Mobile zinc increases rapidly in the retina after optic nerve injury and regulates ganglion cell survival and optic nerve regeneration.

Retinal ganglion cells (RGCs), the projection neurons of the eye, cannot regenerate their axons once the optic nerve has been injured and soon begin to die. Whereas RGC death and regenerative failure are widely viewed as being cell-autonomous or influenced by various types of glia, we report here that the dysregulation of mobile zinc (Zn2+) in retinal interneurons is a primary factor. Within an hour after the optic nerve is injured, Zn2+ increases several-fold in retinal amacrine cell processes and continues to rise over the first day, then transfers slowly to RGCs via vesicular release. Zn2+ accumulation in amacrine cell processes involves the Zn2+ transporter protein ZnT-3, and deletion of slc30a3, the gene encoding ZnT-3, promotes RGC survival and axon regeneration. Intravitreal injection of Zn2+ chelators enables many RGCs to survive for months after nerve injury and regenerate axons, and enhances the prosurvival and regenerative effects of deleting the gene for phosphatase and tensin homolog (pten). Importantly, the therapeutic window for Zn2+ chelation extends for several days after nerve injury. These results show that retinal Zn2+ dysregulation is a major factor limiting the survival and regenerative capacity of injured RGCs, and point to Zn2+ chelation as a strategy to promote long-term RGC protection and enhance axon regeneration.

Comparison of Automated Activity Recognition to Provider Observations of Patient Mobility in the ICU.

OBJECTIVES: To compare noninvasive mobility sensor patient motion signature to direct observations by physicians and nurses. DESIGN: Prospective, observational study. SETTING: Academic hospital surgical ICU. PATIENTS AND MEASUREMENTS: A total of 2,426 1-minute clips from six ICU patients (development dataset) and 4,824 1-minute clips from five patients (test dataset). INTERVENTIONS: None. MAIN RESULTS: Noninvasive mobility sensor achieved a minute-level accuracy of 94.2% (2,138/2,272) and an hour-level accuracy of 81.4% (70/86). CONCLUSIONS: The automated noninvasive mobility sensor system represents a significant departure from current manual measurement and reporting used in clinical care, lowering the burden of measurement and documentation on caregivers.

Measuring Patient Mobility in the ICU Using a Novel Noninvasive Sensor.

OBJECTIVES: To develop and validate a noninvasive mobility sensor to automatically and continuously detect and measure patient mobility in the ICU. DESIGN: Prospective, observational study. SETTING: Surgical ICU at an academic hospital. PATIENTS: Three hundred sixty-two hours of sensor color and depth image data were recorded and curated into 109 segments, each containing 1,000 images, from eight patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three Microsoft Kinect sensors (Microsoft, Beijing, China) were deployed in one ICU room to collect continuous patient mobility data. We developed software that automatically analyzes the sensor data to measure mobility and assign the highest level within a time period. To characterize the highest mobility level, a validated 11-point mobility scale was collapsed into four categories: nothing in bed, in-bed activity, out-of-bed activity, and walking. Of the 109 sensor segments, the noninvasive mobility sensor was developed using 26 of these from three ICU patients and validated on 83 remaining segments from five different patients. Three physicians annotated each segment for the highest mobility level. The weighted Kappa (κ) statistic for agreement between automated noninvasive mobility sensor output versus manual physician annotation was 0.86 (95% CI, 0.72-1.00). Disagreement primarily occurred in the "nothing in bed" versus "in-bed activity" categories because "the sensor assessed movement continuously," which was significantly more sensitive to motion than physician annotations using a discrete manual scale. CONCLUSIONS: Noninvasive mobility sensor is a novel and feasible method for automating evaluation of ICU patient mobility.

Clinical Reasoning: A Woman With Progressive Painless Sequential Monocular Vision Loss.

A 68-year-old woman with a history of diabetes mellitus type 2, depression, and migraines presented with painless, acute, consecutive vision loss affecting the right eye for 1 week and the left eye for 2 weeks. Neuro-ophthalmic examination was notable for visual acuities of finger-counting peripherally, a central scotoma, anterior uveitis, vitritis, and placoid macular pigmentary changes in each eye (OU). Proprioception was diminished in the bilateral lower extremities. Optical coherence tomography (OCT) revealed hyper-reflectivity and attenuation of the outer retina OU with normal inner retinal architecture and reflectivity. Fluorescein angiography (FA) demonstrated normal filling of the central retinal arteries with patchy choroidal perfusion in the right eye and targetoid punctate foci of leakage in the macula OU. Before the recognition of intraocular inflammation and findings on OCT and FA, the patient was treated for presumed central retinal artery occlusion at an outside hospital. Additional diagnostic testing at our institution revealed an alternate diagnosis. This case highlights a rare presentation of a well-known disease entity and underscores the importance of avoiding diagnostic anchoring in clinical practice.

VirScan: High-throughput Profiling of Antiviral Antibody Epitopes.

Profiling the specificities of antibodies can reveal a wealth of information about humoral immune responses and the antigens they target. Here, we present a protocol for VirScan, an application of the phage immunoprecipitation sequencing (PhIP-Seq) method for profiling the specificities of human antiviral antibodies. Accompanying this protocol is a video of the experimental procedure. VirScan and, more generally, PhIP-Seq are techniques that enable high-throughput antibody profiling by combining high-throughput DNA oligo synthesis and bacteriophage display with next-generation sequencing. In the VirScan method, human sera samples are screened against a library of peptides spanning the entire human viral proteome. Bound phage are immunoprecipitated and sequenced, identifying the viral peptides recognized by the antibodies. VirScan Is a powerful tool for uncovering individual viral exposure histories, mapping the epitope landscape of viruses of interest, and studying fundamental mechanisms of viral immunity. Graphical abstract.

Extended Combined Neonatal Treatment With Erythropoietin Plus Melatonin Prevents Posthemorrhagic Hydrocephalus of Prematurity in Rats.

Posthemorrhagic hydrocephalus of prematurity (PHHP) remains a global challenge. Early preterm infants (<32 weeks gestation), particularly those exposed to chorioamnionitis (CAM), are prone to intraventricular hemorrhage (IVH) and PHHP. We established an age-appropriate, preclinical model of PHHP with progressive macrocephaly and ventriculomegaly to test whether non-surgical neonatal treatment could modulate PHHP. We combined prenatal CAM and postnatal day 1 (P1, equivalent to 30 weeks human gestation) IVH in rats, and administered systemic erythropoietin (EPO) plus melatonin (MLT), or vehicle, from P2 to P10. CAM-IVH rats developed progressive macrocephaly through P21. Macrocephaly was accompanied by ventriculomegaly at P5 (histology), and P21 (ex vivo MRI). CAM-IVH rats showed impaired performance of cliff aversion, a neonatal neurodevelopmental test. Neonatal EPO+MLT treatment prevented macrocephaly and cliff aversion impairment, and significantly reduced ventriculomegaly. EPO+MLT treatment prevented matted or missing ependymal motile cilia observed in vehicle-treated CAM-IVH rats. EPO+MLT treatment also normalized ependymal yes-associated protein (YAP) mRNA levels, and reduced ependymal GFAP-immunolabeling. Vehicle-treated CAM-IVH rats exhibited loss of microstructural integrity on diffusion tensor imaging, which was normalized in EPO+MLT-treated CAM-IVH rats. In summary, combined prenatal systemic inflammation plus early postnatal IVH caused progressive macrocephaly, ventriculomegaly and delayed development of cliff aversion reminiscent of PHHP. Neonatal systemic EPO+MLT treatment prevented multiple hallmarks of PHHP, consistent with a clinically viable, non-surgical treatment strategy.

Process Monitoring in the Intensive Care Unit: Assessing Patient Mobility Through Activity Analysis with a Non-Invasive Mobility Sensor.

Throughout a patient's stay in the Intensive Care Unit (ICU), accurate measurement of patient mobility, as part of routine care, is helpful in understanding the harmful effects of bedrest [1]. However, mobility is typically measured through observation by a trained and dedicated observer, which is extremely limiting. In this work, we present a video-based automated mobility measurement system called NIMS: Non-Invasive Mobility Sensor . Our main contributions are: (1) a novel multi-person tracking methodology designed for complex environments with occlusion and pose variations, and (2) an application of human-activity attributes in a clinical setting. We demonstrate NIMS on data collected from an active patient room in an adult ICU and show a high inter-rater reliability using a weighted Kappa statistic of 0.86 for automatic prediction of the highest level of patient mobility as compared to clinical experts.

Neural processing of facial identity and emotion in infants at high-risk for autism spectrum disorders.

Deficits in face processing and social impairment are core characteristics of autism spectrum disorder. The present work examined 7-month-old infants at high-risk for developing autism and typically developing controls at low-risk, using a face perception task designed to differentiate between the effects of face identity and facial emotions on neural response using functional Near-Infrared Spectroscopy. In addition, we employed independent component analysis, as well as a novel method of condition-related component selection and classification to identify group differences in hemodynamic waveforms and response distributions associated with face and emotion processing. The results indicate similarities of waveforms, but differences in the magnitude, spatial distribution, and timing of responses between groups. These early differences in local cortical regions and the hemodynamic response may, in turn, contribute to differences in patterns of functional connectivity.