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1.
Pediatr Infect Dis J ; 42(10): 862-866, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37625080

RESUMEN

BACKGROUND: Toxocariasis, caused the by dog and cat roundworm, is one of the most common zoonotic helminth infections in the United States and can lead to severe lifelong morbidity in children. Although historical seroprevalence studies have identified a high frequency of toxocariasis regionally in the United States, there are few studies linking epidemiology and clinical disease in children. The study objective was to examine the contemporary epidemiology of pediatric toxocariasis within an endemic US region. METHODS: We conducted an epidemiologic study analyzing children diagnosed with toxocariasis presenting to a tertiary pediatric hospital in Texas from 2010 to 2021. We examined risk factors and performed a geospatial analysis, including a comparative analysis of human cases and locations of surrendered infected stray animals in the same region. RESULTS: Children diagnosed with toxocariasis were most commonly of Hispanic/Latino ethnicity (30/46; 65%), white race (41/45; 91%) and receiving Medicaid (34/44, 77%). Many infected children had contact with dogs or cats. Ocular toxocariasis was associated with a lack of peripheral eosinophilia ( P < 0.001). No other Toxocara syndromes were associated with defined absolute eosinophil count levels. Post-treatment resolution of eosinophilia was variable, ranging from 1 to 172 weeks. A Toxocara hotspot was identified in northeast Houston, comprising one of the lowest median household incomes in the region. CONCLUSIONS: Toxocariasis is a devastating zoonotic infection in children living in the US. As it is not a reportable disease, the true burden remains unknown. It is critical to increase awareness of toxocariasis to direct public health interventions and ultimately reduce Toxocara -induced morbidity in US children.


Asunto(s)
Enfermedades de los Gatos , Enfermedades de los Perros , Toxocariasis , Estados Unidos , Humanos , Niño , Animales , Gatos , Perros , Salud Pública , Toxocariasis/epidemiología , Hospitales Pediátricos , Estudios Seroepidemiológicos , Zoonosis/epidemiología
2.
J Comp Pathol ; 205: 11-16, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37506667

RESUMEN

We report the pathological and molecular findings in an adult male Himalayan red panda (Ailurus fulgens fulgens) whose death was attributed to parenchymal brain haemorrhage (PBH) of the thalamus. Post-mortem examination revealed severe, acute PBH and intraventricular haemorrhage with major involvement of the thalamus, as well as scattered chronic microinfarctions. Vascular disease in the brain and other organs was suggestive of systemic hypertension. Histological lesions included arteriolar hyalinosis and varying degrees of arteriosclerosis, arterial tunica media hypertrophy and hyperplasia and infiltration of arterial walls by lipid-laden macrophages. Other relevant findings included marked myocardial fibrosis, lymphoplasmacytic tubulointerstitial nephritis, lymphoplasmacytic meningoencephalitis and chronic mitral valve degeneration. The changes in the cerebral vasculature were consistent with hypertensive encephalopathy and a cerebrovascular accident, specifically PBH, which has not been previously reported in this species. Additionally, polymerase chain reaction analysis for red panda amdoparvovirus (RPAV) was positive in the brain and kidneys. Preceded by hypertensive vascular changes and brain microinfarctions, sudden death in this animal likely resulted from fatal PBH with intraventricular haemorrhage. The clinicopathological role of RPAV infection is unknown in this case, although its contribution to the chronic renal disease is considered possible in the context of our current understanding of RPAV-associated pathology.


Asunto(s)
Ailuridae , Accidente Cerebrovascular , Masculino , Animales , Riñón , Accidente Cerebrovascular/veterinaria , Hemorragia/veterinaria
3.
Aggress Behav ; 49(4): 396-408, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36842143

RESUMEN

Youth violence continues to be a major developmental and health concern. Preventative resources at individual, family, and community levels may reduce risk, yet the extent to which youth violence perpetration differs by patterns of risk and protective factors remains unknown. Using data from the Florida Youth Substance Abuse Survey (N = 4630; 49% female; Mage = 14.69), we conducted person-centered, latent profile analyses to identify four patterns for risk of violence perpetration among middle and high school youth. Youth in the Low Risk-High Protection profile (37%) had low likelihood of violence perpetration. Youth in the Low Risk-Low Protection profile (4%) were characterized by poor family functioning, low school belonging, and low community protection. These youth had similar odds of violence perpetration as youth in the Moderate Risk-Moderate Protection profile (44%), which were elevated compared to the Low Risk-High Protection profile. Youth in the High Risk-Low Protection profile (15%), which had the highest levels of risk factors and lowest levels of protective factors, had the highest likelihood of violence perpetration. The High Risk-Low Protection profile was expected based on past research, but the emergence of the Low Risk-Low Protection profile is a unique contribution to the research. Findings contribute to the literature by going beyond a cumulative risk model, identifying subgroups with various patterns of risk and protection in the population, and highlighting the importance of selected prevention for subgroups of youth with high risk or challenging family and community environments.


Asunto(s)
Conducta del Adolescente , Trastornos Relacionados con Sustancias , Humanos , Adolescente , Femenino , Masculino , Violencia/prevención & control , Instituciones Académicas , Medio Social , Factores de Riesgo , Trastornos Relacionados con Sustancias/epidemiología , Trastornos Relacionados con Sustancias/prevención & control
4.
Crit Rev Oncol Hematol ; 180: 103869, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36356701

RESUMEN

Telehealth facilitates access to cancer care for patients unable to attend in-person consultations, as in COVID-19. This systematic review used the reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework to evaluate telehealth implementation and examine enablers and barriers to optimal implementation in oncology. MEDLINE, PubMed, CINAHL, and the Cochrane Database of Systematic Reviews were searched between January 2011-June 2022. Eighty-two articles representing 73 studies were included. One study explicitly used the RE-AIM framework to guide study design, conduct, or reporting. Reach (44%) and implementation (38%) were most commonly reported, maintenance (5%) least commonly. Key telehealth implementation enablers included professional-led delivery, patient-centred approaches, and positive patient perceptions. Key barriers included patient discomfort with technology, limited supporting clinic infrastructure, and poor access to reliable internet connection and videoconferencing. While a patient-centred and professional-supported approach enables telehealth implementation, technology and infrastructure constraints need surmounting for sustained implementation beyond the COVID-19 pandemic.


Asunto(s)
COVID-19 , Telemedicina , Humanos , COVID-19/epidemiología , Oncología Médica , Pandemias
5.
Patient Educ Couns ; 105(10): 3134-3142, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35688719

RESUMEN

OBJECTIVES: The COVID-19 pandemic has significantly impacted oncology. With pandemic restrictions limiting close contact between individuals, telehealth (the use of teleconferencing/videoconferencing to conduct real-time medical consultations) has been increasingly utilised. This qualitative study aimed to explore adult cancer patient, caregiver, and clinician (doctor, nurse, allied health) telehealth experiences during COVID-19 in urban and rural Australian settings and identify potential enablers and barriers to sustained telehealth implementation. METHODS: English-speaking participants completed semi-structured interviews regarding their telehealth experiences since March 2020. Interviews ceased when data saturation occurred. Iterative thematic analysis was conducted using NVivo 12 Pro. RESULTS: Thirty-four interviews (clinician=14, patient=13, caregiver=7) were conducted from April to August 2021. Analysis generated seven themes relating to telehealth use: 1) Acceptability as a form of consultation, 2) Impacts on healthcare provision, 3) Communication & relationships, 4) Efficient form of consultation, 5) Comfort of conducting telehealth in different environments, 6) Technological barriers and 7) Future preferences. CONCLUSIONS: The rapid uptake of telehealth during the pandemic has mostly been well-received, and telehealth can be appropriately used in oncology. PRACTICE IMPLICATIONS: Barriers including providing appropriate facilities, technology, and telehealth training; and selecting appropriate patients must be addressed to enable sustained telehealth use in future cancer care.


Asunto(s)
COVID-19 , Neoplasias , Telemedicina , Adulto , Australia , COVID-19/epidemiología , Cuidadores , Humanos , Neoplasias/terapia , Pandemias
6.
EMBO Rep ; 23(2): e54396, 2022 02 03.
Artículo en Inglés | MEDLINE | ID: mdl-34910840

RESUMEN

Embryonic development is a complex process in which cells divide, migrate, and differentiate in a precise spatiotemporal pattern. Cell-cell communication among neighboring cells plays a central role in specifying cell fate and in coordinating development. Embryonic development also relies on physical interaction between cells and coordinated changes in cell shape. A more recently investigated phenomenon is the coupling of development of adjacent tissues via inter-tissue adhesion. In this issue of EMBO Reports, Monnot and colleagues identify a role for inter-tissue adhesion in the development of adjacent sensory organs in the zebrafish. Specifically, eye morphogenesis influences the organ shape and retrograde axon growth in the adjacent olfactory placode via a shared extracellular matrix.


Asunto(s)
Proteínas de Pez Cebra , Pez Cebra , Animales , Ectodermo/metabolismo , Organogénesis/genética , Adherencias Tisulares , Pez Cebra/embriología , Proteínas de Pez Cebra/metabolismo
7.
Hum Mol Genet ; 31(5): 733-747, 2022 03 03.
Artículo en Inglés | MEDLINE | ID: mdl-34568901

RESUMEN

Congenital muscular dystrophy type 1A (MDC1A), the most common congenital muscular dystrophy in Western countries, is caused by recessive mutations in LAMA2, the gene encoding laminin alpha 2. Currently, no cure or disease modifying therapy has been successfully developed for MDC1A. Examination of patient muscle biopsies revealed altered distribution of lysosomes. We hypothesized that this redistribution was a novel and potentially druggable aspect of disease pathogenesis. We explored this hypothesis using candyfloss (caf), a zebrafish model of MDC1A. We found that lysosome distribution in caf zebrafish was also abnormal. This altered localization was significantly associated with fiber detachment and could be prevented by blocking myofiber detachment. Overexpression of transcription factor EB, a transcription factor that promotes lysosomal biogenesis, led to increased lysosome content and decreased fiber detachment. We conclude that genetic manipulation of the lysosomal compartment is able to alter the caf zebrafish disease process, suggesting that lysosome function may be a target for disease modification.


Asunto(s)
Distrofias Musculares , Pez Cebra , Animales , Humanos , Laminina/genética , Lisosomas/genética , Lisosomas/patología , Músculo Esquelético/patología , Distrofias Musculares/patología , Factores de Transcripción , Pez Cebra/genética
8.
Prev Sci ; 23(4): 523-537, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34714506

RESUMEN

Past reviews of cyberbullying preventative interventions have critiqued the field regarding scientific rigor, and a meta-analysis found that randomized controlled trials (RCTs) of such interventions were more effective than non-RCTs. However, no review has examined the risk of bias, dosage, modality, and delivery context of such programs to date. The current study addresses this gap through a systematic review of the literature. Potential articles (N = 4,737) from 4 databases were identified and screened (Academic Search Premier including ERIC, PsychINFO, and the Psychology and Behavioral Collection; PubMed; Web of Science; Compendex); 72 articles were reviewed for eligibility. Final articles included (N = 30) were based on a rigorous search process guided by inclusion and exclusion criteria. The majority of studies were conducted in Europe; two were conducted in the USA, three in Australia, and two in the Middle East. Efforts to reduce risk of bias were evaluated using the Cochrane's Risk of Bias tool. Harvest plots were constructed to qualitatively illustrate the rigor, dosage, modality, and context of the interventions, and meta-analytic random effects models were conducted to examine effect sizes of the interventions on cyberbullying perpetration and victimization. Results suggest that cyberbullying interventions delivered through schools are effective, though expanded follow-up time is suggested, and additional evidence is needed for home settings and digital delivery.


Asunto(s)
Acoso Escolar , Víctimas de Crimen , Ciberacoso , Australia , Acoso Escolar/prevención & control , Ciberacoso/prevención & control , Humanos , Instituciones Académicas
9.
Water Res ; 206: 117717, 2021 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-34634641

RESUMEN

Diversion of organic waste from landfills offers an opportunity to recover valuable nutrients such as nitrogen and phosphorus that are typically discarded. Although prior research has explored the potential for buildout of anaerobic digestion (AD) infrastructure to treat organic waste and generate energy, a better understanding is needed of the nutrient recovery potential from the solid and liquid byproducts (digestate) resulting from AD of these waste streams. We quantified the system-wide mass of nutrients that can potentially be recovered in California by integrating current and potential future AD facilities with existing nutrient recovery technologies. Based on a profitable build-out scenario for AD, the potential for nitrogen and phosphorus recovery by mass was greatest from municipal sewage sludge. The nutrient recovery (% total mass) was determined for three different end products for the combined organic waste streams: liquid fertilizer [38% of the total recovered nitrogen (TN)], struvite [50% TN, 66% total phosphorous (TP)], and compost (12% TN, 34% TP). Based on the profitable build-out scenario of AD facilities in California, the recovered nutrients would offset an estimated 11% of TN and 29% of TP of in-state synthetic fertilizer demand, whereas a scenario in which all technically recoverable biomass is collected and treated could offset 44% of TN and 97% of TP demand.


Asunto(s)
Fertilizantes , Fósforo , Anaerobiosis , Nitrógeno/análisis , Nutrientes , Aguas del Alcantarillado , Estruvita , Eliminación de Residuos Líquidos , Aguas Residuales
10.
Plant J ; 106(5): 1387-1400, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33735457

RESUMEN

ATP is secreted to the extracellular matrix, where it activates plasma membrane receptors for controlling plant growth and stress-adaptive processes. DOES NOT RESPOND TO NUCLEOTIDES 1 (DORN1), was the first plant ATP receptor to be identified but key downstream proteins remain sought after. Here, we identified 120 proteins secreted by Arabidopsis cell cultures and screened them for putative stress-responsive proteins using ATP-affinity purification. We report three Arabidopsis proteins isolated by ATP-affinity: PEROXIDASE 52, SUBTILASE-LIKE SERINE PROTEASE 1.7 and PHOSPHOLIPASE C-LIKE 1. In wild-type Arabidopsis, the expression of genes encoding all three proteins responded to fumonisin B1, a cell death-activating mycotoxin. The expression of PEROXIDASE 52 and PHOSPHOLIPASE C-LIKE 1 was altered in fumonisin B1-resistant salicylic acid induction-deficient (sid2) mutants. Exposure to fumonisin B1 suppressed PHOSPHOLIPASE C-LIKE 1 expression in sid2 mutants, suggesting that the inactivation of this gene might provide mycotoxin tolerance. Accordingly, gene knockout mutants of PHOSPHOLIPASE C-LIKE 1 were resistant to fumonisin B1-induced death. The activation of PHOSPHOLIPASE C-LIKE 1 gene expression by exogenous ATP was not blocked in dorn1 loss-of-function mutants, indicating that DORN1 is not required. Furthermore, exogenous ATP rescued both the wild type and the dorn1 mutants from fumonisin-B1 toxicity, suggesting that different ATP receptor(s) are operational in this process. Our results point to the existence of additional plant ATP receptor(s) and provide crucial downstream targets for use in designing screens to identify these receptors. Finally, PHOSPHOLIPASE C-LIKE 1 serves as a convergence point for fumonisin B1 and extracellular ATP signalling, and functions in the Arabidopsis stress response to fumonisin B1.


Asunto(s)
Adenosina Trifosfato/metabolismo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Fumonisinas/metabolismo , Fosfolipasas/metabolismo , Transducción de Señal , Arabidopsis/fisiología , Proteínas de Arabidopsis/genética , Muerte Celular , Membrana Celular/metabolismo , Matriz Extracelular/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Mutación , Peroxidasas/genética , Peroxidasas/metabolismo , Fosfolipasas/genética , Proteínas Quinasas/genética , Proteínas Quinasas/metabolismo , Proteómica , Estrés Fisiológico , Fosfolipasas de Tipo C/genética , Fosfolipasas de Tipo C/metabolismo
11.
BJPsych Open ; 6(6): e137, 2020 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-33153507

RESUMEN

BACKGROUND: The Neuropsychiatric Inventory (NPI) is predicated on the assumption that psychiatric symptoms are manifestations of disease. Biopsychosocial theories suggest behavioural changes viewed as psychiatric may also arise as a result of external behavioural triggers. Knowing the causes of psychiatric symptoms is important since the treatment and management of symptoms relies on this understanding. AIMS: This study sought to understand the causes of psychiatric symptoms recorded in care home settings by investigating qualitatively described symptoms in Neuropsychiatric Inventory-Nursing Home (NPI-NH) interviews. METHOD: The current study examined the NPI-NH interviews of 725 participants across 50 care homes. The qualitatively described symptoms from each of the 12 subscales of the NPI were extracted: 347 interviews included at least one qualitatively described symptom (n = 651 descriptions). A biopsychosocial algorithm developed following a process of independent researcher coding (n = 3) was applied to the symptom descriptions. This determined whether the description had predominantly psychiatric features, or features that were cognitive or attributable to other causes (i.e. issues with orientation and memory; expressions of need; poor care and communication; or understandable reactions). RESULTS: Our findings suggest that the majority (over 80%) of descriptions described symptoms with features that could be attributable to cognitive changes and external triggers (such as poor care and communication). CONCLUSIONS: The finding suggest that in its current form the NPI-NH may over attribute the incidence of psychiatric symptoms in care homes by overlooking triggers for behavioural changes. Measures of psychiatric symptoms should determine the causes of behavioural changes in order to guide treatments more effectively.

12.
PLoS One ; 15(7): e0235821, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32649721

RESUMEN

INTRODUCTION: The emerging epidemiological evidence of increased cardiovascular disease (CVD) risk among persons diagnosed with tuberculosis (TB) has not been systematically reviewed to date. Our aim was to review the existing epidemiological evidence for elevated risk of CVD morbidity and mortality among persons diagnosed with TB compared to controls. MATERIALS AND METHODS: EMBASE, MEDLINE, and Cochrane databases were searched (inception to January 2020) for terms related to "tuberculosis" and "cardiovascular diseases". Inclusion criteria: trial, cohort, or case-control study design; patient population included persons diagnosed with TB infection or disease; relative risk (RR) estimate and confidence interval reported for CVD morbidity or mortality compared to suitable controls. Exclusion criteria: no TB or CVD outcome definition; duplicate study; non-English abstract; non-human participants. Two reviewers screened studies, applied ROBINS-I tool to assess risk of bias, and extracted data independently. Random effects meta-analysis estimated a pooled RR of CVD morbidity and mortality for persons diagnosed with TB compared to controls. RESULTS: 6,042 articles were identified, 244 full texts were reviewed, and 16 were included, meta-analyzing subsets of 8 studies' RR estimates. We estimated a pooled RR of 1.51 (95% CI: 1.16-1.97) for major adverse cardiac events among those diagnosed with TB compared to non-TB controls (p = 0.0024). A 'serious' pooled risk of bias was found across studies with between-study heterogeneity (I2 = 75.3%). CONCLUSIONS: TB appears to be a marker for increased CVD risk; however, the literature is limited and is accompanied by serious risk of confounding bias and evidence of publication bias. Further retrospective and prospective studies are needed. Pending this evidence, best practice may be to consider persons diagnosed with TB at higher risk of CVD as a precautionary measure.


Asunto(s)
Enfermedades Cardiovasculares/etiología , Tuberculosis/complicaciones , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/virología , Humanos , Mycobacterium tuberculosis/aislamiento & purificación , Factores de Riesgo , Tuberculosis/virología
14.
BMC Health Serv Res ; 20(1): 512, 2020 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-32503536

RESUMEN

BACKGROUND: The health and social care workforce requires access to appropriate education and training to provide quality care for people with dementia. Success of a training programme depends on staff ability to put their learning into practice through behaviour change. This study aimed to investigate the barriers and facilitators to implementation of dementia education and training in health and social care services using the Theoretical Domains Framework (TDF) and COM-B model of behaviour change. METHODS: A mixed-methods design. Participants were dementia training leads, training facilitators, managers and staff who had attended training who worked in UK care homes, acute hospitals, mental health services and primary care settings. Methods were an online audit of care and training providers, online survey of trained staff and individual/group interviews with organisational training leads, training facilitators, staff who had attended dementia training and managers. Data were analysed using descriptive statistics and thematic template analysis. RESULTS: Barriers and facilitators were analysed according the COM-B domains. "Capability" factors were not perceived as a significant barrier to training implementation. Factors which supported staff capability included the use of interactive face-to-face training, and training that was relevant to their role. Factors that increased staff "motivation" included skilled facilitation of training, trainees' desire to learn and the provision of incentives (e.g. attendance during paid working hours, badges/certifications). "Opportunity" factors were most prevalent with lack of resources (time, financial, staffing and environmental) being the biggest perceived barrier to training implementation. The presence or not of external support from families and internal factors such as the organisational culture and its supportiveness of good dementia care and training implementation were also influential. CONCLUSIONS: A wide range of factors may present as barriers to or facilitators of dementia training implementation and behaviour change for staff. These should be considered by health and social care providers in the context of dementia training design and delivery in order to maximise potential for implementation.


Asunto(s)
Demencia/terapia , Personal de Salud/educación , Capacitación en Servicio/organización & administración , Servicio Social/organización & administración , Personal de Salud/psicología , Investigación sobre Servicios de Salud , Humanos , Investigación Cualitativa , Encuestas y Cuestionarios , Reino Unido
15.
Front Psychol ; 11: 196, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32116972

RESUMEN

Cognitive training (CT) aims to develop domain general mental abilities to support functions like decision making, multitasking, and performance under pressure. Research to date has indicated that CT likely aids performance on lab-based cognitive tests, but there has been little demonstration of transfer to tasks representative of real-world high performance environments. This study aimed to assess transfer from a CT intervention to near and mid-level transfer tasks, plus a far transfer test representative of real-world multitasking in a military environment. 84 participants were randomized to four independent training groups, using NeuroTracker, a CT task based on 3D object tracking. There was no evidence for near transfer (to another object tracking task) or for far transfer to a route monitoring task designed to replicate real-world multitasking. There may, however, have been some improvement in working memory performance as a result of training. These findings raise further questions about whether domain general CT will transfer to real-world performance. Effective uses of CT may require more task specific training targeting mid-level transfer effects.

16.
Aging Ment Health ; 24(3): 511-521, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-30596270

RESUMEN

Background and objectives: People with dementia occupy around one quarter of general hospital beds, with concerns consistently raised about care quality. Improving workforce knowledge, skills and attitudes is a mechanism for addressing this. However little is known about effective ways of training healthcare staff about dementia. This study aimed to understand models of dementia training most likely to lead to improved practice and better care experiences for people with dementia, and to understand barriers and facilitators to implementation.Method: A collective case study was conducted in three National Health Service Acute Hospital Trusts in England. Multiple data sources were used including interviews with training leads/facilitators, ward managers and staff who had attended training; satisfaction surveys with patients with dementia and/or carers; and observations of care using Dementia Care Mapping.Results: Interactive face-to-face training designed for general hospital staff was valued. Simulation and experiential learning methods were felt to be beneficial by some staff and stressful and distressing by others. Skilled delivery by an experienced and enthusiastic facilitator was identified as important. Staff identified learning and practice changes made following their training. However, observations revealed not all staff had the knowledge, attitudes and skills needed to deliver good care. Patient and carer satisfaction with care was mixed. A major barrier to training implementation was lack of resources. Supportive managers, organisational culture and strong leadership were key facilitators.Conclusion: Dementia training can lead to improved care practices. There are a range of key barriers and facilitators to implementation that must be considered.


Asunto(s)
Demencia , Hospitales Generales , Personal de Hospital/educación , Demencia/terapia , Inglaterra , Humanos , Medicina Estatal
17.
Nat Chem ; 12(1): 48-55, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31767994

RESUMEN

The field of synthetic biology has used the engineered assembly of synthetic gene networks to create a wide range of functions in biological systems. To date, gene-circuit-based sensors have primarily used optical proteins (for example, fluorescent, colorimetric) as reporter outputs, which has limited the potential to measure multiple distinct signals. Here we present an electrochemical interface that permits expanded multiplexed reporting for cell-free gene-circuit-based sensors. We have engineered a scalable system of reporter enzymes that cleave specific DNA sequences in solution, which results in an electrochemical signal when these newly liberated strands are captured at the surface of a nanostructured microelectrode. We describe the development of this interface and show its utility using a ligand-inducible gene circuit and toehold switch-based sensors by demonstrating the detection of multiple antibiotic resistance genes in parallel. This technology has the potential to expand the field of synthetic biology by providing an interface for materials, hardware and software.


Asunto(s)
ADN de Cadena Simple/química , Técnicas Electroquímicas/métodos , Redes Reguladoras de Genes , Genes MDR , Alcanosulfonatos/química , Compuestos Azo/química , Enzimas de Restricción del ADN/química , ADN de Cadena Simple/genética , ARN Polimerasas Dirigidas por ADN/química , Resistencia a Múltiples Medicamentos/genética , Técnicas Electroquímicas/instrumentación , Fluoresceínas/química , Azul de Metileno/química , Microelectrodos , Hibridación de Ácido Nucleico , Prueba de Estudio Conceptual , ARN Mensajero/análisis , Proteínas Virales/química
18.
Qual Life Res ; 29(2): 463-472, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31646416

RESUMEN

PURPOSE: There are many validated quality-of-life (QoL) measures designed for people living with dementia. However, the majority of these are completed via proxy-report, despite indications from community-based studies that consistency between proxy-reporting and self-reporting is limited. The aim of this study was to understand the relationship between self- and proxy-reporting of one generic and three disease-specific quality-of-life measures in people living with dementia in care home settings. METHODS: As part of a randomised controlled trial, four quality-of-life measures (DEMQOL, EQ-5D-5L, QOL-AD and QUALID) were completed by people living with dementia, their friends or relatives or care staff proxies. Data were collected from 726 people living with dementia living in 50 care homes within England. Analyses were conducted to establish the internal consistency of each measure, and inter-rater reliability and correlation between the measures. RESULTS: Residents rated their quality of life higher than both relatives and staff on the EQ-5D-5L. The magnitude of correlations varied greatly, with the strongest correlations between EQ-5D-5L relative proxy and staff proxy. Internal consistency varied greatly between measures, although they seemed to be stable across types of participants. There was poor-to-fair inter-rater reliability on all measures between the different raters. DISCUSSION: There are large differences in how QoL is rated by people living with dementia, their relatives and care staff. These inconsistencies need to be considered when selecting measures and reporters within dementia research.


Asunto(s)
Demencia/psicología , Apoderado , Calidad de Vida/psicología , Autoinforme , Anciano , Anciano de 80 o más Años , Inglaterra , Femenino , Humanos , Masculino , Reproducibilidad de los Resultados , Encuestas y Cuestionarios
19.
New Phytol ; 224(4): 1518-1531, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31549420

RESUMEN

Forward genetic screens play a key role in the identification of genes contributing to plant stress tolerance. Using a screen for freezing sensitivity, we have identified a novel freezing tolerance gene, SENSITIVE-TO-FREEZING8, in Arabidopsis thaliana. We identified SFR8 using recombination-based mapping and whole-genome sequencing. As SFR8 was predicted to have an effect on cell wall composition, we used GC-MS and polyacrylamide gel electrophoresis to measure cell-wall fucose and boron (B)-dependent dimerization of the cell-wall pectic domain rhamnogalacturonan II (RGII) in planta. After treatments to promote borate-bridging of RGII, we assessed freeze-induced damage in wild-type and sfr8 plants by measuring electrolyte leakage from freeze-thawed leaf discs. We mapped the sfr8 mutation to MUR1, a gene encoding the fucose biosynthetic enzyme GDP-d-mannose-4,6-dehydratase. sfr8 cell walls exhibited low cell-wall fucose levels and reduced RGII bridging. Freezing sensitivity of sfr8 mutants was ameliorated by B supplementation, which can restore RGII dimerization. B transport mutants with reduced RGII dimerization were also freezing-sensitive. Our research identifies a role for the structure and composition of the plant primary cell wall in determining basal plant freezing tolerance and highlights the specific importance of fucosylation, most likely through its effect on the ability of RGII pectin to dimerize.


Asunto(s)
Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiología , Pared Celular/metabolismo , Arabidopsis/citología , Proteínas de Arabidopsis/genética , Boro/metabolismo , Clonación Molecular , Congelación , Fucosa/metabolismo , Mutación , Pectinas/química , Pectinas/metabolismo , Células Vegetales/metabolismo , Estrés Fisiológico/fisiología
20.
Ther Adv Neurol Disord ; 12: 1756286419852217, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31320931

RESUMEN

Cognitive stimulation therapy (CST) is widely used with people with dementia, but there is no evidence of its efficacy in mild cognitive impairment or dementia in Parkinson's disease (PD-MCI; PDD) or dementia with Lewy bodies (DLB). We aimed to explore the impact of 'CST-PD', which is home-based, individualized CST adapted for this population. In a single-blind, randomized controlled exploratory pilot trial (RCT), we randomized 76 participant-dyads [PD-MCI (n = 15), PDD (n = 40), DLB (n = 21) and their care partners] to CST-PD or treatment as usual (TAU). CST-PD involves home-based cognitively stimulating and engaging activities delivered by a trained care partner. Exploratory outcomes at 12 weeks included cognition (Addenbrooke's Cognitive Evaluation; ACE-III), neuropsychiatric symptoms and function. In care partners, we assessed burden, stress and general health status. Relationship quality and quality of life were assessed in both dyad members. At 12 weeks, the ACE-III showed a nonstatistically significant improvement in the CST-PD group compared with the TAU group, although neuropsychiatric symptoms increased significantly in the former. In contrast, care partners' quality of life (d = 0.16) and relationship quality ('satisfaction', d = 0.01; 'positive interaction', d = 0.55) improved significantly in the CST-PD group, and care burden (d = 0.16) and stress (d = 0.05) were significantly lower. Qualitative findings in the CST-PD recipients revealed positive 'in the moment' responses to the intervention, supporting the quantitative results. In conclusion, care-partner-delivered CST-PD may improve a range of care-partner outcomes that are important in supporting home-based care. A full-scale follow-up RCT to evaluate clinical and cost effectiveness is warranted.

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