Epigenetic changes to chromatin are thought to be essential to cell senescence, which is key to tumorigenesis and aging. Although many studies focus on heterochromatin gain, this work demonstrates large-scale unraveling of peri/centromeric satellites, which occurs in all models of human and mouse senescence examined. This was not seen in cancer cells, except in a benign senescent tumor in vivo. Senescence-associated distension of satellites (SADS) occurs earlier and more consistently than heterochromatin foci formation, and SADS is not exclusive to either the p16 or p21 pathways. Because Hutchinson Guilford progeria syndrome patient cells do not form excess heterochromatin, the question remained whether or not proliferative arrest in this aging syndrome involved distinct epigenetic mechanisms. Here, we show that SADS provides a unifying event in both progeria and normal senescence. Additionally, SADS represents a novel, cytological-scale unfolding of chromatin, which is not concomitant with change to several canonical histone marks nor a result of DNA hypomethylation. Rather, SADS is likely mediated by changes to higher-order nuclear structural proteins, such as LaminB1.

Numerous publications claim to improve breast projection and upper pole fullness after mastopexy or breast reduction. Fascial sutures and "autoaugmentation" with local flaps are advocated. However, there is no objective evidence that these efforts are effective. The author has proposed a measuring system to quantitate results. Not only is this system useful for assessing one's own results, but it may also be used to assess and compare results in published studies. Eighty-two international publications on mastopexies and breast reductions were analyzed. The studies were grouped by technique: inverted-T (superior/medial, central, and inferior pedicles), vertical, periareolar, inframammary, lateral, and "other." Measurements were made using the definitions and terminology reported separately and included breast projection, upper pole projection, lower pole level, nipple level, breast convexity, breast parenchymal ratio, and lower pole ratio. Areola shape was assessed. Breast projection and upper pole projection were not increased significantly by any of the mastopexy/reduction procedures or by the use of fascial sutures or autoaugmentation techniques. Nipple overelevation was common (41.9 percent). The incidence of the teardrop areola deformity (53.8 percent) was significantly higher (p < 0.001) in patients treated with the open technique of nipple placement. There was no significant difference in results when compared by follow-up times, resection weights, year of publication, or geographic region. Existing mastopexy/reduction techniques do not significantly increase breast projection or upper pole projection. Fascial sutures and autoaugmentation techniques are ineffective. Nipple overelevation and the teardrop areola deformity are common problems and should be avoided.

Despite the growing popularity of breast lift surgery, no published study prospectively evaluates mastopexy and augmentation/mastopexy. Several investigators suggest an inordinate risk in combining augmentation and mastopexy, and recommend staging the surgery in some patients. However, no existing study includes the necessary individual and combined treatment cohorts to allow reliable comparisons of safety and efficacy. This study investigates the clinical outcomes and safety of these cosmetic breast procedures, whether performed individually or in combination. This 10-year prospective study evaluated 759 consecutive women undergoing 784 consecutive cases of breast augmentation (n = 522), mastopexy (n = 57), augmentation/mastopexy (n = 146), reduction (n = 48), and reduction plus implants (n = 11). All patients were treated by the author using submuscular implant placement and vertical parenchymal resection with a medial pedicle and intraoperative determination of nipple positioning. A power analysis confirmed adequacy of the sample sizes. The complication rate was 36.3 percent for augmentation/mastopexy, 33.3 percent for mastopexy alone, and 17.6 percent for breast augmentation alone. Mammaplasties were complicated by persistent ptosis in 9.5 percent of patients. The revision rate after augmentation/mastopexy was 20.5 percent, compared with 24.6 percent for mastopexy and 10.7 percent for breast augmentation. Vertical mammaplasty may be used to correct ptosis in breasts of all sizes. Vertical augmentation/mastopexy provides complication and revision rates that are less than the calculated cumulative rates for the procedures performed separately. The combined procedure offers technical advantages and permits safe single-stage surgery using the vertical technique. Therapeutic, II.

Background: Evaluation of changes in breast shape, particularly “upper pole fullness,” “breast projection,” and “bottoming out,” has been made difficult by the lack of an accepted definition of these entities and no standardized system for measurements and comparison. Three-dimensional imaging is impractical for most surgeons and limited in providing evidence-based assessments. Methods: Using standardized photographs and computer imaging software to match size and orientation, breast shape and size are measured and compared before and after cosmetic breast surgery. Practical landmarks and analysis allow assessment of results using standard two-dimensional frontal and lateral views. A horizontal plane at the level of maximum postoperative breast projection and a vertical plane dropped from the sternal notch serve as the reference planes. Breast projection, upper pole projection, lower pole level, nipple level, lower pole width, breast parenchymal ratio, and lower pole ratio (a measure of the boxiness of the lower pole) are defined and measured. Results: These simple measurements may be easily used by surgeons to evaluate the effectiveness of their techniques in breast augmentation, mastopexy, augmentation/mastopexy, and reduction. Claims regarding changes in breast projection, upper pole projection, and breast mound elevation may be objectively evaluated. Conclusion: This measurement system provides a highly practical means with which to quantitate breast shape changes after surgery and assess surgical results using well-defined references. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Multiple sclerosis (MS) is characterized by demyelinated and inflammatory lesions in the brain and spinal cord that are highly variable in terms of cellular content. Here, we used imaging mass cytometry (IMC) to enable the simultaneous imaging of 15+ proteins within staged MS lesions. To test the potential for IMC to discriminate between different types of lesions, we selected a case with severe rebound MS disease activity after natalizumab cessation. With post-acquisition analysis pipelines we were able to: (1) Discriminate demyelinating macrophages from the resident microglial pool; (2) Determine which types of lymphocytes reside closest to blood vessels; (3) Identify multiple subsets of T and B cells, and (4) Ascertain dynamics of T cell phenotypes vis-à-vis lesion type and location. We propose that IMC will enable a comprehensive analysis of single-cell phenotypes, their functional states and cell-cell interactions in relation to lesion morphometry and demyelinating activity in MS patients.