Search

Background: Adolescent substance use poses a critical public health challenge, intertwined with risk-taking behavior, criminality, functional impairment, and comorbid mental and physical health issues. Adolescents with bipolar spectrum disorders (BSD) exhibit heightened susceptibility to substance use, necessitating a nuanced exploration of the bipolar-substance use relationship., Methods: This study addressed gaps in the literature by employing a prospective, longitudinal design with 443 Philadelphia-area adolescents, tracking BSD symptoms and substance use. We predicted that BSD symptoms would be associated with increases in substance use, and that these effects would be more pronounced for individuals with a BSD and those with high reward sensitivity., Results: Hypomanic symptoms predicted subsequent substance use, with a stronger association observed in individuals diagnosed with BSD. Contrary to expectations, depressive symptoms did not exhibit a similar relationship. Although the hypothesized moderating role of reward sensitivity was not supported, higher reward sensitivity predicted increased substance use., Limitations: Symptoms and substance use are only captured for the month prior to each session due to the assessment timeline. This highlights the benefits of frequent assessments over a shorter time frame to monitor real-time changes. Alternative classification methods for reward sensitivity, such as brain or behavior-based assessments, might yield different results., Conclusions: This study's contributions include evaluating substance use broadly, utilizing a longitudinal design for temporal clarity, and shifting the focus from substance use predicting mood symptoms to the inverse. The findings underscore the need for continued exploration of mood symptom predictors of substance use, emphasizing the role of reward sensitivity., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier B.V.)

Mechanical properties of traditional engineering materials are typically coupled to each other, presenting a challenge to practitioners with multi-dimensional material property requirements. In this work, continuous, independent control over multiple mechanical properties is demonstrated in composite materials realized using additive manufacturing. For the first time, composites additively manufactured from rigid plastic, soft elastomer, and liquid constituents are experimentally characterized, demonstrating materials which span four orders of magnitude in modulus and two orders of magnitude in toughness. By forming analytical mappings between relative concentrations of constituents at the microscale and resulting macroscale material properties, inverse material design is enabled; the method is showcased by printing artifacts with prescribed toughness and elasticity distributions. The properties of these composites are placed in the context of biological tissues, showing they have promise as mechanically plausible tissue mimics., (© 2024 Wiley‐VCH GmbH.)

This systematic review of 52 studies provides a quantitative synthesis of the empirical literature on social and circadian rhythm correlates of suicidal thoughts and behaviors (STB). Small-to-medium pooled effect sizes were observed for associations between evening chronotype and STB and suicidal ideation (SI), although the pooled effect size diminished when accounting for publication bias. Three studies employed longitudinal designs and suggested eveningness was predictive of future STB, with a small-to-medium effect size. Social rhythm irregularity was also a significant correlate of STB with pooled effect sizes in the medium range. Overall circadian rhythm disruption was not associated with STB, although certain circadian rhythm metrics, including mean daytime activity, circadian rhythm sleep-wake disorder diagnosis, and actigraphy-assessed amplitude were associated with STB. Pooled effect sizes for these indices were in the medium to large range. There is a need for additional longitudinal research on actigraphy-based circadian parameters and objective markers of circadian phase (i.e., dim-light melatonin onset) to gain a clearer understanding of associations of endogenous circadian function and STB beyond that which can be captured via self-report., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

A specific type of sleep disruption, social jetlag, involves an incongruence of sleep time between weekends and weekdays. This study investigated relationships between social jetlag and mood symptom lability and trajectories of daily reward responsiveness and mood symptoms. Participants (N = 130) from three groups (moderate reward sensitivity, high reward sensitivity, and high reward sensitivity with a diagnosed bipolar spectrum disorder [BSD]) were recruited from an ongoing longitudinal study based on their self-reported reward sensitivity and a diagnostic interview. For this study, they completed 20 days of ecological momentary assessment (EMA) of reward responsiveness and mood symptoms and a daily sleep diary. Social jetlag was significantly associated with differences in trajectories of depressive symptoms between groups. Specifically, greater social jetlag was associated with a greater increase in depressive symptoms over the 20 days for participants in the high reward sensitivity and BSD groups compared to the moderate reward sensitivity group. Social jetlag also was significantly associated with depressive symptom lability during the EMA period, but this finding was reduced to a trend toward significance when controlling for self-reported sleep duration. The study adds to the literature with methodological strengths including the EMA design and assessment of symptom and reward responsiveness trajectories., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Bipolar spectrum disorders (BSDs) are associated with a heightened sensitivity to rewards and elevated reward-related brain function in cortico-striatal circuitry. A separate literature documents social and circadian rhythm disruption in BSDs. Recently, integrated reward-circadian models of BSDs have been proposed. These models draw on work indicating that the two systems influence each other and interact to affect mood functioning. When dysregulated, reward and circadian system signaling may combine to form a positive feedback loop, whereby dysregulation in one system exacerbates dysregulation in the other. Project CREST (Circadian, Reward, and Emotion Systems in Teens) provides a first systematic test of reward-circadian dysregulation as a synergistic and dynamic vulnerability for first onset of BSD and increases in bipolar symptoms during adolescence., Methods: This NIMH-funded R01 study is a 3-year prospective, longitudinal investigation of approximately 320 community adolescents from the broader Philadelphia area, United States of America. Eligible participants must be 13-16 years old, fluent in English, and without a prior BSD or hypomanic episode. They are being selected along the entire dimension of self-reported reward responsiveness, with oversampling at the high tail of the dimension in order to increase the likelihood of BSD onsets. At Times 1-6, every 6 months, participants will complete assessments of reward-relevant and social rhythm disruption life events and self-report and diagnostic assessments of bipolar symptoms and episodes. Yearly, at Times 1, 3, and 5, participants also will complete self-report measures of circadian chronotype (morningness-eveningness) and social rhythm regularity, a salivary dim light melatonin onset (DLMO) procedure to assess circadian phase, self-report, behavioral, and neural (fMRI) assessments of monetary and social reward responsiveness, and a 7-day ecological momentary assessment (EMA) period. During each EMA period, participants will complete continuous measures of sleep/wake and activity (actigraphy), a daily sleep diary, and three within-day (morning, afternoon, evening) measures of life events coded for reward-relevance and social rhythm disruption, monetary and social reward responsiveness, positive and negative affect, and hypo/manic and depressive symptoms. The fMRI scan will occur on the day before and the DLMO procedure will occur on the first evening of the 7-day EMA period., Discussion: This study is an innovative integration of research on multi-organ systems involved in reward and circadian signaling in understanding first onset of BSD in adolescence. It has the potential to facilitate novel pharmacological, neural, and behavioral interventions to treat, and ideally prevent, bipolar conditions., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objectives: Activation, a construct including energy and activity, is a central feature of Bipolar Spectrum Disorders (BSDs). Prior research found motor activity is associated with affect, and this relationship may be stronger for individuals with BSDs. The aims of this study were to investigate bidirectional relationships between physical activity and mood and evaluate whether bipolar risk status moderated potential associations., Methods: Young adults at low-risk, high-risk, and diagnosed with BSD participated in a 20-day EMA study in which they wore an actiwatch to measure physical activity and sleep/wake cycles. They also reported depressive and hypo/manic symptoms three times daily. Multilevel linear models were estimated to examine how bipolar risk group moderated bidirectional relationships between physical activity and mood symptoms at within-day and between-day timescales., Results: Physical activity was significantly associated with subsequent mood symptoms at the within-day level. The relationship between physical activity and depressive symptoms was moderated by BSD risk group. An increase in physical activity resulted in a greater reduction of depressive symptoms for the BSD group compared to the low-risk and high-risk groups., Conclusions: Interventions targeting activity like behavioral activation may improve residual inter-episode mood symptoms., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: The role of activation in the pathogenesis of bipolar spectrum disorders (BSD) is of growing interest. Physical activity is known to improve mood, but it is unclear whether low activity levels contribute to inter-episode depressive symptoms observed in BSD. This study examined whether sedentary and vigorous activity, as well as the timing of the activity, were differentially associated with next-day depressive symptoms for individuals at low risk for BSD, high-risk for BSD, and diagnosed with BSD., Methods: Young adults (n = 111, ages 18-27) from three groups (low BSD risk, high BSD risk, and BSD diagnosis), participated in a 20-day ecological momentary assessment study. Physical activity was measured via wrist actigraphy counts. The percentage of time awake spent in sedentary, light, moderate, and vigorous activity states was calculated, as was the percentage of morning hours and evening hours in each activity state. Multilevel models examined whether the BSD risk group moderated associations between sedentary and vigorous activity and depressive symptoms, which were assessed three times daily., Results: There were no between-group differences in time spent in each activity state, nor were there main effects of sedentary or vigorous activity on depression. Increased time spent engaging in vigorous activity was associated with a greater reduction in subsequent depressive symptoms for the BSD group. An increase in the evening, but not morning, vigorous activity was significantly associated with a reduction in subsequent depressive symptoms for the BSD group after controlling for chronotype., Conclusions: Interventions targeting physical activity may effectively help regulate inter-episode mood disturbances in BSD., (© 2022 Wiley Periodicals LLC.)

Background: One of the main drivers of maternal and newborn mortality and morbidity in India is a lack of quality of care in health facilities. Inadequate competencies of health workers, insufficient quality of training and infrastructure, and the financial challenges of providing training across the country impede quality care provision. To this end, the Government of India began exploring cost-effective tech and IT-based solutions to support existing quality improvement (QI) initiatives., Method: We describe the process and approach of scaling the Safe Delivery App (hereafter referred to as the App) throughout India. The App is an mHealth learning tool for equipping health workers in managing obstetric and neonatal emergencies by placing evidence-based, and up-to-date clinical guidelines in their hands through their mobile devices. The use of the App was supported by the Ministry of Health and the Department of Health at the state level. Both parties were actively involved in the roll-out of the App and had a clear vision of how the App can complement existing structures/systems/programmes., Results: The App was successfully integrated and implemented in various government-led QI initiatives. Approximately 20 000 healthcare workers (HCWs) have been trained on the App and selected clinical topics since its launch, and between 2018 and 2021 over 86 000 HCWs across all states and union territories used the App. Moreover, project-specific data show a significant increase in the knowledge level of users of the App., Conclusion: Scaling such a tool within existing programmes is not a linear process. In India, the approach, government buy-in and flexibility of implementation modalities led to the successful roll-out of the App. We have demonstrated that an mHealth tool can be used to support the growing desire of governments to use tech in support existing QI initiatives and supporting the improvement of quality of care provided., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Reliably documenting plant diversity is necessary to protect and sustainably benefit from it. At the heart of this documentation lie species concepts and the practical methods used to delimit taxa. Here, we apply a total-evidence, iterative methodology to delimit and document species in the South American genus Victoria (Nymphaeaceae). The systematics of Victoria has thus far been poorly characterized due to difficulty in attributing species identities to biological collections. This research gap stems from an absence of type material and biological collections, also the confused diagnosis of V. cruziana . With the goal of improving systematic knowledge of the genus, we compiled information from historical records, horticulture and geography and assembled a morphological dataset using citizen science and specimens from herbaria and living collections. Finally, we generated genomic data from a subset of these specimens. Morphological and geographical observations suggest four putative species, three of which are supported by nuclear population genomic and plastid phylogenomic inferences. We propose these three confirmed entities as robust species, where two correspond to the currently recognized V. amazonica and V. cruziana , the third being new to science, which we describe, diagnose and name here as V. boliviana Magdalena and L. T. Sm. Importantly, we identify new morphological and molecular characters which serve to distinguish the species and underpin their delimitations. Our study demonstrates how combining different types of character data into a heuristic, total-evidence approach can enhance the reliability with which biological diversity of morphologically challenging groups can be identified, documented and further studied., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Smith, Magdalena, Przelomska, Pérez-Escobar, Melgar-Gómez, Beck, Negrão, Mian, Leitch, Dodsworth, Maurin, Ribero-Guardia, Salazar, Gutierrez-Sibauty, Antonelli and Monro.)

Objective: The aim of this study was to examine ways that older Māori (New Zealand's Indigenous people) enhanced their ability to be peer educators and how this role impacted on their sense of purpose and well-being in later life., Method: Kaupapa Māori and community-based participatory research principles guided the peer intervention involving 26 Māori kaumātua (older people 55 years and older) as peer educators (tuakana) for 121 other kaumātua (teina) facing transitions in later life. Each pair held up to 3 conversations; independent coders rated tuakana communication skills. We used mixed methods in a pre- and post-test, clustered staggered design. Participants completed baseline and post-intervention assessments of health and well-being consistent with Māori worldviews. 5 focus groups involving 22 teina and 1 with 5 tuakana were held., Results: Tuakana communication skills were rated as high by teina and independent coders. Qualitative analysis supported the importance of Māori communication processes for the role. Further, three measures increased significantly from the baseline to the final period for tuakana accounting for about 15% of the variance in these variables: sense of purpose (p = .07), self-rated health (p = .05), and health-related quality of life (p = .04). The qualitative analysis supported the benefits of the peer educator role for older Māori including enhanced sense of identity, well-being, and social connectedness., Discussion: The results demonstrated that kaumātua had strong communication in the peer educator role and that the intervention has positive impacts for them. The study contributes to peer intervention research that may help to improve experiences ofIndigenous and other older people., (© The Author(s) 2020. 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.)

Depression is the leading cause of disability worldwide, yet rates of missed- and mis-diagnoses are alarmingly high. The introduction of objective biomarkers, to aid diagnosis, informed by depression's physiological pathology may alleviate some of the burden on strained mental health services. Three minutes of eyes-closed resting state heart rate and skin conductance response (SCR) data were acquired from 27 participants (16 healthy controls, 11 with major depressive disorder (MDD)). Various classifiers were trained on state-of-the-art and novel features. We are aware of no previous studies analysing the utility of multimodal vs. individual modalities for classification. We found no improvement using multimodal classifiers over using heart rate variability (HRV) alone, which achieved 81% test accuracy. The best multimodal and SCR only classifiers were only slightly less accurate at 78%. Despite not improving depression detection, SCR features did show stronger correlation with suicidal ideation than HRV. SD1/SD2 2 is a novel HRV feature proposed in this paper, similar to the commonly used ratio SD1/SD2 but with more marked separation between classes, having the largest Rank Biserial Correlation of all examined features (p-value = 0.002, RBC = -0.73). We recommend further studies in this area.

Background: Aotearoa/New Zealand has a population that is ageing and there are challenges to health and social outcomes related to related to key life transitions (e.g., retirement, change in health conditions, loss of spouse). Further, there are significant inequities between Māori (Indigenous people) and non-Māori in ageing outcomes. The purpose of this study was to test the impacts and cost effectiveness of a tuakana/teina (peer education) intervention on kaumātua (elders) receiving the intervention. This study was framed by a strengths-based approach based on the key cultural concept of mana motuhake (autonomy and self-actualisation)., Methods: This study was grounded in principles of Kaupapa Māori and community-based participatory research to bring together a diverse group of stakeholders to co-develop and co-evaluate the intervention. The intervention had tuakana (peer educators) having conversations with up to six teina (recipients) and providing information related to health and social services. The research design was a pre- and post-test, clustered staggered design. Participants completed a baseline assessment of health and mana motuhake measures consistent with Māori worldviews along with two follow-up assessments (one after the first intervention group completed its activities and a second after the second intervention group completed its activities). Additionally, five focus groups and open-ended questions on the assessments were used to provide qualitative evaluation., Findings: A total of 180 kaumātua were recruited to the intervention with 121 completing it. The analysis revealed improvements over time in the expected direction on most of the variables. However, only three of the variables had statistically significant intervention effects: received support, tribal identity, and trouble paying bills. Qualitative results supported impacts of the intervention on mana motuhake, social connectedness, and tangible/information support related to services. Cost-effectiveness analysis showed that the intervention is cost effective, with a cost per QALY of less than the conventional threshold of three times gross domestic product per capita., Conclusions: The findings support the relevancy and importance of kaumātua knowledge to create a strengths-based approach to improve health and social outcomes. This study demonstrates that a contextually based and culturally safe age-friendly environments can facilitate engagement and participation by kaumātua for kaumātua., Trial Registry: Australia New Zealand Clinical Trial Registry (ACTRN12617001396314); Date Registered: 3 October 2017 (retrospectively registered); https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373733&isClinicalTrial=False.

Background: Circulating microRNAs (miRNAs) are potential biomarkers for many diseases. However, they can originate from non-disease specific sources, such as blood cells, and compromise the investigations for miRNA biomarkers. While small extracellular vesicles (sEVs) have been suggested to provide a purer source of circulating miRNAs for biomarkers discovery, the most suitable blood sample for sEV miRNA biomarker studies has not been defined., Aim: To compare the miRNA profiles between matched serum and plasma sEV preparations to determine their suitability for biomarker studies., Methods: Matched serum and plasma samples were obtained from 10 healthy controls and 10 patients with esophageal adenocarcinoma. sEV isolates were prepared from serum and plasma using ExoQuick TM and quantified using NanoSight. RNA was extracted from sEV preparations with the miRNeasy Serum/Plasma kit and profiled using the Taqman Openarray qPCR. The overall miRNA content and the expression of specific miRNAs of reported vesicular and non-vesicular origins were compared between serum and plasma sEV preparations. The diagnostic performance of a previously identified multi-miRNA biomarker panel for esophageal adenocarcinoma was also compared., Results: The overall miRNA content was higher in plasma sEV preparations (480 miRNAs) and contained 97.5% of the miRNAs found in the serum sEV preparations (412 miRNAs).The expression of commonly expressed miRNAs was highly correlated (Spearman's R = 0.87, P < 0.0001) between the plasma and serum sEV preparations, but was consistently higher in the plasma sEV preparations. Specific blood-cell miRNAs (hsa-miR-223-3p, hsa-miR-451a, miR-19b-3p, hsa-miR-17-5p, hsa-miR-30b-5p, hsa-miR-106a-5p, hsa-miR-150-5p and hsa-miR-92a-3p) were expressed at 2.7 to 9.6 fold higher levels in the plasma sEV preparations compared to serum sEV preparations ( P < 0.05). In plasma sEV preparations, the percentage of protein-associated miRNAs expressed at relatively higher levels (Ct 20-25) was greater than serum sEV preparations (50% vs 31%). While the percentage of vesicle-associated miRNAs expressed at relatively higher levels was greater in the serum sEV preparations than plasma sEV preparations (70% vs 44%). A 5-miRNA biomarker panel produced a higher cross validated accuracy for discriminating patients with esophageal adenocarcinoma from healthy controls using serum sEV preparations compared with plasma sEV preparations (AUROC 0.80 vs 0.54, P < 0.05)., Conclusion: Although plasma sEV preparations contained more miRNAs than serum sEV preparations, they also contained more miRNAs from non-vesicle origins. Serum appears to be more suitable than plasma for sEV miRNAs biomarkers studies., Competing Interests: Conflict-of-interest statement: The authors have no conflict of interest to declare., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Prune belly syndrome (PBS) is a rare, multi-system congenital myopathy primarily affecting males that is poorly described genetically. Phenotypically, its morbidity spans from mild to lethal, however, all isolated PBS cases manifest three cardinal pathological features: 1) wrinkled flaccid ventral abdominal wall with skeletal muscle deficiency, 2) urinary tract dilation with poorly contractile smooth muscle, and 3) intra-abdominal undescended testes. Despite evidence for a genetic basis, previously reported PBS autosomal candidate genes only account for one consanguineous family and single cases., Methods: We performed whole exome sequencing (WES) of two maternal adult half-brothers with syndromic PBS (PBS + Otopalatodigital spectrum disorder [OPDSD]) and two unrelated sporadic individuals with isolated PBS and further functionally validated the identified mutations., Results: We identified three unreported hemizygous missense point mutations in the X-chromosome gene Filamin A (FLNA) (c.4952 C > T (p.A1448V), c.6727C > T (p.C2160R), c.5966 G > A (p.G2236E)) in two related cases and two unrelated sporadic individuals. Two of the three PBS mutations map to the highly regulatory, stretch-sensing Ig19-21 region of FLNA and enhance binding to intracellular tails of the transmembrane receptor β-integrin 1 (ITGβ1)., Conclusions: FLNA is a regulatory actin-crosslinking protein that functions in smooth muscle cells as a mechanosensing molecular scaffold, transmitting force signals from the actin-myosin motor units and cytoskeleton via binding partners to the extracellular matrix. This is the first evidence for an X-linked cause of PBS in multiple unrelated individuals and expands the phenotypic spectrum associated with FLNA in males surviving even into adulthood.

The coffee berry borer ( Hypothenemus hampei ) is the most damaging insect pest of global coffee production. Despite its importance, our knowledge on the insect's natural habitat, range, and wild host species remains poorly known. Using archival sources (mainly herbaria but also other museum collections), we surveyed 18,667 predominantly wild-collected herbarium specimens mostly from Africa, Madagascar, and Asia for coffee berry borer occurrence. A total of 72 incidences were confirmed for presence of the coffee berry borer, with identifications assisted by micro-CT for SEM. Of the 72 positive infestations, all were from tropical African coffee ( Coffea ) species, of which 32 were from wild (non-cultivated) plants. Of the 32 wild occurrences, 30 were found in C. canephora (robusta coffee), 1 in C. liberica (Liberica coffee), and 1 in C. arabica (Arabica coffee). Our herbarium survey confirms literature and anecdotal reports that the coffee berry borer is indigenous to tropical Africa, and that coffee species, and particularly robusta coffee, are important hosts. We identify the wetter type of Guineo-Congolian forest as either the preferred or exclusive native habitat of the coffee berry borer. Other than coffee, we find no evidence of other naturally occurring hosts. Characters of infestation (e.g., hole position on coffee fruits) infers a certain degree of specificity between the coffee berry borer and its host., (Copyright © 2019 Vega, Smith, Davies, Moat, Góral, O’Sullivan and Davis.)

Background: Research reporting guidelines are increasingly commonplace and shown to improve the quality of published health research and health outcomes. Despite severe health inequities among Indigenous Peoples and the potential for research to address the causes, there is an extended legacy of health research exploiting Indigenous Peoples. This paper describes the development of the CONSolIDated critERtia for strengthening the reporting of health research involving Indigenous Peoples (CONSIDER) statement., Methods: A collaborative prioritization process was conducted based on national and international statements and guidelines about Indigenous health research from the following nations (Peoples): Australia (Aboriginal and Torres Strait Islanders), Canada (First Nations Peoples, Métis), Hawaii (Native Hawaiian), New Zealand (Māori), Taiwan (Taiwan Indigenous Tribes), United States of America (First Nations Peoples) and Northern Scandinavian countries (Sami). A review of seven research guidelines was completed, and meta-synthesis was used to construct a reporting guideline checklist for transparent and comprehensive reporting of research involving Indigenous Peoples., Results: A list of 88 possible checklist items was generated, reconciled, and categorized. Eight research domains and 17 criteria for the reporting of research involving Indigenous Peoples were identified. The research reporting domains were: (i) governance; (ii) relationships; (iii) prioritization; (iv) methodologies; (v) participation; (vi) capacity; (vii) analysis and findings; and (viii) dissemination., Conclusions: The CONSIDER statement is a collaborative synthesis and prioritization of national and international research statements and guidelines. The CONSIDER statement provides a checklist for the reporting of health research involving Indigenous peoples to strengthen research praxis and advance Indigenous health outcomes.

Background: The Aotearoa/New Zealand population is ageing and numerous studies demonstrate with this phenomenon comes increases in non-communicable diseases, injuries and healthcare costs among other issues. Further, significant inequities exist between Māori (Indigenous peoples of Aotearoa/New Zealand) and non-Māori around poor ageing and health. Most research addressing these issues is deficit oriented; however, the current research project takes a strengths-based approach that highlights the potential of kaumātua (elders) by asserting mana motuhake (autonomy, identity and self-actualisation). We believe that the esteem of elders in Māori culture signals transformative potential. Specifically, this project utilises a 'tuakana-teina' (older sibling/younger sibling) peer-educator model, where kaumātua work with other kaumātua in relation to health and wellbeing. The objectives of the project are (a) to develop the capacity of kaumātua as peer educators, whilst having positive impacts on their sense of purpose, health and wellbeing; and (b) to enhance the social and health outcomes for kaumātua receiving the intervention., Methods: The research is grounded in principles of Kaupapa Māori and community-based participatory research, and brings together an Indigenous community of kaumātua, community health researchers, and academic researchers working with two advisory boards. The project intervention involves an orientation programme for tuakana peer educators for other kaumātua (teina). The research design is a pre- and post-test, clustered staggered design. All participants will complete a baseline assessment of health and wellbeing consistent with Māori worldviews (i.e., holistic model). The tuakana and teina participants will be divided into two groups with the first group completing the intervention during the first half of the project and the second group during the second half of the project. All participants will complete post-test assessments following both interventions allowing comparison of the two groups along with repeated measures over time., Discussion: The findings will provide an evidence base for the importance and relevancy of kaumātua knowledge to create contextually based and culturally safe age-friendly environments that facilitate engagement and participation by kaumātua for kaumātua. If the model is effective, we will seek to facilitate the dissemination and scalability of the intervention., Trial Registration: Australia New Zealand Clinical Trial Registry ( ACTRN12617001396314 ); Date Registered: 3 October 2017 (retrospectively registered).

Despite its critical role in the defense against microbial infection and tumor development, little is known about the range of nucleotide and haplotype variation at IFN-γ, or the evolutionary forces that have shaped patterns of diversity at this locus. To address this gap in knowledge, we examined sequence data from the IFN-γ gene in 1461 individuals from 15 worldwide populations. Our analyses uncovered novel patterns of variation in distinct African populations, including an excess of high frequency-derived alleles, unusually long haplotype structure surrounding the IFN-γ gene, and a "star-like" genealogy of African-specific haplotypes carrying variants previously associated with infectious disease. We also inferred a deep time to coalescence of variation at IFN-γ (~ 0.8 million years ago) and ancient ages for common polymorphisms predating the evolution of modern humans. Taken together, these results are congruent with a model of positive selection on standing variation in African populations. Furthermore, we inferred that common variants in intron 3 of IFN-γ are the likely targets of selection. In addition, we observed a paucity of non-synonymous substitutions relative to synonymous changes in the exons of IFN-γ in African and non-African populations, suggestive of strong purifying selection. Therefore, we contend that positive and purifying selection have influenced levels of diversity in different regions of IFN-γ, implying that these distinct genic regions are, or have been, functionally important. Overall, this study provides additional insights into the evolutionary events that have contributed to the frequency and distribution of alleles having a role in human health and disease.

During development metazoan embryos have to establish the molecular coordinates for elaboration of the embryonic body plan. Typically, bilaterian (bilaterally symmetric animals) embryos establish anterior-posterior (AP) and dorsal-ventral (DV) axes, and in most cases the AP axis is established first. For over a century it has been known that formation of the AP axis is strongly influenced by the primary axis of the egg, the animal-vegetal (AV) axis. The molecular basis for how the AV axis influences AP polarity remains poorly understood, but sea urchins have proven to be important for elucidating the molecular basis for this process. In fact, it is the first model system where a critical role for Wnt signaling in specification and patterning the AV and AP axis was first established. One current area of research is focused on identifying the maternal factors that regulate localized activation of Wnt/β-catenin signaling at the vegetal pole during development. An essential tool for this work is the means to identify the AV polarity in oocytes and eggs. This permits investigation into how polarity is established and allows development of experimental strategies to identify maternal factors that contribute to and control axial polarity. This chapter provides protocols to accomplish this in sea urchin eggs and early embryos. We describe simple methods to visualize polarity including direct observation of eggs and oocytes, using a microscope for overt morphological signs of polarity, and more extensive methods involving localization of known factors indicative of inherent embryonic polarity, such as the upstream regulators of the Wnt/β-catenin pathway., (© 2019 Elsevier Inc. All rights reserved.)

The purpose of this study was to identify social determinant and communication correlates of health-related quality of life for kaumātua (Māori elders) in New Zealand. A total of 209 kaumātua completed a self-report survey of self-rated health, physical/mental quality of life, spirituality, and a series of questions about social determinants (e.g., factors related to income) and communication variables (e.g., loneliness, social support, cultural identity, and perceived burden/benefit). The survey was baseline data for a peer education intervention to help kaumātua work through life transitions in older age. The main findings of this study were that social determinants, particularly difficulty paying bills, accounted for a small amount of variance in physical/mental quality of life and self-rated health. Further, the communication correlates of loneliness, perceived burden, and desired support accounted for about three times as much variance in these two outcomes all with negative associations. Strength of tribal identity, importance of whānau (extended family), and knowledge of tikanga (customs and protocols) accounted for a moderate amount variance in spirituality with positive associations. These findings have important theoretical and practical implications for positive aging.

We aimed to determine median cumulative radiation exposure in pediatric intensive care unit (PICU) patients, proportion of patients with high radiation exposure (above annual average radiation per person of 6.2 mSv), and determine risk factors for high exposure. This was a retrospective chart review of PICU patients up to 18 years of age admitted to a large community hospital over 2 years. Radiologic studies and radiation exposure were determined for each patient, and total hospital radiation exposure was classified as high (>6.2 mSv) or not (≤6.2 mSv). Median radiation exposure per patient was 0.2 mSv (interquartile range = 2.1) and 11.7% of patients received >6.2 mSv radiation during their hospitalization. Factors associated with high radiation exposure included admission for trauma or surgery, number of computed tomography scans, age, and PICU length of stay (all P < .0001). We concluded that subsets of PICU patients are at risk of high radiation exposure. Policies and protocols may help minimize radiation exposure among PICU patients.

The sequence-specific hybridization and molecular recognition properties of DNA support the construction of stimulus-responsive hydrogels with precisely controlled crosslink geometry. Here we show that, as predicted by the conformational selection mechanism, the response kinetics of such a hydrogel can be tuned over orders of magnitude by modulating the thermodynamic stability of its crosslinks.

Prior to the development of a localized cancerous tumor, diffuse molecular, and structural alterations occur throughout an organ due to genetic, environmental, and lifestyle factors. This process is known as field carcinogenesis. In this study, we used partial wave spectroscopic (PWS) microscopy to explore the progression of field carcinogenesis by measuring samples collected from 190 patients with a range of colonic history (no history, low-risk history, and high-risk history) and current colon health (healthy, nondiminutive adenomas (NDA; ≥5 mm and <10 mm), and advanced adenoma [AA; ≥10 mm, HGD, or >25% villous features]). The low-risk history groups include patients with a history of NDA. The high-risk history groups include patients with either a history of AA or colorectal cancer (CRC). PWS is a nanoscale-sensitive imaging technique which measures the organization of intracellular structure. Previous studies have shown that PWS is sensitive to changes in the higher-order (20-200 nm) chromatin topology that occur due to field carcinogenesis within histologically normal cells. The results of this study show that these nanoscale structural alterations are correlated with a patient's colonic history, which suggests that PWS can detect altered field carcinogenic signatures even in patients with negative colonoscopies. Furthermore, we developed a model to calculate the 5-year risk of developing CRC for each patient group. We found that our data fit this model remarkably well (R 2  = 0.946). This correlation suggests that PWS could potentially be used to monitor CRC progression less invasively and in patients without adenomas, which opens PWS to many potential cancer care applications., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)