Analysis of Major Histocompatibility Antigens and the Mononuclear Cell Infiltrate in Halo Nevi

A series of monoclonal antibodies was used to characterize the nevomelanocytes and the inflammatory infiltrate of 11 halo nevi in different stages of resolution, employing an immunoperoxidase technique. Three of the 11 halo nevi histologically showed signs of mild or moderate nevomelanocytic atypia. It was found that the vast majority of the nevomelanocytes in halo nevi with a dense inflammatory infiltrate markedly expressed HLA-A,B,C antigens, while expression was not demonstrable in nevocellular nests not adjacent to the mononuclear infiltrate. No difference in expression of HLA-A,B,C antigens was found between the 3 cases with mild or moderate nevomelanocytic atypia and the other eases lacking atypia. Expression of HLA-DR (Ia-like) antigens was found on few nevomelanocytes in only 2 of 11 lesions. The cellular composition of the mononuclear inflammatory infiltrate showed a predominance of T cells (80% or more) with a relatively high proportion of cytotoxic/suppressor T cells. Most of the T cells showed signs of activation as judged by staining for HLA-DR antigens. These results demonstrate that the expression of HLA- A,B,C antigens on the nevomelanocytes and the cellular composition of the mononuclear inflammatory infiltrate in halo nevi are very similar to that in malignant melanomas and dysplastic nevi. These findings also indicate that the expression of HLA-A,B,C antigens on nevomelanocytes is primarily dependent on the presence of T- cell immune response and not necessarily related to the presence of nevomelanocytic atypia

Challenging medical students with an interim assessment: a positive effect on formal examination score in a randomized controlled study

Until now, positive effects of assessment at a medical curriculum level have not been demonstrated. This study was performed to determine whether an interim assessment, taken during a small group work session of an ongoing biomedical course, results in students’ increased performance at the formal course examination. A randomized controlled trial was set up, with an interim assessment without explicit feedback as intervention. It was performed during a regular biomedical Bachelor course of 4 weeks on General Pathology at the Radboud University Nijmegen Medical Centre. Participants were 326 medical and 91 biomedical science students divided into three study arms: arm Intervention-1 (I-1) receiving one interim assessment; arm I-2 receiving two interim assessments, and control arm C, receiving no interim assessment. The study arms were stratified for gender and study discipline. The interim assessment consisted of seven multiple-choice questions on tumour pathology. Main outcome measures were overall score of the formal examination (scale 1–10), and the subscore of the questions on tumour pathology (scale 1–10). We found that students who underwent an interim assessment (arm I) had a 0.29-point (scale 1–10) higher score on the formal examination than the control group (p = 0.037). For the questions in the formal examination on tumour pathology the score amounted to 0.47 points higher (p = 0.007), whereas it was 0.17 points higher for the questions on topics related to the previous 3 weeks. No differences in formal examination score were found between arms I-1 and I-2 (p = 0.817). These findings suggest that an interim assessment during a small group work session in a randomized study setting stimulates students to increase their formal examination score

Functional and Morphologic Analysis of the Fluid-Conducting Meshwork in Xenografted Cutaneous and Primary Uveal Melanoma

PURPOSE. In primary uveal and cutaneous melanoma lesions, extracellular matrix (ECM) is often deposited in arcs, loops, and network patterns. Based on prognostic relevance, these patterns appear to play a significant role in facilitating metastasis. It has been demonstrated that these patterns were capable of transmitting fluid. The current study was undertaken to elucidate further the functional role of these patterns in tumor perfusion and to examine the composition of the patterns by immunohistochemistry. METHODS. To study the role of these patterns in perfusion, fluorochrome-labeled bovine serum albumin, bovine insulin, and dextrans of different molecular sizes were injected intravenously into nude mice bearing subcutaneous human cutaneous melanoma xenografts. Distribution of the human melanoma cells and murine host cells was analyzed by DNA in situ hybridization. To elucidate the composition of these patterns, human uveal melanoma tissues were analyzed for expression of ECM components by immunohistochemistry. RESULTS. Small molecules (Stokes' radius Ͻ4.4 nm) crossed the vessel wall and spread along the ECM patterns within 2 to 10 minutes, whereas larger molecules (Stokes' radius ϳ5.8 nm) required 30 to 45 minutes to enter. Murine host cells were found exclusively in the ECM pattern compartment. In primary uveal melanoma, different types of collagen, ECM-associated heparan sulfate proteoglycans, and different types of cells were present in the patterns. CONCLUSIONS. The data suggest that the ECM deposited as arcs, loops, and network patterns, accommodate the transport of plasma-derived molecules, (e.g., nutrients), to the tumor lesion, thus enhancing tumor growth and progression, and facilitating infiltration of tumor tissue by host-derived cells. (Invest Ophthalmol Vis Sci. 2005;46:3013-3020

A toolbox for the comprehensive analysis of small volume human intestinal samples that can be used with gastrointestinal sampling capsules

Detailed knowledge on the fate of dietary components inside the human intestinal tract is lacking. Access to this inner world of digestion is now possible through novel human gastrointestinal sampling capsules. Due to the novelty of such devices, no methodology has been published to stabilise and analyse the resulting samples. A complicating factor is that excretion of such capsules in faeces may take days, while degradation of the dietary components continues. Therefore a stabilising reagent should be pre-loaded in the capsule to ensure the measurement of a representative sample. Considering the small volume of recovered samples, analytical methods must be optimized to collect as many data as possible from little material. We present a complete workflow for stabilising and analysing the fermentation status of dietary fibres in such samples, including microbiota, fibre degradation, and short chain fatty acids. The final quenching reagent was designed based on safety and effectiveness to inhibit fructo- and galacto-oligosaccharides degradation and short chain fatty acids production by human ileostomy microbiota, and subsequently validated in faecal samples. The final composition of the stock quenching reagent is 175 mM Tris, 525 mM NaCl, 35 mM EDTA, 12% SDS, and 8 M urea at pH 8.5.</p

Wettability-independent bouncing on flat surfaces mediated by thin air films

The impingement of drops onto solid surfaces1, 2 plays a crucial role in a variety of processes, including inkjet printing, fog harvesting, anti-icing, dropwise condensation and spray coating3, 4, 5, 6. Recent efforts in understanding and controlling drop impact behaviour focused on superhydrophobic surfaces with specific surface structures enabling drop bouncing with reduced contact time7, 8. Here, we report a different universal bouncing mechanism that occurs on both wetting and non-wetting flat surfaces for both high and low surface tension liquids. Using high-speed multiple-wavelength interferometry9, we show that this bouncing mechanism is based on the continuous presence of an air film for moderate drop impact velocities. This submicrometre ‘air cushion’ slows down the incoming drop and reverses its momentum. Viscous forces in the air film play a key role in this process: they provide transient stability of the air cushion against squeeze-out, mediate momentum transfer, and contribute a substantial part of the energy dissipation during bouncing

New fossil remains of Homo naledi from the Lesedi Chamber, South Africa

The Rising Star cave system has produced abundant fossil hominin remains within the Dinaledi Chamber, representing a minimum of 15 individuals attributed to Homo naledi. Further exploration led to the discovery of hominin material, now comprising 131 hominin specimens, within a second chamber, the Lesedi Chamber. The Lesedi Chamber is far separated from the Dinaledi Chamber within the Rising Star cave system, and represents a second depositional context for hominin remains. In each of three collection areas within the Lesedi Chamber, diagnostic skeletal material allows a clear attribution to H. naledi. Both adult and immature material is present. The hominin remains represent at least three individuals based upon duplication of elements, but more individuals are likely present based upon the spatial context. The most significant specimen is the near-complete cranium of a large individual, designated LES1, with an endocranial volume of approximately 610 ml and associated postcranial remains. The Lesedi Chamber skeletal sample extends our knowledge of the morphology and variation of H. naledi, and evidence of H. naledi from both recovery localities shows a consistent pattern of differentiation from other hominin species

Trends and overall survival after combined liver resection and thermal ablation of colorectal liver metastases:a nationwide population-based propensity score-matched study

Background: In colorectal liver metastases (CRLM) patients, combination of liver resection and ablation permit a more parenchymal-sparing approach. This study assessed trends in use of combined resection and ablation, outcomes, and overall survival (OS). Methods: This population-based study included all CRLM patients who underwent liver resection between 2014 and 2022. To assess OS, data was linked to two databases containing date of death for patients treated between 2014 and 2018. Hospital variation in the use of combined minor liver resection and ablation versus major liver resection alone in patients with 2–3 CRLM and ≤3 cm was assessed. Propensity score matching (PSM) was applied to evaluate outcomes. Results: This study included 3593 patients, of whom 1336 (37.2%) underwent combined resection and ablation. Combined resection increased from 31.7% in 2014 to 47.9% in 2022. Significant hospital variation (range 5.9–53.8%) was observed in the use of combined minor liver resection and ablation. PSM resulted in 1005 patients in each group. Major morbidity was not different (11.6% vs. 5%, P = 1.00). Liver failure occurred less often after combined resection and ablation (1.9% vs. 0.6%, P = 0.017). Five-year OS rates were not different (39.3% vs. 33.9%, P = 0.145). Conclusion: Combined resection and ablation should be available and considered as an alternative to resection alone in any patient with multiple metastases.</p