Nociception coma scale-revised scores correlate with metabolism in the anterior cingulate cortex.

BACKGROUND: . The Nociception Coma Scale-Revised (NCS-R) was recently validated to assess possible pain perception in patients with disorders of consciousness. OBJECTIVE: . To identify correlations between cerebral glucose metabolism and NCS-R total scores. METHODS: . [18F]-fluorodeoxyglucose positron emission tomography, NCS-R, and Coma Recovery Scale-Revised assessments were performed in 49 patients with disorders of consciousness. RESULTS: . We identified a significant positive correlation between NCS-R total scores and metabolism in the posterior part of the anterior cingulate cortex, known to be involved in pain processing. No other cluster reached significance. No significant effect of clinical diagnosis (vegetative/unresponsive vs minimally conscious states), etiology or interval since insult was observed. CONCLUSIONS: . Our data support the hypothesis that the NCS-R total scores are related to cortical processing of nociception and may constitute an appropriate behavioral tool to assess, monitor, and treat possible pain in brain-damaged noncommunicative patients with disorders of consciousness. Future studies using event-related functional magnetic resonance imaging should investigate the correlation between NCS-R scores and brain activation in response to noxious stimulation at the single-subject level

Quantitative rates of brain glucose metabolism distinguish minimally conscious from vegetative state patients

The differentiation of the vegetative or unresponsive wakefulness syndrome (VS/UWS) from the minimally conscious state (MCS) is an important clinical issue. The cerebral metabolic rate of glucose (CMRglc) declines when consciousness is lost, and may reveal the residual cognitive function of these patients. However, no quantitative comparisons of cerebral glucose metabolism in VS/UWS and MCS have yet been reported. We calculated the regional and whole-brain CMRglc of 41 patients in the states of VS/UWS (n=14), MCS (n=21) or emergence from MCS (EMCS, n=6), and healthy volunteers (n=29). Global cortical CMRglc in VS/UWS and MCS averaged 42% and 55% of normal, respectively. Differences between VS/UWS and MCS were most pronounced in the frontoparietal cortex, at 42% and 60% of normal. In brainstem and thalamus, metabolism declined equally in the two conditions. In EMCS, metabolic rates were indistinguishable from those of MCS. Ordinal logistic regression predicted that patients are likely to emerge into MCS at CMRglc above 45% of normal. Receiver-operating characteristics showed that patients in MCS and VS/UWS can be differentiated with 82% accuracy, based on cortical metabolism. Together these results reveal a significant correlation between whole-brain energy metabolism and level of consciousness, suggesting that quantitative values of CMRglc reveal consciousness in severely brain-injured patients

Converting a Sulfenic Acid Reductase into a Disulfide Bond Isomerase

Abstract Aims: Posttranslational formation of disulfide bonds is essential for the folding of many secreted proteins. Formation of disulfide bonds in a protein with more than two cysteines is inherently fraught with error and can result in incorrect disulfide bond pairing and, consequently, misfolded protein. Protein disulfide bond isomerases, such as DsbC of Escherichia coli, can recognize mis-oxidized proteins and shuffle the disulfide bonds of the substrate protein into their native folded state. Results: We have developed a simple blue/white screen that can detect disulfide bond isomerization in vivo, using a mutant alkaline phosphatase (PhoA*) in E. coli. We utilized this screen to isolate mutants of the sulfenic acid reductase (DsbG) that allowed this protein to act as a disulfide bond isomerase. Characterization of the isolated mutants in vivo and in vitro allowed us to identify key amino acid residues responsible for oxidoreductase properties of thioredoxin-like proteins such as DsbC or DsbG. Innovation and Conclusions: Using these key residues, we also identified and characterized interesting environmental homologs of DsbG with novel properties, thus demonstrating the capacity of this screen to discover and elucidate mechanistic details of in vivo disulfide bond isomerization. Antioxid. Redox Signal. 23, 945–957

Metabolic activity in external and internal awareness networks in severely brain-damaged patients.

OBJECTIVE: An extrinsic cerebral network (encompassing lateral frontoparietal cortices) related to external/sensory awareness and an intrinsic midline network related to internal/self-awareness have been identified recently. This study measured brain metabolism in both networks in patients with severe brain damage. DESIGN: Prospective [18F]-fluorodeoxyglucose-positron emission tomography and Coma Recovery Scale-Revised assessments in a university hospital setting. SUBJECTS: Healthy volunteers and patients in vegetative state/unresponsive wakefulness syndrome (VS/UWS), minimally conscious state (MCS), emergence from MCS (EMCS), and locked-in syndrome (LIS). RESULTS: A total of 70 patients were included in the study: 24 VS/UWS, 28 MCS, 10 EMCS, 8 LIS and 39 age-matched controls. VS/UWS showed metabolic dysfunction in extrinsic and intrinsic networks and thalami. MCS showed dysfunction mostly in intrinsic network and thalami. EMCS showed impairment in posterior cingulate/retrosplenial cortices. LIS showed dysfunction only in infratentorial regions. Coma Recovery Scale-Revised total scores correlated with metabolic activity in both extrinsic and part of the intrinsic network and thalami. CONCLUSION: Progressive recovery of extrinsic and intrinsic awareness network activity was observed in severely brain-damaged patients, ranging from VS/UWS, MCS, EMCS to LIS. The predominance of intrinsic network impairment in MCS could reflect altered internal/self-awareness in these patients, which is difficult to quantify at the bedside

Quantitative rates of brain glucose metabolism distinguish minimally conscious from vegetative state patients

The differentiation of the vegetative or unresponsive wakefulness syndrome (VS/UWS) from the minimally conscious state (MCS) is an important clinical issue. The cerebral metabolic rate of glucose (CMRglc) declines when consciousness is lost, and may reveal the residual cognitive function of these patients. However, no quantitative comparisons of cerebral glucose metabolism in VS/UWS and MCS have yet been reported. We calculated the regional and whole-brain CMRglc of 41 patients in the states of VS/UWS (n = 14), MCS (n = 21) or emergence from MCS (EMCS, n = 6), and healthy volunteers (n = 29). Global cortical CMRglc in VS/UWS and MCS averaged 42% and 55% of normal, respectively. Differences between VS/UWS and MCS were most pronounced in the frontoparietal cortex, at 42% and 60% of normal. In brainstem and thalamus, metabolism declined equally in the two conditions. In EMCS, metabolic rates were indistinguishable from those of MCS. Ordinal logistic regression predicted that patients are likely to emerge into MCS at CMRglc above 45% of normal. Receiver-operating characteristics showed that patients in MCS and VS/UWS can be differentiated with 82% accuracy, based on cortical metabolism. Together these results reveal a significant correlation between whole-brain energy metabolism and level of consciousness, suggesting that quantitative values of CMRglc reveal consciousness in severely brain-injured patients

Flexible thin film pH sensor based on low-temperature atomic layer deposition

Flexible and transparent zinc oxide (ZnO) thin film field-effect transistors (TF-FET) for the use as small volume potentiometric pH sensors are developed. Low temperature atomic layer deposition (ALD) is used for the fabrication of the metal oxides ZnO and aluminum dioxide (Al2O3). Changing the deposition temperature of the ZnO from 150 to 100 °C allowed a significant increase in resistivity by four orders of magnitude. Hence, adjusting the controlled low carrier concentration for the field-effect based sensor is demonstrated. ZnO TF-FET pH sensors fabricated on silicon/silicon dioxide (Si/SiO2) substrates are compared with sensors based on flexible and transparent polyethylene naphthalate (PEN) foil substrates. Comparison of both types of pH sensors showed successful pH sensitivity for pH ranging from 5 to 10 in both cases

Nociception Coma Scale–Revised Scores Correlate With Metabolism in the Anterior Cingulate Cortex

peer reviewedBACKGROUND: . The Nociception Coma Scale-Revised (NCS-R) was recently validated to assess possible pain perception in patients with disorders of consciousness. OBJECTIVE: . To identify correlations between cerebral glucose metabolism and NCS-R total scores. METHODS: . [18F]-fluorodeoxyglucose positron emission tomography, NCS-R, and Coma Recovery Scale-Revised assessments were performed in 49 patients with disorders of consciousness. RESULTS: . We identified a significant positive correlation between NCS-R total scores and metabolism in the posterior part of the anterior cingulate cortex, known to be involved in pain processing. No other cluster reached significance. No significant effect of clinical diagnosis (vegetative/unresponsive vs minimally conscious states), etiology or interval since insult was observed. CONCLUSIONS: . Our data support the hypothesis that the NCS-R total scores are related to cortical processing of nociception and may constitute an appropriate behavioral tool to assess, monitor, and treat possible pain in brain-damaged noncommunicative patients with disorders of consciousness. Future studies using event-related functional magnetic resonance imaging should investigate the correlation between NCS-R scores and brain activation in response to noxious stimulation at the single-subject level

CRISPR/Cas13a‐Powered Electrochemical Microfluidic Biosensor for Nucleic Acid Amplification‐Free miRNA Diagnostics

Noncoding small RNAs, such as microRNAs, are becoming the biomarkers of choice for multiple diseases in clinical diagnostics. A dysregulation of these microRNAs can be associated with many different diseases, such as cancer, dementia, and cardiovascular conditions. The key for effective treatment is an accurate initial diagnosis at an early stage, improving the patient's survival chances. In this work, the first clustered regularly interspaced short palindromic repeats (CRISPR)/Cas13a‐powered microfluidic, integrated electrochemical biosensor for the on‐site detection of microRNAs is introduced. Through this unique combination, the quantification of the potential tumor markers microRNA miR‐19b and miR‐20a is realized without any nucleic acid amplification. With a readout time of 9 min and an overall process time of less than 4 h, a limit of detection of 10 pm is achieved, using a measuring volume of less than 0.6 µL. Furthermore, the feasibility of the biosensor platform to detect miR‐19b in serum samples of children, suffering from brain cancer, is demonstrated. The validation of the obtained results with a standard quantitative real‐time polymerase chain reaction method shows the ability of the electrochemical CRISPR‐powered system to be a low‐cost, easily scalable, and target amplification‐free tool for nucleic acid based diagnostics

CRISPR/Cas13a‐powered electrochemical microfluidic biosensor for nucleic acid amplification‐free miRNA diagnostics

Noncoding small RNAs, such as microRNAs, are becoming the biomarkers of choice for multiple diseases in clinical diagnostics. A dysregulation of these microRNAs can be associated with many different diseases, such as cancer, dementia, and cardiovascular conditions. The key for effective treatment is an accurate initial diagnosis at an early stage, improving the patient's survival chances. In this work, the first clustered regularly interspaced short palindromic repeats (CRISPR)/Cas13a‐powered microfluidic, integrated electrochemical biosensor for the on‐site detection of microRNAs is introduced. Through this unique combination, the quantification of the potential tumor markers microRNA miR‐19b and miR‐20a is realized without any nucleic acid amplification. With a readout time of 9 min and an overall process time of less than 4 h, a limit of detection of 10 pm is achieved, using a measuring volume of less than 0.6 µL. Furthermore, the feasibility of the biosensor platform to detect miR‐19b in serum samples of children, suffering from brain cancer, is demonstrated. The validation of the obtained results with a standard quantitative real‐time polymerase chain reaction method shows the ability of the electrochemical CRISPR‐powered system to be a low‐cost, easily scalable, and target amplification‐free tool for nucleic acid based diagnostics