Nurses' Workplace Social Capital and the Influence of Transformational Leadership: A Theoretical Perspective.

Workplace social capital is the relational network, created by respectful interactions among members of a workforce, can contribute to the formation of a wholesome psychological work environment in an organization. Nurses' workplace social capital is a derivative of the workplace social capital, formed because of the complex interactions among the nursing and between the other healthcare professionals. Transformational leadership is a style of leadership that addresses the emotional wellbeing of its workforce and inspires shared group ethics, norms, and goals. The philosophy of transformational leadership is grounded on the premise of workforce as human beings with specific needs. Transformational leadership has been confirmed as a strong predictor of nurses' workplace social capital. Meanwhile, it is of an academic and/or healthcare industry operational value to scholarly assess and discern the theoretical influence of transformational leadership on nurses' workplace social capital. In this paper, we have attempted to explore the associations between transformational leadership and nurses' workplace social capital from a theoretical perspective. We have discussed the importance of each sub-dimension of transformational leadership (modeling the way, inspiring a shared vision, challenging the process, enabling others to act and encouraging the heart) in building up the social capital relational network. Finally, we have proposed a graphic framework of our analysis to facilitate understanding of the associations between the transformational leadership and nurses' workplace social capital, in formation of a healthy work environment which is the foundation for efficiency and productivity of the workforce.

Frontline Mongolian Healthcare Professionals and Adverse Mental Health Conditions During the Peak of COVID-19 Pandemic.

Background: The relatively young and inexperienced healthcare professionals in Mongolia faced with an unprecedent service demand in response to the COVID-19 pandemic. Due to the small size of the healthcare workforce the Mongolian Health Ministry had no choice but to mandate continuous and long workhours from the healthcare workforce. Many of the healthcare professionals exhibited signs and symptoms of mental health disorders. This study aimed to discern the prevalence various mental health concerns, i.e., depression, anxiety and stress, insomnia, and to discern the factors that increased susceptibility to mental health disorders among frontline healthcare professionals providing healthcare services for COVID-19 patients in Mongolia. Methods: A Cross-sectional research design was implemented. We collected data from 965 healthcare professional, randomly selected from 18 government hospitals, in four regions of Mongolia. Data were collected using the Depression Anxiety Stress-21, the General Self-Efficacy Scale, and the Insomnia Severity Index instruments. We constructed the scale of Pandemic Response Symptoms (PaReSy) which captured stress, depression, and anxiety. Data were analyzed using descriptive statistics, Kruskal-Wallis statistical test and multinominal logistic regression analysis. Results: Prevalence of depression (52.3%, CI 95%: 49.1-55.5%), anxiety (70.2%, CI 95%: 67.2-73.0%), and stress (35.8%, CI 95%: 32.7-38.9%) was documented among Mongolian healthcare professionals. Perception of self-efficacy reduced susceptibility to PaReSy either at mild/moderate (OR = 0.948, 95% CI = 0.911-0.988, P = 0.011) or severe/extremely severe level (OR = 0.911, 95% CI = 0.861-0.963, P = 0.001). Within each stratum of insomnia, the risk of experiencing PaReSy increased almost linearly both in the category of mild/moderate PaReSy and in the category of severe/extremely severe PaReSy. Conclusion: Improving self-efficacy and sleeping quality can assist healthcare workers to manage depression, anxiety, and stress. Findings provide important evidence to implement measures and strategies to assist healthcare professionals in low- and middle-income countries to constructively address their mental health concerns and needs.

Non-coding regions of nuclear-DNA-encoded mitochondrial genes and intergenic sequences are targeted by autoantibodies in breast cancer.

Autoantibodies against mitochondrial-derived antigens play a key role in chronic tissue inflammation in autoimmune disorders and cancers. Here, we identify autoreactive nuclear genomic DNA (nDNA)-encoded mitochondrial gene products (GAPDH, PKM2, GSTP1, SPATA5, MFF, TSPOAP1, PHB2, COA4, and HAGH) recognized by breast cancer (BC) patients' sera as nonself, supporting a direct relationship of mitochondrial autoimmunity to breast carcinogenesis. Autoreactivity of multiple nDNA-encoded mitochondrial gene products was mapped to protein-coding regions, 3' untranslated regions (UTRs), as well as introns. In addition, autoantibodies in BC sera targeted intergenic sequences that may be parts of long non-coding RNA (lncRNA) genes, including LINC02381 and other putative lncRNA neighbors of the protein-coding genes ERCC4, CXCL13, SOX3, PCDH1, EDDM3B, and GRB2. Increasing evidence indicates that lncRNAs play a key role in carcinogenesis. Consistent with this, our findings suggest that lncRNAs, as well as mRNAs of nDNA-encoded mitochondrial genes, mechanistically contribute to BC progression. This work supports a new paradigm of breast carcinogenesis based on a globally dysfunctional genome with altered function of multiple mitochondrial and non-mitochondrial oncogenic pathways caused by the effects of autoreactivity-induced dysregulation of multiple genes and their products. This autoimmunity-based model of carcinogenesis will open novel avenues for BC treatment.

Molecular markers of risk of subsequent invasive breast cancer in women with ductal carcinoma in situ: protocol for a population-based cohort study.

INTRODUCTION: Ductal carcinoma in situ (DCIS) of the breast is a non-obligate precursor of invasive breast cancer (IBC). Many DCIS patients are either undertreated or overtreated. The overarching goal of the study described here is to facilitate detection of patients with DCIS at risk of IBC development. Here, we propose to use risk factor data and formalin-fixed paraffin-embedded (FFPE) DCIS tissue from a large, ethnically diverse, population-based cohort of 8175 women with a first diagnosis of DCIS and followed for subsequent IBC to: identify/validate miRNA expression changes in DCIS tissue associated with risk of subsequent IBC; evaluate ipsilateral IBC risk in association with two previously identified marker sets (triple immunopositivity for p16, COX-2, Ki67; Oncotype DX Breast DCIS score); examine the association of risk factor data with IBC risk. METHODS AND ANALYSIS: We are conducting a series of case-control studies nested within the cohort. Cases are women with DCIS who developed subsequent IBC; controls (2/case) are matched to cases on calendar year of and age at DCIS diagnosis. We project 485 cases/970 controls in the aim focused on risk factors. We estimate obtaining FFPE tissue for 320 cases/640 controls for the aim focused on miRNAs; of these, 173 cases/346 controls will be included in the aim focused on p16, COX-2 and Ki67 immunopositivity, and of the latter, 156 case-control pairs will be included in the aim focused on the Oncotype DX Breast DCIS score®. Multivariate conditional logistic regression will be used for statistical analyses. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Institutional Review Boards of Albert Einstein College of Medicine (IRB 2014-3611), Kaiser Permanente Colorado, Kaiser Permanente Hawaii, Henry Ford Health System, Mayo Clinic, Marshfield Clinic Research Institute and Hackensack Meridian Health, and from Lifespan Research Protection Office. The study results will be presented at meetings and published in peer-reviewed journals.

A conceptual model of nurses' workplace social capital: a theory synthesis.

BACKGROUND: Research has confirmed the importance of workplace social capital in the nursing workforce. Integration of the empirical evidence about nurses' workplace social capital into a scientific collection can provide a comprehensive presentation of this concept. This scientific collection can be a conduit for further research and advancement of nursing management and leadership. The purpose of this paper, therefore, is to discuss the process of developing a conceptual model of nurses' workplace social capital, an effective and concise approach to illustrate a scientific phenomenon. METHODS: The model of nurses' workplace social capital was developed following Walker and Avant's strategy of theory synthesis. Empirical evidence relevant to nurses' workplace social capital was synthesized by systematically examining the existing literature. PubMed, CINAHL, Web of Science and Google Scholar were searched periodically from October 2017 to July 2020. RESULTS: Our proposed conceptual model lays out the determinants and outcomes of nurses' workplace social capital and specifies the relational statements among these concepts. Nurses' workplace social capital is influenced by the organizational and individual determinants shaped by multiple layers of sub-concepts. The development and implementation of nurses' workplace social capital has three themes of consequences: 1) nurses' outcomes; 2) patients' outcomes; and 3) organizational outcomes. All the concepts and statements have been organized and aligned with the principles of "inventory of determinants or results" and "theoretical blocks". CONCLUSION: Our theoretical synthesis offers a comprehensive picture of the current knowledge of nurses' workplace social capital. Efforts should be dedicated to evaluating, revising, and revamping this newly developed model based on future empirical evidence. Our synthesized conceptual model is the segue to more comprehensive studies about nurses' workplace social capital. Interventional programs for the development of social capital can be structured based on the identified determinants.

Development and psychometric testing of quality nursing care scale in Mongolia.

BACKGROUND: Quality Nursing Care (QNC) is fundamental to the profession of nursing practice. Perception of QNC differ across the globe because of differences in social norms, cultural values and political ambiance and economy. This study aimed to develop a QNC instrument congruent with the Mongolian (QNCS-M) healthcare system and cultural values and societal norms. METHODS: Exploratory sequential mixed-method design was implemented to develop and assess performance of QNCS-M. First, we focused on developing the components of QNCS-M and their operational definitions. Second, we dedicated to ascertaining psychometric performance of QNCS-M. The field testing consisted of assessing the construct validity and internal consistency reliability. Correlation between QNCS-M and the criterion tool, Quality of Nursing Care Questionnaire-Registered Nurse was evaluated. RESULTS: The initial version of QNCS-M contained 66 items of which 7 (I-CVI < .78) were deleted after item-content validity assessment. The total-item correlation analysis yielded to exclusion of another 3 items (<.3). Additional 12 items were excluded after inter-item correlation (<.3, >.7). Results from Spearman rank-order correlation analysis of the remaining 44 items indicated relationship between social desirability and 6 items (r = -.09 to r = .11). These items were excluded to reduce the likelihood of potential information bias. A total of 38 items remained for exploratory factor analysis. Results from exploratory factor analysis yielded eigenvalues > 1.0 for the 9 domains. Three domains contained items fewer than 3. These domains and 2 items (factor loading <.4) were eliminated, yielding to 6 domains with 36-item. Results from internal consistency reliability yielded an overall Cronbach's α = .92; the coefficient values for the 6 domains ranging between .72 and .85 and Pearson correlation for stability reliability yielded an acceptable (r = .82, P < .001). CONCLUSION: Improving the quality of healthcare services delivered by nurses is a priority for the Mongolian government. The development of QNCS-M is a major stride in addressing this concern. The final version of QNCS-M which contains 36 items, loaded into 6 domains, was morphed to the specifics of the Mongolian healthcare systems and cultural values and societal norms. QNCS-M demonstrates a high level of content and construct validity with acceptable reliability.

A contemporary understanding of organizational climate in healthcare setting: A concept analysis.

AIM: The overarching objective of this report is to provide an updated definition of the concept of organizational climate and to strengthen its operational application. BACKGROUND: Organizational climate is one of the major contributing factors to the exodus of the nursing workforce from the profession. Extensive research has addressed the impact of "organizational climate" on the nursing workforce; yet variations in the interpretation of the concept calls for an updated definition. DESIGN: Walker and Avant's strategy was implemented. DATA SOURCE: Data were compiled from Medline and CINAHL, Google search engine, and book chapters. REVIEW METHOD: A comprehensive and detailed review of the literature was performed. Nineteen historic publications (1939-2012) and 39 healthcare-related publications (2013-2018) were included in the final review. RESULTS: The climate of an organization reflects a set of core values and behaviors that can be used to implement evidence-based leadership and management within the context of the 21st century. We have revised the definition of organizational climate to capture this context. CONCLUSION: The perception of a supportive and constructive climate in an organization propels the workforce, independent of ethnic or personal background, to a higher level of productivity and encourages loyalty and workforce stability.

A contemporary understanding of nurses' workplace social capital: A response to the rapid changes in the nursing workforce.

AIM: To provide an updated definition of the concept of nurses' workplace social capital that addresses changes in the contemporary nursing workforce. BACKGROUND: Social capital explains the components of a constructive work environment. Advancements in psychology of workplace and changes in the demographic structure of nursing workforce call for a revised version of nurses' workplace social capital. METHOD: Walker and Avant's approach was implemented. Data were compiled from 'Medline' and 'CINAHL', 'Google' search engine, book chapters and expertise of nursing academicians. RESULTS: Nurses' workplace social capital is a relational network that is configured by interactions among healthcare professionals. Although, various attributes influence these interactions, Relational Network, Trust, Shared Understanding, Reciprocity and Social Cohesion are considered as the major attributes. A healthy relational network creates a healthy workplace which can be further fortified by effective communication, active group engagements and a supportive leadership. CONCLUSIONS: Results of our concept analysis should establish a theoretical groundwork for nurse leaders to better build and more effectively lead the contemporary nursing workforce. IMPLICATION FOR NURSING MANAGEMENT: Leaders' dedication to workplace social capital is the tenet of a constructive workplace, which in return can support nurses to flourish in their clinical and the other professional responsibilities.

Mitochondrial autoimmunity and MNRR1 in breast carcinogenesis.

BACKGROUND: Autoantibodies function as markers of tumorigenesis and have been proposed to enhance early detection of malignancies. We recently reported, using immunoscreening of a T7 complementary DNA (cDNA) library of breast cancer (BC) proteins with sera from patients with BC, the presence of autoantibodies targeting several mitochondrial DNA (mtDNA)-encoded subunits of the electron transport chain (ETC) in complexes I, IV, and V. METHODS: In this study, we have characterized the role of Mitochondrial-Nuclear Retrograde Regulator 1 (MNRR1, also known as CHCHD2), identified on immunoscreening, in breast carcinogenesis. We assessed the protein as well as transcript levels of MNRR1 in BC tissues and in derived cell lines representing tumors of graded aggressiveness. Mitochondrial function was also assayed and correlated with the levels of MNRR1. We studied the invasiveness of BC derived cells and the effect of MNRR1 levels on expression of genes associated with cell proliferation and migration such as Rictor and PGC-1α. Finally, we manipulated levels of MNRR1 to assess its effect on mitochondria and on some properties linked to a metastatic phenotype. RESULTS: We identified a nuclear DNA (nDNA)-encoded mitochondrial protein, MNRR1, that was significantly associated with the diagnosis of invasive ductal carcinoma (IDC) of the breast by autoantigen microarray analysis. In focusing on the mechanism of action of MNRR1 we found that its level was nearly twice as high in malignant versus benign breast tissue and up to 18 times as high in BC cell lines compared to MCF10A control cells, suggesting a relationship to aggressive potential. Furthermore, MNRR1 affected levels of multiple genes previously associated with cancer metastasis. CONCLUSIONS: MNRR1 regulates multiple genes that function in cell migration and cancer metastasis and is higher in cell lines derived from aggressive tumors. Since MNRR1 was identified as an autoantigen in breast carcinogenesis, the present data support our proposal that both mitochondrial autoimmunity and MNRR1 activity in particular are involved in breast carcinogenesis. Virtually all other nuclear encoded genes identified on immunoscreening of invasive BC harbor an MNRR1 binding site in their promoters, thereby placing MNRR1 upstream and potentially making it a novel marker for BC metastasis.

Evaluation and Adaptation of a Laboratory-Based cDNA Library Preparation Protocol for Retrospective Sequencing of Archived MicroRNAs from up to 35-Year-Old Clinical FFPE Specimens.

Formalin-fixed paraffin-embedded (FFPE) specimens, when used in conjunction with patient clinical data history, represent an invaluable resource for molecular studies of cancer. Even though nucleic acids extracted from archived FFPE tissues are degraded, their molecular analysis has become possible. In this study, we optimized a laboratory-based next-generation sequencing barcoded cDNA library preparation protocol for analysis of small RNAs recovered from archived FFPE tissues. Using matched fresh and FFPE specimens, we evaluated the robustness and reproducibility of our optimized approach, as well as its applicability to archived clinical specimens stored for up to 35 years. We then evaluated this cDNA library preparation protocol by performing a miRNA expression analysis of archived breast ductal carcinoma in situ (DCIS) specimens, selected for their relation to the risk of subsequent breast cancer development and obtained from six different institutions. Our analyses identified six miRNAs (miR-29a, miR-221, miR-375, miR-184, miR-363, miR-455-5p) differentially expressed between DCIS lesions from women who subsequently developed an invasive breast cancer (cases) and women who did not develop invasive breast cancer within the same time interval (control). Our thorough evaluation and application of this laboratory-based miRNA sequencing analysis indicates that the preparation of small RNA cDNA libraries can reliably be performed on older, archived, clinically-classified specimens.

Association Between Benign Breast Disease in African American and White American Women and Subsequent Triple-Negative Breast Cancer.

IMPORTANCE: Compared with white American (WA) women, African American (AA) women have a 2-fold higher incidence of breast cancers that are negative for estrogen receptor, progesterone receptor, and ERBB2 (triple-negative breast cancer [TNBC]). Triple-negative breast cancer, compared with non-TNBC, likely arises from different pathogenetic pathways, and benign breast disease (BBD) predicts future non-TNBC. OBJECTIVE: To determine whether AA identity remains associated with TNBC for women with a prior diagnosis of BBD. DESIGN, SETTING, AND PARTICIPANTS: This study is a retrospective analysis of data of a cohort of 2588 AA and 3566 WA women aged between 40 and 70 years with a biopsy-proven BBD diagnosis. The data-obtained from the Pathology Information System of Henry Ford Health System (HFHS), an integrated multihospital and multispecialty health care system headquartered in Detroit, Michigan-include specimens of biopsies performed between January 1, 1994, and December 31, 2005. Data analysis was performed from November 1, 2015, to June 15, 2016. MAIN OUTCOMES AND MEASURES: Subsequent breast cancer was stratified on the basis of combinations of hormone receptor and ERBB2 expression. RESULTS: Case management, follow-up, and outcomes received or obtained by our cohort of 2588 AA and 3566 WA patients were similar, demonstrating that HFHS delivered care equitably. Subsequent breast cancers developed in 103 (4.1%) of AA patients (mean follow-up interval of 6.8 years) and 143 (4.0%) of WA patients (mean follow-up interval of 6.1 years). More than three-quarters of subsequent breast cancers in each subset were ductal carcinoma in situ or stage I. The 10-year probability estimate for developing TNBC was 0.56% (95% CI, 0.32%-1.0%) for AA patients and 0.25% (95% CI, 0.12%-0.53%) for WA patients. Among the 66 AA patients who developed subsequent invasive breast cancer, 16 (24.2%) developed TNBC compared with 7 (7.4%) of the 94 WA patients who developed subsequent invasive breast cancers and had complete biomarker data (P = .01). CONCLUSIONS AND RELEVANCE: This study is the largest analysis to date of TNBC in the context of racial/ethnic identity and BBD as risk factors. The study found that AA identity persisted as a significant risk factor for TNBC. This finding suggests that AA identity is associated with inherent susceptibility for TNBC pathogenetic pathways.

Comparative Analysis of Breast Cancer Phenotypes in African American, White American, and West Versus East African patients: Correlation Between African Ancestry and Triple-Negative Breast Cancer.

INTRODUCTION: Triple-negative breast cancer (TNBC) is more common among African American (AA) and western sub-Saharan African breast cancer (BC) patients compared with White/Caucasian Americans (WA) and Europeans. Little is known about TNBC in east Africa. METHODS: Invasive BC diagnosed 1998-2014 were evaluated: WA and AA patients from the Henry Ford Health System in Detroit, Michigan; Ghanaian/west Africans from the Komfo Anokye Teaching Hospital in Kumasi, Ghana; and Ethiopian/east Africans from the St. Paul's Hospital Millennium Medical College in Addis Ababa, Ethiopia. Histopathology and immunohistochemistry for estrogen receptor (ER), progesterone receptor (PR), and HER2/neu expression was performed in Michigan on formalin-fixed, paraffin-embedded samples from all cases. RESULTS: A total of 234 Ghanaian (mean age 49 years), 94 Ethiopian (mean age 43 years), 272 AA (mean age 60 years), and 321 WA (mean age 62 years; p = 0.001) patients were compared. ER-negative and TNBC were more common among Ghanaian and AA compared with WA and Ethiopian cases (frequency ER-negativity 71.1 and 37.1 % vs. 19.8 and 28.6 % respectively, p < 0.0001; frequency TNBC 53.2 and 29.8 % vs. 15.5 and 15.0 %, respectively, p < 0.0001). Among patients younger than 50 years, prevalence of TNBC remained highest among Ghanaians (50.8 %) and AA (34.3 %) compared with WA and Ethiopians (approximately 16 % in each; p = 0.0002). CONCLUSIONS: This study confirms an association between TNBC and West African ancestry; TNBC frequency among AA patients is intermediate between WA and Ghanaian/West Africans consistent with genetic admixture following the west Africa-based trans-Atlantic slave trade. TNBC frequency was low among Ethiopians/East Africans; this may reflect less shared ancestry between AA and Ethiopians.

Breast Cancer and African Ancestry: Lessons Learned at the 10-Year Anniversary of the Ghana-Michigan Research Partnership and International Breast Registry.

Women with African ancestry in western, sub-Saharan Africa and in the United States represent a population subset facing an increased risk of being diagnosed with biologically aggressive phenotypes of breast cancer that are negative for the estrogen receptor, the progesterone receptor, and the HER2/neu marker. These tumors are commonly referred to as triple-negative breast cancer. Disparities in breast cancer incidence and outcome related to racial or ethnic identity motivated the establishment of the International Breast Registry, on the basis of partnerships between the Komfo Anokye Teaching Hospital in Kumasi, Ghana, the University of Michigan Comprehensive Cancer Center in Ann Arbor, Michigan, and the Henry Ford Health System in Detroit, Michigan. This research collaborative has featured educational training programs as well as scientific investigations related to the comparative biology of breast cancer in Ghanaian African, African American, and white/European American patients. Currently, the International Breast Registry has expanded to include African American patients throughout the United States by partnering with the Sisters Network (a national African American breast cancer survivors' organization) and additional sites in Ghana (representing West Africa) as well as Ethiopia (representing East Africa). Its activities are now coordinated through the Henry Ford Health System International Center for the Study of Breast Cancer Subtypes. Herein, we review the history and results of this international program at its 10-year anniversary.

Cervical cancer screening and follow-up in 4 geographically diverse US health care systems, 1998 through 2007.

BACKGROUND: Cervical cancer screening and follow-up guidelines have changed considerably in recent years, but to the authors' knowledge few published reports exist to estimate the impact of these changes in community-based settings. The authors examined the patterns and results of cervical cancer testing and follow-up over a decade in 4 geographically diverse US health care systems to inform the future evaluation of changes resulting from increased uptake of the human papillomavirus (HPV) vaccination. METHODS: The authors studied women aged 21 to 65 years who were members of one of these health systems at any time between 1998 and 2007. Data were collected and standardized across sites, based on receipt of Papanicolaou (Pap) and HPV tests, HPV vaccination, cervical biopsies, and treatment of cervical dysplasia. Annual rates (per 1000 person-years) of Pap testing, HPV testing, and cervical biopsy and treatment procedures were calculated. Screening intervals and trends in the results of screening Pap tests and cervical biopsies also were examined. RESULTS: Pap testing rates decreased (from 483 per 1000 person-years in 2000 to 412 per 1000 person-years in 2007) and HPV testing rates increased over the study period. Screening frequency varied across health care systems, and many women continued to receive annual testing. All 4 sites moved to less frequent screening over the study period without marked changes in the overall use of cervical biopsy or treatment. CONCLUSIONS: Despite differences over time and across health plans in rates of cervical cancer testing and follow-up cervical procedures, the authors found no notable differences in Pap test results, diagnostic or treatment procedure rates, or pathological outcomes. This finding suggests that the longer screening intervals did not lead to more procedures or more cancer diagnoses.

Autoantibodies in breast cancer sera are not epiphenomena and may participate in carcinogenesis.

BACKGROUND: The objective of this work was to demonstrate that autoantibodies in breast cancer sera are not epiphenomena, and exhibit unique immunologic features resembling the rheumatic autoimmune diseases. METHODS: We performed a comprehensive study of autoantibodies on a collection of sera from women with breast cancer or benign breast disease, undergoing annual screening mammography. All women in this study had suspicious mammography assessment and underwent a breast biopsy. We used indirect immunofluorescence, the crithidia assay for anti-dsDNA antibodies, and multiple ELISAs for extractable nuclear antigens. RESULTS: Autoantibodies were detected in virtually all patients with breast cancer, predominantly of the IgG1 and IgG3 isotypes. The profile detected in breast cancer sera showed distinctive features, such as antibodies targeting mitochondria, centrosomes, centromeres, nucleoli, cytoskeleton, and multiple nuclear dots. The majority of sera showing anti-mitochondrial antibodies did not react with the M2 component of pyruvate dehydrogenase, characteristic of primary biliary cirrhosis. Anti-centromere antibodies were mainly anti-CENP-B. ELISAs for extractable nuclear antigens and the assays for dsDNA were negative. CONCLUSIONS: The distinctive autoantibody profile detected in BC sera is the expression of tumor immunogenicity. Although some of these features resemble those in the rheumatic autoimmune diseases and primary biliary cirrhosis, the data suggest the involvement of an entirely different set of epithelial antigens in breast cancer. High titer autoantibodies targeting centrosomes, centromeres, and mitochondria were detected in a small group of healthy women with suspicious mammography assessment and no cancer by biopsy; this suggests that the process triggering autoantibody formation starts in the pre-malignant phase and that future studies using validated autoantibody panels may allow detection of breast cancer risk in asymptomatic women. Autoantibodies developing in breast cancer are not epiphenomena, but likely reflect an antigen-driven autoimmune response triggered by epitopes developing in the mammary gland during breast carcinogenesis. Our results support the validity of the multiple studies reporting association of autoantibodies with breast cancer. Results further suggest significant promise for the development of panels of breast cancer-specific, premalignant-phase autoantibodies, as well as studies on the autoantibody response to tumor associated antigens in the pathogenesis of cancer.

Prevalence of colonoscopy before age 50.

OBJECTIVE: Describe the prevalence of colonoscopy before age 50, when guidelines recommend initiation of colorectal cancer screening for average risk individuals. METHOD: We assembled administrative health records that captured receipt of colonoscopy between 40 and 49-years of age for a cohort of 204,758 50-year-old members of four US health plans and used backward recurrence time models to estimate trends in receipt of colonoscopy before age 50 and variation in early colonoscopy by age and sex. We also used self-reported receipt of colonoscopy from 27,157 40- to 49-year-old respondents to the 2010 National Health Interview Survey (NHIS) to estimate the association between early colonoscopy and sex, race/ethnicity, and geographic location based on logistic regression models that accounted for the complex NHIS sampling design. RESULTS: About 5% of the health plan cohort had a record of colonoscopy before age 50. Receipt of early colonoscopy increased significantly from 1999 to 2010 (test for linear trend, p<0.0001), was more likely among women than men (RR=1.9, 95% CI 1.14-1.24) and in the east coast health plan compared to west coast and Hawaii plans. The NHIS analysis found that early colonoscopy was more likely in Northeastern residents compared to residents in the West (odds ratio=1.75, 95% CI 1.28-2.39). CONCLUSION: Colonoscopy before age 50 is increasingly common.

Follow-up and clinical significance of unsatisfactory liquid-based Papanicolaou tests.

BACKGROUND: To the authors' knowledge, few studies to date have examined adherence to recommended guidelines for follow-up and outcomes after an unsatisfactory Papanicolaou (Pap) test (UPT) with liquid-based technologies. METHODS: Within 4 US health plans, the median time to follow-up and the percentage of patients with follow-up testing by 120 days was calculated after a UPT. Multivariable analyses evaluated the association between clinical factors and follow-up testing. The authors compared the risk of a diagnosis of cervical intraepithelial neoplasia of type 2 or worse (CIN2+) after a UPT with the risk after a satisfactory Pap test while controlling for study site, test year, and other covariates. RESULTS: A total of 634,644 Pap tests performed between 2004 and 2010 were included in the current study. Of 1442 UPTs, 53.4% had follow-up testing within 120 days; follow-up differed across the health plans (P<.001) and was found to be higher among patients aged <50 years (57.2% vs 48.8%; P = .01) and those with positive human papillomavirus (HPV) results (84.6% vs 53.9; P <.01). The risk of CIN2+ was similar for patients with both unsatisfactory and satisfactory Pap tests. However, after a UPT, the variables of age <50 years, having no previous history of Pap testing, having a history of a previous abnormal Pap test, and positive HPV status were all found to be risk factors for CIN2+; a positive HPV test was found to be the strongest risk factor for developing CIN2+. A negative HPV test result was protective for a CIN2+ diagnosis. CONCLUSIONS: Various clinical factors associated with the risk of CIN2+ appear to influence the receipt of follow-up after a UPT. HPV test results in patients with UPTs might be used in follow-up strategies; specifically, a negative test result might reduce the urgency for repeat Pap testing.

Anti-centrosome antibodies in breast cancer are the expression of autoimmunity.

Centrosome abnormalities have been observed in nearly all human solid tumors, but their role in tumorigenesis is unclear. We have demonstrated that autoantibodies reacting with antigens in centrosomes are frequently found in BC sera. In this work, we attempted to characterize the centrosome antigens associated with BC. We immunoscreened a T7 cDNA library of BC proteins with BC sera, and the autoantigens identified were printed as a microarray and hybridized with BC and control sera. We used immunohistochemistry (IHC) to investigate the expression of the cloned autoantigens in BC tissue. Immunoscreening with BC sera led to the cloning of autoantibodies recognizing epitopes developing in a family of proteins located on centrosomes such as peri-centriolar material-1, isomorph CRA, stathmin1, HS actin gamma1, SUMO/sentrin peptidase 2, and ubiquitin-conjugating enzyme E2 variant 1. Antibody reactivity to these proteins that are associated with centrosome assembly and/or microtubule function was highly associated with the diagnosis of BC. IHC staining of formalin-fixed paraffin-embedded sections with specific antibodies showed that aurora and stathmin are expressed in BC. The discovery of autoantibodies to important centrosome antigens associated with BC suggests that this immune reactivity could be related to autoimmunity developing in BC. Our finding that some of these antibodies are also present in a group of healthy women suggests that breakdown of tolerance to centrosome proteins may occur early in breast carcinogenesis and that autoantibodies to centrosome antigens might be biomarkers of early BC.

Adiposity, inflammation, genetic variants and risk of post-menopausal breast cancer findings from a prospective-specimen-collection, retrospective-blinded-evaluation (PRoBE) design approach.

Chronic internal inflammation secondary to adiposity is a risk factor for sporadic breast cancer and Post-Menopausal Breast Cancer (PMBC) is largely defined as such. Adiposity is one of the clinical criteria for the diagnosis of Metabolic Syndrome (MetS) and is a risk factor for PMBC. We examined SNPs of eight genes implicated in adiposity, inflammation and cell proliferation in a Prospective-specimen-collection, Retrospective-Blinded-Evaluation (PRoBE) design approach. A total of 180 cases and 732 age-matched controls were identified from the MyCode prospective biobank database and then linked to the Clinical Decision Information System, an enterprise-wide data warehouse, to retrieve clinico-demographic data. Samples were analyzed in a core laboratory where the personnel were masked to their status. Results from multivariate logistic regression yielded one SNP (rs2922126) in the GHSR as protective against PMBC among homozygotes for the minor allele (A/A) (OR = 0.4, 95% CI 0.18-.89, P-value = .02); homozygosity for the minor allele (C/C) of the SNP (rs889312) of the gene MAP3K1 was associated with the risk of PMBC (OR = 2.41, 95% CI 1.25-4.63 P-value = .008). Advanced age was protective against PMBC (OR = 0.98, 95% CI 0.95-0.99, P-value = .02). Family history of breast cancer (OR = 2.22, 95% CI 1.14-4.43. P = .02), HRT (OR = 3.35; 95% CI 2.15-5.21, P < .001), and MetS (OR = 14.83, 95% CI 5.63-39.08, P < .001) and interaction between HRT and MetS (OR = 39.38, 95% CI 15.71-98.70, P < .001) were associated with the risk of PMBC. We did not detected significant interactions between SNPs or between the SNPs and the clinico-demographic risk factors. Our study further confirms that MetS increases the risk of PMBC and argues in favor of reducing exposure to HRT. Our findings are another confirmation that low penetrance genes involved in the inflammatory pathway, i.e. MAP3KI gene, may have a plausible causative role in PMBC. Given the fact that genetic constitutionality of individuals cannot be changed, efforts should be focused on life style modification.

Assessing patient-centered communication in cancer care: stakeholder perspectives.

PURPOSE: Patient-centered communication is critical to quality cancer care. Effective communication can help patients and family members cope with cancer, make informed decisions, and effectively manage their care; suboptimal communication can contribute to care breakdowns and undermine clinician-patient relationships. The study purpose was to explore stakeholders' views on the feasibility and acceptability of collecting self-reported patient and family perceptions of communication experiences while receiving cancer care. The results were intended to inform the design, development, and implementation of a structured and generalizable patient-level reporting system. METHODS: This was a formative, qualitative study that used semistructured interviews with cancer patients, family members, clinicians, and leaders of health care organizations. The constant comparative method was used to identify major themes in the interview transcripts. RESULTS: A total of 106 stakeholders were interviewed. Thematic saturation was achieved. All stakeholders recognized the importance of communication and endorsed efforts to improve communication during cancer care. Patients, clinicians, and leaders expressed concerns about the potential consequences of reports of suboptimal communication experiences, such as damage to the clinician-patient relationship, and the need for effective improvement strategies. Patients and family members would report good communication experiences in order to encourage such practices. Practical and logistic issues were identified. CONCLUSION: Patient reports of their communication experiences during cancer care could increase understanding of the communication process, stimulate improvements, inform interventions, and provide a basis for evaluating changes in communication practices. This qualitative study provides a foundation for the design and pilot testing of such a patient reporting system.