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1.
BMJ Open Qual ; 13(1)2024 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-38365432

RESUMEN

The reduction of restrictive practices is a priority for mental health inpatient services. Often such practices are considered to increase patients' feelings of anger, loneliness, hopelessness and vulnerability. Moreover, such approaches are counterintuitive to both recovery-orientated and trauma-informed practice.Our project, based in a male 15-bed secure forensic ward, aimed to reduce the duration (outcome measure) and frequency (balancing measure) of the use of seclusion by 10% over 6 months. Following the analysis of our local data systems and feedback from both patients and staff, we identified the high levels of use of seclusion, and reluctance to terminate it. These included a lack of awareness of the effective and appropriate use of such a facility, a hesitancy to use de-escalation techniques and an over-reliance on multidisciplinary team and consultant decision making.We subsequently designed and implemented three tests of change which reviewed seclusion processes, enhanced de-escalation skills and improved decision making. Our tests of change were applied over a 6-month period. During this period, we surpassed our original target of a reduction of frequency and duration by 10% and achieved a 33% reduction overall. Patients reported feeling safer on the ward, and the team reported improvements in relationships with patients.Our project highlights the importance of relational security within the secure setting and provides a template for other wards wishing to reduce the frequency and duration of seclusions.


Asunto(s)
Trastornos Mentales , Aislamiento de Pacientes , Humanos , Masculino , Hospitales Psiquiátricos , Pacientes Internos , Trastornos Mentales/terapia , Trastornos Mentales/psicología
2.
BMJ Lead ; 2024 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-38233121

RESUMEN

As healthcare systems grow increasingly complex and integrate with other services and sectors, creating complex patient pathways, this inevitably leads to additional layers within a system. Consequently, high-tier leaders become progressively detached from the inner workings of the systems in which they operate. Several barriers exist that may deter a leader from embracing uncertainty and acknowledging the limits of their expertise in these systems. These barriers range from personal insecurities about perception to organisational stigmas that compound these concerns through expectations of infallible leadership. In this article, I draw on my experience as an embedded researcher and someone who has taught leadership in healthcare settings to examine the importance of leadership vulnerability, considering not only for the leaders themselves but also for fostering a learning and innovative culture within the organisation. I focus on two fundamental tenets: psychological safety and participatory approaches to innovation. In addition, I offer practical considerations for embracing vulnerability and discuss the ensuing benefits. Given the rapidly evolving complexities in healthcare and paradigm-shifting innovations, such as the integration of digital solutions, this article serves as a call to action. It urges leaders to embrace uncertainty, encourage participation and venture into the unknown.

3.
Res Vet Sci ; 166: 105092, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38029490

RESUMEN

Feline odontoclastic resorptive lesion (FORL) is an inflammatory oral disease of unknown aetiopathogenesis that affects between 20% to 75% of cats. Twenty immune-associated molecules were measured in saliva of 25 healthy and 40 cats with FORL using a multiplex assay. No statistically significant differences were observed in the levels of these proteins between the healthy group and the diseased group of cats. A two-step cluster analysis of the oral microbiome and salivary cytokine data identified two subgroups of cats with FORL: FORL-1 (subset of cats with a less diverse oral microbiome) and FORL-2 (diseased cats with a microbiome similar to that of healthy animals). The level of some key proinflammatory cytokines (IL-1ß, IL-12p40) and chemokines (IL-8, RANTES, KC) were significantly higher in the FORL-1 subgroup than in the FORL-2 subgroup and the healthy group. In addition, TNF-α levels were greater in the FORL-1 subgroup than in the FORL-2 subgroup. These increases in pro-inflammatory cytokines and chemokines indicate active ongoing inflammation that may promote the osteoclastic/odontoclastic activity associated with FORL.


Asunto(s)
Citocinas , Saliva , Animales , Gatos , Osteoclastos , Quimiocinas
4.
Int J Mol Sci ; 24(16)2023 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-37628893

RESUMEN

Migrant birds prepare differently to fly north for breeding in the spring and for the flight to lower latitudes during autumn, avoiding the cold and food shortages of the Northern Hemisphere's harsh winter. The molecular events associated with these fundamental stages in the life history of migrants include the differential gene expression in different tissues. Semipalmated sandpipers (Calidris pusilla) are Arctic-breeding shorebirds that migrate to the coast of South America during the non-breeding season. In a previous study, we demonstrated that between the beginning and the end of the wintering period, substantial glial changes and neurogenesis occur in the brain of C. pusilla. These changes follow the epic journey of the autumn migration when a 5-day non-stop transatlantic flight towards the coast of South America and the subsequent preparation for the long-distance flight of the spring migration takes place. Here, we tested the hypothesis that the differential gene expressions observed in the brains of individuals captured in the autumn and spring windows are consistent with the previously described cellular changes. We searched for differential gene expressions in the brain of the semipalmated sandpiper, of recently arrived birds (RA) from the autumnal migration, and that of individuals in the premigratory period (PM) in the spring. All individuals were collected in the tropical coastal of northern Brazil in the mangrove region of the Amazon River estuary. We generated a de novo neurotranscriptome for C. pusilla individuals and compared the gene expressions across libraries. To that end, we mapped an RNA-Seq that reads to the C. pusilla neurotranscriptome in four brain samples of each group and found that the differential gene expressions in newly arrived and premigratory birds were related with neurogenesis, metabolic pathways (ketone body biosynthetic and the catabolic and lipid biosynthetic processes), and glial changes (astrocyte-dopaminergic neuron signaling, astrocyte differentiation, astrocyte cell migration, and astrocyte activation involved in immune response), as well as genes related to the immune response to virus infections (Type I Interferons), inflammatory cytokines (IL-6, IL-1ß, TNF, and NF-κB), NLRP3 inflammasome, anti-inflammatory cytokines (IL-10), and cell death pathways (pyroptosis- and caspase-related changes).


Asunto(s)
Estuarios , Ríos , Estaciones del Año , Encéfalo , Brasil , Citocinas
5.
GMS Ophthalmol Cases ; 13: Doc12, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37575475

RESUMEN

Background: While complex public health challenges and the emergence of variants have impeded responses to the COVID pandemic, vaccines continue to represent a crucial tool in mitigating the risk of morbidity and mortality. Safety issues weigh heavily upon both the utility and acceptability of every vaccine. Reports of sight-threatening events are scarce. Case description: We report the case of a hypertensive 45-year-old Filipino who noted unilateral (right eye) blurring of vision within 48 hours of his first dose of CoronaVac (Sinovac, China), an inactivated SARS-CoV-2/COVID-19 vaccine, with macular retinal arterial occlusion noted on day 21 post-inoculation. Further work-up revealed abnormal glycemic, metabolic, inflammatory, and bleeding parameters. Vision improved from counting fingers to 20/100 at week 6 with no interventions. Conclusion: A potential association between retinal vasoocclusion and inoculation with CoronaVac in our patient is supported by the temporal sequence of events, multiple mechanisms put forward in other cases, and reports of vascular adverse reactions in large country-level trials. It is mitigated by the profound infrequency of such events and the potentially substantial risk for ocular ischemic events imparted by the patient's baseline clinical background. Continued understanding of vaccine adverse reactions, however rare, is important not only for individual patient safety. This is helpful in ensuring the utility of current vaccines and in preserving the acceptability of vaccines through and beyond the current pandemic.

6.
Viruses ; 15(4)2023 04 19.
Artículo en Inglés | MEDLINE | ID: mdl-37112987

RESUMEN

The genetic basis of antigenic drift of human A/H3N2 influenza virus is crucial to understanding the constraints of influenza evolution and determinants of vaccine escape. Amino acid changes at only seven positions near the receptor binding site of the surface hemagglutinin protein have been shown to be responsible for the major antigenic changes for over forty years. Experimental structures of HA are now available for the majority of the observed antigenic clusters of A/H3N2. An analysis of the HA structures of these viruses reveals the likely consequences of these mutations on the structure of HA and thus, provides a structural basis for the antigenic changes seen in human influenza viruses.


Asunto(s)
Subtipo H3N2 del Virus de la Influenza A , Gripe Humana , Humanos , Subtipo H3N2 del Virus de la Influenza A/genética , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Antígenos Virales/genética , Variación Antigénica
7.
PLoS One ; 18(2): e0281816, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36795775

RESUMEN

PURPOSE: To evaluate the efficacy of a myopia control spectacle lens (DIMS) at slowing the progression of myopia in a population of European children in comparison with 0.01% atropine and combined DIMS and atropine. METHODS: The study was a non-randomised experimenter-masked prospective controlled observational study of individuals aged 6-18 years with progressing myopia but no ocular pathology. Participants were allocated, according to patient/parent choice, to receive 0.01% atropine eyedrops, DIMS (Hoya® MiyoSmart®) spectacles, combined atropine+DIMS or single vision spectacle lenses (control group). The key outcome variables, cycloplegic autorefraction spherical equivalent refraction (SER) and axial length (AL), were measured at baseline and after three, six, and 12 months. RESULTS: Of the 146 participants (mean age 10.3y ±3.2), 53 received atropine, 30 DIMS spectacles, 31 atropine+DIMS, and 32 single vision control spectacles. Generalized linear mixed model analysis revealed for SER, whilst controlling for age and SER at baseline, at each stage all treatment groups had significantly reduced progression compared with the control group (p<0.016). For AL, whilst controlling for baseline age and AL, at 6 and 12 months all treatment groups had significantly less progression than the control group (p<0.005). For SER only, in pairwise comparisons at 12 months the atropine+DIMS group had significantly reduced progression compared with the DIMS only and Atropine only groups (p<0.001). CONCLUSION: In a European population, DIMS and atropine are effective at reducing myopia progression and axial elongation in progressing myopia and are most successful at reducing myopia progression when used in combination.


Asunto(s)
Atropina , Miopía , Humanos , Niño , Adolescente , Atropina/uso terapéutico , Anteojos , Estudios Prospectivos , Miopía/epidemiología , Miopía/prevención & control , Refracción Ocular , Progresión de la Enfermedad
8.
J Evid Based Integr Med ; 27: 2515690X221142352, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36448194

RESUMEN

When arterial serum pH remains near the lower pH limit of 7.35 for protracted periods of time, a low-grade, sub-clinical form of acidosis results, referred to in this review as chronic, sub-clinical, systemic metabolic acidosis (CSSMA). This narrative review explores the scientific basis for CSSMA, its consequences for health, and potential therapeutic interventions. The major etiology of CSSMA is the shift away from the ancestral, alkaline diet which was rich in fruit and vegetables, toward the contemporary, acidogenic 'Westernized' diet characterized by higher animal protein consumption and lack of base forming minerals. Urine pH is reduced with high dietary acid load and may be a convenient marker of CSSMA. Evidence suggests further that CSSMA negatively influences cortisol levels potentially contributing significantly to the pathophysiology thereof. Both CSSMA and high dietary acid load are associated with the risk and prognosis of various chronic diseases. Clinical trials show that CSSMA can be addressed successfully through alkalizing the diet by increasing fruit and vegetable intake and/or supplementing with alkaline minerals. This review confirms the existence of a significant body of evidence regarding this low-grade form of acidosis as well as evidence to support its diverse negative implications for health, and concludes that CSSMA is a condition warranting further research.


Asunto(s)
Acidosis , Enfermedad Injerto contra Huésped , Desequilibrio Hidroelectrolítico , Animales , Inmunoterapia , Verduras
9.
Int Rev Psychiatry ; 34(5): 546-552, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-36165746

RESUMEN

Poor mental health is a global concern and is exacerbated by recent challenges concerning COVID-19 and the climate emergency, with significant consequences to individuals and to society. Increasing evidence demonstrates that nature-based approaches (NBAs) have numerous benefits to mental health services and the people they support with mental health needs. Despite these benefits, understanding how to integrate these approaches into practice is challenging. In this paper, we report our findings from a recent qualitative study with staff from a CAMHS inpatient unit who had recently undergone NatureWell Facilitator training. This is a particular approach to working with people in nature developed by The Natural Academy. Participants identified the importance of implementation of discreet, novel NBAs, as well as integrating nature into current practice, the benefits when fostering psychologically safe and therapeutic relationships with staff, and the clinical and operational factors when carrying out NBAs in these settings.


Asunto(s)
COVID-19 , Servicios de Salud Mental , Humanos , Pacientes Internos , Salud Mental , Investigación Cualitativa
10.
Case Rep Ophthalmol ; 13(2): 429-434, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35950029

RESUMEN

A 44-year-old male presented with unilateral sudden onset reduced visual acuity. The optical coherence tomography (OCT) scan demonstrated submacular fluid with thickening and hyper-reflectivity of the outer retinal layers, together with subfoveal retinal pigment epithelial hyper-reflectivity corresponding to a small area of foveal interdigitation zone/ellipsoid zone (IZ/EZ) loss in the detached retina. An OCT 4 months later showed resolution of the submacular fluid, but the IZ/EZ loss persisted with thinning of the outer nuclear layer, resulting in a poor visual outcome. The clinical findings most likely represent a case of unilateral acute idiopathic maculopathy; however, the OCT features and poor visual outcome are not typical. Differential diagnoses include acute solar maculopathy, central serous chorioretinopathy, poppers maculopathy, whiplash maculopathy, and acute retinal pigment epitheliitis.

11.
BMJ Open Qual ; 11(2)2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35768172

RESUMEN

OBJECTIVES: Mealtimes are an integral part of treatment for patients in an eating disorder inpatient unit. However, they are often distressing and anxiety provoking for both patients and staff. A consequence of patients' distress is an increase in eating disorder behaviours specific to mealtimes. This is the second paper detailing a quality improvement project following on from an initial paper outlining the first test of change. The aim of this quality improvement project was to decrease the number of eating disorder behaviours at mealtimes in the dining room through the implementation of interventions identified through diagnostic work. METHODS/DESIGN: The Model for Improvement was used as the systematic approach for this project. Baseline assessment included observations in the dining room, gathering of qualitative feedback from staff and patients and the development of a form which identifies eating disorder behaviours completed by staff. Interventions in the form of three change ideas have so far been introduced including (1) a host role in the dining room, (2) a guide to the dining room for new staff along with competencies and (3) a dining goals group. The impact of the three interventions is assessed. RESULTS: The introduction of the interventions has overall reduced the average number of eating disorder behaviours per patient in the dining room by 33%. CONCLUSIONS: This paper reports the challenges and successes of continuing a QI project through the COVID-19 pandemic and the need for multiple tests of change to improve a complex problem. The results demonstrate a consistent reduction in eating disorder behaviours over a period of nearly 2 years.


Asunto(s)
COVID-19 , Trastornos de Alimentación y de la Ingestión de Alimentos , Trastornos de Alimentación y de la Ingestión de Alimentos/terapia , Humanos , Comidas , Pandemias
12.
Disabil Rehabil ; 44(18): 5284-5290, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-34088248

RESUMEN

PURPOSE: The aim of this work was to qualitatively explore the personal perspectives of prosthetic and orthotic users, in the context of their past and present experiences and understand their insights for the future. MATERIALS AND METHODS: A narrative exploration study design, employing a phenomenological approach was used. Semi-structured interviews were conducted with three female and two male prosthetic and orthotic users from Australia and the United Kingdom. Interviews were analysed, coded and key themes and sub-themes identified. RESULTS: Three themes were identified. The Maximising Opportunity theme linked sub-themes of recreation and pushing boundaries. The Health Care Network theme included sub-themes of communication, peer support and building a team. The final theme, Changes over time, included sub-themes of disability perception, advice and advancements over time. CONCLUSION: Prosthetic and orthotic users identified that there had been vast changes in disability perception, disability rights, and their role in the health care system, along with the variety of technology and materials available. Key findings were that prosthetic and orthotic users want to be listened to, considered central to the health care team, and had a deep understanding of their own health care needs.Implications for rehabilitationProsthesis and orthosis users want to be listened to and considered central within the health care team.Attending medical and allied health teams must recognise that prosthesis and orthosis users have a fundamental understanding of their own health care needs.Themes, whilst potentially generalisable, are derived from specific individuals and may particularly relate to these individuals.


Asunto(s)
Miembros Artificiales , Personas con Discapacidad , Australia , Atención a la Salud , Femenino , Humanos , Masculino , Aparatos Ortopédicos , Investigación Cualitativa
13.
BMJ Open Qual ; 10(3)2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34404685

RESUMEN

Quality improvement (QI) provides a rigorous and innovative approach to improving patient's lives in the healthcare system. Still, it can pose challenges in understanding what ethical considerations apply to some projects to minimise the possibility of patient harm or prevent other ethical wrongs and potential staff burden. While many commentaries discuss the extent to which QI ethics should match research ethics, there is minimal literature regarding what QI project teams should do when considering ethics at the planning stage. This paper provides a practical walkthrough of some of the ethical considerations across the breadth of QI projects, starting from some of the key questions when planning a QI project and a guide for the different ethical considerations that may apply.


Asunto(s)
Confidencialidad , Mejoramiento de la Calidad , Atención a la Salud , Humanos
14.
Front Immunol ; 12: 683026, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34220831

RESUMEN

Microglial immunosurveillance of the brain parenchyma to detect local perturbations in homeostasis, in all species, results in the adoption of a spectrum of morphological changes that reflect functional adaptations. Here, we review the contribution of these changes in microglia morphology in distantly related species, in homeostatic and non-homeostatic conditions, with three principal goals (1): to review the phylogenetic influences on the morphological diversity of microglia during homeostasis (2); to explore the impact of homeostatic perturbations (Dengue virus challenge) in distantly related species (Mus musculus and Callithrix penicillata) as a proxy for the differential immune response in small and large brains; and (3) to examine the influences of environmental enrichment and aging on the plasticity of the microglial morphological response following an immunological challenge (neurotropic arbovirus infection). Our findings reveal that the differences in microglia morphology across distantly related species under homeostatic condition cannot be attributed to the phylogenetic origin of the species. However, large and small brains, under similar non-homeostatic conditions, display differential microglial morphological responses, and we argue that age and environment interact to affect the microglia morphology after an immunological challenge; in particular, mice living in an enriched environment exhibit a more efficient immune response to the virus resulting in earlier removal of the virus and earlier return to the homeostatic morphological phenotype of microglia than it is observed in sedentary mice.


Asunto(s)
Microglía/citología , Animales , Biomarcadores , Encéfalo/anatomía & histología , Encéfalo/citología , Encéfalo/fisiología , Forma de la Célula , Quirópteros , Cognición , Metabolismo Energético , Ambiente , Homeostasis , Humanos , Ratones , Microglía/fisiología , Tamaño de los Órganos , Filogenia , Desempeño Psicomotor , Especificidad de la Especie
15.
Front Psychol ; 12: 784372, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35185684

RESUMEN

For the epic journey of autumn migration, long-distance migratory birds use innate and learned information and follow strict schedules imposed by genetic and epigenetic mechanisms, the details of which remain largely unknown. In addition, bird migration requires integrated action of different multisensory systems for learning and memory, and the hippocampus appears to be the integration center for this task. In previous studies we found that contrasting long-distance migratory flights differentially affected the morphological complexity of two types of hippocampus astrocytes. Recently, a significant association was found between the latitude of the reproductive site and the size of the ADCYAP1 allele in long distance migratory birds. We tested for correlations between astrocyte morphological complexity, migratory distances, and size of the ADCYAP1 allele in three long-distance migrant species of shorebird and one non-migrant. Significant differences among species were found in the number and morphological complexity of the astrocytes, as well as in the size of the microsatellites of the ADCYAP1 gene. We found significant associations between the size of the ADCYAP1 microsatellites, the migratory distances, and the degree of morphological complexity of the astrocytes. We suggest that associations between astrocyte number and morphological complexity, ADCYAP1 microsatellite size, and migratory behavior may be part of the adaptive response to the migratory process of shorebirds.

16.
Eur J Neurosci ; 54(5): 5687-5704, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-32406131

RESUMEN

Semipalmated sandpiper (Calidris pusilla) migration to the Southern Hemisphere includes a 5-day non-stop flight over the Atlantic Ocean, whereas semipalmated plover (Charadrius semipalmatus) migration, to the same area, is largely over land, with stopovers for feeding and rest. We compared the number and 3D morphology of hippocampal astrocytes of Ch. semipalmatus before and after autumnal migration with those of C. pusilla to test the hypothesis that the contrasting migratory flights of these species could differentially shape hippocampal astrocyte number and morphology. We captured individuals from both species in the Bay of Fundy (Canada) and in the coastal region of Bragança (Brazil) and processed their brains for selective GFAP immunolabeling of astrocytes. Hierarchical cluster analysis of astrocyte morphological features distinguished two families of morphological phenotypes, named type I and type II, which were differentially affected after migratory flights. Stereological counts of hippocampal astrocytes demonstrated that the number of astrocytes decreased significantly in C. pusilla, but did not change in Ch. semipalmatus. In addition, C. pusilla and Ch. semipalmatus hippocampal astrocyte morphological features were differentially affected after autumnal migration. We evaluated whether astrocyte morphometric variables were influenced by phylogenetic differences between C. pusilla and Ch. semipalmatus, using phylogenetically independent contrast approach, and phylogenetic trees generated by nuclear and mitochondrial markers. Our findings suggest that phylogenetic differences do not explain the results and that contrasting long-distance migratory flights shape plasticity of type I and type II astrocytes in different ways, which may imply distinct physiological roles for these cells.


Asunto(s)
Astrocitos , Charadriiformes , Animales , Canadá , Hipocampo , Humanos , Filogenia
17.
Physiol Behav ; 229: 113243, 2021 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-33159929

RESUMEN

The multivariate concentric square field™ (MCSF) is a complex and ethologically relevant apparatus that is designed to measure several behavioral parameters within the same test session including risk-taking, risk-assessment, shelter-seeking (anxiety relieving), exploration, and general activity. While several studies have behaviorally and pharmacologically validated the use of the MCSF in adults, far fewer have used adolescents. Given the well-established link between adolescence and risk-taking, it is important to validate use of the MCSF in adolescence. The present study compared the effects of age, sex, and handling on behavioral categories in the MCSF. In addition, principal component analyses were used to compare the underlying behavioral components in adolescent and adult Sprague-Dawley rats. Results revealed that handling increased risk-taking and reduced shelter-seeking. Females were more exploratory than males, but no compelling age differences in risk-taking or risk-assessment were found. Principal component analyses revealed six major principal components for both adolescents and adults with the first and second components consisting mainly of center/center circle, risk-assessment, and shelter-seeking variables in adolescence, and general activity and center/center circle variables in adults. These results confirm age differences in the underlying behavioral components in the MCSF.


Asunto(s)
Conducta Exploratoria , Asunción de Riesgos , Consumo de Bebidas Alcohólicas , Animales , Conducta Animal , Ratas , Ratas Sprague-Dawley
18.
Theranostics ; 10(23): 10548-10562, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32929365

RESUMEN

The use of reporter genes to non-invasively image molecular processes inside cells has significant translational potential, particularly in the context of systemically administered gene therapy vectors and adoptively administered cells such as immune or stem cell based therapies. Bacterial nitroreductase enzymes possess ideal properties for reporter gene imaging applications, being of non-human origin and possessing the ability to metabolize a range of clinically relevant nitro(hetero)cyclic substrates. Methods: A library of eleven Escherichia coli nitroreductase candidates were screened for the ability to efficiently metabolize 2-nitroimidazole based positron emission tomography (PET) probes originally developed as radiotracers for hypoxic cell imaging. Several complementary methods were utilized to detect formation of cell-entrapped metabolites, including various in vitro and in vivo models to establish the capacity of the 2-nitroimidazole PET agent EF5 to quantify expression of a nitroreductase candidate. Proof-of-principle PET imaging studies were successfully conducted using 18F-HX4. Results: Recombinant enzyme kinetics, bacterial SOS reporter assays, anti-proliferative assays and flow cytometry approaches collectively identified the major oxygen-insensitive nitroreductase NfsA from E. coli (NfsA_Ec) as the most promising nitroreductase reporter gene. Cells expressing NfsA_Ec were demonstrably labelled with the imaging agent EF5 in a manner that was quantitatively superior to hypoxia, in monolayers (2D), multicellular layers (3D), and in human tumor xenograft models. EF5 retention correlated with NfsA_Ec positive cell density over a range of EF5 concentrations in 3D in vitro models and in xenografts in vivo and was predictive of in vivo anti-tumor activity of the cytotoxic prodrug PR-104. Following PET imaging with 18F-HX4, a significantly higher tumor-to-blood ratio was observed in two xenograft models for NfsA_Ec expressing tumors compared to the parental tumors thereof, providing verification of this reporter gene imaging approach. Conclusion: This study establishes that the bacterial nitroreductase NfsA_Ec can be utilized as an imaging capable reporter gene, with the ability to metabolize and trap 2-nitroimidazole PET imaging agents for non-invasive imaging of gene expression.


Asunto(s)
Antineoplásicos Alquilantes/farmacología , Proteínas de Escherichia coli/administración & dosificación , Genes Reporteros , Neoplasias/diagnóstico por imagen , Nitrorreductasas/administración & dosificación , Tomografía de Emisión de Positrones/métodos , Animales , Antineoplásicos Alquilantes/uso terapéutico , Resistencia a Antineoplásicos , Proteínas de Escherichia coli/genética , Etanidazol/administración & dosificación , Etanidazol/análogos & derivados , Etanidazol/farmacocinética , Terapia Genética , Vectores Genéticos/administración & dosificación , Vectores Genéticos/farmacocinética , Células HCT116 , Humanos , Hidrocarburos Fluorados/administración & dosificación , Hidrocarburos Fluorados/farmacocinética , Imidazoles/administración & dosificación , Indicadores y Reactivos/administración & dosificación , Indicadores y Reactivos/farmacocinética , Ratones , Imagen Molecular/métodos , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Neoplasias/patología , Compuestos de Mostaza Nitrogenada/farmacología , Compuestos de Mostaza Nitrogenada/uso terapéutico , Nitrorreductasas/genética , Medicina de Precisión/métodos , Prueba de Estudio Conceptual , Radiofármacos/administración & dosificación , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/genética , Triazoles/administración & dosificación , Hipoxia Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto
19.
J Econ Entomol ; 113(3): 1315-1322, 2020 06 06.
Artículo en Inglés | MEDLINE | ID: mdl-32052835

RESUMEN

Stable fly (Stomoxys calcitrans L.) remain a significant pest affecting livestock and rural communities on the Swan Coastal Plain around Perth, Western Australia. Vegetable crop residues remaining after harvest enable stable fly development. Left untreated they can produce from several hundred to >1,000 stable fly/m2 of post-harvest residues. We studied the effect of burial and compaction of sandy soils on adult emergence of stable fly and house fly (Musca domestica L.) (Diptera: Muscidae). Adults of both fly species can move up through 50 cm of loose, dry sand, however at depths greater than 60 cm, emergence rapidly declines with <5% of adults surviving under 100 cm of soil. Burial of stable fly larvae and pupae under 15 cm of soil followed by compaction using a static weight dramatically reduced adult emergence. Moist soil compacted at ≥3 t/m2 completely prevented stable fly emergence whereas house fly emergence was not affected. One t/m2 of compaction resulted in <5% emergence of stable fly buried as pupae. Soil that was easily compactible (i.e., high silt, fine sand and clay content) reduced stable fly emergence more than soil with more coarse sand and low clay content. This study demonstrates the potential for a novel and chemical-free option for controlling stable fly development from vegetable crop post-harvest residue. Field trials are needed to confirm that burial and compaction of vegetable post-harvest residues using agricultural machinery can dramatically reduce the subsequent emergence of adult stable fly on a large scale.


Asunto(s)
Dípteros , Moscas Domésticas , Muscidae , Animales , Arena , Suelo , Australia Occidental
20.
Prosthet Orthot Int ; 43(5): 556-563, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31256710

RESUMEN

BACKGROUND: High-quality clinical practice guidelines are necessary for effective use of resources both at an individual patient- and national-level. Nordic clinical practice guidelines recommendations for orthotic treatment of knee osteoarthritis vary and little is known about their quality. OBJECTIVES: The aim of the study was to critically evaluate the quality of clinical practice guidelines in orthotic management of knee osteoarthritis in the Nordic countries. STUDY DESIGN: Systematic review. METHODS: Four national clinical practice guidelines for treatment of knee osteoarthritis were assessed for methodological rigour and transparency by four independent assessors using the AGREE II instrument. Summary domain scores and inter-rater agreement (Kendall's W) were calculated. RESULTS: Domain scores indicate that many guidelines have not sufficiently addressed stakeholder involvement (average score: 55%), applicability (20%) and editorial independence (33%) in the development process. Inter-rater agreement for assessors indicated 'good' agreement for clinical practice guidelines from Finland, Norway and Sweden (W = 0.653, p < 0.001; W = 0.512, p = 0.003 and W = 0.532, p = 0.002, respectively) and 'strong' agreement for the clinical practice guideline from Denmark (W = 0.800, p < 0.001). CONCLUSION: Quality of clinical practice guidelines for orthotic treatment of knee osteoarthritis in the Nordic region is variable. Future guideline development should focus on improving methodology by involving relevant stakeholders (e.g. certified prosthetist/orthotists (CPOs)), specifying conflicts of interest and providing guidance for implementation. CLINICAL RELEVANCE: The current review suggests that, for the Nordic region, there are areas of improvement which can be addressed, which ensure clinical practice guidelines are developed under stringent conditions and based on sound methods. These improvements would ensure knee osteoarthritis patients are receiving orthotic interventions based on appropriate guidance from published guidelines.


Asunto(s)
Medicina Basada en la Evidencia/normas , Aparatos Ortopédicos , Osteoartritis de la Rodilla/terapia , Guías de Práctica Clínica como Asunto , Humanos , Reproducibilidad de los Resultados , Países Escandinavos y Nórdicos
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