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This article uses storytelling, poetry, and findings from a humanbecoming inquiry on sadness to explore a humanuniverse living experience involving change and loss., Competing Interests: Declaration of Conflicting InterestsThe author declared no potential conflicts of interest with respect to the authorship and/or publication of this review.

Background: Multiple endocrine neoplasia type 2B (MEN2B) is a rare autosomal dominant syndrome characterized by medullary carcinoma of the early thyroid, pheochromocytoma, and non-endocrine manifestations, such as marfanoid habits and other skeletal abnormalities as well as mucosal neuromas and ganglioneuromatosis of the gastrointestinal tract., Case Description: A 10-year-old male began follow-up at our service at 3 years of age through pediatric gastroenterology due to intestinal constipation. The mother also reported that the child had painless lesions on the tip of the tongue since birth with progressive worsening. The patient simultaneously began follow-up with pediatric endocrinology due to low gains in weight and height, between which only isolated low weight was found, and the onset of follow-up with the pediatric neurology team due to longstanding headache combined with vomiting, photophobia, and phonophobia as well as a specific reading and writing disorder. The patient was sent to clinical genetics. The child's karyotype was 46, XY (normal). Through a physical examination, the pediatric neurology team identified joint hypermobility, important muscle hypotrophy, gingival hypertrophy, and lipodystrophy. The patient was sent to neurogenetics, initiating a set of general laboratory exams for the investigation of the lipodystrophy and a panel of exams for lipodystrophy, neuropathy, and muscle hypotrophy as well as electroneuromyography. MEN2B due to genetic mutation was confirmed and the patient was sent to the pediatric endocrinology clinic for follow-up. Currently 10 years of age and again with the pediatric endocrinology team for the diagnosis of MEN2B, the investigation of pheochromocytoma and medullary thyroid cancer was initiated., Conclusions: An additional mutation occurs in most cases of MEN2B. The diagnosis is only established when the child or, in most cases, adolescent presents with medullary thyroid cancer in an advanced and even metastatic stage. However, non-endocrine manifestations, can lead to an early diagnosis and timely intervention. The diagnosis of MEN2B is made with the confirmation of the autosomal dominant genetic mutation or a mutation of the RET gene. In the absence of these mutations, the majority of clinical manifestations should be present., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-23-114/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

The following article uses storytelling, poetry, and findings from a humanbecoming inquiry on waiting to describe the arduous universal humanuniverse living experience of waiting., Competing Interests: Declaration of Conflicting InterestsThe author declared no potential conflicts of interest with respect to the authorship and/or publication of this review.

Background: Telephone triage is used to optimise patient flow in emergency primary healthcare. Poor communication can lead to misunderstandings and compromise patient safety. To improve quality, a comprehensive understanding of factors affecting communication in medical call centres in primary care is needed. The aim of this review was to identify such factors and to describe how they affect communication during telephone triage., Method: A mixed-method systematic review was performed. In April 2021 and June 2023, MEDLINE, Embase, CINAHL, and Web of Science were searched for original studies describing communication during telephone triage in primary care medical call centres handling all types of medical problems from an unselected population. All studies were screened by two authors, blinded to each other's decisions. Disagreements were resolved by a third author. A framework was created by the thematic synthesis of the qualitative data and later used to synthesise the quantitative data. By using convergent integrated synthesis, the qualitative and quantitative findings were integrated. The Mixed Methods Appraisal Tool was used to assess methodological limitations., Results: Out of 5087 studies identified in the search, 62 studies were included, comprising 40 qualitative, 16 quantitative and six mixed-method studies. Thirteen factors were identified and organised into four main themes: organisational factors, factors related to the operator, factors related to the caller and factors in the interaction. Organisational factors included availability, working conditions and decision support systems. Factors related to the operator were knowledge and experience, personal qualities and communication strategies. Factors related to the caller were individual differences and the presented medical problem. Factors in the interaction were faceless communication, connection between operator and caller, third-person caller and communication barriers. The factors seem interrelated, with organisational factors affecting all parts of the conversation, and the operator's communication in particular., Conclusion: Many factors affect the structure, content, and flow of the conversation. The operators influence the communication directly but rely on the organisation to create a working environment that facilitates good communication. The results are mainly supported by qualitative studies and further studies are needed to explore and substantiate the relevance and effect of individual factors., Systematic Review Registration: PROSPERO CRD42022298022., (© 2024. The Author(s).)

This article uses storytelling and poetry to emphasize the core concepts of taking a risk while highlighting the mystique of the Grand Canyon in Arizona., Competing Interests: Declaration of Conflicting InterestsThe author declared no potential conflicts of interest with respect to the authorship and/or publication of this review.

As an introduction to the inaugural Artistic Expression Column, the construct of artsciencing is briefly discussed and poetry is presented as an avenue of artsciencing., Competing Interests: Declaration of Conflicting InterestsThe author declared no potential conflicts of interest with respect to the authorship and/or publication of this review.

Although ribosomes are generally examined in aggregate, ribosomes can be heterogenous in composition. Evidence is accumulating that changes in ribosome composition may result in altered function, such that ribosome heterogeneity may provide a mechanism to regulate protein synthesis. Ribosome heterogeneity in the human pathogen Francisella tularensis results from incorporation of one of three homologs of bS21, a small ribosomal subunit protein demonstrated to regulate protein synthesis in other bacteria. Loss of one homolog, bS21-2, results in genome-wide post-transcriptional changes in protein abundance. This suggests that bS21-2 can, either directly or indirectly, lead to preferential translation of particular mRNAs. Here, we examine the potential of bS21-2 to function in a leader sequence-dependent manner and to function indirectly, via Hfq. We found that the 5´ untranslated region (UTR) of some bS21-2-responsive genes, including key virulence genes, is sufficient to alter translation in cells lacking bS21-2. We further identify features of a 5´ UTR that allow responsiveness to bS21-2. These include an imperfect Shine-Dalgarno sequence and a particular six nucleotide sequence. Our results are consistent with a model in which a bS21 homolog increases the efficiency of translation initiation through interactions with specific leader sequences. With respect to bS21-2 indirectly regulating translation via the RNA-binding protein Hfq, we found that Hfq controls transcript abundance rather than protein synthesis, impacting virulence gene expression via a distinct mechanism. Together, we determined that ribosome composition in F. tularensis regulates translation in a leader sequence-dependent manner, a regulatory mechanism which may be used in other bacteria. IMPORTANCE Ribosome heterogeneity is common in bacteria, and there is mounting evidence that ribosome composition plays a regulatory role in protein synthesis. However, mechanisms of ribosome-driven gene regulation are not well understood. In the human pathogen Francisella tularensis , which encodes multiple homologs for the ribosomal protein bS21, loss of one homolog impacts protein synthesis and virulence. Here, we explore the mechanism behind bS21-mediated changes in protein synthesis, finding that they can be linked to altered translation initiation and are dependent on specific sequences in the leaders of transcripts. Our data support a model in which ribosome composition regulates gene expression through translation, a strategy that may be conserved in diverse organisms with various sources of ribosome heterogeneity., Competing Interests: The authors declare no conflict of interest.

This article explores the concept of Surprisology and the humanuniverse living experience of surprise. Story is used to enhance understanding of a humanbecoming perspective of surprise.

This article explores several unique constructs of the humanbecoming paradigm including truth for the moment. A dialogue with nurse theorist Rosemarie Rizzo Parse completes this exploration.

This article highlights the findings of the 1998 humanbecoming inquiry considering tomorrow. The participants in this inquiry were women homeless in Chicago. Children's books, recent TV and newspaper articles focusing on the homeless in Pensacola, Florida, and various other humanbecoming inquiries involving homeless populations emphasize the importance of looking up and paying attention to what is occurring in humanuniverse so as to seize opportunities that present themselves with the emerging now.

This article is concerned with being present to what is emerging in the now moment. Theoretical perspectives from spirituality, psychology, western and eastern philosophy, the humanbecoming paradigm, and personal experiences of the author are presented in relation to the importance of focusing on NOW.

The humanbecoming concept of powering is explored in this article with the author describing her experiences with whitewater waves on the Missouri River in South Dakota. The third principle of humanbecoming along with four humanbecoming inquiries on feeling sad, feeling unsure, feeling disrespected, and living hope are also presented in examining the paradoxical processes involved in powering.

Background and Objectives: We conducted a multisite, pragmatic replication trial at 4 New England epilepsy centers to determine the effectiveness of Home-Based Self-Management and Cognitive Training Changes Lives (HOBSCOTCH) in a real-world setting and to assess feasibility of a virtual intervention., Methods: HOBSCOTCH is an 8-session intervention addressing cognitive impairment and quality of life (QoL) for people with epilepsy (PWE). Participants were recruited from epilepsy centers in 4 states and block-randomized into the following groups: in-person HOBSCOTCH (H-IP), virtual HOBSCOTCH (H-V), and waitlist control. Outcome measures were assessed for all groups at baseline, 3 months, and 6 months; intervention groups received long-term follow-up at 9 and 12 months., Results: A total of 108 participants were recruited, of whom 85 were included in this analysis (age at baseline 47.5 ± 11.5 years; 68% female). Participants completing the in-person intervention (H-IP) had a 12.4-point improvement in QoL score compared with controls ( p < 0.001). Pairwise comparisons found a 6.2-point treatment effect for subjective cognition in the H-IP group ( p < 0.001). There were no meaningful group differences in objective cognition or health care utilization at any time points and the treatment effect for QoL diminished by 6 months. The virtual intervention demonstrated feasibility but did not significantly improve outcomes compared with controls. Within-group analysis found improvements in QoL for both H-V and H-IP., Discussion: This study replicated the effectiveness of the HOBSCOTCH program in improving QoL for PWE. The study was conducted prior to the COVID-19 pandemic, but the distance-delivered intervention may be particularly well-suited for the current environment. Future research will explore modifications designed to improve the efficacy of H-V and the sustainability of HOBSCOTCH's treatment effect., Trial Registration Information: ClinicalTrials.gov (NCT02394509)., Classification of Evidence: This study provides Class III evidence that in-person HOBSCOTCH delivery improved subjective measures of cognition in persons with epilepsy., (© 2022 American Academy of Neurology.)

Objectives: To describe how an intervention to limit direct attendance in an emergency primary healthcare service affected the contacts to the clinic and the level of care given, and which factors were associated with a change from direct attendance to telephone contact., Design: Observational study., Setting: Seven Norwegian emergency primary healthcare services. The telephone triage operators are primarily registered nurses., Participants: Registered patient contacts to the services during 2007-2019., Interventions: In 2013, one of the seven services made an intervention to limit direct attendances to the emergency primary healthcare clinic. Through an advertisement in a local newspaper, the public was encouraged to call in advance. Patients who still attended directly, were encouraged to call in advance next time., Measures: We compared the proportions of direct attendance and telephone contact, and of consultation by a general practitioner and telephone consultation by an operator, before and after the intervention. We also compared the proportions of direct attendance regarding gender, age group, time of day and urgency level. Descriptive analyses and log binomial regression analyses were applied., Results: There were 1 105 019 contacts to the seven services during the study period. The average proportion of direct attendance decreased from 68.7% (95% CI 68.4% to 68.9%) to 23.4% (95% CI 23.2% to 23.6%) in the service that carried out the intervention. Telephone consultation by an operator increased from 11.7% (95% CI 11.5% to 11.8%) to 29.2% (95% CI 28.9% to 29.5%) and medical consultation by a general practitioner decreased from 78.3% (95% CI 78.1% to 78.5%) to 57.0% (95% CI 56.7% to 57.3%). The youngest and the oldest age group and women had the largest decrease in direct attendance, by -81%, -74% and -71%, respectively., Conclusion: The intervention influenced how the public contacted the service. Information campaigns on how to contact healthcare services should be implemented on a regular basis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The authors in this article will present storytelling through the lens of the humanbecoming family model. From this perspective, storytelling can be viewed as the following: (a) family storytelling as a mode of fostering personal and family becoming, (b) family storytelling as a confirming of family beliefs and values, and (c) family storytelling as a way of addressing issues of grief and loss. Selected literature is presented to highlight the essences, paradoxes, and processes of the humanbecoming family model.

In this article, the author explores wandering and wondering through the lens of educational theory, philosophy, psychology, complexity theory, and the humanbecoming paradigm. A fictional story concerning wanderers is presented to highlight the creative power of the imagination involved with wandering and wondering.

Background: People with psychogenic nonepileptic seizures (PNES) are at elevated risk of multiple psychiatric comorbidities. Current treatment gaps highlight the need for time-limited, distance-delivered interventions that can be cost-effectively delivered to patients with PNES. Project UPLIFT is a self-management program addressing mood problems in epilepsy that has not previously been adapted for PNES. The purpose of this study was to assess the feasibility and acceptability of UPLIFT for patients with PNES., Methods: Project UPLIFT was minimally adapted by a multidisciplinary research group at Dartmouth-Hitchcock Medical Center. Participants were recruited into a nonrandomized pilot study and were assessed at baseline, after completing the intervention, and at 1-month follow-up., Results: The intervention was adapted and delivered without additional modification. A total of eight participants enrolled in the trial, and six participated in the first session. All six participants who started UPLIFT completed the intervention, with a 98% attendance record across the eight sessions. At follow-up, 100% reported that UPLIFT provided useful tools for daily life. All participants continued using UPLIFT after completing the program, and 83% felt it helped with seizure management. Preliminary results provide proof-of-concept for future efficacy trials., Conclusion: This study provides initial support for the feasibility and acceptability of Project UPLIFT, minimally adapted for patients with PNES. As a time-limited program that can be distance-delivered to groups of patients, UPLIFT may be well-suited for the healthcare environment brought on by the COVID-19 pandemic., Competing Interests: Declaration of Competing Interest The study was funded by an internal grant within the Department of Neurology at Dartmouth-Hitchcock Medical Center. BCJ receives support as the Louis and Ruth Frank Chair of Neuroscience, Geisel School of Medicine at Dartmouth College, in addition to research support from Neuropace, Inc., NIH, the Defense Advanced Research Projects Agency, and CDC. No other financial disclosures were reported by the authors of this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: Use of Motivational Interviewing (MI) in education may improve medication-overuse headache (MOH) patients' ability to cope with pain. In a randomised controlled trial, we evaluated the effect of education focusing on behavioural change among MOH patients., Methods: Ninety-eight MOH patients were randomized (1:1) to standard treatment and 12-weeks of MI-based education versus standard treatment alone after detoxification. Outcome of interest was changes in coping strategies measured by the Coping Strategy Questionnaire at four- and nine months., Results: The educational program improved patients' perceived efficacy in the use of their coping strategies to control pain, both at four-and nine months follow-up (mean±SE): ∆:0.84 ± 0.35, 95% CI:0.16;1.52, p = 0.02 and: ∆: 0.90 ± 0.39, 95% CI:0.14;1.66, p = 0.02, respectively. No between-group differences were detected in the other coping subscales. Within the intervention group, the coping strategy subscales Catastrophizing, and Reinterpretation of pain sensation were significantly improved at nine months follow-up (p = 0.003 vs. p = 0.012, respectively). No changes were found in the control group., Conclusion: MI-based education focused on behavioural changes improved MOH patients' perceived efficacy in the use of their coping strategies to control pain., Practice Implications: Education based on MI could be valuable for MOH patients with respect to behavioural changes and perceived headache control., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: To compare temporal evolution of imaging features of coronavirus disease 2019 (COVID-19) and influenza in computed tomography and evaluate their predictive value for distinction., Methods: In this retrospective, multicenter study 179 CT examinations of 52 COVID-19 and 44 influenza critically ill patients were included. Lung involvement, main pattern (ground glass opacity, crazy paving, consolidation) and additional lung and chest findings were evaluated by two independent observers. Additional findings and clinical data were compared patient-wise. A decision tree analysis was performed to identify imaging features with predictive value in distinguishing both entities., Results: In contrast to influenza patients, lung involvement remains high in COVID-19 patients > 14 days after the diagnosis. The predominant pattern in COVID-19 evolves from ground glass at the beginning to consolidation in later disease. In influenza there is more consolidation at the beginning and overall less ground glass opacity (p = 0.002). Decision tree analysis yielded the following: Earlier in disease course, pleural effusion is a typical feature of influenza (p = 0.007) whereas ground glass opacities indicate COVID-19 (p = 0.04). In later disease, particularly more lung involvement (p < 0.001), but also less pleural (p = 0.005) and pericardial (p = 0.003) effusion favor COVID-19 over influenza. Regardless of time point, less lung involvement (p < 0.001), tree-in-bud (p = 0.002) and pericardial effusion (p = 0.01) make influenza more likely than COVID-19., Conclusions: This study identified differences in temporal evolution of imaging features between COVID-19 and influenza. These findings may help to distinguish both diseases in critically ill patients when laboratory findings are delayed or inconclusive., Competing Interests: The authors declare that they have no conflict of interests., (© 2022 The Authors.)

This article presents descriptions of mentoring from a philosophy of education and a humanbecoming mentoring model perspective. Descriptions of mentoring-protégé relationships experienced by the author are included using the humanbecoming paradigm as a guide in describing such experiences.

Rationale: Cognitive problems are common in adults with epilepsy and significantly affect their quality of life. HOBSCOTCH (HOme Based Self-management and COgnitive Training CHanges lives) was developed to teach problem-solving and compensatory memory strategies to these individuals. This study examined whether HOBSCOTCH is associated with improvement in specific aspects of subjective executive functions., Methods: Fifty-one adults, age 18-65, with epilepsy and subjective cognitive concerns were randomized to receive HOBSCOTCH (n = 31) or a care-as-usual control sample (n = 20). Participants completed the Behavior Rating Inventory of Executive Function-Adult version (BRIEF-A), as well as the Patient Health Questionnaire-9 (PHQ-9) to assess depression. Rates of elevated (i.e., T ≥ 65, impaired) BRIEF-A scores at baseline, as well as pre-post score changes for the BRIEF-A clinical scales were evaluated. Significance was set at α = 0.05, one-tailed, given our directional hypothesis., Results: At baseline, a considerable percentage of patients in the overall sample endorsed executive dysfunction on BRIEF-A scales: Inhibit = 28%, Shift = 51%, Emotional Control = 45%, Self-Monitor = 33%, Initiate = 35%, Working Memory = 88%, Plan/Organize = 45%, Task Monitor = 47%, Organization of Materials = 28%. Significant improvement was seen in mean T-scores for Inhibit, Shift, Initiate, and Working Memory in the treatment group, but only Working Memory improved in the control group. The control group endorsed worse task monitoring and organization of materials at baseline and follow-up. Change in depression was not observed for either group, and there was no association between changes in depression and BRIEF-A scores., Conclusions: A sizeable subset of adults with epilepsy reported experiencing executive dysfunction in their everyday lives, especially for working memory. HOBSCOTCH resulted in amelioration of subjective executive functioning independent of changes in mood., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Study Design: A retrospective review of medical records., Objective: The objective of this study was to examine probability of survival after 90- and 180-days after surgery, to document the rehabilitation needs, patients discharge destination, and whether discharge destination, re-admission, and probability of survival among patients with metastatic spinal cord compression (MSCC) were associated with potential risk factors., Setting: Copenhagen University Hospital, Rigshospitalet that serves a population of 2.8 million people from the Eastern part of Denmark, Faroe Islands, and Greenland., Methods: Adult (≥18 years) patients with MSCC undergoing surgery in 2017-2018 were included. Descriptive statistics were used to investigate the probability of survival after 90- and 180-days, rehabilitation needs documented in the patient's medical record, and discharge destination. Univariate logistic regression analyses were used to examine the associations between a priory defined potential risk factors for mortality and readmission., Results: Seventy-four medical records were included in final analysis. The probability of survival after 90- and 180-days post-surgery were 78% and 57%, respectively. Higher age was the only defined variable that was significantly associated with higher mortality. Ninety-three percent of the patient's medical records described rehabilitation potential, but only 44.6% of the patients were discharged with a rehabilitation plan. Seventy-three percent of the patients were discharged to their home. None had a specialized rehabilitation plan., Conclusion: Almost all patients diagnosed with MSCC have a rehabilitation potential described in their medical records. However, only half of these patients are discharged with a rehabilitation plan indicating an unmet potential for rehabilitation., (© 2021. The Author(s), under exclusive licence to International Spinal Cord Society.)

UV irradiation induces pyrimidine dimers that block polymerases and disrupt the replisome. Restoring replication depends on the recF pathway proteins which process and maintain the replication fork DNA to allow the lesion to be repaired before replication resumes. Oxidative DNA lesions, such as those induced by hydrogen peroxide (H2O2), are often thought to require similar processing events, yet far less is known about how cells process oxidative damage during replication. Here we show that replication is not disrupted by H2O2-induced DNA damage in vivo. Following an initial inhibition, replication resumes in the absence of either lesion removal or RecF-processing. Restoring DNA synthesis depends on the presence of manganese in the medium, which we show is required for replication, but not repair to occur. The results demonstrate that replication is enzymatically inactivated, rather than physically disrupted by H2O2-induced DNA damage; indicate that inactivation is likely caused by oxidation of an iron-dependent replication or replication-associated protein that requires manganese to restore activity and synthesis; and address a long standing paradox as to why oxidative glycosylase mutants are defective in repair, yet not hypersensitive to H2O2. The oxygen-sensitive pausing may represent an adaptation that prevents replication from occurring under potentially lethal or mutagenic conditions., (© The Author(s) 2021. Published by Oxford University Press on behalf of Genetics Society of America.)

Objectives: This study aimed to evaluate the effect of vagotomy, when associated with splenectomy, on adiposity and glucose homeostasis in Wistar rats., Methods: Rats were divided into 4 groups: vagotomized (VAG), splenectomized (SPL), VAG + SPL, and SHAM. Glucose tolerance tests were performed, and physical and biochemical parameters evaluated. Glucose-induced insulin secretion and protein expression (Glut2/glucokinase) were measured in isolated pancreatic islets. Pancreases were submitted to histological and immunohistochemical analyses, and vagus nerve neural activity was recorded., Results: The vagotomized group presented with reduced body weight, growth, and adiposity; high food intake; reduced plasma glucose and triglyceride levels; and insulin resistance. The association of SPL with the VAG surgery attenuated, or abolished, the effects of VAG and reduced glucose-induced insulin secretion and interleukin-1β area in β cells, in addition to lowering vagal activity., Conclusions: The absence of the spleen attenuated or blocked the effects of VAG on adiposity, triglycerides and glucose homeostasis, suggesting a synergistic effect of both on metabolism. The vagus nerve and spleen modulate the presence of interleukin-1β in β cells, possibly because of the reduction of glucose-induced insulin secretion, indicating a bidirectional flow between autonomous neural firing and the spleen, with repercussions for the endocrine pancreas., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Glioblastomas are aggressive primary brain cancers that recur as therapy-resistant tumors. Myeloid cells control glioblastoma malignancy, but their dynamics during disease progression remain poorly understood. Here, we employed single-cell RNA sequencing and CITE-seq to map the glioblastoma immune landscape in mouse tumors and in patients with newly diagnosed disease or recurrence. This revealed a large and diverse myeloid compartment, with dendritic cell and macrophage populations that were conserved across species and dynamic across disease stages. Tumor-associated macrophages (TAMs) consisted of microglia- or monocyte-derived populations, with both exhibiting additional heterogeneity, including subsets with conserved lipid and hypoxic signatures. Microglia- and monocyte-derived TAMs were self-renewing populations that competed for space and could be depleted via CSF1R blockade. Microglia-derived TAMs were predominant in newly diagnosed tumors, but were outnumbered by monocyte-derived TAMs following recurrence, especially in hypoxic tumor environments. Our results unravel the glioblastoma myeloid landscape and provide a framework for future therapeutic interventions.

The author here explores ideas on friendship from a philosophical, theological, sociological, and humanbecoming paradigm perspective. Personal experiences of the author provide examples of how friendship is important to an individual's living quality.

Cortical pathology contributes to chronic cognitive impairment of patients suffering from the neuroinflammatory disease multiple sclerosis (MS). How such gray matter inflammation affects neuronal structure and function is not well understood. In the present study, we use functional and structural in vivo imaging in a mouse model of cortical MS to demonstrate that bouts of cortical inflammation disrupt cortical circuit activity coincident with a widespread, but transient, loss of dendritic spines. Spines destined for removal show local calcium accumulations and are subsequently removed by invading macrophages or activated microglia. Targeting phagocyte activation with a new antagonist of the colony-stimulating factor 1 receptor prevents cortical synapse loss. Overall, our study identifies synapse loss as a key pathological feature of inflammatory gray matter lesions that is amenable to immunomodulatory therapy.

The author in this article explores seven day-to-day living experiences that expand understanding of the humanbecoming concept of fortifying wisdom. Poetry is used to enhance understanding of the seven living experiences of (a) the use of words, (b) the experience of the body, (c) love, (d) compassion, (e) faith, (f) hope, and (g) forgiveness.

This article describes some of the changes occurring with community in the advent of the COVID-19 pandemic. The humanbecoming community change model along with other views on community are presented to address some of the living quality questions and challenges of a community in flux.

In this article, the author examines fragility and vitality as it relates to the COVID-19 pandemic. Fear and courage are also explored from a humanbecoming paradigm perspective as well as from philosophical perspectives. Humanbecoming inquiries related to these topics are presented along with personal experiences of the author.

Background/aim: We conducted a randomized controlled trial to investigate whether minimally access spine surgery (MASS) is less morbid than open surgery (OS) in patients with metastatic spinal cord compression (MSCC)., Patients and Methods: A total of 49 MSCC patients were included in the trial. The outcome measures were bleeding (L), operation time (min), re-operations and prolonged wound healing., Results: The median age was 67 years (range=42-85 years) and 40% were men. The peri-operative blood loss in the MASS-group was significantly lower than that in the OS-group; 0.175L vs. 0.500L, (p=0.002). The median operation time for MASS was 142 min (range=72-203 min) vs. 103 (range=59-435 min) for OS (p=0.001). There was no significant difference between the two groups concerning revision surgery or delayed wound healing., Conclusion: The MASS technique in MSCC patients is associated with less blood loss, but a longer operation time when compared to the OS technique., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

This article explores creativity and innovation through the lens of dispositional realism, a psycho-socio-cultural perspective, a Japanese fable, and the humanbecoming paradigm perspective. New ideas are presented on the understanding of creativity and innovation, feeling overwhelmed, suffering, and living dignity.

Rationale: Cognitive impairment is one of the most common complaints for persons with epilepsy (PWE). These impairments are not only associated with seizures, but are also regularly reported as adverse effects of antiepileptic drugs (AEDs). Previous studies have examined cognitive effects of both AED monotherapy and polytherapy, yet there is limited research on these differences with respect to both subjective and objective cognition. The current study uses data from previous research conducted by the Centers for Disease Control and Prevention (CDC)-sponsored Managing Epilepsy Well (MEW) Network collaborative. We used three distinct archival datasets from the following: (1) the HOBSCOTCH efficacy trial at Dartmouth-Hitchcock Medical Center (HOB-1), (2) the multisite replication trial (HOB-2), and (3) epilepsy self-management research conducted at the NYU School of Medicine., Methods: This retrospective analysis combined baseline data from three datasets to determine how the number of AEDs and the type of AEDs were associated with subjective (patient-reported) and objective (examiner-assessed) cognition. Subjective cognition was captured using the cognitive subscale of the Quality of Life in Epilepsy Inventory (QOLIE-31) in all three datasets (n = 224), while objective cognition was measured using the Repeated Battery for the Assessment of Neuropsychological Status (RBANS) in the HOB-1 dataset (n = 65) and the Brief Test of Adult Cognition by Telephone (BTACT) in the HOB-2 dataset (n = 91). Multivariable linear regression was utilized for our initial assessments, followed by propensity score matching to provide stronger control of covariates. Matching was based on significantly different covariates, such as education, depression, and history of prior epilepsy surgery. Nonparametric statistical tests were utilized to compare these matched subjects., Results: Subjective cognitive impairment was significantly worse among individuals on polytherapy (2 + AEDs) compared with those on monotherapy (1 AED) (adjusted p  =  0.041). These findings were consistent with our propensity score matched comparison of monotherapy and polytherapy, which indicated that polytherapy was associated with worse overall subjective cognition (adjusted p = 0.01), in addition to impairments on the RBANS (Total score p = 0.05) and specific subdomains of the BTACT (Episodic Verbal Memory p < 0.01, Working Memory p < 0.01, Processing Speed p < 0.01). Interestingly, older generation AEDs were associated with better language performance than newer generation and combined generation AED therapy (RBANS Language p = 0.03). These language-specific findings remained significant after controlling for the effects of topiramate and zonisamide (p = 0.04)., Conclusions: A greater number of AEDs is significantly and negatively associated with subjective and objective cognition in PWE, and is in line with previous research. Antiepileptic drug type did not, in itself, appear to be associated with subjective cognition. Our findings suggest that ineffective AEDs should be replaced, rather than introducing additional AEDs to a treatment regimen. Further, while subjective and objective cognition assessments were both sensitive at detecting differences based on AED status, the neuropsychological objective subdomains offer additional and specific insights into how cognition is impaired with AEDs., Competing Interests: Declaration of competing interest On behalf of all the authors, the corresponding author states that there is no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Freedom, one of the four postulates of the humanbecoming paradigm, is the focus of this article. Freedom is explored from a humanbecoming perspective and from the existential/phenomenological perspectives of Heidegger and Sartre.

In this article, the author describes two differing perspectives on paradox: the humanbecoming paradigm perspective and the management/organizational theory perspective. Examples of paradoxes from these two differing views are presented.

Mystery, one of the four postulates of the humanbecoming paradigm, is the focus of this article. The muteness, the transformative power, and the everyday-ness of mystery are discussed. How mystery permeates the three principles of humanbecoming is also explored.

The author in this article explores the humanbecoming paradigm postulate of illimitability as unbounded coming to know. Patterns of constructing knowledge, conversation theory, improvisation pedagogy, children's literature, the humanbecoming teaching-learning model, and personal teaching-learning experiences of the author are presented to expand awareness of the unbounded knowing of illimitability.

Parse's humanbecoming concept inventing model provided a unique method to conduct a group concept inventing of the humanuniverse living experience of hiding. Several insights related to conducting a group concept inventing project are identified along with an ingenuous proclamation for hiding.

The authors of this article present three theoretical models of mentoring informing nursing as well as other disciplines. How these models intersect to expand understanding of the evolution of the role of mentoring in nursing is discussed.

The author in this article explores the humanbecoming dignity tenet of shame. Shame is examined through an extensive literature review, through storytelling, and through surveying humanbecoming inquiries of sadness, feeling fear, feeling overwhelmed, and feeling disrespected.

Background and Purpose: Epilepsy is a chronic neurological disease that represents a tremendous burden on both patients and society in general. Studies have addressed how demographic variables, socioeconomic variables, and psychological comorbidity are related to the quality of life (QOL) of people with epilepsy (PWE). However, there has been less focus on how these factors may differ between patients who exhibit varying degrees of seizure control. This study utilized data from the Managing Epilepsy Well (MEW) Network of the Centers for Disease Control and Prevention with the aim of elucidating differences in demographic variables, depression, and QOL between adult PWE., Methods: Demographic variables, depression, and QOL were compared between PWE who experience clinically relevant differences in seizure occurrence., Results: Gender, ethnicity, race, education, income, and relationship status did not differ significantly between the seizure-frequency categories (p>0.05). People with worse seizure control were significantly younger (p=0.039), more depressed (as assessed using the Patient Health Questionnaire) (p=0.036), and had lower QOL (as determined using the 10-item Quality of Life in Epilepsy for Adults scale) (p<0.001)., Conclusions: The present results underscore the importance of early screening, detection, and treatment of depression, since these factors relate to both seizure occurrence and QOL in PWE., Competing Interests: The authors have no financial conflicts of interest., (Copyright © 2018 Korean Neurological Association.)

The following story is an introduction to an interesting exploration of the concept of shame, providing new insights into this important notion through the humanbecoming theoretical process of concept inventing.

Introduction: As the primary treatment of patients with severe trauma continues to improve, increasing interest has been directed towards long-term survival and Health Related Quality of Life (HRQoL). In trauma patients, there are few studies describing long-term outcome using tools specifically directed at HRQoL., Hypothesis: HRQoL measured with EQ-5D is significantly reduced compared to the Danish norm score 15 years after severe injury., Materials and Methods: All patients more than 18 years of age, admitted to a level 1 trauma center from March 1996 to September 1997 were prospectively included and scored with Injury Severity Score (ISS). Survival status was recorded in May 2012 and EQ-5D questionnaires were sent out., Results: 95 of the original 154 trauma patients were eligible for participation. The response rate was 66%. The average EQ-5D index score in the trauma population was significantly reduced compared to the index score in the Danish norm population (P=0.00, one-sample t-test). In addition, ISS is associated with HRQoL and ISS≥16 predicts poorer HRQoL., Conclusion: EQ-5D is significantly reduced 15years after severe trauma High ISS was associated with low HRQoL. Knowledge of the distribution and predictors of long-term disability can be used to develop more efficient prevention policies and to improve trauma care in general., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Suffering, as a universal humanuniverse living experience, was explored utilizing the Parsesciencing mode of inquiry. Ten Lakota historians engaged in discussion to answer the question, "What is your experience of suffering?" The discovery revealed the discerning extant moment of suffering as follows: Suffering is burdening anguish amid uplifting aspirations surfacing in persevering with divergent encounters.

Purpose: The Tokuhashi revised score from 2005 (TR2005) is the most recommended prognostic scoring system in patients with metastatic spinal cord compression (MSCC). However, recent studies have questioned its prognostic ability and the need for a new revision has been proposed. We aimed to assess whether a revision of the TR2005 can improve the prognostic ability of the scoring system., Methods: In 2011 and 2012, a total of 1143 consecutive patients admitted with MSCC were prospectively included in a 2011 and a 2012 cohort. For the patients admitted in 2011 (n = 544), the components of the TR2005 including primary cancer diagnosis were analyzed regarding the prognostic ability. Based on these findings, a revision of the TR2005 score was defined as the Tokuhashi revised score 2017 (TR2017). The prognostic abilities of the TR2005 and the TR2017 were compared by Kaplan Meyer (KM) curves, and receiver-operating characteristics' (ROC) analysis was compared in a cohort of patients admitted in 2012 (n = 599)., Results: KM curves and ROC analysis showed that the TR2017 had better prognostic ability compared to the TR2005. The ROC areas were as follows: <6-months survival, TR2017 = 0.71 and TR2005 = 0.65, and p = 0.003; for ≥6-month survival, TR2017 = 0.71 and TR2005 = 0.65, and p = 0.003; for ≥12-month survival TR2017 = 0.72 and TR2005 = 0.67, and p = 0.0015., Conclusions: The TR2017 can improve the prognostic ability of the TR2005 in patients with MSCC. This could affect the preoperative evaluation of patients suffering from MSCC.

The author in this article explores theoretical perspectives on the humanbecoming ethical tenet of betrayal. Perspectives on betrayal include betrayal as a breach of promise, a betrayal continuum, betrayal as incidental and intentional, betrayal as moral injury, betrayal trauma, and the humanbecoming perspective of betrayal linked to feeling disappointed.

The authors in this article present the humanbecoming ethical tenets of human dignity: reverence, awe, betrayal, and shame. These four ethical tenets of human dignity are examined from a historical perspective, exploring how Rosemarie Rizzo Parse has conceptualized these ethical tenets with added descriptions from other scholars, and how Florence Nightingale lived human dignity as the founder of modern nursing.

The author in this article identifies two liberating discoveries that foster human flourishing: the potential of new knowledge and the importance of living gratitude. These two liberating discoveries are explored from the humanbecoming perspective and cite important inquiries that expand understanding of the phenomena of new knowledge and feeling grateful.

Leaf-cutter ants cultivate and feed on the mutualistic fungus, Leucoagaricus gongylophorus, which is threatened by parasitic fungi of the genus Escovopsis. The mechanism of Escovopsis parasitism is poorly understood. Here, we assessed the nature of the antagonism of different Escovopsis species against its host. We also evaluated the potential antagonism of Escovopsioides, a recently described fungal genus from the attine ant environment whose role in the colonies of these insects is unknown. We performed dual-culture assays to assess the interactions between L. gongylophorus and both fungi. We also evaluated the antifungal activity of compounds secreted by the latter on L. gongylophorus growth using crude extracts of Escovopsis spp. and Escovopsioides nivea obtained either in (1) absence or (2) presence of the mutualistic fungus. The physical interaction between these fungi and the mutualistic fungus was examined under scanning electron microscopy (SEM). Escovopsis spp. and E. nivea negatively affected the growth of L. gongylophorus, which was also significantly inhibited by both types of crude extract. These results indicate that Escovopsis spp. and E. nivea produce antifungal metabolites against the mutualistic fungus. SEM showed that Escovopsis spp. and E. nivea maintained physical contact with the mutualistic fungus, though no specialised structures related to mycoparasitism were observed. These results showed that Escovopsis is a destructive mycoparasite that needs physical contact for the death of the mutualistic fungus to occur. Also, our findings suggest that E. nivea is an antagonist of the ant fungal cultivar.