Proteomic Alterations of HDL in Youth with Type 1 Diabetes and their Associations with Glycemic Control: A Case-Control Study

Background: Patients with type 1 diabetes (T1DM) typically have normal or even elevated plasma high density lipoprotein (HDL) cholesterol concentrations; however, HDL protein composition can be altered without a change in cholesterol content. Alteration of the HDL proteome can result in dysfunctional HDL particles with reduced ability to protect against cardiovascular disease (CVD). The objective of this study was to compare the HDL proteomes of youth with T1DM and healthy controls (HC) and to evaluate the influence of glycemic control on HDL protein composition. Methods: This was a cross-sectional case–control study. Blood samples were obtained from patients with T1DM and HC. HDL was isolated from plasma by size-exclusion chromatography and further purified using a lipid binding resin. The HDL proteome was analyzed by mass spectrometry using label-free SWATH peptide quantification. Results: Samples from 26 patients with T1DM and 13 HC were analyzed and 78 HDL-bound proteins were measured. Youth with T1DM had significantly increased amounts of complement factor H related protein 2 (FHR2; adjusted P \u3c 0.05), compared to HC. When patients were analyzed based on glucose control, several trends emerged. Some proteins were altered in T1DM and not influenced by glycemic control (e.g. FHR2) while others were partially or completely corrected with optimal glucose control (e.g. alpha-1-beta glycoprotein, A1BG). In a subgroup of poorly controlled T1DM patients, inter alpha trypsin inhibitor 4 (ITIH4) was dramatically elevated (P \u3c 0.0001) and this was partially reversed in patients with optimal glucose control. Some proteins including complement component C3 (CO3) and albumin (ALB) were significantly different only in T1DM patients with optimal glucose control, suggesting a possible effect of exogenous insulin. Conclusions: Youth with T1DM have proteomic alterations of their HDL compared to HC, despite similar concentration of HDL cholesterol. The influence of these compositional changes on HDL function are not yet known. Future efforts should focus on investigating the role of these HDL associated proteins in regard to HDL function and their role in CVD risk in patients with T1DM. Trial registration NCT0227509

Contemporary outcomes of vertebral artery injury

ObjectiveVertebral artery injury (VAI) associated with cervical trauma is being increasingly recognized with more aggressive screening. Disparate results from previous literature have led to uncertainty of the significance, natural history, and optimal therapy for VAI.MethodsTo understand the natural history and treatment outcomes from our experience, we performed a retrospective, single-center review from a level I trauma center for the previous 10 years of all VAI. Injuries were identified from search of an administrative trauma database, a resident-run working database, and all radiology dictations for the same period. All VAI were classified according to segmental involvement, Denver grading scale, and laterality. Analysis of associated injuries, demographics, neurologic outcome, mortality, length of stay, treatment plan, and follow-up imaging was also performed.ResultsFifty-one patients with VAI were identified from 2001 to 2011 from a total of 36,942 trauma admissions (0.13% incidence). Associated injuries were significant with an average New Injury Severity Score of 29.6. Penetrating trauma occurred in 14%. Cervical spine fracture was present in 88% with VAI. Diagnosis was obtained with computed tomographic angiography (CTA) in 95%. Screening was prompted by injury pattern or high-risk mechanism in all cases. Injuries classified according to the Denver grading scale were grade I = 24%, grade II = 35%, grade III = 4%, grade IV = 35%, and grade V = 2%. Distribution across segments included V1 = 18%, V2 = 67%, V3 = 31%, and V4 = 6%. Only one posterior circulation stroke was attributable to VAI. Overall mortality was 8%, with each mortality being associated with significant other organ injuries. Treatment rendered for VAI was antiplatelet therapy (50%), observation (31%), warfarin (17%), and stent (2%). There were no significant differences between treatment groups on any variable with the exception of body mass index (P = .047). Follow-up was obtained for 13% (n = 6) of survivors. The CTA demonstrated injury stability in four patients and resolution in two patients. Accuracy of the administrative trauma database was 53% compared with 96% for the resident-run working database.ConclusionsNeurologic sequelae attributable to VAI were rare. Grade of VAI or vertebral artery segment did not correlate with morbidity. We did not observe any differences in short-term outcomes between systemic anticoagulation and antiplatelet therapy. Of those patients seen at follow-up, injury resolution or stability was documented by CTA. A conservative approach with either observation or antithrombotic therapy is suggested. If the natural history of VAI includes a very low stroke rate, then therapies with a lower therapeutic index, such as systemic anticoagulation, in the severely injured trauma patient are not supported. Our search strategy urges awareness of the limitations of administrative databases for retrospective vascular study

3-manifolds which are spacelike slices of flat spacetimes

We continue work initiated in a 1990 preprint of Mess giving a geometric parameterization of the moduli space of classical solutions to Einstein's equations in 2+1 dimensions with cosmological constant 0 or -1 (the case +1 has been worked out in the interim by the present author). In this paper we make a first step toward the 3+1-dimensional case by determining exactly which closed 3-manifolds M^3 arise as spacelike slices of flat spacetimes, and by finding all possible holonomy homomorphisms pi_1(M^3) to ISO(3,1).Comment: 10 page

The solidification of Al–Pd–Mn studied by high-energy X-ray diffraction from electrostatically levitated samples

We report on the results of a high-energy x-ray diffraction study of Al–Pd–Mn to investigate the solidification products obtained during free-cooling using an electrostatic levitation furnace. The primary solidification product from the melt is i-Al–Pd–Mn which coexists with a significant remaining liquid component. As the sample cools further, we find that the solidification pathway is consistent with the liquidus projection and pseudo-binary cut through the ternary phase diagram reported previously. At ambient temperature we have identified the major phase to be the ξ′-phase orthorhombic approximant, along with minor phases identified as Al and, most likely, the R-phase orthorhombic approximant. We have also observed a distinct prepeak in the liquid at high temperature, signifying the presence of extended atomic order. Interestingly, this prepeak was not observed in previous neutron diffraction measurements on the Al–Pd–Mn system. No undercooling was observed preceding the solidification of the i-Al–Pd–Mn phase from the melt which may signal the close similarity of the short-range order in the solid and liquid. However, this can not be clearly determined because of the potential for heterogenous nucleation associated with the presence of an Al2O3 impurity at the surface of the sample

A sociological exploration of the tensions related to interprofessional collaboration in acute-care discharge planning

Patient discharge is a key concern in hospitals, particularly in acute care, given the multifaceted and challenging nature of patients' healthcare needs. Policies on discharge have identified the importance of interprofessional collaboration, yet research has described its limitations in this clinical context. This study aimed to extend our understanding of interprofessional interactions related to discharge in a general internal medicine setting by using sociological theories to illuminate the existence of, and interplay between, structural factors and microlevel practices. An ethnographic approach was employed to obtain an in-depth insight into healthcare providers' perspectives, behaviours, and interactions regarding discharge. Data collection involved observations, interviews, and document analysis. Approximately 65 hours of observations were undertaken, 23 interviews were conducted with healthcare providers, and government and hospital discharge documents were collected. Data were analysed using a directed content approach. The findings indicate the existence of a medically dominated division of healthcare labour in patient discharge with opportunities for some interprofessional negotiations; the role of organizational routines in facilitating and challenging interprofessional negotiations in patient discharge; and tensions in organizational priorities that impact an interprofessional approach to discharge. The findings provide insight into the various levels at which interventions can be targeted to improve interprofessional collaboration in discharge while recognizing the organizational tensions that challenge an interprofessional approach

Minimally Invasive Mitral Valve Surgery III: Training and Robotic-Assisted Approaches.

Minimally invasive mitral valve operations are increasingly common in the United States, but robotic-assisted approaches have not been widely adopted for a variety of reasons. This expert opinion reviews the state of the art and defines best practices, training, and techniques for developing a successful robotics program

Minimally Invasive Mitral Valve Surgery I: Patient Selection, Evaluation, and Planning.

Widespread adoption of minimally invasive mitral valve repair and replacement may be fostered by practice consensus and standardization. This expert opinion, first of a 3-part series, outlines current best practices in patient evaluation and selection for minimally invasive mitral valve procedures, and discusses preoperative planning for cannulation and myocardial protection