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1.
J Dairy Sci ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38908700

RESUMO

Mastitis is one of the most common diseases of dairy cattle. It has a high impact on farm economy, farmers' working time, and antimicrobial usage (AMU). Selective dry cow therapy (SDCT) is an effective means of reducing AMU without negatively affecting udder health. The objective of our study was to evaluate the impact of SDCT implementation on farmer's income, working time, and AMU, using a bioeconomic model. A stochastic dairy simulation model (DairyHealthSim) based on a weekly model was used to simulate herd dynamics, reproduction, milk production, culling decisions, health outcomes, and the management of health events. A specific module was developed for the simulation of quarter-level intramammary infection (IMI) acquisition and elimination during the lactation and dry-off periods, and 25 different farm settings were defined to represent herds with various udder health situations. We then defined 20 scenarios of SDCT by combining both the use of different thresholds of somatic cell count and milk bacteriology for treatment allocation and the use of internal teat sealant (ITS). All SDCT protocols had a low impact on farmer's income, and we identified some protocols with a positive farm gross margin (up to 15.83 CA$/dried- cow). We also found that adding an ITS to all cows led to greater economic gain. The application of SDCT had a low impact on farmers' working time, except when milk bacteriology was used for decision-making. Antimicrobial treatment to all cows above 200,000 cells/mL at last control, with the use of ITS on all cows, seems a good choice in most dairy farms. These findings could be used to convince farmers to adopt this strategy at dry-off.

2.
AAPS PharmSciTech ; 23(6): 215, 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35922577

RESUMO

The human operator is acknowledged as the greatest potential source of contamination in aseptic processing. To avoid contamination, barrier systems have progressively reduced the amount of human intervention in the critical zone. This study extends the trajectory of enhanced patient safety through the elimination of human intervention in aseptic filling. Eight companies that are users of closed robotic workcells have aggregated their usage data from 2018 to 2021. The study analyzes the critical design elements and performance of the Cytiva SA25 Aseptic Filling Workcell. The SA25 is a standardized, fully closed robotic system for aseptic filling of vials, syringes, and cartridges that eliminates operator intervention in the critical zone. The standardized design means that the system is not modified to suit a particular application and the same environmental monitoring strategy can be used across different installations. The SA25 provides significantly increased sterility assurance when producing sterile injectables. Users have observed non-viable particle levels well within ISO 5/Grade A air requirements, with extremely low probabilities of entering a dosage container. There have been zero cases of microbial growth in more than 250 media fills and good manufacturing practice (GMP) batches. Across all dosage formats and sizes, the aseptic process is repeatable, with more than 99.3% of units meeting acceptance criteria. These data demonstrate that eliminating risk through design is successful in the SA25, with an improved aseptic process in comparison to filling systems using Restricted Access Barrier Systems (RABS) or isolators with glove ports. One of the contributing companies to this article achieved an industry first. The U.S. FDA-approved commercial production of their biologic drugs without the requirement for routine viable environmental monitoring (EM), requiring viable EM only during process simulations. Based on the data presented and planned future research, new regulatory consideration should be made for closed robotic workcells to ensure that regulations meant for previous technologies with different risk profiles are not inappropriately applied.


Assuntos
Procedimentos Cirúrgicos Robóticos , Contaminação de Medicamentos , Monitoramento Ambiental , Humanos , Seringas
3.
Int Psychogeriatr ; 33(9): 917-931, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-30602403

RESUMO

BACKGROUND: Over 400,000 people live in care home settings in the UK. One way of understanding and improving the quality of care provided is by measuring and understanding the quality of life (QoL) of those living in care homes. This review aimed to identify and examine the psychometric properties including feasibility of use of dementia-specific QoL measures developed or validated for use in care settings. DESIGN: Systematic review. METHODS: Instruments were identified using four electronic databases (PubMed, PsycINFO, Web of Science, and CINAHL) and lateral search techniques. Searches were conducted in January 2017. Studies which reported on the development and/or validation of dementia specific QoL instruments for use in care settings written in English were eligible for inclusion. The methodological quality of the studies was assessed using the COSMIN checklist. Feasibility was assessed using a checklist developed specifically for the review. RESULTS: Six hundred and sixteen articles were identified in the initial search. After de-duplication, screening and further lateral searches were performed, 25 studies reporting on 9 dementia-specific QoL instruments for use in care home settings were included in the review. Limited evidence was available on the psychometric properties of many instruments identified. Higher-quality instruments were not easily accessible or had low feasibility of use. CONCLUSIONS: Few high-quality instruments of QoL validated for use in care home settings are readily or freely available. This review highlights the need to develop a well-validated measure of QoL for use within care homes that is also feasible and accessible.


Assuntos
Demência , Qualidade de Vida , Lista de Checagem , Demência/terapia , Estudos de Viabilidade , Humanos , Psicometria
4.
Int J Geriatr Psychiatry ; 34(1): 79-86, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30251443

RESUMO

BACKGROUND: Dementia is a major global health and social care challenge, and family carers are a vital determinant of positive outcomes for people with dementia. This study's aim was to develop a conceptual framework for the Quality of Life (QOL) of family carers of people with dementia. METHODS: We studied family carers of people with dementia and staff working in dementia services iteratively using in-depth individual qualitative interviews and focus groups discussions. Analysis used constant comparison techniques underpinned by a collaborative approach with a study-specific advisory group of family carers. RESULTS: We completed 41 individual interviews with 32 family carers and nine staff and two focus groups with six family carers and five staff. From the analysis, we identified 12 themes that influenced carer QOL. These were organised into three categories focussing on person with dementia, carer, and external environment. CONCLUSIONS: For carers of people with dementia, the QOL construct was found to include condition-specific domains which are not routinely considered in generic assessment of QOL. This has implications for researchers, policy makers, and service providers in addressing and measuring QOL in family carers of people with dementia.


Assuntos
Cuidadores/psicologia , Demência/psicologia , Família/psicologia , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Feminino , Grupos Focais , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa
5.
Ear Hear ; 40(4): 1001-1008, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30531261

RESUMO

OBJECTIVES: To (1) identify the etiologies and risk factors of the patient cohort and determine the degree to which they reflected the incidence for children with hearing loss and (2) quantify practice management patterns in three catchment areas of the United States with available centers of excellence in pediatric hearing loss. DESIGN: Medical information for 307 children with bilateral, mild-to-severe hearing loss was examined retrospectively. Children were participants in the Outcomes of Children with Hearing Loss (OCHL) study, a 5-year longitudinal study that recruited subjects at three different sites. Children aged 6 months to 7 years at time of OCHL enrollment were participants in this study. Children with cochlear implants, children with severe or profound hearing loss, and children with significant cognitive or motor delays were excluded from the OCHL study and, by extension, from this analysis. Medical information was gathered using medical records and participant intake forms, the latter reflecting a caregiver's report. A comparison group included 134 children with normal hearing. A Chi-square test on two-way tables was used to assess for differences in referral patterns by site for the children who are hard of hearing (CHH). Linear regression was performed on gestational age and birth weight as continuous variables. Risk factors were assessed using t tests. The alpha value was set at p < 0.05. RESULTS: Neonatal intensive care unit stay, mechanical ventilation, oxygen requirement, aminoglycoside exposure, and family history were correlated with hearing loss. For this study cohort, congenital cytomegalovirus, strep positivity, bacterial meningitis, extracorporeal membrane oxygenation, and loop diuretic exposure were not associated with hearing loss. Less than 50% of children underwent imaging, although 34.2% of those scanned had abnormalities identified. No single imaging modality was preferred. Differences in referral rates were apparent for neurology, radiology, genetics, and ophthalmology. CONCLUSIONS: The OCHL cohort reflects known etiologies of CHH. Despite available guidelines, centers of excellence, and high-yield rates for imaging, the medical workup for children with hearing loss remains inconsistently implemented and widely variable. There remains limited awareness as to what constitutes appropriate medical assessment for CHH.


Assuntos
Aminoglicosídeos/uso terapêutico , Perda Auditiva Bilateral/epidemiologia , Hospitalização/estatística & dados numéricos , Encaminhamento e Consulta , Respiração Artificial/estatística & dados numéricos , Estudos de Casos e Controles , Área Programática de Saúde , Criança , Pré-Escolar , Feminino , Genética Médica , Perda Auditiva Bilateral/etiologia , Humanos , Lactente , Unidades de Terapia Intensiva Neonatal , Masculino , Anamnese , Neurologia , Oftalmologia , Oxigenoterapia/estatística & dados numéricos , Radiologia , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Estados Unidos/epidemiologia
6.
Qual Life Res ; 28(8): 2299-2310, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31030366

RESUMO

PURPOSE: We aimed to address gaps identified in the evidence base and instruments available to measure the quality of life (QOL) of family carers of people with dementia, and develop a new brief, reliable, condition-specific instrument. METHODS: We generated measurable domains and indicators of carer QOL from systematic literature reviews and qualitative interviews with 32 family carers and 9 support staff, and two focus groups with 6 carers and 5 staff. Statements with five tailored response options, presenting variation on the QOL continuum, were piloted (n = 25), pre-tested (n = 122) and field-tested (n = 300) in individual interviews with family carers from North London and Sussex. The best 30 questions formed the C-DEMQOL questionnaire, which was evaluated for usability, face and construct validity, reliability and convergent/discriminant validity using a range of validation measures. RESULTS: C-DEMQOL was received positively by the carers. Factor analysis confirmed that C-DEMQOL sum scores are reliable in measuring overall QOL (ω = 0.97) and its five subdomains: 'meeting personal needs' (ω = 0.95); 'carer wellbeing' (ω = 0.91); 'carer-patient relationship' (ω = 0.82); 'confidence in the future' (ω = 0.90) and 'feeling supported' (ω = 0.85). The overall QOL and domain scores show the expected pattern of convergent and discriminant relationships with established measures of carer mental health, activities and dementia severity and symptoms. CONCLUSIONS: The robust psychometric properties support the use of C-DEMQOL in evaluation of overall and domain-specific carer QOL; replications in independent samples and studies of responsiveness would be of value.


Assuntos
Cuidadores/psicologia , Psicometria/métodos , Qualidade de Vida/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Demência/psicologia , Emoções , Análise Fatorial , Feminino , Grupos Focais , Humanos , Londres , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Inquéritos e Questionários , Adulto Jovem
7.
Epilepsy Behav ; 84: 166-172, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29803947

RESUMO

OBJECTIVE: Autonomic dysregulation is a possible pathomechanism of sudden unexpected death in epilepsy (SUDEP). Cardiac arrhythmias and autonomic symptoms are most commonly associated with seizures arising from the temporal lobes. The aim of this study was to investigate whether simultaneous seizure activity in both temporal lobes affects the autonomic nervous system differently from seizure activity in one temporal lobe as assessed by heart rate variability (HRV). METHODS: Electrocardiography (ECG) and intracranial electroencephalography (iEEG) data from 13 patients with refractory temporal lobe epilepsy who had seizures that propagated electrically from one temporal lobe to the other during video-EEG-ECG monitoring were retrospectively reviewed. The time domain, frequency domain, and nonlinear parameters of HRV were evaluated by analyzing 4-minute-long ECG epochs, sampling from baseline, preictal and postictal periods as well as epochs constituting unitemporal and bitemporal ictal activity. RESULTS: Heart rate was significantly higher during bitemporal ictal activity compared with all other time points. The time domain and nonlinear parameters of HRV were significantly decreased during bitemporal activity compared with baseline, and multiple components of HRV (standard deviation of RR intervals (SDNN), coefficient of variation (CV), root mean square of successive differences (RMSSD), and standard deviation of short-term variability (SD1)) were significantly lower during bitemporal activity compared with unitemporal activity. Frequency domain analysis showed no significant differences. CONCLUSION: This study shows that bitemporal seizure activity significantly increases heart rate and decreases HRV, indicating increased autonomic imbalance with a shift towards sympathetic predominance, and this may increase the risk of SUDEP.


Assuntos
Doenças do Sistema Nervoso Autônomo/fisiopatologia , Sistema Nervoso Autônomo/fisiopatologia , Epilepsia do Lobo Temporal/fisiopatologia , Frequência Cardíaca/fisiologia , Convulsões/fisiopatologia , Adulto , Eletrocardiografia , Eletroencefalografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
8.
Alzheimers Dement ; 13(5): 572-581, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28167069

RESUMO

INTRODUCTION: Family carers of people with dementia are their most important support in practical, personal, and economic terms. Carers are vital to maintaining the quality of life (QOL) of people with dementia. This review aims to identify factors related to the QOL of family carers of people with dementia. METHODS: Searches on terms including "carers," "dementia," "family," and "quality of life" in research databases. Findings were synthesized inductively, grouping factors associated with carer QOL into themes. RESULTS: A total of 909 abstracts were identified. Following screening, lateral searches, and quality appraisal, 41 studies (n = 5539) were included for synthesis. A total of 10 themes were identified: demographics; carer-patient relationship; dementia characteristics; demands of caring; carer health; carer emotional well-being; support received; carer independence; carer self-efficacy; and future. DISCUSSION: The quality and level of evidence supporting each theme varied. We need further research on what factors predict carer QOL in dementia and how to measure it.


Assuntos
Cuidadores/psicologia , Demência/enfermagem , Qualidade de Vida , Demência/psicologia , Humanos
10.
Aggress Behav ; 42(3): 254-73, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26350167

RESUMO

Sexual harassment represents aggressive behavior that is often enacted instrumentally, in response to a threatened sense of masculinity and male identity. To date, however, theoretical attention to the social cognitive processes that regulate workplace harassment is scant. This article presents the development and preliminary validation of the Moral Disengagement in Sexual Harassment Scale (MDiSH); a self-report measure of moral disengagement in the context of hostile work environment harassment. Three studies (total n = 797) document the excellent psychometric properties of this new scale. Male U.K. university students (Study 1: n = 322) and U.S. working males (Studies 2 and 3: n = 475) completed the MDiSH and an array of measures for construct validation. The MDiSH exhibited positive correlations with sexual harassment myth acceptance, male gender identification, and hostile sexism. In Study 3, participants were exposed to a fictitious case of hostile work environment harassment. The MDiSH attenuated moral judgment, negative emotions (guilt, shame, and anger), sympathy, and endorsement of prosocial behavioral intentions (support for restitution) associated with the harassment case. Conversely, the MDiSH increased positive affect (happiness) about the harassment and attribution of blame to the female complainant. Implications for practice and future research avenues are discussed.


Assuntos
Emoções , Princípios Morais , Sexismo/psicologia , Assédio Sexual/psicologia , Percepção Social , Adolescente , Adulto , Idoso , Hostilidade , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria , Adulto Jovem
11.
Vet Sci ; 10(4)2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37104423

RESUMO

Severe clinical mastitis is a frequent disease of dairy cattle. An effective mean of predicting survival despite treatment would be helpful for making euthanasia decisions in poor prognosis cases. The objective was to develop a nomogram for prediction of death or culling in the 60 days following a severe mastitis episode in dairy cows at first veterinary visit in farm settings. A total of 224 dairy cows presenting severe clinical mastitis and examined for the first time by a veterinarian were included in a prospective study. Clinical and laboratory (complete blood cell count, L-lactate, cardiac troponin I, milk culture) variables were recorded. Animals were followed for 60 days. A nomogram was built with an adaptive elastic-net Cox proportional hazards model. Performances and relevance were evaluated by area under the receiver operating characteristic curve (AUC), Harrell's concordance index (C-index), calibration curve, decision curve analysis (DCA) and misclassification cost term (MCT). The nomogram included: lactation number, recumbency, depression intensity, capillary refilling time, ruminal motility rate, dehydration level, lactates concentration, hematocrit, band neutrophils count, monocyte count, and milk bacteriology. The AUC and C-index showed a good calibration and ability to discriminate. The DCA suggested that the nomogram was clinically relevant. Euthanizing animals having less than 25% probability of survival is economically optimal. It could be used for early euthanasia decisions in animals that would not survive despite treatment. To facilitate the use of this nomogram by veterinarians, a web-based app was developed.

12.
Microorganisms ; 11(4)2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-37110297

RESUMO

Predatory outer membrane vesicles (OMVs) secreted by myxobacteria fuse readily with the outer membranes of Gram-negative bacteria, introducing toxic cargo into their prey. Here we used a strain of the myxobacterium Myxococcus xanthus that produces fluorescent OMVs to assay the uptake of OMVs by a panel of Gram-negative bacteria. M. xanthus strains took up significantly less OMV material than the tested prey strains, suggesting that re-fusion of OMVs with producing organisms is somehow inhibited. The OMV killing activity against different prey correlated strongly with the predatory activity of myxobacterial cells, however, there was no correlation between OMV killing activity and their propensity to fuse with different prey. It has previously been proposed that M. xanthus GAPDH stimulates the predatory activity of OMVs by enhancing OMV fusion with prey cells. Therefore, we expressed and purified active fusion proteins of M. xanthus glyceraldehyde-3-phosphate dehydrogenase and phosphoglycerate kinase (GAPDH and PGK; moonlighting enzymes with additional activities beyond their roles in glycolysis/gluconeogenesis) to investigate any involvement in OMV-mediated predation. Neither GAPDH nor PGK caused lysis of prey cells or enhanced OMV-mediated lysis of prey cells. However, both enzymes were found to inhibit the growth of Escherichia coli, even in the absence of OMVs. Our results suggest that fusion efficiency is not a determinant of prey killing, but instead resistance to the cargo of OMVs and co-secreted enzymes dictates whether organisms can be preyed upon by myxobacteria.

13.
Mar Environ Res ; 191: 106163, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37678098

RESUMO

With thousands of tons of Tyre Wear Particles (TWP) entering the aquatic environment every year, TWP are considered a major contributor to microplastic pollution. TWP leach organic compounds and metals in water, potentially affecting the marine food web. However, little is known about the toxicity of TWP leachates on marine copepods, a major food web constituent, and a key group to determine the environmental risk of pollution in marine ecosystems. In this study, we determined the lethal effect of TWP leachates on marine copepods after 24, 48, and 72-h of exposure to 0.05-100% leachate solutions prepared using a concentration of 5 g TWP L-1. The calanoids Acartia tonsa, Temora longicornis and Centropages hamatus, the cyclopoid Oithona davisae and the harpacticoid Amonardia normanni were used as experimental species. TWP leachates were toxic to all the studied species, with toxicity increasing as leachate solution and exposure time increased. Median lethal concentration (LC50, 72-h) ranged from 0.22 to 3.43 g L-1 and calanoid copepods were more sensitive to TWP leachates than the cyclopoid O. davisae and the harpacticoid A. normanni. Toxicity of TWP leachates was not related to the copepod body size, which suggests that other traits such as foraging behaviour or adaptation to contaminants could explain the higher tolerance of cyclopoid and harpacticoid to TWP leachates compared to calanoid copepods. Although field data on the concentration of TWP and their chemical additives are still limited, our results suggest that TWP leachates can negatively impact planktonic food webs in coastal areas after road runoff events.


Assuntos
Copépodes , Poluentes Químicos da Água , Animais , Plásticos , Ecossistema , Poluentes Químicos da Água/toxicidade , Plâncton
14.
Cancers (Basel) ; 15(17)2023 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-37686623

RESUMO

Multiple myeloma (MM) is an incurable hematological malignancy characterized by the clonal proliferation of malignant plasma cells. Despite the development of a diverse array of targeted drug therapies over the last decade, patients often relapse and develop refractory disease due to multidrug resistance. Obesity is a growing public health threat and a risk factor for multiple myeloma, although the mechanisms by which obesity contributes to MM growth and progression have not been fully elucidated. In the present study, we evaluated whether crosstalk between adipocytes and MM cells promoted drug resistance and whether this was amplified by obesity. Human adipose-derived stem cells (ASCs) from nineteen normal (BMI = 20-25 kg/m2), overweight (25-30 kg/m2), or obese (30-35 kg/m2) patients undergoing elective liposuction were utilized. Cells were differentiated into adipocytes, co-cultured with RPMI 8226 or U266B1 multiple myeloma cell lines, and treated with standard MM therapies, including bortezomib or a triple combination of bortezomib, dexamethasone, and lenalidomide. We found that adipocytes from overweight and obese individuals increased cell adhesion-mediated drug resistance (CAM-DR) survival signals in MM cells, and P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) drug transporter expression. Further, co-culture enhanced in vitro angiogenesis, MMP-2 activity, and protected MM cells from drug-induced decreases in viability. In summary, we provide an underlying mechanism by which obesity can impair the drug response to MM and allow for recurrence and/or disease progression.

15.
Aquat Toxicol ; 252: 106299, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36152424

RESUMO

Tyre wear particles (TWP) are some of the dominant sources of microplastics in the aquatic environment. Once TWP enter aquatic systems, they can leach certain plastic additives that can be potentially toxic to biota. However, little is known about the impact of TWP lixiviates on marine phytoplankton, the base of marine food webs. This study aims to determine the acute toxic effect of leachates derived from TWP on three phytoplankton species: the cryptophyte Rhodomonas salina, the diatom Thalassiosira weissflogii and the dinoflagellate Heterocapsa steinii, using the median effect concentration (EC50) for specific growth rate as endpoint. Leachates were obtained by incubating 1 g L-1 of < 250 µm TWP in artificial seawater for 3 days. Each phytoplankton species was exposed to leachates at five different concentrations, and cell concentrations were measured every 24 h over 3 days. Leachates from TWP were toxic to marine phytoplankton. The dinoflagellate H. steinii was the most sensitive species, with 72-h EC50 of 23% leachate concentration, whereas R. salina and T. weissflogii exhibited EC50 values of 64% and 73%, respectively. Our results suggest that TWP leachates have a negative effect on phytoplankton growth, although more field data on the concentration of TWPs and their leachates is needed to fully evaluate the environmental impact of TWP.


Assuntos
Diatomáceas , Dinoflagellida , Poluentes Químicos da Água , Fitoplâncton , Plásticos , Microplásticos , Poluentes Químicos da Água/toxicidade
16.
Cell Death Differ ; 29(8): 1596-1610, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35322202

RESUMO

Multiciliated cells (MCCs) in the brain reside in the ependyma and the choroid plexus (CP) epithelia. The CP secretes cerebrospinal fluid that circulates within the ventricular system, driven by ependymal cilia movement. Tumors of the CP are rare primary brain neoplasms mostly found in children. CP tumors exist in three forms: CP papilloma (CPP), atypical CPP, and CP carcinoma (CPC). Though CPP and atypical CPP are generally benign and can be resolved by surgery, CPC is a particularly aggressive and little understood cancer with a poor survival rate and a tendency for recurrence and metastasis. In contrast to MCCs in the CP epithelia, CPCs in humans are characterized by solitary cilia, frequent TP53 mutations, and disturbances to multiciliogenesis program directed by the GMNC-MCIDAS transcriptional network. GMNC and MCIDAS are early transcriptional regulators of MCC fate differentiation in diverse tissues. Consistently, components of the GMNC-MCIDAS transcriptional program are expressed during CP development and required for multiciliation in the CP, while CPC driven by deletion of Trp53 and Rb1 in mice exhibits multiciliation defects consequent to deficiencies in the GMNC-MCIDAS program. Previous studies revealed that abnormal NOTCH pathway activation leads to CPP. Here we show that combined defects in NOTCH and Sonic Hedgehog signaling in mice generates tumors that are similar to CPC in humans. NOTCH-driven CP tumors are monociliated, and disruption of the NOTCH complex restores multiciliation and decreases tumor growth. NOTCH suppresses multiciliation in tumor cells by inhibiting the expression of GMNC and MCIDAS, while Gmnc-Mcidas overexpression rescues multiciliation defects and suppresses tumor cell proliferation. Taken together, these findings indicate that reactivation of the GMNC-MCIDAS multiciliogenesis program is critical for inhibiting tumorigenesis in the CP, and it may have therapeutic implications for the treatment of CPC.


Assuntos
Carcinoma , Proteínas de Ciclo Celular , Neoplasias do Plexo Corióideo , Proteínas Nucleares , Animais , Carcinoma/genética , Proteínas de Ciclo Celular/genética , Neoplasias do Plexo Corióideo/genética , Neoplasias do Plexo Corióideo/patologia , Proteínas Hedgehog/genética , Humanos , Camundongos , Proteínas Nucleares/genética
17.
Lang Speech Hear Serv Sch ; 52(2): 512-528, 2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33497582

RESUMO

Purpose The purpose of this study was to examine confidence levels and identify predictors of increased confidence of school-based speech-language pathologists (SLPs) relative to different aspects of the augmentative and alternative communication (AAC) assessment process. Method Surveys were completed by 272 school-based SLPs. Questions were designed to capture demographic information and confidence in areas of assessment such as student capabilities, participation, and feature matching. Results There were variable levels of confidence across aspects of assessment. Respondents were less confident in tasks related to assessing students with severe physical impairments and incorporating aspects related to cultural and linguistic diversity in their assessment. SLPs were more confident assessing student participation and unaided communication. Additionally, respondents had less confidence in matching the features of high-tech speech-generating devices to their students. Self-identification as an AAC specialist, years of experience, percentage of caseload of students with complex communication needs, and length of longest continuing education experiences all contributed to predicting confidence in most areas of assessment. However, years of experience did not contribute to predicting confidence in feature matching. Conclusions Results from this study acknowledge that SLPs are likely to have varied degrees of confidence in aspects of assessment related to preparation, clinical experience, and self-identification of specialty. Findings from this study support increasing training opportunities in AAC assessment. As specialization was the strongest predictor of confidence, further research should investigate the characteristics and preparation of self-identified AAC specialists. This is an important first step in pinpointing ways to increase confidence in school-based SLPs.


Assuntos
Auxiliares de Comunicação para Pessoas com Deficiência , Comunicação , Instituições Acadêmicas , Patologia da Fala e Linguagem/métodos , Humanos , Fala , Estudantes , Inquéritos e Questionários
18.
PLoS One ; 16(5): e0252193, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34038471

RESUMO

BACKGROUND: Cerebral palsy (CP) is a leading cause of childhood disability. The motor impairments of individuals with CP significantly affect the kinematics of an efficient gait pattern. Robotic therapies have become increasingly popular as an intervention to address this. Powered lower limb exoskeletons (PoLLE) are a novel form of robotic therapy that allow the individual to perform over-ground gait training and yet its effectiveness for CP is unknown. PURPOSE: To determine the effectiveness of PoLLE use on gait in individuals with CP. METHOD: A systematic search of eight electronic databases was conducted in March 2020. Studies included children (0-18 years) and or adults (18+ years) diagnosed with CP who used a PoLLE for gait training. This review was conducted and reported in line with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement, with the methodology registered with PROSPERO (CRD42020177160). A modified version of the McMaster critical review form for quantitative studies was used to assess the methodological quality. Due to the heterogeneity of the included studies, a descriptive synthesis using the National Health & Medical Research Council (NHMRC) FORM framework was undertaken. RESULTS: Of the 2089 studies screened, ten case series and three case studies met the inclusion criteria highlighting the current evidence base is emerging and low level. A range of PoLLEs were investigated with effectiveness measured by using a number of outcome measures. Collectively, the body of evidence indicates there is some consistent positive evidence on the effectiveness of PoLLE in improving gait in individuals with CP, with minimal adverse effects. While this is a positive and encouraging finding for an emerging technology, methodological concerns also need to be acknowledged. CONCLUSION: With rapidly evolving technology, PoLLEs could play a transformative role in the lives of people impacted by CP. Ongoing research is required to further strengthen the evidence base and address current methodological concerns.


Assuntos
Paralisia Cerebral/terapia , Exoesqueleto Energizado , Marcha/fisiologia , Adolescente , Adulto , Criança , Pré-Escolar , Metabolismo Energético/fisiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Adulto Jovem
19.
BMJ Open ; 9(8): e028045, 2019 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-31399452

RESUMO

OBJECTIVE: To investigate the routine use of a measure of quality of life (QoL) in care homes and assess its psychometric properties when used by care staff. DESIGN: A cross-sectional two-phase study. SETTING AND PARTICIPANTS: Data were collected from care staff in seven care homes in East Sussex, England. METHOD: Phase I: The ability of care staff from two care homes to use the DEMQOL-Proxy without interviewer administration was assessed using agreement analysis between a self-administered and interviewer-administered version of the instrument. Based on these findings, DEMQOL-Proxy was adapted into a new version, DEMQOL-CH, for use as a self-administered instrument in care homes. We assessed agreement between the new DEMQOL-CH and DEMQOL-Proxy to ensure DEMQOL-CH was used correctly. Phase II: A preliminary assessment of the psychometric properties of DEMQOL-CH when used routinely was completed in a further five care homes. RESULTS: Phase I: Nineteen care staff from two care homes completed QoL measurements for residents. Systematic error was identified when staff self-completed the DEMQOL-Proxy without an interviewer. We modified the DEMOoL-Proxy to create DEMQOL-CH; this reduced the error, producing a version that could be used more accurately by care staff. Phase II: Eleven care staff from five care homes rated resident QoL routinely. DEMQOL-CH showed acceptable psychometric properties with satisfactory reliability and validity and a clear factor structure. CONCLUSIONS: The research presents positive preliminary data on the acceptability, feasibility and performance of routine QoL measurement in care homes using an adapted version of DEMQOL-Proxy, the DEMQOL-CH. Results provide evidence to support the concept that routine measurement of QoL may be possible in care homes. Research is needed to refine and test the methodology and instrument further and to explore the potential for benefits to residents, staff and care homes in larger and more representative populations.


Assuntos
Demência/psicologia , Autoavaliação Diagnóstica , Psicometria/instrumentação , Qualidade de Vida/psicologia , Inquéritos e Questionários , Adolescente , Adulto , Idoso , Cuidadores , Disfunção Cognitiva , Estudos Transversais , Inglaterra , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Adulto Jovem
20.
Alzheimers Dement (Amst) ; 11: 45-52, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30623018

RESUMO

INTRODUCTION: The psychometric properties of the social functioning in dementia scale over different dementia severities are unknown. METHODS: We interviewed 299 family carers of people with mild, moderate, or severe dementia from two UK research sites; examined acceptability (completion rates); conducted exploratory factor analysis; and tested each factor's internal consistency and construct validity. RESULTS: Of 299, 285 (95.3%) carers completed questionnaires. Factor analysis indicated three distinct factors with acceptable internal consistency: spending time with other people, correlating with overall social function (r = 0.56, P < .001) and activities of daily living (r = -0.48, P < .001); communicating with other people correlating with activities of daily living (r = -0.66, P < .001); and sensitivity to other people correlating with quality of life (r = 0.35, P < .001) and inversely with neuropsychiatric symptoms (r = -0.45, P < .001). The three factors' correlations with other domains were similar across all dementia severities. DISCUSSION: The social functioning in dementia scale carer version measures three social functioning domains and has satisfactory psychometric properties in all severities of dementia.

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