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1.
BMJ Open ; 14(3): e075733, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38458782

RESUMO

AIMS: The aim was to evaluate whether standardised exercise performance during the incremental shuttle walk test (ISWT) can be used to assess disease severity in children and young people (CYP) with chronic conditions, through (1) identifying the most appropriate paediatric normative reference equation for the ISWT, (2) assessing how well CYP with haemophilia and cystic fibrosis (CF) perform against the values predicted by the best fit reference equation and (3) evaluating the association between standardised ISWT performance and disease severity. METHODS: A cross-sectional analysis was carried out using existing data from two independent studies (2018-2019) at paediatric hospitals in London,UK. CYP with haemophilia (n=35) and CF (n=134) aged 5-18 years were included. Published reference equations for standardising ISWT were evaluated through a comparison of populations, and Bland-Altman analysis was used to assess the level of agreement between distances predicted by each equation. Associations between ISWT and disease severity were assessed with linear regression. RESULTS: Three relevant reference equations were identified for the ISWT that standardised performance based on age, sex and body mass index (Vardhan, Lanza, Pinho). A systematic proportional bias of standardised ISWT was observed in all equations, most pronounced with Vardhan and Lanza; the male Pinho equation was identified as most appropriate. On average, CYP with CF and haemophilia performed worse than predicted by the Pihno equation, although the range was wide. Standardised ISWT, and not ISWT distance alone, was significantly associated with forced expiratory volume in 1 s in CYP with CF. Standardised ISWT in CYP with haemophilia was slightly associated with haemophilia joint health score, but this was not significant. CONCLUSIONS: ISWT performance may be useful in a clinic to identify those with worsening disease, but only when performance is standardised against a healthy reference population. The development of validated global reference equations is necessary for more robust assessment.


Assuntos
Fibrose Cística , Hemofilia A , Humanos , Masculino , Criança , Adolescente , Teste de Caminhada , Estudos Transversais , Tolerância ao Exercício , Doença Crônica , Gravidade do Paciente , Teste de Esforço , Caminhada
2.
Autism ; 28(4): 816-830, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38145308

RESUMO

LAY ABSTRACT: Difficulties with mental health and low levels of well-being are more common among autistic girls and women than non-autistic people, but we do not fully understand why. Research does not focus enough on what autistic girls and women could tell us about this. This review aims to summarise the studies where autistic girls and women explain things that affect their mental health and well-being to help us understand how to prevent these difficulties from developing. Three research databases were searched to find possibly relevant studies. There were 877 studies found, which two researchers screened according to particular criteria. They found 52 studies that could be included in this review. One researcher evaluated the quality of these studies and extracted the key information from them. This review summarises the views of 973 autistic girls and women aged between 13 and 70+. The findings from the 52 studies were analysed, and we found many factors that affect the mental health and well-being of autistic girls and women. These factors fall into two categories: (1) difficulties living in a world not designed for autistic people and (2) the impact of stigma due to being autistic.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Humanos , Adolescente , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Saúde Mental , Emoções , Pesquisadores
3.
Eur Respir J ; 62(3)2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37652570

RESUMO

BACKGROUND: Cystic fibrosis (CF) is commonly characterised by thick respiratory mucus. From diagnosis, people with CF are prescribed daily physiotherapy, including airway clearance techniques (ACTs). ACTs consume a large proportion of treatment time, yet the efficacy and effectiveness of ACTs are poorly understood. This study aimed to evaluate associations between the quality and quantity of ACTs and lung function in children and young people with CF. METHODS: Project Fizzyo, a longitudinal observational cohort study in the UK, used remote monitoring with electronic pressure sensors attached to four different commercial ACT devices to record real-time, breath-by-breath pressure data during usual ACTs undertaken at home over 16 months in 145 children. ACTs were categorised either as conformant or not with current ACT recommendations based on breath pressure and length measurements, or as missed treatments if not recorded. Daily, weekly and monthly associations between ACT category and lung function were investigated using linear mixed effects regression models adjusting for clinical confounders. RESULTS: After exclusions, 45 224 ACT treatments (135 individuals) and 21 069 days without treatments (141 individuals) were analysed. The mean±sd age of participants was 10.2±2.9 years. Conformant ACTs (21%) had significantly higher forced expiratory volume in 1 s (FEV1) (mean effect size 0.23 (95% CI 0.19-0.27) FEV1 % pred per treatment) than non-conformant (79%) or missed treatments. There was no benefit from non-conformant or missed treatments and no significant difference in FEV1 between them (mean effect size 0.02 (95% CI -0.01-0.05) FEV1 % pred per treatment). CONCLUSIONS: ACTs are beneficial when performed as recommended, but most people use techniques that do not improve lung function. Work is needed to monitor and improve ACT quality and to increase the proportion of people doing effective airway clearance at home.


Assuntos
Fibrose Cística , Humanos , Criança , Adolescente , Fibrose Cística/terapia , Volume Expiratório Forçado , Modelos Lineares , Prednisona , Escarro
4.
Nurs Res ; 72(5): 371-376, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37625179

RESUMO

BACKGROUND: Investigations of chronic physiological stress measured by hair cortisol are rapidly expanding among community samples of adolescents and adults. However, research examining physiological stress among youth experiencing homelessness is nascent despite the youth's increased risk for adverse exposures and subsequent impaired mental health. OBJECTIVE: This article aimed to examine the feasibility of collecting hair for measuring cortisol among diverse youth experiencing homelessness and gain an understanding of variation in participation. METHODS: Analysis of survey and hair participation data from three pilot studies among youth experiencing homelessness was conducted. Survey measures included sociodemographic characteristics (age, race and ethnicity, sex assigned at birth, and sexual orientation) and reasons for nonparticipation. Descriptive analysis examined participation rates in hair collection for cortisol measurement, including sociodemographic differences in participation. RESULTS: Participation in the hair sampling for cortisol was high for the combined sample (88.4%), with some variation across the three pilot studies. Insufficient hair for cutting was the most common reason for not participating; Black and multiracial youth, as well as male youth, had a higher prevalence of nonparticipation. DISCUSSION: The collection of hair for cortisol research among youth experiencing homelessness is feasible, and integration of physiological measures of stress into research with this vulnerable population should be considered, given their high risk for adversity and death by suicide and drug overdose. Methodological considerations and avenues for potential research are discussed.


Assuntos
Hidrocortisona , Pessoas Mal Alojadas , Adulto , Recém-Nascido , Humanos , Masculino , Adolescente , Feminino , Hidrocortisona/análise , Cabelo/química , Etnicidade , Saúde Mental
5.
J Cyst Fibros ; 22(2): 344-351, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36210322

RESUMO

Children and young people with CF (CYPwCF) get advice about using positive expiratory pressure (PEP) or oscillating PEP (OPEP) devices to clear sticky mucus from their lungs. However, little is known about the quantity (number of treatments, breaths, or sets) or quality (breath pressures and lengths) of these daily airway clearance techniques (ACTs) undertaken at home. This study used electronic pressure sensors to record real time breath-by-breath data from 145 CYPwCF (6-16y) during routine ACTs over 2 months. ACT quantity and quality were benchmarked against individual prescriptions and accepted recommendations for device use. In total 742,084 breaths from 9,081 treatments were recorded. Individual CYPwCF maintained consistent patterns of ACT quantity and quality over time. Overall, 60% of CYPwCF did at least half their prescribed treatments, while 27% did fewer than a quarter. About 77% of pre-teens did the right number of daily treatments compared with only 56% of teenagers. CYPwCF usually did the right number of breaths. ACT quality (recommended breath length and pressure) varied between participants and depended on device. Breath pressures, lengths and pressure-length relationships were significantly different between ACT devices. PEP devices encouraged longer breaths with lower pressures, while OPEP devices encouraged shorter breaths with higher pressures. More breaths per treatment were within advised ranges for both pressure and length using PEP (30-31%) than OPEP devices (1-3%). Objective measures of quantity and quality may help to optimise ACT device selection and support CYPwCF to do regular effective ACTs.


Assuntos
Fibrose Cística , Adolescente , Criança , Humanos , Fibrose Cística/terapia , Volume Expiratório Forçado , Muco , Exercícios Respiratórios
6.
Am J Emerg Med ; 60: 228.e3-228.e4, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35909067

RESUMO

Primary central nervous system lymphoma (PCNSL) and central neurogenic hyperventilation (CNH) are both rare occurrences, especially when associated with Epstein-Barr Virus (EBV). We report a case of an immunocompetent individual who presented to the emergency department (ED) with vague neurological symptoms found to have an EBV-associated PCNSL complicated by CNH. This rare occurrence had an insidious presentation initially mistaken for "post-concussive syndrome" at an outside ED. Insidious neurological malignancies, posterior strokes, intracranial hematomas, and other life-threatening pathologies should always be on the differential in patients presenting to the ED with falls with associated neurological symptoms, especially with unexplained blood gas abnormalities.


Assuntos
Neoplasias do Sistema Nervoso Central , Infecções por Vírus Epstein-Barr , Linfoma , Sistema Nervoso Central , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4 , Humanos , Linfoma/complicações , Linfoma/diagnóstico
7.
Autism ; 26(8): 2041-2051, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35068188

RESUMO

LAY ABSTRACT: Autistic young people are often misunderstood by non-autistic young people, and this can lead to difficulties in their friendships. We know that friendship is very important for our mental health. For non-autistic young people, having good friendships is linked to better mental health and having problems in friendship can cause mental health problems. This study aimed to compare the positive and negative features of friendship that autistic non-autistic young people experience. The study also aimed to understand if having positive or negative friendship features is related to signs of mental health problems (anxiety and depression). 306 young people aged 9-16 took part in this study. These were 86 autistic boys, 18 autistic girls, 91 non-autistic boys and 111 non-autistic girls. The findings of this study showed that autistic young people have less positive friendship features than non-autistic young people. For all young people in the study, having more positive friendship features was related to fewer signs of depression, while having more negative friendship features was related to more signs of depression. Just for autistic girls, having more positive friendship features was related to more signs of anxiety. These findings show that support is needed to help autistic young people have more positive friendships. For example, by teaching non-autistic young people how to be supportive friends to their autistic peers.


Assuntos
Transtorno do Espectro Autista , Amigos , Masculino , Feminino , Adolescente , Humanos , Amigos/psicologia , Relações Interpessoais , Saúde Mental , Transtorno do Espectro Autista/psicologia , Fatores de Risco
8.
Autism ; 25(1): 199-209, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32967463

RESUMO

LAY ABSTRACT: Empathy is an important feature to feel for another person, evoking social support for the person in distress, and thus strengthening social cohesion. The question is to what extent empathic reactions can also be observed in autistic adolescents and autistic girls in particular, since their often mentioned good social skills might prevent their direct social environment from recognizing their autism. We examined 194 adolescents (autistic and non-autistic boys and girls) during an in vivo task in which the experimenter pretended to hurt herself while closing a binder. All responses by the participants were videotaped and coded by two independent coders. In line with our predictions, no group or gender differences appeared related to their attention for the event; yet autistic girls and boys showed less visible emotional arousal, which could indicate less affective empathy (feeling for someone), or which could indicate that autistic adolescents know less well how to show empathy. Autistic girls and boys reacted by comforting the experimenter equally often as their non-autistic peers, but autistic boys addressed the problem more often than any other group, while girls (autistic and non-autistic) more often addressed the emotion of the person in need. Our findings highlight that empathic behaviour is remarkably similar between autistic and non-autistic boys and girls. Indeed, only subtle differences exist, in terms of expressed emotional arousal and gender-specific comforting styles. Autistic girls' higher levels of emotion-focused comforting could be explained by well-developed social skills, camouflaging, or emotional investment in relationships with others.


Assuntos
Comportamento do Adolescente , Transtorno do Espectro Autista , Transtorno Autístico , Adolescente , Emoções , Empatia , Feminino , Humanos , Masculino
9.
BMJ Open ; 10(10): e039587, 2020 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-33033031

RESUMO

INTRODUCTION: Daily physiotherapy is believed to mitigate the progression of cystic fibrosis (CF) lung disease. However, physiotherapy airway clearance techniques (ACTs) are burdensome and the evidence guiding practice remains weak. This paper describes the protocol for Project Fizzyo, which uses innovative technology and analysis methods to remotely capture longitudinal daily data from physiotherapy treatments to measure adherence and prospectively evaluate associations with clinical outcomes. METHODS AND ANALYSIS: A cohort of 145 children and young people with CF aged 6-16 years were recruited. Each participant will record their usual physiotherapy sessions daily for 16 months, using remote monitoring sensors: (1) a bespoke ACT sensor, inserted into their usual ACT device and (2) a Fitbit Alta HR activity tracker. Real-time breath pressure during ACTs, and heart rate and daily step counts (Fitbit) are synced using specific software applications. An interrupted time-series design will facilitate evaluation of ACT interventions (feedback and ACT-driven gaming). Baseline, mid and endpoint assessments of spirometry, exercise capacity and quality of life and longitudinal clinical record data will also be collected.This large dataset will be analysed in R using big data analytics approaches. Distinct ACT and physical activity adherence profiles will be identified, using cluster analysis to define groups of individuals based on measured characteristics and any relationships to clinical profiles assessed. Changes in adherence to physiotherapy over time or in relation to ACT interventions will be quantified and evaluated in relation to clinical outcomes. ETHICS AND DISSEMINATION: Ethical approval for this study (IRAS: 228625) was granted by the London-Brighton and Sussex NREC (18/LO/1038). Findings will be disseminated via peer-reviewed publications, at conferences and via CF clinical networks. The statistical code will be published in the Fizzyo GitHub repository and the dataset stored in the Great Ormond Street Hospital Digital Research Environment. TRIAL REGISTRATION NUMBER: ISRCTN51624752; Pre-results.


Assuntos
Fibrose Cística , Modalidades de Fisioterapia , Adolescente , Fatores Etários , Criança , Estudos de Coortes , Fibrose Cística/terapia , Humanos , Estudos Longitudinais , Estudos Observacionais como Assunto , Qualidade de Vida
10.
J Am Vet Med Assoc ; 256(11): 1268-1276, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32412872

RESUMO

OBJECTIVE: To examine companion animal owners' perceptions of appropriate veterinarian attire and investigate potential associations between a veterinarian's attire and clients' ratings of trust in, confidence in, and comfort with a veterinarian. SAMPLE: 449 pet owners. PROCEDURES: Participants were randomly assigned to complete a questionnaire containing photos of a male or female model veterinarian photographed in 8 attire types (formal attire, white dress shirt with black pants, white casual shirt with khaki pants, surgical scrubs, white casual shirt with jeans, surgical scrub top with jeans, surgical scrub top with khaki pants, and white laboratory coat with khaki pants). Participants were asked to rate their trust in, confidence in, and comfort with the pictured individual on a response scale of 1 (low) to 7 (high), rank photos according to their preferences for attire, and provide input on the importance of attire and other appearance-related subjects. Attire and gender of photographed individual and participant demographics were investigated for associations with trust, confidence, and comfort scores. RESULTS: Most (317/445 [71%]) respondents indicated veterinarians' attire was important. Attire type was significantly associated with respondents' trust, confidence, and comfort scores. Model veterinarian gender and participant education level were also associated with trust and comfort scores. CONCLUSIONS AND CLINICAL RELEVANCE: Veterinarians' attire is a form of nonverbal communication that is likely to inform clients' first impressions and may influence clients' trust in, confidence in, and comfort with a veterinarian. Veterinary personnel and veterinary management should consider how attire and general appearance represent staff members or their practice.


Assuntos
Médicos Veterinários , Animais , Canadá , Vestuário , Feminino , Humanos , Masculino , Inquéritos e Questionários , Confiança
11.
J Immunother Cancer ; 8(1)2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32345627

RESUMO

BACKGROUND: CD47 is a broadly expressed cell surface glycoprotein associated with immune evasion. Interaction with the inhibitory receptor signal regulatory protein alpha (SIRPα), primarily expressed on myeloid cells, normally serves to restrict effector function (eg, phagocytosis and immune cell homeostasis). CD47/SIRPα antagonists, commonly referred to as 'macrophage checkpoint' inhibitors, are being developed as cancer interventions. SRF231 is an investigational fully human IgG4 anti-CD47 antibody that is currently under evaluation in a phase 1 clinical trial. The development and preclinical characterization of SRF231 are reported here. METHODS: SRF231 was characterized in assays designed to probe CD47/SIRPα blocking potential and effects on red blood cell (RBC) phagocytosis and agglutination. Additionally, SRF231-mediated phagocytosis and cell death were assessed in macrophage:tumor cell in vitro coculture systems. Further mechanistic studies were conducted within these coculture systems to ascertain the dependency of SRF231-mediated antitumor activity on Fc receptor engagement vs CD47/SIRPα blockade. In vivo, SRF231 was evaluated in a variety of hematologic xenograft models, and the mechanism of antitumor activity was assessed using cytokine and macrophage infiltration analyses following SRF231 treatment. RESULTS: SRF231 binds CD47 and disrupts the CD47/SIRPα interaction without causing hemagglutination or RBC phagocytosis. SRF231 exerts antitumor activity in vitro through both phagocytosis and cell death in a manner dependent on the activating Fc-gamma receptor (FcγR), CD32a. Through its Fc domain, SRF231 engagement with macrophage-derived CD32a serves dual purposes by eliciting FcγR-mediated phagocytosis of cancer cells and acting as a scaffold to drive CD47-mediated death signaling into tumor cells. Robust antitumor activity occurs across multiple hematologic xenograft models either as a single agent or in combination with rituximab. In tumor-bearing mice, SRF231 increases tumor macrophage infiltration and induction of the macrophage cytokines, mouse chemoattractant protein 1 and macrophage inflammatory protein 1 alpha. Macrophage depletion results in diminished SRF231 antitumor activity, underscoring a mechanistic role for macrophage engagement by SRF231. CONCLUSION: SRF231 elicits antitumor activity via apoptosis and phagocytosis involving macrophage engagement in a manner dependent on the FcγR, CD32a.


Assuntos
Antígeno CD47/metabolismo , Neoplasias/genética , Receptores de IgG/metabolismo , Animais , Humanos , Camundongos , Neoplasias/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
12.
J Am Vet Med Assoc ; 256(4): 469-478, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31999518

RESUMO

OBJECTIVE: To examine the effect of 3 diet history questions on the amount and type of diet-related information gathered from pet owners and to assess whether diet-related information obtained with each question in person differed from information obtained with a diet history survey. SAMPLE: 99 pet owners. PROCEDURES: Participants' responses to 1 of 3 randomly selected diet history questions ("Tell me everything he [or she] eats throughout a day, starting first thing in the morning right through to the end of the day"; "What kind of food does she [or he] eat?"; or "What kind of foods does he [or she] eat?") were recorded and coded for analysis. Participants completed a postinteraction diet history survey. Amount and type of diet-related information obtained were compared among responses to the 3 diet history questions and between the response to each question and the diet history survey. RESULTS: The "Tell me…" question elicited a significantly higher total number of diet-related items (combined number of main diet, treat, human food, medication, and dietary supplement items) than did the "What kind of food…" or "What kind of foods…" questions. The diet history survey captured significantly more information than did the "What kind of food…" or "What kind of foods…" questions; there was little difference between results of the diet history survey and the "Tell me…" question, except that treats were more frequently disclosed on the survey. CONCLUSIONS AND CLINICAL RELEVANCE: Findings reinforced the value of using broad, open questions or requests that invite expansion from clients for gathering diet-related information.


Assuntos
Dieta , Animais , Feminino , Humanos , Masculino , Ontário , Inquéritos e Questionários
13.
ACS Omega ; 4(12): 15181-15196, 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31552364

RESUMO

Proliferating cell nuclear antigen (PCNA) is a central factor in DNA replication and repair pathways that plays an essential role in genome stability. The functional roles of PCNA are mediated through an extensive list of protein-protein interactions, each of which transmits specific information in protein assemblies. The flexibility at the PCNA-protein interaction interfaces offers opportunities for the discovery of functionally selective inhibitors of DNA repair pathways. Current fragment-based drug design methodologies can be limited by the flexibility of protein interfaces. These factors motivated an approach to defining compounds that could leverage previously identified subpockets on PCNA that are suitable for fragment-binding sites. Methodologies for screening multiple connected fragment-binding events in distinct subpockets are deployed to improve the selection of fragment combinations. A flexible backbone based on N-alkyl-glycine amides offers a scaffold to combinatorically link multiple fragments for in silico screening libraries that explore the diversity of subpockets at protein interfaces. This approach was applied to discover new potential inhibitors of DNA replication and repair that target PCNA in a multiprotein recognition site. The screens of the libraries were designed to computationally filter ligands based upon the fragments and positions to <1%, which were synthesized and tested for direct binding to PCNA. Molecular dynamics simulations also revealed distinct features of these novel molecules that block key PCNA-protein interactions. Furthermore, a Bayesian classifier predicted 15 of the 16 new inhibitors to be modulators of protein-protein interactions, demonstrating the method's utility as an effective screening filter. The cellular activities of example ligands with similar affinity for PCNA demonstrate unique properties for novel selective synergy with therapeutic DNA-damaging agents in drug-resistant contexts.

14.
Autism Res ; 12(12): 1796-1804, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31364313

RESUMO

Young autistic people have a range of social difficulties, but it is not yet clear how these difficulties can be explained. In addition, emerging research is suggesting that autistic girls may differ from boys in terms of their social behaviors, but yet unknown is if they differ in terms of their pro-social behavior, such as helping. The present study investigated spontaneous helping behavior using an in vivo paradigm and related this to participants' levels of social motivation (based on parent reports). Participants were 233 autistic and non-autistic (pre-)adolescents (M = 12.46 years, SD = 15.54 months). Our results demonstrated that autistic girls and boys have lower levels of social motivation compared to their non-autistic peers, but social motivation was unrelated to helping behavior in both groups. Furthermore, when the experimenter needed help, the autistic boys and girls looked and smiled to the same extent as their peers of the same gender, but they actually helped significantly less than their non-autistic peers. However, most autistic youngsters did help, highlighting the great individual differences in autistic individuals. We discuss the possibility that lower levels of helping behavior are due to difficulty initiating action in a social context, rather than lower social motivation. Autism Res 2019, 12: 1796-1804. © 2019 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc. LAY SUMMARY: This study examined the helping behavior of autistic boys and girls (aged 9-16). Many autistic young people did help, but compared to non-autistic individuals, autistic people did not help as much. This study also showed that when people did/did not help, it was not related to their interest in social relationships. It is important to teach young autistic people when and how to help others, to support them making friends.


Assuntos
Comportamento do Adolescente/psicologia , Transtorno do Espectro Autista/psicologia , Comportamento Infantil/psicologia , Comportamento de Ajuda , Motivação , Comportamento Social , Adolescente , Criança , Feminino , Humanos , Masculino
15.
PLoS Pathog ; 12(4): e1005545, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27082643

RESUMO

Resting CD4+ T-cells harboring inducible HIV proviruses are a critical reservoir in antiretroviral therapy (ART)-treated subjects. These cells express little to no viral protein, and thus neither die by viral cytopathic effects, nor are efficiently cleared by immune effectors. Elimination of this reservoir is theoretically possible by combining latency-reversing agents (LRAs) with immune effectors, such as CD8+ T-cells. However, the relative efficacy of different LRAs in sensitizing latently-infected cells for recognition by HIV-specific CD8+ T-cells has not been determined. To address this, we developed an assay that utilizes HIV-specific CD8+ T-cell clones as biosensors for HIV antigen expression. By testing multiple CD8+ T-cell clones against a primary cell model of HIV latency, we identified several single agents that primed latently-infected cells for CD8+ T-cell recognition, including IL-2, IL-15, two IL-15 superagonists (IL-15SA and ALT-803), prostratin, and the TLR-2 ligand Pam3CSK4. In contrast, we did not observe CD8+ T-cell recognition of target cells following treatment with histone deacetylase inhibitors or with hexamethylene bisacetamide (HMBA). In further experiments we demonstrate that a clinically achievable concentration of the IL-15 superagonist 'ALT-803', an agent presently in clinical trials for solid and hematological tumors, primes the natural ex vivo reservoir for CD8+ T-cell recognition. Thus, our results establish a novel experimental approach for comparative evaluation of LRAs, and highlight ALT-803 as an LRA with the potential to synergize with CD8+ T-cells in HIV eradication strategies.


Assuntos
Antivirais/farmacologia , Linfócitos T CD4-Positivos/virologia , Infecções por HIV/imunologia , Proteínas/farmacologia , Linfócitos T Citotóxicos/imunologia , Latência Viral/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , ELISPOT , Citometria de Fluxo , Humanos , Reação em Cadeia da Polimerase , Proteínas Recombinantes de Fusão , Ativação Viral/efeitos dos fármacos
16.
Mol Cytogenet ; 9: 29, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27034718

RESUMO

BACKGROUND: The use of Microarray (array CGH) analysis has become a widely accepted front-line test replacing G banded chromosome studies for patients with an unexplained phenotype. We detail our findings of over 5300 cases. RESULTS: Of 5369 pre and postnatal samples, copy number variants (CNVs) were detected in 28.3 %, of which ~40 % were deletions and ~60 % were duplications. 96.8 % of cases with a CNV <5 Mb would not have been detected by G banding. At least 4.9 % were determined to meet the minimum criteria for a known syndrome. Chromosome 17 provided the greatest proportion of pathogenic CNVs with 65 % classified as (likely) pathogenic. X chromosome CNVs were the most commonly detected accounting for 4.2 % of cases, 0.7 % of these being classified as cryptic (likely) pathogenic CNVs. CONCLUSIONS: Microarray analysis as a primary testing strategy has led to a significant increase in the detection of CNVs (~29 % overall), with ~9 % carrying pathogenic CNVs and one syndromic case identified per 20 referred patients. We suggest these frequencies are consistent with other heterogeneous studies. Conversely, (likely) pathogenic X chromosome CNVs appear to be greater compared with previous studies.

17.
J Appl Anim Welf Sci ; 19(2): 157-70, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26865430

RESUMO

Human expectations can greatly affect the human-companion animal relationship, sometimes putting nonhuman animals at risk for relinquishment. At 20 animal shelters in Southern Ontario, Canada, potential adopters (N = 234) completed a questionnaire regarding their lifestyle, companion animal-care knowledge, and preadoption expectations of their adopted companion animals. Linear mixed models were used to assess the associations of adopters' lifestyles and companion animal-care knowledge with their expectations for animal behavior, the human-companion animal relationship, and the effort required in companion-animal guardianship. Dog adopters had higher expectations than cat adopters for their companion animal's behavior (p < .001), the human-companion animal relationship (p < .001), and the effort required in companion-animal guardianship (p < .001). Adopters' human relationship statuses were also associated with expectations for the human-companion animal relationship (p = .002). As adopters' companion animal-care knowledge increased, so did their expectations for the effort required in companion-animal guardianship (p < .001). An understanding of adopters' expectations prior to adoption will help animal shelters better match, educate, and prepare adopters for their lives with companion animals.


Assuntos
Criação de Animais Domésticos , Animais de Estimação , Adolescente , Adoção/psicologia , Adulto , Criação de Animais Domésticos/estatística & dados numéricos , Animais , Antecipação Psicológica , Gatos , Cães , Feminino , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Adulto Jovem
19.
Int Wound J ; 12(1): 53-8, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23425603

RESUMO

Patients with severe acute and chronic lower extremity wounds often present a significant challenge in terms of limb salvage. In addition to control of infection, assuring adequate perfusion and providing standard wound care, advanced modalities are often required to facilitate final wound closure. We herein present a case study on a diabetic patient with gangrene and necrotising soft-tissue infection who underwent a forefoot pedal amputation to control the sepsis. Despite his non invasive vascular studies demonstrating poor healing potential at this level, he was not deemed suitable for revascularisation by our vascular surgeons and ankle-level amputation was recommended. Nonetheless, over a 5-month period using multiple advanced wound care therapies, wound closure was ultimately achieved.


Assuntos
Pé Diabético/terapia , Salvamento de Membro/métodos , Infecções dos Tecidos Moles/terapia , Técnicas de Fechamento de Ferimentos , Curativos Biológicos , Materiais Revestidos Biocompatíveis , Pé Diabético/complicações , Pé Diabético/patologia , Gangrena , Humanos , Masculino , Pessoa de Meia-Idade , Infecções dos Tecidos Moles/complicações , Infecções dos Tecidos Moles/patologia , Cicatrização
20.
Pediatr Radiol ; 45(5): 667-74, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25432441

RESUMO

BACKGROUND: Intussusception is a common pediatric abdominal emergency, treated with image-guided reduction. Available techniques include fluoroscopic and ultrasonographic monitoring of liquid and air. OBJECTIVE: The purpose of this study was to determine current practices and establish trends by comparing our findings with reports of previous surveys. MATERIALS AND METHODS: This study is based on an e-mail survey sent to all 1,538 members of the Society for Pediatric Radiology. It included questions about demographics, presence of parents/surgeon during procedure, patient selection/preparation, use of sedation, preferred methods of reduction and technical details, approach to unsuccessful reduction, and self-reported incidence of success/perforation. RESULTS: The 456 respondents (30%) reported attempting 3,834 reductions in the preceding 12 months. Of these, 96% use fluoroscopy and 4% use US guidance for reduction; 78% use air, 20% prefer fluid; 75% require intravenous access; 63% expect a surgeon to be present in hospital; 93% do not sedate. Although inflating a rectal balloon is controversial, 39% do so, and 50% employ a pressure-release valve. Seventy-two percent attempt reductions three times in the same position. In case of unsuccessful reductions, 64% wait and re-attempt later, 19% apply manual pressure, and 15% try again in left decubitus position. About 20% reattempt reduction after waiting 2 h or more. CONCLUSION: By providing a better understanding of both trends in and diversity of current practice, we hope to increase the confidence with which the individual practitioner will approach each case.


Assuntos
Pesquisas sobre Atenção à Saúde/estatística & dados numéricos , Intestinos/diagnóstico por imagem , Intussuscepção/cirurgia , Radiografia Intervencionista , Ultrassonografia de Intervenção , Criança , Feminino , Fluoroscopia , Humanos , Intestinos/cirurgia , Intussuscepção/diagnóstico por imagem , Masculino , Monitorização Intraoperatória
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