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Since its inception, Health Technology Assessment (HTA) has typically determined the value of a technology by collecting information derived from randomized clinical trials (RCTs), in line with the principles of evidence-based medicine (EBM). However, data from RCTs did not constitute the sole source of information, as other types of evidence (such as primary qualitative research) have often been utilized. Recent advances in both generating and collecting other types of evidence are broadening the landscape of evidence, adding complexity to the discussion of "robustness of evidence." What are the consequences of these recent developments for the methodology and conduct of HTA, the HTA community, and its ethical commitments? The aim of this article is to explore some ethical challenges that are emerging in the current evolving evidence landscape, particularly changes in evidence generation and collection (e.g., diversification of data sources), and shifting standards of evidence in the field of HTA (e.g., increasing acceptability of evidence that is thought of as lower quality). Our conclusion is that deciding how to best maintain trustworthiness is common to all these issues.

The purpose of this study was to compare the flexural strength, Weibull modulus (reliability), marginal gap, and internal fit (internal gap) of 4 materials for milling or 3-dimensional (3D) printing of definitive and provisional crowns: IPS e.max CAD (IEC), Paradigm MZ100 Block (PMB), Permanent Crown Resin (PCR), and Temporary CB Resin (TCR). Flexural strength was tested by subjecting sectioned milling blocks (IEC and PMB) or 3D-printed bars (PCR and TCR) to a 3-point bending test in a universal testing machine (n = 15 per material). Crowns were milled or 3D printed, and the marginal gap and internal fit were measured using microcomputed tomography (n = 5 per material). The data were analyzed with a t test and compared using analysis of variance (ANOVA) with Tukey post hoc comparisons (α = 0.05). The groups demonstrated the following mean (SD) flexural strength values: IEC, 335.50 (28.97) MPa; PMB, 154.34 (21.03) MPa; PCR, 128.09 (7.30) MPa; and TCR, 126.29 (9.23) MPa. A 1-way ANOVA revealed significant differences in the flexural strengths of sectioned and 3D-printed bars (P < 0.001). The PMB group showed the lowest Weibull modulus (8.77), indicating its poor reliability. The IEC group showed the smallest marginal gap, 53.42 (31.99) μm; this value was significantly smaller than the gap in the TCR group (P < 0.001) but not the PCR or PMB group. The PMB group had the smallest internal fit discrepancy (87.44 [37.60] μm) but was not significantly different from PCR, while TCR had a significantly greater internal fit discrepancy (130.61 [65.16] μm) than IEC, PMB, and PCR (P < 0.001). The occlusal internal fit discrepancies of 3D-printed crowns were significantly greater than those of milled crowns (P < 0.001). There was no statistically significant difference in flexural strength between the 3D-printed definitive (PCR) and provisional (TCR) materials. When the data were combined according to manufacturing method, the marginal gap and internal fit of crowns fabricated with 3D printing were comparable to those of milled crowns, and all mean marginal gaps were within a clinically acceptable limit of less than 120 μm., Competing Interests: No conflicts of interest reported.

Purpose: Defects in the gene encoding selenocysteine insertion sequence binding protein 2, SECISBP2, result in global impaired selenoprotein synthesis manifesting a complex syndrome with characteristic serum thyroid function tests due to impaired thyroid hormone metabolism. Knowledge about this multisystemic defect remains limited., Methods: Genetic and laboratory investigations were performed in affected members from 6 families presenting with short stature and failure to thrive., Results: Four probands presented a complex neurodevelopmental profile, including absent speech, autistic features, and seizures. Pediatric neurological evaluation prompted genetic investigations leading to the identification of SECISBP2 variants before knowing the characteristic thyroid tests in 2 cases. Thyroid hormone treatment improved motor development, whereas speech and intellectual impairments persisted. This defect poses great diagnostic and treatment challenges for clinicians, as illustrated by a case that escaped detection for 20 years because SECISBP2 was not included in the neurodevelopmental genetic panel, and his complex thyroid status prompted antithyroid treatment instead., Conclusion: This syndrome uncovers the role of selenoproteins in humans. The severe neurodevelopmental disabilities manifested in 4 patients with SECISBP2 deficiency highlight an additional phenotype in this multisystem disorder. Early diagnosis and treatment are required, and long-term evaluation will determine the full spectrum of manifestations and the impact of therapy., Competing Interests: Conflict of Interest The authors declare no conflicts of interest, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

"Evidence" is a key term in medicine and health services research, including Health Technology Assessment (HTA). Randomized clinical trials (RCTs) have undoubtedly dominated the scene of generating evidence for a long period of time, becoming the hallmark of evidence-based medicine (EBM). However, due to a number of misunderstandings, the lay audience and some researchers have sometimes placed too much trust in RCTs compared to other methods of investigation. One of the principal misunderstandings is to consider RCTs findings as isolated and self-apparent pieces of information. In other words, what has been essentially lacking was the awareness of the value-context of the evidence and, in particular, the value- and theory-ladenness (normativity) of scientific knowledge. This paper aims to emphasize the normativity that exists in the production of scientific knowledge, and in particular in the conduct of RCTs as well as in the performance of HTA. The work is based on some lessons learned from Philosophy of Science and the European project "VALIDATE" (VALues In Doing Assessments of healthcare TEchnologies"). VALIDATE was a three-year EU Erasmus+ strategic partnerships project (2018-2021), in which training in the field of HTA was further optimized by using insights from political science and ethics (in accordance with the recent definition of HTA). Our analysis may reveal useful insights for addressing some challenges that HTA is going to face in the future. [ABSTRACT FROM AUTHOR]

Neuropilin-1 (NRP1) is a transmembrane glycoprotein expressed by several cell types including, neurons, endothelial cells (ECs), smooth muscle cells, cardiomyocytes and immune cells comprising macrophages, dendritic cells and T cell subsets. Since NRP1 discovery in 1987 as an adhesion molecule in the frog nervous system, more than 2300 publications on PubMed investigated the function of NRP1 in physiological and pathological contexts. NRP1 has been characterised as a coreceptor for class 3 semaphorins and several members of the vascular endothelial growth factor (VEGF) family. Because the VEGF family is the main regulator of blood and lymphatic vessel growth in addition to promoting neurogenesis, neuronal patterning, neuroprotection and glial growth, the role of NRP1 in these biological processes has been extensively investigated. It is now established that NRP1 promotes the physiological growth of new vessels from pre-existing ones in the process of angiogenesis. Furthermore, several studies have shown that NRP1 mediates signalling pathways regulating pathological vascular growth in ocular neovascular diseases and tumour development. Less defined are the roles of NRP1 in maintaining the function of the quiescent established vasculature in an adult organism. This review will focus on the opposite roles of NRP1 in regulating transforming growth factor β signalling pathways in different cell types, and on the emerging role of endothelial NRP1 as an atheroprotective, anti-inflammatory factor involved in the response of ECs to shear stress., (© 2024 The Author(s).)

Background: The purpose of this study was to evaluate the effect of milling speed on the surface roughness, marginal gap, marginal gap volume, marginal offset, and fracture load of zirconia restorations., Material and Methods: A mandibular molar #30 typodont tooth was digitally scanned and an ideal crown preparation for a zirconia restoration was digitally created. A single master model die of the crown preparation was milled out of a resin material. The master die was scanned, and a final restoration was designed using the bio-copy feature of the typodont tooth. Ten zirconia restorations were milled (CEREC Primemill, Dentsply Sirona) per each of three milling speeds (super-fast, fine, and extra-fine), sintered, and seated on the master die. Surface roughness, marginal gap, marginal gap volume, and marginal offset were measured using a non-contact profilometer. Then, all restorations were cemented to the dies and loaded to failure in a material testing device. Data were analyzed with one-way ANOVA and Tukey's post hoc tests per property (alpha=0.05)., Results: Super-fast milling speed resulted in restorations with statistically significant greater surface roughness and marginal gap volume compared to fine and extra-fine milling speeds. No significant difference in marginal gap, marginal offset, and fracture load were found based on milling speed., Conclusions: Zirconia restorations milled at slower speeds may result in similar or slightly better properties compared to super-fast speed. Key words: Milling speed, properties, zirconia restorations., Competing Interests: Conflicts of interest The authors do not have any financial interest in the companies whose materials are discussed in this manuscript., (Copyright: © 2024 Medicina Oral S.L.)