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At least 973 records · Page 54Linked to original sources
PubMed2003

Abnormal Pap test results and the rurality factor.

OBJECTIVE: To review the published socio-cultural determinants that put women in rural areas at greater risk of having an abnormal Pap test result. DESIGN: Literature review. CONCLUSION: An Australian woman is at increased risk of developing cervical dysplasia if she lives in a rural area, identifies as an Indigenous Australian or is from a non-English speaking country. Being aged over 50 years, increases the risk of cervical cancer but not cervical intra-epithelial neoplasia (CIN) 1, which peaks in the 20-24 year age group. Other connections with cervical dysplasia relate to a woman or her partner's sexual history, her nutritional status and possibly even her personality type. Smoking, social isolation, high negative life change events and having lived a 'troubled' life are all identified in the literature as increasing a woman's risk of having an abnormal Pap test result. Receiving an abnormal Pap test result often leads to feelings of fear, anxiety, guilt, shock, vulnerability, powerlessness, depression, shame and feeling dirty for the woman concerned. Compounding these negative feelings are social, practical and financial difficulties that have to be addressed. It is argued that social and medical models of health must complement each other to improve the well being of rural women experiencing an abnormal Pap result.

Adolescent↗
PubMed2002

Aging successfully: oral health for the prime of life.

Aging is a worldwide phenomena. More adults, particularly those in developed countries, are living longer and healthier lives. The average US life expectancy was 47 years in 1900; by 2000, it had increased to 74 years. As the population ages, the number of adults with acute and chronic illnesses increases. The use of medications also increases with age. People over 65 years of age make up about 12% of the US population, but they consume 30% of all prescription medications, many of which can have a negative impact on oral health. Although tooth loss is declining in US adults, the need for various types of dental services in the adult population continues to increase. Data on the use of dental services has shown that dental visits by older adults correlate with the presence of teeth, not age. Research on the epidemiology of periodontal disease in older adults suggests that the disease in older adults is probably not due to greater susceptibility but, instead, the result of cumulative disease progression over time. Data on root caries has shown that exposed root surfaces, in combination with compromised health status and the use of multiple medications, can increase an older adult's risk for root caries. Oral candidiasis commonly occurs in immunocompromised individuals of any age, but in older adults, nursing home residents are particularly susceptible. Oral cancer is a disease of older adults, with a median age of 64 at diagnosis. Tobacco and alcohol use are the most common risk factors. Mental or physical impairments, such as dementing illnesses, or impaired dexterity as a result of arthritis or stroke, can impair an adult's ability to perform adequate oral self-care. Preventing oral diseases in older adults requires an understanding of the risk factors for oral diseases and how these risk factors change over time. Of particular concern are nursing home residents, who remain the most vulnerable of elders. Incorporating preventive oral health strategies into dental treatment and nursing home care will play a critical role in maintaining oral health for a lifetime. Oral health education of family, caregivers, and nursing home staff is essential if oral diseases are to be avoided later in life.

Adult↗
PubMed2026

Integrative Transcriptomic and Proteomic Profiling Identifies S100P as a Potential Functional Biomarker for Sessile Serrated Lesions.

BACKGROUND: Sessile serrated lesions (SSLs) account for 15% of colorectal cancers (CRCs) but detection remains difficult due to flat morphology, mucinous features, and subtle histology. AIMS: This study aimed to identify novel and functionally relevant biomarkers of SSLs using transcriptomic screening and multi-omics validation. METHODS: Paired SSL and normal mucosa specimens (n = 6) underwent RNA sequencing. Differentially expressed genes (DEGs) were filtered for membrane or secretory proteins and validated across TCGA and adenoma transcriptomes. Functional significance was assessed using CRISPR dependency profiling, proteotranscriptomic concordance, pharmacogenomic sensitivity, and connectivity map analysis. RESULTS: We identified 216 upregulated genes in SSLs, including 68 encoding secretory/membrane proteins that better discriminated SSLs from controls and were enriched for adhesion and neuronal signaling while suppressing TNFα-NFκB inflammatory pathways. Cross-cohort comparison revealed five overlapping candidates between SSLs and TCGA CMS1 tumors. Among them, S100P emerged as the primary biomarker candidate, showing consistent upregulation in SSLs and CMS1 tumors while remaining low in normal mucosa and conventional adenomas. TFF1 also showed RNA-level upregulation but appeared more context-dependent. S100P demonstrated strong RNA-protein concordance in CRC cell-line profiling, supporting its detectability as a biomarker candidate. Pharmacogenomic profiling of LS411N cells revealed marked sensitivity to SN-38 and fluoropyrimidines, consistent with serrated CRC vulnerabilities. Connectivity map analysis identified perturbations, including MAPK1 and histone acetyltransferase suppression, that may reverse parts of the SSL transcriptional program. CONCLUSION: These findings prioritize S100P as a promising biomarker candidate for SSLs that warrants further validation in larger cohorts and clinically applicable platforms.

Humans↗
PubMed1997

Incorporating biomarkers of exposure and genetic susceptibility into smoking cessation treatment: effects on smoking-related cognitions, emotions, and behavior change.

In this article the authors report on the short-term impact of incorporating biomarker feedback about exposure and genetic susceptibility into minimal-contact quit-smoking counseling (QSC). Four hundred and twenty-seven smokers were randomized to 1 of 3 treatments: (a) QSC, (b) QSC + exposure biomarker feedback (EBF) about carbon monoxide in exhaled breath, or (b) QSC + EBF + biomarker feedback about genetic susceptibility to lung cancer (SBF). We observed significant immediate positive effects of SBF, compared with EBF and QSC on perceived risk, perceived quitting benefits, and fear arousal. However, at the 2-month follow-up, there were no group differences in quit rates. SBF did lead to significant reductions in the number of cigarettes smoked for smokers who were in the preparation stage. Smokers in the EBF and QSC conditions showed reductions in depressive symptoms by 2 months, but smokers in the SBF condition did not. In the context of QSC, genetic feedback may heighten vulnerability and possibly promote distress, but may not immediately enhance quitting in most smokers.

Adolescent↗
PubMed2006

Disruption of the Y-box binding protein-1 results in suppression of the epidermal growth factor receptor and HER-2.

The overexpression of the epidermal growth factor receptor (EGFR) and HER-2 underpin the growth of aggressive breast cancer; still, it is unclear what governs the regulation of these receptors. Our laboratories recently determined that the Y-box binding protein-1 (YB-1), an oncogenic transcription/translation factor, induced breast tumor cell growth in monolayer and in soft agar. Importantly, mutating YB-1 at Ser(102), which resides in the DNA-binding domain, prevented growth induction. We reasoned that the underlying cause for growth attenuation by YB-1(Ser(102)) is through the regulation of EGFR and/or HER-2. The initial link between YB-1 and these receptors was sought by screening primary tumor tissue microarrays. We determined that YB-1 (n = 389 cases) was positively associated with EGFR (P < 0.001, r = 0.213), HER-2 (P = 0.008, r = 0.157), and Ki67 (P < 0.0002, r = 0.219). It was inversely linked to the estrogen receptor (P < 0.001, r = -0.291). Overexpression of YB-1 in a breast cancer cell line increased HER-2 and EGFR. Alternatively, mutation of YB-1 at Ser(102) > Ala(102) prevented the induction of these receptors and rendered the cells less responsive to EGF. The mutant YB-1 protein was also unable to optimally bind to the EGFR and HER-2 promoters based on chromatin immunoprecipitation. Furthermore, knocking down YB-1 with small interfering RNA suppressed the expression of EGFR and HER-2. This was coupled with a decrease in tumor cell growth. In conclusion, YB-1(Ser(102)) is a point of molecular vulnerability for maintaining the expression of EGFR and HER-2. Targeting YB-1 or more specifically YB-1(Ser(102)) are novel approaches to inhibiting the expression of these receptors to ultimately suppress tumor cell growth.

Breast Neoplasms↗
PubMed2004

Family caring strategies in neutropenia.

Aggressive chemotherapy protocols result in neutropenia in approximately half of all patients receiving chemotherapy. Thus, neutropenia continues to be a significant and potentially life-threatening side effect of treatment, even with use of colony-stimulating factors. Families of patients with neutropenia often provide the primary healing environment because most chemotherapy protocols are managed on an outpatient basis. To learn about the family's experience of managing chemotherapy-induced neutropenia (CIN), a grounded-theory methodology was used to analyze data from seven families. The central theme revealed by these families was "turbulent waiting with intensified connections." This meant that when families had a sense of greater vulnerability in response to the waiting after diagnosis of CIN, they connected intensely with each other and healthcare providers. Families reported that connections with nurses became more significant when neutropenia interrupted chemotherapy. Families also developed family caring strategies to manage this period of waiting for the chemotherapy to resume. These strategies included family inquiry, family vigilance, and family balancing. Nurses need to be aware of approaches to support the family's ability to manage CIN. Interventions and approaches constructed from the perspective of a family-professional partnership will enhance the family cancer experience as well as ongoing family growth and function.

Adaptation, Psychological↗
PubMed1998

Children's health and the environment: a new agenda for prevention research.

Patterns of illness in American children have changed dramatically in this century. The ancient infectious diseases have largely been controlled. The major diseases confronting children now are chronic and disabling conditions termed the "new pediatric morbidity"--asthma mortality has doubled; leukemia and brain cancer have increased in incidence; neurodevelopmental dysfunction is widespread; hypospadias incidence has doubled. Chemical toxicants in the environment as well as poverty, racism, and inequitable access to medical care are factors known and suspected to contribute to causation of these pediatric diseases. Children are at risk of exposure to over 15,000 high-production-volume synthetic chemicals, nearly all of them developed in the past 50 years. These chemicals are used widely in consumer products and are dispersed in the environment. More than half are untested for toxicity. Children appear uniquely vulnerable to chemical toxicants because of their disproportionately heavy exposures and their inherent biological susceptibility. To prevent disease of environmental origin in America's children, the Children's Environmental Health Network (CEHN) calls for a comprehensive, national, child-centered agenda. This agenda must recognize children's vulnerabilities to environmental toxicants. It must encompass a) a new prevention-oriented research focus; b) a new child-centered paradigm for health risk assessment and policy formulation; and c) a campaign to educate the public, health professionals, and policy makers that environmental disease is caused by preventable exposures and is therefore avoidable. To anchor the agenda, CEHN calls for long-term, stable investment and for creation of a national network of pediatric environmental health research and prevention centers.

Child↗
PubMed2001

[Anti-tumor effect of E1B55kDa-deleted adenovirus on human hepatocellular carcinoma cell lines].

OBJECTIVE: To investigate the in vitro and in vivo anti-tumoral effect of E1B55kDa-deleted adenovirus (dl1520) on human hepatocellular carcinoma (HCC) cell lines. METHODS: Human HCC cell lines with different p53 genotypes were infected with dl1520. Four days after infection, the percentage of survival cells was determined by colorimetric assay. RT-polymerase chain reaction (PCR) was used to examine alterations of p53 and p21Waf-1 expression. Adenovirus hexon gene expression was applied to prove the presence of adenovirus infections. Effects on vivo anti-tumor dl1520 were examined with intra-tumor injection of dl1520 in the SCID mice. RESULTS: After the infection, the p53-null HCC cell line, Hep3B was most vulnerable to dl1520 induced cytotoxic effect with a cell death rate of more than 60%. Whereas, less than 20% PLC/PRF/5 (p53-mutant) and HepG2 (p53-wild type) HCC cell lines were killed. The expression of p53 and p21Waf-1 was considerably enhanced after the dl1520 infection in HepG2. The intra-tumor injection of dl1520 significantly reduced the tumor growth in Hep3B xenografts. In contrast, no obvious tumor repression was observed in HepG2 and PLC/PRF/5 xenografts. CONCLUSION: dl1520 selectively kills the p53-null hepatocellular carcinoma, showing potential application for cancer treatment.

Adenovirus E1B Proteins↗
PubMedDate not supplied

Comparison of lesbian and heterosexual women's response to newly diagnosed breast cancer.

In a study comparing lesbian and heterosexual women's response to newly diagnosed breast cancer, we compared data from 29 lesbians with 246 heterosexual women with breast cancer. Our hypotheses were that lesbian breast cancer patients would report higher scores of mood disturbance; suffer fewer problems with body image and sexual activity; show more expressiveness and cohesiveness and less conflict with their partners; would find social support from their partners and friends; and would have a poorer perception of the medical care system than heterosexual women. Our predictions regarding sexual orientation differences were supported for results regarding body image, social support, and medical care. There were no differences in mood, sexual activity or relational issues. Not predicted were differences in coping, indicating areas of emotional strength and vulnerability among the lesbian sample.

Acute Disease↗
PubMed2003

Age-specific norms and determinants of anxiety and depression in 731 women with breast cancer recruited through a population-based cancer registry.

The aim of this study was to determine population norms and determinants of anxiety and depression in a population-based sample of 731 women with breast cancer (aged 23-60 years) with the Hospital Anxiety and Depression scale (HADS). The prevalence of 'probable' psychological morbidity due to anxiety was 23% and due to depression was 3%. When the women identified as 'possible' cases were included, the respective proportions were 45 and 12%. Higher anxiety was present in younger, less educated women not born in Australia. There was no clear pattern of risk factors for depression. These population-based findings highlight the need for clinicians to be aware that age, education and country of birth may identify a particularly vulnerable subgroup. While brief scales such as the HADS are limited in their ability to accurately predict a clinical diagnosis, high scores identify those who may warrant referral for clinical evaluation.

Adaptation, Psychological↗
PubMed1998

Implementing breast and cervical cancer prevention programs among the Houma Indians of southern Louisiana: cultural and ethical considerations.

This paper provides an overview of the ethical and cultural issues that were taken into account in planning a cross-cultural study of barriers to breast and cervical cancer screening among Houma Indian women who reside in Terrebonne Parish, Louisiana. In such cross-cultural studies, the investigators and members of the target population are from different cultural backgrounds. In planning the study, ethical principles and cultural norms were carefully specified to ensure that the welfare of the participants would be protected and potential benefits maximized. This experience with the Houma Indian Nation illustrates the need for greater participation of research subjects in the planning and implementation of studies on their behalf. An ethical, culturally sensitive approach to cancer control research is needed to address the health concerns of Native American populations.

Adolescent↗
PubMed1993

Individual rights vs the public health: the problem of the Asian hepatitis B carriers in America.

The influx of Asians into the United States (both as refugees and immigrants) presented American public health authorities with a significant challenge because many of them were chronic hepatitis B carriers. The carriers posed a real, but undetermined level of risk of spreading the infection to the larger community. Of special importance was the danger that susceptible children would be infected in day-care centers, because the earlier the age of exposure, the greater the risk of developing chronic carriership; which in turn is associated with cirrhosis and cancer of the liver in later life. The Asian carriers presented both a health problem, and a moral dilemma. If the carrier situation became a subject of public debate, there was danger of a racist and discriminatory reaction to the newcomers. Faced with this problem, American public health authorities opted to protect the Asian carriers by assuring the medical profession and concerned members of the public that there was either no health risk, or the risk was easily controllable, despite the lack of evidence to support such positions. In their attempt to protect a vulnerable group from discrimination, they functioned as humanitarians, but abrogated their duty as scientists and thereby undermined the long-term credibility of those charged with protecting the public health. Thus, despite achieving some immediate benefits for a defenseless group, the price they paid for that protection was too high.

Asian↗
PubMed2001

The association of race/ethnicity, socioeconomic status, and physician recommendation for mammography: who gets the message about breast cancer screening?

OBJECTIVES: This study investigated the association between physician recommendation for mammography and race/ethnicity, socioeconomic status, and other characteristics in a rural population. METHODS: In 1993 through 1994, we surveyed 1933 Black women and White women 52 years and older in 10 rural counties. RESULTS: Fifty-three percent of the women reported a physician recommendation in the past year. White women reported recommendations significantly more often than did Black women (55% vs 45%; odds ratio = 1.49). Controlling for educational attainment and income eliminated the apparent racial/ethnic difference. After control for 5 personal, 4 health, and 3 access characteristics, recommendation for mammography was found to be more frequent among women who had access to the health care system (i.e., had a regular physician and health insurance). Recommendation was less frequent among women who were vulnerable (i.e., were older, had lower educational attainment, had lower annual family income). CONCLUSIONS: Socioeconomic status, age, and other characteristics--but not race/ethnicity--were related to reports of a physician recommendation, a precursor strongly associated with mammography use. Efforts to increase physician recommendation should include complementary efforts to help women address socioeconomic and other barriers to mammography use.

Black or African American↗
PubMed2000

Effect of CT digital image compression on detection of coronary artery calcification.

PURPOSE: To test the effect of digital compression of CT images on the detection of small linear or spotted high attenuation lesions such as coronary artery calcification (CAC). MATERIAL AND METHODS: Fifty cases with and 50 without CAC were randomly selected from a population that had undergone spiral CT of the thorax for screening lung cancer. CT image data were compressed using JPEG (Joint Photographic Experts Group) or wavelet algorithms at ratios of 10:1, 20:1 or 40:1. Five radiologists reviewed the uncompressed and compressed images on a cathode-ray-tube. Observer performance was evaluated with receiver operating characteristic analysis. RESULTS: CT images compressed at a ratio as high as 20:1 were acceptable for primary diagnosis of CAC. There was no significant difference in the detection accuracy for CAC between JPEG and wavelet algorithms at the compression ratios up to 20:1. CT images were more vulnerable to image blurring on the wavelet compression at relatively lower ratios, and "blocking" artifacts occurred on the JPEG compression at relatively higher ratios. CONCLUSION: JPEG and wavelet algorithms allow compression of CT images without compromising their diagnostic value at ratios up to 20:1 in detecting small linear or spotted high attenuation lesions such as CAC, and there was no difference between the two algorithms in diagnostic accuracy.

Adult↗
PubMed1999

Aldehyde dehydrogenase-mediated cellular relative insensitivity to the oxazaphosphorines.

As judged by findings in preclinical models, determinants of cellular sensitivity to cyclophosphamide and other oxazaphosphorines include two cytosolic aldehyde dehydrogenases, viz., ALDH1A1 and ALDH3A1. Each catalyzes the detoxification of the oxazaphosphorines; thus, cellular sensitivity to these agents decreases as cellular levels of ALDH1A1 and/or ALDH3A1 increase. Of particular clinical relevance may be that stable sublines, relatively insensitive to the oxazaphosphorines due to elevated ALDH1A1 or ALDH3A1 levels, emerged when cultured human tumor cells were exposed only once to a high concentration of one of these agents for 30 to 60 minutes. Whether differences in cellular levels of either enzyme accounts for the clinically-encountered uneven therapeutic effectiveness of the oxazaphosphorines remains to be determined. However, it has already been established that measurable levels of these enzymes are found in some, but not all, tumor types, and that in those tumor types where measurable levels are present, e.g., infiltrating ductal carcinomas of the breast, they vary widely from patient to patient. Potentially useful clinical strategies that might be pursued if it turns out that ALDH1A1 and/or ALDH3A1 are, indeed, clinically operative determinants of cellular sensitivity to the oxazaphosphorines include 1) individualizing cancer chemotherapeutic regimens based, at least in part, on the levels of these enzymes in the malignancy of interest, and 2) sensitizing tumor cells that express relatively large amounts of ALDH1A1 and/or ALDH3A1 to the oxazaphosphorines by preventing the synthesis of these enzymes, e.g., with antisense RNA, or by introducing an agent that directly inhibits the catalytic action of the operative enzyme. Further, the fact that ALDH1A1 and ALDH3A1 are determinants of cellular sensitivity to the oxazaphosphorines provides the rationale for the investigation of two additional strategies with clinical potential, viz., decreasing the sensitivity of vulnerable and essential normal cells, e.g., pluripotent hematopoietic cells, to the oxazaphosphorines by selectively transferring into them the genetic information that encodes 1) ALDH1A1 or ALDH3A1, or 2) a signaling factor, the presence of which would directly or indirectly, stably upregulate the expression of these enzymes.

Aldehyde Dehydrogenase↗
PubMed1998

[Mortality during the first six years after cholecystectomy. A review of all cholecystectomies in women in Denmark during 1977-1981].

It has been a prevailing assumption that cholecystectomy patients by and large follow a pattern of survival similar to that of the normal population. This paper presents a population-based study of the long-term survival after cholecystectomy in order to reassess this assumption. Based on data available in the Danish National Hospital Register, the records of all Danish women who were operated between 1977 and 1981 were examined and studied up to six years subsequent to surgery. Cholecystectomy patients who were free of diagnosed cancer and who had no major co-surgery (n = 11,123) were compared to both hysterectomy patients and a sample of the female population. Adjusting for age and other covariates, patients with psychiatric hospital admissions prior to surgery experienced a threefold risk of dying within six years after surgery. Patients with prior somatic admissions and patient with acute admissions had a relative risk (RR) of about 1.5. Cholecystectomy patients had a significantly increased mortality when compared to hysterectomy patients, RR = 1.3 (1.1-1.6), and to the population sample. Heart diseases and cancer occurred significantly more often as causes of death among cholecystectomy patients when compared to hysterectomy patients, but our data suggest that the occurrence of many other causes of death may be increased among cholecystectomy patients as well. The authors concluded that cholecystectomy patients are subject to relatively higher levels of mortality than previously assumed in parts of the literature. Furthermore, the increase seems to be attributable to a multitude of causes of death. The most likely explanation of the excess mortality among cholecystectomy patients is that gallbladder patients are relatively fragile. Indeed, with this vulnerable group of patients the potential trauma of the surgical intervention itself needs careful consideration.

Adult↗
PubMed1998

The patient without a couch: an analysis of a patient with terminal cancer.

The author reports an unusual clinical experience arising from the tragic circumstances of a patient who contracted cancer at the beginning of the fifth year of an analytic process. Instead of interrupting the analysis, the analyst suggested having sessions by telephone, as this patient could no longer leave her home when the terminal phase of her illness set in. The experience proved beneficial for the patient and enriching for the analyst. The patient was able to contain, work through and integrate the meaning and consequences of her disease, make reparations to her objects, and accept death with dignity. The analyst also emerged from the experience strengthened and more aware of her own vulnerability and mortality. The author brings up three relevant questions based on a review of the literature. These questions are: should the patient be told of his/her diagnosis and to what purpose? Can there be a productive analysis with such patients? What psychic structure and emotional conditions allow a patient to bear the truth?

Adaptation, Psychological↗
PubMed2026

Changes in the transcriptome and synthetic lethal dependencies following KRAS mutant expression reveal profound tissue specificity.

Oncogenic KRAS mutations exhibit a striking tissue-restricted tropism, occurring with high frequency in pancreatic, colorectal, and lung adenocarcinomas while remaining rare in other lineages. The molecular basis for why these specific tissues are uniquely permissive to KRAS transformation, and how this context shapes therapeutic vulnerabilities, remains poorly defined. Here, we utilized CRISPR-mediated genome engineering to generate endogenous, conditional KRAS-mutant isogenic cell line models across three primary permissive lineages (lung, colon, and pancreas) and the nonpermissive breast lineage. Integrated genome-wide CRISPR fitness screens and comparative transcriptome analyses revealed that KRAS-driven synthetic lethal (SL) dependencies are profoundly shaped by their tissue of origin. Strikingly, we observed minimal overlap in SL hits across lineages, with only three genes shared among the permissive lines, suggesting that the KRAS oncogene operates through divergent, context-specific genetic networks. Mechanistically, we show that KRAS activation induces a universal MYC-driven metabolic signature, but the specific machinery required to sustain this state is lineage-restricted. We identified a dependency on the diphthamide synthesis pathway to maintain translational fidelity amid a KRAS-induced hypertranslational state. These findings demonstrate that even when driven by the same oncogene, tumors exhibit distinct regulatory landscapes and unique genetic vulnerabilities. Our results provide a framework for developing lineage-aware therapeutic strategies, moving beyond universal KRAS inhibition toward targeted interventions tailored to a tumor's specific tissue context.

Proto-Oncogene Proteins p21(ras)↗