Genetic evaluation of paediatric nephrocalcinosis: phenotype-driven genetic panels reveal a rare diagnosis

Monogenic causes of paediatric nephrocalcinosis are associated with extensive phenotypic variability. We report a 14-year-old male who presented at eight years of age with incidentally identified nephrocalcinosis alongside growth impairment and dental anomalies. Extensive genetic investigation confirmed a molecular diagnosis of Bartter syndrome type II (BSII). This is exceptional in both late presentation and the presence of amelogenesis imperfecta, a very rare association of inherited tubulopathies. Details of the nephrocalcinosis gene panel analysed and associated phenotypes are presented to highlight the utility of a phenotype-driven genetic panel in resolving an atypical presentation of nephrocalcinosis, allowing precise diagnosis, tailored therapy and prognostication

A compromise aspect-adaptive cylindrical projection for world maps

There are two problems with current cylindrical projections for world maps. First, existing cylindrical map projections have a static height-to-width aspect ratio and do not automatically adjust their aspect ratio in order to optimally use available canvas space. Second, many of the commonly used cylindrical compromise projections show areas and shapes at higher latitudes with considerable distortion. This article introduces a new compromise cylindrical map projection that adjusts the distribution of parallels to the aspect ratio of a canvas. The goal of designing this projection was to show land masses at central latitudes with a visually balanced appearance similar to how they appear on a globe. The projection was constructed using a visual design procedure where a series of graphically optimized projections was defined for a select number of aspect ratios. The visually designed projections were approximated by polynomial expressions that define a cylindrical projection for any height-to-width ratio between 0.3:1 and 1:1. The resulting equations for converting spherical to Cartesian coordinates require a small number of coefficients and are fast to execute. The presented aspect-adaptive cylindrical projection is well suited for digital maps embedded in web pages with responsive web design, as well as GIS applications where the size of the map canvas is unknown a priori. We highlight the projection with a height-to-width ratio of 0.6:1, which we call the Compact Miller projection because it is inspired by the Miller Cylindrical projection. Unlike the Miller Cylindrical projection, the Compact Miller projection has a smaller height-to-width ratio and shows the world with less areal distortion at higher latitudes. A user study with 448 participants verified that the Compact Miller – together with the Plate Carrée projection – is the most preferred cylindrical compromise projection.Keywords: adaptive composite map projections, Miller projection, Mercator, aspect-adaptive cylindrical projection, Compact Miller projection, Flex Projecto

Disempowered midwives and traumatised women: exploring the parallel processes of care provider interaction that contribute to women developing Post Traumatic Stress Disorder (PTSD) post childbirth

Background: Around 4% of women develop Post Traumatic Stress Disorder Post Childbirth (PTSD-PC). During childbirth a woman’s perception of her care provider’s interpersonal verbal and nonverbal relationship behaviours, termed ‘Quality of Provider Interaction’ are significantly associated with the development of PTSD-PC.Aims: To understand how women who develop PTSD-PC and midwives, experience their interactions during care provision. In particular, how they feel during their interactions and what this means to them.Methods: The qualitative method of Interpretative Phenomenological Analysis that incorporates a reflective approach, was used to gain deep understanding of the lived experience of care provider interaction. Six women who met full diagnostic criteria for PTSD-PC and six midwives who provided intrapartum care, participated in individual face-to-face interviews. Results: Two key findings were identified: 1) Failing to recognise and meet the human needs of both women and midwives, results in poor quality interactions from midwives and poor perception of care provider interaction by women; 2) The study groups of women and midwives both identified the quality of their relationship as central to positive interactions. Recommendations for practice: (1) Raise the status of psychological wellbeing for childbearing women and make it of equal importance to physical wellbeing, with clear focus upon care provider interaction; (2) Create a midwife centred system that enables midwives to provide optimal care provider interaction and improve relationship-based care; and (3) Challenge underlying toxic cultures that currently persist in the maternity services system, which undermine the work of midwives and consequently the experience of women.Conclusion: Failure to recognise and meet the human and relationship needs of both childbearing women and midwives contributes to poor care provider interactions offered by midwives and negative perceptions of care provider interactions by women. In response, NHS maternity services need to highlight the importance of the quality of care provider interaction alongside perinatal psychological wellbeing. This requires improved working environments for midwives, so they can optimise their quality of interaction with childbearing women. This will in turn impact upon the incidence and levels of trauma and PTSD-PC experienced by women

A systematic integrative review of the literature on midwives and student midwives engaged in problematic substance use

ObjectiveThe objective of this systematic integrative review was to review the literature in relation to problematic substance use (PSU) in midwifery populations. Associated aims were to aggregate existing knowledge about midwives and student midwives’ personal engagement in PSU, to generate a holistic conceptualisation and synthesis of the existing literature regarding midwives and student midwives personally engaged in PSU and to present new understandings and perspectives to inform the development of future research questions. This review is the first of its kind.DesignSystematic searches were conducted in CINAHL, Academic Search Complete, MEDLINE, PSYCInfo, Scopus and the Cochrane Library. Findings were grouped into themes and subthemes relating to both midwives and student midwives and then analysed critically in relation to the wider literature. A quality assessment was conducted using the Mixed Methods Appraisal Tool (MMAT). The PRISMA statement was used to guide reporting.SettingIncluded studies were conducted in Scotland, Ireland, Australia and New Zealand.ParticipantsStudies included a total of 6,182 participants.FindingsA total of 3 studies were included. All included study types comprised quantitative survey designs, yet one also included a mixed methods design with the use of semi structured interviews. Two overarching themes emerged relating to both midwives and student midwives engaged in problematic substance use. For midwives, three subthemes are described: harmful daily alcohol consumption, working hours and harmful daily alcohol consumption and features associated with harmful daily alcohol consumption. For student midwives, two subthemes are presented: escape avoidance and alcohol, tobacco and cannabis use.Key conclusionsThere is limited evidence available in relation to problematic substance use in midwifery populations in comparison to that available for other healthcare populations. Further research is required, and could usefully focus upon midwives and student midwives as distinct professions to be separated out from the wider healthcare workforce.Implications for practiceProblematic substance use among the healthcare workforce is associated with an increase in medical errors and inadequate care. Those affected can be reluctant to seek help, experience psychological distress and even contemplate suicide. Whilst evidence remains lacking for midwifery populations, they form a part of the general healthcare workforce and are exposed to similar workplace stressors. As such, it is likely that they too would be affected in similar ways

A Thematic Analysis of Narratives About Birth Satisfaction and Health Awareness From Postnatal Women Who Have High and Low Trauma Scores on thePosttraumatic Stress Disorder Checklist

BACKGROUND: Around one-third of women experience childbirth trauma, with 3%–15% developing postpartum posttraumatic stress disorder (PP-PTSD).AIM: Explore birth satisfaction and health perception across two groups of postnatal women with either high or low trauma scores.METHOD: Forty postnatal women were divided into groups dependent upon Posttraumatic Stress Disorder Checklist (PCL-5) scores: high severity (n = 20; range 25–57) or low severity (n = 20; range 0–7). Semi-structured interviews explored women’s childbirth experiences related to birth satisfaction and reports of postnatal health. Thematic analysis was performed.FINDINGS: Narrative content differed appreciably between high (A) and low (B) scoring groups. Group A narratives were more negative (A1: Overall, a negative recall), referencing lack of autonomy, support, or being heard (A2: Missing needs) and negative influences (A3: Disrupting my bubble). Group B recalled more birth satisfaction (B1: Mostly positive recall) associated with (B2: Autonomy; B3: Being cared for; B4: Intuition, instinct, and primal force). Group A narratives focused strongly on mental health (A4: Reduced awareness; A6: Experiencing PTSD; A7: Needing help), with some focus on physical health (A5: How I feel physically); Group B spoke less about health (B5: My health).DISCUSSION: High-quality psychological care during labor, with continuity, choice, support, and control, alongside postnatal health follow-up may improve birth satisfaction and reduce the incidence of PP-PTSD.CONCLUSION: To increase birth satisfaction and reduce trauma, maternity care providers must be supported to prioritize high-quality psychological care to women during labor, providing choice, control, and continuity within trusting relationships. Trusting relationships are key to ongoing conversations regarding health and seeking/receiving help. Routine birth satisfaction screening and education for care providers about signs of trauma are important

Targeting Hypoxic Prostate Tumors Using the Novel Hypoxia-Activated Prodrug OCT1002 Inhibits Expression of Genes Associated with Malignant Progression

Purpose: To understand the role of hypoxia in prostate tumor progression and to evaluate the ability of the novel unidirectional hypoxia-activated prodrug OCT1002 to enhance the antitumor effect of bicalutamide. Experimental Design: The effect of OCT1002 on prostate cancer cells (LNCaP, 22Rv1, and PC3) was measured in normoxia and hypoxia in vitro. In vivo, tumor growth and lung metastases were measured in mice treated with bicalutamide, OCT1002, or a combination. Dorsal skin fold chambers were used to image tumor vasculature in vivo. Longitudinal gene expression changes in tumors were analyzed using PCR. Results: Reduction of OCT1002 to its active form (OCT1001) decreased prostate cancer cell viability. In LNCaP-luc spheroids, OCT1002 caused increased apoptosis and decreased clonogenicity. In vivo, treatment with OCT1002 alone, or with bicalutamide, showed significantly greater tumor growth control and reduced lung metastases compared with controls. Reestablishment of the tumor microvasculature following bicalutamide-induced vascular collapse is inhibited by OCT1002. Significantly, the upregulation of RUNX2 and its targets caused by bicalutamide alone was blocked by OCT1002. Conclusions: OCT1002 selectively targets hypoxic tumor cells and enhances the antitumor efficacy of bicalutamide. Furthermore, bicalutamide caused changes in gene expression, which indicated progression to a more malignant genotype; OCT1002 blocked these effects, emphasizing that more attention should be attached to understanding genetic changes that may occur during treatment. Early targeting of hypoxic cells with OCT1002 can provide a means of inhibiting prostate tumor growth and malignant progression. This is of importance for the design and refinement of existing androgen-deprivation regimens in the clinic

Acetylation of H2A.Z is a key epigenetic modification associated with gene deregulation and epigenetic remodeling in cancer

Histone H2A.Z (H2A.Z) is an evolutionarily conserved H2A variant implicated in the regulation of gene expression; however, its role in transcriptional deregulation in cancer remains poorly understood. Using genome-wide studies, we investigated the role of promoter-associated H2A.Z and acetylated H2A.Z (acH2A.Z) in gene deregulation and its relationship with DNA methylation and H3K27me3 in prostate cancer. Our results reconcile the conflicting reports of positive and negative roles for histone H2A.Z and gene expression states. We find that H2A.Z is enriched in a bimodal distribution at nucleosomes, surrounding the transcription start sites (TSSs) of both active and poised gene promoters. In addition, H2A.Z spreads across the entire promoter of inactive genes in a deacetylated state. In contrast, acH2A.Z is only localized at the TSSs of active genes. Gene deregulation in cancer is also associated with a reorganization of acH2A.Z and H2A.Z nucleosome occupancy across the promoter region and TSS of genes. Notably, in cancer cells we find that a gain of acH2A.Z at the TSS occurs with an overall decrease of H2A.Z levels, in concert with oncogene activation. Furthermore, deacetylation of H2A.Z at TSSs is increased with silencing of tumor suppressor genes. We also demonstrate that acH2A.Z anti-correlates with promoter H3K27me3 and DNA methylation. We show for the first time, that acetylation of H2A.Z is a key modification associated with gene activity in normal cells and epigenetic gene deregulation in tumorigenesis

ICD-11 complex Post Traumatic Stress Disorder (CPTSD) in parents with perinatal bereavement: Implications for treatment and care

Introduction The 11th revision of the WHO International Classification of Diseases (ICD-11) has identified Complex PTSD (CPTSD) as a new condition. Aim To explore whether the new diagnosis of CPTSD (ICD11) is relevant to women who have experienced perinatal bereavement and to advance knowledge about the acceptability, feasibility and perceived impact of delivering an innovative flexible Compassionate Focused Therapy (CFT) informed treatment package to alleviate symptoms of this condition. Methods A mixed methods study using survey and interviews was conducted. Participants first completed the International Trauma Questionnaire (ITQ) to assess if they met the criteria for PTSD or CPTSD (n=72), and subsequent semi-structured interviews (n=12) identified participants’ views about different treatment approaches. Participants A convenience sample of women who had experienced perinatal bereavement were recruited from one geographical region in Scotland. Data collection Information was gathered about trauma experiences related to perinatal bereavement; participants’ levels of PTSD or CPTSD using the ITQ; and views regarding the features of treatment options. In-depth interviews with women (n=12) and a focus group with staff (n=5) were also conducted. Findings Of 74 participants (n=74) who fully completed the ITQ, 10.8% (n=8) met the criteria for PTSD and 29.7% (n=22) for CPTSD, equating to a total of 40.5% of participants experiencing traumatic stress. Results suggest that CPTSD is a more common condition than PTSD in people with perinatal bereavement, with qualitative data suggesting that CFT and EMDR can be useful and acceptable interventions for this population group. Conclusion A feasibility study is recommended next to evaluate acceptability of trial processes in preparation for a definitive randomised controlled trial of a new flexible CFT informed treatment package to address PTSD and CPTSD in people with perinatal bereavement. Recommendations for practice Routine assessment of ICD-11 CPTSD is recommended in this population group