The Role of Pediatric Nurses During Preventable Adverse Event Disclosure: A Scoping Review.

OBJECTIVES: Preventable adverse events (PAEs) occur across the healthcare spectrum and unfortunately, errors, adverse events, and PAEs are common in pediatric care. Historically, the role of disclosure of PAEs to patients and their families occurred between the dyad of physician and patient, with physicians assuming the responsibility of disclosure. In recent years, a trend toward a multidisciplinary team-based approach has emerged in some institutions, yet the role of pediatric nurses within the team disclosing a PAE is not fully understood. Given the unique relationship between pediatric nurses and their patients and their families, it is essential to understand does the literature tell us about the role of pediatric nurses during PAE disclosure? METHODS: The Arksey and O'Malley scoping review method guided this study protocol and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews framework guided reporting. RESULTS: The final sample included five articles for synthesis: none reported or described a specific role for pediatric nurses during PAE disclosure. CONCLUSIONS: There is a gap in the literature on the role of pediatric nurses during PAE disclosure. Two themes emerged from this review: the use of a team-based approach to disclosure, and the need to provide emotional support to the pediatric patient and their family. There is a need for additional investigation into the role of pediatric nurses as part of a team-based disclosure process and how pediatric nurses currently provide, or desire to provide, emotional support to the patient and their family.

The Effects of Moral Distress on Resilience in Pediatric Emergency Department Nurses.

INTRODUCTION: Moral distress is widespread in health care, and nurses working in high-pressure environments, such as emergency departments, experience stress at high rates. Understanding how moral distress affects pediatric emergency nursing care is essential to moderate its negative impacts. Increased resilience has been promoted as a tool to mitigate moral distress. The purpose of this study, conducted prior to the pandemic, was to examine patterns of moral distress and the impact of moral distress on resilience among pediatric emergency nurses. METHODS: A cross-sectional exploratory study of pediatric emergency nurses was performed. Moral Distress Scale-Revised (Pediatric) and Connor-Davidson Resilience Scale 25© scores were collected and calculated. Exploratory factor analysis with principal components was used to identify patterns of moral distress that impact resilience. RESULTS: Four distinct patterns of moral distress that impact resilience were identified: (1) incompetent practice, (2) incongruent truth-telling, (3) potentially inappropriate care, and (4) discordant health care teams. DISCUSSION: Our study was the first to identify 4 patterns of moral distress in pediatric emergency nurses. As a result, actions to promote resilience include: (1) supporting competent practice, (2) upholding appropriate truth-telling, (3) recognizing and addressing potentially inappropriate care, and (4) building concordant health care teams and systems. This pre-pandemic data provides a foundational understanding of the relationship between moral distress and resilience in pediatric emergency nurses. Identifying factors of moral distress that impact resilience has significant implications for pediatric emergency nursing, including the development of future initiatives, education, and research.

Neonatal mortality risk of large-for-gestational-age and macrosomic live births in 15 countries, including 115.6 million nationwide linked records, 2000-2020.

OBJECTIVE: We aimed to compare the prevalence and neonatal mortality associated with large for gestational age (LGA) and macrosomia among 115.6 million live births in 15 countries, between 2000 and 2020. DESIGN: Population-based, multi-country study. SETTING: National healthcare systems. POPULATION: Liveborn infants. METHODS: We used individual-level data identified for the Vulnerable Newborn Measurement Collaboration. We calculated the prevalence and relative risk (RR) of neonatal mortality among live births born at term + LGA (>90th centile, and also >95th and >97th centiles when the data were available) versus term + appropriate for gestational age (AGA, 10th-90th centiles) and macrosomic (≥4000, ≥4500 and ≥5000 g, regardless of gestational age) versus 2500-3999 g. INTERGROWTH 21st served as the reference population. MAIN OUTCOME MEASURES: Prevalence and neonatal mortality risks. RESULTS: Large for gestational age was common (median prevalence 18.2%; interquartile range, IQR, 13.5%-22.0%), and overall was associated with a lower neonatal mortality risk compared with AGA (RR 0.83, 95% CI 0.77-0.89). Around one in ten babies were ≥4000 g (median prevalence 9.6% (IQR 6.4%-13.3%), with 1.2% (IQR 0.7%-2.0%) ≥4500 g and with 0.2% (IQR 0.1%-0.2%) ≥5000 g). Overall, macrosomia of ≥4000 g was not associated with increased neonatal mortality risk (RR 0.80, 95% CI 0.69-0.94); however, a higher risk was observed for birthweights of ≥4500 g (RR 1.52, 95% CI 1.10-2.11) and ≥5000 g (RR 4.54, 95% CI 2.58-7.99), compared with birthweights of 2500-3999 g, with the highest risk observed in the first 7 days of life. CONCLUSIONS: In this population, birthweight of ≥4500 g was the most useful marker for early mortality risk in big babies and could be used to guide clinical management decisions.

Improving Use of Antibiotics for Pediatric Pneumonia in Community Hospital Emergency Departments.

BACKGROUND AND OBJECTIVES: The majority of pediatric patients present to community-hospital emergency departments (EDs). Pneumonia is among the most common reasons for ED visits; however, prescribing narrow-spectrum antibiotics occurs at rates below established best practices. We sought to increase prescription of narrow-spectrum antibiotics for pediatric pneumonia in 5 community hospital EDs using an interdisciplinary learning collaborative. We aimed to increase use of narrow spectrum antibiotics from 60% to 80% by December 2018. METHODS: A collaborative of 5 community hospitals developed quality improvement teams who held quarterly meetings over a 1 year period engaging teams in Plan-Do-Study-Act cycles. Interventions included deployment of an evidenced based guideline, educational interventions, and order set modification. Preintervention data were collected for 12 months. Using a standardized data form, teams collected monthly data during the intervention period and for an additional year after to assess for sustainability. Teams evaluated data using statistical process control charts and included any patient 3 months to 18 years with a diagnosis of pneumonia. RESULTS: The aggregated rate of narrow-spectrum antibiotic prescriptions increased from 60% during the baseline period to 78% during the intervention period. During the year after active implementation, this aggregate rate increased to 92%. Differences in prescribing patterns were noted by provider type, but narrow-spectrum antibiotic use improved for both general emergency medicine and pediatric providers. No return visits to the ED for failure of antibiotic treatment within 72 hours occurred. CONCLUSIONS: An interdisciplinary community hospital learning collaborative increased prescribing narrow-spectrum antibiotics by both general and pediatric ED providers.

Efficacy of feeding hydroxy-selenomethionine on plasma and milk selenium in mid-lactation dairy cows.

In this study, we aimed to determine the amount of Se transferred to milk and blood of mid- to late-lactation dairy cows when supplemental Se from hydroxy-selenomethionine (OH-SeMet) was fed compared with an unsupplemented group and a group supplemented with a seleno-yeast (SY). Twenty-four lactating Holstein cows (178 ± 43 d in milk) were used in a complete randomized block design for 91 d (7-d covariate period and 84-d treatment period). Treatments were (1) basal diet with an analyzed Se background of 0.2 mg of Se per kg as-fed (control); (2) basal diet + 0.3 mg of Se/kg as-fed from SY (SY-0.3); (3) basal diet + 0.1 mg of Se/kg as-fed from OH-SeMet (OH-SeMet-0.1); and (4) basal diet + 0.3 mg of Se/kg as-fed from OH-SeMet (OH-SeMet-0.3). During the trial, plasma and milk were analyzed for total Se, and plasma was analyzed for glutathione peroxidase activity. The mean plasma and milk Se concentrations exhibited the same relationship, where OH-SeMet-0.3 resulted in the highest values (142 µg/L of plasma and 104 µg/kg of milk), followed by SY-0.3 (134 µg/L and 85 µg/kg), OH-SeMet-0.1 (122 µg/L and 67 µg/kg), and the control group had the lowest values (120 µg/L and 50 µg/kg). The increment of Se in milk induced by OH-SeMet-0.3 (+54 µg/kg) was 54% higher than that induced by SY-0.3 (+35 µg/kg). Additionally, dietary supplementation of 0.2 mg/kg Se from OH-SeMet in the total mixed ration was estimated to be similar to 0.3 mg/kg Se from SY in the total mixed ration when considering the level of Se in the milk. There was no difference in plasma glutathione peroxidase activity between groups; however, OH-SeMet-0.3 significantly decreased somatic cell count. The results confirmed that supplementation with organic Se increases milk and plasma Se concentrations. Moreover, when administered at the same level of supplementation, OH-SeMet was shown to be more efficient than SY in improving milk quality by increasing Se content and decreasing milk somatic cell count.

The effectiveness of self-care interventions in chronic illness: A meta-analysis of randomized controlled trials.

OBJECTIVE: To characterize and explain variation in the comparative effectiveness of self-care interventions on relevant outcomes of chronic illness compared with controls. DESIGN: Meta-analysis and meta-regression. METHODS: Data extraction was framed within the context of a previously-published scoping review of randomized trials designed to enhance self-care in type 2 diabetes mellitus, heart failure, hypertension, asthma, coronary artery disease, and chronic obstructive pulmonary disease (published between 2008 and 2019). Data were pooled using random-effects meta-analyses. Meta-regression was used to test the effect of potential moderators on trial effectiveness. RESULTS: 145 trials involving 36,853 participants were included. Overall, the effect size of self-care interventions on improving outcomes was small (Hedges' g = 0.29 (95% CI = 0.25-0.33), p < 0.001) with statistically significant heterogeneity across trials (Q = 514.85, p < 0.001, I2 = 72.0%). A majority of trials (n = 83, 57.2%) were rated as having a high risk of bias. There was no statistically significant difference in trial effectiveness based on the use of theory, specific components of self-care addressed, the number of modes of delivery, the number of behavioral change techniques, specific modes of delivery, specific behavioral change techniques, intervention duration, total number of hours of intervention, or either participant age or gender. CONCLUSIONS: Self-care interventions are modestly effective in improving outcomes. Poor trial quality limits the strength of conclusions in this area of science. There is much to be done to enhance the design, conduct and reporting of self-care trials in order to gain more insight into the effectiveness of self-care interventions. TWEETABLE ABSTRACT: New review highlights poor trial design as major impediment to understanding the contribution of self -care to outcomes in chronic illness.

Healthcare costs of investigations for stillbirth from a population-based study in Australia.

Objective Stillbirth investigations incur healthcare costs, but these investigations are necessary to provide information that will help reduce the risk of a recurrent stillbirth, as well as advice regarding family planning and future pregnancies. The aims of this study were to determine the healthcare costs of investigations for stillbirths, identify drivers and assess cost differences between explained and unexplained stillbirths. Methods Data from 697 stillbirths were extracted from the Stillbirth Causes Study covering the period 2013-18. The dataset comprised all investigations related to stillbirth on the mother, baby and placenta. Unit costs applied were sourced from the Australian Medicare Benefits Schedule, local hospital estimates and published literature. Multivariable regression analyses were used to assess key factors in cost estimates. Results In all, 200 (28.7%) stillbirths were unexplained and 76.8% of these had between five and eight core investigations. Unexplained stillbirths were twice as likely to have eight core investigations as explained stillbirths (16.5% vs 7.7%). The estimated aggregated cost of stillbirth investigations for 697 stillbirths was A$2.13 million (mean A$3060, median A$4246). The main cost drivers were autopsies or cytogenetic screening. Mean costs were similar when stillbirths had known or unknown causes and by reason for stillbirth among cases with definable causes. Conclusion Investigations for stillbirth in Australia cost approximately A$4200 per stillbirth on average and are critical for managing future pregnancies and preventing more stillbirths. These findings improve our understanding of the costs that may be averted if stillbirths can be prevented through primary prevention initiatives. What is known about the topic? Approximately 2000 stillbirths occur each year in Australia, and this trend has not changed for several decades. Stillbirth investigations incur healthcare costs, but these investigations are necessary to provide information to help reduce the risk of a recurrent stillbirth and advice regarding family planning and future pregnancies. Recommendations for the core set of stillbirth investigations have recently been agreed upon by consensus. What does this paper add? The costs of stillbirth investigations are unknown in Australia. The assessment of these costs is challenging because not all investigations involved in stillbirths are recorded within formal administrative systems because a stillborn baby is not formally recognised as a patient. The present population-based analysis of 697 stillbirths in Australia estimated that, on average, A$4200 was spent on investigations for each stillbirth, with key drivers being autopsies and cytogenetic screening. These costs are typical, with most cases having between five and eight of the core eight recommended investigations. What are the implications for practitioners? There are cost implications for stillbirth investigations, and this analysis gives a true account of current practice in Australia. Together with the high downstream economic costs of stillbirths, the cost burden of stillbirth investigations is high but ultimately avoidable when practitioners adhere to the core investigations, build knowledge around preventable risk factors and use this information to reduce the number of stillbirths.

Prospective cohort study: Causes of stillbirth in Australia 2013-2018.

BACKGROUND: Stillbirth is a major public health problem that is slow to improve in Australia. Understanding the causes of stillbirth through appropriate investigation is the cornerstone of prevention and important for parents to understand why their baby died. AIM: The aim of this study is to assess compliance with the Perinatal Society of Australia and New Zealand (PSANZ) Perinatal Mortality Clinical Practice Guidelines (2009) for stillbirths. METHODS: This is a prospective multi-centred cohort study of stillbirths at participating hospitals (2013-2018). Data were recorded into a purpose-built database. The frequency of the recommended core investigations was calculated, and χ2 test was performed for subgroup analyses by gestational age groups and timing of fetal death. A 70% compliance threshold was defined for investigations. The cause of death categories was provided according to PSANZ Perinatal Death Classification. RESULTS: Among 697 reported total stillbirths, 562 (81%) were antepartum, and 101 (15%) were intrapartum. The most common cause of death categories were 'congenital abnormality' (12.5%), 'specific perinatal conditions' (12.2%) and 'unexplained antepartum death' (29%). According to 2009 guidelines, there were no stillbirths where all recommended investigations were performed (including or excluding autopsy). A compliance of 70% was observed for comprehensive history (82%), full blood count (94%), cytomegalovirus (71%), toxoplasmosis (70%), renal function (75%), liver function (79%), external examination (86%), post-mortem examination (84%) and placental histopathology (92%). The overall autopsy rate was 52%. CONCLUSIONS: Compliance with recommended investigations for stillbirth was suboptimal, and many stillbirths remain unexplained. Education on the value of investigations for stillbirth is needed. Future studies should focus on understanding the yield and value of investigations and service delivery gaps that impact compliance.

Systematic review of ambient temperature exposure during pregnancy and stillbirth: Methods and evidence.

BACKGROUND: Associations between ambient temperature exposure during pregnancy and stillbirth have been reviewed and described in the literature. However, there is no existing review of environmental and epidemiologic methods applied to measure stillbirths resulting from exposure to ambient temperatures during pregnancy. The objective of this study is to systematically review published methods, data sources, and data linkage practices to characterize associations between ambient temperature and stillbirth to inform stillbirth prevention and risk management strategies. METHODS: A systematic review of published studies that assess the association between ambient temperature exposure during pregnancy using any measures or approach and stillbirth was undertaken in Cochrane Library, PubMed, Medline, Scopus, Embase, and Web of Science of studies (2000-2020, inclusive). Selection of studies were assessed by pre-specified eligibility criteria and documented using PRISMA. Citations were managed using EndNote X8 whilst selection, reviewing, and data extraction were performed using Covidence. The screening, selection, and data extraction process consisted of two blind, independent reviews followed by a tertiary independent review. An adapted Critical Appraisal Skills Program (CASP) checklist was used to assess quality and bias. The main findings and characteristics of all studies was extracted and summarized. Where appropriate, a meta-analysis will be performed for measures of association. RESULTS: Among 538 original records, 12 eligible articles were identified that analysed associations between ambient temperature exposure and stillbirth for 42,848 stillbirths among 3.4 million births across seven countries. Varied definitions of stillbirth were reported based on gestational age, birthweight, both, or neither. The overall rate of stillbirth ranged from 1.9 to 38.4 per 1000 among six high-income countries and one low-middle-income country. All study designs were retrospective and included ten cohort studies, three case-crossover studies, and two additional case-control subgroup analysis. Exposure data for ambient temperature was mostly derived from standard municipal or country-level monitors based on weather stations (66.6%) or a forecasting model (16.7%); otherwise, not reported (16.7%). Results were not statistically pooled for a meta-analysis due to heterogeneity of methods and models among included studies. All studies reported associations of increased risk of stillbirth with ambient temperature exposures throughout pregnancy, particularly in late pregnancy. One study estimates 17-19% (PAR) of stillbirths are potentially attributable to chronic exposure to hot and cold ambient temperatures during pregnancy. Overall, risk of stillbirth was observed to increase below 15 °C and above 23.4 °C, where highest risk is above 29.4 °C. CONCLUSION: Exposure to hot and cold temperatures during pregnancy may increase the risk of stillbirth, although a clear causative mechanism remains unknown. Despite lack of causal evidence, existing evidence across diverse settings observed similar effects of increased risk of stillbirth using a variety of statistical and methodological approaches for exposure assessments, exposure windows, and data linkage. Managing exposure to ambient temperatures during pregnancy could potentially decrease risk of stillbirth, particularly among women in low-resource settings where access to safe antenatal and obstetric care is challenging. To fully understand the effects or dose-response relationship of maternal exposure to ambient temperatures and stillbirth, future studies should focus on biological mechanisms and contributing factors in addition to improving measurement of ambient temperature exposure.

Protocol for the development and validation of a risk prediction model for stillbirths from 35 weeks gestation in Australia.

BACKGROUND: Despite advances in the care of women and their babies in the past century, an estimated 1.7 million babies are born still each year throughout the world. A robust method to estimate a pregnant woman's individualized risk of late-pregnancy stillbirth is needed to inform decision-making around the timing of birth to reduce the risk of stillbirth from 35 weeks of gestation in Australia, a high-resource setting. METHODS: This is a protocol for a cross-sectional study of all late-pregnancy births in Australia (2005-2015) from 35 weeks of gestation including 5188 stillbirths among 3.1 million births at an estimated rate of 1.7 stillbirths per 1000 births. A multivariable logistic regression model will be developed in line with current Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD) guidelines to estimate the gestation-specific probability of stillbirth with prediction intervals. Candidate predictors were identified from systematic reviews and clinical consultation and will be described through univariable regression analysis. To generate a final model, elimination by backward stepwise multivariable logistic regression will be performed. The model will be internally validated using bootstrapping with 1000 repetitions and externally validated using a temporally unique dataset. Overall model performance will be assessed with R2, calibration, and discrimination. Calibration will be reported using a calibration plot with 95% confidence intervals (α = 0.05). Discrimination will be measured by the C-statistic and area underneath the receiver-operator curves. Clinical usefulness will be reported as positive and negative predictive values, and a decision curve analysis will be considered. DISCUSSION: A robust method to predict a pregnant woman's individualized risk of late-pregnancy stillbirth is needed to inform timely, appropriate care to reduce stillbirth. Among existing prediction models designed for obstetric use, few have been subject to internal and external validation and many fail to meet recommended reporting standards. In developing a risk prediction model for late-gestation stillbirth with both providers and pregnant women in mind, we endeavor to develop a validated model for clinical use in Australia that meets current reporting standards.

Stillbirth in Australia 1: The road to now: Two decades of stillbirth research and advocacy in Australia.

Stillbirth is a major public health problem with an enormous mortality burden and psychosocial impact on parents, families and the wider community both globally and in Australia. In 2015, Australia's late gestation stillbirth rate was over 30% higher than that of the best-performing countries globally, highlighting the urgent need for action. We present an overview of the foundations which led to the establishment of Australia's NHMRC Centre of Research Excellence in Stillbirth (Stillbirth CRE) in 2017 and highlight key activities in the following areas: Opportunities to expand and improve collaborations between research teams; Supporting the conduct and development of innovative, high quality, collaborative research that incorporates a strong parent voice; Promoting effective translation of research into health policy and/or practice; and the Regional and global work of the Stillbirth CRE. We highlight the first-ever Senate Inquiry into Stillbirth in Australia in 2018. These events ultimately led to the development of a National Stillbirth Action and Implementation Plan for Australia with the aims of reducing stillbirth rates by 20% over the next five years, reducing the disparity in stillbirth rates between advantaged and disadvantaged communities, and improving care for all families who experience this loss.

Top-Down Enrichment Guides in Formation of Synthetic Microbial Consortia for Biomass Degradation.

Consortium-based approaches are a promising avenue toward efficient bioprocessing. However, many complex microbial interactions dictate community dynamics and stability that must be replicated in synthetic systems. The rumen and/or hindguts of large mammalian herbivores harbor complex communities of biomass-degrading fungi and bacteria, as well as archaea and protozoa that work collectively to degrade lignocellulose, yet the microbial interactions responsible for stability, resilience, and activity of the community remain largely uncharacterized. In this work, we demonstrate a "top-down" enrichment-based methodology for selecting a minimal but effective lignocellulose-degrading community that produces methane-rich fermentation gas (biogas). The resulting enrichment consortium produced 0.75-1.9-fold more fermentation gas at 1.4-2.1 times the rate compared to a monoculture of fungi from the enrichment. Metagenomic sequencing of the top-down enriched consortium revealed genomes encoding for functional compartmentalization of the community, spread across an anaerobic fungus (Piromyces), a bacterium (Sphaerochaeta), and two methanogenic archaea (Methanosphaera and Methanocorpusculum). Guided by the composition of the top-down enrichment, several synthetic cocultures were formed from the "bottom-up" using previously isolated fungi, Neocallimastix californiae and Anaeromyces robustus paired with the methanogen Methanobacterium bryantii. While cross-feeding occurred in synthetic co-cultures, removal of fungal metabolites by methanogens did not increase the rate of gas production or the rate of substrate deconstruction by the synthetic community relative to fungal monocultures. Metabolomic characterization verified that syntrophy was established within synthetic co-cultures, which generated methane at similar concentrations compared to the enriched consortium but lacked the temporal stability (resilience) seen in the native system. Taken together, deciphering the membership and metabolic potential of an enriched gut consortium enables the design of methanogenic synthetic co-cultures. However, differences in the growth rate and stability of enriched versus synthetic consortia underscore the difficulties in mimicking naturally occurring syntrophy in synthetic systems.

Case Report: Ketamine for Pain and Depression in Advanced Cancer.

Patients with advanced cancer often suffer from both severe pain and severe symptoms of depression. Use of traditional antidepressants is often limited by the short prognosis associated with advanced cancer. We present the case of a patient with neuropathic pain from advanced cancer and severe depression that responded dramatically to an intravenous infusion of ketamine resulting in decreased pain and resolution of severe depression symptoms.

Transcriptomic characterization of Caecomyces churrovis: a novel, non-rhizoid-forming lignocellulolytic anaerobic fungus.

Anaerobic gut fungi are the primary colonizers of plant material in the rumen microbiome, but are poorly studied due to a lack of characterized isolates. While most genera of gut fungi form extensive rhizoidal networks, which likely participate in mechanical disruption of plant cell walls, fungi within the Caecomyces genus do not possess these rhizoids. Here, we describe a novel fungal isolate, Caecomyces churrovis, which forms spherical sporangia with a limited rhizoidal network yet secretes a diverse set of carbohydrate active enzymes (CAZymes) for plant cell wall hydrolysis. Despite lacking an extensive rhizoidal system, C. churrovis is capable of growth on fibrous substrates like switchgrass, reed canary grass, and corn stover, although faster growth is observed on soluble sugars. Gut fungi have been shown to use enzyme complexes (fungal cellulosomes) in which CAZymes bind to non-catalytic scaffoldins to improve biomass degradation efficiency. However, transcriptomic analysis and enzyme activity assays reveal that C. churrovis relies more on free enzymes compared to other gut fungal isolates. Only 15% of CAZyme transcripts contain non-catalytic dockerin domains in C. churrovis, compared to 30% in rhizoid-forming fungi. Furthermore, C. churrovis is enriched in GH43 enzymes that provide complementary hemicellulose degrading activities, suggesting that a wider variety of these activities are required to degrade plant biomass in the absence of an extensive fungal rhizoid network. Overall, molecular characterization of a non-rhizoid-forming anaerobic fungus fills a gap in understanding the roles of CAZyme abundance and associated degradation mechanisms during lignocellulose breakdown within the rumen microbiome.

Genomic analysis of methanogenic archaea reveals a shift towards energy conservation.

BACKGROUND: The metabolism of archaeal methanogens drives methane release into the environment and is critical to understanding global carbon cycling. Methanogenesis operates at a very low reducing potential compared to other forms of respiration and is therefore critical to many anaerobic environments. Harnessing or altering methanogen metabolism has the potential to mitigate global warming and even be utilized for energy applications. RESULTS: Here, we report draft genome sequences for the isolated methanogens Methanobacterium bryantii, Methanosarcina spelaei, Methanosphaera cuniculi, and Methanocorpusculum parvum. These anaerobic, methane-producing archaea represent a diverse set of isolates, capable of methylotrophic, acetoclastic, and hydrogenotrophic methanogenesis. Assembly and analysis of the genomes allowed for simple and rapid reconstruction of metabolism in the four methanogens. Comparison of the distribution of Clusters of Orthologous Groups (COG) proteins to a sample of genomes from the RefSeq database revealed a trend towards energy conservation in genome composition of all methanogens sequenced. Further analysis of the predicted membrane proteins and transporters distinguished differing energy conservation methods utilized during methanogenesis, such as chemiosmotic coupling in Msar. spelaei and electron bifurcation linked to chemiosmotic coupling in Mbac. bryantii and Msph. cuniculi. CONCLUSIONS: Methanogens occupy a unique ecological niche, acting as the terminal electron acceptors in anaerobic environments, and their genomes display a significant shift towards energy conservation. The genome-enabled reconstructed metabolisms reported here have significance to diverse anaerobic communities and have led to proposed substrate utilization not previously reported in isolation, such as formate and methanol metabolism in Mbac. bryantii and CO2 metabolism in Msph. cuniculi. The newly proposed substrates establish an important foundation with which to decipher how methanogens behave in native communities, as CO2 and formate are common electron carriers in microbial communities.

Managing Hyperkalemia: Stepping Into a New Frontier.

Maintaining potassium balance in the body is essential for cellular function. Even a slight increase in normal serum potassium levels (3.5-5.0 mEq/L) can interfere with metabolism, electrical action potentials, and cellular processes. Hyperkalemia is commonly seen in patients with chronic kidney disease (CKD) and in patients on renin-angiotensin-aldosterone system (RAAS) inhibitors. Sodium polystyrene sulfonate (SPS), diuretics, and hemodialysis are currently available methods for removing potassium from the body; however, these options have their limitations. Patiromer (Veltassa) and sodium zirconium cyclosilicate are 2 new therapeutic options that can potentially lead a new frontier in the management of hyperkalemia. This article will review these novel treatments.

Gender-based differences in water, sanitation and hygiene-related diarrheal disease and helminthic infections: a systematic review and meta-analysis.

BACKGROUND: Qualitative evidence suggests that inadequate water, sanitation and hygiene (WASH) may affect diarrheal and helminthic infection in women disproportionately. We systematically searched PubMed in June 2014 (updated 2016) and the WHO website, for relevant articles. METHODS: Articles dealing with the public health relevance of helminthic and diarrheal diseases, and highlighting the role of gender in WASH were included. Where possible, we carried out a meta-analysis. RESULTS: In studies of individuals 5 years or older, cholera showed lower prevalence in males (OR 0.56; 95% CI 0.34-0.94), while Schistosoma mansoni (1.38; 95% CI 1.14-1.67), Schistosoma japonicum (1.52; 95% CI 1.13-2.05), hookworm (1.43; 95% CI 1.07-1.89) and all forms of infectious diarrhea (1.21; 95% CI 1.06-1.38) showed a higher prevalence in males. When studies included all participants, S. mansoni and S. japonicum showed higher prevalence with males (OR 1.40; 95% CI 1.27-1.55 and 1.84; 95% CI 1.27-2.67, respectively). Prevalence of Trichiuris and hookworm infection showed effect modification with continent. CONCLUSIONS: Evidence of gender differences in infection may reflect differences in gender norms, suggesting that policy changes at the regional level may help ameliorate gender related disparities in helminthic and diarrheal disease prevalence.

FR171456 is a specific inhibitor of mammalian NSDHL and yeast Erg26p.

FR171456 is a natural product with cholesterol-lowering properties in animal models, but its molecular target is unknown, which hinders further drug development. Here we show that FR171456 specifically targets the sterol-4-alpha-carboxylate-3-dehydrogenase (Saccharomyces cerevisiae--Erg26p, Homo sapiens--NSDHL (NAD(P) dependent steroid dehydrogenase-like)), an essential enzyme in the ergosterol/cholesterol biosynthesis pathway. FR171456 significantly alters the levels of cholesterol pathway intermediates in human and yeast cells. Genome-wide yeast haploinsufficiency profiling experiments highlight the erg26/ERG26 strain, and multiple mutations in ERG26 confer resistance to FR171456 in growth and enzyme assays. Some of these ERG26 mutations likely alter Erg26 binding to FR171456, based on a model of Erg26. Finally, we show that FR171456 inhibits an artificial Hepatitis C viral replicon, and has broad antifungal activity, suggesting potential additional utility as an anti-infective. The discovery of the target and binding site of FR171456 within the target will aid further development of this compound.