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PubMed1994

Radiation protection issues in galactic cosmic ray risk assessment.

Radiation protection involves the limitation of exposure to below threshold doses for direct (or deterministic) effects and a knowledge of the risk of stochastic effects after low doses. The principal stochastic risk associated with low dose rate galactic cosmic rays is the increased risk of cancer. Estimates of this risk depend on two factors (a) estimates of cancer risk for low-LET radiation and (b) values of the appropriate radiation weighting factors, WR, for the high-LET radiations of galactic cosmic rays. Both factors are subject to considerable uncertainty. The low-LET cancer risk derived from the late effects of the atomic bombs is vulnerable to a number of uncertainties including especially that from projection in time, and from extrapolation from high to low dose rate. Nevertheless, recent low dose studies of workers and others tend to confirm these estimates. WR, relies on biological effects studied mainly in non-human systems. Additional laboratory studies could reduce the uncertainties in WR and thus produce a more confident estimate of the overall risk of galactic cosmic rays.

Adolescent↗
PubMed2006

Telomere shortening and mood disorders: preliminary support for a chronic stress model of accelerated aging.

BACKGROUND: Little is known about the biological mechanisms underlying the excess medical morbidity and mortality associated with mood disorders. Substantial evidence supports abnormalities in stress-related biological systems in depression. Accelerated telomere shortening may reflect stress-related oxidative damage to cells and accelerated aging, and severe psychosocial stress has been linked to telomere shortening. We propose that chronic stress associated with mood disorders may contribute to excess vulnerability for diseases of aging such as cardiovascular disease and possibly some cancers through accelerated organismal aging. METHODS: Telomere length was measured by Southern Analysis in 44 individuals with chronic mood disorders and 44 nonpsychiatrically ill age-matched control subjects. RESULTS: Telomere length was significantly shorter in those with mood disorders, representing as much as 10 years of accelerated aging. CONCLUSIONS: These results provide preliminary evidence that mood disorders are associated with accelerated aging and may suggest a novel mechanism for mood disorder-associated morbidity and mortality.

Adult↗
PubMed2004

Male sexuality in theory and practice.

Male sexuality is a complex phenomenon shaped by personal, cultural,and social factors. This article has argued that male sexual function is an important consideration in conditions such as prostate cancer. There are surely other conditions where it is understood even more poorly. Although theorists tend to explore male sexuality in relation to vague concepts such as power, phallocentrism, and aggression, sexuality becomes a personal reality in illness contexts. Using insights from a study into prostate cancer, it has been suggested that men assess embodied risks, such as impotence, in highly individual ways. The uncertainty that characterizes this cancer further compounds the difficulties involved, despite attempts of professionals to provide adequate levels of information and support. Researchers and practitioners alike should begin to question the gap between theoretical constructions of male sexuality and its reality in healthcare situations. More attention should be paid to understanding the importance of sexual function for men who are living with conditions such as prostate cancer. Those men who face up to the threat of such embodied changes, and who learn to cope with physical and emotional (and sexual) vulnerability, may learn to evaluate their lives in new ways. As Kenneth, one of the participants in this study said of his experience of cancer, "It just seems unnecessary for them to have to go through that to learn and understand themselves and be honest with themselves about what is really important."

Adaptation, Psychological↗
PubMed2025

The advent of precision nutrigeroscience in cancer: from clinic towards molecular biology.

Nutrimental patterns have been deemed to have an impact on cancer development and the response to cancer therapy. Our growing understanding of cancer and host metabolism has highlighted that nutrient availability in the tumor ecosystem is a key factor in inhibiting tumor development. Subsequently, dietary interventions must take into account the specific characteristics of both the cancer and the host, which requires a detailed understanding of the mechanisms that determine the metabolic vulnerabilities in the tumor ecosystem. In this review, we provide an overview of various dietary regimens as interventions in both preclinical models and clinical studies. We discuss how dietary intervention can affect the homeostasis of the tumor ecosystem, including neoplastic, micro- and macro-environmental states that impact cancer progression and therapy. Our emphasis is on the prospects of precision nutrigeroscience, which involves developing individualized therapeutic approaches and predictors based on a thorough exploration of the mechanisms and critical factors. This approach has the potential to enhance the efficacy of anti-cancer treatments and prevention strategies.

Humans↗
PubMed2005

Asthma, the ugly duckling of lung disease proteomics?

The human respiratory system represents a vital but vulnerable system. It is a major target for many diseases such as cancer and asthma. The incidence of these diseases has increased dramatically in the last 40-50 years. In the search for possible new therapies, many experimental tools and methods have been developed to study these diseases, ranging from animal models to in vitro studies. In the last decades, genomic and proteomic approaches have gained a lot of attention. After the major scientific breakthroughs in the field of genomics, it is now widely accepted that to understand biological processes, large-scale protein studies through proteomics techniques are required. In the battle against lung cancer, the proteomics approach has already been successfully implemented. Surprisingly, only a few proteomics studies on the ever-increasing global asthma problem have been published so far. And although proteomics also has its limitations and experimental difficulties, in our opinion, proteomics can definitely contribute to the understanding of a complex disease such as asthma. Therefore, the additional values and possibilities of proteomics in asthma research should be thoroughly investigated. A close collaboration between the different scientific disciplines may eventually lead to the development of new therapeutic strategies against asthma.

Asthma↗
PubMed2026

Interplay between DNA and RNA methylation shapes cancer cell plasticity.

Cellular plasticity refers to the ability of healthy cells to shift between phenotypic states and modify their characteristics to maintain tissue homeostasis and integrity. In the tumor context, cancer stem cells (CSCs) exploit this flexibility to withstand stress, facilitate tumor dissemination, and evade therapeutic interventions. Epigenetic regulation, particularly DNA methylation at CpG sites, is recognized as a well-known driver of tumor plasticity by repressing differentiation programs through modulation of chromatin accessibility. More recently, RNA modifications (epitranscriptomics) have emerged as crucial post-transcriptional regulators of gene expression that shape RNA fate and function. Among these, N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), and N7-methylguanosine (m7G) contribute to the regulation of cell identity by modulating stemness-differentiation balance, stress adaptation, and epithelial-to-mesenchymal transition (EMT). Notably, dysregulation of both DNA and RNA methylation signatures is frequently observed in tumors, suggesting potential functional interactions between these regulatory layers. Emerging evidence indicates that DNA CpG methylation and RNA methylation pathways may cooperate to influence stemness, survival, and EMT-associated signaling, thereby supporting CSCs' plasticity. Although the molecular mechanisms underlying this crosstalk remain incompletely understood, accumulating studies suggest that DNA and RNA methylation could converge within interconnected regulatory networks that contribute to the control of cancer cell identity. A deeper understanding of these interactions may uncover novel vulnerabilities for targeting tumor plasticity. In this review, we summarize the current knowledge on the interplay between DNA and RNA methylation in regulating tumor plasticity, highlighting emerging mechanistic insights, functional interactions, and potential implications for future epigenetic and epitranscriptomic therapeutic strategies.

Humans↗
PubMed2002

Delirium in patients with advanced cancer.

Managing delirium is of major importance in end-of-life care and frequently gives rise to controversies and to clinical and ethical dilemmas. These problems arise from a number of causes, including the sometimes-poor recognition or misdiagnosis of delirium despite its frequent occurrence. Delirium generates major symptomatic of distress for the patient, consequent stress for the patient's family, the potential to misinterpret delirium symptomatology, and behavioral management challenges for health care professionals. Paradoxically, delirium is potentially reversible in some episodes, but in many patients delirium presents a nonreversible terminal episode. Greater educational efforts are required to improve the recognition of delirium and lead to a better understanding of its impact in end-of-life care. Future research might focus on phenomenology, the development of low-burden instruments for assessment, communication strategies, and the family education regarding the manifestations of delirium. Further research is needed among patients with advanced cancer to establish a predictive model for reversibility that recognizes both baseline vulnerability factors and superimposed precipitating factors. Evidence-based guidelines should be developed to assist physicians in more appropriate use of sedation in the symptomatic management of delirium.

Causality↗
PubMed2000

Febrile neutropenia in children.

Fever is frequent in neutropenic patients and often related to infection. Two major concepts, have contributed to the marked mortality decrease of those patients by the end of the 1960s: firstly, the duration and severity of neutropenia were the most important variables linked to infection and secondly, prompt administration of broad-spectrum antimicrobials empirically, was life-saving. At the same time it was universally admitted that a careful daily examination of all portals of entry for micro-organisms was mandatory and that laboratory and imaging investigations were needed at regular intervals, keeping constantly in mind the individual type and stage of immunosuppression. Through many studies, paediatricians contributed markedly in standardisation of management of febrile neutropenic patients. Neutropenic patients are not equally prone to infections, partly due to the underlying cancer, chemotherapy and co-morbidity factors. Neutropenic children are not only vulnerable to bacteria, fungi and viruses commonly encountered in adults, but also to common viruses and bacteria. Very few studies included a viral work-up. Epidemiological new trends are observed: Gram-positive bacteria and fungi are on the rise. Simplifying and shortening antibiotic regimens were made possible because new potent antibiotics were launched. Since the mid-1980s, many paediatric centres commonly discharge patients before complete bone marrow recovery, provided that patients meet certain low-risk criteria and do not exhibit any clinical or biological evidence of bacterial infection. However, a few prospective randomised studies have been conducted for assessing the safety of early antibiotics discontinuation and safe early discharge. The choice of oral agents up to now was complicated by the reluctance using fluoroquinolones in children. New challenges are numerous in terms of diagnostic tools, detection of epidemiological trends and emerging pathogens, identification and control of nosocomial threats including drug resistance, assessment of the real impact of prophylaxis, evaluation of new agents, the need for more accurate risk scoring systems, outpatient management and the necessity for an optimal use of resources.

Anti-Bacterial Agents↗
PubMed2005

Tainted water on tap: what to tell patients about preventing illness from drinking water.

Annual cases of waterborne illness in the United States are estimated to number about 900,000, but most experts believe the incidence to be much higher. The U.S. Environmental Protection Agency regulates the nation's drinking water supply, setting maximum allowable levels for 87 known natural and synthetic contaminants; but thousands more go unregulated. This article describes selected contaminants and their known health effects, which range from acute gastroenteritis to cancer and reproductive and developmental effects. It discusses which populations are more vulnerable, outlines assessment, and elucidates nurses' roles in patient education and as community advocates for safer drinking water.

Aged↗
PubMed1996

Ethical and practical problems of early anti-cancer drug trials: a review of the literature.

Early clinical trials for new anti-cancer drug treatments typically use patients with cancer as research subjects. This paper identifies some of the ethical and practical concerns that arise from the recruitment of a vulnerable group of patients and their exposure to a drug of unknown risk or benefit. This review discusses the ethical principles related to recruitment and informed consent in cancer trials, and indicates that there is a lack of consensus concerning the requirements, process and practice of informed consent. It is suggested that, as yet, little is known about patients' decision making framework in this situation, and the need for further work that concentrates on the patient's point of view is highlighted. The paper concludes by discussing some of the difficulties associated with obtaining patients' opinions, and suggests that the use of a qualitative approach may overcome some of these problems.

Antineoplastic Agents↗
PubMed1993

Psychosexual dysfunction in women with gynaecological cancer following radical pelvic surgery.

OBJECTIVE: To assess the prevalence and severity of psychosexual dysfunction in women treated for cancer of the cervix and vulva by radical vulvectomy, Wertheim's hysterectomy and pelvic exenteration; and to identify the risk factors for sexual morbidity and ways in which it might be reduced. DESIGN: Retrospective study of patients by questionnaire and semistructured interview, 6 months to 5 years following surgery. SETTING: Gynaecology-Oncology Unit of a general hospital. PATIENTS: 105 English speaking women with gynaecological cancer. RESULTS: 90% of the women in relationships had been sexually active prior to surgery. Of this group, 24% had no sexual difficulties post-operatively; 66% of the latter still had problems more than 6 months later, and 15% of the latter never resumed intercourse (excluding those with a colpectomy). 82% of those aged less than 50 years who had had radiotherapy suffered sexual dysfunction. Lack of desire was the commonest problem, and half the women felt that their sexual relationship had deteriorated, yet only 16% felt that their marriage had worsened. Younger women were more likely to attribute personal and marital distress to their sexual problems. More information on sexual matters would have been liked by 28% of the women. CONCLUSIONS: Sexual dysfunction is common following radical pelvic surgery and tends to remain a chronic problem. As well as organic causes there is a strong psychogenic element brought about by loss of fertility, disfigurement, depression and anxiety about one's desirability as a sexual partner. The presence of a stable relationship before the diagnosis of cancer helps women cope better, and young single women are a very vulnerable group. Patients want more information on sexual matters and the provision of sexual counselling may improve outcome in the future.

Adult↗
PubMed2006

The role of perceived similarity in supportive responses to victims of negative life events.

The authors examined whether participants' perceived similarity to an ostensible victim of a negative life event influenced their supportiveness during a live interaction. Two competing models were considered: (a) increased similarity would be associated with increased supportiveness through attraction to the target and (b) increased similarity would be associated with decreased supportiveness through anxiety (due to heightened vulnerability). Participants (N = 241) met individually with a confederate posing as a cancer patient. Reactions were assessed, including verbal and nonverbal behaviors, both before and after the interaction, by participants themselves and by observers of the interaction. Results supported a model based on the classic similarity/attraction paradigm: Perceived similarity indirectly predicted participant-reported supportiveness/warmth and smiling through its relationship to attraction. Results extend the literature on similarity and attraction to the stress and coping arena and suggest that emphasizing perceived similarities to victims would be beneficial.

Adaptation, Psychological↗
PubMed2001

Dietary restriction stimulates BDNF production in the brain and thereby protects neurons against excitotoxic injury.

Dietary restriction (DR) increases the lifespan of rodents and increases their resistance to several different age-related diseases including cancer and diabetes. Beneficial effects of DR on brain plasticity and neuronal vulnerability to injury have recently been reported, but the underlying mechanisms are unknown. We report that levels of brain-derived neurotrophic factor (BDNF) are significantly increased in the hippocampus, cerebral cortex, and striatum of rats maintained on a DR regimen compared to animals fed ad libitum (AL). Seizure-induced damage to hippocampal neurons was significantly reduced in rats maintained on DR, and this beneficial effect was attenuated by intraventricular administration of a BDNF-blocking antibody. These findings provide the first evidence that diet can effect expression of a neurotrophic factor, demonstrate that BDNF signaling plays a central role in the neuroprotective effect of DR, and proffer DR as an approach for reducing neuronal damage in neurodegenerative disorders.

Actins↗
PubMed2003

Health outcomes assessment in vulnerable populations: measurement challenges and recommendations.

With growing recognition that some population subgroups are particularly vulnerable to receiving suboptimal health care and achieving poor health outcomes, innovative techniques are required for collecting and evaluating health outcomes data. Research is also needed to better understand the causal pathways linking vulnerability with health outcomes. This article focuses on patients with a chronic illness (cancer) who also have low literacy and/or poor English language skills. We summarize the association among literacy, language, ethnicity, and health outcomes; describe innovative technologies to enhance communication; and discuss the advantages of using psychometric measurement models in health outcomes assessment. Results from our ongoing research projects are presented, including the development of an audiovisual computer-based testing platform for self-administration of questionnaires. Such innovative multimedia technologies allow patients with limited or even no reading ability to participate in outcomes assessment and have the potential to be incorporated into a clinical setting with minimal burden on staff and patients. Appropriate methods are also needed to evaluate measurement equivalence across diverse patient groups, that is, the extent to which items in a questionnaire perform similarly across groups. Item response theory measurement models provide a strategy for differentiating between measurement bias and real differences that may exist between groups. Recommendations for clinical practice and research are offered specifically to address medically underserved and vulnerable populations.

Activities of Daily Living↗
PubMed2001

Improving rates of cervical cancer screening and Pap smear follow-up for low-income women with limited health literacy.

Adult literacy is an independent and important predictor of health behavior. In 1993, the National Adult Literacy Survey conducted by the U.S. Department of Education demonstrated that one-third of the U.S. population over age 16 (44 million adults) is functionally illiterate. Several studies link low health literacy to self-reported poor health status, poor health behavior, and inadequate knowledge about disease. Epidemiologic studies of cancer prevention have not detected strong racial and ethnic disparities in disease detection and progression, resulting in an emphasis on behavioral and intervention-based research. Low literacy presents a wide-reaching barrier to disease prevention that, unlike race/ethnicity, is potentially modifiable. Here, we explore the relationship between health literacy and health behaviors related to cervical cancer prevention in an effort to address concerns about low rates of screening and follow-up in vulnerable populations. Our goal is to improve our understanding of the health impact of low literacy among urban women and to inspire interventions that will promote disease prevention behaviors in this population, particularly with regard to cervical cancer.

Adult↗
PubMed1999

Factors influencing the carcinogenicity of food chemicals.

The relationship between food and cancer is extremely complex. It is generally accepted that diet is a contributory factor in the aetiology of a large proportion of cancers, but with very few exceptions, we are unable to identify specific causal agents. Many food components have genotoxic potential and more are produced endogenously during digestion. Conversely, there is increasing evidence that consumption of some foods may decrease the risk of cancer, and a number of plant constituents have been shown to have the potential to inhibit various stages of the carcinogenic process. Yet we have little understanding of the interactions between the different food-related genotoxic and protective factors. A further complication is the variation in individual susceptibility and vulnerability. As a result we are still not able to determine the optimal diet for minimising cancer risk. In recognition of these issues, the UK Ministry of Agriculture, Fisheries and Food (MAFF) is funding a number of projects aimed at providing greater mechanistic understanding of the links between food and cancer, in order to offer detailed advice to the public. This report summarises the proceedings of a workshop entitled 'Factors influencing the carcinogenicity of food chemicals', held in London on 1 June 1998, providing overviews of some of the key issues, and demonstrating how the MAFF-funded research is contributing to advances in these areas. It includes discussion of genetic polymorphisms and how they may contribute to individual susceptibility and help to identify causal links between food components and colorectal cancer. Biomarkers of DNA damage in human studies and of inhibition of carcinogen activation and endogenous formation of genotoxic reactive nitrogen species are examined. Also considered are the potential uses of physiologically based pharmacokinetic modelling techniques for providing more accurate estimates of risk and reducing the uncertainty in extrapolation between species and doses. Research now in progress will help to establish the critical risk and protective factors involved in diet-related colorectal cancers, in order to provide a sound scientific basis for formulation of dietary advice to the public.

Biomarkers↗
PubMed1990

Family history of cancer and mortality among patients gastrectomized because of benign gastric diseases.

A preliminary result from a cohort study on the association of a family history of cancer with mortality is discussed in this paper. Among 2200 patients (1912 males and 288 females) gastrectomized because of benign gastric diseases, 274 male patients, and 40 female patients had a family history of cancer. During 2750 person-years of observation, 22 patients with the family history of cancer were found to be dead and 111 patients without the family history died during 17,527 person-years, giving a relative risk of 1.26 (not significant). We focused on the male subjects that were followed up for more than 10 years; however, the observed/expected ratio of cancer deaths for subjects with a family history of cancer was about four times higher than that for those without family history. Since case-control studies on family history are vulnerable to biased recall and interchangeability of cases, more cohort studies like the present study should be conducted to assess the association of the family history of cancer.

Case-Control Studies↗
PubMedDate not supplied

Carrying on: the experience of premature menopause in women with early stage breast cancer.

BACKGROUND: The survival benefit of adjuvant chemotherapy for breast cancer is established but the experience of organ system toxicity for women, specifically ovarian toxicity, is not fully known. OBJECTIVES: Th e purpose of the study was to develop asubstantive theory that would describe and explain women's responses to chemotherapy-induced premature menopause within the context of breast cancer. METHODS: Qualitative inquiry with Grounded Theory methodology was used to collect, code, and analyze the data. The purposive sample consisted of 27 women with early stage breast cancer who received adjuvant chemotherapy. The majority of women were married, well educated, and employed with a mean age of 41 years. Amenorrhea was reported by 24 women, a peri-menopausal pattern of bleeding was described by two women, and one woman had return of normal menses. Women participated in interviews ranging from 45 minutes to 2 hours and other data sources, such as informal discussions with oncology care providers, and lay women's writings about menopause and midlife women's health were used to increase interpretation of the data. RESULTS: Vulnerability was identified as the basic social psychological problem for women. Carrying On is the basic process that explains how women respond to vulnerability as they attempt to assimilate drug-induced premature menopause into their breast cancer experience. The stages of Carrying On (Being Focused, Facing Uncertainty, Becoming Menopausal, and Balancing) progressed from minimizing the early menopause experience to developing an awareness to balancing the dynamic relationship of menopause and cancer in their lives. CONCLUSIONS: This study described the complexity of the experience of chemotherapy-induced premature menopause in women with early stage breast cancer and identified gaps in knowledge about menopausal symptom distress and factors influencing symptom management and outcomes in this population. Future research is needed to evaluate interventions during and after adjuvant therapy to improve the quality of survival of women who experience ovarian toxicity related to early stage breast cancer treatment.

Adaptation, Psychological↗