Mitochondrial Channels and their Role in Cardioprotection

Mitochondria play a pivotal role in cardioprotection. The major cardioprotective mechanism is ischemic preconditioning (IpreC), through which short periods of ischemia protect a subsequent prolonged acute ischemic episode. Mitochondria channels, particularly the potassium channels (mitoK) such as ATP-dependent and calcium-activated potassium channels, have been suggested as trigger or end effectors in IpreC. Activators of mitoK are promising therapeutic agents for the treatment of the myocardial injury due to ischemic episodes. In this chapter, we are summarizing our current knowledge on the physiology function of different mitochondrial channels with a focus on the potassium channels and their mechanism in cardioprotection. Furthermore, the currently under development therapy by targeting the mitochondrial channels for the treatment of heart failure are also discussed.

Early Intervention in Severe Autism: Positive Outcome Using Exchange and Development Therapy

Early intervention programs positively affect key behaviors for children with autism spectrum disorder (ASD). However, most of these programs do not target children with severe autistic symptomatology associated with intellectual disability (ID). This study aimed to investigate the psychological and clinical outcomes of children with severe autism and ID enrolled in the Tailored and Inclusive Program for Autism—Tours (TIPA-T). The first step of the TIPA-T is the Exchange and Development Therapy (EDT): an individual neurofunctional intervention consisting of one-to-one exchanges between a child and a therapist taking place in a pared-down environment. It aims to rehabilitate psychophysiological abilities at the roots of social communication through structured sequences of “social play.” Cognitive and socio-emotional skills and general development were evaluated with the Social Cognitive Evaluation Battery scale and the Brunet–Lézine Scale—Revised, respectively, before and after 9 months of intervention in 32 children with ASD and ID. Autistic symptomatology was evaluated with the Behavior Summarized Evaluation—Revised scale at five time-points in a subset of 14 children, both in individual and group settings. Statistically significant post-intervention improvements were found in cognitive and socio-emotional skills. All but one child showed improvements in at least one social domain, and 78% of children gained one level in at least four social domains. Twenty-nine children improved in cognitive domains, with 66% of children improving in at least three cognitive domains. Autistic symptomatology evaluated in one-to-one settings significantly decreased with therapy; this reduction was observed in more than 85% of children. In group settings, autistic symptomatology also decreased in more than 60% of children. Global developmental age significantly increased by 3.8 months. The TIPA-T, including EDT in particular, improves socio-emotional skills of most children with ASD and reduces autistic symptomatology, yet with heterogeneous outcomes profiles, in line with the strong heterogeneity of profiles observed in ASD. At the group level, this study highlights the benefits of the TIPA-T for children with severe autism and associated ID. Assessment of autistic core symptoms showed an improvement of social interaction, both in one-to-one and group evaluations, demonstrating the generalizability of the skills learned during the EDT.

Aurora Kinase B Inhibition: A Potential Therapeutic Strategy for Cancer

Aurora kinase B (AURKB) is a mitotic serine/threonine protein kinase that belongs to the aurora kinase family along with aurora kinase A (AURKA) and aurora kinase C (AURKC). AURKB is a member of the chromosomal passenger protein complex and plays a role in cell cycle progression. Deregulation of AURKB is observed in several tumors and its overexpression is frequently linked to tumor cell invasion, metastasis and drug resistance. AURKB has emerged as an attractive drug target leading to the development of small molecule inhibitors. This review summarizes recent findings pertaining to the role of AURKB in tumor development, therapy related drug resistance, and its inhibition as a potential therapeutic strategy for cancer. We discuss AURKB inhibitors that are in preclinical and clinical development and combination studies of AURKB inhibition with other therapeutic strategies.

Antiphospholipid syndrome: diagnosis, development, therapy.

Приведен обзор литературы по механизму развития антифосфолипидного синдрома (АФС), тактика терапии. Представлены последние рекомендации Европейской антиревматической лиги (англ. European League Against Rheumatism, EULAR) по профилактике и лечению тромбозов при АФС. Обсуждены вопросы целесообразности терапии иммуносупрессивными препаратами при АФС. The review is dedicated the development and the treatment of antiphospholipid syndrome (APS), and the content of the recent guidelines of European League Against Rheumatism (EULAR) for prevention and treatment of thrombosis in APS. The immunosuppressive therapy advisability in APS is discussed.

The RNA-Binding Protein HuR in Digestive System Tumors

Human antigen R (HuR) is a member of the Hu family of RNA-binding proteins. This molecule, which was first described in tumors nearly two decades ago, has recently received much attention in tumor-related research because it regulates the expression of many tumor-associated molecules through posttranscriptional regulatory mechanisms, thereby affecting biological characteristics. It is suggested that HuR might be a novel therapeutic target and a marker for therapeutic response and prognostic assessment. Increasing evidence supports that HuR also plays critical roles in the development, therapy, and prognosis of digestive system tumors. Herein, we review the relationships between HuR and digestive system tumors, demonstrating the importance of HuR in digestive system tumor diagnosis.

Hepatitis-associated Aplastic Anaemia in Children

Background Children with idiopathic acute liver failure (IALF) are at a high risk of developing life-threatening bone marrow failure (BMF). The aim of the study was to describe the development, therapy and prognosis of this hepatitis-associated aplastic anaemia (HAAA) in comparison to isolated acquired aplastic anaemia. Results We retrospectively found 18 patients (9 female) of HAAA between 1984 and 2017 with an age of 1.4–16.4 years. Fifteen of them fulfilled the SAA criteria, 3 had a bone marrow hypoplasia. Eleven of these children received liver transplantation (LTx) (these were 11 of 42 (26%) children receiving LTx for IALF), 6 patients recovered without LTx. The first signs of BMF, thrombocytopaenia and leucocytopaenia, occurred before LTx in all cases. During the follow-up period 8 patients reached haematological remission, 6 received haematopoietic stem cell transplantation (HSCT). Seven children died in a median of 304 days after the first symptoms mostly because of bleedings and infections. To date, extensive investigations failed to detect a genetically, viral or immunological aetiology. No AA was diagnosed in the 41 patients receiving liver transplants during the same period for ALF of known aetiology. As a comparison group, we collected the data of patients with isolated SAA. 73% achieved a remission after Immunosuppressive therapy (IST) without HSCT, and none of them died during the follow-up period. Conclusion Blood counts should be examined early and regularly (0–22 days after onset) in patients with IALF. Aggressive treatment with LTx, IST and HSCT appears to improve the prognosis.

Collaborative technologies and knowledge management in psychiatric hospitals in South West Nigeria

This study examined the relationships among KM (knowledge creation, sharing), professional development, therapy team’s (TT’s) operation modes, interaction modes and collaborative technologies’ use determinants. A sample survey research design and mixed methods approach that combined quantitative research methods guided the study. Quantitative data was collected from 283 therapy team members in two psychiatric hospitals in Nigeria using a self-administered questionnaire. SPSS version 22 and SPSS (AMOS) version 23 were used to analyse the data. Knowledge creation and knowledge sharing impacted significantly on professional development. Therapy team members’ Intellectual capability, increased innovation, disciplinary specialisation and professional learning are dependent on their creation and sharing of knowledge. Disciplinary socialisation, transdisciplinary socialisation, collaboration and communication summarise their day-to-day operations. Collaboration and knowledge creation and sharing have a very strong relationship. Working together with colleagues is directly related with creation and sharing of both tacit and explicit knowledge. Learning by practical experience, brainstorming of ideas, sharing of clinical information and best practice of medical profession are positively impacted by collaboration. Documentation of such knowledge is needed to promote its sharing and safeguard knowledge loss in psychiatric hospitals.