Mutations in KCNK4 that Affect Gating Cause a Recognizable Neurodevelopmental Syndrome.

Aberrant activation or inhibition of potassium (K+) currents across the plasma membrane of cells has been causally linked to altered neurotransmission, cardiac arrhythmias, endocrine dysfunction, and (more rarely) perturbed developmental processes. The K+ channel subfamily K member 4 (KCNK4), also known as TRAAK (TWIK-related arachidonic acid-stimulated K+ channel), belongs to the mechano-gated ion channels of the TRAAK/TREK subfamily of two-pore-domain (K2P) K+ channels. While K2P channels are well known to contribute to the resting membrane potential and cellular excitability, their involvement in pathophysiological processes remains largely uncharacterized. We report that de novo missense mutations in KCNK4 cause a recognizable syndrome with a distinctive facial gestalt, for which we propose the acronym FHEIG (facial dysmorphism, hypertrichosis, epilepsy, intellectual disability/developmental delay, and gingival overgrowth). Patch-clamp analyses documented a significant gain of function of the identified KCNK4 channel mutants basally and impaired sensitivity to mechanical stimulation and arachidonic acid. Co-expression experiments indicated a dominant behavior of the disease-causing mutations. Molecular dynamics simulations consistently indicated that mutations favor sealing of the lateral intramembrane fenestration that has been proposed to negatively control K+ flow by allowing lipid access to the central cavity of the channel. Overall, our findings illustrate the pleiotropic effect of dysregulated KCNK4 function and provide support to the hypothesis of a gating mechanism based on the lateral fenestrations of K2P channels.

Violence against health-care workers in a conflict affected city.

The problem of aggression towards health care staff is global. It negatively impacts on their psychological and physical well-being, and on their performance. This study was set to explore the exposure of healthcare personnel to different forms of violence and the influence of this violence on their work and life. A sample of 700 healthcare workers was collected from six major hospitals and 20 primary health care centers in Baghdad. The questionnaire inquired about exposure to any sort of violence including insult, assaults, and displacement, being arrested, kidnapped, and intentionally injured or threatened at the workplace. More than 85% of respondents reported exposure to violence. The most important reason for violence was the poor medical services and lack of hospital supplies (22.1%). Young doctors were significantly more exposed to violence, especially verbal, mostly during the day. A significant association was seen between exposure to physical violence, male gender and short duration of experience. The most significant source of violence was the patient's relatives.  There is an overwhelming surge of violence against health workers that may adversely reflect on their performance. Passing legislation that protects health workers against violence is an urgent need at this time of unrest.