Dyadic Investigation of Posttraumatic Stress Symptoms and Daily Sleep Health in Patients with Cancer and their Caregivers.

OBJECTIVE: Cancer can be a traumatic experience affecting multidimensional aspects of sleep among patients and caregivers. This study examined the differential associations of cancer-related post-traumatic stress symptoms (PTSS) with various sleep markers in this population. METHODS: Patients newly diagnosed with colorectal cancer (n = 138, mean age = 56.93 years, 31.88% female, 60.14% Hispanic, 6.53 months post-diagnosis) and their sleep-partner caregivers (n = 138, mean age = 55.32 years, 68.12% female, 57.97% Hispanic) completed questionnaires assessing the four PTSS clusters (intrusion, avoidance, alterations in arousal and reactivity, negative alterations in cognitions and mood). Participants also completed daily sleep diaries for 14 consecutive days, from which sleep onset latency (SOL), wake after sleep onset (WASO), and sleep duration were derived. RESULTS: Actor-partner interdependence model revealed that caregivers' greater alterations in arousal and reactivity were associated with their own longer SOL (b = 14.54, p < .001) and their patients' longer sleep duration (b = 0.47, p = .040), whereas patients' arousal and reactivity were associated with their caregivers' shorter SOL (b = -8.34, p = .047) and WASO (b = -8.12, p = .019). Patients' and caregivers' greater negative alterations in cognitions and mood were associated with patients' longer SOL (b = 8.89, p = .016) and shorter sleep duration (b = -0.40, p = .038), respectively. Caregivers' greater intrusion was related to their own shorter SOL (b = -10.92, p = .002). CONCLUSIONS: The four PTSS clusters, particularly arousal and reactivity and negative cognitions and mood, have distinct associations with sleep markers individually and dyadically in patients and caregivers affected by cancer. Investigations of psychosocial and biobehavioral pathways underlying these relations are warranted. Tailored trauma treatments and sleep interventions may improve the well-being of this population.

Dyadic sleep intervention for adult patients with cancer and their sleep-partner caregivers: A feasibility study.

OBJECTIVES: Sleep disturbances are common among adult patients with cancer and their caregivers. To our knowledge, no sleep intervention to date has been designed to be provided to both patients with cancer and their caregivers simultaneously. This single-arm study aimed to pilot test the feasibility and acceptability, and to illustrate the preliminary efficacy on sleep efficiency of the newly developed dyadic sleep intervention, My Sleep Our Sleep (MSOS: NCT04712604). METHODS: Adult patients who were newly diagnosed with a gastrointestinal (GI) cancer and their sleep-partner caregivers (n = 20 persons: 10 dyads, 64 years old, 60% female patients, 20% Hispanic, 28 years relationship duration), both of whom had at least mild levels of sleep disturbance (Pittsburgh Sleep Quality Index [PSQI] ≥ 5) participated in this study. MSOS intervention consists of four 1-hour weekly sessions delivered using Zoom to the patient-caregiver dyad together. RESULTS: We were able to enroll 92.9% of the eligible and screened patient-caregiver dyads within 4 months. Participants reported high satisfaction in 8 domains (average 4.76 on a 1-5 rating). All participants agreed that the number of sessions, interval (weekly), and delivery mode (Zoom) were optimal. Participants also preferred attending the intervention with their partners. Both patients and caregivers showed improvement in sleep efficiency after completing the MSOS intervention: Cohen's d = 1.04 and 1.47, respectively. SIGNIFICANCE OF RESULTS: Results support the feasibility and acceptability, as well as provide the preliminary efficacy of MSOS for adult patients with GI cancer and their sleep-partner caregivers. Findings suggest the need for more rigorous controlled trial designs for further efficacy testing of MSOS intervention.

Working hours, social engagement, and depressive symptoms: an extended work-life balance for older adults.

BACKGROUND: In recent years, researchers have been examining the impact of work-life balance (WLB) on mental health, considering it as a potential risk factor. However, it remains unclear whether the traditional understanding of WLB applies to older adults who worked for fewer hours before full retirement and whose children are likely to be independent adults. Therefore, this study aims to propose a modified form of WLB specifically for older adults. Within this context, we hypothesize that an optimum balance between working hours and social engagement protects against depressive symptoms among older adults. METHOD: We conducted an analysis using data on 5,751 Korean adults older than 55 years from the Korean Longitudinal Study of Aging 2016. Multivariate logistic regression analysis was used to evaluate the relationships among working hours, social engagement, and depressive symptoms. RESULTS: Older adults who worked fewer than 35 h per week were less likely to experience depressive symptoms than were non-working older adults and those working 35 h or more per week. Additionally, older adults with a high level of informal social participation, thus occurring almost every day or two to three times per week, were less likely to experience depressive symptoms than were those with a low level of such participation (once a month or less). Furthermore, depressive symptoms were less frequent among those who worked fewer than 35 h per week and engaged in a high level of informal social participation compared to non-working older individuals and those with a low level of informal social participation. CONCLUSIONS: Maintaining an optimal number of working hours and degree of social engagement are necessary to minimize the risk of depressive symptoms in older adults. Based on these findings, we suggest that fulfillment for work and life and their balance are important for older adults and propose work-life fulfillment balance.

Clinical Correlates of Incidental Probable Benign Pulmonary Nodules with Diameters Less than 8 mm in a Healthy Korean Cohort: A Retrospective Study.

Incidental pulmonary nodules detected via computed tomography (CT) are usually small, solid nodules (diameters less than 8 mm) that are likely benign and are difficult to biopsy. Additional features of the benignity of these small nodules may help determine the need and periodicity of further follow-up and should be identified. This study was conducted to examine the clinical factors associated with benign solid pulmonary nodules measuring less than 8 mm in diameter. This retrospective study enrolled participants who underwent low-dose chest CT scans for 3 consecutive years during routine health check-ups at a university hospital in Korea. We chose a 2-year study period to ensure that the nodule(s) were benign, which meant there was no interval change over this period. Participants were stratified into two groups: no nodule (n = 56) and nodule(s) (n = 355). Multivariable logistic regression analyses were performed to explore associations (adjusted odds ratio [aOR], 95% confidence interval [CI], p-value) between variables and nodule(s). In this study cohort, elevated levels of low-density lipoprotein (LDL) cholesterol were positively associated factors with the presence of benign pulmonary nodule(s) (aOR: 1.10, 95% CI:1.00-1.20, p = 0.0488), whereas current cigarette smoking was negatively associated with nodules (aOR: 0.26, 95% CI: 0.08-0.81, p = 0.0202). Therefore, an elevated LDL cholesterol level was the only factor that was positively associated with the presence of benign small pulmonary nodules.

Anaerobic pathogens associated with OSA may contribute to pathophysiology via amino-acid depletion.

BACKGROUND: The human microbiome is linked to multiple metabolic disorders such as obesity and diabetes. Obstructive sleep apnoea (OSA) is a common sleep disorder with several metabolic risk factors. We investigated the associations between the gut microbiome composition and function, and measures of OSA severity in participants from a prospective community-based cohort study: the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). METHODS: Bacterial-Wide Association Analysis (BWAS) of gut microbiome measured via metagenomics with OSA measures was performed adjusting for clinical, lifestyle and co-morbidities. This was followed by functional analysis of the OSA-enriched bacteria. We utilized additional metabolomic and transcriptomic associations to suggest possible mechanisms explaining the microbiome effects on OSA. FINDINGS: Several uncommon anaerobic human pathogens were associated with OSA severity. These belong to the Lachnospira, Actinomyces, Kingella and Eubacterium genera. Functional analysis revealed enrichment in 49 processes including many anaerobic-related ones. Severe OSA was associated with the depletion of the amino acids glycine and glutamine in the blood, yet neither diet nor gene expression revealed any changes in the production or consumption of these amino acids. INTERPRETATION: We show anaerobic bacterial communities to be a novel component of OSA pathophysiology. These are established in the oxygen-poor environments characteristic of OSA. We hypothesize that these bacteria deplete certain amino acids required for normal human homeostasis and muscle tone, contributing to OSA phenotypes. Future work should test this hypothesis as well as consider diagnostics via anaerobic bacteria detection and possible interventions via antibiotics and amino-acid supplementation. FUNDING: Described in methods.

Correlates of posttraumatic stress in cancer patients and their family caregivers across two years following diagnosis.

OBJECTIVE: To examine risk-factors of cancer-related PTSS in the 2-years post-diagnosis in adult colorectal cancer patients and caregivers. METHODS: Patients with colorectal cancer and their caregivers (N = 130 dyads) self-reported sociodemographic, psychosocial, and medical factors at diagnosis/treatment initiation (T1), at 1- (T2), and 2-year (T3) post-diagnosis. Cancer-related PTSS were assessed, and path analysis examined associations between proposed correlates and PTSS. RESULTS: Among patients, higher neuroticism and greater physical symptom distress were concurrently associated with higher PTSS (Bs ≥ 0.10, ps ≤ 0.02); greater physical symptom distress at T1 and greater social support at T2 were associated with higher PTSS at T3 (Bs ≥ 0.37, ps ≤ 0.04). Among caregivers, female gender, higher neuroticism (Bs ≥ 0.12, ps < 0.01), and lower social support (Bs  ≤ -0.24, ps ≤ 0.02) were associated with higher concurrent PTSS; lower patient physical symptom distress and social support at T1 (Bs  ≤ -0.27, ps ≤ 0.03) and longer hours spent caregiving at T2 (B = 0.03, p = 0.05) were associated with higher PTSS at T3. CONCLUSIONS: Findings identify cancer-specific risk factors (physical symptoms, hours caregiving), in addition to established risk factors (female, neuroticism, social support) in non-medical populations. The identified subgroups should receive ongoing screening and psychosocial referral for cancer-related PTSS.

Healthcare providers' perceptions about the unmet needs of their patients with cancer across healthcare systems: results of the International Psycho-Oncology Society survivorship survey.

OBJECTIVE: Systematic understanding of patients' unmet needs is essential for providing effective supportive care. This study sought to compare the unmet needs of patients with cancer identified by health care providers (HCPs) among four major healthcare systems. METHODS: HCPs (n = 247) participated in the International Psycho-Oncology Society (IPOS) Survivorship Online Survey, evaluating their patients' unmet needs. The country of HCPs was grouped into four major healthcare systems: Beveridge model, Bismarck model, National Health Insurance model, and out-of-pocket model. RESULTS: Most HCPs were from countries with the Bismarck model. Substantial levels (> 50%) of unmet needs in all domains are reported across the four healthcare systems. Pediatric patients/survivors living in countries under out-of-pocket healthcare model were evaluated to have less unmet needs for managing decline in physical or cognitive functioning and insomnia/sleep difficulty/fatigue, than those in countries under Beveridge, Bismarck, and National Health Insurance models. Moreover, middle-aged patients/survivors under Beveridge and National Health Insurance models were likely to have greater unmet needs for dealing with cancer-related financial concerns than those under Bismarck model. CONCLUSION: This study provides valuable insights into the unmet needs of patients with cancer in different healthcare systems, highlighting the significance of targeted interventions to address the unique needs of patients across diverse healthcare systems. Further investigation is warranted to identify the system factors associated with patients' unmet needs, enabling the development of effective healthcare policies and interventions to comprehensively address the multifaceted needs of patients with cancer.

Daldipyrenones A-C: Caged [6,6,6,6,6] Polyketides Derived from an Endolichenic Fungus Daldinia pyrenaica 047188.

Daldipyrenones A-C (1-3), three unprecedented caged xanthone [6,6,6,6,6] polyketides featuring a spiro-azaphilone unit, were discovered from an endolichenic fungus, Daldinia pyrenaica 047188. The structures of 1-3 were determined by using spectroscopic analysis and chemical derivatization. Daldipyrenones are likely derived by combining a chromane biosynthesis intermediate, 1-(2,6-dihydroxyphenyl)but-2-en-2-one, and a spiro-azaphilone, pestafolide A, via radical coupling or Michael addition to form a bicyclo[2.2.2]octane ring. Genome sequencing of the strain revealed two separate biosynthetic gene clusters responsible for forming two biosynthetic intermediates, suggesting a proposed biosynthetic pathway. Daldipyrenone A (1) exhibited significant antimelanogenic activity with lower EC50's than positive controls and moderate adiponectin-secretion promoting activity.

Complement C1q essential for aeroallergen sensitization via CSF1R+ conventional dendritic cells type 2.

BACKGROUND: Dendritic cells (DCs) are heterogeneous, comprising multiple subsets with unique functional specifications. Our previous work has demonstrated that the specific conventional type 2 DC subset, CSF1R+cDC2s, plays a critical role in sensing aeroallergens. OBJECTIVE: It remains to be understood how CSF1R+cDC2s recognize inhaled allergens. We sought to elucidate the transcriptomic programs and receptor-ligand interactions essential for function of this subset in allergen sensitization. METHODS: We applied single-cell RNA sequencing to mouse lung DCs. Conventional DC-selective knockout mouse models were employed, and mice were subjected to inhaled allergen sensitization with multiple readouts of asthma pathology. Under the clinical arm of this work, human lung transcriptomic data were integrated with mouse data, and bronchoalveolar lavage (BAL) specimens were collected from subjects undergoing allergen provocation, with samples assayed for C1q. RESULTS: We found that C1q is selectively enriched in lung CSF1R+cDC2s, but not in other lung cDC2 or cDC1 subsets. Depletion of C1q in conventional DCs significantly attenuates allergen sensing and features of asthma. Additionally, we found that C1q binds directly to human dust mite allergen, and the C1q receptor CD91 (LRP1) is required for lung CSF1R+cDC2s to recognize the C1q-allergen complex and induce allergic lung inflammation. Lastly, C1q is enriched in human BAL samples following subsegmental allergen challenge, and human RNA sequencing data demonstrate close homology between lung IGSF21+DCs and mouse CSF1R+cDC2s. CONCLUSIONS: C1q is secreted from the CSF1R+cDC2 subset among conventional DCs. Our data indicate that the C1q-LRP1 axis represents a candidate for translational therapeutics in the prevention and suppression of allergic lung inflammation.

Roles of benefit finding in psychological and inflammatory adjustments in persons with colorectal cancer: a prospective analysis on the multidimensionality of benefit finding.

OBJECTIVE: This study examined the unique associations of different dimensions of the resilience factor, benefit finding, on concurrent and prospective psychological and biological adjustment outcomes over the first year after a colorectal cancer diagnosis. METHODS AND MEASURES: Individuals newly diagnosed with colorectal cancer (n = 133, mean age = 56 years old, 59% female, 46% Hispanic) completed questionnaires assessing the multidimensional aspects of benefit finding around 4 months post-diagnosis (T1). Psychological (depressive symptoms and life satisfaction) and biological [C-reactive protein (CRP) and interleukin-10 (IL-10)] adjustments were assessed at T1 and one-year post-diagnosis (T2). RESULTS: Structural equation modeling revealed that at T1, greater reprioritization was concurrently related to higher depressive symptoms (p=.020). Lower acceptance, lower empathy, and greater positive self-view predicted higher life satisfaction at T2 (ps<.010). Additionally, lower empathy and greater family valuation predicted higher CRP at T2 (ps<.004), whereas greater positive self-view predicted higher IL-10 at T2 (p=.039). Greater overall benefit finding was associated with lower IL-10 at T1 (p=.013). CONCLUSION: Various aspects of benefit finding differentially relate to psychological and inflammatory markers during the first year after diagnosis in persons with colorectal cancer. Interventions designed to specifically enhance positive self-view may promote both the psychological and biological health of individuals with cancer.

A Lens on Caregiver Stress in Cancer: Longitudinal Investigation of Cancer-Related Stress and Telomere Length Among Family Caregivers of Adult Patients With Cancer.

OBJECTIVE: Family members are typically the primary caregivers of patients with chronic illnesses. Family caregivers of adult relatives with cancer are a fast-growing population, yet the physical consequences of their stress due to the cancer in the family have been poorly understood. This study examined the bidirectional relations of the perceived stress of family caregivers of individuals recently diagnosed with cancer and leukocyte cellular aging indexed by telomere length for 2 years. METHODS: Family caregivers ( N = 168; mean age = 51 years, 70% female, 46% Hispanic, 36% spouse to the patient) of patients with colorectal cancer provided psychological data and peripheral blood samples approximately 4 (T1), 12 (T2), and 21 months (T3) after diagnosis. Time-lagged cross-panel modeling was used to test the associations of perceived cancer-related stress and telomere length, controlling for age, sex, and body mass index. RESULTS: Cancer-related stress was highest at T1 and decreased by 1 year. Greater cancer-related stress predicted longer telomere length at subsequent assessments for 2 years ( ß ≥ 0.911, p ≤ .019). However, telomere length did not change significantly for 2 years overall and did not prospectively predict cancer-related stress over this period. CONCLUSIONS: Findings suggest the need to better understand how the perceived stress of colorectal cancer caregivers, which tends to be intense for a relatively short period compared with dementia caregiving, may impact immune cell distributions and telomere length. These findings emphasize the need for further knowledge about psychobiological mechanisms of how cancer caregiving may impact cellular aging.

Construction of a bioactive copper-based metal organic framework-embedded dual-crosslinked alginate hydrogel for antimicrobial applications.

Metal-organic frameworks (MOFs) containing bioactive metals have the potential to exhibit antimicrobial activity by releasing metal ions or ligands through the cleavage of metal-ligand bonds. Recently, copper-based MOFs (Cu-MOFs) with sustained release capability, porosity, and structural flexibility have shown promising antimicrobial properties. However, for clinical use, the controlled release of Cu2+ over an extended time period is crucial to prevent toxicity. In this study, we developed an alginate-based antimicrobial scaffold and encapsulated MOFs within a dual-crosslinked alginate polymer network. We synthesized Cu-MOFs containing glutarate (Glu) and 4,4'-azopyridine (AZPY) (Cu(AZPY)-MOF) and encapsulated them in an alginate-based hydrogel through a combination of visible light-induced photo and calcium ion-induced chemical crosslinking processes. We confirmed Cu(AZPY)-MOF synthesis using scanning electron microscopy, transmission electron microscopy, powder X-ray diffraction, and thermogravimetric analysis. This antimicrobial hydrogel demonstrated excellent antibacterial and antifungal properties against two bacterial strains (MRSA and S. mutans, with >99.9 % antibacterial rate) and one fungal strain (C. albicans, with >78.7 % antifungal rate) as well as negligible cytotoxicity towards mouse embryonic fibroblasts, making it a promising candidate for various tissue engineering applications in biomedical fields.

Factors associated with successful smoking cessation in men with or without cardiovascular disease or cancer: Nationwide Korean population analysis.

INTRODUCTION: This study was conducted to explore factors associated with smoking cessation in male smokers with cardiovascular disease (CVD) or cancer, the two leading causes of death worldwide, and to compare them with quitting factors in smokers without the two diseases. METHODS: This is a secondary dataset analysis of the Korea National Health and Nutrition Examination Survey (KNHANES), nationally representative data from 2008-2019 (excluding 2013-2014), and included 12998 men without CVD or cancer (group without CVD or cancer), 1027 men with CVD (CVD group), and 616 men with cancer (cancer group). A Wald test with multiple logistic regression analysis was conducted. RESULTS: The quitting success rates in the CVD and cancer groups were consistently higher than those in the group without CVD or cancer. Old age and willpower in the CVD group, and old age and being married in the cancer group were associated with quitting success. Secondhand smoking and methods of quitting other than willpower were related to quitting failure in both groups. When interaction effects between the groups were examined, household income was the only factor associated with successful cessation in the group without CVD or cancer (AOR=1.17, 1.18, and 1.40, among the second, third, and fourth highest income quartiles, respectively; p for interaction=0.023). Higher smoking amounts (AOR=0.85; p<0.001) and poor health perception (AOR=0.64; p=0.035) were associated with quitting failure in the group without CVD or cancer. However, no significant factor was detected related to smoking cessation in both the CVD and cancer groups when the interaction effect was investigated. CONCLUSIONS: The quitting success rates in the CVD and cancer groups were higher, but no disease-specific quitting factors were identified. Therefore, being diagnosed with CVD or cancer itself could be inferred as a motive for quitting smoking.

CX3CR1+ Macrophage Facilitates the Resolution of Allergic Lung Inflammation via Interacting CCL26.

Rationale: The resolution of inflammation is an active process coordinated by mediators and immune cells to restore tissue homeostasis. However, the mechanisms for resolving eosinophilic allergic lung inflammation triggered by inhaled allergens have not been fully elucidated. Objectives: Our objectives were to investigate the cellular mechanism of tissue-resident macrophages involved in the resolution process of eosinophilic lung inflammation. Methods: For the study, we used the institutional review board-approved protocol for human subsegmental bronchoprovocation with allergen, mouse models for allergic lung inflammation, and novel transgenic mice, including a conditional CCL26 knockout. The samples were analyzed using mass cytometry, single-cell RNA sequencing, and biophysical and immunological analyses. Measurements and Main Results: We compared alveolar macrophage (AM) subsets in the BAL before and after allergen provocation. In response to provocation with inhaled allergens, the subsets of AMs are dynamically changed in humans and mice. In the steady state, the AM subset expressing CX3CR1 is a relatively small fraction in bronchoalveolar space and lung tissue but drastically increases after allergen challenges. This subset presents unique patterns of gene expression compared with classical AMs, expressing high C1q family genes. CX3CR1+ macrophages are activated by airway epithelial cell-derived CCL26 via a receptor-ligand interaction. The binding of CCL26 to the CX3CR1+ receptor induces CX3CR1+ macrophages to secrete C1q, subsequently facilitating the clearance of eosinophils. Furthermore, the depletion of CX3CR1 macrophages or CCL26 in airway epithelial cells delays the resolution of allergic lung inflammation displaying prolonged tissue eosinophilia. Conclusions: These findings indicate that the CCL26-CX3CR1 pathway is pivotal in resolving eosinophilic allergic lung inflammation.

Developing a stress induction tool relevant to relationships in a health context.

Concerns pertaining to health and to problems in close relationships are both known to be major stressors, yet existing tools are inadequate to assess individual reactions to such stressors. Thus, we sought to develop and preliminarily validate a stress-inducing task for use in a laboratory setting that pertains to the sorts of health-related concerns people face in close relationships. Heterosexual dating couples (44 individuals: mean age 22) were randomized to be paired with their own partner or a stranger and to play a role of speaker or listener. Participants were asked to imagine a scenario in which one person is hit by a car (listener role) and the partner has no means to provide or seek out help for the victim (speaker role). The session consisted of baseline, speech preparation, stress task, and recovery phases. General linear modeling results revealed that the task induced stress, evidenced in cardiovascular activities and self-reported negative affect. Giving a brief speech about the stressful situation creates physiological and psychological strains, regardless of pairing with one's own partner or stranger. Furthermore, cardiovascular and negative affect reactivity to the STress Induction Tool for Close relationships and Health (STITCH) task tended to vary by individual characteristics that reflect one's sensitivity to close relationship-and health-related stress. This tool is intended to be used for testing relationship theory-driven phenomenon and longer-term implications of physiological and affective reactivities in the quality of life and health outcomes of those who experienced a medically stressful circumstance personally or in the family.

Protocol of a dyadic sleep intervention for adult patients with cancer and their sleep-partner caregivers.

Background: Sleep disturbance is common and problematic among both patients with cancer and their sleep partner caregivers. Although 70% of the general adult population sleep in the same bed with a significant other, as do adult cancer patients and their spousal/partner caregivers, and one's sleep affect the partner's sleep, existing psychobehavioral interventions have targeted patients' and caregivers' sleep problems independently. Methods: We developed a new sleep intervention, My Sleep Our Sleep (MSOS), for both adult patients with cancer and their sleep-partner caregivers together. This protocol is to test the feasibility and acceptability as well as to provide preliminary efficacy of the MSOS intervention, which is a dyadic intervention designed to reduce sleep disturbance and improving sleep quality of both adult cancer patients and their sleep-partner caregivers (dyads). The intervention will be delivered weekly for 4 weeks. Questionnaire and daily sleep logs will be collected at baseline (T1) and one-week after conclusion of the intervention (T2). Satisfaction with the intervention will be assessed weekly for 4 weeks. Results: We estimate 43 dyads be enrolled (43 patients and 43 sleep-partner caregivers). We expect >75% of eligible and screened dyads will enroll within the enrollment period, >80% of enrolled dyads will complete the intervention, and >80% of participants will report satisfaction across all acceptability measures. We also expect MSOS will reveal a small-to-medium effect on sleep efficiency (primary outcome), overall sleep disturbance, subjective sleep quality, and insomnia severity (secondary outcomes). Conclusions: Results will inform the feasibility and acceptability of conducting a dyadic sleep intervention, and provide preliminary efficacy data to guide further refinement of the intervention content and procedure for adult patients with cancer and their sleep-partner caregivers. Trial registration: NCT04712604 Clinicaltrials.gov.

Cancer Patients' Unmet Needs in Three Low- to Middle- Income Countries: Perspectives from Health Care Providers.

We sought to determine differences by low- and middle- income countries (Brazil, Romania, and Turkiye) on the degree to which health care providers (HCPs) note unmet needs among patients with cancer (N = 741). HCPs endorsed sexuality/intimacy and financial concerns as the most common. Investigating age differences in unmet needs between Brazil and Turkiye, were that should be targeted by. Results revealed that unmet needs to manage emotional distress were higher among older patients in Turkiye, whereas unmet needs to manage insomnia/fatigue were higher among pediatric patients in Brazil. Findings may guide the development of programs to address unmet needs among patients.

International collaboration for assessing unmet needs of cancer survivors and family caregivers: Lens of healthcare professionals.

OBJECTIVE: Cancer patients and their family caregivers have reported various needs that are not met. Recognition of the unmet needs by healthcare professionals may be a first step to adequately and systematically addressing them. Thus, the International Psycho-Oncology Society Survivorship Online Survey was developed to measure healthcare professionals' evaluation about the unmet needs of their patients and family caregivers around the globe. METHODS: The survey was developed in English and translated to additional 14 different languages. The survey was distributed on the web-based REDCap application to over 50 psycho-oncology societies and their networking platforms as well as social media and to authors who have published in psycho-oncology journals globally. RESULTS: A total of 1472 participants from 36 countries at least partially completed the survey. Healthcare professionals evaluated needs for managing one's emotional distress and patients' medical care and symptoms as the most common concerns for both patients and their family caregivers across all patient age groups. Less than two-thirds of the participating healthcare professionals reported that their institution had services or programs to address the needs of the patients or caregivers. CONCLUSIONS: Findings suggest several directions for further analyses to provide more specific information that would be readily translated into clinical practices, research, and policy aimed to enhance the quality of life of cancer patients, survivors, and family caregivers around the globe. In addition, this collaborative effort also hints at the importance of establishing international networks to promote equity in care for people touched by cancer worldwide.

Protein disulfide isomerase A1 as a novel redox sensor in VEGFR2 signaling and angiogenesis.

VEGFR2 signaling in endothelial cells (ECs) is regulated by reactive oxygen species (ROS) derived from NADPH oxidases (NOXs) and mitochondria, which plays an important role in postnatal angiogenesis. However, it remains unclear how highly diffusible ROS signal enhances VEGFR2 signaling and reparative angiogenesis. Protein disulfide isomerase A1 (PDIA1) functions as an oxidoreductase depending on the redox environment. We hypothesized that PDIA1 functions as a redox sensor to enhance angiogenesis. Here we showed that PDIA1 co-immunoprecipitated with VEGFR2 or colocalized with either VEGFR2 or an early endosome marker Rab5 at the perinuclear region upon stimulation of human ECs with VEGF. PDIA1 silencing significantly reduced VEGF-induced EC migration, proliferation and spheroid sprouting via inhibiting VEGFR2 signaling. Mechanistically, VEGF stimulation rapidly increased Cys-OH formation of PDIA1 via the NOX4-mitochondrial ROS axis. Overexpression of "redox-dead" mutant PDIA1 with replacement of the active four Cys residues with Ser significantly inhibited VEGF-induced PDIA1-CysOH formation and angiogenic responses via reducing VEGFR2 phosphorylation. Pdia1+/- mice showed impaired angiogenesis in developmental retina and Matrigel plug models as well as ex vivo aortic ring sprouting model. Study using hindlimb ischemia model revealed that PDIA1 expression was markedly increased in angiogenic ECs of ischemic muscles, and that ischemia-induced limb perfusion recovery and neovascularization were impaired in EC-specific Pdia1 conditional knockout mice. These results suggest that PDIA1 can sense VEGF-induced H2O2 signal via CysOH formation to promote VEGFR2 signaling and angiogenesis in ECs, thereby enhancing postnatal angiogenesis. The oxidized PDIA1 is a potential therapeutic target for treatment of ischemic vascular diseases.

Healthcare professionals' perspectives on the unmet needs of cancer patients and family caregivers: global psycho-oncology investigation.

PURPOSE: This international study aimed to compare healthcare professionals' perspectives on the unmet needs of their cancer patients with those of family caregivers and to investigate the degree to which patients' age group moderates the associations. METHODS: Healthcare professionals involved in the care for cancer patients and their family caregivers were invited to participate in the International Psycho-Oncology Society (IPOS) Survivorship Online Survey. A total of 397 healthcare professionals from 34 countries provided valid study data. The participants evaluated whether the unmet need was the same for all age groups of patients and the degree of their patients' needs not being met per patients' age group. They evaluated the same questions for family caregivers. RESULTS: Patients' unmet needs in medical care were evaluated as greater than those of caregivers across all age groups. On the other hand, pediatric patients' unmet needs for spiritual concerns, sexuality/intimacy, and insomnia/fatigue were evaluated as greater than those of caregivers, whereas adolescent and young adult patients' unmet needs for symptom management were greater than those of caregivers. Patients' other unmet needs were evaluated as comparable with those of caregivers regardless of age groups. CONCLUSION: The findings provide insights how best healthcare providers stratify resources to address the unmet needs of patients and caregivers by the patients' age. Development of systematic assessment of unmet needs and provision of interventions tailored for patients' lifespan to address the unmet needs of cancer patients, and caregivers are warranted.