Recurrence of ventricular fibrillation in out-of-hospital cardiac arrest: Clinical evidence and underlying ionic mechanisms.

Defibrillation remains the optimal therapy for terminating ventricular fibrillation (VF) in out-of-hospital cardiac arrest (OHCA) patients, with reported shock success rates of ∼90%. A key persistent challenge, however, is the high rate of VF recurrence (∼50-80%) seen during post-shock cardiopulmonary resuscitation (CPR). Studies have shown that the incidence and time spent in recurrent VF are negatively associated with neurologically-intact survival. Recurrent VF also results in the administration of extra shocks at escalating energy levels, which can cause cardiac dysfunction. Unfortunately, the mechanisms underlying recurrent VF remain poorly understood. In particular, the role of chest-compressions (CC) administered during CPR in mediating recurrent VF remains controversial. In this review, we first summarize the available clinical evidence for refibrillation occurring during CPR in OHCA patients, including the postulated contribution of CC and non-CC related pathways. Next, we examine experimental studies highlighting how CC can re-induce VF via direct mechano-electric feedback. We postulate the ionic mechanisms involved by comparison with similar phenomena seen in commotio cordis. Subsequently, the hypothesized contribution of partial cardiac reperfusion (either as a result of CC or CC independent organized rhythm) in re-initiating VF in a globally ischaemic heart is examined. An overview of the proposed ionic mechanisms contributing to VF recurrence in OHCA during CPR from a cellular level to the whole heart is outlined. Possible therapeutic implications of the proposed mechanistic theories for VF recurrence in OHCA are briefly discussed.

The influence of false interoceptive feedback on emotional state and balance responses to height-induced postural threat.

Postural threat elicits a robust emotional response (e.g., fear and anxiety about falling), with concomitant modifications in balance. Recent theoretical accounts propose that emotional responses to postural threats are manifested, in part, from the conscious monitoring and appraisal of bodily signals ('interoception'). Here, we empirically probe the role of interoception in shaping emotional responses to a postural threat by experimentally manipulating interoceptive cardiac feedback. Sixty young adults completed a single 60-s trial under the following conditions: Ground (no threat) without heart rate (HR) feedback, followed by Threat (standing on the edge of a raised surface), during which participants received either false heart rate feedback (either slow [n=20] or fast [n=20] HR feedback) or no feedback (n=20). Participants provided with false fast HR feedback during postural threat felt more fearful, reported feeling less stable, and rated the task more difficult than participants who did not receive HR feedback, or those who received false slow HR feedback (Cohen's d effect size = 0.79 - 1.78). However, behavioural responses did not significantly differ across the three groups. When compared to the no HR feedback group, false slow HR feedback did not significantly affect emotional or behavioural responses to the postural threat. These observations provide the first experimental evidence for emerging theoretical accounts describing the role of interoception in the generation of emotional responses to postural threats.

The Effect of Stroboscopic Vision Training on Blind-folded Straight-line Walking.

Stroboscopic vision training has shown to improve visual-motor control and dynamic visual acuity in sport performance; however, no studies have considered using this training to enhance kinesthetic awareness during walking, applicable to high fall-risk populations. Purpose: The purpose of this study was to assess the effect of stroboscopic vision training on blind-folded straight-line walking. Methods: Thirty-seven college-aged healthy participants (age: 20.14 ± 1.23 years; females: N = 32, males: N = 5) completed this study. In this pre-posttest quasi-experimental investigation, participants with no epileptic or balance disorder history completed a four-week progressive stroboscopic vision training protocol. To assess sensorimotor feedback participants were instructed to walk a 27.5 m straight line while blindfolded. PRE and POST blind-folded straight line walk tests were completed and deviations from endpoint were measured. A paired-samples t-test was used to analyze the calculated deviation angles. Results: Significant difference was noted from PRE (14.48 ± 5.95) to POST (11.60 ± 6.78) deviation angles (t(36) = 2.71, p = 0.01). Conclusions: This is the first study to examine the effects of stroboscopic training on a vision restricted walking task, which demands feedback re-weighting. These findings may be valuable for clinical settings or performance where reliance on non-visual systems may be beneficial.

The feedback dilemma in medical education: insights from medical residents' perspectives.

BACKGROUND: Feedback is a critical component of the learning process in a clinical setting. This study aims to explore medical residents' perspectives on feedback delivery and identify potential barriers to feedback-seeking in clinical training. METHODS: This cross-sectional study involved 180 medical residents across seventeen specialties. We employed the validated Residency Education Feedback Level Evaluation in Clinical Training (REFLECT) tool to assess residents' perspectives on their attitude toward feedback, quality of feedback, perceived importance, and reaction to feedback. Additionally, we explored barriers to feedback-seeking behavior among medical residents. RESULTS: The majority of medical residents held positive attitudes toward feedback. They agreed that feedback improves their clinical performance (77.7%), professional behavior (67.2%), and academic motivation (56.7%), while also influencing them to become a better specialist in their future career (72.8%). However, the study revealed critical deficiencies in the feedback process. Only 25.6% of residents reported receiving regular feedback and less than half reported that feedback was consistently delivered at suitable times and locations, was sufficiently clear or included actionable plans for improvement. A minority (32.2%) agreed that faculty had sufficient skills to deliver feedback effectively. Moreover, peer-to-peer feedback appeared to be a primary source of feedback among residents. Negative feedback, though necessary, often triggered feelings of stress, embarrassment, or humiliation. Notably, there were no significant differences in feedback perceptions among different specialties. The absence of a feedback-seeking culture emerged as a central barrier to feedback-seeking behavior in the clinical setting. CONCLUSIONS: Establishing shared expectations and promoting a culture of feedback-seeking could bridge the gap between residents' perceptions and faculty feedback delivery. Furthermore, recognizing the role of senior and peer residents as valuable feedback sources can contribute to more effective feedback processes in clinical training, ultimately benefiting resident development and patient care.

Reciprocal negative feedback between Prrx1 and miR-140-3p regulates rapid chondrogenesis in the regenerating antler.

During growth phase, antlers exhibit a very rapid rate of chondrogenesis. The antler is formed from its growth center reserve mesenchyme (RM) cells, which have been found to be the derivatives of paired related homeobox 1 (Prrx1)-positive periosteal cells. However, the underlying mechanism that drives rapid chondrogenesis is not known. Herein, the miRNA expression profiles and chromatin states of three tissue layers (RM, precartilage, and cartilage) at different stages of differentiation within the antler growth center were analyzed by RNA-sequencing and ATAC-sequencing. We found that miR-140-3p was the miRNA that exhibited the greatest degree of upregulation in the rapidly growing antler, increasing from the RM to the cartilage layer. We also showed that Prrx1 was a key upstream regulator of miR-140-3p, which firmly confirmed by Prrx1 CUT&Tag sequencing of RM cells. Through multiple approaches (three-dimensional chondrogenic culture and xenogeneic antler model), we demonstrated that Prrx1 and miR-140-3p functioned as reciprocal negative feedback in the antler growth center, and downregulating PRRX1/upregulating miR-140-3p promoted rapid chondrogenesis of RM cells and xenogeneic antler. Thus, we conclude that the reciprocal negative feedback between Prrx1 and miR-140-3p is essential for balancing mesenchymal proliferation and chondrogenic differentiation in the regenerating antler. We further propose that the mechanism underlying chondrogenesis in the regenerating antler would provide a reference for helping understand the regulation of human cartilage regeneration and repair.

Neural assemblies coordinated by cortical waves are associated with waking and hallucinatory brain states.

The relationship between sensory stimuli and perceptions is brain-state dependent: in wakefulness, suprathreshold stimuli evoke perceptions; under anesthesia, perceptions are abolished; and during dreaming and in dissociated states, percepts are internally generated. Here, we exploit this state dependence to identify brain activity associated with internally generated or stimulus-evoked perceptions. In awake mice, visual stimuli phase reset spontaneous cortical waves to elicit 3-6 Hz feedback traveling waves. These stimulus-evoked waves traverse the cortex and entrain visual and parietal neurons. Under anesthesia as well as during ketamine-induced dissociation, visual stimuli do not disrupt spontaneous waves. Uniquely, in the dissociated state, spontaneous waves traverse the cortex caudally and entrain visual and parietal neurons, akin to stimulus-evoked waves in wakefulness. Thus, coordinated neuronal assemblies orchestrated by traveling cortical waves emerge in states in which perception can manifest. The awake state is privileged in that this coordination is reliably elicited by external visual stimuli.

Enhancing Psychotherapy Outcomes by Encouraging Patients to Regularly Self-Monitor, Reflect on, and Share Their Affective Responses Toward Their Therapist: Protocol for a Randomized Controlled Trial.

BACKGROUND: The quality of the therapeutic relationship is pivotal in determining psychotherapy outcomes. However, facilitating patients' self-awareness, reflection on, and sharing of their affective responses toward their therapist remains underexplored as a potential tool for enhancing this relationship and subsequent treatment outcomes. OBJECTIVE: The primary objective of this study is to examine whether and how the patients' regular self-monitoring and self-reflection (fostered by the systematic compilation of a brief postsession battery) on their affective reactions toward the psychotherapist impact the quality of the therapeutic relationship and treatment outcomes in individual psychotherapy. Secondary objectives are to (1) explore whether and how the characteristics of the patient, the therapist, and the process moderate the effect of regular self-monitoring on the therapeutic relationship and outcomes; (2) examine the relationships between the affective response of the patient, the alliance, and the result of the therapy session outcome; and (3) explore how the affective responses of the patient unfold or change throughout the course of the therapy. METHODS: We conducted a 1:1 randomized controlled trial of adults in individual psychotherapy versus individual psychotherapy plus self-monitoring. Participants will be enrolled through the web-based recruitment platforms "ResearchMatch" and "Research for Me," and data will be collected through web-based surveys. Participants in the control group will receive only their regular individual psychotherapy (treatment as usual) and will not complete postsession questionnaires. Participants in the intervention group will continue their regular individual psychotherapy sessions and complete the "in-Session Patient Affective Reactions Questionnaire" and the "Rift In-Session Questionnaire" following each therapy session in the 10 weeks of the trial. Additionally, after completion of the postsession battery, they will receive general written feedback encouraging them to discuss their feelings and reflections with their therapist. Participants in both groups will complete a comprehensive psychological assessment at baseline, midtrial (week 5), and end-of-trial (week 10). The primary outcome measure of the trial is the "Clinical Outcomes in Routine Evaluation-Outcome Measure," while the secondary outcomes are the "Real Relationship Inventory-Client-Short Form," the "Working Alliance Inventory-Short Revised," and the number of scheduled therapy sessions that the patient has missed or canceled. RESULTS: The trial was approved by the institutional review board of the University of North Carolina at Chapel Hill. Recruitment started in September 2023. A total of 475 individuals completed the baseline assessment. Data collection was completed in February 2024. The results are expected to be published in the autumn of 2024. CONCLUSIONS: This study could reveal key information on how regular self-monitoring and introspection can influence both the therapeutic relationship and treatment outcomes. Findings have the potential to shape interventions, enhance the efficacy of psychotherapeutic sessions, and possibly offer a cost-effective strategy for improving patients' well-being. TRIAL REGISTRATION: ClinicalTrials.gov NCT06038747; https://classic.clinicaltrials.gov/ct2/show/NCT06038747. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/55369.

Specific connectivity optimizes learning in thalamocortical loops.

Thalamocortical loops have a central role in cognition and motor control, but precisely how they contribute to these processes is unclear. Recent studies showing evidence of plasticity in thalamocortical synapses indicate a role for the thalamus in shaping cortical dynamics through learning. Since signals undergo a compression from the cortex to the thalamus, we hypothesized that the computational role of the thalamus depends critically on the structure of corticothalamic connectivity. To test this, we identified the optimal corticothalamic structure that promotes biologically plausible learning in thalamocortical synapses. We found that corticothalamic projections specialized to communicate an efference copy of the cortical output benefit motor control, while communicating the modes of highest variance is optimal for working memory tasks. We analyzed neural recordings from mice performing grasping and delayed discrimination tasks and found corticothalamic communication consistent with these predictions. These results suggest that the thalamus orchestrates cortical dynamics in a functionally precise manner through structured connectivity.

Improved assay development of pharmaceutical modalities using feedback-controlled liquid chromatography optimization.

Development of meaningful and reliable analytical assays in the (bio)pharmaceutical industry can often be challenging, involving tedious trial and error experimentation. In this work, an automated analytical workflow using an AI-based algorithm for streamlined method development and optimization is presented. Chromatographic methods are developed and optimized from start to finish by a feedback-controlled modeling approach using readily available LC instrumentation and software technologies, bypassing manual user intervention. With the use of such tools, the time requirement of the analyst is drastically minimized in the development of a method. Herein key insights on chromatography system control, automatic optimization of mobile phase conditions, and final separation landscape for challenging multicomponent mixtures are presented (e.g., small molecules drug, peptides, proteins, and vaccine products) showcased by a detailed comparison of a chiral method development process. The work presented here illustrates the power of modern chromatography instrumentation and AI-based software to accelerate the development and deployment of new separation assays across (bio)pharmaceutical modalities while yielding substantial cost-savings, method robustness, and fast analytical turnaround.

Improving appropriate use of intravenous albumin: results of a single-centre audit and multifaceted intervention.

BACKGROUND: Intravenous albumin has limited indications supported by randomised controlled trials, yet it is often prescribed for indications not supported by evidence. AIM: To reduce unnecessary transfusion of albumin. INTERVENTIONS: Under the leadership of a multidisciplinary quality improvement team, evidence-based recommendations were disseminated in tandem with a new electronic order set, an educational strategy, qualitative interviews with prescribers and a return policy change to reduce wastage. IMPLEMENTATION AND EVALUATION: Interventions were introduced in a staggered fashion. The primary outcome, appropriate use of albumin, was monitored and quantified using pre-intervention and post-intervention audits. Process measures included statistical process run charts of monthly usage of 5% and 25% albumin and wastage. Data on length of stay (hospital and intensive care), new inpatient starts on kidney replacement and mortality were collected as balancing measures. RESULTS: Appropriate albumin usage based on indication increased from 30% to 50% (p<0.0001). There was significantly less overall albumin usage in the post-intervention period compared with the pre-intervention period (negative coefficient, p<0.0001), driven by a major reduction in the utilisation of the 5% formulation (p<0.0001). Overall albumin usage was significantly lower in the post-intervention period, decreasing from 800 to 450 vials per month. The intervention resulted in significantly less wastage (negative coefficient, p=0.017). Mortality, length of stay and new starts on kidney replacement therapy remained constant throughout the study period. CONCLUSION: Improved prescribing of albumin was achieved with a multifaceted approach. Substantial and sustained reductions in usage were achieved without negatively impacting patient-important outcomes. The estimated annual savings for the purchase cost of albumin was CAN $300 000. We provide a structured process for other organisations to optimise their use of albumin.

Midwives' experiences of professional learning when practicing collegial midwifery assistance during the active second stage of labour: data from the oneplus trial.

BACKGROUND: Learning is a lifelong process and the workplace is an essential arena for professional learning. Workplace learning is particularly relevant for midwives as essential knowledge and skills are gained through clinical work. A clinical practice known as 'Collegial Midwifery Assistance' (CMA), which involves two midwives being present during the active second stage of labour, was found to reduce severe perineal trauma by 30% in the Oneplus trial. Research regarding learning associated with CMA, however, is lacking. The aim was to investigate learning experiences of primary and second midwives with varying levels of work experience when practicing CMA, and to further explore possible factors that influence their learning. METHODS: The study uses an observational design to analyse data from the Oneplus trial. Descriptive statistics and proportions were calculated with 95% confidence intervals. Stratified univariable and multivariable logistic regression analysis were performed. RESULTS: A total of 1430 births performed with CMA were included in the study. Less experienced primary midwives reported professional learning to a higher degree (< 2 years, 76%) than the more experienced (> 20 years, 22%). A similar but less pronounced pattern was seen for the second midwives. Duration of the intervention ≥ 15 min improved learning across groups, especially for the least experienced primary midwives. The colleague's level of experience was found to be of importance for primary midwives with less than five years' work experience, whereas for second midwives it was also important in their mid to late career. Reciprocal feedback had more impact on learning for the primary midwife than the second midwife. CONCLUSIONS: The study provides evidence that CMA has the potential to contribute with professional learning both for primary and second midwives, for all levels of work experience. We found that factors such as the colleague's work experience, the duration of CMA and reciprocal feedback influenced learning, but the importance of these factors were different for the primary and second midwife and varied depending on the level of work experience. The findings may have implications for future implementation of CMA and can be used to guide the practice.

Consulting doctors online after offline treatment: investigating the effects of online information on patients' effective use of online follow-up services.

Introduction: The use of online follow-up services (OFUS) is becoming an increasingly important supplement to hospital care. Through OFUS, patients can find their doctors in online health communities (OHCs) and receive remote medical follow-ups after hospital treatment. However, the rate of effective use of OFUS by current patients is still low, and there is an urgent need for research to investigate the online information factors that affect patients' effective use of OFUS. Methods: Based on the elaboration likelihood model (ELM) of persuasion and an analysis of a panel dataset including 3,672 doctors in a leading OHC in China, this study explores how online information from doctors' knowledge contributions and patient feedback influences patients' effective use of OFUS. Results: The results show that both doctors' knowledge contributions and patient feedback positively influence patients' effective use of OFUS. Doctors' paid knowledge contributions and patients' paid feedback have stronger persuasive effects than doctors' free knowledge contributions and patients' free feedback, respectively. Moreover, there is a substitutional relationship between doctors' paid and free knowledge contributions and between patients' paid and free feedback in influencing patients' effective use of OFUS. Discussion: The findings of this study suggest that OHC platforms and healthcare providers should account not only for the persuasive effects of doctors' knowledge contributions and patient feedback but also for influential differences and relationships between the types of doctors' knowledge contributions and patient feedback to better persuade patients to effectively use OFUS.

Quantifying soil microbial effects on plant species coexistence: A conceptual synthesis.

Soil microorganisms play a critical role in shaping the biodiversity dynamics of plant communities. These microbial effects can arise through direct mediation of plant fitness by pathogens and mutualists, and over the past two decades, numerous studies have shined a spotlight on the role of dynamic feedbacks between plants and soil microorganisms as key determinants of plant species coexistence. Such feedbacks occur when plants modify the composition of the soil community, which in turn affects plant performance. Stimulated by a theoretical model developed in the 1990s, a bulk of the empirical evidence for microbial controls over plant coexistence comes from experiments that quantify plant growth in soil communities that were previously conditioned by conspecific or heterospecific plants. These studies have revealed that soil microbes can generate strong negative to positive frequency-dependent dynamics among plants. Even as soil microbes have become recognized as a key player in determining plant coexistence outcomes, the past few years have seen a renewed interest in expanding the conceptual foundations of this field. New results include re-interpretations of key metrics from classic two-species models, extensions of plant-soil feedback theory to multispecies communities, and frameworks to integrate plant-soil feedbacks with processes like intra- and interspecific competition. Here, I review the implications of theoretical developments for interpreting existing empirical results and highlight proposed analyses and designs for future experiments that can enable a more complete understanding of microbial regulation of plant community dynamics.

Benchmarking System Monitoring on Quality Improvement in Percutaneous Coronary Intervention: A Nationwide Registry in Japan.

Background: Quality indicators (QIs) have been developed to improve and standardize care quality in percutaneous coronary intervention (PCI). In Japan, consecutive PCI procedures are registered in a nationwide database (the Japanese Percutaneous Coronary Intervention registry), which introduces a benchmarking system for comparing individual institutional performance against the national average. Objectives: The aim of this study was to assess the impact of the benchmarking system implementation on QI improvement at the hospital level. Methods: A total of 734,264 PCIs were conducted at 1,194 institutions between January 2019 and December 2021. In January 2018, a web-based benchmarking system encompassing 7 QIs for PCI at the institutional level, including door-to-balloon time and rate of transradial intervention, was introduced. The process by which institutions tracked their QIs was centrally monitored. Results: During the 3-year study period, the benchmarking system was reviewed at least once at 742 institutions (62.1%) (median 4 times; Q1-Q3: 2-7 times). The institutions that reviewed their records had higher PCI volumes. Among these institutions, although door-to-balloon time was not directly associated, the proportion of transradial intervention increased by 2.3% in the system review group during the initial year compared with 0.7% in their counterparts. However, in the subsequent year, the association between system reviews and QI improvement was attenuated. Conclusions: The implementation of a benchmarking system, reviewed by participating institutions in Japan, was partially associated with improved QIs during the first year; however, this improvement was attenuated in the subsequent year, highlighting the need for further efforts to develop effective and sustainable interventions to enhance care quality in PCI.

Transformation of Mandatory Physiotherapy Internship into A Structured Competency-Based Program: A Pilot Study.

Introduction: Health professions education is challenging in terms of developing ways to construct and assess the amalgamation of knowledge, skills and attitudes that result in novice graduates to be self-aware and confident to practice without supervision. Currently, the Physiotherapy internship program in India does not have a comprehensive competency-based framework. With the current batch of interns facing the wrath of the COVID-19 pandemic during their undergraduate training, it is a matter of concern to ensure they have developed the required competencies to handle patients independently. Methods: This is a single-group interventional study using convenience sampling. A competency framework inclusive of a comprehensive assessment and training module was developed and introduced to 27 physiotherapy interns. Every intern underwent 10 training sessions along with 8 competency assessments during 6 months of internship training. A pre-post indigenous questionnaire was used to assess their self-perceived competency along with feedback questionnaire taken at the end of the module. Results: Implementation of the competency framework revealed a statistically significant difference in the self-perceived competency (pre=84.36±10.98, post=98.55±8.74, p≤0.000). Having uniformity in assessment techniques among the faculty, being exposed to challenging cases during assessment, having training module at the beginning of the internship were some of the suggestions given by the participants. Conclusion: Competency based education offers to be an effective technique in health professional program. Incorporating a competency-based training would help the learners to understand their strengths and weaknesses that would go a long way to develop competent health-care professionals. Developing such framework in curriculum will emphasize standardization of learning outcomes, thereby resulting in quality education, further enhancing patient care, and improving the health outcomes worldwide.

Top-down modulation of visual cortical stimulus encoding and gamma independent of firing rates.

Neurons in primary visual cortex integrate sensory input with signals reflecting the animal's internal state to support flexible behavior. Internal variables, such as expectation, attention, or current goals, are imposed in a top-down manner via extensive feedback projections from higher-order areas. We optogenetically activated a high-order visual area, area 21a, in the lightly anesthetized cat (OptoTD), while recording from neuronal populations in V1. OptoTD induced strong, up to several fold, changes in gamma-band synchronization together with much smaller changes in firing rate, and the two effects showed no correlation. OptoTD effects showed specificity for the features of the simultaneously presented visual stimuli. OptoTD-induced changes in gamma synchronization, but not firing rates, were predictive of simultaneous changes in the amount of encoded stimulus information. Our findings suggest that one important role of top-down signals is to modulate synchronization and the information encoded by populations of sensory neurons.

An ascending vagal sensory-central noradrenergic pathway modulates retrieval of passive avoidance memory.

Background: Visceral feedback from the body is often subconscious, but plays an important role in guiding motivated behaviors. Vagal sensory neurons relay "gut feelings" to noradrenergic (NA) neurons in the caudal nucleus of the solitary tract (cNTS), which in turn project to the anterior ventrolateral bed nucleus of the stria terminalis (vlBNST) and other hypothalamic-limbic forebrain regions. Prior work supports a role for these circuits in modulating memory consolidation and extinction, but a potential role in retrieval of conditioned avoidance remains untested. Results: To examine this, adult male rats underwent passive avoidance conditioning. We then lesioned gut-sensing vagal afferents by injecting cholecystokinin-conjugated saporin toxin (CSAP) into the vagal nodose ganglia (Experiment 1), or lesioned NA inputs to the vlBNST by injecting saporin toxin conjugated to an antibody against dopamine-beta hydroxylase (DSAP) into the vlBNST (Experiment 2). When avoidance behavior was later assessed, rats with vagal CSAP lesions or NA DSAP lesions displayed significantly increased conditioned passive avoidance. Conclusions: These new findings support the view that a gut vagal afferent-to-cNTSNA-to-vlBNST circuit plays a role in modulating the expression/retrieval of learned passive avoidance. Overall, our data suggest a dynamic modulatory role of vagal sensory feedback to the limbic forebrain in integrating interoceptive signals with contextual cues that elicit conditioned avoidance behavior.