Engineering Virtuous health habits using Emotion and Neurocognition: Flexibility for Lifestyle Optimization and Weight management (EVEN FLOW)
Creator:
Whitson, Heather E., Merwin, Rhonda M., Strauman, Timothy J., O’Hayer, C. Virginia, and Smith, Patrick J.
Date of publication:
2023
Abstract Tesim:
Interventions to preserve functional independence in older adults are critically needed to optimize ‘successful aging’ among the large and increasing population of older adults in the United States. For most aging adults, the management of chronic diseases is the most common and impactful risk factor for loss of functional independence. Chronic disease management inherently involves the learning and adaptation of new behaviors, such as adopting or modifying physical activity habits and managing weight. Despite the importance of chronic disease management in older adults, vanishingly few individuals optimally manage their health behavior in the service of chronic disease stabilization to preserve functional independence. Contemporary conceptual models of chronic disease management and health habit theory suggest that this lack of optimal management may result from an underappreciated distinction within the health behavior literature: the behavioral domains critical for initiation of new behaviors (Initiation Phase) are largely distinct from those that facilitate their maintenance (Maintenance Phase). Psychological factors, particularly experiential acceptance and trait levels of openness are critical to engagement with new health behaviors, willingness to make difficult lifestyle changes, and the ability to tolerate aversive affective responses in the process. Cognitive factors, particularly executive function, are critical to learning new skills, using them effectively across different areas of life and contextual demands, and updating of skills to facilitate behavioral maintenance. Emerging data therefore suggests that individuals with greater executive function are better able to sustain behavior changes, which in turn protects against cognitive decline. In addition, social and structural supports of behavior change serve a critical buffering role across phases of behavior change. The present review attempts to address these gaps by proposing a novel biobehavioral intervention framework that incorporates both individual-level and social support system-level variables for the purpose of treatment tailoring. Our intervention framework triangulates on the central importance of self-regulatory functioning, proposing that both cognitive and psychological mechanisms ultimately influence an individuals’ ability to engage in different aspects of self-management (individual level) in the service of maintaining independence. Importantly, the proposed linkages of cognitive and affective functioning align with emerging individual difference frameworks, suggesting that lower levels of cognitive and/or psychological flexibility represent an intermediate phenotype of risk. Individuals exhibiting self-regulatory lapses either due to the inability to regulate their emotional responses or due to the presence of executive functioning impairments are therefore the most likely to require assistance to preserve functional independence. In addition, these vulnerabilities will be more easily observable for individuals requiring greater complexity of self-management behavioral demands (e.g. complexity of medication regimen) and/or with lesser social support. Our proposed framework also intuits several distinct intervention pathways based on the profile of self-regulatory behaviors: we propose that individuals with intact affect regulation and impaired executive function will preferentially respond to ‘top-down’ training approaches (e.g., strategy and process work). Individuals with intact executive function and impaired affect regulation will respond to ‘bottom-up’ approaches (e.g., graded exposure). And individuals with impairments in both may require treatments targeting caregiving or structural supports, particularly in the context of elevated behavioral demands.
Resource type:
Article
Affiliation Label Tesim:
Department of Psychiatry
DOI:
https://doi.org/10.17615/9xhn-r856
Edition:
Publisher
Identifier:
https://doi.org/10.3389/fnagi.2023.1256430
ISSN:
1663-4365
Journal Title:
Frontiers in Aging Neuroscience
Journal Volume:
15
Keyword:
self-regulation and self-systems theory, psychological flexibility, executive functioning, self-management, treatment tailoring, and personality
Language Label:
English
License Label:
Attribution 4.0 International
Other Affiliation:
Duke University Medical Center, Duke University, Thomas Jefferson University, and
Person:
Whitson, Heather E., Merwin, Rhonda M., Strauman, Timothy J., O’Hayer, C. Virginia, and Smith, Patrick J.
Empowering stroke survivors beyond inpatient rehabilitation: the STRIDE program
Creator:
Lewek, Michael D., Fitzgerald, Ryan, Marquie, Maureen, Cassidy, Jessica M., Vaughn, Rachel M., Morrison, Blaise, Trei, Anna Claire, Geib, Anna, and Baratta, John M.
Date of publication:
2023
Abstract Tesim:
Objective The timeframe from hospital discharge to the commencement of outpatient therapies represents a crucial yet often overlooked period in post-stroke recovery. We designed an eight-week post-stroke management program (STRIDE, Stroke Management Training and Inpatient Rehabilitation Discharge Education) targeting individuals discharging from an inpatient rehabilitation facility to home. The primary aims of this pilot study were to determine STRIDE feasibility and participant engagement. Methods Participants with first or recurrent stroke were enrolled. Each week, participants monitored and recorded their daily activity, completed a 15-min educational module and quiz, and partook in weekly and biweekly communication with a fellow participant and STRIDE coordinator, respectively. Feasibility was evaluated by successful initiation of STRIDE and enrollment of the target population. We also assessed participant adherence and conducted semi-structured exit interviews. Results Of the 99 individuals screened, 20 individuals were enrolled (7 females, 28.6 ± 15.7 days post-stroke). Several participants were unable to begin the program (n = 6) or complete the program (n = 4). Overall, participants completing at least 1 week of STRIDE (n = 14) demonstrated adherence with education module and quiz completion and communication with the STRIDE coordinator. Participant feedback from interviews was largely positive, underscoring the value of STRIDE during early post-stroke recovery. Conclusions These findings support the feasibility of an initiated multi-faceted stroke management program. Participant dropout was a limitation and serves as a consideration when designing future iterations of STRIDE. With the long-term goal of promoting autonomy and investment in one's continued recovery beyond the inpatient setting, STRIDE bridges the transition from hospital to home.
Resource type:
Article
Affiliation Label Tesim:
Department of Health Sciences and Department of Physical Medicine and Rehabilitation
DOI:
https://doi.org/10.17615/6b7c-v628
Edition:
Publisher
Identifier:
https://doi.org/10.3389/fstro.2023.1281703
ISSN:
2813-3056
Journal Title:
Frontiers in Stroke
Journal Volume:
2
Keyword:
rehabilitation, education, stroke, discharge, and management
Language Label:
English
License Label:
Attribution 4.0 International
Other Affiliation:
Person:
Lewek, Michael D., Fitzgerald, Ryan, Marquie, Maureen, Cassidy, Jessica M., Vaughn, Rachel M., Morrison, Blaise, Trei, Anna Claire, Geib, Anna, and Baratta, John M.
Competing risks modeling of length of hospital stay enhances risk-stratification of patient care: application to under-five children hospitalized in Malawi
Creator:
Zulu, Madalitso, Chinkhumba, Jobiba, Mvalo, Tisungane, Stanley, Christopher C., Phiri, Vincent S., Msuku, Harrison, Mathanga, Don P., and Kazembe, Lawrence N.
Date of publication:
2023
Abstract Tesim:
Introduction Length of hospital stay (LOS), defined as the time from inpatient admission to discharge, death, referral, or abscondment, is one of the key indicators of quality in patient care. Reduced LOS lowers health care expenditure and minimizes the chance of in-hospital acquired infections. Conventional methods for estimating LOS such as the Kaplan-Meier survival curve and the Cox proportional hazards regression for time to discharge cannot account for competing risks such as death, referral, and abscondment. This study applied competing risk methods to investigate factors important for risk-stratifying patients based on LOS in order to enhance patient care. Methods This study analyzed data from ongoing safety surveillance of the malaria vaccine implementation program in Malawi's four district hospitals of Balaka, Machinga, Mchinji, and Ntchisi. Children aged 1–59 months who were hospitalized (spending at least one night in hospital) with a medical illness were consecutively enrolled between 1 November 2019 and 31 July 2021. Sub-distribution-hazard (SDH) ratios for the cumulative incidence of discharge were estimated using the Fine-Gray competing risk model. Results Among the 15,463 children hospitalized, 8,607 (55.7%) were male and 6,856 (44.3%) were female. The median age was 22 months [interquartile range (IQR): 12–33 months]. The cumulative incidence of discharge was 40% lower among HIV-positive children compared to HIV-negative (sub-distribution-hazard ratio [SDHR]: 0.60; [95% CI: 0.46–0.76]; P < 0.001); lower among children with severe and cerebral malaria [SDHR: 0.94; (95% CI: 0.86–0.97); P = 0.04], sepsis or septicemia [SDHR: 0.90; (95% CI: 0.82–0.98); P = 0.027], severe anemia related to malaria [SDHR: 0.54; (95% CI: 0.48–0.61); P < 0.001], and meningitis [SDHR: 0.18; (95% CI: 0.09–0.37); P < 0.001] when compared to non-severe malaria; and also 39% lower among malnourished children compared to those that were well-nourished [SDHR: 0.61; (95% CI: 0.55–0.68); P < 0.001]. Conclusions This study applied the Fine-Gray competing risk approach to more accurately model LOS as the time to discharge when there were significant rates of in-hospital mortality, referrals, and abscondment. Patient care can be enhanced by risk-stratifying by LOS based on children's age, HIV status, diagnosis, and nutritional status.
, Kamuzu University of Health Sciences, and University of Namibia
Person:
Zulu, Madalitso, Chinkhumba, Jobiba, Mvalo, Tisungane, Stanley, Christopher C., Phiri, Vincent S., Msuku, Harrison, Mathanga, Don P., and Kazembe, Lawrence N.
Subordinate Effect of -21M HLA-B Dimorphism on NK Cell Repertoire Diversity and Function in HIV-1 Infected Individuals of African Origin
Creator:
Peppa, D., Cubero, E.M., Haynes, B.F., Cohen, M.S., Ogbe, A., Pedroza-Pacheco, I., and Borrow, P.
Date of publication:
2020
Abstract Tesim:
Natural Killer (NK) cells play an important role in antiviral defense and their potent effector function identifies them as key candidates for immunotherapeutic interventions in chronic viral infections. Their remarkable functional agility is achieved by virtue of a wide array of germline-encoded inhibitory and activating receptors ensuring a self-tolerant and tunable repertoire. NK cell diversity is generated by a combination of factors including genetic determinants and infections/environmental factors, which together shape the NK cell pool and functional potential. Recently a genetic polymorphism at position -21 of HLA-B, which influences the supply of HLA-E binding peptides and availability of HLA-E for recognition by the inhibitory NK cell receptor NKG2A, was shown to have a marked influence on NK cell functionality in healthy human cytomegalovirus (HCMV) seronegative Caucasian individuals. In this study, -21 methionine (M)-expressing alleles supplying HLA-E binding peptides were largely poor ligands for inhibitory killer immunoglobulin-like receptors (KIRs), and a bias to NKG2A-mediated education of functionally-potent NK cells was observed. Here, we investigated the effect of this polymorphism on the phenotype and functional capacity of peripheral blood NK cells in a cohort of 36 African individuals with human immunodeficiency virus type 1 (HIV-1)/HCMV co-infection. A similarly profound influence of dimorphism at position -21 of HLA-B on NK cells was not evident in these subjects. They predominantly expressed African specific HLA-B and -C alleles that contribute a distinct supply of NKG2A and KIR ligands, and these genetic differences were compounded by the marked effect of HIV-1/HCMV co-infection on NK cell differentiation. Together, these factors resulted in a lack of correlation of the HLA-B -21 polymorphism with surface abundance of HLA-E and loss of the NK cell functional advantage in subjects with -21M HLA-B alleles. Instead, our data suggest that during HIV/HCMV co-infection exposure of NK cells to an environment that displays altered HLA-E ligands drives adaptive NKG2C+ NK cell expansions influencing effector responses. Increased efforts to understand how NK cells are functionally calibrated to self-HLA during chronic viral infections will pave the way to developing targeted therapeutic interventions to overcome the current barriers to enhancing immune-based antiviral control.
Resource type:
Article
Affiliation Label Tesim:
School of Medicine
DOI:
https://doi.org/10.17615/3m3b-3h28
Edition:
Publisher
Identifier:
https://doi.org/10.3389/fimmu.2020.00156
ISSN:
1664-3224
Journal Title:
Frontiers in Immunology
Journal Volume:
11
Keyword:
HLA-C, HCMV, HIV-1, HLA-B, and Natural Killer cells
Language Label:
English
License Label:
Attribution 4.0 International
ORCID:
Other Affiliation:
University of Oxford, Duke Human Vaccine Institute, and
Person:
Peppa, D., Cubero, E.M., Haynes, B.F., Cohen, M.S., Ogbe, A., Pedroza-Pacheco, I., and Borrow, P.
Tree representations of brain structural connectivity via persistent homology
Creator:
Li, Didong, Zhang, Zhengwu, Dunson, David, and Nguyen, Phuc
Date of publication:
2023
Abstract Tesim:
The brain structural connectome is generated by a collection of white matter fiber bundles constructed from diffusion weighted MRI (dMRI), acting as highways for neural activity. There has been abundant interest in studying how the structural connectome varies across individuals in relation to their traits, ranging from age and gender to neuropsychiatric outcomes. After applying tractography to dMRI to get white matter fiber bundles, a key question is how to represent the brain connectome to facilitate statistical analyses relating connectomes to traits. The current standard divides the brain into regions of interest (ROIs), and then relies on an adjacency matrix (AM) representation. Each cell in the AM is a measure of connectivity, e.g., number of fiber curves, between a pair of ROIs. Although the AM representation is intuitive, a disadvantage is the high-dimensionality due to the large number of cells in the matrix. This article proposes a simpler tree representation of the brain connectome, which is motivated by ideas in computational topology and takes topological and biological information on the cortical surface into consideration. We demonstrate that our tree representation preserves useful information and interpretability, while reducing dimensionality to improve statistical and computational efficiency. Applications to data from the Human Connectome Project (HCP) are considered and code is provided for reproducing our analyses.
Resource type:
Article
Affiliation Label Tesim:
Department of Biostatistics and Department of Statistics and Operations Research
DOI:
https://doi.org/10.17615/y9qh-6m05
Edition:
Publisher
Identifier:
https://dx.doi.org/10.3389/fnins.2023.1200373
ISSN:
1662-453X
Journal Title:
Frontiers in Neuroscience
Journal Volume:
17
Keyword:
adjacency matrix, tree, persistent homology, structural connectivity, and brain connectome
Language Label:
English
License Label:
Attribution 4.0 International
ORCID:
Other Affiliation:
and Duke University
Person:
Li, Didong, Zhang, Zhengwu, Dunson, David, and Nguyen, Phuc
The G protein biased serotonin 5-HT2A receptor agonist lisuride exerts anti-depressant drug-like activities in mice
Creator:
Pogorelov, Vladimir M., Rodriguiz, Ramona M., Wetsel, William C., and Roth, Bryan L.
Date of publication:
2023
Abstract Tesim:
There is now evidence from multiple Phase II clinical trials that psychedelic drugs can exert long-lasting anxiolytic, anti-depressant, and anti-drug abuse (nicotine and ethanol) effects in patients. Despite these benefits, the hallucinogenic actions of these drugs at the serotonin 2A receptor (5-HT2AR) limit their clinical use in diverse settings. Activation of the 5-HT2AR can stimulate both G protein and β-arrestin (βArr) -mediated signaling. Lisuride is a G protein biased agonist at the 5-HT2AR and, unlike the structurally-related lysergic acid diethylamide (LSD), the drug does not typically produce hallucinations in normal subjects at routine doses. Here, we examined behavioral responses to lisuride, in wild-type (WT), βArr1-knockout (KO), and βArr2-KO mice. In the open field, lisuride reduced locomotor and rearing activities, but produced a U-shaped function for stereotypies in both βArr lines of mice. Locomotion was decreased overall in βArr1-KOs and βArr2-KOs relative to wild-type controls. Incidences of head twitches and retrograde walking to lisuride were low in all genotypes. Grooming was decreased in βArr1 mice, but was increased then decreased in βArr2 animals with lisuride. Serotonin syndrome-associated responses were present at all lisuride doses in WTs, but they were reduced especially in βArr2-KO mice. Prepulse inhibition (PPI) was unaffected in βArr2 mice, whereas 0.5 mg/kg lisuride disrupted PPI in βArr1 animals. The 5-HT2AR antagonist MDL100907 failed to restore PPI in βArr1 mice, whereas the dopamine D2/D3 antagonist raclopride normalized PPI in WTs but not in βArr1-KOs. Clozapine, SCH23390, and GR127935 restored PPI in both βArr1 genotypes. Using vesicular monoamine transporter 2 mice, lisuride reduced immobility times in tail suspension and promoted a preference for sucrose that lasted up to 2 days. Together, it appears βArr1 and βArr2 play minor roles in lisuride’s actions on many behaviors, while this drug exerts anti-depressant drug-like responses without hallucinogenic-like activities.
Resource type:
Article
Affiliation Label Tesim:
Department of Pharmacology
DOI:
https://doi.org/10.17615/rgra-zp80
Edition:
Publisher
Identifier:
https://dx.doi.org/10.3389/fmolb.2023.1233743
ISSN:
2296-889X
Journal Title:
Frontiers in Molecular Biosciences
Journal Volume:
10
Keyword:
lisuride, serotonin-syndrome, head twitch, prepulse inhibition, serotonin 2A receptor, β-arrestin, and mice
Language Label:
English
License Label:
Attribution 4.0 International
ORCID:
Other Affiliation:
Duke University Medical Center and
Person:
Pogorelov, Vladimir M., Rodriguiz, Ramona M., Wetsel, William C., and Roth, Bryan L.
Sciducio: a practical framework for guiding the development and leadership of the academic research environment
Creator:
Paterson, Craig, Woolard, Nathan, Higgins, Simon, Pagan Lassalle, Patricia, Perry, Lane, Stoner, Lee, Lassalle, Yolanda, and Cowley, Emma
Date of publication:
2023
Abstract Tesim:
The goal of this paper is to introduce Sciducio, a practical framework for guiding the development and leadership of an academic research environment. The principal audience for this framework is new academics, that is individuals beginning a tenure-track position in the U.S or a lecturing position elsewhere in the world. However, we also believe this framework will be of use to established academics searching for structure, academics moving to a new institution, and can serve as a training tool for doctoral and postdoctoral mentees. We briefly describe the theory supporting Sciducio, outline the framework and its individual components (blocks), then provide suggested instructions for use. We provide suggested instructions (i.e., descriptive rather than prescriptive), because there is no one-size-fits-all approach for ensuring success. Sciducio incorporates three domains (Plan, Manage, and Deliver), encompasses eight blocks, and is intended to fit on one-sheet of paper or one screen. The Plan domain includes the blocks: value, strategy, and leadership. The Manage domain includes the blocks: activities, key resources, and finances. The Deliver domain includes the blocks: solution and channels. Considering each of the framework blocks is complex, we cannot provide full justice to each component. This paper serves as a general overview and subsequent papers will be more topic specific. Additionally, we encourage others to contribute to and advance this framework.
Resource type:
Article
Affiliation Label Tesim:
Department of Exercise and Sport Science
DOI:
https://doi.org/10.17615/jf7y-0d71
Edition:
Publisher
Identifier:
https://dx.doi.org/10.3389/frma.2023.1205874
ISSN:
2504-0537
Journal Title:
Frontiers in Research Metrics and Analytics
Journal Volume:
8
Keyword:
planning, laboratory, Lean Canvas, mentorship, Business Model Canvas, management, and academia
Language Label:
English
License Label:
Attribution 4.0 International
ORCID:
Other Affiliation:
, University of Tulsa, Western Carolina University, and LaSalle Group LLC
Person:
Paterson, Craig, Woolard, Nathan, Higgins, Simon, Pagan Lassalle, Patricia, Perry, Lane, Stoner, Lee, Lassalle, Yolanda, and Cowley, Emma
Risk factors for health impairments in children after hospitalization for acute COVID-19 or MIS-C
Creator:
Tarquinio, Keiko M., Cullimore, Melissa L., Gertz, Shira J., Hobbs, Charlotte V., Levy, Emily R., Campbell, Angela P., Kucukak, Suden, Mack, Elizabeth H., Chatani, Brandon M., Maddux, Aline B, Zambrano, Laura D., Zinter, Matt S., Flori, Heidi, Young, Cameron C., Loftis, Laura L., Newhams, Margaret M., Overcoming COVID-19 Investigators, Typpo, Katri V., Shein, Steven, Kong, Michele, Fitzgerald, Julie C., Irby, Katherine, Staat, Mary A., Schuster, Jennifer E., Nofziger, Ryan A., Rollins, Caitlin K., Crandall, Hillary, Schwartz, Stephanie, Hume, Janet R., Randolph, Adrienne G., Rowan, Courtney M, Halasa, Natasha B., and Cvijanovich, Natalie Z.
Date of publication:
2023
Abstract Tesim:
ObjectiveTo identify risk factors for persistent impairments after pediatric hospitalization for acute coronavirus disease 2019 (COVID-19) or multisystem inflammatory syndrome in children (MIS-C) during the SARS-CoV-2 pandemic.MethodsAcross 25 U.S. Overcoming COVID-19 Network hospitals, we conducted a prospective cohort study of patients <21-years-old hospitalized for acute COVID-19 or MIS-C (May 2020 to March 2022) surveyed 2- to 4-months post-admission. Multivariable regression was used to calculate adjusted risk ratios (aRR) and 95% confidence intervals (CI).ResultsOf 232 children with acute COVID-19, 71 (30.6%) had persistent symptoms and 50 (21.6%) had activity impairments at follow-up; for MIS-C (n = 241), 56 (23.2%) had persistent symptoms and 58 (24.1%) had activity impairments. In adjusted analyses of patients with acute COVID-19, receipt of mechanical ventilation was associated with persistent symptoms [aRR 1.83 (95% CI: 1.07, 3.13)] whereas obesity [aRR 2.18 (95% CI: 1.05, 4.51)] and greater organ system involvement [aRR 1.35 (95% CI: 1.13, 1.61)] were associated with activity impairment. For patients with MIS-C, having a pre-existing respiratory condition was associated with persistent symptoms [aRR 3.04 (95% CI: 1.70, 5.41)] whereas obesity [aRR 1.86 (95% CI: 1.09, 3.15)] and greater organ system involvement [aRR 1.26 (1.00, 1.58)] were associated with activity impairments.DiscussionAmong patients hospitalized, nearly one in three hospitalized with acute COVID-19 and one in four hospitalized with MIS-C had persistent impairments for ≥2 months post-hospitalization. Persistent impairments were associated with more severe illness and underlying health conditions, identifying populations to target for follow-up.
Resource type:
Article
Affiliation Label Tesim:
Department of Pediatrics
DOI:
https://doi.org/10.17615/2fg0-bg85
Edition:
Publisher
Identifier:
https://dx.doi.org/10.3389/fped.2023.1260372
ISSN:
2296-2360
Journal Title:
Frontiers in Pediatrics
Journal Volume:
11
Keyword:
post-acute COVID-19 syndrome, pediatrics, COVID-19, SARS-CoV-2, COVID-19 post-intensive care syndrome, multisystem inflammatory syndrome in children, critical care outcomes, and MIS-C
Language Label:
English
License Label:
Attribution 4.0 International
ORCID:
Other Affiliation:
Children’s Healthcare of Atlanta, Children’s Hospital and Medical Center, Cooperman Barnabas Medical Center, University of Mississippi Medical Center, Mayo Clinic, Centers for Disease Control and Prevention, Boston Children’s Hospital, Medical University of South Carolina, AdventHealth for Children, University of Colorado School of Medicine, University of California San Francisco, C. S. Mott Children’s Hospital, Texas Children’s Hospital, , University of Arizona, Rainbow Babies and Children’s Hospital, University of Alabama at Birmingham, Children’s Hospital of Philadelphia, Arkansas Children’s Hospital, University of Cincinnati, Children’s Mercy Kansas City, Akron Children’s Hospital, University of Utah, University of Minnesota Masonic Children’s Hospital, Indiana University School of Medicine, Vanderbilt University Medical Center, and UCSF Benioff Children’s Hospital
Person:
Tarquinio, Keiko M., Cullimore, Melissa L., Gertz, Shira J., Hobbs, Charlotte V., Levy, Emily R., Campbell, Angela P., Kucukak, Suden, Mack, Elizabeth H., Chatani, Brandon M., Maddux, Aline B, Zambrano, Laura D., Zinter, Matt S., Flori, Heidi, Young, Cameron C., Loftis, Laura L., Newhams, Margaret M., Overcoming COVID-19 Investigators, Typpo, Katri V., Shein, Steven, Kong, Michele, Fitzgerald, Julie C., Irby, Katherine, Staat, Mary A., Schuster, Jennifer E., Nofziger, Ryan A., Rollins, Caitlin K., Crandall, Hillary, Schwartz, Stephanie, Hume, Janet R., Randolph, Adrienne G., Rowan, Courtney M, Halasa, Natasha B., and Cvijanovich, Natalie Z.
Predicting the effects of spatiotemporal modifications of muscle activation on the tentacle extension in squid
Creator:
van Leeuwen, Johan L. and Kier, William M.
Date of publication:
2023
Abstract Tesim:
Squid use eight arms and two slender tentacles to capture prey. The muscular stalks of the tentacles are elongated approximately 80% in 20–40 ms towards the prey, which is adhered to the terminal clubs by arrays of suckers. Using a previously developed forward dynamics model of the extension of the tentacles of the squid Doryteuthis pealeii (formerly Loligo pealeii), we predict how spatial muscle-activation patterns result in a distribution of muscular power, muscle work, and kinetic and elastic energy along the tentacle. The simulated peak extension speed of the tentacles is remarkably insensitive to delays of activation along the stalk, as well as to random variations in the activation onset. A delay along the tentacle of 50% of the extension time has only a small effect on the peak extension velocity of the tentacle compared with a zero-delay pattern. A slight delay of the distal portion relative to the proximal has a small positive effect on peak extension velocity, whereas negative delays (delay reversed along stalk) always reduce extension performance. In addition, tentacular extension is relatively insensitive to superimposed random variations in the prescribed delays along the stalk. This holds in particular for small positive delays that are similar to delays predicted from measured axonal diameters of motor neurons. This robustness against variation in the activation distribution reduces the accuracy requirements of the neuronal control and is likely due to the non-linear mechanical properties of the muscular tissue in the tentacle.
Interpreting growth hormone and IGF-I results using modern assays and reference ranges for the monitoring of treatment effectiveness in acromegaly
Creator:
Clemmons, David R. and Bidlingmaier, Martin
Date of publication:
2023
Abstract Tesim:
Standard treatment for acromegaly focuses on the achievement of target absolute levels of growth hormone (GH) and insulin-like growth factor (IGF-I). The appropriateness of these targets when measured using modern assay methods is not well defined. This paper reviews biochemical status assessed using methods available at the time and associated clinical outcomes. GH measurements were shown to provide an indication of changes in tumor size, and failure of GH suppression after glucose stimulation is associated with tumor recurrence. IGF-I levels were more closely associated with changes in symptoms and signs. Reduced GH and IGF-I concentrations were shown to be associated with increased longevity, although the degree of increase has only been analyzed for GH. Lowering of GH and IGF-I has consistently been associated with improved outcomes; however, absolute levels reported in previous studies were based on results from methods and reference ranges that are now obsolete. Applying previously described absolute thresholds as targets (e.g. “normal” IGF-I level) when using current methods are best applied to those with active acromegaly symptoms who could benefit from further lowering of biochemical markers. In asymptomatic individuals with mild IGF-I or GH elevations, targeting biochemical “normalization” would result in the need for combination pharmacotherapy in many patients without proven benefit. Measurement of both GH and IGF-I remains an essential component of diagnosis and monitoring the effectiveness of treatment in acromegaly; however, treatment goals based only on previously identified absolute thresholds are not appropriate without taking into account the assay and reference ranges being employed. Treatment goals should be individualized considering biochemical improvement from an untreated baseline, symptoms of disease, risks, burdens and costs of complex treatment regimens, comorbidities, and quality of life.
Resource type:
Article
Affiliation Label Tesim:
Department of Medicine
DOI:
https://doi.org/10.17615/dm1f-je35
Edition:
Publisher
Identifier:
https://dx.doi.org/10.3389/fendo.2023.1266339
ISSN:
1664-2392
Journal Title:
Frontiers in Endocrinology
Journal Volume:
14
Keyword:
therapy, IGF-I, biochemical markers, treatment response, acromegaly, and growth hormone