An exploratory examination of delay discounting in women and girls diagnosed with an eating disorder.

Those with eating disorders (EDs) characterized by purging behaviors tend to show more impulsivity than those diagnosed with restrictive eating, who tend to show more compulsivity. Impulsive choice (i.e. a type of impulsivity) is a common factor among eating disorders that is less understood. Delay discounting is a measure of choice impulsivity, examining the decrease in value of delayed outcomes. In this exploratory study, we examined associations between eating disorder type, age and delay discounting among patients at a residential ED treatment center (N = 178). Our findings showed that those diagnosed with bulimia nervosa had higher delay discounting (i.e. more impulsivity) at intake compared to anorexia nervosa, binge eating disorder, and other eating types but there were no significant differences. Those diagnosed with bulimia nervosa, as well as those with ARFID and unspecified ED showed a preference for delayed rewards at discharge, but there were no significant differences among ED types. Moderation analyses showed that age, ED type, nor the interaction did not significantly predict delay discounting at intake or discharge. To conclude, those with bulimia nervosa demonstrate less impulsive choice at discharge from a residential ED treatment center. However, additional research is needed given the variability of sample sizes in this study.

Scoping Review of Acceptance and Commitment Therapy for Obsessive-Compulsive Disorder in Iran.

Acceptance and commitment therapy (ACT) for obsessive-compulsive disorder (OCD) has been found efficacious in randomized clinical trials (RCTs), but the two widely known RCTs were conducted within the United States with predominantly White samples. Research that evaluates treatments like ACT for OCD outside the typical Western cultures is needed. The current scoping review summarizes the key characteristics and findings from 18 RCTs that evaluated ACT for OCD in Iran. These RCTs are largely unknown in the broader scientific literature despite representing the vast majority of ACT for OCD trials, in part because the majority are published in Persian. The preponderance of RCTs treated participants in groups, and most protocols did not include exposure exercises. Of 18 trials, 5 were single sex. Use of selective serotonin reuptake inhibitors (SSRIs) was common with all participants on stable doses at pretreatment in many of the trials. Methodological quality was low to medium. ACT was inconsistent against nontraditional comparison conditions, slightly favorable to empirically validated treatments, and favorable compared with the waitlist and SSRIs. The process of change data indicated that ACT increased the psychological flexibility more than cognitive behavior therapy or SSRIs. These results highlight that findings on ACT for OCD from Western populations replicate and generalize to individuals in Iran. These findings also offer insights gained from studying ACT in Iran and significantly expand the literature based on ACT for OCD that can be integrated into scholarship by all researchers.

Serial Mediation Analysis of Psychological Inflexibility and Daytime Insomnia Rumination in the Relationship Between Dysfunctional Beliefs About Sleep and Insomnia in College Students.

Emerging research suggests that psychological inflexibility may be a factor contributing to the development and maintenance of insomnia. However, less is known about the potential cognitive pathways that may explain this relationship. In this study, we investigated the serial mediating effects of psychological inflexibility and daytime insomnia-related rumination on the association between dysfunctional beliefs and attitudes about sleep (DBAS) and insomnia symptoms. The sample included 490 college students who underwent assessments at two time points over a 1-month period. The results of our mediational tests yielded significant indirect effects, supporting the prediction that psychological inflexibility and daytime insomnia rumination serially mediate the relationship between DBAS and insomnia. The study provides insights into potential mechanisms for insomnia, emphasizing the role of psychological inflexibility in perpetuating maladaptive cognitive processes associated with insomnia. Future researchers should explore other maladaptive responses to insomnia-related concerns and distress, such as worry and safety behaviors, and replicate findings in clinically elevated insomnia samples.

Bioelectric pharmacology of cancer: A systematic review of ion channel drugs affecting the cancer phenotype.

Cancer is a pernicious and pressing medical problem; moreover, it is a failure of multicellular morphogenesis that sheds much light on evolutionary developmental biology. Numerous classes of pharmacological agents have been considered as cancer therapeutics and evaluated as potential carcinogenic agents; however, these are spread throughout the primary literature. Here, we briefly review recent work on ion channel drugs as promising anti-cancer treatments and present a systematic review of the known cancer-relevant effects of 109 drugs targeting ion channels. The roles of ion channels in cancer are consistent with the importance of bioelectrical parameters in cell regulation and with the functions of bioelectric signaling in morphogenetic signals that act as cancer suppressors. We find that compounds that are well-known for having targets in the nervous system, such as voltage-gated ion channels, ligand-gated ion channels, proton pumps, and gap junctions are especially relevant to cancer. Our review suggests further opportunities for the repurposing of numerous promising candidates in the field of cancer electroceuticals.

Stress sharing as cognitive glue for collective intelligences: A computational model of stress as a coordinator for morphogenesis.

Individual cells have numerous competencies in physiological and metabolic spaces. However, multicellular collectives can reliably navigate anatomical morphospace towards much larger, reliable endpoints. Understanding the robustness and control properties of this process is critical for evolutionary developmental biology, bioengineering, and regenerative medicine. One mechanism that has been proposed for enabling individual cells to coordinate toward specific morphological outcomes is the sharing of stress (where stress is a physiological parameter that reflects the current amount of error in the context of a homeostatic loop). Here, we construct and analyze a multiscale agent-based model of morphogenesis in which we quantitatively examine the impact of stress sharing on the ability to reach target morphology. We found that stress sharing improves the morphogenetic efficiency of multicellular collectives; populations with stress sharing reached anatomical targets faster. Moreover, stress sharing influenced the future fate of distant cells in the multi-cellular collective, enhancing cells' movement and their radius of influence, consistent with the hypothesis that stress sharing works to increase cohesiveness of collectives. During development, anatomical goal states could not be inferred from observation of stress states, revealing the limitations of knowledge of goals by an extern observer outside the system itself. Taken together, our analyses support an important role for stress sharing in natural and engineered systems that seek robust large-scale behaviors to emerge from the activity of their competent components.

Self-Improvising Memory: A Perspective on Memories as Agential, Dynamically Reinterpreting Cognitive Glue.

Many studies on memory emphasize the material substrate and mechanisms by which data can be stored and reliably read out. Here, I focus on complementary aspects: the need for agents to dynamically reinterpret and modify memories to suit their ever-changing selves and environment. Using examples from developmental biology, evolution, and synthetic bioengineering, in addition to neuroscience, I propose that a perspective on memory as preserving salience, not fidelity, is applicable to many phenomena on scales from cells to societies. Continuous commitment to creative, adaptive confabulation, from the molecular to the behavioral levels, is the answer to the persistence paradox as it applies to individuals and whole lineages. I also speculate that a substrate-independent, processual view of life and mind suggests that memories, as patterns in the excitable medium of cognitive systems, could be seen as active agents in the sense-making process. I explore a view of life as a diverse set of embodied perspectives-nested agents who interpret each other's and their own past messages and actions as best as they can (polycomputation). This synthesis suggests unifying symmetries across scales and disciplines, which is of relevance to research programs in Diverse Intelligence and the engineering of novel embodied minds.

A computational framework to improve cross-platform implementation of transcriptomics signatures.

The emergence of next-generation sequencing technologies and computational advances have expanded our understanding of gene expression regulation (i.e., the transcriptome). This has also led to an increased interest in using transcriptomic biomarkers to improve disease diagnosis and stratification, to assess prognosis and predict the response to treatment. Significant progress in identifying transcriptomic signatures for various clinical needs has been made, with large discovery studies accounting for challenges such as patient variability, unwanted batch effects, and data complexities; however, obstacles related to the technical aspects of cross-platform implementation still hinder the successful integration of transcriptomic technologies into standard diagnostic workflows. In this article, we discuss the challenges associated with integrating transcriptomic signatures derived using high-throughput technologies (such as RNA-sequencing) into clinical diagnostic tools using nucleic acid amplification (NAA) techniques. The novelty of the proposed approach lies in our aim to embed constraints related to cross-platform implementation in the process of signature discovery. These constraints could include technical limitations of amplification platform and chemistry, the maximal number of targets imposed by the chosen multiplexing strategy, and the genomic context of identified RNA biomarkers. Finally, we propose to build a computational framework that would integrate these constraints in combination with existing statistical and machine learning models used for signature identification. We envision that this could accelerate the integration of RNA signatures discovered by high-throughput technologies into NAA-based approaches suitable for clinical applications.

Family Caregivers' Progress Toward Values Moderates the Associations between Behavioral Symptoms of Dementia, Caregiver Burden, and Depressive Symptoms.

Increasingly, dementia caregiver interventions are informed by acceptance-based approaches such as Acceptance and Commitment Therapy. These interventions promote psychological skills like psychological flexibility and value-based living. Less is known how these constructs interact within well-established caregiver stress processes. We examined a moderated mediation model (N = 161 dementia caregivers; PROCESS Procedure; SPSS Release 4.1), with BPSD frequency (Revised Memory and Behavior Problems Checklist) predicting depressive symptoms (10-item CES-D), mediated via caregiver burden (short Burden inventory). The moderator was the Values Questionnaire, and we controlled for gender, caregiver duration, age, income, and education. Results: revealed that the indirect effect of BPSD on depressive symptoms through caregiver burden was weakened through higher progress toward values (moderated mediation significant at p < .05). Committed action toward values signify caregivers' success at balancing care-related stress with other priorities. Interventions that build skills in values-based living have promise for caregivers, offering healthier ways to adjust to being a caregiver.

Genome-Wide Association Study Identifies Genes for Hair Growth and Patterning are Associated With Pilonidal Disease.

BACKGROUND: Pilonidal sinus disease is a highly morbid condition characterized by the formation of chronic sinus tracts throughout the sacrococcygeal region. Despite its commonality and strong association with family history, there is no prior investigation of genetic risk factors for pilonidal sinus disease. OBJECTIVE: To identify genetic risk factors for pilonidal sinus disease. DESIGN: Genome-wide association study. SETTINGS: The United Kingdom Biobank, FinnGen Biobank, and PennMedicine Biobank. PATIENTS: There were 772,072 participants. MAIN OUTCOME MEASURE: Genome-wide significant variants (p < 5x10 -8) were mapped to genes using physical distance and gene expression in skin. Genetic correlation between pilonidal sinus disease and morphometric, androgen-driven, and hair phenotypes was estimated with LD score regression. Finally, a genome-first approach to rare, predicted deleterious variants in hair shaft genes TCHH, PADI3, and TGM3 was conducted for association with pilonidal sinus disease via PennMedicine Biobank. RESULTS: Genome-wide association study comprised of 2,835 individuals with pilonidal sinus disease identified 5 genome-wide significant loci, prioritizing HDAC9, TBX15, WARS2, RP11-293M10.1, PRKAR1B, TWIST1, GPATCH2L, NEK9, and EIF2B2, as putative causal genes; several of these genes have known roles in balding and hair patterning. There was significant correlation between the genetic background of pilonidal sinus disease and that of the androgen-driven hair traits male pattern baldness and young age at first facial hair. In a candidate analysis of genes associated with syndromic hair disorders, rare coding variants in TCHH, a monogenic cause of uncombable hair syndrome, were associated with increased prevalence of pilonidal sinus disease (OR 4.81 [5% CI, 2.06-11.2]). LIMITATIONS: This study is limited to European ancestry. However, because there is a higher incidence of pilonidal sinus disease in men of European ancestry, this analysis is focused on the at-risk population. CONCLUSION: Genetic analysis of pilonidal sinus disease identified shared genetic architecture with hair biology and androgen-driven traits. As the first study investigating the genetic basis of pilonidal sinus disease, this provides biological insight into the long-appreciated connection between the disease state, male gender, and hair. See Video abstract.

Uptake of Same-Day Discharge for Patients Undergoing Robot-Assisted Radical Prostatectomy in the Michigan Urological Surgery Improvement Collaborative.

PURPOSE: Postoperative length of stay (LOS) after robot-assisted radical prostatectomy (RARP) is a potentially modifiable aspect of prostate cancer care. Our objective was to evaluate the use of same-day discharge (SDD) RARP and compare pre- and perioperative characteristics of these men with those who underwent hospitalization postoperatively. MATERIALS AND METHODS: Perioperative outcomes for patients undergoing RARP were evaluated from the Michigan Urological Surgery Improvement Collaborative (MUSIC) registry. Men were classified by hospital LOS: SDD, 1 day, and 2 days. Practice and surgeon-level variation of SDD and the change in SDD use over time were assessed. The primary outcome was 30-day readmission after RARP. RESULTS: We identified 10,249 men undergoing RARP in MUSIC from 2018 to 2022. Most patients had 1-day LOS (79.6%), with 2.8% undergoing SDD. The proportion of patients undergoing RARPs with SDD rose from 0.6% in 2018 to 1.2% in 2019 and 4.4% for 2020 to 2022. At least one SDD was performed in 12 of 28 MUSIC practices (42.9%) and by 52 of 138 urologists (37.7%). In multivariable analysis, odds of 30-day readmission were not significantly different between patients undergoing SDD and LOS 1 day (OR: 1.72, 95% CI: 0.92-3.22, P = .090). Limitations include retrospective, registry-based observational study with nonuniform utilization of SDD. CONCLUSIONS: Although more patients have undergone SDD after RARP beginning in 2018, rates across Michigan have remained < 5% annually. Importantly, patients undergoing SDD RARP did not experience significantly more readmissions compared to hospitalized patients. SDD appears safe and feasible for select patients who are motivated by this approach.

Self-Amputating and Interfusing Machines.

Biological organisms exhibit phenomenal adaptation through morphology-shifting mechanisms including self-amputation, regeneration, and collective behavior. For example, reptiles, crustaceans, and insects amputate their own appendages in response to threats. Temporary fusion between individuals enables collective behaviors, such as in ants that temporarily fuse to build bridges. The concept of morphological editing often involves the addition and subtraction of mass and can be linked to modular robotics, wherein synthetic body morphology may be revised by rearranging parts. This work describes a reversible cohesive interface made of thermoplastic elastomer that allows for strong attachment and easy detachment of distributed soft robot modules without direct human handling. The reversible joint boasts a modulus similar to materials commonly used in soft robotics, and can thus be distributed throughout soft robot bodies without introducing mechanical incongruities. To demonstrate utility, the reversible joint is implemented in two embodiments: a soft quadruped robot that self-amputates a limb when stuck, and a cluster of three soft-crawling robots that fuse to cross a land gap. This work points toward future robots capable of radical shape-shifting via changes in mass through autotomy and interfusion, as well as highlights the crucial role that interfacial stiffness change plays in autotomizable biological and artificial systems.

An Overview of Research on Acceptance and Commitment Therapy.

This review summarized recent systematic reviews and meta-analyses on randomized controlled trials evaluating acceptance and commitment therapy (ACT). Although the strength of evidence varies, overall there is plausible evidence for the efficacy of ACT for a wide range of areas including depression, anxiety disorders, obsessive-compulsive and related disorders, psychosis, substance use disorders, chronic pain, coping with chronic health conditions, obesity, stigma, and stress and burnout. ACT is also efficacious when delivered in digital self-help formats. Reviews of mediation research indicate ACT works through increasing psychological flexibility.

A pro-reparative bioelectronic device for controlled delivery of ions and biomolecules.

Wound healing is a complex physiological process that requires precise control and modulation of many parameters. Therapeutic ion and biomolecule delivery has the capability to regulate the wound healing process beneficially. However, achieving controlled delivery through a compact device with the ability to deliver multiple therapeutic species can be a challenge. Bioelectronic devices have emerged as a promising approach for therapeutic delivery. Here, we present a pro-reparative bioelectronic device designed to deliver ions and biomolecules for wound healing applications. The device incorporates ion pumps for the targeted delivery of H+ and zolmitriptan to the wound site. In vivo studies using a mouse model further validated the device's potential for modulating the wound environment via H+ delivery that decreased M1/M2 macrophage ratios. Overall, this bioelectronic ion pump demonstrates potential for accelerating wound healing via targeted and controlled delivery of therapeutic agents to wounds. Continued optimization and development of this device could not only lead to significant advancements in tissue repair and wound healing strategies but also reveal new physiological information about the dynamic wound environment.

Aging as a loss of morphostatic information: A developmental bioelectricity perspective.

Maintaining order at the tissue level is crucial throughout the lifespan, as failure can lead to cancer and an accumulation of molecular and cellular disorders. Perhaps, the most consistent and pervasive result of these failures is aging, which is characterized by the progressive loss of function and decline in the ability to maintain anatomical homeostasis and reproduce. This leads to organ malfunction, diseases, and ultimately death. The traditional understanding of aging is that it is caused by the accumulation of molecular and cellular damage. In this article, we propose a complementary view of aging from the perspective of endogenous bioelectricity which has not yet been integrated into aging research. We propose a view of aging as a morphostasis defect, a loss of biophysical prepattern information, encoding anatomical setpoints used for dynamic tissue and organ homeostasis. We hypothesize that this is specifically driven by abrogation of the endogenous bioelectric signaling that normally harnesses individual cell behaviors toward the creation and upkeep of complex multicellular structures in vivo. Herein, we first describe bioelectricity as the physiological software of life, and then identify and discuss the links between bioelectricity and life extension strategies and age-related diseases. We develop a bridge between aging and regeneration via bioelectric signaling that suggests a research program for healthful longevity via morphoceuticals. Finally, we discuss the broader implications of the homologies between development, aging, cancer and regeneration and how morphoceuticals can be developed for aging.

Unraveling the Enigma of Organismal Death: Insights, Implications, and Unexplored Frontiers.

Significant knowledge gaps exist regarding the responses of cells, tissues, and organs to organismal death. Examining the survival mechanisms influenced by metabolism and environment, this research has the potential to transform regenerative medicine, redefine legal death, and provide insights into life's physiological limits, paralleling inquiries in embryogenesis.

Electroceuticals: emerging applications beyond the nervous system and excitable tissues.

Electroceuticals have evolved beyond devices manipulating neuronal signaling for symptomatic treatment, becoming more precise and disease modulating and expanding beyond the nervous system. These advancements promise transformative applications in arthritis, cancer treatment, tissue regeneration, and more. Here, we discuss these recent advances and offer insights for future research.

Predictors of adherence to a publicly available self-guided digital mental health intervention.

Low adherence to self-guided digital mental health interventions (DMHIs) have raised concerns about their real-world effectiveness. Naturalistic data from self-guided DMHIs are often not available, hindering our ability to assess adherence among real-world users. This study aimed to analyze 3 years of user data from the public launch of an empirically supported 12-session self-guided DMHI, to assess overall program adherence rates and explore predictors of adherence. Data from 984 registered users were analyzed. Results showed that only 14.8% of users completed all 12 modules and 68.6% completed less than half of the modules. Users who were younger, had milder depression, had never seen a mental health provider, and who rejected signing-up for weekly program emails completed significantly more modules. Results add to concerns about the generalizability of controlled research on DMHIs due to lower adherence outside of research trials. This study highlights the potential of user data in identifying key factors that may be related to adherence. By examining adherence patterns among different sub-sets of users, we can pinpoint and focus on individuals who may adhere and benefit more from self-guided programs. Findings could also have implications for guiding intervention personalization for individuals who struggle to complete DMHIs.