These studies elucidate the role of MAGP2 inside the cell and provide a new explanation for why patients with higher MAGP2 expression in tumors are associated with a worse prognosis. In addition, we also determined a mechanism for the stable existence of uPAR in the cell, providing information for the development of tumor drugs targeting uPAR.

Data on the independent association of moderate aortic stenosis (AS) with excess mortality, even when it does not progress to severe AS, are limited. The aims of this study were to evaluate the association of moderate AS with poor survival and to identify clinically important modifiers of that association.

Consecutive patients who underwent echocardiographic evaluation between 2007 and 2019 were included. All-cause mortality and cancer data were available for all patients from national registries. Cox regression survival models were applied, with censoring of patients who developed metastatic cancer, developed more than moderate AS, or underwent aortic valve intervention during follow-up.

The study population included 92,622 patients. There were 2,202 patients (2%) with moderate AS, with a median age of 79years (interquartile range, 70-85years), of whom 1,254 (57%) were men. During median follow-up of 5years (interquartile range, 3-8years), 19,712 patients (21%) died. The cumulative probability of deaths with reduced ejection fractions and those less then 80 years of age.

The clinical burden and prognostic role of diastolic dysfunction (DD), on the basis of the latest (2016) American Society of Echocardiography guidelines, remain unclear in patients with chronic kidney disease (CKD). Moreover, risk mapping of concomitant systolic dysfunction and DD to evaluate the hazard of cardiovascular (CV) mortality in patients with CKD remains unexplored.

This retrospective cohort study identified 20,257 adult patients who underwent comprehensive echocardiography between 2008 and 2016 at a tertiary medical center in central Taiwan. The patients were stratified by CKD stage, and 3-year CV mortality risk in each CKD stratum was estimated through multivariable Cox proportional-hazards modeling using left ventricular ejection fraction (LVEF) and DD grades on the basis of the 2016 American Society of Echocardiography guidelines as the main risk factors.

Compared with patients with stages 1 and 2 CKD, those with stages 4 and 5 CKD had significantly lower left ventricular ejection fractions and more severe DD. Both left ventricular ejection fraction (<40% vs ≥60%; adjusted hazard ratio, 3.17; 95% CI, 2.54-3.97) and DD grade (severe DD vs normal diastolic function; adjusted hazard ratio, 3.33; 95% CI, 2.33-4.76) were independently associated with 3-year CV mortality in the entire study population and had comparable effect sizes. The corresponding adjusted hazard ratios further increased to 4.20 (95% CI, 2.45-7.21) and 4.54 (95% CI, 2.20-9.38) in patients with stages 4 and 5 CKD. Systolic dysfunction and DD demonstrated mutually augmentative effects on CV mortality.

These findings suggest that the current practice of cardioprotection for patients with CKD should be prioritized at an early stage along with conventional nephroprotection.

These findings suggest that the current practice of cardioprotection for patients with CKD should be prioritized at an early stage along with conventional nephroprotection.

Bipolar (BHA) and unipolar hemiarthroplasties (UHA) are interchangeably used in elderly patients with a displaced femoral neck fracture. We ask if there is a difference between BHA and UHA with regards to hip function, in elderly patients.

Systematic review and meta-analysis was conducted of randomized controlled trials comparing BHA to UHA. The primary outcome was postoperative hip function scores. Secondary outcomes were overall health-related quality of life patient-reported outcomes, acetabular erosion, and postoperative complications. Data sources, last searched on June 1, 2020, were MEDLINE, EMBASE, Cochrane Library, and Web of Science.

Fourteen randomized controlled trials were eligible for meta-analysis. There was no difference in hip function scores between BHA and UHA (standardized mean difference 0.32, 95% confidence interval [CI]-0.06 to 0.71, n= 1084, I

= 87%). Patients with BHA with more than 2-year follow-up had better hip function scores (standardized mean difference 0.68, 95% CI 0.18-1.18, n= 700, I

= 87%). There was no difference in European Quality of life- five dimensions scores with BHA (mean difference 0.08, 95% CI-0.01 to 0.17, n= 967, I

=82%). The use of BHA decreased the risk of acetabular erosion (relative risk 0.38, 95% CI 0.17-0.83, n=1239, I

= 0%). There was no difference for revision, mortality, infection, and dislocation (I

= 0%).

There seems to be no difference between BHA and UHA with regards to hip function at 2 years. BHA might decrease the risk of acetabular erosion. There is a need for a large randomized controlled trial with a follow-up >2 years and better measurement tools to assess clinical benefits.

II.

II.

The current American Association of Hip and Knee Surgeons (AAHKS) guidelines recommend preoperative weight loss before total knee arthroplasty (TKA) in patients with body mass index (BMI) ≥40 kg/m

. However, there is a paucity of evidence on TKA outcomes after preoperative weight loss. This study therefore evaluated predictors of preoperative and postoperative BMI changes and their impact on outcomes after TKA.

This is a retrospective review of 3058 primary TKAs at an academic institution from 2015 to 2019. BMI was collected on the day of surgery. Preoperative and postoperative BMI at 6 months and 1 year were also obtained. BMI change of ≥5% was considered clinically significant. Mean follow-up was 3.2 years. Patient demographics, acute postoperative outcomes, and all-cause revisions were compared between patients who gained, lost, or maintained weight using univariate and multivariable analyses.

Preoperative weight loss was predictive of postoperative weight gain (P < .001), and preoperative weight gain was predictive of postoperative weight loss (P < .001). Cox regression analysis revealed that ≥5% BMI loss preoperatively increased risk for all-cause revisions (P= .030), while ≥5% BMI gain postoperatively increased risk for prosthetic joint infections (P= .016). Patients who lost significant weight both before and after surgery had the highest risk for all-cause revisions (P= .022).

Weight gain postoperatively was associated with inferior outcomes. Significant weight loss before surgery led to a “rebound” in weight gain, and independently increased risk for all-cause revision. Therefore, current recommendations for weight loss before TKA in morbidly obese patients should be re-evaluated.

Weight gain postoperatively was associated with inferior outcomes. Significant weight loss before surgery led to a “rebound” in weight gain, and independently increased risk for all-cause revision. Therefore, current recommendations for weight loss before TKA in morbidly obese patients should be re-evaluated.We review here the Stenciling Principle for extracellular matrix mineralization that describes a double-negative process (inhibition of inhibitors) that promotes mineralization in bone and other mineralized tissues, whereas the default condition of inhibition alone prevents mineralization elsewhere in soft connective tissues. The stenciling principle acts across multiple levels from the macroscale (skeleton/dentition vs soft connective tissues), to the microscale (for example, entheses, and the tooth attachment complex where the soft periodontal ligament is situated between mineralized tooth cementum and mineralized alveolar bone), and to the mesoscale (mineral tessellation). It relates to both small-molecule (e.g. pyrophosphate) and protein (e.g. osteopontin) inhibitors of mineralization, and promoters (enzymes, e.g. KRpep-2d TNAP, PHEX) that degrade the inhibitors to permit and regulate mineralization. In this process, an organizational motif for bone mineral arises that we call crossfibrillar mineral tessellation where mineral formations – called tesselles – geometrically approximate prolate ellipsoids and traverse multiple collagen fibrils (laterally). Tesselle growth is directed by the structural anisotropy of collagen, being spatially restrained in the shorter transverse tesselle dimensions (averaging 1.6 × 0.8 × 0.8 μm, aspect ratio 2, length range 1.5-2.5 μm). Temporo-spatially, the tesselles abut in 3D (close ellipsoid packing) to fill the volume of lamellar bone extracellular matrix. Poorly mineralized interfacial gaps between adjacent tesselles remain discernable even in mature lamellar bone. Tessellation of a same, small basic unit to form larger structural assemblies results in numerous 3D interfaces, allows dissipation of critical stresses, and enables fail-safe cyclic deformations. Incomplete tessellation in osteomalacia/odontomalacia may explain why soft osteomalacic bones buckle and deform under loading.In principle, electron cryo-tomography (cryo-ET) of thin portions of cells provides high-resolution images of the three-dimensional spatial arrangement of all members of the proteome. In practice, however, radiation damage creates a tension between recording images at many different tilt angles, but at correspondingly reduced exposure levels, versus limiting the number of tilt angles in order to improve the signal-to-noise ratio (SNR). Either way, it is challenging to read the available information out at the level of atomic structure. Here, we first review work that explores the optimal strategy for data collection, which currently seems to favor the use of a limited angular range for tilting the sample or even the use of a single image to record the high-resolution information. Looking then to the future, we point to the alternative of so-called “deconvolution microscopy”, which may be applied to tilt-series or optically-sectioned, focal series data. Recording data as a focal series has the advantage that little or no translational alignment of frames might be needed, and a three-dimensional reconstruction might require only 2/3 the number of images as does standard tomography. We also point to the unexploited potential of phase plates to increase the contrast, and thus to reduce the electron exposure levels while retaining the ability align and merge the data. In turn, using much lower exposures per image could have the advantage that high-resolution information is retained throughout the full data-set, whether recorded as a tilt series or a focal series of images.An open-source Python library EMDA for cryo-EM map and model manipulation is presented with a specific focus on validation. The use of several functionalities in the library is presented through several examples. The utility of local correlation as a metric for identifying map-model differences and unmodeled regions in maps, and how it is used as a metric of map-model validation is demonstrated. The mapping of local correlation to individual atoms, and its use to draw insights on local signal variations are discussed. EMDA’s likelihood-based map overlay is demonstrated by carrying out a superposition of two domains in two related structures. The overlay is carried out first to bring both maps into the same coordinate frame and then to estimate the relative movement of domains. Finally, the map magnification refinement in EMDA is presented with an example to highlight the importance of adjusting the map magnification in structural comparison studies.