Investigations into bovine luteolytic mechanisms utilizing a long-term cell culture system

Luteal regression in the cow occurs every cycle in which pregnancy does not occur. The agent which induces luteolysis is a uterine prostaglandin, PGF\sb{2\alpha}, although the mechanism of its action remains unknown. The purpose of this study was to investigate the mode of action of PGF\sb{2\alpha} in a long-term, serum-free culture system of bovine luteal cells. Experiment I investigated the influence of LH and PGF\sb{2\alpha} on 3$\beta$-HSD presence in cultured luteal cells. Total numbers of cells dropped slightly throughout the 8 day culture. Numbers of 3$\beta$-positive cells also dropped in all treatment groups. 3$\beta$-HSD was best maintained in the presence of LH. PGF\sb{2\alpha} treatment had no influence on numbers of 3$\beta$-positive cells. Experiment II investigated the role of Ca\sp{++} and calmodulin in the regulation of P\sb4 steroidogenesis. The presence of extracellular Ca\sp{++} is mandatory for LH stimulation of P\sb4 as is seen in EGTA treated medium. Ca\sp{++}-enriched medium (A23187) increased LH-stimulated P\sb4 production. P\sb4 in the PGF\sb{2\alpha} treatment was not altered in either the presence or absence of elevated Ca\sp{++}. The production of endogenous PGF\sb{2\alpha} was not influenced by Ca\sp{++} environment. Ca\sp{++} antagonists TMB-8 and CCCP had no effects on basal P\sb4 production but did inhibit LH-stimulated P\sb4. Calmodulin antagonists, TFP and W-7, were only able to slightly inhibit LH-stimulated P\sb4 and had no effect on basal P\sb4. Experiment III investigated the influence of E\sb2 and phenol red, a weak E\sb2, on luteal P\sb4 steroidogenesis. E\sb2 was shown to suppress LH-stimulated P\sb4 in phenol-containing medium but had no effect on basal or PGF\sb{2\alpha}-induced P\sb4. The use of phenol-free medium resulted in higher absolute P\sb4 levels for control and LH treatments. E\sb2 suppressed LH-stimulated P\sb4 early in the culture but was unable to cause an effect on day 8 and 10. No statistically significant cooperative effects of E\sb2 + PGF\sb{2\alpha} were found but trends suggest lowered P\sb4 in the presence of both of these luteolytic agents. In conclusion, the presence of low levels of LH is suggested to maintain the number of steroidogenically active cells. PGF\sb{2\alpha} does not mediate its action through a reduction in 3$\beta$-HSD. LH-stimulated P\sb4 production requires free, intracellular and extracellular Ca\sp{++} whereas, the role of Ca\sp{++} in PGF\sb{2\alpha} action remains unknown. Also, free Ca\sp{++} appears to be a more important regulator of luteal steroidogenesis than calmodulin-bound Ca\sp{++}. Estrogen appears to have a direct effect on LH-stimulated P\sb4 production. Phenol red appears to influence basal and LH-stimulated P\sb4 production. The complete mechanism of PGF\sb{2\alpha} action remains to be elucidated

Traditionalism and parallel distributed processing as qualitatively distinct models of the mind.

My main concern in this work is answering the question: does parallel distributed processing (PDP) as a model of the mind offer a genuine alternative to traditionalism? There has been vigorous debate within the last eight years on the subject of the relative merits of the one model over the other; however, a detailed examination of the nature of their respective differences has not been attempted. The mental realm is that realm in which causal interaction is governed by laws quantifying over representational states. Traditionalism is the thesis that the law-governed transitions between mental states are transitions between computational states. PDP is the thesis that the transitions between mental states are transitions between distributed representational states in a PDP-type system. The representational content of a distributed state is determined by the causal history of the system as a whole, and results from the changing of system parameters via learning so as to insert this state in the causal chain between the perception of some external state-of-affairs and behavior. Traditionalism and PDP are best considered not as providing a detailed picture of the causal processes involved in mental activity, but rather as providing a general framework that sets broad constraints on how such law-governed transitions proceed. I describe two aspects of qualitative distinctness that can be used even when comparing such non-specific models. The first involves examining the ontological commitment of each: assuming a realist interpretation, what must exist if traditionalism (or PDP) is a true model of the mind? If the two models make the same commitments, one may ask the further question: do the constraints imposed on the form that mental causal transitions take allow the possibility of an isomorphism between causal sequences permitted by the one model with those permitted by the other? An examination of the manner in which representational content is determined within PDP systems shows that there is no possible isomorphism. Therefore, the two models are qualitatively distinct

Myrtle Goodrich Litch Doane Correspondence

Entries include a typed biography with a story about receiving a letter from the White House and a typed letter of correspondence

Implementing the Family-Led Care model for preterm and low birth weight newborns in Malawi : experience of healthcare workers

BACKGROUND : Every Preemie–SCALE developed and piloted the Family-Led Care model, an innovative, locally developed model of care for preterm and low birth weight babies receiving kangaroo mother care. AIM : The aim of this study was to describe healthcare workers’ experience using Family-Led Care. SETTING : This study was conducted in five health facilities and their catchment areas in Balaka district, Malawi. METHODS : The mixed-methods design, with two data collection periods, included record reviews, observations and questionnaires for facility staff and qualitative interviews with health workers of these facilities and their catchment areas. The total convenience sample comprised 123 health professionals, support staff and non-professional community health workers. RESULTS : Facility-based staff generally had positive perceptions of Family-Led Care (83%). Knowledge and application-of-knowledge scores were 69% and 52%, respectively. A major change between the first and the second data periods was improvement in client recordkeeping. Documentation of newborn vital signs increased from 62% to 92%. Themes emerging from the qualitative interview analysis were the following: benefits of Family-Led Care; activities supporting the implementation of Family-Led Care; own care practices; and families’ reaction to and experience of Family-Led Care. CONCLUSION : This article reports improved quality of care through better documentation and better follow-up of preterm and low birth weight babies receiving kangaroo mother care according to the Family-Led Care model. Overall, health workers were positive about their involvement, and they reported positive reactions from families. Lessons learned have been incorporated into a universal Family-Led Care package that is available for adaptation by other countries.The American people through the United States Agency for International Development (USAID) under the terms of Cooperative Agreement No. AID-OAA-A-14-00049 with Project Concern International.http://www.phcfm.oram2020School of Health Systems and Public Health (SHSPH

Nurses' perceptions of using an evidence-based care bundle for initial emergency nursing management of patients with severe traumatic brain injury: A qualitative study.

Evidence to guide initial emergency nursing care of patients with severe traumatic brain injury (TBI) in Thailand is currently not available in a useable form. A care bundle was used to summarise an evidence-based approach to the initial emergency nursing management of patients with severe TBI and was implemented in one Thai emergency department. The aim of this study was to describe Thai emergency nurses' perceptions of care bundle use. A descriptive qualitative study was used to describe emergency nurses' perceptions of care bundle use during the implementation phase (Phase-One) and then post-implementation (Phase-Two). Ten emergency nurses participated in Phase-One, while 12 nurses participated in Phase-Two. In Phase-One, there were five important factors identified in relation to use of the care bundle including quality of care, competing priorities, inadequate equipment, agitated patients, and teamwork. In Phase Two, participants perceived that using the care bundle helped them to improve quality of care, increased nurses' knowledge, skills, and confidence. Care bundles are one strategy to increase integration of research evidence into clinical practice and facilitate healthcare providers to deliver optimal patient care in busy environments with limited resources

Providing oxygen to children in hospitals: a realist review

OBJECTIVE: To identify and describe interventions to improve oxygen therapy in hospitals in low-resource settings, and to determine the factors that contribute to success and failure in different contexts. METHODS: Using realist review methods, we scanned the literature and contacted experts in the field to identify possible mechanistic theories of how interventions to improve oxygen therapy systems might work. Then we systematically searched online databases for evaluations of improved oxygen systems in hospitals in low- or middle-income countries. We extracted data on the effectiveness, processes and underlying theory of selected projects, and used these data to test the candidate theories and identify the features of successful projects. FINDINGS: We included 20 improved oxygen therapy projects (45 papers) from 15 countries. These used various approaches to improving oxygen therapy, and reported clinical, quality of care and technical outcomes. Four effectiveness studies demonstrated positive clinical outcomes for childhood pneumonia, with large variation between programmes and hospitals. We identified factors that help or hinder success, and proposed a practical framework depicting the key requirements for hospitals to effectively provide oxygen therapy to children. To improve clinical outcomes, oxygen improvement programmes must achieve good access to oxygen and good use of oxygen, which should be facilitated by a broad quality improvement capacity, by a strong managerial and policy support and multidisciplinary teamwork. CONCLUSION: Our findings can inform practitioners and policy-makers about how to improve oxygen therapy in low-resource settings, and may be relevant for other interventions involving the introduction of health technologies

The Zambian Preterm Birth Prevention Study (ZAPPS): Cohort characteristics at enrollment [version 2; referees: 2 approved]

Background:Sub-Saharan Africa bears a disproportionate burden of preterm birth and other adverse outcomes. A better understanding of the demographic, clinical, and biologic underpinnings of these adverse outcomes is urgently needed to plan interventions and inform new discovery.  Methods:The Zambian Preterm Birth Prevention Study (ZAPPS) is a prospective observational cohort established at the Women and Newborn Hospital (WNH) in Lusaka, Zambia. We recruit pregnant women from district health centers and the WNH and offer ultrasound examination to determine eligibility. Participants receive routine obstetrical care, lab testing, midtrimester cervical length measurement, and serial fetal growth monitoring. At delivery, we assess gestational age, birthweight, vital status, and sex and assign a delivery phenotype. We collect blood, urine, and vaginal swab specimens at scheduled visits and store them in an on-site biorepository. In September 2017, enrollment of the ZAPPS Phase 1 – the subject of this report – was completed. Phase 2 – which is limited to HIV-uninfected women – reopened in January 2018.  Results:Between August 2015 and September 2017, we screened 1784 women, of whom 1450 (81.2%) met inclusion criteria and were enrolled. The median age at enrollment was 27 years (IQR 23–32) and thee median gestational age was 16 weeks (IQR 13–18). Among parous women (N=866; 64%), 21% (N=182) reported a prior miscarriage, 49% (N=424) reported a prior preterm birth, and 13% (N=116) reported a prior stillbirth. The HIV seroprevalence was 24%. Discussion:We have established a large cohort of pregnant women and newborns at the WHN to characterize the determinants of adverse birth outcomes in Lusaka, Zambia. Our overarching goal is to elucidate biological mechanisms in an effort to identify new strategies for early detection and prevention of adverse outcomes. We hope that findings from this cohort will help guide future studies, clinical care, and policy

Multiomics Characterization of Preterm Birth in Low- and Middle-Income Countries.

Importance: Worldwide, preterm birth (PTB) is the single largest cause of deaths in the perinatal and neonatal period and is associated with increased morbidity in young children. The cause of PTB is multifactorial, and the development of generalizable biological models may enable early detection and guide therapeutic studies. Objective: To investigate the ability of transcriptomics and proteomics profiling of plasma and metabolomics analysis of urine to identify early biological measurements associated with PTB. Design, Setting, and Participants: This diagnostic/prognostic study analyzed plasma and urine samples collected from May 2014 to June 2017 from pregnant women in 5 biorepository cohorts in low- and middle-income countries (LMICs; ie, Matlab, Bangladesh; Lusaka, Zambia; Sylhet, Bangladesh; Karachi, Pakistan; and Pemba, Tanzania). These cohorts were established to study maternal and fetal outcomes and were supported by the Alliance for Maternal and Newborn Health Improvement and the Global Alliance to Prevent Prematurity and Stillbirth biorepositories. Data were analyzed from December 2018 to July 2019. Exposures: Blood and urine specimens that were collected early during pregnancy (median sampling time of 13.6 weeks of gestation, according to ultrasonography) were processed, stored, and shipped to the laboratories under uniform protocols. Plasma samples were assayed for targeted measurement of proteins and untargeted cell-free ribonucleic acid profiling; urine samples were assayed for metabolites. Main Outcomes and Measures: The PTB phenotype was defined as the delivery of a live infant before completing 37 weeks of gestation. Results: Of the 81 pregnant women included in this study, 39 had PTBs (48.1%) and 42 had term pregnancies (51.9%) (mean [SD] age of 24.8 [5.3] years). Univariate analysis demonstrated functional biological differences across the 5 cohorts. A cohort-adjusted machine learning algorithm was applied to each biological data set, and then a higher-level machine learning modeling combined the results into a final integrative model. The integrated model was more accurate, with an area under the receiver operating characteristic curve (AUROC) of 0.83 (95% CI, 0.72-0.91) compared with the models derived for each independent biological modality (transcriptomics AUROC, 0.73 [95% CI, 0.61-0.83]; metabolomics AUROC, 0.59 [95% CI, 0.47-0.72]; and proteomics AUROC, 0.75 [95% CI, 0.64-0.85]). Primary features associated with PTB included an inflammatory module as well as a metabolomic module measured in urine associated with the glutamine and glutamate metabolism and valine, leucine, and isoleucine biosynthesis pathways. Conclusions and Relevance: This study found that, in LMICs and high PTB settings, major biological adaptations during term pregnancy follow a generalizable model and the predictive accuracy for PTB was augmented by combining various omics data sets, suggesting that PTB is a condition that manifests within multiple biological systems. These data sets, with machine learning partnerships, may be a key step in developing valuable predictive tests and intervention candidates for preventing PTB