Search

Microtubule severing enzymes implement a diverse range of tissue-specific molecular functions throughout development and into adulthood. Although microtubule severing is fundamental to many dynamic neural processes, little is known regarding the role of the family member Katanin p60 subunit A-like 1, KATNAL1, in central nervous system (CNS) function. Recent studies reporting that microdeletions incorporating the KATNAL1 locus in humans result in intellectual disability and microcephaly suggest that KATNAL1 may play a prominent role in the CNS; however, such associations lack the functional data required to highlight potential mechanisms which link the gene to disease symptoms. Here we identify and characterise a mouse line carrying a loss of function allele in Katnal1. We show that mutants express behavioural deficits including in circadian rhythms, sleep, anxiety and learning/memory. Furthermore, in the brains of Katnal1 mutant mice we reveal numerous morphological abnormalities and defects in neuronal migration and morphology. Furthermore we demonstrate defects in the motile cilia of the ventricular ependymal cells of mutants, suggesting a role for Katnal1 in the development of ciliary function. We believe the data we present here are the first to associate KATNAL1 with such phenotypes, demonstrating that the protein plays keys roles in a number of processes integral to the development of neuronal function and behaviour.Molecular Psychiatry advance online publication, 4 April 2017; doi:10.1038/mp.2017.54.

Background Physical restraints are frequently used for intensive care patients and are associated with substantial morbidity. The effects of common evidence-based critical care interventions on use of physical restraints remain unclear. Objective To identify independent predictors of new-onset use of physical restraints in critically ill adults. Methods Secondary analysis of a prospective cohort study involving 5 adult intensive care units in a tertiary care medical center in the United States. Use of physical restraints was determined via daily in-person assessments and medical record review. Mixed-effects logistic regression analysis was used to examine factors associated with new-onset use of physical restraints, adjusting for covariates and within-subject correlation among intensive care unit days. Results Of 145 patients who were free of physical restraints within 48 hours of intensive care unit admission, 24 (16.6%) had restraints newly applied during their stay. In adjusted models, delirium (odds ratio [OR], 5.09; 95% CI, 1.83-14.14), endotracheal tube presence (OR, 3.47; 95% CI, 1.22-9.86), and benzodiazepine administration (OR, 3.17; 95% CI, 1.28-7.81) significantly increased the odds of next-day use of physical restraints. Tracheostomy was associated with significantly lowered odds of next-day restraint use (OR, 0.13; 95% CI, 0.02-0.73). Compared with patients with a target sedation level, patients who were in a coma (OR, 2.56; 95% CI, 0.80-8.18) or deeply sedated (OR, 2.53; 95% CI, 0.91-7.08) had higher odds of next-day use of physical restraints, and agitated patients (OR, 0.08; 95% CI, 0.00-2.07) were less likely to experience restraint use. Conclusion Several potentially modifiable risk factors are associated with next-day use of physical restraints.

This work was completed through funding provided by the BBSRC [BB/L005077/1 and BB/M019985/1] and Wellcome Trust [202952/Z/16/Z].

Approximately one-third of all mammalian genes are essential for life. Phenotypes resulting from knockouts of these genes in mice have provided tremendous insight into gene function and congenital disorders. As part of the International Mouse Phenotyping Consortium effort to generate and phenotypically characterize 5,000 knockout mouse lines, here we identify 410 lethal genes during the production of the first 1,751 unique gene knockouts. Using a standardized phenotyping platform that incorporates high-resolution 3D imaging, we identify phenotypes at multiple time points for previously uncharacterized genes and additional phenotypes for genes with previously reported mutant phenotypes. Unexpectedly, our analysis reveals that incomplete penetrance and variable expressivity are common even on a defined genetic background. In addition, we show that human disease genes are enriched for essential genes, thus providing a dataset that facilitates the prioritization and validation of mutations identified in clinical sequencing efforts.

Part of the responsibility of a professional society is to establish the expectations for appropriate behavior for its members. Some codes are so essential to a society that the code itself becomes the central document defining the organization and its tenets, as we see with the Hippocratic Oath. In that tradition, we have revised the code of professional conduct for the Neurocritical Care Society into its current version, which emphasizes guidelines for personal behavior, relationships with fellow members, relationships with patients, and our interactions with society as a whole. This will be a living document and updated as the needs of our society change in time.Available online: http://www.neurocriticalcare.org/about-us/bylaws-procedures-and-code-professional-conduct (1) Code of professional conduct (this document) (2) Leadership code of conduct (3) Disciplinary policy.

Studies have shown that individuals influence their health outcomes, both positively and negatively, through their illness representation. To date, no studies describe the illness representation of persons with systolic heart failure, a significant contributor of morbidity and mortality in older adults. The purpose of this study was to describe illness representation in heart failure. Twenty-two subjects with New York Heart Association class II or III systolic heart failure were recruited at a university-based heart failure clinic. Illness representation was measured using the revised Illness Perception Questionnaire. The means on each of the 9 subscales were found to be significantly different from the neutral point of 3. The results suggest that participants believed that their heart failure was a chronic, cyclic disease with serious consequences that they could control through treatment. In addition, participants believed that they understood their heart failure and did not have a negative affective response to their heart failure.