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Regarding secondary aerosols, in addition to the significant contribution of anthropogenic gases such as NOx and SO2, atmospheric ammonia (NH3) plays a crucial role as the primary basic gaseous species capable of neutralizing acidic compounds. This acid–base reaction is responsible for the formation of ammonium nitrate (NH4NO3), constituting up to 60% of PM10 within the Po River basin in Italy. Ion chromatographic analyses performed on offline samples indicate that this secondary inorganic species exhibits minimal concentration variability over the Po Valley because of limited air circulation due to orography and mesoscale air circulation. Therefore, investigating gaseous precursors becomes crucial. From the northern to the southern part of Lombardy—the region at the center of the basin—NH3 emission amounts account for 2.5, 11.1, and 27.7 t/y/km2, mainly due to agriculture and livestock activities (∼97%). To study NH3 temporal and spatial variability, the Environmental Protection Agency of Lombardy Region has been monitoring NH3 concentrations across its territory since 2007, with 10 active monitoring sites. Annual and seasonal cycles are presented, along with a focus on different stations, including urban, low-mountain background, high-impact livestock, and rural background, highlighting the impact of various sources. Measurements indicate that within the Po basin, NH3 concentrations can reach up to 700 µg/m3 (as an hourly average) in proximity to the main gaseous NH3 source. Instrument intercomparisons among online monitors and passive vials, as well as different online monitors, are presented. Therefore, this paper provides crucial data to understand the formation of secondary inorganic aerosols in one of the most important hotspot sites for air pollution.

In Big Cypress National Preserve, the federally threatened Everglades bully (Sideroxylon reclinatum subsp. austrofloridense) is sympatric with its conspecific, more widespread relative, the Florida bully (Sideroxylon reclinatum subsp. reclinatum). In this area of overlap, the only reliable characters to distinguish the two are cryptic, micromorphological traits of the abaxial laminar surface. In order to better understand the distribution of the federally threatened taxon, we used a combination of habitat suitability modeling (HSM), field surveys, and microscopy. Using models to inform initial surveys, we collected leaf material of 96 individuals in the field, 86 of which we were able to identify to subspecies. Of these, 73 (85%) were identified as the threatened taxon, expanding both the known range and population size within Big Cypress. We used these 73 new occurrences to rerun HSMs to create a more accurate picture of where the taxon is likely to occur. A total of 15,015 hectares were predicted to be suitable habitat within Big Cypress, with 34,069 hectares across the entire study area. These model results could be used to inform the critical habitat designation for this taxon. For at-risk, cryptic taxa, such as the Everglades bully, multiple approaches are needed to inform management and conservation priorities, including the consideration of a hybridization zone.

Background: Since the discovery of SARS-CoV-2, no treatment has been able to completely eradicate the virus. The study aimed to evaluate the virological and clinical impact of the vaccination in SARS-CoV-2 infected patients treated with monoclonal antibodies (mAbs)., Methods: This single-centre, observational, retrospective, real-life study was performed on SARS-CoV-2 symptomatic outpatients and inpatients treated with mAbs from March 2021 to November 2022 includes 726 patients. Each patient received available mAbs (bamlanivimab-etesevimab or casirivimab-indevimab or sotrovimab or tixagevimab-cilgavimab) according to the circulating virus strains. Age, comorbidities, vaccination status, death rates, duration of virological clearance, average length of stay, risk factors, and hospitalization or ICU admission were recorded., Results: Of 726 patients with complete data analyzed (median age 64), 516 outpatients and 210 inpatients were included. Vaccination status was known for all participants: 74.4 % and 51.7 % were vaccinated against SARS-CoV-2 among inpatients and outpatients, respectively. A shorter duration of virological clearance was observed in the vaccinated group, with a median of 16 days (IQR 15-17), compared to 19 days (IQR 18-21) in the unvaccinated group [HR 1.21; p < 0.032]. Multivariate analysis of virological clearance also showed statistical significance with tixagevimab cilgavimab 300 mg/300 mg (HR 2.73, p value < 0.001). No significant difference was found in worsening [OR 1,29; p = 0.57] and mortality [OR 0.65; p = 0.81] rates between vaccinated and unvaccinated patients treated with mAbs., Conclusions: Key findings include a shorter duration of virological clearance in vaccinated outpatients but no significant differences in worsening or mortality rates between vaccinated and unvaccinated patients treated with mAbs. The study suggests a potential synergistic role of mAbs in accelerating virological clearance in vaccinated patients with mild to moderate COVID-19, with differing effects in hospitalized patients. Therefore, it is essential to implement health surveillance in high-risk patients with comorbidities in order to identify early any variants that might otherwise escape neutralizing antibodies., 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 Author(s). Published by Elsevier B.V. All rights reserved.)

Smell and taste are extensively studied in fish species as essential for finding food and selecting mates while avoiding toxic substances and predators. Depending on the evolutionary position and adaptation, a discrete variation in the morphology of these sense organs has been reported in numerous teleost species. Here, for the first time, we approach the phenotypic characterization of the olfactory epithelium and taste buds in the African turquoise killifish (Nothobranchius furzeri), a model organism known for its short lifespan and use in ageing research. Our observations indicate that the olfactory epithelium of N. furzeri is organized as a simple patch, lacking the complex folding into a rosette, with an average size of approximately 600 µm in length, 300 µm in width, and 70 µm in thickness. Three main cytotypes, including olfactory receptor neurons (CalbindinD28K), supporting cells (β-tubulin IV), and basal cells (Ki67), were identified across the epithelium. Further, we determined the taste buds' distribution and quantification between anterior (skin, lips, oral cavity) and posterior (gills, pharynx, oesophagus) systems. We identified the key cytotypes by using immunohistochemical markers, i.e. CalbindinD28K, doublecortin, and neuropeptide Y (NPY) for gustatory receptor cells, glial fibrillary acidic protein (GFAP) for supporting cells, and Ki67, a marker of cellular proliferation for basal cells. Altogether, these results indicate that N. furzeri is a microsmatic species with unique taste and olfactory features and possesses a well-developed posterior taste system compared to the anterior. This study provides fundamental insights into the chemosensory biology of N. furzeri, facilitating future investigations into nutrient-sensing mechanisms and their roles in development, survival, and ageing., Competing Interests: Declarations. Ethical approval: The Animal Welfare Office of the University of Naples Federico II reviewed the study, authorized by the Italian Ministry of Health in accordance with the Italian legislative Decree (n 26/2014) (N° 291/2022-PR). Informed consent: Not applicable. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s).)

Morphological mouse phenotyping plays a pivotal role in the translational setting and even more in the area of auditory research, where mouse is a central model organism due to the evolutionary genetic relationship and morpho-functional analogies with the human auditory system. However, some results obtained in murine models cannot be translated to humans due to the inadequate description of experimental conditions underlying poor reproducibility. We approach the characterization of the aging process of the mouse cochlea in animals up to 18 months of age belonging to two of the most used outbred (CD1) and inbred (C57BL/6N) strains. Striving to reduce any environmental variable we performed our study compliantly to the ARRIVE guidelines. We integrated instrumental data (auditory brainstem response test), with morphological analyses to correlate functional discrepancies to morphological changes and track the differences in the evolution of sensorineural hearing loss in the two strains. We featured the localization of Gipc3, Myosin VIIa, and TMC1 in hair cells of the Corti organ as well as NF 200 and the density of type I neuron in the spiral ganglion. We outlined age-related hearing loss (ARHL) in both strains, and a clear drop in the selected marker localization. However, in CD1 we detected a different trend allowing the identification of potential strain-specific mechanisms, namely an increase in myosin VIIa in 6 months aging mice in comparison to 2 months old animals. Our findings represent an asset to investigate the strain-dependent physiological trigger of ARHL providing new insights in the translational area., (© 2024 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Clinical Relevance: Few studies have investigated the economic burden of keratoconus to patients and society including a patient's lifetime expenditure. Analysing disease cost is important in advocating funding and planning for appropriate management and treatment., Background: Keratoconus can be an expensive disease, including costs associated with visual rehabilitation and surgery. This study aimed to assess direct and indirect expenditures incurred by keratoconus subjects, to estimate the lifetime per capita cost and the total costs of keratoconus per year in Auckland, New Zealand., Methods: A cross-sectional study where participants with keratoconus were recruited from public and private clinics to complete an anonymous questionnaire. A keratoconus health expenditure questionnaire was used to assess direct and indirect expenditures for participants. Estimated lifetime per capita costs and total direct and indirect costs associated with keratoconus were calculated., Results: Responses from 110 participants were recorded. Most participants (55.5%) were between the ages of 21 and 30, 59.1% were male, and Pacific People were over-represented (14.5%) compared to the national population. The prevalence of visual rehabilitation was low with 74.5% of participants never wearing contact lenses and 32.7% of subjects wearing spectacles purchased over 24 months prior. Few participants (26.5%) had subsidised care, including private health insurance with optical cover or the contact lens subsidy. Total direct and indirect costs are estimated to be NZD 30.9 million per year with an estimated lifetime per capita out-of-pocket cost of NZD 79,254., Conclusion: Subjects with keratoconus experience significant direct and indirect costs with limited subsidisation from the government and private health insurance. The significant out-of-pocket costs required for managing keratoconus are likely a significant barrier to accessing appropriate visual rehabilitation in New Zealand.

Aims: The use of loop diuretics in pulmonary arterial hypertension (PAH) is less frequent compared with heart failure. The clinical and prognostic characteristics of PAH patients according to loop diuretic use remain unexplored. In this study, we retrospectively analysed the characteristics and survival of PAH patients requiring different doses of loop diuretics., Methods and Results: Patients diagnosed with PAH between 2001 and 2022 at seven European centres for the management of PAH. According to the median equivalent dose of furosemide in the overall cohort, patients were divided into two subgroups: no/low-dose loop diuretic and high-dose loop diuretic. Primary outcome was 5 year all-cause mortality. Among the 397 patients included, 227 (57%) were treated with loop diuretics. Median daily furosemide equivalent dose was 25 mg, and accordingly patients were divided in no/low dose (i.e. ≤25 mg, n = 257, 65%) vs. high dose (i.e. >25 mg, n = 140, 35%). Patients in the high-dose group were older, more likely to have comorbidities, and had a more severe disease according to the ESC/ERS risk category. Crude 5 year survival was significantly shorter in patients in the high-dose group, but after adjustment for age, sex, and risk category, high loop diuretic dose was not significantly associated with the primary outcome., Conclusions: Use of high dose of loop diuretics in PAH is associated with a higher burden of comorbidities, more severe disease, and worse survival. However, in PAH, the need of high loop diuretic dose is a marker of disease severity and not an independent prognostic factor., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Objective: The Clubhouse model (CM) for serious mental illness is a recovery-oriented and member-driven program that aims to facilitate functional recovery. Efficacy evaluation of the CM is limited by lack of uniform functional disability assessment. The World Health Organization Disability Assessment Schedule 2.0 (WHODAS-2.0) is a widely accepted measure of functional disability, but its psychometric properties have yet to be examined within the CM., Method: This research sought to confirm the generic six-factor structure of the 12-item WHODAS-2.0 using retrospective administrative data from 339 adults with serious mental illness from an accredited Clubhouse. A second-order confirmatory factor analysis was conducted, followed by secondary known-groups analyses to examine whether the WHODAS-2.0 differentiates between subgroups with varying degrees of disability., Results: The WHODAS-2.0 demonstrated good overall reliability. The generic six-factor structure produced nonsignificant loadings due to lack of independence between the "participation" and "getting along" factors. The items of these two factors were combined into a five-factor model, which displayed excellent fit, with all significant paths and adequate-to-strong loadings, and no correlation among errors. The WHODAS-2.0 significantly differentiated members by receipt of public assistance, employment status, and number of medical comorbidities, supporting construct validity., Conclusions and Implications for Practice: These results provide initial support for the use of the 12-item WHODAS-2.0 as a CM-related outcome measure and encourage future research of the full 36-item version. The intentional community approach of the CM is unique and may require adjustments to the factor structure of the WHODAS-2.0 by merging the "participation" and "getting along" domains. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: Pulsed field ablation (PFA) and very high-power short-duration (vHPSD) radiofrequency ablation are the most recently introduced technologies for atrial fibrillation (AF) ablation. The procedural performance, safety, and effectiveness of PFA vs vHPSD are currently unknown., Objective: The study aimed to compare PFA with vHPSD for the treatment of paroxysmal or persistent AF., Methods: We conducted an observational, multicenter study enrolling 534 consecutive patients (63 ± 9 years; 36% female) with paroxysmal (n = 368 [69%]) or persistent (n = 166 [31%]) AF undergoing ablation by either PFA (Farapulse; n = 192) or vHPSD (90 W/4 seconds; QDOT Micro; n = 342) between 2020 and 2023. Atrial tachyarrhythmia recurrence after a 1-month blanking period was the primary efficacy end point and was assessed both overall and in propensity score-matched patients. The primary safety end point was a composite of procedure-related complications., Results: Successful pulmonary vein isolation was achieved in all patients, with shorter procedure duration (PFA,70 minutes; vHPSD, 100 minutes; P < .001) but longer fluoroscopy time (PFA, 15 minutes; vHPSD, 7 minutes; P < .001) in the PFA group. PFA was associated with more frequent use of general anesthesia (P < .001). Primary safety outcome events occurred in 19 patients (3.5%), with similar prevalence in both groups (PFA, 4%; vHPSD, 3%; P = .745). After a median follow-up of 12 (9-12) months, survival free from recurrent atrial tachyarrhythmia was similar between the PFA and vHPSD groups, both overall (12-month estimate: PFA, 75%; vHPSD, 76%; log-rank P = .73) and in propensity score-matched patients (n = 342; 12-month estimate: PFA, 75%; vHPSD, 77%; log-rank P = .980)., Conclusion: In a large, multicenter experience, PFA was associated with more common use of general anesthesia, shorter procedural times, and longer fluoroscopy exposure compared with vHPSD ablation, with both techniques displaying superimposable safety and efficacy., Competing Interests: Disclosures A.D.R. is a consultant for Abbott Medical. M.A. is a consultant for Biosense Webster and Boston Scientific, is a clinical proctor for Medtronic, and has received educational grants from Abbott. M.C. has received speaker honoraria from Biosense Webster. All other authors declare no conflicts of interest., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

In this study, we have investigated the immunolocalization of NGF (Nerve Growth Factor) and BDNF (Brain-Derived Neurotrophic Factor) in the pancreas of two species of marine mammals: Tursiops truncatus (common bottlenose dolphin), belonging to the order of the Artiodactyla, and Otaria flavescens (South American sea lion), belonging to the order of the Carnivora. Our results demonstrated a significant presence of NGF and BDNF in the pancreas of both species with a wide distribution pattern observed in the exocrine and endocrine components. We identified some differences that can be attributed to the different feeding habits of the two species, which possess a different morphological organization of the digestive system. Altogether, these preliminary observations open new perspectives on the function of neurotrophins and the adaptive mechanisms of marine mammals in the aquatic environment, suggesting potential parallels between the physiology of marine and terrestrial mammals.

Background: Idiopathic ventricular arrhythmias (IVAs) arising from different portions of the communicating vein of the left ventricular summit (summit-CV) are not a rare phenomenon. Whereas its electrocardiographic (ECG) and electrophysiological characteristics are not fully investigated., Objective: This study aimed to identify distinct ECG and electrophysiological features of IVAs originating from different portions of summit-CV., Methods: Nineteen patients confirmed arising from summit-CV were included in this study., Results: The 19 patients were divided into proximal and distal portion groups based on their target sites in summit-CV. In the proximal portion group, 100% (11/11) VAs showed dominant negative (rs or QS) waves in lead I, while in the distal portion group, 87.5% (7/8) showed dominant positive waves (R, Rs or r) (p < 0.000). In lead V 1 , 100% (11/11) of the proximal portion group showed dominant positive waves (R or Rs), while 62.50% (5/8) of the distal portion group showed positive and negative bidirectional or negative waves (RS or rS) (p < 0.005). R I >4mV, S I <3.5mV, R V1 <13mV, S V1 >3.5mV, R I /S I >0.83, and R V1 /S V1 < 2.6 indicated a distal portion of summit-CV with the predictive value of 0.909, 1.000, 0.653, 0.972, 0.903, 0.966, respectively. A more positive wave in lead I and a more negative wave in lead V 1 indicated more distal origin in summit-CV. Target sites in proximal and distal summit-CV groups showed similar electrophysiological characteristics during mapping., Conclusions: There were significant differences in ECG characteristics of VAs at different portions of summit-CV, which could aid pre-procedure planning and facilitate radiofrequency catheter ablation (RFCA) procedures., (© 2024. The Author(s).)

Background:  Rapid spread of the SARS-CoV-2 pandemic in 2020 led to an indirect effect on non-COVID patients. Since neuro-oncology cases are unique and brain tumors need a specific therapeutic protocol at proper doses and at the right times, the effects of the pandemic on health care services for patients with glioblastomas (GBs) and their impact on overall survival (OS) and quality of life are not yet known., Methods:  We conducted a retrospective study of 142 GB patients who underwent surgery, radiation, and chemotherapy before and after the lockdown period, aiming to determine the differences in access to care, treatment modality, and adjuvant therapies, and how the lockdown changed the prognosis., Results:  The number of procedures performed for GB during the pandemic was comparable to that of the prepandemic period, and patients received standard care. There was a significant difference in the volume of lesions measured at diagnosis with a decreased number of "accidental" diagnoses and expression of a reduced use by the patient for a checkup or follow-up examinations. Patients expressed a significantly lower performance index in the lockdown period with longer progression-free survival (PFS) in the face of a comparable mean time to OS., Conclusion:  Patients treated surgically for GB during the pandemic period had a more pronounced and earlier reduction in performance status than patients treated during the same period the year before. This appears to be primarily due to lower levels of care in the rehabilitation centers and more frequent discontinuation of adjuvant care., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Several novel technologies allowing catheter ablation (CA) with a favorable safety/efficacy profile have been recently developed, but not yet extensively clinically tested in the setting of ventricular tachycardia CA., Methods: In this technical report, we overview technical aspects and preclinical/clinical information concerning the application of three novel CA technologies in the ventricular milieu: a pulsed field ablation (PFA) generator (CENTAURI™, Galaxy Medical) to be used with linear, contact force-sensing radiofrequency ablation catheters; a contact force-sensing radiofrequency ablation catheter equipped with six thermocouples and three microelectrodes (QDOT Micro™, Biosense-Webster), allowing high-resolution mapping and temperature-controlled CA; and a flexible and mesh-shaped irrigation tip, contact force-sensing radiofrequency ablation catheter (Tactiflex, Abbott). We also report three challenging VT cases in which CA was performed using these technologies., Results: The CENTAURI system was used with the Tacticath™ (Abbott) ablation catheter to perform ventricular PFA in a patient with advanced heart failure, electrical storm, and a deep intramural septal substrate. Microelectrode mapping using QDOT Micro™ helped to refine substrate assessment in a VT patient with congenitally corrected transposition of the great arteries, and allowed the identification of the critical components of the VT circuit, which were successfully ablated. Tactiflex™ was used in two challenging CA cases (one endocardial and one epicardial), allowing acute and mid-term control of VT episodes without adverse events., Conclusion: The ideation and development of novel technologies initially intended to treat atrial arrhythmias and successfully implemented in the ventricular milieu is contributing to the progressive improvement in the clinical benefits derived from VT CA, making this procedure key for successful management of increasingly complex patients., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Pulmonary Embolism (PE) is the third leading cause of cardiovascular death, following myocardial infarction and stroke. The latest European Society of Cardiology (ESC) guidelines on PE recommend short-term prognostic stratification based on right ventricular (RV) overload detected by transthoracic echocardiography (TTE) or contrast-enhanced chest CT. The aim of the study is to find out which of the signs of right ventricular dysfunction best predicts in-hospital mortality (IHM)., Methods: This is a monocentric, retrospective study including adult patients admitted from the emergency department with a c-e cCT confirmed diagnosis of PE between January 2018 and December 2022 who underwent a TTE within 48 h., Results: 509 patients (median age 76 years [IQR 67-84]) were included, with 7.1% IHM. At univariate analysis, RV/LV ratio > 1 (OR 2.23, 95% CI 1.1-4.5), TAPSE < 17 mm (OR 4.73, 95% CI 2.3-9.8), the D-shape (OR 3.73, 95% CI 1.71-8.14), and LVEF < 35% (OR 5.78, 95% CI 1.72-19.47) resulted significantly correlated with IHM. However, at multivariate analysis including also haemodynamic instability, PESI class > II, and abnormal hs-cTnI levels, only LVEF < 35% (OR 5.46, 95% CI 1.32-22.61) resulted an independent predictor of IHM., Conclusion: Despite the recognised role of TTE in the early management of patients with circulatory shock and suspected PE, signs of RV dysfunction have been shown to be poor predictors of IHM, whereas severely reduced LVEF is an independent risk factor for in-hospital death., (© 2024. The Author(s).)

Background: Short- or mid-term fasting, full or partial, triggers metabolic response known to have in turn health effects in an organism. At central level, the metabolic stimulus triggered by fasting is known to be perceived firstly by hypothalamic neurons. In the field of neuroscience, ribosomal protein S6 (S6) phosphorylation is commonly used as a readout of the mammalian target of rapamycin complex 1 signalling activation or as a marker for neuronal activity. The aim of this study is addressed to evaluate whether the phosphorylation of S6 occurs in the central neurons of zebrafish exposed to four (short-term) and seven (mid-term) days of complete fasting., Methods: Group-housed adult zebrafish were exposed to four and seven days of complete food withdrawal. At the end of the experimental period, Western blotting analyses were carried out to measure the expression levels of the phosphorylated S6 (pS6) by comparing the two experimental conditions versus the control group. The same antibody was then used to identify the distribution pattern of pS6 immunoreactive neurons in the whole brain and in the taste buds., Results: We did not observe increased pS6 levels expression in the brain of animals exposed to short-term fasting compared to the control, whereas the expression increased in brain homogenates of animals exposed to mid-term fasting. pS6 immunoreactivity was reported in some hypothalamic neurons, as well as in the dorsal area of telencephalon and preoptic area, a neurosecretory region homolog to the mammalian paraventricular nucleus. Remarkably, we observed pS6 immunostaining in the sensory cells of taste buds lining the oral epithelium., Conclusions: Taken together, our data show that in zebrafish, differently from other fish species, seven days of fasting triggers neuronal activity. Furthermore, the immunostaining on sensory cells of taste buds suggests that metabolic changes may modulate also peripheral sensory cells. This event may have valuable implications when using zebrafish to design metabolic studies involving fasting as well as practical consequences on the animal welfare, in particularly stressful conditions, such as transportation., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Paolo de Girolamo reports financial support was provided by University of Naples Federico II Department of Veterinary Medicine and Animal Production. Maria Raggio, Daniela Giaquinto, Chiara Attanasio, Paolo de Girolamo, Livia D’Angelo reports a relationship with University of Naples Federico II Department of Veterinary Medicine and Animal Production that includes: employment. Livia D’Angelo has patent pending to Optional. Paolo de Girolamo, Giuseppe Radaelli and Livia D’Angelo acted as Guest Editor for a special issue If there are other authors, they 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 GmbH.. All rights reserved.)

A number of research studies, including ours, have spotlighted exosomes as critical facilitators of viral dissemination. While hepatitis B virus (HBV) transmission through exosomes has been studied, the focus on its satellite virus, the hepatitis delta virus (HDV), has been unexplored in this context. HDV, although being a defective virus, can replicate its genome autonomously within hepatocytes, independently of HBV. Investigations on Huh7 cells revealed an intriguing phenomenon: the HDV proteins, S-HDAg and L-HDAg, are transmitted between cells without a complete viral structure. Detailed analysis further revealed that the expression of these proteins not only bolstered exosome secretion but also ensured their enrichment within these vesicles. Our experimental approach utilized transfection of various plasmids to examine the role of HDV RNA and proteins in the process. One salient finding was the differential propagation of the HDV proteins S-HDAg and L-HDAg, suggesting intricate molecular mechanisms behind their transmission. Notably, the purity of our exosome preparations was monitored using markers such as TSG101 and CD81. Importantly, these exosomes were found to carry both HDV RNA and proteins, highlighting their role in HDV dissemination. This novel study underscores the role of exosomes in mediating the transmission of HDV components between hepatocytes independent of HBV. These revelations about the exosomal pathway of HDV transmission provide a foundation for the development of innovative therapeutic strategies against HDV infections.

Undisturbed home cage recording of mouse activity and behavior has received increasing attention in recent years. In parallel, several technologies have been developed in a bid to automate data collection and interpretation. Thanks to these expanding technologies, massive datasets can be recorded and saved in the long term, providing a wealth of information concerning animal wellbeing, clinical status, baseline activity, and subsequent deviations in case of experimental interventions. Such large datasets can also serve as a long-term reservoir of scientific data that can be reanalyzed and repurposed upon need. In this review, we present how the impact of Big Data deriving from home cage monitoring (HCM) data acquisition, particularly through Digital Ventilated Cages (DVCs), can support the application of the 3Rs by enhancing Refinement, Reduction, and even Replacement of research in animals., Competing Interests: MR is employed by Tecniplast S.p.A, that provided economic support to the Author in terms of salary. EO'C is employed by F. Hoffmann-La Roche Ltd. The remaining 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 © 2024 Fuochi, Rigamonti, O'Connor, De Girolamo and D'Angelo.)

Immunosuppressive macrophages restrict anti-cancer immunity in glioblastoma (GBM). Here, we studied the contribution of microglia (MGs) and monocyte-derived macrophages (MDMs) to immunosuppression and mechanisms underlying their regulatory function. MDMs outnumbered MGs at late tumor stages and suppressed T cell activity. Molecular and functional analysis identified a population of glycolytic MDM expressing GLUT1 with potent immunosuppressive activity. GBM-derived factors promoted high glycolysis, lactate, and interleukin-10 (IL-10) production in MDMs. Inhibition of glycolysis or lactate production in MDMs impaired IL-10 expression and T cell suppression. Mechanistically, intracellular lactate-driven histone lactylation promoted IL-10 expression, which was required to suppress T cell activity. GLUT1 expression on MDMs was induced downstream of tumor-derived factors that activated the PERK-ATF4 axis. PERK deletion in MDM abrogated histone lactylation, led to the accumulation of intratumoral T cells and tumor growth delay, and, in combination with immunotherapy, blocked GBM progression. Thus, PERK-driven glucose metabolism promotes MDM immunosuppressive activity via histone lactylation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The role of total bilirubin (TBIL) in cardiovascular disease has been increasingly recognized in recent decades. Studies have shown a correlation between total bilirubin levels and the prognosis of patients after heart surgery. This study aimed to investigate the clinical significance of bilirubin elevation in persistent atrial fibrillation (PAF) patients who received radiofrequency catheter ablation (RFCA)., Methods and Results: A total of 184 patients with PAF who received RFCA were retrospectively studied. Laboratory examinations and demographic data were analyzed to identify independent predictors of TBIL elevation. The relationship between TBIL and prognosis was further investigated. Our results indicated that TBIL increased significantly after RFCA. Multiple linear regression analysis showed that TBIL elevation owned a negative correlation with the percentile of low voltage areas (LVAs) in left atria (β=-0.490, P<0.001). In contrast, a positive correlation was observed with the white blood cell (WBC) ratio (β=0.153, P=0.042) and left atrial diameter (LAD) (β=0.232, P=0.025). It was found that postoperative TBIL levels increased and then gradually decreased to baseline within 5 days without intervention. The bilirubin ratio <1.211 indicated the possibility of 1-year AF recurrence after ablation with a predictive value of 0.743 (specificity = 75.00%, sensitivity = 66.67%)., Conclusion: Bilirubin elevation post PAF RFCA was a common phenomenon and was associated with 1-year recurrence of AF in PAF patients after RFCA., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Shao et al.)

Heart failure (HF) is a leading cause of morbidity worldwide, imposing a significant burden on deaths, hospitalizations, and health costs. Anticipating patients' deterioration is a cornerstone of HF treatment: preventing congestion and end organ damage while titrating HF therapies is the aim of the majority of clinical trials. Anyway, real-life medicine struggles with resource optimization, often reducing the chances of providing a patient-tailored follow-up. Telehealth holds the potential to drive substantial qualitative improvement in clinical practice through the development of patient-centered care, facilitating resource optimization, leading to decreased outpatient visits, hospitalizations, and lengths of hospital stays. Different technologies are rising to offer the best possible care to many subsets of patients, facing any stage of HF, and challenging extreme scenarios such as heart transplantation and ventricular assist devices. This article aims to thoroughly examine the potential advantages and obstacles presented by both existing and emerging telehealth technologies, including artificial intelligence.

Background: Posterior wall ablation (PWA) is commonly added to pulmonary vein isolation (PVI) during catheter ablation (CA) of persistent atrial fibrillation (AF)., Objective: The purpose of this study was to compare PVI plus PWA using very-high-power short-duration (vHPSD) vs standard-power (SP) ablation index-guided CA among consecutive patients with persistent AF and to determine the voltage correlation between microbipolar and bipolar mapping in AF., Methods: We compared 40 patients undergoing PVI plus PWA using vHPSD to 40 controls receiving PVI plus PWA using SP. The primary efficacy endpoint was recurrence of atrial tachyarrhythmias after a 3-month blanking period. The primary safety outcome was a composite of major complications within 30 days after CA. In the vHPSD group, high-density mapping of the posterior wall was performed using both a multipolar catheter and microelectrodes on the tip of the ablation catheter., Results: PVI was more commonly obtained with vHPSD compared to SP ablation (98%vs 75%; P = .007), despite shorter procedural and fluoroscopy times ( P <.001). Survival free from recurrent atrial tachyarrhythmias at 18 months was 68% and 47% in the vHPSD and SP groups, respectively (log-rank P = .071), without major adverse events. The vHPSD approach was significantly associated with reduced risk of recurrent AF at multivariable analysis (hazard ratio 0.39; P = .030). Microbipolar voltage cutoffs of 0.71 and 1.69 mV predicted minimum bipolar values of 0.16 and 0.31 mV in AF, respectively, with accuracies of 0.67 and 0.88., Conclusion: vHPSD PWA plus PVI may be faster and as safe as SP CA among patients with persistent AF, with a trend for superior efficacy. Adapted voltage cutoffs should be used for identifying atrial low-voltage areas with microbipolar mapping., (© 2024 Heart Rhythm Society. Published by Elsevier Inc.)

Aim: To obtain real-world evidence about the features and risk stratification of pulmonary arterial hypertension (PAH) with a left heart disease (LHD) phenotype (PAH-LHD)., Methods and Results: By reviewing the records of consecutive incident PAH patients at 7 tertiary centers from 2001 to 2021, we selected 286 subjects with all parameters needed to determine risk of death at baseline and at first follow-up with COMPERA and COMPERA 2.0 scores. Fifty seven (20%) had PAH-LHD according to the AMBITION definition. Compared with no-LHD ones, they were older, had higher BMI, more cardiovascular comorbidities, higher E/e' ratio and left atrial area, but lower BNP concentrations and better right ventricular function and pulmonary hemodynamics. Survival was comparable between PAH-LHD and no-LHD patients, although the former were less commonly treated with dual PAH therapy. Both COMPERA and COMPERA 2.0 discriminated all-cause mortality risk of PAH-LHD at follow-up, but not at baseline. Risk profile significantly improved during follow-up only when assessed by COMPERA 2.0. At multivariable analysis with low-risk status as reference, intermediate-high and high-risk, but not LHD phenotype, were associated with higher hazard of all-cause mortality. Results were comparable in secondary analyses including patients in the last 10 years and atrial fibrillation and echocardiographic abnormalities as additional criteria for PAH-LHD., Conclusions: In real life, PAH-LHD patients are frequent, have less severe disease and are less likely treated with PAH drug combinations than no-LHD. The COMPERA 2.0 model may be more appropriate to evaluate their mortality risk during follow-up and how it is modulated by therapy., (© 2024. The Author(s).)

Background: The clinical performance of high-power, short-duration (HPSD) pulmonary vein isolation (PVI) with the novel flexible tip TactiFlex™ (TFSE) catheter, as compared to standard-power, long-duration (SPLD) PVI using the TactiCath™ (TCSE) catheter among patients undergoing catheter ablation (CA) of atrial fibrillation (AF) is currently unknown., Methods: We conducted a prospective, observational, single-centre study including 40 consecutive patients undergoing PVI for paroxysmal/persistent AF, using HPSD ablation with the novel TFSE catheter (HPSD/TFSE group). Based on propensity score-matching, forty patients undergoing SPLD PVI with the TCSE catheter were identified (SPLD/TCSE group). In the HPSD/TFSE group, RF lesions were performed by delivering 40-50 W for 10-20 s, while in the SPLD/TCSE group, RF power was 30-35 W, targeting a lesion size index (LSI) of 4.0-5.5. The co-primary study outcomes were time required to complete PVI and first pass isolation (FPI)., Results: PVI was achieved in 100% of patients in both groups, and no major adverse events were observed. Remarkably, PVI time was shorter in the HPSD/TFSE, compared to the SPLD/TCSE group(9 [7-9] min vs. 50 [37-54] min; p < 0.001), while FPI rate was non-significantly higher in the former group(91% [146/160] vs 83% [134/160]; p = 0.063). Shorter procedural (108 [91-120] min vs. 173 [139-187] min, p < 0.001), total RF (9 [7-11] min vs. 43 [32-53] min, p < 0.001), fluoroscopy times(15 [10-19] min vs. 18 [13-26] min, p = 0.014), and lower DAP (1461 [860-2181] vs. 7200 [3400-20,800], p < 0.001) were recorded in the HPSD/TFSE group. A higher average impedance drop was obtained with HPSD/TFSE CA(17[17-18]Ω vs. 16 [15-17] Ω, p < 0.001)., Conclusions: In our initial clinical experience, HPSD PVI with the TFSE catheter proved faster than SPLD PVI with the TCSE catheter, at least equally effective in terms of FPI, and it was associated with greater impedance drop., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Individuals chronically infected with hepatitis B virus (HBV) and hepatitis Delta virus (HDV) present an increased risk of developing cirrhosis and hepatocellular carcinoma in comparison to HBV mono-infected individuals. Although HDV only replicates in individuals coinfected or superinfected with HBV, there is currently no in vitro model that can stably express both viruses simultaneously, mimicking the chronic infections seen in HBV/HDV patients. Here, we present the HepG2BD cell line as a novel in vitro culture system for long-term replication of HBV and HDV. HepG2BD cells derive from HepG2.2.15 cells in which a 2 kb HDV cDNA sequence was inserted into the adeno-associated virus safe harbor integration site 1 (AAVS1) using CRISPR-Cas9. A Tet-Off promoter was placed 5' of the genomic HDV sequence for reliable initiation/repression of viral replication and secretion. HBV and HDV replication were then thoroughly characterized. Of note, non-dividing cells adopt a hepatocyte-like morphology associated with an increased production of both HDV and HBV virions. Finally, HDV seems to negatively interfere with HBV in this model system. Altogether, HepG2BD cells will be instrumental to evaluate, in vitro, the fundamental HBV-HDV interplay during simultaneous chronic replication as well as for antivirals screening targeting both viruses.

There are no investigations about the outcomes of idiopathic PVC catheter ablation (CA) in athletes compared to the sedentary population. We conducted a prospective single-centre observational study. The primary and secondary procedural outcomes were the post-ablation reduction of premature ventricular contractions (PVCs) in an athletes vs. non-athletes group and in agonist vs. leisure-time athletes. The third was the evaluation of the resumption of physical activity and the improvement of symptoms in agonist and leisure-time athletes. From January 2020 to October 2022 we enrolled 79 patients with RVOT/LVOT/fascicular PVC presumed origin. The median percentage of decrease between the pre-procedure and post-procedure Holter monitoring in the non-athletes group was 96 (IQR 68-98) and 98 in the athletes group (IQR 92-99) ( p = 0.08). Considering the athletes, the median percentage of decrease in the number of PVCs was 98 (IQR 93-99) and 98 (IQR 87-99), respectively, in leisure-time and agonistic athletes ( p = 0.42). Sixteen (70%) leisure time and seventeen (90%) agonist athletes ( p = 0.24) have resumed physical activity 3 months after PVC CA; among agonistic athletes, 59% have resumed competitive physical activity. Many leisure-time (88%) and agonist (70%) athletes experienced an improvement in symptoms after ablation. PVC CA was effective and safe in both groups, reducing symptoms and allowing a quick and safe return to sports activities in athletes.

Light-absorbing aerosols heat the atmosphere; an accurate quantification of their absorption coefficient is mandatory. However, standard reference instruments (CAPS, MAAP, PAX, PTAAM) are not always available at each measuring site around the world. By integrating all previous published studies concerning the Aethalometers, the AE33 filter loading parameter, provided by the dual-spot algorithm, were used to determine the multiple scattering enhancement factor from the Aethalometer itself (hereinafter C AE ) on an yearly and a monthly basis. The method was developed in Milan, where Aethalometer measurements were compared with MAAP data; the comparison showed a good agreement in terms of equivalent black carbon (R 2  = 0.93; slope = 1.02 and a negligible intercept = 0.12 μg m -3 ) leading to a yearly experimental multiple scattering enhancement factor of 2.51 ± 0.04 (hereinafter C MAAP ). On a yearly time base the C AE values obtained using the new approach was 2.52 ± 0.01, corresponding to the experimental one (C MAAP ). Considering the seasonal behavior, higher experimental C MAAP and computed C AE values were found in summer (2.83 ± 0.12) whereas, the lower ones in winter/early-spring (2.37 ± 0.03), in agreement with the single scattering albedo behavior in the Po Valley. Overall, the agreement between the experimental C MAAP and C AE showed a root mean squared error (RMSE) of just 0.038 on the C MAAP prediction, characterized by a slope close to 1 (1.001 ± 0.178), a negligible intercept (-0.002 ± 0.455) and a high degree of correlation (R 2  = 0.955). From an environmental point of view, the application of a dynamic (space/time) determination of C AE increases the accuracy of the aerosol heating rate (compared to applying a fixed C value) up to 16 % solely in Milan, and to 114 % when applied in the Arctic at 80°N., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Luca Ferrero reports financial support was provided by University of Milan-Bicocca., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: The aim of this study was to determine the barriers to accessing the crosslinking service in Auckland, New Zealand., Methods: This was a prospective 1-year study of patients at Auckland District Health Board. Studied parameters included age, sex, body mass index, ethnicity, New Zealand Deprivation (NZDep; an area-based measure of socioeconomic status, 1 = low deprivation-10 = high deprivation) score of residence, disease severity (maximum keratometry and thinnest corneal thickness), attendance, distance travelled, car ownership, employment status, and visual outcomes. Statistical analysis was performed using independent t tests, Pearson correlation, independent samples ANOVA, MANCOVA, and binomial logistic regression., Results: Four hundred fifty-four patients with keratoconus were analyzed and had a mean age of 24.1 ± 0.8 years, mean body mass index of 33.0 ± 9.7 kg/m 2 , and 43% were female. Pacific Peoples consisted 40.2% of the population; Māori 27.2%; Europeans 21.2%; Asian 9.9%; and Middle Eastern, Latin American, and African (MELAA) 1.3%. The mean distance travelled was 12.5 ± 9.5 km, NZDep score was 6.8 ± 2.6, and attendance was 69.0 ± 42.5%. The lowest attendance was observed in Pacific Peoples (58.9%) and the highest was in Asians (90%) ( P = 0.019). The mean worst-eye visual acuity at attendance was 0.75 ± 0.47 logMAR (6/35). Unemployment was associated with worse best-eye visual acuity at FSA ( P = 0.01) and follow-up ( P < 0.05). Māori and Pacific Peoples had the highest NZDep ( P < 0.001), were younger at presentation ( P = 0.019), had higher disease severity ( P < 0.001), and worse visual acuity ( P < 0.001)., Conclusions: Poor attendance was seen in this cohort. Pacific Peoples and Māori presented younger with worse disease severity and visual acuity but also had the highest nonattendance. These results suggest that deprivation, factors associated with ethnicity, and unemployment are potential barriers to attendance., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Clinical evaluation of central venous pressure is difficult, depends on experience, and is often inaccurate in patients with chronic advanced heart failure. We assessed the ultrasound-assessed internal jugular vein (JV) distensibility by ultrasound as a noninvasive tool to identify patients with normal right atrial pressure (RAP ≤7 mm Hg) in this population., Methods: We measured JV distensibility as the Valsalva-to-rest ratio of the vein diameter in a calibration cohort (N=100) and a validation cohort (N=101) of consecutive patients with chronic heart failure with reduced ejection fraction who underwent pulmonary artery catheterization for advanced heart failure therapies workup., Results: A JV distensibility threshold of 1.6 was identified as the most accurate to discriminate between patients with RAP ≤7 versus >7 mm Hg (area under the receiver operating characteristic curve, 0.74 [95% CI, 0.64-0.84]) and confirmed in the validation cohort (receiver operating characteristic, 0.82 [95% CI, 0.73-0.92]). A JV distensibility ratio >1.6 had predictive positive values of 0.86 and 0.94, respectively, to identify patients with RAP ≤7 mm Hg in the calibration and validation cohorts. Compared with patients from the calibration cohort with a high JV distensibility ratio (>1.6; n=42; median RAP, 4 mm Hg; pulmonary capillary wedge pressure, 11 mm Hg), those with a low JV distensibility ratio (≤1.6; n=58; median RAP, 8 mm Hg; pulmonary capillary wedge pressure, 22 mm Hg; P <0.0001 for both) were more likely to die or undergo a left ventricular assist device implant or heart transplantation (event rate at 2 years: 42.7% versus 18.2%; log-rank P =0.034)., Conclusions: Ultrasound-assessed JV distensibility identifies patients with chronic advanced heart failure with normal RAP and better outcomes., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03874312., Competing Interests: Disclosures The authors disclose that Dr Ammirati received a grant from the Italian Ministry of Health (GR-2019-12368506) and a grant from the NextGenerationEU (M6C2/2.1 PNRR-MAD-2022-12376225—CUP H43C21000140006) and served as a consultant for Kiniksa Pharmaceuticals, Cytokinetics, and AstraZeneca. Dr Pellicori has received consultancy honoraria and sponsorship support from Boehringer Ingelheim, Pharmacosmos, Novartis, Vifor, AstraZeneca, and Caption Health and research support from Bristol Myers Squibb in the past 5 years, not connected with this article. Prof Metra is the outgoing Editor-in-Chief of the European Journal of Heart Failure. The other authors report no conflicts.

Catheter-based revascularization procedures were developed as an alternative to systemic thrombolysis for patients with intermediate-high- and high-risk pulmonary embolisms. USAT IH-PE is a retrospective and prospective multicenter registry of such patients treated with ultrasound-facilitated, catheter-directed thrombolysis, whose preliminary results are presented in this study. The primary endpoint was the incidence of pulmonary hypertension (PH) at follow-up. Secondary endpoints were short- and mid-term changes in the echocardiographic parameters of right ventricle (RV) function, in-hospital and all-cause mortality, and procedure-related bleeding events. Between March 2018 and July 2023, 102 patients were included. The majority were at intermediate-high-risk PE (86%), were mostly female (57%), and had a mean age of 63.7 ± 14.5 years, and 28.4% had active cancer. Echocardiographic follow-up was available for 70 patients, and in only one, the diagnosis of PH was confirmed by right heart catheterization, resulting in an incidence of 1.43% (CI 95%, 0.036-7.7). RV echocardiographic parameters improved both at 24 h and at follow-up. In-hospital mortality was 3.9% (CI 95%, 1.08-9.74), while all-cause mortality was 11% (CI 95%, 5.4-19.2). Only 12% had bleeding complications, of whom 4.9% were BARC ≥ 3. Preliminary results from the USAT IH-PE registry showed a low incidence of PH, improvement in RV function, and a safe profile.

The mechanism underlying the transition from the pre-symptomatic to the symptomatic state is a crucial aspect of epileptogenesis. SYN2 is a member of a multigene family of synaptic vesicle phosphoproteins playing a fundamental role in controlling neurotransmitter release. Human SYN2 gene mutations are associated with epilepsy and autism spectrum disorder. Mice knocked out for synapsin II (SynII KO) are prone to epileptic seizures that appear after 2 months of age. However, the involvement of the endocannabinoid system, known to regulate seizure development and propagation, in the modulation of the excitatory/inhibitory balance in the epileptic hippocampal network of SynII KO mice has not been explored. In this study, we investigated the impact of endocannabinoids on glutamatergic and GABAergic synapses at hippocampal dentate gyrus granule cells in young pre-symptomatic (1-2 months old) and adult symptomatic (5-8 months old) SynII KO mice. We observed an increase in endocannabinoid-mediated depolarization-induced suppression of excitation in young SynII KO mice, compared to age-matched wild-type controls. In contrast, the endocannabinoid-mediated depolarization-induced suppression of inhibition remained unchanged in SynII KO mice at both ages. This selective alteration of excitatory synaptic transmission was accompanied by changes in hippocampal endocannabinoid levels and cannabinoid receptor type 1 distribution among glutamatergic and GABAergic synaptic terminals contacting the granule cells of the dentate gyrus. Finally, inhibition of type-1 cannabinoid receptors in young pre-symptomatic SynII KO mice induced seizures during a tail suspension test. Our results suggest that endocannabinoids contribute to maintaining network stability in a genetic mouse model of human epilepsy., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Tissue-engineered skin substitutes are promising tools to cover large and deep skin defects. However, the lack of a synergic and fast regeneration of the vascular network, nerves, and skin appendages limits complete skin healing and impairs functional recovery. It has been highlighted that an ideal skin substitute should mimic the structure of the native tissue to enhance clinical effectiveness. Here, we produced a pre-vascularized dermis (PVD) comprised of fibroblasts embedded in their own extracellular matrix (ECM) and a capillary-like network. Upon implantation in a mouse full-thickness skin defect model, we observed a very early innervation of the graft in 2 weeks. In addition, mouse capillaries and complete epithelialization were detectable as early as 1 week after implantation and, skin appendages developed in 2 weeks. These anatomical features underlie the interaction with the skin nerves, thus providing a further cue for reinnervation guidance. Further, the graft displays mechanical properties, collagen density, and assembly features very similar to the host tissue. Taken together our data show that the pre-existing ECM components of the PVD, physiologically organized and assembled similarly to the native tissue, support a rapid regeneration of dermal tissue. Therefore, our results suggest a promising potential for PVD in skin regeneration., Competing Interests: 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., (© 2024 The Author(s).)

Background: Pulmonary embolism (PE) is one of the most common causes of death from cardiovascular disease. Although deep vein thrombosis (DVT) is the leading cause of PE, its prognostic role is unclear. This study investigated the incidence and prognostic value of DVT in predicting in-hospital mortality (IHM) in patients admitted from the emergency department (ED) for PE., Methods: This retrospective cohort study was conducted in the ED of a third-level university hospital. Patients over 18 years admitted for PE between 1 January 2018 and 31 December 2022 were included., Results: Five hundred and thirty patients (mean age 73.13 years, 6% IHM) were included. 69.1% of cases had DVT (36.4% unilateral femoral vein, 3.6% bilateral, 39.1% unilateral popliteal vein, 2.8% bilateral, 45.7% distal vein thrombosis and 7.4% iliocaval involvement). Patients who died in hospital had a higher Pulmonary Embolism Severity Index (PESI) (138.6 vs. 99.65, p < 0.001), European Society of Cardiology risk class (15.6% vs. 1%, intermediate-high in 50% vs. 6.4%, p < 0.001) and more DVT involving the iliac-caval vein axis (18.8% vs. 6.6%, p = 0.011). PESI class >II, right ventricular dysfunction, increased blood markers of myocardial damage and involvement of the iliocaval venous axis were independent predictors of IHM on multivariate analysis., Conclusions: Although further studies are needed to confirm the prognostic role of DVT at PE, involvement of the iliocaval venous axis should considered to be a sign of a higher risk of IHM and may be a key factor in prognostic stratification., (© 2023 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

Objectives: Defining the patterns of practice and referral criteria of optometrists within New Zealand to investigate the diagnosis and management of keratoconus., Methods: Optometrists recruited through the New Zealand Association of Optometrists, Cornea and Contact Lens Society of New Zealand, and private practices were invited to complete an anonymous survey., Results: Responses were received from 168 optometrists (representing 20.0% of the optometrist population). Half (48%) of optometrists had ≥15 years of experience, and 22% prescribed soft contact lenses daily, whereas only 6.4% prescribed rigid gas-permeable (RGP) lenses daily. The main barriers to prescribing RGPs were experience with fitting, low market demand, and patient discomfort. When referring to an ophthalmologist, 41% reported referring on progression of corneal parameters, 27% on initial diagnosis, 21% at no set time, and 10% with a reduction in visual acuity. Most optometrists (64%) would refer for possible surgery when visual acuity dropped between 6/9 and 6/12. Optometrists with greater experience were more likely to prescribe RGP lenses and co-manage patients with ophthalmologists. Ownership of a corneal imaging unit suggested an increased likelihood of prescribing RGP lenses but did not alter referral patterns., Conclusion: This survey provides an overview of current practice and highlights the importance of optometrists in the diagnosis and management of keratoconus. There was a significant discrepancy in keratoconus management, regarding optical correction modality and referral criteria for ophthalmology review. Further interdisciplinary work is required between optometry and ophthalmology to standardize referral guidelines and enhance visual outcomes., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Contact Lens Association of Ophthalmologists.)

This opinion addresses the re-evaluation of erythritol (E 968) as food additive and an application for its exemption from the laxative warning label requirement as established under Regulation (EU) No 1169/2011. Erythritol is a polyol obtained by fermentation with Moniliella pollinis BC or Moniliella megachiliensis KW3-6, followed by purifications and drying. Erythritol is readily and dose-dependently absorbed in humans and can be metabolised to erythronate to a small extent. Erythritol is then excreted unchanged in the urine. It does not raise concerns regarding genotoxicity. The dataset evaluated consisted of human interventional studies. The Panel considered that erythritol has the potential to cause diarrhoea in humans, which was considered adverse because its potential association with electrolyte and water imbalance. The lower bound of the range of no observed adverse effect levels (NOAELs) for diarrhoea of 0.5 g/kg body weight (bw) was identified as reference point. The Panel considered appropriate to set a numerical acceptable daily intake (ADI) at the level of the reference point. An ADI of 0.5 g/kg bw per day was considered by the Panel to be protective for the immediate laxative effect as well as potential chronic effects, secondary to diarrhoea. The highest mean and 95th percentile chronic exposure was in children (742 mg/kg bw per day) and adolescents (1532 mg/kg bw per day). Acute exposure was maximally 3531 mg/kg bw per meal for children at the 99th percentile. Overall, the Panel considered both dietary exposure assessments an overestimation. The Panel concluded that the exposure estimates for both acute and chronic dietary exposure to erythritol (E 968) were above the ADI, indicating that individuals with high intake may be at risk of experiencing adverse effects after single and repeated exposure. Concerning the new application, the Panel concluded that the available data do not support the proposal for exemption., Competing Interests: If you wish to access the declaration of interests of any expert contributing to an EFSA scientific assessment, please contact interestmanagement@efsa.europa.eu., (© 2023 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

Objectives: To assess the survival predictivity of baseline blood cell differential count (BCDC), discretised according to two different methods, in adults visiting an emergency room (ER) for illness or trauma over 1 year., Design: Retrospective cohort study of hospital records., Setting: Tertiary care public hospital in northern Italy., Participants: 11 052 patients aged >18 years, consecutively admitted to the ER in 1 year, and for whom BCDC collection was indicated by ER medical staff at first presentation., Primary Outcome: Survival was the referral outcome for explorative model development. Automated BCDC analysis at baseline assessed haemoglobin, mean cell volume (MCV), red cell distribution width (RDW), platelet distribution width (PDW), platelet haematocrit (PCT), absolute red blood cells, white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, basophils and platelets. Discretisation cut-offs were defined by benchmark and tailored methods. Benchmark cut-offs were stated based on laboratory reference values (Clinical and Laboratory Standards Institute). Tailored cut-offs for linear, sigmoid-shaped and U-shaped distributed variables were discretised by maximally selected rank statistics and by optimal-equal HR, respectively. Explanatory variables (age, gender, ER admission during SARS-CoV2 surges and in-hospital admission) were analysed using Cox multivariable regression. Receiver operating curves were drawn by summing the Cox-significant variables for each method., Results: Of 11 052 patients (median age 67 years, IQR 51-81, 48% female), 59% (n=6489) were discharged and 41% (n=4563) were admitted to the hospital. After a 306-day median follow-up (IQR 208-417 days), 9455 (86%) patients were alive and 1597 (14%) deceased. Increased HRs were associated with age >73 years (HR=4.6, 95% CI=4.0 to 5.2), in-hospital admission (HR=2.2, 95% CI=1.9 to 2.4), ER admission during SARS-CoV2 surges (Wave I: HR=1.7, 95% CI=1.5 to 1.9; Wave II: HR=1.2, 95% CI=1.0 to 1.3). Gender, haemoglobin, MCV, RDW, PDW, neutrophils, lymphocytes and eosinophil counts were significant overall. Benchmark-BCDC model included basophils and platelet count (area under the ROC (AUROC) 0.74). Tailored-BCDC model included monocyte counts and PCT (AUROC 0.79)., Conclusions: Baseline discretised BCDC provides meaningful insight regarding ER patients' survival., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)