Framework to leverage physical therapists for the assessment and treatment of chemotherapy-induced peripheral neurotoxicity (CIPN).

PURPOSE: Chemotherapy-induced peripheral neurotoxicity (CIPN) is a highly prevalent, dose-limiting, costly, and tough-to-treat adverse effect of several chemotherapy agents, presenting as sensory and motor dysfunction in the distal extremities. Due to limited effective treatments, CIPN can permanently reduce patient function, independence, and quality of life. One of the most promising interventions for CIPN is physical therapy which includes exercise, stretching, balance, and manual therapy interventions. Currently, there are no physical therapy guidelines for CIPN, thus limiting its uptake and potential effectiveness. METHODS: Utilizing the authors' collective expertise spanning physical therapy, symptom management research, oncology, neurology, and treating patients with CIPN, we propose a comprehensive clinical workflow for physical therapists to assess and treat CIPN. This workflow is based on (1) physical therapy guidelines for treating neurologic symptoms like those of CIPN, (2) results of clinical research on physical therapy and exercise, and (3) physical therapy clinical judgement. RESULTS: We present detailed tables of pertinent physical therapy assessment and treatment methods that can be used in clinical settings. CIPN assessment should include detailed sensory assessment, objective strength assessments of involved extremities, and validated physical performance measures incorporating static and dynamic balance, gait, and functional mobility components. CIPN treatment should involve sensorimotor, strength, balance, and endurance-focused interventions, alongside a home-based exercise prescription that includes aerobic training. We conclude with action items for oncology teams, physical therapists, patients, and researchers to best apply this framework to address CIPN. CONCLUSIONS: Physical therapists are in a unique position to help assess, prevent, and treat CIPN given their training and prevalence, yet there are no physical therapy clinical practice guidelines for CIPN. Our preliminary suggestions for CIPN assessments and treatments can catalyze the development of guidelines to assess and treat CIPN. We urge oncology teams, physical therapists, patients, and researchers to develop, adapt, and disseminate this framework to help alleviate the burden of chemotherapy on patients with cancer.

Chemotherapy-related symptoms and exercise adherence in older patients with myeloid neoplasms.

PURPOSE: Exercise may ameliorate treatment-related symptoms, but older adults have lower exercise adherence compared to their younger counterparts due to treatment-related symptoms. METHODS: We recruited older patients with myeloid neoplasms receiving chemotherapy to a pilot study of a mobile health exercise intervention. Participants entered their steps and resistance data into the app daily, and symptom data twice a week, over an 8-12 week period. In this proof-of-concept analysis, we used a linear mixed-effects model to assess the association of symptoms from the previous week with exercise adherence in the current week among older adults with myeloid neoplasms. RESULTS: Mean age was 74.3 (SD = 5.0) years (N = 7). At baseline, patients on average walked 2564 daily steps (SD = 1816), which increased to 2967 (SD = 3448) post-intervention. Patients on average performed 3.5 (SD = 2.6) days of resistance training weekly, with mean duration of 21.5 min (SD = 11.6) and rated perceived exertion of 3.68 (SD = 1.78) on a 0-10 scale. Lower average steps in the current week was associated with greater interference with daily activities from pain (ß = - 203.13, p = 0.05), memory (ß = - 492.29, p = 0.09), numbness (ß = - 353.57, p = 0.07), and sadness (ß = - 403.03, p = 0.09) in the previous week. Similarly, lower average resistance minutes in the current week were associated with greater pain, sadness, and anxiety in the previous week. CONCLUSIONS: We found that greater pain, sadness, and anxiety were associated with lower exercise adherence. Symptom monitoring and management in older adults with myeloid neoplasms receiving chemotherapy can promote exercise adherence and in turn improve symptoms. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04035499. Registered 7/29/2019.

The association between cancer-related fatigue and diabetes from pre-chemotherapy to 6 months post-chemotherapy.

PURPOSE: To quantify the relationship between diabetes and fatigue from pre-chemotherapy to 6 months post-chemotherapy for women with breast cancer compared to women without a history of cancer (controls). METHODS: This was a secondary analysis from a nationwide prospective longitudinal study of female patients with breast cancer undergoing chemotherapy and controls. Diabetes diagnosis (yes/no) was obtained at baseline, and cancer-related fatigue was measured using the Multidimensional Fatigue Symptom Inventory (MFSI) pre-, post-, and 6 months post-chemotherapy in patients; controls were assessed at equivalent time points. Repeated measures mixed effects models estimated the association between fatigue and diabetes controlling for cancer (yes/no), body mass index, exercise and smoking habits, baseline anxiety and depressive symptoms, menopausal status, marital status, race, and education. RESULTS: Among 439 patients and 235 controls (52.8 ± 10.5 years old), diabetes was twice as prevalent among patients as controls (11.6% vs. 6.8%). At baseline, diabetes was associated with worse fatigue (4.1 ± 1.7 points, p = 0.017). Also, diabetes was associated with clinically meaningful worse fatigue throughout the study period among all participants (5.2 ± 1.9 points, p = 0.008) and patients alone (4.5 ± 2.0, p = 0.023). For the MFSI subdomains among patients, diabetes was associated with worse general (p = 0.005) and mental fatigue (p = 0.026). CONCLUSIONS: Diabetes was twice as prevalent in women with breast cancer compared to controls, and diabetes was associated with more severe cancer-related fatigue in patients before and after chemotherapy and at 6 months post-chemotherapy. Interventions that address diabetes management may also help address cancer-related fatigue during chemotherapy treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01382082, first posted June 27, 2011.

Exploratory Analysis of Associations Between Whole Blood Mitochondrial Gene Expression and Cancer-Related Fatigue Among Breast Cancer Survivors.

BACKGROUND: Cancer-related fatigue is a prevalent, debilitating, and persistent condition. Mitochondrial dysfunction is a putative contributor to cancer-related fatigue, but relationships between mitochondrial function and cancer-related fatigue are not well understood. OBJECTIVES: We investigated the relationships between mitochondrial DNA (mtDNA) gene expression and cancer-related fatigue, as well as the effects of fish and soybean oil supplementation on these relationships. METHODS: A secondary analysis was performed on data from a randomized controlled trial of breast cancer survivors 4-36 months posttreatment with moderate-severe cancer-related fatigue. Participants were randomized to take 6 g fish oil, 6 g soybean oil, or 3 g each daily for 6 weeks. At pre- and postintervention, participants completed the Functional Assessment of Chronic Illness Therapy-Fatigue questionnaire and provided whole blood for assessment of mtDNA gene expression. The expression of 12 protein-encoding genes was reduced to a single dimension using principal component analysis for use in regression analysis. Relationships between mtDNA expression and cancer-related fatigue were assessed using linear regression. RESULTS: Among 68 participants, cancer-related fatigue improved and expression of all mtDNA genes decreased over 6 weeks with no effect of treatment group on either outcome. Participants with lower baseline mtDNA gene expression had greater improvements in cancer-related fatigue. No significant associations were observed between mtDNA gene expression and cancer-related fatigue at baseline or changes in mtDNA gene expression and changes in cancer-related fatigue. DISCUSSION: Data from this exploratory study add to the growing literature that mitochondrial dysfunction may contribute to the etiology and pathophysiology of cancer-related fatigue.

Longitudinal study of inflammatory, behavioral, clinical, and psychosocial risk factors for chemotherapy-induced peripheral neuropathy.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting side effect of taxane and platinum chemotherapy for breast cancer. Clinicians cannot accurately predict CIPN severity partly because its pathophysiology is poorly understood. Although inflammation may play a role in CIPN, there are limited human studies. Here, we identified the strongest predictors of CIPN using variables measured before taxane- or platinum-based chemotherapy, including serum inflammatory markers. METHODS: 116 sedentary women with breast cancer (mean age 55 years) rated (1) numbness and tingling and (2) hot/coldness in hands/feet on 0-10 scales before and after 6 weeks of taxane- or platinum-based chemotherapy. A sub-study was added to collect cytokine data in the final 55 patients. We examined all linear models to predict CIPN severity at 6 weeks using pre-chemotherapy assessments of inflammatory, behavioral, clinical, and psychosocial factors. The final model was selected via goodness of fit. RESULTS: The strongest pre-chemotherapy predictors of numbness and tingling were worse fatigue/anxiety/depression (explaining 27% of variance), older age (9%), and baseline neuropathy (5%). The strongest predictors of hot/coldness in hands/feet were worse baseline neuropathy (11%) and fatigue/anxiety/depression (6%). Inflammation was a risk for CIPN, per more pro-inflammatory IFN-γ (12%) and IL-1ß (6%) and less anti-inflammatory IL-10 (6%) predicting numbness/tingling and more IFN-γ (17%) and less IL-10 (9%) predicting hot/coldness in hands/feet. CONCLUSIONS: The strongest pre-chemotherapy predictors of CIPN included worse fatigue/anxiety/depression and baseline neuropathy. A pro-inflammatory state also predicted CIPN. Because this is an exploratory study, these results suggest specific outcomes (e.g., IL-1ß) and effect size estimates for designing replication and extension studies. CLINICAL TRIAL REGISTRATION: NCT00924651.

Framework for selecting and benchmarking mobile devices in psychophysiological research.

Commercially available consumer electronics in (smartwatches and wearable biosensors) are increasingly enabling acquisition of peripheral physiological and physical activity data inside and outside of laboratory settings. However, there is scant literature available for selecting and assessing the suitability of these novel devices for scientific use. To overcome this limitation, the current paper offers a framework to aid researchers in choosing and evaluating wearable technologies for use in empirical research. Our seven-step framework includes: (1) identifying signals of interest; (2) characterizing intended use cases; (3) identifying study-specific pragmatic needs; (4) selecting devices for evaluation; (5) establishing an assessment procedure; (6) performing qualitative and quantitative analyses on resulting data; and, if desired, (7) conducting power analyses to determine sample size needed to more rigorously compare performance across devices. We illustrate the application of the framework by comparing electrodermal, cardiovascular, and accelerometry data from a variety of commercial wireless sensors (Affectiva Q, Empatica E3, Empatica E4, Actiwave Cardio, Shimmer) relative to a well-validated, wired MindWare laboratory system. Our evaluations are performed in two studies (N = 10, N = 11) involving psychometrically sound, standardized tasks that include physical activity and affect induction. After applying our framework to this data, we conclude that only some commercially available consumer devices for physiological measurement are capable of wirelessly measuring peripheral physiological and physical activity data of sufficient quality for scientific use cases. Thus, the framework appears to be beneficial at suggesting steps for conducting more systematic, transparent, and rigorous evaluations of mobile physiological devices prior to deployment in studies.

Longitudinal assessment of the impact of higher body mass index on cancer-related fatigue in patients with breast cancer receiving chemotherapy.

PURPOSE: To assess the impact of obesity on cancer-related fatigue (CRF) in patients with breast cancer, through a secondary analysis of a large, longitudinal, nationwide study of breast cancer patients beginning chemotherapy. METHODS: All patients (N = 565; aged 53 ± 10.6) with breast cancer completed the multidimensional fatigue symptom inventory and the symptom inventory to measure CRF symptoms at baseline, post-chemotherapy, and 6 months post-chemotherapy. Height and weight at baseline were used to categorize subjects based on body mass index (BMI): obese (≥ 30.0 kg/m2; n = 294), overweight (25.0-29.9 kg/m2; n = 146), and normal weight (18.5-24.9 kg/m2; n = 125). Multivariate regression models evaluated the relationship of obesity level to CRF over time, controlling for age, menopausal status, race, Karnofsky Performance Status, cancer stage, radiation, and exercise status. RESULTS: At baseline, the obese had significantly higher CRF symptoms than the normal weight subjects for both the Multidimensional fatigue symptom inventory (MFSI) total (obese = 11.2 vs normal weight = 6.3; p = 0.03) and Symptom Inventory (SI) (obese = 3.5 vs normal weight = 2.9; p = 0.03). Significantly higher SI fatigue scores persisted at post-chemotherapy for the obese (obese = 5.0 vs normal weight = 4.4; p = 0.02). At 6 months post-chemotherapy, the obese patients still had significantly higher SI fatigue scores (obese = 3.5 vs normal weight = 3.0; p = 0.05). CONCLUSION: Obese patients suffered greater CRF from pre-chemotherapy through 6 months post-chemotherapy. Recommendations for weight loss or weight maintenance may impact CRF levels in obese breast cancer patients before and after chemotherapy.

Chemotherapy-induced peripheral neuropathy (CIPN) and its treatment: an NIH Collaboratory study of claims data.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a disabling complication of many chemotherapies. We investigated the feasibility of using health plan claims and administrative data to identify CIPN occurrence by comparing patients who received neurotoxic and non-neurotoxic chemotherapies. METHODS: The sample included over 53,000,000 patients from two regional and one national insurer in the USA (> 400,000 exposed to chemotherapy). Peripheral neuropathy was identified using a broad definition (definition 1) and a specific definition (i.e., drug-induced polyneuropathy code) (definition 2). RESULTS: CIPN incidence as measured by definition 1 within 6 months of chemotherapy initiation was 18.1% and 6.2% for patients who received neurotoxic and non-neurotoxic chemotherapy, respectively (relative risk neurotoxic vs. non-neurotoxic (RR), 2.93 (95% CI, 2.87-2.98)). For definition 2, these incidences were 3.6% and 0.1% (RR, 25.2 (95% CI, 22.8-27.8)). The incidences of new analgesic prescriptions for neurotoxic and non-neurotoxic groups were as follows: gabapentin, 7.1%/1.7%; pregabalin, 0.69%/0.31%; and duloxetine, 0.78%/0.76%. The incidence of CIPN as defined by definitions 1 and 2 was low compared with that of published research studies, but the relative risk of CIPN among patients who received neurotoxic chemotherapies compared with those who received non-neurotoxic chemotherapies was high using definition 2. CONCLUSIONS: These data suggest that as used currently by clinicians, administrative codes likely underestimate CIPN incidence. Thus, studies using administrative data to estimate CIPN incidence are not currently feasible. However, the drug-induced polyneuropathy code is a specific indicator of CIPN in administrative data and may be useful for investigating predictors or potentially preventive therapies of CIPN.

Nutritional Interventions for Treating Cancer-Related Fatigue: A Qualitative Review.

Cancer-related fatigue (CRF) is a debilitating syndrome that persists for many cancer survivors for years after treatment. Symptoms include early and persistent fatigue, functional decline, depression, and cognitive difficulties. Inflammation, assessed using pro-inflammatory biomarkers, is increased in cancer survivors with fatigue and treatments for fatigue are often aimed at reducing inflammation. Additionally, cancer and its treatment lead to nutritional complications, changes in body composition, and nutritional deficiencies that potentially weaken the cancer survivor and impact CRF. We conducted a qualitative review of clinical trials that assessed nutritional interventions for preventing and treating CRF. Further studies were examined that used nutritional interventions to address inflammation and fatigue, due to the dearth of nutrition research directly related to CRF. Dietary intake prior to, during, and after cancer treatment appears to affect fatigue levels. Increased protein intake may help preserve lean mass and body composition. Dietary patterns that reduce inflammation, such as the Mediterranean diet and other plant-based diets, appear tolerable to cancer survivors and may reduce fatigue. Supplementation with ginseng, ginger, or probiotics may improve cancer survivors' energy levels. Nutritional interventions, alone or in combination with other interventions should be considered as therapy for fatigue in cancer survivors.

Systematic Review of Randomized Controlled Trials of Exercise Interventions Using Digital Activity Trackers in Patients With Cancer.

Background: Exercise can ameliorate cancer- and treatment-related toxicities, but poor adherence to exercise regimens is a barrier. Exercise interventions using digital activity trackers (E-DATs) may improve exercise adherence, but data are limited for patients with cancer. We conducted a systematic review examining the feasibility of E-DATs in cancer survivors and effects on activity level, body composition, objective fitness outcomes, health-related quality of life (HRQoL), self-reported symptoms, and biomarkers. Methods: We identified randomized controlled trials (RCTs) of E-DATs in adult cancer survivors published in English between January 1, 2008, and July 27, 2017. Two authors independently reviewed article titles (n=160), removed duplicates (n=50), and reviewed the remaining 110 articles for eligibility. Results: A total of 12 RCTs met eligibility criteria, including 1,450 patients (mean age, 50-70 years) with the following cancers: breast (n=5), colon or breast (n=2), prostate (n=1), acute leukemia (n=1), or others (n=3). Duration of E-DATs ranged from 4 to 24 weeks, and the follow-up period ranged from 4 to 52 weeks, with retention rates of 54% to 95%. The technology component of E-DATs included pedometers (n=8); pedometers with smartphone application (n=1), Wii Fit (n=1), heart rate monitor (n=1); and a wireless sensor with accelerometer, gyroscope, and magnetometer (n=1). Adherence by at least one measure to E-DATs was >70% in 8 of 8 RCTs. Compared with controls, E-DATs significantly improved patients' step count in 3 of 5 RCTs, activity level in 6 of 9 RCTs, and HRQoL in 7 of 9 RCTs (all P≤05), with no significant changes in biomarkers (eg, interleukin 6, tumor necrosis factor α, C-reactive protein, c-peptide, lipid panel) in 3 RCTs. Duration of E-DAT was not significantly correlated with adherence or study retention. Conclusions: This systematic review shows that E-DATs are feasible to implement in cancer survivors. Future research should examine the optimal type, dose, and schedule of E-DATs for cancer survivors.

Effects of exercise on inflammation in patients receiving chemotherapy: a nationwide NCORP randomized clinical trial.

PURPOSE: A growing body of research suggests that inflammation plays a role in many chemotherapy-related toxicities such as fatigue, anxiety, and neuropathy. Regular exercise can change levels of individual cytokines (e.g., reducing IL-6, increasing IL-10); however, it is not known whether exercise during chemotherapy affects relationships between cytokines (i.e., whether cytokine concentrations change collectively vs. independently). This study assessed how 6 weeks of exercise during chemotherapy affected relationships between changes in concentrations of several cytokines. METHODS: This is a secondary analysis of a randomized trial studying 6 weeks of moderate-intensity walking and resistance exercise during chemotherapy compared with chemotherapy alone. At pre- and post-intervention, patients provided blood to assess serum concentrations of cytokines IL-1ß, IL-6, IL-8, IL-10, and IFN-γ, and receptor sTNFR1. We investigated relationships between cytokines using the correlations between changes in cytokine concentrations from pre- to post-intervention. RESULTS: We obtained complete data from 293 patients (149 randomized to exercise). Exercise strengthened the correlation between concentration changes of IL-10 and IL-6 (r = 0.44 in exercisers vs. 0.11 in controls; p = 0.001). We observed the same pattern for IL-10:IL-1ß and IL-10:sTNFR1. Exercise also induced an anti-inflammatory cytokine profile, per reductions in pro-inflammatory IFN-γ (p = 0.044) and perhaps IL-1ß (p = 0.099, trend-level significance). CONCLUSIONS: Our hypothesis-generating work suggests that regular exercise during 6 weeks of chemotherapy may cause certain cytokine concentrations to change collectively (not independently). This work enhances our understanding of relationships between cytokines and complements traditional analyses of cytokines in isolation. Future work should test for replication and relationships to patient outcomes. TRIAL REGISTRATION: Clinical Trials.gov, # NCT00924651, http://www.clinicaltrials.gov .

Social Support, Insomnia, and Adherence to Cognitive Behavioral Therapy for Insomnia After Cancer Treatment.

OBJECTIVE/BACKGROUND: While cognitive-behavioral therapy for insomnia (CBT-I) has been shown to be efficacious in treating cancer survivors' insomnia, 30-60% of individuals have difficulty adhering to intervention components. Psychosocial predictors of adherence and response to CBT-I, such as social support, have not been examined in intervention studies for cancer survivors. PARTICIPANTS: Data from a randomized placebo-controlled 2 x 2 trial of CBT-I and armodafinil (a wakefulness promoting agent) were used to assess adherence. Ninety-six cancer survivors participated in the trial (mean age 56, 86% female, 68% breast cancer). METHODS: CBT-I and armodafinil were administered over the course of seven weeks, and participants were assessed at baseline, during intervention, postintervention, and at a three-month follow-up. Social support was assessed using a Functional Assessment of Chronic Illness Therapy subscale, insomnia severity was assessed using the Insomnia Severity Index, and adherence was measured based on CBT-I sleep prescriptions. RESULTS: At baseline, social support was negatively correlated with insomnia severity (r = -0.30, p = 0.002) and associations between social support, CBT-I, and insomnia were maintained through the three-month follow-up. Social support was positively associated with adherence to CBT-I during intervention weeks 3, 4, and 5, and with overall intervention adherence. At postintervention, both social support and treatment with CBT-I independently predicted decreased insomnia severity (p < 0.01) when controlling for baseline insomnia severity. CONCLUSIONS: Higher social support is associated with better intervention adherence and improved sleep independent of CBT-I. Additional research is needed to determine whether social support can be leveraged to improve adherence and response to CBT-I.

Yoga for the Management of Cancer Treatment-Related Toxicities.

PURPOSE OF REVIEW: To (1) explain what yoga is, (2) summarize published literature on the efficacy of yoga for managing cancer treatment-related toxicities, (3) provide clinical recommendations on the use of yoga for oncology professionals, and (4) suggest promising areas for future research. RECENT FINDINGS: Based on a total of 24 phase II and one phase III clinical trials, low-intensity forms of yoga, specifically gentle hatha and restorative, are feasible, safe, and effective for treating sleep disruption, cancer-related fatigue, cognitive impairment, psychosocial distress, and musculoskeletal symptoms in cancer patients receiving chemotherapy and radiation and cancer survivors. Clinicians should consider prescribing yoga for their patients suffering with these toxicities by referring them to qualified yoga professionals. More definitive phase III clinical trials are needed to confirm these findings and to investigate other types, doses, and delivery modes of yoga for treating cancer-related toxicities in patients and survivors.

Effects of exercise during chemotherapy on chemotherapy-induced peripheral neuropathy: a multicenter, randomized controlled trial.

PURPOSE: Over half of all cancer patients receiving taxane-, platinum-, or vinca alkaloid-based chemotherapy experience chemotherapy-induced peripheral neuropathy (CIPN), which includes numbness, tingling, pain, cold sensitivity, and motor impairment in the hands and feet. CIPN is a dose-limiting toxicity, potentially increasing mortality. There are no FDA-approved drugs to treat CIPN, and behavioral interventions such as exercise are promising yet understudied. This secondary analysis of our nationwide phase III randomized controlled trial of exercise for fatigue examines (1) effects of exercise on CIPN symptoms, (2) factors that predict CIPN symptoms, and (3) factors that moderate effects of exercise on CIPN symptoms. METHODS: Cancer patients (N = 355, 56 ± 11 years, 93% female, 79% breast cancer) receiving taxane-, platinum-, or vinca alkaloid-based chemotherapy were randomized to chemotherapy or chemotherapy plus Exercise for Cancer Patients (EXCAP©®). EXCAP is a standardized, individualized, moderate-intensity, home-based, six-week progressive walking and resistance exercise program. Patients reported CIPN symptoms of numbness and tingling and hot/coldness in hands/feet (0-10 scales) pre- and post-intervention. We explored baseline neuropathy, sex, age, body mass index, cancer stage, and cancer type as possible factors associated with CIPN symptoms and exercise effectiveness. RESULTS: Exercise reduced CIPN symptoms of hot/coldness in hands/feet (-0.46 units, p = 0.045) and numbness and tingling (- 0.42 units, p = 0.061) compared to the control. Exercise reduced CIPN symptoms more for patients who were older (p = 0.086), male (p = 0.028), or had breast cancer (p = 0.076). CONCLUSIONS: Exercise appears to reduce CIPN symptoms in patients receiving taxane-, platinum-, or vinca alkaloid-based chemotherapy. Clinicians should consider prescribing exercise for these patients. TRIAL REGISTRATION: Clinical Trials.gov , # NCT00924651, http://www.clinicaltrials.gov .

Racial Differences in Information Needs During and After Cancer Treatment: a Nationwide, Longitudinal Survey by the University of Rochester Cancer Center National Cancer Institute Community Oncology Research Program.

Before treatment, cancer patients need information about side effects and prognosis, while after treatment they need information to transition to survivorship. Research documenting these needs is limited, especially among racial and ethnic minorities. This study evaluated cancer patients' needs according to race both before and after treatment. We compared white (n = 904) to black (n = 52) patients receiving treatment at 17 National Cancer Institute Community Oncology Research Program (NCORP) sites on their cancer-related concerns and need for information before and after cancer treatment. Two-sample t test and chi-squared analyses were used to assess group differences. Compared to white patients, black patients reported significantly higher concerns about diet (44.3 vs. 25.4 %,) and exercise (40.4 vs. 19.7 %,) during the course of treatment. Compared to whites, blacks also had significantly higher concern about treatment-related issues (white vs. black mean, 25.52 vs. 31.78), self-image issues (7.03 vs. 8.60), family-related issues (10.44 vs. 12.84), and financial concerns (6.42 vs. 8.90, all p < 0.05). Blacks, compared to whites, also had significantly greater post-treatment information needs regarding follow-up tests (8.17 vs. 9.44), stress management (4.12 vs. 4.89), and handling stigma after cancer treatment (4.21 vs. 4.89) [all p < 0.05]. Pre-treatment concerns and post-treatment information needs differed by race, with black patients reporting greater information needs and concerns. In clinical practice, tailored approaches may work particularly well in addressing the needs and concerns of black patients.

Mechanistic Models Fit to Variable Temperature Calorimetric Data Provide Insights into Cooperativity.

Allostery pervades macromolecular function and drives cooperative binding of ligands to macromolecules. To decipher the mechanisms of cooperative ligand binding it is necessary to define at a microscopic level the structural and thermodynamic consequences of binding of each ligand to its allosterically coupled site(s). However, dynamic sampling of alternative conformations (microstates) in allosteric molecules complicates interpretation of both structural and thermodynamic data. Isothermal titration calorimetry has the potential to directly quantify the thermodynamics of allosteric interactions, but usually falls short of enabling mechanistic insight. This is because 1) its measurements reflect the sum of overlapping caloric processes involving binding-linked population shifts within and between microstates, and 2) data are generally fit with phenomenological binding polynomials that are underdetermined. Nevertheless, temperature-dependent binding data have the potential to resolve overlapping thermodynamic processes, while mechanistically constrained models enable hypothesis testing and identification of informative parameters. We globally fit temperature-dependent isothermal titration calorimetry data for binding of 11 tryptophan ligands to the homo-undecameric trp RNA-binding Attenuation Protein from Bacillus stearothermophilus using nearest-neighbor statistical thermodynamic models. This approach allowed us to distinguish alternative nearest-neighbor interaction models, and quantifies the thermodynamic contribution of neighboring ligands to individual binding sites. We also perform conventional Hill equation modeling and illustrate how comparatively limited it is in quantitative or mechanistic value. This work illustrates the potential of mechanistically constrained global fitting of binding data to yield the microscopic thermodynamic parameters essential for deciphering mechanisms of cooperativity in a wide range of ligand-regulated homo-oligomeric assemblies.

Gene regulation by substoichiometric heterocomplex formation of undecameric TRAP and trimeric anti-TRAP.

The control of tryptophan production in Bacillus is a paradigmatic example of gene regulation involving the interplay of multiple protein and nucleic acid components. Central to this combinatorial mechanism are the homo-oligomeric proteins TRAP (trp RNA-binding attenuation protein) and anti-TRAP (AT). TRAP forms undecameric rings, and AT assembles into triskelion-shaped trimers. Upon activation by tryptophan, the outer circumference of the TRAP ring binds specifically to a series of tandem sequences present in the 5' UTR of RNA transcripts encoding several tryptophan metabolism genes, leading to their silencing. AT, whose expression is up-regulated upon tryptophan depletion to concentrations not exceeding a ratio of one AT trimer per TRAP 11-mer, restores tryptophan production by binding activated TRAP and preventing RNA binding. How the smaller AT inhibitor prevents RNA binding at such low stoichiometries has remained a puzzle, in part because of the large RNA-binding surface on the tryptophan-activated TRAP ring and its high affinity for RNA. Using X-ray scattering, hydrodynamic, and mass spectrometric data, we show that the polydentate action of AT trimers can condense multiple intact TRAP rings into large heterocomplexes, effectively reducing the available contiguous RNA-binding surfaces. This finding reveals an unprecedented mechanism for substoichiometric inhibition of a gene-regulatory protein, which may be a widespread but underappreciated regulatory mechanism in pathways that involve homo-oligomeric or polyvalent components.

Fear-related psychophysiological patterns are situation and individual dependent: A Bayesian model comparison approach.

Is there a universal mapping of physiology to emotion, or do these mappings vary substantially by person or situation? Psychologists, philosophers, and neuroscientists have debated this question for decades. Most previous studies have focused on differentiating emotions on the basis of accompanying autonomic responses using analytical approaches that often assume within-category homogeneity. In the present study, we took an alternative approach to this question. We determined the extent to which the relationship between subjective experience and autonomic reactivity generalizes across, or depends upon, the individual and situation for instances of a single emotion category, specifically, fear. Electrodermal activity and cardiac activity-two autonomic measures that are often assumed to show robust relationships with instances of fear-were recorded while participants reported fear experience in response to dozens of fear-evoking videos related to three distinct situations: spiders, heights, and social encounters. We formally translated assumptions from diverse theoretical models into a common framework for model comparison analyses. Results exceedingly favored a model that assumed situation-dependency in the relationship between fear experience and autonomic reactivity, with subject variance also significant but constrained by situation. Models that assumed generalization across situations and/or individuals performed much worse by comparison. These results call into question the assumption of generalizability of autonomic-subjective mappings across instances of fear, as required in translational research from nonhuman animals to humans, and advance a situated approach to understanding the autonomic correlates of fear experience. (PsycInfo Database Record (c) 2024 APA, all rights reserved).