Acellular Dermal Matrices and Radiotherapy in Breast Reconstruction: A Systematic Review and Meta-Analysis of the Literature

The increasing use of commercially available acellular dermis matrices for postmastectomy breast reconstruction seems to have simplified the surgical procedure and enhanced the outcome. These materials, generally considered to be highly safe or with only minor contraindications due to the necessary manipulation in preparatory phases, allow an easier one-phase surgical procedure, in comparison with autologous flaps, offering a high patient satisfaction. Unfortunately, the claim for a higher rate of complications associated with irradiation at the implant site, especially when the radiation therapy was given before the reconstructive surgery, suggested a careful behaviour when this technique is preferred. However, this hypothesis was never submitted to a crucial test, and data supporting it are often discordant or incomplete. To provide a comprehensive analysis of the field, we searched and systematically reviewed papers published after year 2005 and registered clinical trials. On the basis of a meta-analysis of data, we conclude that the negative effect of the radiotherapy on the breast reconstruction seems to be evident even in the case of acellular dermis matrices aided surgery. However, more trials are needed to make solid conclusions and clarify the poor comprehension of all the factors negatively influencing outcome

Platelet aggregation studies: autologous platelet-poor plasma inhibits platelet aggregation when added to platelet-rich plasma to normalize platelet count

Adjusting platelet count (PC) in platelet-rich plasma (PRP) using platelet-poor plasma (PPP) is recommended for platelet aggregation (PA) studies, but it could also affect PA independently of the decrease in PC. Analysis of aggregation tracings from healthy controls showed that PC correlated with PA in 47 diluted-PRPs, but not in 104 undiluted-PRPs. Dilution of 9 PRPs with PPP progressively decreased PA, while dilution of washed platelets with buffer hardly affected PA. Apyrase partially prevented the inhibitory effect of PPP. Therefore, the practice of diluting PRP with PPP to adjust platelet count should be avoided because it artefactually inhibits PA

Shear stress reverses dome formation in confluent renal tubular cells.

It has been shown that MDCK cells, a cell line derived from canine renal tubules, develop cell domes due to fluid pumped under cell monolayer and focal detachment from the adhesion surface. In vitro studies have shown that primary cilia of kidney tubular epithelial cells act as mechanosensors, increasing intracellular calcium within seconds upon changes in fluid shear stress (SS) on cell membrane. We then studied the effect of prolonged SS exposure on cell dome formation in confluent MDCK cell monolayers.A parallel plate flow chamber was used to apply laminar SS at 2 dynes/cm(2) to confluent cell monolayers for 6 hours. Control MDCK cell monolayers were maintained in static condition. The effects of Ca(2+) blockade and cell deciliation on SS exposure were also investigated.Seven days after reaching confluence, static cultures developed liquid filled domes, elevating from culture plate. Exposure to SS induced almost complete disappearance of cell domes (0.4±0.8 vs. 11.4±2.8 domes/mm(2), p0.01, n=14). SS induced dome disappearance took place within minutes to hours, as shown by time-lapse videomicroscopy. Exposure to SS importantly affected cell cytoskeleton altering actin stress fibers expression and organization, and the distribution of tight junction protein ZO-1. Dome disappearance induced by flow was completely prevented in the presence of EGTA or after cell deciliation.These data indicate that kidney tubular cells are sensitive to apical flow and that these effects are mediated by primary cilia by regulation of Ca(2+) entry in to the cell. SS induced Ca(2+) entry provokes contraction of cortical actin ring that tenses cell-cell borders and decreases basal stress fibers. These processes may increase paracellular permeability and decrease basal adhesion making dome disappear. Elucidation of the effects of apical fluid flow on tubular cell function may open new insights on the pathophysiology of kidney diseases associated with cilia dysfunction

Neuroantibodies: Ectopic expression of a recombinant anti-substance P antibody in the central nervous system of transgenic mice

AbstractRecombinant antibodies are efficiently secreted by cells of the nervous system. Thus, their local expression in the CNS of transgenic mice could be used to perturb the function of the corresponding antigen. As a first application of this approach, we have generated transgenic mice that express antibodies against the neuropeptide substance P, under the transcriptional control of the promoter of the neuronal gene vgf. The transgenic antibodies are expressed in a tissue-specific and developmentally regulated manner and are effective in competing with the endogenous substance P, as demonstrated by a marked Inhibition of neurogenic inflammation and by motor deficits. This phenotypic knockout approach may provide a complementary alternative to gene knockout by homologous recombination

A functional variant in the serotonin receptor 7 gene (HTR7), rs7905446, is associated with good response to SSRIs in bipolar and unipolar depression.

Predicting antidepressant response has been a clinical challenge for mood disorder. Although several genome-wide association studies have suggested a number of genetic variants to be associated with antidepressant response, the sample sizes are small and the results are difficult to replicate. Previous animal studies have shown that knockout of the serotonin receptor 7 gene (HTR7) resulted in an antidepressant-like phenotype, suggesting it was important to antidepressant action. In this report, in the first stage, we used a cost-effective pooled-sequencing strategy to sequence the entire HTR7 gene and its regulatory regions to investigate the association of common variants in HTR7 and clinical response to four selective serotonin reuptake inhibitors (SSRIs: citalopram, paroxetine, fluoxetine and sertraline) in a retrospective cohort mainly consisting of subjects with bipolar disorder (n = 359). We found 80 single-nucleotide polymorphisms (SNPs) with false discovery rate < 0.05 associated with response to paroxetine. Among the significant SNPs, rs7905446 (T/G), which is located at the promoter region, also showed nominal significance (P < 0.05) in fluoxetine group. GG/TG genotypes for rs7905446 and female gender were associated with better response to two SSRIs (paroxetine and fluoxetine). In the second stage, we replicated this association in two independent prospective samples of SSRI-treated patients with major depressive disorder: the MARS (n = 253, P = 0.0169) and GENDEP studies (n = 432, P = 0.008). The GG/TG genotypes were consistently associated with response in all three samples. Functional study of rs7905446 showed greater activity of the G allele in regulating expression of HTR7. The G allele displayed higher luciferase activity in two neuronal-related cell lines, and estrogen treatment decreased the activity of only the G allele. Electrophoretic mobility shift assay suggested that the G allele interacted with CCAAT/enhancer-binding protein beta transcription factor (TF), while the T allele did not show any interaction with any TFs. Our results provided novel pharmacogenomic evidence to support the role of HTR7 in association with antidepressant response

Intracellular calcium changes induced by the endozepine triakontatetraneuropeptide in human polymorphonuclear leukocytes: role of protein kinase C and effect of calcium channel blockers

BACKGROUND: The endozepine triakontatetraneuropeptide (TTN) induces intracellular calcium ([Ca(++)](i)) changes followed by activation in human polymorphonuclear leukocytes (PMNs). The present study was undertaken to investigate the role of protein kinase (PK) C in the modulation of the response to TTN by human PMNs, and to examine the pharmacology of TTN-induced Ca(++ )entry through the plasma membrane of these cells. RESULTS: The PKC activator 12-O-tetradecanoylphorbol-13-acetate (PMA) concentration-dependently inhibited TTN-induced [Ca(++)](i )rise, and this effect was reverted by the PKC inhibitors rottlerin (partially) and Ro 32-0432 (completely). PMA also inhibited TTN-induced IL-8 mRNA expression. In the absence of PMA, however, rottlerin (but not Ro 32-0432) per se partially inhibited TTN-induced [Ca(++)](i )rise. The response of [Ca(++)](i )to TTN was also sensitive to mibefradil and flunarizine (T-type Ca(++)-channel blockers), but not to nifedipine, verapamil (L-type) or ω-conotoxin GVIA (N-type). In agreement with this observation, PCR analysis showed the expression in human PMNs of the mRNA for all the α1 subunits of T-type Ca(++ )channels (namely, α1G, α1H, and α1I). CONCLUSIONS: In human PMNs TTN activates PKC-modulated pathways leading to Ca(++ )entry possibly through T-type Ca(++ )channels

The Importance of Satellite Quenching for the Build-Up of the Red Sequence of Present Day Galaxies

In the current paradigm, red sequence galaxies are believed to have formed as blue disk galaxies that subsequently had their star formation quenched. Since red-sequence galaxies typically have an early-type morphology, the transition from the blue to the red sequence also involves a morphological transformation. In this paper we study the impact of transformation mechanisms that operate only on satellite galaxies, such as strangulation, ram-pressure stripping and galaxy harassment. Using a large galaxy group catalogue constructed from the SDSS, we compare the colors and concentrations of satellites galaxies to those of central galaxies of the same stellar mass, adopting the hypothesis that the latter are the progenitors of the former. On average, satellites are redder and more concentrated than central galaxies of the same stellar mass. Central-satellite pairs that are matched in both stellar mass and color, however, show no average concentration difference, indicating that the transformation mechanisms affect color more than morphology. The color and concentration differences of matched central-satellite pairs are completely independent of the halo mass of the satellite galaxy, indicating that satellite-specific transformation mechanisms are equally efficient in haloes of all masses. This strongly favors strangulation as the main quenching mechanism for satellite galaxies. Finally, we determine the relative importance of satellite quenching for the build-up of the red sequence. We find that roughly 70 percent of red sequence satellite galaxies with a stellar mass of 10^9 Msun had their star formation quenched as satellites. This drops rapidly to zero with increasing stellar mass, indicating that a significant fraction of red satellites were already quenched before they became a satellite.Comment: 14 pages, 10 figures. Submitted for publication in MNRA

Do freshwater gastropods avoid the benthic cyanobacterium Lyngbya wollei?

We experimentally assessed the mechanisms underlying the reduction in gastropod abundance in areas dominated by the filamentous, toxin-producing cyanobacterium Lyngbya wollei, which has replaced the large beds of Vallisneria americana in some areas of the St. Lawrence River. We hypothesized that the reduction in gastropod abundance was due to adult avoidance of cyanobacterial mats in favour of filamentous chlorophytes or vascular macrophytes. Of the 4 gastropod taxa offered a choice between L. wollei and filamentous chlorophytes, 3 (Pleurocera acuta, Amnicola limosa, and Gyraulus parvus) were either indifferent or even attracted to the cyanobacterium, and only Viviparus sp. preferred the chlorophytes. Lyngbya wollei exhibited higher nitrogen (N) contents (5–6%) and a lower carbon to nitrogen (C:N) ratio (6.1–7.6) than filamentous chlorophytes (3–5% N, C:N ratio 8.2–11.6). When offered a choice between L. wollei and the ribbon-leaved V. americana supporting either natural or partially removed epiphyte cover, P. acuta and A. limosa preferred the macrophyte with its natural epiphyte cover. Epiphytes on V. americana were twice as abundant and had a lower C:N ratio than natural epiphytes on L. wollei. Additional experiments exposing juvenile Bithynia tentaculata and Physa gyrina to different filamentous substrata showed similar growth but lower survival when gastropods were reared with L. wollei rather than with chlorophytes. Overall, our results showed that direct avoidance of L. wollei by adult gastropods did not explain their decline in areas dominated by cyanobacterial mats. Instead, gastropod decline likely resulted from habitat degradation coincident with reduced macrophyte abundance combined with decreased survival of juveniles exposed to L. wollei