Pinoresinol rescues developmental phenotypes of Arabidopsis phenylpropanoid mutants overexpressing FERULATE 5-HYDROXYLASE.

Most phenylpropanoid pathway flux is directed toward the production of monolignols, but this pathway also generates multiple bioactive metabolites. The monolignols coniferyl and sinapyl alcohol polymerize to form guaiacyl (G) and syringyl (S) units in lignin, components that are characteristic of plant secondary cell walls. Lignin negatively impacts the saccharification potential of lignocellulosic biomass. Although manipulation of its content and composition through genetic engineering has reduced biomass recalcitrance, in some cases, these genetic manipulations lead to impaired growth. The reduced-growth phenotype is often attributed to poor water transport due to xylem collapse in low-lignin mutants, but alternative models suggest that it could be caused by the hyper- or hypoaccumulation of phenylpropanoid intermediates. In Arabidopsis thaliana, overexpression of FERULATE 5-HYDROXYLASE (F5H) shifts the normal G/S lignin ratio to nearly pure S lignin and does not result in substantial changes to plant growth. In contrast, when we overexpressed F5H in the low-lignin mutants cinnamyl dehydrogenase c and d (cadc cadd), cinnamoyl-CoA reductase 1, and reduced epidermal fluorescence 3, plant growth was severely compromised. In addition, cadc cadd plants overexpressing F5H exhibited defects in lateral root development. Exogenous coniferyl alcohol (CA) and its dimeric coupling product, pinoresinol, rescue these phenotypes. These data suggest that mutations in the phenylpropanoid pathway limit the biosynthesis of pinoresinol, and this effect is exacerbated by overexpression of F5H, which further draws down cellular pools of its precursor, CA. Overall, these genetic manipulations appear to restrict the synthesis of pinoresinol or a downstream metabolite that is necessary for plant growth.

Neurodegenerative disease pathways are perturbed in patients with cancer who self-report cognitive changes and anxiety: A pathway impact analysis.

BACKGROUND: Cancer-related cognitive impairment (CRCI) and anxiety co-occur in patients with cancer. Little is known about mechanisms for the co-occurrence of these two symptoms. The purposes of this secondary analysis were to evaluate for perturbed pathways associated with the co-occurrence of self-reported CRCI and anxiety in patients with low versus high levels of these two symptoms and to identify potential mechanisms for the co-occurrence of CRCI and anxiety using biological processes common across any perturbed neurodegenerative disease pathways. METHODS: Patients completed the Attentional Function Index and the Spielberger State-Trait Anxiety Inventory six times over two cycles of chemotherapy. Based on findings from a previous latent profile analysis, patients were grouped into none versus both high levels of these symptoms. Gene expression was quantified, and pathway impact analyses were performed. Signaling pathways for evaluation were defined with the Kyoto Encyclopedia of Genes and Genomes database. RESULTS: A total of 451 patients had data available for analysis. Approximately 85.0% of patients were in the none class and 15.0% were in the both high class. Pathway impact analyses identified five perturbed pathways related to neurodegenerative diseases (i.e., amyotrophic lateral sclerosis, Huntington disease, Parkinson disease, prion disease, and pathways of neurodegeneration-multiple diseases). Apoptosis, mitochondrial dysfunction, oxidative stress, and endoplasmic reticulum stress were common biological processes across these pathways. CONCLUSIONS: This study is the first to describe perturbations in neurodegenerative disease pathways associated with CRCI and anxiety in patients receiving chemotherapy. These findings provide new insights into potential targets for the development of mechanistically based interventions.

Exposure to prenatal stressors and infant autonomic nervous system regulation of stress.

OBJECTIVES: The purpose of this study was to determine the relationship between fetal exposure to maternal prenatal stressors and infant parasympathetic (PNS) and sympathetic (SNS) nervous function at 3 timepoints across the first year of life. BACKGROUND: Autonomic nervous system impairments may mediate associations between gestational exposure to stressors and later infant health problems. Heart rate variability (HRV) provides a sensitive index of PNS and SNS function. However, no studies have assessed longitudinal associations between prenatal stressors and infant HRV measures of both PNS and SNS over the first year of life. METHODS: During the third trimester of pregnancy, 233 women completed measures of life stressors and depression. At 1, 6 and 12 months of age, a stressor protocol was administered while infant electrocardiographic (ECG) data were collected from a baseline through a post-stressor period. HRV measures of PNS and SNS activity (HF, LF, LF/HF ratio) were generated from ECG data. We used multilevel regression to examine the aims, adjusting for maternal depression and neonatal morbidity. RESULTS: There were no associations between prenatal stressors and any baseline or reactivity HRV metric over the infant's first year of life. However, exposure to more stressors was associated with lower post-stressor LF HRV at both 6 (ß = -.44, p = .001) and 12 (ß = -.37, p = .005) months of age. CONCLUSIONS: Findings suggest potential alterations in development of the vagally mediated baroreflex function as a result of exposure to prenatal stressors, with implications for the infants' ability to generate a resilient recovery in response to stressors.

Perturbations in inflammatory pathways are associated with shortness of breath profiles in oncology patients receiving chemotherapy.

PURPOSE: One plausible mechanistic hypothesis is the potential contribution of inflammatory mechanisms to shortness of breath. This study was aimed to evaluate for associations between the occurrence of shortness of breath and perturbations in inflammatory pathways. METHODS: Patients with cancer reported the occurrence of shortness of breath six times over two cycles of chemotherapy. Latent class analysis was used to identify subgroups of patients with distinct shortness of breath occurrence profiles (i.e., none (70.5%), decreasing (8.2%), increasing (7.8%), high (13.5%)). Using an extreme phenotype approach, whole transcriptome differential gene expression and pathway impact analyses were performed to evaluate for perturbed signaling pathways associated with shortness of breath between the none and high classes. Two independent samples (RNA-sequencing (n = 293) and microarray (n = 295) methodologies) were evaluated. Fisher's combined probability method was used to combine these results to obtain a global test of the null hypothesis. In addition, an unweighted knowledge network was created using the specific pathway maps to evaluate for interconnections among these pathways. RESULTS: Twenty-nine Kyoto Encyclopedia of Genes and Genomes inflammatory signaling pathways were perturbed. The mitogen-activated protein kinase signaling pathway node had the highest closeness, betweenness, and degree scores. In addition, five common respiratory disease-related pathways, that may share mechanisms with cancer-related shortness of breath, were perturbed. CONCLUSIONS: Findings provide preliminary support for the hypothesis that inflammation contribute to the occurrence of shortness of breath in patients with cancer. In addition, the mechanisms that underlie shortness of breath in oncology patients may be similar to other respiratory diseases.

Stability and consistency of symptom clusters in younger versus older patients receiving chemotherapy.

BACKGROUND: By 2035, the number of newly diagnosed cancer cases will double and over 50% will be in older adults. Given this rapidly growing demographic, a need exists to understand how age influences oncology patients' symptom burden. The study purposes were to evaluate for differences in the occurrence, severity, and distress of 38 symptoms in younger (< 60 years) versus older (≥ 60 years) oncology patients undergoing chemotherapy and to evaluate for differences in the stability and consistency of symptom clusters across the two age groups. METHODS: A total of 1329 patients were dichotomized into the younger and older groups. Patients completed demographic and clinical questionnaires prior to the initiation of their second or third cycle of chemotherapy. A modified version of Memorial Symptom Assessment Scale was used to evaluate the occurrence, severity, and distress of 38 common symptoms associated with cancer and its treatment. Differences between the two age groups in demographic and clinical characteristics and ratings of occurrence, severity, and distress for the 38 symptoms were evaluated using parametric and nonparametric tests. Exploratory factor analyses were done within each age group to identify symptom clusters using symptom occurrence rates. RESULTS: Compared to the younger group (14.8 (± 7.0)), older adults reported a lower mean number of symptoms (12.9 (± 7.2)). Older patients experienced lower occurrence rates for almost 50% of the symptoms. Regarding symptom clusters, an eight-factor solution was selected for both age groups. Across the two age groups, the eight symptom clusters (i.e., physical and cognitive fatigue, respiratory, psychological, hormonal, chemotherapy-related toxicity, weight gain, gastrointestinal, epithelial) were stable. However, symptoms within the physical and cognitive, chemotherapy-related toxicity, and gastrointestinal clusters were not consistent across the age groups. CONCLUSIONS: To be able to provide tailored and effective symptom management interventions to older oncology patients, routine assessments of the core symptoms unique to the symptom clusters identified for this group warrants consideration. The underlying mechanism(s) for these inconsistencies in symptom burden is an important focus for future studies.

Chronic Pain and Pain Management in Older Adults: Protocol and Pilot Results.

BACKGROUND: Chronic pain occurs in 30% of older adults. This prevalence rate is expected to increase, given the growth in the older adult population and the associated growth of chronic conditions contributing to pain. No population-based studies have provided detailed, longitudinal information on the experience of chronic pain in older adults; the pharmacological and nonpharmacological strategies that older adults use to manage their chronic pain; and the effect of chronic pain on patient-reported outcomes. OBJECTIVES: This article aims to describe the protocol for a population-based, longitudinal study focused on understanding the experience of chronic pain in older adults. The objectives are to determine the prevalence and characteristics of chronic pain; identify the pharmacological and nonpharmacological pain treatments used; evaluate for longitudinal differences in biopsychosocial factors; and examine how pain types and pain trajectories affect important patient-reported outcomes. Also included are the results of a pilot study. METHODS: A population-based sample of approximately 1,888 older adults will be recruited from the National Opinion Research Center at the University of Chicago's AmeriSpeak Panel to complete surveys at three waves: enrollment (Wave 1), 6 months (Wave 2), and 12 months (Wave 3). To determine the feasibility, a pilot test of the enrollment survey was conducted among 123 older adults. RESULTS: In the pilot study, older adults with chronic pain reported a range of pain conditions, with osteoarthritis being the most common. Participants reported an array of pharmacological and nonpharmacological pain strategies. Compared to participants without chronic pain, those with chronic pain reported lower physical and cognitive function and poorer quality of life. Data collection for the primary, longitudinal study is ongoing. DISCUSSION: This project will be the first longitudinal population-based study to examine the experience and overall effect of chronic pain in older adults. Pilot study results provide evidence of the feasibility of study methods. Ultimately, this work will inform the development of tailored interventions for older patients targeted to decrease pain and improve function and quality of life.

Increases in stress and adverse childhood experiences are associated with the co-occurrence of anxiety and depression in oncology patients.

PURPOSE: Identify subgroups of patients with distinct joint anxiety AND depression profiles and evaluate for differences in demographic and clinical characteristics, as well as stress, resilience, and coping. DESIGN: Longitudinal study. PARTICIPANTS: Patients (n = 1328) receiving chemotherapy. METHODS: Measures of state anxiety and depression were done six times over two cycles of chemotherapy. All of the other measures were completed prior to second or third cycle of chemotherapy. Latent profile analysis was used to identify the distinct joint anxiety and depression profiles. FINDINGS: Three classes were identified (i.e. Low Anxiety and Low Depression (57.5%); Moderate Anxiety and Moderate Depression (33.7%), High Anxiety and High Depression (8.8%)). For all of the stress measures, a dose response effect was seen among the profiles. Two worst profiles reported higher occurrence rates for a number of adverse childhood experiences. IMPLICATIONS FOR PROVIDERS: Patients need referrals for stress reduction techniques and mental health and social services.

Identification of health-related quality of life profiles among long-term survivors of primary central nervous system tumors.

PURPOSE: We aimed to identify health-related quality of life (HRQOL) latent classes among primary central nervous system tumor (PCNST) long-term survivors (LTS) and to evaluate differences between classes in survivor sociodemographic characteristics, clinical characteristics, and symptoms to guide  the development of survivorship care programs tailored to unique class needs. METHODS: Data from 298 PCNST LTS reporting HRQOL on the EQ-5D-3L were analyzed using latent profile analysis. Correlations and independent group t-tests were performed to identify differences between identified HRQOL classes by sociodemographic, clinical characteristics, and symptoms. RESULTS: Sample mean age was 48 years, 54% were male, 82% Caucasian, 56% employed, 60% had a high-grade glioma, and 52% had a KPS ≥ 90. Two HRQOL classes, good (61%) and poor (39%), were identified. The good HRQOL class reported no problems with self-care and few problems with mobility or usual activities. Thirty-eight percent reported anxiety and depression and 21% pain. Over 94% of the poor HRQOL class had at least moderate problems with mobility and usual activities, and over 50% had pain, self-care issues, anxiety, and depression. Older age (φ = 0.21), unemployment (φ = 0.30), spine tumors (φ = 0.18), active treatment (φ = 0.20), tumor recurrence (φ = 0.28), and poorer KPS scores (φ = 0.61) were associated with membership in the poor HRQOL class. CONCLUSIONS: In the poor PCNST LTS HRQOL class, an overwhelming majority faced significant physical challenges, and the good HRQOL class experienced mood-related disturbance but limited physical challenges. These HRQOL profiles can be used to guide survivorship programs and tailored interventions.

Identification of distinct symptom profiles in patients with gynecologic cancers using a pre-specified symptom cluster.

PURPOSE: Pain, fatigue, sleep disturbance, and depression are four of the most common symptoms in patients with gynecologic cancer. The purposes were to identify subgroups of patients with distinct co-occurring pain, fatigue, sleep disturbance, and depression profiles (i.e., pre-specified symptom cluster) in a sample of patients with gynecologic cancer receiving chemotherapy and assess for differences in demographic and clinical characteristics, as well as the severity of other common symptoms and QOL outcomes among these subgroups. METHODS: Patients completed symptom questionnaires prior to their second or third cycle of chemotherapy. Latent profile analysis was used to identify subgroups of patients using the pre-specified symptom cluster. Parametric and nonparametric tests were used to evaluate for differences between the subgroups. RESULTS: In the sample of 233 patients, two distinct latent classes were identified (i.e., low (64.8%) and high (35.2%)) indicating lower and higher levels of symptom burden. Patients in high class were younger, had child care responsibilities, were unemployed, and had a lower annual income. In addition, these women had a higher body mass index, a higher comorbidity burden, and a lower functional status. Patients in the high class reported higher levels of anxiety, as well as lower levels of energy and cognitive function and poorer quality of life scores. CONCLUSIONS: This study identified a number of modifiable and non-modifiable risk factors associated with membership in the high class. Clinicians can use this information to refer patients to dieticians and physical therapists for tailored interventions.

Anxiety in oncology outpatients is associated with perturbations in pathways identified in anxiety focused network pharmacology research.

PURPOSE: Evaluate for perturbed signaling pathways associated with subgroups of patients with low versus high levels of state anxiety. These pathways were compared to the pathways identified across eight network pharmacology studies of the anxiolytic effect(s) of a variety of compounds. METHODS: Adult outpatients had a diagnosis of breast, gastrointestinal, gynecological, or lung cancer; had received chemotherapy within the preceding four weeks; and were scheduled to receive at least two additional cycles of chemotherapy. Latent profile analysis was used to identify subgroups of patients with distinct anxiety profiles based on Spielberger State Anxiety Inventory scores that were obtained six times over two cycles of chemotherapy. Blood samples were processed using RNA sequencing (i.e., RNA-seq sample, n = 244) and microarray (i.e., microarray sample; n = 256) technologies. Pathway perturbations were assessed using pathway impact analysis. Fisher's combined probability method was used to combine test results using a false discovery rate of 0.01. RESULTS: In the RNA-seq sample, 62.3% and 37.7% of the patients were in the low- and high-anxiety classes, respectively. In the microarray sample, 61.3% and 38.7% were in the low and high-anxiety classes, respectively. Forty-one perturbed signaling pathways were identified. Eight of these pathways were common to those identified in the network pharmacology studies. CONCLUSIONS: Findings increase our knowledge of the molecular mechanisms that underlie anxiety in patients receiving chemotherapy. This study provides initial insights into how anxiety in patients with cancer may share common mechanisms with anxiety in patients with other clinical conditions.

Quantitative Proteomic and Metabolomic Profiling Reveals Altered Mitochondrial Metabolism and Folate Biosynthesis Pathways in the Aging Drosophila Eye.

Aging is associated with increased risk of ocular disease, suggesting that age-associated molecular changes in the eye increase its vulnerability to damage. Although there are common pathways involved in aging at an organismal level, different tissues and cell types exhibit specific changes in gene expression with advanced age. Drosophila melanogaster is an established model system for studying aging and neurodegenerative disease that also provides a valuable model for studying age-associated ocular disease. Flies, like humans, exhibit decreased visual function and increased risk of retinal degeneration with age. Here, we profiled the aging proteome and metabolome of the Drosophila eye and compared these data with age-associated transcriptomic changes from both eyes and photoreceptors to identify alterations in pathways that could lead to age-related phenotypes in the eye. Of note, the proteomic and metabolomic changes observed in the aging eye are distinct from those observed in the head or whole fly, suggesting that tissue-specific changes in protein abundance and metabolism occur in the aging fly. Our integration of the proteomic, metabolomic, and transcriptomic data reveals that changes in metabolism, potentially due to decreases in availability of B vitamins, together with chronic activation of the immune response, may underpin many of the events observed in the aging Drosophila eye. We propose that targeting these pathways in the genetically tractable Drosophila system may help to identify potential neuroprotective approaches for neurodegenerative and age-related ocular diseases. Data are available via ProteomeXchange with identifier PXD027090.

Distinct Profiles of Morning and Evening Fatigue Co-Occurrence in Patients During Chemotherapy.

BACKGROUND: Morning and evening fatigue are distinct and distressing symptoms experienced during chemotherapy that demonstrate a large amount of interindividual variability. OBJECTIVES: The objectives of this study were to identify subgroups of patients with distinct morning and evening fatigue co-occurrence profiles and evaluate for differences among these subgroups in demographic, clinical, and symptom characteristics and quality of life. METHODS: Oncology patients ( n = 1,334) completed the Lee Fatigue Scale to self-report morning and evening fatigue, six times over two cycles of chemotherapy. Latent profile analysis was used to identify subgroups of patients with distinct morning and evening physical fatigue profiles. RESULTS: Four distinct morning and evening fatigue profiles were identified (i.e., Both Low, Low Morning + Moderate Evening, Both Moderate, and Both High). Compared to the Both Low profile, the Both High profile was significantly younger, less likely to be married or partnered, more likely to live alone, had a higher comorbidity burden, and lower functional status. The Both High profile had higher levels of anxiety, depressive symptoms, sleep disturbance, and pain and lower levels of quality of life. DISCUSSION: The variability in the morning and evening severity scores among the four profiles supports the hypothesis that morning and evening fatigue are distinct but related symptoms. Clinically meaningful levels of both morning and evening fatigue were reported by 50.4% of our sample, which suggests that the co-occurrence of these two symptoms is relatively common. Patients in Both Moderate and Both High profiles experienced an extremely high symptom burden that warrants ongoing assessments and aggressive symptom management interventions.

An Evaluation of the Multifactorial Model of Cancer-Related Cognitive Impairment.

BACKGROUND: Up to 45% of patients report cancer-related cognitive impairment (CRCI). A variety of characteristics are associated with the occurrence and/or severity of CRCI. However, an important gap in knowledge of risk factors for CRCI is the relative contribution of each factor. The multifactorial model of cancer-related cognitive impairment (MMCRCI) is a conceptual model of CRCI that can be used to evaluate the strength of relationships between various factors and CRCI. OBJECTIVES: The purpose of this study was to use structural regression methods to evaluate the MMCRCI using data from a large sample of outpatients receiving chemotherapy ( n = 1,343). Specifically, the relationships between self-reported CRCI and four MMCRCI concepts (i.e., social determinants of health, patient-specific factors, treatment factors, and co-occurring symptoms) were examined. The goals were to determine how well the four concepts predicted CRCI and determine the relative contribution of each concept to deficits in perceived cognitive function. METHODS: This study is part of a larger, longitudinal study that evaluated the symptom experience of oncology outpatients receiving chemotherapy. Adult patients were diagnosed with breast, gastrointestinal, gynecological, or lung cancer; had received chemotherapy within the preceding 4 weeks; were scheduled to receive at least two additional cycles of chemotherapy; were able to read, write, and understand English; and gave written informed consent. Self-reported CRCI was assessed using the attentional function index. Available study data were used to define the latent variables. RESULTS: On average, patients were 57 years of age, college educated, and with a mean Karnofsky Performance Status score of 80. Of the four concepts evaluated, whereas co-occurring symptoms explained the largest amount of variance in CRCI, treatment factors explained the smallest amount of variance. A simultaneous structural regression model that estimated the joint effect of the four exogenous latent variables on the CRCI latent variable was not significant. DISCUSSION: These findings suggest that testing individual components of the MMCRCI may provide useful information on the relationships among various risk factors, as well as refinements of the model. In terms of risk factors for CRCI, co-occurring symptoms may be more significant than treatment factors, patient-specific factors, and/or social determinants of health in patients receiving chemotherapy.

Metabolomic signature of spermatozoa established during holding time is responsible for differences in boar sperm freezability†.

Holding at room temperature is the first step in most boar semen cryopreservation protocols. It is well accepted that a holding time (HT) of 24 h increases sperm cryotolerance. However, the effect of HT on ejaculates with different freezability is not entirely clear. The aim of this study was to understand how HT influences spermatic and seminal plasma metabolite profiles of boar ejaculates and how these possible changes affect freezability. A total of 27 ejaculates were collected and extended to 1:1 (v: v) with BTS and split into two aliquots. The first aliquot was cryopreserved without HT (0 h), and the second was held at 17°C for 24 h before cryopreservation. Spermatozoa and seminal plasma were collected by centrifugation at two times, before HT (0 h) and after HT (24 h), and subsequently frozen until metabolite extraction and UPLC-MS analysis. After thawing, the semen samples were evaluated for kinetics, membrane integrity, mitochondrial potential, membrane lipid peroxidation, and fluidity. The ejaculates were then allocated into two phenotypes (good ejaculate freezers [GEF] and poor ejaculate freezers [PEF]) based on the percent reduction in sperm quality (%RSQ) as determined by the difference in total motility and membrane integrity between raw and post-thaw samples cryopreserved after 24 h of HT. The metabolic profile of the seminal plasma did not seem to influence ejaculate freezability, but that of the spermatozoa were markedly different between GEF and PEF. We identified a number of metabolic markers in the sperm cells (including inosine, hypoxanthine, creatine, ADP, niacinamide, spermine, and 2-methylbutyrylcarnitine) that were directly related to the improvement of ejaculate freezability during HT; these were components of metabolic pathways associated with energy production. Furthermore, PEF showed an upregulation in the arginine and proline as well as the glutathione metabolism pathways. These findings help to better understand the effect of HT on boar sperm freezability and propose prospective metabolic markers that may predict freezability; this has implications in both basic and applied sciences.

Symptom clusters in outpatients with cancer using different dimensions of the symptom experience.

PURPOSE: Relatively few studies have evaluated for symptom clusters across multiple dimensions. It is unknown whether the symptom dimension used to create symptom clusters influences the number and types of clusters that are identified. Study purposes were to describe ratings of occurrence, severity, and distress for 38 symptoms in a heterogeneous sample of oncology patients (n = 1329) undergoing chemotherapy; identify and compare the number and types of symptom clusters based on three dimensions (i.e., occurrence, severity, and distress); and identify common and distinct clusters. METHODS: A modified version of the Memorial Symptom Assessment Scale was used to assess the occurrence, severity, and distress ratings of 38 symptoms in the week prior to patients' next cycle of chemotherapy. Symptom clusters for each dimension were identified using exploratory factor analysis. RESULTS: Patients reported an average of 13.9 (±7.2) concurrent symptoms. Lack of energy was both the most common and severe symptom while "I don't look like myself" was the most distressing. Psychological, gastrointestinal, weight gain, respiratory, and hormonal clusters were identified across all three dimensions. Findings suggest that psychological, gastrointestinal, and weight gain clusters are common while respiratory and hormonal clusters are distinct. CONCLUSIONS: Psychological, gastrointestinal, weight gain, hormonal, and respiratory clusters are stable across occurrence, severity, and distress in oncology patients receiving chemotherapy. Given the stability of these clusters and the consistency of the symptoms across dimensions, the use of a single dimension to identify these clusters may be sufficient. However, comprehensive and disease-specific inventories need to be used to identify distinct clusters.

Impact of worst pain severity and morning fatigue profiles on oncology outpatients' symptom burden and quality of life.

PURPOSE: Pain and fatigue are common symptoms in oncology patients. In a sample of oncology outpatients receiving chemotherapy (n = 1342), the study purposes were to identify subgroups of patients with distinct worst pain and morning fatigue profiles and evaluate for differences among the subgroups in demographic and clinical characteristics, as well as the severity of common symptoms and quality of life (QOL) outcomes. METHODS: Oncology outpatients receiving chemotherapy (n = 1342) completed self-report questionnaires to assess pain and morning fatigue, a total of six times over two cycles of chemotherapy. Joint latent profile analysis was used to identify subgroups of patients with distinct pain and morning fatigue profiles. Differences among the classes were evaluated using parametric and non-parametric tests. RESULTS: Five distinct profiles were identified (no pain and low morning fatigue (27.6%), moderate pain and low morning fatigue (28.2%), moderate pain and morning fatigue (28.0%), moderate pain and increasing and decreasing morning fatigue (6.9%), severe pain and very high morning fatigue (9.3%)). Patients with the three worst profiles had clinically meaningful levels of depression and sleep disturbance and decrements in QOL. CONCLUSIONS: Over 44% of the sample had moderate to high levels of both pain and morning fatigue. Unrelieved pain may contribute to disturbed sleep which results in higher levels of morning fatigue. Clinicians need to assess for pain and fatigue, as well as sleep disturbance during chemotherapy.

Characteristics associated with inter-individual variability in financial distress in patients with breast cancer prior to and for 12 months following surgery.

PURPOSE: To evaluate for inter-individual differences in financial distress and identify demographic, clinical, and symptom characteristics associated with higher levels of financial distress. METHODS: Patients (n = 387) were enrolled prior to breast cancer surgery and followed for 12 months. Financial distress was measured using a 0 (no problem) to 10 (severe problem) numeric rating scale. Hierarchical linear modeling was used to evaluate for inter-individual differences in trajectories of financial distress and characteristics associated with financial distress at enrollment and over 12 months. RESULTS: Patients' mean age was 55.0 (± 11.7) years and the majority underwent breast conservation surgery (80.6%). Mean financial distress score prior to surgery was 3.3 (± 3.4; range 0 to 10). Unconditional model for financial distress demonstrated no significant changes over time (-0.006/month). Younger age, lower income, receipt of an axillary lymph node dissection and adjuvant chemotherapy, and lower attentional function were associated with higher preoperative levels of financial distress. CONCLUSION: Risk factors identified in this study can be used to inform clinicians regarding the need to initiate financial discussions and social work referrals for some patients. Additional clinical or system level interventions should be considered for vulnerable groups with these risk factors.

Distinct sleep disturbance and cognitive dysfunction profiles in oncology outpatients receiving chemotherapy.

PURPOSE: Sleep disturbance and cancer-related cognitive impairment (CRCI) are two of the most common symptoms reported by patients undergoing chemotherapy. Less is known about how these symptoms co-occur and their associated risk factors. Study purposes were to identify subgroups of patients with distinct sleep disturbance and CRCI profiles and evaluate for differences among the subgroups in demographic and clinical characteristics, symptom severity scores, and QOL outcomes. METHODS: A total of 1,333 oncology outpatients receiving chemotherapy completed self-report questionnaires on sleep disturbance and cognitive dysfunction six times over two cycles of chemotherapy. Latent profile analysis was used to identify distinct sleep disturbance AND cognitive dysfunction profiles. Parametric and non-parametric tests were used to evaluate for differences among the classes. RESULTS: Two distinct profiles were identified (i.e., Low = low levels of both sleep disturbance and cognitive dysfunction (53.5%); High = high levels of both sleep disturbance and cognitive dysfunction (45.5%)). Patients in the High class were younger, more likely to be female, had a lower functional status and a higher level of comorbidity. In addition, these patients had a higher symptom burden and a lower quality of life. CONCLUSION: Almost half of the patients undergoing chemotherapy experienced clinically meaningful levels of both symptoms. Of note, sleep disturbance is frequently overlooked by both clinicians and patients. Clinicians need to recommend cognitive rehabilitation and physical activity programs to decrease patients' symptom burden.

Repurposing FDA-approved sulphonamide carbonic anhydrase inhibitors for treatment of Neisseria gonorrhoeae.

Neisseria gonorrhoeae is a high-priority pathogen of concern due to the growing prevalence of resistance development against approved antibiotics. Herein, we report the anti-gonococcal activity of ethoxzolamide, the FDA-approved human carbonic anhydrase inhibitor. Ethoxzolamide displayed an MIC50, against a panel of N. gonorrhoeae isolates, of 0.125 µg/mL, 16-fold more potent than acetazolamide, although both molecules exhibited almost similar potency against the gonococcal carbonic anhydrase enzyme (NgCA) in vitro. Acetazolamide displayed an inhibition constant (Ki) versus NgCA of 74 nM, while Ethoxzolamide's Ki was estimated to 94 nM. Therefore, the increased anti-gonococcal potency of ethoxzolamide was attributed to its increased permeability in N. gonorrhoeae as compared to that of acetazolamide. Both drugs demonstrated bacteriostatic activity against N. gonorrhoeae, exhibited post-antibiotic effects up to 10 hours, and resistance was not observed against both. Taken together, these results indicate that acetazolamide and ethoxzolamide warrant further investigation for translation into effective anti-N. gonorrhoeae agents.

Loneliness and symptom burden in oncology patients during the COVID-19 pandemic.

BACKGROUND: Loneliness and social isolation are significant public health problems that are being exacerbated during the coronavirus disease 2019 pandemic. Little is known about the associations between loneliness and symptom burden in oncology patients before and during the pandemic. Study purposes include determining the prevalence of loneliness in a sample of oncology patients; evaluating for differences in demographic, clinical, and symptom characteristics between lonely and nonlonely patients; and determining which demographic, clinical, and symptom characteristics were associated with membership in the lonely group. METHODS: A convenience sample (n = 606) completed online surveys that evaluated the severity of loneliness, social isolation, and common symptoms (ie, anxiety, depression, fatigue, sleep disturbance, cognitive dysfunction, and pain) in oncology patients. Parametric and nonparametric tests were used to evaluate for differences in scores between the lonely and nonlonely groups. Logistic regression analysis was used to determine risk factors for membership in the loneliness group. RESULTS: Of the 606 patients, 53.0% were categorized in the lonely group. The lonely group reported higher levels of social isolation, as well as higher symptom severity scores for all of the symptoms evaluated. In the multivariate model, being unmarried, having higher levels of social isolation, as well as higher levels of anxiety and depressive symptoms were associated with membership in the lonely group. CONCLUSIONS: Study findings suggest that a significant number of oncology patients are experiencing loneliness, most likely as a result of mandate social distancing and isolation procedures. The symptom burden of these patients is extremely high and warrants clinical evaluation and interventions.