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Abstract Valvular heart disease is an increasing population health problem and, especially in the elderly, a significant cause of morbidity and mortality. The current treatment options, such as mechanical and bioprosthetic heart valve replacements, have significant restrictions and limitations. Considering the increased life expectancy of our aging population, there is an urgent need for novel heart valve concepts that remain functional throughout life to prevent the need for reoperation. Heart valve tissue engineering aims to overcome these constraints by creating regenerative, self-repairing valve substitutes with life-long durability. In this review, we give an overview of advances in the development of tissue engineered heart valves, and describe the steps required to design and validate a novel valve prosthesis before reaching first-in-men clinical trials. In-silico and in-vitro models are proposed as tools for the assessment of valve design, functionality and compatibility, while in-vivo preclinical models are required to confirm the remodeling and growth potential of the tissue engineered heart valves. An overview of the tissue engineered heart valve studies that have reached clinical translation is also presented. Final remarks highlight the possibilities as well as the obstacles to overcome in translating heart valve prostheses into clinical application. [ABSTRACT FROM AUTHOR]

Overactivity of the dopaminergic system in the brain is considered to be a contributing factor to the development and symptomatology of schizophrenia. Therefore, the GABAergic control of dopamine functions was assessed by disrupting the gene encoding the α3 subunit of the GABAA receptor. α3 knockout (α3KO) mice exhibited neither an obvious developmental defect nor apparent morphological brain abnormalities, and there was no evidence for compensatory up-regulation of other major GABAA-receptor subunits. Anxiety-related behavior in the elevated-plus-maze test was undisturbed, and the anxiolytic-like effect of diazepam, which is mediated by α2-containing GABAA receptors, was preserved. As a result of the loss of α3 GABAA receptors, the GABA-induced whole-cell current recorded from midbrain dopamine neurons was significantly reduced. Spontaneous locomotor activity was slightly elevated in α3KO mice. Most notably, prepulse inhibition of the acoustic startle reflex was markedly attenuated in the α3KO mice, pointing to a deficit in sensorimotor information processing. This deficit was completely normalized by treatment with the antipsychotic D2-receptor antagonist haloperidol. The amphetamine-induced hyperlocomotion was not altered in α3KO mice compared with WT mice. These results suggest that the absence of α3- subunit-containing GABAA receptors induces a hyperdopaminergic phenotype, including a severe deficit in sensorimotor gating, a common feature among psychiatric conditions, including schizophrenia. Hence, agonists acting at α3-containing GABAA receptors may constitute an avenue for an effective treatment of sensori- motor-gating deficits in various psychiatric conditions. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the presence of CT7 T cells in the bone marrow of patients with multiple myeloma (MM). It analyzes the CT7-specific CD4+ T cells in peripheral blood mononuclear cell of MM patients through in vitro stimulation approach. Findings reveal that CD4+ CT7 T-cell responses in patients were controlled by T regulatory cells (Tregs).

A letter to the editor about the dominant cancer-testis antigen by humoral immune responses in patients with multiple myeloma is presented.