Serum Concentrations of Oocyte-Secreted Factors BMP15 and GDF9 During IVF and in Women With Reproductive Pathologies.

Oocyte-secreted factors bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) are critical for folliculogenesis and fertility. This study developed ELISAs for the measurement of BMP15 and GDF9 in serum and investigated their usefulness as biomarkers of female reproductive function. Serum samples were obtained from women undergoing infertility treatments (n = 154) and from perimenopausal and postmenopausal women (n = 28). Serum concentrations of BMP15 and GDF9 were analyzed in women relative to age, anti-Müllerian hormone, number of oocytes retrieved, and polycystic ovary syndrome (PCOS) after superovulation for in vitro fertilization. BMP15 and GDF9 immunoassays were validated for specificity, sensitivity (24 and 26 pg/mL, respectively), and reproducibility. BMP15 and GDF9 were detectable in 61% and 29% of women, respectively. BMP15 and GDF9 varied 64-fold and 15-fold, respectively, between women, but they did not change within subjects following ovarian stimulation with gonadotropins. Serum GDF9 concentration, but not BMP15 concentration, was associated with oocyte number retrieved in patients without PCOS (P = 0.018). GDF9 and BMP15 associations with oocyte number differed significantly (P < 0.05) with PCOS status. GDF9 concentrations were lower in poor responders (women with fewer than four oocytes retrieved or with cancelled cycles; P = 0.020). Serum BMP15, but not GDF9, was lower in women >55 years of age, compared with women of reproductive age (P < 0.01). This study develops and validates immunoassays to quantitate BMP15 and GDF9 in human serum and to correlate concentrations with female reproductive potential. Although assay sensitivities require improvement, this study demonstrates the diagnostic potential of oocyte-secreted BMP15 and GDF9 as serum biomarkers in reproductive medicine.

Statewide At-Risk Tracking and Intervention for Nurses: Identifying and Intervening With Nursing Students at Risk of Attrition in Texas.

AIM: The purpose of this study was to identify students at risk of attrition and implement interventions to decrease the risk. BACKGROUND: The ability to identify and intervene with students deemed at risk of attrition can be a valuable tool for increasing the RN workforce. "Statewide At-Risk Tracking and Interventions for Nurses" (SATIN) involved students from 27 initial RN licensure nursing programs in Texas. METHOD: At-risk status of each nursing student was identified, and each nursing program provided interventions based on students' needs. RESULTS: The Weaver Reading Program was the most effective of the six intervention strategies used with SATIN participants. Lack of utilization of the interventions was the number one limitation of the study. CONCLUSION: Use of the Weaver Reading Program as well as personal engagement with students, one-on-one mentoring, and continued time investment are recommended to all programs.

A regional academic partnership for the early identification and retention of at-risk nursing students.

UNLABELLED: In a 2006 Texas Higher Education Coordinating Board report (Increasing RN Graduates in Texas: A Report to the 79th Legislature), nursing programs in Texas were challenged to increase the number of graduates to deal with the nursing shortage. This article describes the East Texas region's efforts to identify and intervene in the nursing student attrition rates of participating partners nursing programs. The primary purpose of this study was to identify and intervene with students at risk for attrition. Nine nursing programs participated in the study. METHODS: Online surveys were used to assess variables associated with attrition. Online interventions and an intensive test review protocol were used as intervention methods. RESULTS: Across the nine nursing programs, 898 students participated in the study. Regression and categorical data analysis revealed that lack of reading comprehension was the best predictor of a student being off track or out of a nursing program (P < .0001). Two other highly predictive variables of attrition were entrance examination composite scores (P = .0271) and a student's grades in anatomy and physiology (P = .005). Grant intervention protocols were effective in reducing the attrition rate (P = .0002) between students who participated during the grant period and those prior to implementation of the grant.

Biomarkers in Clinical Trials--SMi Conference. 23-24 September 2009, London, UK.

The Biomarkers in Clinical Trials conference, held in London, included topics covering new developments in the field of biomarkers. This conference report highlights selected presentations on the definition of biomarkers, the use of biomarkers to support decisions in drug development and to improve treatment outcomes, and the aims of the Biomarkers Consortium. A case study of the investigational drug selumetinib (AstraZeneca plc) is also discussed.

Against the oxidative damage theory of aging: superoxide dismutases protect against oxidative stress but have little or no effect on life span in Caenorhabditis elegans.

The superoxide radical (O(2)(-)) has long been considered a major cause of aging. O(2)(-) in cytosolic, extracellular, and mitochondrial pools is detoxified by dedicated superoxide dismutase (SOD) isoforms. We tested the impact of each SOD isoform in Caenorhabditis elegans by manipulating its five sod genes and saw no major effects on life span. sod genes are not required for daf-2 insulin/IGF-1 receptor mutant longevity. However, loss of the extracellular Cu/ZnSOD sod-4 enhances daf-2 longevity and constitutive diapause, suggesting a signaling role for sod-4. Overall, these findings imply that O(2)(-) is not a major determinant of aging in C. elegans.

Dietary restriction of Caenorhabditis elegans by axenic culture reflects nutritional requirement for constituents provided by metabolically active microbes.

In Caenorhabditis elegans, several manipulations that affect nutrition slow development, reduce fecundity, and increase life span. These are viewed as dietary restriction (DR) and include culture in semidefined, nutrient-rich liquid medium that is axenic (i.e., there is no microbial food source). Here we describe convenient ways to exert DR by culture on agar plates containing axenic medium. We used these to explore whether effects of axenic culture really reflect DR. Our results imply that major nutrient components of axenic medium, and overall caloric content, are not limiting for life span. However, adding growth-arrested Escherichia coli as an additional food source rescued the effects of axenic culture. We then sought to identify the component of E. coli that is critical for normal C. elegans nutrition using add-back experiments. Our results suggest that C. elegans has a nutritional requirement for live, metabolically active microbes or, possibly, an unidentified, heat-labile, nonsoluble component present in live microbes.

No influence of Indy on lifespan in Drosophila after correction for genetic and cytoplasmic background effects.

To investigate whether alterations in mitochondrial metabolism affect longevity in Drosophila melanogaster, we studied lifespan in various single gene mutants, using inbred and outbred genetic backgrounds. As positive controls we included the two most intensively studied mutants of Indy, which encodes a Drosophila Krebs cycle intermediate transporter. It has been reported that flies heterozygous for these Indy mutations, which lie outside the coding region, show almost a doubling of lifespan. We report that only one of the two mutants lowers mRNA levels, implying that the lifespan extension observed is not attributable to the Indy mutations themselves. Moreover, neither Indy mutation extended lifespan in female flies in any genetic background tested. In the original genetic background, only the Indy mutation associated with altered RNA expression extended lifespan in male flies. However, this effect was abolished by backcrossing into standard outbred genetic backgrounds, and was associated with an unidentified locus on the X chromosome. The original Indy line with long-lived males is infected by the cytoplasmic symbiont Wolbachia, and the longevity of Indy males disappeared after tetracycline clearance of this endosymbiont. These findings underscore the critical importance of standardisation of genetic background and of cytoplasm in genetic studies of lifespan, and show that the lifespan extension previously claimed for Indy mutants was entirely attributable to confounding variation from these two sources. In addition, we saw no effects on lifespan of expression knockdown of the Indy orthologues nac-2 and nac-3 in the nematode Caenorhabditis elegans.

Nursing in tele-mental health.

This article discusses a cooperative project involving an academic health sciences center, a state university, a women's shelter, and a community mental health center in East Texas, a medically underserved, rural region of Texas. The U.S. Department of Commerce provided grant funding to develop a telehealth network to provide an evaluation, referral, and treatment program for victims of domestic violence. Nurses were involved in all phases of the project, from initial conception through development, implementation, and evaluation. The authors concluded that all of the women involved in the study had significant mental health issues and other health concerns that were not being addressed by the existing health care delivery system. Without the use of telehealth, these women would have had limited access to primary health care and virtually no access to mental health services. The East Texas Tele-Mental Health Network demonstrates the value of the clinical and organizational skills that nurses bring to innovative models of mental health service delivery.

Telepsychiatry program for rural victims of domestic violence.

Domestic violence is a significant public health problem and is correlated with serious mental and physical disorders. Victims' fear and isolation seriously limit access to psychiatric evaluation and treatment. Telemedicine provides a means to overcome these obstacles. This article describes a telemedicine program that provides psychiatric screening, evaluation, treatment, and referral for ongoing care to clients of a rural women's crisis center. Psychiatric evaluation and treatment were provided to a rural women's shelter program using telepsychiatry. The shelter program had difficulty accessing traditional mental health service. All new clients entering the program were screened for mental health problems. Those requiring further evaluation received a physical examination with medical history and initial psychological interview on site, followed by psychiatric evaluation by videoconference. Appropriate treatment was initiated, and referral for ongoing psychiatric care through the local community mental health clinic was arranged. Of the 38 women referred for mental health services by clinic staff, 35 completed a psychiatric evaluation using telepsychiatry and 31 entered treatment. The most commonly identified disorders were anxiety and major affective disorders, followed by substance use disorders. Telepsychiatry can provide rapid crisis intervention and effective mental health services to victims of domestic violence in a rural setting.

Dietary restriction in C. elegans: from rate-of-living effects to nutrient sensing pathways.

The nematode Caenorhabditis elegans has been subjected to dietary restriction (DR) by a number of means, with varying results in terms of fecundity and lifespan. Two possible mechanisms by which DR increases lifespan are reduction of metabolic rate and reduction of insulin/IGF-1 signalling. Experimental tests have not supported either possibility. However, interaction studies suggest that DR and insulin/IGF-1 signalling may act in parallel on common regulated processes. In this review, we discuss recent developments in C. elegans DR research, including new discoveries about the biology of nutrient uptake in the gut, and the importance of invasion by the bacterial food source as a determinant of lifespan. The evidence that the effect of DR on lifespan in C. elegans is mediated by the TOR pathway is discussed. We conclude that the effect of DR on lifespan is likely to involve multiple mechanisms, which may differ according to the DR regimen used and the organism under study.

Participation in community health screenings: a qualitative evaluation.

Community health screenings and education programs have been widely used to identify individual health risks and promote early diagnosis and treatment of disease. Participation in these community activities is dependent on the initial health-seeking behaviors of the individual. Focus group interviews1 were conducted with both attendees and nonattendees of a program offering health education and screenings in various settings in a semirural area. The purpose of these group interviews was to better understand issues associated with participation. A domain analysis of the qualitative data revealed that multiple aspects of self-care orientations as well as interpersonal and environmental factors influenced participation. A paradoxical facilitator-inhibitor effect was apparent. The companionship and support inherent in a community setting was an incentive for participation, but also presented concerns about confidentiality. However, concern about getting knowledge about self-care and the fear and anxiety of learning the results of screening tests creates a push-pull dilemma that is a challenge for health care providers. Factors that influence participation in semirural community health screenings are varied and complex and suggest multidimensional approaches be used in designing programs.

Don't let the grievance process cause grief.

Faculty in a division of nursing at a state university has developed a unique way to handle student grievances. Community nurses serve on arbitration boards. These boards hear relevant evidence from both sides and render decisions, which are binding within the division. The process has been successful and has helped take "grief" out of the grievance process.

HRP-2, a heterogeneous nuclear ribonucleoprotein, is essential for embryogenesis and oogenesis in Caenorhabditis elegans.

Heterogeneous nuclear ribonucleoproteins (hnRNPs) have fundamental roles in the posttranscriptional control of gene expression. Here, we describe an hnRNP from Caenorhabditis elegans(HRP-2), which shares significant homology with mammalian hnRNP R, hnRNP Q and ACF, the essential complementation factor in ApoB mRNA editing. All four proteins possess a similar molecular architecture, with three closely linked RNA-binding domains and a C-terminus that contains RG/RGG repeat motifs. An HRP-2::GFP fusion protein was ubiquitously expressed in C. elegans during embryogenesis and subsequent larval development. Expression was also detected in the hermaphrodite gonad using a specific antibody, suggesting that HRP-2 is provided maternally. HRP-2 was predominantly localised to nuclei and analysis of transgenic lines expressing C-terminal deletions of HRP-2 defined a functional nuclear localisation signal. Analysis by RNAi demonstrated that HRP-2 was essential for embryogenesis and fertility. Cell divisions were slower in hrp-2(RNAi) embryos and the majority showed an early embryonic arrest phenotype. Shorter exposure to dsRNA allowed development to the twofold stage and the few embryos that hatched were abnormal. Adult worms that developed from embryos exposed to RNAi were completely sterile due to a failure in oocyte formation. These results demonstrate that HRP-2 or its RNA targets are essential for normal embryonic development and oogenesis in C. elegans.

Heat shock factor functions at the convergence of the stress response and developmental pathways in Caenorhabditis elegans.

Heat shock factor (HSF) is best characterized as the transcriptional regulator of heat shock protein genes, required by all cells to survive periods of stress. Recent evidence suggests that HSF also functions to regulate the expression of genes involved in growth and development under normal physiological conditions. In this study, we used RNA interference (RNAi) assays to investigate the role of HSF in Caenorhabditis elegans. Exposure of wild-type worms to hsf dsRNAi constructs caused a temperature-sensitive developmental arrest at the L2/L3 stage. At normal growth temperatures, hsf(RNAi) worms that developed to adults were small and scrawny, largely infertile, and showed a significant reduction in life span. These results demonstrate that HSF is required for normal postembryonic development under physiological conditions. Following heat shock, hsf(RNAi) worms were thermosensitive and displayed a significant reduction of hsp16 expression. When hsf(RNAi) was carried out in various dauer-constitutive mutant backgrounds, a dramatic reversal of dauer formation was observed, indicating that HSF is also required in the dauer pathway. In its natural habitat of the soil, where C. elegans is exposed to a constantly fluctuating environment; the ability to integrate the stress response with development may be an essential element of its ecology.

Lifespan extension in C. elegans by a molecular chaperone dependent upon insulin-like signals.

Insulin-like signalling is a key determinate of lifespan in diverse species including mammals but the mechanism by which this pathway influences the rate of aging is unknown. In the roundworm Caenorhabditis elegans, mutations in the insulin-like signalling pathway extend adult lifespan and are associated with up-regulation of stress response genes including those for heat shock proteins (HSPs). We tested the hypothesis that the C. elegans insulin-like signalling pathway determines longevity through modulating HSP levels. We introduced extra copies of the gene encoding HSP-16 and this conferred stress resistance and longevity both in a wildtype and a long-lived mutant strain. The DAF-16 transcription factor is essential for maximal hsp-16 expression and for lifespan extension conferred by hsp-16. This demonstrates that lifespan is determined in part by insulin-like regulation of molecular chaperones.

Biochemical and molecular characterization of two cytidine deaminases in the nematode Caenorhabditis elegans.

Two cytidine deaminases (CDDs) from the free-living nematode Caenorhabditis elegans have been cloned and characterized. Both Ce-CDD-1 and Ce-CDD-2 are authentic deaminases and both exhibit RNA-binding activity towards AU-rich templates. In order to study their temporal and spatial expression patterns in the worm, reporter gene constructs were made using approx. 2 kb of upstream sequence. Transfection of C. elegans revealed that both genes localized to the cells of the intestine, although their temporal expression patterns were different. Expression of Ce-cdd-1 peaked in the early larval stages, whereas Ce-cdd-2 was expressed in all life cycle stages examined. RNA-interference (RNAi) assays were performed for both genes, either alone or in combination, but only cdd-2 RNAi produced a consistent visible phenotype. A proportion of eggs laid from these worms were swollen and distorted in shape.

Stress resistance as a determinate of C. elegans lifespan.

It is difficult to exaggerate the progress that has been made in biogerontology over the last 15 years. As with all scientific revolutions, a few experiments in a small number of laboratories have changed the way in which we think about and design experiments. As a result of these experiments, there is much evidence to suggest that a rudimentary understanding of some of the processes that cause aging will be available in the next decade. One particular area of progress is the molecular genetics of lifespan. Although one may draw some distinctions between chronological lifespan and normal aging, extended lifespan remains one of the best indicators that an intervention in an aging process has been made. The isolation of a long-lived variant of a laboratory invertebrate is now essentially a trivial project but the information obtained from this approach is proving invaluable. As with most other biological problems, the most important experimental developments are coming from studying simple organisms in a reductionist fashion.