Crystallization and preliminary X-ray diffraction data for a purple acid phosphatase from sweet potato

Purple acid phosphatase from sweet potato is a homodimer of 110 kDa. Two forms of the enzyme have been characterized. One contains an Fe±Zn centre similar to that previously reported for red kidney bean purple acid phosphatase. Another isoform, the subject of this work, is the ®rst con®rmed example of an Fe±Mn-containing enzyme. Crystals of this protein have been grown from PEG 6000. They have unit-cell parameters a = b = 118.4, c = 287.4 A Ê and have the symmetry of space group P6522, with one dimer per asymmetric unit. Diffraction data collected using a conventional X-ray source from a cryocooled crystal extend to 2.90 A Ê resolution. The three-dimensional structure of the enzyme will provide insight into the coordination of this novel binuclear metal centre

Individual nutrition therapy and exercise regime: A controlled trial of injured, vulnerable elderly (INTERACTIVE trial)

Trial registration Australian Clinical Trials Registry: ACTRN12607000017426.Background Proximal femoral fractures are amongst the most devastating consequences of osteoporosis and injurious accidental falls with 25–35% of patients dying in the first year post-fracture. Effective rehabilitation strategies are evolving however, despite established associations between nutrition, mobility, strength and strength-related functional outcomes; there has been only one small study with older adults immediately following fragility fracture where a combination of both exercise and nutrition have been provided. The aim of the INTERACTIVE trial is to establish whether a six month, individualised exercise and nutrition program commencing within fourteen days of surgery for proximal femur fracture, results in clinically and statistically significant improvements in physical function, body composition and quality of life at an acceptable level of cost and resource use and without increasing the burden of caregivers. Methods and Design This randomised controlled trial will be performed across two sites, a 500 bed acute hospital in Adelaide, South Australia and a 250 bed acute hospital in Sydney, New South Wales. Four hundred and sixty community-dwelling older adults aged > 70 will be recruited after suffering a proximal femoral fracture and followed into the community over a 12-month period. Participants allocated to the intervention group will receive a six month individualised care plan combining resistance training and nutrition therapy commencing within 14 days post-surgery. Outcomes will be assessed by an individual masked to treatment allocation at six and 12 months. To determine differences between the groups at the primary end-point (six months), ANCOVA or logistic regression will be used with models adjusted according to potential confounders. Discussion The INTERACTIVE trial is among the first to combine nutrition and exercise therapy as an early intervention to address the serious consequence of rapid deconditioning and weight loss and subsequent ability to regain pre-morbid function in older patients post proximal femoral fracture. The results of this trial will guide the development of more effective rehabilitation programs, which may ultimately lead to reduced health care costs, and improvements in mobility, independence and quality of life for proximal femoral fracture sufferers

The vertical distribution and biological transport of marine microplastics across the epipelagic and mesopelagic water column.

Plastic waste has been documented in nearly all types of marine environments and has been found in species spanning all levels of marine food webs. Within these marine environments, deep pelagic waters encompass the largest ecosystems on Earth. We lack a comprehensive understanding of the concentrations, cycling, and fate of plastic waste in sub-surface waters, constraining our ability to implement effective, large-scale policy and conservation strategies. We used remotely operated vehicles and engineered purpose-built samplers to collect and examine the distribution of microplastics in the Monterey Bay pelagic ecosystem at water column depths ranging from 5 to 1000 m. Laser Raman spectroscopy was used to identify microplastic particles collected from throughout the deep pelagic water column, with the highest concentrations present at depths between 200 and 600 m. Examination of two abundant particle feeders in this ecosystem, pelagic red crabs (Pleuroncodes planipes) and giant larvaceans (Bathochordaeus stygius), showed that microplastic particles readily flow from the environment into coupled water column and seafloor food webs. Our findings suggest that one of the largest and currently underappreciated reservoirs of marine microplastics may be contained within the water column and animal communities of the deep sea

APC-targeted proinsulin expression inactivates insulin-specific memory CD8+ T cells in NOD mice

Type 1 diabetes (T1D) results from T-cell-mediated autoimmune destruction of pancreatic β cells. Effector T-cell responses emerge early in disease development and expand as disease progresses. Following β-cell destruction, a long-lived T-cell memory is generated that represents a barrier to islet transplantation and other cellular insulin-replacement therapies. Development of effective immunotherapies that control or ablate β-cell destructive effector and memory T-cell responses has the potential to prevent disease progression and recurrence. Targeting antigen expression to antigen-presenting cells inactivates cognate CD8+ effector and memory T-cell responses and has therapeutic potential. Here we investigated this in the context of insulin-specific responses in the non-obese diabetic mouse where genetic immune tolerance defects could impact on therapeutic tolerance induction. Insulin-specific CD8+ memory T cells transferred to mice expressing proinsulin in antigen-presenting cells proliferated in response to transgenically expressed proinsulin and the majority were rapidly deleted. A small proportion of transferred insulin-specific Tmem remained undeleted and these were antigen-unresponsive, exhibited reduced T cell receptor (TCR) expression and H-2Kd/insB15-23 tetramer binding and expressed co-inhibitory molecules. Expression of proinsulin in antigen-presenting cells also abolished the diabetogenic capacity of CD8+ effector T cells. Therefore, destructive insulin-specific CD8+ T cells are effectively inactivated by enforced proinsulin expression despite tolerance defects that exist in diabetes-prone NOD mice. These findings have important implications in developing immunotherapeutic approaches to T1D and other T-cell-mediated autoimmune diseases

A Patient-Centered Primary Care Practice Approach Using Evidence-Based Quality Improvement: Rationale, Methods, and Early Assessment of Implementation

BACKGROUND: Healthcare systems and their primary care practices are redesigning to achieve goals identified in Patient-Centered Medical Home (PCMH) models such as Veterans Affairs (VA)’s Patient Aligned Care Teams (PACT). Implementation of these models, however, requires major transformation. Evidence-Based Quality Improvement (EBQI) is a multi-level approach for supporting organizational change and innovation spread. OBJECTIVE: To describe EBQI as an approach for promoting VA’s PACT and to assess initial implementation of planned EBQI elements. DESIGN: Descriptive. PARTICIPANTS: Regional and local interdisciplinary clinical leaders, patient representatives, Quality Council Coordinators, practicing primary care clinicians and staff, and researchers from six demonstration site practices in three local healthcare systems in one VA region. INTERVENTION: EBQI promotes bottom-up local innovation and spread within top-down organizational priorities. EBQI innovations are supported by a research-clinical partnership, use continuous quality improvement methods, and are developed in regional demonstration sites. APPROACH: We developed a logic model for EBQI for PACT (EBQI-PACT) with inputs, outputs, and expected outcomes. We describe implementation of logic model outputs over 18 months, using qualitative data from 84 key stakeholders (104 interviews from two waves) and review of study documents. RESULTS: Nearly all implementation elements of the EBQI-PACT logic model were fully or partially implemented. Elements not fully achieved included patient engagement in Quality Councils (4/6) and consistent local primary care practice interdisciplinary leadership (4/6). Fourteen of 15 regionally approved innovation projects have been completed, three have undergone initial spread, five are prepared to spread, and two have completed toolkits that have been pretested in two to three sites and are now ready for external spread. DISCUSSION: EBQI-PACT has been feasible to implement in three participating healthcare systems in one VA region. Further development of methods for engaging patients in care design and for promoting interdisciplinary leadership is needed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11606-013-2703-y) contains supplementary material, which is available to authorized users

Acceptability of a cessation intervention for pregnant smokers: a qualitative study guided by Normalization Process Theory

Abstract: Background: Smoking during pregnancy has serious consequences for maternal and child health. An intervention package to embed National Institute for Health and Care Excellence guidance (babyClear©) was delivered across maternity and stop smoking services (SSS) within an English region, to support pregnant women to stop smoking. We aimed to ascertain acceptability among pregnant smokers receiving the intervention. Methods: Pregnant smokers who received the intervention and participated in the study were interviewed, first at around 16 weeks of pregnancy (n = 17) and again several weeks later (n = 8) or postpartum (n = 3). Interview schedules were informed by Normalization Process Theory (NPT) and Theoretical Domains Framework; interviews were audio-recorded, transcribed and analysed thematically, using the Framework method and NPT. Findings are grouped according to the four NPT concepts. Results: Coherence: Carbon monoxide monitoring appeared to make sense; women were motivated to quit by being monitored. Cognitive participation: When linked to a professional discourse of caring and concern, some women were prompted to engage with the SS message. Women were more guarded in their reaction to initial contact from the SSS; reporting attending appointments successfully, or in some cases, experiencing problems that decreased engagement and made quitting harder. Collective action: Where women continued to smoke or failed to attend SSS appointments, an extra intervention was delivered, the Risk Perception Tool (RPT), which often prompted pregnant women to act. Reflexive monitoring: Most women accepted the need for a hard-hitting approach (RPT) and, while it distressed them at the time, they claimed they were subsequently grateful for it. SSS intervention post-RPT was seen as supportive, partly because it often involved home visits. Aspects of family inclusion in babyClear© were reported as beneficial. In Trusts where women experienced services as less focused on prioritising the stop smoking message, less well integrated or reported maternity staff as less adept at delivering the RPT, women found babyClear© less acceptable overall. Conclusions: The babyClear© package was acceptable to pregnant smokers interviewed during and shortly after pregnancy and, in some cases, to promote quitting. However, some contexts were more optimal than others, leading to variation in acceptability overall

Cerebral Small Vessel Disease burden is increased in Systemic Lupus Erythematosus

BACKGROUND AND PURPOSE—: Systemic lupus erythematosus (SLE) increases stroke risk, but the mechanism is uncertain. This study aimed to determine the association between SLE and features on neuroimaging of cerebral small vessel disease (SVD), a risk factor for stroke. METHODS—: Consecutive patients attending a clinic for SLE were recruited. All patients underwent brain magnetic resonance imaging; had blood samples taken for markers of inflammation, endothelial dysfunction, cholesterol, and autoantibodies; and underwent cognitive and psychiatric testing. The data were compared with sex- and age-matched healthy controls and patients with minor stroke. Features of SVD were measured, a total SVD score calculated, and associations sought with vascular risk factors, cognition, SLE activity, and disease duration. RESULTS—: Fifty-one SLE patients (age: 48.8 years; SD: 14.3 years) had a greater total SVD score compared with healthy controls (1 versus 0; P<0.0001) and stroke patients (1 versus 0; P=0.02). There were higher perivascular spaces and deep white matter hyperintensity scores and more superficial brain atrophy in SLE patients versus healthy controls. Despite fewer vascular risk factors than similarly aged stroke patients, SLE patients had similar or more of some SVD features. The total SVD score was not associated with SLE activity, cognition, disease duration, or any blood measure. CONCLUSIONS—: In this data set, SLE patients had a high burden of SVD features on magnetic resonance imaging, particularly perivascular spaces. A larger longitudinal study is warranted to determine the causes of SVD features in SLE and clinical implications

Effect of Implementing Discharge Readiness Assessment in Adult Medical-Surgical Units on 30-Day Return to Hospital The READI Randomized Clinical Trial

Importance: The downward trend in readmissions has recently slowed. New enhancements to hospital readmission reduction efforts are needed. Structured assessment of patient readiness for discharge has been recommended as an addition to discharge preparation standards of care to assist with tailoring of risk-mitigating actions. Objective: To determine the effect of unit-based implementation of readiness evaluation and discharge intervention protocols on readmissions and emergency department or observation visits. Design, Setting, and Participants: The Readiness Evaluation and Discharge Interventions (READI) cluster randomized clinical trial conducted in medical-surgical units of 33 Magnet hospitals between September 15, 2014, and March 31, 2017, included all adult (aged ≥18 years) patients discharged to home. Baseline and risk-adjusted intent-to-treat analyses used difference-in-differences multilevel logistic regression models with controls for patient characteristics. Interventions: Of 2 adult medical-surgical nursing units from each hospital, 1 was randomized to the intervention and 1 to usual care conditions. Using the 8-item Readiness for Hospital Discharge Scale, the 33 intervention units implemented a sequence of protocols with increasing numbers of components: READI1, in which nurses assessed patients to inform discharge preparation; READI2, which added patient self-assessment; and READI3, which added an instruction to act on a specified Readiness for Hospital Discharge Scale cutoff score indicative of low readiness. Main Outcomes and Measures: Thirty-day return to hospital (readmission or emergency department and observation visits). Intervention units above median baseline readmission rate (\u3e11.3%) were categorized as high-readmission units. Among the 33 intervention units, 17 were low-readmission units and 16 were high-readmission units. Results: The sample included 144 868 patient discharges (mean [SD] age, 59.6 [17.5] years; 51% female; 74 605 in the intervention group and 70 263 in the control group); 17 667 (12.2%) were readmitted and 12 732 (8.8%) had an emergency department visit or observation stay. None of the READI protocols reduced the primary outcome of return to hospital in intent-to-treat analysis of the full sample. In exploratory subgroup analysis, when patient self-assessments were combined with readiness assessment by nurses (READI2), readmissions were reduced by 1.79 percentage points (95% CI, −3.20 to −0.40 percentage points; P = .009) on high-readmission units. With nurse assessment alone and on low-readmission units, results were mixed. Conclusions and Relevance: Implemented in a broad range of hospitals and patients, the READI interventions were not effective in reducing return to hospital. However, adding a structured discharge readiness assessment that incorporates the patient’s own perspective to usual discharge care practices holds promise for mitigating high rates of return to the hospital following discharge

Type III collagen modulates fracture callus bone formation and early remodeling

Type III collagen (Col3) has been proposed to play a key role in tissue repair based upon its temporospatial expression during the healing process of many tissues, including bone. Given our previous finding that Col3 regulates the quality of cutaneous repair, as well as our recent data supporting its role in regulating osteoblast differentiation and trabecular bone quantity, we hypothesized that mice with diminished Col3 expression would exhibit altered long‐bone fracture healing. To determine the role of Col3 in bone repair, young adult wild‐type (Col3+/+) and haploinsufficent (Col3+/−) mice underwent bilateral tibial fractures. Healing was assessed 7, 14, 21, and 28 days following fracture utilizing microcomputed tomography (microCT), immunohistochemistry, and histomorphometry. MicroCT analysis revealed a small but significant increase in bone volume fraction in Col3+/− mice at day 21. However, histological analysis revealed that Col3+/− mice have less bone within the callus at days 21 and 28, which is consistent with the established role for Col3 in osteogenesis. Finally, a reduction in fracture callus osteoclastic activity in Col3+/− mice suggests Col3 also modulates callus remodeling. Although Col3 haploinsufficiency affected biological aspects of bone repair, it did not affect the regain of mechanical function in the young mice that were evaluated in this study. These findings provide evidence for a modulatory role for Col3 in fracture repair and support further investigations into its role in impaired bone healing. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:675–684, 2015.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111249/1/jor22838.pd