Brain state transitions primarily impact the spontaneous rate of slow-firing neurons.

The spontaneous firing of neurons is modulated by brain state. Here, we examine how such modulation impacts the overall distribution of firing rates in neuronal populations of neocortical, hippocampal, and thalamic areas across natural and pharmacologically driven brain state transitions. We report that across all the examined combinations of brain area and state transition category, the structure of rate modulation is similar, with almost all fast-firing neurons experiencing proportionally weak modulation, while slow-firing neurons exhibit high inter-neuron variability in the modulation magnitude, leading to a stronger modulation on average. We further demonstrate that this modulation structure is linked to the left-skewed distribution of firing rates on the logarithmic scale and is recapitulated by bivariate log-gamma, but not Gaussian, distributions. Our findings indicate that a preconfigured log-rate distribution with rigid fast-firing neurons and a long left tail of malleable slow-firing neurons is a generic property of forebrain neuronal circuits.

Inositol in Disease and Development: Roles of Catabolism via myo-Inositol Oxygenase in Drosophila melanogaster.

Inositol depletion has been associated with diabetes and related complications. Increased inositol catabolism, via myo-inositol oxygenase (MIOX), has been implicated in decreased renal function. This study demonstrates that the fruit fly Drosophila melanogaster catabolizes myo-inositol via MIOX. The levels of mRNA encoding MIOX and MIOX specific activity are increased when fruit flies are grown on a diet with inositol as the sole sugar. Inositol as the sole dietary sugar can support D. melanogaster survival, indicating that there is sufficient catabolism for basic energy requirements, allowing for adaptation to various environments. The elimination of MIOX activity, via a piggyBac WH-element inserted into the MIOX gene, results in developmental defects including pupal lethality and pharate flies without proboscises. In contrast, RNAi strains with reduced levels of mRNA encoding MIOX and reduced MIOX specific activity develop to become phenotypically wild-type-appearing adult flies. myo-Inositol levels in larval tissues are highest in the strain with this most extreme loss of myo-inositol catabolism. Larval tissues from the RNAi strains have inositol levels higher than wild-type larval tissues but lower levels than the piggyBac WH-element insertion strain. myo-Inositol supplementation of the diet further increases the myo-inositol levels in the larval tissues of all the strains, without any noticeable effects on development. Obesity and blood (hemolymph) glucose, two hallmarks of diabetes, were reduced in the RNAi strains and further reduced in the piggyBac WH-element insertion strain. Collectively, these data suggest that moderately increased myo-inositol levels do not cause developmental defects and directly correspond to reduced larval obesity and blood (hemolymph) glucose.

Consensus definition of essential, optimal, and suggested components of a pediatric sickle cell disease center.

Sickle cell disease (SCD) requires coordinated, specialized medical care for optimal outcomes. There are no United States (US) guidelines that define a pediatric comprehensive SCD program. We report a modified Delphi consensus-seeking process to determine essential, optimal, and suggested elements of a comprehensive pediatric SCD center. Nineteen pediatric SCD specialists participated from the US. Consensus was predefined as 2/3 agreement on each element's categorization. Twenty-six elements were considered essential (required for guideline-based SCD care), 10 were optimal (recommended but not required), and five were suggested. This work lays the foundation for a formal recognition process of pediatric comprehensive SCD centers.

Common Factors in Biofeedback Administered by Psychotherapists.

Common factors are nonspecific therapeutic elements common across different varieties of psychotherapy. In a recent study, 68 expert psychotherapy researchers with a variety of allegiances collectively rated biofeedback as being negatively associated with many common factors (Tschacher et al. in Clin Psychol Psychother 21(1):82-96, 2014), including the therapeutic alliance. However, it seems implausible that biofeedback could benefit so many people while being incompatible with the therapeutic alliance and other common factors. The present study investigated the experiences of biofeedback clients who participated in a brief heart rate variability biofeedback protocol in order to explore the potential roles of common factors in biofeedback. The results of this study offer preliminary evidence that many common factors-including therapeutic alliance, self-efficacy expectation, mastery experiences, provision of explanatory scheme, mindfulness, and even cognitive restructuring-may play a role in biofeedback outcomes. Future research on this topic should include mediation and moderation models investigating the role of specific common factors on outcome and process studies to help determine what clinician behaviors are most helpful. Deeper investigation of common factors in biofeedback may benefit future biofeedback research and practice and address the concerns of colleagues outside of the biofeedback community who believe that biofeedback is at odds with common factors.

Perceptions of Bedside Cardiac Critical Care Registered Nurses on 24 Hour Attending Intensivist Coverage.

OBJECTIVE: To elicit the perceptions of bedside critical care nurses toward continual in-house attending coverage and its effect on patient safety, communication, and nursing education. DESIGN: A 5-point Likert-type questionnaire was designed to evaluate the perception of bedside nurses in the pediatric cardiac intensive care unit (PCICU) toward the presence of a 24 hour in-house attending physician. SETTING: Single tertiary referral PCICU in Washington, DC SUBJECTS: The 46 PCICU nurses who participated in the study were separated into two groups based on exposure to the recent implementation of continual in-house attending coverage at our institution. Group one consisted of 14 nurses with only exposure to the new 24/7 in-house coverage while group two encompassed 32 nurses who had experienced both the new and old system (off-site on-demand attending physician). MEASUREMENTS AND MAIN RESULTS: Surveys demonstrated that both groups found that the new system has a positive impact on nursing education (median score of 5) as well as a positive impact on the communication between multidisciplinary teams and between care team and families (median score of 5). Nurses who experienced only the new system scored one point lower (median score of 4) regarding the effect of this staffing model on patient outcomes than nurses who had experienced both systems (median score of 5, P = .016). Between 83% and 98% of all 46 nurses who participated indicated they agree or strongly agree with each of the questions regarding the benefit of 24 hour in-house attending coverage. CONCLUSION: Our study suggests that regardless of differences in experience, pediatric cardiac nurses believe the presence of an on-site intensivist to be beneficial to both nursing and patients.

Toward correlation in in vivo and in vitro nanotoxicology studies.

Nanomaterials have the promise of revolutionizing current treatment and diagnosis of diseases, which has led to 33 nanotherapeutics drugs currently on the market and many more in various stages of clinical trials. With an increasing number of products available and in development, along with the unique, emergent properties of the nanoparticle therapeutics themselves, regulatory agencies are now faced with decisions regarding the regulation of such novel technologies. Regulatory guidance, particularly in pre-clinical stages, has the potential to facilitate quick and safe development of these novel materials, but new regulation beyond what is currently in place must be justified in a clear and distinctive toxic response. Herein, we examine literature that compares and correlates in vivo and in vitro nanotoxicity studies to gain a deeper understanding of the modes of nanoparticle toxicity. Additionally, this comparison aims to identify clear and unique toxicity responses caused by nanoparticles, which informs our perspective on pre-clinical nanotherapeutic oversight.