Search

Abstract In this pilot study, we assessed the role of autophagy in Crohn’s Disease (CD), particularly in patients with a stenosing phenotype. Through the analysis of biopsied specimens from 36 patients, including 11 controls and 25 CD patients, categorized into inflammatory and stenosing groups, we identified a significant reduction in the autophagosomal marker Lc3b-II in patients with active inflammation and stenosis. This was paralleled by an increase in oxidative stress markers, including sNOX2-dp and H2O2, and a decrease in the antioxidant capacity measured by HBA, suggesting an imbalance in autophagy and oxidative stress mechanisms. Additionally, our findings show a correlation between autophagy markers and oxidative stress levels, indicating that autophagy dysfunction may play a pivotal role in CD and in the progression of a stenosing disease phenotype, by failing to eliminate detrimental molecules and pathogenic bacteria, thereby promoting fibrosis. This study is the first to demonstrate in vivo autophagy inhibition in stenosing CD patients and suggests that stimulating autophagic processes could offer a new avenue for the prevention and treatment of intestinal fibrosis in CD. Our results highlight the importance of exploring the interactions between autophagy, the fibrotic process, and the inflammatory cascade, opening avenues for potential therapeutic interventions in CD management.

The complete mitochondrial genome of the shining leaf chafer Mimela junii was sequenced and is herein described. The mitogenome consists of a circular molecule of 16,805 bp, with an overall AT content of 75.7%. It encodes for 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), two ribosomal RNA genes (rRNAs) and contains a non-coding Control Region (CR) characterized by the presence of tandem repeats. The gene order corresponds to the ancestral Pancrustacea model and mitogenome characteristics are congruous with those of hexapods. In the phylogenetic analysis, M. junii is nested within a paraphyletic Anomala with high support, and is herein associated with Anomala corpulenta with medium/low support.

Abstract Background Operators in the obituary and necropsy sectors are exposed to various environmental hazards during specific tasks. Despite this exposure, occupational risks have often been underestimated, resulting in a lack of substantial evidence. The primary objectives of this study were to identify sources of chemical risk, establish procedures for monitoring and quantifying exposure during necropsy activities, and recommend adjustments to regulatory guidelines to protect the health of the operators. The study was conducted at the Legal Medicine Unit of the Umberto I General Hospital in Rome, focusing on the quantitative measurement of particulate matter (PM) exposure among at-risk operators during necropsy activities. Environmental levels of total suspended particles, PM10, PM4, PM2.5, and PM1 were assessed by evaluating the average, minimum, and maximum instantaneous indoor concentrations using an airborne analyzer. Results The monitoring activities revealed that the PM concentrations were significantly lower than the recognized reference values. However, bone sawing, body removal, and cleaning were identified as high-risk maneuvers for dust suspension. Conclusions Our study highlighted specific risks associated with necropsy activities, particularly concerning timing and certain maneuvers. These results may lead to interventions for improving current prevention procedures, implementing good practices, and developing specific guidelines to enhance operator safety.

Abstract Background SmithRNAs (Small MITochondrial Highly-transcribed RNAs) are a novel class of small RNA molecules that are encoded in the mitochondrial genome and regulate the expression of nuclear transcripts. Initial evidence for their existence came from the Manila clam Ruditapes philippinarum, where they have been described and whose activity has been biologically validated through RNA injection experiments. Current evidence on the existence of these RNAs in other species is based only on small RNA sequencing. As a preliminary step to characterize smithRNAs across different metazoan lineages, a dedicated, unified, analytical workflow is needed. Results We propose a novel workflow specifically designed for smithRNAs. Sequence data (from small RNA sequencing) uniquely mapping to the mitochondrial genome are clustered into putative smithRNAs and prefiltered based on their abundance, presence in replicate libraries and 5′ and 3′ transcription boundary conservation. The surviving sequences are subsequently compared to the untranslated regions of nuclear transcripts based on seed pairing, overall match and thermodynamic stability to identify possible targets. Ample collateral information and graphics are produced to help characterize these molecules in the species of choice and guide the operator through the analysis. The workflow was tested on the original Manila clam data. Under basic settings, the results of the original study are largely replicated. The effect of additional parameter customization (clustering threshold, stringency, minimum number of replicates, seed matching) was further evaluated. Conclusions The study of smithRNAs is still in its infancy and no dedicated analytical workflow is currently available. At its core, the SmithHunter workflow builds over the bioinformatic procedure originally applied to identify candidate smithRNAs in the Manila clam. In fact, this is currently the only evidence for smithRNAs that has been biologically validated and, therefore, the elective starting point for characterizing smithRNAs in other species. The original analysis was readapted using current software implementations and some minor issues were solved. Moreover, the workflow was improved by allowing the customization of different analytical parameters, mostly focusing on stringency and the possibility of accounting for a minimal level of genetic differentiation among samples.

Abstract Background Vestibular schwannomas (VS) are slowly growing tumor, deriving from the vestibular component of cranial nerve VIII. Primary treatment modalities include microsurgery, radiosurgery, a combination of microsurgery and radiosurgery, and conservative treatment. The management of VS is a matter of debate, particularly in case of small tumors (less than 2 cm in diameter size). Methods We performed an institutional retrospective review of a consecutive series of 28 surgically treated patients suffering from VS, operated in our institution. Patients were assigned on the ground of the preoperative imaging in two groups: tumors with major diameter of extra-meatal portion measuring ≥ 3 cm (Group I, 16 patients) and tumors with major diameter

Background Colorectal cancer (CRC) remains a significant healthcare burden worldwide, characterized by a complex interplay between obesity and chronic inflammation. While the relationship between CRC, obesity and altered lipid metabolism is not fully understood, there are evidences suggesting a link between them. In this study, we hypothesized that dysregulated lipid metabolism contributes to local accumulation of foam cells (FC) in CRC, which in turn disrupts antitumor immunosurveillance.Methods Tumor infiltrating FC and CD8+ were quantified by digital pathology in patients affected by T2–T4 CRC with any N stage undergoing radical upfront surgery (n=65) and correlated with patients’ clinical outcomes. Multiparametric high-resolution flow cytometry analysis and bulk RNAseq of CRC tissue were conducted to evaluate the phenotype and transcriptomic program of immune cell infiltrate in relation to FC accumulation. The immunosuppressive effects of FC and mechanistic studies on FC-associated transforming growth factor-beta (TGF-β) and anti-PD-L1 inhibition were explored using an in-vitro human model of lipid-engulfed macrophages.Results FC (large CD68+ Bodipy+ macrophages) accumulated at the tumor margin in CRC samples. FChigh tumors exhibited reduced CD8+ T cells and increased regulatory T cells (Tregs). Functional transcriptional profiling depicted an immunosuppressed milieu characterized by reduced interferon gamma, memory CD8+ T cells, and activated macrophages mirrored by increased T-cell exhaustion and Treg enrichment. Furthermore, FChigh tumor phenotype was independent of standard clinical factors but correlated with high body mass index (BMI) and plasma saturated fatty acid levels. In CD8low tumors, the FChigh phenotype was associated with a 3-year disease-free survival rate of 8.6% compared with 28.7% of FClow (p=0.001). In-vitro studies demonstrated that FC significantly impact on CD8 proliferation in TFG-β dependent manner, while inhibition of TGF-β FC-related factors restored antitumor immunity.Conclusions FC exert immunosuppressive activity through a TGF-β-related pathway, resulting in a CD8-excluded microenvironment and identifying immunosuppressed tumors with worse prognosis in patients with primary CRC. FC association with patient BMI and dyslipidemia might explain the link of CRC with obesity, and offers novel therapeutic and preventive perspectives in this specific clinical setting.

Hyperventilation induces metabolic changes that can elicit nystagmus (hyperventilation-induced nystagmus, HVIN) in various vestibular disorders, revealing vestibular imbalance and bringing out central or peripheral asymmetries. In acute unilateral vestibulopathy (AUVP, namely vestibular neuritis), hyperventilation can induce different patterns of nystagmus (excitatory, inhibitory, or negative), disclosing or modifying existing static vestibular asymmetries through its ability to invalidate compensation or increase peripheral excitability. In this context, we followed the evolutionary stages of HVIN in AUVP across 35 consecutive patients, with the goal of assessing alterations in the oculomotor pattern caused by hyperventilation over time. In the acute phase, the incidence of the excitatory pattern (and the strongly excitatory one, consisting of a reversal nystagmus evoked by hyperventilation) was significantly higher compared to the inhibitory pattern; then, a progressive reduction in the incidence of the excitatory pattern and a concomitant gradual increase in the incidence of the inhibitory one were observed in the follow-up period. Assuming the role of the ephaptic effect and the transient loss of vestibular compensation as opposing mechanisms, i.e., excitatory and inhibitory, respectively, the oculomotor pattern evoked by hyperventilation is the result of the interaction of these two factors. The data obtained allowed us to hypothesize an interpretative model regarding the pathogenetic aspects of responses evoked by hyperventilation and the etiologies of the disease: according to our hypotheses, the excitatory pattern implies a neuritic (viral) form of AUVP; instead, the inhibitory (and negative) one can be an expression of both the neuritic (viral) and vascular forms of the disease.

Abstract Family-based obesity management interventions targeting child, adolescent and parental lifestyle behaviour modifications have shown promising results. Further intervening on the family system may lead to greater improvements in obesity management outcomes due to the broader focus on family patterns and dynamics that shape behaviours and health. This review aimed to summarize the scope of pediatric obesity management interventions informed by family systems theory (FST). Medline, Embase, CINAHL and PsycInfo were searched for articles where FST was used to inform pediatric obesity management interventions published from January 1980 to October 2023. After removal of duplicates, 6053 records were screened to determine eligibility. Data were extracted from 50 articles which met inclusion criteria; these described 27 unique FST-informed interventions. Most interventions targeted adolescents (44%), were delivered in outpatient hospital settings (37%), and were delivered in person (81%) using group session modalities (44%). Professionals most often involved were dieticians and nutritionists (48%). We identified 11 FST-related concepts that guided intervention components, including parenting skills, family communication, and social/family support. Among included studies, 33 reported intervention effects on at least one outcome, including body mass index (BMI) (n = 24), lifestyle behaviours (physical activity, diet, and sedentary behaviours) (n = 18), mental health (n = 12), FST-related outcomes (n = 10), and other outcomes (e.g., adiposity, cardiometabolic health) (n = 18). BMI generally improved following interventions, however studies relied on a variety of comparison groups to evaluate intervention effects. This scoping review synthesises the characteristics and breadth of existing FST-informed pediatric obesity management interventions and provides considerations for future practice and research.

Soggetti che si amano. La vita della coppia dal miele dell’amore romantico all’acido del calo del desiderio e oltre is the latest book publishedby Giuseppe D'Amore (Psychologist, Psychotherapist and Psychoanalyst, MemberOrdinary of the Italian Society of Relationship Psychoanalysis). Released at the beginning of 2023, it represents at least in part the ideal continuation of the previous volume by the same author, 'Subjects that meet.From the relationship with others to the relationship with oneself... and vice versa',printed in 2021 also with the same publisher and whose review was published in No. 3, Year XXXIII, 2022 of Ricerca Psicoanalitica(pp. 637-641). [...]

Nei loro percorsi di affermazione della propria identità di genere, le persone transgender possono a volte trovarsi ‘invischiate’ in una sorta di ‘doppio doppio legame’, di cui uno fondato sulla percezione della contrapposizione tra il proprio sesso anatomico e la propria identità di genere e l’altro provocato dalla divergenza tra le proprie aspettative di genere individuali e quelle che verso di esse sono invece manifestate dal proprio ambiente familiare e sociale. Per cercare di aiutare queste persone a superare questa situazione, spesso fonte per esse di sofferenze soggettive non trascurabili, l’autore propone in questo lavoro un trattamento psicologico o di psicoterapia, ascrivibile al cosiddetto ‘modello affermativo di genere del consenso informato’ e fondato essenzialmente sul modello della Psicoanalisi della Relazione italiana integrato da contributi provenienti dalla ‘Teoria dei sistemi complessi dinamici nonlineari’, dalla Infant Research, dai contributi di vari altri autori di ambito psicoanalitico, dalla Neurofenomenologia e, infine, dal concetto di campo psicoanalitico come introdotto nel secolo scorso dai coniugi Baranger e in seguito sviluppato da vari autori anche italiani.

Platelet hyperactivity leads to thrombosis, the primary cause of cardiovascular and cerebrovascular adverse events. Emerging evidence suggests that autophagy plays a fundamental role in platelet function, both at baseline and in response to stress. Autophagy is an intracellular mechanism devoted to the removal and recycling of damaged cytoplasmic cargoes. Basal level of autophagy ensures physiological platelet aggregation and hemostasis. Autophagy is impaired in platelets isolated from subjects at high cardiovascular risk whereas autophagy stimulation reduces platelet hyperactivity, along with an overall amelioration of oxidative stress status. In this mini-review, we explore the current literature on the role of autophagy in platelet biology and its relevance as a therapeutic target for counteracting cardiovascular diseases.

Robotics and artificial intelligence have marked the beginning of a new era in the care and integration of people with disabilities, helping to promote their independence, autonomy and social participation. In this area, bioethical reflection assumes a key role at anthropological, ethical, legal and socio-political levels. However, there is currently a substantial diversity of opinions and ethical arguments, as well as a lack of consensus on the use of assistive robots, while the focus remains predominantly on the usability of products. The article presents a bioethical analysis that highlights the risk arising from using embodied artificial intelligence according to a functionalist model. Failure to recognize disability as the result of a complex interplay between health, personal and situational factors could result in potential damage to the intrinsic dignity of the person and human relations with healthcare workers. Furthermore, the danger of discrimination in accessing these new technologies is highlighted, emphasizing the need for an ethical approach that considers the social and moral implications of implementing embodied AI in the field of rehabilitation.

Purpose: Brain metastases (BMs) most frequently originate from the primary tumors of the lung and breast. Survival in patients with BM can improve if they are detected early. No studies attempt to consider all potential surgical predictive factors together by including clinical, radiological variables for their recognition. Methods: The study aims to simultaneously analyze all clinical, radiologic, and surgical variables on a cohort of 314 patients with surgically-treated BMs to recognize the main features and differences between the two histotypes. Results: The two groups consisted of 179 BM patients from lung cancer (Group A) and 135 patients from breast cancer (Group B). Analysis showed that BMs from breast carcinoma are more likely to appear in younger patients, tend to occur in the infratentorial site and are frequently found in patients who have other metastases outside of the brain (46 %, p = 0.05), particularly in bones. On the other hand, BMs from lung cancer often occur simultaneously with primitive diagnosis, are more commonly cystic, and have a larger edema volume. However, no differences were found in the extent of resection, postoperative complications or the presence of decreased postoperative performance status. Conclusion: The data presented in this study reveal that while the two most prevalent forms of BM exhibit distinctions with respect to clinical onset, age, tumor location, presence of extra-cranial metastases, and lesion morphology from a strictly surgical standpoint, they are indistinguishable with regard to outcome, demonstrating comparable resection rates and a low risk of complications.

ABSTRACT Purpose: The purpose of this study is to assess whether the Dunning-Kruger effect occurs in surgical residents when performing laparoscopic cholecystectomy in a porcine model. Methods: Prospective blinded study, which counted with forty PGY-1 general surgery residents who agreed to participate in the study were blindly recruited to perform a laparoscopic cholecystectomy in a porcine model. At the end of the procedure, the participants assigned a score of 0-10 for their own performance and the video of the operation was independently assessed by 2 experienced laparoscopic surgeons using a validated tool. Results: Participants were divided into groups of 10 individuals according to objective performance and compared. The group with the worst objective result was inferior to the group with the best objective result (3.77 ± 0.44 vs. 8.1 ± 0.44, p < 0.001), but they were similar in self-perception of performance (5.11 ± 1.69 vs. 6.1 ± 1.79, p = 0.999). Conclusions: In the studied sample, it was possible to demonstrate the presence of the Dunning-Kruger effect.