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David C Houghton,1,2 Christina R Merritt,1,3 Sierra N Miller,1 Jasmine M Mitchell,4 David Parker,1 Jonathan D Hommel,1,3 Kathryn A Cunningham,1– 3,&ast; Denise M Wilkes1,5,&ast; 1Center for Addiction Sciences and Therapeutics, University of Texas Medical Branch, Galveston, TX, USA; 2Department of Psychiatry and Behavioral Sciences, University of Texas Medical Branch, Galveston, TX, USA; 3Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX, USA; 4Department of Family and Community Medicine, UT McGovern Medical School, Houston, TX, USA; 5Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA&ast;These authors contributed equally to this workCorrespondence: David C Houghton, Center for Addiction Sciences and Therapeutics, University of Texas Medical Branch, 301 University Blvd, Texas, Galveston, TX 77555, USA, Tel +1 (409)747-9785, Email dahought@utmb.eduBackground: Pain management physicians are increasingly focused on limiting prescription opioid abuse, yet existing tools for monitoring adherence have limited accuracy. Medication event monitoring system (MEMS) is an emerging technology for tracking medication usage in real-time but has not been tested in chronic pain patients on long-term opioid regimens.Objective: We conducted a pilot clinical trial to investigate the utility of MEMS for monitoring opioid adherence and compared to traditional methods including self-report diaries, urine drug screen (UDS), and physicians’ opinions.Methods: Opioid-maintained chronic pain patients were recruited from a pain management clinic. Participants (n=28) were randomly assigned to either receive MEMS bottles containing their opioid medication for a 90-day period or to continue using standard medication bottles. MEMS bottles were configured to record and timestamp all bottle openings and the number of pills that were removed from the bottle (via measurement of weight change).Results: Participants who received MEMS demonstrated highly heterogenous dosing patterns, with a substantial number of patients rapidly removing excessive amounts of medication and/or “stockpiling” medication. By comparison, physicians rated all participants as either “totally compliant” or “mostly compliant”. UDS results did not reveal any illicit drug use, but 25% of participants (n=7) tested negative for their prescribed opioid metabolite. MEMS data did not correlate with physician-rated adherence (P=0.24) and UDS results (P=0.77). MEMS data consistently revealed greater non-adherence than self-report data (P< 0.001).Conclusion: These results highlight the limits in our understanding of naturalistic patterns of daily opioid use in chronic pain patients as well as support the use of MEMS for detecting potential misuse as compared to routine adherence monitoring methods. Future research directions include the need to determine how MEMS could be used to improve patient outcomes, minimize harm, and aid in clinical decision-making.Trial Registration: This study was preregistered on ClinicalTrials.gov (NCT03752411).Keywords: medication event monitoring systems, chronic pain, medication adherence

Sarah N Miller,1 Michelle Nichols,1 Ronald J Teufel II,2 Erin P Silverman,3 Marta Walentynowicz4 1College of Nursing, Medical University of South Carolina, Charleston, South Carolina, SC, USA; 2College of Medicine, Medical University of South Carolina, Charleston, South Carolina, SC, USA; 3Division of Pulmonary, Critical Care, and Sleep Medicine, University of Florida, Gainesville, FL, USA; 4Center for the Psychology of Learning and Experimental Psychopathology, KU Leuven, Leuven, BelgiumCorrespondence: Sarah N Miller, Medical University of South Carolina, College of Nursing, 99 Jonathan Lucas Street, Charleston, SC, 29425, USA, Tel +18437921692, Email millesar@musc.eduAbstract: Dyspnea is an unpredictable and distressing symptom of chronic obstructive pulmonary disease (COPD). Dyspnea is challenging to measure due to the heterogeneity of COPD and recall bias associated with retrospective reports. Ecological Momentary Assessment (EMA) is a technique used to collect symptoms in real-time within a natural environment, useful for monitoring symptom trends and risks of exacerbation in COPD. EMA can be integrated into mobile health (mHealth) platforms for repeated data collection and used alongside physiological measures and behavioral activity monitors. The purpose of this paper is to discuss the use of mHealth and EMA for dyspnea measurement, consider clinical implications of EMA in COPD management, and identify needs for future research in this area.Keywords: COPD, ecological momentary assessment, mobile health, dyspnea, mHealth, telehealth

Background: Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disease associated with respiratory muscle weakness and activity-limiting symptoms such as dyspnea. Respiratory muscle strength training (RMST) is an empirically validated therapy to increase respiratory muscle strength. The theoretically-informed, technology-enhanced RESP-FIT intervention for COPD is a 6-week combined inspiratory and expiratory muscle strength training program with symptom measurement in real time via ecological momentary assessment (EMA)., Objectives: In addition to hypothesis generating purposes, the purpose of this randomized control pilot study was to explore whether observed effects (on symptoms, patient-reported outcomes, and respiratory muscle strength) support carrying out a future large-scale trial of RESP-FIT., Methods: Thirty adults with COPD were randomized to intervention (n=15) or control, with intervention group undergoing 6 weeks of mHealth-enhanced RMST. Daily symptom data were collected in real time over the 6-week intervention period using EMA., Results: Compared to the control group, participants in the intervention group reported decreased dyspnea and anxiety, increased happiness, and improved respiratory muscle strength (PIMax). However, reports of fatigue and sleep disturbance increased in the intervention group compared to the control group., Conclusion: Results support the hypothesis that the 6-week RESP-FIT program will improve respiratory muscle strength, emotional state (anxiety and happiness), and breathlessness in COPD but may contribute to fatigue, at least in the short-term. Future work is needed to determine efficacy of RESP-FIT, determine mechanisms of action on dyspnea and fatigue, and conduct within-subject comparisons of EMA data to explore individual or environmental fluctuations in COPD symptoms., (JCOPDF © 2024.)

Objectives: Patients with hematologic cancer experience severe symptoms (i.e. insomnia, fatigue, pain, distress). Few interventions addressing insomnia and other symptoms exist for this population. Mindfulness-Based Therapy for Insomnia (MBTI) may be appropriate but has only been tested in healthy outpatients. This study aimed to develop and test an adapted MBTI protocol for hematologic cancer patients., Methods: Patient ( n  = 3) and clinician ( n  = 1) focus groups, and user-testing ( N  = 5) informed adaptation of Mindful Night-to-Day (MBTI+). A single-arm pilot trial ( N  = 32) evaluated feasibility (accrual, attrition, adherence), acceptability (intervention satisfaction), and changes to insomnia symptom severity (Insomnia Severity Index; primary outcome) and secondary outcomes (fatigue, pain, distress, pre-sleep arousal, mindfulness, symptom management self-efficacy) at baseline, post-intervention, and 1-month post-intervention. Descriptive statistics and paired sample t-tests were conducted., Results: Qualitative feedback informed MBTI+ content, format, and delivery. Mindfulness was used to increase symptom awareness (sleepiness vs. fatigue). Meditations and behavioral skills were applied to inpatient treatment. MBTI+ met feasibility ( N  = 32/12 months; 8.1% attrition; 83.8% adherence) and acceptability ( M  = 3.52/4.00) benchmarks. Insomnia symptom severity decreased (d = 1.20) from baseline to post-intervention, as did most secondary outcomes., Conclusions: MBTI+ was feasible, acceptable, and showed promise for benefits throughout inpatient and outpatient treatment. Findings warrant further evaluation in a randomized trial.

Stochastic diffusion is the noisy and uncertain process through which dynamics like epidemics, or agents like animal species, disperse over a larger area. Understanding these processes is becoming increasingly important as we attempt to better prepare for potential pandemics and as species ranges shift in response to climate change. Unfortunately, modeling of stochastic diffusion is mostly done through inaccurate deterministic tools that fail to capture the random nature of dispersal or else through expensive computational simulations. In particular, standard tools fail to fully capture the heterogeneity of the area over which this diffusion occurs. Rural areas with low population density require different epidemic models than urban areas; likewise, the edges of a species range require us to explicitly track low integer numbers of individuals rather than vague averages. In this work, we introduce a series of new tools called "mean-FLAME" models that track stochastic dispersion using approximate master equations that explicitly follow the probability distribution of an area of interest over all of its possible states, up to states that are active enough to be approximated using a mean-field model. In one limit, this approach is locally exact if we explicitly track enough states, and in the other limit collapses back to traditional deterministic models if we track no state explicitly. Applying this approach, we show how deterministic tools fail to capture the uncertainty around the speed of nonlinear dynamical processes. This is especially true for marginal areas that are close to unsuitable for diffusion, like the edge of a species range or epidemics in small populations. Capturing the uncertainty in such areas is key to producing accurate forecasts and guiding potential interventions.

The hypothalamus in the mammalian brain is responsible for regulating functions associated with survival and reproduction representing a complex set of highly interconnected, yet anatomically and functionally distinct, sub-regions. It remains unclear what factors drive the spatial organization of sub-regions within the hypothalamus. One potential factor may be structural connectivity of the network that promotes efficient function with well-connected sub-regions placed closer together geometrically, i.e., the strongest axonal signal transferred through the shortest geometrical distance. To empirically test for such efficiency, we use hypothalamic data derived from the Allen Mouse Brain Connectivity Atlas, which provides a structural connectivity map of mouse brain regions derived from a series of viral tracing experiments. Using both cost function minimization and comparison with a weighted, sphere-packing ensemble, we demonstrate that the sum of the distances between hypothalamic sub-regions are not close to the minimum possible distance, consistent with prior whole brain studies. However, if such distances are weighted by the inverse of the magnitude of the connectivity, their sum is among the lowest possible values. Specifically, the hypothalamus appears within the top 94th percentile of neural efficiencies of randomly packed configurations and within one standard deviation of the median efficiency when packings are optimized for maximal neural efficiency. Our results, therefore, indicate that a combination of geometrical and topological constraints help govern the structure of the hypothalamus., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Smith, Ameen, Miller, Kasper, Schwarz, Hommel and Borzou.)

Dyspnea is the most common and activity-limiting symptom for those with chronic obstructive pulmonary disease (COPD). Treatment is complex, palliative care (PC) dyspnea relief interventions are poorly understood, and PC remains underutilized in COPD despite national guidelines and recommendations. The purpose of this rapid review was to explore the concept of dyspnea and role of PC through the lens of providers, caregivers, and patients with COPD. A systematic approach for synthesis was used to identify 13 articles published between January 2018 and October 2023. Team members compared data via visualization and theme clustering to identify key conclusions describing operationalization of dyspnea, management, and PC implications. Dyspnea operationalization was challenging, with inconsistent measurement and terminology. Dyspnea was a significant burden in COPD and contributed to complexity of treatment. Opioids were used most often to treat dyspnea, but provider perspectives and biases can influence treatment decisions and perceptions of opioid therapy by the patient and caregiver. Evidence-based clinical practice guidelines and policies are needed to clarify the use of opioid therapy for dyspnea management to reduce stigmatization and barriers to treatment. Provider education should emphasize a multipronged approach to treatment of dyspnea in COPD with integration of PC early in the care continuum., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 by The Hospice and Palliative Nurses Association. All rights reserved.)

The prevalence of autism has been increasing at an alarming rate. Even accounting for the expansion of autism spectrum disorder diagnostic (ASD) criteria throughout the 1990's, there has been an over 300% increase in ASD prevalence since the year 2000. The often debilitating personal, familial, and societal sequelae of autism are generally believed to be lifelong. However, there have been several encouraging case reports demonstrating the reversal of autism diagnoses, with a therapeutic focus on addressing the environmental and modifiable lifestyle factors believed to be largely underlying the condition. This case report describes the reversal of autism symptoms among dizygotic, female twin toddlers and provides a review of related literature describing associations between modifiable lifestyle factors, environmental exposures, and various clinical approaches to treating autism. The twins were diagnosed with Level 3 severity ASD "requiring very substantial support" at approximately 20 months of age following concerns of limited verbal and non-verbal communication, repetitive behaviors, rigidity around transitions, and extensive gastrointestinal symptoms, among other common symptoms. A parent-driven, multidisciplinary, therapeutic intervention involving a variety of licensed clinicians focusing primarily on addressing environmental and modifiable lifestyle factors was personalized to each of the twin's symptoms, labs, and other outcome measures. Dramatic improvements were noted within several months in most domains of the twins' symptoms, which manifested in reductions of Autism Treatment Evaluation Checklist (ATEC) scores from 76 to 32 in one of the twins and from 43 to 4 in the other twin. The improvement in symptoms and ATEC scores has remained relatively stable for six months at last assessment. While prospective studies are required, this case offers further encouraging evidence of ASD reversal through a personalized, multidisciplinary approach focusing predominantly on addressing modifiable environmental and lifestyle risk factors., Competing Interests: The authors declare no conflicts of interest.

Objective: Two Cownose Rays Rhinoptera bonasus were presented for management of a severe capsalid monogenean infection Benedeniella posterocolpa in a mixed species habitat at an aquarium., Methods: A series of freshwater (FW) dips were elected to mitigate parasite resistance to praziquantel due to the endemic monogenean population in the system. A pretreatment blood sample was opportunistically obtained, and subsequent samples were processed due to development of clinical signs., Result: While the first FW dip was tolerated well and did not induce abnormal behavior, the second led to one individual presenting with tachypnea, pallor, and lethargy. Marked hematological abnormalities requiring medical intervention occurred in both individuals after the second dip. After treatment with elasmobranch Ringer's fluid therapy, sodium bicarbonate, prednisolone acetate, and vitamin E/selenium in the more severely affected ray, and elasmobranch Ringer's alone in the second ray, hematologic derangements and symptoms resolved. Hemoconcentration, hyperproteinemia, hyperlactatemia, and hyperglycemia were attributed to a stress response. A selective loss of urea after exposure to FW resulted in decreased plasma osmolality., Conclusion: Given the severity of the stress response and associated complications observed, hyposalinity treatments should be utilized with caution in this species. If this therapy is employed, the clinician is advised to be prepared to administer supportive care coinciding with the FW dip if necessary., (© 2023 The Authors. Journal of Aquatic Animal Health published by Wiley Periodicals LLC on behalf of American Fisheries Society.)

Conserving Nature's Stage (CNS) is a concept from conservation planning that promotes the protection of areas encompassing a broad range of enduring geophysical traits to provide long-term habitat for diverse species. The efficacy of using enduring geophysical characteristics as surrogates for biodiversity, independent of non-geophysical features and when considering finer resolution area selections, has yet to be investigated. Here, we evaluated CNS using 33 fine-scale inventories of vascular plant, non-vascular plant, invertebrate or vertebrate species from 13 areas across three continents. For each inventory, we estimated a continuous multidimensional surrogate defined from topographic and soil estimates of the surveyed plots. We assessed surrogate effectiveness by comparing the species representation of surrogate selected plots to the representation from plots picked randomly and using species information. We then used correlation coefficients to assess the link between the performance and qualities of the inventories, surroundings and surrogates. The CNS surrogate showed positive performance for 24 of the 33 inventories, and among these tests, represented 28 more species than random and 83% of the total number of species on average. We also found a small number of weak correlations between performance and environmental variability, as well as qualities of the surrogate. Our study demonstrates that prioritizing areas for a variety of geophysical characteristics will, in most cases, promote the representation of species. Our findings also point to areas for future research that might enhance CNS surrogacy. This article is part of the Theo Murphy meeting issue 'Geodiversity for science and society'.

We present analysis of neuronal activity recordings from a subset of neurons in the medial prefrontal cortex of rats before and after the administration of cocaine. Using an underlying modern Hopfield model as a description for the neuronal network, combined with a machine learning approach, we compute the underlying functional connectivity of the neuronal network. We find that the functional connectivity changes after the administration of cocaine with both functional-excitatory and functional-inhibitory neurons being affected. Using conventional network analysis, we find that the diameter of the graph, or the shortest length between the two most distant nodes, increases with cocaine, suggesting that the neuronal network is less robust. We also find that the betweenness centrality scores for several of the functional-excitatory and functional-inhibitory neurons decrease significantly, while other scores remain essentially unchanged, to also suggest that the neuronal network is less robust. Finally, we study the distribution of neuronal activity and relate it to energy to find that cocaine drives the neuronal network towards destabilization in the energy landscape of neuronal activation. While this destabilization is presumably temporary given one administration of cocaine, perhaps this initial destabilization indicates a transition towards a new stable state with repeated cocaine administration. However, such analyses are useful more generally to understand how neuronal networks respond to perturbations., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

It has been proposed that climate adaptation research can benefit from an evolutionary approach. But related empirical research is lacking. We advance the evolutionary study of climate adaptation with two case studies from contemporary United States agriculture. First, we define 'cultural adaptation to climate change' as a mechanistic process of population-level cultural change. We argue this definition enables rigorous comparisons, yields testable hypotheses from mathematical theory and distinguishes adaptive change, non-adaptive change and desirable policy outcomes. Next, we develop an operational approach to identify 'cultural adaptation to climate change' based on established empirical criteria. We apply this approach to data on crop choices and the use of cover crops between 2008 and 2021 from the United States. We find evidence that crop choices are adapting to local trends in two separate climate variables in some regions of the USA. But evidence suggests that cover cropping may be adapting more to the economic environment than climatic conditions. Further research is needed to characterize the process of cultural adaptation, particularly the routes and mechanisms of cultural transmission. Furthermore, climate adaptation policy could benefit from research on factors that differentiate regions exhibiting adaptive trends in crop choice from those that do not. This article is part of the theme issue 'Climate change adaptation needs a science of culture'.

Purpose: Overweight and obesity are common for breast cancer survivors and associated with high symptom burden (i.e., pain, fatigue, depressive symptoms). Physical activity may protect breast cancer survivors with higher body mass indexes (BMI) from increased symptoms. However, the role of physical activity in buffering the relationship between higher BMI and greater symptoms is unclear., Methods: Baseline data from a randomized trial investigating Pain Coping Skills Training among breast cancer survivors (N = 327) with pain were used to examine the relationship between self-reported BMI (kg/m 2 ) and physical activity level (Rapid Assessment of Physical Activity; suboptimal vs. optimal) with pain (Brief Pain Inventory; severity and interference), fatigue (PROMIS-Fatigue short form), and depressive symptoms (Center for Epidemiological Studies Depression Scale). Analyses were conducted in SPSS. Hayes PROCESS macro (Model 1) assessed whether physical activity moderated the relationship between BMI and symptoms., Results: Lower BMI (B = .06, p < .01) and optimal physical activity (B =  - .69, p < .01) were independently associated with lower pain interference. Lower BMI was also associated with lower pain severity (B = .04, p < .001). Neither BMI nor physical activity was associated with fatigue or depressive symptoms. Physical activity did not moderate the relationship between BMI and symptoms., Conclusions: Among breast cancer survivors experiencing pain, higher BMI and being less physically active were related to greater pain (i.e., severity and/or interference). Physical activity did not buffer the relationships between BMI and pain, fatigue, and depressive symptoms, suggesting that physical activity alone may not be sufficient to influence the strength of the relationships between BMI and symptoms., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Pain coping skills training (PCST) is efficacious in patients with cancer, but clinical access is limited. To inform implementation, as a secondary outcome, we estimated the cost-effectiveness of 8 dosing strategies of PCST evaluated in a sequential multiple assignment randomized trial among women with breast cancer and pain (N = 327). Women were randomized to initial doses and re-randomized to subsequent doses based on their initial response (ie, ≥30% pain reduction). A decision-analytic model was designed to incorporate costs and benefits associated with 8 different PCST dosing strategies. In the primary analysis, costs were limited to resources required to deliver PCST. Quality-adjusted life-years (QALYs) were modeled based on utility weights measured with the EuroQol-5 dimension 5-level at 4 assessments over 10 months. A probabilistic sensitivity analysis was performed to account for parameter uncertainty. Implementation of PCST initiated with the 5-session protocol was more costly ($693-853) than strategies initiated with the 1-session protocol ($288-496). QALYs for strategies beginning with the 5-session protocol were greater than for strategies beginning with the 1-session protocol. With the goal of implementing PCST as part of comprehensive cancer treatment and with willingness-to-pay thresholds ranging beyond $20,000 per QALY, the strategy most likely to provide the greatest number of QALYs at an acceptable cost was a 1-session PCST protocol followed by either 5 maintenance telephone calls for responders or 5 sessions of PCST for nonresponders. A PCST program with 1 initial session and subsequent dosing based on response provides good value and improved outcomes. PERSPECTIVE: This article presents the results of a cost analysis of the delivery of PCST, a nonpharmacological intervention, to women with breast cancer and pain. Results could potentially provide important cost-related information to health care providers and systems on the use of an efficacious and accessible nonmedication strategy for pain management. TRIALS REGISTRATION: ClinicalTrials.gov: NCT02791646, registered 6/2/2016., (Copyright © 2023 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Abstract: Behavioral pain management interventions are efficacious for reducing pain in patients with cancer. However, optimal dosing of behavioral pain interventions for pain reduction is unknown, and this hinders routine clinical use. A Sequential Multiple Assignment Randomized Trial (SMART) was used to evaluate whether varying doses of Pain Coping Skills Training (PCST) and response-based dose adaptation can improve pain management in women with breast cancer. Participants (N = 327) had stage I-IIIC breast cancer and a worst pain score of > 5/10. Pain severity (a priori primary outcome) was assessed before initial randomization (1:1 allocation) to PCST-Full (5 sessions) or PCST-Brief (1 session) and 5 to 8 weeks later. Responders ( > 30% pain reduction) were rerandomized to a maintenance dose or no dose and nonresponders (<30% pain reduction) to an increased or maintenance dose. Pain severity was assessed again 5 to 8 weeks later (assessment 3) and 6 months later (assessment 4). As hypothesized, PCST-Full resulted in greater mean percent pain reduction than PCST-Brief (M [SD] = -28.5% [39.6%] vs M [SD]= -14.8% [71.8%]; P = 0.041). At assessment 3 after second dosing, all intervention sequences evidenced pain reduction from assessment 1 with no differences between sequences. At assessment 4, all sequences evidenced pain reduction from assessment 1 with differences between sequences ( P = 0.027). Participants initially receiving PCST-Full had greater pain reduction at assessment 4 ( P = 0.056). Varying PCST doses led to pain reduction over time. Intervention sequences demonstrating the most durable decreases in pain reduction included PCST-Full. Pain Coping Skills Training with intervention adjustment based on response can produce sustainable pain reduction., (Copyright © 2023 International Association for the Study of Pain.)

Context: Pain is distressing for women with breast cancer. Pain medication may not provide full relief and can have negative side-effects. Cognitive-behavioral pain intervention protocols reduce pain severity and improve self-efficacy for pain management. These interventions' impact on pain medication use is less clear. Intervention length and coping skills use might play a role in pain outcomes., Objectives: Secondary analysis to examine differences in pain severity, pain medication use, pain self-efficacy, and coping skill use after five- and one-session cognitive-behavioral pain intervention protocols. Pain self-efficacy and coping skills use were assessed as mediators of intervention effects on pain and pain medication use., Methods: Women (N = 327) with stage I-III breast cancer were enrolled in a randomized trial comparing individually-delivered, five- and one-session pain coping skills training (PCST). Pain severity, pain medication use, pain self-efficacy, and coping skills use were assessed preintervention and five to eight weeks later (postintervention)., Results: Pain and pain medication use significantly decreased, while pain self-efficacy increased pre-post for women randomized to both conditions (P's <.05). Five-session PCST participants demonstrated less pain (P =.03) and pain medication use (P =.04), and more pain self-efficacy (P =.02) and coping skills use (P =.04) at postintervention compared to one-session PCST participants. Pain self-efficacy mediated the relationship of intervention condition with pain and pain medication use., Conclusion: Both conditions led to improvements in pain, pain medication use, pain self-efficacy, and coping skills use, and 5-session PCST showed the greatest benefits. Brief cognitive-behavioral pain intervention improve pain outcomes, and pain self-efficacy may play a role in these effects., Competing Interests: Disclosures and Acknowledgment This work was supported by the National Institutes of Health [NIH/NCI R01CA202779]. The authors have no relevant financial or nonfinancial interests to disclose., (Copyright © 2023 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Colorectal cancer (CRC) patients in early to mid-adulthood (≤50 years) are challenged by high symptom burden (i.e., pain, fatigue, distress) and age-related stressors (e.g., managing family, work). Cognitive behavioral theory (CBT)-based coping skills training interventions reduce symptoms and improve quality of life in cancer patients. However, traditional CBT-based interventions are not accessible to these patients (e.g., in-person sessions, during work day), nor designed to address symptoms within the context of this stage of life. We developed a mobile health (mHealth) coping skills training program for pain, fatigue and distress (mCOPE) for CRC patients in early to mid-adulthood. We utilize a randomized controlled trial to test the extent to which mCOPE reduces pain, fatigue and distress (multiple primary outcomes) and improves quality of life and symptom self-efficacy (secondary outcomes)., Methods/design: Patients (N = 160) ≤50 years with CRC endorsing pain, fatigue and/or distress are randomized 1:1 to mCOPE or standard care. mCOPE is a five-session CBT-based coping skills training program (e.g., relaxation, activity pacing, cognitive restructuring) that was adapted for CRC patients in early to mid-adulthood. mCOPE utilizes mHealth technology (e.g., videoconference, mobile app) to deliver coping skills training, capture symptom and skills use data, and provide personalized support and feedback. Self-report assessments are completed at baseline, post-treatment (5-8 weeks post-baseline; primary endpoint), and 3- and 6-months later., Conclusions: mCOPE is innovative and potentially impactful for CRC patients in early to mid-adulthood. Hypothesis confirmation would demonstrate initial efficacy of a mHealth cognitive behavioral intervention to reduce symptom burden in younger CRC patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (©2023PublishedbyElsevierInc.)

Objective: To evaluate the surgical technique and subsequent clinical observations (reproductive and ultrasound findings) of left unilateral ovariectomy in 3 species of Potamotrygon rays-Potamotrygon castexi, Potamotrygon leopoldi, and Potamotrygon motoro-for reproductive management., Animals: Between 2018 and 2019, multiple Potamotrygon rays (P castexi, n = 1; P leopoldi, 1; P motoro, 6) underwent left ovariectomies to evaluate this technique for reproductive management., Procedures: At time of surgery, patient age ranged from juvenile to adult. Rays were anesthetized with MS222 buffered with sodium bicarbonate, and a left craniodorsal surgical approach was made to isolate and excise the left ovary. All rays had uneventful recoveries. Eight unilateral ovariectomized females and 6 males were combined in a mixed-species freshwater touch pool of Potamotrygon rays and teleost species., Results: In December 2020, 3 live and 1 premature autolyzed pup were noted in the habitat. The following day, the adult females were examined via ultrasound and separated from the males. Four dams were identified that produced 8 viable offspring and 4 premature abortions. A large right ovary was observed in all females, with no evidence of left ovarian tissue present via ultrasound., Clinical Relevance: Previous histologic evaluation of freshwater ray ovarian tissue suggests both ovaries may be functionally active yet maintain left dominance like some other elasmobranch species. This manuscript provides proof the right ovary alone can produce live offspring. Furthermore, the enlarged right ovary observed in these females suggests that removal of the left ovary may result in compensatory enlargement of the right ovary.

Purpose: This study evaluated the relationship between pain and depressive symptoms through pain self-efficacy and pain catastrophizing in breast cancer patients with pain., Design: Secondary analysis of a randomized trial investigating a cognitive-behavioral pain management protocol., Sample: Females ( N  = 327) with stage I-III breast cancer and report of at least moderate pain., Methods: Pain severity, pain self-efficacy, pain catastrophizing, and depressive symptoms were measured. The proposed model was assessed using structural equation modeling., Results: Higher pain severity was significantly related to lower pain self-efficacy and higher pain catastrophizing. Lower pain self-efficacy and higher pain catastrophizing were significantly related to more depressive symptoms. Higher pain severity was significantly associated with more depressive symptoms through lower pain self-efficacy and higher pain catastrophizing. The association between pain severity and depressive symptoms was not significant when specified as a direct effect., Conclusion: Pain severity related to depressive symptoms in breast cancer patients via pain self-efficacy and pain catastrophizing., Implications for Psychosocial Providers: Measurement of pain self-efficacy and pain catastrophizing should be incorporated into comprehensive pain assessments for women with breast cancer, as these variables may be relevant therapeutic targets. Psychosocial symptom management interventions should include strategies that increase pain self-efficacy and decrease pain catastrophizing because these pain-related cognitive variables appear to drive the relationship between pain severity and depressive symptoms.

Objective: Develop and pilot test a mobile health (mHealth) cognitive behavioral coping skills training and activity coaching protocol (HCT Symptoms and Steps) for hematopoietic stem cell transplant (HCT) patients., Design: Two-phase, mixed methods study., Sample: HCT patients and healthcare providers., Methods: Phase I was patient (n = 5) and provider (n = 1) focus groups and user testing (N = 5) to develop the HCT Symptoms and Steps protocol. Phase II was a pilot randomized trial (N = 40) to evaluate feasibility, acceptability, and pre-to-post outcomes (e.g., physical disability, pain, fatigue, distress, physical activity, symptom self-efficacy) compared to an education control., Findings: Qualitative feedback on symptoms, recruitment strategies, coping skills, and mHealth components (e.g., Fitbit, mobile app) were integrated into the protocol. HCT Symptoms and Steps were feasible and acceptable. Pre-post changes suggest physical disability and activity improved while symptoms (e.g., fatigue, distress) decreased., Conclusions: HCT Symptoms and Steps have strong feasibility and acceptability and shows promise for benefits. Larger, fully-powered randomized trials are needed to examine intervention efficacy., Implications: HCT Symptoms and Steps may reduce physical disability and improve health outcomes post-transplant., Clinical Trial Registration Number: NCT03859765.

BACKGROUND Prior studies suggest CT can identify bezoars under certain circumstances. Endoscopy provides diagnostic and therapeutic benefit in the setting of suspected aspirin bezoar. Does the absence of findings on CT scan exclude the presence of an aspirin bezoar? CASE REPORT A 64-year-old woman called the police and stated she ingested a bottle of aspirin to harm herself. Upon arrival to the Emergency Department, she was tachypneic with a GCS of 15. Initial laboratory results were: salicylate level of 1143 mcg/mL, respiratory alkalosis, bicarbonate of 9 meq/L, anion gap of 23, and normal renal function. Initial therapeutic intervention included infusions of glucose and bicarbonate, multiple doses of activated charcoal, intubation, and emergent hemodialysis. After hemodialysis, the salicylate level rebounded, and a Gastroenterology (GI) consultation was requested to rule out bezoar. On day 2, GI requested an abdominal CT scan with Gastrografin in place of endoscopy due to hemodynamic instability. A CT scan was negative for bezoar. After multiple hemodialysis sessions and whole-bowel irrigation with rebounding salicylate levels, GI was consulted again for reevaluation for endoscopy. On day 5, an endoscopy discovered a concretion containing pill fragments. Another endoscopy performed on day 7 removed further fragments. Salicylate levels began to consistently decline. Unfortunately, the patient's neurologic status did not improve, and on day 11 she was switched to palliative care and died. CONCLUSIONS Endoscopy with direct visualization is diagnostic and therapeutic in the setting of a possible bezoar. The absence of pharmacobezoar on imaging should not delay endoscopy in a clinical setting suggesting bezoar.

The nucleus accumbens shell (NAcSh) and its afferent and efferent neuronal projections control key aspects of motivation for cocaine. A recently described regulator of γ-aminobutyric acid (GABA) projections from the dorsal raphe nucleus (DRN) to the NAcSh (DRN → NAcSh) is the neuropeptide neuromedin U (NMU). Here, we find that systemic administration of NMU decreases breakpoint for cocaine on a progressive ratio schedule of reinforcement in male rats. Employing a retrograde adeno-associated virus (AAV), we found that RNAi-mediated knockdown of the NMU receptor 2 (NMUR2) in afferent DRN projections to the NAcSh increases the breakpoint for cocaine. Our previous studies demonstrated that NMU regulates GABA release in the NAcSh, and our current investigation found that systemic NMU administration suppresses cocaine-evoked GABA release in the NAcSh and increases phosphorylated c-Fos expression in neurons projecting from the NAcSh to the ventral pallidum (VP). To further probe the impact of NMU/NMUR2 on neuroanatomical pathways regulating motivation for cocaine, we employed multi-viral transsynaptic studies. Using a combination of rabies virus and retrograde AAV helper virus, we mapped the impact of NMU across three distinct brain regions simultaneously and found a direct connection of GABAergic DRN neurons to the NAcSh → VP pathway. Together, these data reveal that NMU/NMUR2 modulates a direct connection within the GABAergic DRN → NAcSh → VP circuit that diminishes breakpoints for cocaine. These findings importantly advance our understanding of the neurochemical underpinnings of pathway-specific regulation of neurocircuitry that may regulate cocaine self-administration, providing a unique therapeutic perspective., (© 2021. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

Purpose: African-American women with breast cancer face significant disparities, including high levels of pain. Depressive symptoms and self-efficacy for pain management impact how women with breast cancer manage pain, yet little is known about how these variables relate to pain specifically for African-American women with breast cancer., Methods: Baseline linear regression analyses were conducted using a sample of women (n = 98) with stage I-III breast cancer identifying as Black or African-American who were part of a larger intervention trial. Linear regressions explored the effect of depressive symptoms on pain (i.e., severity and interference), and the effect of self-efficacy for pain management on pain. Covariates were age (M = 57.22, SD = 10.76), cancer stage (50% = stage 1), and education level (36% = some college)., Results: Participants reported moderate levels of pain severity and interference. Higher depressive symptoms were related to both higher pain severity and interference; (B = 0.06, p < 0.01, 95% CI [0.02,0.09]) and (B = 0.13, p < 0.001, 95% CI [0.09, 0.17]) respectively. Likewise, lower self-efficacy for pain management was also related to both higher pain severity and interference; (B =  - 0.04, p < 0.001, 95% CI [- 0.05, - 0.02]) and (B =  - 0.06, p < 0.001, 95% CI [- 0.08, - 0.04]) respectively. Women reporting less than a high school diploma endorsed significantly higher pain severity and interference than women reporting some college. Age and cancer stage were not significantly related to pain., Conclusion: Pain for African-American women with breast cancer may be influenced by depressive symptoms and self-efficacy for pain management, in addition to other important variables. Attending to better assessment and treatment of depressive symptoms and self-efficacy for pain management may improve outcomes., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Virtual reality (VR) has the potential to improve pain and pain-related symptoms. We examined the feasibility, acceptability, safety, and impact of a 30-min virtual underwater/sea environment (VR Blue) for reducing pain and pain-related symptoms in advanced colorectal cancer patients. A qualitative exit interview was conducted to understand preferences, thoughts, and feelings about the VR session., Method: Participants ( N = 20) had stage IV colorectal cancer and moderate-to-severe pain. Participants completed a 30-min VR Blue session that visually and aurally immersed them in virtual ocean scenarios. Feasibility was assessed by accrual ( N = 20), protocol adherence (≥80% completing VR Blue), and completed data (≥80% assessment completion). Acceptability was determined by patients reporting ≥80% intervention satisfaction. Safety was determined by ≥80% of patients completing the session without self-reported side effects. Measures of pain, tension, relaxation, stress, anxiety, and mood were collected before, during, and after the VR Blue session. A semi-structured qualitative interview was conducted after VR Blue to assess participants' VR experiences., Results: All participants (100%) completed the VR Blue session. There was 100% data collection at the pre- and post-assessments. Satisfaction with VR Blue was high M = 3.3 (SD = 0.4) (83%). No significant side effects were reported. Pain decreased by 59% (Pre- M = 3 [1]; Post- M = 1 [1]). Tension decreased by 74% (Pre- M = 30 [24]; Post- M = 8 [13]). Relaxation improved by 38% (Pre- M = 62 [21]); Post- M = 86 [17]). Stress decreased by 68% (Pre- M = 24 [24]; Post- M = 8 [14]). Anxiety decreased by 65% (Pre- M = 20 [23]; Post- M = 7 [13]). Mood improved by 70% (Pre- M = 13 [16]; Post- M = 4 [11]). Qualitative data suggested a positive response to the VR Blue protocol., Significance of Results: This work supports the feasibility, acceptability, and safety of VR Blue for advanced colorectal cancer patients. Participants showed significant pre-post improvement in pain and pain-related symptoms hinting to the potential feasibility of VR interventions in this population. Larger, randomized trials with a control condition are needed to examine the efficacy of VR-based interventions for patients with advanced colorectal cancer and pain.

Background: Obesity is associated with poor outcomes for patients with rheumatoid arthritis (RA). Effective weight management is imperative. Although traditional lifestyle behavioral weight loss programs have demonstrated efficacy for reducing weight, these interventions do not meet the pain-related weight loss challenges of RA patients with obesity., Objective: A 12-session group program (90 minutes per session) was developed integrating pain coping skills training into a lifestyle behavioral weight loss intervention. In addition to the weekly group sessions, participants engaged in supervised exercise sessions 3 times per week., Methods: Through a small, pilot randomized trial, 50 participants were randomized to receive the intervention (n = 29) or standard care of RA (n = 21). Feasibility data (i.e., accrual, attrition, adherence) was examined using descriptive statistics (e.g., percent). We examined patterns of change in study outcomes from baseline to follow-up separately for the intervention and standard care arms using descriptive statistics and paired t tests. Effect sizes are also presented., Results: Of those randomized to the intervention group,79.3% initiated treatment, with participants attending 74.3% of group skills sessions and 64.2% of exercise sessions. Intervention participants evidenced reductions in weight (mean, -2.28 kg) and waist circumference (mean, -4.76 cm) and improvements in physical functioning, eating behaviors, pain, and self-efficacy for weight control., Conclusions: Findings suggest that incorporating a combined pain coping skills training and behavioral weight loss intervention into medical management of RA may improve outcomes. Study accrual and attrition, as well as intervention adherence, will inform future, larger randomized efficacy trials of the intervention.Retrospectively registered: January 29, 2020, NCT04246827., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

RBFOX2, which has a well-established role in alternative splicing, is linked to heart diseases. However, it is unclear whether RBFOX2 has other roles in RNA processing that can influence gene expression in muscle cells, contributing to heart disease. Here, we employ both 3'-end and nanopore cDNA sequencing to reveal a previously unrecognized role for RBFOX2 in maintaining alternative polyadenylation (APA) signatures in myoblasts. RBFOX2-mediated APA modulates mRNA levels and/or isoform expression of a collection of genes, including contractile and mitochondrial genes. Depletion of RBFOX2 adversely affects mitochondrial health in myoblasts, correlating with disrupted APA of mitochondrial gene Slc25a4. Mechanistically, RBFOX2 regulation of Slc25a4 APA is mediated through consensus RBFOX2 binding motifs near the distal polyadenylation site, enforcing the use of the proximal polyadenylation site. In sum, our results unveil a role for RBFOX2 in fine-tuning expression of mitochondrial and contractile genes via APA in myoblasts relevant to heart diseases., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Microorganisms drive soil carbon mineralization and changes in their activity with increased temperature could feedback to climate change. Variation in microbial biodiversity and the temperature sensitivities (Q 10 ) of individual taxa may explain differences in the Q 10 of soil respiration, a possibility not previously examined due to methodological limitations. Here, we show phylogenetic and taxonomic variation in the Q 10 of growth (5-35 °C) among soil bacteria from four sites, one from each of Arctic, boreal, temperate, and tropical biomes. Differences in the temperature sensitivities of taxa and the taxonomic composition of communities determined community-assembled bacterial growth Q 10 , which was strongly predictive of soil respiration Q 10 within and across biomes. Our results suggest community-assembled traits of microbial taxa may enable enhanced prediction of carbon cycling feedbacks to climate change in ecosystems across the globe., (© 2021. The Author(s), under exclusive licence to International Society for Microbial Ecology.)

Purpose: Fatigue and pain are common among women with breast cancer, and often related to depressive symptoms. Social support may influence levels of fatigue, pain interference, and depressive symptoms. We tested a theory-based, structural model examining the relationship between social support (i.e., emotional and instrumental) and depressive symptoms via fatigue and pain interference in women with breast cancer., Methods: Women (N = 327) with stages I-III breast cancer were enrolled in a randomized trial investigating a behavioral pain intervention. Measures of social support, fatigue, pain interference, and depressive symptoms were completed at enrollment. Data were analyzed using structural equation modeling to test direct and indirect pathways relating social support, fatigue, pain interference, and depressive symptoms., Results: Our model evidenced good fit. Significant direct effects emerged linking higher levels of emotional support with lower levels of fatigue (β = -.30), pain interference (β = -.32), and depressive symptoms (β = -.31). More instrumental support was significantly associated with more depressive symptoms (β = .11), but not fatigue or pain interference. Higher levels of fatigue (β = .30) and pain interference (β = .34) were significantly related to higher levels of depressive symptoms. More emotional support related to less depressive symptoms via lower levels of fatigue (β = -.09) and pain interference (β = -.11)., Conclusion: Women reporting higher levels of emotional support endorsed fewer depressive symptoms, and that relationship was driven by lower levels of fatigue and pain interference. Our results highlight novel pathways that healthcare professionals can leverage to optimize social support topics in psychosocial interventions targeting breast cancer symptoms. This model should be replicated using longitudinal data., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Moss-associated N 2 fixation by epiphytic microbes is a key biogeochemical process in nutrient-limited high-latitude ecosystems. Abiotic drivers, such as temperature and moisture, and the identity of host mosses are critical sources of variation in N 2 fixation rates. An understanding of the potential interaction between these factors is essential for predicting N inputs as moss communities change with the climate. To further understand the drivers and results of N 2 fixation rate variation, we obtained natural abundance values of C and N isotopes and an associated rate of N 2 fixation with 15 N 2 gas incubations in 34 moss species collected in three regions across Alaska, USA. We hypothesized that δ 15 N values would increase toward 0‰ with higher N 2 fixation to reflect the increasing contribution of fixed N 2 in moss biomass. Second, we hypothesized that δ 13 C and N 2 fixation would be positively related, as enriched δ 13 C signatures reflect abiotic conditions favorable to N 2 fixation. We expected that the magnitude of these relationships would vary among types of host mosses, reflecting differences in anatomy and habitat. We found little support for our first hypothesis, with only a modest positive relationship between N 2 fixation rates and δ 15 N in a structural equation model. We found a significant positive relationship between δ 13 C and N 2 fixation only in Hypnales, where the probability of N 2 fixation activity reached 95% when δ 13 C values exceeded - 30.4‰. We conclude that moisture and temperature interact strongly with host moss identity in determining the extent to which abiotic conditions impact associated N 2 fixation rates., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Management of food and nutrition systems (MFNS) encompasses the varied roles of registered dietitian nutritionists (RDNs) with administrative responsibilities for food and nutrition services within an organization. RDNs in MFNS are frequently employed in acute care, but also expand into a multitude of other settings in which management of nutrition and foodservice is required, for example, foodservice departments in assisted living and post-acute and long-term care; colleges and universities, kindergarten through grade 12 and pre-kindergarten schools and childcare; retail foodservice operations; correctional facilities; and companies that produce, distribute, and sell food products. RDNs in MFNS aim to create work environments that support high-quality customer-centered care and services, attract and retain talented staff, and foster an atmosphere of collaboration and innovation. The Management in Food and Nutrition Systems Dietetic Practice Group, with guidance from the Academy of Nutrition and Dietetics Quality Management Committee, has revised the Standards of Professional Performance (SOPP) for RDNs in MFNS for 3 levels of practice: competent, proficient, and expert. The SOPP describes 6 domains that focus on professional performance: Quality in Practice, Competence and Accountability, Provision of Services, Application of Research, Communication and Application of Knowledge, and Utilization and Management of Resources. Indicators outlined in the SOPP depict how these standards apply to practice. The standards and indicators for RDNs in MFNS are written with the leader in mind-to support an individual in a leadership role or who has leadership aspirations. The SOPP is intended to be used by RDNs for self-evaluation to assure competent professional practice., (Copyright © 2021 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Predation structures food webs, influences energy flow, and alters rates and pathways of nutrient cycling through ecosystems, effects that are well documented for macroscopic predators. In the microbial world, predatory bacteria are common, yet little is known about their rates of growth and roles in energy flows through microbial food webs, in part because these are difficult to quantify. Here, we show that growth and carbon uptake were higher in predatory bacteria compared to nonpredatory bacteria, a finding across 15 sites, synthesizing 82 experiments and over 100,000 taxon-specific measurements of element flow into newly synthesized bacterial DNA. Obligate predatory bacteria grew 36% faster and assimilated carbon at rates 211% higher than nonpredatory bacteria. These differences were less pronounced for facultative predators (6% higher growth rates, 17% higher carbon assimilation rates), though high growth and carbon assimilation rates were observed for some facultative predators, such as members of the genera Lysobacter and Cytophaga , both capable of gliding motility and wolf-pack hunting behavior. Added carbon substrates disproportionately stimulated growth of obligate predators, with responses 63% higher than those of nonpredators for the Bdellovibrionales and 81% higher for the Vampirovibrionales , whereas responses of facultative predators to substrate addition were no different from those of nonpredators. This finding supports the ecological theory that higher productivity increases predator control of lower trophic levels. These findings also indicate that the functional significance of bacterial predators increases with energy flow and that predatory bacteria influence element flow through microbial food webs. IMPORTANCE The word "predator" may conjure images of leopards killing and eating impala on the African savannah or of great white sharks attacking elephant seals off the coast of California. But microorganisms are also predators, including bacteria that kill and eat other bacteria. While predatory bacteria have been found in many environments, it has been challenging to document their importance in nature. This study quantified the growth of predatory and nonpredatory bacteria in soils (and one stream) by tracking isotopically labeled substrates into newly synthesized DNA. Predatory bacteria were more active than nonpredators, and obligate predators, such as Bdellovibrionales and Vampirovibrionales , increased in growth rate in response to added substrates at the base of the food chain, strong evidence of trophic control. This work provides quantitative measures of predator activity and suggests that predatory bacteria-along with protists, nematodes, and phages-are active and important in microbial food webs., (Copyright © 2021 Hungate et al.)

In boreal forests, climate warming is shifting the wildfire disturbance regime to more frequent fires that burn more deeply into organic soils, releasing sequestered carbon to the atmosphere. To understand the destabilization of carbon storage, it is necessary to consider these effects in the context of long-term ecological change. In Alaskan boreal forests, we found that shifts in dominant plant species catalyzed by severe fire compensated for greater combustion of soil carbon over decadal time scales. Severe burning of organic soils shifted tree dominance from slow-growing black spruce to fast-growing deciduous broadleaf trees, resulting in a net increase in carbon storage by a factor of 5 over the disturbance cycle. Reduced fire activity in future deciduous-dominated boreal forests could increase the tenure of this carbon on the landscape, thereby mitigating the feedback to climate warming., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Background: Women with breast cancer in medically underserved areas are particularly vulnerable to persistent pain and disability. Behavioral pain interventions reduce pain and improve outcomes. Cancer patients in medically underserved areas receive limited adjunctive cancer care, as many lack access to pain therapists trained in behavioral interventions, face travel barriers to regional medical centers, and may have low literacy and limited resources. mHealth technologies have the potential to decrease barriers but must be carefully adapted for, and efficacy-tested with, medically underserved patients. We developed an mHealth behavioral pain coping skills training intervention (mPCST-Community). We now utilize a multisite randomized controlled trial to: 1) test the extent mPCST-Community reduces breast cancer patients' pain severity (primary outcome), pain interference, fatigue, physical disability, and psychological distress; 2) examine potential mediators of intervention effects; and 3) evaluate the intervention's cost and cost-effectiveness., Methods/design: Breast cancer patients (N = 180) will be randomized to mPCST-Community or an attention control. mPCST-Community's four-session protocol will be delivered via videoconferencing at an underserved community clinic by a remote pain therapist at a major medical center. Videoconference sessions will be supplemented with a mobile application. Participants will complete self-report measures at baseline, post-intervention, and 3- and 6-month follow-ups., Conclusions: mPCST-Community has the potential to reduce pain and disability, and decrease barriers for cancer patients in medically underserved areas. This is one of the first trials to test an mHealth behavioral cancer pain intervention developed specifically for medically underserved communities. If successful, it could lead to widespread implementation and decreased health disparities., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Mosses in high-latitude ecosystems harbor diverse bacterial taxa, including N 2 -fixers which are key contributors to nitrogen dynamics in these systems. Yet the relative importance of moss host species, and environmental factors, in structuring these microbial communities and their N 2 -fixing potential remains unclear. We studied 26 boreal and tundra moss species across 24 sites in Alaska, USA, from 61 to 69° N. We used cultivation-independent approaches to characterize the variation in moss-associated bacterial communities as a function of host species identity and site characteristics. We also measured N 2 -fixation rates via 15 N 2 isotopic enrichment and identified potential N 2 -fixing bacteria using available literature and genomic information., Results: Host species identity and host evolutionary history were both highly predictive of moss microbiome composition, highlighting strong phylogenetic coherence in these microbial communities. Although less important, light availability and temperature also influenced composition of the moss microbiome. Finally, we identified putative N 2 -fixing bacteria specific to some moss hosts, including potential N 2 -fixing bacteria outside well-studied cyanobacterial clades., Conclusions: The strong effect of host identity on moss-associated bacterial communities demonstrates mosses' utility for understanding plant-microbe interactions in non-leguminous systems. Our work also highlights the likely importance of novel bacterial taxa to N 2 -fixation in high-latitude ecosystems. Video Abstract.

Backgrounds and Objectives: Eliminating veteran suicide is a top priority for the US Department of Veterans Affairs (VA). Veterans with cancer may be at particular risk for suicidal ideation (SI). The current study aimed to understand factors associated with distress in veterans with cancer who were referred for psychology services, and identify problems associated with SI., Methods: Health records of veterans with cancer (N = 174) were reviewed to abstract data, including results of National Comprehensive Cancer Network (NCCN) Distress Thermometer and Problems List and clinical suicide risk assessments., Results: Veterans with severe distress were significantly more likely to endorse SI and have a history of suicide attempt(s) when compared with veterans with mild or moderate distress (χ 2 = 18.36, P < .001). Of the problems endorsed on the NCCN Problems List, family problems were most strongly linked to SI (χ 2 = 5.54, degrees of freedom [ df ] = 1, P = .02). Specifically, veterans who endorsed problems with their partner were 5 times more likely to experience SI when compared with veterans who did not endorse this problem (Wald = 15.142; df = 1, P < .001)., Conclusions: This study is among the first to find partner problems as a suicide risk factor for veterans with cancer; and, underscore the importance of assessing for partner problems and suicidal ideation among veterans with cancer. This study supports the VA mission to end veteran suicide and addresses a gap in current literature by investigating the understudied population of veterans living with cancer and risk factors for SI., Competing Interests: Author disclosures The authors report no actual or potential conflicts of interest for this article., (Copyright © 2020 Frontline Medical Communications Inc., Parsippany, NJ, USA.)

The current study aim was to examine mental health characteristics in a sample of returning OEF/OIF/OND veterans initially enrolling in Department of Veterans Affairs (VA) health care (N = 1,307), with a particular focus on a subgroup considered at risk for suicide (N = 445). Methods included examination of mental health screening measures and clinical interview data from a VA postdeployment clinic. Half of the sample met criteria for a mental health disorder, whereas 10% reported current suicidal or death ideation (e.g., thoughts of being better off dead or hurting oneself in some way) and 6% reported a history of suicide attempt. Sixty-eight percent of the at-risk subgroup accepted a referral for mental health treatment and a promising majority (78%) of those individuals attended their initial specialty mental health visit. At-risk veterans who accepted mental health referral were more likely to report current suicidal/death ideation; they were also more likely to have a diagnosis of a depressive disorder, anxiety disorder, or posttraumatic stress disorder. Factors associated with mental health appointment attendance included older age, being enrolled in college, and more years of military service. Results highlight the importance of early screening and referral to appropriate mental health follow-up. Implications for clinical practice and increasing engagement in VA mental health services among veterans at risk for suicide are discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Objectives : Eliminating Veteran suicide is a top priority for the Department of Veterans' Affairs (VA). This study identified factors associated with suicidal ideation (SI) among a rarely studied subgroup of Veterans: those with cancer. Methods : Veterans (age M = 61.83) with cancer ( N = 175) referred for psychological evaluation completed measures of pain, sleep, depressive, anxiety, and PTSD symptoms. SI was defined by endorsing on paper-and-pencil questionnaire thoughts of killing oneself in the past 2 weeks or during clinical interview. Results : 25.1% reported SI. Compared to those without SI, Veterans with SI had higher ratings on measures of depression, anxiety, and PTSD symptoms. History of suicide attempt(s) was included in the model due to clinical significance. Logistic regression was performed with these variables as predictors of SI. The omnibus model was significant ( p < .001). However, only anhedonia and depressed mood had a statistically significant contribution to the model (β = 0.540, p = .001). Conclusions : Anhedonia and depressed mood predicted SI among Veterans with cancer above and beyond other risk factors. Clinical Implications : This study's findings highlight the importance of incorporating suicide risk screenings in oncology clinics across VA medical centers.

Suicide occurs at high rates among veterans, underscoring a need for improved identification of veterans at risk of engaging in suicidal behavior. Considering dimensions of psychopathology in the context of an ideation-to-action framework, the present study examined the utility of the Minnesota Multiphasic Personality Inventory-2-Restructured Form in distinguishing depressed, psychiatrically hospitalized male veterans ( N = 430) at varying levels of suicide risk. Analysis of variance and hierarchical logistic regression analyses indicated that internalizing scales differentiated depressed ideators ( n = 147) and depressed controls ( n = 143); and in line with expectations, both broad and narrowly focused externalizing scales provided incremental validity in distinguishing depressed attempters ( n = 140) from depressed ideators. Interactions between Suicidal/Death Ideation and externalizing scale scores were found to differentiate only depressed ideators from depressed controls. Clinical implications in the areas of suicide risk assessment and therapeutic interventions with suicidal veterans are discussed.

Background: Evaluation and treatment of the acutely ill patient is typically complicated by multiple comorbidities and incomplete medical histories. This is exemplified by patients with sepsis, whose care is complicated by variable presentations, shifting definitions, and a variety of potential sources. Many practitioners fail to consider and recognize less-common sources of infection in a timely manner. Additionally, multiple noninfectious conditions can present with the fever and tachycardia typical of the septic patient. The errors of anchoring and premature closure may lead to delay in, or failure of, diagnosis of these conditions., Objective: This review addresses the evaluation of the acutely ill-appearing patient without an apparent source, focusing on occult sources of infection and conditions that mimic sepsis., Discussion: Musculoskeletal, cardiac, neuraxial, and abdominal sources of sepsis should be considered in the acutely ill patient. Indwelling devices should be carefully examined for signs of infection. Consideration for sepsis mimics, such as neuroleptic malignant syndrome, malignant hyperthermia, medication toxicity, and thyroid storm, in patients who fail to respond to standard therapies for sepsis, may lead the physician to potentially reversible life-threatening diagnoses and management., Conclusion: In the seemingly septic patient who does not respond to antimicrobials and fluids, the differential should be broadened to include acutely life-threatening conditions that can mimic sepsis. A review of the patient's medical history, medications, and recent exposures can assist in identifying the source of the patient's elevated body temperature and tachycardia. Consideration of potential sources and other mimics of sepsis is needed in the emergency department., (Published by Elsevier Inc.)

Background: The Veterans Health Administration (VHA) health-care system utilizes a multilevel suicide prevention intervention that features the use of standardized safety plans with veterans considered to be at high risk for suicide., Aims: Little is known about clinician perceptions on the value of safety planning with veterans at high risk for suicide., Method: Audio-recorded interviews with 29 VHA behavioral health treatment providers in a southeastern city were transcribed and analyzed using qualitative methodology., Results: Clinical providers consider safety planning feasible, acceptable, and valuable to veterans at high risk for suicide owing to the collaborative and interactive nature of the intervention. Providers identified the types of veterans who easily engaged in safety planning and those who may experience more difficulty with the process., Conclusion: Additional research with VHA providers in other locations and with veteran consumers is needed.

The vast bacteriophage population harbors an immense reservoir of genetic information. Almost 2000 phage genomes have been sequenced from phages infecting hosts in the phylum Actinobacteria, and analysis of these genomes reveals substantial diversity, pervasive mosaicism, and novel mechanisms for phage replication and lysogeny. Here, we describe the isolation and genomic characterization of 46 phages from environmental samples at various geographic locations in the U.S. infecting a single Arthrobacter sp. strain. These phages include representatives of all three virion morphologies, and Jasmine is the first sequenced podovirus of an actinobacterial host. The phages also span considerable sequence diversity, and can be grouped into 10 clusters according to their nucleotide diversity, and two singletons each with no close relatives. However, the clusters/singletons appear to be genomically well separated from each other, and relatively few genes are shared between clusters. Genome size varies from among the smallest of siphoviral phages (15,319 bp) to over 70 kbp, and G+C contents range from 45-68%, compared to 63.4% for the host genome. Although temperate phages are common among other actinobacterial hosts, these Arthrobacter phages are primarily lytic, and only the singleton Galaxy is likely temperate.

Antivenom is the definitive treatment for venomous snakebites. Alternative treatments warrant investigation because antivenom is sometimes unavailable, expensive, and can have deleterious side effects. This study assesses the efficacy of trypsin to treat coral snake envenomation in an in vivo porcine model. A randomized, blinded study was conducted. Subjects were 13 pigs injected subcutaneously with 1 mL of eastern coral snake venom (10 mg/mL) in the right distal hind limb. After 1 min, subjects were randomized to have the envenomation site injected with either 1 mL of saline or 1 mL of trypsin (100 mg/mL) by a blinded investigator. Clinical endpoint was survival for 72 h or respiratory depression defined as respiratory rate <15 breaths per minute, falling pulse oximetry, or agonal respirations. Fisher's exact t test was used for between group comparisons. Average time to toxicity for the saline control was 263 min (191-305 min). The development of respiratory depression occurred more frequently in control pigs than treated pigs (p = 0.009). Four of the six pigs that received trypsin survived to the end of the 3-day study. No control pigs survived. Two of the trypsin treatment pigs died with times to toxicity of 718 and 971 min. Survival to 12 and 24 h was significantly greater in the trypsin treatment group (p = 0.002, p = 0.009, respectively). Local injection of trypsin, a proteolytic enzyme, at the site of envenomation decreased the toxicity of eastern coral snake venom and increased survival significantly. Further investigation is required before these results can be extended to human snakebites.

Conserving a declining species that is facing many threats, including overlap of its habitats with energy extraction activities, depends upon identifying and prioritizing the value of the habitats that remain. In addition, habitat quality is often compromised when source habitats are lost or fragmented due to anthropogenic development. Our objective was to build an ecological model to classify and map habitat quality in terms of source or sink dynamics for Greater Sage-Grouse (Centrocercus urophasianus) in the Atlantic Rim Project Area (ARPA), a developing coalbed natural gas field in south-central Wyoming, USA. We used occurrence and survival modeling to evaluate relationships between environmental and anthropogenic variables at multiple spatial scales and for all female summer life stages, including nesting, brood-rearing, and non-brooding females. For each life stage, we created resource selection functions (RSFs). We weighted the RSFs and combined them to form a female summer occurrence map. We modeled survival also as a function of spatial variables for nest, brood, and adult female summer survival. Our survival-models were mapped as survival probability functions individually and then combined with fixed vital rates in a fitness metric model that, when mapped, predicted habitat productivity (productivity map). Our results demonstrate a suite of environmental and anthropogenic variables at multiple scales that were predictive of occurrence and survival. We created a source-sink map by overlaying our female summer occurrence map and productivity map to predict habitats contributing to population surpluses (source habitats) or deficits (sink habitat) and low-occurrence habitats on the landscape. The source-sink map predicted that of the Sage-Grouse habitat within the ARPA, 30% was primary source, 29% was secondary source, 4% was primary sink, 6% was secondary sink, and 31% was low occurrence. Our results provide evidence that energy development and avoidance of energy infrastructure were probably reducing the amount of source habitat within the ARPA landscape. Our source-sink map provides managers with a means of prioritizing habitats for conservation planning based on source and sink dynamics. The spatial identification of high value (i.e., primary source) as well as suboptimal (i.e., primary sink) habitats allows for informed energy development to minimize effects on local wildlife populations.

Brown recluse spider bites result in necrotic skin lesions for which there is no known antidote. Since venom toxins are proteins, a proteolytic enzyme like trypsin might be effective in reducing toxicity. The aim of this study was to conduct a randomized controlled trial of trypsin to treat brown recluse spider bites in guinea pigs. Subjects were 18 female guinea pigs. Anesthesia for injections was inhaled isoflurane. Analgesia was 0.05 mg/kg of buprenorphine twice a day as needed. Intervention was intradermal injection of 30 μg of brown recluse venom (Spider Pharm, Yarnell, AZ). Immediately after envenomation, subjects were randomized to two groups of nine: trypsin 10 μg in 1 mL normal saline and 1 mL of normal saline. The primary outcome was lesion area over a 10-day time period. Statistical analysis was performed with repeated measures ANOVA. Mean lesion area was smaller but not statistically different in the placebo group. Maximum lesion size occurred at day 4 in both groups, when lesion area was 76.1 ± 108.2 mm(2) in the placebo group and 149.7 ± 127.3 mm(2) in the treatment group. P value was 0.15 for placebo vs. treatment. This study did not establish a role for trypsin as a treatment for brown recluse spider bites in a guinea pig model.

Unlabelled: CONTEXT. Antivenom is expensive and not always available, so alternative treatments are being investigated. OBJECTIVE. The efficacy of trypsin or rosmarinic acid (RA) in treating Micrurus fulvius in a murine model is determined. MATERIALS AND METHODS., Design: randomized controlled blinded study., Subjects: Fifty mice (20-30 g). Study groups: Intraperitoneal injections of: 1) 2 mg/kg M. fulvius venom (approximately twice the LD50 for mice; n = 10); 2) 2 mg/kg M. fulvius venom incubated in vitro for 1 h prior to injection with RA at a 1:10 ratio (n = 17); 3) 2 mg/kg M. fulvius venom incubated in vitro for 1 h prior to injection with 1 mg of trypsin (n = 17); 4)1 mg trypsin IP without venom (n = 3); and 5) RA IP without venom (n = 3)., Main Outcome: time to toxicity (respiratory distress (< 25 breaths/min.), loss of spontaneous locomotor activity, or inability to upright self)., Statistical Analysis: Time to toxicity using Tukey-Kramer HSD; Survival to 4, 6, and 12 h using Chi-square analysis. RESULTS. Onset of toxicity: venom + saline, 120.3 + 64.4 min; venom + rosmarinic acid, 238.1 ± 139.2 min (p = 0.15 relative to venom + saline); venom + trypsin, 319.7 + 201.0 min (p = 0.007 relative to venom + saline). Venom + trypsin but not venom + RA survival to 4 h was significant compared to venom + saline (p = 0.023). Two mice in the venom + trypsin group and one mouse in the venom + RA group survived to 12 h. Mice receiving trypsin without venom or RA without venom survived to 12 h without toxicity. Discussion. This work suggests that trypsin and RA may have efficacy in treatment M. fulvius envenomation. CONCLUSION. In vitro neutralization of M. Fulvius venom by trypsin justifies progressing to an in vivo model in future studies.

A geographical information systems model that identifies regions of the United States of America (USA) susceptible to West Nile virus (WNV) transmission risk is presented. This system has previously been calibrated and tested in the western USA; in this paper we use datasets of WNV-killed birds from South Carolina and Connecticut to test the model in the eastern USA. Because their response to WNV infection is highly predictable, American crows were chosen as the primary source for model calibration and testing. Where crow data are absent, other birds are shown to be an effective substitute. Model results show that the same calibrated model demonstrated to work in the western USA has the same predictive ability in the eastern USA, allowing for a continental-scale evaluation of the transmission risk of WNV at a daily time step. The calibrated model is independent of mosquito species and requires inputs of only local maximum and minimum temperatures. Of benefit to the general public and vector control districts, the model predicts the onset of seasonal transmission risk, although it is less effective at identifying the end of the transmission risk season.