Tinagl1 Gene Therapy Suppresses Growth and Remodels the Microenvironment of Triple Negative Breast Cancer

Triple negative breast cancer (TNBC) remains one of the most challenging subtypes of breast cancer to treat and is responsible for approximately 12% of breast cancer cases in the US per year. In 2019, the protein Tinagl1 was identified as a key factor for improved prognoses in certain TNBC patients. While the intracellular mechanism of action has been thoroughly studied, little is known about the role of Tinagl1 in the tumor microenvironment. In this study, we developed a lipid nanoparticle-based gene therapy to directly target the expression of Tinagl1 in tumor cells for localized expression. Additionally, we sought to characterize the changes to the tumor microenvironment induced by Tinagl1 treatment, with the goal of informing future choices for combination therapies including Tinagl1. We found that Tinagl1 gene therapy was able to slow tumor growth from the first dose and that the effects held steady for nearly a week following the final dose. No toxicity was found with this treatment. Additionally, the use of Tinagl1 increases the tumor vasculature by 3-fold but does not increase the tumor permeability or risk of metastasis. However, the increase in vasculature arising from Tinagl1 therapy reduced the expression of Hif1a significantly (p < 0.01), which may decrease the risk of drug resistance

Exposure to animal suffering, adult attachment styles, and professional quality of life in a sample of Italian veterinarians

Contextual and individual risk factors of veterinarians’ professional quality of life are being debated. Research suggests that attachment styles are relevant predictors of professional quality of life; however, their role in work-related well-being of veterinarians is yet to be ascertained. In the present study, self-report measures on exposure to animal suffering, adult attachment styles, and professional quality of life were administered to 1,445 Italian veterinarians (70% females) aged 24 to 74 years old; sociodemographic information and information on workload were also collected. Female gender, higher levels of ordinary workload, on-call hours per week, exposure to animal suffering, together with fearful and preoccupied attachment styles were significantly associated with lower levels of veterinarians’ quality of life. This suggests that work-related factors may combine with individual psychological features in promoting or disadvantaging the professional quality of life of veterinarians. Implications of these findings for promoting veterinarians’ quality of life and directions for future research are discussed

Language-Related Skills in Bilingual Children With Specific Learning Disorders

Purpose: The purpose of this study is to better understand the characteristics of the language-related skills of bilingual children with specific learning disorders (SLD). The aim is achieved by analyzing language-related skills in a sample of bilingual (Italian plus another language) and Italian monolingual children, with and without SLD. Patients and methods: A total of 72 minors aged between 9 and 11 were recruited and divided into four groups: 18 Italian monolingual children with SLD, 18 bilingual children with SLD, 18 Italian monolingual children without SLD, and 18 bilingual children without SLD. Each child underwent tests to evaluate different aspects of language skills: lexical and grammar, metalanguage and executive functions. Results: With regard to lexical and grammatical skills, the conditions of SLD and bilingualism both impact naming in terms of total number of errors for words with low frequency of use, while the condition of SLD has an effect on semantic errors for words with low frequency of use. The condition of bilingualism impacts on the total errors for words with high frequency of use and on circumlocution-type errors for words with low frequency of use. There were significant effects of bilingualism and SLD on the metalinguistic test for understanding implicit meaning, and an impact of SLD on phonological awareness was also found. Conclusion: The results suggest that both SLD and bilingualism have an effect on some lexical skills, in particular for words with low frequency of use. Both conditions, bilingualism and SLD, seem to impact on metalinguistic abilities that depend on lexical knowledge. These findings reinforce the importance of improving understanding of the neuropsychological profile of bilingual children with SLD

RNA Interference-Based Cancer Drugs: The Roadblocks, and the "Delivery" of the Promise

Nucleic acid-based therapeutics like synthetic small interfering RNAs have been exploited to modulate gene function, taking advantage of RNA interference (RNAi), an evolutionally conserved biological process. Recently, the world's first RNAi drug was approved for a rare genetic disorder in the liver. However, there are significant challenges that need to be resolved before RNAi can be translated in other genetic diseases like cancer. Current drug delivery platforms for therapeutic silencing RNAs are tailored to hepatic targets. RNAi therapies for nonhepatic conditions are still at early clinical phases. In this study, we discuss the critical design considerations in anticancer RNAi drug development, insights gained from initial clinical trials, and new strategies that are entering clinical development, shaping the future of RNAi in cancer

'Candidatus Phytoplasma solani' interferes with the distribution and uptake of iron in tomato

Background: \u2018Candidatus Phytoplasma solani\u2019 is endemic in Europe and infects a wide range of weeds and cultivated plants. Phytoplasmas are prokaryotic plant pathogens that colonize the sieve elements of their host plant, causing severe alterations in phloem function and impairment of assimilate translocation. Typical symptoms of infected plants include yellowing of leaves or shoots, leaf curling, and general stunting, but the molecular mechanisms underlying most of the reported changes remain largely enigmatic. To infer a possible involvement of Fe in the host-phytoplasma interaction, we investigated the effects of \u2018Candidatus Phytoplasma solani\u2019 infection on tomato plants (Solanum lycopersicum cv. Micro-Tom) grown under different Fe regimes. Results: Both phytoplasma infection and Fe starvation led to the development of chlorotic leaves and altered thylakoid organization. In infected plants, Fe accumulated in phloem tissue, altering the local distribution of Fe. In infected plants, Fe starvation had additive effects on chlorophyll content and leaf chlorosis, suggesting that the two conditions affected the phenotypic readout via separate routes. To gain insights into the transcriptional response to phytoplasma infection, or Fe deficiency, transcriptome profiling was performed on midrib-enriched leaves. RNA-seq analysis revealed that both stress conditions altered the expression of a large (> 800) subset of common genes involved in photosynthetic light reactions, porphyrin / chlorophyll metabolism, and in flowering control. In Fe-deficient plants, phytoplasma infection perturbed the Fe deficiency response in roots, possibly by interference with the synthesis or transport of a promotive signal transmitted from the leaves to the roots. Conclusions: \u2018Candidatus Phytoplasma solani\u2019 infection changes the Fe distribution in tomato leaves, affects the photosynthetic machinery and perturbs the orchestration of root-mediated transport processes by compromising shoot-to-root communication

Deconstructing the components model of addiction: an illustration through "addictive" use of social media.

The components model of addiction posits that all addictions share six components, namely salience, tolerance, mood modification, relapse, withdrawal, and conflict. This highly influential model has resulted in the development of numerous psychometric instruments that measure addictive behaviors according to these criteria. However, recent research suggests that, in the context of behavioral addictions, certain components constitute peripheral features that do not distinguish non-pathological from pathological behavior. Using "addictive" use of social media as a representative example, we examined this perspective by testing whether these six components actually assess central features of addiction, or whether some of them constitute peripheral features that are not indicative of a disorder. Four independent samples totaling 4,256 participants from the general population completed the Bergen Social Media Addiction Scale, a six-item psychometric instrument derived from the components model of addiction to assess social media "addiction". By performing structural equation modeling and network analyses, we showed that the six components did not form a unitary construct and, crucially, that some components (i.e., salience, tolerance) were not associated with measures assessing psychopathological symptoms. Taken together, these results suggest that psychometric instruments based on the components model conflate central and peripheral features of addiction when applied to behavioral addictions. This implies that such instruments pathologize involvement in appetitive behaviors. Our findings thus call for renewing the conceptualization and assessment of behavioral addictions

Further evidence for the bidimensionality of the components model of addiction: a reply to Amendola (2023)

In our original research article entitled “Deconstructing the components model of addiction: an illustration through “addictive” use of social media” (Fournier et al., 2023), we showed that the Bergen Social Media Addiction Scale, a six-item psychometric instrument derived from the components model of addiction to assess social media “addiction”, did not form a unitary, but a bidimensional construct in which some components (i.e., salience, tolerance) were not associated with psychopathological symptoms, thus conflating central and peripheral features of addiction. Subsequently, in a recent commentary, Amendola (2023) sought to determine whether our findings were driven by the use of data aggregated from multiple independent datasets, i.e., a decision we transparently acknowledged as a limitation in our original research article. Following their re-analysis, Amendola (2023) claimed to have demonstrated that a unidimensional model best fitted the data. However, they only reported results for a partial set of models relevant to this investigation. In the present reply, through a transparent assessment and reporting of all unidimensional and bidimensional models relevant to this investigation, we show that the bidimensionality of the Bergen Social Media Addiction Scale is, in fact, tenable, robust, and consistent across multiple independent datasets. In line with the growing evidence demonstrating that many sets of criteria involved in operationalizing behavioral addictions pathologize involvement in appetitive behaviors, these results highlight the necessity to renew the conceptualization and assessment of behavioral addictions

From Parental Bonding to Problematic Gaming: The Mediating Role of Adult Attachment Styles

Background: Research has found that parental failures of care during childhood and insecure attachment styles are positively associated with problematic gaming. From a developmental framework, it is possible to hypothesize that attachment styles mediate the relationship between parental bonding and problematic gaming. Methods: This hypothesis was tested in a sample of 598 videogame players (410 males, 68.56%) aged between 18 and 61 years old (M = 26.68, SD = 7.23). Participants were recruited through an online survey. Self-report instruments were administered to assess problematic gaming, parental bonding, and adult attachment styles. Results: Positive paternal care was a direct and negative predictor of problematic gaming, whereas maternal overprotection indirectly predicted problematic gaming through preoccupied attachment. Conclusions: These findings suggest that positive paternal care represents a protective factor for problematic gaming; in contrast, maternal overprotection might foster a negative view of the self in the child, which increases the risk to excessively use videogames, perhaps as a maladaptive coping strategy to regulate negative feelings. Prevention programs might be aimed to improve the responsiveness of parents towards the child’s emotional needs, to prevent the development of problematic gaming. Also, clinical intervention with problematic gamers might foster their feelings of security toward relationships, to promote both a healthier use of videogames and a better quality of life

Studies on the aetiology of kiwifruit decline: interaction between soil-borne pathogens and waterlogging

Aims: In 2012, Italian kiwifruit orchards were hit by a serious root disease of unknown aetiology (kiwifruit decline, KD) that still causes extensive damage to the sector. While waterlogging was soon observed to be associated with its outbreak, the putative role of soil microbiota remains unknown. This work investigates the role of these two factors in the onset of the disease. Methods: Historical rainfall data were analysed to identify changes that might explain KD outbreak and mimic the flooding conditions required to reproduce the disease in a controlled environment. A greenhouse experiment was thus designed, and vines were grown in either unsterilized (U) or sterilized (S) soil collected from KD-affected orchards, and subjected (F) or not (N) to artificial flooding. Treatments were compared in terms of mortality rate, growth, and tissue modifications. Results: KD symptoms were only displayed by FU-treated vines, with an incidence of 90%. Ultrastructural observations detected tyloses and fibrils in the xylem vessels of all plants, irrespective of the treatment. Phytopythium vexans and Phytopythium chamaehyphon, isolated from roots of FU plants, emerged as the associated microorganisms. Conclusions: We succeeded in reproducing KD under controlled conditions and confirmed its association with both waterlogging and soil-borne microorganism(s)

Insecure adult attachment and reflective functioning as mechanisms of the relationship between traumatic life events and suicidal ideation: A path analysis

The relationship between traumatic life events and increased suicide risk has been well reported in literature. However, the complex nature of suicidality phenomena still hinders our ability to comprehend the mediation mechanism underlying this association. In this study, we examined the mediating role of adult attachment and reflective functioning in the relationship between traumatic life events and suicidal ideation. Nine hundred and fifty Italian adults completed an online survey evaluating traumatic life events, adult attachment, reflective functioning and suicidal ideation. The path analysis showed that the positive relationship between traumatic life events and suicidal ideation was partially mediated by attachment anxiety and reflective functioning. From a clinical point of view, these results support the relevance of evaluating and improving patients’ ability to mentalize as a part of psychotherapeutic intervention aimed at reducing suicidality in people with a history of traumatic experiences and attachment anxiety