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1.
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
2.
Gait Posture ; 99: 104-110, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36375214

RESUMO

BACKGROUND: In addition to a range of functional impairments seen in individuals with a lower-limb amputation, this population is at a substantially elevated risk of falls. Studies postulate that the lack of sensory feedback from the prosthetic limb contributes heavily to these impairments, but the extent to which sensation affects functional measures remains unclear. RESEARCH QUESTION: The purpose of this study is to determine how sensory impairments in the lower extremities relate to performance with common clinical functional measures of balance and gait in individuals with a lower-limb amputation. Here we evaluate the effects of somatosensory integrity to clinical and lab measures of static, reactive and dynamic balance, and gait stability. METHODS: In 20 individuals with lower-limb amputation (AMP) and 20 age and gender-matched able-bodied controls (CON), we evaluated the effects of sensory integrity (pressure, proprioception, and vibration) on measures of balance and gait. Static, reactive, and dynamic balance were assessed using the Sensory Organization Test (SOT), Motor Control Test (MCT), and Functional Gait Assessment (FGA), respectively. Gait stability was assessed through measures of step length asymmetry and step width variability. Sensation was categorized into intact or impaired sensation by pressure thresholds and differences across groups were analyzed. RESULTS: There were significant differences between AMP and CON groups for reliance on vision for static balance in the SOT, MCT, and FGA (p < 0.01). Despite differences across groups, there were no significant differences within the AMP group based on intact or impaired sensation across all functional measures. SIGNIFICANCE: Despite being able to detect differences between able-bodied individuals and individuals with an amputation, these functional measures cannot distinguish between levels of impairment within participants with an amputation. These findings suggest that more challenging and robust metrics are needed to evaluate the effects of sensation and function in individuals with an amputation.


Assuntos
Membros Artificiais , Equilíbrio Postural , Humanos , Amputação Cirúrgica , Marcha , Hipestesia
3.
J Diabetes Complications ; 36(8): 108256, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35810147

RESUMO

AIMS: To establish cut-points and thresholds for elevated diabetes distress; document change over time; and define minimal clinically important differences (MCID) using the new Type 2 Diabetes Distress Assessment System (T2-DDAS). METHODS: A national sample of adults with type 2 diabetes completed the T2-DDAS CORE distress scale and the 7 T2-DDAS SOURCE distress scales at baseline and 6-months. Scores were computed separately for insulin- and non-insulin users. Spline regression models defined CORE cut-points and SEM formulas defined MCID. A rational "threshold" approach defined elevated SOURCE scores. RESULTS: 471 participants (205 insulin, 266 non-insulin) completed both assessments. Analyses yielded ≥2.0 as the cut-point for both elevated CORE and elevated SOURCE. Prevalence of elevated CORE was 61.8 % (69.9 % over 6 months). Elevated SOURCE scores varied from 30.6 % (Stigma/Shame) to 76.4 % (Management); 87.5 % indicated at least 1 elevated SOURCE score. Most (77.1 %) reported multiple elevated SOURCES. 81.8 % with elevated CORE distress at baseline remained elevated at 6 months. MCID analyses yielded +/- 0.25 as significant change. Few differences between insulin- and non-insulin users occurred. CONCLUSIONS: Elevated CORE distress is highly prevalent and persistent over time; most participants reported multiple SOURCES of distress. Findings highlight the need for comprehensive assessment of diabetes distress.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Adulto , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Insulina/uso terapêutico , Insulina Regular Humana , Prevalência
4.
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
5.
J Diabetes Complications ; 35(6): 107925, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33836966

RESUMO

AIMS: To investigate the problem of adults with type 1 diabetes (T1D) who purposefully keep their glucose levels low, and to explore contributors to, and possible impact of, this potentially dangerous phenomenon. METHODS: We developed three self-report items as a means to identify individuals who endorse a consistent preference for hypoglycemia over hyperglycemia ("Hyperglycemia Aversives"). In a large T1D survey (n = 219), validated measures of well-being, emotional distress and hypoglycemic awareness, and glycemic metrics derived from the past 14-day period, were used to examine whether Hyperglycemia Aversives could be characterized as a distinct group. RESULTS: Hyperglycemia Aversives comprised 16.4% of the sample. This unique group demonstrated significantly higher mean %TIR (71.6% vs. 63.6%) and %TBR (5.1% vs. 2.2%), lower mean %TAR > 250 mg/dL (6.0% vs. 10.1%), and higher rates of impaired hypoglycemic awareness and recurrent severe hypoglycemia episodes than the remaining study sample ("Non-Aversives") (all ps < 0.01). The two groups did not demonstrate significant differences on psychosocial outcomes. CONCLUSIONS: We identified a group of T1D adults reporting a consistent preference for hypoglycemia over hyperglycemia. These individuals achieve significantly greater %TIR and less %TAR, but at the cost of greater %TBR and more frequent severe hypoglycemia episodes.


Assuntos
Diabetes Mellitus Tipo 1 , Hiperglicemia , Hipoglicemia , Adulto , Glicemia , Automonitorização da Glicemia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Humanos , Hiperglicemia/epidemiologia , Hiperglicemia/prevenção & controle , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Hipoglicemia/prevenção & controle , Hipoglicemiantes/uso terapêutico
6.
J Med Chem ; 64(9): 6329-6357, 2021 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-33929852

RESUMO

Herein, we describe the discovery and optimization of a novel series that inhibits bacterial DNA gyrase and topoisomerase IV via binding to, and stabilization of, DNA cleavage complexes. Optimization of this series led to the identification of compound 25, which has potent activity against Gram-positive bacteria, a favorable in vitro safety profile, and excellent in vivo pharmacokinetic properties. Compound 25 was found to be efficacious against fluoroquinolone-sensitive Staphylococcus aureus infection in a mouse thigh model at lower doses than moxifloxacin. An X-ray crystal structure of the ternary complex formed by topoisomerase IV from Klebsiella pneumoniae, compound 25, and cleaved DNA indicates that this compound does not engage in a water-metal ion bridge interaction and forms no direct contacts with residues in the quinolone resistance determining region (QRDR). This suggests a structural basis for the reduced impact of QRDR mutations on antibacterial activity of 25 compared to fluoroquinolones.


Assuntos
Antibacterianos/farmacologia , DNA Girase/metabolismo , DNA Topoisomerase IV/antagonistas & inibidores , Desenho de Fármacos , Fluoroquinolonas/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Inibidores da Topoisomerase II/farmacologia , Animais , Antibacterianos/química , Farmacorresistência Bacteriana/efeitos dos fármacos , Camundongos , Inibidores da Topoisomerase II/química
7.
J Med Chem ; 63(14): 7773-7816, 2020 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-32634310

RESUMO

Since their discovery over 5 decades ago, quinolone antibiotics have found enormous success as broad spectrum agents that exert their activity through dual inhibition of bacterial DNA gyrase and topoisomerase IV. Increasing rates of resistance, driven largely by target-based mutations in the GyrA/ParC quinolone resistance determining region, have eroded the utility and threaten the future use of this vital class of antibiotics. Herein we describe the discovery and optimization of a series of 4-(aminomethyl)quinolin-2(1H)-ones, exemplified by 34, that inhibit bacterial DNA gyrase and topoisomerase IV and display potent activity against ciprofloxacin-resistant Gram-negative pathogens. X-ray crystallography reveals that 34 occupies the classical quinolone binding site in the topoisomerase IV-DNA cleavage complex but does not form significant contacts with residues in the quinolone resistance determining region.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Fluoroquinolonas/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Inibidores da Topoisomerase II/farmacologia , Antibacterianos/síntese química , Antibacterianos/metabolismo , Antibacterianos/toxicidade , Sítios de Ligação , Linhagem Celular Tumoral , DNA Girase/metabolismo , DNA Topoisomerase IV/antagonistas & inibidores , DNA Topoisomerase IV/química , Fluoroquinolonas/síntese química , Fluoroquinolonas/metabolismo , Fluoroquinolonas/toxicidade , Bactérias Gram-Negativas/enzimologia , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade , Inibidores da Topoisomerase II/síntese química , Inibidores da Topoisomerase II/metabolismo , Inibidores da Topoisomerase II/toxicidade
8.
J Diabetes Complications ; 34(7): 107606, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32354623

RESUMO

AIMS: To examine the factor structure, validity and reliability of the Hypoglycemic Attitudes and Behavior Scale (HABS) in T1D adults (previously examined only in T2D adults), and to determine if it has unique value, after controlling for hypoglycemic fear. METHODS: The original 14 HABS items were submitted to a confirmatory factor analysis (CFA) with T1D participants. Construct validity criteria included diabetes distress, generalized anxiety, well-being, hypoglycemic fear, hypoglycemia history and self-reported glycemic control. RESULTS: A CFA yielded a similar 3-factor solution, with all items loading on the same factors as in the analyses with T2D adults: Hypoglycemia Anxiety, Avoidance and Confidence. Higher levels of Anxiety and Avoidance were significantly associated with poorer well-being and higher levels of generalized anxiety, diabetes distress and hypoglycemic fear, with correlations in the reverse direction for Confidence. After controls (including hypoglycemic fear), the HABS subscales were significantly linked to several criterion variables. CONCLUSIONS: Though originally developed and validated with T2D adults, the HABS demonstrates sufficient validity and reliability for use with a T1D population; and it captures unique critical elements of hypoglycemic concerns. Thus, it may contribute to a greater understanding of hypoglycemia management and more targeted clinical interventions in a T1D population.


Assuntos
Atitude , Diabetes Mellitus Tipo 1 , Comportamentos Relacionados com a Saúde , Hipoglicemia , Adulto , Ansiedade/epidemiologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2 , Humanos , Hipoglicemia/diagnóstico , Hipoglicemia/prevenção & controle , Hipoglicemiantes/uso terapêutico , Reprodutibilidade dos Testes
9.
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
10.
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
11.
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
13.
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
14.
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
15.
Nat Commun ; 9(1): 2579, 2018 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-29968711

RESUMO

Type II topoisomerases alter DNA topology to control DNA supercoiling and chromosome segregation and are targets of clinically important anti-infective and anticancer therapeutics. They act as ATP-operated clamps to trap a DNA helix and transport it through a transient break in a second DNA. Here, we present the first X-ray crystal structure solved at 2.83 Å of a closed clamp complete with trapped T-segment DNA obtained by co-crystallizing the ATPase domain of S. pneumoniae topoisomerase IV with a nonhydrolyzable ATP analogue and 14-mer duplex DNA. The ATPase dimer forms a 22 Å protein hole occupied by the kinked DNA bound asymmetrically through positively charged residues lining the hole, and whose mutagenesis impacts the DNA decatenation, DNA relaxation and DNA-dependent ATPase activities of topo IV. These results and a side-bound DNA-ParE structure help explain how the T-segment DNA is captured and transported by a type II topoisomerase, and reveal a new enzyme-DNA interface for drug discovery.


Assuntos
DNA Topoisomerase IV/metabolismo , DNA Bacteriano/metabolismo , DNA/metabolismo , Domínios Proteicos/fisiologia , Trifosfato de Adenosina/química , Trifosfato de Adenosina/metabolismo , Cristalografia por Raios X , DNA/química , DNA Topoisomerase IV/química , DNA Topoisomerase IV/genética , DNA Bacteriano/química , Mutagênese Sítio-Dirigida
16.
J Diabetes Complications ; 32(7): 665-669, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29887299

RESUMO

OBJECTIVE: To identify and assess patient motivation to initiate or maintain behavior changes. METHODS: Attitudinal statements were developed from structured patient interviews and translated into 18 survey items. Items were analyzed with exploratory factor analysis (EFA). RESULTS: An EFA with 340 type 2 diabetes patients identified three areas of patient attitudes toward changing health behaviors: (1) willingness to make changes (3 items; α = 0.69), (2) perceived ability to make or maintain changes (3 items; α = 0.74), and (3) and feeling changes are worthwhile (3 items; α = 0.61). Greater perceived ability and feelings of worthwhileness were associated with positive psychosocial and behavioral management indicators. All three areas were associated with confidence and attitudes toward making a specific behavioral change (e.g., improve diet). CONCLUSIONS: MATCH is an internally consistent and valid 9-item scale that provides a profile of factors influencing motivation that can be used in clinical and research settings.


Assuntos
Atitude Frente a Saúde , Terapia Comportamental , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/psicologia , Motivação , Autocuidado , Adulto , Idoso , Terapia Comportamental/estatística & dados numéricos , Diabetes Mellitus Tipo 2/terapia , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Relações Médico-Paciente , Autocuidado/métodos , Autocuidado/psicologia , Inquéritos e Questionários
17.
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
18.
J Diabetes Complications ; 32(4): 373-378, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29496364

RESUMO

AIMS: To determine the impact of frequency of non-severe hypoglycemic events (NSHE) and the perceived burden of NSHE on quality of life (QOL) over time. METHODS: T2D adults (n = 424) were re-contacted two years after initial QOL assessment. Responding subjects (n = 290) reported the frequency and burden of NSHE over time and completed six generic and diabetes-specific QOL measures. RESULTS: Most subjects (86%) reported ≥ one NSHE over time. Higher frequency of NSHE was significantly associated with decrements in QOL. Greater perceived burden of NSHE was significantly linked to decreases in QOL over time for all six QOL measures. Interaction terms indicated that participants with a higher frequency of NSHE and higher perceived burden reported the greatest decrease in QOL; participants who experienced frequent NSHE but did not perceive these events as burdensome evidenced little worsening in QOL over time. CONCLUSIONS: NSHE have a negative impact on QOL over time in T2D adults. However, it is not just the occurrence of NSHE that affects QOL; it is the individual's felt burden of these events that is critical. The greatest reductions in QOL are seen among those subjects reporting a higher frequency of NSHE and indicating that such events are burdensome.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Hipoglicemia/sangue , Qualidade de Vida , Idoso , Glicemia/análise , Automonitorização da Glicemia , Efeitos Psicossociais da Doença , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemia/diagnóstico , Hipoglicemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade
19.
Bone ; 105: 134-147, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28866368

RESUMO

Although acellular cementum is essential for tooth attachment, factors directing its development and regeneration remain poorly understood. Inorganic pyrophosphate (PPi), a mineralization inhibitor, is a key regulator of cementum formation: tissue-nonspecific alkaline phosphatase (Alpl/TNAP) null mice (increased PPi) feature deficient cementum, while progressive ankylosis protein (Ank/ANK) null mice (decreased PPi) feature increased cementum. Bone sialoprotein (Bsp/BSP) and osteopontin (Spp1/OPN) are multifunctional extracellular matrix components of cementum proposed to have direct and indirect effects on cell activities and mineralization. Studies on dentoalveolar development of Bsp knockout (Bsp-/-) mice revealed severely reduced acellular cementum, however underlying mechanisms remain unclear. The similarity in defective cementum phenotypes between Bsp-/- mice and Alpl-/- mice (the latter featuring elevated PPi and OPN), prompted us to examine whether BSP is operating by modulating PPi-associated genes. Genetic ablation of Bsp caused a 2-fold increase in circulating PPi, altered mRNA expression of Alpl, Spp1, and Ank, and increased OPN protein in the periodontia. Generation of a Bsp knock-out (KO) cementoblast cell line revealed significantly decreased mineralization capacity, 50% increased PPi in culture media, and increased Spp1 and Ank mRNA expression. While addition of 2µg/ml recombinant BSP altered Spp1, Ank, and Enpp1 expression in cementoblasts, changes resulting from this dose were not dependent on the integrin-binding RGD motif or MAPK/ERK signaling pathway. Decreasing PPi by genetic ablation of Ank on the Bsp-/- mouse background reestablished cementum formation, allowing >3-fold increased acellular cementum volume compared to wild-type (WT). However, deleting Ank did not fully compensate for the absence of BSP. Bsp-/-; Ank-/- double-deficient mice exhibited mean 20-27% reduced cementum thickness and volume compared to Ank-/- mice. From these data, we conclude that the perturbations in PPi metabolism are not solely driving the cementum pathology in Bsp-/- mice, and that PPi is more potent than BSP as a cementum regulator, as shown by the ability to override loss of BSP by lowering PPi. We propose that BSP and PPi work in concert to direct mineralization in cementum and likely other mineralized tissues.


Assuntos
Calcificação Fisiológica , Cementogênese/efeitos dos fármacos , Difosfatos/farmacologia , Sialoproteína de Ligação à Integrina/metabolismo , Animais , Calcificação Fisiológica/efeitos dos fármacos , Cemento Dentário/efeitos dos fármacos , Cemento Dentário/metabolismo , Deleção de Genes , Regulação da Expressão Gênica/efeitos dos fármacos , Sialoproteína de Ligação à Integrina/deficiência , Camundongos Knockout , Periodonto/metabolismo , Fenótipo , Proteínas de Transporte de Fosfato/metabolismo , Fosforilação/efeitos dos fármacos
20.
Diabetol Metab Syndr ; 9: 61, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28794803

RESUMO

BACKGROUND: Diabetes related distress is common in type 1 diabetes patients (T1D). High levels of diabetes distress are related to poor metabolic control. An instrument to evaluate diabetes distress in T1D patients is "type 1 diabetes scale-T1DDS". The aim of this study was to translate and culturally adapt the T1DDS into Brazilian culture. METHODS: T1DDS scale was translated into Portuguese. Back translation was performed and evaluated by a specialists committee. Pre-test was performed with 40 T1D outpatients at State University of Campinas hospital. Internal consistency, external consistency and re-test were performed. RESULTS: 72% women, mean age: 32, 1 ± 9, 7 years, mean diabetes duration: 15, 8 ± 9, 1 years, mean scholarity: 11, 5 ± 3, 6, glycosylated hemoglobin mean: 9 ± 2%. Internal consistency: Cronbach alpha of T1DDS Brazilian version was 0.93. External consistency: Spearman's coefficient between T1DDS and PAID, Brazilian version, was 0.7781; (p < 0.0001). CONCLUSIONS: The T1DDS Brazilian version is a reliable tool to evaluate diabetes distress in T1D patients in the Brazilian Population. This tool can be useful in clinical care and to identify patiens at risk and in need for psychosocial intervention.

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