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Purpose: To describe health consequences associated with poor diet in persons with spinal cord injuries and disorders (SCI/D)., Materials/methods: Descriptive qualitative design using in-depth interviews with SCI/D health providers. Audio-recorded and transcribed verbatim transcripts were coded and analyzed using thematic analysis., Results: Participants ( n  = 12) were from 11 nationwide VA hospitals. Participants were male (75%), white (67%), 26-49 years of age, and most were dietitians (75%) and physiatrists (17%). Seven key themes identified consequences associated with poor diet in persons with SCI/D, including (1) Weight gain and body composition changes, (2) cardiometabolic conditions, (3) bowel dysfunction, (4) pressure injuries/wounds, (5) other SCI/D secondary conditions/complications (renal/kidney; immune function/susceptibility to infections; autonomic dysreflexia; bone health/osteoporosis; pain), (6) physical fatigue, and (7) poor mental health., Conclusions: Excess weight, cardiometabolic conditions, SCI/D secondary conditions/complications (e.g., bowel dysfunction, pressure injuries), and poor mental health were identified as health consequences of inadequate nutrition. Health providers should make individuals with SCI/D aware of the risks and health consequences to incentivize healthier dietary behaviors. Efforts to identify nutrition shortcomings and to develop interventions and tailored care plans are needed to improve a myriad of health consequences due to poor diet and nutrition in persons with SCI/D.

Background: Programs to improve student writing have been deployed widely in nursing graduate education, but few operational indicators exist for measuring their value., Problem: The challenge of measuring outcomes reflects the complexity of what transpires when graduate students write. Better understanding is needed of what it means to students to "learn" from writing support., Approach: A full-semester writing course was implemented in a nursing science PhD program. In formative course assessment activities, students identified problems in early drafts of their work, which they subsequently learned to detect and resolve. In this article, students report what was learned., Conclusion: Writing skills, like clinical skills, are intertwined with intellectual maturation and sense of professional identity. Writing, like clinical learning, requires an investment of time and labor far beyond what is typical in didactic approaches to classroom-based graduate education. Our experience suggests a need to reconceptualize writing pedagogy in nursing., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Anti-obesity medications (AOMs) may provide a viable option for obesity management. However, little is known about the use of AOMs in persons with SCI/D., Objective: Describe health care providers' (HCPs) views about barriers to AOM use in persons living with SCI/D., Methods: Descriptive qualitative design using in-depth interviews Descriptive statistics were used to calculate demographic and employment characteristics. Interviews were audio-recorded and transcribed verbatim. Transcripts were coded and analyzed using Braun and Clarke's (2006) six thematic analysis phases., Results: HCPs (n = 12) were from 11 different nationwide facilities. Most HCPs were male (75%), a large majority were white (67%), and most were 26-49 years of age. Participants were dietitians (75%), physicians (17%), and psychologists (8%). HCPs ranged from 1.5 to 15 years of providing SCI/D care. HCPs described four main thematic barriers to AOM use in persons with SCI/D: (1) AOM side effects that are especially concerning in persons with SCI/D; (2) AOMs contribute to poor eating habits; (3) availability, accessibility, and administration; and (4) lack of evidence, clinical agreement, and knowledge about AOM use in the SCI/D population., Conclusions: There are several potential barriers to AOM use in the SCI/D population. Barriers include AOM side effects which may cause or exacerbate conditions that are already concerns in persons with SCI/D, such as bowel and skin problems, and muscle loss. SCI/D HCPs reported a lack of evidence about AOM use in persons with SCI/D, but interest in obtaining more knowledge., Competing Interests: The authors do not have any conflicts of interest or commercial interests to disclose., (© 2024 The Author(s). Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.)

Context: The growing number of females entering the armed forces has led to an increase in the number of female Veterans with spinal cord injury and diseases (SCI/D) requiring mobility devices. Limited research exists that explores whether mobility devices meet their needs in terms of comfort, fit and design., Objective: To characterize respondents with SCI/D who use mobility devices and determine if these devices are meeting their daily needs., Design: Online survey., Settings: Veterans Health Administration., Participants: Female Veterans with SCI/D who received mobility devices in the past five years.Interventions: Participants completed an online survey regarding their challenges in obtaining and using mobility devices for their daily needs., Results: 101 women with SCI/D participated in a nation-wide online survey. Respondents were mainly in their 50s and 59% were not currently employed due to their disability. Most used manual (35%) or power wheelchairs (34%). Many female Veterans felt their devices were not made with female users in mind and some felt they did not meet their needs. Opportunities to improve the assessment, follow-up, maintenance and repair processes were identified., Conclusions: Given that some female Veterans with SCI/D felt their devices did not meet all their needs, it is important for researchers to engage women in user-centered design of mobility devices and for providers to be mindful of Veterans' daily needs within all steps of the provision process in order for mobility devices to support overall function and usability.

Purpose/objective: Individuals with spinal cord injuries and disorders (SCI/D) are at increased risk for experiencing loneliness and social isolation. The aim is to describe facilitators identified by individuals living with SCI/D to alleviate loneliness and perceived social isolation., Research Method/design: Descriptive qualitative design using in-depth interviews with veterans with SCI/D ( n = 23). Descriptive statistics was used to calculate demographic and injury characteristics. Audio-recorded and transcribed verbatim transcripts were coded and analyzed using Braun and Clarke's (2006) six thematic analysis phases., Results: Participants were male (70%), white (78%), and not currently married (35%), with an average age of 66 years (42-88). Participants had paraplegia (61%), with traumatic etiology (65%) and were injured 14 years (1-45) on average. Eight themes were identified by participants living with SCI/D that described facilitators to alleviate loneliness and perceived social isolation. (a) Engage in/pursue interests; (b) Interact with/spend time with others; (c) Embrace acceptance; (d) Take part in reciprocity; (e) Find a purpose/accomplish goals; (f) Get out of residence, get outside; (g) Connect with SCI/D community/SCI/D peers; and (h) Seek help from (mental) healthcare professionals., Conclusions/implications: Individuals with SCI/D identified facilitators to alleviate loneliness that encompasses changes in ways of thinking, actions to expand participation in life, and efforts focused on involving others. Findings can be used to guide healthcare delivery and develop interventions to target feelings of loneliness and social isolation in persons with SCI/D, which may be particularly impactful if they involve reciprocal interactions with peers with SCI/D. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Objective: To identify variables independently associated with moderate to high loneliness in individuals living with Spinal Cord Injuries or Disorders (SCI/D)., Design: A cross-sectional, national survey of a random sample of community-dwelling Veterans with SCI/D in the United States. Survey methodology was used to collect data on demographic and injury characteristics, general health, chronic and SCI-secondary conditions, and loneliness., Setting: The VHA SCI/D System of Care including 25 regional SCI/D Centers (or Hubs)., Participants: Among 2466 Veterans with SCI/D, 592 completed surveys (24%). Most participants were men (91%), white (81%), not currently married (42%), had tetraplegia (33%), and on average injured for 18 years at the time of data collection (N=562)., Interventions: Not applicable., Main Outcome Measure: The dependent variable, loneliness, was collected using the UCLA-3 instrument. Loneliness was dichotomized into never/low loneliness and moderate/high loneliness (UCLA score ≥ 4)., Results: Bivariate analyses assessed unadjusted associations in demographics, injury characteristics, chronic disease, and SCI-secondary conditions. Multivariable logistic regression was used to identify factors independently associated with moderate/high loneliness. Participants had a mean loneliness score of 5.04, SD=1.99. The point prevalence of moderate to high loneliness was 66%. Lower duration of injury, paraplegia, being unmarried, being in fair/poor general health, having dysfunctional sleep, and having a diagnosis of bowel dysfunction were each independently associated with greater odds of moderate/high loneliness., Conclusions: Findings suggest that interventions to reduce/manage loneliness in the Veteran SCI/D population should focus on those who are more newly injured, have paraplegia, currently unmarried, have bowel problems, and experience dysfunctional sleep., (Published by Elsevier Inc.)

Background: Providers in the Department of Veterans Affairs (VA) system are caught between two opposing sets of laws regarding cannabis and cannabidiol (CBD) use by their patients. As VA is a federal agency, it must abide by federal regulations, including that the Food and Drug Administration classifies cannabis as a Schedule 1 drug and therefore cannot recommend or help Veterans obtain it. Meanwhile, 38 states have passed legislation, legalizing medical use of cannabis. Objective: The goal of this project is to examine how VA providers understand state and federal laws, and VA policies about cannabis and CBD use, and to learn more about providers' experiences with patients who use cannabis and CBD within a legalized and nonlegalized state. Materials and Methods: We identified 432 health care providers from two VA facilities in northern Illinois (IL) where medical and recreational cannabis is legal, and two VA facilities in southern Wisconsin (WI) where medical and recreational cannabis is illegal. Participants were invited via e-mail to complete an anonymous online survey, including 31 closed- and open-ended questions about knowledge of state and federal laws and VA policies regarding cannabis and CBD oil, thoughts about the value of cannabis or CBD for treating medical conditions, and behaviors regarding cannabis use by their patients. Results: We received 50 responses (IL N =20, WI N =30). Providers in both states were knowledgeable about cannabis laws in their state but unsure whether they could recommend cannabis. There were more providers who were unclear if they could have a conversation about cannabis with their VA patients in WI compared with IL. Providers were more likely to agree than disagree that cannabis can be beneficial, χ 2 (1, 49)=4.74, p =0.030. Providers in both states (81.6%) believe cannabis use is acceptable for end-of-life care, but responses varied for other conditions and symptoms. Discussion: Findings suggest that VA providers could use more guidance on what is allowable within their VA facilities and how state laws affect their practice. Education about safety related to cannabis and other drug interactions would be helpful. There is limited information about possible interactions, warranting future research.

The N1, Tb, and P2 components of the event-related potential (ERP) are thought to reflect the sequential processing of auditory stimuli in the human brain. Despite their extensive use in biological, cognitive, and clinical neuroscience, there are no guidelines for how to appropriately power ERP studies using these components. In the present study, we investigated how the number of trials, number of participants, effect magnitude, and study design influenced statistical power. Using Monte Carlo simulations of ERP data from a passive listening task, we determined the probability of finding a statistically significant effect in 58,900 experiments repeated 1,000 times each. We found that as the number of trials, number of participants, and effect magnitude increased, so did statistical power. We also found that increasing the number of trials had a bigger effect on statistical power for within-subject designs than for between-subject designs, and that within-subject designs required a smaller number of trials and participants to provide the same level of statistical power for a given effect magnitude than between-subject designs. These results show that it is important to carefully consider these factors when designing ERP studies, rather than relying on tradition or anecdotal evidence. To improve the robustness and reproducibility of ERP research, we have built an online statistical power calculator (https://bradleynjack.shinyapps.io/ErpPowerCalculator), which we hope will allow researchers to estimate the statistical power of previous studies, as well as help them design appropriately-powered studies in the future., (© 2023 The Authors. Psychophysiology published by Wiley Periodicals LLC on behalf of Society for Psychophysiological Research.)

Contemplative practices are a staple of modern life and have historically been intertwined with morality. However, do these practices in fact improve our morality? The answer remains unclear because the science of contemplative practices has focused on unidimensional aspects of morality, which do not align with the type of interdependent moral functioning these practices aspire to cultivate. Here, we appeal to a multifactor construct, which allows the assessment of outcomes from a contemplative intervention across multiple dimensions of moral cognition and behavior. This offers an open-minded and empirically rigorous investigation into the impact of contemplative practices on moral actions. Using this framework, we gain insight into the effect of mindfulness meditation on morality, which we show does indeed have positive influences, but also some negative influences, distributed across our moral functioning., Competing Interests: Declaration of interests None declared by authors., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: The study aimed to describe the postmortem investigation patterns for perinatal deaths and compare the degree of investigation between stillbirths and early neonatal deaths., Study Design: We conducted a single-center retrospective review of all perinatal deaths from 2011 to 2017. Perinatal death was defined as intrauterine fetal death at ≥20 weeks' gestation, plus neonatal deaths within the first 7 days of life. Rates of postmortem investigation were compared., Results: There were 97 perinatal deaths, with 54 stillbirths (56%) and 43 neonatal deaths (44%). Stillbirths were significantly more likely to receive autopsy ( p  = 0.013) and postmortem genetic testing ( p  = 0.0004) when compared with neonatal deaths. Maternal testing was also more likely in stillbirths than neonatal deaths. A total of 32 deaths (33%) had no postmortem evaluation beyond placental pathology., Conclusion: Investigation following perinatal death is more likely in stillbirths than neonatal deaths. Methods to improve postmortem investigation following perinatal death are needed, particularly for neonatal deaths., Key Points: · Investigation into perinatal death is recommended.. · Rates of investigation remain low.. · Neonatal deaths with less investigation than stillbirths.., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: There is growing interest in palliative care within Indigenous communities, and within Aotearoa New Zealand, of the significant role that Māori (Indigenous people) families play in caring for older relatives. This study explored the centrality of culture in how Māori extended families ( whānau ) in Aotearoa New Zealand interpret and enact family-based care roles within the Māori world ( Te Ao Māori )., Methods: Applying Māori-centered and community-based participatory research principles, we examined 17 interviews with older Māori who shared experiences of palliative care for a partner or family member. The thematic analysis used a cultural-discursive framework incorporating Māori principles of wellbeing and values expressed within the care relationship., Results: The findings centered on three whānau roles in palliative care: whānau as (1) Holders and protectors of Māori knowledge; (2) Weavers of spiritual connection; and (3) Navigators in different worlds., Conclusion: The study problematizes the notion of a single 'primary caregiver', privileges whānau as an inter-woven relational, dynamic care network, and encourages health professionals to recognize the cultural embeddedness of dominant approaches to palliative care., Competing Interests: Competing interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2022.)

Often young indigenous women are framed in ways that problematize and pathologize them, which overlooks their strengths. We interviewed 16 young Indigenous Māori women aged 14 to 18 years about their understandings of safety, being safe, and how they kept themselves and their friends safe. Reflecting and Learning, aided by progressing age and maturity, is the process that mediated their feeling unsafe and keeping safe and resulted in being safe . Young Māori women's reflecting and learning facilitates relatively mature levels of resourcefulness for navigating being safe, including situations they encountered appear unsafe.

Excessive accumulation of misfolded proteins was recently demonstrated in preeclampsia. We examined levels and activity of circulatory proteasome and immunoproteasome (inflammatory subtype) in preeclampsia and hemolysis, elevated liver enzymes, and thrombocytopenia (HELLP) syndrome. We analyzed samples from women with hypertensive pregnancy disorders (n=115), including preeclampsia with severe features (sPE) and HELLP syndrome, and normotensive controls (n=45). Plasma proteasome and immunoproteasome immunoreactivity were determined by quantifying the α-subunit of the 20S core and β5i (proteasome subunit beta 8 [PSMB8]), respectively. Plasma proteasome activity was analyzed with fluorogenic substrates. MG132, lactacystin, and ONX0914 were used to inhibit the circulating proteasome and immunoproteasome, respectively. Plasma cytokine profiles were evaluated by multiplex immunoassay. Placental expression of β5 (constitutive proteasome) and β5i (immunoproteasome) was interrogated by immunohistochemistry. Women with sPE had increased plasma 20S levels ( P<0.001) and elevated lytic activities (chymotrypsin-like 7-fold, caspase-like 4.2-fold, trypsin-like 2.2-fold; P <0.001 for all) compared with pregnant controls. Women with features of HELLP displayed the highest plasma proteasome levels and activity, which correlated with decreased IFN-γ (interferon-γ), and increased IL (interleukin)-8 and IL-10. In sPE and HELLP, chymotrypsin-like activity was suppressed by proteasome inhibitors including ONX0914. Compared with gestational age-matched controls, sPE placentas harbored increased β5 and β5i immunostaining in trophoblasts. β5i signal was elevated in HELLP with predominant staining in villous core, extravillous trophoblasts in placental islands, and extracellular vesicles in intervillous spaces. Pregnancy represents a state of increased proteostatic stress. sPE and HELLP were characterized by significant upregulation in circulating levels and lytic activity of the proteasome that was partially explained by placental immunoproteasome upregulation.

Purpose: Observational studies suggest that dietary and serum calcium are risk factors for prostate cancer. However, such studies suffer from residual confounding (due to unmeasured or imprecisely measured confounders), undermining causal inference. Mendelian randomization uses randomly assigned (hence unconfounded and pre-disease onset) germline genetic variation to proxy for phenotypes and strengthen causal inference in observational studies. We tested the hypothesis that serum calcium is associated with an increased risk of overall and advanced prostate cancer., Methods: A genetic instrument was constructed using five single-nucleotide polymorphisms robustly associated with serum calcium in a genome-wide association study (n ≤ 61,079). This instrument was then used to test the effect of a 0.5 mg/dL increase (1 standard deviation, SD) in serum calcium on risk of prostate cancer in 72,729 men in the PRACTICAL (Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome) Consortium (44,825 cases, 27,904 controls) and risk of advanced prostate cancer in 33,498 men (6,263 cases, 27,235 controls)., Results: We found weak evidence for a protective effect of serum calcium on prostate cancer risk (odds ratio [OR] per 0.5 mg/dL increase in calcium: 0.83, 95% CI 0.63-1.08; p = 0.12). We did not find strong evidence for an effect of serum calcium on advanced prostate cancer (OR per 0.5 mg/dL increase in calcium: 0.98, 95% CI 0.57-1.70; p = 0.93)., Conclusions: Our Mendelian randomization analysis does not support the hypothesis that serum calcium increases risk of overall or advanced prostate cancer.

An adequate intake of vitamin B12 during pregnancy plays an important role in offspring neurodevelopment, potentially via epigenetic processes. We used a two-step Mendelian randomization approach to assess whether DNA methylation plays a mediating and causal role in associations between maternal vitamin B12 status and offspring's cognition. Firstly, we estimated the causal effect of maternal vitamin B12 levels on cord blood DNA methylation using the maternal FUT2 genotypes rs492602:A > G and rs1047781:A > T as proxies for circulating vitamin B12 levels in the Avon Longitudinal Study of Parents and Children (ALSPAC) and we tested the observed associations in a replication cohort. Secondly, we estimated the causal effect of DNA methylation on IQ using the offspring genotype at sites close to the methylated CpG site as a proxy for DNA methylation in ALSPAC and in a replication sample. The first step Mendelian randomization estimated that maternal vitamin B12 had a small causal effect on DNA methylation in offspring at three CpG sites, which was replicated for one of the sites. The second step Mendelian randomization found weak evidence of a causal effect of DNA methylation at two of these sites on childhood performance IQ which was replicated for one of the sites. The findings support a causal effect of maternal vitamin B12 levels on cord blood DNA methylation, and a causal effect of vitamin B12-responsive DNA methylation changes on children's cognition. Some limitations were identified and future studies using a similar approach should aim to overcome such issues., (© The Author 2017. Published by Oxford University Press.)

Low utilization of palliative care services by Māori remains despite increases in services designed to meet Māori needs. The purpose of this study is to explore palliative care information brochures in the context of Māori principles of well-being and communication protocols, and health literacy. We examined 99 brochures from palliative care services in New Zealand and held two focus groups with 12 Māori elders (kaumātua) and extended family (whanau) members. Taking a cultural-discursive approach incorporating Māori worldviews, we analysed textual and conceptual features of the brochures. The findings centred on cultural connection and disconnection within the brochures and serve as a critique of the prominent messages currently presented in these brochures. The findings raise questions about the capacity of agencies to convey culturally resonant messages to kaumātua and their whānau. We identify implications of palliative care brochures for health literacy of provider organizations as well as kaumātua and whanau., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objectives: Relationships among cognitive and motivational factors in predicting medical help-seeking for Alzheimer's disease (AD) symptoms were tested., Method: Community residents awaiting jury service (N = 280) completed questionnaires, including responses to a vignette depicting prototypical early symptoms of AD in a hypothetical mother. Cognitive responses to the vignette included AD symptom identification and AD attribution. Affective-motivational responses to vignettes were symptom impact and behavior appraisals. General knowledge of AD was assessed. Intention to seek medical help was the dependent variable., Results: The impact and identification of AD symptoms, appraisals of risk, and attribution of the scenario to AD were modest, yet all contributed to prediction of medical-help-seeking intentions. The best fitting model had distinct but interrelated cognitive and motivational paths explaining 49% of the variability in medical help-seeking. Motivational variables had particularly important direct and indirect effects on help-seeking., Discussion: Findings are interpreted as evidence of the importance of motivational as well as cognitive aspects of perceptions of illness behavior in another person. The substantial impact of the tested variables on the desired outcome of medical help-seeking may suggest options for public health efforts to enhance early medical help-seeking for AD that sets the stage for early intervention., (© The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The purpose of this study is to explore the cultural practices and communication tensions perceived among Māori kaumātua (elders) and their whānaunga (extended family) during the end-of-life journey. Further, the study aims to explore the manner in which the tensions are managed. The study was framed by relational dialectics theory and included interviews with 21 kaumātua and focus groups with 39 whānau members. The study identified three cultural practices (dying at home, prayer, and song) that helped to build connection among the family members and also helped to connect the dying person to the spiritual world. Further, four communication tensions were noted: (a) autonomy and connection; (b) conflict and connection; (c) isolation and connection; and (d) balancing the needs of self and other. To manage these tensions, the following strategies were used: (a) coordination conversations; (b) inclusion in decision-making conversations; (c) emotional support within the whānau; and (d) passing on lessons to the next generation.

Objectives: To report on oral-health-related characteristics, beliefs, and behaviours among participants in a randomised control trial of an intervention to prevent early childhood caries (ECC) among Māori children, and to determine whether there were any systematic differences between the intervention and control groups at baseline., Design: Baseline measurements from a randomised control trial (involving 222 pregnant Māori women allocated randomly to either Intervention or Delayed groups) which is currently underway., Setting: The rohe (tribal area) of Waikato-Tainui., Methods: Self-report information collected on sociodemographic characteristics, pregnancy details, self-reported general and oral health and health-related behaviours, and oral health beliefs., Results: Other than those in the Delayed group being slightly older, on average, there were no significant differences between the two groups. Some 37.0% were expecting their first child. Most reported good health; 43.6% were current smokers, and 26.4% had never smoked. Only 8.2% were current users of alcohol. Almost all were dentate, and 57.7% described their oral health as fair or poor. One in six had had toothache in the previous year; 33.8% reported being uncomfortable about the appearance of their teeth, and 27.7% reported difficulty in eating. Dental service-use was relatively low and symptom-related; 78.9% needed to see a dentist. Overall, most of the sample believed that it was important to avoid sweet foods, visit dentists and to brush the teeth, while about half thought that using fluoride toothpaste and using floss were important. Some 38.2% felt that drinking fluoridated water was important. Oral-health-related fatalism was apparent, with 74.2% believing that most people usually get dental problems, 58.6% believing that most people will need extractions at some stage, and that most children eventually get dental caries., Conclusions: Mothers' important role in nurturing the well-being of the young child includes the protection and maintenance of the growing child's oral health (or ukaipo niho). The findings provide important insights into Māori mothers' oral health knowledge, beliefs and practices.

Background: Maaori are the Indigenous people of New Zealand and do not enjoy the same oral health status as the non-Indigenous majority. To overcome oral health disparities, the life course approach affords a valid foundation on which to develop a process that will contribute to the protection of the oral health of young infants. The key to this process is the support that could be provided to the parents or care givers of Maaori infants during the pregnancy of the mother and the early years of the child. This study seeks to determine whether implementing a kaupapa Maaori (Maaori philosophical viewpoint) in an early childhood caries (ECC) intervention reduces dental disease burden among Maaori children. The intervention consists of four approaches to prevent early childhood caries: dental care provided during pregnancy, fluoride varnish application to the teeth of children, motivational interviewing, and anticipatory guidance., Methods/design: The participants are Maaori women who are expecting a child and who reside within the Maaori tribal area of Waikato-Tainui.This randomised-control trial will be undertaken utilising the principles of kaupapa Maaori research, which encompasses Maaori leadership, Maaori relationships, Maaori customary practices, etiquette and protocol. Participants will be monitored through clinical and self-reported information collected throughout the ECC intervention. Self-report information will be collected in a baseline questionnaire during pregnancy and when children are aged 24 and 36 months. Clinical oral health data will be collected during standardised examinations at ages 24 and 36 months by calibrated dental professionals. All participants receive the ECC intervention benefits, with the intervention delayed by 24 months for participants who are randomised to the control-delayed arm., Discussion: The development and evaluation of oral health interventions may produce evidence that supports the application of the principles of kaupapa Maaori research in the research processes. This study will assess an ECC intervention which could provide a meaningful approach for Maaori for the protection and maintenance of oral health for Maaori children and their family, thus reducing oral health disparities., Trial Registration: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12611000111976.

Potent and selective thrombin inhibitors have been prepared with a piperazinedione template and L-amino acids. Likewise, incorporation of D-amino acids led to potent inhibitors with a novel mode of binding. Herein, the structure activity relationships and structural aspects of these compounds will be described.

The synthesis and antithrombotic activity of a series of nonpeptide bicyclic thrombin inhibitors are described. We have explored the SAR around the P1' site. Modification of the P1' site has been found to affect potency and selectivity.

The synthesis and antithrombotic activity of a series of nonpeptide bicyclic thrombin inhibitors is described. We have explored the SAR with modifications to the P1 site. The introduction of arginine mimetics at the P1 site led to potent and selective thrombin inhibitors.

Peptidomimetic inhibitors of general structure 1 have been prepared. Optimization of the binding affinities of these compounds through variation of the P3 hydrophobic residue is described. Selected substituted bicylic lactams displayed interesting pharmacological profiles both in vitro and in vivo.

The development of benzothiazine-1,1-dioxide derivatives as a new structural class of potent endothelin receptor antagonists is described. Structure-activity relationships (SAR) revealed that PD164800 (1) is a potent antagonist of the ETA receptor subtype.

The design of potent and selective non-peptide antagonists of endothelin-1 (ET-1) and its related isopeptides are important tools defining the role of ET in human diseases. In this report we will describe the detailed structure-activity relationship (SAR) studies that led to the discovery of a potent series of butenolide ETA selective antagonists. Starting from a micromolar screening hit, PD012527, use of Topliss decision tree analysis led to the discovery of the nanomolar ET(A) selective antagonist PD155080. Further structural modifications around the butenolide ring led directly to the subnanomolar ETA selective antagonist PD156707, IC50's = 0.3 (ET(A)) and 780 nM (ET(B)). This series of compounds exhibited functional activity exemplified by PD156707. This derivative inhibited the ETA receptor mediated release of arachidonic acid from rabbit renal artery vascular smooth muscle cells with an IC50 = 1.1 nM and also inhibited the ET-1 induced contraction of rabbit femoral artery rings (ETA mediated) with a pA2 = 7.6. PD156707 also displayed in vivo functional activity inhibiting the hemodynamic responses due to exogenous administration of ET-1 in rats in a dose dependent fashion. Evidence for the pH dependence of the open and closed tautomerization forms of PD156707 was demonstrated by an NMR study. X-ray crystallographic analysis of the closed butenolide form of PD156707 shows the benzylic group located on the same side of the butenolide ring as the gamma-hydroxyl and the remaining two phenyl groups on the butenolide ring essentially orthogonal to the butenolide ring. Pharmacokinetic parameters for PD156707 in dogs are also presented.

The development of nonpeptide, low molecular weight antagonists with high potency, oral activity, and selectivity is an important objective to adequately define the potential role of endothelin (ET) and its isopeptides in human diseases. This report describes the structure-activity relationships, ETA/ETB selectivity, and pharmacokinetics of the PD 155080 and PD 156707 series of orally active nonpeptide ET receptor-selective antagonists. Modification of the substituents around the butenolide ring has led to compounds with differing selectivity for human ETA and ETB receptors. Thus, compounds with increased lipophilicity at R2 show increased ETB affinity and a more balanced ETA/ETB profile. For example, the 4-O-n-pentyl analogue of PD 156707 is a potent competitive inhibitor of [125I]ET-1 and [125I]ET-3 binding to human cloned ETA and ETB receptors, with IC50s of 0.8 nM and 44 nM, respectively. Pharmacokinetic properties can also be significantly influenced by structural modifications at the R2 group. The pharmacokinetics of PD 155719, PD 155080, and PD 156707 were compared in male Wistar rats after a 15 mg/kg intravenous or oral gavage dose (three animals per dose). Plasma concentrations were determined by a specific HPLC assay. Oral bioavailability ranged from less than 5% for PD 155719 to 41% for PD 156707 and 87% for PD 155080.

Our aim was to synthesize a new endothelin ETA selective radioligand, [125I]-PD151242 and characterize the compound in human vascular tissue. Binding of [125I]-PD151242 to sections of human aorta was time-dependent and reached equilibrium after 120 min at 23 degrees C with an association rate constant of 1.26 +/- 0.17 x 10(8) M-1 min-1 (n = 3 individuals +/- s.e.mean). The binding was reversible at 23 degrees C with an observed dissociation rate constant of 0.0025 +/- 0.0006 min-1 (n = 3). Saturation binding assays using [125I]-PD151242 revealed a single population of high affinity ET receptors (n = 3) in aorta (KD = 0.76 +/- 0.17 nM; Bmax = 5.98 +/- 1.56 fmol mg-1 protein), pulmonary (KD = 1.75 +/- 0.20 nM; Bmax = 12.78 +/- 1.39 fmol mg-1 protein) and coronary arteries (KD = 0.51 +/- 0.07 nM; Bmax = 44.9 +/- 1.67 fmol mg-1 protein). ETA selective ligands competed for [125I]-PD151242 binding in aorta with nanomolar affinity (BQ123, KD = 0.41 +/- 0.26 nM; FR139317, KD = 0.55 +/- 0.11 nM) whereas the ETB selective compound, BQ3020, competed with micromolar affinity (KD = 1.36 +/- 0.25 microM). In isolated coronary arteries, PD151242 was a functional antagonist and caused a significant, parallel rightward shift of the ET-1 dose-response curve with a pA2 value of 5.92 (n = 5) and a slope of unity. The high affinity and selectivity of [125I]-PD151242 for ETA receptors will facilitate the characterization of this sub-type in human tissues.