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 posttraumatic 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 after 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 = 15.59, p < .001) and their patients' longer sleep duration ( b = 0.61, p = .014), whereas patients' arousal and reactivity were associated with their caregivers' shorter SOL ( b = -8.47, p = .050). Patients' and caregivers' greater negative alterations in cognitions and mood were associated with patients' longer SOL ( b = 9.15, p = .014) and shorter sleep duration ( b = -0.41, p = .050), respectively. Caregivers' greater intrusion was related to their own shorter SOL ( b = -10.14, p = .004). 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Mitophagy mediates metabolic reprogramming of induced pluripotent stem cells undergoing endothelial differentiation.

Pluripotent stem cells are known to shift their mitochondrial metabolism upon differentiation, but the mechanisms underlying such metabolic rewiring are not fully understood. We hypothesized that during differentiation of human induced pluripotent stem cells (hiPSCs), mitochondria undergo mitophagy and are then replenished by the biogenesis of new mitochondria adapted to the metabolic needs of the differentiated cell. To evaluate mitophagy during iPSC differentiation, we performed live cell imaging of mitochondria and lysosomes in hiPSCs differentiating into vascular endothelial cells using confocal microscopy. We observed a burst of mitophagy during the initial phases of hiPSC differentiation into the endothelial lineage, followed by subsequent mitochondrial biogenesis as assessed by the mitochondrial biogenesis biosensor MitoTimer. Furthermore, hiPSCs undergoing differentiation showed greater mitochondrial oxidation of fatty acids and an increase in ATP levels as assessed by an ATP biosensor. We also found that during mitophagy, the mitochondrial phosphatase PGAM5 is cleaved in hiPSC-derived endothelial progenitor cells and in turn activates ß-catenin-mediated transcription of the transcriptional coactivator PGC-1α, which upregulates mitochondrial biogenesis. These data suggest that mitophagy itself initiates the increase in mitochondrial biogenesis and oxidative metabolism through transcriptional changes during endothelial cell differentiation. In summary, these findings reveal a mitophagy-mediated mechanism for metabolic rewiring and maturation of differentiating cells via the ß-catenin signaling pathway. We propose that such mitochondrial-nuclear cross talk during hiPSC differentiation could be leveraged to enhance the metabolic maturation of differentiated cells.

Caregiving stress and burden associated with cardiometabolic risk in family caregivers of individuals with cancer.

Chronic stress is a well-established risk factor for cardiometabolic disease. Caregiving for individuals with cancer is perceived as a chronic stressor yet research on the risk for cardiometabolic disease in this population, opposed to the elderly and those with Alzheimer's disease, is limited. Additionally, few studies have explored the early physiological changes that occur in family caregivers suggesting an elevated risk for illness. This cross-sectional study was designed to examine levels of cardiometabolic risk biomarkers and their correlates in caregivers of patients with colorectal cancer. Caregivers completed questionnaires that measure exposures to stress and vulnerability factors, psychological distress, and health habits as potential correlates. Traditional lipid and nontraditional lipoprotein particle biomarkers (e.g. concentration and size for all lipoprotein classes) were assayed from blood serum. Caregivers (N = 83, mean age = 49.8, 73% female) displayed levels of cardiometabolic biomarkers that suggest an elevated risk for cardiometabolic disease. Caregivers who were Hispanic, married, highly educated, employed, reported more hours spent caregiving daily, experienced higher caregiver burden associated with the lack of family support and impact on schedule, and psychological distress, demonstrated an elevated risk for cardiometabolic disease; primarily determined by nontraditional lipid biomarkers - large TRL-P, LDL-P, small HDL-P, large HDL-P, TRL-Z, LDL-Z and HDL-Z. These findings suggest that traditional lipid biomarkers may not be robust enough to detect early physiological changes associated with cardiometabolic disease risk in family caregivers. Moreover, findings reiterate the importance of assessing caregiver burden and providing evidence-based interventions to manage caregiving stress with the potential to improve caregivers' cardiometabolic health.

ß-glucan, "the knight of health sector": critical insights on physiochemical heterogeneities, action mechanisms and health implications.

ß-glucans, the class of biological response modifier has unceasing attention, not only for its immune stimulating but also for its role as prebiotics, modulator of physiological events etc. and is widely used in the treatment of cancer, diabetes, gastrointestinal disorders, cardiovascular diseases etc. However, ß-glucan with different physiochemical properties is found to have discrete clinical functions and thus careful selection of the types of ß-glucan plays pivotal role in providing significant and expected clinical outcome. Herein this review, we presented the factors responsible for diverse functional properties of ß-glucan, their distinct mode of actions in regulating human health etc. Further, clinical aspects of different ß-glucans toward the management of wound care, metabolic dysbiosis, fatty liver disorders and endurance training associated energy metabolism were compiled and exhibited in detail.

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.

Remarkable enantioselectivity enhancement of the extractors with nonaxial chirality in liquid-liquid extraction of underivatized amino acids by introducing t-butyl group.

A class of carbonyl extractors, (R)-3, (R)-4, and (R)-5, with nonaxial chirality containing asymmetric carbons has been synthesized and studied for their efficiencies in enantioselective liquid-liquid extraction for underivatized amino acids. The bulky t-butyl ketone extractors, (R)-4 and (R)-5, showed the stereoselectivities ranging 5.4-9.4 of l/d ratio much better than those of the aldehyde extractor, (R)-3, ranging 2.4-5.2. The imine formation rates and yields of the t-butyl ketones were not significantly affected by their bulkiness and even in the absence of resonance-assisted hydrogen bond. This work confirms that a bulky t-butyl ketone can be a good choice in the development of an extractor not only with axial chirality but also with nonaxial chirality for the enantioselective extraction of unprotected amino acids.

Marital Status and Gender Associated with Sleep Health among Hispanics/Latinos in the US: Results from HCHS/SOL and Sueño Ancillary Studies.

Poor sleep and different patterns of marital status among Hispanics/Latinos have been documented, yet the extent to which marital status is associated with sleep health and the moderating role of gender in this association among Hispanics/Latinos is poorly understood.Demographic and sleep data were obtained from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL: n= 16,415), an epidemiological cohort study, and the Sueño Study (n= 2,252) that is an ancillary to HCHS/SOL. Sleep duration, insomnia symptoms, daytime sleepiness, napping, and snoring were self-reported and drawn from HCHS/SOL. Sleep efficiency, sleep fragmentation, and inter-day stability were objectively assessed in the Sueño Study.Complex sample analyses indicated that being married or cohabiting was associated with better sleep health in general, including having normal sleep duration, fewer insomnia symptoms, and higher sleep efficiency (F> 2.804, p< .044). These associations were more prominent in objectively measured sleep indices and among females.Findings suggest being in a committed relationship associated with better sleep health in Hispanics/Latinos in the US, a diverse and under-represented population. Findings may have implications for tailoring sleep health interventions to at-risk populations who may less likely to be in a committed relationship.

Controllable Nitric Oxide Storage and Release in Cu-BTC: Crystallographic Insights and Bioactivity.

Crystalline metal-organic frameworks (MOFs) are extensively used in areas such as gas storage and small-molecule drug delivery. Although Cu-BTC (1, MOF-199, BTC: benzene-1,3,5-tricarboxylate) has versatile applications, its NO storage and release characteristics are not amenable to therapeutic usage. In this work, micro-sized Cu-BTC was prepared solvothermally and then processed by ball-milling to prepare nano-sized Cu-BTC (2). The NO storage and release properties of the micro- and nano-sized Cu-BTC MOFs were morphology dependent. Control of the hydration degree and morphology of the NO delivery vehicle improved the NO release characteristics significantly. In particular, the nano-sized NO-loaded Cu-BTC (NO⊂nano-Cu-BTC, 4) released NO at 1.81 µmol·mg-1 in 1.2 h in PBS, which meets the requirements for clinical usage. The solid-state structural formula of NO⊂Cu-BTC was successfully determined to be [CuC6H2O5]·(NO)0.167 through single-crystal X-ray diffraction, suggesting no structural changes in Cu-BTC upon the intercalation of 0.167 equivalents of NO within the pores of Cu-BTC after NO loading. The structure of Cu-BTC was also stably maintained after NO release. NO⊂Cu-BTC exhibited significant antibacterial activity against six bacterial strains, including Gram-negative and positive bacteria. NO⊂Cu-BTC could be utilized as a hybrid NO donor to explore the synergistic effects of the known antibacterial properties of Cu-BTC.

Only the Lonely: Expression of Proinflammatory Genes Through Family Cancer Caregiving Experiences.

OBJECTIVE: The experience of cancer elicits not only turmoil but also resilience in the family, which has been related to psychological adjustment and physical health of family caregivers. The biological pathways linking family cancer caregiving to health, however, remain poorly understood. This study examined the extent to which psychological risk and resilience factors related to a proinflammatory gene expression profile (conserved transcriptional response to adversity, or CTRA) among caregivers during the first-year postdiagnosis of a patient with colorectal cancer. METHODS: A total of 41 caregivers (mean age = 54 years, 74% female, 40% Hispanic) provided psychological data and peripheral blood samples around 4 and 12 months after diagnosis. Mixed regression models controlling for demographic and biometric factors were used to test the associations of caregiver CTRA gene expression with caregiving stress, loneliness, and lack of social support (risk factors), as well as benefit finding and meaning (resilience factors). RESULTS: When individually tested, all but benefit finding were significantly related to CTRA (R2 ≥ 0.112, p < .045). When adjusted for other factors in either the risk or resilience group, loneliness, social support, and meaning effects remained significant (R2 ≥ 0.120, p < .041). When all study factors were simultaneously adjusted (R2 = 0.139), only loneliness remained significant (p = .034). CONCLUSIONS: Findings suggest that caregiving-related transcriptional effects seem to be most pronounced when caregivers experience low social support and loneliness, as well as little meaning or purpose in their caregiving. These findings suggest that the development of new intervention strategies that prioritize reductions in caregiver loneliness may favorably impact biological mechanisms related to caregiver health.

Effect of multiple comorbidities on mortality in chronic obstructive pulmonary disease among Korean population: a nationwide cohort study.

BACKGROUND: The effects of comorbidities on chronic obstructive pulmonary disease (COPD) have been usually studied individually in the past. In this study, we aimed to investigate the comorbidities associated with mortality, the effect of multimorbidity on mortality and other factors associated with mortality among Korean COPD population. METHODS: The Korean National Health Insurance Service-National Sample Cohort version 2.0, collected between 2002 and 2015, was used. Among COPD patients [entire cohort (EC), N = 12,779], 44% of the participants underwent additional health examination, and they were analysed separately [health-screening cohort (HSC), N = 5624]. Fifteen comorbidities previously reported as risk factors for mortality were studied using Cox proportional hazards regression models. RESULTS: Total mortality rates were 38.6 per 1000 person-years (95% CI 37.32-40.01) and 27.4 per 1000 person-years (95% CI 25.68-29.22) in EC and HSC, respectively. The most common causes of death were disease progression, lung cancer, and pneumonia. Only some of the comorbidities had a direct impact on mortality. Multimorbidity, assessed by the number of comorbid diseases, was an independent risk factor of all-cause mortality in both cohorts and was a risk factor of respiratory mortality only in HSC. The Kaplan-Meier analysis showed significant differences in survival trajectories according to the number of comorbidities in all-cause mortality but not in respiratory mortality. Low BMI, old age and male sex were independent risk factors for both mortalities in both cohorts. CONCLUSIONS: The number of comorbidities might be an independent risk factor of COPD mortality. Multimorbidity contributes to all-cause mortality in COPD, but the effect of multimorbidity is less evident on respiratory mortality.