Effect of Departmental and Physician-Selected Interventions on Point-of-Care Ultrasound Documentation Completion.

Background Point-of-care ultrasound (POCUS) has been disruptive to many experienced emergency physicians as it requires competence in a new physical skill, real-time image interpretation, and navigation of novel software for submission to the electronic health record (EHR). Incomplete documentation of a performed POCUS study used for clinical decision-making represents a potential medicolegal liability, may expose the patient to repetitive or potentially unnecessary imaging, and is a missed opportunity for reimbursement. Identifying effective facilitators of ED POCUS documentation completion requires additional investigation. Methods In the first part of this mixed-methods study, eligible attending physicians were stratified into levels of use ("high"/"low"/"never") based on recent POCUS documentation performance. Semi-structured interviews were conducted with high and low utilizers to explore their perceptions of the POCUS submission workflow and their receptivity to various proposed interventions. Qualitative data were analyzed using a thematic analysis that explored perceived usefulness and usability. The second part of the study consisted of two intervention phases. First, physicians achieving minimum POCUS documentation numbers were rewarded with additional shift scheduling flexibility. In the second phase, the intervention that garnered the most interview support, daily documentation reminder emails, was implemented. The primary outcome was the individual POCUS documentation rates calculated as all studies submitted divided by all studies performed (submitted plus unsubmitted) per month. Provider-level monthly data was aggregated into a departmental rate. Results Interviews were conducted with 12 physicians, six from the highest and six from the lowest documentation quartiles. Both groups supported the same two proposed interventions: reminder emails ranked first, then monetary rewards ranked second. High utilizers emphasized the clinical utility of POCUS, whereas low utilizers expressed concerns over "double billing" and exposure to medicolegal liability with uncertain scan interpretations. For low utilizers, a documentation decision could be dependent on the performing resident physician's displayed confidence. Both groups voiced frustration with the need to use a separate program, Qpath (Telexy Healthcare, Inc, Maple Ridge, British Columbia, Canada), for POCUS documentation. During intervention phase one, the aggregate departmental documentation rate increased from 44.6% to 60.1% with the introduction of the schedule request incentive. This improvement was seen across all documentation quartiles. The departmental rate remained stable and did not improve further following the addition of the daily documentation reminder emails in intervention phase two. When reminder emails ceased yet the day-off request incentive continued, the departmental rate did not drop. Conclusions The implementation of a non-financial shift scheduling incentive correlated with the largest increase in departmental POCUS documentation rate. Interviewees incorrectly predicted that email reminders would be the most influential intervention highlighting a mismatch between physician perception and effective drivers of behavior change. Further investigation may focus on determining the size and longevity of the isolated impact of a schedule request incentive, as one might expect diminishing marginal utility.

The Effect of Patient-Physician Concordance on Perinatal Care: The Family Physicians' Perspective.

Demographic concordance between patients and clinicians has been associated with better outcomes. The current perinatal care workforce is not adequately diverse to allow for patient-clinician concordance. In this mixed-methods study, we aimed to understand family physicians' perception of the impact of patient-clinician concordance on perinatal care. The predominantly (91%) non-Hispanic White sample of 1,505 family physicians (FPs) perceived gender and language concordance to affect perinatal care more than racial or ethnic concordance. Religious concordance is not perceived to greatly affect perinatal care. Nearly half (721) of the respondents chose to leave a free-text comment on the impact of concordance on perinatal care. Four categories emerged (patients, physicians, the patient-physician relationship, and potential ways to mitigate the impact of discordance). Based on the perceptions of FPs experienced in perinatal care, intentionally supporting continuity of care between patients and clinicians may help to mitigate the negative impact of discordance on perinatal outcomes.

Soluble Glycoprotein VI Predicts Abdominal Aortic Aneurysm Growth Rate and is a Novel Therapeutic Target.

A common feature in patients with abdominal aortic aneurysms (AAA) is the formation of a nonocclusive intraluminal thrombus (ILT) in regions of aortic dilation. Platelets are known to maintain hemostasis and propagate thrombosis through several redundant activation mechanisms, yet the role of platelet activation in the pathogenesis of AAA associated ILT is still poorly understood. Thus, we sought to investigate how platelet activation impacts the pathogenesis of AAA. Using RNA-sequencing, we identify that the platelet-associated transcripts are significantly enriched in the ILT compared to the adjacent aneurysm wall and healthy control aortas. We found that the platelet specific receptor glycoprotein VI (GPVI) is among the top enriched genes in AAA ILT and is increased on the platelet surface of AAA patients. Examination of a specific indicator of platelet activity, soluble GPVI (sGPVI), in two independent AAA patient cohorts is highly predictive of a AAA diagnosis and associates more strongly with aneurysm growth rate when compared to D-dimer in humans. Finally, intervention with the anti-GPVI antibody (JAQ1) in mice with established aneurysms blunted the progression of AAA in two independent mouse models. In conclusion, we show that levels of sGPVI in humans can predict a diagnosis of AAA and AAA growth rate, which may be critical in the identification of high-risk patients. We also identify GPVI as a novel platelet-specific AAA therapeutic target, with minimal risk of adverse bleeding complications, where none currently exist.

The impact of six-week dihydrogen-pyrroloquinoline quinone supplementation on mitochondrial biomarkers, brain metabolism, and cognition in elderly individuals with mild cognitive impairment: a randomized controlled trial.

OBJECTIVES: To assess the impact of medium-term supplementation with dihydrogen and pyrroloquinoline quinone (PQQ) on mitochondrial biomarkers, brain metabolism, and cognition in elderly individuals diagnosed with mild cognitive impairment. DESIGN: A parallel-group, randomized, placebo-controlled, double-blind experimental design, maintaining a 1:1 allocation ratio between the experimental group (receiving the dihydrogen-producing minerals and PQQ) and the control group (receiving the placebo) throughout the trial. SETTING AND PARTICIPANTS: Thirty-four elderly individuals with mild cognitive impairment (mean age 71.9 ± 3.8 years; 28 females) voluntarily provided written consent to participate in this trial. Participants were assigned in a double-blind parallel-group design to receive either a dihydrogen-PQQ mixture (Alpha Hope®, CalerieLife, Irvine, CA) or placebo twice daily for a 6-week intervention period. METHODS: The primary endpoint was the change in serum brain-derived neurotrophic factor (BDNF) from baseline to the 6-week follow-up; secondary outcomes included cognitive function indices, specific metabolites in brain tissue, brain oxygenation, and the prevalence and severity of side effects. Interaction effects (time vs. intervention) were evaluated using two-way ANOVA with repeated measures and Friedman's 2-way ANOVA by ranks, for normally distributed data with homogeneous variances and non-homogeneous variances, respectively. RESULTS: Dihydrogen-PQQ resulted in a significant elevation in serum BDNF levels at the six-week follow-up (P = 0.01); conversely, no changes in BDNF levels were observed in the placebo group throughout the study duration (P = 0.27). A non-significant trend in the impact of interventions on BDNF levels was observed (treatment vs. time interaction, P = 0.14), suggesting a tendency for dihydrogen-PQQ to upregulate BDNF levels compared to the placebo. A significant interaction effect was observed for the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) scores in the orientation domain (P = 0.03), indicating the superiority of dihydrogen-PQQ over placebo in enhancing this cognitive aspect. Cerebral oxygenation saturation exhibited a significant increase following the administration of the dihydrogen-PQQ mixture, from 48.4 ± 7.2% at baseline to 52.8 ± 6.6% at 6-week post-administration (P = 0.005). In addition, brain N-acetyl aspartate levels significantly increased at seven out of thirteen locations post-intervention in participants receiving the mixture (P ≤ 0.05). CONCLUSIONS: Despite the limited number of participants included in the study for interpreting clinical parameters, the dihydrogen-PQQ mixture blend shows promise as a potential dietary intervention for enhancing mental orientation and brain metabolism in individuals with age-related mild cognitive decline.

Cost Savings of Whole Blood Versus Component Therapy at a Community Level 1 Trauma Center.

BACKGROUND: Blood product component-only resuscitation (CORe) has been the standard of practice in both military and civilian trauma care with a 1:1:1 ratio used in attempt to recreate whole blood (WB) until recent data demonstrated WB to confer a survival advantage, leading to the emergence of WB as the contemporary resuscitation strategy of choice. Little is known about the cost and waste reduction associated with WB vs CORe. METHODS: This study is a retrospective single-center review of adult trauma patients admitted to a community trauma center who received WB or CORe as part of their massive transfusion protocol (MTP) resuscitation from 2017 to 2021. The WB group received a minimum of one unit WB while CORe received no WB. Univariate and multivariate analyses were completed. Statistical analysis was conducted using a 95% confidence level. Non-normally distributed, continuous data were analyzed using the Wilcoxon rank sum test. RESULTS: 576 patients were included (201 in WB and 375 in CORe). Whole blood conveyed a survival benefit vs CORe (OR 1.49 P < .05, 1.02-2.17). Whole blood use resulted in an overall reduction in products prepared (25.8%), volumes transfused (16.5%), product waste (38.7%), and MTP activation (56.3%). Cost savings were $849 923 annually and $3 399 693 over the study period. DISCUSSION: Despite increased patient volumes over the study period (43.7%), the utilization of WB as compared to CORe resulted in an overall $3.39 million cost savings while improving mortality. As such, we propose WB should be utilized in all resuscitation strategies for the exsanguinating trauma patient.

Mesenchymal Stem Cell Priming: Potential Benefits of Administration of Molecular Hydrogen.

Stem cell therapy has emerged as a promising avenue for regenerative medicine, offering the potential to treat a wide range of debilitating diseases and injuries. Among the various types of stem cells, mesenchymal stem cells (MSCs) have garnered significant attention due to their unique properties and therapeutic potential. In recent years, researchers have been exploring novel approaches to enhance the effectiveness of MSC-based therapies. One such approach that has gained traction is the priming of MSCs with molecular hydrogen (H2). This article delves into the fascinating world of mesenchymal stem cell priming with molecular hydrogen and the potential benefits it holds for regenerative medicine.

National Beef Quality Audit-2022 Phase 1: face-to-face and digital interviews.

The National Beef Quality Audit (NBQA) has been conducted regularly since 1991 to assess and benchmark quality in the U.S. beef industry, with the most recent iteration conducted in 2022. The goal of NBQA Phase I is to evaluate what needs to be managed to improve beef quality and demand. Interviews (n = 130) of industry personnel were conducted with the aid of routing software. In total, packers (n = 24), retailers (n = 20), further processors (n = 26), foodservice (n = 18), and allied government agencies and trade organizations (n = 42) were interviewed. Interviews were routed in software based on interviewee involvement in either the fed steer and heifer market cow and bull sectors, or both. Interviews were structured to elicit random responses in the order of determining "must-have" criteria (quality factors that are required to make a purchase), best/worst ranking (of quality factors based on importance), how interviewees defined quality terms, a strength, weakness, opportunities, threats (SWOT) analysis, general beef industry questions, and sustainability goals (the latter four being open-ended). Quality factors were 1) visual characteristics, 2) cattle genetics, 3) food safety, 4) eating satisfaction, 5) animal well-being, 6) weight and size, and 7) lean, fat, and bone. Best/worst analysis revealed that "food safety" was the most (P < 0.05) important factor in beef purchasing decisions for all market sectors and frequently was described as "everything" and "a way of business." Culture surrounding food safety changed compared to previous NBQAs with interviewees no longer considering food safety as a purchasing criterion, but rather as a market expectation. The SWOT analysis indicated that "eating quality of U.S. beef" was the greatest strength, and cited that educating both consumers and producers on beef production would benefit the industry. Irrespective of whether companies' products were fed or market cow/bull beef, respondents said that they believed "environmental concerns" were among the major threats to the industry. Perceived image of the beef industry in the market sectors has improved since NBQA-2016 for both fed cattle and market cow/bull beef.

The effect of hydrogen-rich water consumption on premenstrual symptoms and quality of life: a randomized controlled trial.

BACKGROUND: Premenstrual syndrome (PMS) consists of psychiatric or somatic symptoms negatively affecting the daily life. PMS treatment can involve the use of complementary-alternative approaches. Hydrogen-rich water (HRW) has antioxidant and anti-inflammatory properties that may treat PMS. This study aimed to investigate the effect of drinking HRW on the severity of premenstrual symptoms and the quality of life of women who suffer from PMS. METHODS: This study is a randomized controlled trial. Participants were randomized into two groups (intervention group=33, control group=32) using the block randomization method. Participants were requested to consume 1500-2000 mL of HRW daily in the intervention group and drink water in the placebo group. Participants began drinking either HRW or placebo water from day 16 of their menstrual cycle until day 2 of the following cycle for three menstrual cycles. The research data were collected using a Demographic Information Form, Premenstrual Syndrome Scale (PMSS), and Short form of the World Health Organization Quality of Life Questionnaire (WHOQOL- BREF). RESULTS: The intervention group had significantly lower mean scores than the control group in both the first and second follow-ups on the PMSS (P<0.05). In the first follow-up, the intervention group had significantly higher mean scores in the Physical Health and Psychological domains of the WHOQOL-BREF compared to the control group (P<0.05). Group × time interaction was significant for PMSS (F = 10.54, P<0.001). Group × time interaction was insignificant for WHOQOL- BREF (P>0.05). CONCLUSIONS: The consumption of HRW reduces the severity of premenstrual symptoms and improves individuals' quality of life in physical and psychological domains.

Surprising Gendered Age Differences in Rural Malawians' Early COVID-19 Pandemic Prevention Efforts.

OBJECTIVES: We assess how age, the presence of mature adults aged 45+ years, and recent deaths in rural households are associated with coronavirus disease 2019 (COVID-19) preventative actions and the likelihood of getting vaccinated against the virus in Malawi during early stages of the pandemic. METHODS: We draw upon data from 2,187 rural Malawians who participated in a 2020 COVID-19 Phone Survey. We estimate the log odds of engaging in "low-cost" and "high-cost" COVID-19 preventative actions based on age, gender, household composition, and recent household deaths. Low-cost prevention efforts were washing hands with soap and water frequently, avoiding close contact with people when going out, and avoiding shaking hands. High-cost actions included staying at home and decreasing time spent close to people not living in their household. We also estimate the chances of acquiring the COVID-19 vaccine in early stages of its availability. RESULTS: Mature women (45+ years) in general and younger men (<45 years)-living with at least one mature adult in the household-were less likely than others to comply with low-cost actions. Mature men were more likely than younger men (<45 years) to take on high-cost actions. To some extent, individuals who experienced a recent family death were more likely to engage in high-cost COVID-19 preventative actions as well as getting vaccinated. DISCUSSION: Gendered age differences in preventing the transmission of COVID-19 offer hints of larger social norms affecting protective efforts. The analyses also inform future COVID-19 public health outreach efforts in Malawi and other rural SSA contexts.

Effect of etranacogene dezaparvovec on quality of life for severe and moderately severe haemophilia B participants: Results from the phase III HOPE-B trial 2 years after gene therapy.

INTRODUCTION: For people with haemophilia B (PwHB), bleeding may occur despite prophylaxis, negatively affecting health-related quality of life (HRQoL). The pivotal phase 3 HOPE-B trial investigating the adeno-associated virus gene transfer product, etranacogene dezaparvovec (EDZ), demonstrated sustained factor IX (FIX) activity and bleed protection in PwHB with baseline FIX levels ≤2%. AIM: Assess how EDZ affects HRQoL in HOPE-B trial participants. METHODS: HRQoL was evaluated using generic and disease-specific patient reported outcomes (PROs) including the EQ-5D-5L and the Hem-A-QoL questionnaires. Mean domain and total scores were compared 6 months pre- and the first 2 years post-EDZ administration using repeated measures linear mixed models. The percentage of participants with minimal clinically important improvements in HRQoL was also evaluated. RESULTS: Two years post-EDZ, there were nominally significant increases in the least squares (LS) mean score for the EQ-5D-5L Index Value (.04; p = .0129), reflecting better HRQoL. Nominally significant decreases in the LS mean scores, reflecting better HRQoL, were also found for the Hem-A-QoL total score (-6.0; p < .0001) and the Treatment (-13.94; p < .0001), Feelings (-9.01; p < .0001), Future (-6.45; p = .0004) and Work/School (-5.21; p = .0098) domains. The percentage of participants with ≥15-point improvement ranged from 45.83% (95% CI: 31.37%, 60.83%) for Treatment to 13.89% (95% CI: 4.67%, 29.50%) for Family Planning. Results were similar for Year 1. CONCLUSION: In conclusion, gene therapy with EDZ improved HRQoL in the first and second years in several Hem-A-QoL domains, including Treatment, Feelings, Work/School and Future domains, whereas improvement in other aspects of HRQoL were not demonstrated.

Radiology Reports Do Not Accurately Portray the Severity of Cervical Neural Foraminal Stenosis.

STUDY DESIGN: Retrospective study. OBJECTIVE: (1) To compare cervical magnetic resonance imaging (MRI) radiology reports to a validated grading system for cervical foraminal stenosis (FS) and (2) to evaluate whether the severity of cervical neural FS on MRI correlates to motor weakness or patient-reported outcomes. BACKGROUND: Radiology reports of cervical spine MRI are often reviewed to assess the degree of neural FS. However, research looking at the association between these reports and objective MRI findings, as well as clinical symptoms, is lacking. PATIENTS AND METHODS: We retrospectively identified all adult patients undergoing primary 1 or 2-level anterior cervical discectomy and fusion at a single academic center for an indication of cervical radiculopathy. Preoperative MRI was assessed for neural FS severity using the grading system described by Kim and colleagues for each level of fusion, as well as adjacent levels. Neural FS severity was recorded from diagnostic radiologist MRI reports. Motor weakness was defined as an examination grade <4/5 on the final preoperative encounter. Regression analysis was conducted to evaluate whether the degree of FS by either classification was related to patient-reported outcome measure severity. RESULTS: A total of 283 patients were included in the study, and 998 total levels were assessed. There were significant differences between the MRI grading system and the assessment by radio-logists (P< 0.001). In levels with moderate stenosis, 28.9% were classified as having no stenosis by radiology. In levels with severe stenosis, 29.7% were classified as having mild-moderate stenosis or less. Motor weakness was found similarly often in levels of moderate or severe stenosis (6.9% and 9.2%, respectively). On regression analysis, no associations were found between baseline patient-reported outcome measures and stenosis severity assessed by radiologists or MRI grading systems. CONCLUSION: Radiology reports on the severity of cervical neural FS are not consistent with a validated MRI grading system. These radiology reports underestimated the severity of neural foraminal compression and may be inappropriate when used for clinical decision-making. LEVEL OF EVIDENCE: Level III.

Can Peers Help Sustain the Positive Effects of an Early Childhood Mathematics Intervention?

Our study assessed whether the peer environment in kindergarten and first grade affected student learning following an early mathematics intervention. We leveraged longitudinal data from a cluster-RCT to examine whether math achievement in kindergarten (n = 1,218) and first grade (n = 1,126) was affected by either the share of high-achieving classmates or the proportion of classroom peers who received a preschool math curriculum intervention. Analyses indicated that exposure to treated peers in first grade, but not kindergarten, was significantly associated with small gains in end-of-year achievement. Some analyses also suggested that average peer math achievement was generally positively related to children's kindergarten and first-grade achievement across conditions, though these results were less robust. We did not find consistent evidence to suggest that the proportion of treated peers coincided with better teaching practices. Taken together, these findings suggest that classroom peer effects may play only a limited role in sustaining early intervention effects.

Investigating if high-quality kindergarten teachers sustain the pre-K boost to children's emergent literacy skill development in North Carolina.

This study tested the hypothesis that high-quality kindergarten teachers sustain and amplify the skill development of children who participated in North Carolina's NC Pre-K program during the previous year, compared to matched non-participants (N = 17,330; 42% African American, 40% Non-Hispanic White, 15% Hispanic; 51% male; Mage = 4.5 years at fall of pre-K). Kindergarten teacher quality was measured using a "value-added" approach. NC Pre-K participants outperformed non-participants in the fall of kindergarten (ß = .22) and 11% of this boost remained evident by the spring of kindergarten. Higher value-added teachers promoted the skill development of all children (ß = .30 in the spring) but did not differentially benefit the skill development of former NC Pre-K participants compared to non-participants.

Does Operative Level Impact Dysphagia Severity After Anterior Cervical Discectomy and Fusion?: A Multicenter Prospective Analysis.

STUDY DESIGN: Prospective multicenter cohort study. OBJECTIVE: To explore the association between operative level and postoperative dysphagia after anterior cervical discectomy and fusion (ACDF). BACKGROUND: Dysphagia is common after ACDF and has several risk factors, including soft tissue edema. The degree of prevertebral soft tissue edema varies based on the operative cervical level. However, the operative level has not been evaluated as a source of postoperative dysphagia. PATIENTS AND METHODS: Adult patients undergoing elective ACDF were prospectively enrolled at 3 academic centers. Dysphagia was assessed using the Bazaz Questionnaire, Dysphagia Short Questionnaire, and Eating Assessment Tool-10 (EAT-10) preoperatively and at 2, 6, 12, and 24 weeks postoperatively. Patients were grouped based on the inclusion of specific surgical levels in the fusion construct. Multivariable regression analyses were performed to evaluate the independent effects of the number of surgical levels and the inclusion of each particular level on dysphagia symptoms. RESULTS: A total of 130 patients were included. Overall, 24 (18.5%) patients had persistent postoperative dysphagia at 24 weeks and these patients were older, female, and less likely to drink alcohol. There was no difference in operative duration or dexamethasone administration. Patients with persistent dysphagia were significantly more likely to have C4-C5 included in the fusion construct (62.5% vs . 34.9%, P = 0.024) but there were no differences based on the inclusion of other levels. On multivariable regression, the inclusion of C3-C4 or C6-C7 was associated with more severe EAT-10 (ß: 9.56, P = 0.016 and ß: 8.15, P = 0.040) and Dysphagia Short Questionnaire (ß: 4.44, P = 0.023 and (ß: 4.27, P = 0.030) at 6 weeks. At 12 weeks, C3-C4 fusion was also independently associated with more severe dysphagia (EAT-10 ß: 4.74, P = 0.024). CONCLUSION: The location of prevertebral soft tissue swelling may impact the duration and severity of patient-reported dysphagia outcomes at up to 24 weeks postoperatively. In particular, the inclusion of C3-C4 and C4-C5 into the fusion may be associated with dysphagia severity.

Effects of noninvasive neuromodulation targeting the spinal cord on early learning of force control by the digits.

AIMS: Control of finger forces underlies our capacity for skilled hand movements acquired during development and reacquired after neurological injury. Learning force control by the digits, therefore, predicates our functional independence. Noninvasive neuromodulation targeting synapses that link corticospinal neurons onto the final common pathway via spike-timing-dependent mechanisms can alter distal limb motor output on a transient basis, yet these effects appear subject to individual differences. Here, we investigated how this form of noninvasive neuromodulation interacts with task repetition to influence early learning of force control during precision grip. METHODS: The unique effects of neuromodulation, task repetition, and neuromodulation coinciding with task repetition were tested in three separate conditions using a within-subject, cross-over design (n = 23). RESULTS: We found that synchronizing depolarization events within milliseconds of stabilizing precision grip accelerated learning but only after accounting for individual differences through inclusion of subjects who showed upregulated corticospinal excitability at 2 of 3 time points following conditioning stimulation (n = 19). CONCLUSIONS: Our findings provide insights into how the state of the corticospinal system can be leveraged to drive early motor skill learning, further emphasizing individual differences in the response to noninvasive neuromodulation. We interpret these findings in the context of biological mechanisms underlying the observed effects and implications for emerging therapeutic applications.

Diamino-Substituted Quinones as Cathodes for Lithium-Ion Batteries.

This study introduces a sustainable approach to designing organic cathode materials (OCMs) for lithium-ion batteries as a potential replacement for traditional metal-based electrodes. Utilizing green synthetic methodologies, we synthesized and characterized five distinct quinone derivatives and investigated their electrochemical attributes within Li-ion battery architectures. Notably, the observed specific capacities were lower than the theoretical predictions, suggesting limitations in achieving efficient redox reactions in a coin-cell configuration. Among the quinone derivatives studied, one variant derived from natural vanillin showed superior cycle stability, maintaining 58% capacity retention over 95 charge-discharge cycles, and achieving a Coulombic efficiency of 90%. Importantly, we discovered that the commonly used Super-P conductive carbon did not yield any measurable battery performance; instead, these quinones necessitated the incorporation of graphene nanoplatelets as the conductive matrix. Through a facile one-step synthesis in ethanol or water, we have demonstrated a viable synthetic route for producing OCMs, albeit with moderate performances, which have attempted to address common concerns of high solubility and poor redox reactivity of previous OCMs, thereby offering a sustainable pathway for the development of organic-based energy storage devices.

Signaling Specificity and Kinetics of the Human Metabotropic Glutamate Receptors.

Metabotropic glutamate receptors (mGluRs) are obligate dimer G protein coupled receptors that can all function as homodimers. Here, each mGluR homodimer was examined for its G protein coupling profile using a bioluminescence resonance energy transfer-based assay that detects the interaction between a split YFP-tagged Gß 1γ2 and a Nanoluciferase tagged free Gßγ sensor, MAS-GRK3-ct- nanoluciferase with 14 specific Gα proteins heterologously expressed, representing each family. Canonically, the group II and III mGluRs (2 and 3 and 4, 6, 7, and 8, respectively) are thought to couple to Gi/o exclusively. In addition, the group I mGluRs (1 and 5) are known to couple to the Gq/11 family and generally thought to also couple to the pertussis toxin-sensitive Gi/o family some reports have suggested Gs coupling is possible as cAMP elevations have been noted. In this study, coupling was observed with all eight mGluRs through the Gi/o proteins and only mGluR1 and mGluR5 through Gq/11, and, perhaps surprisingly, not G14 None activated any Gs protein. Interestingly, coupling was seen with the group I and II but not the group III mGluRs to G16 Slow but significant coupling to Gz was also seen with the group II receptors. SIGNIFICANCE STATEMENT: Metabotropic glutamate receptor (mGluR)-G protein coupling has not been thoroughly examined, and some controversy remains about whether some mGluRs can activate Gαs family members. Here we examine the ability of each mGluR to activate representative members of every Gα protein family. While all mGluRs can activate Gαi/o proteins, only the group I mGluRs couple to Gαq/11, and no members of the family can activate Gαs family members, including the group I receptors alone or with positive allosteric modulators.

Hydrogen-rich water improves sleep consolidation and enhances forebrain neuronal activation in mice.

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.