Ageing exacerbates ribosome pausing to disrupt cotranslational proteostasis.

Ageing is accompanied by a decline in cellular proteostasis, which underlies many age-related protein misfolding diseases1,2. Yet, how ageing impairs proteostasis remains unclear. As nascent polypeptides represent a substantial burden on the proteostasis network3, we hypothesized that altered translational efficiency during ageing could help to drive the collapse of proteostasis. Here we show that ageing alters the kinetics of translation elongation in both Caenorhabditis elegans and Saccharomyces cerevisiae. Ribosome pausing was exacerbated at specific positions in aged yeast and worms, including polybasic stretches, leading to increased ribosome collisions known to trigger ribosome-associated quality control (RQC)4-6. Notably, aged yeast cells exhibited impaired clearance and increased aggregation of RQC substrates, indicating that ageing overwhelms this pathway. Indeed, long-lived yeast mutants reduced age-dependent ribosome pausing, and extended lifespan correlated with greater flux through the RQC pathway. Further linking altered translation to proteostasis collapse, we found that nascent polypeptides exhibiting age-dependent ribosome pausing in C. elegans were strongly enriched among age-dependent protein aggregates. Notably, ageing increased the pausing and aggregation of many components of proteostasis, which could initiate a cycle of proteostasis collapse. We propose that increased ribosome pausing, leading to RQC overload and nascent polypeptide aggregation, critically contributes to proteostasis impairment and systemic decline during ageing.

Nascent Polypeptide Domain Topology and Elongation Rate Direct the Cotranslational Hierarchy of Hsp70 and TRiC/CCT.

Cotranslational protein folding requires assistance from elaborate ribosome-associated chaperone networks. It remains unclear how the changing information in a growing nascent polypeptide dictates the recruitment of functionally distinct chaperones. Here, we used ribosome profiling to define the principles governing the cotranslational action of the chaperones TRiC/CCT and Hsp70/Ssb. We show that these chaperones are sequentially recruited to specific sites within domain-encoding regions of select nascent polypeptides. Hsp70 associates first, binding select sites throughout domains, whereas TRiC associates later, upon the emergence of nearly complete domains that expose an unprotected hydrophobic surface. This suggests that transient topological properties of nascent folding intermediates drive sequential chaperone association. Moreover, cotranslational recruitment of both TRiC and Hsp70 correlated with translation elongation slowdowns. We propose that the temporal modulation of the nascent chain structural landscape is coordinated with local elongation rates to regulate the hierarchical action of Hsp70 and TRiC for cotranslational folding.

Prognostic value of near-infrared spectroscopy regional oxygen saturation and cerebrovascular reactivity index in acute traumatic neural injury: a CAnadian High-Resolution Traumatic Brain Injury (CAHR-TBI) Cohort Study.

BACKGROUND: Near-infrared spectroscopy regional cerebral oxygen saturation (rSO2) has gained interest as a raw parameter and as a basis for measuring cerebrovascular reactivity (CVR) due to its noninvasive nature and high spatial resolution. However, the prognostic utility of these parameters has not yet been determined. This study aimed to identify threshold values of rSO2 and rSO2-based CVR at which outcomes worsened following traumatic brain injury (TBI). METHODS: A retrospective multi-institutional cohort study was performed. The cohort included TBI patients treated in four adult intensive care units (ICU). The cerebral oxygen indices, COx (using rSO2 and cerebral perfusion pressure) as well as COx_a (using rSO2 and arterial blood pressure) were calculated for each patient. Grand mean thresholds along with exposure-based thresholds were determined utilizing sequential chi-squared analysis and univariate logistic regression, respectively. RESULTS: In the cohort of 129 patients, there was no identifiable threshold for raw rSO2 at which outcomes were found to worsen. For both COx and COx_a, an optimal grand mean threshold value of 0.2 was identified for both survival and favorable outcomes, while percent time above - 0.05 was uniformly found to have the best discriminative value. CONCLUSIONS: In this multi-institutional cohort study, raw rSO2was found to contain no significant prognostic information. However, rSO2-based indices of CVR, COx and COx_a, were found to have a uniform grand mean threshold of 0.2 and exposure-based threshold of - 0.05, above which clinical outcomes markedly worsened. This study lays the groundwork to transition to less invasive means of continuously measuring CVR.

Non-Invasive Estimation of Intracranial Pressure-Derived Cerebrovascular Reactivity Using Near-Infrared Spectroscopy Sensor Technology in Acute Neural Injury: A Time-Series Analysis.

The contemporary monitoring of cerebrovascular reactivity (CVR) relies on invasive intracranial pressure (ICP) monitoring which limits its application. Interest is shifting towards near-infrared spectroscopic regional cerebral oxygen saturation (rSO2)-based indices of CVR which are less invasive and have improved spatial resolution. This study aims to examine and model the relationship between ICP and rSO2-based indices of CVR. Through a retrospective cohort study of prospectively collected physiologic data in moderate to severe traumatic brain injury (TBI) patients, linear mixed effects modeling techniques, augmented with time-series analysis, were utilized to evaluate the ability of rSO2-based indices of CVR to model ICP-based indices. It was found that rSO2-based indices of CVR had a statistically significant linear relationship with ICP-based indices, even when the hierarchical and autocorrelative nature of the data was accounted for. This strengthens the body of literature indicating the validity of rSO2-based indices of CVR and potential greatly expands the scope of CVR monitoring.

Time-Series Modeling and Forecasting of Cerebral Pressure-Flow Physiology: A Scoping Systematic Review of the Human and Animal Literature.

The modeling and forecasting of cerebral pressure-flow dynamics in the time-frequency domain have promising implications for veterinary and human life sciences research, enhancing clinical care by predicting cerebral blood flow (CBF)/perfusion, nutrient delivery, and intracranial pressure (ICP)/compliance behavior in advance. Despite its potential, the literature lacks coherence regarding the optimal model type, structure, data streams, and performance. This systematic scoping review comprehensively examines the current landscape of cerebral physiological time-series modeling and forecasting. It focuses on temporally resolved cerebral pressure-flow and oxygen delivery data streams obtained from invasive/non-invasive cerebral sensors. A thorough search of databases identified 88 studies for evaluation, covering diverse cerebral physiologic signals from healthy volunteers, patients with various conditions, and animal subjects. Methodologies range from traditional statistical time-series analysis to innovative machine learning algorithms. A total of 30 studies in healthy cohorts and 23 studies in patient cohorts with traumatic brain injury (TBI) concentrated on modeling CBFv and predicting ICP, respectively. Animal studies exclusively analyzed CBF/CBFv. Of the 88 studies, 65 predominantly used traditional statistical time-series analysis, with transfer function analysis (TFA), wavelet analysis, and autoregressive (AR) models being prominent. Among machine learning algorithms, support vector machine (SVM) was widely utilized, and decision trees showed promise, especially in ICP prediction. Nonlinear models and multi-input models were prevalent, emphasizing the significance of multivariate modeling and forecasting. This review clarifies knowledge gaps and sets the stage for future research to advance cerebral physiologic signal analysis, benefiting neurocritical care applications.

Optimal bispectral index exists in healthy patients undergoing general anesthesia: A validation study.

PURPOSE: Continuous cerebrovascular reactivity monitoring in both neurocritical and intra-operative care has gained extensive interest in recent years, as it has documented associations with long-term outcomes (in neurocritical care populations) and cognitive outcomes (in operative cohorts). This has sparked further interest into the exploration and evaluation of methods to achieve an optimal cerebrovascular reactivity measure, where the individual patient is exposed to the lowest insult burden of impaired cerebrovascular reactivity. Recent literature has documented, in neural injury populations, the presence of a potential optimal sedation level in neurocritical care, based on the relationship between cerebrovascular reactivity and quantitative depth of sedation (using bispectral index (BIS)) - termed BISopt. The presence of this measure outside of neural injury patients has yet to be proven. METHODS: We explore the relationship between BIS and continuous cerebrovascular reactivity in two cohorts: (A) healthy population undergoing elective spinal surgery under general anesthesia, and (B) healthy volunteer cohort of awake controls. RESULTS: We demonstrate the presence of BISopt in the general anesthesia population (96% of patients), and its absence in awake controls, providing preliminary validation of its existence outside of neural injury populations. Furthermore, we found BIS to be sufficiently separate from overall systemic blood pressure, this indicates that they impact different pathophysiological phenomena to mediate cerebrovascular reactivity. CONCLUSIONS: Findings here carry implications for the adaptation of the individualized physiologic BISopt concept to non-neural injury populations, both within critical care and the operative theater. However, this work is currently exploratory, and future work is required.

Mediators of physical activity outcomes in a peer-led intervention for breast cancer survivors.

OBJECTIVES: Physical activity (PA) adoption can reduce treatment-related sequelae of breast cancer. Peer-led PA interventions are a promising and relatively inexpensive approach to scaling up interventions. The current study seeks to identify mediators of PA change amongst cancer survivors enrolled in a peer-led behavior change intervention. The study team partnered with the American Cancer Society's Reach to Recovery program (RTR) whose volunteers' provided information and support to breast cancer survivors. METHODS: Participants were 76 survivors (mean age 55.6 years, 1.1 years since diagnosis) who were randomized to PA Plus RTR (12-week PA telephone counseling delivered by RTR volunteers) or contact control. Data was collected on PA (self-reported and objectively measured) and potential mediators (self-efficacy, exercise decisional balance [ratio of the pros/advantages to the cons/disadvantages] and social support) at baseline and 12 weeks. Using a multiple mediation approach with bootstrapped standard errors, we examined mediators of the intervention effect on PA outcomes. RESULTS: Compared to control, PA Plus RTR participants had higher mean self-efficacy, lower decisional balance cons and social support at 12 weeks controlling for baseline. Higher mean self-efficacy was associated with greater minutes of self-reported PA, whereas higher decisional balance pros was associated with higher objectively measured PA at 12 weeks. There were significant indirect effects of self-efficacy on self-reported PA and decisional balance on objectively measured PA. CONCLUSIONS: PA Plus RTR increased self-reported and objectively measured PA by changing theoretical constructs hypothesized to be associated with behavior change. Peers delivering a PA intervention should focus on increasing survivors' self-efficacy for exercise especially in challenging circumstances such as being on vacation, and also help to overcome disadvantages of exercise such as taking time away from family.

Cancer treatment and survivorship statistics, 2016.

The number of cancer survivors continues to increase because of both advances in early detection and treatment and the aging and growth of the population. For the public health community to better serve these survivors, the American Cancer Society and the National Cancer Institute collaborate to estimate the number of current and future cancer survivors using data from the Surveillance, Epidemiology, and End Results cancer registries. In addition, current treatment patterns for the most prevalent cancer types are presented based on information in the National Cancer Data Base and treatment-related side effects are briefly described. More than 15.5 million Americans with a history of cancer were alive on January 1, 2016, and this number is projected to reach more than 20 million by January 1, 2026. The 3 most prevalent cancers are prostate (3,306,760), colon and rectum (724,690), and melanoma (614,460) among males and breast (3,560,570), uterine corpus (757,190), and colon and rectum (727,350) among females. More than one-half (56%) of survivors were diagnosed within the past 10 years, and almost one-half (47%) are aged 70 years or older. People with a history of cancer have unique medical and psychosocial needs that require proactive assessment and management by primary care providers. Although there are a growing number of tools that can assist patients, caregivers, and clinicians in navigating the various phases of cancer survivorship, further evidence-based resources are needed to optimize care. CA Cancer J Clin 2016;66:271-289. © 2016 American Cancer Society.

American Cancer Society Head and Neck Cancer Survivorship Care Guideline.

Answer questions and earn CME/CNE The American Cancer Society Head and Neck Cancer Survivorship Care Guideline was developed to assist primary care clinicians and other health practitioners with the care of head and neck cancer survivors, including monitoring for recurrence, screening for second primary cancers, assessment and management of long-term and late effects, health promotion, and care coordination. A systematic review of the literature was conducted using PubMed through April 2015, and a multidisciplinary expert workgroup with expertise in primary care, dentistry, surgical oncology, medical oncology, radiation oncology, clinical psychology, speech-language pathology, physical medicine and rehabilitation, the patient perspective, and nursing was assembled. While the guideline is based on a systematic review of the current literature, most evidence is not sufficient to warrant a strong recommendation. Therefore, recommendations should be viewed as consensus-based management strategies for assisting patients with physical and psychosocial effects of head and neck cancer and its treatment. CA Cancer J Clin 2016;66:203-239. © 2016 American Cancer Society.

Associations between intracranial pressure thresholds and multimodal monitoring in acute traumatic neural injury: a scoping review.

BACKGROUND: Current moderate/severe traumatic brain injury (TBI) guidelines suggest the use of an intracranial pressure (ICP) treatment threshold of 20 mmHg or 22 mmHg. Over the past decade, the use of various cerebral physiology monitoring devices has been incorporated into neurocritical care practice and termed "multimodal monitoring." Such modalities include those that monitor systemic hemodynamics, systemic and brain oxygenation, cerebral blood flow (CBF), cerebral autoregulation, electrophysiology, and cerebral metabolism. Given that the relationship between ICP and outcomes is not yet entirely understood, a comprehensive review of the literature on the associations between ICP thresholds and multimodal monitoring is still needed. METHODS: We conducted a scoping review of the literature for studies that present an objective statistical association between ICP above/below threshold and any multimodal monitoring variable. MEDLINE, BIOSIS, Cochrane library, EMBASE, Global Health, and SCOPUS were searched from inception to July 2022 for relevant articles. Full-length, peer-reviewed, original works with a sample size of ≥50 moderate-severe TBI patients were included in this study. RESULTS: A total of 13 articles were deemed eligible for final inclusion. The included articles were significantly heterogenous in terms of their designs, demographics, and results, making it difficult to draw any definitive conclusions. No literature describing the association between guideline-based ICP thresholds and measures of brain electrophysiology, cerebral metabolism, or direct metrics of CBF was found. CONCLUSION: There is currently little literature that presents objective statistical associations between ICP thresholds and multimodal monitoring physiology. However, overall, the literature indicates that having ICP above guideline based thresholds is associated with increased blood pressure, increased cardiac decoupling, reduced parenchymal brain oxygen tension, and impaired cerebral autoregulation, with no association with CBF velocity within the therapeutic range of ICP. There was insufficient literature to comment on other multimodal monitoring measures.

American Cancer Society Colorectal Cancer Survivorship Care Guidelines.

Colorectal cancer (CRC) is the third most common cancer and third leading cause of cancer death in both men and women and second leading cause of cancer death when men and women are combined in the United States (US). Almost two-thirds of CRC survivors are living 5 years after diagnosis. Considering the recent decline in both incidence and mortality, the prevalence of CRC survivors is likely to increase dramatically over the coming decades with the increase in rates of CRC screening, further advances in early detection and treatment and the aging and growth of the US population. Survivors are at risk for a CRC recurrence, a new primary CRC, other cancers, as well as both short-term and long-term adverse effects of the CRC and the modalities used to treat it. CRC survivors may also have psychological, reproductive, genetic, social, and employment concerns after treatment. Communication and coordination of care between the treating oncologist and the primary care clinician is critical to effectively and efficiently manage the long-term care of CRC survivors. The guidelines in this article are intended to assist primary care clinicians in delivering risk-based health care for CRC survivors who have completed active therapy.

Movement markers of schizophrenia: a detailed analysis of patients' gait patterns.

Motor abnormalities occur in the majority of persons with schizophrenia but are generally neglected in clinical care. Psychiatric diagnostics fail to include quantifiable motor variables and few assessment tools examine full-body movement. We assessed full-body movement during gait of 20 patients and 20 controls with motion capture technology, symptom load (PANSS, BPRS) and Neurological Soft Signs (NSS). In a data-driven analysis, participants' motion patterns were quantified and compared between groups. Resulting movement markers (MM) were correlated with the clinical assessment. We identified 16 quantifiable MM of schizophrenia. While walking, patients and controls display significant differences in movement patterns related to posture, velocity, regularity of gait as well as sway, flexibility and integration of body parts. Specifically, the adjustment of body sides, limbs and movement direction were affected. The MM remain significant when controlling for medication load. They are systematically related to NSS. Results add assessment tools, analysis methods as well as theory-independent MM to the growing body of research on motor abnormalities in schizophrenia.

Association between cerebrovascular reactivity in adult traumatic brain injury and improvement in patient outcome over time: an exploratory analysis.

BACKGROUND: Impaired cerebrovascular reactivity following moderate/severe traumatic brain injury (TBI) has emerged as a key potential driver of morbidity and mortality. However, the major contributions to the literature so far have been solely focused on single point measures of long-term outcome. Therefore, it remains unknown whether cerebrovascular reactivity impairment, during the acute phase of TBI, is associated with failure to improve in outcome across time. METHODS: Cerebrovascular reactivity was measured using three intracranial pressure-based surrogate metrics. For each patient, % time spent above various literature-defined thresholds was calculated. Patients were dichotomized based on outcome transition into Improved vs Not Improved between 1 and 3 months, 3 and 6 months, and 1 and 6 months, based on the Glasgow Outcome Scale-Extended (GOSE). Univariate and multivariable logistic regression analyses were performed, adjusting for the International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) variables. RESULTS: Seventy-eight patients from the Winnipeg Acute TBI Database were included in this study. On univariate logistic regression analysis, higher % time with cerebrovascular reactivity metrics above clinically defined thresholds was associated with a lack of clinical improvement between 1 and 3 months and 1 and 6 months post injury (p < 0.05). These relationships held true on multivariable logistic regression analysis. CONCLUSION: Our study demonstrates that impaired cerebrovascular reactivity, during the acute phase of TBI, is associated with failure to improve clinically over time. These preliminary findings highlight the significance that cerebrovascular reactivity monitoring carries in outcome recovery association in moderate/severe TBI.

Cancer treatment and survivorship statistics, 2014.

The number of cancer survivors continues to increase due to the aging and growth of the population and improvements in early detection and treatment. In order for the public health community to better serve these survivors, the American Cancer Society and the National Cancer Institute collaborated to estimate the number of current and future cancer survivors using data from the Surveillance, Epidemiology, and End Results (SEER) program registries. In addition, current treatment patterns for the most common cancer types are described based on information in the National Cancer Data Base and the SEER and SEER-Medicare linked databases; treatment-related side effects are also briefly described. Nearly 14.5 million Americans with a history of cancer were alive on January 1, 2014; by January 1, 2024, that number will increase to nearly 19 million. The 3 most common prevalent cancers among males are prostate cancer (43%), colorectal cancer (9%), and melanoma (8%), and those among females are cancers of the breast (41%), uterine corpus (8%), and colon and rectum (8%). The age distribution of survivors varies substantially by cancer type. For example, the majority of prostate cancer survivors (62%) are aged 70 years or older, whereas less than one-third (32%) of melanoma survivors are in this older age group. It is important for clinicians to understand the unique medical and psychosocial needs of cancer survivors and to proactively assess and manage these issues. There are a growing number of resources that can assist patients, caregivers, and health care providers in navigating the various phases of cancer survivorship.

Impact of caregivers' negative response to cancer on long-term survivors' quality of life.

Cancer survivors' quality of life (QoL) is consistently shown to be positively impacted by social support from family and friends, including informal caregivers. In contrast, a loved one's negative response to cancer can diminish survivors' QoL, and these negative responses can be more impactful than supportive behaviors. Nonetheless, negative caregiver response has not been extensively researched, and few studies have explored the potential interaction of negative caregiver response and perceived social support on survivors' QoL. Therefore, we examined direct effects of perceived negative caregiver response, and the potential moderating role of social support, on QoL in a population-based sample of cancer survivors (N = 7543) using generalized linear models. Findings indicate that survivors who rated their caregiver's response to their cancer diagnosis more negatively reported worse physical and mental health, even up to 10 years after their initial cancer diagnosis. Perceived social support was not significantly associated with physical health, but it was positively associated with mental health. However, social support was not shown to moderate the relationship between negative caregiver response and mental health. Findings suggest that positive support from others within a survivor's social network may not be enough to attenuate the negative effects of their primary caregiver's unsupportive behaviors. Accordingly, cancer survivorship research and practice must consider the critical role that negative caregiver responses have on survivors' QoL and develop strategies that focus on the survivor-caregiver dynamic.

The stop-and-go traffic regulating protein biogenesis: How translation kinetics controls proteostasis.

Generating a functional proteome requires the ribosome to carefully regulate disparate co-translational processes that determine the fate of nascent polypeptides. With protein synthesis being energetically expensive, the ribosome must balance the costs of efficiently making a protein with those of properly folding it. Emerging as a primary means of regulating this trade-off is the nonuniform rate of translation elongation that defines translation kinetics. The varying speeds with which the ribosome progresses along a transcript have been implicated in several aspects of protein biogenesis, including co-translational protein folding and translational fidelity, as well as gene expression by mediating mRNA decay and protein quality control pathways. The optimal translation kinetics required to efficiently execute these processes can be distinct. Thus, the ribosome is tasked with tightly regulating translation kinetics to balance these processes while maintaining adaptability for changing cellular conditions. In this review, we first discuss the regulatory role of translation elongation in protein biogenesis and what factors influence elongation kinetics. We then describe how changes in translation kinetics signal downstream pathways that dictate the fate of nascent polypeptides. By regulating these pathways, the kinetics of translation elongation has emerged as a critical tool for driving gene expression and maintaining proteostasis through varied mechanisms, including nascent chain folding and binding different ribosome-associated machinery. Indeed, a growing number of examples demonstrate the important role of local changes in elongation kinetics in modulating the pathophysiology of human disease.

Examining the impact of cancer on survivors' religious faith: A report from the American Cancer Society study of cancer survivors-I.

OBJECTIVES: The impact of religion/spirituality (R/S) on cancer outcomes, including health-related quality of life (HRQoL), has been the topic of much investigation. Reports of the opposite, that is, the impact of cancer on R/S and associations with HRQoL, are few. The current study sought to explore the positive and negative impacts of cancer on the religious faith of survivors as well as the associations of such impacts with HRQoL. METHODS: Participants included 2309 9-year survivors of cancer from the American Cancer Society's Studies of Cancer Survivors-I. The impact of cancer on R/S was measured using items from the Patient-Reported Outcomes Measurement Information System (PROMIS) psychosocial impact of illness-faith, and HRQoL was measured with the 12-item short form (SF-12). Hierarchical regressions were used to examine the impact of cancer on R/S controlling for medical and demographic covariates. RESULTS: Consistent with hypotheses, the majority of survivors (70%) reported that cancer had a positive impact on religious faith, while the negative impact of cancer on religious faith was relatively rare (17%). In multivariable models, the negative impact of cancer on faith was associated with poorer HRQoL, both mental and physical, while the positive impact of cancer on faith was associated with greater mental well-being. CONCLUSIONS: Cancer has a negative impact on religious faith for a minority of survivors. However, when it is reported, such negative impact is indicative of poorer mental and physical well-being. As such, it is important to identify those survivors at risk early in survivorship and provide support and intervention as needed.

Advancing survivorship care through the National Cancer Survivorship Resource Center: developing American Cancer Society guidelines for primary care providers.

The National Cancer Survivorship Resource Center (The Survivorship Center) began in 2010 as a collaboration between the American Cancer Society and the George Washington University Cancer Institute and was funded by the Centers for Disease Control and Prevention. The Survivorship Center aims to improve the overall health and quality of life of posttreatment cancer survivors. One key to addressing the needs of this ever-growing population is to develop clinical follow-up care guidelines that emphasize not only the importance of surveillance for cancer recurrence, but also address the assessment and management of the physical and psychosocial long-term and late effects that may result from having cancer and undergoing cancer treatment as well as highlight the importance of healthy behaviors that can reduce the risk of cancer recurrence, second primary cancers, and other chronic diseases. Currently, The Survivorship Center is coordinating the work of experts in oncology, primary care, and other health care professions to develop follow-up care guidelines for 10 priority cancer sites.

Effectiveness trial of an online self-help intervention for sexual problems after cancer.

Sexual dysfunction affects over 60% of cancer survivors. Internet interventions have improved sexual function, but with considerable clinician guidance, restricting scalability. This pragmatic trial evaluated an online, self-help intervention. As with many unguided digital interventions, attrition was high. Given low numbers in other groups, this paper focuses on 30% of female patient participants who completed 3-month questionnaires and visited the intervention site (N = 60). Benefits included increased sexually active individuals at follow-up (p < 0.001, Effect size = 0.54), improved sexual function (p < 0.001, Effect size = -0.76, N = 41), and increased use of sexual aids (p = 0.01, Effect size=-0.14, N = 58). The intervention has been revised to improve patient engagement.

Unintentional weight loss, its associated burden, and perceived weight status in people with cancer.

PURPOSE: Unintentional weight loss (UWL) is a prevalent problem in people with cancer and is associated with poorer psychosocial outcomes. A gap exists in understanding whether and how perceived and/or weight status impacts experiences of UWL. Thus, we sought to examine subjective experiences of UWL in people with cancer, and whether perceived and/or actual weight status impacts these experiences. METHODS: Participants were recruited through Cancer Support Community's Cancer Experience Registry® and related networks. Participants completed an online survey that included the FAACT Anorexia-Cachexia subscale, and 19 items that captured six themes related to "beliefs and concerns" (positive beliefs, psychosocial impact, physical impact, cancer outcomes, self-esteem, relationships with others). Perceived weight status (PWS) was assessed using a single item. Body mass index (BMI) was calculated using self-reported weight and height measurements. RESULTS: Of 326 respondents, 114 reported experiencing UWL. Over one-third misperceived their weight, with 29% perceiving weight status as below their BMI status. UWL in those with perceived weight status of overweight/obese was associated with positive beliefs. However, being underweight by BMI or perceiving oneself as underweight were both associated with greater concerns about weight loss. Perceived weight status of underweight compared to normal or overweight/obese weight status was associated with poorer psychosocial well-being, personal control, self-esteem, and relationships with others. CONCLUSION: In people with cancer, perceived weight status, rather than BMI, had greater impact on negative "beliefs and concerns" about UWL. Findings suggest assessment of both perceived and actual BMI to address the impact of UWL on psychosocial wellbeing.