Implant-based immediate reconstruction in prophylactic mastectomy: is the caudal dermis flap a reliable alternative to synthetic mesh or acellular dermal matrix?

Introduction The demand for prophylactic mastectomy has increased significantly over the last 10 years. This can be explained by a substantial gain of knowledge about the clinical risk and outcome of patients with high risk mutations such as BRCA1 and 2, the improved diagnostic possibilities for detecting the genetic predisposition for the development of breast cancer and the awareness for those mutations by health care professionals as well as patients. In addition to expander-to-implant reconstruction and microsurgical flap surgery, definitive immediate reconstruction with subpectoral insertion of breast implants is often preferred. The prosthesis is covered at its inferior pole by a synthetic mesh or acellular dermal matrix. In these cases, in addition to the silicone prosthesis, a further foreign body must be implanted. This can be exposed in the event of wound healing disorder or necrosis of the usually thin soft tissue covering after subcutaneous mastectomy, thus calling into question the reconstructive result. In this study, the coverage of the lower pole by a caudal deepithelialized dermis flap, which allows the implant to be completely covered with well vascularized tissue, is compared to coverage by a synthetic mesh or acellular dermal matrix. Patients and methods From January 2014 to June 2020, 74 patients (106 breasts) underwent breast reconstruction following uni or bilateral prophylactic mastectomy. Reconstruction was performed with autologous tissue (15 breasts), with tissue expander or implant without implant support (15 breasts), with implant and use of an acellular dermal matrix or synthetic mesh (39 breasts) and with implant and caudal dermis flap (37 breasts). In this study, we compared the patients with implant and dermal matrix/mesh to the group reconstructed with implant and dermal flap. Results In the group with the caudal dermis flap, 4 patients developed skin necrosis, which all healed conservatively due to the sufficient blood supply through the dermis flap. In the group with the use of a synthetic mesh or acellular dermal matrix, skin necrosis was found in three cases. In one of these patients the implant was exposed and had to be removed. Discussion For patients with excess skin or macromastia, the caudal dermis flap is a reliable and less expensive option for complete coverage of an implant after prophylactic mastectomy. In particular, the vascularized dermis flap can protect the implant from the consequences of skin necrosis after prophylactic mastectomy

Entry Into Afferent Lymphatics and Maturation In Situ of Migrating Murine Cutaneous Dendritic Cells

An important property of dendritic cells (DC), which contributes crucially to their strong immunogenic function, is their capacity to migrate from sites of antigen capture to the draining lymphoid organs. Here we studied in detail the migratory pathway and the differentiation of DC during migration in a skin organ culture model and, for comparison, in the conventional contact hypersensitivity system. We report several observations on the capacity of cutaneous DC to migrate in mouse ear skin. (i) Upon application of contact allergens in vivo the density of Langerhans cells in epidermal sheets decreased, as determined by immunostaining for major histocompatibility complex class II, ADPase, F4/80, CD11b, CD32, NLDC-145/DEC-205, and the cytoskeleton protein vimentin. Evaluation was performed by computer assisted morphometry. (ii) Chemically related nonsensitizing or tolerizing compounds left the density of Langerhans cells unchanged. (iii) Immunohistochemical double-staining of dermal sheets from skin organ cultures for major histocompatibility complex class II and CD54 excluded blood vessels as a cutaneous pathway of DC migration. (iv) Electron microscopy of organ cultures revealed dermal accumulations of DC (including Birbeck granule containing Langerhans cells) within typical lymphatic vessels. (v) Populations of migrating DC in organ cultures upregulated markers of maturity (the antigen recognized by monoclonal antibody 2A1, CD86), but retained indicators of immaturity (invariant chain, residual antigen processing function). These data provide additional evidence that during both the induction of contact hypersensitivity and in skin organ culture, Langerhans cells physically leave the epidermis. Both Langerhans cells and dermal DC enter lymphatic vessels. DC mature while they migrate through the skin

Recommendations for the Use of Antibiotics in Primary and Secondary Esthetic Breast Surgery

The use of systemic prophylactic antibiotics to reduce surgical-site infection in esthetic breast surgery remains controversial, although the majority of surgeons prefer to utilize antibiotics to prevent infection. Nonetheless, postoperative acute and subclinical infection and capsular fibrosis are among the most common complications following implant-based breast reconstruction. After esthetic breast augmentation, up to 2.9% of women develop infection, with an incidence rate of 1.7% for acute infections and 0.8% for late infections. After postmastectomy reconstruction (secondary reconstruction), the rates are even higher. The microorganisms seen in acute infections are Gram-positive, whereas subclinical late infections involving microorganisms are typically Gram-negative and from normal skin flora with low virulence. In primary implantation, a weight-based dosing of cefazolin is adequate, an extra duration of antibiotic cover does not provide further reduction in superficial or periprosthetic infections. Clindamycin and vancomycin are recommended alternative for patients with β-lactam allergies. The spectrum of microorganism found in late infections varies (Gram-positive and Gram-negative), and the antibiotic prophylaxis (fluoroquinolones) should be extended by vancomycin and according to the antibiogram when replacing implants and in secondary breast reconstruction, to target microorganisms associated with capsular contracture. All preoperative antibiotics should be administered <60 minutes before incision to guarantee high serum levels during surgical procedure

The rocket experiment demonstration of a soft x-ray polarimeter (REDSoX Polarimeter)

The Rocket Experiment Demonstration of a Soft X-ray Polarimeter (REDSoX Polarimeter) is a sounding rocket instrument that can make the first measurement of the linear X-ray p olarization of an extragalactic source in the 0.2-0.8 keV band as low as 10%. We employ multilayer-coated mirrors as Bragg reflectors at the Brewster angle. By matching the dispersion of a spectrometer using replicated optics from MSFC and critical angle transmission gratings from MIT to three laterally graded multilayer mirrors (LGMLs), we achieve polarization modulation factors over 90%. We present a novel arrangement of gratings, designed optimally for the purpose of polarimetry with a converging beam. The entrance aperture is divided into six equal sectors; pairs of blazed gratings from opposite sectors are oriented to disperse to the same LGML. The LGML position angles are 120 degrees to each other. CCD detectors then measure the intensities of the dispersed spectra after reflection and polarizing by the LGMLs, giving the three Stokes parameters needed to determine a source's linear polarization fraction and orientation. A current grant is funding further development to improve the LGMLs. Sample gratings for the project have been fabricated at MIT and the development team continues to improve them under separate funding. Our technological approach is the basis for a possible orbital mission. Keywords: X-ray, polarimeter, astronomy, multilayer, mirror, gratingUnited States. National Aeronautics and Space Administration (Grant NNX17AE11G)United States. National Aeronautics and Space Administration (Grant NNX12AH12G)Kavli Institute for Astrophysics and Space Research (Research Investment Grant)United States. National Aeronautics and Space Administration (Grant NNX17AG43G)United States. National Aeronautics and Space Administration (Grant NNX15AC43G

A small satellite version of a soft x-ray polarimeter

We describe a new implementation of a broad-band soft X-ray polarimeter, substantially based on a previous design. This implementation, the Pioneer Soft X-ray Polarimeter (PiSoX) is a SmallSat, designed for NASA’s call for Astrophysics Pioneers, small missions that could be CubeSats, balloon experiments, or SmallSats. As in REDSoX, the grating arrangement is designed optimally for the purpose of polarimetry with broad-band focussing optics by matching the dispersion of the spectrometer channels to laterally graded multilayers (LGMLs). The system can achieve polarization modulation factors over 90%. For PiSoX, the optics are lightweight Si mirrors in a one-bounce parabolic configuration. High efficiency, blazed gratings from opposite sectors are oriented to disperse to a LGML forming a channel covering the wavelength range from 35 Å to 75 Å (165 - 350 eV). Upon satellite rotation, the intensities of the dispersed spectra, after reflection and polarizing by the LGMLs, give the three Stokes parameters needed to determine a source’s linear polarization fraction and orientation. The design can be extended to higher energies as LGMLs are developed further. We describe examples of the potential scientific return from instruments based on this design

A Small Satellite Version of a Broad-band Soft X-ray Polarimeter

We describe a new implementation of a broad-band soft X-ray polarimeter, substantially based on a previous design. This implementation, the Pioneer Soft X-ray Polarimeter (PiSoX) is a SmallSat, designed for NASA's call for Astrophysics Pioneers, small missions that could be CubeSats, balloon experiments, or SmallSats. As in the REDSoX Polarimeter, the grating arrangement is designed optimally for the purpose of polarimetry with broad-band focussing optics by matching the dispersion of the spectrometer channels to laterally graded multilayers (LGMLs). The system can achieve polarization modulation factors over 90%. For PiSoX, the optics are lightweight Si mirrors in a one-bounce parabolic configuration. High efficiency, blazed gratings from opposite sectors are oriented to disperse to a LGML forming a channel covering the wavelength range from 35 to 75 Angstroms (165 - 350 eV). Upon satellite rotation, the intensities of the dispersed spectra, after reflection and polarizing by the LGMLs, give the three Stokes parameters needed to determine a source's linear polarization fraction and orientation. The design can be extended to higher energies as LGMLs are developed further. We describe examples of the potential scientific return from instruments based on this design.Comment: 20 pages, 8 figures, to appear in Proceedings SPIE, volume 1144

Cloning and characterization of the ecto-nucleotidase NTPDase3 from rat brain: Predicted secondary structure and relation to other members of the E-NTPDase family and actin

The protein family of ecto-nucleoside triphosphate diphosphohydrolases (E-NTPDase family) contains multiple members that hydrolyze nucleoside 5’-triphosphates and nucleoside 5’-diphosphates with varying preference for the individual type of nucleotide. We report the cloning and functional expression of rat NTPDase3. The rat brain-derived cDNA has an open reading frame of 1590 bp encoding 529 amino acid residues, a calculated molecular mass of 59.1 kDa and predicted N- and C-terminal hydrophobic sequences. It shares 94.3% and 81.7% amino acid identity with the mouse and human NTPDase3, respectively, and is more closely related to cell surface-located than to the intracellularly located members of the enzyme family. The NTPDase3 gene is allocated to chromosome 8q32 and organized into 11 exons. Rat NTPDase3 expressed in CHO cells hydrolyzed both nucleoside triphosphates and nucleoside diphosphates with hydrolysis ratios of ATP:ADP of 5:1 and UTP:UDP of 8:1. After addition of ATP, ADP is formed as an intermediate product that is further hydrolyzed to AMP. The enzyme is preferentially activated by Ca2+ over Mg2+ and reveals an alkaline pH optimum. Immunocytochemistry confirmed expression of heterologously expressed NTPDase3 to the surface of CHO cells. PC12 cells express endogenous surface-located NTPDase3. An immunoblot analysis detects NTPDase3 in all rat brain regions investigated. An alignment of the secondary structure domains of actin conserved within the actin/HSP70/sugar kinase superfamily to those of all members of the NTPDase family reveals apparent similarity. It infers that NTPDases share the two-domain structure with members of this enzyme superfamily

Design of a broadband soft x-ray polarimeter

We describe an optical design and possible implementation of a broadband soft x-ray polarimeter. Our arrangement of gratings is designed optimally for the purpose of polarimetry with broadband focusing optics by matching the dispersion of the spectrometer channels to laterally graded multilayers (LGMLs). The system can achieve polarization modulation factors over 90%. We implement this design using a single optical system by dividing the entrance aperture into six sectors; high efficiency, blazed gratings from opposite sectors are oriented to disperse to a common LGML forming three channels covering the wavelength range from 35 to 75 Å (165 to 350 eV). The grating dispersions and LGML position angles for each channel are 120 deg to each other. CCD detectors then measure the intensities of the dispersed spectra after reflection and polarizing by the LGMLs, giving the three Stokes parameters needed to determine a source's linear polarization fraction and orientation. The design can be extended to higher energies as LGMLs are developed further. We describe examples of the potential scientific return from instruments based on this design

A capillary electrophoresis method for the characterization of ecto-nucleoside triphosphate diphosphohydrolases (NTPDases) and the analysis of inhibitors by in-capillary enzymatic microreaction

A capillary electrophoresis (CE) method for the characterization of recombinant NTPDases 1, 2, and 3, and for assaying NTPDase inhibitors has been developed performing the enzymatic reaction within the capillary. After hydrodynamic injection of plugs of substrate solution with or without inhibitor in reaction buffer, followed by a suspension of an enzyme-containing membrane preparation, and subsequent injection of another plug of substrate solution with or without inhibitor, the reaction took place close to the capillary inlet. After 5 min, the electrophoretic separation of the reaction products was initiated by applying a constant current of  μA. The method employing a polyacrylamide-coated capillary and reverse polarity mode provided baseline resolution of substrates and products within a short separation time of less than 7 min. A 50 mM phosphate buffer (pH 6.5) was used for the separations and the products were detected by their UV absorbance at 210 nm. The Michaelis–Menten constants (Km) for the recombinant rat NTPDases 1, 2, and 3 obtained with this method were consistent with previously reported data. The inhibition studies revealed pronounced differences in the potency of reactive blue 2, pyridoxalphosphate-6-azophenyl-2-4-disulfonic acid (PPADS), suramin, and N6-diethyl-β,γ-dibromomethylene-ATP (ARL67156) towards the NTPDase isoforms. Notably, ARL67156 does not inhibit all NTPDases, having only a minor inhibitory effect on NTPDase2. Dipyridamole is not an inhibitor of the NTPDase isoforms investigated. The new method is fast and accurate, it requires only tiny amounts of material (nanoliter scale), no sample pretreatment and can be fully automated; thus it is clearly superior to the current standard methods