Coenzyme Q10 levels are low and may be associated with the inflammatory cascade in septic shock

Mitochondrial dysfunction is associated with increased mortality in septic shock. Coenzyme Q10 (CoQ10) is a key cofactor in the mitochondrial respiratory chain, but whether CoQ10 is depleted in septic shock remains unknown. Moreover, statin therapy may decrease CoQ10 levels, but whether this occurs acutely remains unknown. We measured CoQ10 levels in septic shock patients enrolled in a randomized trial of simvastatin versus placebo. We conducted a post hoc analysis of a prospective, randomized trial of simvastatin versus placebo in patients with septic shock (ClinicalTrials.gov ID: NCT00676897). Adult patients with suspected or confirmed infection and the need for vasopressor support were included in the initial trial. For the current analysis, blood specimens were analyzed for plasma CoQ10 and low-density lipoprotein (LDL) levels. The relationship between CoQ10 levels and inflammatory and vascular endothelial biomarkers was assessed using either the Pearson or Spearman correlation coefficient. We analyzed 28 samples from 14 patients. CoQ10 levels were low, with a median of 0.49 (interquartile range 0.26 to 0.62) compared to levels in healthy control patients (CoQ10 = 0.95 μmol/L ± 0.29; P < 0.0001). Statin therapy had no effect on plasma CoQ10 levels over time (P = 0.13). There was a statistically significant relationship between plasma CoQ10 levels and levels of vascular cell adhesion molecule (VCAM) (r2 = 0.2; P = 0.008), TNF-α (r2 = 0.28; P = 0.004), IL-8 (r2 = 0.21; P = 0.015), IL-10 (r2 = 0.18; P = 0.025), E-selectin (r2 = 0.17; P = -0.03), IL-1ra (r2 = 0.21; P = 0.014), IL-6 (r2 = 0.17; P = 0.029) and IL-2 (r2 = 0.23; P = 0.009). After adjusting for LDL levels, there was a statistically significant inverse relationship between plasma CoQ10 levels and levels of VCAM (r2 = 0.24; P = 0.01) (Figure 3) and IL-10 (r2 = 0.24; P = 0.02). CoQ10 levels are significantly lower in septic shock patients than in healthy controls. CoQ10 is negatively associated with vascular endothelial markers and inflammatory molecules, though this association diminishes after adjusting for LDL levels

Measuring the quality of inpatient specialist consultation in the intensive care unit: Nursing and family experiences of communication

Rationale: Critically ill patients in the intensive care unit (ICU) often require the care of specialist physicians for clinical or procedural expertise. The current state of communication between specialist physicians and families and nurses has not been explored. Objectives: To document the receipt of communication by nurses and family members regarding consultations performed on their patient or loved one, and to quantify how this impacts their overall perceptions of the quality of specialty care. Methods: Prospective survey of 60 adult family members and 90 nurses of 189 ICU patients who received a specialist consultation between March and October of 2015 in a single academic medical center in the United States. Surveys measured the prevalence of direct communication—defined as communication conducted in person, via telephone, or via text-page in which the specialist team gathered information about the patient from the nurse/family member and/or shared recommendations for care—and perceived quality of care. Results: In about two-thirds of family surveys (40/60) and one-half of nurse surveys (75/160), respondents had no direct communication with the specialist team that performed the consultation. Compared to nurses who had no direct communication with the specialists, those who did were 1.5 times more likely to rate the consultation as “excellent” (RR 1.48, 95% CI 1.2–1.8, p Conclusions: Most ICU families and nurses have no interaction with specialist providers. Nurses’ frequent exclusion from conversations about specialty care may pose safety risks and increase the likelihood of mixed messages for patients and families, most of whom desire some interaction with specialists. Future research is needed to identify effective mechanisms for information sharing that keep nurses and families aware of consultation requests, delivery, and outcomes without increasing the risk of mixed messages.</p

Dynamic interactions between anterior insula and anterior cingulate cortex link perceptual features and heart rate variability during movie viewing

AbstractThe dynamic integration of sensory and bodily signals is central to adaptive behaviour. Although the anterior cingulate cortex (ACC) and the anterior insular cortex (AIC) play key roles in this process, their context-dependent dynamic interactions remain unclear. Here, we studied the spectral features and interplay of these two brain regions using high-fidelity intracranial-EEG recordings from five patients (ACC: 13 contacts, AIC: 14 contacts) acquired during movie viewing with validation analyses performed on an independent resting intracranial-EEG dataset. ACC and AIC both showed a power peak and positive functional connectivity in the gamma (30–35 Hz) frequency while this power peak was absent in the resting data. We then used a neurobiologically informed computational model investigating dynamic effective connectivity asking how it linked to the movie’s perceptual (visual, audio) features and the viewer’s heart rate variability (HRV). Exteroceptive features related to effective connectivity of ACC highlighting its crucial role in processing ongoing sensory information. AIC connectivity was related to HRV and audio emphasising its core role in dynamically linking sensory and bodily signals. Our findings provide new evidence for complementary, yet dissociable, roles of neural dynamics between the ACC and the AIC in supporting brain-body interactions during an emotional experience

Transcranial magnetic stimulation in obsessive-compulsive disorder: a focus on network mechanisms and state dependence

Background: Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique that has shown promise as an adjunct treatment for the symptoms of Obsessive-Compulsive Disorder (OCD). Establishing a clear clinical role for TMS in the treatment of OCD is contingent upon evidence of significant efficacy and reliability in reducing symptoms. Objectives: We present the basic principles supporting the effects of TMS on brain activity with a focus on network-based theories of brain function. We discuss the promises and pitfalls of this technique as a means of modulating brain activity and reducing OCD symptoms. Methods: Synthesis of trends and critical perspective on the potential benefits and limitations of TMS interventions in OCD. Findings: Our critical synthesis suggests the need to better quantify the role of TMS in a clinical setting. The context in which the stimulation is performed, the neural principles supporting the effects of local stimulation on brain networks, and the heterogeneity of neuroanatomy are often overlooked in the clinical application of TMS. The lack of consideration of these factors may partly explain the variable efficacy of TMS interventions for OCD symptoms. Conclusions: Results from existing clinical studies and emerging knowledge about the effects of TMS on brain networks are encouraging but also highlight the need for further research into the use of TMS as a means of selectively normalising OCD brain network dynamics and reducing related symptoms. The combination of neuroimaging, computational modelling, and behavioural protocols known to engage brain networks affected by OCD has the potential to improve the precision and therapeutic efficacy of TMS interventions. The efficacy of this multimodal approach remains, however, to be established and its effective translation in clinical contexts presents technical and implementation challenges. Addressing these practical, scientific and technical issues is required to assess whether OCD can take its place alongside major depressive disorder as an indication for the use of TMS

Large-scale brain modes reorganize between infant sleep states and carry prognostic information for preterms

Sleep architecture carries vital information about brain health across the lifespan. In particular, the ability to express distinct vigilance states is a key physiological marker of neurological wellbeing in the newborn infant although systems-level mechanisms remain elusive. Here, we demonstrate that the transition from quiet to active sleep in newborn infants is marked by a substantial reorganization of large-scale cortical activity and functional brain networks. This reorganization is attenuated in preterm infants and predicts visual performance at two years. We find a striking match between these empirical effects and a computational model of large-scale brain states which uncovers fundamental biophysical mechanisms not evident from inspection of the data. Active sleep is defined by reduced energy in a uniform mode of neural activity and increased energy in two more complex anteroposterior modes. Preterm-born infants show a deficit in this sleep-related reorganization of modal energy that carries novel prognostic information.Peer reviewe

Attosecond state-resolved carrier motion in quantum materials probed by soft x-ray XANES

Recent developments in attosecond technology led to table-top x-ray spectroscopy in the soft x-ray range, thus uniting the element- and state-specificity of core-level x-ray absorption spectroscopy with the time resolution to follow electronic dynamics in real-time. We describe recent work in attosecond technology and investigations into materials such as Si, SiO2, GaN, Al2O3, Ti, and TiO2, enabled by the convergence of these two capabilities. We showcase the state-of-the-art on isolated attosecond soft x-ray pulses for x-ray absorption near-edge spectroscopy to observe the 3d-state dynamics of the semi-metal TiS2 with attosecond resolution at the Ti L-edge (460 eV). We describe how the element- and state-specificity at the transition metal L-edge of the quantum material allows us to unambiguously identify how and where the optical field influences charge carriers. This precision elucidates that the Ti:3d conduction band states are efficiently photo-doped to a density of 1.9 x 1021 cm 3. The light-field induces coherent motion of intra-band carriers across 38% of the first Brillouin zone. Lastly, we describe the prospects with such unambiguous real-time observation of carrier dynamics in specific bonding or anti-bonding states and speculate that such capability will bring unprecedented opportunities toward an engineered approach for designer materials with pre-defined properties and efficiency. Examples are composites of semiconductors and insulators like Si, Ge, SiO2, GaN, BN, and quantum materials like graphene, transition metal dichalcogens, or high-Tc superconductors like NbN or LaBaCuO. Exiting are prospects to scrutinize canonical questions in multi-body physics, such as whether the electrons or lattice trigger phase transitions

HIV-1 Entry, Inhibitors, and Resistance

Entry inhibitors represent a new class of antiretroviral agents for the treatment of infection with HIV-1. While resistance to other HIV drug classes has been well described, resistance to this new class is still ill defined despite considerable clinical use. Several potential mechanisms have been proposed: tropism switching (utilization of CXCR4 instead of CCR5 for entry), increased affinity for the coreceptor, increased rate of virus entry into host cells, and utilization of inhibitor-bound receptor for entry. In this review we will address the development of attachment, fusion, and coreceptor entry inhibitors and explore recent studies describing potential mechanisms of resistance