ATP13A2/PARK9 regulates endo-/lysosomal cargo sorting and proteostasis through a novel PI(3, 5)P2-mediated scaffolding function.

ATP13A2 (also called PARK9), is a transmembrane endo-/lysosomal-associated P5 type transport ATPase. Loss-of-function mutations in ATP13A2 result in the Kufor-Rakeb Syndrome (KRS), a form of autosomal Parkinson's disease (PD). In spite of a growing interest in ATP13A2, very little is known about its physiological role in stressed cells. Recent studies suggest that the N-terminal domain of ATP13A2 may hold key regulatory functions, but their nature remains incompletely understood. To this end, we generated a set of melanoma and neuroblastoma cell lines stably overexpressing wild-type (WT), catalytically inactive (D508N) and N-terminal mutants, or shRNA against ATP13A2. We found that under proteotoxic stress conditions, evoked by the proteasome inhibitor Bortezomib, endo-/lysosomal associated full-length ATP13A2 WT, catalytically-inactive or N-terminal fragment mutants, reduced the intracellular accumulation of ubiquitin-conjugated (Ub) proteins, independent of autophagic degradation. In contrast, ATP13A2 silencing increased the intracellular accumulation of Ub-proteins, a pattern also observed in patient-derived fibroblasts harbouring ATP13A2 loss-of function mutations. In treated cells, ATP13A2 evoked endocytic vesicle relocation and increased cargo export through nanovesicles. Expression of an ATP13A2 mutant abrogating PI(3,5)P2 binding or chemical inhibition of the PI(3,5)P2-generating enzyme PIKfyve, compromised vesicular trafficking/nanovesicles export and rescued intracellular accumulation of Ub-proteins in response to proteasomal inhibition. Hence, our study unravels a novel activity-independent scaffolding role of ATP13A2 in trafficking/export of intracellular cargo in response to proteotoxic stress.

The effect of continuous pressure monitoring on strategic shifting of medical inpatients at risk for PUs.

OBJECTIVE: To assess the impact of continuous pressure imaging technology on strategic turning of patients by health professionals. METHOD: This pilot study of a newly-developed continuous pressure imaging technology (XSENSOR ForeSite PatientTurn System) involved two phases of videotaped observation of medical inpatients, with each patient serving as his/her own control: a control phase in which continuous pressure imaging was not available to health-care providers and an intervention phase where it was. The primary outcome was to determine whether access to the technology influenced the rate of patient turns/shifts by nursing staff. Secondary outcomes included a comparison of the rates of other care provider shifts, patient self-shifts, and family assisted shifts. Qualitative data regarding nurse and patient/family perspectives were also obtained. RESULTS: Complete control/intervention data were available for nine patients.The mean rate of two-person assisted turns was 0.274 +/- 0.087 turns per hour in the control phase versus 0.413 +/- 0.091 turns per hour in the intervention phase (p = 0.08). For the combined endpoint of two-person assisted turns or patient transfers off the bed into a wheelchair/chair, there was a statistically significant difference in the mean number of turns per hour: mean of 0.491 +/- 0.271 turns per hour for the intervention group versus 0.327 +/- 0.235 turns per hour for the control group (p = 0.04). Provider interviews confirmed that nurses used information from the technology to inform their patient shifting strategies and behaviours. CONCLUSION: This pilot study provides some initial data supporting the hypothesis that continuous pressure imaging technology could positively impact the frequency of patient turns by care providers, as well as provide impetus to inspect specific skin locations,thereby providing a potential targeted risk mitigation strategy for the development of pressure ulcers. DECLARATION OF INTEREST: Funding for the study was obtained from PreCarn Inc., an independent, nonprofit company supporting the pre-commercial development of new technologies, and from the Alberta Enterprise and Advanced Education (formally Alberta Advanced Education and Technology). The industry partner, XSENSOR, was involved in setup and maintenance of the technology, but was not involved in the evaluative research protocol. Specifically, XSENSOR personnel were not involved in the collection, coding, or analysis of outcome data, nor in the compilation and writing of this paper. None of the listed authors have any conflicts of interest, financial or otherwise, relating to the technology tested.

Trauma care system in Iran.

OBJECTIVE: The high burden of injuries in Iran necessitates the establishment of a comprehensive trauma care system. The purpose of this paper is to describe the current status of trauma system regarding the components and function. METHODS: The current status of trauma system in all components of a trauma system was described through expert panels and semi-structured interviews with trauma specialists and policy makers. RESULTS: Currently, various organizations are involved in prevention, management and rehabilitation of injuries, but an integrative system approach to trauma is rather deficient. There has been ongoing progress in areas of public education through media, traffic regulation reinforcement, hospital care and prehospital services. Meanwhile, there are gaps regarding financing, legislations and education of high risk groups. The issues on education and training standards of the front line medical team and continuing education and evaluation are yet to be addressed. Trauma registry has been piloted in some provinces, but as it needs the well-developed infrastructure (regarding staff, maintenance, financial resources), it is not yet established in our system of trauma care. CONCLUSIONS: It seems that one of the problems with trauma care in Iran is lack of coordination among trauma system organizations. Although the clinical management of trauma patients has improved in our country in the recent decade, decreasing the burden of injuries necessitates an organized approach to prevention and management of trauma in the context of a trauma system.

A new modified multi-electrode stimulation method for ECAP recording in cochlear implant.

Cochlear implant systems are based on stimulation of the auditory nerve fibers by electrical current with implanted electrodes. In the clinical tests, based on stimulation by electrical current and recording the evoked compound action potential (CCAP) same as neural response telemetry (NRT), electrical behavior and population distribution of the nerve fibers can be evaluated. Stimulation parameter in mimicking the normal hearing can be determined by the results of these tests. Condition of these tests is different from the actual stimulation for hearing, both in amplitude and time sequence of the stimulation current pulses. Therefore, there are some problems in the mapping the test results to stimulation parameters. At this paper, we have presented a new selective nonsimultaneous multi-electrode stimulation (NSMES) method based on applying the inhibitory pre-pulses by lateral electrodes that changes the initial conditions of the fibers to focus on the target fibers. The results of simulations show that this method will penalize undesired population distribution of the remained excitable fibers and it has been distinguished from the desired one. To estimate the electrical behavior of the fibers in normal use of the system for hearing, which has much more pulse rate than the test condition, we assumed a probabilistic function for recovery time of the fibers to map the test results to hearing condition parameters. Simulation results show that the stimulation electrode array parameters can be determined more accurately by the presented modification qualitatively and quantitatively.

A new fuzzy logic filter for image enhancement.

This paper presents a new fuzzy-logic-control based filter with the ability to remove impulsive noise and smooth Gaussian noise, while, simultaneously, preserving edges and image details efficiently. To achieve these three image enhancement goals, we first develop filters that have excellent edge-preserving capability but do not perform well in smoothing Gaussian noise. Next, we modify the filters so that they perform all three image enhancement tasks. These filters are based on the idea that individual pixels should not be uniformly fired by each of the fuzzy rules. To demonstrate the capability of our filtering approach, it was tested on several different image enhancement problems. These experimental results demonstrate the speed, filtering quality, and image sharpening ability of the new filter.