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Nanogels with tailored hydrophobicity and their behavior at air/water interfaces†
Get PDFThe interfacial behavior of micro-/nanogels is governed to a large extent by the hydrophobicity of their polymeric network. Prevailing studies to examine this influence mostly rely on external stimuli like temperature or pH to modulate the particle hydrophobicity. Here, a sudden transition between hydrophilic and hydrophobic state prevents systematic and gradual modulation of hydrophobicity. This limits detailed correlations between interfacial behavior and network hydrophobicity. To address this challenge, we introduce a nanogel platform that allows accurate tuning of hydrophobicity on a molecular level. For this, via post-functionalization of active ester-based particles, we prepare poly( N -(2-hydroxypropyl)methacrylamide) (PHPMA) nanogels as a hydrophilic benchmark and introduce gradually varied amounts of hydrophobic propyl or dodecyl moieties to increase the nanogel hydrophobicity. We study the deformation and arrangement of these particles at an air/water interface and correlate the results with quantitative measures for nanogel hydrophobicity. We observe that increasing hydrophobicity of nanogels, either by increasing the hydrophobic moiety ratio or the alkyl chain length, leads to decreased particle deformability and aggregation of an interfacially-adsorbed monolayer. Contrary to what may be intuitively assumed, these changes are not gradual, but rather occur suddenly above a threshold in hydrophobicity. Our study further shows that the effect of hydrophobicity affects the nanogel properties differently in bulk and when adsorbed at liquid interfaces. Thus, this study establishes the transition of interfacial behavior between soft gel-like particles to a solid spherical morphology triggered by the increase in hydrophobicity.We investigate the interfacial morphology of colloidal nanogels with increasing hydrophobicity. The transition from deformable to solid-like characteristics occurs suddenly above a threshold in hydrophobicity.Deutsche Forschungsgemeinschaft 10.13039/501100001659China Scholarship Council 10.13039/50110000454
Individualised computerised cognitive training (iCCT) for community-dwelling people with mild cognitive impairment (MCI): results on cognition in the 6-month intervention period of a randomised controlled trial (MCI-CCT study)
Get PDFBackground Computerised cognitive training (CCT) can improve the cognitive abilities of people with mild cognitive impairment (MCI), especially when the CCT contains a learning system, which is a type of machine learning (ML) that automatically selects exercises at a difficulty that corresponds to the person’s peak performance and thus enables individualised training. Methods We developed one individualised CCT (iCCT) with ML and one basic CCT (bCCT) for an active control group (CG). The study aimed to determine whether iCCT in the intervention group (IG) resulted in significantly greater enhancements in overall cognitive functioning for individuals with MCI (age 60+) compared with bCCT in the CG across a 6-month period. This double-blind randomised controlled study was conducted entirely virtually. The 89 participants were community-dwelling people with a psychometric diagnosis of MCI living in Germany. The iCCT stimulates various cognitive functions, especially working memory, visuo-constructional reasoning, and decision-making. The bCCT includes fewer and simpler tasks. Both CCTs were used at home. At baseline and after 6 months, we assessed cognitive functioning with the Montreal Cognitive Assessment (MoCA). A mixed-model ANCOVA was conducted as the main analysis. Results Both CCTs led to significant increases in average global cognition. The estimated marginal means of the MoCA score increased significantly in the CG by an average of 0.9 points (95% CI [0.2, 1.7]) from 22.3 ( SE = 0.25) to 23.2 ( SE = 0.41) points ( p = 0.018); in the IG, the MoCA score increased by an average of 2.2 points (95% CI [1.4, 2.9]) from 21.9 ( SE = 0.26) to 24.1 ( SE = 0.42) points ( p < 0.001). In a confound-adjusted multiple regression model, the interaction between time and group was statistically significant ( F = 4.92; p = 0.029). The effect size was small to medium (partial η 2 = 0.057). On average, the participants used the CCTs three times per week with an average duration of 34.9 min per application. The iCCT was evaluated as more attractive and more stimulating than the bCCT. Conclusions By using a multi-tasking CCT three times a week for 30 min, people with MCI living at home can significantly improve their cognitive abilities within 6 months. The use of ML significantly increases the effectiveness of cognitive training and improves user satisfaction. Trial registration ISRCTN14437015; registered February 27, 2020.Open Access funding enabled and organized by Projekt DEAL.Open Access funding enabled and organized by Projekt DEAL.Universitätsklinikum Erlangen (8546)Universitätsklinikum Erlangen (8546
Johnson, Paul Elliott: I the People. The Rhetoric of Conservative Populism in the United States, 336 pp., UAP, Tuscaloosa, AL 2022.
Get PDFOpen Access funding enabled and organized by Projekt DEAL.Friedrich-Alexander-Universität Erlangen-Nürnberg (1041
CT-basierte fraktionelle Flussreserve (FFRCT) und zukünftige kardiovaskuläre Ereignisse
Get PDFZielsetzung: Diese Studie untersuchte die auf der koronaren CT-Angiographie basierte fraktionelle Flussreserve (FFRCT) hinsichtlich ihrer Fähigkeit und möglicher Grenzwerte zur Vorhersage zukünftiger kardiovaskulärer Ereignisse im Langzeitverlauf. Methoden: In diese Studie wurden insgesamt 563 Patientinnen und Patienten eingeschlossen, bei denen im Zeitraum 2005-2009 eine CT-Angiographie der Koronararterien (Coronary CT Angiography, CCTA) am Universitätsklinikum Erlangen durchgeführt worden war. Für die FFRCT-Berechnung wurde ein Software-Prototyp eines PC-basierten Algorithmus (cFFR Versionen 3.0-3.5.2, Siemens Healthineers, Forchheim, Deutschland) eingesetzt. Durch eine erfahrene Untersucherin wurden FFRCT-Werte an den proximalen und distalen Endpunkten jedes einzelnen Koronararteriensegments erhoben. Aus der Differenz der proximalen und distalen Werte wurde der Gradient ∆FFRCT über jedes Koronararteriensegment berechnet. Erfasst wurde jeweils der minimale FFRCT-Wert pro Patientin/Patient sowie der maximale Gradient (∆FFRCT) pro Patientin/Patient. Die Nachverfolgung umfasste MACE (zerebrale Ischämie, ACS, kardialer Tod) und Revaskularisation (PCI, CABG). Ergebnisse: Die Mittelwerte für minimale FFRCT pro Patientin/Patient lagen bei 0,801 ± 0,155 bzw. für maximale ∆FFRCT pro Patientin/Patient bei 0,135 ± 0,127. Die mittlere Bearbeitungszeit mit dem Software-Prototyp lag bei 11,9 ± 6,1 Minuten pro Fall. Von den 563 eingeschlossenen Personen (62,4 ± 11,3 Jahre, 57,7% männlich) erlitten über eine mediane Nachverfolgungszeit von 6,25 ± 1,49 Jahren 57 (10,1%) Patientinnen und Patienten den Endpunkt MACE (12 ACS, 9 kardiale Todesfälle, 36 zerebrale Ischämien), Revaskularisierungen traten in 146 Fällen auf (25,9%). Bei Personen, die den Endpunkt MACE bzw. Revaskularisierung erreichten, lag die minimale FFRCT pro Patientin/Patient signifikant niedriger (MACE: 0,766 ± 0,165 vs. 0,805 ± 0,154, p = 0,041; Revaskularisierung: 0,649 ± 0,188 vs. 0,854 ± 0,097, p <0,001). Für maximale ∆FFRCT pro Patientin/Patient zeigte sich ein signifikanter Unterschied für den Endpunkt Revaskularisierung (0,256 ± 0,160 vs. 0,093 ± 0,076, p < 0,001), jedoch nicht für MACE (0,156 ± 0,122 vs. 0,132 ± 0,127; p = 0,073). Als AUC für die Vorhersage von MACE durch minimale FFRCT bzw. maximale ∆FFRCT pro Patientin/Patient ergaben sich 0,582 bzw. 0,570. Die AUC für den Endpunkt Revaskularisierung lag bei 0,867 (minimale FFRCT) bzw. 0,882 (maximale ∆FFRCT). Als Grenzwerte zur Vorhersage einer Revaskularisierung wurde eine minimale FFRCT pro Patientin/Patient von ≤ 0,765 (Sensitivität 90%, Spezifität 66%) bzw. ≤ 0,815 (Sensitivität 81%, Spezifität 77%) sowie eine maximale ∆FFRCT pro Patientin/Patient ≥ 0,090 (Sensitivität 90%, Spezifität 70%) bzw. ≥ 0,115 (Sensitivität 84%, Spezifität 81%) ermittelt. Schlussfolgerung: Die CT-basierte FFR bietet prognostischen Nutzen zur Vorhersage kardiovaskulärer Ereignisse im Langzeit-Verlauf, insbesondere für die Vorhersage von Revaskularisationen.Objectives: We aimed at evaluating the prognostic potential of CT-derived fractional flow reserve (FFRCT) to predict future cardio-vascular events during long-term follow-up and to establish prognostically relevant FFRCT-thresholds as secondary objective. Methods: This study included 563 patients with suspected CAD undergoing CCTA from 2005-2009 at the University Hospital Erlangen, Germany. FFRCT was measured by an experienced observer using prototype software (cFFR Versions 3.0-3.5.2, Siemens Healthineers, Forchheim, Germany). FFRCT values were measured for each coronary segment (proximal and distal end), the gradient (∆FFRCT) across each coronary segment was calculated respectively. Minimal FFRCT per patient and maximum ∆FFRCT per patient were recorded. Follow up data was gathered from medical records and included MACE (ACS, cardiac death, stroke) and revascularization (PCI, CABG). Results: Mean processing time with the cFFR-prototype was 11.9 ± 6.1 minutes per case. Mean minimal FFRCT per patient was 0.801 ± 0.155, mean maximum ∆FFRCT per patient was 0.135 ± 0.127. Of the enrolled 563 patients (62.4 ± 11.3 years, 57.7% male) a total of 57 (10.1%) suffered MACE (12 ACS, 9 cardiac deaths, 36 strokes) during a median follow up of 6.25 ± 1.49 years. Revascularization occurred in 146 (25.9%) cases. Mean minimal FFRCT per patient was significantly lower in patients with future MACE (0.766 ± 0.165 vs. 0.805 ± 0.154, p = 0.041) and revascularization (0.649 ± 0.188 vs. 0.854 ± 0.097, p <0.001). No significant difference was observed for maximum ∆FFRCT per patient in cases with MACE (0.156 ± 0.122 vs. 0.132 ± 0.127, p = 0.073) yet maximum ∆FFRCT per patient was significantly higher in cases with revascularization (0.256 ± 0.160 vs. 0.093 ± 0.076, p < 0.001). AUC for MACE was 0.582 (minimal FFRCT) and 0.570 (maximum ∆FFRCT), AUC for revascularization was 0.867 (minimal FFRCT) and 0.882 (maximum ∆FFRCT). Respective thresholds were identified for minimal FFRCT per patient at ≤ 0.765 (sensitivity 90%, specificity 66%) and ≤ 0.815 (sensitivity 81%, specificity 77%) as well as for maximum ∆FFRCT per patient at ≥ 0.090 (sensitivity 90%, specificity 70%) and ≥ 0.115 (sensitivity 84%, specificity 81%). Conclusion: CT-derived FFR can inform long-term risk stratification and is a good predictor of future cardiovascular events, particularly revascularization
Impact of manual therapy on body posture-3-D analysis with rasterstereography – pilotstudy
Get PDFIntroduction The relationship between posture and temporomandibular disease (TMD) is unclear. The aim of our study was to determine the influence of manual therapy (MT) on posture in TMD patients compared with healthy subjects. Material/method After consideration of inclusion and exclusion criteria, 30 subjects were included. These were divided into two groups: group A comprised 15 healthy subjects and group B 15 patients with present proven TMD disease. Rasterstereographic images were taken at different times. Group A subjects were scanned twice within half a year and group B before initiation as well as after the first MT and after completion of the prescribed MT. The different posture variables were calculated using DIERS Formetric software. Results To illustrate the differences between the two groups, 10 different postural variables were examined. Significant differences between the two groups were observed in pelvic tilt, surface rotation, and kyphotic apex. Pelvic tilt: mean = 7.581, p -value = 0.029; surface rotation: mean = 3.098, p = 0.049; and mean kyphotic apex = 11.538 and 11.946, respectively, with p -values of 0.037 and 0.029, respectively. Conclusion MT leads to a change in posture in TMD patients. This could influence the course of TMD treatment.Open Access funding enabled and organized by Projekt DEAL.Universitätsklinikum Erlangen (8546
Rapid Evolution of Metastases in Patients with Treated G3 Neuroendocrine Tumors Associated with NEC-Like Transformation and TP53 Mutation
Get PDFLittle is known about the morphomolecular features of G3 neuroendocrine tumors (G3NETs) under prolonged systemic treatments, although rapid progression is increasingly observed. This longitudinal study aims to elucidate the course and morphomolecular features of metastasized G3NETs with high-grade transformation. Clinical and histological findings in 40 patients with metastasized and treated G3NETs, which were histologically examined at least twice with an interval time of more than 6 months (median 27), were reviewed and the morphomolecular changes recorded and assigned to treatment. Neuroendocrine carcinoma (NEC)-like histology defined by high-grade atypia, diffuse growth pattern, and/or necrosis was identified in nine (22%) G3NETs (seven pancreatic, two rectal) patients. All NEC-like tumors showed a significantly higher Ki67 increase and longer interval time between first and last examination than non-NEC-like G3NETs (53 vs. 19% and 60 vs. 24 months, respectively). Moreover, all NEC-like G3NETs had TP53 (100%), but rarely RB1 (12%) mutations, and retained NET-typical mutations such as MEN1 or DAXX (five of the pancreatic NETs). The last treatments received prior to the NEC-like transformation included PRRT ( n = 3), somatostatin analog, everolimus, sunitinib ( n = 1 each), and alkylating agents ( n = 2). Abrupt clinical progression in patients with metastasized G3NETs is associated with a significant increase in Ki67, accelerated growth, and NEC-like histology. These findings are most likely attributable to the novel TP53 mutation, which was detected in all nine cases at the last evaluation. However, none of the cases exhibited a complete transformation to a typical NEC, as the tumors retained partial histological and genetic features of NETs.Open Access funding enabled and organized by Projekt DEAL.Technische Universität München (1025
Neurocysticercosis Prevalence and Characteristics in Communities of Sinda District in Zambia: A Cross-Sectional Study
Get PDFBackground This study aimed at describing the epidemiology of (neuro)cysticercosis as well as its clinical and radiological characteristics in a Taenia solium endemic district of Zambia. Methods This was part of a cross-sectional community-based study conducted in Sinda district to evaluate an antibody-detecting T. solium point-of-care (TS POC) test for taeniosis and (neuro)cysticercosis. All TS POC cysticercosis positive (CC+) participants and a subset of the TS POC cysticercosis negative (CC-) received a clinical evaluation and cerebral computed tomography (CT) examination for neurocysticercosis (NCC) diagnosis and staging. Results Of the 1249 participants with a valid TS POC test result, 177 (14%) were TS POC CC+ . Cysticercosis sero-prevalence was estimated to be 20.1% (95% confidence intervals [CI] 14.6–27.0%). In total, 233 participants received a CT examination (151 TS POC CC+ , 82 TS POC CC-). Typical NCC lesions were present in 35/151 (23%) TS POC CC+ , and in 10/82 (12%) TS POC CC- participants. NCC prevalence was 13.5% (95% CI 8.4–21.1%) in the study population and 38.0% (95% CI 5.2–87.4%) among people reporting epileptic seizures. Participants with NCC were more likely to experience epileptic seizures (OR = 3.98, 95% CI 1.34–11.78, p = 0.01) than those without NCC, although only 7/45 (16%) people with NCC ever experienced epileptic seizures. The number of lesions did not differ by TS POC CC status (median: 3 [IQR 1–6] versus 2.5 [IQR 1–5.3], p = 0.64). Eight (23%) of the 35 TS POC CC+ participants with NCC had active stage lesions; in contrast none of the TS POC CC- participants was diagnosed with active NCC. Conclusion NCC is common in communities in the Eastern province of Zambia, but a large proportion of people remain asymptomatic.European and Developing Countries Clinical Trials Partnershiphttp://dx.doi.org/10.13039/501100001713German Federal Ministry of Education and Researc
Spatial expression of claudin 18.2 in matched primaries and metastases of tubo-ovarian carcinoma of all subtypes
Get PDFPhysiologically, claudin 18 splice variant 2 (CLDN18.2) expression is restricted to the gastric epithelium, but its expression has been detected in solid cancers. Zolbetuximab, a chimeric IgG1 antibody targeting CLDN18.2, has demonstrated promising effects in patients suffering from CLDN18.2-positive, HER2-negative locally advanced gastric cancer and is currently being studied further. To date, little is known about CLDN18.2 expression in other histological subtypes of tubo-ovarian carcinoma (TOC) and their matching metastases. Using a cohort of all histological TOC subtypes, we investigated the immunohistochemical (IHC) CLDN18.2 expression in both TOCs ( n = 536), their matching metastatic tissue ( n = 385) and in 93 metastases without primary. Tissue microarrays comprised both the tumor center and periphery. IHC positivity was defined as biomarker expression of ≥ 75% in tumor cells with moderate-to-strong membranous staining. Overall CLDN18.2 positivity was 4.1% (21/515) in the TOC centers and 3.6% (18/498) in their peripheries. In primaries of mucinous tubo-ovarian carcinoma (MTOC), CLDN18.2 positivity rates were 45% (18/40) and 36.6% (15/41), respectively. Positivity rates for the corresponding metastases were 33% (4/12, center) and 27% (3/11, periphery). The expression was relatively homogenous throughout all tumor sites. With no expression in 99.5% of nonmucinous tumors, CLDN18.2 positivity was almost exclusively seen in the mucinous subtype. In tubo-ovarian carcinoma, CLDN18.2 expression was, with rare exceptions, restricted to the mucinous subtype. Among them, 33% of metastasized MTOCs presented with CLDN18.2 positivity. Hence, CLDN18.2 might display a promising target for personalized therapy in patients with advanced MTOC.Open Access funding enabled and organized by Projekt DEAL.Interdisziplinäres Zentrum für Klinische Forschung, Universitätsklinikum Würzburghttp://dx.doi.org/10.13039/501100009379Universitätsklinikum Erlangen (8546
Biomechanical conditioning of engineered heart muscle tissue
No full textZusammenfassung Hintergrund Künstlich hergestelltes Myokard („engineered heart tissue“, EHT) ist vielversprechend als Ersatz für beschädigtes Herzmuskelgewebe und als Modell zur Erforschung kardialer Erkrankungen, doch seine Unreife in Morphologie und Funktion bleibt eine Herausforderung. In dieser Arbeit wurde progressive Dehnung als eine innovative Stimulation zur Förderung der Ausreifung von EHT entwickelt und systematisch evaluiert. Methoden Ringförmige EHT wurden aus humanen induziert-pluripotenten Stammzellen erstellt und in einem biomimetischen Gewebekultursystem schrittweise in 4 verschiedenen Geschwindigkeiten gedehnt. Der selbst entwickelte Bioreaktor ermöglichte eine kontinuierliche elektrische Stimulation und Messung der Kontraktionskräfte von 8 parallel kultivierten EHT. Ergebnisse Die durch Dehnung konditionierten EHT entwickelten innerhalb von 3 Wochen eine dem menschlichen Herzmuskel vergleichbare Kontraktionskraft. Nach dieser Phase wiesen sie charakteristische funktionelle Eigenschaften des menschlichen Myokards auf, inklusive einer positiven Kraft-Frequenz-Abhängigkeit, einer deutlichen Zunahme der Kontraktionskraft bei Steigerung der Vorlast und eines physiologischen Aktionspotenzials. Zudem führte die progressive Dehnung zu Längenwachstum und linearer Ausrichtung der Kardiomyozyten sowie zu verbesserter Dichte und Reifung der Sarkomere. Schlussfolgerung Konditionierung durch progressive Dehnung unterstützt die mechanische, elektrische und strukturelle Reifung von künstlich hergestelltem Myokard. Dieser Ansatz verringert den Unterschied zwischen künstlichem Gewebe und dem adulten menschlichen Myokard und könnte so wichtige Anforderungen der Krankheitsmodellierung und des myokardialen Gewebeersatzes erfüllen.Background Engineered heart tissue (EHT) shows promise as a replacement for damaged myocardial tissue and for understanding cardiac disease but immaturity in morphology and function remains a challenge. In this work, progressive stretching was developed and systematically evaluated as an innovative stimulation to promote EHT maturation. Methods Ring-shaped EHT were produced from human induced-pluripotent stem cells (iPSC) and were progressively stretched at four different rates in a custom-built biomimetic tissue culture system. The self-developed bioreactor provided continuous electrical stimulation and measurement of contraction forces of eight EHT in parallel. Results Within 3 weeks of stretch conditioning the EHT developed contractile forces comparable to human heart muscle. After this phase the EHT exhibited functional properties characteristic of human myocardium, including a positive force-frequency dependency, a significant response of contractility to alterations of preload and a physiological action potential. In addition, progressive stretching improved longitudinal growth and linear alignment of iPS cardiomyocytes as well as improved the density and maturation of sarcomeres. Conclusion Conditioning with progressive stretching supports the mechanical, electrical, and structural maturation of engineered myocardium. This approach reduces the difference between engineered tissue and the adult human myocardium and could thus fulfil important requirements of cardiac disease modelling and myocardial tissue replacement
