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Introduction: Chronic pain is one of the most common and severe complications after surgery, affecting quality of life and overall wellbeing of patients. Several risk factors have been identified but the mechanisms of chronic postsurgical pain development remain unclear. This study aimed to identify single-nucleotide polymorphisms associated with developing chronic postsurgical pain after abdominal surgery, one of the most common types of surgery., Methods: A genome-wide association study was performed on 27,603 patients from the UK Biobank who underwent abdominal surgery. The robustness of identified loci was validated by split-half validation analysis. Functionally related top loci were selected for expression validation in clinical samples of adhesions from patients with and without pain., Results: One locus (rs185545327) reached genome-wide significance for association with chronic postsurgical pain development, and 10 loci surpassed the suggestively significant threshold (p < 1 × 10 -6 ). In the robustness analysis, eight loci had at least nominal significance. The loci passing the suggestively significant threshold were mapped to 15 genes, of which two loci contained pain-related genes (SRPK2, PDE4D). Although marginally approaching statistical significance in the expression validation of clinical samples, the detection rate and expression level of PDE4D were modestly higher in patients with pain compared with those in the control group., Discussion: This study provides preliminary evidence for genetic risk factors implicated in chronic postsurgical pain following abdominal surgery, particularly the PDE4D gene, which has been associated with pain in previous studies. The findings add to evidence suggesting potential for the future development of a clinically applicable tool for personalised risk prediction, aiding clinicians in stratifying patients and enhancing clinical decision-making through individualised risk assessments., (© 2024 The Author(s). Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists.)

Purpose: Radiation doses to adult patients submitted to cerebral angiography and intracranial aneurysms treatments were assessed by using DICOM Radiation Dose Structured Reports (RDSR) and Monte Carlo simulations. Conversion factors to estimate effective and organ doses from Kerma-Area Product (P KA ) values were determined., Methods: 77 cerebral procedures performed with five angiographic equipment installed in three Italian centres were analyzed. Local settings and acquisition protocols were considered. The geometrical, technical and dosimetric data of 16,244 irradiation events (13305 fluoroscopy, 2811 digital subtraction angiography, 128 cone-beam CT) were extracted from RDSRs by local dose monitoring systems and were input in MonteCarlo PCXMC software to calculate effective and organ doses. Finally, conversion factors to determine effective and organ doses from P KA were determined. Differences between centres were assessed through statistical analysis and accuracy of dose calculation method based on conversion factors was assessed through Bland-Altman analysis., Results: Large variations in P KA (14-561 Gycm 2 ) and effective dose (1.2-73.5 mSv) were observed due to different degrees of complexity in the procedures and angiographic system technology. The most exposed organs were brain, salivary glands, oral mucosa, thyroid and skeleton. The study highlights the importance of recent technology in reducing patient exposure (about fourfold, even more in DSA). No statistically significant difference was observed in conversion factors between centres, except for some organs. A conversion factor of 0.09 ± 0.02 mSv/Gycm 2 was obtained for effective dose., Conclusions: Organ and effective doses were assessed for neuro-interventional procedures. Conversion factors for calculating effective and organ doses from P KA were provided., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

The most important factor in determining coffee quality and consumer choice is the flavour. During roasting, hundreds of simultaneous chemical reactions take place that contribute to the formation of the basic flavour of the coffee drink, imparting bitterness, astringency and acidity. The main chemical compounds responsible for these qualitative sensory properties are chlorogenic acids (CQAs), hydroxycinnamic acids and alkaloids. However, during storage, roasted and ground coffee can undergo several chemical and physical reactions that alter its flavour. This study focuses on LC-DAD analysis to investigate the effects of storing commercial coffee blends in different packaging, namely standard (multilayer film with aluminium barrier) and Eco-capsules. The results show relative stability of the phenolic and alkaloid fractions, although the CQA isomers behave differently and a decrease in caffeine and caffeic acid is observed during prolonged storage under 75% relative humidity compared to 65%, especially in Eco-friendly packaging., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr.ssa Gloria Pellegrino and Giulia Ravaioli are employees of Lavazza S.p.a., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Long non-coding RNAs (lncRNAs) are transcripts without coding potential that are pervasively expressed from the genome and have been increasingly reported to play crucial roles in all aspects of cell biology. They have been also heavily implicated in cancer development and progression, with both oncogenic and tumor suppressor functions. In this work, we identified and characterized a novel lncRNA, TAZ-AS202, expressed from the TAZ genomic locus and exerting pro-oncogenic functions in non-small cell lung cancer. TAZ-AS202 expression is under the control of YAP/TAZ-containing transcriptional complexes. We demonstrated that TAZ-AS202 is overexpressed in lung cancer tissue, compared with surrounding lung epithelium. In lung cancer cell lines TAZ-AS202 promotes cell migration and cell invasion. TAZ-AS202 regulates the expression of a set of genes belonging to cancer-associated pathways, including WNT and EPH-Ephrin signaling. The molecular mechanism underlying TAZ-AS202 function does not involve change of TAZ expression or activity, but increases the protein level of the transcription factor E2F1, which in turn regulates the expression of a large set of target genes, including the EPHB2 receptor. Notably, the silencing of both E2F1 and EPHB2 recapitulates TAZ-AS202 silencing cellular phenotype, indicating that they are essential mediators of its activity. Overall, this work unveiled a new regulatory mechanism that, by increasing E2F1 protein, modifies the non-small cell lung cancer cells transcriptional program, leading to enhanced aggressiveness features. The TAZ-AS202/E2F1/EPHB2 axis may be the target for new therapeutic strategies., (© 2023. The Author(s).)

Gaucher Disease (GD), the most common lysosomal disorder, arises from mutations in the GBA1 gene and is characterized by a wide spectrum of phenotypes, ranging from mild hematological and visceral involvement to severe neurological disease. Neuronopathic patients display dramatic neuronal loss and increased neuroinflammation, whose molecular basis are still unclear. Using a combination of Drosophila dGBA1b loss-of-function models and GD patient-derived iPSCs differentiated towards neuronal precursors and mature neurons we showed that different GD- tissues and neuronal cells display an impairment of growth mechanisms with an increased cell death and reduced proliferation. These phenotypes are coupled with the downregulation of several Hippo transcriptional targets, mainly involved in cells and tissue growth, and YAP exclusion from nuclei. Interestingly, Hippo knock-down in the GBA-KO flies rescues the proliferative defect, suggesting that targeting the Hippo pathway can be a promising therapeutic approach to neuronopathic GD., (© 2023. The Author(s).)

Heart failure (HF) is marked by distinctive changes in myocardial uptake and utilization of energy substrates. Among the different types of HF, HF with preserved ejection fraction (HFpEF) is a highly prevalent, complex, and heterogeneous condition for which metabolic derangements seem to dictate disease progression. Changes in intermediate metabolism in cardiometabolic HFpEF-among the most prevalent forms of HFpEF-have a large impact both on energy provision and on a number of signalling pathways in the heart. This dual, metabolic vs. signalling, role is played in particular by long-chain fatty acids (LCFAs) and short-chain carbon sources [namely, short-chain fatty acids (SCFAs) and ketone bodies (KBs)]. LCFAs are key fuels for the heart, but their excess can be harmful, as in the case of toxic accumulation of lipid by-products (i.e. lipotoxicity). SCFAs and KBs have been proposed as a potential major, alternative source of energy in HFpEF. At the same time, both LCFAs and short-chain carbon sources are substrate for protein post-translational modifications and other forms of direct and indirect signalling of pivotal importance in HFpEF pathogenesis. An in-depth molecular understanding of the biological functions of energy substrates and their signalling role will be instrumental in the development of novel therapeutic approaches to HFpEF. Here, we summarize the current evidence on changes in energy metabolism in HFpEF, discuss the signalling role of intermediate metabolites through, at least in part, their fate as substrates for post-translational modifications, and highlight clinical and translational challenges around metabolic therapy in HFpEF., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Alzheimer's disease (AD), the most common type of dementia, currently represents an extremely challenging and unmet medical need worldwide. Amyloid-β (Aβ) and Tau proteins are prototypical AD hallmarks, as well as validated drug targets. Accumulating evidence now suggests that they synergistically contribute to disease pathogenesis. This could not only help explain negative results from anti-Aβ clinical trials but also indicate that therapies solely directed at one of them may have to be reconsidered. Based on this, herein, we describe the development of a focused library of 2,4-thiazolidinedione (TZD)-based bivalent derivatives as dual Aβ and Tau aggregation inhibitors. The aggregating activity of the 24 synthesized derivatives was tested in intact Escherichia coli cells overexpressing Aβ 42 and Tau proteins. We then evaluated their neuronal toxicity and ability to cross the blood-brain barrier (BBB), together with the in vitro interaction with the two isolated proteins. Finally, the most promising (most active, nontoxic, and BBB-permeable) compounds 22 and 23 were tested in vivo , in a Drosophila melanogaster model of AD. The carbazole derivative 22 (20 μM) showed extremely encouraging results, being able to improve both the lifespan and the climbing abilities of Aβ 42 expressing flies and generating a better outcome than doxycycline (50 μM). Moreover, 22 proved to be able to decrease Aβ 42 aggregates in the brains of the flies. We conclude that bivalent small molecules based on 22 deserve further attention as hits for dual Aβ/Tau aggregation inhibition in AD.

EGLN1, EGLN2 and EGLN3 are proline hydroxylase whose main function is the regulation of the HIF factors. They work as oxygen sensors and are the main responsible of HIFα subunits degradation in normoxia. Being their activity strictly oxygen-dependent, when oxygen tension lowers, their control on HIFα is released, leading to activation of systemic and cellular response to hypoxia. However, EGLN family members activity is not limited to HIF modulation, but it includes the regulation of essential mechanisms for cell survival, cell cycle metabolism, proliferation and transcription. This is due to their reported hydroxylase activity on a number of non-HIF targets and sometimes to hydroxylase-independent functions. For these reasons, EGLN enzymes appear fundamental for development and progression of different cancer types, playing either a tumor-suppressive or a tumor-promoting role, according to EGLN isoform and to tumor context. Notably, EGLN1, the most studied isoform, has been shown to have also a central role in tumor micro-environment modulation, mediating CAF activation and impairing HIF1α -related angiogenesis, thus covering an important function in cancer metastasis promotion. Considering the recent knowledge acquired on EGLNs, the possibility to target these enzymes for cancer treatment is emerging. However, due to their multifaceted and controversial roles in different cancer types, the use of EGLN inhibitors as anti-cancer drugs should be carefully evaluated in each context., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Objectives/hypothesis: The aim of the present study is to validate and compare four of the most widely used staging systems for juvenile angiofibroma on a homogeneous cohort of patients., Study Design: Retrospective case series., Methods: A retrospective review of patients treated with endoscopic or endoscopic-assisted surgical resection between 1999 and 2020 was carried out. Each case was classified according to the following staging systems: Andrews-Fisch (1989), Radkowski (1996), University of Pittsburgh Medical Center (2010), and Janakiram (2017). Spearman's rank correlation test and areas under the curve of receiver operator curves were used to assess the correlation between outcomes of interests (blood loss, surgical time, need for transfusion, and persistence of disease) and stage of disease., Results: Seventy-nine patients were included, with a median follow-up time of 25 months (range 12-127 months). Median surgical time was 217 minutes (range 52-625). Median blood loss was 500 mL (range 40-5200) and 27 patients (34.2%) required blood transfusions. Seven patients (8.9%) showed persistence of disease. All classification systems showed a similar association with blood loss, surgical time, persistence of disease, and need for transfusion., Conclusions: Involvement of the infratemporal fossa and intracranial extension was identified as red flags for surgical planning and preoperative counseling, as associated with increased risk for transfusion and persistent/recurrent disease, respectively. No classification system was found to be better than the others in predicting the most important outcomes. Therefore, the simplest and most easily applicable system would be the preferred one to be used in clinical practice., Level of Evidence: 4 Laryngoscope, 132:1160-1165, 2022., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

The evaluation of radiation burden in vivo is crucial in modern radiology as stated also in the European Directive 2013/59/Euratom-Basic Safety Standard. Although radiation dose monitoring can impact the justification and optimization of radiological procedure, as well as effective patient communication, standardization of radiation monitoring software is far to be achieved. Toward this goal, the Italian Association of Medical Physics (AIFM) published a report describing the state of the art and standard guidelines in radiation dose monitoring system quality assurance. This article reports the AIFM statement about radiation dose monitoring systems (RDMSs) summarizing the different critical points of the systems related to Medical Physicist Expert (MPE) activities before, during, and after their clinical implementation. In particular, the article describes the general aspects of radiation dose data management, radiation dose monitoring systems, data integrity, and data responsibilities. Furthermore, the acceptance tests that need to be implemented and the most relevant dosimetric data for each radiological modalities are reported under the MPE responsibility., (© 2022. The Author(s).)