The role of Plasmodium V-ATPase in vacuolar physiology and antimalarial drug uptake.

To ensure their survival in the human bloodstream, malaria parasites degrade up to 80% of the host erythrocyte hemoglobin in an acidified digestive vacuole. Here, we combine conditional reverse genetics and quantitative imaging approaches to demonstrate that the human malaria pathogen Plasmodium falciparum employs a heteromultimeric V-ATPase complex to acidify the digestive vacuole matrix, which is essential for intravacuolar hemoglobin release, heme detoxification, and parasite survival. We reveal an additional function of the membrane-embedded V-ATPase subunits in regulating morphogenesis of the digestive vacuole independent of proton translocation. We further show that intravacuolar accumulation of antimalarial chemotherapeutics is surprisingly resilient to severe deacidification of the vacuole and that modulation of V-ATPase activity does not affect parasite sensitivity toward these drugs.

An Azospirillum brasilense chemoreceptor that mediates nitrate chemotaxis has conditional roles in the colonization of plant roots.

Motile plant-associated bacteria use chemotaxis and dedicated chemoreceptors to navigate gradients in their surroundings and to colonize host plant surfaces. Here, we characterize a chemoreceptor that we named Tlp2 in the soil alphaproteobacterium Azospirillum brasilense. We show that the Tlp2 ligand-binding domain is related to the 4-helix bundle family and is conserved in chemoreceptors found in the genomes of many soil- and sediment-dwelling alphaproteobacteria. The promoter of tlp2 is regulated in an NtrC- and RpoN-dependent manner and is most upregulated under conditions of nitrogen fixation or in the presence of nitrate. Using fluorescently tagged Tlp2 (Tlp2-YFP), we show that this chemoreceptor is present in low abundance in chemotaxis-signaling clusters and is prone to degradation. We also obtained evidence that the presence of ammonium rapidly disrupts Tlp2-YFP localization. Behavioral experiments using a strain lacking Tlp2 and variants of Tlp2 lacking conserved arginine residues suggest that Tlp2 mediates chemotaxis in gradients of nitrate and nitrite, with the R159 residue being essential for Tlp2 function. We also provide evidence that Tlp2 is essential for root surface colonization of some plants (teff, red clover, and cowpea) but not others (wheat, sorghum, alfalfa, and pea). These results highlight the selective role of nitrate sensing and chemotaxis in plant root surface colonization and illustrate the relative contribution of chemoreceptors to chemotaxis and root surface colonization.IMPORTANCEBacterial chemotaxis mediates host-microbe associations, including the association of beneficial bacteria with the roots of host plants. Dedicated chemoreceptors specify sensory preferences during chemotaxis. Here, we show that a chemoreceptor mediating chemotaxis to nitrate is important in the beneficial soil bacterium colonization of some but not all plant hosts tested. Nitrate is the preferred nitrogen source for plant nutrition, and plants sense and tightly control nitrate transport, resulting in varying nitrate uptake rates depending on the plant and its physiological state. Nitrate is thus a limiting nutrient in the rhizosphere. Chemotaxis and dedicated chemoreceptors for nitrate likely provide motile bacteria with a competitive advantage to access this nutrient in the rhizosphere.

Screening for Substance Use Disorders during Pregnancy: A Decision at the Intersection of Racial and Reproductive Justice.

OBJECTIVE: Improve racial equity with routine universal drug screening / Study Design: Commentary on the medicolegal and social history of the United States and the field of obstetrics and gynecology regarding drug screening policy / Results: Critical aspects to inform an equitable drug screening policy include (1) racial bias and stigma related to substance use, (2) the legislative history surrounding substance use during pregnancy, (3) the relationship between substance use and mass incarceration which disproportionately affects persons of color, (4) propensity toward punitive measures for Black mothers with substance use, including termination of parental rights, (5) the role of the medical field in fostering mistrust among our patients / Conclusion: new practices in screening for substance use during pregnancy are needed. KEY POINTS: · Increasing demand for racial justice warrants reframing the issue of urine drug screening.. · The current legal constructs continue to disproportionately impact women of color.. · Routine verbal screening can replace urine drug screening and diminish implicit biases..

Tracking 20 years of forest demographics in east Texas, USA, using national forest inventory data.

Forest resource reporting techniques primarily use the two most recent measurements for understanding forest change. Multiple remeasurements now exist within the US national forest inventory (NFI), providing an opportunity to examine long-term forest demographics. We leverage two decades of remeasurements to quantify live-dead wood demographics which can better inform estimates of resource changes in forest ecosystems. Our overall objective is to identify opportunities and gaps in tracking 20 years of forest demographics within the US NFI using east Texas as a pilot study region given its diversity of tree species, prevalence of managed conditions, frequency of disturbances, and relatively rapid change driven by a warm, humid climate. We examine growth and mortality rates, identify transitions to downed dead wood/litter and removal via harvest, and describe implications of these processes focusing on key species groups (i.e., loblolly pine, post oak, and water oak) and size classes (i.e., saplings, small and large trees). Growth and mortality rates fluctuated differently over time by species and stem sizes in response to large-scale disturbances, namely the 2011 drought in Texas. Tree-fall rates were highest in saplings and snag-fall rates trended higher in smaller trees. For removal rates, different stem sizes generally followed similar patterns within each species group. Forest demographics from the field-based US NFI are informative for identifying diffuse lagged mortality, species- and size-specific effects, and management effects. Moreover, researchers continually seek to employ ancillary data and develop new statistical methods to enhance understanding of forest resource changes from field-based inventories.

Magnetic Resonance Imaging Prognostic Findings for Visual and Mortality Outcomes in Acute Invasive Fungal Rhinosinusitis.

PURPOSE: To identify initial, preintervention magnetic resonance imaging (MRI) findings that are predictive of visual and mortality outcomes in acute invasive fungal rhinosinusitis (AIFRS). DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with histopathologically or microbiologically confirmed AIFRS cared for at a single, tertiary academic institution between January 2000 and February 2020. METHODS: A retrospective review of MRI scans and clinical records of patients with confirmed diagnosis of AIFRS was performed. For each radiologic characteristic, a modified Poisson regression with robust standard errors was used to estimate the risk ratio for blindness. A multivariate Cox proportional hazards model was used to study AIFRS-specific risk factors associated with mortality. MAIN OUTCOME MEASURE: Identification of initial, preintervention MRI findings associated with visual and mortality outcomes. RESULTS: The study comprised 78 patients (93 orbits, 63 with unilateral disease and 15 with bilateral disease) with AIFRS. The leading causes of immunosuppression were hematologic malignancy (38%) and diabetes mellitus (36%). Mucormycota constituted 56% of infections, and Ascomycota constituted 37%. The overall death rate resulting from infection was 38%. Risk factors for poor visual acuity outcomes on initial MRI included involvement of the orbital apex (relative risk [RR], 2.0; 95% confidence interval [CI], 1.1-3.8; P = 0.026) and cerebral arteries (RR, 1.8; 95% CI, 1.3-2.5; P < 0.001). Increased mortality was associated with involvement of the facial soft tissues (hazard ratio [HR], 4.9; 95% CI, 1.3-18.2; P = 0.017), nasolacrimal drainage apparatus (HR, 5.0; 95% CI, 1.5-16.1; P = 0.008), and intracranial space (HR, 3.5; 95% CI, 1.4-8.6; P = 0.006). Orbital soft tissue involvement was associated with decreased mortality (HR, 0.3; 95% CI, 0.1-0.6; P = 0.001). CONCLUSIONS: Extrasinonasal involvement in AIFRS typically signals advanced infection with the facial soft tissues most commonly affected. The initial, preintervention MRI is prognostic for a poor visual acuity outcome when orbital apex or cerebral arterial involvement, or both, are present. Facial soft tissues, nasolacrimal drainage apparatus, intracranial involvement, or a combination thereof is associated with increased mortality risk, whereas orbital soft tissue involvement is correlated with a reduced risk of mortality.

Traumatic brain injuries among veterans and the risk of incident dementia: A systematic review & meta-analysis.

BACKGROUND: Traumatic brain injuries (TBI) among military veterans are increasingly recognized as important causes of both short and long-term neuropsychological dysfunction. However, the association between TBI and the development of dementia is controversial. This systematic review and meta-analysis sought to quantify the risks of all-cause dementia including Alzheimer's diseases and related dementias (ADRD), and to explore whether the relationships are influenced by the severity and recurrence of head injuries. METHODS: Database searches of Medline, Embase, Ovid Healthstar, PubMed and PROSPERO were undertaken from inception to December 2020 and supplemented with grey literature searches without language restrictions. Observational cohort studies examining TBI and incident dementia among veterans were analysed using Dersimonian-Laird random-effects models. RESULTS: Thirteen cohort studies totalling over 7.1 million observations with veterans were included. TBI was associated with an increased risk of all-cause dementia (hazard ratio [HR] = 1.95, 95% confidence interval [CI]: 1.55-2.45), vascular dementia (HR = 2.02, 95% CI: 1.46-2.80), but not Alzheimer's disease (HR = 1.30, 95% CI: 0.88-1.91). Severe and penetrating injuries were associated with a higher risk of all-cause dementia (HR = 3.35, 95% CI: 2.47-4.55) than moderate injuries (HR = 2.82, 95% CI: 1.44-5.52) and mild injuries (HR = 1.91, 95% CI: 1.30-2.80). However, the dose-response relationship was attenuated when additional studies with sufficient data to classify trauma severity were included. CONCLUSION: TBI is a significant risk factor for incident all-cause dementia and vascular dementia. These results need to be interpreted cautiously in the presence of significant heterogeneity.

Characterization of ophthalmic presentations to emergency departments in the United States: 2010-2018.

BACKGROUND: Both traumatic and nontraumatic ocular issues often present to the emergency department. Understanding the epidemiology of ocular presentations to the emergency department not only informs current resource allocation, but also provides opportunities to evaluate the efficacy of prior healthcare access interventions. PURPOSE: To characterize emergency department utilization in the United States for ophthalmic encounters between 2010 and 2018. METHODS: Cross-sectional analysis of the National Hospital Ambulatory Medical Care Survey database, a nationally representative sample of United States emergency department visits. 4284 deidentified emergency department patient encounters with an ICD-10 ophthalmic diagnosis from 2010 to 2018 were analyzed. The main outcome measures were the composition and characteristics of ophthalmic emergency department encounters over time. MAIN FINDINGS: 4284 ophthalmic visits were identified which represented an estimated 23.1 million visits (95% CI, 20.8 million-25.5 million). 31.6% (95% CI, 29.6-33.8) of ophthalmic visits were traumatic. Conjunctivitis was the most common non-traumatic diagnosis (32.8%, 95% CI, 30.7-35.0), while superficial injury of the cornea was the most common traumatic diagnosis (13.9%, 95% CI, 12.5-15.3). A greater proportion of emergency department visits involving the sclera and cornea were made by men (58.7%, 95% CI, 53.7%-63.6%; P = 0.02), whereas more women visited for visual disturbances (57.8%, 95% CI, 51.3%-64.4%; P = 0.01). Longitudinal trends of ophthalmic visits revealed an increase in public insurance payers in 2014, which corresponds to Medicaid expansion and implementation of mandated coverage for pediatric vision care. After stratification, this increase continued to be present in nontraumatic visits, but not traumatic ones. CONCLUSIONS: Ophthalmic emergency department visits in the United States between 2010 and 2018 were typically for non-traumatic eye issues. Diagnoses varied greatly by patient demographics, such as age and gender. Understanding these variations is valuable for preparing emergency departments for ocular presentations and providing guidance for future practice.

WormBase: a modern Model Organism Information Resource.

WormBase (https://wormbase.org/) is a mature Model Organism Information Resource supporting researchers using the nematode Caenorhabditis elegans as a model system for studies across a broad range of basic biological processes. Toward this mission, WormBase efforts are arranged in three primary facets: curation, user interface and architecture. In this update, we describe progress in each of these three areas. In particular, we discuss the status of literature curation and recently added data, detail new features of the web interface and options for users wishing to conduct data mining workflows, and discuss our efforts to build a robust and scalable architecture by leveraging commercial cloud offerings. We conclude with a description of WormBase's role as a founding member of the nascent Alliance of Genome Resources.

Ensembl Genomes 2020-enabling non-vertebrate genomic research.

Ensembl Genomes (http://www.ensemblgenomes.org) is an integrating resource for genome-scale data from non-vertebrate species, complementing the resources for vertebrate genomics developed in the context of the Ensembl project (http://www.ensembl.org). Together, the two resources provide a consistent set of interfaces to genomic data across the tree of life, including reference genome sequence, gene models, transcriptional data, genetic variation and comparative analysis. Data may be accessed via our website, online tools platform and programmatic interfaces, with updates made four times per year (in synchrony with Ensembl). Here, we provide an overview of Ensembl Genomes, with a focus on recent developments. These include the continued growth, more robust and reproducible sets of orthologues and paralogues, and enriched views of gene expression and gene function in plants. Finally, we report on our continued deeper integration with the Ensembl project, which forms a key part of our future strategy for dealing with the increasing quantity of available genome-scale data across the tree of life.

Comparing methods that quantify forest disturbances in the United States' national forest inventory.

Forest disturbances play a critical role in ecosystem dynamics. However, the methods for quantifying these disturbances at broad scales may underestimate disturbances that affect individual trees. Utilizing individual tree variables may provide early disturbance detection that directly affects tree demographics and forest dynamics. The goals of this study were to (1) describe different methods for quantifying disturbances at individual tree and condition-level scales, (2) compare the differences between disturbance variables, and (3) provide a methodology for selecting an appropriate disturbance variable from national forest inventories for diverse applications depending on user needs. To achieve these goals, we used all the remeasurements available from the USDA Forest Inventory and Analysis (FIA) database since the start of the annual inventory for the lower 48 US states. Variables used included disturbance code, treatment code, agent of mortality, and damage code. Chi-square tests of independence were used to verify how the choice of the variable that represents disturbance affects its magnitude. Disturbed plots, as classified by each disturbance variable, were mapped to observe their spatial distribution. We found that the Chi-square tests were significant when using all the states and comparing each state individually, indicating that different results exist depending on which variable is used to represent disturbance. Our results will be a useful tool to help researchers measure the magnitude and scale of disturbance since the manner in which disturbances are categorized will impact forest management plans, national and international reports of forest carbon stocks, and sequestration potential under future global change scenarios.

Identification and characterization of bisbenzimide compounds that inhibit human cytomegalovirus replication.

The shortcomings of current anti-human cytomegalovirus (HCMV) drugs has stimulated a search for anti-HCMV compounds with novel targets. We screened collections of bioactive compounds and identified a range of compounds with the potential to inhibit HCMV replication. Of these compounds, we selected bisbenzimide compound RO-90-7501 for further study. We generated analogues of RO-90-7501 and found that one compound, MRT00210423, had increased anti-HCMV activity compared to RO-90-7501. Using a combination of compound analogues, microscopy and biochemical assays we found RO-90-7501 and MRT00210423 interacted with DNA. In single molecule microscopy experiments we found RO-90-7501, but not MRT00210423, was able to compact DNA, suggesting that compaction of DNA was non-obligatory for anti-HCMV effects. Using bioinformatics analysis, we found that there were many putative bisbenzimide binding sites in the HCMV DNA genome. However, using western blotting, quantitative PCR and electron microscopy, we found that at a concentration able to inhibit HCMV replication our compounds had little or no effect on production of certain HCMV proteins or DNA synthesis, but did have a notable inhibitory effect on HCMV capsid production. We reasoned that these effects may have involved binding of our compounds to the HCMV genome and/or host cell chromatin. Therefore, our data expand our understanding of compounds with anti-HCMV activity and suggest targeting of DNA with bisbenzimide compounds may be a useful anti-HCMV strategy.

The Plasmodium falciparum rhoptry bulb protein RAMA plays an essential role in rhoptry neck morphogenesis and host red blood cell invasion.

The malaria parasite Plasmodium falciparum invades, replicates within and destroys red blood cells in an asexual blood stage life cycle that is responsible for clinical disease and crucial for parasite propagation. Invasive malaria merozoites possess a characteristic apical complex of secretory organelles that are discharged in a tightly controlled and highly regulated order during merozoite egress and host cell invasion. The most prominent of these organelles, the rhoptries, are twinned, club-shaped structures with a body or bulb region that tapers to a narrow neck as it meets the apical prominence of the merozoite. Different protein populations localise to the rhoptry bulb and neck, but the function of many of these proteins and how they are spatially segregated within the rhoptries is unknown. Using conditional disruption of the gene encoding the only known glycolipid-anchored malarial rhoptry bulb protein, rhoptry-associated membrane antigen (RAMA), we demonstrate that RAMA is indispensable for blood stage parasite survival. Contrary to previous suggestions, RAMA is not required for trafficking of all rhoptry bulb proteins. Instead, RAMA-null parasites display selective mislocalisation of a subset of rhoptry bulb and neck proteins (RONs) and produce dysmorphic rhoptries that lack a distinct neck region. The mutant parasites undergo normal intracellular development and egress but display a fatal defect in invasion and do not induce echinocytosis in target red blood cells. Our results indicate that distinct pathways regulate biogenesis of the two main rhoptry sub-compartments in the malaria parasite.

Disseminated Legionella micdadei infection in a liver transplant patient presenting as pulmonary nodules and a laryngeal lesion.

We report a liver transplant patient with disseminated Legionella micdadei infection with pulmonary, laryngeal, and suspected muscle involvement. This organism, which stains weakly acid-fast, primarily affects immunocompromised patients. The diagnosis is difficult to make; in this case, the organism was identified via molecular diagnostics on laryngeal and pulmonary biopsy tissue.

Treatment of post-transplant lymphoproliferative disorder (PTLD) in a heart transplant recipient with chimeric antigen receptor T-cell therapy.

Post-transplant lymphoproliferative disorders (PTLD) are a group of lesions that can complicate solid organ or hematopoietic stem cell transplantation and are often associated with Epstein-Barr virus (EBV). The treatment of PTLD is dependent on the type of lesion and includes a wide range of therapies, but chimeric antigen receptor (CAR) T-cell therapy has not previously been reported as a treatment option for PTLD. We present a patient who developed refractory PTLD in her right retroperitoneum, right inguinal and iliac chains, and right axillary region shortly after heart transplantation and was treated with CAR T-cell therapy. She could not tolerate complete discontinuation of immunosuppression due to the risk of rejection of a life-supporting graft. The patient's PTLD responded to CAR T-cell therapy, and her heart was monitored throughout the treatment course without any signs of rejection or ventricular dysfunction. CAR T-cell therapy may be a viable treatment option in patients who develop PTLD after a solid organ transplant.

Use of family disability service by families with young children with disabilities.

AIM: To investigate which families with young children with disabilities used disability services and when they used services to inform policy on service delivery. METHOD: We used linked administrative data from different ministries in Alberta to describe families' use of disability services when their children were between the ages of 3 and 8 years old. Disability was investigated on the basis of the presence of a severe special education code for children, and level of special education code. The outcome was the use of family disability services. RESULTS: Of 31 346 children, 24 761 (79.0%) had no special education code, 3982 (12.7%) had a mild special education code, and 2603 (8.3%) had a severe special education code. Level of special education code was associated with child characteristics and service use. Children with severe special education codes generally were more likely to report service use and have poor outcomes than those with less severe codes. Of note, 26% of children with severe special education codes used family disability services. In addition, among children with severe special education codes, many years of severe coding (compared with fewer years) had the strongest association with family disability service use (prevalence ratio 5.50; 95% confidence interval 4.10-7.37). Associations with family disability service use were seen with mental health, health care, and educational achievement. Interactions between child characteristics and service use were observed. INTERPRETATION: This study provides evidence that families were more likely to use disability services when they were involved with other services, and that use interacts with various factors. The findings highlight the importance of considering service eligibility, referral, and integration.

Assessing Single Ventricle Function in the Fontan Circulation using Wave Intensity Analysis.

Single ventricle hearts palliated with the Fontan operation present complications later in life as a result of increased venous pressures and abnormal ventricle function. Wave intensity analysis uses measurements of blood velocity and pressure to represent arterial hemodynamics as summations of energy waves. This methodology could potentially be a useful tool in assessment of Fontan patients. The clinical value of wave intensity parameters was utilized to evaluate the functional performance of the single ventricle in Fontan patients. A retrospective analysis of invasive hemodynamic data was retrospectively obtained from routine cardiac catheterization of patients with Fontan circulation (n = 20) and comparison to those with biventricular circulation (n = 10) who presented to the catheterization laboratory for closure of small patent ductus arteriosus (PDAs). Wave intensity analysis and wave energy flux was calculated using aortic pressure waveforms and echocardiography aortic Doppler measurements as previously described. Significant differences were seen in the peak forward compression wave (p = 0.013), early systolic energy flux (p = 0.005) and the systolic and diastolic ratio (p = 0.006) in Fontan patients versus controls. Within the Fontan group, there was a positive correlation (0.54, p = 0.02) between the wave speed and pulmonary vascular resistance. Early systolic energy flux was a potential individual indicator of a Fontan patients heart failure classification (AUC = 0.71). Wave intensity analysis could be a useful tool in screening Fontan patients and predicting clinical outcomes and Fontan failure. Future prospective analyses of Fontan hemodynamics and WIA are needed.

A multicenter survey on post-transplant lymphoproliferative disorders in pediatric heart transplant recipients: A case for development of consensus guidelines for screening, surveillance, and treatment?

Post-transplant lymphoproliferative disorders (PTLD) are the main malignancy seen after pediatric heart transplant and are a significant cause of morbidity and mortality. Prior to the development of detailed guidelines, we sought to identify trends in screening, diagnosis, and treatment of pediatric PTLD. All Pediatric Heart Transplant Society (PHTS) institutions were surveyed. No identifiable patient information was shared. From 56 PHTS centers, 22 responses were received (39.3%). 100% agree PTLD cannot be diagnosed solely based on elevated Epstein-Barr virus (EBV) load. All respondents routinely screen for EBV by blood PCR, but frequency of screening varies. There was intermediate consensus regarding the use of computed tomography (CT) and/or positron emission tomography (PET) in surveillance management for PTLD. Most centers require a diagnostic biopsy before initiating new treatment for PTLD (14 of 18, 77.8%), but many reduce immune suppression based on elevated EBV without pathologic PTLD (16 of 22, 72.7%). Beyond immune modulation, rituximab is most commonly used (9 of 13, 69.2%). Consultation with oncology is common (17 of 17, 100%), but timing varies widely. Our survey highlights significant elements of agreement and significant practice variation among PHTS institutions regarding pediatric PTLD. Reduction of immune suppression prior to pathologic diagnosis of PTLD is a common management strategy. When this fails, rituximab is used, but is most often reserved until after confirmation of the diagnosis. Oncology subspecialists are commonly involved in these cases. Our findings highlight the need to develop improved guidelines for evaluation and treatment of pediatric PTLD.

Health care service for families with children at early risk of developmental delay: an All Our Families cohort study.

AIM: This study examined children's health care service use, mothers' workforce participation, and mothers' community engagement based on children's risk of developmental delay. METHOD: We used data from the All Our Families study, a prospective pregnancy cohort. Ages and Stages Questionnaire (ASQ) scores at year 2 indicated risk of developmental delay. To investigate the impact of risk of developmental delay when children were not diagnosed, a sensitivity analysis excluded reports of neurodevelopmental disorder (NDD) diagnosis at year 3. Outcomes were maternal reports of children's health and allied health visits (and estimated costs), and maternal workforce participation and community engagement from year 2 to 3. RESULTS: Among 1314 mother-child dyads, 209 (16%) children were classified as being at risk of developmental delay by the ASQ, and 42 (3%) had a reported diagnosis of NDD. Risk of developmental delay was related to increased use of allied health care services (incidence risk ratio 5.04 [year 3]; 95% confidence interval 2.49-10.2) and health visits (incidence risk ratio 1.33 [year 3]; 95% confidence interval 1.14-1.54). The average expected allied health costs were greater for children at risk versus not at risk of developmental delay. However, when excluding children with reported diagnoses of an NDD from this analysis, increased service use and costs in the remaining at-risk population were not observed. Community engagement and workplace participation among families did not differ on the basis of risk of developmental delay. INTERPRETATION: These results suggest increased health care service use by families of children at risk of developmental delay is driven by those receiving a diagnosis of an NDD in the subsequent year. WHAT THIS PAPER ADDS: Early developmental delay risk was related to health care service use and costs. Diagnosis of neurodevelopmental disorder drove increased health care service use and costs. Early developmental delay risk did not relate to parental workforce participation. Early developmental delay risk did not relate to community engagement participation.

SERVICIO DE ATENCIÓN MÉDICA PARA FAMILIAS CON NIÑOS EN RIESGO TEMPRANO DE RETRASO EN EL DESARROLLO: UN ESTUDIO DE COHORTE DE TODAS NUESTRAS FAMILIAS: OBJETIVO: Este estudio examinó el uso del servicio de atención médica de los niños en riesgo de retraso en el desarrollo, y a su vez la participación de las madres en el mercado laboral y su participación comunitaria basada en el riesgo de los niños de presentar retraso en el desarrollo. MÉTODO: Utilizamos datos del estudio All Our Families, una cohorte de embarazo longitudinal. Las puntuaciones del Cuestionario de edades y etapas (ASQ) a los 2 años se usaron para identificar riesgo de retraso en el desarrollo. Para investigar el impacto del riesgo de retraso del desarrollo cuando los niños no fueron diagnosticados, un análisis de sensibilidad excluyó los informes de diagnóstico de trastornos del neurodesarrollo (NDD) a los 3 años. Los resultados se recolectaron de informes maternos de salud infantil y visitas de salud a diferentes profesionales de la salud (y costos estimados), y la participación materna en el mercado laboral y la participación materna en la comunidad entre el 2 a 3 año de vida de sus hijos. RESULTADOS: Entre 1.314 díadas madre-hijo, 209 (16%) niños fueron clasificados como en riesgo de retraso en el neurodesarrollo por el ASQ, y 42 (3%) tenían un diagnóstico informado de NDD. El riesgo de retraso en el desarrollo se relacionó con un mayor uso de servicios de atención médica por diversos profesionales de la salud (incidencia cociente de riesgos 5.04 [año 3]; Intervalo de confianza del 95% 2.49-10.2) y visitas de salud (riesgo de incidencia relación 1,33 [año 3]; 95% intervalo de confianza 1.14-1.54). La proyección de los costos promedio de salud aliada esperada fueron mayores para los niños en riesgo versus no en riesgo de retraso en el desarrollo. Sin embargo, al excluir a los niños con diagnósticos informados de un NDD de este análisis, no se observaron un aumento en el uso del servicio y los costos en la población en riesgo restante. Cuando se comparó la participación en la comunidad y la participación en el mercado laboral entre las familias, los resultados no difirieron en función del riesgo de retraso en el desarrollo de los niños. INTERPRETACIÓN: Estos resultados sugieren que el mayor uso de servicios de atención médica por parte de las familias de los niños en riesgo de retraso del desarrollo son impulsados por aquellos que reciben un diagnóstico de NDD en el año siguiente.

SERVIÇOS DE SAÚDE PARA FAMÍLIAS COM CRIANÇAS EM RISCO PRECOCE PARA ATRASO NO DESENVOLVIMENTO: UM ESTUDO DE COORTE TODAS AS NOSSAS FAMÍLIAS: OBJETIVO: Este estudo examinou o uso de serviços de saúde por crianças, participação das mães na força de trabalho, e engajamento das mães na comunidade com base no risco da criança para atraso no desenvolvimento. MÉTODO: Usamos dados do estudo All Our Families, uma coorte prospectiva de gestantes. Os escores no Questionário Idades e Fases (QIF) na idade de 2 anos indicou risco de atraso no desenvolvimento. Para investigar o impacto do risco para atraso no desenvolviemnto quando crianças não tinham diagnóstico, uma análise de sensibilidade excluiu os relatos de desordem neurodesenvolvimental (DND) na idade de 3 anos. Os desfechos foram os relatos maternos sobre a saúde da criança e visitas a serviços de saúde (com custos estimados), e a participação das mães na força de trabalho e engajamento na comunidade nos anos 2 e 3. RESULTADOS: Entre 1314 díades mãe-criança, 209 (16%) crianças foram classificadas como tendo risco para atraso no desenvolvimento, e 42 (3%) tiveram diagnóstico de DND. O risco de atraso no desenvolvimento foi relacionado a um aumento no uso de serviços aliados de saúde (razão do risco de incidência 5,04 [ano 3]; intervalo de confiança a 95% 2,49-10,2) e consultas de saúde (razão do risco de incidência 1,33 [ano 3]; intervalo de confiança a 95% 1,14-1,54). A média esperada dos custos dos serviços aliados de saúde foi maior para crianças de risco versus aquelas sem risco para atraso no desenvolvimento. No entanto, quando excluídas da análise as crianças com diagnóstico reportado de DND, o maior uso dos serviços e custos no restante da população de risco não foram observados. O engajamento na comunidade e participação na força de trabalho entre famílias não diferiu com base no risco para atraso do desenvolvimento. INTERPRETAÇÃO: Os resultados sugerem que o uso aumentado de serviços de saúde por famílias com crianças com risco para atraso no desenvolvimento é causado por aqueles que receberam diagnóstico de DND no ano subsequente.

Ensembl Genomes 2018: an integrated omics infrastructure for non-vertebrate species.

Ensembl Genomes (http://www.ensemblgenomes.org) is an integrating resource for genome-scale data from non-vertebrate species, complementing the resources for vertebrate genomics developed in the Ensembl project (http://www.ensembl.org). Together, the two resources provide a consistent set of programmatic and interactive interfaces to a rich range of data including genome sequence, gene models, transcript sequence, genetic variation, and comparative analysis. This paper provides an update to the previous publications about the resource, with a focus on recent developments and expansions. These include the incorporation of almost 20 000 additional genome sequences and over 35 000 tracks of RNA-Seq data, which have been aligned to genomic sequence and made available for visualization. Other advances since 2015 include the release of the database in Resource Description Framework (RDF) format, a large increase in community-derived curation, a new high-performance protein sequence search, additional cross-references, improved annotation of non-protein-coding genes, and the launch of pre-release and archival sites. Collectively, these changes are part of a continuing response to the increasing quantity of publicly-available genome-scale data, and the consequent need to archive, integrate, annotate and disseminate these using automated, scalable methods.

Predisposing and Precipitating Factors Associated With Postoperative Delirium in Patients Undergoing Cardiac Surgery at a Veterans Affairs Medical Center: A Pilot Retrospective Analysis.

OBJECTIVE: Patients treated at Veterans Affairs (VA) medical centers are in poorer health, experience more medical and psychiatric conditions, and make greater use of medical resources than do patients in the general population. In the present pilot study, the authors examined their recent experience at a VA medical center to determine the incidence and risk factors associated with the development of postoperative delirium in VA patients after cardiac surgery and hypothesized that the risk factors for postoperative delirium after cardiac surgery are different between VA and non-VA patients. DESIGN: Retrospective cohort study. SETTING: Clement J. Zablocki Veterans Affairs Medical Center. PARTICIPANTS: The study comprised 250 consecutive patients undergoing cardiac surgery from July 2014 to March 2016. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographics, coexisting diseases, and medications were obtained from the VA electronic medical record. The European System for Cardiac Operative Evaluation II mortality risk index was calculated for each patient. The type and duration of the procedure and the duration of bypass were recorded. Intraoperative crystalloid, colloid, cell saver, and blood product volumes were compiled. Progress notes and International Classification of Diseases, Tenth Revision, Clinical Modification codes were searched for documentation of postoperative delirium. Thirty-eight patients (15.2%) developed postoperative delirium. Stepwise logistic regression analysis demonstrated that the European System for Cardiac Operative Evaluation II mortality risk index (odds ratio [OR] 1.036, 95% confidence interval [CI] [1.003-1.070]; p = 0.0344), congestive heart failure (OR 2.223 [95% CI 1.046-4.722]; p = 0.0377), pre-existing cognitive impairment (OR 5.147 [95% CI 1.994-13.28]; p = 0.0007), and the presence of a neuropsychiatric disorder (OR 2.015 [95% CI 1.004-4.043]; p = 0.0487) were predisposing factors associated with higher odds of postoperative delirium. The duration of surgery; transfusion of blood products (including packed red blood cells, fresh frozen plasma, and platelets); the durations of mechanical ventilation and conscious sedation (using either propofol or dexmedetomidine); and the length of intensive care unit stay were precipitating factors associated with higher odds of postoperative delirium. CONCLUSIONS: The results demonstrate that congestive heart failure, pre-existing cognitive impairment, and the presence of a neuropsychiatric disorder are predisposing risk factors for postoperative delirium after cardiac surgery in VA patients, whereas the duration of surgery, transfusion of blood products, durations of mechanical ventilation and conscious sedation, and length of intensive care unit stay are precipitating factors for postoperative delirium. These findings in VA patients generally are similar to those observed in the civilian population despite the differences between these cohorts.