaluated for a sample of 13 water and sewage companies in the UK and Ireland, using a double-bootstrap data envelopment analysis (DEA) approach. Bias correction for economic and environmental efficiency changed the rankings of nine and eight companies, respectively. On average, companies could reduce economic inputs by 19% and carbon outputs by 16% if they performed at the efficiency frontier. Variables explaining efficiency were: source of water, leakage rate, per capita consumption and population density. Population density showed statistical significance with both economic (p-value 0.002) and environmental (p-value 0.001) efficiency. Consequently, a rurality factor was defined for each company's operational area, which was then regressed against normalised water company performance data. More rural water companies spend more per property (R2 of 0.633), in part reflecting a larger number of smaller sewage treatment works serving rural populations (R2 of 0.823). These findings provide new insight into methods for benchmarking, and factors affecting, water company efficiency, pertinent for both regulators and water companies.


Assuntos
População Rural , Água , Eficiência , Eficiência Organizacional , Humanos , Irlanda , Reino Unido
11.
Plant Dis ; 103(1): 89-94, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30398944

RESUMO

Twenty-eight isolates of Sclerotinia homoeocarpa, causal agent of dollar spot disease in turf, were assessed for fungicide hormesis at sublethal concentrations of thiophanate-methyl (T-methyl). Each isolate was grown in corn meal agar amended with 11 concentrations of T-methyl (30,500 to 0.047 µg/liter), and the area of mycelial growth was determined relative to the control. Three replicates were used per concentration, and the experiment was repeated three to five times for each isolate. Reference isolates (EC50 > 20 µg/liter), with no prior history of T-methyl exposure, were highly sensitive and not stimulated by low doses. Likewise, no stimulation was observed in two highly sensitive isolates (EC50 > 30 µg/liter) that had been preconditioned by exposure to T-methyl, or in four T-methyl-tolerant isolates. Seventeen (81%) preconditioned T-methyl-tolerant isolates (EC50 = 294 to1,550 µg/liter) had statistically significant growth stimulation, in the range of 2.8 to 19.7% relative to the control. These results support that hormesis (low-dose stimulation, high-dose inhibition) is a common dose response in preconditioned S. homoeocarpa, particularly in response to subtoxic doses of T-methyl.


Assuntos
Ascomicetos , Fungicidas Industriais , Farmacorresistência Fúngica , Hormese , Tiofanato
12.
J Nematol ; 48(2): 87-94, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27418701

RESUMO

Summer-active (continental) and summer-dormant (Mediterranean) tall fescue morphotypes are each adapted to different environmental conditions. Endophyte presence provides plant parasitic nematode resistance, but not with all endophyte strains and cultivar combinations. This study sought to compare effects of four nematode genera on continental and Mediterranean cultivars infected with common toxic or novel endophyte strains. A 6-mon greenhouse study was conducted with continental cultivars, Kentucky 31 (common toxic) and Texoma MaxQ II (novel endophyte) and the Mediterranean cultivar Flecha MaxQ (novel endophyte). Endophyte-free plants of each cultivar were controls. Each cultivar × endophyte combination was randomly assigned to a control, low or high inoculation rate of a mixed nematode culture containing stunt nematodes (Tylenchorhynchus spp.), ring nematodes (Criconemella spp.), spiral nematodes (Helicotylenchus spp.), and lesion nematodes (Pratylenchus spp.). Endophyte infection had no effect on nematode population densities. The cultivar × endophyte interaction was significant. Population densities of stunt nematode, spiral nematode, and ring nematodes were higher for Flecha MaxQ than other cultivar × endophyte combinations. Novel endophyte infection enhances suitability of Flecha MaxQ as a nematode host.

13.
Gene Ther ; 23(11): 767-774, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27416076

RESUMO

Gene therapy using adeno-associated viral (AAV) vectors for the treatment of retinal degenerations has shown safety and efficacy in clinical trials. However, very high levels of vector expression may be necessary for the treatment of conditions such as Stargardt disease where a dual vector approach is potentially needed, or in optogenetic strategies for end-stage degeneration in order to achieve maximal light sensitivity. In this study, we assessed two vectors with single capsid mutations, rAAV2/2(Y444F) and rAAV2/8(Y733F) in their ability to transduce retina in the Abca4-/- and rd1 mouse models of retinal degeneration. We noted significantly increased photoreceptor transduction using rAAV2/8(Y733F) in the Abca4-/- mouse, in contrast to previous work where vectors tested in this model have shown low levels of photoreceptor transduction. Bipolar cell transduction was achieved following subretinal delivery of both vectors in the rd1 mouse, and via intravitreal delivery of rAAV2/2(Y444F). The successful use of rAAV2/8(Y733F) to target bipolar cells was further validated on human tissue using an ex vivo culture system of retinal explants. Capsid mutant AAV vectors transduce human retinal cells and may be particularly suited to treat retinal degenerations in which high levels of transgene expression are required.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Proteínas do Capsídeo/genética , Dependovirus/genética , Terapia Genética , Mutação de Sentido Incorreto , Células Fotorreceptoras/metabolismo , Degeneração Retiniana/terapia , Animais , Linhagem Celular Tumoral , Vetores Genéticos/administração & dosagem , Vetores Genéticos/genética , Humanos , Injeções Intravítreas , Camundongos , Camundongos Endogâmicos C57BL , Degeneração Retiniana/genética
14.
Am J Public Health ; 105 Suppl 2: e30-6, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25689192

RESUMO

OBJECTIVES: We analyzed data from the TrainingFinder Real-time Affiliate Integrated Network (TRAIN), the most widely used public health workforce training system in the United States, to describe the public health workforce and characteristics of individual public health workers. METHODS: We extracted self-reported demographic data of 405,095 learners registered in the TRAIN online system in 2012. RESULTS: Mirroring the results of other public health workforce studies, TRAIN learners are disproportionately women, college educated, and White compared with the populations they serve. TRAIN learners live in every state and half of all zip codes, with a concentration in states whose public health departments are TRAIN affiliates. TRAIN learners' median age is 46 years, and one third of TRAIN learners will reach retirement age in the next 10 years. CONCLUSIONS: TRAIN data provide a limited but useful profile of public health workers and highlight the utility and limitations of using TRAIN for future research.


Assuntos
Planejamento em Desastres/organização & administração , Pessoal de Saúde/educação , Capacitação em Serviço/estatística & dados numéricos , Internet , Saúde Pública , Educação a Distância , Humanos , Prática de Saúde Pública , Fatores Sexuais , Fatores Socioeconômicos , Estados Unidos , Recursos Humanos
15.
J Mol Med (Berl) ; 91(7): 825-37, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23756766

RESUMO

Choroideremia (CHM) is an X-linked retinal degeneration of photoreceptors, the retinal pigment epithelium (RPE) and choroid caused by loss of function mutations in the CHM/REP1 gene that encodes Rab escort protein 1. As a slowly progressing monogenic retinal degeneration with a clearly identifiable phenotype and a reliable diagnosis, CHM is an ideal candidate for gene therapy. We developed a serotype 2 adeno-associated viral vector AAV2/2-CBA-REP1, which expresses REP1 under control of CMV-enhanced chicken ß-actin promoter (CBA) augmented by a Woodchuck hepatitis virus post-transcriptional regulatory element. We show that the AAV2/2-CBA-REP1 vector provides strong and functional transgene expression in the D17 dog osteosarcoma cell line, CHM patient fibroblasts and CHM mouse RPE cells in vitro and in vivo. The ability to transduce human photoreceptors highly effectively with this expression cassette was confirmed in AAV2/2-CBA-GFP transduced human retinal explants ex vivo. Electroretinogram (ERG) analysis of AAV2/2-CBA-REP1 and AAV2/2-CBA-GFP-injected wild-type mouse eyes did not show toxic effects resulting from REP1 overexpression. Subretinal injections of AAV2/2-CBA-REP1 into CHM mouse retinas led to a significant increase in a- and b-wave of ERG responses in comparison to sham-injected eyes confirming that AAV2/2-CBA-REP1 is a promising vector suitable for choroideremia gene therapy in human clinical trials.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Coroideremia/genética , Dependovirus/genética , Técnicas de Transferência de Genes , Retina/metabolismo , Animais , Linhagem Celular Tumoral , Células Cultivadas , DNA Complementar/genética , Cães , Feminino , Fibroblastos/metabolismo , Humanos , Camundongos , Camundongos Transgênicos
16.
Biomaterials ; 34(10): 2501-15, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23317813

RESUMO

Mesenchymal stem cells (MSCs) have properties which make them promising for the treatment of chronic non-healing wounds. A major so far unmet challenge is the efficient, safe and painless delivery of MSCs to skin wounds. Recently, a surface carrier of medical-grade silicone coated by plasma polymerisation with a thin layer of acrylic acid (ppAAc) was developed, and shown to successfully deliver MSCs to deepithelialised human dermis in vitro. Here we studied the potential of the ppAAc carrier to deliver human adipose tissue derived MSCs (AT-MSCs) to murine full-thickness excisional skin wounds in vivo. Further we investigate the mechanism of action of MSCs in accelerating wound healing in these wounds. AT-MSCs cultured on ppAAc carriers for 4 days or longer fully retained their cell surface marker expression profile, colony-forming-, differentiation- and immunosuppressive potential. Importantly, AT-MSCs delivered to murine wounds by ppAAc carriers significantly accelerated wound healing, similar to AT-MSCs delivered by intradermal injection. More than 80% of AT-MSCs were transferred from carriers to wounds in 3 days. AT-MSCs were detectable in wounds for at least 5 days after wounding. Carrier delivered AT-MSCs were demonstrated to have the capacity to down-modulate TNF-α-dependent inflammation, increase anti-inflammatory M2 macrophage numbers, and induce TGF-ß(1)-dependent angiogenesis, myofibroblast differentiation and granulation tissue formation, thereby enhancing overall tissue repair.


Assuntos
Tecido Adiposo/citologia , Células-Tronco Mesenquimais/citologia , Cicatrização/fisiologia , Adipogenia/fisiologia , Animais , Western Blotting , Proliferação de Células , Sobrevivência Celular/fisiologia , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Macrófagos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Osteogênese/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Crescimento Transformador beta1/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
17.
Tissue Eng Part C Methods ; 18(2): 143-55, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21943098

RESUMO

Skin has a remarkable capacity for regeneration, but age- and diabetes-related vascular problems lead to chronic non-healing wounds for many thousands of U.K. patients. There is a need for new therapeutic approaches to treat these resistant wounds. Donor mesenchymal stem/stromal cells (MSCs) have been shown to assist cutaneous wound healing by accelerating re-epithelialization. The aim of this work was to devise a low risk and convenient delivery method for transferring these cells to wound beds. Plasma polymerization was used to functionalize the surface of medical-grade silicone with acrylic acid. Cells attached well to these carriers, and culture for up to 3 days on the carriers did not significantly affect their phenotype or ability to support vascular tubule formation. These carriers were then used to transfer MSCs onto human dermis. Cell transfer was confirmed using an MTT assay to assess viable cell numbers and enhanced green fluorescent protein-labeled MSCs to demonstrate that the cells post-transfer attached to the dermis. We conclude that this synthetic carrier membrane is a promising approach for delivery of therapeutic MSCs and opens the way for future studies to evaluate its impact on repairing difficult skin wounds.


Assuntos
Acrilatos/farmacologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Silicones/farmacologia , Pele/patologia , Cicatrização/efeitos dos fármacos , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Derme/efeitos dos fármacos , Epitélio/efeitos dos fármacos , Proteínas de Fluorescência Verde/metabolismo , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Neovascularização Fisiológica/efeitos dos fármacos , Fenótipo , Espectroscopia Fotoeletrônica , Pele/efeitos dos fármacos
18.
Hum Brain Mapp ; 32(12): 2241-55, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21305666

RESUMO

Both sighted and blind individuals can readily interpret meaning behind everyday real-world sounds. In sighted listeners, we previously reported that regions along the bilateral posterior superior temporal sulci (pSTS) and middle temporal gyri (pMTG) are preferentially activated when presented with recognizable action sounds. These regions have generally been hypothesized to represent primary loci for complex motion processing, including visual biological motion processing and audio-visual integration. However, it remained unclear whether, or to what degree, life-long visual experience might impact functions related to hearing perception or memory of sound-source actions. Using functional magnetic resonance imaging (fMRI), we compared brain regions activated in congenitally blind versus sighted listeners in response to hearing a wide range of recognizable human-produced action sounds (excluding vocalizations) versus unrecognized, backward-played versions of those sounds. Here, we show that recognized human action sounds commonly evoked activity in both groups along most of the left pSTS/pMTG complex, though with relatively greater activity in the right pSTS/pMTG by the blind group. These results indicate that portions of the postero-lateral temporal cortices contain domain-specific hubs for biological and/or complex motion processing independent of sensory-modality experience. Contrasting the two groups, the sighted listeners preferentially activated bilateral parietal plus medial and lateral frontal networks, whereas the blind listeners preferentially activated left anterior insula plus bilateral anterior calcarine and medial occipital regions, including what would otherwise have been visual-related cortex. These global-level network differences suggest that blind and sighted listeners may preferentially use different memory retrieval strategies when hearing and attempting to recognize action sounds.


Assuntos
Percepção Auditiva/fisiologia , Cegueira/fisiopatologia , Mapeamento Encefálico , Córtex Cerebral/fisiologia , Reconhecimento Psicológico/fisiologia , Adulto , Potenciais Evocados Auditivos/fisiologia , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Memória Episódica , Pessoa de Meia-Idade , Som
19.
J Cataract Refract Surg ; 36(8): 1427-31, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20656168

RESUMO

UNLABELLED: Two cases of postoperative intraocular lens (IOL) calcification in patients implanted with the Akreos Adapt IOL at the time of combined phacovitrectomy are described, along with clinical review of all patients implanted with this IOL type at our institution between November 2006 and September 2008. The IOLs explanted from the 2 cases were examined using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). The SEM of the explanted IOLs showed crystalline anterior surface and subsurface deposits; by EDX, the deposits showed high concentrations of calcium and phosphorous, consistent with calcium apatite. Twenty patients (20 eyes) attended for cohort review, and none showed IOL opacification. The reason calcification occurred in the 2 cases remains unknown, but clinicians should be aware of this potential complication. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.


Assuntos
Resinas Acrílicas , Calcinose/etiologia , Lentes Intraoculares , Facoemulsificação , Complicações Pós-Operatórias , Vitrectomia , Idoso , Cálcio/análise , Remoção de Dispositivo , Microanálise por Sonda Eletrônica , Feminino , Humanos , Implante de Lente Intraocular , Masculino , Microscopia Eletrônica de Varredura , Pessoa de Meia-Idade , Fósforo/análise
20.
Clin Exp Ophthalmol ; 38(3): 309-13, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20447128

RESUMO

Herpes simplex virus (HSV) keratitis is a common cause of ocular morbidity. Resistance to aciclovir is probably under recognized. We describe three cases of aciclovir-resistant herpes simplex virus keratitis treated with systemic foscarnet and present a review of the pharmacological options available to manage this condition.


Assuntos
Aciclovir/uso terapêutico , Antivirais/uso terapêutico , Farmacorresistência Viral , Ceratite Herpética/tratamento farmacológico , Aciclovir/administração & dosagem , Administração Oral , Administração Tópica , Idoso de 80 Anos ou mais , Antivirais/administração & dosagem , Cegueira/virologia , Humanos , Ceratite Herpética/complicações , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...