Bioengineered viral nanorings for the insertion into bio-hybrid systems

Filtereinheiten mit nanoskopischer Porengröße werden zunehmend für medizinische Anwendungen und analytische Verfahren eingesetzt. DNA-Moleküle lassen sich bereits durch Nanoporen sequenzieren, und auch für schnelle und exakte Analysen niedermolekularer Substanzen bergen sie ein hohes Potential. Besonders schwierig ist es allerdings, nanoporöse Membranen mit Millionen von identischen Poren herzustellen. Hybridmembranen könnten hier einen Ausweg bieten, indem sich selbst organisierende biologische Komponenten als "Porenadapter" in poröse anorganische Festkörpermembranen (solid-state membranes, SSMs) integriert werden. Die biologischen Einheiten definieren dann Durchmesser und physikochemische Eigenschaften der effektiven Poren und damit die Selektivität der Filtermembran. Im Rahmen dieses Promotionsprojekts wurde ein neuer stabiler, aber zugleich auch genetisch und chemisch leicht manipulierbarer Porenadapter aus Pflanzenvirusbausteinen entwickelt und für die Insertion in SSM-Poren erprobt und optimiert. Er ist sowohl an seinem äußeren Rand, als auch im Innenkanal spezifisch funktionalisierbar. Als Ausgangsmaterial diente das pflanzenpathogene Tabakmosaikvirus (TMV), ein Nukleoprotein-Röhrchen, das aus einem einzelsträngige (ss)RNA-Molekül und ca. 2130 Hüllprotein-(coat protein, CP)- Untereinheiten besteht. Sowohl die Länge der Partikel, gesteuert über die RNA- Länge, als auch die Protein-Sequenz des CP sind leicht manipulierbar, weshalb TMV zu einem beliebten multifunktionalen Nanobaustein in Hybridmaterialien avanciert ist. Der neuartige Porenadapter aus TMV-Komponenten wurde speziell an die Insertion in eine SSM mit konisch geformten Poren angepasst, wie sie im Labor von Projektpartnern in Ulm hergestellt wird. Aus einem kurzen RNA-Konstrukt, das über In-vitro-Transkription präpariert wurde, und ca. 68 CPs organisiert sich dieser Adapter selbst als eine vierwindige 10 nm lange Nukleoprotein-Helix, die angesichts ihrer lochscheibenähnlichen Form im Folgenden auch „Disk“ genannt wird. Da die „Disks“ in den SSM-Poren unter leicht alkalischen Bedingungen irreversibel fixierbar sein sollen, wurde ihre Struktur im Bereich von pH 7.2 bis 9.0 untersucht und erwies sich als stabil. Damit waren sie den natürlich vorkommenden ringförmigen RNA- freien TMV-CP-Aggregaten klar überlegen, die innerhalb dieses pH-Regimes oligomerisierten und im alkalischen Milieu zerfielen. Auf Isothiocyanat- funktionalisierten Substraten konnten die RNA-haltigen „Disks“ kovalent immobilisiert werden, sodass alle Voraussetzungen für ihre Integration in SSM-Poren bestanden. Bereits in ersten Kombinationsversuchen ließen sich die „Disks“ mit guter Effizienz in SSM-Porenkanäle inserieren, waren aber in den Poren oft nicht richtig orientiert. Deshalb wurde im zweiten Teil des Projekts ein verfeinertes Adapter-Konstrukt mit einer stark polaren Achse konzipiert, das sich, ausgerichtet in einem elektrischen Feld, in die SSM-Poren einfädeln lässt. Es besteht aus einer Nukleoprotein-„Disk“ mit herausragender freier doppelstängiger (ds)RNA, wodurch es über eine wesentlich höhere negative Ladung als die Porenadapter der ersten Generation verfügt. Dank der spezifischen Interaktion der CPs mit ssRNA konnte ein RNA-Konstrukt, das partiell einzel- und partiell doppelsträngig ist, als Grundgerüst für solche „Disks an der Leine" dienen. In gelelektrophoretischen Analysen zeigten die Produkte tatsächlich eine höhere Mobilität als herkömmliche „Disks“. Ziel ist schließlich eine robuste Hybridmembran, in der biologische Porenadapter irreversibel in die SSM-Kanäle implantiert und Leckströme gering sind. Dies ließe sich durch das Abscheiden von anorganischem Material zwischen SSM-Poreninnenwand und „Disk“-Rand erreichen, wenn die Lücke zwischen beiden Komponenten an der Grenzfläche ortsselektiv versiegelt werden könnte. Dafür sind im letzten Teil der Arbeit „Disks“ mit spezifisch mineralisierbarer Außenfläche entstanden, welche ihre Silikat-Ummantelung aus löslichen anorganischen Vorstufen induzieren. Verschiedene mineralisationsvermittelnde Peptide wurden chemisch an TMV-Partikel gebunden und die SiO2-Abscheidungseffizienzen vergleichend untersucht. Besonders vielversprechend war ein Peptid mit alternierendem Lysin-Aspartat-Motiv, (KD)10C, das auf Grundlage von Literaturdaten entworfen wurde. Es lieferte tatsächlich auch nach Konjugation an „Disk“-Außenflächen ausgezeichnete Ergebnisse: Die so mit Peptiden funktionalisierten „Disks“ bewirkten eine ringförmige Abscheidung von SiO2, was bei unmodifizierten „Disks“ nicht beobachtet wurde. Die neuartigen RNA-stabilisierten und leicht funktionalisierbaren „Disks“ aus TMV- Derivaten sind somit aussichtsreiche biologische Porenadapter zur lipidfreien Insertion in Festkörper-Template. Dank der großen Adaptierbarkeit dieser Nanobausteine könnten davon vielfältige Anwendungen profitieren

Laparoscopic Inguinal Hernia Repair: Technical Details, Pitfalls and Current Results

Expanding view of minimal invasive surgery horizon reveals new practice areas for surgeons and patients. Laparoscopic inguinal hernia repair is an example in progress wondered by many patients and surgeons. Advantages in laparoscopic repair motivate surgeons to discover this popular field. In addition, patients search the most convenient surgical method for themselves today. Laparoscopic approaches to inguinal hernia surgery have become popular as a result of the development of experience about different laparoscopic interventions, and these techniques are increasingly used these days. As other laparoscopic surgical methods, experience is the most important point in order to obtain good results. This chapter aims to show technical details, pitfalls and the literature results about two methods that are commonly used in laparoscopic inguinal hernia repair

Laparoscopic Rare Abdominal Hernia Treatment

Diaphragm and abdominal wall hernias are rare, and they may be congenital or acquired. Spiegel hernia incidence is between 0.1 and 2%. Morgagni hernia is comprising only 2–3% of all diaphragmatic hernias. Most Spiegel and Morgagni hernias are diagnosed late because of their non-specific symptoms and asymptomatic clinical presentation. The major symptoms are abdominal pain, vomiting, and dyspnea. Computed tomography (CT) shows the hernia sac content, strangulation or incarceration in the content, and detailed anatomical information about surrounding tissue. Surgery is the main treatment option except patients who have severe comorbidity. Spiegel hernia surgery can be performed open or laparoscopic. Intraperitoneal onlay mesh (IPOM), total extraperitoneal procedure (TEP), transabdominal preperitoneal (TAPP) procedure, or partial transabdominal laparoscopic methods are minimal invasive surgery options. In the repair of Morgagni hernia, surgical options may be laparoscopy, laparotomy, thoracotomy, or thoracoscopy

Laparoscopic treatment of morgagni hernia: Two case reports

Morgagni hernias account for only 2–3% of all diaphragmatic hernias, and most of them (91%) are rightsided. Most Morgagni hernias are diagnosed in childhood, but rarely diagnosis may be late because they can be asymptomatic or present nonspecific-nonrespiratory symptoms. Thus, Morgagni hernia diagnosis is incidental in the majority of adulthood cases. The defect arises from a fusion failure of the diaphragm with the central arches. Surgery is the main treatment modality of the Morgagni hernia due to defect enlargement and strangulation- incarceration risks. In this paper, we present two Morgagni hernia cases treated with laparoscopic surgery. Minimal invasive techniques can be used in Morgagni hernia with all advantages

Topical Steroids to Treat Granulomatous Mastitis: A Case Report

Idiopathic granulomatous mastitis (IGM) is a rare and chronic benign disease of the breast. Histologically, the disease presents as an intense inflammatory reaction with non-caseated granulomas that are the characteristic symptom of the disease. No consensus exists on the best treatment modality for this disease. In this report, we present a patient with granulomatous mastitis who was treated successfully with low-dose oral and topical steroids. Our aim here is to discuss various approaches for IGM in view of the literature and present treatment with topical steroids, which has not been reported

Analiza rezultata dijagnostičke ekscizijske biopsije limfnih čvorova: 12-godišnje iskustvo jednog centra

Lymph node biopsy is indicated in patients with suspected malignancy or lymphadenopathy due to unclarified reasons. Lymph node biopsy can be performed as fine needle aspiration biopsy, core biopsy, or excisional lymph node biopsy. In particular, the diagnosis of malignant lymphoma is considered insufficient for oncological treatment unless classified into subgroups. Core biopsy and excisional biopsy can be performed to diagnose lymphoma and classify it into subgroups. Core biopsy may also be limited in some cases for the diagnosis of lymphoma. Therefore, patients are referred to surgical departments for excisional lymph node biopsy. It was aimed herein to analyze the results of excisional lymph node biopsies performed for diagnostic purposes in our department. Data on 73 patients having undergone diagnostic excisional lymph node biopsy at Sakarya University Medical Faculty Training and Research Hospital between January 2008 and January 2020 were retrospectively analyzed. Patients were evaluated in terms of age, gender, biopsy site, pathological diagnosis, number and diameter of lymph nodes excised. Patients younger than 18 years of age, those with sentinel lymph node biopsies, and lymph node dissections performed for any known malignancy were excluded from the study. Statistical data analysis was done using SPSS statistical software. There were 37 (50.7%) female and 36 (49.3%) male patients, mean age 52.07 (18-90) years. Axillary lymph node biopsy was performed in 32 patients, inguinal lymph node biopsy in 29 patients, cervical lymph node biopsy in 3 patients, intra-abdominal lymph node biopsy in 6 patients, mediastinal lymph node biopsy in 1 patient, and supraclavicular lymph node biopsy in 2 patients. All of the lymph node biopsies were performed as excisional biopsy. Malignancy was detected in 36 (49.3%) patients. In 37 (50.3%) patients, the causes of lymphadenopathy were found to be benign pathologies. When the causes of malignant disease were examined, it was observed that 23 (31.5%) patients were diagnosed with lymphoma. Hodgkin lymphoma was detected in 5 patients diagnosed with lymphoma, and non-Hodgkin lymphoma was found in 18 patients. Metastatic lymphadenopathy was observed in 13 (17.8%) patients. Reactive lymphoid hyperplasia (26%) and lymphadenitis (20.5%) were found among the causes of benign lymphadenopathy. The number of excised lymph nodes was between 1 and 4, and their diameter was between 9 and 75 mm (mean: 29.53±15.56 mm). There was no statistically significant difference between benign and malignant patients according to gender, age, lymph node diameter, number of lymph nodes excised, and excisional lymph node biopsy site. For diagnostic lymph node biopsy, fine-needle aspiration biopsy and core biopsy should be performed primarily. If lymphoma is suspected in the diagnosis, fine-needle aspiration biopsy is not necessary. In this case, it is believed that it is more appropriate to perform core biopsy first. If the core biopsy is insufficient for diagnosis, it is more appropriate to perform surgical biopsy in order to cause no delay in diagnosis and treatment. Excisional biopsy is a method that can be safely performed and does not cause severe morbidity in palpable peripheral lymphadenopathies. Although it does not cause severe morbidity because it is an invasive procedure, excisional biopsy should be performed in a selected patient group.Biopsija limfnih čvorova indicirana je u bolesnika sa sumnjom na zloćudnu bolest ili s limfadenopatijom nejasnog uzroka. Biopsija limfnih čvorova može se izvesti kao tankoiglena aspiracijska biopsija, širokoiglena biopsija ili ekscizijska biopsija limfnih čvorova. Dijagnoza zloćudnog limfoma smatra se naročito nedostatnom za onkološko liječenje ako nije provedena klasifikacija u podskupine. Širokoiglena biopsija i ekscizijska biopsija mogu se provesti kako bi se dijagnosticirao limfom i klasificirao u podskupine. Širokoiglena biopsija može se također u nekim slučajevima pokazati ograničenom u dijagnosticiranju limfoma. Zato se bolesnici upućuju u kirurške odjele na ekscizijsku biopsiju limfnih čvorova. Cilj ovoga istraživanja bio je analizirati rezultate ekscizijskih biopsija limfnih čvorova izvedenih u dijagnostičke svrhe na našem odjelu. Retrospektivno su analizirani podaci za 73 bolesnika podvrgnutih dijagnostičkoj ekscizijskoj biopsiji limfnih čvorova u Sveučilišnoj bolnici Sakarya između siječnja 2008. i siječnja 2020. godine. Analizirani su sljedeći podaci: dob, spol, mjesto gdje je izvedena biopsija, patološka dijagnoza, broj i promjer ekscidiranih limfnih čvorova. Iz istraživanja su bili isključeni bolesnici mlađi od 18 godina, oni s biopsijom sentinel limfnih čvorova te oni s disekcijom limfnih čvorova zbog bilo kakve poznate zloćudne bolesti. Statistička analiza podataka provedena je pomoću statističkog programa SPSS. Bilo je 37 (50,7%) ženskih i 36 (49,3%) muških bolesnika srednje dobi od 52,07 (18-90) godina. Biopsija aksilarnih limfnih čvorova izvedena je u 32, ingvinalnih limfnih čvorova u 29, cervikalnih limfnih čvorova u 3, intra-abdominalnih limfnih čvorova u 6 bolesnika, mediastinalnih limfnih čvorova u 1 bolesnika i supraklavikularnih limfnih čvorova u 2 bolesnika. Sve biopsije limfnih čvorova izvedene su kao ekscizijske biopsije. Malignitet je otkriven u 36 (49,3%) bolesnika, dok su u 37 (50,3%) bolesnika uzroci limfadenopatije bile dobroćudne patologije. Ispitivanje uzroka zloćudne bolesti pokazalo je da je limfom bio dijagnosticiran u 23 (31,5%) bolesnika. Hodgkinov limfom otkriven je u 5 bolesnika u kojih je dijagnosticiran limfom, dok je ne-Hodgkinov limfom utvrđen u 18 bolesnika. Metastatska limfadenopatija zabilježena je u 13 (17,8%) bolesnika. Među uzrocima dobroćudne limfadenopatije nađeni su reaktivna limfoidna hiperplazija (26%) i limfadenitis (20,5%). Broj izvađenih limfnih čvorova bio je od 1 do 4, a njihov promjer bio je od 9 do 75 (srednja vrijednost 29,53±15,56) mm. Nije bilo statistički značajne razlike između bolesnika s dobroćudnom i zloćudnom limfadenopatijom u dobi, spolu, promjeru limfnih čvorova, broju izvađenih limfnih čvorova i mjesta izvođenja ekscizijske biopsije limfnih čvorova. Za dijagnostičku biopsiju limfnih čvorova treba najprije napraviti tankoiglenu aspiracijsku biopsiju i širokoiglenu biopsiju. Ako se dijagnostički posumnja na limfom tada tankoiglena aspiracijska biopsija nije potrebna. U tom slučaju smatra se da je primjerenije najprije napraviti širokoiglenu biopsiju. Ako se širokoiglena biopsija pokaže nedostanom za postavljanje dijagnoze tada je primjerenije napraviti kiruršku biopsiju kako ne bi došlo do kašnjenja u dijagnozi i liječenju. Ekscizijska biopsija je metoda koja se može sigurno izvoditi i ne uzrokuje teži pobol kod palpabilnih perifernih limfadenopatija. Iako ne uzrokuje teži pobol s obzirom na to da je invazivni postupak, ekscizijsku biopsiju treba izvoditi u odabranoj skupini bolesnika

Primary Small Cell Carcinoma of the Lung Presenting with Breast and Skin Metastases

Cutaneous metastases originating from an internal cancer are relatively uncommon in clinical practice, and metastatic lesions to the breast are rarer than those to the skin. Skin metastases of lung cancer, which may be the first sign of the disease, usually indicate progressive disease and a poor prognosis. We describe a 47-year-old male who presented with recurring masses in the lumbar region bilaterally and the right breast. Immunohistochemical findings and radiological imaging suggested lung cancer. This is the first reported case of small cell lung cancer metastasizing to two separate, uncommon sites, the skin and breast

Biocompatibilità e durata in vivo di cinque nuovi polimeri sintetici testati su coniglio

I materiali alloplastici vengono frequentemente utilizzati negli interventi di chirurgia plastica sul volto, quali la rinoplastica e la chirurgia ricostruttiva del naso. Ad oggi non è stato ancora individuato un materiale alloplastico con caratteristiche ottimali. Il presente studio sperimentale si propone di valutare la risposta tissutale e la resistenza nel tempo di cinque nuovi polimeri proposti come materiali alloplastici. Il presente studio è stato condotto presso un ospedale universitario di terzo livello. Sono state ricavate sei tasche sottocutanee sul dorso di 10 conigli che sono state usate per l’impianto di ciascuno dei polimeri testati più una tasca di controllo. Ciascuna delle tasche è stata escissa congiuntamente al tessuto circostante dopo tre mesi, ed è stata sottoposta ad un esame istopatologico. È stata quindi condotta una valutazione semi quantitativa con focus su neo angiogenesi, infiammazione, fibrosi, formazione di ascessi, presenza di cellule giganti multinucleate contenenti corpi estranei e stato dei polimeri testati. E’ stata inoltre effettuata una valutazione statistica, che per quanto riguarda la comparazione diretta fra la tasca di controllo e i polimeri II, III e IV non ha mostrato differenze significative in merito alla neo vascolarizzazione, all’infiammazione, alla fibrosi, alla presenza di ascessi ed alla presenza di cellule giganti multinucleate. Il polimero I ha invece mostrato un grado di fibrosi inferiore rispetto alla tasca di controllo (p = .027) and V (p = .018), benché le altre variabili prese in considerazione fossero sostanzialmente uguali. L’integrità nel tempo dei polimeri III (9 intatti, uno frammentato) e IV (8 intatti, 2 assenti) è stata migliore di quella ottenuta con gli altri polimeri testati. Questo gruppo di nuovi polimeri può essere considerato interessante per future applicazioni cliniche. Tutti i polimeri hanno mostrato risultati accettabili in termini di risposta dei tessuti, tuttavia i fenomeni di integrazione fibrovascolare sono stati maggiori nel caso dei polimeri II, III e IV. Inoltre la durata nel tempo dei polimeri III e IV è stata la migliore in assoluto

Granulomatous lobular mastitis

AbstractGranulomatous lobular mastitis is an unusual breast benign inflammatory disorder with unknown aetiology. It is generally emerged with the clinical symptoms of breast mass, abscess, inflammation and mammary duct fistula. The diagnosis is made by histopathology with a chronic non-necrotizing granulomatous inflammation in lobules of the breast tissue as the microscopic feature. Therapy of granulomatous lobular mastitis consists of surgical, medication treatment or combination of both, but now researches suggest that observational management is an acceptable treatment

CT Findings of Patients with Small Bowel Obstruction due to Bezoar: A Descriptive Study

Purpose. The aim of this study was to present the computed tomography (CT) findings of bezoars that cause obstruction in the small bowel and to emphasize that some CT findings can be considered specific to some bezoar types. Materials and Methods. The records of 39 patients who underwent preoperative abdominal CT and subsequent operation with a diagnosis of intestinal obstruction due to bezoars were retrospectively analyzed. Results. In total, 56 bezoars were surgically removed from 39 patients. Bezoars were most commonly located in the jejunum (n=26/56, 46.4%). Sixteen (41.0%) patients had multiple bezoar locations in the gastrointestinal tract. Common CT findings in all patients were a mottled gas pattern and a focal ovoid or round intraluminal mass with regular margins and a heterogeneous internal structure. Furthermore, some CT findings were determined to be specific to bezoars caused by persimmons. Conclusions. Preoperative CT is valuable in patients admitted with signs of intestinal obstruction in geographic regions with a high bezoar prevalence. We believe that the correct diagnosis of bezoars and the identification of their number and location provide a great advantage for all physicians and surgeons. In addition, some types of bezoars have unique CT findings, and we believe that these findings may help to establish a diagnosis