Pelvic floor health in the nursing and midwifery workforce

University of Technology Sydney. Faculty of Health.BACKGROUND Integral to pelvic floor (PF) health are social practices that preserve continence. When PF health is diminished, urinary symptoms may be experienced, which by their very nature remain under-reported despite negative effects on quality of life. Many people spend large portions of their lives at work; employers and organisations have a duty to support PF health in the workplace. AIMS This research sought to investigate PF health in the female nursing and midwifery workforce. The questions addressed were: 1. What is the prevalence and impact of PF dysfunction in the nursing and midwifery workforce? 2. What factors negatively influence the experience of symptoms at work, and what strategies will ameliorate these? 3. Based on these findings, what are key recommendations to nurses, midwives, managers and policy makers for PF health promotion in this workforce? METHODS Firstly, an operational definition for the concept ‘PF health’ is offered. Then, a review of the literature with respect to the prevalence and impact of PF dysfunctions in workforce groups determined gaps in knowledge. A mixed methods observational study using surveys and focus groups investigates PF dysfunctions in female nurses and midwives. The first survey is a state-wide investigation, the second involves three urban hospitals, examining the relationship of urinary symptoms to work ability and future work plans. Experiences of symptoms in the workplace, explored though focus group discussion, provide in-depth understanding, informing recommendations for PF health at work. FINDINGS PF health encompasses the physical and functional integrity of the PF unit through an individual’s life stages to permit optimal quality of life, where access to knowledge empowers the ability to prevent or manage dysfunctions. Of the nurses and midwives surveyed in this research, half experience urinary symptoms while at work. Those with severe incontinence are likely to leave their job and moderate incontinence negatively impacts concentration and time management at work. Delaying voiding and limiting fluid intakes are common work practices linked to nurses’ and midwives’ experiences of urinary symptoms, reflecting poor self-care. Workplace team relationships, workforce management and adequacy of amenities are key influences on nurses’ and midwives’ health practices. SIGNIFICANCE PF dysfunctions are common in this workforce, associated with poor self-care and reduced work ability. Policies for PF health at work will support cultural, social and organisational change. Equitable and dignified access to amenities will empower female nurses and midwives to self-care, enabling them to care for others

A strategic framework for community engagement in oceans and human health

© The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Carson, M., Doberneck, D., Hart, Z., Kelsey, H., Pierce, J., Porter, D., Richlen, M., Schandera, L., & Triezenberg, H. A strategic framework for community engagement in oceans and human health, Community Science, 1(1), (2022): e2022CSJ000001, https://doi.org/10.1029/2022csj000001.Over the past two decades, scientific research on the connections between the health and resilience of marine ecosystems and human health, well-being, and community prosperity has expanded and evolved into a distinct “metadiscipline” known as Oceans and Human Health (OHH), recognized by the scientific community as well as policy makers. OHH goals are diverse and seek to improve public health outcomes, promote sustainable use of aquatic systems and resources, and strengthen community resilience. OHH research has historically included some level of community outreach and partner involvement; however, the increasing disruption of aquatic environments and urgency of public health impacts calls for a more systematic approach to effectively identify and engage with community partners to achieve project goals and outcomes. Herein, we present a strategic framework developed collaboratively by community engagement personnel from the four recently established U.S. Centers for Oceans and Human Health (COHH). This framework supports researchers in defining levels of community engagement and in aligning partners, purpose, activities, and approaches intentionally in their community engagement efforts. Specifically, we describe: (a) a framework for a range of outreach and engagement approaches; (b) the need for identifying partners, purpose, activities, and approaches; and (c) the importance of making intentional alignment among them. Misalignment across these dimensions may lead to wasting time or resources, eroding public trust, or failing to achieve intended outcomes. We illustrate the framework with examples from current COHH case studies and conclude with future directions for strategic community engagement in OHH and other environmental health contexts.This publication was prepared by Heather Triezenberg and the team under award NA180AR4170102 from the National Oceanic and Atmospheric Administration, U.S. Department of Commerce through the Regents of the University of Michigan, and supported by funding from the NIH (1P01ES028939-01) and the NSF (1840715) to the Bowling Green State University Great Lakes Center for Fresh Waters and Human Health. Funding for M. L. Richlen was provided by the NSF (OCE1840381) and NIH (1P01-ES028938-01) through the Woods Hole Center for Oceans and Human Health. Research at the Center for Oceans and Human Health and Climate Change Interactions (OHHC2I) at the University of South Carolina is supported by the NIH Award Number P01ES028942, granted to Principal Investigators Geoffrey Scott and Paul Sandifer. M. A. Carson, Z. Hart, H. Kelsey, D. E. Porter, and L. Schandera are Community Engagement Core investigators at this Center. Funding for J. Pierce is provided by the NSF (grant number OCE-1841811) and the NIH (P01ES028949) through the Greater Caribbean Center for Ciguatera Research at the Florida Gulf Coast University

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Discovering Santa Clara University\u27s prehistoric past: CA-SCI-755

The following report , brought together with great skill and insight by editors Russell K. Skowronek and Margaret A. Graham , provides a rich trovel of valuable information about what has been found there archaeologically and what it means. Some of this meaning reflects the kinds of lives people were leading in ancient times where students now cross over the Alameda Mall, and the very different kinds of activities people were conducting in those ancient times. Part reflects how these discoveries have already affected present-day consciousness, and what some of the changes have been in regard to public appreciation of the place. People who belong to the Ohlone Native American culture in this part of the state now have a feeling of connection with the Santa Clara University campus that did not previously exist. Many people in the area who reflect differing cultural backgrounds can now perceive the Ohlone association with the campus in a way that did not previously occur. Readers of this insightfully-written and richly-informed study of the campus \u27 prehistoric past can now enrich and deepen their own appreciations of the campus\u27 remarkable heritage

Sequencing-based fine-mapping and in silico functional characterization of the 10q24.32 arsenic metabolism efficiency locus across multiple arsenic-exposed populations

Inorganic arsenic is highly toxic and carcinogenic to humans. Exposed individuals vary in their ability to metabolize arsenic, and variability in arsenic metabolism efficiency (AME) is associated with risks of arsenic-related toxicities. Inherited genetic variation in the 10q24.32 region, near the arsenic methyltransferase (AS3MT) gene, is associated with urine-based measures of AME in multiple arsenic-exposed populations. To identify potential causal variants in this region, we applied fine mapping approaches to targeted sequencing data generated for exposed individuals from Bangladeshi, American Indian, and European American populations (n = 2,357, 557, and 648 respectively). We identified three independent association signals for Bangladeshis, two for American Indians, and one for European Americans. The size of the confidence sets for each signal varied from 4 to 85 variants. There was one signal shared across all three populations, represented by the same SNP in American Indians and European Americans (rs191177668) and in strong linkage disequilibrium (LD) with a lead SNP in Bangladesh (rs145537350). Beyond this shared signal, differences in LD patterns, minor allele frequency (MAF) (e.g., rs12573221 ~13% in Bangladesh ~0.2% among American Indians), and/or heterogeneity in effect sizes across populations likely contributed to the apparent population specificity of the additional identified signals. One of our potential causal variants influences AS3MT expression and nearby DNA methylation in numerous GTEx tissue types (with rs4919690 as a likely causal variant). Several SNPs in our confidence sets overlap transcription factor binding sites and cis-regulatory elements (from ENCODE). Taken together, our analyses reveal multiple potential causal variants in the 10q24.32 region influencing AME, including a variant shared across populations, and elucidate potential biological mechanisms underlying the impact of genetic variation on AME

Sequencing-based fine-mapping and in silico functional characterization of the 10q24.32 arsenic metabolism efficiency locus across multiple arsenic-exposed populations.

Inorganic arsenic is highly toxic and carcinogenic to humans. Exposed individuals vary in their ability to metabolize arsenic, and variability in arsenic metabolism efficiency (AME) is associated with risks of arsenic-related toxicities. Inherited genetic variation in the 10q24.32 region, near the arsenic methyltransferase (AS3MT) gene, is associated with urine-based measures of AME in multiple arsenic-exposed populations. To identify potential causal variants in this region, we applied fine mapping approaches to targeted sequencing data generated for exposed individuals from Bangladeshi, American Indian, and European American populations (n = 2,357, 557, and 648 respectively). We identified three independent association signals for Bangladeshis, two for American Indians, and one for European Americans. The size of the confidence sets for each signal varied from 4 to 85 variants. There was one signal shared across all three populations, represented by the same SNP in American Indians and European Americans (rs191177668) and in strong linkage disequilibrium (LD) with a lead SNP in Bangladesh (rs145537350). Beyond this shared signal, differences in LD patterns, minor allele frequency (MAF) (e.g., rs12573221 ~13% in Bangladesh ~0.2% among American Indians), and/or heterogeneity in effect sizes across populations likely contributed to the apparent population specificity of the additional identified signals. One of our potential causal variants influences AS3MT expression and nearby DNA methylation in numerous GTEx tissue types (with rs4919690 as a likely causal variant). Several SNPs in our confidence sets overlap transcription factor binding sites and cis-regulatory elements (from ENCODE). Taken together, our analyses reveal multiple potential causal variants in the 10q24.32 region influencing AME, including a variant shared across populations, and elucidate potential biological mechanisms underlying the impact of genetic variation on AME

Assessing the landscape of STXBP1-related disorders in 534 individuals

Disease-causing variants in STXBP1 are among the most common genetic causes of neurodevelopmental disorders. However, the phenotypic spectrum in STXBP1-related disorders is wide and clear correlations between variant type and clinical features have not been observed so far. Here, we harmonized clinical data across 534 individuals with STXBP1-related disorders and analysed 19 973 derived phenotypic terms, including phenotypes of 253 individuals previously unreported in the scientific literature. The overall phenotypic landscape in STXBP1-related disorders is characterized by neurodevelopmental abnormalities in 95% and seizures in 89% of individuals, including focal-onset seizures as the most common seizure type (47%). More than 88% of individuals with STXBP1-related disorders have seizure onset in the first year of life, including neonatal seizure onset in 47%. Individuals with protein-truncating variants and deletions in STXBP1 (n = 261) were almost twice as likely to present with West syndrome and were more phenotypically similar than expected by chance. Five genetic hotspots with recurrent variants were identified in more than 10 individuals, including p.Arg406Cys/His (n = 40), p.Arg292Cys/His/Leu/Pro (n = 30), p.Arg551Cys/Gly/His/Leu (n = 24), p.Pro139Leu (n = 12), and p.Arg190Trp (n = 11). None of the recurrent variants were significantly associated with distinct electroclinical syndromes, single phenotypic features, or showed overall clinical similarity, indicating that the baseline variability in STXBP1-related disorders is too high for discrete phenotypic subgroups to emerge. We then reconstructed the seizure history in 62 individuals with STXBP1-related disorders in detail, retrospectively assigning seizure type and seizure frequency monthly across 4433 time intervals, and retrieved 251 anti-seizure medication prescriptions from the electronic medical records. We demonstrate a dynamic pattern of seizure control and complex interplay with response to specific medications particularly in the first year of life when seizures in STXBP1-related disorders are the most prominent. Adrenocorticotropic hormone and phenobarbital were more likely to initially reduce seizure frequency in infantile spasms and focal seizures compared to other treatment options, while the ketogenic diet was most effective in maintaining seizure freedom. In summary, we demonstrate how the multidimensional spectrum of phenotypic features in STXBP1-related disorders can be assessed using a computational phenotype framework to facilitate the development of future precision-medicine approaches

Assessing the landscape of STXBP1-related disorders in 534 individuals.

Disease-causing variants in STXBP1 are among the most common genetic causes of neurodevelopmental disorders. However, the phenotypic spectrum in STXBP1-related disorders is wide and clear correlations between variant type and clinical features have not been observed so far. Here, we harmonized clinical data across 534 individuals with STXBP1-related disorders and analysed 19 973 derived phenotypic terms, including phenotypes of 253 individuals previously unreported in the scientific literature. The overall phenotypic landscape in STXBP1-related disorders is characterized by neurodevelopmental abnormalities in 95% and seizures in 89% of individuals, including focal-onset seizures as the most common seizure type (47%). More than 88% of individuals with STXBP1-related disorders have seizure onset in the first year of life, including neonatal seizure onset in 47%. Individuals with protein-truncating variants and deletions in STXBP1 (n = 261) were almost twice as likely to present with West syndrome and were more phenotypically similar than expected by chance. Five genetic hotspots with recurrent variants were identified in more than 10 individuals, including p.Arg406Cys/His (n = 40), p.Arg292Cys/His/Leu/Pro (n = 30), p.Arg551Cys/Gly/His/Leu (n = 24), p.Pro139Leu (n = 12), and p.Arg190Trp (n = 11). None of the recurrent variants were significantly associated with distinct electroclinical syndromes, single phenotypic features, or showed overall clinical similarity, indicating that the baseline variability in STXBP1-related disorders is too high for discrete phenotypic subgroups to emerge. We then reconstructed the seizure history in 62 individuals with STXBP1-related disorders in detail, retrospectively assigning seizure type and seizure frequency monthly across 4433 time intervals, and retrieved 251 anti-seizure medication prescriptions from the electronic medical records. We demonstrate a dynamic pattern of seizure control and complex interplay with response to specific medications particularly in the first year of life when seizures in STXBP1-related disorders are the most prominent. Adrenocorticotropic hormone and phenobarbital were more likely to initially reduce seizure frequency in infantile spasms and focal seizures compared to other treatment options, while the ketogenic diet was most effective in maintaining seizure freedom. In summary, we demonstrate how the multidimensional spectrum of phenotypic features in STXBP1-related disorders can be assessed using a computational phenotype framework to facilitate the development of future precision-medicine approaches