Cerebellar Functions Beyond Movement and Learning.

The cerebellum has a well-established role in controlling motor functions, including coordination, posture, and the learning of skilled movements. The mechanisms for how it carries out motor behavior remain under intense investigation. Interestingly though, in recent years the mechanisms of cerebellar function have faced additional scrutiny since nonmotor behaviors may also be controlled by the cerebellum. With such complexity arising, there is now a pressing need to better understand how cerebellar structure, function, and behavior intersect to influence behaviors that are dynamically called upon as an animal experiences its environment. Here, we discuss recent experimental work that frames possible neural mechanisms for how the cerebellum shapes disparate behaviors and why its dysfunction is catastrophic in hereditary and acquired conditions-both motor and nonmotor. For these reasons, the cerebellum might be the ideal therapeutic target.

Integration of valence and conflict processing through cellular-field interactions in human subgenual cingulate during emotional face processing in treatment-resistant depression.

The subgenual anterior cingulate cortex (sgACC) has been identified as a key brain area involved in various cognitive and emotional processes. While the sgACC has been implicated in both emotional valuation and emotional conflict monitoring, it is still unclear how this area integrates multiple functions. We characterized both single neuron and local field oscillatory activity in 14 patients undergoing sgACC deep brain stimulation for treatment-resistant depression. During recording, patients were presented with a modified Stroop task containing emotional face images that varied in valence and congruence. We further analyzed spike-field interactions to understand how network dynamics influence single neuron activity in this area. Most single neurons responded to both valence and congruence, revealing that sgACC neuronal activity can encode multiple processes within the same task, indicative of multifunctionality. During peak neuronal response, we observed increased spectral power in low frequency oscillations, including theta-band synchronization (4-8 Hz), as well as desynchronization in beta-band frequencies (13-30 Hz). Theta activity was modulated by current trial congruency with greater increases in spectral power following non-congruent stimuli, while beta desynchronizations occurred regardless of emotional valence. Spike-field interactions revealed that local sgACC spiking was phase-locked most prominently to the beta band, whereas phase-locking to the theta band occurred in fewer neurons overall but was modulated more strongly for neurons that were responsive to task. Our findings provide the first direct evidence of spike-field interactions relating to emotional cognitive processing in the human sgACC. Furthermore, we directly related theta oscillatory dynamics in human sgACC to current trial congruency, demonstrating it as an important regulator during conflict detection. Our data endorse the sgACC as an integrative hub for cognitive emotional processing through modulation of beta and theta network activity.

Development of a comprehensive approach to adult hereditary cancer testing in Ontario.

BACKGROUND: Genetic testing for hereditary cancer susceptibility has advanced over time due to the discovery of new risk genes, improved technology and decreased cost. In the province of Ontario, testing eligibility criteria were initially developed to include hereditary breast, ovarian and colorectal cancer syndromes. The rapid evolution of genetic technologies has facilitated the ability to interrogate a large number of genes concurrently. This, coupled with new knowledge about risk genes, necessitated a coordinated approach to expanding the scope of genes and indications tested and synchronisation of access and test utilisation across the province as required in a publicly funded universal healthcare system. METHODS: Ontario Health-Cancer Care Ontario convened expert working groups to develop a standardised and comprehensive cancer gene list for adults and accompanying hereditary cancer testing (HCT) criteria using an evidence-based framework and broad laboratory and clinical genetics engagement. RESULTS: A standardised 76-cancer-gene panel, organised into 13 larger disease site panels and 25 single/small gene panels, was developed and endorsed by the working groups. Provincial genetic testing eligibility criteria were updated to align with the new panels and to guide clinical decision-making. In the first year following the implementation of these changes, 10 564 HCT panels were performed with an overall mutation detection rate of 12.2%. CONCLUSION: Using an evidence framework and broad clinical engagement to develop and endorse an updated guidance document, cancer genetic testing for adults in Ontario is now standardised and coordinated across the province.

Real-Life Patient Educational Recording Before Esophageal Manometry.

High-resolution esophageal manometry (HREM) is a fundamental diagnostic tool in esophagology. Educational tools for this procedure have remained scarce. This quality improvement project aimed to develop an enhanced digital recording about HREM and assess the effect on patient knowledge, anxiety, satisfaction, and procedure abortion rates. The Institute for Healthcare Improvement Model for Improvement and the self-regulation theory guided this project. An interprofessional team was formed. A video recording of the pre-, peri-, and post-HREM care was created. Participants were recruited in the following four cycles: Baseline, Workstation, Manometry, and Home. Questionnaires were collected pre- and postvideo education. The results demonstrated a significant increase in knowledge from 60% to 96% ( p < .001), 58% to 96% ( p < .001), 79% to 96% ( p < .001), and 92% to 97% ( p = .02) and reductions in anxiety from 7.1 to 5.5 ( p = .003), 7.6 to 6.1 ( p = .003), 7.1 to 6.5 ( p < .001), and 6.4 to 6.1 ( p = .03) in all four groups. Almost all (99.5%) participants liked the recorded education and only 2.6% of cases were aborted during the 1-year project implementation period from June 2020 to May 2021. Findings from this project support the positive impact of recorded patient education. An educational recording is standardized and has the potential to be implemented in variable settings.

High-throughput gait acquisition system for freely moving mice.

Normal and pathological locomotion can be discriminated by analyzing an animal's gait on a linear walkway. This step is labor intensive and introduces experimental bias due to the handling involved while placing and removing the animal between trials. We designed a system consisting of a runway embedded within a larger arena, which can be traversed ad libitum by unsupervised, freely moving mice, triggering the recording of short clips of locomotor activity. Multiple body parts were tracked using DeepLabCut and fed to an analysis pipeline (GaitGrapher) to extract gait metrics. We compared the results from unsupervised against the standard experimenter-supervised approach and found that gait parameters analyzed via the new approach were similar to a previously validated approach (Visual Gait Lab). These data show the utility of incorporating an unsupervised, automated, approach for collecting kinematic data for gait analysis.NEW & NOTEWORTHY The acquisition and analysis of walkway data is a time-consuming task. Here, we provide an unmonitored approach for collecting gait metrics that reduces the handling and stress of mice and saves time. A detailed pipeline is outlined that provides for the collection and analysis of data using an integrated suite of tools.

Pharmacodynamic Model-Based Safety Management of Eribulin-Induced Myelosuppression in Patients With Breast Cancer.

BACKGROUND: Neutropenia is a major dose-limiting toxicity of cancer chemotherapy. Semimechanistic mathematical models have been applied to describe the time course of neutrophil counts. The objectives of this study were to develop a mathematical model describing changes in neutrophil counts during eribulin treatment, to apply the empirical Bayes method to predict the probability of developing neutropenia ≥ grade 3 during eribulin treatment in each patient, and to propose the implementation of this mathematical tool in clinical practice for individual safety management. METHODS: The present model analysis and subsequent external evaluation were performed using the data of 481 patients with breast cancer, previously obtained from a postmarketing surveillance (training set) and a phase 2 clinical study (validation set). The model we previously reported (Kawamura et al 2018) was modified to improve its predictive capability. The individual time course of neutrophil changes during the treatment period was predicted by the empirical Bayes method using the observed neutrophil counts at baseline and the first measurement after the first eribulin dose. To evaluate the predictability of this method, the predicted neutrophil counts were compared with those of the observed values. RESULTS: The developed model provided good individual predictions, as indicated by the goodness-of-fit plots between the predicted and observed neutrophil counts, especially for a lower neutrophil count range. Days required to reach the nadir after the dose were also well-predicted. The sensitivity, specificity, and accuracy of the prediction of neutropenia grade ≥3 were 76%, 53%, and 71%, respectively. CONCLUSIONS: We developed a mathematical method for predicting and managing the risk of neutropenia during eribulin treatment. This method is generally applicable to other cases of chemotherapy-induced neutropenia and can be a new practical tool for individual safety management.

Symptomology following mRNA vaccination against SARS-CoV-2.

Despite demonstrated efficacy of vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus disease-2019 (COVID-19), widespread hesitancy to vaccination persists. Improved knowledge regarding frequency, severity, and duration of vaccine-associated symptoms may help reduce hesitancy. In this prospective observational study, we studied 1032 healthcare workers who received both doses of the Pfizer-BioNTech SARS-CoV-2 mRNA vaccine and completed post-vaccine symptom surveys both after dose 1 and after dose 2. We defined appreciable post-vaccine symptoms as those of at least moderate severity and lasting at least 2 days. We found that symptoms were more frequent following the second vaccine dose than the first (74% vs. 60%, P < 0.001), with >80% of all symptoms resolving within 2 days. The most common symptom was injection site pain, followed by fatigue and malaise. Overall, 20% of participants experienced appreciable symptoms after dose 1 and 30% after dose 2. In multivariable analyses, female sex was associated with greater odds of appreciable symptoms after both dose 1 (OR, 95% CI 1.73, 1.19-2.51) and dose 2 (1.76, 1.28-2.42). Prior COVID-19 was also associated with appreciable symptoms following dose 1, while younger age and history of hypertension were associated with appreciable symptoms after dose 2. We conclude that most post-vaccine symptoms are reportedly mild and last <2 days. Appreciable post-vaccine symptoms are associated with female sex, prior COVID-19, younger age, and hypertension. This information can aid clinicians in advising patients on the safety and expected symptomatology associated with vaccination.

Quality Improvement: Using Teach-Back to Improve Patient Satisfaction during Discharge in the Emergency Department.

INTRODUCTION: Patients discharged in the emergency department often have poor understanding of their discharge instructions. Teach-back is a communication method that involves asking patients to explain in their own words what a health care provider just told them. The purpose of this project was to determine whether nurse-led teach-back at discharge could improve patient satisfaction with discharge information. METHODS: A teach-back method was used to educate patients on what to do if they do not feel better after leaving, using a single site quality improvement design. Patient satisfaction was measured using a standardized benchmark question on whether providers explained what to do if they did not feel better after leaving. The department goal for this question was established as achieving a response of "Yes, definitely" for 64.4% or more of the satisfaction surveys. Patient satisfaction data were collected before and after intervention through a survey given to patients within 24 hours after their visit. A statistical process chart was used to analyze whether the observed improvements coincided with implementation of the teach-back intervention. RESULTS: Although there was an overall increase in post-intervention scores (61%) from baseline scores (59%), there were no special cause variations signaling that the intervention had a significant impact. DISCUSSION: Teach-back may improve patient satisfaction with discharge information. Future implementation with measures of intervention adoption, fidelity, accountability, and sustainability are needed.

Elements of the healthy work environment associated with lower primary care nurse burnout.

BACKGROUND: Little is known about the relationship between primary care nurses' work environment and burnout, particularly in settings where patient-centered medical homes (PCMH) have been implemented. PURPOSE: To investigate the relationship between PCMH nurses' work environment and burnout. METHODS: Multivariable analyses were performed using two waves of survey data from PCMH registered nurses (RNs; n = 170) and PCMH licensed vocational nurses (LVNs; n = 181) in 23 primary care clinics. FINDINGS: True collaboration was inversely associated with PCMH RN burnout (b = -2.6, 95% confidence interval [CI] = -4.29, -0.08, p < .01). Meaningful recognition was inversely associated with PCMH LVN burnout (b = -5.1, 95% CI = -8.36, -1.82, p < .01). In models with all nurses, RN (vs. LVN) position was associated with higher levels of burnout (b = 6.2, 95% CI = 2.47, 9.84, p < .01). DISCUSSION: This study highlights the important role of the work environment in reducing PCMH nurse burnout. Strategies to foster team collaboration and meaningful recognition should be investigated to reduce PCMH nurse burnout.

Long-Lasting Electrophysiological After-Effects of High-Frequency Stimulation in the Globus Pallidus: Human and Rodent Slice Studies.

Deep-brain stimulation (DBS) of the globus pallidus pars interna (GPi) is a highly effective therapy for movement disorders, yet its mechanism of action remains controversial. Inhibition of local neurons because of release of GABA from afferents to the GPi is a proposed mechanism in patients. Yet, high-frequency stimulation (HFS) produces prolonged membrane depolarization mediated by cholinergic neurotransmission in endopeduncular nucleus (EP, GPi equivalent in rodent) neurons. We applied HFS while recording neuronal firing from an adjacent electrode during microelectrode mapping of GPi in awake patients (both male and female) with Parkinson disease (PD) and dystonia. Aside from after-suppression and no change in neuronal firing, high-frequency microstimulation induced after-facilitation in 38% (26/69) of GPi neurons. In neurons displaying after-facilitation, 10 s HFS led to an immediate decrease of bursting in PD, but not dystonia patients. Moreover, the changes of bursting patterns in neurons with after-suppression or no change after HFS, were similar in both patient groups. To explore the mechanisms responsible, we applied HFS in EP brain slices from rats of either sex. As in humans, HFS in EP induced two subtypes of after-excitation: excitation or excitation with late inhibition. Pharmacological experiments determined that the excitation subtype, induced by lower charge density, was dependent on glutamatergic transmission. HFS with higher charge density induced excitation with late inhibition, which involved cholinergic modulation. Therefore HFS with different charge density may affect the local neurons through multiple synaptic mechanisms. The cholinergic system plays a role in mediating the after-facilitatory effects in GPi neurons, and because of their modulatory nature, may provide a basis for both the immediate and delayed effects of GPi-DBS. We propose a new model to explain the mechanisms of DBS in GPi.SIGNIFICANCE STATEMENT Deep-brain stimulation (DBS) in the globus pallidus pars interna (GPi) improves Parkinson disease (PD) and dystonia, yet its mechanisms in GPi remain controversial. Inhibition has been previously described and thought to indicate activation of GABAergic synaptic terminals, which dominate in GPi. Here we report that 10 s high-frequency microstimulation induced after-facilitation of neural firing in a substantial proportion of GPi neurons in humans. The neurons with after-facilitation, also immediately reduced their bursting activities after high-frequency stimulation in PD, but not dystonia patients. Based on these data and further animal experiments, a mechanistic hypothesis involving glutamatergic, GABAergic, and cholinergic synaptic transmission is proposed to explain both short- and longer-term therapeutic effects of DBS in GPi.

What makes team communication effective: a qualitative analysis of interprofessional primary care team members' perspectives.

Although numerous scholars have emphasized the need for effective communication between members of interprofessional teams, few studies provide a clear understanding of what constitutes effective team communication in primary care settings, specifically where patient-centered medical home (PCMH) teams have been implemented. This paper describes the elements of effective communication as perceived by members of interprofessional PCMH primary care teams, and identifies elements of effective communication that have persisted over time. Using transcribed text from 75 semi-structured interviews, we applied the grounded theory method of constant comparison to categorize emergent themes relating to elements of team communication. Interprofessional PCMH team members described the elements of effective communication as: 1) shared knowledge, 2) situation/goal awareness, 3) problem-solving, 4) mutual respect; and communication that is 5) transparent, 6) timely, 7) frequent, 8) consistent, and 9) parsimonious. Parsimony is an emergent theme that may be especially relevant for interprofessional PCMH teams challenged with structured clinic schedules. Future work could focus on understanding how to teach and sustain effective parsimonious communication. Comprehensive quality improvement efforts incorporating a variety of strategies, including team communication training, information and communication technologies, and standardized communication tools may facilitate communication of pertinent patient information in a brief and concise manner.

Primary Care Tasks Associated with Provider Burnout: Findings from a Veterans Health Administration Survey.

BACKGROUND: The patient-centered medical home (PCMH) is a primary care delivery model predicated on shared responsibility for patient care among members of an interprofessional team. Effective task sharing may reduce burnout among primary care providers (PCPs). However, little is known about the extent to which PCPs share these responsibilities, and which, if any, of the primary care tasks performed independently by the PCPs (vs. shared with the team) are particularly associated with PCP burnout. A better understanding of the relationship between these tasks and their effects on PCP burnout may help guide focused efforts aimed at reducing burnout. OBJECTIVE: To investigate (1) the extent to which PCPs share responsibility for 14 discrete primary care tasks with other team members, and (2) which, if any, of the primary care tasks performed by the PCPs (without reliance on team members) are associated with PCP burnout. DESIGN: Secondary data analysis of Veterans Health Administration (VHA) survey data from two time periods. PARTICIPANTS: 327 providers from 23 VA primary care practices within one VHA regional network. MAIN MEASURES: The dependent variable was PCP report of burnout. Independent variables included PCP report of the extent to which they performed 14 discrete primary care tasks without reliance on team members; team functioning; and PCP-, clinic-, and system-level variables. KEY RESULTS: In adjusted models, PCP reports of intervening on patient lifestyle factors and educating patients about disease-specific self-care activities, without reliance on their teams, were significantly associated with burnout (intervening on lifestyle: b = 4.11, 95% CI = 0.39, 7.83, p = 0.03; educating patients: b = 3.83, 95% CI = 0.33, 7.32, p = 0.03). CONCLUSIONS: Performing behavioral counseling and self-management education tasks without relying on other team members for assistance was associated with PCP burnout. Expanding the roles of nurses and other healthcare professionals to assume responsibility for these tasks may ease PCP burden and reduce burnout.

Organisational strategies to implement hospital pressure ulcer prevention programmes: findings from a national survey.

AIM: To describe the presence and operationalisation of organisational strategies to support implementation of pressure ulcer prevention programmes across acute care hospitals in a large, integrated health-care system. BACKGROUND: Comprehensive pressure ulcer programmes include nursing interventions such as use of a risk assessment tool and organisational strategies such as policies and performance monitoring to embed these interventions into routine care. The current literature provides little detail about strategies used to implement pressure ulcer prevention programmes. METHODS: Data were collected by an e-mail survey to all chief nursing officers in Veterans Health Administration acute care hospitals. Descriptive and bivariate statistics were used to summarise survey responses and evaluate relationships between some variables. RESULTS: Organisational strategies that support implementation of a pressure ulcer prevention programme (policy, committee, staff education, wound care specialists, and use of performance data) were reported at high levels. Considerable variations were noted in how these strategies were operationalised within individual hospitals. CONCLUSION: Organisational strategies to support implementation of pressure ulcer preventive programmes are often not optimally operationalised to achieve consistent, sustainable performance. IMPLICATIONS FOR NURSING MANAGEMENT: The results of the present study highlight the role and influence of nurse leaders on pressure ulcer prevention program implementation.

Defining attributes of patient safety through a concept analysis.

AIM: The aim of this study was to report an analysis of the concept of patient safety. BACKGROUND: Despite recent increase in the number of work being done to clarify the concept and standardize measurement of patient safety, there are still huge variations in how the term is conceptualized and how to measure patient safety data across various healthcare settings and in research. DESIGN: Concept analysis. DATA SOURCES: A literature search was conducted through PubMed and Cumulative Index to Nursing and Allied Health Literature, Plus using the terms 'patient safety' in the title and 'concept analysis,' 'attributes' or 'definition' in the title and or abstract. All English language literature published between 2002-2014 were considered for the review. METHODS: Walker and Avant's method guided this analysis. RESULTS: The defining attributes of patient safety include prevention of medical errors and avoidable adverse events, protection of patients from harm or injury and collaborative efforts by individual healthcare providers and a strong, well-integrated healthcare system. The application of Collaborative Alliance of Nursing Outcomes indicators as empirical referents would facilitate the measurement of patient safety. CONCLUSION: With the knowledge gained from this analysis, nurses may improve patient surveillance efforts that identify potential hazards before they become adverse events and have a stronger voice in health policy decision-making that influence implementation efforts aimed at promoting patient safety, worldwide. Further studies are needed on development of a conceptual model and framework that can aid with collection and measurement of standardized patient safety data.

Implications for Socio-environmental Determinants of Health-Informed Health Worker Wellness Programs: Findings from a Cross-Sectional Study.

PURPOSE: To explore how socio-environmental factors may potentially impact health outcomes across different groups of health workers (HW). METHOD: Data from the California Healthy Places Index (HPI) and administrative dataset including 12,715 HWs were analyzed using analysis of variance and two-step cluster analysis to evaluate variations in socio-environmental factors across 11 HW job categories. RESULTS: While physicians had the highest average HPI percentiles (69th percentile) across almost all HPI components, the lower-wage HWs consistently ranked below the state average (50th percentile). Overall, the HPI percentile was lowest for environmental living conditions and pollution for all HCWs (30th percentile). The education (52nd percentile) and economic components (59th percentile) were higher than the state average. CONCLUSIONS: The findings from this highlight the importance of socio-environmental determinants of health-informed employee wellness programs and research studies.

The effects of ambient air pollution exposure on Thoroughbred racehorse performance.

BACKGROUND: Limited research exists on impacts of air pollution on non-human mammals, particularly animal athletes such as Thoroughbred racehorses. Athletes have a greater risk of exposure as heightened exertion and increased airflow carry more pollutants deeper into the respiratory tract. OBJECTIVES: To provide insights into the impact of ambient air pollution, particularly fine particulate matter (PM2.5), on race speed. STUDY DESIGN: Retrospective observational study. METHODS: Data were obtained from The Jockey Club Information Systems, covering 31 407 winning races by Thoroughbred horses in California spanning 10 years (2011-2020) and evaluated the association between air pollution and winning race speeds. For race days, we collected PM2.5 data from the nearest U.S. Environmental Protection Agency (EPA) monitoring site within 100 km of each racetrack (n = 12). We assessed the associations between daily average PM2.5 concentrations and speed of winning horses with linear mixed effects regression. We adjusted for horse characteristics, race-related covariates, temporal indicators (e.g., year), other air pollutants and temperature. We conducted sensitivity analyses by adjusting extreme air pollution days by reassigning values to the 95th percentile value and conducting linear mixed effects regression on series of datasets with incremental cutpoints of PM2.5. RESULTS: In the cutpoint analysis, we found that for PM2.5 between 4 and 23.6 µg/m3, speed decreased 0.0008 m/s (95% CI: -0.0014562 to -0.00018) for every 1 µg/m3 increase of PM2.5. MAIN LIMITATIONS: Limitations include the use of offsite monitors leading to imprecise exposure measurements, not using training practice data, and generalisability as the study focuses on California racetracks. CONCLUSION: This study highlights the need to create advisories to safeguard the performance of horses during periods of poor air quality. Further research is recommended to explore additional factors influencing the relationship between air pollution and equine welfare.

Engaging an African American Church-based Community in Developing a Technology-focused Virtual Reality Hypertension Program.

BACKGROUND: African Americans are disproportionately affected by cardiovascular disease and hypertension. To address this, we partnered with local church leaders in developing a virtual reality (VR) hypertension reduction program. OBJECTIVES: A community-based participatory research approach was adopted to develop a hypertension education program using VR, incorporating feedback from the African American church congregation members. METHODS: Using a qualitative approach, a modified Delphi exercise, and member checking, the research team collaborated with congregation members who provided feedback and assisted in the development of the intervention. LESSONS LEARNED: Incorporating feedback from church members significantly impacted the educational platform. Encouraged by the reverend, church members were engaged and participated in the 12-week program designed to reduce blood pressure. Novel approaches like VR may need more time to pilot to achieve desired results, particularly with vulnerable populations. CONCLUSIONS: This participatory research platform highlights the importance of incorporating external stakeholders throughout the research process in order to develop a meaningful health intervention using new technology that is tailored to the church members.

The cerebellum modulates thirst.

The cerebellum, a phylogenetically ancient brain region, has long been considered strictly a motor control structure. Recent studies have implicated the cerebellum in cognition, sensation, emotion and autonomic function, making it an important target for further investigation. Here, we show that cerebellar Purkinje neurons in mice are activated by the hormone asprosin, leading to enhanced thirst, and that optogenetic or chemogenetic activation of Purkinje neurons induces rapid manifestation of water drinking. Purkinje neuron-specific asprosin receptor (Ptprd) deletion results in reduced water intake without affecting food intake and abolishes asprosin's dipsogenic effect. Purkinje neuron-mediated motor learning and coordination were unaffected by these manipulations, indicating independent control of two divergent functions by Purkinje neurons. Our results show that the cerebellum is a thirst-modulating brain area and that asprosin-Ptprd signaling may be a potential therapeutic target for the management of thirst disorders.

Cerebellar deep brain stimulation as a dual-function therapeutic for restoring movement and sleep in dystonic mice.

Dystonia arises with cerebellar dysfunction, which plays a key role in the emergence of multiple pathophysiological deficits that range from abnormal movements and postures to disrupted sleep. Current therapeutic interventions typically do not simultaneously address both the motor and non-motor (sleep-related) symptoms of dystonia, underscoring the necessity for a multi-functional therapeutic strategy. Deep brain stimulation (DBS) is effectively used to reduce motor symptoms in dystonia, with existing parallel evidence arguing for its potential to correct sleep disturbances. However, the simultaneous efficacy of DBS for improving sleep and motor dysfunction, specifically by targeting the cerebellum, remains underexplored. Here, we test the effect of cerebellar DBS in two genetic mouse models with dystonia that exhibit sleep defects- Ptf1a Cre ;Vglut2 fx/fx and Pdx1 Cre ;Vglut2 fx/fx -which have overlapping cerebellar circuit miswiring defects but differing severity in motor phenotypes. By targeting DBS to the cerebellar fastigial and interposed nuclei, we modulated sleep dysfunction by enhancing sleep quality and timing in both models. This DBS paradigm improved wakefulness (decreased) and rapid eye movement (REM) sleep (increased) in both mutants. Additionally, the latency to reach REM sleep, a deficit observed in human dystonia patients, was reduced in both models. Cerebellar DBS also induced alterations in the electrocorticogram (ECoG) patterns that define sleep states. As expected, DBS reduced the severe dystonic twisting motor symptoms that are observed in the Ptf1a Cre ;Vglut2 fx/fx mutant mice. These findings highlight the potential for using cerebellar DBS to improve sleep and reduce motor dysfunction in dystonia and uncover its potential as a dual-effect in vivo therapeutic strategy.

Stress and excessive alcohol consumption among insured and uninsured adults during the COVID-19 pandemic.

Aim: This study examined the relationships between stress, excessive drinking, including binge and heavy drinking, and health insurance status among a regionally representative sample of adults living in Northern Larimer County, Colorado, during the COVID-19 pandemic. Subject and methods: Data from 551 adults aged 18 to 64 years (62.98% aged 45 to 65 years; 73.22% female; 92.98% non-Hispanic White) were used. The sample was weighted by age and binary sex. A series of logistic regressions were applied to examine bivariate associations among stress, drinking, and health insurance status, with and without accounting for the effects of sociodemographic and health-related covariates. Stratified analyses were applied to explore differential associations of stress and drinking among individuals with different health insurance coverage. Results: A total of 23.23% of the adult sample reported binge drinking, and 16.15% reported heavy drinking; 10.53% of the sample reported both binge and heavy drinking. Individuals with higher levels of stress were more likely to report binge drinking (OR: 1.65; 95% CI: 1.65, 1.68) and heavy drinking (OR: 2.61; 95% CI: 2.54, 2.67), after adjusting for sociodemographic and health-related covariates. Relative to individuals with private health insurance coverage, adults enrolled in Medicaid and those without health insurance coverage were more susceptible to the effect of stress on binge and heavy drinking. Conclusion: Our results highlighted a need for continuing statewide and/or national efforts in closing the insurance coverage gap and providing affordable marketplace health insurance in the hope of preventing excessive drinking due to high levels of stress during a challenging time.