Steroidal saponin profiles and their key genes for synthesis and regulation in Asparagus officinalis L. by joint analysis of metabolomics and transcriptomics.

BACKGROUND: Asparagus officinalis L. is a worldwide cultivated vegetable enrichened in both nutrient and steroidal saponins with multiple pharmacological activities. The upstream biosynthetic pathway of steroidal saponins (USSP) for cholesterol (CHOL) synthesis has been studied, while the downstream pathway of steroidal saponins (DSSP) starting from cholesterol and its regulation in asparagus remains unknown. RESULTS: Metabolomics, Illumina RNAseq, and PacBio IsoSeq strategies were applied to different organs of both cultivated green and purple asparagus to detect the steroidal metabolite profiles & contents and to screen their key genes for biosynthesis and regulation. The results showed that there is a total of 427 compounds, among which 18 steroids were detected with fluctuated concentrations in roots, spears and flowering twigs of two garden asparagus cultivars. The key genes of DSSP include; steroid-16-hydroxylase (S16H), steroid-22-hydroxylase (S22H) and steroid-22-oxidase-16-hydroxylase (S22O-16H), steroid-26-hydroxylase (S26H), steroid-3-ß-glycosyltransferase (S3ßGT) and furostanol glycoside 26-O-beta-glucosidases (F26GHs) which were correlated with the contents of major steroidal saponins were screened, and the transcriptional factors (TFs) co-expressing with the resulted from synthetic key genes, including zinc fingers (ZFs), MYBs and WRKYs family genes were also screened. CONCLUSIONS: Based on the detected steroidal chemical structures, profiles and contents which correlated to the expressions of screened synthetic and TFs genes, the full steroidal saponin synthetic pathway (SSP) of asparagus, including its key regulation networks was proposed for the first time.

Factors Associated with Cancer Screening Among Hopi Men.

Cancer screening rates remain low among American Indian men, and cancer screening behaviors and barriers to cancer screening among American Indian men are not well understood. This study evaluated cancer screening behaviors in 102 Hopi men who were 50 years of age or older from the Hopi Survey of Cancer and Chronic Disease. Reported cancer screening frequencies were 15.7%, 45.1%, and 35.3% for fecal occult blood test (FOBT), colonoscopy, and prostate-specific antigen (PSA) test, respectively. Among men who reported having had a FOBT, 81.2% had the test more than 1 year ago. Among men who reported a colonoscopy, 60.8% had colonoscopy within the past 3 years. Similarly, among men who reported having had PSA, 72.3% had PSA within the past 3 years. "No one told me" was the most common answer for not undergoing FOBT (33.7%), colonoscopy (48.2%), and PSA (39.4%). Men who reported having had a PSA or digital rectal exam were three times as likely to also report having a FOBT or colonoscopy (odds ratio [OR] 3.19, 95% confidence interval [CI]: 1.21-8.46). Younger age (< 65) was associated with reduced odds of ever having prostate cancer screening (OR 0.28, 95% CI: 0.10-0.77). Ever having colorectal cancer screening and previous diagnosis of cancer increased odds of ever having prostate cancer screening (OR 3.15, 95% CI: 1.13-8.81 and OR 5.28, 95% CI: 1.15-24.18 respectively). This study illustrates the importance of community cancer education for men to improve cancer screening participation.

Caregiving on the Hopi Reservation: Findings from the 2012 Hopi Survey of Cancer and Chronic Disease.

A family caregiver provides unpaid assistance to a family member/friend with a chronic disease, illness or disability. The caregiving process can affect a caregiver's quality of life by reducing time for themselves, for other family members and for work. The 2000 Behavioral Risk Factor Surveillance Survey estimates that 16 % of adult American Indians (AIs) are caregivers. A 2012 survey collected knowledge and personal experience data from a random sample of Hopi men and women (248 men and 252 women). Self-identified caregivers answered questions on time spent caregiving, caregiver difficulties and services requested. Approximately 20 % of the 500 Hopi participants self-identified as caregivers (N = 98), with 56 % female. Caregivers in contrast to non-caregivers had a lower percentage of ever having a mammogram (86, 89 %), a higher percentage of ever having had a Pap smear test (89.1, 85.6 %), a prostate specific antigen test (35, 30.6 %) and ever having had a colonoscopy (51.2, 44 %). Almost 21 % of caregivers reported difficulty with stress and 49 % reported it as their greatest caregiver difficulty. More males (28.6 %) identified financial burden as the greatest difficulty than females (p = 0.01). Training on patient care was the service that caregivers would like to receive most (18.2 %). The percentage of Hopi's providing caregiving was similar to national averages, although among men, was somewhat higher than national data (44 vs. 34 %). Stress was identified as a difficulty, similar to national studies.

Cancer Screening on the Hopi Reservation: A Model for Success in a Native American Community.

American Indian women have lower cancer survival rates compared to non-Hispanic White women. Increased cancer screening fostered by culturally sensitive education and community programs may help decrease this disparity. This study assesses the effectiveness of Hopi Cancer Support Services (HCSS) in maintaining high rates of breast and cervical cancer screening among Hopi women and evaluates the impact of participation in HCSS programs on colorectal cancer (CRC) screening. A population-based survey was conducted on the Hopi reservation in 2012 (n = 252 women). Frequency of breast, cervical, and colorectal cancer screenings, participation in HCSS programs and barriers to screening were evaluated. Unconditional multiple logistic regression estimated the independent effect of the HCSS program on CRC screening. Approximately 88 % of Hopi women 40+ reported ever having had a mammogram; 71 % did so within the past 2 years. Approximately 66 % of women 50+ were ever screened for colorectal cancer (FOBT and/or colonoscopy). Women who had their last mammogram through HCSS were 2.81 (95 % CI 1.12, 7.07) times more likely to have been screened for CRC. Breast and cervical cancer screening continues at a high rate among Hopi women and is substantially greater than that reported prior to the inception of HCSS. Furthermore, participation in programs offered by HCSS is strongly associated with increased colorectal cancer screening. This tribal health program (HCSS) has strongly influenced cancer screening among Hopi women and is a model of a tribally run cancer prevention program.

Profiles of phenolics and their synthetic pathways in Asparagus officinalis L.

The synthetic pathways of some phenolics compounds in asparagus have been reported, however, the diversified phenolics compounds including their modification and transcription regulation remains unknown. Thus, multi-omics strategies were applied to detect the phenolics profiles, contents, and screen the key genes for phenolics biosynthesis and regulation in asparagus. A total of 437 compounds, among which 204 phenolics including 105 flavonoids and 82 phenolic acids were detected with fluctuated concentrations in roots (Rs), spears (Ss) and flowering twigs (Fs) of the both green and purple cultivars. Based on the detected phenolics profiles and contents correlated to the gene expressions of screened synthetic enzymes and regulatory TFs, a full phenolics synthetic pathway of asparagus was proposed for the first time, essential for future breeding of asparagus and scaled healthy phenolics production using synthetic biological strategies.

AoSAP8-P encoding A20 and/or AN1 type zinc finger protein in asparagus officinalis L. Improving stress tolerance in transgenic Nicotiana sylvestris.

The full length CDS of an A20 and AN1 type zinc finger gene (named AoSAP8-P), located nearby the male specific Y chromosome (MSY) region of Asparagus officinalis (garden asparagus) was amplified by RT-PCR from purple passion. This gene, predicted as the stress associated protein (SAPs) gene families, encodes 172 amino acids with multiple cis elements including light, stress response box, MYB and ERF binding sites on its promoter. To analyze its function, the gene expression of different organs in different asparagus gender were analyzed and the overexpressed transgenic Nicotiana sylvestris lines were generated. The results showed the gene was highly expressed in both flower and root of male garden asparagus; the germination rate of seeds of the T2 transgenic lines (T2-5-4 and T2-7-1) under the stress conditions of 125 mM NaCl and 150 mM mannitol were significantly higher than the wild type (WT) respectively. When the potted T2-5-4, T2-7-1 lines and WT were subjected to drought stress for 24 days and the leaf discs immerged into 20 % PEG6000 and 300 mM NaCl solution for 48 h respectively, the T2-5-4 and T2-7-1 with AoSAP8-P expression showed stronger drought, salt and osmotic stress tolerance. When compared, the effects of AoSAP8-P overexpression on productive development showed that the flowering time of transgenic lines, were âˆ¼ 9 day earlier with larger but fewer pollens than its WT counterparts. However, there were no significant differences in anthers, stigmas and pollen viability between the transgenic lines and WT. Our results suggested that, the AoSAP8-P gene plays a role in improving the stress resistance and shortening seeds generation time for perianal survival during the growth and development of garden asparagus.

Identification of Bioactive Components of Stephania epigaea Lo and Their Potential Therapeutic Targets by UPLC-MS/MS and Network Pharmacology.

Stephania epigaea, an important traditional folk medicinal plant, elucidating its bioactive compound profiles and their molecular mechanisms of action on human health, would better understand its traditional therapies and guide their use in preclinical and clinical. This study aims to detect the critical therapeutic compounds, predict their targets, and explore potential therapeutic molecular mechanisms. This work first determined metabolites from roots, stems, and flowering twigs of S. epigaea by a widely targeted metabolomic analysis assay. Then, the drug likeness of the compounds and their pharmacokinetic profiles were screened by the ADMETlab server. The target proteins of active compounds were further analyzed by PPI combing with GO and KEGG cluster enrichment analysis. Finally, the interaction networks between essential compounds, targets, and disease-associated pathways were constructed, and the essential compounds binding to their possible target proteins were verified by molecular docking. Five key target proteins (EGFR, HSP90AA1, SRC, TNF, and CASP3) and twelve correlated metabolites, including aknadinine, cephakicine, homostephanoline, and N-methylliriodendronine associated with medical applications of S. epigaea, were identified, and the compounds and protein interactions were verified. The key active ingredients are mainly accumulated in the root, which indicates that the root is the main medicinal tissue. This study demonstrated that S. epigaea might exert the desired disease efficacy mainly through twelve components interacting via five essential target proteins. EGFR is the most critical one, which deserves further verification by biological studies.

Pain experience of the elderly.

Too often, the elderly suffer silently and needlessly with chronic pain. To investigate the pain experience of the elderly living in the community, a descriptive research design was used. The aims of the study were to determine the prevalence of pain in an older population living in the community, to obtain a description of the older adult's pain experience, and to determine strategies used to manage their pain. The results of the study indicated that >90% of the elderly living in the community experienced pain within the past month, with 41% reporting discomforting, distressing, horrible, or excruciating pain. Musculoskeletal pain was found to be the most predominant pain, and inactivity was the most effective strategy used to lessen pain. Pain in the elderly continues to be a challenge which needs to be addressed more effectively by health care providers. Based on the high prevalence of pain experienced by the elderly and the expected demographic shifts in the next two decades, it is imperative to continue research in this area to assure the highest quality of life, as well as maximum functional ability, for the elderly. Health care providers need to understand the multidimensional pain experience that occurs in the daily life of the community-dwelling older adult and the most effective management strategies that can be used to provide pain relief.

Is expression or activation of Src kinase associated with cancer-specific survival in ER-, PR- and HER2-negative breast cancer patients?

The aim of the current study was to assess the expression levels of c-Src and phosphorylated Src kinase in human breast cancers and to establish if these are linked to oestrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status or patient survival. Tissue microarray technology was used to analyze 314 breast cancer specimens. Immunohistochemistry was performed using antibodies to c-Src, Y419Src, and Y215Src, and expression was assessed using the weighted histoscore method. High cytoplasmic c-Src kinase and high membrane phosphorylated activated Y419Src kinase was associated with decreased disease-specific survival. In contrast, phosphorylated activated nuclear and cytoplasmic Y215Src kinase expression levels were significantly associated with improved disease-specific survival. When the cohort was subdivided according to ER/PR/HER2 status, the ER-negative subgroup (105 patients) was associated with improved disease-specific survival and was found to be independent by multivariate analysis with a hazard ratio of 0.4 (interquartile range 0.2-0.8). High cytoplasmic c-Src expression was associated with decreased survival; high expression of activated c-Src (Y215) was associated with improved survival. This was potentiated in the ER/HER2-negative subgroup. Hence, administration of Src kinase inhibitors aiming to decrease phosphorylation should be approached with caution, especially in ER-negative patients. It is therefore essential to appropriately identify with the correct biomarkers which patients are most likely to respond to Src inhibitors.

Process for determining the cancer burden of the Hopi Tribe.

The Hopi Tribe is located in the northeastern part of Arizona on more than one million acres of federally reserved land. Tribally based community research, conducted in collaboration with University of Arizona researchers, has been successfully implemented on Hopi beginning with a cross-sectional community survey in 1993 and continuing with a second survey in 2006. Both surveys identified a strong community interest in cancer. This article reports on the process involved in a third study, in which official Hopi enrollment data were matched with Arizona Cancer Registry data. The process involved bringing in a new partner and obtaining tribal, state, and university approvals, as well as a signed data exchange agreement between the state and the Hopi Tribe. Technical implementation of the data match required computer programming and epidemiologic expertise, as well as an understanding of the community and the culture. Close collaboration among Hopi residents and university epidemiologists was critical.

Perceptions of the use of reflective learning journals in online graduate nursing education.

The purpose of this study was to examine the perceptions of graduate nursing students and a small sample of faculty regarding learning outcomes associated with reflective learning journals (RLJ) in online education. Reflective journaling is used extensively in nursing curricula, yet few studies have explored perceptions of learning outcomes with online students, specifically those preparing to become nurse educators.An electronic survey was developed utilizing items associated with four learning outcomes of reflective journaling: professional development, personal growth, empowerment, and facilitation of the learning process. Positive outcomes such as the connection between theory and practice, recognition of strengths and weaknesses, and integration of new ideas and concepts were identified. Obstacles included the amount of time needed for reflection and grading, and the development of trust between students and faculty. The results of this study indicate that graduate students and faculty perceive positive learning outcomes with the use of reflective journals in online education.

Learner-centered characteristics of nurse educators.

The purpose of this study was to describe the learner-centered teaching characteristics of nurse faculty who report using contemporary pedagogy. A secondary analysis of data collected by an international survey of nurse educators regarding pedagogical teaching approaches and strategies was used to answer the research questions. The study sought to: 1) describe characteristics emerging from faculty response, 2) make inferences from faculty responses regarding meaning, and 3) make inferences regarding the importance of the meaning to nursing. A qualitative research design was used to address the research question. Themes that emerged were placed under the concepts of power, role of teacher, responsibility of learner, and philosophy of evaluation guided by Weimer's (2002) conceptual framework of a learner-centered philosophy of teaching. Themes and meaning units derived from the study helped to generate textual and structure statements that represent the characterizations of learner-centered nurse educators.

Increasing incidence of breast cancer: distinguishing between the effects of birth cohort and a national breast screening programme.

The incidence of breast cancer in post-menopausal women has been affected by the introduction of national breast screening programmes. The study describes the incidence of breast cancer in Scottish women aged 50-64 by year of birth before, during, and after the prevalent round of screening. Breast cancer registrations in Scotland for women aged 45-69 years from 1977 to 2003 were obtained. Birth cohort incidence rates were calculated and interpreted in the light of screening patterns at particular calendar time points. In the years before screening, there was a small rise in breast cancer incidence by birth cohort in women aged 50-54 which was not seen in other ages. During the prevalent screening round, incidence increased significantly with increasing birth cohort and thereafter continued rises in incidence by birth cohort occurred. The observed rise in breast cancer incidence among post-menopausal women is likely to be due to both screening effects and a true increase in incidence.

The use of innovative pedagogies in nursing education: an international perspective.

The purpose of this global study was to explore the types of innovative pedagogies used in nursing education worldwide; transformative learning theory served as the theoretical basis for the study. A descriptive, mixed-method design with a researcher-developed instrument was used to conduct the electronic survey. Respondents were 946 nurse educator members of Sigma Theta Tau International; more than 93 percent were Caucasian women. Respondents indicated that the conventional teacher-centered approach remains the most prevalent pedagogical style (56 percent); fewer than 20 percent of respondents used feminist or postmodern approaches. Ninety percent of respondents reported using instruments to evaluate the effectiveness of their teaching. The majority viewed their faculty role as facilitator (88 percent) or information provider (65 percent). Greater efforts are needed to create an evidence base for nursing education through research that focuses on the effectiveness of innovative pedagogical strategies. This study, by describing the current patterns of teaching/learning strategies and approaches used by nurse educators, provides a beginning research base for improving nursing education.

Intestinal volvulus following laparoscopic surgery: a literature review and case report.

Since its introduction in the early 1990s, the laparoscopic cholecystectomy has become the standard surgical intervention for cholelithiasis. The laparoscopic technique is being used in an increasing number of abdominal procedures. Intestinal volvulus is a rare complication of laparoscopic procedures, such as the laparoscopic cholecystectomy. A review of the literature revealed 12 reports of this complication occurring without a clear cause. Etiologic factors that have been postulated include congenital malrotation, previous surgery, and intraoperative factors, such as pneumoperitoneum, mobilization of the bowel, and patient position. In this paper, we review the literature for this rare complication and report on a case of cecal bascule (a type of cecal volvulus) occurring following the laparoscopic cholecystectomy. Of the 12 prior reports of intestinal volvulus following laparoscopic procedures, 8 of these followed the laparoscopic cholecystectomy, of which two were cecal volvulae. This is the first reported case of a cecal bascule occurring following the laparoscopic cholecystectomy.

A review of narrative pedagogy strategies to transform traditional nursing education.

Traditional nursing pedagogies using teacher-centered learning approaches have produced efficient, knowledgeable nursing graduates for many years. However, 21st century learners will require and demand new educational approaches. The information age of computers has challenged all facets of education to keep pace. Nursing education must evolve with ever-changing forms of communication and technology and recognize generational differences in learning. The creation of partnerships in learning, rather than the traditional hierarchy of education, is projected to meet the needs of today's learners more effectively. The National League for Nursing, in its position statements, has challenged nurse educators to develop new research-based pedagogies responsive to the changing health care environment and reflective of new partnerships between and among students, teachers, and clinicians. This article will explore examples of one approach, narrative pedagogy, and its usefulness in nursing education as a way to expand the pedagogical literacy of nurse educators.

Leadership development in geriatric care through the Intergeneration Make a Difference Project.

The Intergeneration Make a Difference Project (MADP) is designed to develop leadership skills in geriatric nursing for seniors in a baccalaureate nursing program. This service-learning project with octogenarians and older individuals is based on theoretical constructs of caring. Stories and journaling are of great importance in the project. Expected outcomes are cognitive, affective, personal, and interpersonal. Students are expected to engage in critical/reflective thinking and develop leadership skills, heightened respect for the elderly, and interest in lifelong learning and a service orientation to society. Empowered to influence their clients, students receive the reciprocal benefits of an intergenerational relationship that, it is hoped, will affect how they care for the elderly in the future.

Improving self-directed learning/intercultural competencies: breaking the silence.

Nurse educators need to develop innovative, technological curricula that foster intercultural competencies as essential components of a university education and break the silence with respect to lesbian, gay, bisexual, transgender, and queer (LGBTQ) health. Goals are to foster using these competencies to make LGBTQ content explicit in nursing curricula and in their professional organizations to promote equality and lessen disparities in this group.

Effect of a 4-month tea intervention on oxidative DNA damage among heavy smokers: role of glutathione S-transferase genotypes.

Glutathione S-transferase (GST), a member of the phase II group of xenobiotic metabolizing enzymes, has been intensively studied at the levels of phenotype and genotype. The GST mu 1 (GSTM1) and GST theta 1 (GSTT1) genes have a null-allele variant in which the entire gene is absent. The null genotype for both enzymes has been associated with many different types of tumors. The aim of this study was to determine the possible differences in increased oxidative stress susceptibility to smoking within the GSTM1 and GSTT1 genotypes and the impact of high tea drinking on this. We designed a Phase II randomized, controlled, three-arm tea intervention trial to study the effect of high consumption (4 cups/day) of decaffeinated green or black tea, or water on oxidative DNA damage, as measured by urinary 8-hydroxydeoxyguanosine (8-OHdG), among heavy smokers over a 4-month period and to evaluate the roles of GSTM1 and GSTT1 genotypes as effect modifiers. A total of 133 heavy smokers (100 females and 33 males) completed the intervention. GSTM1 and GSTT1 genotype statuses were determined with a PCR-based approach. Multiple linear regression models were used to estimate the main effects and interaction effect of green and black tea consumption on creatinine-adjusted urinary 8-OHdG, with or without adjustment for potential confounders. Finally, we studied whether the effect of treatment varied by GSTM1 and GSTT1 status of the individual. Although there were no differences in urinary 8-OHdG between the groups at baseline, the between-group 8-OHdG levels at month 4 were statistically significant for GSTM1-positive smokers (P = 0.05) and GSTT1-positive smokers (P = 0.02). GSTM1-positive and GSTT1-positive smokers consuming green tea showed a decrease in urinary 8-OHdG levels after 4 months. Assessment of urinary 8-OHdG after adjustment for baseline measurements and other potential confounders revealed significant effect for green tea consumption (P = 0.001). The change from baseline was significant in both GSTM1-positive (t = -2.99; P = 0.006) and GSTT1-positive (P = 0.004) green tea groups, but not in the GSTM1-negative (P = 0.07) or GSTT1-negative (P = 0.909) green tea groups. Decaffeinated black tea consumption had no effect on urinary 8-OHdG levels among heavy smokers. Our data show that consumption of 4 cups of tea/day is a feasible and safe approach and is associated with a significant decrease in urinary 8-OHdG among green tea consumers after 4 months of consumption. This finding also suggests that green tea intervention may be effective in the subgroup of smokers who are GSTM1 and/or GSTT1 positive.

Characteristics of labor pain at two stages of cervical dilation.

This study characterized the pain reported in a selected group of obstetrical patients in labor and compared the pain experienced at 2 stages of dilation, dilation of 2-5 cm and of 6-10 cm. Pain was defined as the perception of an unpleasant sensory and emotional experience with multidimensional factors that evoke behavioral responses. The characteristics of pain were operationalized as responses of 78 laboring women to 3 self-report measures, the Visual Analogue Scale (VAS), Present Pain Intensity (PPI), and the McGill Pain Questionnaire (PRI-R), and 1 observational measure, the nurse-rated Behavioral Index of Pain (BIP). As cervical dilation increased, there were significant increases in self-reported pain and observed pain on all the cited measures. Pain was characterized as 'discomforting' during early dilation and as 'distressing, horrible, excruciating' as dilation progressed. Significant increases in pain with increased dilation occurred on all measures for multigravidas but only on the VAS for primigravidas.