Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL): Breast Imaging Perspective

Breast implant-associated anaplastic large cell lymphoma is a rare disease first described in 1997. Since then, its incidence has continued to increase. Current estimated lifetime risk in women with textured breast implants range from 1:1000 to 1:30,000. Most cases present with rapid and dramatic breast swelling resulting from peri-implant fluid collection. Palpable mass, pain, and skin lesions also occur. A high index of suspicion in patients who develop a seroma around the breast implant more than one year after implant placement is required. The combination of clinical history, physical exam findings, and appropriate imaging workup can lead to a timely and accurate diagnosis. The disease has excellent prognosis when it is diagnosed earlier, and complete surgery is performed. Radiologists, particularly those involved in breast imaging, can play an essential role in early diagnosis. This chapter presents an overview of the disease, including relevant imaging findings

Synthesis of fluorescent dendrimeric antigen efficiently internalized by human dendritic cells

A new fluorescent dendrimeric antigen (DeAn) based on a dendron with amoxicilloyl terminal groups has been synthetized. The synthesis implies a novel class of all-aliphatic polyamide dendrimer (BisAminoalkylPolyAmide Dendrimers, or BAPAD).[1] The introduction of a cystamine core allows the incorporation of this dendrons into a 1,8-naphthalimide fluorofore functionalized with a maleimide group. The fluorescence properties of this DeAn has been studied and compared with the properties of an equivalent dendron possessing amino-terminal groups. This DeAn has been used as a synthetic antigen in a biomedical assay that tests the amoxicillin sensitivity of dendritic cells (DC) from tolerant and allergic patients.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Synthesis of fluorescent BAPAD dendrimeric structrures for biomedical applications

Comunicación oral presentada en el Congreso IV Encuentro sobre Dendrímeros, Santiago de Compostela, 2014In this work, we present the synthesis and characterization of BAPAD1 fluorescent Dendrimeric-Antigens (DeAn), to study the dendritic cell maturation as a test to detect drug allergy reactions. Recently our research group developed a new kind of dendrimer, called BAPAD1, that we have used in this work to obtain the dendrimeric moiety of the target molecule. To this avail we synthesized a generation two BAPAD dendrimer using cystamine as core. Then, the free amine groups on the surface of the dendrimer were functionalized with an amoxiciloyl group (AXO), the allergenic determinant to the beta-lactam antibiotic amoxicillin. By the reduction of the disulfur bond we obtained two dendrons with a thiol group in the focal point, useful to attach a fluorescent probe. We synthesize as fluorescent moiety a naphthalimide derivative with a maleimide group upon which the thiol group of the dendron is added by a click reaction.2 In this way we obtained the target molecule to be used in the basophil activation test. The fluorescent DeAn (F-DeAn) has been fully characterized by NMR and MS techniques, and their fluorescent properties well established in aqueous biological media. The fluorescent dendron without the haptenic moieties at the periphery has been also obtained and fully characterized as a control assay. Both molecules have been also characterized using molecular dynamics simulation calculations. We show also here how these dendrimeric structures interact with dendritic cells and are internalized by them.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Managing with (fluorescent)-biomimetic dendrimers

Dendrimers that are modified through their peripheral groups have been employed for many biomedical purposes. Diagnosis via specific interactions with target proteins is one of the objectives that has been given more attention. In this way, we have been developing different methodologies for the detection of immunoglobulins, as an in vitro method for the diagnosis of allergic reactions to drugs [1], [2]. Specific cell interactions of surfaces grafted dendrimers have been applied to the study of cell adhesion. We have studied also the application of dendrimer-based uneven nanopatterns to evaluate the local RGD surface density effects on cell adhesion, as bioactive substrates to evaluate the impact of the RGD local surface density on the chondrogenic induction of adult human mesenchymal stem cells [3], [4], [5]. Although the use of PAMAM dendrimer has allowed us to develop useful methods for this purpose, for certain objectives we have required the development of new dendrimeric models. We have developed a new approach for the production of allaliphatic polyamide dendrimers (BAPAD) by iterative 3,3′-diaminopivalic acid connections as building blocks for dendrimer construction. These dendrimers were studied in explicit solvent by atomistic forcefield-based molecular dynamics to characterize structural properties such as shape, radius and monomer distribution [6]. Fluorescent labeling of these biomimetic dendrimers has been used as a tool to study their interaction with cells.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Preparation, photophysical properties and cell image of Naphthalimide-based fluorescent nanostructures for biomedical applications: BAPAD dendrimeric antigens and silica nanoparticles

We present here the synthesis and characterization of BAPAD [1] fluorescent Dendrimeric-Antigens (DeAn), to be applied in basophil activation as a test to detect drug allergy reactions. A second generation BAPAD dendrimer using cystamine as core that can be reducced to obtain two dendrons with a thiol group in the focal point, useful to attach a fluorescent probe, have been synthesized. The free amine groups on the surface of the dendrimer were functionalized with an amoxiciloyl group (AXO), the allergenic determinant to the beta-lactam antibiotic amoxicillin. The fluorescent DeAn (F-DeAn) has been fully characterized by NMR and MS techniques, and their fluorescent properties well established in aqueous biological media. F-DeAn without the haptenic moieties at the periphery has been also obtained and fully characterized as a control assay. Both molecules have been also characterized using molecular dynamics simulation calculations. We show here how these dendrimeric structures interacts with dendritic cells and are internalized by them. In a secon approximation, Naphthalimide-fluorscent silica nanoparticles have been prepared and characterized, to be used also in basophil activation test.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Functional characterization of Arabidopsis thaliana Synaptotagmin1 domains using Tricalbin3 chimeras in Saccharomyces cerevisiae

Synaptotagmin1 (SYT1) is an Arabidopsis thaliana endoplasmic reticulum (ER)-plasma membrane contact site tether involved in biotic and abiotic stress resistance. These resistance roles have been related to SYT1 tethering and lipid-transport functions. However, the specific contributions of SYT1 domains to these functions and their relevance in stress resistance remain unknown. To efficiently investigate each SYT1 domain in vivo, we carried out domain interchanges in the model organism Saccharomyces cerevisiae (yeast). Tricalbin3 (Tcb3) is a SYT1 homolog in yeast, and it is essential for heat-shock tolerance. Tcb3 also mediates the formation of high-curvature peaks at the ER, which is promotes during heat, and would facilitate lipid homeostasis between the PM and the ER. We generated constructs expressing SYT1/Tcb3 chimeras tagged to fluorescent proteins, transformed them into tcb3Δ yeast cells and studied their subcellular localization and ability to complement the heat-shock hypersensitivity of tcb3Δ. We are further analyzing the ER-peak formation ability of these chimeras by cryo-electron tomography. Our work revealed that SYT1 did not show the localization pattern of Tcb3, nor could complement the heat-shock hypersensitivity of tcb3Δ. However, Tcb3 chimeras containing either SYT1 SMP or C2 domains showed a Tcb3 subcellular pattern and a heat-shock tolerance similar to that of tcb3Δ/Tcb3- GFP complemented strains. Further, Tcb3 N-terminal region was required, although not sufficient, for heat-shock tolerance and localization. Preliminary data suggests that chimeras complementing tcb3Δ heat-shock hypersensitivity also mediate ER peak formation.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Synthesis of all-aliphatic polyamide dendrimers based on a 3,3′-diaminopivalic acid scaffold.

Over recent years the importance of dendrimers has continued to increase in both life and material sciences. Multiple chemical strategies have been described toward the preparation of dendrimeric structures. Here, we present a new approach for the production of all-aliphatic polyamide dendrimers. In our approach, iterative 3,3′-diaminopivalic acid connections act as building blocks for dendrimer construction. 3,3′-Diazidopivalic acid units underpin a two-step pathway involving carboxylic acid–amine condensation, followed by azide reduction. The carboxylic acid–amine condensation step can be carried out by conventional methods, while the hydrogen-catalyzed azide-to-amine reduction is a clean process particularly appropriate for dendrimer preparation. Spectroscopic characterization of functionalized surface azides (Gn-N3) and amines (Gn-NH2) confirm the proposed structures. These dendrimers were studied in explicit solvent by atomistic forcefield-based molecular dynamics to characterize structural properties such as shape, radius and monomer distribution. Our results show that these compounds are similar in size and shape, with Gn-NH2 having a slightly bigger size and exhibiting lower terminal unit backfolding

Analysis of Arabidopsis SYT1 mutants and chimeras reveal insights about its dynamic and function on ER-PM MCS.

The endoplasmic reticulum (ER) extends throughout the cell and forms Membrane Contact Sites (MCS) with other organelles. MCS are essential for lipid transport, calcium signaling and organelle communication. In plants, ER-Plasma Membrane (ER-PM) MCS contain some proteins which, while being anchored to the ER, can attach with the PM through electrostatic interactions. Arabidopsis thaliana SYT1 is one of the most studied ER-PM tethers in plants, as it contributes to both biotic and abiotic stress tolerance. To study SYT1 dynamics and function, our group has generated Arabidopsis stable lines expressing mutant versions of SYT1, to remove SYT1 Ca2+ binding site (SYT1MutC2), and to cause a blockage of the SMP hydrophobic channel (SYT1MutSMP). Additionally, we generated chimeric versions of SYT1, switching the SMP domain by its analogue of human E-Syt1 and TMEM24 proteins (SYT1ESYT1 and SYT1TMEM24 respectively). Our results demonstrate that both SYT1MutC2 and SYT1MutSMP lines complement the cold and salt stress phenotypes of the syt1 mutant. On the other side, SYT1ESYT1 and SYTTMEM24 chimeras do not complement such phenotypes, which confirms the essential role of SYT1 SMP domain in cold and salt stress tolerance, as well as the functional differences of SYT1 SMP domain compared to E-Syt1 and TMEM24 SMP domains. Moreover, confocal analysis of SYT1MutC2 line evidenced an altered dynamic of SYT1 in terms of cortical ER relocalization upon prolonged salt stress treatment. Altogether, these findings indicate that SYT1 Ca2+ binding site is not essential for SYT1 salt stress tolerance, but influences SYT1 dynamics on salt-induced ER-PM MCS expansion

LA CUEVA CHIQUITA O DE ÁLVAREZ (CAÑAMERO, CÁCERES): RECIENTES INTERVENCIONES Y REVISIÓN DE SUS MANIFESTACIONES RUPESTRES

Las labores de limpieza sistemática efectuadas en los paneles pintados y grabados de la Cueva Chiquita (Cañamero, Cáceres) durante los meses de junio y julio de 2008 con el fin de acondicionar su interior y entorno para la visita pública, acompañadas de los oportunos sondeos arqueológicos y análisis de pigmentos, han posibilitado la revisión y recuperación para el público de uno de los conjuntos de pintura rupestre esquemática más tempranamente conocidos y más notables de la Alta Extremadura. En el presente trabajo se detallan las principales conclusiones de estos nuevos estudios operados en el abrigo, junto a una relectura de sus figuraciones rupestres favorecida por la mejora de su visibilidad

Association of Type 1 Diabetes With Month of Birth Among U.S. Youth: The SEARCH for Diabetes in Youth Study

OBJECTIVE - Seasonal environment at birth may influence diabetes incidence in later life. We sought evidence for this effect in a large sample of diabetic youth residing in the U.S. RESEARCH DESIGN AND METHODS— We compared the distribution of birth months within the SEARCH for Diabetes in Youth Study (SEARCH study) with the monthly distributions in U.S. births tabulated by race for years 1982-2005. SEARCH study participants (9,737 youth with type 1 diabetes and 1,749 with type 2 diabetes) were identified by six collaborating U.S. centers. RESULTS— Among type 1 diabetic youth, the percentage of observed to expected births differed across the months (P = 0.0092; decreased in October-February and increased in March―July). Their smoothed birth-month estimates demonstrated a deficit in November-February births and an excess in April-July births (smoothed May versus January relative risk [RR] = 1.06 [95% CI 1.02―1.11]). Stratifications by sex or by three racial groups showed similar patterns relating type 1 diabetes to month of birth. Stratification by geographic regions showed a peak-to-nadir RR of 1.10 [1.04-1.16] in study regions from the northern latitudes (Colorado, western Washington State, and southern Ohio) but no birth-month effect (P > 0.9) in study regions from more southern locations. Among type 2 diabetic youth, associations with birth month were inconclusive. CONCLUSIONS— Spring births were associated with increased likelihood of type 1 diabetes but possibly not in all U.S. regions. Causal mechanisms may involve factors dependent on geographic latitude such as solar irradiance, but it is unknown whether they influence prenatal or early postnatal development