Use of Absorbable Dermal Staples in Bilateral Breast Reduction Surgery: Effects on Operative Times, Surgical Outcomes, and Procedure Charges.

BACKGROUND: Use of the absorbable deep dermal stapler in wound closure has become more common in plastic surgery because of its possible reduction in operative times and subsequent decrease in operative room costs. In this study, we examine the effects of this stapler on operative times and postoperative complications in bilateral reduction mammaplasties. METHODS: A retrospective, observational cohort study was conducted via electronic chart review on patients who underwent bilateral reduction mammaplasties. Patients were stratified by wound closure method. One group was closed with sutures only, and in the other group, deep dermal staples were used during closure of the inframammary fold incision. Incidences of patient comorbidities and postoperative complications were compared. In addition, a financial cost analysis was performed. RESULTS: The final patient cohort included 62 patients. Operative time was reduced by an average of 21.8 minutes when using deep dermal staples during closure, compared with when closing solely with sutures (P = 0.032). When controlling for mass of breast tissue removed and type of pedicle, deep dermal staple closure still predicted a reduction of 26.5 (SE, 9.9) minutes in operative time (P = 0.010). Postoperative complications were not affected by wound closure method (odds ratio, 4.36; 95% confidence interval, 0.91-31.7, P = 0.087). Though not statistically significant, financial charge was decreased with usage of deep dermal staples (P = 0.34). CONCLUSIONS: Use of absorbable deep dermal staples produces a significant decrease in operative time for reduction mammaplasties with no increase in postoperative complication rates.

Accessing Mg-Ion Storage in V2PS10 via Combined Cationic-Anionic Redox with Selective Bond Cleavage.

Magnesium batteries attract interest as alternative energy-storage devices because of elemental abundance and potential for high energy density. Development is limited by the absence of suitable cathodes, associated with poor diffusion kinetics resulting from strong interactions between Mg2+ and the host structure. V2PS10 is reported as a positive electrode material for rechargeable magnesium batteries. Cyclable capacity of 100 mAh g-1 is achieved with fast Mg2+ diffusion of 7.2 × ${\times }$ 10-11-4 × ${\times }$ 10-14 cm2 s-1. The fast insertion mechanism results from combined cationic redox on the V site and anionic redox on the (S2)2- site; enabled by reversible cleavage of S-S bonds, identified by X-ray photoelectron and X-ray absorption spectroscopy. Detailed structural characterisation with maximum entropy method analysis, supported by density functional theory and projected density of states analysis, reveals that the sulphur species involved in anion redox are not connected to the transition metal centres, spatially separating the two redox processes. This facilitates fast and reversible Mg insertion in which the nature of the redox process depends on the cation insertion site, creating a synergy between the occupancy of specific Mg sites and the location of the electrons transferred.

Reducing Peri-implant Capsule Thickness in Submuscular Rodent Model of Breast Reconstruction With Delayed Radiotherapy.

INTRODUCTION: Capsular contracture remains the most common complication following device-based breast reconstruction, occurring in up to 50% of women who also undergo adjuvant radiotherapy either before or after device-based reconstruction. While certain risk factors for capsular contracture have been identified, there remains no clinically effective method of prevention. The purpose of the present study is to determine the effect of coating the implant with the novel small molecule Met-Z2-Y12, with and without delayed, targeted radiotherapy, on capsule thickness and morphologic change around smooth silicone implants placed under the latissimus dorsi in a rodent model. METHODS: Twenty-four female Sprague Dawley rats each had 2 mL smooth round silicone breast implants implanted bilaterally under the latissimus dorsi muscle. Twelve received uncoated implants and twelve received implants coated with Met-Z2-Y12. Half of the animals from each group received targeted radiotherapy (20 Gray) on postoperative day ten. At three and 6 months after implantation, the tissue surrounding the implants was harvested for analysis of capsular histology including capsule thickness. Additionally, microCT scans were qualitatively analyzed for morphologic change. RESULTS: Capsules surrounding Met-Z2-Y12-coated implants were significantly thinner (P = 0.006). The greatest difference in capsule thickness was seen in the irradiated 6-month groups, where mean capsule thickness was 79.1 ± 27.3 µm for uncoated versus 50.9 ± 9.6 µm for Met-Z2-Y12-coated implants (P = 0.038). At the time of explant, there were no capsular morphologic differences between the groups either grossly or per microCT. CONCLUSIONS: Met-Z2-Y12 coating of smooth silicone breast implants significantly reduces capsule thickness in a rodent model of submuscular breast reconstruction with delayed radiotherapy.

BrainLine: An Open Pipeline for Connectivity Analysis of Heterogeneous Whole-Brain Fluorescence Volumes.

Whole-brain fluorescence images require several stages of computational processing to fully reveal the neuron morphology and connectivity information they contain. However, these computational tools are rarely part of an integrated pipeline. Here we present BrainLine, an open-source pipeline that interfaces with existing software to provide registration, axon segmentation, soma detection, visualization and analysis of results. By implementing a feedback based training paradigm with BrainLine, we were able to use a single learning algorithm to accurately process a diverse set of whole-brain images generated by light-sheet microscopy. BrainLine is available as part of our Python package brainlit: http://brainlit.neurodata.io/ .

Microsurgical Head and Neck Reconstruction in Patients With Fanconi Anemia.

ABSTRACT: Patients with Fanconi anemia (FA) are at increased risk for head and neck cancers that often necessitate extensive reconstructions. Such patients have multiple comorbidities including anemia and thrombocytopenia frequently requiring bone marrow transplant, and they are at an increased risk of cancer recurrence and need for further extirpation. in the present study, charts from 3 patients with FA who underwent microvascular free tissue transfer by the senior author were retrospectively reviewed for pertinent pre- and peri-operative details in addition to functional and cosmetic outcomes. Two of these patients ultimately required metachronous free flap reconstructions for recurrence. All patients had acceptable functional and cosmetic outcomes following each instance of free flap reconstruction, thereby demonstrating the utility of microvas- cular free tissue transfer in patients with FA. The authors herein present each patient's clinical history in addition to a discussion of the current literature and an outline of our approach to these challenging cases.

Topical α-Gal Nanoparticles Enhance Wound Healing in Radiated Skin.

PURPOSE: Surgery within radiated tissue is associated with increased complication rates. It is hypothesized that impaired wound healing may result from aberrant inflammatory responses that occur in previously radiated tissues. Previous work has demonstrated that the topical application of naturally occurring antigen α-gal (Galα1-3Galß1-(3)4GlcNAc-R) nanoparticles (AGNs) within wounds accelerates macrophage recruitment and subsequent healing in both normal and diabetic wounds. Herein, we hypothesize that application of this antigen would similarly enhance wound healing in irradiated tissues. METHODS: To simulate human physiology, α-1,3-galactosyltransferase knockout (KO) mice were exposed to the antigen to produce anti-α-gal antibodies (anti-Gal). Ten days prior to wounding, the dorsal skin was irradiated with 1 session of 40 Gy. Bilateral dorsal 6-mm splinted full-thickness wounds were created within the radiated skin and treated with 50 µL of AGNs (50 mg/mL) immediately after wounding and again on postoperative day 1. A control KO group underwent similar irradiation and wounding protocols but was treated with phosphate-buffered saline (PBS) vehicle. Wild-type (WT) mice, which do not produce anti-Gal, went through the same irradiation and wounding. RESULTS: Histologic analysis demonstrated enhanced epithelial migration in the radiated/AGN-treated KO wounds, which was significantly elevated in comparison to radiated/PBS-treated KO wounds beginning by day 15 and continuing until the end of the study (p < 0.01). In WT mice, treatment with AGNs showed no effect on epithelial migration. CONCLUSIONS: Topical application of AGNs onto irradiated wounds significantly ameliorates the delayed wound healing classically seen in radiated skin and results in faster wound closure with only transient application.

Primary Cleft Rhinoplasty: Long-Term Outcomes of a Single Technique Used Over 2 Decades.

BACKGROUND: Primary cleft rhinoplasty has become widely accepted owing to evidence of improved outcomes and need for fewer revisions. Several techniques have been described, but few surgeons have reported long-term outcomes of repairs performed via a single method. The present study examines long-term outcomes of a single surgeon's experience over 22 years using the same primary cleft rhinoplasty technique. METHODS: All consecutive cases of primary cleft rhinoplasty performed by the senior author at the time of unilateral cleft lip repair from 1996 to 2018 were selected for retrospective review. Patients older than 3 years or lacking documented follow-up were excluded. The primary outcome was the need for secondary rhinoplasty at age 15 years or later. RESULTS: Fifty-six patients met inclusion criteria. Median follow-up time was 7.52 years (interquartile range, 1.38-14.82). Twelve patients required minor long-term lip revision. No school-aged patients required additional correction of the nasal deformity before beginning school. Fifteen patients had follow-up beyond 14 years of age, 5 of whom had undergone definitive rhinoplasties as adolescents (8.9% of cohort; 33.3% of patients with follow-up beyond 14 years). Of the remaining 10 patients older than 14 years at last follow-up, none were seeking additional rhinoplasty. CONCLUSIONS: This series represents one of the longest-running published experiences of primary cleft rhinoplasty. Using a technique that requires no nasal incisions, the senior author has had excellent long-term results, with no need for any elementary school age rhinoplasties and with the majority of patients with follow-up older than 14 years not requiring a rhinoplasty in adolescence.

Nipple Engineering: Maintaining Nipple Geometry with Externally Scaffolded Processed Autologous Costal Cartilage.

INTRODUCTION: Nipple reconstruction is the essential last step of breast reconstruction after total mastectomy, resulting in improved general and aesthetic satisfaction. However, most techniques are limited by secondary scar contracture and loss of neo-nipple projection leading to patient dissatisfaction. Approximately, 16,000 patients undergo autologous flap breast reconstruction annually, during which the excised costal cartilage (CC) is discarded. We propose utilizing processed CC placed within biocompatible 3D-printed external scaffolds to generate tissue cylinders that mimic the shape, size and biomechanical properties of native human nipple tissue while mitigating contracture and projection loss. METHODS: External scaffolds were designed and then 3D-printed using polylactic acid (PLA). Patient-derived CC was processed by mincing or zesting, then packed into the scaffolds, implanted into nude rats and explanted after 3 months for volumetric, histologic and biomechanical analyses. Similar analyses were performed on native human nipple tissue and unprocessed CC. RESULTS: After 3 months in vivo, gross analysis demonstrated significantly greater preservation of contour, projection and volume of the scaffolded nipples. Mechanical analysis demonstrated that processing of the cartilage resulted in implant equilibrium modulus values closer to that of the human nipple. Histologic analysis showed the presence of healthy and viable cartilage after 3 months in vivo, invested with fibrovascular tissue. CONCLUSIONS: Autologous CC can be processed intraoperatively and placed within biocompatible external scaffolds to mimic the shape and biomechanical properties of the native human nipple. This allows for custom design and fabrication of individualized engineered autologous implants tailored to patient desire, without the loss of projection seen with traditional approaches.

One Site, Two Cations, Three Environments: s2 and s0 Electronic Configurations Generate Pb-Free Relaxor Behavior in a Perovskite Oxide.

The piezoelectric devices widespread in society use noncentrosymmetric Pb-based oxides because of their outstanding functional properties. The highest figures of merit reported are for perovskites based on the parent Pb(Mg1/3Nb2/3)O3 (PMN), which is a relaxor: a centrosymmetric material with local symmetry breaking that enables functional properties, which resemble those of a noncentrosymmetric material. We present the Pb-free relaxor (K1/2Bi1/2)(Mg1/3Nb2/3)O3 (KBMN), where the thermal and (di)electric behavior emerges from the discrete structural roles of the s0 K+ and s2 Bi3+ cations occupying the same A site in the perovskite structure, as revealed by diffraction methods. This opens a distinctive route to Pb-free piezoelectrics based on relaxor parents, which we demonstrate in a solid solution of KBMN with the Pb-free ferroelectric (K1/2Bi1/2)TiO3, where the structure and function evolve together, revealing a morphotropic phase boundary, as seen in PMN-derived systems. The detailed multiple-length-scale understanding of the functional behavior of KBMN suggests that precise chemical manipulation of the more diverse local displacements in the Pb-free relaxor will enhance performance.

Muscle Flap Closure following Complex Spine Surgery: A Decade of Experience.

BACKGROUND: Advances in surgical technology and adjuvant therapies along with an aging and increasingly morbid U.S. population have led to an increase in complex spine surgery. With this increase comes an elevated risk of complications, including those related to the surgical wound, with some studies demonstrating wound complication incidences approaching 45 percent. The authors hypothesize that immediate muscle flap closure improves outcomes in high-risk patients. METHODS: Three hundred one consecutive index cases of spinal wound closure using local muscle flaps performed by the senior author at a single institution between 2006 and 2018 were reviewed. The primary outcome was major wound complication (reoperation and/or readmission because of surgical-site infection, late infection, dehiscence, seroma, or hematoma). Logistic regression analysis was performed to identify predictors of this endpoint. RESULTS: Major wound complications occurred in 6.6 percent of patients (reoperation, 3.6 percent; readmission, 3.0 percent), with a 6.0 percent infection rate and five cases requiring instrumentation removal because of infection. Risk factors identified included radiotherapy (OR, 5.9; p = 0.004), age 65 years or older (OR, 2.8; p = 0.046), and prior spine surgery (OR, 4.3; p = 0.027). The incidence of major wound complication increased dramatically with each additional risk factor. Mean drain dwell duration was 21.1 ± 10.0 days and not associated with major wound complications, including infection (OR, 1.04; p = 0.112). CONCLUSIONS: Immediate local muscle flap closure following complex spine surgery on high-risk patients is associated with an acceptable rate of wound complications and, as these data demonstrate, is safe and effective. Consideration should be given to immediate muscle flap closure in appropriately selected patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Periprosthetic Capsule Formation and Contracture in a Rodent Model of Implant-Based Breast Reconstruction With Delayed Radiotherapy.

INTRODUCTION: Capsular contracture (CC) is the most common complication of breast implantation, with an incidence of nearly 50% in patients undergoing breast reconstruction with subsequent radiotherapy. Although the move toward submuscular (SM) device placement led to a decreased incidence of CC, subcutaneous (SQ) implantation has seen a resurgence. The purpose of this study was to use a rodent model of breast reconstruction with smooth silicone implants and delayed radiotherapy to assess the occurrence of CC in SQ versus SM implantation. METHODS: Custom 2 mL smooth round silicone implants were placed bilaterally into 12 female Sprague Dawley rats that were randomized into 4 groups of 3, with each group differing by implantation plane (SQ vs SM) and irradiation status (irradiated vs nonirradiated). Rats from the SQ group received implants bilaterally underlying the skin on the flank. Rats in the SM groups received implants bilaterally under the latissimus dorsi muscle. Irradiated rats received 20 Gy localized to each implant on postoperative day 10. One rat from each group was imaged with a micro-computed tomography scanner at baseline and at explant 3 months later, whereupon capsules from all rats were examined histologically. RESULTS: Rats in the SQ group showed evidence of contracture on gross examination and greater evidence of morphologic disruption per micro-computed tomography scan. There was no evidence of contracture or morphologic disruption in either SM group. Mean ± SD capsule thickness was 39.0 ± 9.0 µm in the SQ versus 37.6 ± 9.8 µm in the SM nonirradiated groups and 43.9 ± 14.9 µm in the SQ versus 34.3 ± 8.3 µm in the SM irradiated groups (all P > 0.05). CONCLUSIONS: In a rodent model of smooth silicone breast implantation and delayed radiotherapy, although there did not appear to be differences in capsule thickness regardless of device placement plane, SQ implants demonstrated gross evidence of CC. These data indicate that capsule thickness is only part of a larger pathogenetic picture, which should take into consideration the contribution from all peri-implant tissue.

Three-dimensional intact-tissue sequencing of single-cell transcriptional states.

Retrieving high-content gene-expression information while retaining three-dimensional (3D) positional anatomy at cellular resolution has been difficult, limiting integrative understanding of structure and function in complex biological tissues. We developed and applied a technology for 3D intact-tissue RNA sequencing, termed STARmap (spatially-resolved transcript amplicon readout mapping), which integrates hydrogel-tissue chemistry, targeted signal amplification, and in situ sequencing. The capabilities of STARmap were tested by mapping 160 to 1020 genes simultaneously in sections of mouse brain at single-cell resolution with high efficiency, accuracy, and reproducibility. Moving to thick tissue blocks, we observed a molecularly defined gradient distribution of excitatory-neuron subtypes across cubic millimeter-scale volumes (>30,000 cells) and a short-range 3D self-clustering in many inhibitory-neuron subtypes that could be identified and described with 3D STARmap.

Anxiety Cells in a Hippocampal-Hypothalamic Circuit.

The hippocampus is traditionally thought to transmit contextual information to limbic structures where it acquires valence. Using freely moving calcium imaging and optogenetics, we show that while the dorsal CA1 subregion of the hippocampus is enriched in place cells, ventral CA1 (vCA1) is enriched in anxiety cells that are activated by anxiogenic environments and required for avoidance behavior. Imaging cells defined by their projection target revealed that anxiety cells were enriched in the vCA1 population projecting to the lateral hypothalamic area (LHA) but not to the basal amygdala (BA). Consistent with this selectivity, optogenetic activation of vCA1 terminals in LHA but not BA increased anxiety and avoidance, while activation of terminals in BA but not LHA impaired contextual fear memory. Thus, the hippocampus encodes not only neutral but also valence-related contextual information, and the vCA1-LHA pathway is a direct route by which the hippocampus can rapidly influence innate anxiety behavior.

The three-dimensional architecture of a bacterial genome and its alteration by genetic perturbation.

We have determined the three-dimensional (3D) architecture of the Caulobacter crescentus genome by combining genome-wide chromatin interaction detection, live-cell imaging, and computational modeling. Using chromosome conformation capture carbon copy (5C), we derive ~13 kb resolution 3D models of the Caulobacter genome. The resulting models illustrate that the genome is ellipsoidal with periodically arranged arms. The parS sites, a pair of short contiguous sequence elements known to be involved in chromosome segregation, are positioned at one pole, where they anchor the chromosome to the cell and contribute to the formation of a compact chromatin conformation. Repositioning these elements resulted in rotations of the chromosome that changed the subcellular positions of most genes. Such rotations did not lead to large-scale changes in gene expression, indicating that genome folding does not strongly affect gene regulation. Collectively, our data suggest that genome folding is globally dictated by the parS sites and chromosome segregation.

Choreography of the transcriptome, photophysiology, and cell cycle of a minimal photoautotroph, prochlorococcus.

The marine cyanobacterium Prochlorococcus MED4 has the smallest genome and cell size of all known photosynthetic organisms. Like all phototrophs at temperate latitudes, it experiences predictable daily variation in available light energy which leads to temporal regulation and partitioning of key cellular processes. To better understand the tempo and choreography of this minimal phototroph, we studied the entire transcriptome of the cell over a simulated daily light-dark cycle, and placed it in the context of diagnostic physiological and cell cycle parameters. All cells in the culture progressed through their cell cycles in synchrony, thus ensuring that our measurements reflected the behavior of individual cells. Ninety percent of the annotated genes were expressed, and 80% had cyclic expression over the diel cycle. For most genes, expression peaked near sunrise or sunset, although more subtle phasing of gene expression was also evident. Periodicities of the transcripts of genes involved in physiological processes such as in cell cycle progression, photosynthesis, and phosphorus metabolism tracked the timing of these activities relative to the light-dark cycle. Furthermore, the transitions between photosynthesis during the day and catabolic consumption of energy reserves at night- metabolic processes that share some of the same enzymes--appear to be tightly choreographed at the level of RNA expression. In-depth investigation of these patterns identified potential regulatory proteins involved in balancing these opposing pathways. Finally, while this analysis has not helped resolve how a cell with so little regulatory capacity, and a 'deficient' circadian mechanism, aligns its cell cycle and metabolism so tightly to a light-dark cycle, it does provide us with a valuable framework upon which to build when the Prochlorococcus proteome and metabolome become available.

Introduction to DICOM for the practicing veterinarian.

Digital Imaging and Communication in Medicine (DICOM) is a communication protocol that imaging devices use to communicate. The universal acceptance of the DICOM standard by the major medical vendors means that the digital transition in veterinary medicine should be relatively smooth provided DICOM is used. DICOM service objects, roles, service classes, and conformance standards are discussed. The authors strongly encourage the use of image acquisition software and image archive systems that support the DICOM standard.

Chromosomal periodicity of evolutionarily conserved gene pairs.

Chromosomes are compacted hundreds of times to fit in the cell, packaged into dynamic folds whose structures are largely unknown. Here, we examine patterns in gene locations to infer large-scale features of bacterial chromosomes. Specifically, we analyzed >100 genomes and identified thousands of gene pairs that display two types of evolutionary correlations: a tendency to co-occur and a tendency to be located close together in many genomes. We then analyzed the detailed distribution of these pairs in Escherichia coli and found that genes in a pair tend to be separated by integral multiples of 117 kb along the genome and to be positioned in a 117-kb grid of genomic locations. In addition, the most pair-dense locations coincide with regions of intense transcriptional activity and the positions of top transcribed and conserved genes. These patterns suggest that the E. coli chromosome may be organized into a 117-kb helix-like topology that localizes a subset of the most essential and highly transcribed genes along a specific face of this structure. Our approach indicates an evolutionarily maintained preference in the spacing of genes along the chromosome and offers a general comparative genomics framework for studying chromosome structure, broadly applicable to other organisms.