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1.
BMC Psychiatry ; 24(1): 492, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977965

RESUMO

BACKGROUND: In recognition of the burden of Perinatal Mental Health problems, NHS England invested £365 million to transform women's access to mental health care, including investment in Community Perinatal Mental Health Services. This study examined how elements of provider care affected women's engagement with these services. METHODS: Semi-structured interviews were conducted with 139 women and explored their experiences of care from 10 different Community Perinatal Mental Health Teams; including which service components participants believed made a difference to their initial and continued engagement. Realist analysis was used to create context-mechanism-outcome configurations (CMOCs) across interviews, since not all parts of the configurations were always articulated within singular interviews. RESULTS: Four key pillars for engagement were identified: perinatal competence, relationship building, accurate reassurance, and reliability. The way perinatal competencies were relayed to women mattered; compassion, understanding and consistency were critical interactional styles. The extent to which these factors affected women's engagement varied by their context and personal characteristics. CONCLUSIONS: As mental health problems increase, disproportionately affecting vulnerable populations, it is critical to continue to ensure support is not only available, but appropriately meets the needs of those individuals. Our findings suggest that key staff behaviours applied at the right time can support women's engagement and potentially contribute to better treatment outcomes.


Assuntos
Serviços Comunitários de Saúde Mental , Assistência Perinatal , Humanos , Feminino , Adulto , Gravidez , Inglaterra , Transtornos Mentais/terapia , Pesquisa Qualitativa , Adulto Jovem
2.
Anaesthesia ; 78(6): 692-700, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36958018

RESUMO

Surgical decision-making after SARS-CoV-2 infection is influenced by the presence of comorbidity, infection severity and whether the surgical problem is time-sensitive. Contemporary surgical policy to delay surgery is informed by highly heterogeneous country-specific guidance. We evaluated surgical provision in England during the COVID-19 pandemic to assess real-world practice and whether deferral remains necessary. Using the OpenSAFELY platform, we adapted the COVIDSurg protocol for a service evaluation of surgical procedures that took place within the English NHS from 17 March 2018 to 17 March 2022. We assessed whether hospitals adhered to guidance not to operate on patients within 7 weeks of an indication of SARS-CoV-2 infection. Additional outcomes were postoperative all-cause mortality (30 days, 6 months) and complications (pulmonary, cardiac, cerebrovascular). The exposure was the interval between the most recent indication of SARS-CoV-2 infection and subsequent surgery. In any 6-month window, < 3% of surgical procedures were conducted within 7 weeks of an indication of SARS-CoV-2 infection. Mortality for surgery conducted within 2 weeks of a positive test in the era since widespread SARS-CoV-2 vaccine availability was 1.1%, declining to 0.3% by 4 weeks. Compared with the COVIDSurg study cohort, outcomes for patients in the English NHS cohort were better during the COVIDSurg data collection period and the pandemic era before vaccines became available. Clinicians within the English NHS followed national guidance by operating on very few patients within 7 weeks of a positive indication of SARS-CoV-2 infection. In England, surgical patients' overall risk following an indication of SARS-CoV-2 infection is lower than previously thought.


Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Vacinas contra COVID-19 , Pandemias/prevenção & controle , Medicina Estatal
3.
Dev Psychopathol ; 34(3): 1079-1087, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-33752771

RESUMO

Incremental prediction of aggression from callous-unemotional (CU) traits is well established, but cross-cultural replication and studies of young children are needed. Little is understood about the contribution of CU traits in children who are already aggressive. We addressed these issues in prospective studies in the United Kingdom and Colombia. In a UK epidemiological cohort, CU traits and aggression were assessed at age 3.5 years, and aggression at 5.0 years by mothers (N = 687) and partners (N = 397). In a Colombian general population sample, CU traits were assessed at age 3.5 years and aggression at 3.5 and 5.0 years by mother report (N = 220). Analyses consistently showed prediction of age-5.0 aggression by age-3.5 CU traits controlling for age-3.5 aggression. Associations between age-3.5 CU traits and age-5.0 aggression were moderated by aggression at 3.5 years, with UK interaction terms, same informant, ß = .07 p = .014 cross-informant, ß = .14 p = .002, and in Colombia, ß = .09 p = .128. The interactions arose from stronger associations between CU traits and later aggression in those already aggressive. Our findings with preschoolers replicated across culturally diverse settings imply a major role for CU traits in the maintenance and amplification of already established aggression, and cast doubt on their contribution to its origins.


Assuntos
Transtorno da Conduta , Agressão/psicologia , Criança , Saúde da Criança , Pré-Escolar , Colômbia , Comparação Transcultural , Emoções , Humanos , Relações Pais-Filho , Estudos Prospectivos
4.
Brain Behav Immun ; 88: 151-160, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32173454

RESUMO

Maternal obesity during pregnancy is associated with a greater risk for obesity and neurodevelopmental deficits in offspring. This developmental programming of disease is proposed to involve neuroendocrine, inflammatory, and epigenetic factors during gestation that disrupt normal fetal brain development. The hormones leptin and insulin are each intrinsically linked to metabolism, inflammation, and neurodevelopment, which led us to hypothesise that maternal obesity may disrupt leptin or insulin receptor signalling in the developing brain of offspring. Using a C57BL/6 mouse model of high fat diet-induced maternal obesity (mHFD), we performed qPCR to examine leptin receptor (Lepr) and insulin receptor (Insr) gene expression in gestational day (GD) 17.5 fetal brain. We found a significant effect of maternal diet and offspring sex on Lepr regulation in the developing hippocampus, with increased Lepr expression in female mHFD offspring (p < 0.05) compared to controls. Maternal diet did not alter hippocampal Insr in the fetal brain, or Lepr or Insr in prefrontal cortex, amygdala, or hypothalamus of female or male offspring. Chromatin immunoprecipitation revealed decreased binding of histones possessing the repressive histone mark H3K9me3 at the Lepr promoter (p < 0.05) in hippocampus of female mHFD offspring compared to controls, but not in males. Sex-specific deregulation of Lepr could be reproduced in vitro by exposing female hippocampal neurons to the obesity related proinflammatory cytokine IL-6, but not IL-17a or IFNG. Our findings indicate that the obesity-related proinflammatory cytokine IL-6 during pregnancy leads to sexually dimorphic changes in the modifications of histones binding at the Lepr gene promoter, and concomitant changes to Lepr transcription in the developing hippocampus. This suggests that exposure of the fetus to metabolic inflammatory molecules can impact epigenetic regulation of gene expression in the developing hippocampus.


Assuntos
Obesidade Materna , Efeitos Tardios da Exposição Pré-Natal , Animais , Dieta Hiperlipídica , Epigênese Genética , Feminino , Hipocampo , Leptina , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , Efeitos Tardios da Exposição Pré-Natal/genética , Receptores para Leptina/genética
5.
Diabet Med ; 37(1): 71-74, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31314907

RESUMO

AIM: To compare the effect of targeted interventions to reduce high diabetes distress among adults with Type 1 diabetes with a comparison sample of similar but untreated individuals, and to document the stability of untreated diabetes distress over time. METHODS: A total of 51 adults with Type 1 diabetes with elevated baseline diabetes distress (distress score ≥ 2.0) and HbA1c levels (≥ 58 mmol/mol) were identified from a longitudinal, non-intervention study, and compared with a similar sample of 51 participants in an intervention study. Both groups completed the T1-DDS diabetes distress questionnaire at baseline and 9 months. RESULTS: Large and significant reductions in diabetes distress scores were recorded in the intervention group (mean ± sd change = -0.6 ± 0.6), while minimal change was found in the non-intervention group (-0.2 ± 0.6, group effect P = 0.002; effect size d = 0.67). Additional analyses using the established minimal clinically important difference for the T1-DDS showed that diabetes distress increased significantly (minimal clinically important difference ≥ 1) or persisted at high levels for 51% of participants in the non-intervention group, compared with 23.5% in the intervention group. CONCLUSION: Our results showed that targeted interventions led to dramatic reductions in diabetes distress compared with a lack of treatment. We also conclude that elevated diabetes distress, when left unaddressed, does not resolve over time and often remains chronic. (Clinical Trials Registry no.: NCT02175732).


Assuntos
Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hemoglobinas Glicadas/análise , Hipoglicemiantes/uso terapêutico , Adulto , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
6.
Diabet Med ; 36(7): 803-812, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30985025

RESUMO

Addressing the emotional side of diabetes and its management has received considerable attention in recent years. At the centre of most of these efforts is the concept of 'diabetes distress', a generic term that captures the primary sources and intensity of emotional distress associated with diabetes and its management over time. As interest in diabetes distress has grown, however, it has been difficult to integrate and translate the various strands of clinical research in a manner that can guide diabetes distress intervention efforts in the real world of clinical care. The aim of this paper is to fill this gap by outlining practical strategies for intervention in clinical settings and to assist diabetes healthcare professionals in thinking through how diabetes distress might be addressed practically in their clinics. To address these goals, this review is divided into five sections: a definition of diabetes distress, ways diabetes distress can be assessed and monitored, information about diabetes distress for use in intervention planning, topics to be considered for inclusion in diabetes distress interventions, and alternatives for where in the care process a diabetes distress intervention might be considered. We focus on diabetes distress experienced by adults with both Type 1 and Type 2 diabetes.


Assuntos
Ansiedade/diagnóstico , Diabetes Mellitus Tipo 1/psicologia , Diabetes Mellitus Tipo 2/psicologia , Adesão à Medicação/psicologia , Autocuidado/psicologia , Estresse Psicológico/diagnóstico , Ansiedade/etiologia , Automonitorização da Glicemia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Emoções , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Guias de Prática Clínica como Assunto , Estresse Psicológico/etiologia
7.
Diabet Med ; 36(7): 847-853, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30315608

RESUMO

AIMS: To identify challenges and solutions to integrating psychosocial support into routine diabetes care from the perspective of stakeholders with expertise in diabetes self-management education and support. METHODS: Ninety-four people attended the annual international Diabetes Self-Management Alliance meeting in 2016, which included plenary sessions and workshops on self-management education, support and prevention. One workshop focused on how to integrate psychosocial support into routine diabetes care; this was run four times consecutively, allowing all conference participants to attend the workshops in groups of 20-25 people. RESULTS: Challenges and solutions associated with integrating psychosocial support into routine diabetes care concern the patient-provider relationship, the healthcare system and the community. Challenges identified were: lack of time, skills and resources to deal with psychological well-being; a culture of patient blame and care expectations; the complexity of person-centred assessment of psychological issues; and the substantial healthcare system focus on productivity and biomedical indicators. Lack of involvement of local communities and of inclusion of social determinants of health were also highlighted as challenging. Solutions identified were more patient-provider dialogue; more training and better skills among care providers; system incentives for psychosocial outcomes; and targeting social determinants of health and involvement of family and peers. CONCLUSIONS: From the perspective of international stakeholders with an expertise in diabetes self-management and support attending the conference in Denmark, substantial new incentives and systematic cultural changes are needed in healthcare systems to integrate psychosocial support into routine diabetes care, as recommended in international guidelines.


Assuntos
Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 2/terapia , Pessoal de Saúde/educação , Autogestão/educação , Congressos como Assunto , Dinamarca , Educação , Seguimentos , Pessoal de Saúde/organização & administração , Promoção da Saúde , Humanos , Educação de Pacientes como Assunto , Grupos de Autoajuda , Autogestão/métodos , Apoio Social
8.
Diabet Med ; 36(4): 473-481, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30485516

RESUMO

AIMS: To compare the outcomes of partners who participated in a telephone couples behavioural intervention to improve glycaemic control in persons with Type 2 diabetes with those of untreated partners of participants in an individual intervention or education; to explore 'ripple effects', i.e. positive behaviour changes seen in untreated partners. METHODS: The Diabetes Support Project was a three-arm randomized telephone intervention trial comparing outcomes of couples calls (CC), individual calls (IC) and diabetes education calls (DE). Couples included one partner with Type 2 diabetes and HbA1c ≥ 58 mmol/mol (7.5%). All arms received self-management education (two calls). CC and IC arms participated in 10 additional behaviour change calls. CC included partners, emphasizing partner communication, collaboration and support. Blinded assessments were performed at 4, 8 and 12 months. Partner outcomes were psychosocial (diabetes distress, relationship satisfaction, depressive symptoms), medical (BMI, blood pressure) and behavioural (fat intake, activity). RESULTS: Partners' (N = 268) mean age was 55.8 years, 64.6% were female and 29.9% were from minority ethnic groups. CC (vs. IC and DE) partners had greater reductions in diabetes distress, greater increases in marital satisfaction (4 and 8 months), and some improvements in diastolic BP. There were no consistent differences among arms in other outcomes. There was no evidence of a dietary or activity behaviour ripple effect on untreated partners, i.e. comparing partners in the IC and DE arms. CONCLUSIONS: A collaborative couples intervention resulted in significant improvements in partner diabetes distress and relationship satisfaction. There were no consistent effects on behavioural or medical partner outcomes, and no evidence of diet or activity behaviour ripple effects, suggesting that partners should be targeted directly to achieve these changes. (Clinical Trial Registry No: NCT01017523).


Assuntos
Terapia Comportamental/métodos , Diabetes Mellitus Tipo 2/terapia , Características da Família , Educação em Saúde/métodos , Relações Interpessoais , Adulto , Idoso , Cuidadores/educação , Cuidadores/psicologia , Comportamento Cooperativo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Autogestão/educação , Autogestão/métodos , Autogestão/psicologia , Telefone
9.
Subst Use Misuse ; 53(13): 2199-2209, 2018 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-29708456

RESUMO

Binge drinking (BD) and alcohol related problems (ARP) are highly prevalent among college students. However, current models examining ARP suggest drinking quantity only accounts for a portion of the variance, suggesting other variables contribute to ARP. Distress tolerance (DT), or the ability to withstand negative affect, is associated with alcohol misuse and may be an important mechanism related to ARP. However, studies have reported inconsistent findings on this association, which may be due to the use of only global scores to measure DT rather than specific DT components. Furthermore, the mechanisms underlying this association remain unknown. Drinking to cope with negative affect has been associated with both DT and ARP, suggesting it may be a mechanism explaining the relationship between DT and ARP. The current study examined the association between specific proposed DT components (i.e., tolerance, absorption, appraisal, and regulation) and drinking to cope and ARP in 147 college students who BD. A hierarchical linear regression was performed in order to examine which DT component best predicted ARP. Four follow-up mediation models were then tested to examine whether drinking to cope mediated the relationship between each DT component and ARP. Appraisal of DT was the only DT component that significantly predicted ARP, in the model controlling for drinking quantity and sex differences. Drinking to cope mediated the relationship between ARP and tolerance, absorption, and regulation, but not appraisal of DT. Implications for furthering our understanding of DT and treatment of BD as it relates to DT are explored.


Assuntos
Adaptação Psicológica , Transtornos Relacionados ao Uso de Álcool/psicologia , Consumo Excessivo de Bebidas Alcoólicas/psicologia , Estresse Psicológico/complicações , Adolescente , Feminino , Humanos , Masculino , Motivação , Pesquisa Qualitativa , Fatores de Risco , Caracteres Sexuais , Estresse Psicológico/psicologia , Estudantes , Adulto Jovem
10.
Diabet Med ; 34(12): 1658-1666, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28636745

RESUMO

A wide range of diabetes-directed interventions - including novel medications, devices and comprehensive education programmes - have been shown to be effective in clinical trials. But in the real world of diabetes care their efficacy is often dependent upon on how well a clinician is able to support personal engagement and motivation of the person with diabetes to use these new tools and knowledge consistently, and as directed. Although many person-centred motivational and behavioural strategies have been developed, for example, action planning, motivational interviewing and empowerment-based communication, the sheer number and apparent lack of clear differences among them have led to considerable confusion. The primary goal of this review, therefore, is to provide a practical framework that organizes and structures these programmes to enhance their more systematic use in clinical care. Its purpose is to enhance clinician efforts to respectfully encourage and support engagement and motivation for behaviour change in people with diabetes. The three-step framework for organizing and describing the specific clinical processes involved is based on self-determination theory and includes: clinician preparation for a different type of clinical encounter, clinician/person with diabetes relationship building, and clinician utilization of specific behavioural tools. We conclude with practical considerations for application of this framework to the real world of clinical care.


Assuntos
Diabetes Mellitus/terapia , Comportamentos Relacionados com a Saúde , Motivação , Participação do Paciente/métodos , Sistemas de Apoio Psicossocial , Autocuidado , Diabetes Mellitus/psicologia , Humanos , Autonomia Pessoal
11.
Diabet Med ; 34(9): 1228-1234, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28498610

RESUMO

AIM: To determine the cross-sectional and longitudinal associations between diabetes distress and diabetes management. METHODS: In a non-interventional study, 224 adults with Type 1 diabetes were assessed for diabetes distress, missed insulin boluses, hypoglycaemic episodes, and HbA1c at baseline and 9 months. RESULTS: At baseline, greater distress was associated with higher HbA1c and a greater percentage of missed insulin boluses. Longitudinally, elevated baseline distress was related to increased missed insulin boluses, and decreases in distress were associated with decreases in HbA1c . In supplementary analyses, neither depression symptoms nor a diagnosis of major depressive disorder was associated with missed insulin boluses, HbA1c or hypoglycaemic episodes in cross-sectional or longitudinal analyses. CONCLUSIONS: Significant cross-sectional and longitudinal associations were found between diabetes distress and management; in contrast, no parallel associations were found for major depressive disorder or depression symptoms. Findings suggest that elevated distress may lead to more missed insulin boluses over time, suggesting a potential intervention target. The covarying association between distress and HbA1c points to the complex and likely interactive associations between these constructs. Findings highlight the need to address distress as an integral part of diabetes management in routine care.


Assuntos
Diabetes Mellitus Tipo 1/psicologia , Diabetes Mellitus Tipo 1/terapia , Estresse Psicológico/etiologia , Adolescente , Adulto , Glicemia/metabolismo , Criança , Estudos Transversais , Complicações do Diabetes/epidemiologia , Complicações do Diabetes/etiologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Progressão da Doença , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estresse Psicológico/epidemiologia , Fatores de Tempo , Adulto Jovem
12.
Diabet Med ; 33(11): 1590-1597, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-26433004

RESUMO

AIMS: To determine the prevalence of depression and diabetes distress in adults with Type 1 diabetes and the rate of false-positives when compared with rates of major depressive disorder. METHODS: The sample consisted of 368 individuals with Type 1 diabetes, aged > 19 years. Individuals completed: the eight-item Patient Health Questionnaire depression scale (PHQ8), which was coded using four scoring criteria (scores > 10, >12 and >15, and Diagnostic and Statistical Manual of Mental Disorders 5 (DSM) algorithm scores); the Type 1 Diabetes Distress Scale; and the Structured Clinical Interview for DSM Disorders (SCID) to assess major depressive disorder. RESULTS: The prevalence rates of depression according to the eight-item Patient Health Questionnaire were: score >10, 11.4%; score >12, 7.1%; score >15, 3.8%; and positive algorithm result, 4.6%. The prevalence of major depressive disorder was 3.5%; and the prevalence of at least moderate diabetes distress was 42.1%. Depending on the criterion used, the false-positive rate when using the Patient Health Questionnaire compared with the results when using the SCID varied from 52 to 71%. Of those classified as depressed on the PHQ-8 or Structured Clinical Interview for DSM Disorders, between 92.3 and 96.2% also reported elevated diabetes distress. No significant association was found between any group classed as having depression according to the PHQ8 or the SCID and HbA1c concentration. Depression was significantly associated with more other life stress, more complications and a lower level of education. CONCLUSIONS: We found an unexpectedly low rate of current depression and major depressive disorder in this diverse sample of adults with Type 1 diabetes, and a very high rate of false-positive results using the Patient Health Questionnaire. Considering the high prevalence of diabetes distress, much of what has been considered depression in adults with Type 1 diabetes may be attributed to the emotional distress associated with managing a demanding chronic disease and other life stressors and not necessarily to underlying psychopathology.


Assuntos
Depressão/diagnóstico , Depressão/epidemiologia , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/psicologia , Uso Excessivo dos Serviços de Saúde/estatística & dados numéricos , Adulto , Depressão/etiologia , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/epidemiologia , Reações Falso-Positivas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Psicometria , Estresse Psicológico/diagnóstico , Estresse Psicológico/epidemiologia , Inquéritos e Questionários , Adulto Jovem
13.
Nucleic Acids Res ; 41(20): 9411-23, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23939623

RESUMO

Antibacterial fluoroquinolones trap a cleavage complex of gyrase and topoisomerase (topo) IV inducing site-specific DNA breakage within a bent DNA gate engaged in DNA transport. Despite its importance for drug action and in revealing potential sites of topoisomerase catalysis, the mechanism of DNA selectivity is poorly understood. To explore its functional basis, we generated mutant versions of the strongly cleaved E-site and used a novel competitive assay to examine their gemifloxacin-mediated DNA breakage by Streptococcus pneumoniae topo IV and gyrase. Parallel studies of Ca(2+)-induced cleavage distinguished 'intrinsic recognition' of DNA cleavage sites by topo IV from drug-induced preferences. Analysis revealed strong enzyme-determined requirements for -4G, -2A and -1T bases preceding the breakage site (between -1 and +1) and enzyme-unique or degenerate determinants at -3, plus drug-specific preferences at +2/+3 and for +1 purines associated with drug intercalation. Similar cleavage rules were seen additionally at the novel V-site identified here in ColE1-derived plasmids. In concert with DNA binding data, our results provide functional evidence for DNA, enzyme and drug contributions to DNA cleavage at the gate, suggest a mechanism for DNA discrimination involving enzyme-induced DNA bending/helix distortion and cleavage complex stabilization and advance understanding of fluoroquinolones as important cleavage-enhancing therapeutics.


Assuntos
Clivagem do DNA , DNA Girase/metabolismo , DNA Topoisomerase IV/metabolismo , Streptococcus pneumoniae/enzimologia , Antibacterianos/farmacologia , DNA Bacteriano/química , DNA Bacteriano/metabolismo , Fluoroquinolonas/farmacologia , Gemifloxacina , Naftiridinas/farmacologia , Plasmídeos , Inibidores da Topoisomerase II/farmacologia
14.
Nucleic Acids Res ; 41(21): 9911-23, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23965305

RESUMO

Type II topoisomerases regulate DNA supercoiling and chromosome segregation. They act as ATP-operated clamps that capture a DNA duplex and pass it through a transient DNA break in a second DNA segment via the sequential opening and closure of ATPase-, G-DNA- and C-gates. Here, we present the first 'open clamp' structures of a 3-gate topoisomerase II-DNA complex, the seminal complex engaged in DNA recognition and capture. A high-resolution structure was solved for a (full-length ParE-ParC55)2 dimer of Streptococcus pneumoniae topoisomerase IV bound to two DNA molecules: a closed DNA gate in a B-A-B form double-helical conformation and a second B-form duplex associated with closed C-gate helices at a novel site neighbouring the catalytically important ß-pinwheel DNA-binding domain. The protein N gate is present in an 'arms-wide-open' state with the undimerized N-terminal ParE ATPase domains connected to TOPRIM domains via a flexible joint and folded back allowing ready access both for gate and transported DNA segments and cleavage-stabilizing antibacterial drugs. The structure shows the molecular conformations of all three gates at 3.7 Å, the highest resolution achieved for the full complex to date, and illuminates the mechanism of DNA capture and transport by a type II topoisomerase.


Assuntos
DNA Topoisomerase IV/química , DNA/química , Adenosina Trifosfatases/química , Trifosfato de Adenosina/química , Sítios de Ligação , Transporte Biológico , DNA/metabolismo , DNA Topoisomerase IV/metabolismo , Modelos Moleculares , Estrutura Terciária de Proteína , Streptococcus pneumoniae/enzimologia
15.
Diabet Med ; 31(7): 764-72, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24606397

RESUMO

Studies have identified significant linkages between depression and diabetes, with depression associated with poor self-management behaviour, poor clinical outcomes and high rates of mortality. However, findings are not consistent across studies, yielding confusing and contradictory results about these relationships. We suggest that there has been a failure to define and measure 'depression' in a consistent manner. Because the diagnosis of depression is symptom-based only, without reference to source or content, the context of diabetes is not considered when addressing the emotional distress experienced by individuals struggling with diabetes. To reduce this confusion, we suggest that an underlying construct of 'emotional distress' be considered as a core construct to link diabetes-related distress, subclinical depression, elevated depression symptoms and major depressive disorder (MDD). We view emotional distress as a single, continuous dimension that has two primary characteristics: content and severity; that the primary content of emotional distress among these individuals include diabetes and its management, other life stresses and other contributors; and that both the content and severity of distress be addressed directly in clinical care. We suggest further that all patients, even those whose emotional distress rises to the level of MDD or anxiety disorders, can benefit from consideration of the content of distress to direct care effectively, and we suggest strategies for integrating the emotional side of diabetes into regular diabetes care. This approach can reduce confusion between depression and distress so that appropriate and targeted patient-centred interventions can occur.


Assuntos
Ansiedade/diagnóstico , Depressão/diagnóstico , Diabetes Mellitus/psicologia , Adesão à Medicação/psicologia , Autocuidado/psicologia , Afeto , Ansiedade/etiologia , Depressão/etiologia , Emoções , Humanos , Índice de Gravidade de Doença
16.
Diabet Med ; 31(6): 739-46, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24494593

RESUMO

AIMS: To improve patient-centred care by determining the impact of baseline levels of conscientiousness and diabetes self-efficacy on the outcomes of efficacious interventions to reduce diabetes distress and improve disease management. METHODS: Adults with Type 2 diabetes with diabetes distress and self-care problems (N = 392) were randomized to one of three distress reduction interventions: computer-assisted self-management; computer-assisted self-management plus problem-solving therapy; and health education. The baseline assessment included conscientiousness and self-efficacy, demographics, diabetes status, regimen distress, emotional burden, medication adherence, diet and physical activity. Changes in regimen distress, emotional burden and self-care between baseline and 12 months were recorded and ancova models assessed how conscientiousness and self-efficacy qualified the significant improvements in distress and management outcomes. RESULTS: Participants with high baseline conscientiousness displayed significantly larger improvements in medication adherence and emotional burden than participants with low baseline conscientiousness. Participants with high baseline self-efficacy showed greater improvements in diet, physical activity and regimen distress than participants with low baseline self-efficacy. The impact of conscientiousness and self-efficacy were independent of each other and occurred across all three intervention groups. A significant interaction indicated that those with both high self-efficacy and high conscientiousness at baseline had the biggest improvement in physical activity by 12 months. CONCLUSIONS: Both broad personal traits and disease-specific expectations qualify the outcomes of efficacious interventions. These findings reinforce the need to change from a one-size-fits-all approach to diabetes interventions to an approach that crafts clinical interventions in ways that fit the personal traits and skills of individual people.


Assuntos
Diabetes Mellitus Tipo 2/psicologia , Autocuidado/métodos , Estresse Psicológico/prevenção & controle , Adulto , Sintomas Afetivos/psicologia , Idoso , Consciência , Efeitos Psicossociais da Doença , Exercício Físico/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Autoeficácia , Terapia Assistida por Computador , Adulto Jovem
17.
Diabet Med ; 31(1): 40-6, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23819529

RESUMO

AIMS: To identify patient-reported obstacles to self-monitoring of blood glucose among those with Type 2, both insulin users and non-insulin users, and to investigate how obstacles are associated with frequency of self-monitoring and use of self-monitoring data. METHODS: Patients with Type 2 diabetes (n = 886, 65% insulin users) who attended a 1-day diabetes education conference in cities across the USA completed a survey on current and recommended self-monitoring of blood glucose frequency, how they used self-monitoring results and perceived obstacles to self-monitoring use. Exploratory factor analysis examined 12 obstacle items to identify underlying factors. Regression analyses examined associations between self-monitoring of blood glucose use and the key obstacle factors identified in the exploratory factor analysis. RESULTS: Three obstacle factors emerged: Avoidance, Pointlessness and Burden. Avoidance was the only significant independent predictor of self-monitoring frequency (ß = -0.23, P < 0.001). Avoidance (ß = -0.12, P < 0.01) and Pointlessness (ß = -0.15, P < 0.001) independently predicted how often self-monitoring data were shared with healthcare professionals and whether or not data were used to make management adjustments (Avoidance: odds ratio = 0.74, P < 0.001; Pointlessness: odds ratio = 0.75, P < 0.01). Burden was not associated with any of the self-monitoring behavioural measures. Few differences between insulin users and non-insulin users were noted. CONCLUSIONS: Obstacles to self-monitoring of blood glucose use, both practical and emotional, were common. Higher levels of Avoidance and Pointlessness, but not Burden, were associated with less frequent self-monitoring use. Addressing patients' self-monitoring-related emotional concerns (Avoidance and Pointlessness) may be more beneficial in enhancing interest and engagement with self-monitoring of blood glucose than focusing on day-to-day, behavioural issues (Burden).


Assuntos
Automonitorização da Glicemia/psicologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/psicologia , Autocuidado/psicologia , Glicemia/metabolismo , Automonitorização da Glicemia/estatística & dados numéricos , Efeitos Psicossociais da Doença , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Comportamentos Relacionados com a Saúde , Conhecimentos, Atitudes e Prática em Saúde , Inquéritos Epidemiológicos , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Percepção Social , Inquéritos e Questionários , Estados Unidos
19.
Biofouling ; 30(8): 911-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25184432

RESUMO

Titanium dioxide (TiO2) surfaces doped with molybdenum (Mo) were investigated to determine if their photocatalytic ability could enhance process hygiene in the brewery industry. Doping TiO2 with Mo showed a 5-log reduction in bacterial counts within 4 to 24 h and a 1-log reduction in yeast numbers within 72 h. The presence of a dilute brewery soil on the surface did not interfere with antimicrobial activity. The TiO2-Mo surface was also active in the dark, showing a 5-log reduction in bacteria within 4 to 24 h and a 1-log reduction in yeast numbers within 72 h, suggesting it could have a novel dual function, being antimicrobial and photocatalytic. The study suggests the TiO2-Mo coating could act as a secondary barrier in helping prevent the build-up of microbial contamination on surfaces within the brewery industry, in particular in between cleaning/disinfection regimes during long production runs.


Assuntos
Bactérias/efeitos dos fármacos , Desinfetantes/farmacologia , Desinfecção/métodos , Molibdênio/farmacologia , Fotólise , Titânio/farmacologia , Catálise , Escherichia coli/efeitos dos fármacos , Escherichia coli/fisiologia , Aço Inoxidável
20.
Microb Ecol ; 66(1): 49-59, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23314095

RESUMO

The efficiency of a novel integrated treatment system for biological removal of ammonium, nitrite, nitrate, and heavy metals from fossil power plant effluent was evaluated. Microbial communities were analyzed using bacterial and archaeal 16S rRNA gene clone libraries (Sanger sequences) and 454 pyrosequencing technology. While seasonal changes in microbial community composition were observed, the significant (P = 0.001) changes in bacterial and archaeal communities were consistent with variations in ammonium concentration. Phylogenetic analysis of 16S rRNA gene sequences revealed an increase of potential ammonium-oxidizing bacteria (AOB), Nitrosomonas, Nitrosococcus, Planctomycetes, and OD1, in samples with elevated ammonium concentration. Other bacteria, such as Nitrospira, Nitrococcus, Nitrobacter, Thiobacillus, ε-Proteobacteria, Firmicutes, and Acidobacteria, which play roles in nitrification and denitrification, were also detected. The AOB oxidized 56 % of the ammonium with the concomitant increase in nitrite and ultimately nitrate in the trickling filters at the beginning of the treatment system. Thermoprotei within the phylum Crenarchaeota thrived in the splitter box and especially in zero-valent iron extraction trenches, where an additional 25 % of the ammonium was removed. The potential ammonium-oxidizing Archaea (AOA) (Candidatus Nitrosocaldus) were detected towards the downstream end of the treatment system. The design of an integrated treatment system consisting of trickling filters, zero-valent iron reaction cells, settling pond, and anaerobic wetlands was efficient for the biological removal of ammonium and several other contaminants from wastewater generated at a coal burning power plant equipped with selective catalytic reducers for nitrogen oxide removal.


Assuntos
Compostos de Amônio/metabolismo , Archaea/isolamento & purificação , Archaea/metabolismo , Bactérias/isolamento & purificação , Bactérias/metabolismo , Águas Residuárias/microbiologia , Archaea/classificação , Archaea/genética , Bactérias/classificação , Bactérias/genética , Biodegradação Ambiental , Carvão Mineral/análise , Dados de Sequência Molecular , Nitrificação , Oxirredução , Filogenia , Águas Residuárias/análise
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