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Elisa Principi,1,* Rossana Girardello,2,* Antonino Bruno,1,* Isabella Manni,3 Elisabetta Gini,2 Arianna Pagani,1 Annalisa Grimaldi,2 Federico Ivaldi,4 Terenzio Congiu,5 Daniela De Stefano,1 Giulia Piaggio,3 Magda de Eguileor,2 Douglas M Noonan,1,2 Adriana Albini1 1Vascular Biology and Angiogenesis, Scientific and Technology Pole, IRCCS MultiMedica, Milano, 2Department of Biotechnology and Life Sciences, University of Insubria, Varese, 3Department of Research, Advanced Diagnosis and Innovation, Regina Elena National Cancer Institute, Rome, 4Department of Neuroscience, Ophthalmology and Genetics, University of Genoa, Genoa, 5Department of Surgical and Morphological Sciences, University of Insubria, Varese, Italy *These authors contributed equally to this work Abstract: The increasing use of carbon nanotubes (CNTs) in several industrial applications raises concerns on their potential toxicity due to factors such as tissue penetrance, small dimensions, and biopersistence. Using an in vivo model for CNT environmental exposure, mimicking CNT exposition at the workplace, we previously found that CNTs rapidly enter and disseminate in the organism, initially accumulating in the lungs and brain and later reaching the liver and kidneys via the bloodstream in CD1 mice. Here, we monitored and traced the accumulation of single-walled CNTs (SWCNTs), administered systemically in mice, in different organs and the subsequent biological responses. Using the novel in vivo model, MITO-Luc bioluminescence reporter mice, we found that SWCNTs induce systemic cell proliferation, indicating a dynamic response of cells of both bone marrow and the immune system. We then examined metabolic (water/food consumption and dejections), functional (serum enzymes), and morphological (organs and tissues) alterations in CD1 mice treated with SWCNTs, using metabolic cages, performing serum analyses, and applying histological, immunohistochemical, and ultrastructural (transmission electron microscopy) methods. We observed a transient accumulation of SWCNTs in the lungs, spleen, and kidneys of CD1 mice exposed to SWCNTs. A dose- and time-dependent accumulation was found in the liver, associated with increases in levels of aspartate aminotransferase, alanine aminotransferase and bilirubinemia, which are metabolic markers associated with liver damage. Our data suggest that hepatic accumulation of SWCNTs associated with liver damage results in an M1 macrophage-driven inflammation. Keywords: single-walled carbon nanotubes, nanotoxicity, metabolism, hepatic function, inflammation, Kupffer cells, mouse models

Inflammatory bowel diseases are idiopathic relapsing disorders characterized by chronic inflammation of the intestinal tract. The aim of the present study was to examine the effect of ultramicronized palmitoylethanolamide (PEAultra), underlining its correlation with PPARα and TLR4; in particular, we aimed at evaluating its anti-inflammatory effect in mice subjected to experimental colitis. Colitis was induced in mice by intracolonic instillation of dinitrobenzene sulfonic acid (DNBS), PEAultra was administered daily intraperitoneally (10 mg/kg) for 4 days. On day 4, animals were sacrificed and tissues were taken for histological and biochemical analysis. Four days after DNBS administration, TNF-α and IL-1β productions were increased in association with colon damage. Neutrophil infiltration, evaluated by MPO activity, in the mucosa was associated with upregulation of ICAM-1 and P-selectin. Immunohistochemistry for nitrotyrosine and PARP showed an intense staining in the inflamed colon. Treatment with PEAultra significantly reduced the appearance of colon damage and the loss of body weight. These effects were associated with a remarkable amelioration in the disruption of the colonic architecture and reduction in colonic MPO activity. PEAultra also reduced the pro-inflammatory cytokine release, the appearance of nitrotyrosine and PARP immunoreactivity as well as the upregulation of ICAM-1 and P-selectin; moreover, pro-MMP-9 and MMP-2 expressions were significantly inhibited in the colon of DNBS-treated mice. Furthermore, we studied PEAultra correlation with PPARα and TLR4, demonstrating that PEAultra inhibited TLR4 pathway through a PPARα independent pathway. Taken together, our results clearly show that this new formulation of PEA may be considered as a possible therapeutic approach against Th1-induced colitis. [ABSTRACT FROM PUBLISHER]

Background: While the prognostic role of tertiary lymphoid structures (TLS) has been well studied in solid cancers, the prevalence and impact of immature precursor lymphoid structures known as lymphoid aggregates (LA) remain unresolved in relation to the disease process. In this study, we examined characteristics and the prognostic utility of LA and TLS status in histological samples from patients with melanoma., Methods: We assessed The Cancer Genomic Atlas-skin cutaneous melanoma digital slides and melanoma specimens from the University of Pittsburgh for the presence of LA and TLS using H&E staining, multiplex immunofluorescence (mIF) and transcriptomic analyses. Cox proportional hazard regression models were used to assess the prognostic value associated with the presence of lymphoid structures in melanomas., Results: A total of 278 evaluable samples were analyzed and split into primary melanomas in skin (N=195) and metastatic melanomas involving skin/subcutaneous/soft tissue sites (N=83). 72% of tumor specimens contained histologically defined LA located in peritumoral (34%), intratumoral (5.6%) or stromal (6.1%) locations, with the remaining samples (54.3%) exhibiting LA in multiple locations. In contrast to LA which tended to form more commonly in primary melanoma samples, TLS with germinal centers predominantly formed in peritumoral (45.2%) or stromal (35.5%) locations in metastatic melanomas (p=0.02), with TLS observed in 11% of all melanoma specimens evaluated. mIF analyses revealed cellular heterogeneity of lymphoid structures, with CD20 + (B) cells present in nodule-shaped and stromal locations where they exhibited a high degree of colocalization with CD4 + and CD8 + T cells. A previously defined 12-chemokine gene expression score was significantly higher in samples with evidence of LA versus none (p<0.001), and samples without LA/TLS were enriched with pigmentation/neural network gene signatures. The presence of LA was significantly associated with tumor-free regional lymph node status (p=0.002). In multivariable analysis, after adjusting for age, sex, sample type, and stage, the presence of LA was associated with improved patient overall survival (OS) (HR=0.52, 95% CI 0.31 to 0.87, p=0.01)., Conclusion: Melanoma frequently contains LA, which tends to form in diverse locations in the tumor microenvironment in association with improved overall survival and tumor-free regional lymph node status in patients with primary disease., Competing Interests: Competing interests: JMK: consultation with Amgen (with Davar and Najjar), Ankyra Therapeutics, Applied Clinical Intelligence, Axio Research, Becker Pharmaceutical Consulting, Bristol Myers Squibb, Cancer Network, Cancer Study Group, Checkmate Pharmaceuticals, CytomX Therapeutics, DermTech, Fenix Group International, Harbour BioMed, Immunocore, iOnctura, Iovance Biotherapeutics, IQVIA, Istari Oncology, Jazz Pharmaceuticals, Lytix Biopharma AS, Magnolia Innovation, Merck, Natera, Novartis Pharmaceuticals, OncoCyte Corporation, OncoSec Medical, PathAI, Pfizer, Piper Sandler & Co., PyrOjas Corporation, Regeneron Pharmaceuticals, Replimune, Scopus BioPharma, SR One Capital Management, Takeda, Valar Labs. JJM is Associate Center Director at Moffitt Cancer Center, has ownership interest in Aleta Biotherapeutics, CG Oncology, Turnstone Biologics, Ankyra Therapeutics, and AffyImmune Therapeutics, and is a paid consultant/paid advisory board member for ONCoPEP, CG Oncology, Turnstone Biologics, Vault Pharma, Ankyra Therapeutics, AffyImmune Therapeutics, UbiVac, Vycellix, and Aleta Biotherapeutics., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: This study aimed to investigate factors contributing to non-sustained viral suppression, including intermittent viremia and persistent low-level viremia, during cabotegravir (CAB) plus rilpivirine (RPV) long-acting (LA) injectable therapy, with a focus on pharmacokinetics (PK)., Methods: A prospective cohort study was conducted on people with HIV (PWH) transitioning from stable oral antiretroviral therapy (ART) to bimonthly CAB+RPV LA. Standardized follow-up included close monitoring through blood sampling for plasma HIV-1 viral load (VL) and multiple plasma drug concentrations measurements to analyze the connection between PK parameters and virologic outcomes., Results: Among 173 patients with a median (IQR) follow-up of 11.1(7.1-13.2) months and 789 pre-dose measurements, 38.7% experienced VL≥20 copies/mL, and 16.2% had levels ≥50 copies/mL. Intermittent viremia occurred in 34.7% of patients, and persistent low-level viremia in 4%. Virological failure developed in two cases. Predictors of non-sustained viral suppression included VL at HIV diagnosis [AHR: 1.49 per log10 VL, 95% CI: 1.04-2.12, P =.027], detectable viremia on oral ART [AHR: 2.45, 95% CI: 1.29-4.65, P =.006], and the level of viral suppression at transition [AHR: 0.38, 95% CI: 0.19-0.75, P =.004]. We found a significant association between low trough concentrations of CAB and RPV and episodes of detectable viremia exceeding 50 copies/mL. However, none of the assessed PK covariates predicted non-sustained viral suppression in multivariable models., Conclusion: Non-sustained viral suppression in PWH transitioning from stable oral ART to CAB+RPV LA was linked to pre-existing factors before transition. Higher VL pre-ART and incomplete suppression on oral therapy increased the risk, independent of PK parameters., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare condition; late adult presentation is extremely rare but, with modern diagnostics, more asymptomatic or mildly symptomatic elderly patients with ALCAPA are found. A 76-year-old woman was admitted to our emergency department in December 2021 with fever, fatigue, cognitive-motor slowing, and hyposthenia of left hemisoma. Cranium computed tomography (CT) was performed, with no signs of stroke. Contrast-enhanced CT, performed with electrocardiogram-gated technique, showed a dilatated left coronary artery arising directly from the main pulmonary artery; right coronary artery was markedly dilated and tortuous and characterized by multiple inter-coronary collateral arteries with left coronary artery, in particular in the retro-aortic side and along the cone artery. ALCAPA syndrome represents one of the most common causes of myocardial ischemia in children and, if left untreated, results in a mortality rate of up to 80-90 % within the first year of life. In our case, no previous history of cardiological disease was found that could have suggested this type of condition. This is extremely rare, especially if we consider that our patient reached the 8th decade of life., Learning Objectives: •ALCAPA syndrome can present in adulthood.•Collaterals between coronary arteries are essential to guarantee the survival into adulthood.•Cardiac computed tomography imaging is essential for the diagnosis., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2024 Japanese College of Cardiology. Published by Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Study Objectives: Sleep disorders are a frequent comorbidity among children with autism spectrum disorder (ASD). Among sleep-related issues of ASD, restless sleep is a common complaint. In recent years, restless sleep disorder (RSD) has been proposed as a new clinical entity, characterized by agitated sleep as its predominant manifestation. Despite the high prevalence of sleep disorders and data reporting restless sleep among ASD patients, to date no study has yet characterized RSD within patients with ASD. Therefore, the aim of our study was to assess the occurrence of RSD in a sample of children and adolescents with ASD through clinical and polysomnographic assessment., Methods: Children and adolescents with ASD ages 6-18 years were recruited for the study. Through parental interviews, patients with a suspected RSD were selected and offered diagnostic investigation by video-polysomnography and blood tests to assess martial balance., Results: Among the 129 participants included, 16 patients (12.4%) were found to have a suspected RSD. Only 6 (4.7%) underwent video-polysomnography due to lack of compliance or family refusal. In 6/6 participants examined, the disorder was confirmed by video-polysomnography movement analysis (total movement index ≥ 5 events/h) and ferritin values were found in the normal range., Conclusions: RSD does not appear to be particularly frequent among patients with ASD and that of iron metabolism may not be the main factor implicated in the pathogenesis of RSD within this population. Additional evaluation is needed to confirm the result and further investigate the etiological mechanisms underlying the disorder., Citation: Voci A, Mazzone L, De Stefano D, Valeriani M, Bruni O, Moavero R. Restless sleep disorder in a sample of children and adolescents with autism spectrum disorder: preliminary results from a case series. J Clin Sleep Med . 2024;20(3):427-432., (© 2024 American Academy of Sleep Medicine.)

Genome sequencing of the human parasite Schistosoma mansoni revealed an interesting gene superfamily, called micro-exon gene ( meg ), that encodes secreted MEG proteins. The genes are composed of short exons (3-81 base pairs) regularly interspersed with long introns (up to 5 kbp). This article recollects 35 S. mansoni specific meg genes that are distributed over 7 autosomes and one pair of sex chromosomes and that code for at least 87 verified MEG proteins. We used various bioinformatics tools to produce an optimal alignment and propose a phylogenetic analysis. This work highlighted intriguing conserved patterns/motifs in the sequences of the highly variable MEG proteins. Based on the analyses, we were able to classify the verified MEG proteins into two subfamilies and to hypothesize their duplication and colonization of all the chromosomes. Together with motif identification, we also proposed to revisit MEGs' common names and annotation in order to avoid duplication, to help the reproducibility of research results and to avoid possible misunderstandings.

The most common organic etiology of mitral regurgitation is degenerative and consists of mitral valve prolapse (MVP). Volume overload because of mitral regurgitation is the most common complication of MVP. Advocating surgery before the consequences of volume overload become irreparable restores life expectancy, but carries a risk of mortality in patients who are often asymptomatic. On the other hand, the post-surgical outcome of symptomatic patients is dismal and life expectancy is impaired. In the present article, we aim to bridge the gap between these two therapeutic approaches, unifying the concepts of watchful waiting and early surgery in a "watchful surgery approach"., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Carpenito, Gelfusa, Mega, Cammalleri, Benfari, De Stefano, Ussia, Tribouilloy, Enriquez-Sarano and Grigioni.)

Background: Acinic cell carcinoma (AciCC) is the second most common pediatric malignant salivary gland tumor. However, there are limited pathology publications about this tumor in the pediatric population., Methods: We describe four pediatric AciCC cases diagnosed between 2000 and 2021 in our institute. Reticulin histochemistry plus immunohistochemistry for NR4A3 and DOG1 were performed on all cases., Results: Histologically, all four cases featured a tumor-associated lymphoid proliferation and collagenous stroma, in which two formed central scars. The tumors were predominantly solid, with a lobular pattern and variably sized dilated spaces, including one case with focal microcysts. High-grade transformation was not observed in any of our cases. Reticulin stain and immunohistochemistry for NR4A3 showed distinct features between AciCC and non-neoplastic salivary gland parenchyma. DOG1 immunohistochemistry confirmed the acinar origin of AciCC., Conclusions: Our study reveals that pediatric AciCCs often present with tumor-associated lymphoid proliferation (TALP) and sclerosis. Special stains such as reticulin histochemistry and NR4A3 immunohistochemistry are helpful to separate tumor from adjacent benign parenchyma. The ancillary study is helpful for the diagnosis of small specimens. Our study is limited by its low case number, but we hope that our results will promote more studies on this rare salivary gland tumor in the pediatric population., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Cardiac computed tomography (CT) provides important insights into the geometrical configuration of the tricuspid valve (TV). The purpose of the present study was to assess the geometrical changes of TV in patients with functional tricuspid regurgitation (TR) using novel CT scan parameters and to correlate these findings with echocardiography., Methods: This single-center study enrolled 86 patients undergoing cardiac CT and divided them into two groups according to the presence or not of severe TR (43 patients with TR ≥ 3+ and 43 controls). The measurements collected were as follows: TV annulus area and perimeter, septal-lateral and antero-posterior annulus diameters, eccentricity, distance between commissures, segment between the geometrical centroid and commissures, and the angles of commissures., Results: We found a significant correlation between all annulus measurements and the grade of TR, except in regard to angles. TR ≥ 3+ patients had significantly larger TV annulus area and perimeter, larger septal-lateral, and antero-posterior annulus dimensions, as well as larger commissural distance and centroid-commissural distance. In patients with TR ≥ 3+ and controls, the eccentricity index predicted a circular shape and an oval shape of the annulus, respectively., Conclusions: These novel CT variables focusing on commissures increase the anatomical understanding of the TV apparatus and the TV geometrical changes in patients with severe functional TR.

We sought to develop a sentinel lymph node gene expression signature score predictive of disease recurrence in patients with cutaneous melanoma. Gene expression profiling was performed on SLN biopsies using U133A 2.0 Affymetrix gene chips. The top 25 genes associated with recurrence-free survival (RFS) were selected and a penalized regression function was used to select 12 genes with a non-zero coefficient. A proportional hazards regression model was used to evaluate the association between clinical covariates, gene signature score, and RFS. Among the 45 patients evaluated, 23 (51%) had a positive SLN. Twenty-one (46.7%) patients developed disease recurrence. For the top 25 differentially expressed genes (DEG), 12 non-zero penalized coefficients were estimated (CLGN, C1QTNF3, ADORA3, ARHGAP8, DCTN1, ASPSCR1, CHRFAM7A, ZNF223, PDE6G, CXCL3, HEXIM1, HLA-DRB). This 12-gene signature score was significantly associated with RFS (p < 0.0001) and produced a bootstrap C index of 0.888. In univariate analysis, Breslow thickness, presence of primary tumor ulceration, SLN positivity were each significantly associated with RFS. After simultaneously adjusting for these prognostic factors in relation to the gene signature, the 12-gene score remained a significant independent predictor for RFS (p < 0.0001). This SLN 12-gene signature risk score is associated with melanoma recurrence regardless of SLN status and may be used as a prognostic factor for RFS.

An anomalous aortic origin of a coronary artery (AAOCA) from the opposite sinus, with an interarterial course, has been associated with an increased risk of myocardial ischemia and sudden death. As the exact pathophysiology of AAOCA is not well understood, the clinical management is also not well defined. With increased use of non-invasive imaging, the diagnosis of AAOCA is increasing and the association of anomalous origin and atherosclerotic disease is becoming a more important topic. We report a rare case of AAOCA chronic total occlusion (CTO). A 40-year-old Caucasian man was referred for invasive coronary angiography (ICA) due to typical chest pain and positive myocardial scintigraphy. ICA demonstrated CTO of an anomalous right coronary artery (ARCA) originating from the left side of the ascending aorta with an interarterial course. There was no lesion in the left coronary artery. During the procedure, unexpected rupture of the coronary artery occurred after dilatation with a small balloon at low pressure. The complication in this case was handled with good procedural final result but was an occasion for a food for thought. Coronary artery perforations are rare but life-threatening procedural complications that are usually caused by predisposing anatomical and procedural factors. We issue a warning on the risk of complications during complex percutaneous coronary intervention of these arteries, and we reconsidered the pathophysiology of the anomaly in a way that could change the approach to the disease. Based on this complication, we hypothesized that the wall of the artery could be fragile due to histopathological alterations, which could have a role in the pathophysiology of coronary malignancy. Future autopsy studies should be focused on the analysis of the arterial wall of the patient affected by sudden death with this anomaly., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cocco, Madonna, Cammalleri, Cocco, De Stefano, Ricciardi, Grigioni and Ussia.)

Background: Computed tomography (CT) is the recommended imaging technique for defining the anatomical suitability for current transcatheter technologies and planning tricuspid valve (TV) intervention. The aim of the Tricuspid Regurgitation IMAging (TRIMA) study was to assess the geometrical characteristics of the TV complex using novel CT parameters., Methods: This prospective, single-center study enrolled 22 consecutive patients with severe tricuspid regurgitation, who underwent a cardiac CT study dedicated to the right chambers. The following variables were obtained: annulus area and perimeter, septal-lateral and antero-posterior diameters, tenting height, and anatomical regurgitant orifice area. Moreover, the following novel annular parameters were assessed: distance between commissures, distance between TV centroid and commissures, and angles between centroid and commissures., Results: A significant phasic variability during the cardiac cycle existed for all variables except for eccentricity, angles, and distance between the postero-septal and antero-posterior commissure and distance between the centroid and antero-posterior commissure. There was a significant relationship between the TV annulus area and novel annular parameters, except for annular angles. Additionally, novel annular variables were found to predict the annulus area., Conclusions: These novel additional variables may provide an initial platform from which the complexity of the TV annular morphology can continue to be better understood for further improving transcatheter therapies.

Background Acute chest pain with mild troponin rise and inconclusive diagnosis after clinical evaluation represents a diagnostic challenge. Triple-rule-out (TRO) CT may exclude coronary artery disease (CAD), as well as acute aortic syndrome and pulmonary embolism, but cannot help identify other causes of myocardial injury. Purpose To investigate the diagnostic value of a comprehensive CT protocol including both an angiographic and a late contrast enhancement (LCE) scan in participants with troponin-positive acute chest pain. Materials and Methods In this prospective study, consecutive patients with troponin-positive acute chest pain or anginal equivalent and inconclusive diagnosis after clinical evaluation (symptoms, markers, electrocardiography, and echocardiography) who underwent TRO CT between June 2018 and September 2020 were enrolled. TRO CT was performed to evaluate the presence of obstructive CAD (stenosis ≥50%), acute aortic syndrome, and pulmonary embolism. If the findings on the TRO CT scan were negative, an LCE CT scan was acquired after 10 minutes to assess the presence and pattern of scar and quantify the myocardial extracellular volume fraction. CT-based diagnoses were compared with diagnoses obtained with reference standard methods, including invasive coronary angiography, cardiac MRI, and endomyocardial biopsy. Results Eighty-four patients (median age, 69 years [interquartile range, 50-77 years]; 45 men) were enrolled. TRO CT helped identify obstructive CAD in 35 participants (42%), acute aortic syndrome in one (1.2%), and pulmonary embolism in six (7.1%). LCE CT scans were acquired in the remaining 42 participants. The following diagnoses were reached with use of LCE CT: myocarditis (22 of 42 participants [52%]), takotsubo cardiomyopathy (four of 42 [10%]), amyloidosis (three of 42 [7.1%]), myocardial infarction with nonobstructed coronary arteries (three of 42 [7.1%]), dilated cardiomyopathy (two of 42 [4.8%]), and negative or inconclusive findings (eight of 42 [19%]). The addition of LCE CT improved the diagnostic rate of TRO CT from 42 of 84 participants (50% [95% CI: 38.9, 61.1]) to 76 of 84 (90% [95% CI: 82.1, 95.8]) ( P < .001). Conclusion A CT protocol including triple-rule-out and late contrast enhancement CT scans improved diagnostic rate in participants presenting with acute chest pain syndrome. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Nagpal and Bluemke in this issue.

Background: A systematic examination of low-dose CT (LDCT) scan, beside lung nodules, may disclose the presence of undiagnosed diseases, improving the efficacy and the cost/efficacy of these programs. The study was aimed at evaluating the association between LDCT scan findings and non-oncologic and oncologic diseases., Methods: The LDCT scan of participants to the "Un Respiro per la vita" ® lung cancer screening program were checked and abnormal findings, beside lung nodules, recorded. First admission to the acute care because of cardiovascular (CD), respiratory (RD) and oncological diseases (OD) in the following three years were retrieved. The association of LDCT scan abnormal findings with CD, RD and OD was assessed through univariable and multivariable logistic regression models., Results: Mean age of 746 participants was 62 years (SD:5), 62% were male. 11 (1.5%) received a diagnosis of lung cancer. 16.1% participants were admitted to the acute care in the following three years: 8.6% for CD, 4.3% for RD and 5.2% for OD. Valve calcification (OR 2.02, p:0.02) and mucus plugs (OR 3.37, p:0.04) were positively associated with CD, while sub-pleural fibrosis had a protective role (OR 0.47, p:0.01). Lung nodules > 8 mm (OR 5.54, p: < 0.01), tracheal deviation (OR 6.04, p:0.01) and mucus plugs (OR 4.00, p:0.04) were positively associated with OD admissions. Centrilobular emphysema OR for RD admissions was 1.97 (p:0.06)., Conclusions: The observed association between selected LDCT findings and ensuing CD, RD and OD suggests that the information potential of LCDT goes beyond the screening of lung cancer., (© 2022. The Author(s).)

Background and Aim: Tuberous sclerosis complex (TSC) is associated with a high rate of attention deficit-hyperactivity disorder (ADHD), usually with more severe symptoms than in idiopathic cases. Event-related potentials have been used in idiopathic ADHD, and they have been proposed as a possible biomarker of symptoms severity. Aim of this study was to investigate event-related potential (ERP) characteristics in patients with ADHD secondary to TSC, compared to patients with drug-naive idiopathic ADHD and healthy controls (HCs), to investigate whether (1) distinct clinical features can be due to different pathophysiological mechanisms, and (2) ERPs may reliably predict ADHD symptoms severity in TSC. Materials and Methods: We enrolled 13 patients with idiopathic ADHD (iADHD), 6 patients with ADHD associated with TSC (tscADHD), and 14 age-matched HCs (7-17 years). All of them underwent ERP recording, with mismatch negativity (MMN) preceding the P300 recording. All patients underwent neurocognitive evaluations. Results: Mismatch negativity latency was shorter in iADHD ( P = 0.04) and tscADHD ( P = 0.06) than in HC, with no difference between patients' groups. Mismatch negativity amplitude was significantly higher in patients (both iADHD and tscADHD) than in HC. The P300 amplitude was significantly lower in iADHD patients than in both tscADHD patients ( P = 0.03) and HCs ( P < 0.001). No difference was found between tscADHD patients and HCs ( P = 0.2). Conclusion: While patients with iADHD present lower P300 amplitude than HC, in tscADHD patients P300 amplitude was not different from that in HC, suggesting that in TSC P300 amplitude does not really reflect symptom severity., (Copyright © 2020 Moavero, Marciano, Pro, De Stefano, Vigevano, Curatolo and Valeriani.)

Dietary phytochemicals are particularly attractive for chemoprevention and are able to modulate several signal transduction pathways linked with cancer. Olive oil, a major component of the Mediterranean diet, is an abundant source of phenolic compounds. Olive oil production is associated with the generation of a waste material, termed 'olive mill wastewater' (OMWW) that have been reported to contain water-soluble polyphenols. Prostate cancer (PCa) is considered as an ideal cancer type for chemopreventive approaches, due to its wide incidence but relatively long latency period and progression time. Here, we investigated activities associated with potential preventive properties of a polyphenol-rich olive mill wastewater extract, OMWW (A009), on three in vitro models of PCa. A009 was able to inhibit PCa cell proliferation, adhesion, migration, and invasion. Molecularly, we found that A009 targeted NF-κB and reduced pro-angiogenic growth factor, VEGF, CXCL8, and CXCL12 production. IL-6/STAT3 axis was also regulated by the extract. A009 shows promising properties, and purified hydroxytyrosol (HyT), the major polyphenol component of A009, was also active but not always as effective as A009. Finally, our results support the idea of repositioning a food waste-derived material for nutraceutical employment, with environmental and industrial cost management benefits.

Cofilin is an essential actin remodeling protein promoting depolymerization and severing of actin filaments. To address the relevance of cofilin for the development and function of T cells in vivo, we generated knock-in mice in which T-cell-specific nonfunctional (nf) cofilin was expressed instead of wild-type (WT) cofilin. Nf cofilin mice lacked peripheral αβ T cells and showed a severe thymus atrophy. This was caused by an early developmental arrest of thymocytes at the double negative (DN) stage. Importantly, even though DN thymocytes expressed the TCRβ chain intracellularly, they completely lacked TCRβ surface expression. In contrast, nf cofilin mice possessed normal numbers of γδ T cells. Their functionality was confirmed in the γδ T-cell-driven, imiquimod (IMQ)-induced, psoriasis-like murine model. Overall, this study not only highlights the importance of cofilin for early αβ T-cell development but also shows for the first time that an actin-binding protein is differentially involved in αβ versus γδ T-cell development., Competing Interests: The authors have declared that no competing interests exist.