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Background: The use of energy-based tissue-sealing and cutting instruments is becoming more and more popular in visceral, urological, and gynecological surgery. For their safe and efficacious use in clinical practice, such instruments have to reliably seal vessels with a minimal sealing failure rate, cause minimal thermal damage to adjacent tissue, and have good cutting qualities.Methods: The efficacy and safety of the novel energy-based instrument for dissection, hemostasis and cutting (BiCision(®), ERBE) was compared to a commercially available device (EnSeal(®), Ethicon Endo-Surgery). We investigated vessel-sealing reliability (success rate), sealing quality and sealing time, lateral thermal damage cutting quality, tissue sticking to the instrument, burst pressure and delayed complications in an acute and chronic pig model after splenectomy, small bowel resection, nephrectomy, salpingo-oophorectomy, and sealing of peripheral vessels.Results: For all parameters investigated, BiCision(®) was at least equivalent to EnSeal(®). BiCision(®) was even superior to EnSeal(®) with respect to the burst pressure in arteries (p = 0.044) and veins (p = 0.023) and the cut quality in all locations (arteries, p = 0.0009; veins, p = 0.043). The course of the 7-day chronic study was uneventful except for one animal that developed an intestinal obstruction. None of the animals showed any signs of postoperative bleeding. On second-look laparotomy at day 7, macroscopic inspection of the sealed tissue and vessels did not show any signs of complications or evidence that bleeding had occurred. Histologically, the integrity of vessel wall fusion, thermal alterations, and inflammatory reactions were comparable, confirming substantial equivalence.Conclusion: We demonstrated that the efficacy and quality of vessel sealing with BiCision(®) is at least equivalent to those of EnSeal(®) for vessel diameters up to 7 mm. Since EnSeal(®) has already been shown to be safe in clinical practice, BiCision(®) should be as reliable as EnSeal(®) under clinical conditions. [ABSTRACT FROM AUTHOR]

In contrast to mammals, adult zebrafish achieve complete heart regeneration via proliferation of cardiomyocytes. Surprisingly, we found that regenerating cardiomyocytes experience DNA replication stress, which represents one reason for declining tissue regeneration during aging in mammals. Pharmacological inhibition of ATM and ATR kinases revealed that DNA damage response signaling is essential for zebrafish heart regeneration. Manipulation of Bone Morphogenetic Protein (BMP)-Smad signaling using transgenics and mutants showed that BMP signaling alleviates cardiomyocyte replication stress. BMP signaling also rescues neonatal mouse cardiomyocytes, human fibroblasts and human hematopoietic stem and progenitor cells (HSPCs) from replication stress. DNA fiber spreading assays indicate that BMP signaling facilitates re-start of replication forks after replication stress-induced stalling. Our results identify the ability to overcome replication stress as key factor for the elevated zebrafish heart regeneration capacity and reveal a conserved role for BMP signaling in promotion of stress-free DNA replication., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Objective:  The aim of this study was to assess the outcome of arthroscopic subtotal coronoidectomy in treating medial coronoid disease and the effect of concurrent autologous conditioned plasma (ACP) in dogs using force plate analysis., Study Design:  This study included 16 dogs with unilateral medial coronoid disease based on computed tomographic imaging. Treatment consisted of an arthroscopic subtotal coronoidectomy. As concurrent therapy, eight dogs received ACP at the end of the arthroscopy and eight dogs a placebo. Force plate analysis, including vertical forces, braking and propulsive forces, corresponding impulses and symmetry indices, was performed prior to arthroscopy and at 4, 12 and 26 weeks postoperatively., Results:  After an initial reduction of all force plate analysis parameters, vertical and propulsive parameters gradually improved to the level of healthy dogs at 26 weeks postoperatively. In contrast, braking parameters did not reach normal values at 26 weeks, demonstrating ongoing loss of elbow joint function. The ACP and placebo group did not show any significant difference in force plate analysis parameters during the 26 weeks study period., Conclusion:  Arthroscopic subtotal coronoidectomy did not result in complete normalization of ground reaction forces, impulses and symmetry indices. Concurrent treatment with ACP, immediately after arthroscopy, did not improve outcome. Our results show that outcome of arthroscopic subtotal coronoidectomy in treating medial coronoid disease is less favourable than previously reported., Competing Interests: None declared., (Thieme. All rights reserved.)

The impact of space radiation and microgravity on DNA damage responses has been discussed controversially, largely due to the variety of model systems engaged. Here, we performed side-by-side analyses of human hematopoietic stem/progenitor cells (HSPC) and peripheral blood lymphocytes (PBL) cultivated in a 2D clinostat to simulate microgravity before, during and after photon and particle irradiation. We demonstrate that simulated microgravity (SMG) accelerates the early phase of non-homologous end joining (NHEJ)-mediated repair of simple, X-ray-induced DNA double-strand breaks (DSBs) in PBL, while repair kinetics in HSPC remained unaltered. Repair acceleration was lost with increasing LET of ion exposures, which increases the complexity of DSBs, precluding NHEJ and requiring end resection for successful repair. Such cell-type specific effect of SMG on DSB repair was dependent on the NF-кB pathway pre-activated in PBL but not HSPC. Already under unperturbed growth conditions HSPC and PBL suffered from SMG-induced replication stress associated with accumulation of single-stranded DNA and DSBs, respectively. We conclude that in PBL, SMG-induced DSBs promote repair of radiation-induced damage in an adaptive-like response. HSPC feature SMG-induced single-stranded DNA and FANCD2 foci, i.e., markers of persistent replication stress and senescence that may contribute to a premature decline of the immune system in space.

C-X-C Motif Chemokine Receptor 4 (CXCR4) is part of the human chemokine system and involved in progression and metastasis in renal cell carcinoma (RCC). However, the role of CXCR4 protein expression in RCC remains controversial. In particular, data regarding the subcellular distribution of CXCR4 in RCC and RCC metastasis as well as CXCR4 expression in renal tumors of variant histology are limited. The aim of the present study was the evaluation of the differential CXCR4 expression in RCC primary tumor and metastatic tissue as well as in variant renal histologies. In addition, the prognostic capacity of CXCR4 expression in organ-confined clear cell RCC (ccRCC) was evaluated. Three independent renal tumor cohorts (primary ccRCC cohort n 1 = 64; cohort of various histological entities n 2 = 146; metastatic RCC tissue cohort n 3 = 92) were evaluated using tissue microarrays (TMA). After immunohistochemical staining for CXCR4, nuclear and cytoplasmic expression patterns were evaluated. CXCR4 expression was correlated with validated pathologic prognosticators, clinical data, and overall and cancer-specific survival. Positive cytoplasmic staining was observed in 98% of the benign and 38.9% of the malignant samples. Nuclear staining was positive for 94.1% of the benign samples and 83% of the malignant samples. The median cytoplasmic expression score was found to be higher in benign tissue than in ccRCC (130.00 vs. 0.00); median nuclear expression score analysis indicated the opposite (56.0 vs. 71.0). Within malignant subtypes, the highest expression score was seen in papillary renal cell carcinomas (cytoplasmic: 117.50, nuclear: 41.50). Within benign renal tumors, high cytoplasmic and nuclear CXCR4 expression scores were seen for oncocytomas (cytoplasmic: 100.00, nuclear: 31.00). Expression scores in RCC metastasis ranked between benign renal tissue and ccRCC in cytoplasmic and nuclear expression. Cytoplasmic CXCR4 expression was identified as a prognostic factor for OS and CSS ( p = 0.042; p = 0.019). Multivariate analysis including clinicopathological parameters did not reveal an independent prognostic character of CXCR4 expression. CXCR4 expression differs significantly within benign lesions and renal neoplasms. Cytoplasmic and nuclear expression of CXCR4 could be detected across all RCC subtypes. The prognostic value of CXCR4 in ccRCC was confirmed in univariate analysis.