Early postpartum resting‐state functional connectivity for mothers receiving buprenorphine treatment for opioid use disorder: A pilot study

Between 1999 and 2014, the prevalence of opioid use disorder (OUD) among pregnant women quadrupled in the USA. The standard treatment for peripartum women with OUD is buprenorphine. However, the maternal behavior neurocircuit that regulates maternal behavior and mother‐infant bonding has not been previously studied for human mothers receiving buprenorphine treatment for OUD (BT). Rodent research shows opioid effects on reciprocal inhibition between maternal care and defence maternal brain subsystems: the hypothalamus and periaqueductal gray, respectively. We conducted a longitudinal functional magnetic resonance imaging (fMRI) pilot study in humans to specifically examine resting‐state functional connectivity (rs‐FC) between the periaqueductal gray and hypothalamus, as well as to explore associations with maternal bonding for BT. We studied 32 mothers who completed fMRI scans at 1 month (T1) and 4 months postpartum (T2), including seven mothers receiving buprenorphine for OUD and 25 non‐OUD mothers as a comparison group (CG). The participants underwent a 6‐minute resting‐state fMRI scan at each time point. We measured potential bonding impairments using the Postpartum Bonding Questionnaire to explore how rs‐FC with periaqueductal gray is associated with bonding impairments. Compared to CG, BT mothers differed in periaqueductal gray‐dependent rs‐FC with the hypothalamus, amygdala, insular cortex and other brain regions at T1, with many of these differences disappearing at T2, suggesting potential therapeutic effects of continuing buprenorphine treatment. In contrast, the “rejection and pathological anger” subscale of the Postpartum Bonding Questionnaire at T1 and T2 was associated with the T1‐to‐T2 increases in periaqueductal gray‐dependent rs‐FC with the hypothalamus and amygdala. Preliminary evidence links maternal bonding problems for mothers with OUD early in the postpartum to connectivity between specific care and defence maternal brain circuits, which may be mitigated by buprenorphine treatment. This exploratory study supports a potential mechanism for investigating both the therapeutic benefits and risks of opioids for maternal care and bonding with infants.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151866/1/jne12770.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151866/2/jne12770_am.pd

Are we there yet?:An update on transitional care in rheumatology

Abstract Significant progress has been made in the understanding of transitional care in rheumatology over the last few decades, yet universal implementation has not been realised and unmet needs continue to be reported. Possible explanations for this include lack of evidence as to which model is most effective; lack of attention to the multiple dimensions, stakeholders and systems involved in health transitions; and lack of consideration of the developmental appropriateness of transition interventions and the services/organisations/systems where such interventions are delivered. Successful transition has major implications to both the young people with juvenile-onset rheumatic disease and their families. Future research in this area will need to reflect both the multidimensional (biopsychosocial) and the multisystemic (multiple systems and stakeholders across personal/social/family support networks and health/social care/education systems). Only then will we be able to determine which aspects of transition readiness and service components influence which dimension. It is therefore imperative we continue to research and develop this area, involving both paediatric and adult rheumatology clinicians and researchers, remembering to look beyond both the condition and our discipline. Neither should we forget to tap into the exciting potential associated with digital technology to ensure further advances in transitional care are brought about in and beyond rheumatology

Measures of satisfaction with care during labour and birth: a comparative review

Background Satisfaction is the one of the most frequently reported outcome measures for quality of care. Assessment of satisfaction with maternity services is crucial, and psychometrically sound measures are needed if this is to inform health practices. This paper comparatively reviews current measures of satisfaction with care during labour and birth. Methods A review of the literature was conducted. Studies were located through computerised databases and hand searching references of identified articles and reviews. Inclusion criteria were that the questionnaire was a multi-item scale of satisfaction with care during labour and birth, and some form of psychometric information (either information about questionnaire construction, or reliability, or validity) had to be reported. Results Nine questionnaires of satisfaction with care during labour and birth were identified. Instruments varied in psychometric properties and dimensions. Most described questionnaire construction and tested some form of reliability and validity. Measures were generally not based on the main theoretical models of satisfaction and varied in scope and application to different types of samples (e.g. satisfaction following caesarean section). For an in-depth measure of satisfaction with intrapartum care, the Intrapartal-Specific Quality from the Patient’s Perspective questionnaire (QPP-I) is recommended. Brief measures with good reliability and validity are provided by the Six Simple Questions (SSQ) or Perceptions of Care Adjective Checklist (PCACL-R). Conclusions Despite the interest in measures of satisfaction there are only a small number of validated measures of satisfaction with care during labour and birth. It is important that brief, reliable and valid measures are available for use in general and specific populations in order to assist research and inform practice

Production and characterization of murine models of classic and intermediate maple syrup urine disease

BACKGROUND: Maple Syrup Urine Disease (MSUD) is an inborn error of metabolism caused by a deficiency of branched-chain keto acid dehydrogenase. MSUD has several clinical phenotypes depending on the degree of enzyme deficiency. Current treatments are not satisfactory and require new approaches to combat this disease. A major hurdle in developing new treatments has been the lack of a suitable animal model. METHODS: To create a murine model of classic MSUD, we used gene targeting and embryonic stem cell technologies to create a mouse line that lacked a functional E2 subunit gene of branched-chain keto acid dehydrogenase. To create a murine model of intermediate MSUD, we used transgenic technology to express a human E2 cDNA on the knockout background. Mice of both models were characterized at the molecular, biochemical, and whole animal levels. RESULTS: By disrupting the E2 subunit gene of branched-chain keto acid dehydrogenase, we created a gene knockout mouse model of classic MSUD. The homozygous knockout mice lacked branched-chain keto acid dehydrogenase activity, E2 immunoreactivity, and had a 3-fold increase in circulating branched-chain amino acids. These metabolic derangements resulted in neonatal lethality. Transgenic expression of a human E2 cDNA in the liver of the E2 knockout animals produced a model of intermediate MSUD. Branched-chain keto acid dehydrogenase activity was 5–6% of normal and was sufficient to allow survival, but was insufficient to normalize circulating branched-chain amino acids levels, which were intermediate between wildtype and the classic MSUD mouse model. CONCLUSION: These mice represent important animal models that closely approximate the phenotype of humans with the classic and intermediate forms of MSUD. These animals provide useful models to further characterize the pathogenesis of MSUD, as well as models to test novel therapeutic strategies, such as gene and cellular therapies, to treat this devastating metabolic disease

Growth and welfare in mixed health system financing with physician dual practice in a developing economy: a case of Indonesia

Based on Indonesia’s hybrid BPJS Kesehatan health system, we analyze for welfare-optimal government financing strategy in an economy with a mixed health system using an endogenous growth framework with physician dual practice. We find the model solution to produce two vastly different regimes in terms of policy implications: a “high” public-sector congestion regime as in the benchmark case of Indonesia, and a “low” public-sector congestion, high capacity regime. In the former, welfare-optimal health financing strategy appears to be promoting private health service. In contrast, in the low-congestion, high capacity regime, a welfare-optimal strategy is to do the opposite of increasing government physician wage at the expense of private health subsidy. These results highlight the importance of developing a benchmarking system that measures the actual degree of congestion faced by the public health service in a developing economy, as it ultimately would influence the optimal health financing strategy to be pursued

Proteomics-Based Systems Biology Modeling of Bovine Germinal Vesicle Stage Oocyte and Cumulus Cell Interaction

BACKGROUND: Oocytes are the female gametes which establish the program of life after fertilization. Interactions between oocyte and the surrounding cumulus cells at germinal vesicle (GV) stage are considered essential for proper maturation or 'programming' of oocytes, which is crucial for normal fertilization and embryonic development. However, despite its importance, little is known about the molecular events and pathways involved in this bidirectional communication. METHODOLOGY/PRINCIPAL FINDINGS: We used differential detergent fractionation multidimensional protein identification technology (DDF-Mud PIT) on bovine GV oocyte and cumulus cells and identified 811 and 1247 proteins in GV oocyte and cumulus cells, respectively; 371 proteins were significantly differentially expressed between each cell type. Systems biology modeling, which included Gene Ontology (GO) and canonical genetic pathway analysis, showed that cumulus cells have higher expression of proteins involved in cell communication, generation of precursor metabolites and energy, as well as transport than GV oocytes. Our data also suggests a hypothesis that oocytes may depend on the presence of cumulus cells to generate specific cellular signals to coordinate their growth and maturation. CONCLUSIONS/SIGNIFICANCE: Systems biology modeling of bovine oocytes and cumulus cells in the context of GO and protein interaction networks identified the signaling pathways associated with the proteins involved in cell-to-cell signaling biological process that may have implications in oocyte competence and maturation. This first comprehensive systems biology modeling of bovine oocytes and cumulus cell proteomes not only provides a foundation for signaling and cell physiology at the GV stage of oocyte development, but are also valuable for comparative studies of other stages of oocyte development at the molecular level

System differentiation in England: the imposition of supply and demand

This chapter describes changing state and sector policy in relation to differentiation and how it has emerged in the English HE context: specifically, the attempts to concentrate the highest qualified applicants and the most prestigious institutions in a 'premium' market segment; the significance of the growing involvement of private providers; and the rise of the ‘student-as-consumer’ and 'value for money' in recent government policy discourse (e.g. the White Papers Students at the Heart of the System (DBIS 2011a) and Success as a Knowledge Economy (DBIS 2016). The chapter situates the development of a market hierarchy (in the form of a vertical differentiation of institutions, Archer 2007) following the demise of the university-polytechnic binary system in 1992 (Further and Higher Education Act, HMSO 1992). This co-existed for several years with the institutional diversity often celebrated by the Higher Education Funding Council for England (e.g. HEFCE 1994; 2000) that can be conceptualised as the horizontal differentiation of valued types of higher education provision and provider (e.g. part-time or vocationally orientated). The introduction of market mechanisms, in various stages beginning with the 2004 Higher Education Act (DfES 2004) and the introduction of variable tuition fees, coincided with the publication of institutional league tables from 2005. Taken together, these have reinforced a hierarchical system in which all institutions and courses are henceforth differentiated only by reference to a set of criteria dominated by the entry requirements demanded, and the amount of research carried out by the institution. Given the implications of the most recent legislation – the Higher Education and Research Act (HMSO 2017) this hierarchy is likely to be matched by one signalled by tuition fee levels, as new cheaper 'challenger' institutions come to the market

Single nucleotide polymorphisms unravel hierarchical divergence and signatures of selection among Alaskan sockeye salmon (Oncorhynchus nerka) populations

<p>Abstract</p> <p>Background</p> <p>Disentangling the roles of geography and ecology driving population divergence and distinguishing adaptive from neutral evolution at the molecular level have been common goals among evolutionary and conservation biologists. Using single nucleotide polymorphism (SNP) multilocus genotypes for 31 sockeye salmon (<it>Oncorhynchus nerka</it>) populations from the Kvichak River, Alaska, we assessed the relative roles of geography (discrete boundaries or continuous distance) and ecology (spawning habitat and timing) driving genetic divergence in this species at varying spatial scales within the drainage. We also evaluated two outlier detection methods to characterize candidate SNPs responding to environmental selection, emphasizing which mechanism(s) may maintain the genetic variation of outlier loci.</p> <p>Results</p> <p>For the entire drainage, Mantel tests suggested a greater role of geographic distance on population divergence than differences in spawn timing when each variable was correlated with pairwise genetic distances. Clustering and hierarchical analyses of molecular variance indicated that the largest genetic differentiation occurred between populations from distinct lakes or subdrainages. Within one population-rich lake, however, Mantel tests suggested a greater role of spawn timing than geographic distance on population divergence when each variable was correlated with pairwise genetic distances. Variable spawn timing among populations was linked to specific spawning habitats as revealed by principal coordinate analyses. We additionally identified two outlier SNPs located in the major histocompatibility complex (MHC) class II that appeared robust to violations of demographic assumptions from an initial pool of eight candidates for selection.</p> <p>Conclusions</p> <p>First, our results suggest that geography and ecology have influenced genetic divergence between Alaskan sockeye salmon populations in a hierarchical manner depending on the spatial scale. Second, we found consistent evidence for diversifying selection in two loci located in the MHC class II by means of outlier detection methods; yet, alternative scenarios for the evolution of these loci were also evaluated. Both conclusions argue that historical contingency and contemporary adaptation have likely driven differentiation between Kvichak River sockeye salmon populations, as revealed by a suite of SNPs. Our findings highlight the need for conservation of complex population structure, because it provides resilience in the face of environmental change, both natural and anthropogenic.</p

An analysis of benign human prostrate offers insight into the mechanism of apocrine secretion and the origin of prostasomes

The structure and function of normal human prostate is still not fully understood. Herein, we concentrate on the different cell types present in normal prostate, describing some previously unreported types and provide evidence that prostasomes are primarily produced by apocrine secretion. Patients (n = 10) undergoing TURP were prospectively consented based on their having a low risk of harbouring CaP. Scanning electron microscopy and transmission electron microscopy was used to characterise cell types and modes of secretion. Zinc levels were determined using Inductively Coupled Plasma Mass Spectrometry. Although merocrine secretory cells were noted, the majority of secretory cells appear to be apocrine; for the first time, we clearly show high-resolution images of the stages of aposome secretion in human prostate. We also report a previously undescribed type of epithelial cell and the first ultrastructural image of wrapping cells in human prostate stroma. The zinc levels in the tissues examined were uniformly high and X-ray microanalysis detected zinc in merocrine cells but not in prostasomes. We conclude that a significant proportion of prostasomes, possibly the majority, are generated via apocrine secretion. This finding provides an explanation as to why so many large proteins, without a signal peptide sequence, are present in the prostatic fluid