The use of mHealth apps to improve hospital nurses' mental health and well-being: A systematic review.

BACKGROUND: Nursing well-being has become a heightened focus since the COVID-19 pandemic. Nurses are leaving the profession early in their careers or retiring sooner than expected. Those who remain in the workforce report higher levels of burnout, anxiety, depression, and exhaustion. There is concern that there may be a shortage of at least half a million nurses by 2030. AIMS: This systematic review aimed to investigate the evidence of using a mental health promotion mHealth app to improve the mental health of hospital nurses. METHODS: A systematic search was conducted in CINAHL Plus with Full Text, MEDLINE with Full Text, Professional Development Collection, Psychology and Behavioral Sciences Collection, Sociological Collection, PsycInfo, Embase, and PubMed with search dates of January 2012-November 15, 2022. The mHealth intervention needed to be asynchronously delivered through a smartphone with hospital nurse participants to be included in this review. RESULTS: Of the 157 articles screened for this review, six were included. Primary outcome variables were anxiety, burnout, coping, depression, self-efficacy, stress, well-being, and work engagement. Intervention types included mindfulness-based interventions (MBIs), cognitive behavioral therapy (CBT), stress inoculation therapy (SIT), psychoeducation, and stress management. Anxiety, depression, well-being, and burnout improved with MBIs; depression improved with CBT; and anxiety and active coping improved with SIT. LINKING EVIDENCE TO ACTION: This review demonstrated promising findings in using mHealth apps to improve the mental health of hospital nurses. However, more randomized controlled trials with larger sample sizes may reveal which type of mHealth app and how much exposure to the intervention is more effective in improving specific mental health symptoms. Longitudinal follow-up is also recommended to study sustainability of the mental health improvements.

A cognitive-behavioral skills building program improves mental health and enhances healthy lifestyle behaviors in nurses and other hospital employees.

BACKGROUND: Mental health outcomes in nurses have historically indicated a greater prevalence of anxiety, depression, and suicide than the general population. It is vital to provide programming for healthcare workers to gain the necessary skills to reduce burnout and improve their mental and physical health. AIMS: The aims of this study were to evaluate mental health outcomes and healthy lifestyle beliefs and behaviors among nurses and other hospital employees who completed MINDBODYSTRONG, a cognitive-behavioral skill building program. METHODS: A pre-experimental, pre- and poststudy design was used to examine mental health and well-being outcomes among 100 hospital personnel who participated in MINDBODYSTRONG, a program designed to improve coping and resiliency and decrease stress, anxiety, and depressive symptoms. Outcomes measured included healthy lifestyle behaviors, healthy lifestyle beliefs, anxiety, depression, stress, and burnout. RESULTS: One hundred hospital personnel, including 93 nurses, completed the pre- and post-survey. Among all participants, post- MINDBODYSTRONG scores for healthy lifestyle beliefs (p = .00; Cohen's d = 0.52) and healthy lifestyle behaviors (p = .00; Cohen's d = -0.74) increased significantly with medium effects, while depression (p = .00; Cohen's d = -0.51), anxiety (p = .00; Cohen's d = -0.54), stress (p = .00; Cohen's d = -0.33), and burnout (p = .00; Cohen's d = -0.37) decreased significantly with small and medium effects. The program produced even stronger positive effects on mental health outcomes for participants who started the study with higher levels of depression and anxiety. LINKING EVIDENCE TO PRACTICE: Anxiety, depression, stress, and burnout decreased significantly postintervention. Participants also significantly improved their healthy lifestyle beliefs and behaviors with the MINDBODYSTRONG program. MINDBODYSTRONG is an effective program that reduces anxiety, depression, burnout, and stress and improves healthy lifestyle beliefs and behaviors in hospital-based clinicians. It is of utmost importance to provide evidence-based programs to improve mental resiliency and decrease stress, anxiety, burnout, and depressive symptoms, which will ultimately improve the safety and quality of health care.

Enhancing the Workforce Pathway: A Physical and Occupational Therapy Career Exploration Camp for High School Youth.

There is a workforce shortage in the physical therapy (PT) and occupational therapy (OT) fields. Pathway programs may help guide students with career exploration. This retrospective study assessed changes in students' knowledge about health careers and intent to pursue a health career based on their experience at a PT OT career exploration camp. Between 2018 and 2022, 60 high-school students participated in the camp and completed a pre- and post-program evaluation survey. The results showed a significant improvement in participants' knowledge about health careers and plans to pursue education to become a health professional. Partnering with organizations with the resources to offer career exploration programs help build a strong pathway of students into the PT and OT professions.

The Relationship between Nurses' Training and Perceptions of Electronic Documentation Systems.

Electronic documentation systems have been widely implemented in the healthcare field. These systems have become a critical part of the nursing profession. This research examines how nurses' general computer skills, training, and self-efficacy affect their perceptions of using these systems. A sample of 248 nurses was surveyed to examine their general computer skills, self-efficacy, and training in electronic documentation systems in nursing programs. We propose a model to investigate the extent to which nurses' computer skills, self-efficacy, and training in electronic documentation influence perceptions of using electronic documentation systems in hospitals. The data supports a mediated model in which general computer skills, self-efficacy, and training influence perceived usefulness through perceived ease of use. The significance of these findings was confirmed through structural equation modeling. As the electronic documentation systems are customized for every organization, our findings suggest value in nurses receiving training to learn these specific systems in the workplace or during their internships. Doing so may improve patient outcomes by ensuring that nurses use the systems consistently and effectively.

Multi-Organ Dysfunction in Cerebral Palsy.

Cerebral Palsy (CP) describes a heterogenous group of non-progressive disorders of posture or movement, causing activity limitation, due to a lesion in the developing brain. CP is an umbrella term for a heterogenous condition and is, therefore, descriptive rather than a diagnosis. Each case requires detailed consideration of etiology. Our understanding of the underlying cause of CP has developed significantly, with areas such as inflammation, epigenetics and genetic susceptibility to subsequent insults providing new insights. Alongside this, there has been increasing recognition of the multi-organ dysfunction (MOD) associated with CP, in particular in children with higher levels of motor impairment. Therefore, CP should not be seen as an unchanging disorder caused by a solitary insult but rather, as a condition which evolves over time. Assessment of multi-organ function may help to prevent complications in later childhood or adulthood. It may also contribute to an improved understanding of the etiology and thus may have an implication in prevention, interventional methods and therapies. MOD in CP has not yet been quantified and a scoring system may prove useful in allowing advanced clinical planning and follow-up of children with CP. Additionally, several biomarkers hold promise in assisting with long-term monitoring. Clinicians should be aware of the multi-system complications that are associated with CP and which may present significant diagnostic challenges given that many children with CP communicate non-verbally. A step-wise, logical, multi-system approach is required to ensure that the best care is provided to these children. This review summarizes multi-organ dysfunction in children with CP whilst highlighting emerging research and gaps in our knowledge. We identify some potential organ-specific biomarkers which may prove useful in developing guidelines for follow-up and management of these children throughout their lifespan.

Lipid lowering with bempedoic acid added to a proprotein convertase subtilisin/kexin type 9 inhibitor therapy: A randomized, controlled trial.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9is) lower low-density lipoprotein cholesterol (LDL-C) in patients with hypercholesterolemia. However, some patients receiving PCSK9i therapy might require additional lipid-lowering therapy (LLT) to reach LDL-C goals. Bempedoic acid is an oral, once-daily, ATP-citrate lyase inhibitor that significantly lowers LDL-C in patients with hypercholesterolemia when given alone or as add-on therapy to statins and/or ezetimibe. OBJECTIVE: Assess safety and efficacy of bempedoic acid added to PCSK9i (evolocumab) background therapy in patients with hypercholesterolemia. METHODS: This phase 2, randomized, double-blind, placebo-controlled study was conducted in three phases: 1.5-month screening/washout period including discontinuation of all LLTs, a 3-month period wherein patients initiated background PCSK9i therapy, and a 2-month treatment period in which patients were randomized 1:1 to receive bempedoic acid 180 mg or placebo once daily while continuing PCSK9i therapy. RESULTS: Of 59 patients randomized, 57 completed the study. Mean baseline LDL-C after 3 months of PCSK9i background therapy was 103.1 ± ±â€¯30.4 mg/dL. Bempedoic acid added to background PCSK9i therapy significantly lowered LDL-C by 30.3% (P < .001) vs placebo. Compared with placebo, bempedoic acid significantly lowered apolipoprotein B, non-high-density lipoprotein cholesterol, and total cholesterol (nominal P < .001 for all), and high-sensitivity C-reactive protein (P = .029). When added to background PCSK9i therapy, the safety profile of bempedoic acid was comparable to that observed for placebo. CONCLUSIONS: When added to a background of PCSK9i therapy, bempedoic acid significantly lowered LDL-C levels with a safety profile comparable to placebo in patients with hypercholesterolemia.

Implementation and Assessment of a Proning Protocol for Nonintubated Patients With COVID-19.

INTRODUCTION: The COVID-19 pandemic has caused over 1,250,000 deaths worldwide. With limited therapeutic options, proning nonintubated patients emerged as a safe and affordable intervention to manage hypoxemia. METHODS: A proning protocol to identify and prone eligible patients was implemented. Patients were encouraged to self-prone for 2-3 hours, 3 times daily. Investigators created educational materials for nurses and patients and developed a COVID-19-specific proning order within the electronic health record (EHR). Investigators completed an 800-person retrospective chart review to study the implementation of this protocol. RESULTS: From March 22, 2020, to June 5, 2020, 586 patients were admitted to the COVID-19 floor. Of these patients, 42.8% were eligible for proning. Common contraindications were lack of hypoxia, altered mental status, and fall risk. The proning protocol led to a significant improvement in provider awareness of patients appropriate for proning, increasing from 12% to 83%, as measured by placement of a proning order into the EHR. There was a significant improvement in all appropriate patients documented as proned, increasing from 18% to 45% of eligible patients. CONCLUSIONS: The creation of an effective hospital-wide proning protocol to address the exigencies of the COVID-19 pandemic is possible and may be accomplished in a short period of time.

Community health worker interventions for older adults with complex health needs: A systematic review.

BACKGROUND/OBJECTIVES: The number of older adults with complex health needs is growing, and this population experiences disproportionate morbidity and mortality. Interventions led by community health workers (CHWs) can improve clinical outcomes in the general adult population with multimorbidity, but few studies have investigated CHW-delivered interventions in older adults. DESIGN: We systematically reviewed the impact of CHW interventions on health outcomes among older adults with complex health needs. We searched for English-language articles from database inception through April 2020 using seven databases. PROSPERO protocol registration CRD42019118761. SETTING: Any U.S. or international setting, including clinical and community-based settings. PARTICIPANTS: Adults aged 60 years or older with complex health needs, defined in this review as multimorbidity, frailty, disability, or high-utilization. INTERVENTIONS: Interventions led by a CHW or similar role consistent with the American Public Health Association's definition of CHWs. MEASUREMENTS: Pre-defined health outcomes (chronic disease measures, general health measures, treatment adherence, quality of life, or functional measures) as well as qualitative findings. RESULTS: Of 5671 unique records, nine studies met eligibility criteria, including four randomized controlled trials, three quasi-experimental studies, and two qualitative studies. Target population and intervention characteristics were variable, and studies were generally of low-to-moderate methodological quality. Outcomes included mood, functional status and disability, social support, well-being and quality of life, medication knowledge, and certain health conditions (e.g., falls, cognition). Results were mixed with several studies demonstrating significant effects on mood and function, including one high-quality RCT, while others noted no significant intervention effects on outcomes. CONCLUSION: CHW-led interventions may have benefit for older adults with complex health needs, but additional high-quality studies are needed to definitively determine the effectiveness of CHW interventions in this population. Integration of CHWs into geriatric clinical settings may be a strategy to deliver evidence-based interventions and improve clinical outcomes in complex older adults.

Psychometric Properties of the Healthy Lifestyle Beliefs Scale for Adolescents.

INTRODUCTION: Healthy lifestyle behaviors are at the core of maintaining health. This study analyzed the psychometric properties of the 16-item healthy lifestyle beliefs (HLB) scale that measures a person's beliefs about their ability to live a healthy lifestyle. METHOD: Descriptive statistics, exploratory factor analysis, confirmatory analysis, and measurement invariance were conducted for this study. RESULTS: Cronbach alpha was 0.894. The Exploratory factor analysis scree plot identified two factors with eigenvalues greater than one. All factor loadings were greater than 0.40 and no items cross-loaded. A two-factor solution was retained for Confirmatory factor analysis. The measurement invariance results suggested that there was no gender difference in HLB regarding factor structure, factor loading, threshold, and residual variances. DISCUSSION: The HLB scale was found to have adequate internal consistency and fit with the data. Findings show it is valid and acceptable for both boys and girls.

Mobility Technicians: A Viable Solution to Early Ambulation of Total Joint Replacement Patients.

BACKGROUND: Early ambulation of patients with total joint replacement (TJR) has been shown to improve outcomes while reducing length of stay and postoperative complications. Limited physical therapy (PT) resources and late-in-the-day cases may challenge day-of-surgery (POD0) ambulation. At our institution, a Mobility Technician (MT) program, composed of specially trained nurse's aides, was developed to address this issue. PURPOSE: The purpose of this study was to compare the effectiveness of the MT model with a traditional PT model in the early ambulation of patients with TJR. METHODS: Patients undergoing unilateral primary TJR at a single institution between June 1, 2014, and October 31, 2018, were included. Ambulation measures were retrospectively assessed between pre- and post-MT program groups. RESULTS: This study included 11,777 patients with TJR. Following the MT program, number of POD0 ambulations, POD0 ambulation distance, and total distance ambulated all increased while time-to-first ambulation decreased. CONCLUSION: Preliminary analyses indicate that the MT program has been successful in the early ambulation of patients with TJR.

Adolescents as Agents of Parental Healthy Lifestyle Behavior Change: COPE Healthy Lifestyles TEEN Program.

INTRODUCTION: Obesity is a leading health crisis around the world. An intervention strategy scarcely utilized for behavior change is that of a child as change agent. The purpose of this study was to describe the impact of teens reviewing newsletters from a healthy lifestyle intervention with their parents. METHOD: Evaluation data from a randomized controlled trial, COPE Healthy Lifestyle TEEN Program, was analyzed. A descriptive study was conducted of parents' and teens' lifestyle behaviors as reported by parents. RESULTS: One hundred sixty-nine parents completed evaluations. Two thirds of parents reported changing a behavior as a result of the program. Nearly three quarters of parents reported behavior changes in their teens. Over 90% reported they would recommend this or a similar program. DISCUSSION: The obesity epidemic shows no signs of reversal, and hence multiple approaches to impact healthy lifestyles are urgent. Including children as a change agent is a potential target for interventions addressing obesity.

Interventions to Improve Mental Health, Well-Being, Physical Health, and Lifestyle Behaviors in Physicians and Nurses: A Systematic Review.

OBJECTIVE: This systematic review focused on randomized controlled trials (RCTs) with physicians and nurses that tested interventions designed to improve their mental health, well-being, physical health, and lifestyle behaviors. DATA SOURCE: A systematic search of electronic databases from 2008 to May 2018 included PubMed, CINAHL, PsycINFO, SPORTDiscus, and the Cochrane Library. STUDY INCLUSION AND EXCLUSION CRITERIA: Inclusion criteria included an RCT design, samples of physicians and/or nurses, and publication year 2008 or later with outcomes targeting mental health, well-being/resiliency, healthy lifestyle behaviors, and/or physical health. Exclusion criteria included studies with a focus on burnout without measures of mood, resiliency, mindfulness, or stress; primary focus on an area other than health promotion; and non-English papers. DATA EXTRACTION: Quantitative and qualitative data were extracted from each study by 2 independent researchers using a standardized template created in Covidence. DATA SYNTHESIS: Although meta-analytic pooling across all studies was desired, a wide array of outcome measures made quantitative pooling unsuitable. Therefore, effect sizes were calculated and a mini meta-analysis was completed. RESULTS: Twenty-nine studies (N = 2708 participants) met the inclusion criteria. Results indicated that mindfulness and cognitive-behavioral therapy-based interventions are effective in reducing stress, anxiety, and depression. Brief interventions that incorporate deep breathing and gratitude may be beneficial. Visual triggers, pedometers, and health coaching with texting increased physical activity. CONCLUSION: Healthcare systems must promote the health and well-being of physicians and nurses with evidence-based interventions to improve population health and enhance the quality and safety of the care that is delivered.

Likelihood of depressive symptoms in US older adults by prescribed opioid potency: National Health and Nutrition Examination Survey 2005-2013.

OBJECTIVES: To investigate the relationships between depressive symptoms and opioid potency among adults aged 50 years and older reporting use of one or more prescription opioids in the past 30 days. MATERIALS/DESIGN: Adjusted multiple linear regression models were conducted with 2005-2013 files from a secondary cross-sectional dataset, the National Health and Nutrition Examination Survey (NHANES). Respondents were community-dwelling, noninstitutionalized adults 50 years or older (n = 1036). Predictor variables included a positive screen for minor depression symptoms (Patient Health Questionnaire [PHQ-9] score greater than or equal to 5 and less than or equal to 9), moderate depression symptoms (PHQ-9 greater than or equal to 10 and less than or equal to 14), and severe depression symptoms (PHQ-9 greater than or equal to 15). Criterion variables included weaker-than-morphine analgesics (eg, codeine and tramadol) and morphine-equivalent opioids (eg, morphine and hydrocodone), which served as the reference category, as well as stronger-than-morphine opioid analgesics (eg, fentanyl and oxycodone). RESULTS: Prevalence rates for symptoms of minor depression, moderate depression, and severe depression were n = 236 (22.8%), n = 135 (13.0%), and n = 122 (11.8%), respectively. Severe depression was significantly associated with high-potency opioid use (odds ratio [OR]: 2.27; confidence interval [CI], 1.16-4.46). In post hoc tests, severe depression remained significantly associated with high-potency opioid use only among respondents without arthritis (OR: 5.80; CI, 1.59-21.13). CONCLUSIONS: Compared with older adults without depressive symptoms, older adults with severe depressive symptoms are more likely to be taking high-potency opioid medications. Future prescription opioid medication research should prioritize investigations among older adults with pain-related diagnoses, other than arthritis, reporting preexisting or new symptoms of severe depression.

Natural polymorphism in protein kinase G modulates functional senescence in Drosophilamelanogaster.

The common fruit fly, Drosophila melanogaster, is a well-characterized model for neurological disorders and is widely used to investigate the biology of aging, stress tolerance and pleiotropy. The foraging (for) gene encodes a cGMP-dependent protein kinase (PKG), which has been implicated in several behavioral phenotypes including feeding, sleep, learning and memory, and environmental stress tolerance. We used the well-established Drosophila activity monitor (DAM) to investigate the effects of the conserved NO/cGMP/PKG signaling pathway on functional senescence. Our results show that the polymorphic for gene confers protection during low oxygen stress at the expense of longevity and a decline in locomotor activity with age in D. melanogaster, which suggests a novel role for the PKG pathway in healthy aging and senescence.

Efficacy and Safety of Bempedoic Acid in Patients With Hypercholesterolemia and Statin Intolerance.

Background Inability to tolerate statins because of muscle symptoms contributes to uncontrolled cholesterol levels and insufficient cardiovascular risk reduction. Bempedoic acid, a prodrug that is activated by a hepatic enzyme not present in skeletal muscle, inhibits ATP -citrate lyase, an enzyme upstream of ß-hydroxy ß-methylglutaryl-coenzyme A reductase in the cholesterol biosynthesis pathway. Methods and Results The phase 3, double-blind, placebo-controlled CLEAR (Cholesterol Lowering via Bempedoic acid, an ACL-Inhibiting Regimen) Serenity study randomized 345 patients with hypercholesterolemia and a history of intolerance to at least 2 statins (1 at the lowest available dose) 2:1 to bempedoic acid 180 mg or placebo once daily for 24 weeks. The primary end point was mean percent change from baseline to week 12 in low-density lipoprotein cholesterol. The mean age was 65.2 years, mean baseline low-density lipoprotein cholesterol was 157.6 mg/dL, and 93% of patients reported a history of statin-associated muscle symptoms. Bempedoic acid treatment significantly reduced low-density lipoprotein cholesterol from baseline to week 12 (placebo-corrected difference, -21.4% [95% CI, -25.1% to -17.7%]; P<0.001). Significant reductions with bempedoic acid versus placebo were also observed in non-high-density lipoprotein cholesterol (-17.9%), total cholesterol (-14.8%), apolipoprotein B (-15.0%), and high-sensitivity C-reactive protein (-24.3%; P<0.001 for all comparisons). Bempedoic acid was safe and well tolerated. The most common muscle-related adverse event, myalgia, occurred in 4.7% and 7.2% of patients who received bempedoic acid or placebo, respectively. Conclusions Bempedoic acid offers a safe and effective oral therapeutic option for lipid lowering in patients who cannot tolerate statins. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifier: NCT 02988115.

Penetration and efficacy of transdermal NSAIDs in a model of acute joint inflammation.

PURPOSE: Prescription and OTC non-steroidal anti-inflammatory drugs (NSAIDs) are ubiquitous treatments for pain and inflammation; however, oral administration of these drugs may produce gastrointestinal (GI) side effects. Transdermal (TD) administration of NSAIDs circumvents these adverse events by avoiding the GI tract and, presumably, achieves regional drug levels of therapeutic effect and thereby, fewer off-target complications. METHODS: A drug quantification method was developed for ibuprofen and celecoxib in canine plasma and synovial fluid using liquid chromatography and mass spectrometry. This method was employed to evaluate the penetrance of ibuprofen and celecoxib topical formulations in dogs. Effectiveness of these topical NSAID formulations was compared to the equivalent oral drug concentration in a canine sodium-urate model of acute joint inflammation. In this model, pain was quantified using a modified Canine Brief Pain Inventory questionnaire and regional inflammation using joint caliper measurements; the significance of intervention was evaluated using linear mixed models for repeated measures along with Bonferroni corrections. RESULTS: After seven days of chronic topical administration, Delivra™ (DEL) formulations of ibuprofen and celecoxib generated serum levels of 2.9µg/mL and 220ng/mL and synovial fluid levels of 1.8 µg/mL and 203 ng/mL (respectively). In the canine model of acute inflammation, the overall treatment effects as well as the treatment by time interactions were strongly significant (P<0.001) for both drugs. Oral ibuprofen proved uniquely effective at the earliest time point, while all ibuprofen formulations were effective at treating pain at 8.5 and 24.5 hours post-induction. Similarly, all celecoxib formulations (oral and topical) were equally effective at 8.5 and 24.5 hours post-induction. CONCLUSION: DEL formulations of ibuprofen and celecoxib successfully introduced these NSAIDs into synovial fluid at concentrations similar to those observed in circulation. Furthermore, these formulations reduced symptoms of pain associated with acute inflammation. Oral and transdermally delivered NSAIDs have similar pain relief effects; therefore, a replacement or combinatorial treatment may provide a more stable pain relief profile. In conclusion, this work supports further investigation of TD products in the treatment of regional inflammatory events.

A Review of Systematic Reviews Targeting the Prevention and Treatment of Overweight and Obesity in Adolescent Populations.

PURPOSE: Adolescent obesity is a powerful predictor of morbidity and mortality, yet amenable to modifiable behaviors. To accurately summarize the effects of behavioral interventions on changes in adolescent body mass index and/or weight status, we assessed existing systematic reviews for reporting transparency and methodological quality. METHODS: Five databases were searched through September 2017 to identify relevant systematic reviews. Reviews were evaluated for reporting transparency and methodological quality using PRISMA Reporting Checklist and Assessment of Multiple Systematic Reviews Instrument. Evidence was synthesized across high-quality reviews. RESULTS: Four of twelve systematic reviews were of high methodological quality. All four focused on the treatment of overweight/obesity in adolescent populations, representing 97 international studies. Findings indicate intervention compared with no intervention/wait list showed larger effects for improving BMI/BMI z-scores. Small improvements (averaging a 3.7-kg decrease) in weight/weight percentile were observed following a supervised exercise plus dietary and/or behavior support intervention. Health-related quality of life may improve following interventions, but overall attention to associated psychological variables (depression, self-esteem/perception) is limited. CONCLUSIONS: Adherence to objective checklists and protocols for rigorous conduct and reporting of systematic reviews is warranted. Consensus evidence is urgently needed to define and report behavior change interventions related to obesity prevention and treatment.

Contribution of a natural polymorphism in protein kinase G modulates electroconvulsive seizure recovery in Drosophila melanogaster.

Drosophila melanogaster is a well-characterized model for neurological disorders and is widely used for investigating causes of altered neuronal excitability leading to seizure-like behavior. One method used to analyze behavioral output of neuronal perturbance is recording the time to locomotor recovery from an electroconvulsive shock. Based on this behavior, we sought to quantify seizure susceptibility in larval D. melanogaster with differences in the enzymatic activity levels of a major protein, cGMP-dependent protein kinase (PKG). PKG, encoded by foraging, has two natural allelic variants and has previously been implicated in several important physiological characteristics including: foraging patterns, learning and memory, and environmental stress tolerance. The well-established NO/cGMP/PKG signaling pathway found in the fly, which potentially targets downstream K+ channel(s), ultimately impacts membrane excitability, leading to our hypothesis: altering PKG enzymatic activity modulates time to recovery from an electroconvulsive seizure. Our results show that by both genetically and pharmacologically increasing PKG enzymatic activity, we can decrease the locomotor recovery time from an electroconvulsive seizure in larval D. melanogaster.

egl-4 modulates electroconvulsive seizure duration in C. elegans.

Increased neuronal excitability causes seizures with debilitating symptoms. Effective and noninvasive treatments are limited for easing symptoms, partially due to the complexity of the disorder and lack of knowledge of specific molecular faults. An unexplored, novel target for seizure therapeutics is the cGMP/protein kinase G (PKG) pathway, which targets downstream K+ channels, a mechanism similar to Retigabine, a recently FDA-approved antiepileptic drug. Our results demonstrate that increased PKG activity decreased seizure duration in C. elegans utilizing a recently developed electroconvulsive seizure assay. While the fly is a well-established seizure model, C. elegans are an ideal yet unexploited model which easily uptakes drugs and can be utilized for high-throughput screens. In this study, we show that treating the worms with either a potassium channel opener, Retigabine or published pharmaceuticals that increase PKG activity, significantly reduces seizure recovery times. Our results suggest that PKG signaling modulates downstream K+ channel conductance to control seizure recovery time in C. elegans. Hence, we provide powerful evidence, suggesting that pharmacological manipulation of the PKG signaling cascade may control seizure duration across phyla.