Magnetic nanoparticles in primary neural cell cultures are mainly taken up by microglia

<p>Abstract</p> <p>Background</p> <p>Magnetic nanoparticles (MNPs) offer a large range of applications in life sciences. Applications in neurosciences are one focus of interest. Unfortunately, not all groups have access to nanoparticles or the possibility to develop and produce them for their applications. Hence, they have to focus on commercially available particles. Little is known about the uptake of nanoparticles in primary cells. Previously studies mostly reported cellular uptake in cell lines. Here we present a systematic study on the uptake of magnetic nanoparticles (MNPs) by primary cells of the nervous system.</p> <p>Results</p> <p>We assessed the internalization in different cell types with confocal and electron microscopy. The analysis confirmed the uptake of MNPs in the cells, probably with endocytotic mechanisms. Furthermore, we compared the uptake in PC12 cells, a rat pheochromocytoma cell line, which is often used as a neuronal cell model, with primary neuronal cells. It was found that the percentage of PC12 cells loaded with MNPs was significantly higher than for neurons. Uptake studies in primary mixed neuronal/glial cultures revealed predominant uptake of MNPs by microglia and an increase in their number. The number of astroglia and oligodendroglia which incorporated MNPs was lower and stable. Primary mixed Schwann cell/fibroblast cultures showed similar MNP uptake of both cell types, but the Schwann cell number decreased after MNP incubation. Organotypic co-cultures of spinal cord slices and peripheral nerve grafts resembled the results of the dispersed primary cell cultures.</p> <p>Conclusions</p> <p>The commercial MNPs used activated microglial phagocytosis in both disperse and organotypic culture systems. It can be assumed that <it>in vivo </it>application would induce immune system reactivity, too. Because of this, their usefulness for <it>in vivo </it>neuroscientific implementations can be questioned. Future studies will need to overcome this issue with the use of cell-specific targeting strategies. Additionally, we found that PC12 cells took up significantly more MNPs than primary neurons. This difference indicates that PC12 cells are not a suitable model for natural neuronal uptake of nanoparticles and qualify previous results in PC12 cells.</p

NERVEN AUS DEM LABOR: DAS TISSUE ENGINEERING PERIPHERER NERVEN ZUR VERSORGUNG VON NERVENVERLETZUNGEN

Verletzungen peripherer Nerven sind häufiger als gemeinhin angenommen und werden in Deutschland noch nicht optimal behandelt. Die besten Vorraussetzungen für eine gute Rekonstruktion bietet die primäre mikrochirurgische Nervennaht. Bei Defekten wird ein körpereigenes Transplantat benötigt. Dessen Entnahme führt allerdings zu Funktionsausfällen. Unsere interdisziplinäre Forschungsgruppe aus Plastischen Chirurgen und Neurobiologen beschäftigt sich mit der labortechnischen Herstellung von Nervenersatzgewebe aus einer biogenen Trägermatrix und den nerveneigenen Hüllzellen (sog. Schwannsche Zellen), die die Regeneration der Nerven verbessern

Разработка малогабаритного передвижного ультразвукового метеокомплекса

Объектом исследования являются электроакустический преобразователь для работы в воздушной среде с повышенной эффективностью преобразования. Цель работы – разработка ЭАП обладающего высокой эффективностью преобразования при достаточно малых габаритах, разработка конструкции и технологии его изготовления. В процессе исследования проводились теоретические расчёты основных элементов ЭАП, экспериментальные исследования. В результате исследования были получены основные зависимости, связывающие эффективность преобразования с характеристиками материалов протектора и демпфера и их геометрических характеристик, разработан ЭАП.The object of the study are electroacoustic transducer for use in air with high conversion efficiency. The purpose of work - development of EAP has high conversion efficiency at a sufficiently small size, design development and manufacture technology. The study carried out theoretical calculations of basic elements of EMAT experimental studies. The study was prepared according to the main connecting conversion efficiency with the characteristics of the tread material and damper, and their geometric characteristics, developed EAP

ERBB2‐amplified lobular breast carcinoma exhibits concomitant CDK12 co‐amplification associated with poor prognostic features

Most invasive lobular breast carcinomas (ILBCs) are luminal‐type carcinomas with an HER2‐negative phenotype (ERBB2 or HER2 un‐amplified) and CDH1 mutations. Rare variants include ERBB2‐amplified subtypes associated with an unfavorable prognosis and less response to anti‐HER2 targeted therapies. We analyzed the clinicopathological and molecular features of ERBB2‐amplified ILBC and compared these characteristics with ERBB2‐unamplified ILBC. A total of 253 patients with ILBC were analyzed. Paraffin‐embedded formalin‐fixed tumor samples from 250 of these patients were added to a tissue microarray. Protein expression of prognostic, stem cell and breast‐specific markers was tested by immunohistochemistry (IHC). Hybrid capture‐based comprehensive genomic profiling (CGP) was performed for 10 ILBCs that were either fluorescent in situ hybridization (FISH) or IHC positive for HER2 amplification/overexpression and 10 ILBCs that were either FISH or IHC negative. Results were compared with a CGP database of 44,293 invasive breast carcinomas. The CGP definition of ERBB2 amplification was five copies or greater. A total of 17 of 255 ILBC (5%) were ERBB2 amplified. ERBB2‐amplified ILBC had higher tumor stage (p < 0.0001), more frequent positive nodal status (p = 0.00022), more distant metastases (p = 0.012), and higher histological grade (p < 0.0001), and were more often hormone receptor negative (p < 0.001) and more often SOX10 positive (p = 0.005). ERBB2 short variant sequence mutations were more often detected in ERBB2‐unamplified tumors (6/10, p = 0.027), whereas CDH1 mutations/copy loss were frequently present in both subgroups (9/10 and 7/10, respectively). Amplification of pathogenic genes were more common in HER2‐positive ILBC (p = 0.0009). CDK12 gene amplification (≥6 copies) was detected in 7 of 10 ERBB2‐amplified ILBC (p = 0.018). There were no CDK12 gene amplifications reported in 44,293 invasive breast carcinomas in the FMI Insights CGP database. ERBB2‐amplified ILBC is a distinct molecular subgroup with frequent coamplification of CDK12, whereas ERBB2 sequence mutations occur only in ERBB2‐unamplified ILBC. CDK12/ERBB2 co‐amplification may explain the poor prognosis and therapy resistance of ERBB2‐amplified ILBC

Overall complication rates of DIEP flap breast reconstructions in Germany – a multi-center analysis based on the DGPRÄC prospective national online registry for microsurgical breast reconstructions

While autologous breast reconstruction has gained momentum over recent years, there is limited data on the structure and quality of care of microsurgical breast reconstruction in Germany. Using the breast reconstruction database established by the German Society of Plastic, Reconstructive and Aesthetic Surgeons (DGPRÄC), the presented study investigated the overall outcomes of deep inferior epigastric perforator (DIEP) flap reconstructions in Germany. Data of 3926 patients and 4577 DIEP flaps performed by 22 centers were included in this study. Demographics, patient characteristics, perioperative details and postoperative outcomes were accounted for. Centers performing < Ø 40 (low-volume (LV)) vs. ≥ Ø 40 (high-volume (HV)) annual DIEP flaps were analyzed separately. Overall, total and partial flap loss rates were as low as 2.0% and 1.1% respectively, and emergent vascular revision surgery was performed in 4.3% of cases. Revision surgery due to wound complications was conducted in 8.3% of all cases. Mean operative time and length of hospital stay was significantly shorter in the HV group (LV: 385.82 min vs. HV: 287.14 min; LV: 9.04 (18.87) days vs. HV: 8.21 (5.04) days; both p < 0.05). The outcome and complication rates deduced from the national registry underline the high standard of microsurgical breast reconstruction on a national level in Germany

Complex reconstructions in head and neck cancer surgery: decision making

Defects in head and neck after tumor resection often provide significant functional and cosmetic deformity. The challenge for reconstruction is not only the aesthetic result, but the functional repair. Cancer may involve composite elements and the in sano resection may lead to an extensive tissue defect. No prospective randomized controlled studies for comparison of different free flaps are available. There are many options to cover defects and restore function in the head and neck area, however we conclude from experience that nearly all defects in head and neck can be closed by 5 different free flaps: radial forearm flap, free fibula flap, anterior lateral thigh flap, lateral arm flap and parascapular flap

Autologous Breast Reconstruction with Free Nipple&ndash;Areola Graft after Circumareolar (Skin Reducing) Mastectomy

Introduction of skin-sparing mastectomy (SSM) led to a paradigm shift in breast reconstruction. Primary reconstructions have become the therapy of choice. At the same time, immediate autologous reconstructions are oncologically safe and aesthetically pleasing. Our preferred SSM incision is the circumareolar with removal of nipple and areola (NAC). Adjustment of the skin envelope is well accomplished in mild-to-moderate ptotic breasts. We describe our technique consisting of circumareolar incision in SSM, keeping the NAC as a free graft, and immediate autologous reconstruction and immediate free NAC grafting on the flap. Aesthetic indications are slight asymmetries, ptotic breasts, large breasts where the reconstructed breast will be smaller than the original breast and where a Wise pattern is not indicated. Oncologic indications are risk-reducing mastectomies and tumors close to the NAC where resection would compromise the vitality of the NAC. We evaluated the healing of the NAC and the NAC position with regard to the breast shape. From 2019&ndash;2022, 296 autologous flaps were used for breast reconstruction. In 36 flaps, this technique was applied. Eighteen flaps were bilateral (nine patients). In total, we performed 15 inner thigh flaps and 21 DIEP flaps. No flap or NAC loss occurred. There was no wound healing complication at the breast, and no adjuvant chemotherapy or radiation therapy needed to be postponed. The advantages of this technique are (1) scar reduction with only one periareolar scar on the breast, which is also well concealed; (2) oncological safety in relation to the nipple and optimal visibility of the mastectomy cavity, which allows a meticulous mastectomy, especially important in risk-reducing mastectomies; (3) generally, fewer wound healing problems, especially fewer than with Wise pattern incision; (4) primary adjustment of the skin envelope and positioning of the NAC are easier to perform than in a secondary procedure; and (5) that the NAC is spared, and no secondary reconstruction is necessary. Disadvantages are that (1) the NAC must heal as a free graft and (2) that the sensitivity of the NAC is lower than in pedicled NAC transposition

Biocompatibility of Different Nerve Tubes

Bridging nerve gaps with suitable grafts is a major clinical problem. The autologous nerve graft is considered to be the gold standard, providing the best functional results; however, donor site morbidity is still a major disadvantage. Various attempts have been made to overcome the problems of autologous nerve grafts with artificial nerve tubes, which are “ready-to-use” in almost every situation. A wide range of materials have been used in animal models but only few have been applied to date clinically, where biocompatibility is an inevitable prerequisite. This review gives an idea about artificial nerve tubes with special focus on their biocompatibility in animals and humans

Технологические решения для строительства эксплуатационной скважины методом горизонтально направленного бурения глубиной 1350 метров на Ашальчинском нефтяном месторождении (Республики Татарстан)

РЕФЕРАТ Выпускная квалификационная работа бакалавра содержит 80 стр., 14 рис., 47 табл., 31 источник, 2 приложения, 2-листа графического материала. Ключевые слова: Республика Татарстан, Шешминский горизонт, конструкция забоя, обсадная колонна , буровой раствор. Объектом работы является технология строительства эксплуатационной горизонтально направленной скважины для добычи нефти. Работа выполнена по геологическим условиям Ашальчинского нефтяного месторождения. В процессе исследования проводились обоснованные расчеты подбора ВЗД, буровые растворы, конструкция скважины, долота. По результатам работы была подобрана техника и технология расчета обустройства скважины глубиной 1350 метров. Экономическая эффективность заключается в небольшом залегании пласта, и введенные правительством РФ льготANNOTATION Final qualifying work of bachelor contains 80 p., 14 fig., 47 tab., 31 sources of literature, 2 annexes, 2 sheets of graphic material. Keywords: the republic of Tatarstan, Sheshminsky horizon, bottomhole design, casing column, drilling mud. The object of the work is the construction technology of operational horizontal oil well. The work is made according to the geological conditions of Ashalchinskoye oil field. The study carried out reasonable calculations selection of PDM motor, drilling mud, well design and drilling bit. As a result of the work engineering and technology calculation of well ties (1350 meters in deep) was selected. Cost-effectiveness is caused by shallow formation. The Russian government grants connected with MET for the production of superviscous oil. I