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Background: Little is known regarding the characteristics, treatment patterns, and outcomes in patients with adult congenital heart disease (ACHD) admitted to cardiac intensive care units (CICUs). Objectives: The authors sought to better define the contemporary epidemiology, treatment patterns, and outcomes of ACHD admissions in the CICU. Methods: The Critical Care Cardiology Trials Network is a multicenter network of CICUs in North America. Participating centers contributed prospective data from consecutive admissions during 2-month annual snapshots from 2017 to 2022. We analyzed characteristics and outcomes of admissions with ACHD compared with those without ACHD. Multivariable logistic regression was used to assess mortality in ACHD vs non-ACHD admissions. Results: Of 23,299 CICU admissions across 42 sites, there were 441 (1.9%) ACHD admissions. Shunt lesions were most common (46.1%), followed by right-sided lesions (29.5%) and complex lesions (28.7%). ACHD admissions were younger (median age 46 vs 67 years) than non-ACHD admissions. ACHD admissions were more commonly for heart failure (21.3% vs 15.7%, P < 0.001), general medical problems (15.6% vs 6.0%, P < 0.001), and atrial arrhythmias (8.6% vs 4.9%, P < 0.001). ACHD admissions had a higher median presenting Sequential Organ Failure Assessment score (5.0 vs 3.0, P < 0.001). Total hospital stay was longer for ACHD admissions (8.2 vs 5.9 days, P < 0.01), though in-hospital mortality was not different (12.7% vs 13.6%; age- and sex-adjusted OR: 1.19 [95% CI: 0.89-1.59], P = 0.239). Conclusions: This study illustrates the unique aspects of the ACHD CICU admission. Further investigation into the best approach to manage specific ACHD-related CICU admissions, such as cardiogenic shock and acute respiratory failure, is warranted.
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OBJECTIVES: The objective of this study is to evaluate whether anti-neutrophil cytoplasmic antibody (ANCA) seropositivity and antigen specificity at diagnosis have predictive utility in paediatric-onset small vessel vasculitis. METHODS: Children and adolescents with small vessel vasculitis (n=406) stratified according to the absence (n=41) or presence of ANCA for myeloperoxidase (MPO) (n=129) and proteinase-3 (PR3) (n=236) were compared for overall and kidney-specific disease activity at diagnosis and outcomes between 1 and 2 years using retrospective clinical data from the ARChiVe/Paediatric Vasculitis Initiative registry to fit generalised linear models. RESULTS: Overall disease activity at diagnosis was higher in PR3-ANCA and MPO-ANCA-seropositive individuals compared with ANCA-negative vasculitis. By 1 year, there were no significant differences, based on ANCA positivity or specificity, in the likelihood of achieving inactive disease (~68%), experiencing improvement (≥87%) or acquiring damage (~58%). Similarly, and in contrast to adult-onset ANCA-associated vasculitis, there were no significant differences in the likelihood of having a relapse (~11%) between 1 and 2 years after diagnosis. Relative to PR3-ANCA, MPO-ANCA seropositivity was associated with a higher likelihood of kidney involvement (OR 2.4, 95% CI 1.3 to 4.7, p=0.008) and severe kidney dysfunction (Kidney Disease Improving Global Outcomes (KDIGO) stages 4-5; OR 6.04, 95% CI 2.77 to 13.57, p<0.001) at onset. Nonetheless, MPO-ANCA seropositive individuals were more likely to demonstrate improvement in kidney function (improved KDIGO category) within 1 year of diagnosis than PR3-ANCA seropositive individuals with similarly severe kidney disease at onset (p<0.001). CONCLUSIONS: The results of this study suggest important paediatric-specific differences in the predictive value of ANCA compared with adult patients that should be considered when making treatment decisions in this population.
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Anticorpos Anticitoplasma de Neutrófilos , Mieloblastina , Peroxidase , Humanos , Anticorpos Anticitoplasma de Neutrófilos/sangue , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Masculino , Feminino , Criança , Adolescente , Peroxidase/imunologia , Mieloblastina/imunologia , Estudos Retrospectivos , Nefropatias/diagnóstico , Nefropatias/etiologia , Nefropatias/imunologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/sangue , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Biomarcadores/sangue , Pré-Escolar , Prognóstico , Valor Preditivo dos TestesRESUMO
Chronic primary systemic vasculitis (PSV) comprises a group of heterogeneous diseases that are broadly classified by affected blood vessel size, clinical traits and the presence (or absence) of anti-neutrophil cytoplasmic antibodies (ANCA) against proteinase 3 (PR3) and myeloperoxidase (MPO). In small vessel vasculitis (SVV), ANCA are not present in all patients, and they are rarely detected in patients with vasculitis involving medium (MVV) and large (LVV) blood vessels. Some studies have demonstrated that lysosome-associated membrane protein-2 (LAMP-2/CD107b) is a target of ANCA in SVV, but its presence and prognostic value in childhood MVV and LVV is not known. This study utilized retrospective sera and clinical data obtained from 90 children and adolescents with chronic PSV affecting small (SVV, n = 53), medium (MVV, n = 16), and large (LVV, n = 21) blood vessels. LAMP-2-ANCA were measured in time-of-diagnosis sera using a custom electrochemiluminescence assay. The threshold for seropositivity was established in a comparator cohort of patients with systemic autoinflammatory disease. The proportion of LAMP-2-ANCA-seropositive individuals and sera concentrations of LAMP-2-ANCA were assessed for associations with overall and organ-specific disease activity at diagnosis and one-year follow up. This study demonstrated a greater time-of-diagnosis prevalence and sera concentration of LAMP-2-ANCA in MVV (52.9% seropositive) and LVV (76.2%) compared to SVV (45.3%). Further, LAMP-2-ANCA-seropositive individuals had significantly lower overall, but not organ-specific, disease activity at diagnosis. This did not, however, result in a greater reduction in disease activity or the likelihood of achieving inactive disease one-year after diagnosis. The results of this study demonstrate particularly high prevalence and concentration of LAMP-2-ANCA in chronic PSV that affects large blood vessels and is seronegative for traditional ANCA. Our findings invite reconsideration of roles for autoantigens other than MPO and PR3 in pediatric vasculitis, particularly in medium- and large-sized blood vessels.
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Vasculite Sistêmica , Adolescente , Criança , Humanos , Anticorpos Anticitoplasma de Neutrófilos , Autoantígenos , Mieloblastina , Estudos RetrospectivosRESUMO
Behçet's syndrome is a recurring inflammatory multiorgan disorder affecting the skin, mucosa, eyes, joints, stomach, and central nervous system. Behçet's syndrome epidemiology varies greatly among populations (0.64-420/100,000), and Behçet's syndrome has gained increasing international acclaim in the recent 50 years due to raising awareness of the syndrome, although it is rare in most population. In addition to the unclear etiology of the syndrome, the diagnosis of Behçet's syndrome is complicated by a vague clinical presentation, phenotypic heterogeneity and/or incomplete representation, and the lack of any specific laboratory, radiographic, or histological findings. There exists a dire need to elucidate factors that contribute to disease pathogenesis and/or are associated with clinical features of Behçet's syndrome and the classification of different forms of the syndrome. The identification of such molecular, cellular, and/or clinical factors are crucial for timely diagnosis and efficacious management of Behçet's syndrome. We discuss recent advances in the clinical diagnosis of Behçet's syndrome and related contributions of genetics, epigenetics, microbiome, inflammasomes, and autoantibodies to the improved diagnosis, management, and understanding of Behçet's syndrome.
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Síndrome de Behçet , Humanos , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/epidemiologia , Síndrome de Behçet/genética , Pele/patologiaRESUMO
OBJECTIVES: Posttraumatic stress disorder (PTSD) is associated with sleep disturbances including insomnia and nightmares. This study compared cognitive behavioral therapy for insomnia (CBT-I) with CBT-I combined with imagery rehearsal therapy (IRT) for nightmares to evaluate if the combined treatment led to greater reductions in trauma-related sleep disturbances in Australian veterans. METHODS: Veterans with diagnosed PTSD, high insomnia symptom severity, and nightmares (N = 31) were randomized to eight group CBT-I sessions or eight group CBT-I + IRT sessions. Self-reported sleep, nightmare, and psychological measures (primary outcome: Pittsburgh Sleep Quality Index), and objective actigraphy data were collected; the effect of obstructive sleep apnea (OSA) risk on treatment outcomes was also examined. RESULTS: No treatment condition effects were detected for the combined treatment compared to CBT-I alone, and no moderating effect of OSA risk was detected. On average, participants from both groups improved on various self-report measures over time (baseline to 3 months posttreatment). Despite the improvements, mean scores for sleep-specific measures remained indicative of poor sleep quality. There were also no significant differences between the groups on the actigraphy indices. CONCLUSIONS: The findings indicate that there is potential to optimize both treatments for veterans with trauma-related sleep disturbances.
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Terapia Cognitivo-Comportamental , Apneia Obstrutiva do Sono , Distúrbios do Início e da Manutenção do Sono , Transtornos de Estresse Pós-Traumáticos , Veteranos , Humanos , Distúrbios do Início e da Manutenção do Sono/terapia , Veteranos/psicologia , Projetos Piloto , Austrália , Sono , Resultado do Tratamento , Transtornos de Estresse Pós-Traumáticos/psicologia , Apneia Obstrutiva do Sono/complicaçõesRESUMO
Adenosinergic signaling has potent, context-specific effects on immune cells, particularly on the dysregulation of lymphocytes. This in turn may have a role in immune activation and loss of tolerance in such diseases as chronic graft-versus-host disease (chronic GVHD). We assessed whether changes in the enzymatic activity of adenosine deaminase 2 (ADA2), an enzyme that depletes adenosine in the extracellular space via conversion to inosine, may be associated with the onset of chronic GVHD. ADA2-specific enzyme activity was measured in plasma samples from 230 pediatric hematopoietic stem cell transplantation (HSCT) recipients enrolled on the Applied Biomarkers of Late Effects of Childhood Cancer (ABLE)/Pediatric Blood and Marrow Transplant Consortium (PBMTC) 1202 study and compared between patients developing chronic GVHD and those not developing chronic GVHD within 12 months of transplantation. ADA2 and its relationships with 219 previously measured plasma-soluble proteins, metabolites, and immune cell populations were evaluated as well. Plasma ADA2 enzyme activity was significantly elevated in pediatric HSCT recipients at the onset of chronic GVHD compared to patients without chronic GVHD and was not associated with prior history of acute GVHD or generalized inflammation as measured by C-reactive protein concentration. ADA2-specific enzyme activity met our criteria as a potential diagnostic biomarker of chronic GVHD (effect ratio ≥1.30 or ≤.75; area under the receiver operating characteristic curve ≥.60; P < .05) and was positively associated with markers of immune activation previously identified in pediatric chronic GVHD patients. These results support the potential of ADA2 enzyme activity, in combination with other biomarkers and subject to future validation, to aid the diagnosis of chronic GVHD in children post-HSCT.
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Síndrome de Bronquiolite Obliterante , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Criança , Adenosina Desaminase , Doença Enxerto-Hospedeiro/diagnóstico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , BiomarcadoresRESUMO
Background: Hyaluronan (HA) is an important structural component of the extracellular matrix and has well-described roles in maintaining tissue integrity and homeostasis. With inflammation, HA metabolism (synthesis and degradation) increases and results in higher concentrations of soluble HA. Previously, we demonstrated that (soluble) HA primed resting neutrophils for the oxidative burst in response to a secondary stimulus. Notably, HA-mediated priming was not dependent on degranulation, which is a hallmark of priming by classical agents such as TNFα. In this study, we queried the ability of HA to prime neutrophils to different stimuli and its capacity to modulate neutrophil function in the presence of TNFα. Methods: Blood neutrophils from healthy donors were stimulated ex vivo with HA in the absence and presence of classic neutrophil agonists, inclusive of TNFα. Western blotting was used to assess the activation (phosphorylation) of p38 MAPK, and key neutrophil functions associated with priming and activation, such as intracellular and extracellular ROS production, degranulation, and apoptosis, were evaluated by standard chemiluminescence assays (ROS) and flow cytometry. Results: Hyaluronan is capable of atypical priming and, with TNFα, co-priming neutrophils for an enhanced (rate and/or magnitude) oxidative burst to various secondary stimuli. In addition, HA can augment intracellular ROS production that is directly induced by TNFα in resting neutrophils, which coincided with the activation of p38 MAPK and apoptosis. Conclusions: These data demonstrate that the extracellular matrix component HA is a key modulator of neutrophil function(s) in the presence of inflammatory agents such as TNFα. Moreover, it provides additional evidence for the diversity and complexity of neutrophil priming and activation during inflammation.
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Neutrófilos , Fator de Necrose Tumoral alfa , Humanos , Fator de Necrose Tumoral alfa/metabolismo , Neutrófilos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ácido Hialurônico/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Inflamação/metabolismo , ApoptoseRESUMO
BACKGROUND: The burden of waiting to access specialist expertise may contribute to poorer health outcomes and causes distress for patients and providers. One solution to improve access to specialist care is to use innovative tools such as remote asynchronous electronic consultation (eConsult). Modeled after the Champlain BASE™ (Building Access to Specialist Advice) eConsult service, BASE™ eConsult Manitoba was launched in 2017 to help address long waits for patients to access specialist advice. OBJECTIVE: We aimed to evaluate patients' experiences after obtaining a BASE™ eConsult Manitoba service in their primary care setting. METHODS: Patients whose Primary Care Providers (PCPs) used BASE™ eConsult as part of their care were asked to participate and complete a telephone-based or online 29-question survey between January 2021 and October 2021. The survey questions were created in consultation with patient partners and based on questions asked in studies done in other jurisdictions. RESULTS: Of the 36 patients who chose to participate, 29 completed the entire survey (80%). Two-thirds (n = 22) agreed that eConsult has been helpful in their situation, and over 80% (n = 24) of participants agreed that eConsult was an acceptable way to access specialist care. During the visit when their PCP sent the eConsult, 7 patients were expecting to be referred to a specialist for a face-to-face consultation. Over half of all respondents (n = 15) reported that before the eConsult occurred, their PCP asked them what questions they wanted to be answered by the specialist. Almost all of these respondents' questions were fully answered by the eConsult. All of the respondents were satisfied with the experience of receiving an eConsult. CONCLUSION: Using eConsult is an acceptable way to improve access to specialist advice from patients' perspectives. Consideration should be given to expanding the use of eConsult services to improve access to specialist expertise for PCPs and their patients.
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Medicina , Consulta Remota , Humanos , Manitoba , Acessibilidade aos Serviços de Saúde , Estudos Transversais , Encaminhamento e ConsultaRESUMO
Posttraumatic stress disorder (PTSD) is a significant issue for a substantial proportion of Australian ex-service personnel. In addition to the functional impact on individuals, PTSD can have a significant impact on intimate partner relationships. Research has demonstrated that practicing compassion and self-compassion may be an important component of psychological therapy for survivors of trauma, while also demonstrating benefits to intimate relationships. This pilot study aimed to investigate the utility of a Compassionate Mind Training intervention for ex-service personnel with PTSD and their partners. An uncontrolled, within-subjects, longitudinal design was utilized with assessment at pre-intervention, post-intervention and 3-month follow-up. Twenty-four participants attended 12 biweekly group sessions. Self-report measures of compassion, quality of life and psychological symptoms were administered at each time point. Findings demonstrated a significant reduction in fears of compassion and PTSD symptoms for ex-service personnel at 3-month follow-up and a reduction in depressive symptoms and increase in quality-of-life and social safeness at post-intervention. Additionally, significant reductions in anxiety, stress, external shame and self-criticism at 3-month follow-up were found, and couples reported significant increases in relationship satisfaction. Findings from this pilot study demonstrate promising outcomes, warranting further investigation in a larger randomized controlled trial of Compassionate Mind Training for ex-service personnel and their partners.
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Transtornos de Estresse Pós-Traumáticos , Veteranos , Humanos , Transtornos de Estresse Pós-Traumáticos/terapia , Transtornos de Estresse Pós-Traumáticos/psicologia , Empatia , Projetos Piloto , Qualidade de Vida , Austrália , Veteranos/psicologiaRESUMO
OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare, life-threatening inflammation of blood vessels that can affect both adults and children. Compared to adult-onset disease, AAV is especially rare in children, with an annual prevalence of 0.5-6.4 cases per million children. The etiology of AAV remains largely unknown, and both environmental and genetic factors are likely involved. The present study was undertaken to explore the genetic susceptibility factors recently identified in adult patients, including HLA-DP and HLA-DQ, in pediatric patients. METHODS: We performed a genome-wide association study of pediatric AAV in patients of European ancestry (n = 63 AAV cases, n = 315 population-matched controls). RESULTS: We identified a significant genetic association between pediatric AAV and the HLA-DPB1*04:01 allele (P = 1.5 × 10-8 , odds ratio [OR] 3.5), with a stronger association observed in children with proteinase 3-ANCA positivity than in children with myeloperoxidase-ANCA positivity. Among the HLA alleles, the HLA-DPB1*04:01 allele was the most highly associated with AAV, although not significantly, in a follow-up adult AAV cohort (P = 2.6 × 10-4 , OR 0.4). T cell receptor and interferon signaling pathways were also shown to be enriched in the pediatric AAV cohort. CONCLUSION: The HLA-DPB1 locus showed an association with pediatric AAV, as similarly shown previously in adult AAV. Despite the difference in the age of onset, these findings suggest that childhood- and adult-onset vasculitis share a common genetic predisposition. The identification of genetic variants contributing to AAV is an important step to improved classification tools and treatment strategies.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Anticorpos Anticitoplasma de Neutrófilos , Adulto , Humanos , Criança , Estudo de Associação Genômica Ampla , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/genética , Cadeias beta de HLA-DP/genética , Predisposição Genética para Doença , PeroxidaseRESUMO
BACKGROUND: Cardiac arrest (CA) is a common reason for admission to the cardiac intensive care unit (CICU), though the relative burden of morbidity, mortality, and resource use between admissions with in-hospital (IH) and out-of-hospital (OH) CA is unknown. We compared characteristics, care patterns, and outcomes of admissions to contemporary CICUs after IHCA or OHCA. METHODS: The Critical Care Cardiology Trials Network is a multicenter network of tertiary CICUs in the US and Canada. Participating centers contributed data from consecutive admissions during 2-month annual snapshots from 2017 to 2021. We analyzed characteristics and outcomes of admissions by IHCA vs OHCA. RESULTS: We analyzed 2,075 admissions across 29 centers (50.3% IHCA, 49.7% OHCA). Admissions with IHCA were older (median 66 vs 62 years), more commonly had coronary disease (38.3% vs 29.7%), atrial fibrillation (26.7% vs 15.6%), and heart failure (36.3% vs 22.1%), and were less commonly comatose on CICU arrival (34.2% vs 71.7%), p < 0.001 for all. IHCA admissions had lower lactate (median 4.3 vs 5.9) but greater utilization of invasive hemodynamics (34.3% vs 23.6%), mechanical circulatory support (28.4% vs 16.8%), and renal replacement therapy (15.5% vs 9.4%); p < 0.001 for all. Comatose IHCA patients underwent targeted temperature management less frequently than OHCA patients (63.3% vs 84.9%, p < 0.001). IHCA admissions had lower unadjusted CICU (30.8% vs 39.0%, p < 0.001) and in-hospital mortality (36.1% vs 44.1%, p < 0.001). CONCLUSION: Despite a greater burden of comorbidities, CICU admissions after IHCA have lower lactate, greater invasive therapy utilization, and lower crude mortality than admissions after OHCA.
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Cardiologia , Reanimação Cardiopulmonar , Parada Cardíaca Extra-Hospitalar , Humanos , Parada Cardíaca Extra-Hospitalar/terapia , Coma , Unidades de Terapia Intensiva , Cuidados Críticos , Hospitais , Estudos RetrospectivosRESUMO
Background: Adenosine deaminase 2 (ADA2) is a homodimeric, extracellular enzyme and putative growth factor that is produced by cells of the myeloid lineage and, catalytically, deaminates extracellular adenosine to inosine. Loss-of-(catalytic)-function variants in the ADA2 gene are associated with Deficiency of ADA2 (DADA2), an autosomal recessive disease associated with an unusually broad range of inflammatory manifestations including vasculitis, hematological defects and cytopenia. Previous work by our group led to the identification of ADA2 variants of novel association with DADA2, among which was a unique c.1052T>A (p.Leu351Gln; herein referred to as L351Q) variant located in the catalytic domain of the protein. Methods: Mammalian (Flp-IN CHO) cells were engineered to stably express wild-type ADA2 and ADA2 protein variants, including the pathogenic L351Q variant identified in DADA2 patients. An enzyme assay and immunoblotting were used to assess ADA2 catalytic activity and secretion, respectively, and the outcome of experimentally induced inhibition of protein processing (Golgi transport and N-linked glycosylation) was assessed. Reverse transcription quantitative real-time PCR (RT-qPCR) was applied to determine the relative expression of Type I Interferon stimulated genes (ISGs), IFIT3 and IRF7. Results: In addition to abrogating catalytic activity, the L351Q variant impaired secretion of L351Q ADA2 resulting in an intracellular accumulation of L351Q ADA2 protein that was not observed in cells expressing wild-type ADA2 or other ADA2 protein variants. Retention of L351Q ADA2 was not attributable to impaired glycosylation on neighboring asparagine residues and did not impact cell growth or integrity. Constitutive expression of Type I ISGs IFIT3 and IRF7 was observed in cells expressing L351Q ADA2. Conclusions: The impaired secretion of L351Q ADA2 may be an important factor leading to the severe phenotype observed in patients with this variant further emphasizing the importance of assessing impacts beyond catalytic activity when evaluating genotype-phenotype relationships in DADA2.
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Adenosina Desaminase , Interferon Tipo I , Adenosina , Adenosina Desaminase/genética , Animais , Asparagina/genética , Expressão Gênica , Inosina , Peptídeos e Proteínas de Sinalização Intercelular/genética , Interferon Tipo I/genética , Mamíferos/genética , MutaçãoRESUMO
The sea cucumber Holothuria (Metriatyla) scabra, known as sandfish, is a high-value tropical echinoderm central to the global bêche-de-mer (BDM) trade. This species has been heavily exploited across its natural range, with overharvesting and ineffective fishery management leaving stocks in the Pacific region heavily depleted. In Fiji, sandfish stocks have not recovered since a 1988 harvest ban, with surveys reporting declining populations and recruitment failure. Therefore, to inform fishery management policy for the wild sandfish resource and to guide hatchery-based restocking efforts, a high-resolution genomic audit of Fijian populations was carried out. A total of 6,896 selectively-neutral and 186 putatively-adaptive genome-wide SNPs (DArTseq) together with an independent oceanographic particle dispersal model were used to investigate genetic structure, diversity, signatures of selection, relatedness and connectivity in six wild populations. Three genetically distinct populations were identified with shallow but significant differentiation (average Fst = 0.034, p≤0.05), comprising (1) Lakeba island (Lau archipelago), (2) Macuata (Vanua Levu), and (3) individuals from Yasawa, Ra, Serua island and Kadavu comprising the final unit. Small reductions in allelic diversity were observed in marginal populations in eastern Fiji (overall mean A = 1.956 vs. Lau, A = 1.912 and Macuata, A = 1.939). Signatures of putative local adaptation were also discovered in individuals from Lakeba island, suggesting that they be managed as a discrete unit. An isolation-by-distance model of genetic structure for Fijian sandfish is apparent, with population fragmentation occurring towards the east. Hatchery-based production of juveniles is promising for stock replenishment, however great care is required during broodstock source population selection and juvenile releases into source areas only. The successful use of genomic data here has the potential to be applied to other sea cucumber species in Fiji, and other regions involved in the global BDM trade. While preliminary insights into the genetic structure and connectivity of sandfish in Fiji have been obtained, further local, regional and distribution-wide investigations are required to better inform conservation efforts, wild stock management and hatchery-based restocking interventions for this valuable invertebrate.
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Holothuria , Pepinos-do-Mar , Animais , Equinodermos , Pesqueiros , Holothuria/genética , Humanos , Metagenômica , Pepinos-do-Mar/genéticaRESUMO
Approaches to control basal ganglia neural activity in real-time are needed to clarify the causal role of 13-35 Hz ("beta band") oscillatory dynamics in the manifestation of Parkinson's disease (PD) motor signs. Here, we show that resonant beta oscillations evoked by electrical pulses with precise amplitude and timing can be used to predictably suppress or amplify spontaneous beta band activity in the internal segment of the globus pallidus (GPi) in the human. Using this approach, referred to as closed-loop evoked interference deep brain stimulation (eiDBS), we could suppress or amplify frequency-specific (16-22 Hz) neural activity in a PD patient. Our results highlight the utility of eiDBS to characterize the role of oscillatory dynamics in PD and other brain conditions, and to develop personalized neuromodulation systems.
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Estimulação Encefálica Profunda , Doença de Parkinson , Gânglios da Base , Estimulação Encefálica Profunda/métodos , Globo Pálido/fisiologia , Humanos , Doença de Parkinson/terapiaAssuntos
Icterícia , Nascimento Prematuro , Feminino , Humanos , Recém-Nascido , Readmissão do PacienteRESUMO
With a rise in the development and subsequent employment of precision medicine, their lies an immediate necessity for the development of technology to enable the implementation of such treatment plans into the healthcare environment. Electrochemistry stands to offer one of the most viable techniques for such technologies given its success within current medical devices. One electrochemical technique, electrochemiluminescence (ECL), warrants investigation. Previously we have determined the inability to reliably detect cancer therapy gemcitabine via traditional ruthenium based ECL. Here we demonstrate how the addition of gold nanoparticles into the ECL film can promote GMB detection via enhanced electrocatalytic oxidation, generating the required ECL radicals. Via this approach we have been able to improve the ECL signal intensity 60-fold and achieve detection down to 6.25 µM across a linear range of 6.25-50 µM. Which lies within the therapeutically relevant range. This approach has successfully addressed the prior limitations encountered for the employment of traditional ruthenium based ECL for substance identification, where species exhibit limited electro-activity and suffer from electrochemically induced side reactions.
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Nanopartículas Metálicas , Rutênio , Desoxicitidina/análogos & derivados , Técnicas Eletroquímicas/métodos , Ouro/química , Medições Luminescentes/métodos , Nanopartículas Metálicas/química , Rutênio/química , GencitabinaRESUMO
Veterinary science or veterinary medicine is a diverse and significant field. Concerned not only with the diagnosis and treatment of domestic animals and livestock, but it also places focus upon zoonotic diseases, the development and effectiveness of potential vaccines and the possibility of transmission of veterinary medication or viruses into animal food products. Electrochemiluminescence (ECL) is a powerful analytical technique, which despite its significant intrinsic benefits has not seen enormous adoption into the wider analytical chemical community. In contrast, the veterinary science sector has reaped the merit of ECL as far back as the late 90's and continue to benefit from development of the technique a further three decades later. ECL offers the superb sensitivity, low running costs, rapid results and high reliability required within the veterinary science sector, as such its employment in this area shouldn't be surprising. To this end this article aims to summarise the standing of ECL within the veterinary science field, in an attempt increase the awareness of its successful employment within this area to the electro-analytical and wider analytical chemistry communities. Where it is hope veterinary science will gain recognition as possible end user targets for academic and industrial electrochemical researchers.
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Medições Luminescentes , Animais , Medições Luminescentes/métodos , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Families with complex needs face significant challenges accessing and navigating health and social services. For veteran families, these challenges are exacerbated by interactions between military and civilian systems of care, and the density of the veterans' non-profit sector. This qualitative study was designed to gather rich, detailed information on complex needs in veteran families; and explore service providers' and families' experiences of accessing and navigating the veterans' support system. METHODS: The study comprised participant background questionnaires (n = 34), focus groups with frontline service providers (n = 18), and one-on-one interviews with veteran families (n = 16) in Australia. The semi-structured focus groups and interviews were designed to gather rich, detailed information on four study topics: (i) health and wellbeing needs in veteran families; (ii) service-access barriers and facilitators; (iii) unmet needs and gaps in service provision; and (iv) practical solutions for improving service delivery. The study recruited participants who could best address the focus on veteran families with complex needs. The questionnaire data was used to describe relevant characteristics of the participant sample. The focus groups and interviews were audio-recorded, transcribed, and a reflexive thematic analysis was conducted to identify patterns of shared meaning in the qualitative data. RESULTS: Both service providers and families found the veterans' support system difficult to access and navigate. System fragmentation was perceived to impede care coordination, and delay access to holistic care for veteran families with complex needs. The medico-legal aspects of compensation and rehabilitation processes were perceived to harm veteran identity, and undermine health and wellbeing outcomes. Recovery-oriented practice was viewed as a way to promote veteran independence and self-management. Participants expressed a strong preference for family-centred care that was informed by an understanding of military lifestyle and culture. CONCLUSION: The health and wellbeing needs of veteran families intensify during the transition from full-time military service to civilian environments, and service- or reintegration-related difficulties may emerge (or persist) for a significant period of time thereafter. Veteran families with complex needs are unduly burdened by care coordination demands. There is a pressing need for high-quality implementation studies that evaluate initiatives for integrating fragmented systems of care.
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Militares , Veteranos , Grupos Focais , Humanos , Pesquisa Qualitativa , Serviço SocialRESUMO
Existing research on individual preparedness in the United States indicates that we are generally unprepared for disasters. While there is an abundance of research on emergency preparedness, there are gaps in our knowledge. For example, the results of extant research are unclear regarding what factors influence individual preparedness. The preparedness literature is also limited in the types of disasters examined and in understanding the timing of preparedness activities. The current COVID-19 global pandemic provides a tragic but albeit unique opportunity to address these limitations of previous research and examine emergency preparedness activities before and immediately following the onset of the COVID-19 outbreak in the United States. This research is further distinctive because it examines preparedness activities related to the global pandemic rather than other types of disasters. Policy and research implications of the findings are presented.