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Alessio Lucarini, Giovanni Maria Garbarino, Pierfrancesco Orlandi, Eleonora Garofalo, Lorenzo Bragaglia, Giovanni Guglielmo Laracca, Giulia Canali, Alessandra Pecoraro, Paolo Mercantini On behalf of the Sant’Andrea GLAM collaborative groupDepartment of Medical and Surgical Sciences and Translational Medicine, Sapienza University of Rome, Sant’Andrea Hospital, Rome, ItalyCorrespondence: Alessio Lucarini, Department of Medical and Surgical Sciences and Translational Medicine, Sapienza University of Rome, Sant’Andrea Hospital, Rome, Italy, Email alessio.lucarini@uniroma1.itBackground: MultiDisciplinary Team (MDT) are held to undertake decisions regarding the whole aspect of oncological diseases. Over the years, they acquired a collaborative approach where clinical decisions are shared by all members. Different guidelines recommend the implementation of MDT, in order to improve the outcomes of these patients. Our aim is to evaluate how the implementation of MDT affects the patients’ satisfaction and adherence to treatment.Methods: A survey was submitted to every patient affected by colorectal cancer treated by the MDT of Sant’Andrea Hospital (Rome, IT). The investigation period was January 2017–March 2020. Data from patients inside the MDT were compared with patients outside the MDT to evaluate a reduction in waiting times.Results: A total of 591 patients were collected. A total of 355 patients with colorectal neoplasia were included in our analysis. Cumulative overall survival was 79%. The average waiting time for computed tomography or colonoscopy was 14.9 days for patients in the MDT versus 24.5. A total of 201 patients were eligible for our satisfaction survey. An 89.5% of patients felt followed in their treatment. A 93.5% of patients expressed a high grade of satisfaction for the MDT design.Conclusion: Our study confirms the importance of a well-structured MDT. Dedicated slots shorten the waiting time, leading to better satisfaction and faster diagnosis. Patients’ satisfaction should be considered as an index of good practice when it comes to oncological patients’ treatment.Keywords: cancer, multidisciplinary team meeting, patient assessment, patient management, patient outcomes

We report the first observations regarding the presence of the leaf-toed gecko, Euleptes europaea, in Sicily. During field activities for environmental impact assessment several leaf-toed gecko individuals were found in a restricted coastal area in the north-west of the island, near the city of Palermo. Further surveys were then carried out to better assess the presence of the species. A total of 21 E. europaea individuals were observed in a small area of approximately 4.4 hectares, consisting of mixed eucalyptus and pine reforestation. Out of the 21 individuals, there were 14 males, 5 females, and 2 whose sex could not be determined. Additionally, at least two pregnant females were observed. Leaf-toed geckos were found exclusively under eucalyptus bark, syntopic with two other Gekkota species (Tarentola mauritanica and Hemidactylus turcicus). The presence of such a breeding population of E. europaea is probably limited to a small area. However, our results do not allow us to clearly assess either its origin or its actual distribution and demography, therefore new field investigations are necessary.

Rabies is controlled by mass animal vaccination campaigns. Cats, dogs, and wild animals (e.g., bats) are large reservoirs of this virus and can pose a significant threat to the human health, especially in the developing countries. The nucleoprotein of the rabies virus is of great scientific interest since it has the potential to generate immunity in animals and can be used as for immunochemical diagnostics. The study aimed to test a large-scale expression of the rabies N protein in a prokaryotic system. The recombinant N protein was successfully expressed and purified. It was immunologically recognized by specific antibodies and was able to induce the production of specific antibodies in a mouse immunization assay. These encouraging results indicate that the recombinant N protein can be evaluated as an antigen for the development of a subunit vaccine or for a diagnostic assay.

Most neurodegenerative diseases share a common etiopathogenesis, the accumulation of protein aggregates. An imbalance in homeostasis brought on by the buildup of misfolded proteins within the endoplasmic reticulum (ER) results in ER stress in the cell. Three distinct proteins found in the ER membrane—IRE1α, PERK, and ATF6—control the unfolded protein response (UPR), a signal transduction pathway that is triggered to restore normal physiological conditions. Buildup of misfolded proteins in ER lumen leads to a shunting of GRP78/BiP, thus triggering the UPR. PERK autophosphorylation leads to activation of ATF4, the transcription factor; finally, ATF6 activates the UPR’s target genes, including GRP78/Bip. Accordingly, the UPR is a cellular reaction to an ER stress state that, if left unchecked for an extended period, results in apoptosis and irreversible damage. The identification of caspase 4, which is in the ER and is selectively activated by apoptotic stimuli caused by reticular stress, further demonstrated the connection between reticular stress and programed cell death. Moreover, oxidative stress and ER stress are linked. Oxidative stress is brought on by elevated quantities of radical oxygen species, both mitochondrial and cytosolic, that are not under the enzymatic regulation of superoxide dismutases, whose levels fall with increasing stress. Here, we evaluated the activity of Vx-809 (Lumacaftor), a drug used in cystic fibrosis, in SH-SY5Y neuronal cells, in which an ER stress condition was induced by Thapsigargin, to verify whether the drug could improve protein folding, suggesting its possible therapeutic use in proteinopathies, such as neurodegenerative diseases (NDs). Our data show that Vx-809 is involved in the significant reduction in protein produced under ER stress, particularly in the levels of Bip, ATF4, and ATF6 by Western blotting analysis, the reduction in ROS in the cytosol and mitochondria, and the reduction in the activation of the apoptotic pathway, measured by flow cytofluorimetry analysis and in restoring calcium homeostasis.

Abstract Background An equal distribution of hospital structures represents an important factor to achieve Universal Health Coverage. Generally, the most diffused approach to measure the potential availability to healthcare is the provider-to-population ratio based on the number of beds or professionals. However, this approach considers only the availability of resources provided at regional or local level ignoring the spatial accessibility of interregional facilities that are particularly accessed by patients living at the borders. Aim of this study is to outline the distribution of the intra and interregional services in Italy to capture the level of equity across the country. Moreover, it explores the impact of the accessibility to these resources on interregional patient’s mobility to receive care. Methods To compute spatial accessibility, we propose an alternative approach that applies the enhanced two-step floating catchment area (ESFCA) to capture the level of attraction of intra and interregional hospitals to a given population. Moreover, the adoption of process and outcome indices captured to what extent the quality of structures influenced patients in choosing services located inside or outside their region of residence. Results The study confirms that there is an unequal distribution of high-quality resources at regional and national level with a high level of inequality in the availability and accessibility of quality resources between the north and south part of Italy. This is particularly true considering the accessibility of intraregional resources in the southern part of the country that clearly influences patient choice and contribute to a significant cross border passive mobility to northern regions. This is confirmed by an econometric model that showed a significant effect of spatial accessibility with the propensity of patients of travel from the region of residence to receive care. Conclusions The analysis of intra and interregional components of spatial accessibility may contribute to identify to what extent patients are willing to travel outside their region of residence to access to care services. Moreover, it can contribute to gain a deeper understanding of the allocation of health resources providing input for policy makers on the basis of the principles of service accessibility in order to contain patient mobility.

Abstract Background The effect of plasma hepcidin concentrations on the long-term risk of developing adverse cardiovascular outcomes in people with type 2 diabetes mellitus (T2DM) is unclear. Methods We followed for a median of 55.6 months 213 outpatients with established T2DM (45.5% women, mean age 69 ± 10 years; BMI 28.7 ± 4.7 kg/m2; median diabetes duration 11 years). Baseline plasma ferritin and hepcidin concentrations were measured with an electrochemiluminescence immunoassay and mass spectrometry-based assay, respectively. The primary study outcome was a composite of all-cause mortality or incident nonfatal cardiovascular events (inclusive of myocardial infarction, permanent atrial fibrillation, ischemic stroke, or new hospitalization for heart failure). Results 42 patients developed the primary composite outcome over a median follow-up of 55.6 months. After stratifying patients by baseline hepcidin tertiles [1st tertile: median hepcidin 1.04 (IQR 0.50–1.95) nmol/L, 2nd tertile: 3.81 (IQR 3.01-4-42) nmol/L and 3rd tertile: 7.72 (IQR 6.37–10.4) nmol/L], the risk of developing the primary composite outcome in patients in the 3rd tertile was double that of patients in the 1st and 2nd tertile combined (unadjusted hazard ratio [HR] 2.32, 95%CI 1.27–4.26; p = 0.007). This risk was not attenuated after adjustment for age, sex, adiposity measures, smoking, hypertension, statin use, antiplatelet medication use, plasma hs-C-reactive protein and ferritin concentrations (adjusted HR 2.53, 95%CI 1.27–5.03; p = 0.008). Conclusions In outpatients with T2DM, higher baseline hepcidin concentrations were strongly associated with an increased long-term risk of overall mortality or nonfatal cardiovascular events, even after adjustment for established cardiovascular risk factors, plasma ferritin concentrations, medication use, and other potential confounders.

Abstract Background Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disorder with minimally effective treatment options. An important hurdle in ALS drug development is the non-invasive therapeutic access to the motor cortex currently limited by the presence of the blood-brain barrier (BBB). Focused ultrasound and microbubble (FUS+ MB) treatment is an emerging technology that was successfully used in ALS patients to temporarily open the cortical BBB. However, FUS+ MB-mediated drug delivery across ALS patients’ BBB has not yet been reported. Similarly, the effects of FUS+ MB on human ALS BBB cells remain unexplored. Methods Here we established the first FUS+ MB-compatible, fully-human ALS patient-cell-derived BBB model based on induced brain endothelial-like cells (iBECs) to study anti-TDP-43 antibody delivery and FUS+ MB bioeffects in vitro. Results Generated ALS iBECs recapitulated disease-specific hallmarks of BBB pathology, including reduced BBB integrity and permeability, and TDP-43 proteinopathy. The results also identified differences between sporadic ALS and familial (C9orf72 expansion carrying) ALS iBECs reflecting patient heterogeneity associated with disease subgroups. Studies in these models revealed successful ALS iBEC monolayer opening in vitro with no adverse cellular effects of FUS+ MB as reflected by lactate dehydrogenase (LDH) release viability assay and the lack of visible monolayer damage or morphology change in FUS+ MB treated cells. This was accompanied by the molecular bioeffects of FUS+ MB in ALS iBECs including changes in expression of tight and adherens junction markers, and drug transporter and inflammatory mediators, with sporadic and C9orf72 ALS iBECs generating transient specific responses. Additionally, we demonstrated an effective increase in the delivery of anti-TDP-43 antibody with FUS+ MB in C9orf72 (2.7-fold) and sporadic (1.9-fold) ALS iBECs providing the first proof-of-concept evidence that FUS+ MB can be used to enhance the permeability of large molecule therapeutics across the BBB in a human ALS in vitro model. Conclusions Together, this study describes the first characterisation of cellular and molecular responses of ALS iBECs to FUS+ MB and provides a fully-human platform for FUS+ MB-mediated drug delivery screening on an ALS BBB in vitro model.

Abstract Castration-resistant prostate cancer (CRPC) is a frequently occurring disease with adverse clinical outcomes and limited therapeutic options. Here, we identify methionine adenosyltransferase 2a (MAT2A) as a critical driver of the androgen-indifferent state in ERG fusion-positive CRPC. MAT2A is upregulated in CRPC and cooperates with ERG in promoting cell plasticity, stemness and tumorigenesis. RNA, ATAC and ChIP-sequencing coupled with histone post-translational modification analysis by mass spectrometry show that MAT2A broadly impacts the transcriptional and epigenetic landscape. MAT2A enhances H3K4me2 at multiple genomic sites, promoting the expression of pro-tumorigenic non-canonical AR target genes. Genetic and pharmacological inhibition of MAT2A reverses the transcriptional and epigenetic remodeling in CRPC models and improves the response to AR and EZH2 inhibitors. These data reveal a role of MAT2A in epigenetic reprogramming and provide a proof of concept for testing MAT2A inhibitors in CRPC patients to improve clinical responses and prevent treatment resistance.

Abstract Idiopathic anaphylaxis (IA) remains a frustrating challenge for both patients and physicians. The aim of this paper is to focus on IA in pediatric ages and suggest possible diagnostic algorithms according to specific age ranges (infants, children, and adolescents). In fact, in a variable percentage of patients, despite extensive diagnostic tests, the cause of anaphylactic episodes cannot be identified. Moreover, the lack of a unanimous IA definition requires a careful and detailed diagnostic workup. Prompt recognition of signs and symptoms, especially in younger children, and an accurate clinical history often allow a choice of the most appropriate diagnostic tests and a correct differential diagnosis.

Little is known about the effect of car traffic on airborne fungal communities. We investigated the environmental factors affecting the diversity and concentration of airborne fungi at high-traffic density junctions, in Tianjin, China. A total of 244 fungal strains belonging to 78 species and 45 genera of Ascomycota (78.69%) and Basidiomycota (21.31%) were isolated and identified using morphological and molecular analysis. Aspergillus was the species-richest genus, with 9 recorded species, followed by Alternaria and Cladosporium, both with 8 species. Coprinellus radians was the most abundant fungal species, with 31 isolated strains, followed by Alternaria alternata (26 strains), Cladosporium cladosporioides (21), Alternaria compacta (13), and Cladosporium tenuissimum (11). We found a higher diversity and concentration of airborne fungi in the analysed urban air environments when the road traffic was at its highest intensity. Higher level of car traffic resulted in higher concentrations of fungal particles in the air for various taxa, including Alternaria, Aspergillus, and Cladosporium, which are known to cause respiratory allergies and infections. This result suggests that reducing vehicular traffic could be an effective measure to control airborne fungal exposure and microbial pollution.

Objective: Many cases of subacute thyroiditis (SAT) have been described related to SARS-CoV-2 infection, but no prospective data about follow-up are known. This prospective, longitudinal, 3-year, multicentre study aims to explore the clinical peculiarities and outcome of SAT in relation to SARS-CoV-2 infection, ascertained with antibody dosage. Methods: All patients receiving SAT diagnosis from November 2020 to May 2022 were enrolled. Data on anamnesis, physical examination, blood tests (TSH, freeT4, freeT3, thyroglobulin, anti-thyroid antibodies, C-reactive protein, erythrocyte sedimentation rate, complete blood count), and thyroid ultrasound were collected. At baseline, the presence of IgG against the SARS-CoV-2 spike protein or nucleocapsid was investigated. Patients were evaluated after 1, 3, 6, and 12 months. Results: Sixty-six subjects were enrolled. At baseline, 54 presented with pain, 36 (67%) for at least 15 days. Serum SARS-CoV-2 IgG measurements documented that 7 out of 52 subjects (13.5%) had infection before SAT diagnosis (COVID+). No significant differences between the COVID+ and COVID− groups were found at baseline, except for respiratory symptoms and fever, which were more common in COVID+ (P = 0.039 and P = 0.021, respectively). Among the 41 subjects who completed follow-up, COVID+ and COVID− did not differ for therapeutic approach to SAT or outcome, all having an improvement in neck pain, inflammation parameters, and ultrasound features. Conclusion: This is the first prospective study investigating any difference both at diagnosis and at follow-up between SAT presentation in patients with previous SARS-CoV-2 infection and those without. Our data demonstrate that SARS-CoV-2 does not impact on SAT onset, evolution, and outcome.

In an era where the search for innovative drug leads faces challenges, our study pivots towards exploring the untapped potential of plant-derived compounds, focusing on the period of 2021 to 2022. We assess the classes of compounds these new structures belong to; the plants and families these compounds belong to; and the degree of novelty of the compound compared with already-known structures. The review was conducted following the Preferred Reporting Items for Systematics Reviews and Meta-Analyses (PRISMA) statement checklist for the guided reporting of systematic reviews. A total of 464 articles were selected for the new compounds of natural origin survey. We included 117 complete articles in this review and reported approximately 109 new structures elucidated during the years 2021 and 2022. Many of the compounds showed small structural variations in relation to already-known molecules. For some, however, this small modification was decisive for the biological activity reported, demonstrating the importance of descriptive phytochemical studies.

The PI3K/AKT/mTOR (PAM) signaling pathway is a highly conserved signal transduction network in eukaryotic cells that promotes cell survival, cell growth, and cell cycle progression. Growth factor signalling to transcription factors in the PAM axis is highly regulated by multiple cross-interactions with several other signaling pathways, and dysregulation of signal transduction can predispose to cancer development. The PAM axis is the most frequently activated signaling pathway in human cancer and is often implicated in resistance to anticancer therapies. Dysfunction of components of this pathway such as hyperactivity of PI3K, loss of function of PTEN, and gain-of-function of AKT, are notorious drivers of treatment resistance and disease progression in cancer. In this review we highlight the major dysregulations in the PAM signaling pathway in cancer, and discuss the results of PI3K, AKT and mTOR inhibitors as monotherapy and in co-administation with other antineoplastic agents in clinical trials as a strategy for overcoming treatment resistance. Finally, the major mechanisms of resistance to PAM signaling targeted therapies, including PAM signaling in immunology and immunotherapies are also discussed.

OBJECTIVE: Describe and analyze the sociodemographic and clinical profile and the interval between diagnosis and cancer treatment according to the gender of patients navigated by nurses in high complexity. METHOD: Observational, descriptive study conducted between December 2022 and September 2023, collected in October 2023, in an institutional database in supplementary health, including 119 patients navigated by nurses, in a pilot project carried out in Rio de Janeiro (Brazil). Descriptive and inferential statistics analyzed the data. RESULT: There were 76 (63.87%) females; 77 (64.71%) over 60 years old; 60 (50.85%) with initial stage IV, p-value 0.077 for palliative treatment; treatment started after 60 days of diagnosis with similar percentages between genders, 30 women (39.47%) and 18 men (41.86%). CONCLUSION: Patient navigation by nurses reduces access barriers and improves care coordination, contributing to faster treatment initiation and better clinical outcomes in oncology practice.

OBJETIVO: Describir y analizar el perfil sociodemográfico, clínico y el intervalo entre el diagnóstico y el tratamiento del cáncer, según el sexo de los pacientes navegados por enfermeros en alta complejidad. MÉTODO: Estudio observacional, descriptivo realizado entre diciembre de 2022 y septiembre de 2023, recopilado en octubre de 2023, en una base de datos institucional en salud suplementaria, incluyendo 119 pacientes navegados por enfermeros, en un proyecto piloto realizado en Rio de Janeiro (Brasil). Datos analizados a la estadística descriptiva e inferencial. RESULTADO: Hubo 76 (63,87%) del sexo femenino; 77 (64,71%) con edad superior a 60 años; 60 (50,85%) con estadificación inicial IV, p-valor 0,077 para tratamientos paliativos; tratamiento iniciado después de 60 días del diagnóstico con porcentajes similares entre los sexos, 30 mujeres (39,47%) y 18 hombres (41,86%). CONCLUSIÓN: La navegación de pacientes por enfermeros reduce las barreras de acceso, mejora la coordinación del cuidado contribuyendo a un inicio de tratamiento más rápido y mejores resultados clínicos en la práctica oncológica.

Monkeypox is an emerging zoonotic viral disease caused by the Monkeypox virus, traditionally confined to central and west Africa, which has recently spread to other regions worldwide, making it a global health concern...