RESUMO
Licensed behavioral health providers (LBHPs) were integrated into 5 pediatric primary care practices in southeast and east Texas from October 2018 through March 2020. LBHPs Licensed behavioral health providers across the sites were 3 licensed clinical social workers (LCSW), 1 psychologist, and 1 nurse practitioner (NP). Practices provided data for 6 to 15 months. Overall, 2769 units of behavioral health services were provided to 746 children over 2243 hours. Across 4 sites, 44.3% of behavioral health patients were diagnosed with trauma disorders, 22.1% with anxiety, 19.3% with attention-deficit hyperactivity disorder, 15.1% with depression, and 10.9% with disruptive behavior disorders. Overall, the model was financially successful at 2 sites (LCSWs) and unsuccessful at 1 site (NP). The other 2 sites demonstrated potential for financial sustainability with increased behavioral health patient volume. Overall, this model is a financially viable option for pediatric primary care practices with adequate patient volumes to provide integrated behavioral health services.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Atenção Primária à Saúde , Criança , Humanos , Transtornos de Deficit da Atenção e do Comportamento Disruptivo , Ansiedade , TexasRESUMO
INTRODUCTION: We examined the predictive ability of red cell distribution width (RDW) and the change in RDW during hospitalization (ΔRDW) for length of stay (LOS) and 30-day outcomes after heart failure (HF) inpatient stay. METHODS: Electronic query of Intermountain Healthcare medical records identified patients (N = 6414) with a primary diagnosis of HF who were discharged between 2004 and 2013, had RDW measured within 24 h after admission, and had RDW tested at least once more during the same hospitalization. ΔRDW was defined as the last RDW within 24 h prior to discharge minus the first RDW. RESULTS: Median LOS by initial RDW quartiles was Q1: 3.0, Q2: 3.1, Q3: 3.7, and Q4: 4.0 days (P-trend<0.001), and by ΔRDW quartiles was Q1: 4.1, Q2: 3.4, Q3: 3.6, and Q4: 4.7 days (P-trend<0.001). Both initial RDW (16.8 ± 2.8% vs. 16.3 ± 2.7%, P < 0.001) and ΔRDW (0.21 ± 1.09% vs. 0.14 ± 1.04%, P = 0.039) predicted 30-day readmission vs. no readmit. For 30-day decedents vs. survivors, initial RDW was 17.3 ± 3.0% vs. 16.3 ± 2.6% (P < 0.001), while ΔRDW was +0.20 ± 1.14% vs. +0.14 ± 1.04% (P = 0.15). CONCLUSIONS: Greater initial RDW and ΔRDW during HF hospitalization were associated with 30-day mortality, longer LOS, and 30-day all-cause readmission, suggesting both ΔRDW and initial RDW may aid in personalizing prognosis and treatment.
Assuntos
Registros Eletrônicos de Saúde , Índices de Eritrócitos , Mortalidade Hospitalar , Tempo de Internação , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , MasculinoRESUMO
The purpose of this project was to develop and evaluate a specifically designed website (ALLograft INformation EXchange - ALLINEX) for adult allogeneic haematopoietic stem cell transplant (allo-HSCT) patients in Leeds. Specifications included information on the transplant journey and supportive care services, discussion forum and patient-clinical team electronic messaging service. The method followed a participatory action research approach in a five-phase project involving stakeholders. Phase 1 involved information gathering; Phase 2 development of content; Phase 3 building of website and usability testing; Phase 4 preliminary evaluation; and Phase 5 clinical implementation. Results concluded that Phase 1 patients were unaware of all services and reported unmet needs; gaps in support services were identified from a service evaluation; Phase 2 content was collected from experts, collated and synthesised; Phase 3 patient and staff feedback was positive and constructive resulting in more than 50 changes; Phase 4 ALLINEX evaluation demonstrated acceptable usability with good layout, content and aesthetics reported; Phase 5, over 15 weeks, ALLINEX had 6630 page hits, 9 new forum topics posted and received 3 clinical messages. The clinical team embraced responsibility for reviewing and monitoring ALLINEX. Financial and indemnity cover was secured for 3 years. ALLINEX, adopted locally, is sustainable and has functionality to roll-out to other UK allo-HSCT centres.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Internet , Adulto , Serviços de Saúde Comunitária/estatística & dados numéricos , Coleta de Dados , Atenção à Saúde , Inglaterra , Retroalimentação , Feminino , Humanos , Serviços de Informação , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Portais do Paciente , Satisfação do Paciente , Desenvolvimento de Programas , Apoio Social , Transplante Homólogo , Interface Usuário-Computador , Adulto JovemRESUMO
Following haematopoietic stem cell transplant (HSCT) some patients experience long-term physical and psychosocial problems which impact on everyday life. The aim of this service evaluation was to investigate the psychosocial supportive care available for HSCT patients in three UK centres, particularly related to five identified areas of concern: fatigue; psychological distress; vocational and financial issues; sexuality, and fertility. HSCT health professionals were invited to audio-recorded semi-structured interviews. Enquiry was made into supportive care provided routinely (proactive), provided in response to a need (reactive) and missing (gaps in service) from pre-transplant to 18 months post transplant. Information gathered was transcribed and subjected to framework analysis. Interviews were conducted with 84 staff including nurses, doctors, psychologists, social workers, physiotherapists, dieticians and occupational therapists. Support for the five main areas of concern was variable across centres particularly with limitation of services for psychology; sexual dysfunction and fertility. Pro-active interventions such as psychological screening were rare with support being more commonly provided in response to an identified need. Support provided reactively for the areas of concern was comprehensive across professional groups and centres. Further work explores patients' psychosocial issues and other ways of providing adjuvant support.
Assuntos
Transplante de Células-Tronco Hematopoéticas/psicologia , Serviços de Saúde Mental , Apoio Social , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Reino UnidoRESUMO
OBJECTIVE: The development and evaluation of a labor risk model consisting of a combination of antepartum risk factors and intrapartum fetal heart rate (FHR) characteristics that can reliably identify those infants at risk for adverse neonatal outcome in labor. STUDY DESIGN: A nested case-control study of term singleton deliveries at the nine hospitals between March 2007 and December 2009. Eligibility criteria included: gestational age ≥ 37.0 weeks; singleton pregnancy; documented continuous FHR monitoring for ≥ 2 h before delivery; assessment of FHR tracing at least every 20 min; and, available maternal and neonatal outcomes. Adverse neonatal outcome was defined as nonanomalous infants admitted to the newborn intensive care unit with either a 5 minute Apgar score <7 or an umbilical artery pH<7.1. Initial risk score was determined using data available at 1 h after admission. Patients with an initial risk score between 7 and 15 were considered high risk. Intrapartum risk scores were then created for these patients using FHR tracing data and labor characteristics. RESULT: A total of 51 244 patients were identified meeting study criteria. Of the antepartum variables evaluated (n=31), 10 were associated with an adverse outcome. The high-risk group made up 28% of the population and accounted for 59.8% of the adverse outcomes. Intrapartum characteristics were then evaluated in this high-risk group. Intrapartum evaluation identified the highest risk group with a C/S rate of 40% and adverse outcome rate of 11.3%. CONCLUSION: Incorporation of maternal and antepartum risk factors with FHR analysis can improve the ability to identify the fetus at risk in labor.
Assuntos
Frequência Cardíaca Fetal , Trabalho de Parto , Resultado da Gravidez , Medição de Risco/métodos , Adulto , Algoritmos , Cardiotocografia , Estudos de Casos e Controles , Feminino , Humanos , Recém-Nascido , Idade Materna , Gravidez , Complicações na Gravidez , Prognóstico , Fatores de RiscoRESUMO
BACKGROUND AND AIMS: Routine, periodic fasting is associated with a lower prevalence of coronary artery disease (CAD). Animal studies show that fasting may increase longevity and alter biological parameters related to longevity. We evaluated whether fasting initiates acute changes in biomarker expression in humans that may impact short- and long-term health. METHODS AND RESULTS: Apparently-healthy volunteers (N = 30) without a recent history of fasting were enrolled in a randomized cross-over trial. A one-day water-only fast was the intervention and changes in biomarkers were the study endpoints. Bonferroni correction required p ≤ 0.00167 for significance (p < 0.05 was a trend that was only suggestively significant). The one-day fasting intervention acutely increased human growth hormone (p = 1.1 × 10â»4), hemoglobin (p = 4.8 × 10â»7), red blood cell count (p = 2.5 × 10â»6), hematocrit (p = 3.0 × 10â»6), total cholesterol (p = 5.8 × 10â»5), and high-density lipoprotein cholesterol (p = 0.0015), and decreased triglycerides (p = 1.3 × 10â»4), bicarbonate (p = 3.9 × 10â»4), and weight (p = 1.0 × 10â»7), compared to a day of usual eating. For those randomized to fast the first day (n = 16), most factors including human growth hormone and cholesterol returned to baseline after the full 48 h, with the exception of weight (p = 2.5 × 10â»4) and (suggestively significant) triglycerides (p = 0.028). CONCLUSION: Fasting induced acute changes in biomarkers of metabolic, cardiovascular, and general health. The long-term consequences of these short-term changes are unknown but repeated episodes of periodic short-term fasting should be evaluated as a preventive treatment with the potential to reduce metabolic disease risk. Clinical trial registration (ClinicalTrials.gov): NCT01059760 (Expression of Longevity Genes in Response to Extended Fasting [The Fasting and Expression of Longevity Genes during Food abstinence {FEELGOOD} Trial]).
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Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/prevenção & controle , Jejum/efeitos adversos , Síndrome Metabólica/prevenção & controle , Água/administração & dosagem , Adulto , Biomarcadores/sangue , Índice de Massa Corporal , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Estudos Cross-Over , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Jejum/fisiologia , Feminino , Humanos , Hipertrigliceridemia/sangue , Hipertrigliceridemia/epidemiologia , Hipertrigliceridemia/prevenção & controle , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Fatores de Risco , Triglicerídeos/sangue , Utah/epidemiologia , Redução de PesoRESUMO
A systematic review and a meta-analysis were performed to quantify the accumulated information from genetic association studies investigating the impact of the CYP4F2 rs2108622 (p.V433M) polymorphism on coumarin dose requirement. An additional aim was to explore the contribution of the CYP4F2 variant in comparison with, as well as after stratification for, the VKORC1 and CYP2C9 variants. Thirty studies involving 9,470 participants met prespecified inclusion criteria. As compared with CC-homozygotes, T-allele carriers required an 8.3% (95% confidence interval (CI): 5.6-11.1%; P < 0.0001) higher mean daily coumarin dose than CC homozygotes to reach a stable international normalized ratio (INR). There was no evidence of publication bias. Heterogeneity among studies was present (I(2) = 43%). Our results show that the CYP4F2 p.V433M polymorphism is associated with interindividual variability in response to coumarin drugs, but with a low effect size that is confirmed to be lower than those contributed by VKORC1 and CYP2C9 polymorphisms.
Assuntos
Cumarínicos/administração & dosagem , Sistema Enzimático do Citocromo P-450/genética , Polimorfismo Genético/genética , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Alelos , Hidrocarboneto de Aril Hidroxilases/genética , Estudos de Coortes , Cumarínicos/uso terapêutico , Estudos Transversais , Citocromo P-450 CYP2C9 , Família 4 do Citocromo P450 , Etnicidade , Humanos , Coeficiente Internacional Normatizado , Pessoa de Meia-Idade , Oxigenases de Função Mista/genética , Viés de Publicação , Fatores Sexuais , Vitamina K Epóxido RedutasesRESUMO
BACKGROUND: Blood product transfusion has been successfully used in solid-organ transplantation to induce tolerance. Whether a similar protective effect of blood product transfusion exists in heart transplantation is controversial. OBJECTIVE: To investigate the effect of cellular blood product transfusion within 2 weeks posttransplantation on the incidence of cellular and antibody-mediated rejection. PATIENTS AND METHODS: Patients were grouped on the basis of number of blood transfusions; group 1 received no transfusions, and groups 2, 3, and 4 each received an incremental number of transfusion units. All endomyocardial biopsy samples were routinely studied using immunofluorescence in the first 12 weeks posttransplantation. RESULTS: Baseline characteristics including age, sex, body mass index, history of diabetes, donor characteristics, and pretransplantation laboratory values were similar except that group 4 had a higher rate of previous sternotomy and longer ischemic time during transplantation. Approximately 9200 endomyocardial biopsy samples composed the data. Short- and long-term freedom from the International Society for Heart & Lung Transplantation grade 3A or higher cellular rejection and from antibody-mediated rejection were comparable between groups. CONCLUSIONS: Blood transfusions within the first 2 weeks post-transplantation do not seem to confer any protective effect against posttransplantation cellular rejection or antibody- mediated rejection. Whether other unmeasured confounding factors mask their effect requires further prospective studies.
Assuntos
Transfusão de Componentes Sanguíneos/métodos , Rejeição de Enxerto/prevenção & controle , Transplante de Coração/patologia , Tolerância Imunológica/efeitos dos fármacos , Adulto , Biópsia , Feminino , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/imunologia , Transplante de Coração-Pulmão/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Resultado do TratamentoRESUMO
The Escherichia coli Hsp40 DnaJ uses its J-domain (Jd) to couple ATP hydrolysis and client protein capture in Hsp70 DnaK. Fusion of the Jd to peptide p5 (as in Jdp5) dramatically increases the apparent affinity of the p5 moiety for DnaK in the presence of ATP, and Jdp5 stimulates ATP hydrolysis in DnaK by several orders of magnitude. NMR experiments with [(15)N]Jdp5 demonstrated that the peptide tethers the Jd to the ATPase domain. Thus, ATP hydrolysis and client protein binding in DnaK are coupled principally through the association of the client with DnaJ. Overexpression of a recombinant Jd was specifically toxic to cells that simultaneously expressed DnaK. No toxicity was observed when overexpressing Jdp5 or mutant Jd or when co-overexpressing the Jd and the nucleotide exchange factor GrpE. The results suggest that the Jd shifts DnaK to a client-bound form by stimulating the DnaK ATPase but only when the Jd is brought to DnaK by a client-Hsp40 complex.
Assuntos
Adenosina Trifosfatases/química , Escherichia coli/enzimologia , Proteínas de Choque Térmico HSP40/química , Proteínas de Choque Térmico HSP70/química , Chaperoninas/química , Proteínas de Escherichia coli/química , Hidrólise , Espectroscopia de Ressonância Magnética , Chaperonas Moleculares , Mutação , Ligação Proteica , Estrutura Terciária de Proteína , Proteínas Recombinantes/químicaRESUMO
Well-characterized genes that affect warfarin metabolism (cytochrome P450 (CYP) 2C9) and sensitivity (vitamin K epoxide reductase complex 1 (VKORC1)) explain one-third of the variability in therapeutic dose before the international normalized ratio (INR) is measured. To determine genotypic relevance after INR becomes available, we derived clinical and pharmacogenetic refinement algorithms on the basis of INR values (on day 4 or 5 of therapy), clinical factors, and genotype. After adjusting for INR, CYP2C9 and VKORC1 genotypes remained significant predictors (P < 0.001) of warfarin dose. The clinical algorithm had an R(2) of 48% (median absolute error (MAE): 7.0 mg/week) and the pharmacogenetic algorithm had an R(2) of 63% (MAE: 5.5 mg/week) in the derivation set (N = 969). In independent validation sets, the R(2) was 26-43% with the clinical algorithm and 42-58% when genotype was added (P = 0.002). After several days of therapy, a pharmacogenetic algorithm estimates the therapeutic warfarin dose more accurately than one using clinical factors and INR response alone.
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Variação Genética/genética , Coeficiente Internacional Normatizado/normas , Integração de Sistemas , Varfarina/administração & dosagem , Idoso , Hidrocarboneto de Aril Hidroxilases/genética , Estudos de Coortes , Citocromo P-450 CYP2C9 , Relação Dose-Resposta a Droga , Feminino , Genótipo , Humanos , Coeficiente Internacional Normatizado/métodos , Masculino , Pessoa de Meia-Idade , Oxigenases de Função Mista/genética , Farmacogenética/métodos , Vitamina K Epóxido Redutases , Varfarina/farmacocinéticaRESUMO
Mineral exploration is increasing in Canada, particularly in the north where extensive diamond mining and exploration are occurring. This study measured the under-ice noise produced by a variety of anthropogenic sources (drilling rigs, helicopters, aircraft landing and takeoff, ice-road traffic, augers, snowmobiles, and chisels) at a winter-based diamond exploration project on Kennady Lake in the Northwest Territories, Canada to infer the potential impact of noise on fishes in the lake. The root-mean-square noise level measured 5 m from a small diameter drill was approximately 46 dB greater (22 kHz bandwidth) than ambient noise, while the acoustic particle velocity was approximately 40 dB higher than ambient levels. The loudest sounds at the exploration site were produced by ice cracking, both natural and during landing and takeoff of a C130 Hercules aircraft. However, even walking on the snow above the ice raised ambient sound levels by approximately 30 dB. Most of the anthropogenic sounds are likely detectable by fishes with hearing specializations, such as chubs and suckers. Other species without specialized hearing adaptations will detect these sounds only close to the source. The greatest potential impact of noise from diamond exploration is likely to be the masking of sounds for fishes with sensitive hearing.
Assuntos
Peixes , Audição , Camada de Gelo , Mineração/instrumentação , Ruído Ocupacional , Acústica , Adaptação Fisiológica , Aeronaves , Animais , Limiar Auditivo , Canadá , Diamante , Ecossistema , Mascaramento PerceptivoRESUMO
To perform effectively as a molecular chaperone, DnaK (Hsp70) necessitates the assistance of its DnaJ (Hsp40) co-chaperone partner, which efficiently stimulates its intrinsically weak ATPase activity and facilitates its interaction with polypeptide substrates. In this study, we address the function of the conserved glycine- and phenylalanine-rich (G/F-rich) region of the Escherichia coli DnaJ in the DnaK chaperone cycle. We show that the G/F-rich region is critical for DnaJ co-chaperone functions in vivo and that despite a significant degree of sequence conservation among the G/F-rich regions of Hsp40 homologs from bacteria, yeast, or humans, functional complementation in the context of the E. coli DnaJ is limited. Furthermore, we found that the deletion of the whole G/F-rich region is mirrored by mutations in the conserved Asp-Ile/Val-Phe (DIF) motif contained in this region. Further genetic and biochemical analyses revealed that this amino acid triplet plays a critical role in regulation of the DnaK chaperone cycle, possibly by modulating a crucial step subsequent to DnaK-mediated ATP hydrolysis.
Assuntos
Proteínas de Escherichia coli/química , Proteínas de Choque Térmico HSP40/química , Proteínas de Choque Térmico HSP70/química , Trifosfato de Adenosina/química , Motivos de Aminoácidos , Sequência de Aminoácidos , Animais , Sequência Conservada , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Glicina/química , Proteínas de Choque Térmico HSP40/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Humanos , Hidrólise , Chaperonas Moleculares/química , Dados de Sequência Molecular , Fenilalanina/químicaRESUMO
BACKGROUND: We report the health-related quality of life (QOL) of survivors of childhood cancer (acute lymphoblastic leukaemia, ALL, or central nervous system, CNS, tumour), and whether or not they had growth hormone deficiency (GHD) requiring growth hormone treatment (GHT). METHOD: We assessed 77 survivors of childhood ALL (n = 51) or CNS tumours (n = 26), aged between 8-18 years, and free from disease for > or = 4 years. Survivors and their mothers independently rated survivors' QOL, and mothers completed semi-structured interviews to determine their views of the benefits and disadvantages of GHT. RESULTS: Survivors, especially those treated for a CNS tumour, reported poorer QOL compared with UK population norms. Although survivors of ALL reported better QOL than survivors of CNS tumours, there were no differences depending on whether or not they were prescribed GHT. However, mothers reported that those prescribed GHT had worse QOL than those not. All but 2 survivors were responsible for their own injections. A minority of mothers were disappointed with the child's rate of growth, and reported that children experienced pain with injections. CONCLUSION: We conclude that QOL in survivors of childhood cancer is compromised compared with the normal population, especially following CNS tumours. Longitudinal studies are vital to determine whether GHT can contribute to improved QOL for cancer survivors, especially those who experience more intensive initial therapy regimes.
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Neoplasias do Sistema Nervoso Central/complicações , Nanismo Hipofisário/tratamento farmacológico , Hormônio do Crescimento Humano/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Adolescente , Neoplasias do Sistema Nervoso Central/psicologia , Criança , Nanismo Hipofisário/etiologia , Nanismo Hipofisário/psicologia , Feminino , Humanos , Entrevistas como Assunto , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/psicologia , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
While previous results of genetic association studies for common, complex diseases (eg., coronary artery disease, CAD) have been disappointing, examination of multiple related genes within a physiologic pathway may provide improved resolution. This paper describes a method of calculating a genetic risk score (GRS) for a clinical endpoint by integrating data from many candidate genes and multiple intermediate phenotypes (IPs). First, the association of all single nucleotide polymorphisms (SNPs) to an IP is determined and regression beta-coefficients are used to calculate an IP-specific GRS for each individual, repeating this analysis for every IP. Next, the IPs are assessed by a second regression as predictors of the clinical endpoint. Each IP's individual GRS is then weighted by the regression beta-coefficients from the second step, creating a single, composite GRS. As an example, 3,172 patients undergoing coronary angiography were evaluated for 3 SNPs from the cholesterol metabolism pathway. Although these data provide only a preliminary example, the GRS method detected significant differences in CAD by GRS group, whereas separate genotypes did not. These results illustrate the potential of the GRS methodology for multigenic risk evaluation and suggest that such approaches deserve further examination in common, complex diseases such as CAD.
Assuntos
Medição de Risco , Doença das Coronárias/genética , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Fenótipo , Polimorfismo de Nucleotídeo ÚnicoRESUMO
AIMS: To identify attendance patterns in a childhood cancer long term follow up clinic, in order to inform decision making strategies for efficient, cost effective local and national surveillance of survivors. METHODS: Cross-sectional review of 385 individuals >5 years from completion of cancer therapy in childhood or adolescence, attending a regional paediatric oncology and haematology centre. RESULTS: Attenders were younger than non-attenders in the <18 age group; no differences were found for > or =18 year age group. Those attending clinic were more recently off treatment; no significant difference existed for those <7 years from completion of therapy. A greater proportion of attenders were in the most affluent socioeconomic groups with a greater proportion of non-attenders in the lower groups. Those in full time education or training were more likely to attend and those unemployed were less likely. Multiple regression analysis confirmed a significant trend in reduction in attendance with increasing social deprivation, and that attenders were more than twice as likely to be in full time education or training. CONCLUSIONS: Following cancer treatment in childhood and adolescence, attendance at long term follow up programmes is determined by social factors including education, employment, and deprivation.
Assuntos
Assistência Ambulatorial/estatística & dados numéricos , Institutos de Câncer/estatística & dados numéricos , Neoplasias/terapia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Adolescente , Adulto , Criança , Pré-Escolar , Estudos Transversais , Escolaridade , Emprego , Inglaterra , Feminino , Humanos , Assistência de Longa Duração , Masculino , Pobreza , Análise de Regressão , Classe Social , SobreviventesRESUMO
The Escherichia coli Hsp40 DnaJ uses its J-domain to target substrate polypeptides for binding to the Hsp70 DnaK, but the mechanism of J-domain function has been obscured by a substrate-like interaction between DnaJ and DnaK. ATP hydrolysis in DnaK is associated with a conformational change that captures the substrate, and both DnaJ and substrate can stimulate ATP hydrolysis. However, substrates cannot trigger capture by DnaK in the presence of ATP, and substrates stimulate a DnaK conformational change that is uncoupled from ATP hydrolysis. The role of the J-domain was examined using the fluorescent derivative of a fusion protein composed of the J-domain and a DnaK-binding peptide. In the absence of ATP, DnaK-binding affinity of the fusion protein is similar to that of the unfused peptide. However, in the presence of ATP, the affinity of the fusion protein is dramatically increased, which is opposite to the decrease in DnaK affinity typically exhibited by peptides. Binding of a fusion protein that contains a defective J-domain is insensitive to ATP. According to results from isothermal titration calorimetry, the J-domain binds to the DnaK ATPase domain with weak affinity (K(D) = 23 microM at 20 degrees C). The interaction is characterized by a positive enthalpy, small heat capacity change (DeltaC(p)= -33 kcal mol(-1)), and increasing binding affinity for increasing temperatures in the physiological range. In conditions that support binding of the J-domain to the ATPase domain, the J-domain accelerates ATP hydrolysis and a simultaneous conformational change in DnaK that is associated with peptide capture. The defective J-domain is inactive, despite the fact that it binds to the DnaK ATPase domain with higher than wild-type affinity. The results are most consistent with an allosteric mechanism of J-domain action in which the J-domain couples ATP hydrolysis to peptide capture by accelerating ATP hydrolysis and delaying DnaK closure until ATP is hydrolyzed.
Assuntos
Trifosfato de Adenosina/metabolismo , Proteínas de Escherichia coli/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico/metabolismo , Substituição de Aminoácidos , Sítios de Ligação , Proteínas de Escherichia coli/química , Proteínas de Choque Térmico HSP40 , Proteínas de Choque Térmico HSP70/química , Cinética , Modelos Moleculares , Mutagênese Sítio-Dirigida , Conformação Proteica , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , TermodinâmicaRESUMO
AIMS: To determine differences in ratings of quality of life (QOL) depending on respondent (mother or child) and implications for the validity of measures of QOL, and interpretation of scores. METHOD: Forty-five survivors of acute lymphoblastic leukaemia (ALL) and 23 survivors of central nervous system (CNS) tumours and their mothers completed a generic measure of QOL: the Pediatric Quality of Life Inventory Version 4.0 (PedsQL 4.0; Varni et al., 2001). RESULTS: Although correlations between mother and survivor ratings were largely moderate to good, further analyses showed that mothers reported QOL to be worse than survivors. Both mothers and survivors rated physical health worse than psychological health, and survivors of a CNS tumour had poorer QOL than survivors of ALL. Although survivors of ALL reported reasonably good physical health, their psychosocial health was more adversely affected. CONCLUSIONS: Implications for further use of the PedsQL 4.0 in the clinical or research context are discussed. Incidental findings highlight some limitations of the PedsQL 4.0 for work with this population.
Assuntos
Indicadores Básicos de Saúde , Neoplasias/psicologia , Qualidade de Vida , Sobreviventes/psicologia , Adolescente , Adulto , Fatores Etários , Neoplasias do Sistema Nervoso Central/psicologia , Criança , Inglaterra , Feminino , Humanos , Masculino , Mães , Leucemia-Linfoma Linfoblástico de Células Precursoras/psicologia , Psicometria , Reprodutibilidade dos Testes , Fatores Sexuais , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Vascular access site management is crucial to safe, efficient and comfortable diagnostic or interventional transfemoral percutaneous coronary procedures. Two new femoral access site closure devices, Perclose and Angio-Seal , have been proposed as alternative methods to manual compression (MC). We compared these two devices and tested them in reference to standard MC for safety, effectiveness and patient preference. METHODS: Prospective demographic, peri-procedural, and late follow-up data for 1,500 patients undergoing percutaneous coronary procedures were collected from patients receiving femoral artery closure by MC (n = 469), Perclose (n = 492), or Angio-Seal (n = 539). Peri-procedural, post-procedural, and post-hospitalization endpoints were: 1) safety of closure method; 2) efficacy of closure method; and 3) patient satisfaction. RESULTS: Patients treated with Angio-Seal experienced shorter times to hemostasis (p < 0.0001, diagnostic and interventional) and ambulation (diagnostic, p = 0.05; interventional, p < 0.0001) than those treated with Perclose. Those treated with Perclose experienced greater access site complications (Perclose vs. Angio-Seal, p = 0.008; Perclose vs. MC, p = 0.06). Patients treated with Angio-Seal reported greater overall satisfaction, better wound healing and lower discomfort (each vs. Perclose or vs. MC, all p < or = 0.0001). For diagnostic cath only, median post-procedural length of stay was reduced by Angio-Seal (Angio-Seal vs. MC, p < 0.0001; Angio-Seal vs. Perclose, p = 0.009). No difference was seen in length of stay for interventional cases. CONCLUSIONS: Overall, Angio-Seal performed better than Perclose or MC in reducing time to ambulation and length of stay among patients undergoing diagnostic procedures. There was a higher rate of successful deployment and shorter time to hemostasis for Angio-Seal, and this was accomplished with no increase in bleeding complications throughout the follow-up. Additionally, Angio-Seal performed better than Perclose in exhibiting a superior 30-day patient satisfaction and patient assessment of wound healing with less discomfort.
Assuntos
Angioplastia Coronária com Balão , Artéria Femoral/cirurgia , Doenças Vasculares Periféricas/psicologia , Doenças Vasculares Periféricas/terapia , Abciximab , Idoso , Anticorpos Monoclonais/uso terapêutico , Anticoagulantes/uso terapêutico , Doença das Coronárias/complicações , Doença das Coronárias/terapia , Feminino , Seguimentos , Hemostasia/fisiologia , Técnicas Hemostáticas/instrumentação , Humanos , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Incidência , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Satisfação do Paciente , Doenças Vasculares Periféricas/etiologia , Complicações Pós-Operatórias/psicologia , Complicações Pós-Operatórias/terapia , Valor Preditivo dos Testes , Estudos Prospectivos , Punções/instrumentação , Punções/psicologia , Resultado do TratamentoRESUMO
We perform a detailed fixed-point analysis of two-unit recurrent neural networks with sigmoid-shaped transfer functions. Using geometrical arguments in the space of transfer function derivatives, we partition the network state-space into distinct regions corresponding to stability types of the fixed points. Unlike in the previous studies, we do not assume any special form of connectivity pattern between the neurons, and all free parameters are allowed to vary. We also prove that when both neurons have excitatory self-connections and the mutual interaction pattern is the same (i.e., the neurons mutually inhibit or excite themselves), new attractive fixed points are created through the saddle-node bifurcation. Finally, for an N-neuron recurrent network, we give lower bounds on the rate of convergence of attractive periodic points toward the saturation values of neuron activations, as the absolute values of connection weights grow.
Assuntos
Modelos Neurológicos , Rede Nervosa/fisiologia , Redes Neurais de Computação , Neurônios/fisiologia , MatemáticaRESUMO
Despite well-documented clinical benefit of the use of statins in patients with coronary artery disease (CAD) and even mild lipid elevations, studies have documented the presence of a significant "treatment gap" between those patients in whom treatment is indicated and those patients who actually receive it. It has been proposed that a prescription for statin therapy given to indicated patients at the time of initial angiographic diagnosis of CAD has the potential to improve long-term medication compliance, but this requires further evaluation. We prospectively followed 600 patients with angiographically demonstrated CAD (diameter stenosis > or = 70%) who met the National Cholesterol Education Project (NCEP) guidelines for statin therapy for an average of 3.0 years (range 2.0 to 4.6). Patients were an average of 65 years of age, 78% were men, 77% presented initially with acute ischemic syndrome, and 64 (10.7%) died during follow-up. Overall, 105 patients (18%) were discharged from the initial hospitalization with a statin prescription. At long-term follow-up, the number of patients taking statins had increased to 47%. However, long-term statin compliance was significantly higher among patients initially discharged with a statin prescription than those who were not (77% vs 40%; p < 0.0001). Additionally, those patients discharged with a statin prescription had significantly reduced mortality rate at long-term follow-up (5.7% vs 11.7%; p = 0.05). Cox hazard regression analysis, controlling for all known clinical baseline variables, confirmed the absence of a prehospital discharge statin prescription to be an independent predictor of increased mortality (hazard ratio 2.4) with a statistical trend (p = 0.06). Thus, this study demonstrates that after angiographic diagnosis of CAD, prescription of appropriate statin therapy at the time of hospital discharge improves long-term statin compliance and may significantly enhance survival.