Tissue Reinforcement in Implant-based Breast Reconstruction

Background: Tissue reinforcement with allogeneic or xenogeneic acellular dermal matrices (ADMs) is increasingly used in single-stage (direct-to-implant) and 2-stage implant-based breast reconstruction following mastectomy. ADMs allow surgeons to control implant position and obviate the need for submuscular implant placement. Here, we review the benefits and risks of using ADMs in implant-based breast reconstruction based on available data. Methods: A comprehensive analysis of the literature with focus on recent publications was performed. Additional information regarding the proper use of ADMs was based on our institutional experience. Results: ADM use may improve definition of the lateral confines of the breast and lower pole projection. It may facilitate direct-to-implant procedures and improve aesthetic outcomes. The effect of ADMs on complication rates remains controversial. Known patient risk factors such as obesity, smoking, and radiotherapy should be considered during patient selection. For patients with healthy, well-vascularized skin envelopes, ADM-assisted direct-to- implant reconstruction is a safe and cost-effective alternative to 2-stage implant reconstruction, with low complication rates. ADMs may be used to treat capsular contracture, and limited available data further suggest the possibility that ADMs may reduce the risk of capsular contracture. Novel synthetic or biosynthetic tissue reinforcement devices with different physical and ease-of-use properties than ADMs are emerging options for reconstructive surgeons and patients who seek to avoid tissue products from human or mammalian cadavers. Conclusions: ADM-assisted implant-based breast reconstruction may improve aesthetic outcomes. However, appropriate patient selection, surgical technique, and postoperative management are critical for its success, including minimizing the risk of complications

Charge as a Selection Criterion for Translocation through the Nuclear Pore Complex

Nuclear pore complexes (NPCs) are highly selective filters that control the exchange of material between nucleus and cytoplasm. The principles that govern selective filtering by NPCs are not fully understood. Previous studies find that cellular proteins capable of fast translocation through NPCs (transport receptors) are characterized by a high proportion of hydrophobic surface regions. Our analysis finds that transport receptors and their complexes are also highly negatively charged. Moreover, NPC components that constitute the permeability barrier are positively charged. We estimate that electrostatic interactions between a transport receptor and the NPC result in an energy gain of several kBT, which would enable significantly increased translocation rates of transport receptors relative to other cellular proteins. We suggest that negative charge is an essential criterion for selective passage through the NPC.Merck Research LaboratoriesNational Science Foundation (U.S.) (Division of Mathematical Sciences)Kavli Institute for Bionano Science & Technology at Harvard UniversityNational Centers for Systems Biology (U.S.) (NIGMS grant GM068763)National Institute of General Medical Sciences (U.S.

Energy Gradients Structure Microbial Communities Across Sediment Horizons in Deep Marine Sediments of the South China Sea

The deep marine subsurface is a heterogeneous environment in which the assembly of microbial communities is thought to be controlled by a combination of organic matter deposition, electron acceptor availability, and sedimentology. However, the relative importance of these factors in structuring microbial communities in marine sediments remains unclear. The South China Sea (SCS) experiences significant variability in sedimentation across the basin and features discrete changes in sedimentology as a result of episodic deposition of turbidites and volcanic ashes within lithogenic clays and siliceous or calcareous ooze deposits throughout the basin\u27s history. Deep subsurface microbial communities were recently sampled by the International Ocean Discovery Program (IODP) at three locations in the SCS with sedimentation rates of 5, 12, and 20 cm per thousand years. Here, we used Illumina sequencing of the 16S ribosomal RNA gene to characterize deep subsurface microbial communities from distinct sediment types at these sites. Communities across all sites were dominated by several poorly characterized taxa implicated in organic matter degradation, including Atribacteria, Dehalococcoidia, and Aerophobetes. Sulfate-reducing bacteria comprised only 4% of the community across sulfate-bearing sediments from multiple cores and did not change in abundance in sediments from the methanogenic zone at the site with the lowest sedimentation rate. Microbial communities were significantly structured by sediment age and the availability of sulfate as an electron acceptor in pore waters. However, microbial communities demonstrated no partitioning based on the sediment type they inhabited. These results indicate that microbial communities in the SCS are structured by the availability of electron donors and acceptors rather than sedimentological characteristics

Conservation Weighting Functions Enable Covariance Analyses to Detect Functionally Important Amino Acids

The explosive growth in the number of protein sequences gives rise to the possibility of using the natural variation in sequences of homologous proteins to find residues that control different protein phenotypes. Because in many cases different phenotypes are each controlled by a group of residues, the mutations that separate one version of a phenotype from another will be correlated. Here we incorporate biological knowledge about protein phenotypes and their variability in the sequence alignment of interest into algorithms that detect correlated mutations, improving their ability to detect the residues that control those phenotypes. We demonstrate the power of this approach using simulations and recent experimental data. Applying these principles to the protein families encoded by Dscam and Protocadherin allows us to make testable predictions about the residues that dictate the specificity of molecular interactions

Oral Metallo-Beta-Lactamase Protects the Gut Microbiome From Carbapenem-Mediated Damage and Reduces Propagation of Antibiotic Resistance in Pigs

Antibiotics can damage the gut microbiome, leading to serious adventitious infections and emergence of antibiotic resistant pathogens. Antibiotic inactivation in the GI tract represents a strategy to protect colonic microbiota integrity and reduce antibiotic resistance. Clinical utility of this approach was established when SYN-004 (ribaxamase), an orally-administered beta-lactamase, was demonstrated to degrade ceftriaxone in the GI tract and preserve the gut microbiome. Ribaxamase degrades penicillins and cephalosporin beta-lactams, but not carbapenems. To expand this prophylactic approach to include all classes of beta-lactam antibiotics, a novel carbapenemase, formulated for oral administration, SYN-006, was evaluated in a porcine model of antibiotic-mediated gut dysbiosis. Pigs (20 kg, n = 16) were treated with the carbapenem, ertapenem (ERT), (IV, 30 mg/kg, SID) for 4 days and a cohort (n = 8) also received SYN-006 (PO, 50 mg, QID), beginning the day before antibiotic administration. ERT serum levels were not statistically different in ERT and ERT + SYN-006 groups, indicating that SYN-006 did not alter systemic antibiotic levels. Microbiomes were evaluated using whole genome shotgun metagenomics analyses of fecal DNA collected prior to and after antibiotic treatment. ERT caused significant changes to the gut microbiome that were mitigated in the presence of SYN-006. In addition, SYN-006 attenuated emergence of antibiotic resistance, including encoded beta-lactamases and genes conferring resistance to a broad range of antibiotics such as aminoglycosides and macrolides. SYN-006 has the potential to become the first therapy designed to protect the gut microbiome from all classes of beta-lactam antibiotics and reduce emergence of carbapenem-resistant pathogens

27630 Assessing signs and symptoms of hidradenitis suppurativa from the patient perspective

Background: Qualitative research was conducted to develop a patient reported outcome (PRO) measure assessing symptoms/signs of hidradenitis suppurativa (HS), the HS Symptom Diary (HSSD). Methods: Concept elicitation (CE) and combined CE/cognitive debriefing (CD) interviews were conducted with adult patients with moderate-to-severe HS from 5 dermatology practices in North America. The CE portion of the interview sought to fully understand important concepts of HS. Subjects then completed the draft HSSD, and answered questions to evaluate its content, clarity, and relevance. Revisions were made iteratively to the HSSD. The study received institutional review board approval; subjects provided written informed consent. Results: 36 subjects were interviewed [6 = CE and 30 = CE/CD, 65% female; mean age = 39]. The most commonly reported lesion locations were armpits (81%), groin (75%), or under the breasts (31%). Subjects reported pain (100%), drainage (100%), itching (100%), swelling/ inflammation (94%), odor (86%), tenderness (81%), heat (64%), and pressure (64%) related to their lesions. The most bothersome symptoms were pain (94%), drainage (50%), swelling/inflammation (42%), and itching (33%). Pain was the most difficult symptom to manage (53%). In general, respondents were able to paraphrase each item and found the content to be clear and relevant. The final HSSD, developed as a daily diary with a 24-hour recall period, contains 8 items evaluating severity of each symptom/sign using an 11-point numeric rating scale. A 7-day version was also developed. Conclusion: Content validity of the HSSD in patients with moderate-to-severe HS has been demonstrated. Its measurement properties will be assessed using data from upcoming clinical studies

Environment-Induced Changes in Selective Constraints on Social Learning During the Peopling of the Americas

The weaponry technology associated with Clovis and related Early Paleoindians represents the earliest well-defined evidence of humans in Pleistocene North America. We assess the technological diversity of these fluted stone points found at archaeological sites in the western and eastern halves of North America by employing statistical tools used in the quantification of ecological biodiversity. Our results demonstrate that the earliest hunters in the environmentally heterogeneous East used a more diverse set of points than those in the environmentally homogenous West. This and other evidence shows that environmental heterogeneity in the East promoted the relaxation of selective constraints on social learning and increased experimentation with point designs

Optimal Design of Experiments by Combining Coarse and Fine Measurements.

In many contexts, it is extremely costly to perform enough high-quality experimental measurements to accurately parametrize a predictive quantitative model. However, it is often much easier to carry out large numbers of experiments that indicate whether each sample is above or below a given threshold. Can many such categorical or "coarse" measurements be combined with a much smaller number of high-resolution or "fine" measurements to yield accurate models? Here, we demonstrate an intuitive strategy, inspired by statistical physics, wherein the coarse measurements are used to identify the salient features of the data, while the fine measurements determine the relative importance of these features. A linear model is inferred from the fine measurements, augmented by a quadratic term that captures the correlation structure of the coarse data. We illustrate our strategy by considering the problems of predicting the antimalarial potency and aqueous solubility of small organic molecules from their 2D molecular structure.. L. J. C. acknowledges a Next Generation fellowship and a Marie Curie CIG [Evo-Couplings, Grant No. 631609]. M. P. B. acknowledges support from the Simons Foundation and from the National Science Foundation through DMS-1715477