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Metal ions have important roles in supporting the catalytic activity of DNA-regulating enzymes such as topoisomerases (topos). Bacterial type II topos, gyrases and topo IV, are primary drug targets for fluoroquinolones, a class of clinically relevant antibacterials requiring metal ions for efficient drug binding. While the presence of metal ions in topos has been elucidated in biochemical studies, accurate location and assignment of metal ions in structural studies have historically posed significant challenges. Recent advances in X-ray crystallography address these limitations by extending the experimental capabilities into the long-wavelength range, exploiting the anomalous contrast from light elements of biological relevance. This breakthrough enables us to confirm experimentally the locations of Mg2+ in the fluoroquinolone-stabilized Streptococcus pneumoniae topo IV complex. Moreover, we can unambiguously identify the presence of K+ and Cl-ions in the complex with one pair of K+ ions functioning as an additional intersubunit bridge. Overall, our data extend current knowledge on the functional and structural roles of metal ions in type II topos. [ABSTRACT FROM AUTHOR]

ObjectiveTo identify and assess patient motivation to initiate or maintain behavior changes.MethodsAttitudinal statements were developed from structured patient interviews and translated into 18 survey items. Items were analyzed with exploratory factor analysis (EFA).ResultsAn 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).ConclusionsMATCH 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.

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.

Samaneh Kalirai,1 Jasmina I Ivanova,2 Magaly Perez-Nieves,1 Judith J Stephenson,3 Irene Hadjiyianni,1 Michael Grabner,3 Roy Daniel Pollom,1 Caroline Geremakis,3 Beverly L Reed,1 Lawrence Fisher4 1Eli Lilly and Company, Indianapolis, IN, USA; 2Analysis Group Inc., New York, NY, USA; 3HealthCore Inc., Wilmington, DE, USA; 4Department of Family and Community Medicine, UC San Francisco, San Francisco, CA, USACorrespondence: Michael GrabnerHealthCore, Inc., 123 Justison St, Suite 200, Wilmington, DE 19801, USATel +1 302 230-2000Email mgrabner@healthcore.comObjective: A survey of US adults with type 2 diabetes mellitus was conducted to better understand patients’ insulin initiation experiences and treatment persistence behaviors.Research Design and Methods: Participants were recruited from consumer panels and grouped by basal insulin treatment pattern: continuers (no gap of ≥ 7 days within 6 months of initiation); interrupters (gap ≥ 7 days, resumed treatment); discontinuers (stopped for ≥ 7 days, not resumed). A quota of approximately 50 respondents per persistence category was set.Results: A total of 154 respondents (52 continuers, 52 interrupters, 50 discontinuers) completed the survey. Mean age was 51.4 years; 51.9% male. Continuers were more likely to report their views being considered during initiation, and less likely to report a sense of failure. Concerns included insulin dependence (64.3% agree/strongly agree), frequent blood glucose monitoring (55.2%), costs/ability to pay (53.9%), fears of or mistakes during self-injection (52.6%), and weight gain (52.6%). Continuers were motivated by benefits of insulin therapy; experienced or potential side effects were notable factors for interruption/discontinuation. Healthcare provider instruction was indicated as a reason for continuing, stopping, and restarting therapy.Conclusion: Benefits of basal insulin therapy motivated continuers while side effects impacted interruption/discontinuation. Persistence on basal insulin is often influenced by provider actions. Earlier provider intervention upon signs of treatment discontinuation may promote persistence.Keywords: type 2 diabetes mellitus, basal insulin, patient survey, medication persistence

AimsTo 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.MethodsAdults 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.ResultsParticipants 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.ConclusionsBoth 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.

Researchers have traditionally relied on institutionally-defined, native speaker conceptions of linguistic competence to define whether or not individual learners are multilingual. However, to better understand the relationship between language and identity in the context of additional language learning, there is a need to widen the definition of multilingualism by including a larger repertoire of semiotic competences and a wider range of levels of linguistic competence. To date, little systematic research has investigated the relationship between different key variables influencing language learners' construction of their multilingual identity (MI). Based on surveys completed by 1338 learners in seven secondary schools in England, this paper reports on a structural equation modelling of key latent variables influencing MI. The analysis suggests that MI is more strongly correlated with direct experiential contact with languages and with social interaction than with explicit beliefs about language learning. Similarly, the influence of parental beliefs is greater than those of teachers or friends. The paper also considers the significance of potential differences between EAL and non-EAL respondents and urban and rural school contexts. Having conducted SEM we offer support for our theorisation of MI as an outcome latent variable composed of three main components, namely, experience, evaluation and emotion. [ABSTRACT FROM AUTHOR]

Alexander Fisher,1–3 Wichat Srikusalanukul,1 Leon Fisher,4 Paul N Smith2,3 1Department of Geriatric Medicine, The Canberra Hospital, ACT Health, Canberra, Australia; 2Department of Orthopaedic Surgery, The Canberra Hospital, ACT Health, Canberra, Australia; 3Australian National University Medical School, Canberra, ACT, Australia; 4Department of Gastroenterology, Frankston Hospital, Peninsula Health, Melbourne, Australia Purpose: To estimate the discriminative value of serum P1NP/βCTX ratio and albumin levels in hospitalized orthogeriatric patients with and without nonvertebral fractures. Methods: In 1,239 orthogeriatric patients (mean age 78.1±9.52 years, 69.1% women) including 854 (68.9%) with osteoporotic nonvertebral fractures (455 [36.7%] with hip fracture [HF]) and 385 (31.1%) without fractures, markers of bone formation (procollagen type 1 N-terminal propeptide [P1NP], osteocalcin [OC], and bone resorption (beta-C-terminal cross-linking telopeptide of type 1 collagen [βCTX]), indices of mineral metabolism, and parameters of liver and renal functions were assessed; data on clinical and laboratory characteristics were collected prospectively. Results: Both lower serum P1NP/βCTX ratio and albumin concentration (as continuous or categorical variables) were independently associated with fracture presence in multivariate logistic regressions. Compared with the highest P1NP/βCTX tertile, the prevalence of HF, after adjustment for multiple covariates, was 3-fold higher in the lowest tertile and 1.5 times higher in the middle tertile; presence of any fracture was 2.3- and 1.6-fold higher, respectively; patients with albumin levels in the lowest tertile had multivariate odds ratio (OR) of 4.6 for HF and 2.8 for any fracture, in the middle tertile the ORs were 2.2 and 1.3, respectively. The P1NP/βCTX

Summary: 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. [ABSTRACT FROM AUTHOR]