Prognostic significance of the controlling nutritional status (CONUT) score in patients undergoing hepatectomy for hepatocellular carcinoma: a systematic review and meta-analysis

Background: The clinical value of the controlling nutritional status (CONUT) score in hepatocellular carcinoma (HCC) has increased. The aim of this meta-analysis was to systematically review the association between the CONUT score and outcomes in patients undergoing hepatectomy for HCC. Methods: Embase, Medline Ovid, Web of Science, Cochrane CENTRAL, and Google Scholar were systematically searched. Random effects meta-analyses were conducted to examine the prognostic value of the CONUT score in HCC patients. Results: A total of five studies including 4679 patients were found to be eligible and analyzed in the meta-analysis. The CONUT score was significantly associated with overall survival (HR 1.78, 95%CI = 1.20-2.64, P = 0.004, I-2 = 79%), recurrence-free survival (HR 1.34, 95%CI = 1.17-1.53, P Conclusions: The CONUT score is an independent prognostic indicator of the prognosis and is associated with postoperative major complications and hepatic functional reserve in HCC patients

Biomechanical comparison of menisci from different species and artificial constructs

Background: Loss of meniscal tissue is correlated with early osteoarthritis but few data exist regarding detailed biomechanical properties (e. g. viscoelastic behavior) of menisci in different species commonly used as animal models. The purpose of the current study was to biomechanically characterize bovine, ovine, and porcine menisci (each n = 6, midpart of the medial meniscus) and compare their properties to that of normal and degenerated human menisci (n = 6) and two commercially available artificial scaffolds (each n = 3). Methods: Samples were tested in a cyclic, minimally constraint compression-relaxation test with a universal testing machine allowing the characterization of the viscoelastic properties including stiffness, residual force and relative sample compression. T-tests were used to compare the biomechanical parameters of all samples. Significance level was set at p < 0.05. Results: Throughout cyclic testing stiffness, residual force and relative sample compression increased significantly (p < 0.05) in all tested meniscus samples. From the tested animal meniscus samples the ovine menisci showed the highest biomechanical similarity to human menisci in terms of stiffness (human: 8.54 N/mm +/- 1.87, cycle 1; ovine: 11.24 N/mm +/- 2.36, cycle 1, p = 0.0528), residual force (human: 2.99 N +/- 0.63, cycle 1 vs. ovine 3.24 N +/- 0.13, cycle 1, p = 0.364) and relative sample compression (human 19.92\% +/- 0.63, cycle 1 vs. 18.72\% +/- 1.84 in ovine samples at cycle 1, p = 0.162). The artificial constructs - as hypothesized- revealed statistically significant inferior biomechanical properties. Conclusions: For future research the use of ovine meniscus would be desirable showing the highest biomechanical similarities to human meniscus tissue. The significantly different biomechanical properties of the artificial scaffolds highlight the necessity of cellular ingrowth and formation of extracellular matrix to gain viscoelastic properties. As a consequence, a period of unloading (at least partial weight bearing) is necessary, until the remodeling process in the scaffold is sufficient to withstand forces during weight bearing

Mimicking acute airway tissue damage using femtosecond laser nanosurgery in airway organoids

Airway organoids derived from adult murine epithelial cells represent a complex 3D in vitro system mimicking the airway epithelial tissue’s native cell composition and physiological properties. In combination with a precise damage induction via femtosecond laser-based nanosurgery, this model might allow for the examination of intra- and intercellular dynamics in the course of repair processes with a high spatio-temporal resolution, which can hardly be reached using in vivo approaches. For characterization of the organoids’ response to single or multiple-cell ablation, we first analyzed overall organoid survival and found that airway organoids were capable of efficiently repairing damage induced by femtosecond laser-based ablation of a single to ten cells within 24 h. An EdU staining assay further revealed a steady proliferative potential of airway organoid cells. Especially in the case of ablation of five cells, proliferation was enhanced within the first 4 h upon damage induction, whereas ablation of ten cells was followed by a slight decrease in proliferation within this time frame. Analyzing individual trajectories of single cells within airway organoids, we found an increased migratory behavior in cells within close proximity to the ablation site following the ablation of ten, but not five cells. Bulk RNA sequencing and subsequent enrichment analysis revealed the differential expression of sets of genes involved in the regulation of epithelial repair, distinct signaling pathway activities such as Notch signaling, as well as cell migration after laser-based ablation. Together, our findings demonstrate that organoid repair upon ablation of ten cells involves key processes by which native airway epithelial wound healing is regulated. This marks the herein presented in vitro damage model suitable to study repair processes following localized airway injury, thereby posing a novel approach to gain insights into the mechanisms driving epithelial repair on a single-cell level

Evaluation of Electrospun Poly(ε-Caprolactone)/Gelatin Nanofiber Mats Containing Clove Essential Oil for Antibacterial Wound Dressing

The objective of this study was to produce antibacterial poly(ε-caprolactone) (PCL)-gelatin (GEL) electrospun nanofiber mats containing clove essential oil (CLV) using glacial acetic acid (GAA) as a “benign” (non-toxic) solvent. The addition of CLV increased the fiber diameter from 241 ± 96 to 305 ± 82 nm. Aside from this, the wettability of PCL-GEL nanofiber mats was increased by the addition of CLV. Fourier-transform infrared spectroscopy (FTIR) analysis confirmed the presence of CLV, and the actual content of CLV was determined by gas chromatography–mass spectrometry (GC-MS). Our investigations showed that CLV-loaded PCL-GEL nanofiber mats did not have cytotoxic effects on normal human dermal fibroblast (NHDF) cells. On the other hand, the fibers exhibited antibacterial activity against Staphylococcus aureus and Escherichia coli. Consequently, PCL-GEL/CLV nanofiber mats are potential candidates for antibiotic-free wound healing applications

CD14 and ALPK1 Affect Expression of Tight Junction Components and Proinflammatory Mediators upon Bacterial Stimulation in a Colonic 3D Organoid Model

Cd14 and Alpk1 both encode pathogen recognition receptors and are known candidate genes for affecting severity in inflammatory bowel diseases. CD14 acts as a coreceptor for bacterial lipopolysaccharide (LPS), while ALPK1 senses ADP-D-glycero-beta-D-manno-heptose, a metabolic intermediate of LPS biosynthesis. Intestinal barrier integrity can be influenced by CD14, whereas to date, the role of ALPK1 in maintaining barrier function remains unknown. We used colon-derived 3D organoids, first characterised for growth, proliferation, stem cell markers, and expression of tight junction (TJ) components using qPCR and immunohistochemistry. They showed characteristic crypt stem cells, apical shedding of dead cells, and TJ formation. Afterwards, organoids of different genotypes (WT, Il10-/-, Cd14-/-, and Alpk1-/-) were then stimulated with either LPS or Escherichia coli Nissle 1917 (EcN). Gene expression and protein levels of cytokines and TJ components were analysed. WT organoids increased expression of Tnfα and tight junction components. Cd14-/- organoids expressed significantly less Tnfα and Ocln after LPS stimulation than WT organoids but reacted similarly to WT organoids after EcN stimulation. In contrast, compared to WT, Alpk1-/- organoids showed decreased expression of different TJ and cytokine genes in response to EcN but not LPS. However, Western blotting revealed an effect of ALPK1 on TJ protein levels. These findings demonstrate that Cd14, but not Alpk1, alters the response to LPS stimulation in colonic epithelial cells, whereas Alpk1 is involved in the response upon bacterial challenge. © 2020 Pascal Brooks et al

Impact of sarcopenia on clinical outcomes for patients with resected hepatocellular carcinoma:a retrospective comparison of Eastern and Western cohorts

BACKGROUND: Patient fitness is important for guiding treatment. Muscle mass, as a reflection thereof, can be objectively measured. However, the role of East-West differences remains unclear. Therefore, we compared the impact of muscle mass on clinical outcomes after liver resection for hepatocellular carcinoma (HCC) in a Dutch [the Netherlands (NL)] and Japanese [Japan (JP)] setting and evaluated the predictive performance of different cutoff values for sarcopenia. METHOD: In this multicenter retrospective cohort study, patients with HCC undergoing liver resection were included. The skeletal muscle mass index (SMI) was determined on computed tomography scans obtained within 3 months before surgery. The primary outcome measure was overall survival (OS). Secondary outcome measures were: 90-day mortality, severe complications, length of stay, and recurrence-free survival. The predictive performance of several sarcopenia cutoff values was studied using the concordance index (C-index) and area under the curve. Interaction terms were used to study the geographic effect modification of muscle mass. RESULTS: Demographics differed between NL and JP. Gender, age, and body mass index were associated with SMI. Significant effect modification between NL and JP was found for BMI. The predictive performance of sarcopenia for both short-term and long-term outcomes was higher in JP compared to NL (maximum C-index: 0.58 vs. 0.55, respectively). However, differences between cutoff values were small. For the association between sarcopenia and OS, a strong association was found in JP [hazard ratio (HR) 2.00, 95% CI [1.230-3.08], P =0.002], where this was not found in NL (0.76 [0.42-1.36], P =0.351). The interaction term confirmed that this difference was significant (HR 0.37, 95% CI [0.19-0.73], P =0.005). CONCLUSIONS: The impact of sarcopenia on survival differs between the East and West. Clinical trials and treatment guidelines using sarcopenia for risk stratification should be validated in race-dependent populations prior to clinical adoption.</p

Investigation of Colonic Regeneration via Precise Damage Application Using Femtosecond Laser-Based Nanosurgery

Organoids represent the cellular composition of natural tissue. So called colonoids, organoids derived from colon tissue, are a good model for understanding regeneration. However, next to the cellular composition, the surrounding matrix, the cell–cell interactions, and environmental factors have to be considered. This requires new approaches for the manipulation of a colonoid. Of key interest is the precise application of localized damage and the following cellular reaction. We have established multiphoton imaging in combination with femtosecond laser-based cellular nanosurgery in colonoids to ablate single cells in the colonoids’ crypts, the proliferative zones, and the differentiated zones. We observed that half of the colonoids recovered within six hours after manipulation. An invagination of the damaged cell and closing of the structure was observed. In about a third of the cases of targeted crypt damage, it caused a stop in crypt proliferation. In the majority of colonoids ablated in the crypt, the damage led to an increase in Wnt signalling, indicated via a fluorescent lentiviral biosensor. qRT-PCR analysis showed increased expression of various proliferation and Wnt-associated genes in response to damage. Our new model of probing colonoid regeneration paves the way to better understand organoid dynamics on a single cell level. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

Establishment of a guided, in vivo, multi-channel, abdominal, tissue imaging approach

Novel tools in humane animal research should benefit the animal as well as the experimentally obtained data. Imaging technologies have proven to be versatile and also in accordance with the demands of the 3 R principle. However, most imaging technologies are either limited by the target organs, number of repetitive imaging sessions, or the maximal resolution. We present a technique-, which enables multicolor abdominal imaging on a tissue level. It is based on a small imaging fiber endoscope, which is guided by a second commercial endoscope. The imaging fiber endoscope allows the distinction of four different fluorescence channels. It has a size of less than 1 mm and can approximately resolve single cells. The imaging fiber was successfully tested on cells in vitro, excised organ tissue, and in mice in vivo. Combined with neural networks for image restauration, high quality images from various abdominal organs of interest were realized. The second endoscope ensured a precise placement of the imaging fiber in vivo. Our approach of guided tissue imaging in vivo, combined with neuronal networks for image restauration, permits the acquisition of fluorescence-microscope like images with minimal invasive surgery in vivo. Therefore, it is possible to extend our approach to repetitive imaging sessions. The cost below 30 thousand euros allows an establishment of this approach in various scenarios. © 2020, The Author(s)

Electric field modification of magnetotransport in Ni thin films on (011) PMN-PT piezosubstrates

This study reports the magnetotransport and magnetic properties of 20 nm-thick polycrystalline Ni films deposited by magnetron sputtering on unpoled piezoelectric (011) [PbMg1/3Nb2/3O3](0.68)-[PbTiO3](0.32) (PMN-PT) substrates. The longitudinal magnetoresistance (MR) of the Ni films on (011) PMN-PT, measured at room temperature in the magnetic field range of -0.3T < mu H-0 < 0.3 T, is found to depend on the crystallographic direction and polarization state of piezosubstrate. Upon poling the PMN-PT substrate, which results in a transfer of strain to the Ni film, the MR value decreases by factor of 20 for the current along [100] of PMN-PT and slightly increases for the [01 (1) over bar] current direction. Simultaneously, a strong increase (decrease) in the field value, where the MR saturates, is observed for the [01 (1) over bar] ([100]) current direction. The anisotropic magnetoresistance is also strongly affected by the remanent strain induced by the electric field pulses applied to the PMN-PT in the non-linear regime revealing a large (132 mT) magnetic anisotropy field. Applying a critical electric field of 2.4 kV/cm, the anisotropy field value changes back to the original value, opening a path to voltage-tuned magnetic field sensor or storage devices. This strain mediated voltage control of the MR and its dependence on the crystallographic direction is correlated with the results of magnetization reversal measurements. (C) 2015 AIP Publishing LLC

A 15-year review of lightning deaths in Germany-with a focus on pathognomonic findings

DATA AVAILABILITY : The data sets analyzed for the current study are available upon request from the corresponding author.Lethal accidents caused by lightning are divided into observed and unobserved events. Pathognomonic or characteristic findings are often overlooked during external postmortem examination. Classical mistakes may be made which may often lead to an incorrect diagnosis. An analysis of 270 fatalities was performed on a historical collection of the Committee for Lightning Conductor Construction for the United Economic Area e. V. (ABBW) on lethal accidents due to lightning that occurred in Germany for the period 1951–1965. Furthermore, a selective literature research was carried out. The aim of the study was to analyze the death scene, the clothing, and the victim. The authors focused on chief findings which were relevant to the correct diagnosis of “death by lightning.” Both Lichtenberg figures and singed body hair were considered pathognomonic for a lightning strike. The question arose as to whether Lichtenberg figures, for example, represented the finding that most often led to the correct diagnosis. Of the 270 lightning-struck victims from the case collection, 129 (47.8%) had singed body hair and 25 (9.3%) had Lichtenberg figures. A comparison of the frequency of the two reported findings, singed body hair versus Lichtenberg figures, has only been performed in the literature for case numbers below 40. This study is the first evaluation of a relatively large number of lethal accidents due to lightning. Singed body hair was reported more frequently in lightning-struck victims than Lichtenberg figures. This study showed that singed body hair is probably more diagnostically important than Lichtenberg figures.Open Access funding enabled and organized by Projekt DEAL.https://www.springer.com/journal/414hj2024Forensic MedicineSDG-03:Good heatlh and well-bein