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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 Maori 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 Maori 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 Maori mothers' oral health knowledge, beliefs and practices. [ABSTRACT FROM AUTHOR]

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.

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.

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.)

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.

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.)

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.

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.