Explore the vast range of titles available.

The fungus Ophidiomyces ophiodiicola is the etiologic agent of snake fungal disease. Recent findings date US occurrence at least as far back as 1945. We analyzed 22 free-ranging snakes with gross lesions consistent with snake fungal disease from museum collections from Europe. We found 5 positive samples, the oldest collected in 1959.

Here we report the discovery and partial characterization of a novel herpesvirus tentatively named Bufonid herpesvirus 1 (BfHV1) from severe dermatitis in free ranging common toads ( Bufo bufo ) in Switzerland. The disease has been observed in toads every year since 2014, in spring, during the mating season, at different and distant locations. The virus is found in the skin and occasionally in the brain of infected toads. The genome of the virus is at least 158 Kb long and contains at least 152 open reading frames with a minimal length of 270 nt. The genome of BfHV1 contains all the signature genes that are present in alloherpesviruses. Phylogenetic analysis based on the amino acid sequence of the DNA polymerase and terminase proteins positions the novel virus among the members of the genus Batrachovirus , family Alloherpesviridae . This is the first herpesvirus ever characterized in common toads.

The fungus Ophiodimyces ophiodiicola is the etiologic agent of snake fungal disease. Recent findings date US occurrence at least as far back as 1945. We analyzed 22 free-ranging snakes with gross lesions consistent with snake fungal disease from museum collections from Europe. We found 5 positive samples, the oldest collected in 1959.The fungus Ophiodimyces ophiodiicola is the etiologic agent of snake fungal disease. Recent findings date US occurrence at least as far back as 1945. We analyzed 22 free-ranging snakes with gross lesions consistent with snake fungal disease from museum collections from Europe. We found 5 positive samples, the oldest collected in 1959.

Background Treating advanced ovarian cancer (OC) is challenging due to the immunosuppressive tumor microenvironment. This study investigates tumor-immune cell interactions using organotypic spheroid models that simulate the in vivo microenvironment. Methods A dual-model spheroid system was established combining serous adenocarcinoma SKOV-3 cells with monocytes, pro-inflammatory (MΦ1) or anti-inflammatory (MΦ2) macrophages, or their derived exosomes (EXOs). In Model A, immune cells or EXOs were co-seeded with tumor cells to replicate early heterotypic aggregation. In Model B, immune cells or EXOs were introduced 24 h post-spheroid formation to simulate immune infiltration into established spheroids. Spheroid morphology was quantified by diameter and circularity, while the distribution of immune cells and EXOs was assessed via fluorescence intensity profiling in 2D and 3D. epithelial-to-mesenchymal transition (EMT) marker expression was analyzed to assess tumor cell phenotypic changes. Results Spheroids formed with SKOV-3 cells and ThP-1 monocytes developed a dense monocyte-enriched outer layer. Macrophage subtypes differentially influenced spheroid morphology: MΦ2 macrophages promoted the formation of multiple, loosely organized spheroids and increased N-cadherin expression, indicative of enhanced EMT. Similarly, MΦ-EXOs modulated EMT marker expression, underscoring the contribution of both direct cell interactions and paracrine signaling in regulating spheroid dynamics. Conclusions Macrophages and their exosomes play a critical role in modulating the architecture and functional behavior of spheroids, reflecting two key aspects of OC progression: the formation of immune cell-enriched spheroids in ascitic fluid and tumor-immune interactions at peritoneal metastatic sites. This model provides a clinically relevant platform for preclinical testing of therapeutic strategies targeting peritoneal dissemination in OC.

Liver fibrosis, characterized by scar tissue accumulation due to liver injury, poses significant barriers to liver-targeted gene therapy. Current clinical trials exclude patients with fibrosis, as intact liver architecture is considered essential for efficient and safe adeno-associated viral vector (AAV)-mediated gene delivery. Here, we show that liver fibrosis reduces the efficiency of hepatocyte transduction by AAV8 vectors across three mouse models with diverse fibrotic patterns. This inefficiency stems primarily from decreased vector uptake by the liver rather than loss of vector genomes due to hepatocyte turnover. Additionally, fibrosis alters blood vector clearance and redistributes AAV particles to extra-hepatic organs, such as spleen, lung, and kidney. At the cellular level, fibrosis decreases AAV genome content in hepatocytes while increasing it in non-parenchymal liver cells and splenic immune cells. Importantly, the capsid variant AAV-KP1 retains transduction efficiency in fibrotic livers, highlighting its potential for expanding gene therapy applications to fibrotic diseases. Ferriero et al . show that liver fibrosis reduces the efficiency of AAV-based gene therapy by limiting liver uptake and altering vector distribution to other organs. The impact of fibrosis varies depending on the AAV variant, highlighting the need for tailored approaches in fibrotic diseases.

Trofinetide is a first-in-class pharmacological treatment proposed for patients with Rett Syndrome. It is a long half-life derivative of glycine-proline-glutamate, the tripeptide normally excided from Insulin-like Growth Factor 1 upon degradation. Due to containing glutamate and glycine in its structure, trofinetide is thought to act through NMDA receptor modulation, thus providing a normalization of neuronal activity and survival. Trofinetide was tested in a series of short and long-term trials, showing good efficacy at improving scores on the Clinical Global Impression-Improvement scale and Rett Syndrome Behavior Questionnaire, with specific effect only on some subscales, ie General Mood subscale and Repetitive Face Movement subscale. No effects were documented on other subscales or on epilepsy, heart and bone -related symptoms. The main adverse effects of trofinetide, severe enough to determine discontinuation, include diarrhea, vomiting, and consequent weight loss. These may be scarcely avoidable, given the need to assume a very large amount of trofinetide per day. Other inherent limitations of use possibly regard the limited duration of drug supplies, as one bottle may last three days only, depending on weight, and the relatively high cost per bottle. Trofinetide has no direct competitors: single symptoms of the Rett Syndrome, for instance, seizures or aggressive behaviors, are currently treated with drugs that have been developed for patients without the Rett Syndrome. This leads to suboptimal efficacy and increased risk of adverse effects. The place in therapy of trofinetide is yet to be determined, based on the results of clinical trials, on its practical usability, and on the windows of opportunity for intervention. Moreover, trofinetide may be curative if given early enough during brain development, or merely symptomatic if given to young adults, and no data exist on this aspect. The place in therapy of trofinetide will require reassessment after competing treatments enter the market.

Exosomes are physiologically secreted nanoparticles recently established as natural delivery systems involved in cell-to-cell communication and content exchange. Due to their inherent targeting potential, exosomes are currently being harnessed for the development of anti-cancer therapeutics. Clinical trials evaluating their effectiveness are demonstrating safety and promising outcomes. However, challenging large-scale production, isolation, modification and purification of exosomes are current limitations for the use of naturally occurring exosomes in the clinic. Exosome mimetics hold the promise to improve the delivery of bioactive molecules with therapeutic efficacy, while achieving scalability and increasing bioavailability. In this study, we propose the development of Immune Derived Exosome Mimetics (IDEM) as a scalable approach to target and defeat ovarian cancer cells. IDEM were fabricated from monocytic cells by combining sequential filtration steps through filter membranes with different porosity and size exclusion chromatography columns. The physiochemical and molecular characteristics of IDEM were compared to those of natural exosomes (EXO). Nanoparticle Tracking Analysis confirmed a 2.48-fold increase in the IDEM production yields compared to EXO, with similar exosomal markers profiles (CD81, CD63) as demonstrated by flow cytometry and ELISA. To exploit the prospective of IDEM to deliver chemotherapeutics, doxorubicin (DOXO) was used as a model drug. IDEM showed higher encapsulation efficiency and drug release over time compared to EXO. The uptake of both formulations by SKOV-3 ovarian cancer cells was assessed by confocal microscopy and flow cytometry, showing an incremental drug uptake over time. The analysis of the cytotoxic and apoptotic effect of DOXO-loaded nanoparticles both in 2D and 3D culture systems proved IDEM as a more efficient system as compared to free DOXO, unraveling the advantage of IDEM in reducing side-effects while increasing cytotoxicity of targeted cells, by delivering smaller amount of the chemotherapeutic agent. The high yields of IDEM obtained compared to natural exosomes together with the time-effectiveness and reproducibility of their production method make this approach potentially exploitable for clinical applications. Most importantly, the appreciable cytotoxic effect observed on ovarian cancer systems sets the ground for the development of compelling nanotherapeutic candidates for the treatment of this malady and will be further evaluated.

Conduct Disorder (CD) is a psychiatric diagnosis characterized by a repetitive and persistent pattern of behaviour in which the basic rights of others and major age-appropriate social norms or rules are violated. Callous Unemotional (CU) traits are a meaningful specifier in subtyping CD for more severe antisocial and aggressive behaviours in adult psychopathology; they represent the affective dimension of adult psychopathy, but they can be also detected in childhood and adolescence. The CU traits include lack of empathy, sense of guilt and shallow emotion, and their characterization in youth can improve our diagnostic, prognostic and therapeutic abilities. A strong genetic liability, in interaction with parenting and relevant environmental factors, can lead to elevated levels of CU traits in children. We pointed out that CU traits can be detected in early childhood, may remain stable along the adolescence, but a decrease following intensive and specialized treatment is possible. We here provide a narrative review of the available evidences on CU traits in three main domains: aetiology (encompassing genetic liability and environmental risk factors), presentation (early signs and longitudinal trajectories) and treatments.

Background Depression is a prevalent and often persistent mental disorder, with onset frequently occurring during adolescence and associated with serious long-term consequences. Consequently, the availability of valid, age-appropriate, and easily administered screening instruments is essential. The Short Mood and Feelings Questionnaire (SMFQ) is a widely used tool, available in multiple languages, for the screening of depressive symptoms in young people. Although an Italian version of the SMFQ has already been used in previous studies, it has not yet undergone formal validation. The present study aimed to evaluate the psychometric properties of the Italian SMFQ, assess measurement invariance (MI) across sex and age, and provide preliminary normative data. Methods A sample of 580 adolescents (317 males, 263 females), aged 14–20 years, completed the Italian SMFQ along with additional instruments to assess validity: the Personality Assessment Questionnaire and the Strengths and Difficulties Questionnaire for convergent validity, and the Weinstein’s Noise Sensitivity Scale for divergent validity. Analyses focused on dimensionality, measurement invariance, reliability, and validity. Results As regards dimensionality, both one- and two-factor models showed adequate fit, with the two-factor model showing better fit. MI analyses supported full invariance across age for the 13-item version and partial invariance across sex. The 12-item version (excluding item 6) achieved full invariance across both sex and age. The scale showed good internal consistency and good convergent and divergent validity. Finally, given the significant effects of sex and age, normative data were computed as a function of both factors. Conclusions The Italian SMFQ demonstrated excellent psychometric properties for assessing depressive symptoms in adolescents. However, its use for clinical diagnostic purposes requires further validation through clinical studies.

Background Several studies have shown that during COVID-19 pandemic outbreak, emotional symptoms increased in the general population. Less is known about youths. Methods We surveyed a sample of Italian adolescents during the strictest quarantine period and assessed the effects of socio-demographic and psychological factors on current emotional symptoms. A convenient sample of 326 adolescents (age range 14–19 years) participated in a web-based survey. We collected data on several socio-demographic and psychological variables (summarized into three indexes: environmental context, changes in lifestyle, and worries about infection) and psychopathological symptoms (previous psychopathological status, current anxiety and depressive symptoms). Results Descriptive analysis showed that adolescents have experienced quarantine under very different conditions; they reported 47.5 and 14.1% of anxiety and depressive symptoms, respectively. Regression analyses indicated that previous psychopathological status and worries about infection are linked to anxiety and that female gender, previous psychopathological status (moderated by change in lifestyle), worse environmental context are linked to depression. Conclusion This study indicates that, facing the COVID-19 pandemic and its related safety measures, adolescents show relevant emotional symptoms and therefore should be monitored, assessed and supported.