Sensitivity optimization of a rhodopsin-based fluorescent voltage indicator.

The ability to optically image cellular transmembrane voltages at millisecond-timescale resolutions can offer unprecedented insight into the function of living brains in behaving animals. Here, we present a point mutation that increases the sensitivity of Ace2 opsin-based voltage indicators. We use the mutation to develop Voltron2, an improved chemigeneic voltage indicator that has a 65% higher sensitivity to single APs and 3-fold higher sensitivity to subthreshold potentials than Voltron. Voltron2 retained the sub-millisecond kinetics and photostability of its predecessor, although with lower baseline fluorescence. In multiple in vitro and in vivo comparisons with its predecessor across multiple species, we found Voltron2 to be more sensitive to APs and subthreshold fluctuations. Finally, we used Voltron2 to study and evaluate the possible mechanisms of interneuron synchronization in the mouse hippocampus. Overall, we have discovered a generalizable mutation that significantly increases the sensitivity of Ace2 rhodopsin-based sensors, improving their voltage reporting capability.

Syndromic and non-syndromic etiologies causing neonatal hypocalcemic seizures.

Background: The diagnosis of neonatal hypocalcemic seizures (HS) in newborns is made based on clinical signs and serum calcium level. Their etiology is broad and diverse, and timely detection and initiation of treatment is essential. Methods: We retrospectively reviewed 1029 patients admitted to the neonatal intensive care unit. Neonatal HS were diagnosed in 16 patients, and we compared etiologies and clinical outcomes, including clinical seizures and neurodevelopment at least over 1 year old. Results: The etiologies can be broadly categorized into 5 syndromic and 11 non-syndromic neonatal HS. Syndromic neonatal HS included 3 Digeorge syndrome, 1 Kleefstra syndrome and 1 Alström syndrome. Non-syndromic neonatal HS included 8 vitamin D deficiency, 1 hypoparathyroidism, and 2 hypoxic-ischemic encephalopathy. Patients with syndromic neonatal HS were found to have worse clinical outcomes than those with nonsyndromic HS. In eight patients with vitamin D deficiency, neurodevelopment was normal. Five of five patients (100%) with syndromic HS used two or more antiseizure drugs. However, among patients with non-syndromic neonatal HS, only one of 11 (9.1%) used more than one drug (p = 0.001). Conclusion: This finding highlighted that syndromic hypocalcemic seizures in newborns have worse neurodevelopmental outcomes and are more often difficult to manage, and would benefit from a genetic diagnostic approach.

Systematic Review and Meta-Analysis of Home-Based Rehabilitation on Improving Physical Function Among Home-Dwelling Patients With a Stroke.

OBJECTIVE: To evaluate the effects of home-based rehabilitation on improving physical function in home-dwelling patients after a stroke. DATA SOURCES: Various electronic databases, including PubMed, Cumulative Index to Nursing and Allied Health, Embase, the Cochrane Central Register of Controlled Trials, and 2 Chinese data sets (ie, Chinese Electronic Periodical Services and China Knowledge Resource Integrated) were searched for studies published before March 20, 2019. STUDY SELECTION: Randomized controlled trials conducted to examine the effect of home-based rehabilitation on improving physical function in home-dwelling patients with a stroke and published in English or Chinese were included. In total, 49 articles in English (n=23) and Chinese (n=26) met the inclusion criteria. DATA EXTRACTION: Data related to patient characteristics, study characteristics, intervention details, and outcomes were extracted by 2 independent reviewers. DATA SYNTHESIS: A random-effects model with a sensitivity analysis showed that home-based rehabilitation exerted moderate improvements on physical function in home-dwelling patients with a stroke (g=0.58; 95% CI, 0.45∼0.70). Moderator analyses revealed that those patients with stroke of a younger age, of male sex, with a first-ever stroke episode, in the acute stage, and receiving rehabilitation training from their caregiver showed greater improvements in physical function. CONCLUSIONS: Home rehabilitation can improve functional outcome in survivors of stroke and should be considered appropriate during discharge planning if continuation care is required.

Bright and photostable chemigenetic indicators for extended in vivo voltage imaging.

Genetically encoded voltage indicators (GEVIs) enable monitoring of neuronal activity at high spatial and temporal resolution. However, the utility of existing GEVIs has been limited by the brightness and photostability of fluorescent proteins and rhodopsins. We engineered a GEVI, called Voltron, that uses bright and photostable synthetic dyes instead of protein-based fluorophores, thereby extending the number of neurons imaged simultaneously in vivo by a factor of 10 and enabling imaging for significantly longer durations relative to existing GEVIs. We used Voltron for in vivo voltage imaging in mice, zebrafish, and fruit flies. In the mouse cortex, Voltron allowed single-trial recording of spikes and subthreshold voltage signals from dozens of neurons simultaneously over a 15-minute period of continuous imaging. In larval zebrafish, Voltron enabled the precise correlation of spike timing with behavior.

Effects of Home-Based Supportive Care on Improvements in Physical Function and Depressive Symptoms in Patients With Stroke: A Meta-Analysis.

OBJECTIVE: To examine the effects of home-based supportive care on improvements in physical function and depressive symptoms in home-dwelling patients after stroke. DATA SOURCES: Seven electronic databases (eg, MEDLINE, PubMed, CINAL, EMBASE, the Cochrane Central Register of Controlled Trials, ProQuest, and Google Scholar) and 4 Chinese databases (eg, WANFANG MED ONLINE, Chinese Electronic Periodical Services, China Academic Journals Full-text Database, and National Central Library) were fully searched for all relevant articles up to June 25, 2016. STUDY SELECTION: Randomized controlled trials examining the effects of home-based supportive care on physical function and depressive symptoms in home-dwelling patients after stroke were included. Finally, 16 articles in Chinese (n=4) and English (n=12) met the inclusion criteria. DATA EXTRACTION: Data on patient characteristics, study characteristics, intervention details, and outcome were extracted. Two reviewers independently extracted data and assessed methodological quality using the Cochrane risk of bias tool. DATA SYNTHESIS: Home-based supportive care had a small size effect on physical function (Hedges' g=.17; 95% confidence interval, .09-.26) and a moderate size effect on depressive symptoms (Hedges' g=-.44; 95% confidence interval, -.83 to -.05) in home-dwelling patients after stroke. The moderator analysis revealed that some components of study participants and intervention programs improved the effects on physical function and depressive symptoms; however, no significant moderators were further identified to have superiorly improved physical function and depressive symptoms. CONCLUSIONS: Regular performance of home-based supportive interventions should be considered for inclusion as routine care for managing and improving physical function and depressive symptoms in home-dwelling patients after stroke. The present findings provide further evidence with which to design appropriate supportive interventions for home-dwelling stroke survivors.

Higher glucose on admission is associated with need for angioembolization in stable pelvic fracture.

BACKGROUND: Angioembolization is an effective adjunct to the management of retroperitoneal hemorrhage in pelvic fractures. Most patients with stable-type pelvic fracture are treated conservatively. However, in some stable pelvic fracture cases, patients should receive angioembolization for hemostasis upon incidental finding of contrast extravasation on computed tomography (CT). In this study, we attempted to define the characteristics of patients with stable pelvic fracture requiring angioembolization. METHODS: We retrospectively reviewed the charts of patients with pelvic fractures between January 2005 and November 2009. We focused on stable pelvic fracture patients with contrast extravasation on CT who then received angioembolization. The demographics, Injury Severity Score (ISS), Abbreviated Injury Scale score, and the blood glucose levels on admission were analyzed. RESULTS: In total, 334 patients were enrolled. Patients with higher blood glucose level on admission with stable pelvic fracture had a higher rate of angioembolization. Furthermore, these patients presented with a higher Abbreviated Injury Scale score and ISS. CONCLUSIONS: In patients with stable pelvic fracture, higher blood glucose level on admission was associated with a higher likelihood of needing angioembolization. Blood glucose level should be checked during the initial survey of a pelvic fracture, and greater attention should be given to patients with higher blood glucose level or with an ISS of 25 or greater, even when the imaging study only reveals a stable pelvic fracture.

Angioembolization provides benefits in patients with concomitant unstable pelvic fracture and unstable hemodynamics.

INTRODUCTION: Pelvic fractures result in hemodynamic instability in 5% to 20% of patients, and the reported mortality rate is 18% to 40%. Previous studies have reported the application of angioembolization in pelvic fracture patients with a systolic blood pressure (SBP) less than 90 mm Hg, a fluid resuscitation requirement of more than 2000 mL, or a blood transfusion of more than 4 to 6 units within 24 hours. In the current study, we attempted to delineate the efficacy and outcome of angioembolization in unstable pelvic fracture patients with concomitant unstable hypotension status. METHODS: We retrospectively reviewed the charts of patients with pelvic fractures between January 2005 and May 2010. We focused on unstable pelvic fracture patients with an SBP less than 90 mm Hg after fluid resuscitation who did not receive computed tomography scans. The demographics, injury severity score, abbreviated injury scale, and hemodynamic status after angioembolization were analyzed. RESULTS: In total, 26 patients were enrolled. There were 16 patients receiving angioembolization directly without computed tomography scans and 12 patients receiving emergency laparotomy due to a finding of hemoperitoneum on sonography, followed by angioembolization. In both groups, the SBP improved significantly after angioembolization. The overall survival rate was 85.7%. CONCLUSIONS: In patients with concomitant unstable hemodynamics and unstable pelvic fracture, angioembolization serves as an effective adjunct to hemostasis. Aggressive embolization should be performed even in patients without contrast extravasation in angiography.

Tomographic findings are not always predictive of failed nonoperative management in blunt hepatic injury.

BACKGROUND: Nonoperative management (NOM) has become the standard treatment of blunt hepatic injury (BHI) for stable patients. Contrast extravasation (CE) on computed tomography (CT) scan had been reported as a sign that is associated with NOM failure. The goal of this study was to further investigate the risk factors of NOM failure in patients with CE on CT scan. METHODS: From January 2005 to September 2009, patients with CE noted on a CT scan as a result of BHI were studied retrospectively. Physiological parameters, severity of injury, amount of transfusion, type of contrast extravasation, as well as treatment outcome were compared between patients with NOM failure and NOM success. RESULTS: A total of 130 patients were enrolled. Injury severity scores, amount of blood transfusion before hemostatic procedure, and grade of liver injury were significantly higher in NOM failure than in NOM success patients. There was no statistical difference in the NOM success rate between patients with contrast leakage into the peritoneum and those with contrast confined in the hepatic parenchyma. CONCLUSIONS: Higher injury severity score, more blood transfusion, and higher grade of liver injury are factors that correlate with NOM failure in patients with BHI. Contrast leakage into the peritoneum is not always a definite sign of NOM failure in BHI. Early and aggressive angioembolization is an effective adjunct of NOM in BHI patients, even with contrast leakage into peritoneum.