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Hearing instruments (HIs) aim at helping people with hearing impairment who often have difficulties to understand speech in noisy environments. This chapter provides an overview of the current technological trends and challenges in the field of HI applications. It covers the state-of-the-art of signal-processing algorithms used in modern digital HIs. Focus is given on the extensions of such algorithms for applications, where microphone signals are employed from both the left and right HIs (binaural case). Furthermore, the chapter refers to the challenges for the optimal parametrization and steering of the HI algorithms. The concepts of environment classification for automatically controlling the settings of an HI in different listening situations are discussed and a brief summary of sound-source-localization methods is given. Finally, this chapter discusses the current trends of adding sensors in HIs that can potentially further enhance the hearing performance of the devices and improve the life of hearing-impaired people.

The IKK complex represents the core component of the canonical pathway of NF-κB activation. Any mutation affecting it should therefore impact on NF-κB signaling to some extent. Nevertheless, since IKK-1 and IKK-2 have also been shown to play NF-κB-independent functions, those functions may be affected as well, complicating the picture. Generating further complexity is the location of NEMO on the X-chromosome that can cause lyonization-related effects. Over the years, all this predictable intricacy has been confirmed with the discovery of a set of seemingly disparate pathologies, complemented with pathologies caused by mutations of NF-κB subunits regulating exclusively the canonical pathway. They allowed to confirm the essential role of canonical NF-κB activation in innate and acquired immunity or inflammation but also revealed new functions of this pathway.

Activation of NF-κB signaling pathways requires ubiquitination processes controlled by a collection of E3 ligases and deubiquitinases. More specifically, modifications by K63- and linear-linked polyubiquitin chains allow the recruitment and activation of essential kinases such as TAK1 and IKK1/IKK2. Human pathologies linked to impaired ubiquitination were recently identified with mutations affecting LUBAC, the main E3 complex catalyzing linear chain formation; TRAF6, a key regulator in immunity and skin appendages development; and CYLD, a deubiquitinase negatively regulating the NF-κB activation process at several levels. They provide an alternative entry point to analyze the consequences of deregulated NF-κB activity.

The family of inducible nuclear factor κB (NF-κB) transcription factors plays critical functions as sensor of stressful changes in the cell environment modulating the expression of hundreds of genes that regulate key physiological processes such as immunity, inflammation, cell death, and cell proliferation. Located in the cytoplasm, NF-κB proteins can be activated by a plethora of stimuli in a large variety of cell types. Two pathways of NF-κB activation exist, a canonical one and a non-canonical one, both of them requiring intricate molecular interplays involving adaptor proteins and enzymes that control phosphorylation and ubiquitination events. This culminates in translocation of NF-κB in the nucleus and modulation of gene expression.

The inherited diseases caused by impaired NF-κB signaling display a broad range of abnormalities affecting the immune and vascular systems, the skin, the bones, and the central nervous system (CNS). On one side, this allows to compare these abnormalities with those observed in mouse strains affected for the same components and, on the other, to assign specific defects in humans to discrete molecular impairments. All these information should contribute to the design and validation of therapeutic treatments.