Human Trafficking in Correctional Institutions: A Survey of Correctional and Anti-Trafficking Leaders.

Growing awareness of the overlap between justice involvement and human trafficking victimization has led to calls for correctional institutions to prevent, identify, and respond to trafficking. However, it is unclear how correctional facilities (i.e., jails and prisons) are responding to such calls to action. To examine current efforts to address human trafficking in U.S. correctional facilities, this study surveyed correctional and anti-trafficking leaders (n = 46) about their perceptions and experiences with human trafficking screening, response, and training in correctional facilities. Although the majority of leaders (89%) agreed individuals in their state's correctional facilities have experienced human trafficking, they generally did not perceive that correctional staff were prepared to respond. Bivariate tests revealed that correctional and anti-trafficking leaders differed on their perceptions regarding correctional staffs' knowledge about human trafficking risk factors (p = .014), identification ability (p = .006), and response knowledge (p = .036), with anti-trafficking leaders perceiving correctional staff to be less prepared in these areas. Approximately 16% of leaders reported strategies to identify and respond to trafficking in correctional facilities, and about 27% reported human trafficking training for corrections staff. To promote a just society, study findings offer preliminary guidance for anti-trafficking correctional initiatives and future research.

Veteran Beliefs About the Causes of Gulf War Illness and Expectations for Improvement.

BACKGROUND: Individuals' beliefs about the etiology of persistent physical symptoms (PPS) are linked to differences in coping style. However, it is unclear which attributions are related to greater expectations for improvement. METHOD AND RESULTS: A cross-sectional regression analysis (N = 262) indicated that Veterans with Gulf War Illness (GWI) who attributed their GWI to behavior, (e.g., diet and exercise), had greater expectations for improvement (p = .001) than those who attributed their GWI to deployment, physical, or psychological causes (p values > .05). CONCLUSIONS: Findings support the possible clinical utility of exploring perceived contributing factors of PPS, which may increase perceptions that improvement of PPS is possible. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02161133.

Treatment and life goals among veterans with Gulf War illness.

Medically unexplained syndromes (MUS), also termed persistent physical symptoms, are both prevalent and disabling. Yet treatments for MUS are marked by high rates of patient dissatisfaction, as well as disagreement between patients and providers on the management of persistent physical symptoms. A better understanding of patient-generated goals could increase collaborative goal setting and promote person-centered care, a critical component of MUS treatment; yet research in this area is lacking. This paper aimed to develop a typology of treatment and life goals among Gulf War veterans with a medically unexplained syndrome (Gulf War Illness). We examined participants' responses to open-ended questions about treatment and life goals using Braun and Clarke's thematic analysis methodology. Results showed that treatment goals could be categorized into four overarching themes: 1) Get better/healthier, 2) Improve quality of life, 3) Improve or seek additional treatment, and 4) Don't know/Don't have any. Life goals were categorized into six overarching themes: 1) Live a fulfilling life, 2) Live a happy life, 3) Live a healthy life, 4) Be productive/financially successful, 5) Manage GWI, and 6) Don't know/Don't have any. Treatment goals were largely focused on getting better/healthier (e.g., improving symptoms), whereas life goals focused on living a fulfilling life. Implications for the treatment of Gulf War Illness and patient-provider communication are discussed. ClinicalTrials.gov Identifier: NCT02161133.

Phage-derived anti-idiotype and anti-YTE antibodies in development of MK-1654 pharmacokinetic and immune response assays.

Background: MK-1654 is a fully human monoclonal antibody with YTE mutations currently in phase III clinical trials for prophylactic use in protecting infants from human respiratory syncytial virus infection. Materials & methods: We generated anti-idiotype (anti-ID) and anti-YTE antibodies against MK-1654 by panning with MorphoSys HuCal phage libraries, and used the antibodies in the development of MK-1654 pharmacokinetic (PK) and immune response (IR) assays. Results: Detection of MK-1654 in nonhuman primate and human nasal wash samples showed combined use of anti-ID and anti-YTE antibodies can deliver desired sensitivity and accuracy in PK studies. IR studies showed anti-ID can serve as suitable positive control in neutralizing antibody assays. Conclusion: Phage-derived anti-IDs and anti-YTEs are suitable for PK and IR assays.

Motherhood and DREADD manipulation of the nucleus accumbens weaken established pair bonds in female prairie voles.

Monogamous pair bonding has evolved to enhance reproductive success and ensure offspring survival. Although the behavioral and neural mechanisms regulating the formation of pair bonds have been relatively well outlined, how these relationships are regulated and maintained across the lifetime of an individual remains relatively unexplored. One way to explore this is to study the maintenance of a social bond across a major life-history transition. The transition to motherhood is among the most poignant moments in the life history of a female, and is associated with significant neural and behavioral changes and shifting priorities. The nucleus accumbens (NAc) is known to modulate social valence and is central to mammalian pair bonding. In this study, we investigated two mechanisms driving variation in bond strength in the socially monogamous prairie vole (Microtus ochrogaster). We manipulated neural activity of the NAc at two distinct stages of life-history, before and after the birth of offspring, to assess how neural activity and social contexts modulate female pair bond strength. Our results showed DREADD (Designer Receptor Exclusively Activated by Designer Drugs) inhibition of the NAc decreases affiliative behavior towards the mating partner, whereas DREADD activation of the NAc increases affiliative behavior of strangers, thereby decreasing social selectivity. We also found a robust "birth effect" on pair bond strength, such that bonds with partners were weakened after the birth of offspring, an effect not attributable to the amount of cohabitation time with a partner. Overall, our data support the hypotheses that NAc activity modulates reward/saliency within the social brain in different ways, and that motherhood comes with a cost for the bond strength between mating partners.

Randomized controlled trial protocol of health coaching for veterans with complex chronic pain.

BACKGROUND: Pain predominant multisymptom illness (pain-CMI) refers to symptom-based conditions where pain is a primary symptom. There is initial evidence that health coaching may be efficacious in treating pain-CMI because it can be tailored to the veteran's goals and emphasizes long-term behavior change, which may indirectly impact the maintaining factors of pain-CMI (e.g., catastrophizing, poor pain control, and limited activity). This paper describes the study protocol and rationale of a randomized controlled trial that will compare the efficacy of remote-delivered health coaching in reducing disability and pain impairment for veterans with pain-CMI to remote-delivered supportive psychotherapy. METHODS: This randomized controlled trial will consist of two treatment arms: remote-delivered health coaching and remote-delivered supportive psychotherapy, the active control. Each treatment condition will consist of twelve, weekly one-on-one meetings with a study provider. In addition to the baseline assessment, participants will also complete 6-week (mid-treatment), 12-week (post-treatment), and 24-week (follow-up) assessments that consist of questionnaires that can be completed remotely. The primary aims for this study are to determine whether health coaching reduces disability and pain impairment as compared to supportive psychotherapy. We will also examine whether health coaching reduces physical symptoms, catastrophizing, limiting activity, and increasing pain control as compared to supportive psychotherapy. DISCUSSION: This study will contribute to the existing literature on pain-CMI and report the effectiveness of a novel, remote-delivered behavioral intervention.

Single cell multi-omic reference atlases of non-human primate immune tissues reveals CD102 as a biomarker for long-lived plasma cells.

In response to infection or immunization, antibodies are produced that provide protection against re-exposure with the same pathogen. These antibodies can persist at high titers for decades and are maintained by bone marrow-resident long-lived plasma cells (LLPC). However, the durability of antibody responses to immunization varies amongst vaccines. It is unknown what factors contribute to the differential longevity of serum antibody responses and whether heterogeneity in LLPC contributes to this phenomenon. While LLPC differentiation has been studied extensively in mice, little is known about this population in humans or non-human primates (NHP). Here, we use multi-omic single-cell profiling to identify and characterize the LLPC compartment in NHP. We identify LLPC biomarkers including the marker CD102 and show that CD102 in combination with CD31 identifies LLPC in NHP bone marrow. Additionally, we find that CD102 is expressed by LLPC in mouse and humans. These results further our understanding of the LLPC compartment in NHP, identify biomarkers of LLPC, and provide tissue-specific single cell references for future studies.

Profiling of hMPV F-specific antibodies isolated from human memory B cells.

Human metapneumovirus (hMPV) belongs to the Pneumoviridae family and is closely related to respiratory syncytial virus (RSV). The surface fusion (F) glycoprotein mediates viral fusion and is the primary target of neutralizing antibodies against hMPV. Here we report 113 hMPV-F specific monoclonal antibodies (mAbs) isolated from memory B cells of human donors. We characterize the antibodies' germline usage, epitopes, neutralization potencies, and binding specificities. We find that unlike RSV-F specific mAbs, antibody responses to hMPV F are less dominant against the apex of the antigen, and the majority of the potent neutralizing mAbs recognize epitopes on the side of hMPV F. Furthermore, neutralizing epitopes that differ from previously defined antigenic sites on RSV F are identified, and multiple binding modes of site V and II mAbs are discovered. Interestingly, mAbs that bind preferentially to the unprocessed prefusion F show poor neutralization potency. These results elucidate the immune recognition of hMPV infection and provide novel insights for future hMPV antibody and vaccine development.

Protocol for a type 1 hybrid effectiveness/implementation clinical trial of collaborative specialty care for Veterans with Gulf War Illness.

AIMS: We describe a clinical trial which is seeking to determine the effectiveness and understand implementation outcomes for tele-collaborative specialty care for Veterans with Gulf War Illness (GWI). MAIN METHODS: This study will be a hybrid type 1 randomized effectiveness-implementation trial comparing tele-collaborative specialty care to electronic consultation for Gulf War Veterans with GWI (N = 220). In tele-collaborative specialty care, the specialty provider team will deliver health coaching and problem-solving treatment to Veterans and recommend a plan for analgesic optimization. In electronic consultation, the specialty provider team will make a one-time recommendation to the primary care team for locally delivered health coaching, problem-solving treatment and analgesic optimization. The primary aim will be to determine the effectiveness of tele-collaborative specialty care as compared to electronic consultation to reduce disability related to GWI. Our secondary aim will be to understand implementation outcomes. SIGNIFICANCE: There is a need to improve care for Veterans with GWI. A potentially useful model to improve care is tele-collaborative specialty care, where the specialists work with the primary care provider to synergistically treat the patients. DISCUSSION: This is the first clinical trial to prospectively compare different models of care for Veterans with GWI. This responds to multiple calls for research to improve treatment for Veterans with GWI, including from the National Academy of Medicine.

Development of a microneutralization assay for HSV-2.

BACKGROUND: Plaque Reduction Neutralization Test (PRNT) is the standard assay used for measuring neutralizing antibody responses to Herpes simplex virus type-2 (HSV-2). The PRNT is a cumbersome, time-consuming and laborious assay. The development of a faster, high throughput microneutralization assay (MNA) for HSV-2 viruses carried out in a 96-well format will allow for rapid testing of large numbers of samples for drug and vaccine development. METHODS: We describe the generation of a MNA that utilizes a pair of anti-HSV human monoclonal antibodies (mAbs) for virus detection in HSV-2 infected Vero cells. Antibodies were generated by B-cell cloning from PBMC's isolated from HSV-1 negative/HSV-2 positive donors. We describe the selection and characterization of the antibodies used for virus detection by ELISA with purified, recombinant anti-HSV glycoproteins, antibody binding in infected cells, and Western Blot. We determine the anti-HSV-2 neutralizing titers of immune sera from mice by MNA and PRNT and compare these results by linear regression analysis. RESULTS: We show that neutralization titers for HSV-2, determined by the 96-well MNA correlate with titers determined by a PRNT completed in 24-well plates in both the absence (R2 = 0.8250) and presence (R2 = 0.7075) of complement. CONCLUSIONS: We have successfully developed an MNA that can be used in place of the burdensome PRNT to determine anti-HSV-2 neutralizing activity in serum. This MNA has much greater throughput than the PRNT, allowing many more samples to be processed in a shorter time saving ∼90 % of the time required by the laboratory scientist to complete the task as compared to the traditional PRNT.

Occupational Therapy for Functional Impairments Resulting From COVID-19 Infection: A Case Report.

This case report examines the role of occupational therapy in the recovery of a client who became critically ill with severe acute respiratory syndrome coronavirus 2. In it, we describe evaluation and treatment methods, functional impairments, and special considerations when working with a client with severe coronavirus disease 2019 infection. The client was a 43-yr-old Hispanic man treated in a long-term acute-care hospital. Client-centered treatment sessions focused on activities of daily living (ADLs), self-feeding, medication management, and leisure and were implemented in 30- to 45-min sessions 3 times per week for 5 wk. The Activity Measure for Post Acute Care Daily Activities Short Form was used to measure basic mobility, daily activities, and applied cognition in the acute setting. A manual dynamometer was used to measure grip strength, and the Nine-Hole Peg Test was used to measure digit dexterity. Both were used in the context of occupational engagement. Data were collected at evaluation, every 2 wk, and at discharge. The client achieved his goals and demonstrated marked improvement in independence with basic ADLs, leisure activities, bilateral grip strength, and manual dexterity.

Healthcare providers' perceived learning needs and barriers to providing care for chronic multisymptom illness and environmental exposure concerns.

OBJECTIVE: Patient provider encounters for chronic multisympom illness (CMI) and/or environmental exposures are difficult often resulting in Veterans and providers having high levels of dissatisfaction. Patients attribute these difficulties to providers lacking knowledge about these health concerns. It is not known whether providers perceive themselves as lacking expertise in CMI and environmental exposure concerns. METHODS: This needs assessment used a descriptive online survey design. A total of 3632 VA healthcare providers across disciplines were surveyed. RESULTS: Healthcare providers reported speaking with Veterans about CMI and environmental exposures despite feeling they have minimal to no knowledge of these topics. At the same time, only half of the providers had taken an available training on CMI or environmental exposure within the last year. CONCLUSION: Healthcare providers recognize a knowledge gap regarding CMI and environmental exposures, despite this, there is low uptake of provider education on these topics. PRACTICE IMPLICATIONS: A better understanding of barriers to uptake of training on CMI and environmental exposures is needed to increase engagement with these important trainings.

Veterans with Gulf War Illness perceptions of management strategies.

AIMS: Gulf War Illness (GWI) is a prevalent and disabling condition characterized by persistent physical symptoms. Clinical practice guidelines recommend self-management to reduce the disability from GWI. This study evaluated which GWI self-management strategies patients currently utilize and view as most effective and ineffective. MATERIALS AND METHODS: Data were collected from 267 Veterans during the baseline assessment of a randomized clinical trial for GWI. Respondents answered 3 open-ended questions regarding which self-management strategies they use, view as effective, and view as ineffective. Response themes were coded, and code frequencies were analyzed. KEY FINDINGS: Response frequencies varied across questions (in-use: n = 578; effective: n = 470; ineffective: n = 297). Healthcare use was the most commonly used management strategy (38.6% of 578), followed by lifestyle changes (28.5% of 578), positive coping (13% of 578), and avoidance (13.7% of 578). When asked about effective strategies, healthcare use (25.9% of 470), lifestyle change (35.7% of 470), and positive coping (17.4% of 470) were identified. Avoidance was frequently identified as ineffective (20.2% of 297 codes), as was invalidating experiences (14.1% of 297) and negative coping (10.4% of 297). SIGNIFICANCE: Patients with GWI use a variety of self-management strategies, many of which are consistent with clinical practice guidelines for treating GWI, including lifestyle change and non-pharmacological strategies. This suggests opportunities for providers to encourage effective self-management approaches that patients want to use.

Student veterans and adjustment to college: Making meaning of military experiences.

OBJECTIVE: This study examined the relationships among meaning making, military stressor severity, and adjustment to college among student service members/veterans (SSM/Vs). PARTICIPANTS: Participants were 128 SSM/Vs enrolled in postsecondary education from April to June 2016. METHODS: Participants completed online self-report rating scales of stressor severity for their most stressful military event, meaning made of that stressor, and adjustment to college. RESULTS: Regression analyses revealed that made meaning of military stressors was associated with more positive academic, social, and emotional adjustment to college. Stressor severity was not associated with adjustment, nor did made meaning moderate the relationship between stressor severity and adjustment to college. CONCLUSION: These findings provide preliminary evidence that making meaning of stressful military experiences can promote academic, social, and emotional adjustment to college among SSM/Vs and has implications for incorporating meaning making strategies into university and clinical programs aimed at promoting adjustment to college in this population.

Understanding Veterans' Causal Attributions of Physical Symptoms.

BACKGROUND: Illness beliefs are significant contributors to health outcomes. Beliefs about the cause of physical symptoms are considered particularly important among those with medically unexplained symptoms and illnesses (MUS); yet little is known about causal beliefs among those with the most severe MUS (i.e., Veterans). The goal of the current study was to examine Veteran's causal attributions of their physical symptoms. METHOD: A total of 91 combat Veterans with MUS were surveyed using a mixed-methods design about the cause of their physical symptoms, physical symptom severity, and PTSD symptoms. Causal attributions of physical symptoms were analyzed through thematic response analysis and grouped into categories. Chi-square analysis was used to assess the distribution of causal attribution types across Veterans with varying physical symptom severity and PTSD symptom severity. RESULTS: Veterans with MUS reported an average of 7.9 physical symptoms, and attributed the cause of their symptoms to seven different categories ("Do not Know," "Stress/Mental Health," "Deployment/Environment," "Functional/Symptom," "Medically Explained," "Medically Unexplained Syndrome," and "Lifestyle"). Exploratory chi-square analysis revealed significant differences in causal attributions across physical symptom severity and severity of PTSD symptoms. Veterans with more severe PTSD and Veterans with more severe physical symptoms were more likely to attribute their MUS to stress/mental health or to a medically unexplained syndrome compared with those with low/no PTSD symptoms and physical symptom severity. Veterans with minimal PTSD and Veterans with minimal physical symptom severity were more likely to attribute the cause of their MUS to lifestyle choices (e.g., exercise/diet) compared with those with high PTSD and physical symptom severity. CONCLUSION: Veterans with MUS endorse multiple, varied causal attributions for their physical symptoms, suggesting more complex causal beliefs than typically assumed. This has important implications for patient-provider communication and development of concordance around MUS treatment.

Immunogenicity generated by mRNA vaccine encoding VZV gE antigen is comparable to adjuvanted subunit vaccine and better than live attenuated vaccine in nonhuman primates.

Shingles is a painful, blistering rash caused by reactivation of latent varicella-zoster virus (VZV) and most frequently occurs in elderly and immunocompromised individuals. Currently, two approved vaccines for the prevention of shingles are on the market, a live attenuated virus vaccine ZOSTAVAX® (Merck & Co., Inc., Kenilworth, NJ, USA) and an AS01B adjuvanted subunit protein vaccine Shingrix™ (Glaxo Smith Kline, Rockville, MD, USA). Human clinical immunogenicity and vaccine efficacy data is available for these two benchmark vaccines, offering a unique opportunity for comparative analyses with novel vaccine platforms and animal model translatability studies. The studies presented here utilized non-human primates (NHP) to evaluate humoral and cellular immune response by three vaccine modalities: the new platform of lipid nanoparticle (LNP) formulated mRNA encoding VZV gE antigen (VZV gE mRNA/LNP) as compared with well-established platforms of live attenuated VZV (VZV LAV) and adjuvanted VZV gE subunit protein (VZV gE protein/adjuvant). The magnitude of response to vaccination with a single 100-200 µg mRNA dose or two 50 µg mRNA doses of VZV gE mRNA/LNP were comparable to two 50 µg protein doses of VZV gE protein/adjuvant, suggesting the VZV gE mRNA/LNP platform has the potential to elicit a robust immune response, and both modalities generated markedly higher responses than VZV LAV. Additionally, the slopes of decay for VZV-specific antibody titers were roughly similar across all three vaccines, indicating the magnitude of peak immunogenicity was the driving force in determining immune response longevity. Finally, vaccine-induced immunogenicity with VZV LAV and VZV gE protein/adjuvant in NHP closely resembled human clinical trials immune response data for ZOSTAVAX® and Shingrix™, helping to validate NHP as an appropriate preclinical model for evaluating these vaccines.

Effects of Bluetooth-Enabled Desk Ellipticals on Office Work Performance: Rationale, Design, and Protocol for a Randomized Trial With Overweight and Obese Adults.

BACKGROUND: Workplaces that provide opportunities for physical activity without requiring extra time for activity could help counteract the obesity epidemic. Desk ellipticals can contribute to activity-supportive workplace environments; however, the feasibility of engaging employees in pedaling ellipticals during simultaneous office work has not been well evaluated. OBJECTIVE: We aim to present the rationale and methods from an ongoing randomized trial with overweight and obese employees that will evaluate (1) the effects of pedaling a compact desk elliptical on work performance and (2) the influence of different incentive types and schedules on desk pedaling quantity. METHODS: Overweight and obese medical center employees are being recruited in dyads for a 2 (gift card type: healthier food vs Amazon) by 3 (gift card schedule: immediate incentive contingent on individual pedaling quantity; immediate incentive partially contingent on dyads' joint pedaling quantity; and delayed noncontingent pedaling incentive) cluster randomized within-subjects factorial trial. All participants receive a Bluetooth-enabled desk elliptical for 4 weeks and access to a mobile app that provides real-time pedaling feedback. The primary aims are to assess (1) change in employee work performance from pre- to postelliptical installation via employee and supervisor ratings and (2) effects of gift card type and schedule on quantity of objectively measured desk pedaling completed. RESULTS: Data collection is ongoing. We expect to complete main outcome analyses in 2020. CONCLUSIONS: This trial represents one of the earliest attempts to assess the effects of desk pedaling and pedaling-incentive types in real-world offices. It could help bridge the research-to-practice gap by providing evidence on whether desk pedaling can be sustained without compromising work performance. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/16275.

Coping with Medically Unexplained Physical Symptoms: the Role of Illness Beliefs and Behaviors.

BACKGROUND: Medically unexplained syndromes (MUS) are both prevalent and disabling. While illness beliefs and behaviors are thought to maintain MUS-related disability, little is known about which specific behavioral responses to MUS are related to disability or the way in which beliefs and behaviors interact to impact functioning. The purpose of the present study was to examine the relationship between illness beliefs and disability among patients with MUS, and assess the extent to which behaviors mediate this relationship. METHODS: The study examined data from the baseline assessment of a multi-site randomized controlled trial (RCT). Participants were 248 veterans with MUS. Illness beliefs, behavioral responses to illness, and disability were assessed through self-report questionnaire. Data were analyzed using mediation analysis. RESULTS: Threat-related beliefs predicted greater disability through decreased activity and increased practical support seeking. Protective beliefs predicted less disability through reductions in all-or-nothing behavior and limiting behavior. CONCLUSIONS: These outcomes suggest that all-or-nothing behavior, limiting behavior, and practical support seeking are important in the perpetuation of disability among those with MUS. This has implications for improving MUS treatment by highlighting potential treatment targets. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02161133.

Characterization of potent RSV neutralizing antibodies isolated from human memory B cells and identification of diverse RSV/hMPV cross-neutralizing epitopes.

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection in young children and older adults. Currently, no licensed vaccine is available, and therapeutic options are limited. The primary target of neutralizing antibodies to RSV is the surface fusion (F) glycoprotein. Understanding the recognition of antibodies with high neutralization potencies to RSV F antigen will provide critical insights in developing efficacious RSV antibodies and vaccines. In this study, we isolated and characterized a panel of monoclonal antibodies (mAbs) with high binding affinity to RSV prefusion F trimer and neutralization potency to RSV viruses. The mAbs were mapped to previously defined antigenic sites, and some that mapped to the same antigenic sites showed remarkable diversity in specificity, binding, and neutralization potencies. We found that the isolated site III mAbs shared highly conserved germline V-gene usage, but had different cross-reactivities to human metapneumovirus (hMPV), possibly due to the distinct modes/angles of interaction with RSV and hMPV F proteins. Furthermore, we identified a subset of potent RSV/hMPV cross-neutralizing mAbs that target antigenic site IV and the recently defined antigenic site V, while the majority of the mAbs targeting these two sites only neutralize RSV. Additionally, the isolated mAbs targeting site Ø were mono-specific for RSV and showed a wide range of neutralizing potencies on different RSV subtypes. Our data exemplify the diversity of anti-RSV mAbs and provide new insights into the immune recognition of respiratory viruses in the Pneumoviridae family.

Interneurons Regulate Locomotion Quiescence via Cyclic Adenosine Monophosphate Signaling During Stress-Induced Sleep in Caenorhabditis elegans.

Sleep is evolutionarily conserved, thus studying simple invertebrates such as Caenorhabditis elegans can provide mechanistic insight into sleep with single cell resolution. A conserved pathway regulating sleep across phylogeny involves cyclic adenosine monophosphate (cAMP), a ubiquitous second messenger that functions in neurons by activating protein kinase A. C. elegans sleep in response to cellular stress caused by environmental insults [stress-induced sleep (SIS)], a model for studying sleep during sickness. SIS is controlled by simple neural circuitry, thus allowing for cellular dissection of cAMP signaling during sleep. We employed a red-light activated adenylyl cyclase, IlaC22, to identify cells involved in SIS regulation. We found that pan-neuronal activation of IlaC22 disrupts SIS through mechanisms independent of the cAMP response element binding protein. Activating IlaC22 in the single DVA interneuron, the paired RIF interneurons, and in the CEPsh glia identified these cells as wake-promoting. Using a cAMP biosensor, epac1-camps, we found that cAMP is decreased in the RIF and DVA interneurons by neuropeptidergic signaling from the ALA neuron. Ectopic overexpression of sleep-promoting neuropeptides coded by flp-13 and flp-24, released from the ALA, reduced cAMP in the DVA and RIFs, respectively. Overexpression of the wake-promoting neuropeptides coded by pdf-1 increased cAMP levels in the RIFs. Using a combination of optogenetic manipulation and in vivo imaging of cAMP we have identified wake-promoting neurons downstream of the neuropeptidergic output of the ALA. Our data suggest that sleep- and wake-promoting neuropeptides signal to reduce and heighten cAMP levels during sleep, respectively.