Tug-of-War between DNA Chelation and Silver Agglomeration in DNA-Silver Cluster Chromophores.

Supramolecular chromophores form when a DNA traps silvers that then coalesce into clusters with discrete, molecular electronic states. However, DNA strands are polymeric ligands that disperse silvers and thus curb agglomeration. We study this competition using two chromophores that share three common components: a dimeric DNA scaffold, Ag+-nucleobase base pairs, and Ag0 chromophores. The DNA host C4-A2-iC4T mimics structural elements in a DNA-cluster crystal structure using a phosphodiester backbone with combined 5' → 3' and 3' → 5' (indicated by "i") directions. The backbone directions must alternate to form the two silver clusters, and this interdependence supports a silver-linked structure. This template creates two chromophores with distinct sizes, charges, and hence spectra: (C4-A2-iC4T)2/Ag117+ with λabs/λem = 430/520 nm and (C4-A2-iC4T)2/Ag148+ with λabs/λem = 510/630 nm. The Ag+ and Ag0 constituents in these partially oxidized clusters are linked with structural elements in C4-A2-iC4T. Ag+ alone binds sparsely but strongly to form C4-A2-iC4T/3-4 Ag+ and (C4-A2-iC4T)2/7-8 Ag+ complexes, and these stoichiometries suggest that Ag+ cross-links pairs of cytosines to form a hairpin with a metallo-C4/iC4 duplex and an adenine loop. The Ag0 are chemically orthogonal because they can be oxidatively etched without disrupting the underlying Ag+-DNA matrix, and their reactivity is attributed to their valence electrons and weaker chelation by the adenines. These studies suggest that Ag+ disperses with the cytosines to create an adenine binding pocket for the Ag0 cluster chromophores.

Incidence and predictors of post-traumatic stress symptoms in a cohort of patients with intracerebral hemorrhage.

OBJECTIVES: Examine the incidence and predictors of PTSD symptoms in a cohort of patients with ICH. PATIENTS AND METHODS: This study uses a prospective cohort of 108 patients with complete follow-up data including a questionnaire regarding stress symptoms (PCL-S: PTSD checklist specific for a stressor) at 3, 6, and 12 months. RESULTS: The incidence of novel stress symptoms following ICH was approximately 6.5%. Age was negatively associated with PTSD symptoms with only trend-level significance (3 months: OR = 0.83, p = 0.087; 6 months: OR = 0.70, p = 0.015; 12 months: OR = 0.88, p = 0.087). Gender did not affect PTSD symptom development, (t = 1.34, p = 0.18). Pre-morbid functioning, initial stroke prognosis, total number of complications, and length of hospital/ICU stay were not associated with PTSD symptoms; however, each was significantly correlated with poorer functional outcomes. Yet, poorer functional outcomes were observed in those with higher reports of PTSD symptoms (r = 0.24, p = 0.01). CONCLUSION: Functional outcomes in ICH are correlated with PTSD symptoms, however the mechanism and relationship are difficult to elucidate. Further research is needed to determine possible mechanisms by which a stroke patient may develop PTSD.

Detection of Brain Activation in Unresponsive Patients with Acute Brain Injury.

BACKGROUND: Brain activation in response to spoken motor commands can be detected by electroencephalography (EEG) in clinically unresponsive patients. The prevalence and prognostic importance of a dissociation between commanded motor behavior and brain activation in the first few days after brain injury are not well understood. METHODS: We studied a prospective, consecutive series of patients in a single intensive care unit who had acute brain injury from a variety of causes and who were unresponsive to spoken commands, including some patients with the ability to localize painful stimuli or to fixate on or track visual stimuli. Machine learning was applied to EEG recordings to detect brain activation in response to commands that patients move their hands. The functional outcome at 12 months was determined with the Glasgow Outcome Scale-Extended (GOS-E; levels range from 1 to 8, with higher levels indicating better outcomes). RESULTS: A total of 16 of 104 unresponsive patients (15%) had brain activation detected by EEG at a median of 4 days after injury. The condition in 8 of these 16 patients (50%) and in 23 of 88 patients (26%) without brain activation improved such that they were able to follow commands before discharge. At 12 months, 7 of 16 patients (44%) with brain activation and 12 of 84 patients (14%) without brain activation had a GOS-E level of 4 or higher, denoting the ability to function independently for 8 hours (odds ratio, 4.6; 95% confidence interval, 1.2 to 17.1). CONCLUSIONS: A dissociation between the absence of behavioral responses to motor commands and the evidence of brain activation in response to these commands in EEG recordings was found in 15% of patients in a consecutive series of patients with acute brain injury. (Supported by the Dana Foundation and the James S. McDonnell Foundation.).

Deep structural brain lesions associated with consciousness impairment early after hemorrhagic stroke.

The purpose of this study was to determine the significance of deep structural lesions for impairment of consciousness following hemorrhagic stroke and recovery at ICU discharge. Our study focused on deep lesions that previously were implicated in studies of disorders of consciousness. We analyzed MRI measures obtained within the first week of the bleed and command following throughout the ICU stay. A machine learning approach was applied to identify MRI findings that best predicted the level consciousness. From 158 intracerebral hemorrhage patients that underwent MRI, one third was unconscious at the time of MRI and half of these patients recovered consciousness by ICU discharge. Deep structural lesions predicted both, impairment and recovery of consciousness, together with established measures of mass effect. Lesions in the midbrain peduncle and pontine tegmentum alongside the caudate nucleus were implicated as critical structures. Unconscious patients predicted to recover consciousness by ICU discharge had better long-term functional outcomes than those predicted to remain unconscious.

Dispersion in Scores on the Richmond Agitation and Sedation Scale as a Measure of Delirium in Patients with Subdural Hematomas.

BACKGROUND: Delirium is a frequent complication of critical illness, but its diagnosis is more difficult in brain-injured patients due to language impairment and disorders of consciousness. We conducted a prospective cohort study to determine whether Richmond Agitation and Sedation Scale (RASS) scores could be used to reliably diagnose delirium in the setting of brain injury. We also examined clinical factors associated with delirium in patients with subdural hematomas (SDH) and assessed its impact on functional outcome at discharge. METHODS: We prospectively enrolled 55 patients with the primary diagnosis of SDH admitted to the neurological intensive care unit (ICU) and screened them for delirium with the Confusion Assessment Method-ICU (CAM-ICU). As our primary outcome, we examined whether the standard deviation of RASS scores (RASS dispersion) could be used to diagnose delirium. We also looked at trends in RASS scores as a way to distinguish different causes of delirium. Then, using logistic regression, we identified factors associated with delirium in patients with SDH and quantified the impact of delirium on the modified Rankin Scale at discharge. RESULTS: Delirium as defined by the CAM-ICU was present in 35% (N = 19) of patients. RASS dispersion correlated well with the CAM-ICU (AUC of the ROC was 0.84). Analyzing the temporal trend of changes in the RASS was helpful in identifying new brain injuries as the underlying etiology of CAM-ICU positivity. Age, APACHE II scores on admission, baseline functional impairment, midline shift on initial imaging, and infections were associated with an increased risk of delirium. Delirium was associated with a worse functional outcome. CONCLUSIONS: RASS dispersion correlates highly with CAM-ICU positivity, and monitoring trends in RASS scores can identify delirium caused by new brain injuries. Delirium as defined by the CAM-ICU is common in patients with SDH and portends worse outcomes.

Early myoclonus following anoxic brain injury.

BACKGROUND: It is unknown whether postanoxic cortical and subcortical myoclonus are distinct entities with different prognoses. METHODS: In this retrospective cohort study of 604 adult survivors of cardiac arrest over 8.5 years, we identified 111 (18%) patients with myoclonus. Basic demographics and clinical characteristics of myoclonus were collected. EEG reports, and, when available, raw video EEG, were reviewed, and all findings adjudicated by 3 authors blinded to outcomes. Myoclonus was classified as cortical if there was a preceding, time-locked electrographic correlate and otherwise as subcortical. Outcome at discharge was determined using Cerebral Performance Category. RESULTS: Patients with myoclonus had longer arrests with less favorable characteristics compared to patients without myoclonus. Cortical myoclonus occurred twice as often as subcortical myoclonus (59% vs 23%, respectively). Clinical characteristics during hospitalization did not distinguish the two. Rates of electrographic seizures were higher in patients with cortical myoclonus (43%, vs 8% with subcortical). Survival to discharge was worse for patients with myoclonus compared to those without (26% vs 39%, respectively), but did not differ between subcortical and cortical myoclonus (24% and 26%, respectively). Patients with cortical myoclonus were more likely to be discharged in a comatose state than those with subcortical myoclonus (82% vs 33%, respectively). Among survivors, good functional outcome at discharge was equally possible between those with cortical and subcortical myoclonus (12% and 16%, respectively). CONCLUSIONS: Cortical and subcortical myoclonus are seen in every sixth patient with cardiac arrest and cannot be distinguished using clinical criteria. Either condition may have good functional outcomes.

Sphingosine's role in epithelial host defense: A natural antimicrobial and novel therapeutic.

Sphingosine is a natural sphingolipid found in membranes of all eukaryotic cells. In addition to its functions in cell signaling, sphingosine has broad-spectrum antimicrobial properties. Sphingosine's role as an antimicrobial is important in tissues such as the skin and respiratory epithelium. Reduction in the normal sphingosine level is associated with problems related to infection susceptibility. Therefore, exogenous sphingosine may be an effective antimicrobial therapeutic. Inhaled nebulized sphingosine has been shown to be effective at both preventing and treating pneumonia in multiple mouse models. We now show that inhaled sphingosine has low toxicity to the respiratory system, strengthening its case as an excellent candidate for a novel inhaled antimicrobial drug.