"Oh My Sleeping Child" Narcolepsy Type 1 in a 22-Month-Old Boy.

Pediatric narcolepsy is a complex disorder with unique diagnostic challenges. It is diagnosed with a combination of clinical presentation, polysomnogram with multiple sleep latency test (PSG with MSLT), and occasionally, hypocretin-1 (orexin) levels in the cerebrospinal fluid (CSF). This report describes a 22-month-old boy experiencing excessive daytime sleepiness (EDS) and frequent falls. The patient was subsequently diagnosed with narcolepsy using hypocretin-1 (orexin) levels. The intent of this report is to establish the utility of using hypocretin-1 (orexin) levels to diagnose narcolepsy type 1 in children who are too young to undergo PSG with MSLT. To our knowledge, there are no reports of narcolepsy in a patient this young. Early recognition and treatment of narcolepsy in children younger than age five may lead to a substantial impact on their cognitive development and minimize potential long- term complications.

Causes of Childhood Cancer: A Review of the Recent Literature: Part I-Childhood Factors.

PURPOSE: To review the childhood risk factors for pediatric cancer (diagnosis before age 20). METHODS: We conducted literature searches using Ovid Medline and Scopus to find primary research studies, review articles, and meta-analyses published from 2014 to 3 March 2021. RESULTS: Strong evidence indicates that an array of genetic and epigenetic phenomena, structural birth defects, and chromosomal anomalies are associated with an increased risk of various childhood cancers. Increased risk is also associated with prior cancer, likely due to previous treatment agents and therapeutic ionizing radiation. Convincing evidence supports associations between several pediatric cancers and ionizing radiation, immunosuppression, and carcinogenic virus infection both in healthy children and in association with immune suppression following organ transplantation. Breastfeeding and a childhood diet rich in fruits and vegetables appears to reduce the risk of pediatric leukemia but the evidence is less strong. Childhood vaccination against carcinogenic viruses is associated with a lower risk of several cancers; there is less strong evidence that other childhood vaccinations more broadly may also lower risk. Ultraviolet (UV) radiation is associated with increased melanoma risk, although most melanomas following childhood UV exposure occur later, in adulthood. Evidence is weak or conflicting for the role of body mass index, other childhood infections, allergies, and certain treatments, including immunomodulator medications and human growth therapy.

Universal PCR for bacteria, mycobacteria, and fungi: a 10-year retrospective review of clinical indications and patient outcomes.

IMPORTANCE: Our work provides a retrospective analysis of universal PCR orders for bacteria, mycobacteria, and fungi across our institution across a 10-year period. We assessed the positivity rates for this diagnostic tool by test type and specimen type and, critically, studied whether and how the results influenced the outcomes from treatment change, to readmission, to death.

Gastrojejunal Fistula Following Gastrostomy Tube.

Gastrostomy tubes are often placed in patients with poor voluntary intake, oropharyngeal dysphagia, or chronic illness to provide definitive nutritional access. Despite the widespread use of gastrostomy tubes, some patients can experience complications associated with this procedure including gastrocolic-cutaneous fistula and dislodgement of gastrostomy tube. This case discusses an instance of gastrojejunal fistula formation over one year after gastrostomy tube placement likely due to tube dislodgement. Imaging showed gastrostomy tube traversing the posterior wall of the stomach and creating a fistula into the jejunum, with the balloon inflated within the jejunum. Gastrostomy tube was removed and replaced, with gastrostomy tube study showing no extravasation of contrast. Patient is now doing well-tolerating tube feeds at goal.

CD8 T cell response and its released cytokine IFN-γ are necessary for lung alveolar epithelial repair during bacterial pneumonia.

Introduction: Alveolar epithelial regeneration depends on the activity of resident quiescent progenitor cells. Alveolar epithelial type II (AT2) cells are known as the alveolar epithelial progenitor cells. They exit quiescent state, proliferate rapidly in response to injury and differentiate into alveolar epithelial type I (AT1) cells to regenerate the damaged alveolar epithelium. Although AT2 cell plasticity has been a very intense field of research, the role of CD8 T cell response and their released cytokine IFN-γ, in regulating AT2 cell plasticity and alveolar epithelial repair and regeneration after injury remains largely unknown. Methods: We used flow cytometry to quantify the amount of CD8 T cells in mouse lungs after bacterial pneumonia caused by Streptococcus pneumoniae. To determine whether CD8 T cells and their released cytokine IFN-γ are necessary for AT2 cell activity during alveolar epithelial regeneration, we performed loss of function studies using anti-CD8 or anti-IFN-γ monoclonal antibody (mAb) treatment in vivo. We assessed the effects of CD8 T cells and cytokine IFN-γ on AT2 cell differentiation capacity using the AT2- CD8 T cell co-culture system in vitro. Results: We detected a transient wave of accumulation of CD8 T cells in mouse lungs, which coincided with the burst of AT2 cell proliferation during alveolar epithelial repair and regeneration in mice following bacterial pneumonia caused by Streptococcus pneumoniae. Depletion of CD8 T cells or neutralization of cytokine IFN-γ using anti-CD8 or anti-IFN-γ monoclonal antibody significantly reduced AT2 cell proliferation and differentiation into AT1 cells in mice after bacterial pneumonia. Furthermore, co-culture of CD8 T cells or cytokine IFN-γ with AT2 cells promoted AT2-to-AT1 cell differentiation in both murine and human systems. Conversely, blockade of IFN-γ signaling abrogated the increase in AT2-to-AT1 cell differentiation in the AT2- CD8 T cell co-culture system. Discussion: Our data demonstrate that CD8 T-cell response and cytokine IFN-γ are necessary for promoting AT2 cell activity during alveolar epithelial repair and regeneration after acute lung injury caused by bacterial pneumonia.

Pyloric Duplication Cyst in Newborn Male.

An enteric duplication cyst (EDC) is a rare congenital anomaly. Although EDCs can occur at any point throughout the gastrointestinal tract, they are most commonly reported in the ileum and only around 5-7% are of gastroduodenal origin. We report a case of a pyloric duplication cyst in a 3 hour old male with prenatal ultrasound showing a cystic mass. The patient had an abdominal ultrasound after birth that showed a mass with probable trilaminar wall. The diagnosis of pyloric duplication cyst was made in surgery and confirmed with histopathologic examination following resection. The patient is doing well with appropriate weight gain at follow-up appointments.

Emotional memories are enhanced when reactivated in slow wave sleep, but impaired when reactivated in REM.

Sleep supports memory consolidation. However, it is not completely clear how different sleep stages contribute to this process. While rapid eye movement sleep (REM) has traditionally been implicated in the processing of emotionally charged material, recent studies indicate a role for slow wave sleep (SWS) in strengthening emotional memories. Here, to directly examine which sleep stage is primarily involved in emotional memory consolidation, we used targeted memory reactivation (TMR) in REM and SWS during a daytime nap. Contrary to our hypothesis, reactivation of emotional stimuli during REM led to impaired memory. Consistent with this, REM% was correlated with worse recall in the group that took a nap without TMR. Meanwhile, cueing benefit in SWS was strongly correlated with the product of times spent in REM and SWS (SWS-REM product), and reactivation significantly enhanced memory in those with high SWS-REM product. Surprisingly, SWS-REM product was associated with better memory for reactivated items and poorer memory for non-reactivated items, suggesting that sleep both preserved and eliminated emotional memories, depending on whether they were reactivated. Notably, the emotional valence of cued items modulated both sleep spindles and delta/theta power. Finally, we found that emotional memories benefited from TMR more than did neutral ones. Our results suggest that emotional memories decay during REM, unless they are reactivated during prior SWS. Furthermore, we show that active forgetting complements memory consolidation, and both take place across SWS and REM. In addition, our findings expand upon recent evidence indicating a link between sleep spindles and emotional processing.

Unravelling G protein-coupled receptor signalling networks using global phosphoproteomics.

G protein-coupled receptor (GPCR) activation initiates signalling via a complex network of intracellular effectors that combine to produce diverse cellular and tissue responses. Although we have an advanced understanding of the proximal events following receptor stimulation, the molecular detail of GPCR signalling further downstream often remains obscure. Unravelling these GPCR-mediated signalling networks has important implications for receptor biology and drug discovery. In this context, phosphoproteomics has emerged as a powerful approach for investigating global GPCR signal transduction. Here, we provide a brief overview of the phosphoproteomic workflow and discuss current limitations and future directions for this technology. By highlighting some of the novel insights into GPCR signalling networks gained using phosphoproteomics, we demonstrate the utility of global phosphoproteomics to dissect GPCR signalling networks and to accelerate discovery of new targets for therapeutic development.

Morphology and morphometry of the human obturator nerve in males and females.

Peripheral nerve injury and the nerves' subsequent repair and regeneration continues to be marked clinically by poor functional recovery. The analysis of nerve morphology is an aspect which may provide an impact on successful clinical outcomes through better prediction of donor and recipient matching. In this study, we evaluated the morphological aspects of the human obturator nerve for a better understanding of its potential in nerve transplantation. Morphological characteristics of donor obturator nerves were analysed, including nerve diameter and length, fascicle count and the ratio of neural to non-neural tissue present within the cross-sectional area of the nerve's epineurium, with respect to laterality and sex. Statistical significance (p < 0.10) was determined for male obturator nerves having an average diameter of 2.67 mm compared to female obturator nerves at 1.91 mm, as well as left obturator nerves having an average of 11.21 fascicles compared to the right having an average of 10.17 fascicles. Strong positive correlations were determined between cross-sectional nerve area and limb size index, as well as between percentage of non-neural tissue and area of non-neural tissue, among males. Separately, strong correlation between percentage of non-neural tissue and area of non-neural tissue among right obturator nerves in males and females was determined . These findings indicate that there are associations and predictions that can be made about nerve morphology and that these when combined with other patient characteristics may enhance patient functional recovery following a peripheral nerve's repair.

A failure of sleep-dependent consolidation of visuoperceptual procedural learning in young adults with ADHD.

ADHD has been associated with cortico-striatal dysfunction that may lead to procedural memory abnormalities. Sleep plays a critical role in consolidating procedural memories, and sleep problems are an integral part of the psychopathology of ADHD. This raises the possibility that altered sleep processes characterizing those with ADHD could contribute to their skill-learning impairments. On this basis, the present study tested the hypothesis that young adults with ADHD have altered sleep-dependent procedural memory consolidation. Participants with ADHD and neurotypicals were trained on a visual discrimination task that has been shown to benefit from sleep. Half of the participants were tested after a 12-h break that included nocturnal sleep (sleep condition), whereas the other half were tested after a 12-h daytime break that did not include sleep (wakefulness condition) to assess the specific contribution of sleep to improvement in task performance. Despite having a similar degree of initial learning, participants with ADHD did not improve in the visual discrimination task following a sleep interval compared to neurotypicals, while they were on par with neurotypicals during the wakefulness condition. These findings represent the first demonstration of a failure in sleep-dependent consolidation of procedural learning in young adults with ADHD. Such a failure is likely to disrupt automatic control routines that are normally provided by the non-declarative memory system, thereby increasing the load on attentional resources of individuals with ADHD.

Loot box spending is associated with problem gambling but not mental wellbeing.

There are emerging concerns that loot boxes-digital video game items that can be purchased for a chance at randomized rewards-are associated with problematic gambling behaviours and, in turn, are potentially harmful. Current research suggests consistent correlations between loot box spending (LS) and problematic gambling symptomology; however, little research has looked at relationships with mental wellbeing. Here, we used a Bayesian hypothesis testing framework to assess the relative strength of evidence for relationships between LS, excessive gaming, problem gambling, mental wellbeing and psychological distress. Two thousand seven hundred twenty-eight participants who reported playing games containing loot box mechanics in the past month answered a survey assessing the above measures, as well as other forms of digital spending. The results showed extremely strong evidence for a positive correlation between LS and problem gambling; however, there was no evidence to suggest relationships between such spending and mental wellbeing or psychological distress. Exploratory results suggested that individuals who spend money on loot boxes also spend more across a range of digital purchases generally. The findings highlight an urgent need to understand what constitutes harm when considering LS effects and provide further context for discussions regarding how best to regulate such mechanisms.

Pineal Gland from the Cell Culture to Animal Models: A Review.

This review demonstrates current literature on pineal gland physiology, pathology, and animal model experiments to concisely explore future needs in research development with respect to pineal gland function and neuro-regenerative properties. The pineal gland plays an integral role in sleep and recovery by promoting physiologic circadian rhythms via production and release of melatonin. Yet, the current literature shows that the pineal gland has neuroprotective effects that modulate both peripheral and central nerve injuries through several direct and indirect mechanisms, such as angiogenesis and induction of growth factors and anti-inflammatory mediators. Animal models have also shown correlations between pineal gland function and metabolic homeostasis. Studies have shown that a functional pineal gland is essential in preventing and slowing the progression of certain diseases such as diabetes, osteoporosis, vertebral osteoarthritis, and neurodegenerative processes. Lastly, the array of cell culturing methods and animal models that can be used to further develop the study of pineal gland function and nervous system injury were reviewed.

Absence of microglia promotes diverse pathologies and early lethality in Alzheimer's disease mice.

Microglia are strongly implicated in the development and progression of Alzheimer's disease (AD), yet their impact on pathology and lifespan remains unclear. Here we utilize a CSF1R hypomorphic mouse to generate a model of AD that genetically lacks microglia. The resulting microglial-deficient mice exhibit a profound shift from parenchymal amyloid plaques to cerebral amyloid angiopathy (CAA), which is accompanied by numerous transcriptional changes, greatly increased brain calcification and hemorrhages, and premature lethality. Remarkably, a single injection of wild-type microglia into adult mice repopulates the microglial niche and prevents each of these pathological changes. Taken together, these results indicate the protective functions of microglia in reducing CAA, blood-brain barrier dysfunction, and brain calcification. To further understand the clinical implications of these findings, human AD tissue and iPSC-microglia were examined, providing evidence that microglia phagocytose calcium crystals, and this process is impaired by loss of the AD risk gene, TREM2.

The roles of item exposure and visualization success in the consolidation of memories across wake and sleep.

Memory consolidation during sleep does not benefit all memories equally. Initial encoding strength appears to play a role in governing where sleep effects are seen, but it is unclear whether sleep preferentially consolidates weaker or stronger memories. We manipulated encoding strength along two dimensions-the number of item presentations, and success at visualizing each item, in a sample of 82 participants. Sleep benefited memory of successfully visualized items only. Within these, the sleep-wake difference was largest for more weakly encoded information. These results suggest that the benefit of sleep on memory is seen most clearly for items that are encoded to a lower initial strength.

Nutrition Transition and Climate Risks in Nigeria: Moving Towards Food Systems Policy Coherence.

PURPOSE OF REVIEW: The purpose of this review is to describe the combined impacts of the nutrition transition and climate change in Nigeria and analyze the country's national food-related policy options that could support human and planetary health outcomes. RECENT FINDINGS: This paper uses a food systems framework to analyze how the nutrition transition and climate change interact in Nigeria affecting both diets and the double burden of malnutrition, resulting in what has been termed the syndemic. Interactions between climate change and the nutrition transition in Nigeria are exacerbating diet-related inequities and will continue to do so if food systems continue on their current trajectory and without significant transformation. Siloed policy actions that attempt to mitigate one aspect of food system risk can create a negative feedback loop in another aspect of the food system. Our analysis finds that Nigeria has five national policies that include actionable steps to address food system insufficiencies; however, each of these policies is constrained by the boundaries of singular nutrition, climate change, and agricultural objectives. The country should consider a coherent policy environment that explicitly identifies and links underlying systemic and institutional drivers between climate change and malnutrition that simultaneously and comprehensively address both human and planetary health outcomes of food systems. The systemic and institutional outcomes of this emerging syndemic-undernutrition, obesity, and climate change-are inexorably linked. Nigeria lacks a coherent policy environment taking on this challenging syndemic landscape. The analysis in this paper highlights the need for Nigeria to prioritize their national nutrition and agricultural and climate policies that uncouple feedback loops within food systems to address climate change and malnutrition in all its forms.

The effects of eszopiclone on sleep spindles and memory consolidation in schizophrenia: a randomized clinical trial.

Sleep spindles, defining oscillations of stage 2 non-rapid eye movement sleep (N2), mediate memory consolidation. Schizophrenia is characterized by reduced spindle activity that correlates with impaired sleep-dependent memory consolidation. In a small, randomized, placebo-controlled pilot study of schizophrenia, eszopiclone (Lunesta®), a nonbenzodiazepine sedative hypnotic, increased N2 spindle density (number/minute) but did not significantly improve memory. This larger double-blind crossover study that included healthy controls investigated whether eszopiclone could both increase N2 spindle density and improve memory. Twenty-six medicated schizophrenia outpatients and 29 healthy controls were randomly assigned to have a placebo or eszopiclone (3 mg) sleep visit first. Each visit involved two consecutive nights of high density polysomnography with training on the Motor Sequence Task (MST) on the second night and testing the following morning. Patients showed a widespread reduction of spindle density and, in both groups, eszopiclone increased spindle density but failed to enhance sleep-dependent procedural memory consolidation. Follow-up analyses revealed that eszopiclone also affected cortical slow oscillations: it decreased their amplitude, increased their duration, and rendered their phase locking with spindles more variable. Regardless of group or visit, the density of coupled spindle-slow oscillation events predicted memory consolidation significantly better than spindle density alone, suggesting that they are a better biomarker of memory consolidation. In conclusion, sleep oscillations are promising targets for improving memory consolidation in schizophrenia, but enhancing spindles is not enough. Effective therapies also need to preserve or enhance cortical slow oscillations and their coordination with thalamic spindles, an interregional dialog that is necessary for sleep-dependent memory consolidation.

The hippocampus is necessary for the consolidation of a task that does not require the hippocampus for initial learning.

During sleep, the hippocampus plays an active role in consolidating memories that depend on it for initial encoding. There are hints in the literature that the hippocampus may have a broader influence, contributing to the consolidation of memories that may not initially require the area. We tested this possibility by evaluating learning and consolidation of the motor sequence task (MST) in hippocampal amnesics and demographically matched control participants. While the groups showed similar initial learning, only controls exhibited evidence of overnight consolidation. These results demonstrate that the hippocampus can be required for normal consolidation of a task without being required for its acquisition, suggesting that the area plays a broader role in coordinating memory consolidation than has previously been assumed.

Non-sulfated cholecystokinin-8 reduces meal size and prolongs the intermeal interval in male Sprague Dawley rats.

The current study measured seven feeding responses by non-sulfated cholecystokinin-8 (NS CCK-8) in freely fed adult male Sprague Dawley rats. The peptide (0, 0.5, 1, 3, 5 and 10 nmol/kg) was given intraperitoneally (ip) prior to the onset of the dark cycle, and first meal size (MS), second meal size, intermeal interval (IMI) length, satiety ratio (SR = IMI/MS), latency to first meal, duration of first meal, number of meals and 24-hour food intake were measured. We found that NS CCK-8 (0.5 and 1.0 nmol/kg) reduced MS, prolonged IMI length and increased SR during the dark cycle. Furthermore, the specific CCK-B receptor antagonist L365, 260 (1 mg/kg, ip) attenuated these responses. These results support a possible role for NS CCK-8 in regulating food intake.

Spared and impaired sleep-dependent memory consolidation in schizophrenia.

OBJECTIVE: Cognitive deficits in schizophrenia are the strongest predictor of disability and effective treatment is lacking. This reflects our limited mechanistic understanding and consequent lack of treatment targets. In schizophrenia, impaired sleep-dependent memory consolidation correlates with reduced sleep spindle activity, suggesting sleep spindles as a potentially treatable mechanism. In the present study we investigated whether sleep-dependent memory consolidation deficits in schizophrenia are selective. METHODS: Schizophrenia patients and healthy individuals performed three tasks that have been shown to undergo sleep-dependent consolidation: the Word Pair Task (verbal declarative memory), the Visual Discrimination Task (visuoperceptual procedural memory), and the Tone Task (statistical learning). Memory consolidation was tested 24 h later, after a night of sleep. RESULTS: Compared with controls, schizophrenia patients showed reduced overnight consolidation of word pair learning. In contrast, both groups showed similar significant overnight consolidation of visuoperceptual procedural memory. Neither group showed overnight consolidation of statistical learning. CONCLUSION: The present findings extend the known deficits in sleep-dependent memory consolidation in schizophrenia to verbal declarative memory, a core, disabling cognitive deficit. In contrast, visuoperceptual procedural memory was spared. These findings support the hypothesis that sleep-dependent memory consolidation deficits in schizophrenia are selective, possibly limited to tasks that rely on spindles. These findings reinforce the importance of deficient sleep-dependent memory consolidation among the cognitive deficits of schizophrenia and suggest sleep physiology as a potentially treatable mechanism.

The Relative Impact of Sleep and Circadian Drive on Motor Skill Acquisition and Memory Consolidation.

Study Objectives: Sleep during the biological night facilitates memory consolidation. Here we determined the impact of sleep and wake on motor skill learning (acquisition) and subsequent off-line skill improvement (memory consolidation), independent of circadian phase, and compared this to the impact of the endogenous circadian system, independent of whether sleep occurred during the biological night or day. Methods: Participants completed two 8-day sleep laboratory visits, adhering on one visit to a circadian aligned ("normal") sleep schedule for the full duration of the protocol, and on the other to a circadian misaligned (12-hour inverted) schedule, with alignment during the first 3 days, a 12-hour 'slam shift' on Day 4, followed by circadian misalignment during the last 4 days of the protocol. Participants were repeatedly trained and tested on different versions of the finger-tapping motor sequence task across each visit. Results: Sleep facilitated offline memory consolidation regardless of whether it occurred during the biological day or night, while circadian phase had no significant impact. These sleep-related benefits remained after accounting for general motor speed, measured in the absence of learning. In addition, motor skill acquisition was facilitated when the training session followed shortly after sleep, without significant impact of circadian phase (biological morning vs. evening). This effect was largely driven by heightened acquisition in participants who slept during the day and were trained shortly thereafter, that is, when acquisition occurred during the biological evening. These benefits were also retained after controlling for general motor speed. Conclusions: Sleep benefits both the acquisition and consolidation of motor skill regardless of whether they occur during the biological day or night. After controlling for general motor speed, a critical adjustment that few studies perform, these sleep benefits remain intact. Our findings have clear implications for night shift workers who obtain their sleep during the day.