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Aims The Craving Typology Questionnaire (CTQ) is a psychometric instrument used to assess alcohol craving in normal controls and subjects with alcohol use disorder (AUD). It allows a dimensional self-rating assessment of craving according to a three-pathway psychobiological model of craving distinguishing craving into a reward, relief and obsessive component. The aim of the present study is to evaluate psychometric properties of the CTQ-15, a revised version of CTQ with 15 items. Methods The CTQ-15 was firstly administered to two groups of control subjects, one (414 subjects) used for the exploratory factor analysis and the other one (415 subjects) for the confirmatory factor analysis. A three-factor model was assessed and compared to alternative models. Results The resulting structure was in line with the original scale CTQ. Obsessive craving accounted for 15.20% of the total variance, relief craving for the 13.99% and reward craving for 13.13% of the total variance. The three-factor model (M1) reached good fit indices (CFI = 0.96, TLI = 0.95, RMSEA = 0.06 and SRMR = 0.05) and was significantly better than other alternative models. Reliability showed good internal consistency for each scale, i.e. obsessive craving (α = 0.92), relief craving (α = 0.82) and reward craving (α = 0.81). Conclusions The CTQ-15 proved to be reliable and practical for identifying the three dimensions of craving in clinical practice. Craving plays a crucial role in the mechanisms of dependence and relapse; thus, characterizing the craving can be fundamental to a targeted drug therapy.

The subscapularis (SSc) is the most powerful muscle of the rotator cuff. His role in shoulder stability and shoulder motion is well studied and due to functional and frequent association with concomitant other lesions, the repair of the SSc tendon is always desirable to restore force and stability to the shoulder.

Background About 80% of the roughly 7,000 known rare diseases are single gene disorders, about 85% of which are ultra-rare, affecting less than one in one million individuals. NGS technologies, in particular whole genome sequencing (WGS) in paediatric patients suffering from severe disorders of likely genetic origin improve the diagnostic yield allowing targeted, effective care and management. The aim of this study is to perform a systematic review and meta-analysis to assess the effectiveness of WGS, with respect to whole exome sequencing (WES) and/or usual care, for the diagnosis of suspected genetic disorders among the paediatric population. Methods A systematic review of the literature was conducted querying relevant electronic databases, including MEDLINE, EMBASE, ISI Web of Science, and Scopus from January 2010 to June 2022. A random-effect meta-analysis was run to inspect the diagnostic yield of different techniques. A network meta-analysis was also performed to directly assess the comparison between WGS and WES. Results Of the 4,927 initially retrieved articles, thirty-nine met the inclusion criteria. Overall results highlighted a significantly higher pooled diagnostic yield for WGS, 38.6% (95% CI: [32.6 – 45.0]), in respect to WES, 37.8% (95% CI: [32.9 – 42.9]) and usual care, 7.8% (95% CI: [4.4 – 13.2]). The meta-regression output suggested a higher diagnostic yield of the WGS compared to WES after controlling for the type of disease (monogenic vs non-monogenic), with a tendency to better diagnostic performances for Mendelian diseases. The network meta-analysis showed a higher diagnostic yield for WGS compared to WES (OR = 1.54, 95%CI: [1.11 – 2.12]). Conclusions Although whole genome sequencing for the paediatric population with suspected genetic disorders provided an accurate and early genetic diagnosis in a high proportion of cases, further research is needed for evaluating costs, effectiveness, and cost-effectiveness of WGS and achieving an informed decision-making process. Trial Registration This systematic review has not been registered.

New climate regimes, variability and extreme events affect the livestock sector in many aspects, ranging from animal welfare, production, reproduction, diseases and their spread, feed quality and availability. Heat stress, especially when combined with excess or low humidity, exacerbates the perceived temperature or the drought conditions, respectively, increasing hazards for animals. Also, cold extremes, extraordinary windy conditions and altered radiation regimes are detrimental to both animals and fodder.In this context, the EU-funded SEBASTIEN project aims to provide stakeholders with a Decision Support System (DSS) for more efficient and sustainable management, and consequent valuation, of the livestock sector in Italy. SEBASTIEN DSS will integrate GIS, environmental and biological variables to generate updated risk maps for livestock diseases and zoonoses and their spread, alerting about the expected occurrence of stressing conditions for animals due to abiotic and biotic factors.The presence of parasites, vectors, and outbreaks will be combined with environmental data, gathered by spatially distributed meteorological and satellite monitoring, to detect conditions that can potentially favor or trigger the spread of related diseases. Sensor-based monitoring data will be integrated with the above information to determine ranges in animal parameters potentially associated with a higher risk of critical pathogen load or density of vectors potential carriers of diseases. Medium to long-term climate forecasts will support predicting possible shifts of favorable conditions that will open up new areas for parasites and pathogens. The vast amounts of data will be integrated and summarized into user-tailored information through a range of techniques, from empirical/statistical indicators to Machine Learning algorithms.

Objectives: Excellent knee stability is necessary to achieve good postoperative clinical results in anterior cruciate ligament (ACL) reconstruction. However, there is little evidence in the literature regarding hamstring graft choice for ACL reconstruction. Our study intended to debate the best autograft choice for this procedure. We aimed to examine the functional and biomechanical outcomes of three different autografts used in ACL reconstruction, namely, Semitendinosus and Gracilis quadrupled (STGR) autograft, tripled or quadrupled ST autograft, and tripled Gracilis tendon autograft (GR). Methods: We conducted an observational, comparative, prospective cohort on 248 ACL reconstructed patients spanning 2 years (2009–2010) and evaluated the primary outcome with KT-1000 knee arthrometer and secondary outcomes with International Knee Documentation Committee (IKDC), Tegner ctivity cale, and Lysholm score. Results: The data suggest a statistically significant increase in IKDC score and Lysholm score in the GR group – standing for better subjective outcomes like pain – compared to the STGR and ST groups (P = 0.0018 and P = 0.0034, respectively) and statistically non-significant differences between the STGR and ST groups for all evaluated parameters. KT-1000 side-to-side evaluation demonstrates that STGR autograft offers less structural knee laxity compared to GR autograft in ACL reconstruction (P = 0.044). Conclusion: The study found that STGR autograft offers more stability to the knee compared to the GR autograft alone yet is associated with inferior subjective outcomes compared to the GR group. GR autograft is a valid substitute for ACL reconstruction, especially in patients presenting with hyperlaxity or demanding lower functional performance.

Objective: To assess the variations of Interleukin-6 (IL-6) in patients with SARS-CoV-2 infection treated with Tocilizumab (TCZ) alone or in association with hemoadsorption (HA). Design: Retrospective. Setting: An Intensive Care Unit (ICU) admitting mechanically ventilated patients with SARS-CoV-2 pneumonia. Patients: Four adult patients. Interventions: We compared the blood values of IL-6, C-reactive protein (CRP) and of other biochemical variables including the PaO2/FiO2 in two patients who received TCZ alone and in other 2 in whom it was associated with the HA (TCZ-HA) due to the presence of impending or established organ failures other than the lung. All variables were measured before, during and after the treatment. Main results: In all patients, the IL-6 increased during the treatment; after its termination, its values sharply decreased only in those treated also with HA; conversely, the CRP decreased in all patients; the PaO2/FiO2 increased in three patients and remained stable in the remaining one. Both the TCZ and the HA were well tolerated; all patients were weaned from the mechanical ventilation and discharged from the hospital. Limitations: Although the limited number of patients does not allow to draw firm conclusions, the increase of the IL-6 of can be ascribed to its displacement from cellular and soluble receptors, whereas its decrease is likely due to the scavenging effect exerted by the HA. Although the association TCZ-HA could be valuable in the treatment of the Cytokine Release Storm (CRS) associated with the SARS-CoV-2, the HA could be more effective as it neutralizes a wider panel of inflammatory mediators.

Papillomaviruses (PVs) are small, non-enveloped viruses, ubiquitous across the animal kingdom. PVs induce diverse forms of infection, such as cutaneous papillomas, genital papillomatosis, and carcinomas. During a survey on the fertility status of a mare, a novel Equus caballus PV (EcPV) has been identified using Next Generation Sequencing, and it was further confirmed with genome-walking PCR and Sanger sequencing. The complete circular genome 7607 bp long shares 67% average percentage of identity with EcPV9, EcPV2, EcPV1, and EcPV6, justifying a new classification as Equus caballus PV 10 (EcPV10). All EcPV genes are conserved in EcPV10, and phylogenetic analysis indicates that EcPV10 is closely related to EcPV9 and EcPV2, genus Dyoiota 1. A preliminary EcPV10 genoprevalence study, carried out on 216 horses using Real Time PCRs, suggested a low incidence of this isolate (3.7%) compared to EcPVs of the same genus such as EcPV2 and EcPV9 in the same horse population. We hypothesize a transmission mechanism different from the one observed in the closely related EcPV9 and EcPV2 that particularly infect Thoroughbreds. This horse breed is usually submitted to natural mating, thus indicating a possible sexual diffusion. No differences were detected for breeds in terms of susceptibility to EcPV10. Further studies are needed to investigate the molecular mechanisms behind the host and EcPV10 infection to explain the reduced viral spread.

Many bimanual activities of daily living require quick shifts between symmetric and asymmetric motor output generated by the right and left hand. Bimanual motor control has been mostly studied during continuous repetitive tasks, while little research has been carried out in experimental settings requiring dynamic changes in motor output generated by both hands. Here, we performed functional magnetic resonance imaging (MRI) while healthy volunteers performed a visually guided, bimanual pinch force task. This enabled us to map functional activity and connectivity of premotor and motor areas during bimanual pinch force control in different task contexts, requiring mirror-symmetric or inverse-asymmetric changes in discrete pinch force exerted with the right and left hand. The bilateral dorsal premotor cortex showed increased activity and effective coupling to the ipsilateral supplementary motor area (SMA) in the inverse-asymmetric context compared to the mirror-symmetric context of bimanual pitch force control. Compared to unilateral pinches, all bimanual pinch force conditions were characterized by an increased level of activation in the bilateral primary motor hand area (M1-HAND) and stronger coupling from SMA to the ipsilateral M1-HAND. Task-related activity of a cluster in the left caudal SMA scaled positively with the degree of synchronous initiation of bilateral pinch force adjustments, irrespectively of the task context. The results suggest that the dorsal premotor cortex mediates increasing complexity of bimanual coordination by increasing coupling to the SMA-M1 network.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein binds angiotensin-converting enzyme 2 (ACE2) at the cell surface, which constitutes the primary mechanism driving SARS-CoV-2 infection. Molecular interactions between the transduced S and endogenous proteins likely occur post-infection, but such interactions are not well understood. We used an unbiased primary screen to profile the binding of full-length S against >9,000 human proteins and found significant S-host protein interactions, including one between S and human estrogen receptor alpha (ERα). After confirming this interaction in a secondary assay, we used bioinformatics, supercomputing, and experimental assays to identify a highly conserved and functional nuclear receptor coregulator (NRC) LXD-like motif on the S2 subunit and an S-ERα binding mode. In cultured cells, S DNA transfection increased ERα cytoplasmic accumulation, and S treatment induced ER-dependent biological effects and ACE2 expression. Noninvasive multimodal PET/CT imaging in SARS-CoV-2-infected hamsters using [18F]fluoroestradiol (FES) localized lung pathology with increased ERα lung levels. Postmortem experiments in lung tissues from SARS-CoV-2-infected hamsters and humans confirmed an increase in cytoplasmic ERα expression and its colocalization with S protein in alveolar macrophages. These findings describe the discovery and characterization of a novel S-ERα interaction, imply a role for S as an NRC, and are poised to advance knowledge of SARS-CoV-2 biology, COVID-19 pathology, and mechanisms of sex differences in the pathology of infectious disease.

Germline-activating mutations in HRAS cause Costello syndrome (CS), a cancer prone multisystem disorder characterized by reduced postnatal growth. In CS, poor weight gain and growth are not caused by low caloric intake. Here, we show that constitutive plasma membrane translocation and activation of the GLUT4 glucose transporter, via reactive oxygen species-dependent AMP-activated protein kinase α and p38 hyperactivation, occurs in primary fibroblasts of CS patients, resulting in accelerated glycolysis and increased fatty acid synthesis and storage as lipid droplets. An accelerated autophagic flux was also identified as contributing to the increased energetic expenditure in CS. Concomitant inhibition of p38 and PI3K signaling by wortmannin was able to rescue both the dysregulated glucose intake and accelerated autophagic flux. Our findings provide a mechanistic link between upregulated HRAS function, defective growth and increased resting energetic expenditure in CS, and document that targeting p38 and PI3K signaling is able to revert this metabolic dysfunction.

To explore to what extent intrauterine device (IUD) expulsion is associated with demographic and clinical risk factors.The APEX-IUD (Association of Perforation and Expulsion of IntraUterine Devices) study was a U.S. cohort study using electronic health records from three integrated health care systems (Kaiser Permanente Northern California, Southern California, and Washington) and a health care information exchange (Regenstrief Institute). These analyses included individuals aged 50 years or younger with IUD insertions from 2001 to 2018. Intrauterine device expulsion cumulative incidence and incidence rates were estimated. Using Cox regression models, hazard ratios with 95% CIs were estimated before and after adjustment for risk factors of interest (age, race and ethnicity, parity, body mass index [BMI], heavy menstrual bleeding, and dysmenorrhea) and potential confounders.In total, 228,834 individuals with IUD insertion and no delivery in the previous 52 weeks were identified (184,733 [80.7%] with levonorgestrel-releasing intrauterine system). Diagnosis of heavy menstrual bleeding-particularly a diagnosis in both recent and past periods-was the strongest risk factor for IUD expulsion. Categories with the highest risk of IUD expulsion within each risk factor included individuals diagnosed with overweight, obesity, and morbid obesity; those in younger age groups, especially among those aged 24 years or younger; and in those with parity of four or more. Non-Hispanic White individuals had the lowest incidence and risk, and after adjustment, Asian or Pacific Islander individuals had the highest risk. Dysmenorrhea was not independently associated with expulsion risk when adjusting for heavy menstrual bleeding.Most risk factors for expulsion identified in this study appear consistent with known physiologic factors that affect uterine anatomy and physiology (age, BMI, heavy menstrual bleeding, parity). The increased risk of IUD expulsion among individuals of color warrants further investigation. Intrauterine devices are an effective long-term contraceptive; expulsion is uncommon, but patients should be counseled accordingly.Bayer AG.EU PAS register, EUPAS33461.

A large number of SARS-CoV-2 mutations in a short period of time has driven scientific research related to vaccines, new drugs, and antibodies to combat the new variants of the virus. Herein, we present a web portal containing the structural information, the tridimensional coordinates, and the molecular dynamics trajectories of the SARS-CoV-2 spike protein and its main variants. The Spike Mutants website can serve as a rapid online tool for investigating the impact of novel mutations on virus fitness. Taking into account the high variability of SARS-CoV-2, this application can help the scientific community when prioritizing molecules for experimental assays, thus, accelerating the identification of promising drug candidates for COVID-19 treatment. Below we describe the main features of the platform and illustrate the possible applications for speeding up the drug discovery process and hypothesize new effective strategies to overcome the recurrent mutations in SARS-CoV-2 genome.

Gut represents a major immunological defense barrier with mucosal immune system and intestinal epithelial cells (IECs). In all intestinal diseases, in particular inflammatory bowel disease (IBD), both the absorption and the local immune system are compromised and alternative effective therapies are sought after. Extracellular Vesicles (EVs) have the capability to regulate immune cells within the inflammatory microenvironment, by dampening inflammation and restoring intestinal barrier integrity. Recently, the immune-modulatory role of EVs has also been confirmed for milk EVs (mEVs), notable for their easy production, high sample volumes, cost-effective scalable production and non-toxic and non-immunogenic behavior. In this context, the aim of this study was to evaluate goat mEV anti-inflammatory and immuno-modulating effects on an in vitro model (IPEC-J2) of intestinal inflammation through gene expression evaluation with RT-qPCR and cytokine release dosage with ELISA test. After the establishment of a pro-inflammatory environment due to LPS stimuli, IL6, CXCL8, IL12p35, IL12p40, IFNB, IL18, TLR7 and NOS2 resulted significantly up-regulated in stimulated IPEC-J2 cells compared to those of the basal culture. After 48 h of mEV treatment in inflamed IPEC-J2 a partial restoration of initial conditions was detected, with the IL18 and IL12p40 significant down-regulation, and IL12p35, EBI3, TLR7, BD1 and BD3 up-regulation. IL-18 reduced protein production was also detected in supernatants. Moreover, a decrease of MMP9 and NOS2 together with a strong up-regulation of MUC2 indicated a recovery of cellular homeostasis and, therefore, potential beneficial effects on the intestinal mucosa. Nevertheless, 48 h post-treatment, an increased gene expression and protein release of IL-8 was observed. This paper is one of the firsts to assess the effect of goat mEVs and the first one, in particular, of doing this on an in vitro model of gut inflammation. The obtained results show a potential capability of goat mEVs to modulate inflammation and to play beneficial effects on the intestinal mucosa.

In recent years, the involvement of the gut microbiota in disease and health has been investigated by sequencing the 16S gene from fecal samples. Dysbiotic gut microbiota was also observed in Autism Spectrum Disorder (ASD), a neurodevelopmental disorder characterized by gastrointestinal symptoms. However, despite the relevant number of studies, it is still difficult to identify a typical dysbiotic profile in ASD patients. The discrepancies among these studies are due to technical factors (i.e., experimental procedures) and external parameters (i.e., dietary habits). In this paper, we collected 959 samples from eight available projects (540 ASD and 419 Healthy Controls, HC) and reduced the observed bias among studies. Then, we applied a Machine Learning (ML) approach to create a predictor able to discriminate between ASD and HC. We tested and optimized three algorithms: Random Forest, Support Vector Machine and Gradient Boosting Machine. All three algorithms confirmed the importance of five different genera, including Parasutterella and Alloprevotella. Furthermore, our results show that ML algorithms could identify common taxonomic features by comparing datasets obtained from countries characterized by latent confounding variables.

We previously molecularly and clinically characterized Mazzanti syndrome, a RASopathy related to Noonan syndrome that is mostly caused by a single recurrent missense variant (c.4A?>?G, p.Ser2Gly) in SHOC2, which encodes a leucine-rich repeat-containing protein facilitating signal flow through the RAS-mitogen-associated protein kinase (MAPK) pathway. We also documented that the pathogenic p.Ser2Gly substitution causes upregulation of MAPK signaling and constitutive targeting of SHOC2 to the plasma membrane due to the introduction of an N-myristoylation recognition motif. The almost invariant occurrence of the pathogenic c.4A?>?G missense change in SHOC2 is mirrored by a relatively homogeneous clinical phenotype of Mazzanti syndrome. Here, we provide new data on the clinical spectrum and molecular diversity of this disorder and functionally characterize new pathogenic variants. The clinical phenotype of six unrelated individuals carrying novel disease-causing SHOC2 variants is delineated, and public and newly collected clinical data are utilized to profile the disorder. In silico, in vitro and in vivo characterization of the newly identified variants provides evidence that the consequences of these missense changes on SHOC2 functional behavior differ from what had been observed for the canonical p.Ser2Gly change but converge toward an enhanced activation of the RAS-MAPK pathway. Our findings expand the molecular spectrum of pathogenic SHOC2 variants, provide a more accurate picture of the phenotypic expression associated with variants in this gene and definitively establish a gain-of-function behavior as the mechanism of disease., European Union (EU); Horizon 2020; European Joint Program on Rare Diseases (EJP-RD); Associazione Italiana per la Ricerca sul Cancro (AIRC); Italian Ministry of Health (Ricerca Corrente 2022); Italian Ministry of Research (FOE 2019); German Federal Ministry of Education and Research; BMBF (German Network for RASopathy Research ""GeNeRARe""); European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability (ERN-ITHACA)

Biallelic mutations in B3GALT6, coding for a galactosyltransferase involved in the synthesis of glycosaminoglycans (GAGs), have been associated with various clinical conditions, causing spondyloepimetaphyseal dysplasia with joint laxity type 1 (SEMDJL1 or SEMDJL Beighton type), Al-Gazali syndrome (ALGAZ), and a severe progeroid form of Ehlers-Danlos syndrome (EDSSPD2). In the 2017 Ehlers-Danlos syndrome (EDS) classification, Beta3GalT6-related disorders were grouped in the spondylodysplastic EDSs together with spondylodysplastic EDSs due to B4GALT7 and SLC39A13 mutations. Herein, we describe a patient with a previously unreported homozygous pathogenic B3GALT6 variant resulting in a complex phenotype more severe than spondyloepimetaphyseal dysplasia with joint laxity type 1, and having dural ectasia and aortic dilation as additionally associated features, further broadening the phenotypic spectrum of the Beta3GalT6-related syndromes. We also document the utility of repeating sequencing in patients with uninformative exomes, particularly when performed by using "first generations" enrichment capture methods.

The aim of the study was to evaluate the results of an all arthroscopic technique for the treatment of massive rotator cuff tears using the long head of biceps as a graft to reconstruct the superior capsule and to reinforce the cuff. A retrospective review of a consecutive series of arthroscopic repair of massive rotator cuff tears using the long head of biceps tendon was conducted. Twenty-five patients underwent surgery, and none were lost at follow-up. Minimum follow-up period was more than 12 months. Constant, UCLA and VAS scores as clinical outcome were analyzed. Time for surgical procedures was also registered. Two alternative procedures (transosseous or anchors) were employed to fix laterally the long head of biceps to the greater tuberosity and to reinforce the cuff. This choice was essentially determined by the bone quality of the greater tuberosity. All patients of both groups (Transosseous: 15 and Anchors: 10) showed a significant improvement of clinical and functional scores. Difference of the operative times between two procedures was statistically significant in favor of the anchor approach. No intraoperative complications were recorded. Postoperative shoulder stiffness was found in two male patients. In no case biceps tenodesis was performed: Popeye sign was easily detected in 16 patients but they did not complain any superior arm pain and weakness. This technique represents a valid solution for treatment of massive rotator cuff tears resulting safe, easier and cost saving in comparison with other published techniques.

El objetivo de esta Memoria de máster es el análisis y la traducción al italiano de los pasajes del Nafḥ al-ṭīb más relevantes, cuyo objeto es el conocimiento en al-Andalus y su transmisión. El Nafḥ al-ṭīb min ġuṣn al-Andalus al-raṭīb wa-ḏikr wazīrihā Lisān al-Dīn Ibn al-Ḫaṭīb, en español Efluvio de perfumes sobre la memoria de al-Andalus y de su visir Lisān al-Dīn ibn al-Ḫaṭīb, es una obra escrita por al-Maqqarī (m. 1632 d. C.) en 1628/9 d. C., donde el autor recorre la historia de al-Andalus desde la ocupación musulmana hasta la conquista de Granada en 1492 d. C.

Background: There is evidence that temporal duration is spatially represented on a horizontal mental timeline (MTL) with relatively short durations represented on the left and long duration on the right side. Most of this evidence comes from the visual domain. Objective: With the present study, we investigated whether temporal duration judgements of visual and auditory stimuli might be affected by spatial biases in time representation. Methods: Participants were asked to estimate the temporal duration of a target with respect to a reference stimulus. Two different exposure times were used for the reference (fast and slow), and three exposure times for the target with respect to the reference (shorter, equal, longer). Two versions of the task were implemented to probe visual and auditory temporal processing. Results: Participants showed enhanced performance when the target had longer duration than the reference independently of the type of task, but they were affected in opposite ways by the reference exposure time, in the two tasks. Best performance was observed for the fast reference in the visual domain and for the slow reference in the auditory one. Discussion: We argue that these findings provide evidence that temporal judgments of visual and auditory stimuli are affected by the duration of the reference stimulus, besides the duration of the target stimulus. Interestingly, they suggest putative leftward and rightward spatial biases in time representation for the visual and auditory domains, respectively, although future studies are necessary to further investigate these initial findings.

In recent years, the involvement of the gut microbiota in disease and health has been investigated by sequencing the 16S gene from fecal samples. Dysbiotic gut microbiota was also observed in Autism Spectrum Disorder (ASD), a neurodevelopmental disorder characterized by gastrointestinal symptoms. However, despite the relevant number of studies, it is still difficult to identify a typical dysbiotic profile in ASD patients. The discrepancies among these studies are due to technical factors (i.e., experimental procedures) and external parameters (i.e., dietary habits). In this paper, we collected 959 samples from eight available projects (540 ASD and 419 Healthy Controls, HC) and reduced the observed bias among studies. Then, we applied a Machine Learning (ML) approach to create a predictor able to discriminate between ASD and HC. We tested and optimized three algorithms: Random Forest, Support Vector Machine and Gradient Boosting Machine. All three algorithms confirmed the importance of five different genera, including

Smyd2 lysine methyltransferase regulates monomethylation of histone and nonhistone lysine residues using S‐adenosylmethionine cofactor as the methyl donor. The nonhistone interactors include several tumorigenic targets, including p53. Understanding this interaction would allow the structural principles that underpin Smyd2‐mediated p53 methylation to be elucidated. Here, we performed μ‐second molecular dynamics (MD) simulations on binary Smyd2‐cofactor and ternary Smyd2‐cofactor‐p53 peptide complexes. We considered both unmethylated and monomethylated p53 peptides (at Lys370 and Lys372). The results indicate that (a) the degree of conformational freedom of the C‐terminal domain of Smyd2 is restricted by the presence of the p53 peptide substrate, (b) the Smyd2 C‐terminal domain shows distinct dynamic properties when interacting with unmethylated and methylated p53 peptides, and (c) Lys372 methylation confines the p53 peptide conformation, with detectable influence on Lys370 accessibility to the cofactor. These MD results are therefore of relevance for studying the biology of p53 in cancer progression.

The study of plant and animal remains from archaeological sites provides important evidence about past human diets and habits: this includes species selection, food preparation, consumption and dis...

Objective To develop a longitudinal algorithm combining two biomarkers, CA125 and HE4, for early detection of ovarian cancer in women with BRCA mutations. Methods Women with BRCA mutations and intact ovaries were invited to participate in a novel ovarian cancer early detection prospective study. The Risk of Ovarian Cancer Algorithm (ROCA) identifying significant increases above each woman's baseline in serum CA125 and HE4 was performed every four months; abnormal risks triggered a subsequent ultrasound. The study first used a risk algorithm for only CA125, a second algorithm was developed for HE4 and finally a risk algorithm combining the two biomarkers was implemented. The ROCA strategy was compared to Standard of Care (SOC) surveillance strategy. Results A total of 149 women enrolled in the ROCA arm while 43 women enrolled in the SOC arm. Abnormal scores were found in 24% of ROCA CA125 tests, 16% if ROCA CA125 or the novel ROCA HE4 were used independently and reduced to 8% using the new two-marker ROCA, significantly lower than the 15% of abnormal tests seen in the SOC arm (p = 0.042). The average false positive rate among women without ovarian cancer for two-marker ROCA for referral to ultrasound was 6.6% (specificity 93.4%), and for the two-marker ROCA plus ultrasound for referral to surgical consultation was 1.7% (specificity 98.3%). Conclusion A newly developed two-marker ROCA administered every 4 months had lower call-back rates than SOC surveillance. Having established high specificity, the two-marker ROCA score deserves further evaluation for sensitivity in a larger trial.

Stressful experiences are part of everyday life and animals have evolved physiological and behavioral responses aimed at coping with stress and maintaining homeostasis. However, repeated or intense stress can induce maladaptive reactions leading to behavioral disorders. Adaptations in the brain, mediated by changes in gene expression, have a crucial role in the stress response. Recent years have seen a tremendous increase in studies on the transcriptional effects of stress. The input raw data are freely available from public repositories and represent a wealth of information for further global and integrative retrospective analyses. We downloaded from the Sequence Read Archive 751 samples (SRA-experiments), from 18 independent BioProjects studying the effects of different stressors on the brain transcriptome in mice. We performed a massive bioinformatics re-analysis applying a single, standardized pipeline for computing differential gene expression. This data mining allowed the identification of novel candidate stress-related genes and specific signatures associated with different stress conditions. The large amount of computational results produced was systematized in the interactive “Stress Mice Portal”.

Rotavirus group A remains a major cause of diarrhea in infants and young children worldwide. The permanent emergence of new genotypes puts the potential effectiveness of vaccines under serious questions. Thirteen VP1 structures with mutations mapping to the RNA entry site were analyzed using molecular dynamics simulations, and the results were combined with the experimental findings reported previously. The results revealed structural fluctuations in the protein-protein recognition sites and in the bottleneck of the RNA entry site that may affect the interaction of different proteins and delay the initiation of the viral replication, respectively. Altogether, the structural analysis of VP1 in the region crucial for the initiation of the viral replication, mainly the bottleneck site, may boost efforts to develop antivirals, as they might complement the available vaccines.

Background: Humeral shaft fractures account for 1% to 3% of all fractures and approximately 20% of all fracture involving the humerus. The prevalence of non-union for diaphyseal humeral fractures has been reported as 1% to 10% after non-surgical and 10% to 15% after surgical management. Various devices used in treatment of humeral diaphyseal non-union are limited contact dynamic compression plates, locking compression plate (LCP), wave plates, humerus interlocking nail (IMN), Ilizarov external fixators and bone graft struts. Case Description: A 68-year-old man reported a humeral shaft fracture on the left side, due to a simple fall. It was reduced and fixed by IMN. He underwent clinical and radiological follow up. Three months after the intervention, due to persistent pain and impaired function of the left shoulder, the nail was removed and a cemented endoprosthesis was implanted. 3 years later, unsatisfied with the results, he came to our attention and was diagnosed an atrophic non-union in the site of the previous humeral shaft fracture. Moreover, the exams showed a rotator cuff insufficiency. It was decided to perform a single-stage intervention to achieve two goals: cure the humeral shaft non-union and restore the function of the left shoulder. The cemented endoprosthesis was removed, followed by an extensive curettage of the non-union site. A reverse prosthesis was implanted, with an extra-long stem used to stabilize the non-union site, as it was an IMN. An allograft was harvested from a cadaver femur and fixed with two metal cerclages. The patient underwent clinical and radiological follow-up. Complete healing was achieved 8 months later. Conclusion: Humeral shaft nonunion still represent a pathology that pose a serious problem to the surgeon. A correct management should include an accurate pre-operative planning, to achieve the best result possible for the patient.

Different surgical techniques (open and arthroscopic) have been described for the treatment of post-traumatic recurrent anterior instability. The aim of the surgery is to restore when possible, normal shoulder anatomy by repairing the underlying pathology responsible for the instability. Sometimes other surgical techniques are indicated. The purpose of this retrospective study was to investigate the long-term clinical and radiographic results and complications of the open Latarjet procedure after a minimum follow-up of 24 years.A retrospective study was performed for 67 patients treated with an open Latarjet procedure in a single center. Forty of these 67 patients returned for follow-up evaluation and clinical/radiological examination during the year 2018, having had a minimum of 24-year follow-up. Clinical outcomes were analyzed using two functional scores, in addition to the ROM and strength assessment. Radiographic evaluation included several views (AP views in neutral, internal and external rotation and a comparative Bernageau view) RESULTS: A total of 40 patients underwent an open Latarjet procedure. All the patients were avaible for follow-up at an average of 25.6 years. Clinically, no patient reported any episode of dislocation at the time of follow-up. The mean Rowe score and the Walch-Duplay score were 84.5 (range 45-100) and 83.5 (range 55-100), respectively. Non-union/fibrous union was reported in 12.5% of cases, partial resorption of the graft was found in 7.5% of cases, while total resorption was found in 5% of cases. Osteoarthritis was identified in 52.5% (21) of the patients.This long-term follow-up study demonstrated that the open Latarjet procedure is a safe and reliable technique for recurrent anterior shoulder instability. The Latarjet procedure provides good long-term stability although associated with a slight limitation in external rotation.Level III; retrospective cohort comparison; treatment study.

Mycobacterium avium ssp. paratuberculosis (MAP) is the causative agent of paratuberculosis (PTB), a widespread chronic enteritis of ruminants. The progression of the infection depends on the containment action of innate and cell-mediated immunity (CMI), and it is related to environmental and genetic factors. In particular, PTB susceptibility seems to be associated with specific genes coding for immune regulators involved in the cell-mediated response during the infection. The aim of this preliminary study was to verify, in Italian beef cattle, an association between MAP infectious status and the presence of single nucleotide polymorphisms (SNPs) in candidate genes. To the best of our knowledge, this is the first investigation conducted on a native beef cattle breed, known as Marchigiana, reared in Central Italy. The present research, based on a longitudinal study, aimed to identify and correlate phenotypic and genetic profiles characteristic of the subjects potentially able to contrast or contain PTB. In a MAP-infected herd, ELISA, IFN-γ tests, qPCR, and cultures were performed at a follow-up, occurring within a period ranging from three to six years, to evaluate the individual state of infection. Animals testing positive for at least one test were considered infected. DNA samples of 112 bovines, with known MAP statuses, were analyzed to verify an association with SNPs in the genes encoding gamma-interferon (BoIFNG), interleukin receptor 10 (IL10RA), interleukin receptor 12 (IL12RB2), and toll-like receptors (TLR1, TLR2, TLR4). Regarding statistical analysis, the differences among target genes and pairs of alleles in the analyzed groups of animals, were evaluated at a significance level of p < 0.05. For IL10RA and for IL12RB2 genes, relevant differences in genotypic frequencies among the considered cattle groups were observed. For all candidate genes studied in this investigation, SNP genotypes already associated with PTB resistance were found more frequently in our population, suggesting potential resistance traits in the Marchigiana breed.

Objective: To assess the variations of the blood levels of immunoglobulins (Ig) in septic shock patients treated with an Ig preparation enriched in IgM and IgA (eIg).Design: The blood levels of Ig in survivors (S) and non-survivors (NS) of a group of septic shock patients were measured before the initial administration (D0) and 1 (D1), 4 (D4), and 7 (D7) days thereafter. The SAPS II score, the capillary permeability, the primary site of infection, the antibiotic appropriateness, and the outcome at 28 days were also assessed.Results: In the interval D0–D7, the IgM increased significantly only in the S while remained stable in NS; the IgA significantly increased in both groups; the IgG did not vary significantly in both groups. At D4, the capillary permeability significantly decreased in S but not in NS.Conclusions: The kinetics of the different classes of Ig after eIg were different between S and NS. This could be related either to (a) different capillary permeability in the two groups or to (b) higher Ig consumption in NS. Further studies to confirm the benefits of eIg in the treatment of sepsis syndrome and to define the specific target population and the correct eIg dose are warranted.

Extracellular vesicles (EVs) are lipid bilayer nano-dimensional spherical structures and act mainly as signaling mediators between cells, in particular modulating immunity and inflammation. Milk-derived EVs (mEVs) can have immunomodulatory and anti-inflammatory effects, and milk is one of the most promising food sources of EVs. In this context, this study aimed to evaluate bovine mEVs anti-inflammatory and immunomodulating effects on an in vitro co-culture (Caco-2 and THP-1) model of intestinal inflammation through gene expression evaluation with RT-qPCR and cytokine release through ELISA. After establishing a pro-inflammatory environment due to IFN-γ and LPS stimuli,CXCL8, IL1B, TNFA, IL12A, IL23A, TGFB1, NOS2,andMMP9were significantly up-regulated in inflamed Caco-2 compared to the basal co-culture. Moreover, IL-17, IL-1β, IL-6, TNF-α release was increased in supernatants of THP-1. The mEV administration partially restored initial conditions with an effective anti-inflammatory activity. Indeed, a decrease in gene expression and protein production of most of the tested cytokines was detected, together with a significant gene expression decrease inMMP9and the up-regulation ofMUC2andTJP1. These results showed a fundamental capability of mEVs to modulate inflammation and their potential beneficial effect on the intestinal mucosa.

Papillomavirus (PV) infections may be related to anogenital lesions and cancer development in humans and several other animal species. To date, 11 different PVs have been reported in horses. Among them, a newly described PV named Equus caballus Papillomavirus Type9 (EcPV9) was thus far only reported in the semen of a stallion with penile lesions in Australia. This study reports for the first time the presence of EcPV9 in asymptomatic Italian horses. From July 2020 to January 2022, genital brush samples were collected from 209 horses with no apparent signs of neoplastic disease and no PV-associated lesions, clinically examined at the Didactic Veterinary University Hospital (OVUD) of Perugia and at the Veterinary University Hospital (OVU) of Turin. Brushes were submitted to real-time PCR targeting the EcPV9-L1 region. The first amplification targeted a region of ~116 bp, followed by the amplification and sequencing of ~533 bp of the positive samples. EcPV9-L1 DNA was found in eleven horses (5.3%), all female and mainly English Thoroughbred. Co-infection with EcPV2-L1 was found in 7 out of the 11 EcPV9-L1 positive horses (63.6%). This study contributes to the description of the prevalence of exposure or infection of EcPVs in the horse population in Italy, for which data are still limited. In this regard, here we provide a phylogenetic analysis and the completely reconstructed viral genomes of two Italian EcPV type 9 isolates, as well as four EcPV type 2 obtained from co-infected animals.

Cognitive impairment, also known as cognitive decline, can occur gradually or suddenly and can be temporary or more permanent. It represents an increasingly important public health problem and can depend on normal aging or be linked to different neurodegenerative disorders, including Alzheimer’s disease (AD). It is now well-established that lifestyle factors including dietary patterns play an important role in healthy aging as well as in the prevention of cognitive decline in later life. Among the natural compounds, dietary polyphenols including phenolic acids have been recently the focus of major attention, with their supplementation being associated with better cognitive status and prevention of cognitive decline. Despite their therapeutic potential, human studies investigating the relation between phenolic acids intake and cognitive outcomes are rather scarce. In this review, we provide preclinical evidence that different dietary polyphenols such as rosmarinic acid, ellagic acid, and cinnamic aldehyde can exert neuroprotective and pro-cognitive activities through different molecular mechanisms including the modulation of pro-oxidant and antioxidant machinery as well as inflammatory status. Future and more numerous in vivo studies are needed to strengthen the promising results obtained at the preclinical level. Despite the excellent pharmacokinetic properties of phenolic acids, which are able to be accumulated in the brain at pharmacologically relevant levels, future studies should also identify which among the different metabolites produced as a consequence of phenolic acids’ consumption may be responsible for the potential neuroprotective effects of this subgroup of polyphenols.

Vesicle biogenesis, trafficking and signaling via Endoplasmic reticulum-Golgi network support essential developmental processes and their disruption lead to neurodevelopmental disorders and neurodegeneration. We report that de novo missense variants in ARF3, encoding a small GTPase regulating Golgi dynamics, cause a developmental disease in humans impairing nervous system and skeletal formation. Microcephaly-associated ARF3 variants affect residues within the guanine nucleotide binding pocket and variably perturb protein stability and GTP/GDP binding. Functional analysis demonstrates variably disruptive consequences of ARF3 variants on Golgi morphology, vesicles assembly and trafficking. Disease modeling in zebrafish validates further the dominant behavior of the mutants and their differential impact on brain and body plan formation, recapitulating the variable disease expression. In-depth in vivo analyses traces back impaired neural precursors’ proliferation and planar cell polarity-dependent cell movements as the earliest detectable effects. Our findings document a key role of ARF3 in Golgi function and demonstrate its pleiotropic impact on development.

The introduction of massive parallel sequencing has contributed to a decline in sequencing costs. In recent years, whole-exome sequencing (WES) and whole-genome sequencing (WGS) have been increasingly adopted for diagnostic purposes in individuals with suspected genetic diseases. However, a debate is still ongoing in the scientific community about the superiority of WGS over WES in terms of cost-effectiveness. The aim of this study is to assess whether WGS, for the pediatric population with suspected genetic disorders, is cost-effective with respect to WES and chromosomal microarray (CMA) by pooling incremental net benefits.Articles were retrieved from PubMed, Web of Science, Embase and Scopus from 2015 to 2021. The dominance ranking matrix (DRM) tool was adopted to provide a qualitative synthesis of all the included studies. Incremental net benefits (INBs) were estimated and meta-analysis was implemented to pool INBs across studies.The database search identified 1600 publications of which four articles were considered eligible for the meta-analysis. The pooled INB of WGS over WES was estimated at I$4073 (95% CI I$2426 - I$5720). The pooled INB of WGS over CMA amounted to I$6003 (95% CI I$2863 - I$9143).WGS could be cost-effective in the diagnostic workup of affected infants and children. Further economic evaluations however are needed for comparing WGS versus WES and confirm the present conclusions.

Equine Papillomavirus 2 (EcPV2) is responsible for squamous cell carcinomas (eSCCs) of external genitalia of both male and female horses. However, few studies report the EcPV2 prevalence among healthy horses. Currently, the lack of these data does not permit identifying at-risk populations and, thus, developing screening protocols aimed at the early detection of the infection, as for humans. The aim of our study was to estimate the genoprevalence of EcPV2 in clinically healthy horses in Italy and to evaluate their innate immune response. For this purpose, penile and vulvar swabs of 234 healthy horses were collected through sampling with sterile cytobrushes. Nucleic acids were isolated and EcPV2-L1 presence (DNA) and gene expression (RNA) were checked by RT-qPCR. Our results showed EcPV2-L1 DNA presence in 30.3% of the samples and L1 expression in 48% of the positive samples. No statistically significant differences were found in genoprevalence in relation to sex, age, and origin, while, concerning breeds, the Thoroughbred had the highest risk of infection. Concerning specifically the mares, 40.2% of them resulted in being positive for EcPV2; our findings show a major positivity in pluriparous (p = 0.0111) and mares subjected to natural reproduction (p = 0.0037). Moreover, samples expressing L1 showed an increased expression of IL1B (p = 0.0139) and IL12p40 (p = 0.0133) and a decreased expression of RANKL (p = 0.0229) and TGFB (p = 0.0177). This finding suggests the presence of an effective immune response, which could explain the low incidence of SCCs in positive horses, despite a high EcPV2 genoprevalence (30%).

Extracellular Vesicles (EVs) are nano-sized double-lipid-membrane-bound structures, acting mainly as signalling mediators between distant cells and, in particular, modulating the immune response and inflammation of targeted cells. Milk and colostrum contain high amounts of EVs that could be exploited as alternative natural systems in antimicrobial fighting. The aim of this study is to evaluate cow colostrum-derived EVs (colosEVs) for their antimicrobial, anti-inflammatory and immunomodulating effects in vitro to assess their suitability as natural antimicrobial agents as a strategy to cope with the drug resistance problem. ColosEVs were evaluated on a model of neonatal calf diarrhoea caused by Escherichia coli infection, a livestock disease where antibiotic therapy often has poor results. Colostrum from Piedmontese cows was collected within 24 h of calving and colosEVs were immediately isolated. IPEC-J2 cell line was pre-treated with colosEVs for 48 h and then infected with EPEC/NTEC field strains for 2 h. Bacterial adherence and IPEC-J2 gene expression analysis (RT-qPCR) of CXCL8, DEFB1, DEFB4A, TLR4, TLR5, NFKB1, MYD88, CGAS, RIGI and STING were evaluated. The colosEVs pre-treatment significantly reduced the ability of EPEC/NTEC strains to adhere to cell surfaces (p = 0.006), suggesting a role of ColosEVs in modulating host–pathogen interactions. Moreover, our results showed a significant decrease in TLR5 (p < 0.05), CGAS (p < 0.05) and STING (p < 0.01) gene expression in cells that were pre-treated with ColosEVs and then infected, thus highlighting a potential antimicrobial activity of ColosEVs. This is the first preliminarily study investigating ColosEV immunomodulatory and anti-inflammatory effects on an in vitro model of neonatal calf diarrhoea, showing its potential as a therapeutic and prophylactic tool.

International audience; We propose a fast nonlinear method for assessing quantitatively both the existence and directionality of linear and nonlinear couplings between a pair of time series. We test this method, called Boolean Slope Coherence (BSC), on bivariate time series generated by various models, and compare our results with those obtained from different well-known methods. A similar approach is employed to test the BSC’s capability to determine the prevalent coupling directionality. Our results show that the BSC method is successful for both quantifying the coupling level between a pair of signals and determining their directionality. Moreover, the BSC method also works for noisy as well as chaotic signals and, as an example of its application to real data, we tested it by analyzing neurophysiological recordings from visual cortices.

El trabajo constituye una propuesta para la evaluación de la implementación del Plan de estudios de la Licenciatura en Trabajo Social, carrera fundante de la Facultad que concentra la mayor cantidad de estudiantes de la totalidad de propuestas académicas que la casa de estudios dispone en la actualidad. Se trabaja sobre la perspectiva de la evaluación como una herramienta estratégica en los procesos de gestión, generadora de insumos de calidad para la toma de decisiones. El problema sobre el cual se desarrolla la es la ausencia de un diseño evaluativo que permita implementar la evaluación prevista al finalizar la primera cohorte de la Licenciatura en Trabajo Social Plan 2015. Se intenta construir por lo tanto, un diseño evaluativo posible, que retome las distintas dimensiones que abarca la puesta en marcha de un proyecto curricular. Una articulación entre dos funciones fundamentales que caracterizan al trabajo de la Secretaria Académica: la mirada en los procesos de formación como política institucional y el aprendizaje sobre los procesos de implementación en el día a día, que permiten retroalimentar el diseño de las políticas institucionales en función de los ajustes situacionales necesarios. Todo esto en el marco de una concepción de planificación que concibe como proceso continuo el diseño, la implementación y la evaluación. En este sentido, la propuesta pondrá el foco en poder evaluar la consistencia entre el diseño del mismo y su implementación, a partir de cruzarlo con las trayectorias académicas reales de los estudiantes, la mirada de los equipos de trabajo implicados, los resultados esperados y la sistematización de la información producida en los años que llevó la culminación de la primera cohorte. Con relación a su metodología propone una combinación de métodos cuantitativos de análisis de datos y de métodos cualitativos vinculados principalmente al desarrollo de entrevistas y grupos focales., The work constitutes a proposal for the evaluation of the implementation of the Study Plan of the Bachelor of Social Work, the founding career of the Faculty that concentrates the largest number of students of the totality of academic proposals that the house of studies currently has. We work on the perspective of evaluation as a strategic tool in management processes, generating quality inputs for decision-making. The problem on which the is developed is the absence of an evaluative design that allows to implement the evaluation planned at the end of the first cohort of the Bachelor of Social Work Plan 2015. Therefore, an attempt is made to construct a possible evaluative design that takes up the different dimensions that the implementation of a curricular project encompasses. An articulation between two fundamental functions that characterize the work of the Academic Secretary: the look at the training processes as institutional policy and the learning about the implementation processes on a day-to-day basis, which allow feedback on the design of institutional policies based on of the necessary situational adjustments. All this within the framework of a planning concept that conceives design, implementation and evaluation as a continuous process. In this sense, the proposal will focus on being able to evaluate the consistency between its design and its implementation, starting from crossing it with the students' real academic trajectories, the look of the work teams involved, the expected results and the systematization of the information produced in the years that led to the completion of the first cohort. Regarding its methodology, it proposes a combination of quantitative data analysis methods and qualitative methods mainly linked to the development of interviews and focus groups., O trabalho constitui uma proposta de avaliação da implementação do Plano de Estudos do Bacharelado em Serviço Social, a carreira fundadora da Faculdade que concentra o maior número de alunos da totalidade das propostas acadêmicas que a casa de estudos possui atualmente. Atuamos na perspectiva da avaliação como ferramenta estratégica nos processos de gestão, gerando insumos de qualidade para a tomada de decisões. O problema em que o é desenvolvido é a ausência de um desenho avaliativo que permita implementar a avaliação prevista no final da primeira coorte do Plano de Licenciatura em Serviço Social 2015. Procura-se, portanto, construir um possível desenho avaliativo que assuma as diferentes dimensões que engloba a implementação de um projeto curricular. Uma articulação entre duas funções fundamentais que caracterizam a atuação do Secretário Acadêmico: o olhar para os processos formativos como política institucional e o aprendizado sobre os processos de implantação no dia a dia, que permitem retroalimentar o desenho de políticas institucionais com base sobre os ajustes situacionais necessários. Tudo isso dentro de um conceito de planejamento que concebe o projeto, a implementação e a avaliação como um processo contínuo. Nesse sentido, a proposta se concentrará em poder avaliar a consistência entre o seu desenho e sua implementação, a partir do cruzamento com as trajetórias acadêmicas reais dos alunos, o olhar das equipes de trabalho envolvidas, os resultados esperados e a sistematização dos informações produzidas nos anos que levaram à conclusão da primeira coorte. Quanto à sua metodologia, propõe uma combinação de métodos de análise de dados quantitativos com métodos qualitativos principalmente ligados ao desenvolvimento de entrevistas e grupos focais., Instituto de Investigaciones en Educación Superior

Milk extracellular vesicles (mEVs) seem to be one of the main maternal messages delivery systems. Extracellular vesicles (EVs) are micro/nano-sized membrane-bound structures enclosing signaling molecules and thus acting as signal mediators between distant cells and/or tissues, exerting biological effects such as immune modulation and pro-regenerative activity. Milk is also a unique, scalable, and reliable source of EVs. Our aim was to characterize the RNA content of cow, donkey, and goat mEVs through transcriptomic analysis of mRNA and small RNA libraries. Over 10,000 transcripts and 2000 small RNAs were expressed in mEVs of each species. Among the most represented transcripts, 110 mRNAs were common between the species with cow acting as the most divergent. The most represented small RNA class was miRNA in all the species, with 10 shared miRNAs having high impact on the immune regulatory function. Functional analysis for the most abundant mRNAs shows epigenetic functions such as histone modification, telomere maintenance, and chromatin remodeling for cow; lipid catabolism, oxidative stress, and vitamin metabolism for donkey; and terms related to chemokine receptor interaction, leukocytes migration, and transcriptional regulation in response to stress for goat. For miRNA targets, shared terms emerged as the main functions for all the species: immunity modulation, protein synthesis, cellular cycle regulation, transmembrane exchanges, and ion channels. Moreover, donkey and goat showed additional terms related to epigenetic modification and DNA maintenance. Our results showed a potential mEVs immune regulatory purpose through their RNA cargo, although in vivo validation studies are necessary.