The placenta is a critical organ during pregnancy, essential for the provision of an optimal intrauterine environment, with fetal survival, growth, and development relying on correct placental ...function. It must allow nutritional compounds and relevant hormones to pass into the fetal bloodstream and metabolic waste products to be cleared. It also acts as a semipermeable barrier to potentially harmful chemicals, both endogenous and exogenous. Transporter proteins allow for bidirectional transport and are found in the syncytiotrophoblast of the placenta and endothelium of fetal capillaries. The major transporter families in the human placenta are ATP-binding cassette (ABC) and solute carrier (SLC), and insufficiency of these transporters may lead to deleterious effects on the fetus. Transporter expression levels are gestation-dependent and this is of considerable clinical interest as levels of drug resistance may be altered from one trimester to the next. This highlights the importance of these transporters in mediating correct and timely transplacental passage of essential compounds but also for efflux of potentially toxic drugs and xenobiotics. We review the current literature on placental molecular transporters with respect to their localization and ontogeny, the influence of fetal sex, and the relevance of animal models. We conclude that a paucity of information exists, and further studies are required to unlock the enigma of this dynamic organ. Summary Sentence This review summarises the existing knowledge of human placental molecular transporters (SLC and ABC superfamilies). We highlight areas where greater andmore accurate knowledge is required and discuss weaknesses of animal models for the human.
Masculinization of the external genitalia in humans is dependent on formation of 5α-dihydrotestosterone (DHT) through both the canonical androgenic pathway and an alternative (backdoor) pathway. The ...fetal testes are essential for canonical androgen production, but little is known about the synthesis of backdoor androgens, despite their known critical role in masculinization. In this study, we have measured plasma and tissue levels of endogenous steroids in second trimester human fetuses using multidimensional and high-resolution mass spectrometry. Results show that androsterone is the principal backdoor androgen in the male fetal circulation and that DHT is undetectable (<1 ng/mL), while in female fetuses, there are significantly lower levels of androsterone and testosterone. In the male, intermediates in the backdoor pathway are found primarily in the placenta and fetal liver, with significant androsterone levels also in the fetal adrenal. Backdoor intermediates, including androsterone, are only present at very low levels in the fetal testes. This is consistent with transcript levels of enzymes involved in the alternate pathway (steroid 5α-reductase type 1 SRD5A1, aldo-keto reductase type 1C2 AKR1C2, aldo-keto reductase type 1C4 AKR1C4, cytochrome P450 17A1 CYP17A1), as measured by quantitative PCR (qPCR). These data identify androsterone as the predominant backdoor androgen in the human fetus and show that circulating levels are sex dependent, but also that there is little de novo synthesis in the testis. Instead, the data indicate that placental progesterone acts as substrate for synthesis of backdoor androgens, which occurs across several tissues. Masculinization of the human fetus depends, therefore, on testosterone and androsterone synthesis by both the fetal testes and nongonadal tissues, leading to DHT formation at the genital tubercle. Our findings also provide a solid basis to explain why placental insufficiency is associated with disorders of sex development in humans.
Background
Arts‐based methodologies and methods (ABM) can elicit rich and meaningful data with seldom‐heard groups and empower participants in research. Young people with complex psychosocial needs ...could be better engaged in research using arts‐based approaches to overcome communication and literacy issues as well as distrust of those with power, including researchers. A critical review of the use and impact of ABM among this population is timely. The purpose of this review is to synthesize and examine the experience and use of ABM with young people with complex psychosocial needs.
Methods
A systematic narrative literature review was conducted with a search of the literature from 2009 to 2021. All s were reviewed independently by two authors and full papers were screened for eligibility against inclusion and exclusion criteria. Data synthesis focused on a descriptive numerical summary and a thematic analysis focused on key patterns across papers relating to the review objectives.
Results and Discussion
A total of 25 papers were included. The most common issues of focus were mental health (n = 10) and homelessness (n = 11) and methods using Photovoice (n = 12) and Body Mapping (n = 5). Individual interview data (n = 20) were the most commonly analysed, followed by created works (n = 19). Less than half the studies involved young people in the interpretation of the data collected. Knowledge translation was not described in almost half the studies, with public exhibits (n = 7) and forums with service providers (n = 4) being the most common activities. Key themes across the studies were valued over traditional methods in eliciting data, ABM as an approach to engage these young people in research and the impact of the use of ABM on participants and on key stakeholders through knowledge translation.
Conclusions
The growing field of ABM presents opportunities to enhance research with young people with complex psychosocial needs by promoting meaningful exploration of experiences, engaging participants in research and strengthening knowledge translation. The involvement of young people in the interpretation of data and ensuring that knowledge translation occurs are key areas for future attention.
Patient or Public Contribution
The findings of this review will inform future research to improve the engagement of young people with complex psychosocial needs in research and promote power sharing between researchers and research participants.
ObjectivesThis study aimed to describe mental health emergency department (ED) presentations among young people aged 8–26 years in New South Wales, Australia, and to identify key characteristics ...associated with higher risk of ED mental health re-presentation.Design, setting and participantsRetrospective analysis of linked ED data records for mental health presentations between 1 January 2015 and 30 June 2018.Main outcome measuresThe main outcome was the total number of mental health ED re-presentations within 1 year, following initial presentation. Count regression models were fitted to estimate factors associated with higher likelihood of re-presentations.ResultsForty thousand two hundred and ninety patients were included in the analyses, and 9713 (~25%) re-presented during the following year; 1831 (20%) presented at least three times. On average, patients re-presented 0.61 times per 365 person-days, with average time until first re-presentation of ~92 days but greatest risk of re-presentation within first 30–60 days. Young people with self-harm or suicidal diagnoses at initial presentation were more likely to re-present. Re-presentations were highest among young people <15 years (IRR 1.18 vs ≥20 years old), female (IRR=1.13 vs male), young people residing outside of major cities (IRR 1.08 vs major cities) and Aboriginal and Torres Strait Islander young people (IRR 1.27 vs non-Indigenous).ConclusionsED mental health re-presentation is high among young people. We demonstrate factors associated with re-presentation that EDs could target for timely, high-quality care that is youth friendly and culturally safe, with appropriate referral pathways into community-based primary and mental healthcare services.
The increased incidence of diseases, including metabolic syndrome and infertility, may be related to exposure to the mixture of chemicals, which are ubiquitous in the modern environment ...(environmental chemicals, ECs). Xeno-detoxification occurs within the liver which is also the source of many plasma proteins and growth factors and plays an important role in the regulation of homeostasis.
The objective of this study was to investigate the effects of ECs on aspects of liver function, in a well characterized ovine model of exposure to a real-life EC mixture.
Four groups of sheep (n = 10–12/sex/treatment) were maintained long-term on control or sewage sludge-fertilized pastures: from conception to culling at 19 months of age in females and from conception to 7 months of age and thereafter in control plots until culling at 19 months of age in males. Environmental chemicals were measured in sheep livers and RNA and protein extracts were assessed for exposure markers. Liver proteins were resolved using 2D differential in-gel electrophoresis and differentially expressed protein spots were identified by liquid chromatography/tandem mass spectroscopy.
Higher levels of polycyclic aromatic hydrocarbons (PAHs) and lower levels of polychlorinated biphenyls (PCBs) in the livers of control males compared to control females indicated sexually dimorphic EC body burdens. Increased levels of the PAHs Benzoaanthracene and chrysene and reduced levels of PCB 153 and PCB 180 were observed in the livers of continuously exposed females. EC exposure affected xenobiotic and detoxification responses and the liver proteome in both sexes and included major plasma-secreted and blood proteins, and metabolic enzymes whose pathway analysis predicted dysregulation of cancer-related pathways and altered lipid dynamics. The latter were confirmed by a reduction in total lipids in female livers and up-regulation of cancer-related transcript markers in male livers respectively by sewage sludge exposure.
Our results demonstrate that chronic exposure to ECs causes major physiological changes in the liver, likely to affect multiple systems in the body and which may predispose individuals to increased disease risks.
•Chronic exposure to environmental chemicals affects liver physiology.•Proteomic measurements showed widespread dysregulation in the exposed livers.•Exposure dysregulated important plasma proteins such as albumin and transferrin•Reduction in total lipids in the exposed female livers•Increase in cancer markers in the exposed male livers
Abstract The Galactic center lobe (GCL) is an object ∼1° across that is located north of the Galactic center. In the mid-infrared (MIR) the GCL appears as two 8.0 μ m filaments between which there is ...strong 24 μ m and radio continuum emission. Due to its morphology and location in the sky, previous authors have argued that the GCL is located in the Galactic center region, created by outflows from star formation or by activity of the central black hole Sagittarius A*. In an associated paper, low-frequency radio emission indicates that the GCL must instead lie foreground to the Galactic center. If the GCL is foreground to the Galactic center, it is likely to be a type of object common throughout the Galactic disk; we here investigate whether its properties are similar to those of Galactic H ii regions. We find that the GCL’s MIR morphology, MIR flux densities, dust temperatures, and radio recombination line properties as traced by the Green Bank Telescope Diffuse Ionized Gas Survey are consistent with those of known Galactic H ii regions, although the derived electron temperature is low. We search for the ionizing source(s) of the possible H ii region and identify a stellar cluster candidate (Camargo #1092/Ryu & Lee #532) and a cluster of young stellar objects (the SPICY cluster G359.3+0.3) whose members have Gaia parallaxes distances of 1.7 ± 0.4 kpc. Taken together, the results of our companion paper and those shown here suggest that the GCL has properties consistent with those of an H ii region located ∼2 kpc from the Sun.
Working in Africa provides neuroscientists with opportunities that are not available in other continents. Populations in this region exhibit the greatest genetic diversity; they live in ecosystems ...with diverse flora and fauna; and they face unique stresses to brain health, including child brain health and development, due to high levels of traumatic brain injury and diseases endemic to the region. However, the neuroscience community in Africa has yet to reach its full potential. In this article we report the outcomes from a series of meetings at which the African neuroscience community came together to identify barriers and opportunities, and to discuss ways forward. This exercise resulted in the identification of six domains of distinction in African neuroscience: the diverse DNA of African populations; diverse flora, fauna and ecosystems for comparative research; child brain health and development; the impact of climate change on mental and neurological health; access to clinical populations with important conditions less prevalent in the global North; and resourcefulness in the reuse and adaption of existing technologies and resources to answer new questions. The article also outlines plans to advance the field of neuroscience in Africa in order to unlock the potential of African neuroscientists to address regional and global mental health and neurological problems.
Abstract
We report the discovery of a young, highly scattered pulsar in a search for highly circularly polarized radio sources as part of the Australian Square Kilometre Array Pathfinder Variables ...and Slow Transients survey. In follow-up observations with the Parkes radio telescope, Murriyang, we identified PSR J1032−5804 and measured a period of 78.7 ms, a dispersion measure of 819 ± 4 pc cm
−3
, a rotation measure of −2000 ± 1 rad m
−2
, and a characteristic age of 34.6 kyr. We found a pulse scattering timescale at 3 GHz of ∼22 ms, implying a timescale at 1 GHz of ∼3845 ms, which is the third most scattered pulsar known and explains its nondetection in previous pulsar surveys. We discuss the identification of a possible pulsar wind nebula and supernova remnant in the pulsar’s local environment by analyzing the pulsar spectral energy distribution and the surrounding extended emission from multiwavelength images. Our result highlights the possibility of identifying extremely scattered pulsars from radio continuum images. Ongoing and future large-scale radio continuum surveys will offer us an unprecedented opportunity to find more extreme pulsars (e.g., highly scattered, highly intermittent, and highly accelerated), which will enhance our understanding of the characteristics of pulsars and the interstellar medium.
ObjectivesHousing is a social determinant of health that impacts the health and well-being of children and families. Screening and referral to address social determinants of health in clinical and ...social service settings has been proposed to support families with housing problems. This study aims to identify housing screening questions asked of families in healthcare and social services, determine validated screening tools and extract information about recommendations for action after screening for housing issues.MethodsThe electronic databases MEDLINE, PsycINFO, EMBASE, Ovid Emcare, Scopus and CINAHL were searched from 2009 to 2021. Inclusion criteria were peer-reviewed literature that included questions about housing being asked of children or young people aged 0–18 years and their families accessing any healthcare or social service. We extracted data on the housing questions asked, source of housing questions, validity and descriptions of actions to address housing issues.ResultsForty-nine peer-reviewed papers met the inclusion criteria. The housing questions in social screening tools vary widely. There are no standard housing-related questions that clinical and social service providers ask families. Fourteen screening tools were validated. An action was embedded as part of social screening activities in 27 of 42 studies. Actions for identified housing problems included provision of a community-based or clinic-based resource guide, and social prescribing included referral to a social worker, care coordinator or care navigation service, community health worker, social service agency, referral to a housing and child welfare demonstration project or provided intensive case management and wraparound services.ConclusionThis review provides a catalogue of housing questions that can be asked of families in the clinical and/or social service setting, and potential subsequent actions.
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