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1.
Neuropsychol Rehabil ; : 1-40, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38727637

RESUMO

Spatial neglect commonly occurs after a stroke, resulting in diverse impacts depending on the type and severity. There are almost 300 tools for assessing neglect, yet there is a lack of knowledge on the psychometric properties of these tools. The objective of this systematic review, registered on Prospero (CRD42021271779), was to determine the quality of the evidence for assessing spatial neglect, categorized by neglect subtype. The following databases were searched on 3rd May 2022 from database inception: Ovid Emcare, Embase, Ovid MEDLINE, APA PsycINFO, Web of Science (SCI-EXPANDED; SSCI; A&HCI; ESCI) and Scopus. All primary peer-reviewed studies (>5 participants) of adults post stroke, reporting any psychometric property of 33 commonly used neglect assessment tools were included. The COSMIN (COnsensus-based Standards for the selection of health Measurement INstruments) risk of bias tool was used to assess the methodological quality of the studies and summarize the psychometric properties of each tool. 164 articles were included, with a total of 12,463 people with stroke. The general quality of the evidence was poor and no one tool had high-quality evidence of both validity and reliability. Eleven tools show some promise as they meet the minimum criteria for good measurement properties for both validity and reliability.

2.
Eur J Neurol ; 29(9): 2596-2606, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35510782

RESUMO

BACKGROUND AND PURPOSE: Unilateral neglect is a common cognitive disorder following stroke. Neglect has a significant impact on functional outcomes, so it is important to detect. However, there is no consensus on which are the best screening tests to administer to detect neglect in time-limited clinical environments. METHODS: Members of the European Academy of Neurology Scientific Panel on Higher Cortical Functions, neuropsychologists, occupational therapists, and researchers produced recommendations for primary and secondary tests for bedside neglect testing based on a rigorous literature review, data extraction, online consensus meeting, and subsequent iterations. RESULTS: A total of 512 articles were screened, and 42 were included. These reported data from 3367 stroke survivors assessed using 62 neglect screens. Tests were grouped into cancellation, line bisection, copying, reading/writing, and behavioral. Cancellation tasks were most frequently used (97.6% of studies), followed by bisection, copying, behavioral, and reading/writing assessments. The panel recommended a cancellation test as the primary screening test if there is time to administer only one test. One of several cancellation tests might be used, depending on availability. If time permits, one or more of line bisection, figure copying, and baking tray task were recommended as secondary tests. Finally, if a functional and ecological test is feasible, the Catherine Bergego Scale was recommended. Overall, the literature suggests that no single test on its own is sufficient to exclude a diagnosis of neglect. Therefore, the panel recommended that multiple neglect tests should be used whenever possible. CONCLUSIONS: This study provides consensus recommendations for rapid bedside detection of neglect in real-world, clinical environments.


Assuntos
Agnosia , Neurologia , Transtornos da Percepção , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Testes Neuropsicológicos , Transtornos da Percepção/diagnóstico , Transtornos da Percepção/etiologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico
3.
Aust Occup Ther J ; 69(2): 129-139, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34825714

RESUMO

INTRODUCTION: Assistance dogs perform multiple tasks to support people with disabilities and bring various benefits. Occupational therapists play a key role in assessing or referring clients for assistive technology, which includes assistance dogs. However, little is known about Australian occupational therapists' experiences with assistance dogs and how they perceive their roles in this area of practice. METHODS: A cross-sectional online survey was developed and distributed nationally to Australian occupational therapists to glean their experiences and perceptions of assistance dogs and their recommendations to support future practice. RESULTS: A total of 220 completed surveys were received with all perceiving assistance dogs as beneficial for clients with disabilities. Over 60% agreed it was within their scope to assess or refer clients for assistance dogs, but more than two thirds had not had the occasion to do so and/or lacked relevant education and training. Common difficulties experienced in the referral or assessment process include challenges with accessing and navigating funding, lack of resources and/or assistance dogs, and perceived insufficient evidence to support the use of assistance dogs. CONCLUSION: Findings indicate that occupational therapists' lack experience and knowledge of assistance dogs although they perceive assistance dogs as within the scope of occupational therapy practice. This study highlights a need for increasing professional development opportunities for occupational therapists regarding assistance dogs, including assessment and referral processes. This will be steadily more important given the increasing profile and expanding application of assistance dogs, and funding organisation requests for occupational therapists in assessing clients for assistance dogs.


Assuntos
Terapeutas Ocupacionais , Terapia Ocupacional , Animais , Austrália , Estudos Transversais , Cães , Humanos , Animais de Trabalho
4.
J Biol Chem ; 295(27): 8901-8911, 2020 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-32341128

RESUMO

Within the pancreatic ß-cells, insulin secretory granules (SGs) exist in functionally distinct pools, displaying variations in motility as well as docking and fusion capability. Current therapies that increase insulin secretion do not consider the existence of these distinct SG pools. Accordingly, these approaches are effective only for a short period, with a worsening of glycemia associated with continued decline in ß-cell function. Insulin granule age is underappreciated as a determinant for why an insulin granule is selected for secretion and may explain why newly synthesized insulin is preferentially secreted from ß-cells. Here, using a novel fluorescent timer protein, we aimed to investigate the preferential secretion model of insulin secretion and identify how granule aging is affected by variation in the ß-cell environment, such as hyperglycemia. We demonstrate the use of a fluorescent timer construct, syncollin-dsRedE5TIMER, which changes its fluorescence from green to red over 18 h, in both microscopy and fluorescence-assisted organelle-sorting techniques. We confirm that the SG-targeting construct localizes to insulin granules in ß-cells and does not interfere with normal insulin SG behavior. We visualize insulin SG aging behavior in MIN6 and INS1 ß-cell lines and in primary C57BL/6J mouse and nondiabetic human islet cells. Finally, we separated young and old insulin SGs, revealing that preferential secretion of younger granules occurs in glucose-stimulated insulin secretion. We also show that SG population age is modulated by the ß-cell environment in vivo in the db/db mouse islets and ex vivo in C57BL/6J islets exposed to different glucose environments.


Assuntos
Secreção de Insulina/fisiologia , Insulina/metabolismo , Vesículas Secretórias/metabolismo , Animais , Linhagem Celular , Exocitose/fisiologia , Corantes Fluorescentes/química , Glucose/metabolismo , Humanos , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/fisiologia , Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/fisiologia , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Microscopia de Fluorescência/métodos , Fatores de Tempo
5.
Eur Radiol ; 31(10): 7925-7935, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33856514

RESUMO

OBJECTIVES: To develop and validate a machine learning model for the prediction of adverse outcomes in hospitalized patients with COVID-19. METHODS: We included 424 patients with non-severe COVID-19 on admission from January 17, 2020, to February 17, 2020, in the primary cohort of this retrospective multicenter study. The extent of lung involvement was quantified on chest CT images by a deep learning-based framework. The composite endpoint was the occurrence of severe or critical COVID-19 or death during hospitalization. The optimal machine learning classifier and feature subset were selected for model construction. The performance was further tested in an external validation cohort consisting of 98 patients. RESULTS: There was no significant difference in the prevalence of adverse outcomes (8.7% vs. 8.2%, p = 0.858) between the primary and validation cohorts. The machine learning method extreme gradient boosting (XGBoost) and optimal feature subset including lactic dehydrogenase (LDH), presence of comorbidity, CT lesion ratio (lesion%), and hypersensitive cardiac troponin I (hs-cTnI) were selected for model construction. The XGBoost classifier based on the optimal feature subset performed well for the prediction of developing adverse outcomes in the primary and validation cohorts, with AUCs of 0.959 (95% confidence interval [CI]: 0.936-0.976) and 0.953 (95% CI: 0.891-0.986), respectively. Furthermore, the XGBoost classifier also showed clinical usefulness. CONCLUSIONS: We presented a machine learning model that could be effectively used as a predictor of adverse outcomes in hospitalized patients with COVID-19, opening up the possibility for patient stratification and treatment allocation. KEY POINTS: • Developing an individually prognostic model for COVID-19 has the potential to allow efficient allocation of medical resources. • We proposed a deep learning-based framework for accurate lung involvement quantification on chest CT images. • Machine learning based on clinical and CT variables can facilitate the prediction of adverse outcomes of COVID-19.


Assuntos
COVID-19 , Humanos , Aprendizado de Máquina , Estudos Retrospectivos , SARS-CoV-2 , Tomografia Computadorizada por Raios X
6.
Adv Exp Med Biol ; 938: 89-122, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27586424

RESUMO

The overarching success of islet transplantation relies on the success in the laboratory to isolate the islets. This chapter focuses on the processes of human islet cell isolation and the ways to optimally provide islet cells for transplantation. The major improvements in regards to the choice of enzyme type, way the digested pancreas tissue is handled to best separate islets from the acinar and surrounding tissues, the various methods of purification of the islets, their subsequent culture and quality assurance to improve outcomes to culminate in safe and effective islet transplantation will be discussed. After decades of improvements, islet cell isolation and transplantation now clearly offer a safe, effective and feasible therapeutic treatment option for an increasing number of patients suffering from type 1 diabetes specifically for those with severe hypoglycaemic unawareness.


Assuntos
Ilhotas Pancreáticas/fisiologia , Técnicas de Cultura de Tecidos/métodos , Animais , Bioensaio , Sobrevivência Celular , Humanos , Transplante das Ilhotas Pancreáticas , Camundongos , Temperatura
7.
Disabil Rehabil ; 45(19): 3177-3198, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36189909

RESUMO

PURPOSE: To summarise body awareness assessment tools and interventions relevant for stroke rehabilitation using a framework that categorises key body awareness constructs, disorders and impairments. MATERIALS AND METHODS: Online electronic databases and trial registries were searched from inception until July 2021, in addition to hand searching reference lists of included studies and reviews. Study selection included any study design where the investigation involved assessing and/or intervening in body awareness following stroke. Data were extracted based on predefined criteria by two independent reviewers and mapped to the emergent framework. RESULTS: The final analysis included 144 papers that reported 43 assessment tools and 8 types of interventions for body awareness. Consensus was reached on a synthesised body awareness framework. This comprised specific impairments and disorders, constructs, sub-categories and main categories leading to the overarching term of body awareness. Clinical and psychometric properties of the assessment tools were not reported or poorly evaluated, and the interventions lacked robust study designs and rigorous methods. CONCLUSIONS: The framework produced will enable future research and clinical practice to be based on consistent concepts and definitions. Clinicians can also use this information to cautiously select assessment tools and/or interventions but are reminded of the limitations identified in this review.Implications for rehabilitationThere is limited understanding, compounded by inconsistent terminology and definitions regarding body awareness after stroke.A synthesized framework to define key constructs and definitions of body awareness is proposed.Assessment tools and interventions reported in the literature are mapped to the proposed framework.Psychometric properties of available tools are reported.Significant work remains to refine concepts of body awareness, develop and evaluate assessment tools and interventions.


Assuntos
Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Extremidade Superior , Mãos , Projetos de Pesquisa
8.
Health Soc Care Community ; 30(6): e4113-e4121, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35352418

RESUMO

Autism assistance dogs (AADs) increase safety for children with autism and their families. Autism assistance dogs can also decrease familial stress and the isolation which families may experience due to fear for their child's safety and judgement from others within the community. Currently there is a paucity of literature on parents' experiences of AADs. Therefore, this study aimed to develop a rich understanding of parents' experiences of owning an AAD. A mixed methods design was utilised, with a qualitative descriptive design and the use of occupational mapping. Eight families were recruited through an Australian AAD programme and participated in semi-structured in-depth interviews throughout 2017. The interviews were analysed thematically. Mobility in the community before and after introduction of the dog was measured using occupational mapping. Families plotted on Google Map printouts the places they frequented before and after placement of their dog. Five major themes emerged from the analysis of the interviews: freedom through restraint; expanding our world; a calming/sensory tool (AAD); "at the end of the day they're dogs"; and, friendship and personal growth. The occupational maps demonstrated a median increase of 8.5 more places and 20.50 km further travelled from home after having the dog for over a year. Families with an AAD experienced an expanded world for the child and their family. Families experienced freedom in the places they could go, decreased isolation due to the safety which the dog provides. Occupational mapping supported the qualitative data, showing increased mobility and decreased isolation of the family. The paradox of freedom through restraint is a new and key finding which requires further exploration. The results provide support for funding and increased awareness of AAD programmes. Future longitudinal comparative studies are needed to explore the long-term impact of AADs on the child and family.


Assuntos
Transtorno Autístico , Humanos , Cães , Animais , Animais de Trabalho , Austrália , Pais , Emoções , Pesquisa Qualitativa
9.
J Neurol ; 268(4): 1474-1484, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33219421

RESUMO

OBJECTIVE: Despite high incidence of depression after stroke, few trials have investigated the therapeutic efficacy of repetitive transcranial magnetic stimulation (rTMS). Here, we aimed to evaluate clinical benefit of delivering a higher dose of rTMS compared to previous stroke trials. Secondary aims were to document adverse effects and investigate the role of functional connectivity as a potential mechanism of clinical response to rTMS treatment. METHODS: Eleven chronic stroke survivors were recruited to a double-blind, Sham-controlled, randomised trial to investigate 10 sessions of high-frequency rTMS for depression. Clinical assessments were obtained at baseline, after treatment and a 1-month follow-up. Adverse events were documented at completion of the treatment. Resting electroencephalography recordings were performed at baseline and after treatment to estimate functional connectivity. RESULTS: There were no differences in baseline characteristics between groups (all p ≥ 0.42). Beck Depression Inventory scores decreased for the Active rTMS group from baseline to 1-month follow-up (p = 0.04), but did not change for the Sham group at post-treatment or follow-up (p ≥ 0.17). Stronger theta frequency functional connectivity between the left frontal cortex and right parietal cortex was associated with lower baseline depression (r = - 0.71, p = 0.05). This network strength increased following Active rTMS, with change in connectivity associated with improvement in BDI scores (r = 0.98, p = 0.001). Adverse events were transient and minor and were not statistically different between groups (p ≥ 0.21). CONCLUSIONS: Active rTMS significantly improved depression and was well tolerated. The mechanistic role of theta frequency functional connectivity appears worthy of further investigation. The trial was registered on the Australian and New Zealand Clinical Trials Registry (ACTRN12619001303134) on September 23, 2019.


Assuntos
Acidente Vascular Cerebral , Estimulação Magnética Transcraniana , Austrália , Depressão/etiologia , Depressão/terapia , Humanos , Nova Zelândia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Resultado do Tratamento
10.
Front Neurol ; 12: 742365, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34899565

RESUMO

Objective: The objective of this scoping review was to capture the reported definitions for the subtypes of neglect post stroke and map the range of assessment tools employed for each neglect subtype. Methods: EMBASE, Emcare, Medline, and psychINFO were searched from database inception. Searching included all allied terms and mesh headings for stroke, spatial neglect, measurement, screening tools, psychometric properties. Two reviewers independently screened studies for inclusion. Primary studies with documented protocols of a spatial neglect tool for adults post stroke, with some aspect of validity or reliability were included. Two reviewers independently reviewed the documented protocols of each tool to determine the underlying subtypes and disagreements were resolved through discussion. Results: There were 371 articles included with 292 tools used for the screening or diagnosis of neglect. The majority of studies (67%) included a tool that did not specify the neglect subtype being assessed, therefore an analysis of the underlying subtypes for each tool is presented. Conclusions: There is no consistency with the terms used to refer to the syndrome of spatial neglect with over 200 different terms used within the included studies to refer to the syndrome as a whole or one of its subtypes. It is essential to unify the terminology and definition for each neglect subtype. There are hundreds of neglect tools available, however many are not able to differentiate presenting subtypes. It is important for clinicians and researchers to critically evaluate the neglect tools being used for the screening and diagnosis of neglect.

11.
Metabolites ; 11(6)2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34198953

RESUMO

Cold ischemia and hence travel time can adversely affect outcomes of islet isolation. The aim of this study was to compare the isolation and transplant outcomes of donor pancreata according to the distance from islet isolation facility. Principally, those within a 50 km radius of the centre were compared with those from regional areas within the state and those from interstate donors within Australia. Organ donors were categorised according to distance from National Pancreas Transplant Unit Westmead (NPTU). Donor characteristics were analysed statistically against islet isolation outcomes. These were age, BMI, cause and mechanism of death, days in ICU, gender, inotrope and steroid use, cold ischemia time (CIT) and retrieval surgical team. Between March 2007 and December 2020, 297 islet isolations were performed at our centre. A total of 149 donor pancreata were local area, and 148 non-local regions. Mean distance from the isolation facility was 780.05 km. Mean pancreas CIT was 401.07 ± 137.71 min and was significantly different between local and non-local groups (297.2 vs. 487.5 min, p < 0.01). Mean age of donors was 45.22 years, mean BMI was 28.82, sex ratio was 48:52 F:M and mean time in ICU was 3.07 days. There was no significant difference between local and non-local for these characteristics. The mean CIT resulting in islet transplantation was 297.1 ± 91.5 min and longest CIT resulting in transplantation was 676 min. There was no significant difference in islet isolation outcomes between local and non-local donors for characteristics other than CIT. There was also no significant effect of distance from the isolation facility on positive islet transplant outcomes (C-peptide > 0.2 at 1 month post-transplant). Conclusions: Distance from the isolation centre did not impact on isolation or transplant outcomes supporting the ongoing nationwide use of shipping pancreata for islet isolation and transplantation.

12.
Diabetes ; 69(8): 1735-1748, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32381646

RESUMO

Islet transplantation is an emerging therapy for type 1 diabetes and hypoglycemic unawareness. However, a key challenge for islet transplantation is cellular rejection and the requirement for long-term immunosuppression. In this study, we established a diabetic humanized NOD-scidIL2Rγnull (NSG) mouse model of T-cell-mediated human islet allograft rejection and developed a therapeutic regimen of low-dose recombinant human interleukin-2 (IL-2) combined with low-dose rapamycin to prolong graft survival. NSG mice that had received renal subcapsular human islet allografts and were transfused with 1 × 107 of human spleen mononuclear cells reconstituted human CD45+ cells that were predominantly CD3+ T cells and rejected their grafts with a median survival time of 27 days. IL-2 alone (0.3 × 106 IU/m2 or 1 × 106 IU/m2) or rapamycin alone (0.5-1 mg/kg) for 3 weeks did not prolong survival. However, the combination of rapamycin with IL-2 for 3 weeks significantly prolonged human islet allograft survival. Graft survival was associated with expansion of CD4+CD25+FOXP3+ regulatory T cells (Tregs) and enhanced transforming growth factor-ß production by CD4+ T cells. CD8+ T cells showed reduced interferon-γ production and reduced expression of perforin-1. The combination of IL-2 and rapamycin has the potential to inhibit human islet allograft rejection by expanding CD4+FOXP3+ Tregs in vivo and suppressing effector cell function and could be the basis of effective tolerance-based regimens.


Assuntos
Linfócitos T CD4-Positivos/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Interleucina-2/farmacologia , Sirolimo/farmacologia , Aloenxertos , Animais , Linfócitos T CD4-Positivos/efeitos dos fármacos , Células Cultivadas , Citometria de Fluxo , Rejeição de Enxerto , Humanos , Camundongos , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/metabolismo
13.
Pilot Feasibility Stud ; 5: 147, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31871733

RESUMO

BACKGROUND: Efforts to combat the epidemic of childhood obesity have approached the issue from many different angles, with a family approach being the gold standard. While most efforts focus on the parents, few have viewed the child as the agent of change. In this study, we explored the feasibility of implementing a cooking curriculum into a summer day camp to determine its reception and explore the potential of home reach. METHODS: In partnership with a local YMCA, a child-focused cooking curriculum was developed, designed to be delivered to various age groups with key nutritional messages. Interviews were conducted with participating children and their parents to determine acceptability and potential to influence the home environment as well as explore children's understanding of nutrition and cooking topics. RESULTS: Children in the study ranged from 7 to 15 years of age. Children overwhelmingly enjoyed the cooking camp and talked about it with their parents at home. Almost all parents had plans to try the recipes at home, and many had already made one or more of the recipes. CONCLUSIONS: It is feasible to incorporate cooking lessons into a children's summer day camp, with some evidence of reach into the home. Future studies should evaluate children as agents of change in cooking and meal preparation, and assess if this could increase the number and quality of family meals.

14.
Musculoskelet Sci Pract ; 40: 45-52, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30703633

RESUMO

BACKGROUND: Left/right judgement (LRJ) of body parts is commonly used to assess the ability to perform implicit motor imagery and the integrity of brain-grounded maps of the body. Clinically, LRJ are often undertaken using a mobile tablet, but the concurrent validity and reliability of this approach has not yet been established. OBJECTIVES: To evaluate the concurrent validity and test-retest reliability of a mobile tablet for assessing LRJ. METHOD: Participants completed LRJ for 50 hand images (Experiment 1), and 40 back, foot, or neck images (Experiment 2) using a mobile tablet and desktop computer in random order. Participants in Experiment 2 performed a repeat test the following day to assess test-retest reliability. Accuracy and response time (RT) were recorded. RESULTS: Twenty participants aged 55.3 (±6.7) years in Experiment 1, and 37 participants aged 38.2 (±12.3) years in Experiment 2, were recruited. Concurrent validity of the mobile tablet was good to excellent for hand judgements (ICC3,1 = 0.836 for RT; ICC = 0.909 for accuracy), and was good for back, foot, and neck judgements (ICC = 0.781 for accuracy; ICC = 0.880 for RT). Test-retest reliability of the mobile tablet was good to excellent (ICC = 0.824 for accuracy; ICC = 0.903 for RT). CONCLUSIONS: The mobile tablet demonstrated good to excellent concurrent validity with the desktop computer in two separate samples. The mobile tablet also demonstrated good to excellent test-retest reliability. The mobile tablet for LRJ is a valid alternative to the original desktop version.


Assuntos
Computadores de Mão , Tempo de Reação/fisiologia , Adulto , Fatores Etários , Avaliação da Deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Análise e Desempenho de Tarefas
15.
JCI Insight ; 52019 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-31361602

RESUMO

Human islet isolation is a cost-/resource-intensive program generating islets for cell therapy in Type 1 diabetes. However, only a third of cadaveric pancreas get to clinical transplantation due to low quality/number of islets. There is a need to identify biomarker(s) that predict the quality of islets, prior to initiating their isolation. Here, we sequenced transcriptome from 18 human islet preparations stratified into three groups (Gr.1: Best quality/transplantable islets, Gr.2: Intermediary quality, Gr.3: Inferior quality/non-transplantable islets) based on routine measurements including islet purity/viability. Machine-learning algorithms involving penalized regression analyses identified 10 long-non-coding(lnc)RNAs significantly different across all group-wise comparisons (Gr1VsGr2, Gr2vsGr3, Gr1vsGr3). Two variants of Metastasis-Associated Lung Adenocarcinoma Transcript-1(MALAT1) lncRNA were common across all comparisons. We confirmed RNA-seq findings in a "validation set" of 75 human islet preparations. Finally, in 19 pancreas samples, we demonstrate that assessing the levels of MALAT1 variants alone (ROC curve AUC: 0.83) offers highest specificity in predicting post-isolation islet quality and improves the predictive potential for clinical islet transplantation when combined with Edmonton Donor Points/Body Mass Index(BMI)/North American Islet Donor Score(NAIDS). We present this resource of islet-quality-stratified lncRNA transcriptome data and identify MALAT1 as a biomarker that significantly enhances current selection methods for clinical (GMP)-grade islet isolation.


Assuntos
Transplante das Ilhotas Pancreáticas/métodos , Ilhotas Pancreáticas/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Animais , Biomarcadores , Índice de Massa Corporal , Modelos Animais de Doenças , Humanos , Camundongos Nus , Pâncreas/patologia , Transplante de Pâncreas , Doadores de Tecidos , Transcriptoma , Transplante Heterólogo
16.
PLoS One ; 14(5): e0217163, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31116766

RESUMO

Understanding the immunological phenotype of transplant recipients is important to improve outcomes and develop new therapies. Immunophenotyping of whole peripheral blood (WPB) by flow cytometry is a rapid method to obtain large amounts of data relating to the outcomes of different transplant treatments with limited patient impact. Healthy individuals and patients with type 1 diabetes (T1D) enrolled in islet transplantation were recruited and WPB was collected. 46 fluorochrome-conjugated mouse-anti-human antibodies were used (43 of 46 antibodies were titrated). BD cytometer setup and tracking beads were used to characterize and adjust for cytometer performance. Antibody cocktails were pre-mixed <60 minutes before staining. Multicolour panels were designed based on fluorochrome brightness, antigen density, co-expression, and fluorochrome spillover into non-primary detectors in each panel on a 5 laser flow cytometer. WPB sample staining used 50-300 µl WPB for each panel and was performed within 2 hours of blood sample collection. Samples were acquired on a BD-LSRFortessa. The operating procedures, including specimen collection, antibody cocktails, staining protocol, flow-cytometer setup and data analysis, were standardized. The staining index of 43 antibodies and the spillover spreading matrix for each panel was calculated. The final concentrations for the 46 antibodies used was determined for staining of WPB samples. Absolute cell-count and 7 leukocyte profiling panels consisting of subsets and/or status of granulocytes, monocytes, dendritic, B, NK, and T cells including regulatory T cells (Tregs) and NKT were designed and established on a 5 laser BD-LSR Fortessa. 13 T1D patients, including 4 islet transplant recipients and 8 healthy controls, were evaluated. The ability to reproducibly measure immune subsets and immune-profiles of islet transplant patients up to 18 months post transplantation has been established as a tool to measure immune cell reconstitution after transplantation.


Assuntos
Anticorpos/imunologia , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/terapia , Citometria de Fluxo/normas , Imunofenotipagem/métodos , Transplante das Ilhotas Pancreáticas/métodos , Transplantados/estatística & dados numéricos , Anticorpos/sangue , Estudos de Casos e Controles , Ensaios Clínicos como Assunto , Diabetes Mellitus Tipo 1/sangue , Humanos
17.
Transplantation ; 83(11): 1440-8, 2007 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-17565317

RESUMO

BACKGROUND: Fetal beta cells are a potential form of cell therapy for type 1 diabetes. To protect transplanted cells from cellular immune attack, microencapsulation using barium alginate can be employed. Whether microencapsulated fetal pancreatic cells will differentiate as occurs with nonencapsulated fetal pancreatic cells is presently unknown. It is suggested that such differentiation would occur in encapsulated cells, similar to previous experiments conducted using encapsulated embryonic stem cells. METHODS: Streptozotocin-induced diabetic severe combined immunodeficient mice were transplanted with 5,000 to 38,000 fetal pig islet-like cell clusters (ICCs) within barium alginate microcapsules of diameter 300, 600, or 1000 microm. Viability, insulin secretion, and content of encapsulated cells were measured prior to transplantation. Blood glucose levels (BGL) were measured twice weekly and porcine C-peptide monthly. Encapsulated cells were recovered from mice at 6 months posttransplantation for analysis. RESULTS: Encapsulated cells became glucose responsive and normalized BGL within 13 to 68 days posttransplantation, with 5,000 to 10,000 ICCs required. Microcapsule diameter did not affect the time required to achieve normoglycemia. BGL remained normal for the 6-month duration of the experiments. After removal of grafts at 25 weeks posttransplantation, glucose stimulated insulin secretion of the explants was enhanced 96-fold, insulin content was enhanced 34-fold, and the percentage of insulin and glucagon positive cells increased 10-fold and threefold, respectively, from the time of transplantation. CONCLUSIONS: This study demonstrates that fetal pancreatic cells differentiate and function normally when placed within barium alginate microcapsules and transplanted.


Assuntos
Diferenciação Celular , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/cirurgia , Transplante de Tecido Fetal/métodos , Células Secretoras de Insulina/patologia , Células Secretoras de Insulina/transplante , Alginatos , Animais , Glicemia/metabolismo , Cápsulas , Agregação Celular , Sobrevivência Celular , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/metabolismo , Imunofluorescência , Glucagon/metabolismo , Glucose/farmacologia , Ácido Glucurônico , Ácidos Hexurônicos , Insulina/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Ilhotas Pancreáticas/embriologia , Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/patologia , Masculino , Camundongos , Camundongos SCID , Pâncreas/metabolismo , Coloração e Rotulagem , Fatores de Tempo
18.
SSM Popul Health ; 3: 20-36, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29349201

RESUMO

Evidence is accumulating about the association between strong family ties and the emotional and physical welfare of older adults, and researchers have identified negative consequences of being unmarried, being childless, and/or living alone. These associations have been recognized in multiple contexts, including in Asia where living with a spouse and/or grown children has been shown in some studies to improve elderly well-being. Social support, especially family support, is expected to continue to be important where populations are aging and social safety nets are weak. Using longitudinal data from the 2010 and 2012 waves of the China Family Panel Studies, we focus on the effects of marital status at times 1 and 2, changes in marital status between the two surveys, and other family-related indicators of social connectedness on ratings of depression, levels of life satisfaction, and self-reported physical health among those aged 50 and over. Our sample includes 9831 respondents who have valid data on wellbeing indicators for Wave 1 and Wave 2, as well as complete information on the other covariates controlled in our analysis. In analyses of the full sample, those who were married at both points in time reported lower depression scores than those who were never-married, divorced, or widowed at both time points, and those whose unions dissolved in the interval. Those who were married at both times also generally reported greater levels of life satisfaction than those who were never married at both time points and those who became divorced during the interval. Important underlying gender differences are observed both for life satisfaction and depression. In addition, those who were married at both time points reported being in better physical health than those who became widowed during the interval (significant primarily for women), and those who had never been married (significant primarily for men). Our study contributes to the literature on social ties and the wellbeing by highlighting the importance of marital status and changing marital status, net of child co-residence and proximity, in China.

19.
Front Neurol ; 8: 563, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29163331

RESUMO

Spatial neglect after stroke can be a challenging syndrome to diagnose under standard neuropsychological assessment. There is now sufficient evidence that those affected might demonstrate neglect behavior in everyday settings despite showing no signs of neglect during common neglect tasks. This discrepancy is attributed to the simplified and unrealistic nature of common pen and paper based tasks that do not match the demanding, novel, and complex environment of everyday life. As such, increasing task demands under more ecologically valid scenarios has become an important method of increasing test sensitivity. The main aim of the current study was to evaluate the diagnostic utility of the Mobility Assessment Course (MAC), an ecological task, for the assessment of neglect. If neglect becomes more apparent under more challenging task demands the MAC could prove to be more diagnostically accurate at detecting neglect than conventional methods, particularly as the time from initial brain damage increases. Data collected by Guide Dogs of SA/NT were retrospectively analyzed. The Receiver Operating Characteristic (ROC) curve, a measure of sensitivity and specificity, was used to investigate the diagnostic utility of the MAC and a series of paper and pencil tests in 67 right hemisphere stroke survivors. While the MAC proved to be a more sensitive neglect test (74.2%) when compared to the Star Cancellation (43.3%) and Line Bisection (35.7%) tests, this was at the expense of relatively low specificity. As a result, the ROC curve analysis showed no statistically discernable differences between tasks (p > 0.12), or between subacute and chronic groups for individual tasks (p > 0.45). It is concluded that, while the MAC is an ecologically valid alternative for assessing neglect, regarding its diagnostic accuracy, there is currently not enough evidence to suggest that it is a big step forward in comparison to the accuracy of conventional tests.

20.
Endocrinology ; 143(9): 3505-14, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12193564

RESUMO

Fetal beta-cells are immature in their responsiveness to glucose, and maturation occurs after oral feeding commences at birth. The incretin hormones glucagon-like peptide 1 (GLP-1) and cholecystokinin (CCK) are known to be released from the gut in response to oral feeding and enhance insulin secretion from pancreatic beta-cells. We hypothesized that these fetal beta-cells would mature in their glucose responsiveness if they were previously exposed to incretins. We exposed fetal pig islet-like cell clusters (ICCs) to 100 nM GLP-1, 5 micro M CCK, or 10 mM nicotinamide (NIC; a positive control) for 6 h and demonstrated 3- and 1.7-fold increases in glucose-induced insulin secretion for GLP-1 and CCK, respectively. This effect did not reach statistical significance if the ICCs were exposed to the incretins for 3 d. However, exposure for 4 d enhanced formation of beta-cells from undifferentiated cells, from 8 +/- 1% (controls) to 17 +/- 3% for GLP-1, 20 +/- 4% for CCK, and 15 +/- 1 for NIC (P < 0.001). ICCs exposed to GLP-1 for 3 d also showed a 1.9-fold increase in the intensity of PDX-1(+) cells, as assessed by semiquantitative fluorescent immunocytochemistry. Exposure of ICCs to incretins for 3 d did not show any increase in size of the islet clusters. ICCs exposed to either incretin as well as controls were transplanted into severe combined immunodeficient mice and examined at 1 and 2 months. We found a significant increase in the number of beta-cells in the GLP-1- and NIC-treated groups compared with the untreated controls or CCK. Perfusion of these grafts at 2 months showed that ICCs previously exposed to GLP-1, CCK, and NIC (but not controls), were functional and mature. In conclusion, GLP-1 and CCK have a dual effect on fetal pig ICCs, causing maturation of glucose-induced insulin secretion from beta-cells as well as enhancement of differentiation from undifferentiated precursors.


Assuntos
Colecistocinina/farmacologia , Glucagon/farmacologia , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/embriologia , Fragmentos de Peptídeos/farmacologia , Precursores de Proteínas/farmacologia , Animais , Diferenciação Celular/efeitos dos fármacos , Divisão Celular , Tamanho Celular , Técnicas de Cultura , Imunofluorescência , Peptídeo 1 Semelhante ao Glucagon , Glucose/farmacologia , Insulina/análise , Ilhotas Pancreáticas/química , Transplante das Ilhotas Pancreáticas , Niacinamida/farmacologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Suínos , Fatores de Tempo
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