Evaluating and Enhancing Nursing Caregiver Well-being Using a Systematic Approach.

OBJECTIVE: The aims of this study were to evaluate nursing caregiver well-being and identify interventions for improving well-being and practice environments. BACKGROUND: Healthcare worker well-being and burnout command increasing attention in the wake of the pandemic. Experts recommend utilization of validated measurements to assess burnout, well-being, and contributing factors. METHODS: Using a descriptive, cross-sectional, mixed-methods study design, an online survey, which included the Professional Quality of Life-5, Meaning and Joy in Work Questionnaire, and open-ended questions, was administered to nurses and unlicensed assistive caregivers in an academic health system. RESULTS: Caregivers reported moderate compassion satisfaction, low burnout and compassion fatigue, and low-moderate levels of meaning and joy in work. Overall and subscale scores varied primarily based on age, experience, and role. Top causes of stress and recommendations for improvement were identified. CONCLUSION: The levels of meaning and joy in work among nursing caregivers continue to be of concern for organizational leaders. The engagement of nurses and other caregiver team members in a systematic mixed-methods approach, including using validated tools to evaluate caregiver well-being, can lead to meaningful, data-driven action planning to promote well-being and increase the meaning and joy of the work they perform.

Thalamic deep brain stimulation paradigm to reduce consciousness: Cortico-striatal dynamics implicated in mechanisms of consciousness.

Anesthetic manipulations provide much-needed causal evidence for neural correlates of consciousness, but non-specific drug effects complicate their interpretation. Evidence suggests that thalamic deep brain stimulation (DBS) can either increase or decrease consciousness, depending on the stimulation target and parameters. The putative role of the central lateral thalamus (CL) in consciousness makes it an ideal DBS target to manipulate circuit-level mechanisms in cortico-striato-thalamic (CST) systems, thereby influencing consciousness and related processes. We used multi-microelectrode DBS targeted to CL in macaques while recording from frontal, parietal, and striatal regions. DBS induced episodes of abnormally long, vacant staring with low-frequency oscillations here termed vacant, perturbed consciousness (VPC). DBS modulated VPC likelihood in a frequency-specific manner. VPC events corresponded to decreases in measures of neural complexity (entropy) and integration (Φ*), proposed indices of consciousness, and substantial changes to communication in CST circuits. During VPC, power spectral density and coherence at low frequencies increased across CST circuits, especially in thalamo-parietal and cortico-striatal pathways. Decreased consciousness and neural integration corresponded to shifts in cortico-striatal network configurations that dissociated parietal and subcortical structures. Overall, the features of VPC and implicated networks were similar to those of absence epilepsy. As this same multi-microelectrode DBS method-but at different stimulation frequencies-can also increase consciousness in anesthetized macaques, it can be used to flexibly address questions of consciousness with limited confounds, as well as inform clinical investigations of other consciousness disorders.

Predictive Feedback, Early Sensory Representations, and Fast Responses to Predicted Stimuli Depend on NMDA Receptors.

Learned associations between stimuli allow us to model the world and make predictions, crucial for efficient behavior (e.g., hearing a siren, we expect to see an ambulance and quickly make way). While there are theoretical and computational frameworks for prediction, the circuit and receptor-level mechanisms are unclear. Using high-density EEG, Bayesian modeling, and machine learning, we show that inferred "causal" relationships between stimuli and frontal alpha activity account for reaction times (a proxy for predictions) on a trial-by-trial basis in an audiovisual delayed match-to-sample task which elicited predictions. Predictive ß feedback activated sensory representations in advance of predicted stimuli. Low-dose ketamine, an NMDAR blocker, but not the control drug dexmedetomidine, perturbed behavioral indices of predictions, their representation in higher-order cortex, feedback to posterior cortex, and pre-activation of sensory templates in higher-order sensory cortex. This study suggests that predictions depend on alpha activity in higher-order cortex, ß feedback, and NMDARs, and ketamine blocks access to learned predictive information.SIGNIFICANCE STATEMENT We learn the statistical regularities around us, creating associations between sensory stimuli. These associations can be exploited by generating predictions, which enable fast and efficient behavior. When predictions are perturbed, it can negatively influence perception and even contribute to psychiatric disorders, such as schizophrenia. Here we show that the frontal lobe generates predictions and sends them to posterior brain areas, to activate representations of predicted sensory stimuli before their appearance. Oscillations in neural activity (α and ß waves) are vital for these predictive mechanisms. The drug ketamine blocks predictions and the underlying mechanisms. This suggests that the generation of predictions in the frontal lobe, and the feedback pre-activating sensory representations in advance of stimuli, depend on NMDARs.

Topographic organization of connections between prefrontal cortex and mediodorsal thalamus: Evidence for a general principle of indirect thalamic pathways between directly connected cortical areas.

Our ability to act flexibly, according to goals and context, is known as cognitive control. Hierarchical levels of control, reflecting different levels of abstraction, are represented across prefrontal cortex (PFC). Although the mediodorsal thalamic nucleus (MD) is extensively interconnected with PFC, the role of MD in cognitive control is unclear. Tract tracer studies in macaques, involving subsets of PFC areas, have converged on coarse MD-PFC connectivity principles; but proposed finer-grained topographic schemes, which constrain interactions between MD and PFC, disagree in many respects. To investigate a unifying topographic scheme, we performed probabilistic tractography on diffusion MRI data from eight macaque monkeys, and estimated the probable paths connecting MD with each of all 19 architectonic areas of PFC. We found a connectional topography where the orderly progression from ventromedial to anterior to posterolateral PFC was represented from anteromedial to posterolateral MD. The projection zones of posterolateral PFC areas in MD showed substantial overlap, and those of ventral and anteromedial PFC areas in MD overlapped. The exception was cingulate area 24: its projection zone overlapped with projections zones of all other PFC areas. Overall, our data suggest that nearby, functionally related, directly connected PFC areas have partially overlapping projection zones in MD, consistent with a role for MD in coordinating communication across PFC. Indeed, the organizing principle for PFC projection zones in MD appears to reflect the flow of information across the hierarchical, multi-level PFC architecture. In addition, cingulate area 24 may have privileged access to influence thalamocortical interactions involving all other PFC areas.

Axially Chiral Enamides: Substituent Effects, Rotation Barriers, and Implications for their Cyclization Reactions.

The barrier to rotation around the N-alkenyl bond of 38 N-alkenyl-N-alkylacetamide derivatives was measured (ΔG(⧧) rotation varied between <8.0 and 31.0 kcal mol(-1)). The most important factor in controlling the rate of rotation was the level of alkene substitution, followed by the size of the nitrogen substituent and, finally, the size of the acyl substituent. Tertiary enamides with four alkenyl substituents exhibited half-lives for rotation between 5.5 days and 99 years at 298 K, sufficient to isolate enantiomerically enriched atropisomers. The radical cyclizations of a subset of N-alkenyl-N-benzyl-α-haloacetamides exhibiting relatively high barriers to rotation round the N-alkenyl bond (ΔG(⧧) rotation >20 kcal mol(-1)) were studied to determine the regiochemistry of cyclization. Those with high barriers (>27 kcal mol(-1)) did not lead to cyclization, but those with lower values produced highly functionalized γ-lactams via a 5-endo-trig radical-polar crossover process that was terminated by reduction, an unusual cyclopropanation sequence, or trapping with H2O, depending upon the reaction conditions. Because elevated temperatures were necessary for cyclization, this precluded study of the asymmetric transfer in the reaction of individual atropisomers. However, enantiomerically enriched atropsiomeric enamides should be regarded as potential asymmetric building blocks for reactions that can be accomplished at room temperature.

A long-range fronto-parietal 5- to 10-Hz network predicts "top-down" controlled guidance in a task-switch paradigm.

The capacity to rapidly adjust behavioral strategies according to changing task demands is closely associated with coordinated activity in lateral and medial prefrontal cortices. Subdivisions within prefrontal cortex are implicated to encode attentional task sets and to update changing task rules, particularly when changing task demands require top-down control. Here, we tested whether these top-down processes precede stimulus processing and constitute a preparatory attentional state that functionally couples with parietal cortex. We examined this functional coupling by recording from intracranial EEG electrodes in macaques during performance of a task-switching paradigm that separates task performance that is based on controlled top-down guidance from automatic, stimulus-triggered processing modes. We identify a prefrontal-parietal network that phase synchronizes at 5-10 Hz, particularly during preparatory states that indicate top-down controlled task-processing modes. Phase relations in the network suggest that medial and lateral prefrontal cortices synchronize bidirectionally, with medial prefrontal cortex showing a phase-lead relative to left parietal recorded 5- to 10-Hz preparatory signals. These findings reveal a 5- to 10-Hz coordinated, long-range fronto-parietal network prior to actual task-relevant stimulus processing, particularly when subjects engage in controlled task processing modes.

Event-related potentials associated with performance monitoring in non-human primates.

The abilities to monitor performance outcomes and, when appropriate, impose strategic adjustments in behavior, are core features of the intact human cognitive control system. Errors committed in choice reaction time tasks are typically followed by two scalp potentials, the error negativity (Ne) and error positivity (Pe). These components are considered physiological signatures of the performance monitoring system. Several theories have been proposed to account for these error-related potentials and their functional and behavioral significance. These ideas were inspired by empirical data in humans and other mammalian species, and supported by the results of experiments in which performance monitoring, in humans and computational models, was investigated. However, an appropriate animal model is required to rigorously test the predictions that arise from these theories. Here, using a variant of the anti-saccade task, we demonstrate that event-related signals recorded from macaque monkeys, following errors in choice, resemble the human Ne and Pe. These components were modulated by cognitive variables, namely the degree of cognitive control associated with the applied rule, which implies the existence of hierarchical error processing systems in monkeys, and the degree of response control associated with the saccade. Error-related potential amplitudes were also correlated with remedial action, in a rule-dependent manner. These results demonstrate that error-related potentials in macaque monkeys and human subjects show important similarities, thus supporting the use of the macaque monkey as an animal model for the neurophysiological study of performance monitoring, and potentially, post-error adjustments.

Effect of a Virtual Reality Simulation Modality on Registered Nurse Knowledge and Behavior Related to Clostridioides difficile Prevention : An Experimental, Cluster Randomized Controlled Trial.

Virtual reality simulation (VRS) has emerged as an educational methodology in nursing professional development. A cluster randomized controlled trial was conducted with a sample of clinical registered nurses to compare effectiveness of VRS and traditional education on knowledge and behavior related to Clostridioides difficile prevention. No significant differences were found in the effectiveness of the two modalities, suggesting the usefulness of VRS as a teaching methodology.

Effect of Virtual Reality Simulation Versus Traditional Education on Rates of Clostridium difficile Infection: An Experimental Cluster Randomized Controlled Trial and Return on Investment Analysis.

BACKGROUND: Virtual reality simulation (VRS) is an innovative modality in nursing professional development that has the potential to affect patient outcomes. METHOD: An experimental cluster randomized controlled trial was performed with RNs on two inpatient units at a large academic health system. The purpose of this study was to evaluate the effect of VRS compared with traditional education on Clostridium difficile rates. Return on investment of nursing professional development activities was also measured to support decision-making and resource allocation. RESULTS: Rates of C. difficile infection were significantly lower for both groups for the 3-month postintervention period compared with the 10-month period preintervention. Financial analysis showed a return on investment for both modalities, with VRS having higher yields over time. CONCLUSION: Findings showed that VRS was an effective instructional method. [J Contin Educ Nurs. 2024;55(7):351-358.].

Primate thalamic nuclei select abstract rules and shape prefrontal dynamics.

Flexible behavior depends on abstract rules to generalize beyond specific instances, and outcome monitoring to adjust actions. Cortical circuits are posited to read out rules from high-dimensional representations of task-relevant variables in prefrontal cortex (PFC). We instead hypothesized that converging inputs from PFC, directly or via basal ganglia (BG), enable primate-specific thalamus to select rules. To test this, we simultaneously measured spiking activity across PFC and two connected thalamic nuclei of monkeys applying rules. Abstract rule information first appeared in the ventroanterior thalamus (VA) - the main thalamic hub between BG and PFC. The mediodorsal thalamus (MD) also represented rule information before PFC, which persisted after rule cues were removed, to help maintain activation of relevant posterior PFC cell ensembles. MD, a major recipient of midbrain dopamine input, was first to represent information about behavioral outcomes. This persisted after the trial (also in PFC). A PFC-BG-thalamus model reproduced key findings, and thalamic-lesion modeling disrupted PFC rule representations. These results suggest a revised view of the neural basis of flexible behavior in primates, featuring a central role for thalamus in selecting high-level cognitive information from PFC and implementing post-error behavioral adjustments, and of the functional organization of PFC along its anterior-posterior dimension.

Effects of anterior cingulate microstimulation on pro- and antisaccades in nonhuman primates.

Numerous studies have established a role for the ACC in cognitive control. Current theories are at odds as to whether ACC itself directly engages or alternatively recruits other frontal cortical areas that implement control. The antisaccade task, in which subjects are required to make a saccade to the location opposite a suddenly appearing visual stimulus, is a simple oculomotor paradigm that has been used extensively to investigate flexible oculomotor control. Here, we tested a causal role of the dorsal ACC in cognitive control by applying electrical microstimulation during a preparatory period while monkeys performed alternating blocks of pro- and antisaccade trials. Microstimulation induced significant changes in saccadic RTs (SRTs) in both tasks. On prosaccade trials, SRTs were increased for saccades contralateral to and decreased for saccades ipsilateral to the stimulated hemisphere. In contrast, SRTs were decreased for both ipsi- and contralaterally directed antisaccades. These data show that microstimulation administered during response preparation facilitated the performance of antisaccades and are suggestive of a direct role of ACC in the implementation of cognitive control.

The Impact of Boost Methodology on Nurse Knowledge Retention: A Longitudinal, Quasi-Experimental Sepsis Simulation Pilot Study.

Boost methods for reinforcing educational content have been found to train the brain to designate information as important. A longitudinal, quasi-experimental study design evaluated the effect of an interprofessional simulated patient sepsis video with educational boosts on knowledge retention among acute care nurses at a large academic health system using linear mixed-effects modeling. Findings suggest that boost methods may impact nurse knowledge retention, potentially eliminating the need to repeat costly, traditional educational efforts.

Disentangling the influences of multiple thalamic nuclei on prefrontal cortex and cognitive control.

The prefrontal cortex (PFC) has a complex relationship with the thalamus, involving many nuclei which occupy predominantly medial zones along its anterior-to-posterior extent. Thalamocortical neurons in most of these nuclei are modulated by the affective and cognitive signals which funnel through the basal ganglia. We review how PFC-connected thalamic nuclei likely contribute to all aspects of cognitive control: from the processing of information on internal states and goals, facilitating its interactions with mnemonic information and learned values of stimuli and actions, to their influence on high-level cognitive processes, attentional allocation and goal-directed behavior. This includes contributions to transformations such as rule-to-choice (parvocellular mediodorsal nucleus), value-to-choice (magnocellular mediodorsal nucleus), mnemonic-to-choice (anteromedial nucleus) and sensory-to-choice (medial pulvinar). Common mechanisms appear to be thalamic modulation of cortical gain and cortico-cortical functional connectivity. The anatomy also implies a unique role for medial PFC in modulating processing in thalamocortical circuits involving other orbital and lateral PFC regions. We further discuss how cortico-basal ganglia circuits may provide a mechanism through which PFC controls cortico-cortical functional connectivity.

Consciousness depends on integration between parietal cortex, striatum, and thalamus.

The neural substrates of consciousness remain elusive. Competing theories that attempt to explain consciousness disagree on the contribution of frontal versus posterior cortex and omit subcortical influences. This lack of understanding impedes the ability to monitor consciousness, which can lead to adverse clinical consequences. To test substrates and measures of consciousness, we recorded simultaneously from frontal cortex, parietal cortex, and subcortical structures, the striatum and thalamus, in awake, sleeping, and anesthetized macaques. We manipulated consciousness on a finer scale using thalamic stimulation, rousing macaques from continuously administered anesthesia. Our results show that, unlike measures targeting complexity, a measure additionally capturing neural integration (Φ∗) robustly correlated with changes in consciousness. Machine learning approaches show parietal cortex, striatum, and thalamus contributed more than frontal cortex to decoding differences in consciousness. These findings highlight the importance of integration between parietal and subcortical structures and challenge a key role for frontal cortex in consciousness.

Vortex fluidics-mediated DNA rescue from formalin-fixed museum specimens.

DNA from formalin-preserved tissue could unlock a vast repository of genetic information stored in museums worldwide. However, formaldehyde crosslinks proteins and DNA, and prevents ready amplification and DNA sequencing. Formaldehyde acylation also fragments the DNA. Treatment with proteinase K proteolyzes crosslinked proteins to rescue the DNA, though the process is quite slow. To reduce processing time and improve rescue efficiency, we applied the mechanical energy of a vortex fluidic device (VFD) to drive the catalytic activity of proteinase K and recover DNA from American lobster tissue (Homarus americanus) fixed in 3.7% formalin for >1-year. A scan of VFD rotational speeds identified the optimal rotational speed for recovery of PCR-amplifiable DNA and while 500+ base pairs were sequenced, shorter read lengths were more consistently obtained. This VFD-based method also effectively recovered DNA from formalin-preserved samples. The results provide a roadmap for exploring DNA from millions of historical and even extinct species.

Thalamus Modulates Consciousness via Layer-Specific Control of Cortex.

Functional MRI and electrophysiology studies suggest that consciousness depends on large-scale thalamocortical and corticocortical interactions. However, it is unclear how neurons in different cortical layers and circuits contribute. We simultaneously recorded from central lateral thalamus (CL) and across layers of the frontoparietal cortex in awake, sleeping, and anesthetized macaques. We found that neurons in thalamus and deep cortical layers are most sensitive to changes in consciousness level, consistent across different anesthetic agents and sleep. Deep-layer activity is sustained by interactions with CL. Consciousness also depends on deep-layer neurons providing feedback to superficial layers (not to deep layers), suggesting that long-range feedback and intracolumnar signaling are important. To show causality, we stimulated CL in anesthetized macaques and effectively restored arousal and wake-like neural processing. This effect was location and frequency specific. Our findings suggest layer-specific thalamocortical correlates of consciousness and inform how targeted deep brain stimulation can alleviate disorders of consciousness.

Chemoselective and Continuous Flow Hydrogenations in Thin Films Using a Palladium Nanoparticle Catalyst Embedded in Cellulose Paper.

Cellulose immobilized palladium (0) nanoparticles (PdNPs) were prepared for the use in scalable catalytic reactions in flow. Preparation of the catalyst is remarkably simple and fast, where a palladium acetate solution is drop-casted onto cellulose paper and then exposed to 1 atm of hydrogen for a mere 90 s to produce embedded Pd(0) nanoparticles. This catalyst system is efficient in the hydrogenation of alkenes, nitroarenes, ketones, and enamides, with products formed in high yields, under ambient pressure and temperature. The system is also effective for transfer hydrogenation using ammonium formate as an alternative hydrogen source. A high catalyst stability and reusability are demonstrated along with the chemoselective and scalable synthesis of industrially important fine chemicals, including the biobased molecule cyrene.

A Subcortical Pathway for Rapid, Goal-Driven, Attentional Filtering.

Prefrontal cortex can exercise goal-driven attentional control over sensory information via cortical pathways. However, recent work demonstrates that prefrontal cortex can also influence thalamic relay nuclei via the thalamic reticular nucleus. This suggests the prefrontal-thalamic pathway mediates rapid and goal-driven attentional filtering at the earliest stages of sensory processing.

Trapping five-coordinate platinum(iv) intermediates.

The oxidation of three different complexes of the doubly cycloplatinated 2,6-di(4-fluorophenyl)pyridine ligand (namely DMSO, PPh3 and PPr3 derivatives, 1a, 1b and 1c, respectively) with the electrophilic oxidant iodobenzenedichloride was studied. In each case oxidation can yield a simple trans-dichloro platinum(iv) complex (2(t)), which subsequently isomerises to the cis isomer (2(c)). However, by changing the solvent, or performing the reaction in the presence of an additional ligating species, a five-coordinate intermediate can be trapped out and isolated. Thus, cationic species with additional DMSO or pyridine coordinated could be collected for the DMSO and PPh3 derivatives. The PPr3 derivative traps out the reactive five-coordinate species with an agostic interaction that subsequently induces a transcyclometallation reaction to give a complex with a singly cyclometallated pyridine and a cyclometallated phosphine, which was characterised crystallographically, (6c

Intramolecular transcyclometallation: the exchange of an aryl-Pt bond for an alkyl-Pt bond via an agostic intermediate.

Oxidation of a square-planar platinum complex leads to a five coordinate cationic intermediate that can be stabilized and trapped out via an agostic interaction with the alkyl chain of a ligand. Subsequent reaction of this species leads to the formation of an alkyl-Pt bond at the expense of an aryl-Pt bond: an intramolecular transcyclometallation.