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The impact of literacy on health-related quality of life measurement and outcomes in cancer outpatients.

BACKGROUND: Limited evidence exists regarding the relationship between literacy and health-related quality of life (HRQL). Research is needed to develop measurement techniques for low literacy populations and to evaluate potential literacy-related measurement bias. METHODS: A Talking Touchscreen (TT) was developed for an HRQL study. Low (n = 214) and high literacy (n = 201) adult cancer outpatients participated, 70% of whom were from racial/ethnic minorities. Patients completed three questionnaires by TT: FACT-G (cancer-specific), SF-36 (generic health status), and a standard gamble utility questionnaire. Measurement bias was evaluated using item response theory (IRT). Effects of literacy on HRQL were evaluated using regression models. RESULTS: Most (97%) patients rated the TT easy to use. In IRT analysis, 6/27 FACT-G and 12/31 SF-36 items demonstrated literacy bias; this was relatively balanced (10 items 'biased against' low literacy; 8 'biased against' high literacy). Mean literacy group differences were statistically and clinically non-significant for 9/14 HRQL outcomes. Adjustment for bias and/or covariates eliminated most remaining differences. CONCLUSIONS: The TT is valid and useful for HRQL assessment in low literacy populations. There appears to be no systematic literacy bias in reporting HRQL, and low literacy is not an independent risk factor for poorer HRQL.

Cancer Care Facilities↗

How and why we age.

After performing the miracles that takes us from conception to birth, and then to sexual maturation and adulthood, natural selection was unable to favor the development of a more elementary mechanism that would simply maintain those earlier miracles forever. The manifestations of this failure are called aging. Because few feral animals age, evolution could not have favored a genetic program for age changes. Natural selection favors animals that are most likely to become reproductively successful by developing better survival strategies and greater reserve capacity in vital systems to better escape predation, disease, accidents, and environmental extremes. Natural selection diminishes after reproductive success because the species will not benefit from members favored for greater longevity. The level of physiological reserve remaining after reproductive maturity determines longevity and evolves incidental to the selection process that acts on earlier developmental events. Physiological reserve does not renew at the same rate that it incurs losses because molecular disorder increases at a rate greater than the capacity for repair. These are age changes, and they increase vulnerability to predation, accidents, or disease. Failure to distinguish aging from disease has not only blurred our efforts to understand the fundamental biology of aging, but it has profound political and economic consequences that compromise the field of biogerontology. Changes attributable to disease, or pathological change, can be distinguished from age changes for at least four important reasons. Unlike any known disease, (1) age changes occur in every human given sufficient time, (2) age changes cross virtually all species barriers, (3) no disease afflicts all members of a species only after the age of reproductive success, and (4) aging occurs in all feral animals subsequently protected by humans, even when that species probably has not experienced aging for thousands or millions of years. The resolution of age-associated diseases will not advance our knowledge of aging, just as the resolution of the diseases of childhood did not advance our knowledge of childhood development. We have failed to convey that greater support must be given to a question that is rarely posed. It is a question that is applicable to all age-associated diseases, and its resolution will also advance our fundamental knowledge of aging: "Why are old cells more vulnerable to pathology and disease than are young cells?" During the first half of this century it was believed that because cultured normal cells were immortal, aging must be caused by extra-cellular events. Thirty-five years ago we overthrough this dogma when we found that normal cells do have a limited capacity to divide, and that age changes can occur intracellularly. We also observed that only abnormal or cancer cells are immortal. Normal cells are mortal because telomeres shorten at each division. Immortal cancer cells express the enzyme telomerase that prevents shortening. Recently, it was discovered that when the catalytic subunit of the telomerase gene is inserted into normal cells they become immortal.

Aging↗

Psychoneuroimmunology and health consequences: data and shared mechanisms.

There is evidence linking psychosocially mediated immunological alterations with cancer, infectious illness, and HIV progression. The data reviewed suggest that immune modulation by psychosocial stressors and/or interventions may importantly influence health status. The research literature also suggests that the impact of chronic stressors and psychosocial factors on sympathetic nervous system and endocrine function influences the immune system, thereby providing shared mechanisms that may impact on disease susceptibility and progression across a broad spectrum of disorders. A better understanding of individual vulnerability, such as occurs with aging, may help to pinpoint those at greatest risk.

Adult↗

Decoding age-stratified clinical and molecular heterogeneity in male breast cancer through multiomic profiling.

OBJECTIVE: Age-associated molecular heterogeneity is well described in female breast cancer but remains insufficiently characterized in male breast cancer (MBC). We profiled age-stratified clinical and molecular differences between younger (&#x2264;55 years) male breast cancer (YMBC) and older (>55 years) male breast cancer (OMBC). METHODS: We retrospectively analyzed 347 patients with MBC diagnosed at Fudan University Shanghai Cancer Center by integrating clinicopathological data, RNA sequencing, and whole-exome sequencing (WES). Survival, differential expression, and mutational signature analyses were performed. Tumor microenvironment features were inferred using xCell and ESTIMATE, and weighted gene co-expression network analysis (WGCNA) was conducted to identify age-associated co-expression modules. Candidate therapeutics were prioritized using the Genomics of Drug Sensitivity in Cancer (GDSC) resource and evaluated using patient-derived organoids (PDOs). RESULTS: Compared with OMBC, YMBC more frequently had human epidermal growth factor receptor 2 (HER2)-positive status (14.91% vs. 4.02%) and triple-negative tumors (4.92% vs. 1.78%), and had worse 5-year recurrence-free survival (hazard ratio=2.19, P=0.018). Transcriptomic analyses indicated enrichment of neural-related programs and reduced immune-related signaling in YMBC, and xCell/ESTIMATE supported lower immune infiltration. Consistently, WGCNA identified age-associated modules linking neural-related programs with reduced immune infiltration. Immunohistochemistry supported increased perineural invasion and lower CD8+ T cell infiltration in YMBC. GDSC-guided prioritization with PDO testing nominated sepantronium bromide (YM155) as a candidate vulnerability in YMBC. WES showed a higher NBPF10 mutation frequency in YMBC (54.5% vs. 14.3%, P<0.05). CONCLUSIONS: Integrated multi-omics profiling revealed age-stratified clinical and molecular heterogeneity in MBC. YMBC patients demonstrated inferior recurrence-free survival, neural signaling enrichment, an immune-cold microenvironment, and enriched NBPF10 mutations. These findings support age as a meaningful stratification variable in MBC risk assessment and treatment planning, and highlight the need for caution when considering treatment de-escalation in younger patients, while nominating YM155 as a candidate agent for prospective evaluation.

Male breast cancer↗

Sex differences in human mortality: the role of genetic factors.

This paper reviews evidence concerning genetic factors that influence sex differences in human mortality, with attention to the interactions between genetic and environmental factors. Some widely quoted earlier conclusions, for example, that males have consistently higher fetal mortality than females, are not supported by current evidence. For example, for late fetal mortality, males had higher rates than females in earlier historical data, but not in recent data for several advanced industrial countries. This reflects a changing balance between an inherently greater female vulnerability for one major type of late fetal mortality and inherently greater male vulnerability for several other types of late fetal mortality that have declined in importance as health care has improved. Males appear to be inherently more vulnerable than females to infant mortality, although the causes of this vulnerability are poorly understood. X-linked immunoregulatory genes appear to contribute to greater female resistance to infectious diseases. Despite these apparent inherent advantages for females, in some situations females have had higher infant mortality and higher infectious disease mortality than males, apparently due to environmental disadvantages for females, such as less adequate diet and health care. Inherent sex differences in reproductive physiology and anatomy contribute to higher female mortality for breast cancer and maternal mortality. For these causes of death, as for the other categories discussed, the death rates and thus the contributions to sex differences in total mortality vary considerably depending on environmental conditions. Several hypothesized contributions of sex hormones to sex differences in mortality are at present controversial due to contradictions and limitations in the available data. There may be effects of male sex hormones on sex differences in behavior which contribute to males' higher death rates for accidents and other violent causes. Women's endogenous sex hormones may reduce women's risk of ischemic heart disease. For both violent deaths and ischemic heart disease it appears that any genetic contributions to sex differences in mortality are strongly reinforced by the cultural influences that foster more risky behavior in males, including more use of weapons, employment in hazardous occupations, heavy alcohol consumption and cigarette smoking. It appears that these cultural influences on sex differences in behavior are widespread cross-culturally in part because of the effects of inherent sex differences in reproductive functions on the cultural evolution of sex roles. These examples illustrate the complexity and importance of interactions between genetic and environmental factors in determining sex differences in human mortality.

Accidents↗

Health problems of women with severe mental illness.

PURPOSE: To provide a review of the health problems of women with severe mental illness (SMI) that are related to their psychiatric disorders and disabilities, prolonged use of psychotropic medications, and high-risk lifestyle practices. DATA SOURCES: Review of current literature uncovered through MEDLINE, Cumulated Index to Nursing and Allied Health, and Psychological Abstracts as well as the authors' clinical experiences. CONCLUSIONS: Women with SMI are at increased risk for obesity as well as cardiovascular, endocrine, and infectious disorders. They also experience psychotropic medication-related disorders such as amenorrhea, galactorrhea, sexual dysfunction, breast cancer, and osteoporosis. High-risk lifestyle practices, excessive weight gain, low physical activity, substance abuse and unprotected sexual activity increase risk for health problems. The mental illness, residual disabilities, sequelae of childhood abuse, poverty, limited social support and health knowledge deficits affect their ability to maintain optimum health. IMPLICATIONS FOR PRACTICE: Knowledge about women with SMI and their health problems will enable nurse practitioners to better meet the needs of this vulnerable population.

Female↗

Social barriers to emotional expression and their relations to distress in male and female cancer patients.

OBJECTIVE: Emotional expression is an important means of coping with stressful experiences such as cancer. Social barriers to expression may have adverse effects. Research has suggested that men are less likely to express their emotions and have different patterns of social support compared to women. We examined whether male cancer patients have a lower tendency to express emotions, are less likely to perceive social barriers to expression, and are differentially affected by social barriers from different support sources as compared to women. DESIGN: Questionnaires were administered to 41 women and 41 men using a cross-sectional study design. METHOD: Patients diagnosed with gynaecological or prostate cancer within the past 5 years completed questionnaires on moods, intrusive thoughts, social constraints and emotional expressivity. RESULTS: There was a trend towards greater emotional expressivity in women as compared to men, but no significant gender differences in perceptions of social constraints from spouse/partner or others. Multiple regression analyses revealed that men experienced significantly greater distress in association with social constraints from their spouse/partner than did women. CONCLUSION: Men may be more vulnerable to social barriers to expression than previously assumed. Gender differences in emotional expressivity may be less important than the social context in which expression takes place.

Adaptation, Psychological↗

Quality of life one year following bone marrow transplantation: psychometric evaluation of the quality of life in bone marrow transplant survivors tool.

PURPOSE/OBJECTIVES: To examine a comprehensive view of quality of life (QOL) post-bone marrow transplant (post-BMT) and to evaluate the psychometric properties of an instrument designed to measure QOL in this population. DESIGN: Cross-sectional, descriptive, mailed survey. SETTING: A large, major BMT referral center for central, eastern, and southern Kentucky. SAMPLE: 41 BMT survivors with an age range of 18-71 years who were an average of 30 months post-BMT. METHODS: Seven mailed questionnaires, including an investigator-developed demographic questionnaire and the Quality of Life in Bone Marrow Transplant Survivors Tool (QOL-BMT-ST). MAIN RESEARCH VARIABLES: QOL, BMT treatment, sexual activities, employment, and uncertainty. FINDINGS: Global QOL was good (x = 6.4 on a 0-10 scale). Subjects experienced several long-term areas of concern: physical strength, sexual activities, fear of cancer recurrence, fear of developing a secondary cancer, unemployment, family distress, and uncertainty toward the future. Psychometric testing of the QOL-BMT-ST revealed adequate to excellent reliability and validity. CONCLUSIONS: Most BMT survivors reported few long-term disruptions and above average QOL. The QOL-BMT-ST has a promising utility in clinical trials. IMPLICATIONS FOR NURSING PRACTICE: Individually structured pre- and post-BMT assessment of physical, psychosocial, and spiritual functioning is significant in identifying vulnerable patients and treating them accordingly.

Adaptation, Psychological↗

Chronological ageing and photoageing of the fibroblasts and the dermal connective tissue.

In recent years, the exposure of human skin to environmental and artificial UV irradiation has increased dramatically. This is due not only to increased solar UV irradiation as a consequence of stratospheric ozone depletion, but also to inappropriate social behaviour with the use of tanning salons still being very popular in the public view. Besides this, leisure activities and a lifestyle that often includes travel to equatorial regions add to the individual annual UV load. In addition to the common long-term detrimental effects such as immunosuppression and skin cancer, the photo-oxidative damage due to energy absorption of UV photons in an oxygenized environment leads to quantitative and qualitative alterations of cells and structural macromolecules of the dermal connective tissue responsible for tensile strength, resilience and stability of the skin. The clinical manifestations of UV/reactive oxygen species (ROS)-induced disturbances result in photoaged skin with wrinkle formation, laxity, leathery appearance as well as fragility, impaired wound healing capacities and higher vulnerability. Strategies to prevent or at least minimize ROS-induced photo-ageing and intrinsic ageing of the skin necessarily include protection against UV irradiation and antioxidant homeostasis.

Animals↗

Meaning in life and psycho-spiritual functioning: a comparison of breast cancer survivors and healthy women.

PURPOSE: Incorporating holistic health perspectives, this study compared and examined relationships among meaning in life, spirituality, perceived stress, and psychological distress in breast cancer survivors (BCS) and healthy women. METHODS: Standardized self-report measures were completed once by all participants (N = 78). FINDINGS: Group comparison revealed statistically significant variances across the measures. Covariate analysis identified BCS without children had less meaningful lives and greater stress and distress than BCS with children and participants without cancer. Significant correlations (p > .001) between meaning in life and spirituality (r = .43), stress (r = -.39), and distress (r = -.41) were also identified. CONCLUSION: Personal factors (i.e., being a parent) may be especially important in BCS. Also, psychological and spiritual variables are highly correlated, suggesting the use of an integrated term psycho-spiritual functioning. IMPLICATIONS: Holistic nursing interventions can facilitate self-awareness, interpersonal connection, and living a meaningful life, particularly in vulnerable patients such as BCS without children.

Adaptation, Psychological↗

Metabolic-cell-death gene trio predicts survival and cuproptosis sensitivity in colorectal cancer.

BACKGROUND: Metabolic cell death (MCD) modulates colorectal cancer (CRC) progression, yet its prognostic value remains unexplored. We aimed to build an MCD-centred gene signature for outcome prediction and precision therapy. METHODS: Transcriptomes of 1,174 CRC patients were integrated. Weighted gene co-expression network analysis, differential expressions and least absolute shrinkage and selection operator (LASSO) + random survival forest were successively applied to derive a three-gene (CDKN2A/MPC1/AHCY) risk model. Functional, immune-infiltration, drug-sensitivity and genomic analyses were performed, followed by validation in fresh clinical specimens and cell lines. RESULTS: Integrative metabolic-death transcriptomics identified CDKN2A, MPC1 and AHCY as the hub drivers of CRC. Their three-gene signature robustly stratified patients into high- and low-risk subsets [3-year area under the curve (AUC) 0.83-0.85, P<0.001]. High-risk tumors were enriched for extracellular matrix (ECM)-receptor-interaction pathways, displayed abundant myeloid-derived suppressor cell (MDSC) infiltration and were more vulnerable to AZD8186, AZ960 and JAK inhibitors. Guided by these in-silico findings, we functionally confirmed that CDKN2A silencing markedly repressed proliferation, invasion and migration of SW480/HCT116 cells and potentiated cuproptosis via up-regulation of lipoylated DLAT/DLST and CTR1. CONCLUSIONS: We report the first MCD-derived prognostic platform for CRC that simultaneously predicts survival and therapeutic response. Targeting CDKN2A-enhanced cuproptosis represents a promising metabolic-precision strategy for high-risk patients.

Colorectal cancer (CRC)↗

The impact of narcolepsy on psychological health and role behaviours: negative effects and comparisons with other illness groups.

OBJECTIVES: The study sought to (i) assess psychosocial adjustment, disruption due to symptoms, and medication problems in narcolepsy, (ii) determine how these variables changed with gender, age and medication status, and (iii) compare narcolepsy adjustment with three other illness groups. BACKGROUND: Psychosocial adjustment to an illness can be conceptualized in terms of people's ability to function in their life roles and assessed using the Psychosocial Adjustment to Illness Scale-Self Report (PAIS-SR) questionnaire. METHODS: Participants (n=129) were recruited via a support group using posted questionnaires. The PAIS-SR was supplemented with additional questionnaire material. RESULTS: Males were more vulnerable than females in terms of adjustment (notably health care orientation and sexual relationships) and younger narcoleptics may have particular vocational problems. Unmedicated narcoleptics were least inclined to participate in social/leisure activities. Reported disruption due to symptoms was strongly associated with both psychological distress and overall psychosocial adjustment and was most notable in those taking both stimulants and tricyclic antidepressants. Narcoleptics reported more adjustment problems in comparison to three other illness groups (cardiac, mixed cancer and diabetes). A table of normative PAIS-SR values for narcolepsy was developed. CONCLUSIONS: Poor adjustment in terms of health care orientation and psychological distress are of particular concern. Health care that can reduce the disruption due to symptoms is especially important for adjustment.

Journal Article↗

The blood vessels of the skin.

During the last 25 years, cutaneous biologists have been particularly interested in abnormal cutaneous vascular patterns, the profusion of capillary anastomoses, the leakiness of venules, clotting, fibrinolysis, and blood viscosity. As a result, the effects of hypoxia and the factors that encourage new vessel proliferation are better understood than before. Only when the biologic behavior of the two extremes of growth from hypoplasia to hyperplasia is studied and compared can the blood supply of a tissue be understood. Hyperplastic tissues are seen in wounds, psoriasis, cancer, and in selected sites of chronic stasis and hypoxia where the vessels are extremely permeable, where blood cells easily escape, and where lymphatics dilate and proliferate. The proliferation of other tissues, such as endothelium, epithelium, mast cells, and probably of locally infective organisms, is also encouraged in hyperplasia. Moreover, fibrinolysis does not occur and fibrin is deposited, the electrostatic charge on the internal vascular surface becomes more positive, and the organ is more vulnerable to subsequent injury. Atrophic or hypoplastic tissues have a reduced cellular turnover and are less hypoxic. The vessels are less permeable, blood cells do not escape, there is only a slight tendency to clot, and fibrinolysis is often increased. Lymphatics are sparse and infection is not a feature. The electrostatic charge on the internal surface of the vessel is negative.

Animals↗

[Deglutition disorders in the elderly. Epidemiological aspects].

THE PREVALENCE: The exact prevalence of deglutition disorders in the elderly is not known. It appears frequent in very old patients and in those suffering from polypathological symptoms, affecting 50% of the populations in long-term care units. THE EFFECTS OF AGING: Physiological aging alters various parameters of swallowing, however it seems that these modifications related to age have little effect on healthy subjects. However, they may increase vulnerability in those presenting with intercurrent pathologies. CONCOMITANT DISORDERS: Other than the decrease in efficient mastication and the existence of xerostomia, frequently observed contributing factors, many diseases may be responsible for dysphagia in the elderly. Neurological disorders, particularly cerebral vascular diseases, central nervous system degenerative disorders and neuro-motor diseases predominate. In the aging, muscular disorders and after effects of various diseases can set-in. Modifications in oropharyngeal anatomy generally results from cancerous lesions of the aero-digestive junction, but also, occasionally from extrinsic compression that does not necessarily reflect a neoplastic etiology. Zenker's diverticulitis represents a cause of dysphagia specific to the elderly. Problems in swallowing of iatrogenic origin are also frequent, following cervical radiotherapy or after oropharyngeal surgery, during tracheal intubation or when using feeding tubes and also during various medical treatments. UNDERRATED CONSEQUENCES: Dysphagia leads to multiple morbid after effects, primarily alteration in quality of life, dehydration, undernutrition, asphyxia and congestion and recurrent infections of the respiratory tract. The responsibility of deglutition disorders in the occurrence of these complications is difficult to assess in weak elderly subjects because of the frequent concomitance with multiple deficiencies and incapacities.

Age Factors↗

The present state of development of cancer chemotherapy.

Cancer chemotherapy has evolved through 3 decades of remarkable progress. At the present time over 40 drugs and biologicals are employed in the treatment of cancer, and hundreds of promising compounds and analogs await their turn in the clinic. The medical management of cancer patients with chemotherapy has developed into a recognized subspecialty--medical oncology, a discipline that now works closely and effectively with surgery and radiotherapy in planning treatment strategies. Major areas of progress to date include the concept of combination chemotherapy, the development of hematologic and microbiologic supportive care, and the demonstration of effective adjuvant chemotherapy. Further progress is anticipated in a number of areas: rational selection of anticancer compounds based on metabolic or kinetic vulnerability; increased attention to biologic substances that modify neoplastic cell behavior; continued refinement of doses and schedules of active compounds to optimize therapeutic benefit and minimize toxicity; awareness of novel methods of drug delivery; and development of physical or chemical modifications to enhance drug effects.

Antineoplastic Agents↗

Effect of 6-diazo-5-oxo-L-norleucine (DON) on human carcinoid tumor cell aggregates.

The induction of glutamine starvation has been suggested as a potential target for antitumoral treatment using inhibitors of amidotransferase, an enzyme which mediates the conversion of glutamate to glutamine. Using multicellular aggregates from tumor cell lines, the effect of treatment with a suggested glutamine antagonist, 6-diazo-5-axo-L-norleucine (DON), was investigated. As indicators of treatment response, three different parameters were measured: aggregate size, uptake of 14C-methionine and secretion of Chromogranin A. Of six cell types evaluated (carcinoid, glioma, neuroblastoma pancreas and bladder cancer), the largest inhibition of 14Cmethionine uptake, amounting to 60%, was found in the carcinoid cell line BON. In this cell line the maximum effect was reached already at 10 microM concentration. DON induced marked growth inhibition in the BON aggregates which lasted 3-4 weeks after which regrowth started. During this period the secretion of chromogranin and methionine uptake was also inhibited. These studies suggest that the neuroendocrine cell line BON is especially vulnerable to treatment by DON and show that strong inhibitory effects are found at concentrations lower than that achieved in patient blood in previous clinical trials.

2-Aminoadipic Acid↗

Coping with a partner's cancer: adjustment at four stages of the illness trajectory.

PURPOSE/OBJECTIVES: To study the psychosocial adjustment of partners/spouses of patients with cancer at four specific stages of the illness trajectory time of diagnosis, period of first remission, first recurrence, and period of metastatic disease. DESIGN: A cross-sectional, descriptive survey. SETTINGS: A university cancer center, a private cancer clinic, and a clinic in a large city serving people who are uninsured and unable to pay for their treatment. SAMPLE: 175 partners of patients who were in one of four specific stages of the illness trajectory participated in this study, Various types of cancer were represented. Seventy-seven participants were men, and 98 were women; their mean age was 49 years. METHODS: A survey questionnaire was used to collect data on psychosocial adjustment, specific sources of social support, dyadic adjustment, coping strategies, emotional response, cognitive response, and personal control. FINDINGS: Results indicate that partners of patients who were experiencing a recurrence of their illness or who were in the metastatic stage of the disease were more vulnerable to increased distress and problems of adjustment. Women also reported higher levels of distress than men. Variables that had the most significant direct affect on adjustment were emotional response, cognitive response, family support, and partner cohesion. Coping strategies influenced emotion and cognition. CONCLUSIONS: Caring for partners is essential to promoting quality of life for the patient and the family. IMPLICATIONS FOR NURSING PRACTICE: Assessment, providing an opportunity to express concerns, and referral for psychosocial intervention as necessary are important to promote the highest possible quality of life for partners and patients.

Adaptation, Psychological↗

[The importance of psychosocial oncology in the treatment of cancer patients].

Better medical care leads to an increased life expectancy but also to a growing psychosocial burden on the patients and their relatives. This development has led to the establishment of a new discipline: "Psychosocial Oncology". The psychosocial support of patients and their relatives as well as of nurses and physicians is described using the psychosocial aftercare unit attached to the department of surgery of the Heidelberg University Clinic as an example. Generally speaking two types of co-operation are possible-the consultation model and the integrated liaison model. Of these the latter seems to be the most appropriate but also the one most vulnerable to dysfunctions caused by professional and personal rivalries. In this paper the conditions necessary for a patient centered co-operation are discussed. If these requirements are met the patient centered approach, described by the three aspects of support, counseling and psychotherapy can be successful.

Adaptation, Psychological↗