An interaction study in mammalian cells demonstrates weak binding of HSPB2 to BAG3, which is regulated by HSPB3 and abrogated by HSPB8

The ten mammalian small heat shock proteins (sHSPs/HSPBs) show a different expression profile, although the majority of them are abundant in skeletal and cardiac muscles. HSPBs form hetero-oligomers and homo-oligomers by interacting together and complexes containing, e.g., HSPB2/HSPB3 or HSPB1/HSPB5 have been documented in mammalian cells and muscles. Moreover, HSPB8 associates with the Hsc70/Hsp70 co-chaperone BAG3, in mammalian, skeletal, and cardiac muscle cells. Interaction of HSPB8 with BAG3 regulates its stability and function. Weak association of HSPB5 and HSPB6 with BAG3 has been also reported upon overexpression in cells, supporting the idea that BAG3 might indirectly modulate the function of several HSPBs. However, it is yet unknown whether other HSPBs highly expressed in muscles such as HSPB2 and HSPB3 also bind to BAG3. Here, we report that in mammalian cells, upon overexpression, HSPB2 binds to BAG3 with an affinity weaker than HSPB8. HSPB2 competes with HSPB8 for binding to BAG3. In contrast, HSPB3 negatively regulates HSPB2 association with BAG3. In human myoblasts that express HSPB2, HSPB3, HSPB8, and BAG3, the latter interacts selectively with HSPB8. Combining these data, it supports the interpretation that HSPB8-BAG3 is the preferred interaction

Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care

Introduction: This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide. Methods: A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified. Results: The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42%  60% of patients, and more often than sitagliptin or empagliflozin. Conclusion: The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management

Monoaminergic and histaminergic strategies and treatments in brain diseases

The monoaminergic systems are the target of several drugs for the treatment of mood, motor and cognitive disorders as well as neurological conditions. In most cases, advances have occurred through serendipity, except for Parkinson's disease where the pathophysiology led almost immediately to the introduction of dopamine restoring agents. Extensive neuropharmacological studies first showed that the primary target of antipsychotics, antidepressants, and anxiolytic drugs were specific components of the monoaminergic systems. Later, some dramatic side effects associated with older medicines were shown to disappear with new chemical compounds targeting the origin of the therapeutic benefit more specifically. The increased knowledge regarding the function and interaction of the monoaminergic systems in the brain resulting from in vivo neurochemical and neurophysiological studies indicated new monoaminergic targets that could achieve the efficacy of the older medicines with fewer side-effects. Yet, this accumulated knowledge regarding monoamines did not produce valuable strategies for diseases where no monoaminergic drug has been shown to be effective. Here, we emphasize the new therapeutic and monoaminergic-based strategies for the treatment of psychiatric diseases. We will consider three main groups of diseases, based on the evidence of monoamines involvement (schizophrenia, depression, obesity), the identification of monoamines in the diseases processes (Parkinson's disease, addiction) and the prospect of the involvement of monoaminergic mechanisms (epilepsy, Alzheimer's disease, stroke). In most cases, the clinically available monoaminergic drugs induce widespread modifications of amine tone or excitability through neurobiological networks and exemplify the overlap between therapeutic approaches to psychiatric and neurological conditions. More recent developments that have resulted in improved drug specificity and responses will be discussed in this review.peer-reviewe

Trabalhar com gêneros ou ensinar gramática? Entre a tradição e a inovação nas aulas de língua portuguesa = Working with genre or teaching grammar? Between tradition and innovation in the Portuguese language classes

Este artigo apresenta uma reflexão a partir da análise de duas aulas de Língua Portuguesa de uma 5ª série do Ensino Fundamental de uma escola pública situada no interior do Rio Grande do Sul. Objetivamos analisar as ações da professora e suas reações e de seus alunos em duas aulas: uma mais tradicional e outra caracterizada como inovadora. A pesquisa, de cunho etnográfico, caracteriza-se como estudo de caso de natureza qualitativointerpretativista. Para a geração dos dados, utilizamos diversos procedimentos: gravação emáudio e em vídeo e anotações de campo. Na aula tradicional, a professora segue os exercícios de um livro didático; já na aula inovadora, ao trabalhar com gêneros textuais, ela cria um ambiente em que os alunos interagem de forma mais espontânea e mais rica, e juntosconstroem conhecimento. Nessa aula, os alunos foram convidados a participar ativamente e seus conhecimentos de mundo foram mobilizados. Um trabalho nessa direção parece promover uma aprendizagem mais proveitosa da língua portuguesa.This paper presents a reflection based on the observation of two Portuguese classes of a 5th-grade class from a public elementaryschool in the Brazilian state of Rio Grande do Sul. Our aim is to analyze the teacher's actions and reactions towards student´s behavior and vice versa in two different moments: one traditional class and another classified as an innovative one. The ethnographic-based research is characterized by a qualitative-interpretive case study. We used several procedures to generate the data: audio and video recording and field notes taking. In the traditional class the teacher applies the exercises from a schoolbook, while in the other hand, in the innovative class she works with textual genres, creating an environment where studentsinteract more spontaneously and more fruitfully, and construct knowledge together. In this moment, students were invited to participate actively in class, and their world knowledge was mobilized. This way of conducting a class seems to promote more effective learning of the Portuguese language

The feasibility of using passive injectable transponders in field operations for individual identification of sheep in Italy

This trial evaluates the feasibility of using passive injectable transponders (PITs) in field operations by testing identification procedures on 185 one-year-old Biellese ewes reared under nomadic farming conditions. Commercial PITs of 3.85 ± 0.05 mm × 31.2 mm were used at two application sites, the armpit and the retro-auricular region. The two application sites were compared taking into account the ease of injection, animal reaction, injection duration, inflammatory response, PIT readability at up to 12 months post-injection and PIT recovery at the slaughterhouse. The injection site influenced the reaction of the animal and the ease and duration of the injection, but it did not affect the palpation and the reading findings during the rearing period. The injection site also influenced the PIT retrieval at the slaughterhouse depending on the operator who recovered the PIT. The readability values observed at the end of the observation period for both injection sites (83% in the retro-auricular region and 79% in the armpit region) were too low to be suitable for long-term animal identification. In addition, the failed retrieval of PITs at slaughter, determined the destruction of 40 (22%) carcases to avoid any risks in the food chain. These findings suggest that the limited use of PITs is indicated when other methods of electronic identification cannot be employed, while a wider application of the device tested in the present study is not recommended in farming practices

A Scoping Review on GIS Technologies Applied to Farmed Fish Health Management

Finfish aquaculture, one of the fastest growing intensive sectors worldwide, is threatened by numerous transmissible diseases that may have devastating impacts on its economic sustainability. This review (2010–2022) used a PRISMA extension for scoping reviews and a text mining approach to explore the extent to which geographical information systems (GIS) are used in farmed fish health management and to unveil the main GIS technologies, databases, and functions used to update the spatiotemporal data underpinning risk and predictive models in aquatic surveillance programmes. After filtering for eligibility criteria, the literature search provided 54 records, highlighting the limited use of GIS technologies for disease prevention and control, as well as the prevalence of GIS application in marine salmonid farming, especially for viruses and parasitic diseases typically associated with these species. The text mining generated five main research areas, underlining a limited range of investigated species, rearing environments, and diseases, as well as highlighting the lack of GIS-based methodologies at the core of such publications. This scoping review provides a source of information for future more detailed literature analyses and outcomes to support the development of geospatial disease spread models and expand in-field GIS technologies for the prevention and mitigation of fish disease epidemics

Management of anaemia in oncohaematological patients treated with biosimilar epoetin alfa: Results of an Italian observational, retrospective study

Background: Many patients with solid tumours or nonmyeloid haematopoietic tumours develop symptomatic anaemia, which has a major impact on quality of life (QoL). The efficacy of erythropoiesis-stimulating agents (ESAs) in improving QoL and reducing blood transfusions has been widely demonstrated. Binocrit® (biosimilar epoetin alfa) is an ESA indicated in the European Union for treating chemotherapy-induced anaemia. The aim of this study was to investigate the effect of Binocrit® on haemoglobin (Hb) levels in anaemic cancer patients in Italian clinical practice. Methods: The ANEMONE study was a national, longitudinal, retrospective, multicentre observational study. Patients had to be 18 years or older, with a solid tumour or non-Hodgkin's lymphoma, Hodgkin's disease or multiple myeloma, receiving chemotherapy, and treated with Binocrit® to manage chemotherapy-induced anaemia. The primary outcomes were the proportion of patients with a Hb increase â\u89¥3/41 g/dl during the first 4 weeks and with a Hb increase â\u89¥3/42 g/dl during the first 12 weeks. Results: A total of 245 patients were enrolled and 215 patients were evaluable for statistical analysis. In the first 4 weeks, 49.3% of patients showed an increase in Hb of â\u89¥3/41 g/dl: 45.5% in patients with solid tumours and 52.1% in patients with haematological malignancies. In the first 12 weeks, 51.6% of patients showed an increase in Hb of â\u89¥3/42 g/dl (48.4% solid tumours, 54.2% haematological diseases). Treatment with Binocrit® was well tolerated. Conclusions: These results confirm the effectiveness and safety of Binocrit® for chemotherapy-induced anaemia in routine practice in patients with solid tumours, lymphoma and myeloma

The Pivotal Role of Protein Phosphatase 2A (PP2A) in Brain Tumors

Protein phosphatase 2A (PP2A) is a highly complex heterotrimeric Ser/Thr phosphatase that regulates many cellular processes. PP2A is dysregulated in several human diseases, including oncological pathology; interestingly, PP2A appears to be essential for controlling cell growth and may be involved in cancer development. The role of PP2A as a tumor suppressor has been extensively studied and reviewed. To leverage the potential clinical utility of combination PP2A inhibition and radiotherapy treatment, it is vital that novel highly specific PP2A inhibitors be developed. In this review, the existing literature on the role of PP2A in brain tumors, especially in gliomas and glioblastoma (GBM), was analyzed. Interestingly, the review focused on the role of PP2A inhibitors, focusing on CIP2A inhibition, as CIP2A participated in tumor cell growth by stimulating cell-renewal survival, cellular proliferation, evasion of senescence and inhibition of apoptosis. This review suggested CIP2A inhibition as a promising strategy in oncology target therapy