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BACKGROUND: Sleep disturbances are a prevalent and complex comorbidity in neurodevelopmental disorders (NDDs). Dup15q syndrome (duplications of 15q11.2-13.1) is a genetic disorder highly penetrant for NDDs such as autism and intellectual disability and it is frequently accompanied by significant disruptions in sleep patterns. The 15q critical region harbors genes crucial for brain development, notably UBE3A and a cluster of gamma-aminobutyric acid type A receptor (GABAAR) genes. We previously described an electrophysiological biomarker of the syndrome, marked by heightened beta oscillations (12-30 Hz) in individuals with Dup15q syndrome, akin to electroencephalogram (EEG) alterations induced by allosteric modulation of GABAARs. Those with Dup15q syndrome exhibited increased beta oscillations during the awake resting state and during sleep, and they showed profoundly abnormal NREM sleep. This study aims to assess the translational validity of these EEG signatures and to delve into their neurobiological underpinnings by quantifying sleep physiology in chromosome-engineered mice with maternal (matDp/ + mice) or paternal (patDp/ + mice) inheritance of the full 15q11.2-13.1-equivalent duplication, and mice with duplication of just the UBE3A gene (Ube3a overexpression mice; Ube3a OE mice) and comparing the sleep metrics with their respective wildtype (WT) littermate controls. METHODS: We collected 48-h EEG/EMG recordings from 35 (23 male, 12 female) 12-24-week-old matDp/ + , patDp/ + , Ube3a OE mice, and their WT littermate controls. We quantified baseline sleep, sleep fragmentation, spectral power dynamics during sleep states, and recovery following sleep deprivation. Within each group, distinctions between Dup15q mutant mice and WT littermate controls were evaluated using analysis of variance (ANOVA) and student's t-test. The impact of genotype and time was discerned through repeated measures ANOVA, and significance was established at p < 0.05. RESULTS: Our study revealed that across brain states, matDp/ + mice mirrored the elevated beta oscillation phenotype observed in clinical EEGs from individuals with Dup15q syndrome. Time to sleep onset after light onset was significantly reduced in matDp/ + and Ube3a OE mice. However, NREM sleep between Dup15q mutant and WT littermate mice remained unaltered, suggesting a divergence from the clinical presentation in humans. Additionally, while increased beta oscillations persisted in matDp/ + mice after 6-h of sleep deprivation, recovery NREM sleep remained unaltered in all groups, thus suggesting that these mice exhibit resilience in the fundamental processes governing sleep-wake regulation. CONCLUSIONS: Quantification of mechanistic and translatable EEG biomarkers is essential for advancing our understanding of NDDs and their underlying pathophysiology. Our study of sleep physiology in the Dup15q mice underscores that the beta EEG biomarker has strong translational validity, thus opening the door for pre-clinical studies of putative drug targets, using the biomarker as a translational measure of drug-target engagement. The unaltered NREM sleep may be due to inherent differences in neurobiology between mice and humans. These nuanced distinctions highlight the complexity of sleep disruptions in Dup15q syndrome and emphasize the need for a comprehensive understanding that encompasses both shared and distinct features between murine models and clinical populations.
Subject(s)
Chromosomes, Human, Pair 15 , Disease Models, Animal , Electroencephalography , Animals , Mice , Chromosomes, Human, Pair 15/genetics , Male , Female , Sleep Wake Disorders/genetics , Sleep Wake Disorders/physiopathology , Sleep/physiology , Sleep/genetics , Trisomy/physiopathology , Trisomy/genetics , Chromosome Aberrations , Intellectual DisabilityABSTRACT
The influence of light spectral properties on circadian rhythms is of substantial interest to laboratory-based investigation of the circadian system and to field-based understanding of the effects of artificial light at night. The trade-offs between intensity and spectrum regarding masking behaviors are largely unknown, even for well-studied organisms. We used a custom LED illumination system to document the response of wild-type house mice (Mus musculus) to 1-h nocturnal exposure of all combinations of four intensity levels (0.01, 0.5, 5 and 50â lx) and three correlated color temperatures (CCT; 1750, 1950 and 3000â K). Higher intensities of light (50â lx) suppressed cage activity substantially, and consistently more for the higher CCT light (91% for 3000â K, 53% for 1750â K). At the lowest intensity (0.01â lx), mean activity was increased, with the greatest increases for the lowest CCT (12.3% increase at 1750â K, 3% increase at 3000â K). Multiple linear regression confirmed the influence of both CCT and intensity on changes in activity, with the scaled effect size of intensity 3.6 times greater than that of CCT. Activity suppression was significantly lower for male than for female mice. Assessment of light-evoked cFos expression in the suprachiasmatic nucleus at 50â lx showed no significant difference between high and low CCT exposure. The significant differences by spectral composition illustrate a need to account for light spectrum in circadian studies of behavior, and confirm that spectral controls can mitigate some, but certainly not all, of the effects of light pollution on species in the wild.
Subject(s)
Circadian Rhythm , Light , Lighting , Animals , Mice/physiology , Male , Circadian Rhythm/physiology , Circadian Rhythm/radiation effects , Female , Behavior, Animal/radiation effects , Behavior, Animal/physiology , Motor Activity/radiation effects , TemperatureABSTRACT
Sleep disturbances are common features of neurodegenerative disorders including Huntington's disease (HD). The sleep and circadian disruptions are recapitulated in animal models, and these models provide the opportunity to evaluate whether circadian interventions can be effective countermeasures for neurodegenerative disease. Time restricted feeding (TRF) interventions successfully improve activity rhythms, sleep behavior and motor performance in mouse models of HD. Seeking to determine if these benefits of scheduled feeding extend to physiological measures of sleep, electroencephalography (EEG) was used to measure sleep/wake states and polysomnographic patterns in adult mice (six mo-old) under TRF and ad lib feeding (ALF). With each diet, both male and female wild-type (WT) and bacterial artificial chromosome transgenic (BACHD) mice were evaluated. Our findings show that male, but not female, BACHD mice exhibited significant changes in the temporal patterning of wake and nonrapid eye movement (NREM) sleep. The TRF intervention reduced the inappropriate early morning activity by increasing NREM sleep in the male BACHD mice. In addition, the scheduled feeding reduced sleep fragmentation (# bouts) in the male BACHD mice. The phase of the rhythm in rapid-eye movement (REM) sleep was significantly altered by the scheduled feeding. The treatment did impact the power spectral curves during the day in male but not female mice. Sleep homeostasis, as measured by the response to six hours of gentle handling, was not altered by the diet. Thus, TRF improves the temporal patterning and fragmentation of NREM sleep without impacting sleep homeostasis. This work adds critical support to the view that sleep is a modifiable risk factor in neurodegenerative diseases.
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Aims: Increasing nicotinamide adenine dinucleotide (NAD+) availability has been proposed as a therapeutic approach to prevent neurodegeneration in amyotrophic lateral sclerosis (ALS). Accordingly, NAD+ precursor supplementation appears to exert neuroprotective effects in ALS patients and mouse models. The mechanisms mediating neuroprotection remain uncertain but could involve changes in multiple cell types. We investigated a potential direct effect of the NAD+ precursor nicotinamide mononucleotide (NMN) on the health of cultured induced pluripotent stem cell (iPSC)-derived human motor neurons and in motor neurons isolated from two ALS mouse models, that is, mice overexpressing wild-type transactive response DNA binding protein-43 (TDP-43) or the ALS-linked human superoxide dismutase 1 with the G93A mutation (hSOD1G93A). Results: NMN treatment increased the complexity of neuronal processes in motor neurons isolated from both mouse models and in iPSC-derived human motor neurons. In addition, NMN prevented neuronal death induced by trophic factor deprivation. In mouse and human motor neurons expressing ALS-linked mutant superoxide dismutase 1, NMN induced an increase in glutathione levels, but this effect was not observed in nontransgenic or TDP-43 overexpressing motor neurons. In contrast, NMN treatment normalized the TDP-43 cytoplasmic mislocalization induced by its overexpression. Innovation: NMN can directly act on motor neurons to increase the growth and complexity of neuronal processes and prevent the death induced by trophic factor deprivation. Conclusion: Our results support a direct beneficial effect of NAD+ precursor supplementation on the maintenance of the neuritic arbor in motor neurons. Importantly, this was observed in motor neurons isolated from two different ALS models, with and without involvement of TDP-43 pathology, supporting its therapeutic potential in sporadic and familial ALS.
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The present study examined rates of sleep disorders and sleep medication use, and predictors of sleep disturbance in children with persistent tic disorders (PTD). Sixty-three parents of children aged 10 to 17 years with PTDs completed an internet survey evaluating sleep patterns and clinical symptoms. Insomnia (19.4%), nightmares (16.1%), and bruxism (13.1%) were the most commonly reported lifetime sleep disorders. Fifty-two percent endorsed current sleep medication use. Higher ADHD severity, overall life impairment, and female sex predicted greater sleep disturbance. Findings suggest the utility of clinical management of co-occurring ADHD and impairment to mitigate sleep disturbance in children with PTDs.
ABSTRACT
Sleep and circadian rhythm disturbances are common features of Huntington's disease (HD). HD is an autosomal dominant neurodegenerative disorder that affects men and women in equal numbers, but some epidemiological studies as well as preclinical work indicate there may be sex differences in disease presentation and progression. Since sex differences in HD could provide important insights to understand cellular and molecular mechanism(s), we used the bacterial artificial chromosome transgenic mouse model of HD (BACHD) to examine whether sex differences in sleep/wake cycles are detectable in an animal model of the disease. Electroencephalography/electromyography (EEG/EMG) was used to measure sleep/wake states and polysomnographic patterns in young adult (12-week-old) male and female wild-type and BACHD mice. Our findings show that male, but not female, BACHD mice exhibited increased variation in phases of the rhythms as compared to age- and sex-matched wild-types. For both rapid-eye movement (REM) and non-rapid eye movement (NREM) sleep, genotypic and sex differences were detected. In particular, the BACHD males spent less time in NREM sleep and exhibited a more fragmented sleep than the other groups. Finally, in response to 6 h of sleep deprivation, both genotypes and sexes displayed the predicted homeostatic responses to sleep loss. These findings suggest that females are relatively protected early in disease progression in this HD model.
Subject(s)
Huntington Disease , Sex Characteristics , Young Adult , Female , Male , Humans , Animals , Mice , Huntington Disease/genetics , Sleep , Disease Models, Animal , Mice, TransgenicABSTRACT
Study Objectives: Sleep loss contributes to various health issues and impairs neurological function. Molecular hydrogen has recently gained popularity as a nontoxic ergogenic and health promoter. The effect of molecular hydrogen on sleep and sleep-related neural systems remains unexplored. This study investigates the impact of hydrogen-rich water (HRW) on sleep behavior and neuronal activation in sleep-deprived mice. Methods: Adult C57BL/6J mice were implanted with electroencephalography (EEG) and electromyography (EMG) recording electrodes and given HRW (0.7-1.4 mM) or regular water for 7 days ad libitum. Sleep-wake cycles were recorded under baseline conditions and after acute sleep loss. Neuronal activation in sleep- and wake-related regions was assessed using cFos immunostaining. Results: HRW increased sleep consolidation in undisturbed mice and increased non-rapid-eye movement and rapid-eye-movement sleep amount in sleep-deprived mice. HRW also decreased the average amount of time for mice to fall asleep after light onset. Neuronal activation in the lateral septum, medial septum, ventrolateral preoptic area, and median preoptic area was significantly altered in all mice treated with HRW. Conclusions: HRW improves sleep consolidation and increases neuronal activation in sleep-related brain regions. It may serve as a simple, effective treatment to improve recovery after sleep loss.
ABSTRACT
Collegiate athletes must satisfy the academic obligations common to all undergraduates, but they have the additional structural and social stressors of extensive practice time, competition schedules, and frequent travel away from their home campus. Clearly such stressors can have negative impacts on both their academic and athletic performances as well as on their health. These concerns are made more acute by recent proposals and decisions to reorganize major collegiate athletic conferences. These rearrangements will require more multi-day travel that interferes with the academic work and personal schedules of athletes. Of particular concern is additional east-west travel that results in circadian rhythm disruptions commonly called jet lag that contribute to the loss of amount as well as quality of sleep. Circadian misalignment and sleep deprivation and/or sleep disturbances have profound effects on physical and mental health and performance. We, as concerned scientists and physicians with relevant expertise, developed this white paper to raise awareness of these challenges to the wellbeing of our student-athletes and their co-travelers. We also offer practical steps to mitigate the negative consequences of collegiate travel schedules. We discuss the importance of bedtime protocols, the availability of early afternoon naps, and adherence to scheduled lighting exposure protocols before, during, and after travel, with support from wearables and apps. We call upon departments of athletics to engage with sleep and circadian experts to advise and help design tailored implementation of these mitigating practices that could contribute to the current and long-term health and wellbeing of their students and their staff members.
Subject(s)
Circadian Rhythm , Sleep , Humans , Jet Lag Syndrome , Athletes , Students , TravelABSTRACT
BACKGROUND: Clinical evidence on the use of cannabidiol (CBD) for sleep remains limited. Even fewer studies have tested the comparative effectiveness of cannabinoid formulations found within CBD products used for sleep or how they compare to other complementary therapies such as melatonin. METHODS: Participants (N = 1,793 adults experiencing symptoms of sleep disturbance) were randomly assigned to receive a 4-week supply of 1 of 6 products (all capsules) containing either 15 mg CBD or 5 mg melatonin, alone or in combination with minor cannabinoids. Sleep disturbance was assessed over a period of 5 weeks (baseline week and 4 weeks of product use) using Patient-Reported Outcomes Measurement Information System (PROMIS™) Sleep Disturbance SF 8A, administered via weekly online surveys. A linear mixed-effects regression model was used to assess the differences in the change in sleep disturbance through time between each active product arm and CBD isolate. RESULTS: All formulations exhibited a favorable safety profile (12% of participants reported a side effect and none were severe) and led to significant improvements in sleep disturbance (p < 0.001 in within-group comparisons). Most participants (56% to 75%) across all formulations experienced a clinically important improvement in their sleep quality. There were no significant differences in effect, however, between 15 mg CBD isolate and formulations containing 15 mg CBD and 15 mg cannabinol (CBN), alone or in combination with 5 mg cannabichromene (CBC). There were also no significant differences in effect between 15 mg CBD isolate and formulations containing 5 mg melatonin, alone or in combination with 15 mg CBD and 15 mg CBN. CONCLUSIONS: Our findings suggest that chronic use of a low dose of CBD is safe and could improve sleep quality, though these effects do not exceed that of 5 mg melatonin. Moreover, the addition of low doses of CBN and CBC may not improve the effect of formulations containing CBD or melatonin isolate.
Subject(s)
Cannabidiol , Cannabinoids , Melatonin , Adult , Humans , Melatonin/adverse effects , Cannabinoids/adverse effects , Cannabinol , Cannabidiol/adverse effects , SleepABSTRACT
Subcortical white matter stroke (WMS) is a progressive disorder which is demarcated by the formation of small ischemic lesions along white matter tracts in the CNS. As lesions accumulate, patients begin to experience severe motor and cognitive decline. Despite its high rate of incidence in the human population, our understanding of the cause and outcome of WMS is extremely limited. As such, viable therapies for WMS remain to be seen. This study characterizes myelin recovery following stroke and motor learning-based rehabilitation in a mouse model of subcortical WMS. Following WMS, a transient increase in differentiating oligodendrocytes occurs within the peri-infarct in young male adult mice, which is completely abolished in male aged mice. Compound action potential recording demonstrates a decrease in conduction velocity of myelinated axons at the peri-infarct. Animals were then tested on one of three distinct motor learning-based rehabilitation strategies (skilled reach, restricted access to a complex running wheel, and unrestricted access to a complex running wheel) for their capacity to induce repair. These studies determined that unrestricted access to a complex running wheel alone increases the density of differentiating oligodendrocytes in infarcted white matter in young adult male mice, which is abolished in aged male mice. Unrestricted access to a complex running wheel was also able to enhance conduction velocity of myelinated axons at the peri-infarct to a speed comparable to naive controls suggesting functional recovery. However, there was no evidence of motor rehabilitation-induced remyelination or myelin protection.SIGNIFICANCE STATEMENT White matter stroke is a common disease with no medical therapy. A form of motor rehabilitation improves some aspects of white matter repair and recovery.
Subject(s)
Stroke , White Matter , Humans , Male , Mice , Animals , Aged , White Matter/pathology , Stroke/pathology , Myelin Sheath/pathology , Oligodendroglia/physiology , Infarction/pathology , Motor ActivityABSTRACT
Inadequate sleep is a global health concern. Sleep is multidimensional and complex; new multi-ingredient agents are needed. This study assessed the comparative effects of two multi-ingredient supplements on sleep relative to placebo. Adults (N = 620) seeking better sleep were randomly assigned to receive one of three study products. Sleep A (contained lower (0.35 mg THC and higher levels of botanicals (75 mg each hops oil and valerian oil), Sleep B (contained higher THC (0.85 mg) and lower botanicals (20 mg each hops oil and valerian oil) or placebo) for 4 weeks. Sleep disturbance was assessed at baseline and weekly using NIH's Patient-Reported Outcomes Measurement Information System (PROMIS™) Sleep Disturbance SF 8A survey. Anxiety, stress, pain, and well-being were assessed using validated measures at baseline and weekly. A linear mixed-effects regression model was used to assess the change in health outcome score between active product groups and the placebo. There was a significant difference in sleep disturbance, anxiety, stress, and well-being between Sleep A and placebo. There was no significant difference in any health parameter between Sleep B and placebo. Side effects were mild or moderate. There were no significant differences in the frequency of side effects between the study groups. A botanical blend containing a low concentration of THC improved sleep disturbance, anxiety, stress, and well-being in healthy individuals that reported better sleep as a primary health concern.
Subject(s)
Drug-Related Side Effects and Adverse Reactions , Sleep Wake Disorders , Humans , Adult , Sleep , Sleep Deprivation , Anxiety , Sleep Wake Disorders/drug therapy , Outcome Assessment, Health CareABSTRACT
Purpose of review: Sleep disturbance is common in TD. However, our understanding of the pathophysiological mechanisms involved is preliminary. This review summarizes findings from neuroimaging, genetic, and animal studies to elucidate potential underlying mechanisms of sleep disruption in TD. Recent findings: Preliminary neuroimaging research indicates increased activity in the premotor cortex, and decreased activity in the prefrontal cortex is associated with NREM sleep in TD. Striatal dopamine exhibits a circadian rhythm; and is influenced by the suprachiasmatic nucleus via multiple molecular mechanisms. Conversely, dopamine receptors regulate circadian function and striatal expression of circadian genes. The association of TD with restless legs syndrome and periodic limb movements indicates shared pathophysiology, including iron deficiency, and variants in the BTDB9 gene. A mutations in the L-Histidine Decarboxylase gene in TD, suggests the involvement of the histaminergic system, implicated in arousal, in TD. Summary: These biological markers have implications for application of novel, targeted interventions, including noninvasive neuromodulation, iron supplementation, histamine receptor antagonists, and circadian-based therapies for tic symptoms and/or sleep and circadian rhythms in TD.
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Circadian disruptions impact nearly all people with Alzheimer's disease (AD), emphasizing both their potential role in pathology and the critical need to investigate the therapeutic potential of circadian-modulating interventions. Here, we show that time-restricted feeding (TRF) without caloric restriction improved key disease components including behavioral timing, disease pathology, hippocampal transcription, and memory in two transgenic (TG) mouse models of AD. We found that TRF had the remarkable capability of simultaneously reducing amyloid deposition, increasing Aß42 clearance, improving sleep and memory, and normalizing daily transcription patterns of multiple genes, including those associated with AD and neuroinflammation. Thus, our study unveils for the first time the pleiotropic nature of timed feeding on AD, which has far-reaching effects beyond metabolism, ameliorating neurodegeneration and the misalignment of circadian rhythmicity. Since TRF can substantially modify disease trajectory, this intervention has immediate translational potential, addressing the urgent demand for accessible approaches to reduce or halt AD progression.
Subject(s)
Alzheimer Disease , Mice , Animals , Humans , Alzheimer Disease/therapy , Alzheimer Disease/genetics , Mice, Transgenic , Disease Models, Animal , Circadian Rhythm , Brain/metabolism , Amyloid beta-PeptidesABSTRACT
BACKGROUND: People experiencing homelessness may use emergency medical services to access health care. We sought to examine the relationship between homelessness and prehospital evaluation and treatment of chest pain. METHODS: We obtained 2019 data of all emergency medical services activations from a single 9-1-1 provider in San Francisco, California with a clinician's primary impression of chest pain. Using chart review, we categorized patients as experiencing homelessness or not and determined treatment rates between the two groups based on local chest pain/acute coronary syndrome protocol. We then stratified the two groups based on primary impression subcategories: "chest pain-not cardiac" and "chest-pain-cardiac/STEMI"; ST elevation myocardial infarction (STEMI). RESULTS: A total of 601 chest pain calls were analyzed after excluding non-transports and pediatric patients. 120 incidents (20%) involved patients experiencing homelessness. Across all chest pain impressions, people experiencing homelessness were less likely to receive aspirin (35% vs 53%; p < 0.001), intravenous access (38% vs 62%; p < 0.001), and nitroglycerin (21% vs 39%; p < 0.001). No patients experiencing homelessness received analgesic medication, though only 4% of other patients received this intervention (0% vs 4%; p = 0.020). People experiencing homelessness were more likely to receive a clinical impression of "chest pain-not cardiac" compared to "chest pain-cardiac/STEMI" (68% vs 32%; p < 0.001). Results were less significant in most fields when adjusted for impression sub categorizations: "chest pain-not cardiac" versus "chest pain-cardiac/STEMI." Greater than 97% of all patients received 12 lead electrocardiograms. CONCLUSIONS: Significant disparities were observed between patients experiencing and not experiencing homelessness in the prehospital treatment of chest pain. Larger scale evaluations are needed to further assess potential disparities in care for people experiencing homelessness in the prehospital setting. Using prehospital clinician impression as a proxy for acuity may mask existing bias and disparity; however, 12-lead ECG acquisition, the key diagnostic tool, was appropriately performed in more than 97% of all chest pain patients.
Subject(s)
Emergency Medical Services , Ill-Housed Persons , Myocardial Infarction , ST Elevation Myocardial Infarction , Humans , Child , Emergency Medical Services/methods , Myocardial Infarction/diagnosis , Chest Pain/therapy , Chest Pain/diagnosis , ElectrocardiographyABSTRACT
Sleep and circadian rhythm disturbances are common features of Huntington's disease (HD). HD is an autosomal dominant neurodegenerative disorder that affects men and women in equal numbers, but some epidemiological studies as well as preclinical work indicate there may be sex differences in disease progression. Since sex differences in HD could provide important insights to understand cellular and molecular mechanism(s), we used the bacterial artificial chromosome transgenic mouse model of HD (BACHD) to examine whether sex differences in sleep/wake cycles are detectable in an animal model of the disease. Electroencephalography/electromyography (EEG/EMG) was used to measure sleep/wake states and polysomnographic patterns in young adult (12 week-old) male and female wild-type and BACHD mice. Our findings show that male, but not female, BACHD mice exhibited increased variation in phases of the rhythms as compared to age and sex matched wild-types. For both Rapid-eye movement (REM) and Non-rapid eye movement (NREM) sleep, genotypic and sex differences were detected. In particular, the BACHD males spent less time in NREM and exhibited a more fragmented sleep than the other groups. Both male and female BACHD mice exhibited significant changes in delta but not in gamma power compared to wild-type mice. Finally, in response to a 6-hrs sleep deprivation, both genotypes and sexes displayed predicted homeostatic responses to sleep loss. These findings suggest that females are relatively protected early in disease progression in this HD model.
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Background: Anticipating an increased utilization of healthcare facilities during the COVID-19 surge, the San Francisco Department of Public Health developed a plan to deploy neighborhood-based Field Care Clinics (FCCs) that would decompress emergency departments by serving patients with low acuity complaints. These clinics would receive patients directly from the Emergency Medical Services (EMS) system. Transports were initiated by a paramedic-driven protocol, originally by EMS crews and later by the Centralized Ambulance Destination Determination (CADDiE) System. In this study, we evaluated the outcomes of EMS patients who were transported to the FCC, specifically as to whether they required subsequent transfer to the emergency department. Methods: We performed a retrospective study of all patients transported to the Bayview-Hunters Point (BHP) neighborhood FCC by EMS between April 11th, 2020, and December 16th, 2020. Descriptive statistics and Chi-Square Tests were used to analyze patient data. Results: In total, 35 patients (20 men, 15 women, average age of 50.9 years) were transported to the FCC. Of these, 16 were Black/African American, 7 were White, 3 were Asian, with 9 identifying as of other races and 9 of Hispanic ethnicity. Twenty-three of these transports resulted from a CADDiE recommendation. Approximately half (n=20) of calls originated within the BHP neighborhood. The most frequent patient complaint was "Pain." Of patients transported to the FCC, 23 were treated and discharged. The 12 remaining patients required hospital transfer, with 3 being discharged after receiving treatment in the emergency department and 9 requiring hospital admission, psychiatric, or sobering services. The likelihood of hospital transfer did not significantly vary by sex (p=0.41), 9-1-1 call origination relative to BHP neighborhood (p=0.92), or CADDiE recommendation (p=0.51). Conclusion: Three-fourths of patients who required subsequent hospital transfer were admitted or required specialized services, suggesting that the FCC was viable for managing low acuity conditions. However, the underutilization of the FCC by EMS as a transport destination and a high hospital transfer rate indicates training and protocol refinement opportunities. Despite the small cohort size, this study demonstrates that an FCC alternative care site can act as a viable source for urgent and emergency care during a pandemic.
ABSTRACT
In mammals, photic information delivered to the suprachiasmatic nucleus (SCN) via the retinohypothalamic tract (RHT) plays a crucial role in synchronizing the master circadian clock located in the SCN to the solar cycle. It is well known that glutamate released from the RHT terminals initiates the synchronizing process by activating ionotropic glutamate receptors (iGluRs) on retinorecipient SCN neurons. The potential role of metabotropic glutamate receptors (mGluRs) in modulating this signaling pathway has received less attention. In this study, using extracellular single-unit recordings in mouse SCN slices, we investigated the possible roles of the Gq/11 protein-coupled mGluRs, mGluR1 and mGluR5, in photic resetting. We found that mGluR1 activation in the early night produced phase advances in neural activity rhythms in the SCN, while activation in the late night produced phase delays. In contrast, mGluR5 activation had no significant effect on the phase of these rhythms. Interestingly, mGluR1 activation antagonized phase shifts induced by glutamate through a mechanism that was dependent upon CaV1.3 L-type voltage-gated Ca2+ channels (VGCCs). While both mGluR1-evoked phase delays and advances were inhibited by knockout (KO) of CaV1.3 L-type VGCCs, different signaling pathways appeared to be involved in mediating these effects, with mGluR1 working via protein kinase G in the early night and via protein kinase A signaling in the late night. We conclude that, in the mouse SCN, mGluR1s function to negatively modulate glutamate-evoked phase shifts.
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Emergency medical services (EMS) systems are designed to provide care in the field and while transporting patients to a hospital; however, patients enrolled in hospice may not want invasive therapies nor benefit from hospitalization. For many reasons, encounters with hospice patients can be challenging for EMS systems, EMS clinicians, hospice clinicians, hospice patients, and their families.
EMS clinicians should receive hospice-focused education that fosters a basic understanding of hospice, palliative therapies, and advance care planning documents (e.g., Physician Orders for Life Sustaining Treatment). This education should emphasize the ongoing development of end-of-life communication skills.EMS medical directors and local hospice organizations should collaborate to develop hospice patient-centered EMS protocols that address symptom management and delineate appropriate and goal concordant clinical interventions, and that are within the agency-level scope of practice for local EMS clinicians. Partnerships between EMS and hospice organizations can facilitate access to hospice teams who can provide clear guidance on whether to treat-in-place with follow-up care or to transport hospice patients to the hospital.EMS medical directors and local hospice organizations should collaborate to perform needs assessments of hospice patient EMS utilization.EMS medical directors should consider including a focus on EMS care of hospice patients as part of their overall quality management program(s). Ideally these efforts should be collaborative with local hospice agencies in order to facilitate meaningful process improvement strategies that include both EMS and hospice stakeholders.Reimbursement programs should reasonably compensate EMS agencies for scene treatment in place, as well as transport to alternative destinations such as in-patient hospice facilities.