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Background: The diversity of patients' symptomatology among people seeking treatment on community-based mental health services poses significant challenges to traditional models of care. Recent approaches favor identifying transdiagnostic factors that allow a better understanding of patient heterogeneity and designing more effective and quality interventions. This study examines the heterogeneity of patients with internalizing symptoms based on profiles identified with cognitive and motivational control variables. Differences between these profiles on dimensional measures of psychopathology and quality of life are examined. Methods: 263 patients were selected by non-probabilistic sampling procedures on mental health services in the province of Huelva (Spain). A latent class analysis on the standardized scale scores of The Behavioral Inhibition/Behavioral Activation System Scales and the Effortful Control Scale of the Adult Temperament Questionnaire Short-Form was conducted. Profiles were compared on the scores of the Inventory of Depression and Anxiety Symptoms-II, the WHO Disability Assessment Schedule II, and the Health Assessment Questionnaire SF-36. Results: The four latent profile solution is the one that showed the best fit indicators and substantive interpretability, with a kappa of 0.94 in the cross-validation procedure with 75% of the sample. No sex differences were found between the profiles (χ32 5.17, p = .160). Profiles #1 and #3, both characterized by an imbalance between low activation and high inhibition, had lower well-being, lower functionality, and quality of life. When comparing profile #2 (featuring the highest inhibitory control) lower scores on most internalizing scales are observed, specially claustrophobia, social anxiety, panic mania. Profile #4 (low control, high activation, and high inhibition) showed greater scores on both mania and euphoria and lower scores on emotional role. Conclusions: We identified four distinctive profiles that had overly increased behavioral inhibition (as expected in internalizing disorders) and differed in the degree of imbalance between inhibition and activation systems, and between motivational systems and top-down cognitive control. The profile characterized by high activation and reduced cognitive (inhibitory) control was the one showing greater mood-related symptoms and lower levels of quality of life. These profiles could be generated by treatment providers to guide clinical management in an evidence-based manner.

Background and Aims: Inflammatory bowel disease (IBD) is associated with increased circulating damage-associated molecular patterns, in particular, the highly pro-inflammatory mitochondrial DNA (mtDNA). Here, we study the importance of blood neutrophils in mtDNA release via neutrophil extracellular trap (NET) formation and mitochondrial NETosis, where neutrophils specifically expulse mtDNA as potential targetable biological pathways. Methods: We investigated the roles of A23187 (a known NET stimulant), granulocyte macrophage stimulating factor, lipopolysaccharide (LPS), and human IBD plasma in their ability to induce NET formation, mitochondrial NETosis, mtDNA, and total DNA release from human blood neutrophils; and the evidence for increased NET formation in IBD. Results: We demonstrated that NET formation resulted in significant DNA (P < .0001) and mtDNA release (P < .0001) with long DNA fragments (>1000 base pairs) with NETs containing high levels of mtDNA. Using previously described in vitro conditions for mitochondrial NETosis, granulocyte macrophage stimulating factor + LPS triggered neutrophil mtDNA release at lower levels but not NETosis. LPS alone can trigger neutrophilic DNA release without NET formation. Heterologous coculture with plasma from patients with active IBD (vs remission [n = 6/group]) were not associated with significantly higher levels of NETs and mtDNA release. During coculture with active IBD plasma (vs remission), citrullinated histone 3 (CitH3) (a NETs biomarker) levels were significantly lower (P < .001). Similarly, CitH3 levels were lower in stool supernatants of patients with active IBD vs remission (n = 19/12, P = .0001). Stool CitH3 negatively correlates with stool calprotectin, a biomarker for gut inflammation (r = −0.47, P = .03). Conclusion: Hence, although blood neutrophils remain an important source of circulating mtDNA with defined mechanisms for release via NET formation and during neutrophil activation, our data do not support excessive systemic NET formation as a dominant underpinning pathobiological process in IBD.

Fluorescence spectroscopy coupled with chemometric tools is a powerful analytical method, largely used for rapid food quality and safety evaluations. However, its potential has not yet been explored in the novel food sector. In the present study, excitation emission matrices (EEMs) of 15 insect powders produced by milling insects belonging to 5 Orthoptera species (Acheta domesticus, Gryllus assimilis, Gryllus bimaculatus, Locusta migratoria, Schistocerca gregaria) from 3 different origins were investigated. Parallel factor (PARAFAC) analysis performed on the overall averaged dataset was validated for five components, highlighting the presence of five different fluorescence peaks. The presence of these peaks was confirmed on each species, suggesting that fluorescence compounds of edible insects are the same in several species. PARAFAC analysis performed on the overall averaged dataset after alternatively adding the EEM recorded from one standard compound allowed to speculate that edible insects fluorescence raises from mixtures of: tryptophan + tyrosine (PARAFAC component-1), tryptophan + tyrosine + tocopherol (PARAFAC component-2), collagen + pyridoxine + pterins (PARAFAC component-3). This study suggests that fluorescence spectroscopy may represent a powerful method for investigating composition and quality of insect-based foods.

Herein is described the case of a 64-year-old patient affected by metastatic clear-cell carcinoma, with exclusive bone disease, subjected after the initial cytoreductive nephrectomy to 3 successive lines of medical treatment (sunitinib, everolimus, and sorafenib) and multiple locoregional treatments (spinal surgery, radiation therapy, and selective arterial embolization), resulting in a surprisingly long survival of over 75 months. In the era of target therapy, integration strategies, including additional locoregional treatment to medical therapy, are essential to optimize the clinical benefit, to maximize treatment duration overcoming focal progressive disease, and to improve the quality of life. In this context, we would highlight that selective transcatheter embolization of bone metastases from renal cell carcinoma should be considered as an effective and safe option in the palliative setting for patients with bone metastasis, especially for pain relief.

Neutrophils are peripheral blood leukocytes that represent the first line of immune cell defense against bacterial and fungal infections but are also crucial players in the generation of the inflammatory response. Many neutrophil cell surface receptors regulate important cellular processes via activation of agonist-activated PI3Ks. We show here that activation of human neutrophils with insoluble immune complexes drives a previously uncharacterized, PI3K-dependent, non-canonical, pro-apoptotic signaling pathway, FcγR-PI3Kβ/δ-Cdc42-Pak-Mek-Erk. This is a rare demonstration of Ras/Raf-independent activation of Erk and of PI3K-mediated activation of Cdc42. In addition, comparative analysis of immune-complex- and fMLF-induced signaling uncovers key differences in pathways used by human and murine neutrophils. The non-canonical pathway we identify in this study may be important for the resolution of inflammation in chronic inflammatory diseases that rely on immune-complex-driven neutrophil activation.

Objective: This study aimed to analyze early and midterm results of custom-made proximal scallop and fenestrated stent grafts for thoracic endovascular aortic repair (TEVAR) with a proximal landing zone (PLZ) in the aortic arch., Methods: All consecutive patients treated with the custom made proximal scalloped and fenestrated Relay stent grafts (Terumo Aortic Bolton Medical Inc.) in 10 Italian centers between January 2014 and December 2022 were included. The primary end points were technical success, incidence of intraoperative major adverse events, deployment accuracy, and rate of early neurological complications, endoleaks (ELs) and retrograde aortic dissection., Results: During the study period, 49 patients received TEVAR with Relay custom-made endograft in Italy were enrolled. The median patient age was 70.1 years (interquartile range, 23-86 years) and 65.3% were male. The indication for treatment was atherosclerotic aneurysms in 59.2% of cases and penetrating aortic ulcer in 22.4%. The endograft configuration was proximal fenestration in 55.1% and scallop in 44.9%. The proximal landing zone was zone 0 in 25 cases (51%), zone 1 in 14 cases (28.6%), and zone 2 in 10 cases (20.4%). The supra-aortic debranching procedures were 38 (77.5%). Technical success was 97.9% (48/49) owing to one case (2.0%) of inaccurate deployment. Intraoperatively, one (2.0%) type Ia and one (2.0%) type III EL were detected. There were no cases of in-hospital mortality, major adverse events, or retrograde dissection. Three minor strokes (6.1%) (National Institutes of Health Stroke Scale score of ≤4) were observed. At a mean follow-up time of 36.3 ± 21.3 months the rate of types I to III ELs and reintervention was 4.1%, respectively. Four patients (8.2%) died during the follow-up period, one (2.1%) from abdominal aortic rupture and three (6.1%) from nonaortic causes., Conclusions: Our early and midterm outcomes suggest that scalloped and fenestrated TEVAR may provide an acceptable alternative treatment option for aortic arch pathologies. Large-scale studies are needed to assess the long-term durability of this technique., Competing Interests: Disclosures None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The challenge of transplant waiting-lists is to provide organs for all candidates while maintaining efficiency and equity., Aims: We investigated the probability of being transplanted or of waiting-list dropout in Italy., Methods: Data from 12,749 adult patients waitlisted for primary liver-transplantation from January 2012 to December 2022 were collected from the National Transplant-Registry.The cohort was divided into Eras:1 (2012-2014);2 (2015-2018);and 3 (2019-2022)., Results: The one-year probability of undergoing transplant increased (67.6 % in Era 1vs73.8 % in Era 3,p < 0001) with a complementary 46 % decrease in waiting-list failures. Patients with hepatocellular-carcinoma were transplanted more often than cirrhotics[at model for end-stage liver-disease (MELD)-15:HR = 1.28,95 %CI:1.21-1.35;at MELD-25:HR = 1.04,95 %CI:0.92-1.19) and those with other indications (at MELD-15:HR = 1.27,95 %CI:1.11-1.46) across all eras. Candidates with Hepatitis-B-virus (HBV)related disease had a greater probability of transplant than those with Hepatitis-C virus-related (HR = 1.13,95 %CI:1.07-1.20), alcohol-related (HR = 1.13,95 %CI:1.05-1.21), and metabolic-related (HR = 1.18,95 %CI:1.09-1.28)disease. Waiting-list failures increased by 27 % every 5 MELD-points and by 14 % for every 5-year increase in recipient-age and decreased by 10 % with each 10-cm increase in stature. Blood-group O patients showed the highest probability of waiting-list failure (HR = 1.28,95 %CI:1.15-1.43)., Conclusions: Liver-transplantation waiting-list success-rates have significantly improved in Italy, with patients with hepatocellular-carcinoma and/or HBV-related diseases being favored. High MELD-score, old-age, short-stature, and blood-group O were significant risk-factors for waiting-list failure. Efforts to improve organ-allocation and prioritization-policies are underway., Competing Interests: Conflict of interest The authors of this manuscript have no conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier Ltd.)

Background: The narrow aortic bifurcation (NAB) is considered a risk factor for endograft thrombosis after aorto-biiliac endovascular aneurysm repair (EVAR) for aortic or iliac aneurysm. Nowadays, no consensus on the threshold diameter for the definition of NAB is reached and other aortic bifurcation features are rarely considered. The aim of the study is to assess the EVAR outcomes using bifurcated endograft according to anatomical characteristics of aortic bifurcation., Methods: The study included patients treated with primary EVAR from 2016 to 2022. A retrospective analysis of single-center prospectively collected database was performed. Patients were classified in standard aortic bifurcation (SAB) (aortic bifurcation diameter >20 mm), NAB (≤20 mm and >16 mm), and extremely NAB (eNAB) (≤16 mm). The 3 groups were compared in terms of patient demographics, risk factors, procedure setting (elective or urgent/emergent), and type of deployed endograft. In NAB and eNAB groups, severe calcification (SC) and length of stenotic aortic bifurcation >10 mm (long-NAB) were assessed from preoperative imaging. In SAB, NAB, and eNAB groups, following outcomes were evaluated: rate of intraoperative iliac endograft stenting (unilateral or kissing stenting), primary patency (PP), freedom from endograft-related reintervention, and overall survival during follow-up., Results: The total number of deployed aorto-biiliac endografts was 365 (mean age: 76.6 ± 7.4 years; male 89.3%): SAB 298 (81.6%), NAB 57 (15.6%), and eNAB 10 (2.7%) cases. Female gender, chronic obstructive pulmonary disease patients, and active smokers were more frequent in patients with smaller aortic bifurcation diameter (P = 0.002, 0.039, and 0.010, respectively). In NAB and eNAB groups, SC was reported in 18/67 cases (26.9%) and long-NAB in 15/67 cases (25.4%). Patients with eNAB have more frequent SC of aortic bifurcation (60% vs. NAB 21.1%, P = 0.018) and long-NAB (50% vs. NAB 17.5%, P = 0.023). In SAB, NAB, and eNAB, intraoperative iliac endograft stenting was performed in 34/298 (11.4%), 9/57 (15.8%), and 5/10 (50%), respectively (P = 0.001). Kissing stenting was performed more frequently in groups with smaller aortic bifurcation diameter (P = 0.010). Mean follow-up was 30.2 ± 21.5 months. At 1, 3, and 5 years, PP was 98.5%, 96.6%, and 95.6%, respectively. eNAB had lower rate of PP compared to NAB group (P = 0.030). Long-NAB had lower rate of PP (P = 0.035). At 1, 3, and 5 years, endograft-related reintervention was 96.8%, 86.7%, and 76.7%, respectively, with no differences between 3 groups (P = 0.423). At 1, 3, and 5 years, survival was 92.5%, 77.6%, and 58.1%, respectively, with no difference between SAB, NAB, and eNAB (P = 0.673)., Conclusions: Female gender, chronic obstructive pulmonary disease patients, and active smokers have more frequently smaller aortic bifurcation diameter. eNAB patients have more challenging anatomical characteristics compared with NAB group, requiring higher rate of intraoperative stenting, especially kissing stenting. Mid-term PP seems to be negatively influenced by aortic bifurcation ≤16 mm and long-NAB., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: The aim of this study was to evaluate changes in geometry following root canal preparation using R-Motion instruments with different apical sizes and tapers., Methods: Fifty-four mesial canals of mandibular molars with single curvature of angles ranging between 20° and 30° were stratified into 3 groups according to their internal anatomy (R-Motion 25/.06, 30/.04, Reciproc Blue) (n = 18 per group). Micro-computed tomography was used to standardize the samples before instrumentation and, after instrumentation, to assess canal transportation, changes in canal volume and centering ability. Canals were irrigated with 17% EDTA and sodium hypochlorite, and the final rinse included subsonic agitation of these solutions. Measurements were analyzed automatically using the Dragonfly software (Come, Montreal, Canada) and were confirmed by a technician and an endodontist, based on a previously validated methodology. The results were analyzed using the Kruskal-Wallis's and Mann-Whitney's tests. The level of statistical significance was set at 5%., Results: Significant differences were found in the coronal third for canal transportation, with Reciproc Blue R25 having greater values compared with both R-Motion instruments (P < .05) and greater changes in volume when compared with R-Motion 30/.04 (P < .05)., Conclusions: R-Motion of apical size and taper 25/.06 and 30/.04 were associated with similar changes in geometry following root canal preparation in curved mesial canals of mandibular molars, whereas Reciproc Blue was associated with greater canal transportation in the coronal root third., (Copyright © 2024 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Background: Molecular characterization is pivotal for managing non-small cell lung cancer (NSCLC), although this process is often time-consuming and patients' conditions might worsen while molecular analyses are processed. Our primary aim was to evaluate the performance of "up-front" next-generation sequencing (NGS) through liquid biopsy (LB) of hospitalized patients with newly detected lung neoplasm in parallel with conventional diagnosis. The secondary aim included longitudinal monitoring through LB of patients with oncogenic alterations at baseline., Methods: We enrolled 47 consecutive patients immediately after hospitalization and radiological detection of symptomatic lung neoplasm. LB from peripheral blood was performed at baseline, in parallel with conventional biopsy (CB), when feasible. Additionally, LBs were repeated during treatment in patients with actionable gene alterations at baseline. Oncomine™ Lung cfTNA Research Assay panel was employed for processing plasma samples in NGS., Results: 47 hospitalized patients were enrolled. LB identified 28 patients with gene alterations, including mutations of EGFR (n = 7), KRAS (n = 12), ERBB2 (n = 1), TP53 (n = 2), BRAF (n = 1), one ALK rearrangement, and 4 patients with combined mutations involving EGFR, KRAS and PIK3CA. LB and CB were consistent, except for two patients. Three patients with positive LB for oncogenic drivers did not undergo CB due to contraindications. Median time to molecular results after LB was significantly lower compared to time to molecular report after CB (11 versus 22 days, p < 0.001)., Conclusions: Despite limited numbers, our study supports the role of front-line LB for improving management of symptomatic patients with lung cancer, potentially leading to early targeted therapy initiation., Competing Interests: Declaration of competing interest Chiara Dellepiane has received honoraria for consulting activities of Astra Zeneca, Merck Sharp and Dohme, Bristol-Myers-Squibb, Roche. Francesco Spagnolo has been an advisory boards member for MSD, Novartis, Pierre Fabre, Sun Pharma, Philogen and has received lecture fees/honoraria for consulting activities of BMS, MSD, Novartis, Pierre Fabre, Merck, Sanofi, Sun Pharma, IGEA. Matteo Lambertini reports advisory role for Roche, Lilly, Novartis, Astrazeneca, Pfizer, Seagen, Gilead, MSD and Exact Sciences and speaker honoraria from Roche, Lilly, Novartis, Pfizer, Sandoz, Libbs, Daiichi Sankyo, Knight and Takeda, Travel Grants from Gilead and Daiichi Sankyo, and research support (to the Institution) from Gilead outside the submitted work. Lucia Del Mastro has received honoraria for consulting activities, speaker bureau or advisory boards from Roche, Novartis, Pfizer, Eli Lilly, Astra Zeneca, Merck-Sharp-Dohme, Seagen, Gilead, Pierre Fabre, Eisai, Exact sciences, Ipsen, GSK, Agendia, Stemline Menarini, Daiichi Sakyo. Carlo Genova has received honoraria for consulting activities, speaker bureau or advisory boards from Astra Zeneca, Bristol-Myers-Squibb, Eli Lilly, Janssen, Merck Sharp and Dohme, Novartis, Roche, Sanofi, Takeda. The other authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Amyloid deposition in tenosynovial structures precedes cardiac involvement up to 20 years. Therefore, a cardiological screening in patients with a history of tenosynovial manifestations of cardiac amyloidosis (CA) could lead to an increased number of early diagnoses., Methods: Patients with tenosynovial manifestations of CA (carpal tunnel syndrome, atraumatic biceps tendon rupture, lumbar spinal stenosis) have been identified by general practitioners and evaluated in a Referral Center for CA. Patients with a high suspicion of CA underwent the CA diagnostic pathway., Results: Among 50 General Practitioners (GP) contacted, 10 (20%) agreed to participate in the study for a total of 5615 patients ≥60 years. One hundred forty-five patients met the inclusion criteria, 2 of them already had a diagnosis of CA, and 57 agreed to undergo a cardiological evaluation (electrocardiography, echocardiography, NTproBNP assay). The median age was 73 [67-80] years and 31 (54%) were women. Eight patients were suggested to start the CA diagnostic pathway, five of them underwent a complete diagnostic evaluation for CA, three refused to complete the diagnostic exams and no new diagnoses were made., Conclusion: A screening program for CA in patients with tenosynovial manifestations identified by general practitioners is feasible, but may not yield a high rate of new diagnosis. In this study, we identified two patients who already had a diagnosis of CA, and among patients at high risk for CA, 37% refused to complete the diagnostic pathway. Increased awareness of CA among patients might increase participation and diagnostic yield in screening studies. Further validation of this protocol is needed to evaluate its diagnostic performance., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Objective: The aim of this study was to investigate the mid-term results of stented-assisted balloon-induced intimal disruption and relamination (STABILISE) in patients with aortic dissection with the implementation of volumetric analysis., Methods: This was a single-center retrospective analysis of prospectively collected data. From May 2017 to September 2022, 42 patients underwent STABILISE for acute complicated or subacute high-risk aortic dissection. STABILISE was completed with distal extended endovascular aortic repair in 24 patients. A computed tomography scan was performed at baseline, before hospital discharge, and at 1, 3, and 5 years. Perfused total aortic, true lumen, and false lumen volumes were assessed for thoracic, visceral, and aorto-iliac segment. The ratio between false lumen and total volume was named perfusion dissection index (PDI). Complete remodeling was defined as PDI = 0, and positive remodeling as PDI ≤0.1., Results: Technical success was 97.6%. No 30-day deaths, spinal cord injuries, or retrograde dissections were observed. Mean follow-up was 44 ± 19.4 months. Thoracic diameter was lower at last available computed tomography scan (36.7 vs 33.0 mm; P = .01). Aortic growth >5 mm was observed in 9.5% of the patients. Thoracic and visceral aortic complete remodeling were 92.8% and 83.3%, respectively, with no difference between acute and subacute group. Distal extended endovascular aortic repair significantly increased complete remodeling in the aorto-iliac segment, compared with STABILISE alone (69.6% vs 21.4%; P < .001). Freedom from vascular reinterventions at 3 years was 83.1% (95% confidence interval, 71.5%-96.6%). Total PDI ≤0.1 at first postoperative control was a predictor of vascular reinterventions (P < .0001)., Conclusions: STABILISE is a safe and feasible technique associated with high mid-term rates of complete remodeling in the thoracic and visceral aorta. Volumetric analysis allows the quantification of aortic remodeling and represents a predictor of aortic reinterventions., Competing Interests: Disclosures None., (Copyright © 2024 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Distinguishing mucinous (M) pancreatic cystic neoplasms (PCNs) from non-mucinous (NM) is challenging but crucial. Low intracystic glucose level has shown diagnostic tool promise, however further investigation is needed to understand metabolic processes., Aims: To compare the diagnostic accuracy of intracystic glucose and CEA levels in a large cohort and explore lactate levels as potential marker., Methods: PCNs≥15 mm which underwent EUS-fine needle aspiration were prospectively enrolled. Glucose, CEA and lactate levels were measured. Diagnostic accuracy for M-PCN diagnosis was evaluated using surgical/cytology reports or multidisciplinary evaluations., Results: 169 PCNs were included (64 % M-PCNs). Median intracystic glucose was significantly lower in M-PCNs (1 mg/dL) compared to NM-PCNs (101 mg/dL); mean intracystic CEA was significantly higher in M-PCNs (152.5 ng/mL) compared to NM-PCNs (0.3 ng/mL). ROC curve analysis revealed best glucose cut-off ≤58 mg/dL (accuracy 93.5 %) and CEA cut-off >2.5 ng/mL (accuracy 90.5 %) for M-PCNs. Intracystic lactates were significantly lower in M-PCNs correlating directly with glucose. Single glucose dosage evidenced best diagnostic accuracy respect markers combination., Conclusion: Intracystic glucose demonstrated high diagnostic utility for M-PCNs differentiation, surpassing CEA. Lactate levels correlated with glucose, suggesting their uptake by M-PCNs cells. These findings contribute to a better metabolic landscape understanding glucose use as diagnostic marker., Competing Interests: Conflict of interest None., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Most electroanalytical detection schemes for DNA markers require considerable time and effort from expert personnel to thoroughly follow the analysis and obtain reliable outcomes. This work aims to present an electrochemical assay performed inside a small card-based platform powered by microfluidic manipulation, requiring minimal human intervention and consumables. The assay couples a sample/signal dual amplification and DNA-modified magnetic particles for the detection of DNA amplification products. Particularly, the sul1 and sul4 genes involved in the resistance against sulfonamide antibiotics were analyzed. As recognized by the World Health Organization, antimicrobial resistance threatens global public health by hampering medication efficacy against infections. Consequently, analytical methods for the determination of such genes in environmental and clinical matrices are imperative. Herein, the resistance genes were extracted from E. coli cells and amplified using an enzyme-assisted isothermal amplification at 37 °C. The amplification products were analyzed in an easily-produced, low-cost, card-based set-up implementing a microfluidic system, demanding limited manual work and small sample volumes. The target amplicon was thus captured and isolated using versatile DNA-modified magnetic beads injected into the microchannel and exposed to the various reagents in a continuously controlled microfluidic flow. After the optimization of the efficiency of each phase of the assay, the platform achieved limits of detections of 44.2 pmol L -1 for sul1 and 48.5 pmol L -1 for sul4, and was able to detect down to ≥500-fold diluted amplification products of sul1 extracted from E. coli living cells in around 1 h, thus enabling numerous end-point analyses with a single amplification reaction., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

The aim of this study was to describe the gross and histopathological features of a neurological syndrome in endangered Western Australian Carnaby's black cockatoos (Zanda laitirostris) that was first observed in 2012. The syndrome, named hindlimb paralysis syndrome in Carnaby's cockatoos (CHiPS), is characterized by annual outbreaks of hindlimb paralysis with occasional loss of deep pain and cloacal tone, typically occurring between January and March. Previous limited investigations suggested a possible toxic aetiology. Full gross necropsy and histopathology examinations were performed on 17 CHiPS cases and on 11 control birds for reference. Histopathological examination was carried out on all major organs including brain, spinal cord, brachial plexus, sciatic nerve and wing and hindlimb muscles. Gross and histopathological examinations did not elucidate a definitive cause of the clinical signs seen in CHiPS cases. There were no substantial gross or histopathological changes within the brain, spinal cord, sciatic nerve or brachial plexus that could explain the hindlimb paralysis. The most noteworthy changes were seen in the hindlimb and wing muscles, with a monophasic to polyphasic myopathy present in the hindlimb muscles of 15 of the 17 CHiPS cases and in the wing muscles in 11 of those cases. The cause and significance of the myopathy is unclear and requires further investigation. Based on the above findings, the most likely differential diagnoses include neurotoxicoses (eg, organophosphate, organochlorine and carbamate) and, less likely, myotoxicosis (eg, ionophore toxicosis), nutritional myopathy (eg, vitamin E/selenium deficiency) or botulism., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

A plethora of studies have so far described the toxic effects of bisphenol A (BPA) on organism health, highlighting the urgent need to find new strategies not only to reduce the presence of this toxicant but also to counteract its adverse effects. In this context, probiotics emerged as a potential tool since they promote organism welfare. Using a multidisciplinary approach, this study explores the effects of SLAB51 dietary administration to counteract BPA toxicity using zebrafish as a model. Adult males and females were maintained under standard conditions (control group; C), exposed for 28 days via the water to an environmental relevant dose of BPA (10 μg/L; BPA), dietary treated with SLAB51 (10 9  CFU/g of body weight; P) and co-treated with BPA plus SLAB51 (BPA + P). In the gut, exposure to BPA resulted in altered architecture in both males and females, with females also experiencing an increase of pathogenic bacterial species. Co-administration of BPA + P led to the restoration of normal gut architecture, favored beneficial bacteria colonization, and decreased the abundance of pathogenic species. In the liver, male BPA exposure led to steatosis and glycogen depletion, which was partially mitigated by SLAB51 co-administration. In contrast, in females exposed to BPA, the lack of steatosis along with the greater glycogen depletion, suggested an increase in energy demand as supported by the metabolomic phenotype. The analysis of liver metabolites in BPA + P males revealed increased levels of anserine and reduced levels of glutamine, which could lie behind the counteraction of the brain histopathological damage caused by BPA. In BPA + P females, a reduction of retinoic acid was found in the liver, suggesting an increase in retinoids responsible for BPA detoxification. Overall, these results demonstrate that SLAB51 exerts its beneficial effects on the gut microbiota-brain-liver axis through distinct molecular pathways, effectively mitigating the pleiotropic toxicity of BPA., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: To provide evidence explaining the poor association between pCR and patients' long-term outcome at trial-level in neoadjuvant RCTs for breast cancer (BC), we performed a systematic-review and meta-analysis of all RCTs testing neoadjuvant treatments for early-BC and reporting the hazard ratio of DFS (HR DFS ) for the intervention versus control arm stratified by pathological response type (i.e., pCR yes versus no)., Methods: The objective was to explore differences of treatment effects on DFS across patients with and without pCR. We calculated the pooled HR DFS in the two strata of pathological response (i.e., pCR yes versus no) using a random-effects model, and assessed the difference between these two estimates using an interaction test., Results: Ten RCTs and 8496 patients were included in the analysis. Patients obtaining pCR in the intervention-arm had a higher, although not statistically significant, risk of DFS-event as compared with patients obtaining pCR in the control-arm: the pooled HR DFS for the experimental versus control arm was 1.23 (95%CI, 0.91-1.65). On the opposite, the risk of DFS-event was higher for control as compared with the intervention-arm in the stratum of patients without pCR: the pooled HR DFS was 0.86 (95%CI, 0.78-0.95). Treatment effect on DFS was significantly different according to pathological response type (interaction test p: 0.014)., Conclusion: We reported new evidence that contributes to explaining the poor surrogacy value of pCR at trial-level in neoadjuvant RCTs for early-BC., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Data on the incidence and factors associated with de novo atrial fibrillation (AF) in patients with wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) is limited. We described the incidence and factors associated with de novo AF in patients diagnosed with ATTRwt-CA to drive tailored arrhythmia screening., Methods: Multicenter, retrospective, observational cohort study performed in six referral centers for CA. All consecutive patients diagnosed with ATTRwt-CA between 2004 and 2020 with >6-month follow up (FU) were enrolled and divided into three groups according to presence of AF: (1)patients with 'known AF'; (2)patients in 'sinus rhythm' and (3)patients developing 'de novo AF' during FU. Incidence and factors associated with AF in patients with ATTRwt were the primary outcomes., Results: Overall, 266 patients were followed for a median of 19 [11-33] months: 148 (56%) with known AF, 84 (31.6%) with sinus rhythm, and 34 (12.8%) with de novo AF. At Fine-Gray competing risk analysis to account for mortality, PR (sub-distribution hazard ratio [SHR] per Δms: 1.008, 95% C.I. 1.001-1.013, p = 0.008), QRS (SHR per Δms: 1.012, 95% C.I. 1.001-1.022, p = 0.046) and left atrial diameter ≥ 50 mm (SHR: 2.815,95% C.I. 1.483-5.342, p = 0.002) were associated with de novo AF. Patients with at least two risk factors (PR ≥ 200 ms, QRS ≥ 120 ms or LAD≥50 mm) had a higher risk of developing de novo AF compared to patients with no risk factors (HR 14.918 95% C.I. 3.242-31.646, p = 0.008)., Conclusions: At the end of the study almost 70% patients had AF. Longer PR and QRS duration and left atrial dilation are associated with arrhythmia onset., Competing Interests: Declaration of Competing Interest none to declare for the present work. All authors participated in the research and preparation of the manuscript., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: Elderly patients with hematologic malignancies face the highest risk of severe COVID-19 outcomes. The infection's impact on different age groups remains unstudied in detail., Methods: We analyzed elderly patients (age groups: 65-70, 71-75, 76-80, and >80 years old) with hematologic malignancies included in the EPICOVIDEHA registry between January 2020 and July 2022. Univariable and multivariable Cox regression models were conducted to identify factors influencing death in COVID-19 patients with hematological malignancy., Results: The study included data from 3,603 elderly patients (aged 65 or older) with hematological malignancy, with a majority being male (58.1%) and a significant proportion having comorbidities. The patients were divided into four age groups, and the analysis assessed COVID-19 outcomes, vaccination status, and other variables in relation to age and pandemic waves. The 90-day survival rate for patients with COVID-19 was 71.2%, with significant differences between groups. The pandemic waves had varying impacts, with the first wave affecting patients over 80 years old, the second being more severe in 65-70, and the third being the least severe in all age groups. Factors contributing to 90-day mortality included age, comorbidities, lymphopenia, active malignancy, acute leukemia, less than three vaccine doses, severe COVID-19, and using only corticosteroids as treatment., Conclusion: These data underscore the heterogeneity of elderly hematological patients, highlight the different impacts of COVID-19 waves and the pivotal importance of vaccination, and may help in planning future healthcare efforts., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: This study aimed to compare the curvature severity of mesio-buccal (MB) canals between sagittal and coronal planes using cone-beam computed tomography., Methods: In a Brazilian subpopulation, untreated MB1 (n = 141) and MB2 (n = 72) with single curvatures in sagittal and coronal planes were measured to determine their angle and radius (r), plus the prevalence of S-shaped canals was recorded. Curvature severity was defined according to the American Association of Endodontists Case Difficulty Assessment form (AAE) and EndoApp (EA), as well as their modified versions that consider angle and radii (AAE-r, EA-r). Data were converted into mean angle and r, percentage of canals >30°, AAE, EA, AAE-r and EA-r categories. The influence of r on case severity was assessed. Statistical analysis was performed using t-tests and chi-squared tests. The level of significance was set as P ≤ .05., Results: For single curvatures, significantly higher mean degrees (SD) angles were found in the sagittal views in both canals (MB1 sagittal: 35 [11]; MB1 coronal: 13 [13]; MB2 sagittal: 29 [14]; MB2 coronal: 22 [15] [P < .05]). A greater percentage of angles >30° (MB1: 56.7% vs 6.4%; MB2: 44.4% vs 22.2%) in sagittal planes compared to coronal planes was also found. Conversely, a higher prevalence of S-shaped canals (MB1: 33.3% vs 7.1% MB2: 31.9% vs 15.3%) was observed in coronal planes. Significant differences between AAE and AAE-r were present with greater case severity when radii were considered (P < .05)., Conclusions: Sagittal planes were associated with more severe single curvatures, while coronal planes had a greater prevalence of S-shaped canals., (Copyright © 2023 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: Amoebic liver abscess (ALA) is the fourth cause of mortality by parasitic infection. This study aimed to assess clinical, radiological and therapeutic characteristics of patients admitted for amoebic liver abscess compared to pyogenic abscess in a French digestive tertiary care-centre., Material and Method: The charts of patients hospitalized for a liver abscess between 2010 and 2020 were retrospectively assessed then separated in two groups: amoebic liver abscess and pyogenic liver abscess from portal underlying cause. Clinical and radiological data were collected for univariate comparison., Results: Twenty-one patients were hospitalized during the time of the study for ALA, and 21 patients for pyogenic liver abscess with a portal mechanism. All patients hospitalized for ALA lived in and/or had travelled recently in an endemic area. In comparison with patients hospitalized for pyogenic abscess, patients admitted for ALA were younger (44years old vs. 63years old, P<0.001), had less comorbidities (5% vs. 43% of patients with at least one comorbidity, P<0.01), a longer median duration of symptoms (10days vs. 3days, P=0.015), abdominal pain (86% vs. 52%, P=0.019), and a slighter leucocytosis (9600G/L vs. 15,500G/L, P=0.041) were more frequent. On the abdominal tomodensitometry, density of ALA was higher (34 vs. 25 UH, P<0.01), associated with a focal intra-hepatic biliary dilatation and less often multiloculated., Conclusion: While rare in western countries, amoebic liver abscess care should not be underestimated. The presence of a solitary liver abscess of intermediate density on computed tomography, occurring on a patient returning from an endemic zone should lead the physician to a possible diagnosis of ALA., (Copyright © 2023 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Introduction: This study aimed to calculate the correlation between the radiopacity levels of various intracanal medicaments and radiolucent streak formation using cone-beam computed tomography (CBCT)., Methods: Seven commercially-available intracanal medicaments were tested, which contained different amounts of radiopacifier [Consepsis, Ca(OH) 2 , UltraCal XS, Calmix, Odontopaste, Odontocide, and Diapex Plus]. Their radiopacity levels were measured according to the International Organization for Standardization 13116 testing standards (mmAl). Subsequently, the medicaments were placed in 3 canals of radiopaque artificial printed maxillary molars (n = 15 roots per medicament), leaving the second mesiobuccal canal empty. CBCT imaging was carried out using an Orthophos SL 3-dimensional scanner under recommended manufacturer exposure settings. Radiopaque streak formation was assessed by a calibrated examiner using a previously published grading system (0-3). The Kruskal-Wallis and Mann-Whitney U tests with and without Bonferroni correction were used to compare radiopacity levels and radiopaque streak scores for the medicaments. Their relationship was assessed using the Pearson correlation coefficient. The level of significance was set as (α = 0.05)., Results: Diapex plus presented with the highest radiopacity levels (4.98 ± 0.01) and radiopaque streak scores [middle third (2.8 ± 0.18); apical third (2.73 ± 0.43)]; which was similar to UltraCal XS's radiopaque streak scores [middle third (2.8 ± 0.92); apical third (2.73 ± 0.77)]. Consepsis had the lowest radiopacity levels (0.12 ± 0.05), followed by Odontocide (0.60 ± 0.05). Consepsis and Ca(OH) 2 were scored 0 for artifacts in all roots at all levels. A high positive correlation (R = 0.95) was found between radiopacity and streak formation., Conclusions: The radiopacity of intracanal medicaments varies and strongly correlates with the formation of radiolucent streak artifacts during CBCT., (Copyright © 2023 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Diabetic kidney disease (DKD) is the first cause of end-stage kidney disease in patients with diabetes and its prevalence is increasing worldwide. It encompasses histological alterations that mainly affect the glomerular filtration unit, which include thickening of the basement membrane, mesangial cell proliferation, endothelial alteration, and podocyte injury. These morphological abnormalities further result in a persistent increase of urinary albumin-to-creatinine ratio and in a reduction of the estimated glomerular filtration rate. Several molecular and cellular mechanisms have been recognized, up to date, as major players in mediating such clinical and histological features and many more are being under investigation. This review summarizes the most recent advances in understanding cell death mechanisms, intracellular signaling pathways and molecular effectors that play a role in the onset and progression of diabetic kidney damage. Some of those molecular and cellular mechanisms have been already successfully targeted in preclinical models of DKD and, in some cases, strategies have been tested in clinical trials. Finally, this report sheds light on the relevance of novel pathways that may become therapeutic targets for future applications in DKD., 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 © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

T-cell acute lymphoblastic leukemia (T-ALL) is a T-cell malignancy characterized by cell subsets and enriched with leukemia-initiating cells (LICs). β-Catenin modulates LIC activity in T-ALL. However, its role in maintaining established leukemia stem cells remains largely unknown. To identify functionally relevant protein interactions of β-catenin in T-ALL, we performed coimmunoprecipitation followed by liquid chromatography-mass spectrometry. Here, we report that a noncanonical functional interaction of β-catenin with the Forkhead box O3 (FOXO3) transcription factor positively regulates LIC-related genes, including the cyclin-dependent kinase 4, which is a crucial modulator of cell cycle and tumor maintenance. We also confirm the relevance of these findings using stably integrated fluorescent reporters of β-catenin and FOXO3 activity in patient-derived xenografts, which identify minor subpopulations with enriched LIC activity. In addition, gene expression data at the single-cell level of leukemic cells of primary patients at the time of diagnosis and minimal residual disease (MRD) up to 30 days after the standard treatments reveal that the expression of β-catenin- and FOXO3-dependent genes is present in the CD82+CD117+ cell fraction, which is substantially enriched with LICs in MRD as well as in early T-cell precursor ALL. These findings highlight key functional roles for β-catenin and FOXO3 and suggest novel therapeutic strategies to eradicate aggressive cell subsets in T-ALL., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)