Sex-hormone-driven innate antibodies protect females and infants against EPEC infection.

Females have an overall advantage over males in resisting Gram-negative bacteremias, thus hinting at sexual dimorphism of immunity during infections. Here, through intravital microscopy, we observed a sex-biased difference in the capture of blood-borne bacteria by liver macrophages, a process that is critical for the clearance of systemic infections. Complement opsonization was indispensable for the capture of enteropathogenic Escherichia coli (EPEC) in male mice; however, a faster complement component 3-independent process involving abundant preexisting antibodies to EPEC was detected in female mice. These antibodies were elicited predominantly in female mice at puberty in response to estrogen regardless of microbiota-colonization conditions. Estrogen-driven antibodies were maternally transferrable to offspring and conferred protection during infancy. These antibodies were conserved in humans and recognized specialized oligosaccharides integrated into the bacterial lipopolysaccharide and capsule. Thus, an estrogen-driven, innate antibody-mediated immunological strategy conferred protection to females and their offspring.

Apirhabdus apintestini gen. nov., sp. nov., a member of a novel genus of the family Enterobacteriaceae, isolated from the gut of the western honey bee Apis mellifera.

A Gram-negative, motile, rod-shaped bacterial strain, CA-0114T, was isolated from the midgut of a western honey bee, Apis mellifera. The isolate exhibited ≤96.43 % 16S rRNA gene sequence identity (1540 bp) to members of the families Enterobacteriaceae and Erwiniaceae. Phylogenetic trees based on genome blast distance phylogeny and concatenated protein sequences encoded by conserved genes atpD, fusA, gyrB, infB, leuS, pyrG and rpoB separated the isolate from other genera forming a distinct lineage in the Enterobacteriaceae. In both trees, the closest relatives were Tenebrionicola larvae YMB-R21T and Tenebrionibacter intestinalis BIT-L3T, which were isolated previously from Tenebrio molitor L., a plastic-eating mealworm. Digital DNA-DNA hybridization, orthologous average nucleotide identity and average amino acid identity values between strain CA-0114T and the closest related members within the Enterobacteriaceae were ≤23.1, 75.45 and 76.04 %, respectively. The complete genome of strain CA-0114T was 4 451669 bp with a G+C content of 52.12 mol%. Notably, the apparent inability of strain CA-0114T to ferment d-glucose, inositol and l-rhamnose in the API 20E system is unique among closely related members of the Enterobacteriaceae. Based on the results obtained through genotypic and phenotypic analysis, we propose that strain CA-0114T represents a novel species and genus within the family Enterobacteriaceae, for which we propose the name Apirhabdus apintestini gen. nov., sp. nov. (type strain CA-0114T=ATCC TSD-396T=DSM 116385T).

"The Cost in the Individual": Longitudinal Burnout Prevalence Among Pediatric Emergency Physicians Through 9 Months of the COVID-19 Pandemic.

OBJECTIVES: Emergency medicine (EM) confers a high risk of burnout that may be exacerbated by the COVID-19 pandemic. We aimed to determine the longitudinal prevalence of burnout in pediatric EM (PEM) physicians/fellows working in tertiary PEM departments across Canada and its fluctuation during the pandemic. METHODS: A national mixed-methods survey using a validated 2-question proxy for burnout was distributed monthly through 9 months. The primary outcome was the trajectory in probability of burnout, which was examined as both emotional exhaustion (EE) and depersonalization (DP), EE alone, and DP alone. Secondary outcomes investigated burnout and its association with demographic variables. Quantitative data were analyzed using logistic regression for primary outcomes and subanalyses for secondary outcomes. Conventional content analysis was used to analyze qualitative data and generate themes. RESULTS: From February to October 2021, 92 of 98 respondents completed at least 1 survey, 78% completed at least 3 consecutive surveys, and 48% completed at least 6 consecutive surveys. Predicted probability of EE was bimodal with peaks in May (25%) and October (22%) 2021. Rates of DP alone or having both EE and DP were approximately 1% and stable over the study period. Mid-career physicians were at lower risk of EE (odds ratio, 0.02; 95% confidence interval, 0-0.22) compared with early-career physicians. Underlying drivers of burnout were multifaceted. CONCLUSIONS: Our study suggests that increased COVID-19 case burden was correlated with EE levels during the third and fourth waves of the pandemic. Emotional exhaustion was worsened by systemic factors, and interventions must target common themes of unsustainable workloads and overwhelming lack of control.

Metabolomics in pediatric lower respiratory tract infections and sepsis: a literature review.

Lower respiratory tract infections (LRTIs) are a leading cause of morbidity and mortality in children. The ability of healthcare providers to diagnose and prognose LRTIs in the pediatric population remains a challenge, as children can present with similar clinical features regardless of the underlying pathogen or ultimate severity. Metabolomics, the large-scale analysis of metabolites and metabolic pathways offers new tools and insights that may aid in diagnosing and predicting the outcomes of LRTIs in children. This review highlights the latest literature on the clinical utility of metabolomics in providing care for children with bronchiolitis, pneumonia, COVID-19, and sepsis. IMPACT: This article summarizes current metabolomics approaches to diagnosing and predicting the course of pediatric lower respiratory infections. This article highlights the limitations to current metabolomics research and highlights future directions for the field.

A kin-selection model of fairness in heterogeneous populations.

Humans and other primates exhibit pro-social preferences for fairness. These preferences are thought to be reinforced by strong reciprocity, a policy that rewards fair actors and punishes unfair ones. Theories of fairness based on strong reciprocity have been criticized for overlooking the importance of individual differences in socially heterogeneous populations. Here, we explore the evolution of fairness in a heterogeneous population. We analyse the Ultimatum Game in cases where players' roles in the game are determined by their status. Importantly, our model allows for non-random pairing of players, and so we also explore the role played by kin selection in shaping fairness. Our kin-selection model shows that, when individuals condition their behaviour on their role in the game, fairness can be understood as either altruistic or spiteful. Altruistic fairness directs resources from less valuable members of a genetic lineage to more valuable members of the same lineage, whereas spiteful fairness keeps resources away from the competitors of the actor's high-value relatives. When individuals express fairness unconditionally it can be understood as altruistic or selfish. When it is altruistic, unconditional fairness again serves to direct resources to high-value members of genetic lineages. When it is selfish, unconditional fairness simply improves an individual's own standing. Overall, we expand kin-selection based explanations for fairness to include motivations other than spite. We show, therefore, that one need not invoke strong reciprocity to explain the advantage of fairness in heterogeneous populations.

Probiotics and in-hive fermentation as a source of beneficial microbes to support the gut microbial health of honey bees.

Managed populations of honey bees (Apis mellifera Linnaeus; Hymenoptera: Apidae) are regularly exposed to infectious diseases. Good hive management including the occasional application of antibiotics can help mitigate infectious outbreaks, but new beekeeping tools and techniques that bolster immunity and help control disease transmission are welcome. In this review, we focus on the applications of beneficial microbes for disease management as well as to support hive health and sustainability within the apicultural industry. We draw attention to the latest advances in probiotic approaches as well as the integration of fermented foods (such as water kefir) with disease-fighting properties that might ultimately be delivered to hives as an alternative or partial antidote to antibiotics. There is substantial evidence from in vitro laboratory studies that suggest beneficial microbes could be an effective method for improving disease resistance in honey bees. However, colony level evidence is lacking and there is urgent need for further validation via controlled field trials experimentally designed to test defined microbial compositions against specific diseases of interest.

Ecological interchangeability: supporting team adaptive expertise in moments of disruption.

While undesirable, unexpected disruptions offer unique opportunities to enact adaptive expertise. For adaptive expertise to flourish, individuals and teams must embrace both efficiency and adaptation. While some industries do it readily, others continue to struggle with the tension between efficiency and adaptation, particularly when otherwise stable situations are unexpectedly disrupted. For instance, in healthcare settings, the efficiency mandate for strict compliance with scopes of practice can deter teams from using the adaptive strategy of making their members interchangeable. Yet, interchangeability has been hinted as a key capacity of today' teams that are required to navigate fluid team structures. Because interchangeability - as an adaptive strategy - can generate antagonistic reactions, it has not been well studied in fluid teams. Thus, in this exploratory qualitative study we sought to gain insights into how interchangeability manifests when fluid teams from five different contexts (healthcare, emergency services, orchestras, military, and business) deal with disruptive events. According to our participants, successful interchangeability was possible when people knew how to work within one's role while being aware of their teammates' roles. However, interchangeability included more than just role switching. Interchangeability took various forms and was most successful when teams capitalized on the procedural, emotional, and social dimensions of their work. To reflect this added complexity, we refer to interchangeability in fluid teams as Ecological Interchangeability. We suggest that ecological interchangeability may become a desired feature in the training of adaptive expertise in teams, if its underlying properties and enabling mechanisms are more fully understood.

Willingness to Vaccinate Children against Influenza after the Coronavirus Disease 2019 Pandemic.

OBJECTIVES: To determine factors associated with parents who plan to vaccinate their children against influenza next year, especially those who did not vaccinate against influenza last year using a global survey. STUDY DESIGN: A survey of caregivers accompanying their children aged 1-19 years old in 17 pediatric emergency departments in 6 countries at the peak of the coronavirus disease 2019 (COVID-19) pandemic. Anonymous online survey included caregiver and child demographic information, vaccination history and future intentions, and concern about the child and caregiver having COVID-19 at the time of emergency department visit. RESULTS: Of 2422 surveys, 1314 (54.2%) caregivers stated they plan to vaccinate their child against influenza next year, an increase of 15.8% from the previous year. Of 1459 caregivers who did not vaccinate their children last year, 418 (28.6%) plan to do so next year. Factors predicting willingness to change and vaccinate included child's up-to-date vaccination status (aOR 2.03, 95% CI 1.29-3.32, P = .003); caregivers' influenza vaccine history (aOR 3.26, 95% CI 2.41-4.40, P < .010), and level of concern their child had COVID-19 (aOR 1.09, 95% CI 1.01-1.17, P = .022). CONCLUSIONS: Changes in risk perception due to COVID-19, and previous vaccination, may serve to influence decision-making among caregivers regarding influenza vaccination in the coming season. To promote influenza vaccination among children, public health programs can leverage this information.

No obvious transcriptome-wide signature of indirect selection in termites.

The evolution of sterile helper castes in social insects implies selection on genes that underlie variation in this nonreproductive phenotype. These focal genes confer no direct fitness and are presumed to evolve through indirect fitness effects on the helper's reproducing relatives. This separation of a gene's phenotypic effect on one caste and its fitness effect on another suggests that genes for this and other forms of reproductive altruism are buffered from selection and will thus evolve closer to the neutral rate than genes directly selected for selfish reproduction. We test this hypothesis by comparing the strength of selection at loci associated in their expression with reproductive versus sterile castes in termites. Specifically, we gather caste-biased gene expression data from four termite transcriptomes and measure the global dN/dS ratio across gene sets and phylogenetic lineages. We find that the majority of examined orthologous gene groups show patterns of nucleotide substitution that are consistent with strong purifying selection and display little evidence for distinct signatures of direct versus indirect selection in reproductive and sterile castes. For one particular species (Reticulitermes flavipes), the strength of purifying selection is relaxed in a reproductive nymph-biased gene set, which opposes the nearly neutral idea. In other species, the synonymous rate (dS) alone was often found to be the highest in the sterile worker caste, suggesting a more subtle signature of indirect selection or an altogether different relationship between caste-biased expression and rates of molecular evolution.

Magnetic Resonance Imaging Provides Useful Diagnostic Information Following Equivocal Ultrasound in Children With Suspected Appendicitis [Formula: see text].

PURPOSE: In Canada, ultrasonography is the primary imaging modality for children with suspected appendicitis, yet equivocal studies are common. Magnetic resonance imaging provides promise as an adjunct imaging strategy. The primary objective of this study was to determine the proportion of children with suspected appendicitis and equivocal ultrasound where magnetic resonance imaging determined a diagnosis. METHODS: A prospective consecutive cohort of children aged 5-17 years presenting to a tertiary pediatric Emergency Department with suspected appendicitis were enrolled. Participants underwent diagnostic and management strategies according to our local suspected appendicitis pathway, followed by magnetic resonance (Siemens Avanto 1.5 Tesla) imaging. Sub-specialty pediatric radiologists reported all images. RESULTS: Magnetic resonance imaging was performed in 101 children with suspected appendicitis. The mean age was 11.9 (SD 3.4) years and median Pediatric Appendicitis Score was 6 [IQR 4,8]. Ultrasonography was completed in 98/101 (97.0%). Of 53/98 (54.1%) with equivocal ultrasound, magnetic resonance imaging provided further diagnostic information in 41 (77.4%; 10 positive, 31 negative; 12 remained equivocal). Secondary findings of appendicitis on magnetic resonance imaging in children with equivocal ultrasound included abdominal free fluid (24, 45.3%), peri-appendiceal fluid (12, 22.6%), intraluminal appendiceal fluid (9, 17.0%), fat stranding (8, 15.1%), appendicolith (2, 3.8%), and peri-appendiceal abscess (1, 1.9%). The observed agreement between magnetic resonance imaging results and final diagnosis was 94.9% (kappa = 0.89).

Hyoscine butylbromide versus acetaminophen for nonspecific colicky abdominal pain in children: a randomized controlled trial.

BACKGROUND: Less than two-thirds of children with abdominal pain in the emergency department receive analgesia. We sought to determine whether hyoscine butylbromide was superior to acetaminophen for children with nonspecific colicky abdominal pain. METHODS: We randomly allocated children aged 8-17 years with nonspecific colicky abdominal pain who presented to the pediatric emergency department of London Health Sciences Centre, London, Ontario to receive hyoscine butylbromide, 10 mg given orally, or acetaminophen, 15 mg/kg given orally (maximum 975 mg). We considered the minimal clinically important difference for the primary outcome (self-reported pain at 80 min) to be 13 mm on a 100 mm visual analogue scale. Secondary outcomes included administration of rescue analgesia, adverse effects and pain score less than 30 mm at 80 minutes. RESULTS: A total of 236 participants (120 in the hyoscine butylbromide group and 116 in the acetaminophen group) were included in the trial. The mean visual analogue scale scores at 80 minutes were 29 mm (standard deviation [SD] 26 mm) and 30 mm (SD 29 mm) with hyoscine butylbromide and acetaminophen, respectively (adjusted difference 1, 95% confidence interval -7 to 7). Rescue analgesia was administered to 4 participants (3.3%) in the hyoscine butylbromide group and 1 participant (0.9%) in the acetaminophen groups (p = 0.2). We found no significant differences in rates of adverse effects between hyoscine butylbromide (32/116 [27.6%]) and acetaminophen (28/115 [24.3]) (p = 0.5); no serious adverse effects were observed. The proportion with a pain score less than 30 mm at 80 minutes was 66 (55.0%) with hyoscine butylbromide and 63 (54.3%) with acetaminophen (p = 0.9). INTERPRETATION: Hyoscine butylbromide was not superior to acetaminophen in this setting. Both agents were associated with clinically important pain reduction, and either can be considered for children presenting to the emergency department with nonspecific colicky abdominal pain. Trial registration: Clinicaltrials.gov, no. NCT02582307.

Effect of Nebulized Magnesium vs Placebo Added to Albuterol on Hospitalization Among Children With Refractory Acute Asthma Treated in the Emergency Department: A Randomized Clinical Trial.

Importance: While intravenous magnesium decreases hospitalizations in refractory pediatric acute asthma, it is variably used because of invasiveness and safety concerns. The benefit of nebulized magnesium to prevent hospitalization is unknown. Objective: To evaluate the effectiveness of nebulized magnesium in children with acute asthma remaining in moderate or severe respiratory distress after initial therapy. Design, Setting, and Participants: A randomized double-blind parallel-group clinical trial from September 26, 2011, to November 19, 2019, in 7 tertiary-care pediatric emergency departments in Canada. The participants were otherwise healthy children aged 2 to 17 years with moderate to severe asthma defined by a Pediatric Respiratory Assessment Measure (PRAM) score of 5 or greater (on a 12-point scale) after a 1-hour treatment with an oral corticosteroid and 3 inhaled albuterol and ipratropium treatments. Of 5846 screened patients, 4332 were excluded for criteria, 273 declined participation, 423 otherwise excluded, 818 randomized, and 816 analyzed. Interventions: Participants were randomized to 3 nebulized albuterol treatments with either magnesium sulfate (n = 410) or 5.5% saline placebo (n = 408). Main Outcomes and Measures: The primary outcome was hospitalization for asthma within 24 hours. Secondary outcomes included PRAM score; respiratory rate; oxygen saturation at 60, 120, 180, and 240 minutes; blood pressure at 20, 40, 60, 120, 180, and 240 minutes; and albuterol treatments within 240 minutes. Results: Among 818 randomized patients (median age, 5 years; 63% males), 816 completed the trial (409 received magnesium; 407, placebo). A total of 178 of the 409 children who received magnesium (43.5%) were hospitalized vs 194 of the 407 who received placebo (47.7%) (difference, -4.2%; absolute risk difference 95% [exact] CI, -11% to 2.8%]; P = .26). There were no significant between-group differences in changes from baseline to 240 minutes in PRAM score (difference of changes, 0.14 points [95% CI, -0.23 to 0.50]; P = .46); respiratory rate (0.17 breaths/min [95% CI, -1.32 to 1.67]; P = .82); oxygen saturation (-0.04% [95% CI, -0.53% to 0.46%]; P = .88); systolic blood pressure (0.78 mm Hg [95% CI, -1.48 to 3.03]; P = .50); or mean number of additional albuterol treatments (magnesium: 1.49, placebo: 1.59; risk ratio, 0.94 [95% CI, 0.79 to 1.11]; P = .47). Nausea/vomiting or sore throat/nose occurred in 17 of the 409 children who received magnesium (4%) and 5 of the 407 who received placebo (1%). Conclusions and Relevance: Among children with refractory acute asthma in the emergency department, nebulized magnesium with albuterol, compared with placebo with albuterol, did not significantly decrease the hospitalization rate for asthma within 24 hours. The findings do not support use of nebulized magnesium with albuterol among children with refractory acute asthma. Trial Registration: ClinicalTrials.gov Identifier: NCT01429415.

Cytokines and Chemokines in Pediatric Appendicitis: A Multiplex Analysis of Inflammatory Protein Mediators.

OBJECTIVES: We aimed to demonstrate the potential of precision medicine to describe the inflammatory landscape present in children with suspected appendicitis. Our primary objective was to determine levels of seven inflammatory protein mediators previously associated with intra-abdominal inflammation (C-reactive protein-CRP, procalcitonin-PCT, interleukin-6 (IL), IL-8, IL-10, monocyte chemoattractant protein-1-MCP-1, and serum amyloid A-SAA) in a cohort of children with suspected appendicitis. Subsequently, using a multiplex proteomics approach, we examined an expansive array of novel candidate cytokine and chemokines within this population. METHODS: We performed a secondary analysis of targeted proteomics data from Alberta Sepsis Network studies. Plasma mediator levels, analyzed by Luminex multiplex assays, were evaluated in children aged 5-17 years with nonappendicitis abdominal pain (NAAP), acute appendicitis (AA), and nonappendicitis sepsis (NAS). We used multivariate regression analysis to evaluate the seven target proteins, followed by decision tree and heat mapping analyses for all proteins evaluated. RESULTS: 185 children were included: 83 with NAAP, 79 AA, and 23 NAS. Plasma levels of IL-6, CRP, MCP-1, PCT, and SAA were significantly different in children with AA compared to those with NAAP (p < 0.001). Expansive proteomic analysis demonstrated 6 patterns in inflammatory mediator profiles based on severity of illness. A decision tree incorporating the proteins CRP, ferritin, SAA, regulated on activation normal T-cell expressed and secreted (RANTES), monokine induced by gamma interferon (MIG), and PCT demonstrated excellent specificity (0.920) and negative predictive value (0.882) for children with appendicitis. CONCLUSIONS: Multiplex proteomic analyses described the inflammatory landscape of children presenting to the ED with suspected appendicitis. We have demonstrated the feasibility of this approach to identify potential novel candidate cytokines/chemokine patterns associated with a specific illness (appendicitis) amongst those with a broad ED presentation (abdominal pain). This approach can be modelled for future research initiatives in pediatric emergency medicine.

Soldier-biased gene expression in a subterranean termite implies functional specialization of the defensive caste.

In a termite colony, reproduction is typically monopolized by a small number of sexuals that are supported by reproductively altruistic soldiers and workers. We expect caste differentiation to be associated with clear-cut differences in gene expression, and for these differences to reflect caste function and development. Here, we use RNA-Sequencing to compare the gene expression profiles of sexual nymphs and two non-reproductive helper castes (i.e., workers and soldiers) of the Eastern subterranean termite Reticulitermes flavipes. We found that of n = 93 genes that are strictly expressed as a function of caste, a majority (78%) show a soldier-specific pattern. This conspicuous soldier-bias in genome-wide expression suggests that this defensively specialized caste is functionally well-differentiated from both the reproductive and the other non-reproductive caste of this species, despite a shared developmental program with workers. Gene ontology analysis supports the notion of functional specialization by soldiers, as soldier-biased gene sets are enriched for novel biological processes. Whether this pattern reflects ancient or more recent bouts of selection for caste novelty at the gene-regulatory level is not known, but because soldiers are sterile and thus have no direct fitness, any selection for novelty must have been mediated indirectly, through reproducing relatives.

Meeting report: FDA public meeting on patient-focused drug development and medication adherence in solid organ transplant patients.

The Food and Drug Administration (FDA) held a public meeting and scientific workshop in September 2016 to obtain perspectives from solid organ transplant recipients, family caregivers, and other patient representatives. The morning sessions focused on the impact of organ transplantation on patients' daily lives and the spectrum of activities undertaken to maintain grafts. Participants described the physical, emotional, and social impacts of their transplant on daily life. They also discussed their posttransplant treatment regimens, including the most burdensome side effects and their hopes for future treatment. The afternoon scientific session consisted of presentations on prevalence and risk factors for medication nonadherence after transplantation in adults and children, and interventions to manage it. As new modalities of Immunosuppressive Drug Therapy are being developed, the patient perceptions and input must play larger roles if organ transplantation is to be truly successful.

From gene list to gene network: Recognizing functional connections that regulate behavioral traits.

The study of social breeding systems is often gene focused, and the field of insect sociobiology has been successful at assimilating tools and techniques from molecular biology. One common output from sociogenomic studies is a gene list. Gene lists are readily generated from microarray, RNA sequencing, or other molecular screens that typically aim to prioritize genes based on the differences in their expression. Gene lists, however, are often unsatisfying because the information they provide is simply tabular and does not explain how genes interact with each other, or how genetic interactions change in real time under social or environmental circumstances. Here, we promote a view that is relatively common to molecular systems biology, where gene lists are converted into gene networks that better describe the functional connections that regulate behavioral traits. We present a narrative related to honeybee worker sterility to show how network analysis can be used to reprioritize candidate genes based on connectivity rather than their freestanding expression values. Networks can also reveal multigene modules, motifs, clusters or other system-wide properties that might not be apparent from an ab initio list. We argue that because network analyses are not restricted to "genes" as nodes, their implementation can potentially connect multiple levels of biological organization into a single, progressively complex study system.

The association between oxidative stress-induced galectins and differentiation of human promyelocytic HL-60 cells.

Galectins are multifunctional ß-galactoside-binding proteins that are involved in the regulation of cellular stress responses and differentiation. The relationship between these processes is unclear and we report here that galectins display oxidative-stress specific expression patterns in neutrophil-like differentiated HL-60 cells. Three galectins (-1, -3, and -10) are upregulated in response to either menadione or DMSO exposure whereas galectins -9 and -12 exhibited a stimulus-dependent downregulation. Changes in galectin expression are oxidant dependent based on the observations that 1) oxidative stress biomarkers HMOX1 (heme oxygenase-1) and NCF1 (neutrophil cytosolic factor 1, which is also a biomarker of neutrophil differentiation) are elevated in both cases, and 2) the antioxidant N-acetyl-L-cysteine restores basal expression of galectin-3 following oxidant exposure. In addition, our results suggest that the regulation of oxidative stress-sensitive galectins involves DNA hypomethylation mechanisms. Expression of galectin-3 and galectin-12 exhibits an opposite relationship to the expression of HMOX1/NCF1, suggesting a stimulatory and inhibitory role of these galectins in neutrophil-like differentiation of HL-60 cells. We also show that the inhibition of galectins reduces the growth rate of HL-60 cells, and facilitates their neutrophil-like differentiation. Collectively, our findings indicate that the process of cellular differentiation implicates, in part, oxidative stress-sensitive galectins, which further highlights a biological significance of galectin network remodeling in cells.

Two Novel DNAs That Enhance Symptoms and Overcome CMD2 Resistance to Cassava Mosaic Disease.

UNLABELLED: Cassava mosaic begomoviruses (CMBs) cause cassava mosaic disease (CMD) across Africa and the Indian subcontinent. Like all members of the geminivirus family, CMBs have small, circular single-stranded DNA genomes. We report here the discovery of two novel DNA sequences, designated SEGS-1 and SEGS-2 (forsequencesenhancinggeminivirussymptoms), that enhance symptoms and break resistance to CMD. The SEGS are characterized by GC-rich regions and the absence of long open reading frames. Both SEGS enhanced CMD symptoms in cassava (Manihot esculentaCrantz) when coinoculated withAfrican cassava mosaic virus(ACMV),East African cassava mosaic Cameroon virus(EACMCV), orEast African cassava mosaic virus-Uganda(EACMV-UG). SEGS-1 also overcame resistance of a cassava landrace carrying the CMD2 resistance locus when coinoculated with EACMV-UG. Episomal forms of both SEGS were detected in CMB-infected cassava but not in healthy cassava. SEGS-2 episomes were also found in virions and whiteflies. SEGS-1 has no homology to geminiviruses or their associated satellites, but the cassava genome contains a sequence that is 99% identical to full-length SEGS-1. The cassava genome also includes three sequences with 84 to 89% identity to SEGS-2 that together encompass all of SEGS-2 except for a 52-bp region, which includes the episomal junction and a 26-bp sequence related to alphasatellite replication origins. These results suggest that SEGS-1 is derived from the cassava genome and facilitates CMB infection as an integrated copy and/or an episome, while SEGS-2 was originally from the cassava genome but now is encapsidated into virions and transmitted as an episome by whiteflies. IMPORTANCE: Cassava is a major crop in the developing world, with its production in Africa being second only to maize. CMD is one of the most important diseases of cassava and a serious constraint to production across Africa. CMD2 is a major CMD resistance locus that has been deployed in many cassava cultivars through large-scale breeding programs. In recent years, severe, atypical CMD symptoms have been observed occasionally on resistant cultivars, some of which carry the CMD2 locus, in African fields. In this report, we identified and characterized two DNA sequences, SEGS-1 and SEGS-2, which produce similar symptoms when coinoculated with cassava mosaic begomoviruses onto a susceptible cultivar or a CMD2-resistant landrace. The ability of SEGS-1 to overcome CMD2 resistance and the transmission of SEGS-2 by whiteflies has major implications for the long-term durability of CMD2 resistance and underscore the need for alternative sources of resistance in cassava.

Sexual response of male Drosophila to honey bee queen mandibular pheromone: implications for genetic studies of social insects.

Honey bees secrete a queen mandibular pheromone that renders workers reproductively altruistic and drones sexually attentive. This sex-specific function of QMP may have evolved from a sexually dimorphic signaling mechanism derived from pre-social ancestors. If so, there is potential for pre-social insects to respond to QMP, and in a manner that is comparable to its normal effect on workers and drones. Remarkably, QMP applied to female Drosophila does induce worker-like qualities [Camiletti et al. (Entomol Exp Appl 147:262, 2013)], and we here extend this comparison to examine the effects of bee pheromone on male fruit flies. We find that male Drosophila melanogaster consistently orient towards a source of queen pheromone in a T-maze, suggesting a recruitment response comparable to the pheromone's normal effect on drones. Moreover, exposure to QMP renders male flies more sexually attentive; they display intensified pre-copulatory behavior towards conspecific females. We can inhibit this sexual effect through a loss-of-olfactory-function mutation, which suggests that the pheromone-responsive behavioral mechanism is olfactory-driven. These pheromone-induced changes to male Drosophila behavior suggest that aspects of sexual signaling are conserved between these two distantly related taxa. Our results highlight a role for Drosophila as a genetically tractable pre-social model for studies of social insect biology.

The Use of Routine Blood Cultures in Pediatric Appendicitis.

OBJECTIVES: To determine the proportion of true-positive blood culture results in children presenting to the ED with suspected appendicitis. To describe the current practice of obtaining blood cultures in children with suspected appendicitis. METHODS: We performed a 2-year retrospective health record review of all children aged 2 through 17 years investigated for suspected appendicitis at a tertiary Pediatric Emergency Department. Subjects were identified by searching (a) institutional records for ICD-10-CA coding, (b) diagnostic imaging records of ultrasounds for appendicitis, and (c) surgical database records for nonincidental appendectomies. Abstracted demographic and clinical data were matched to regional laboratory services data to describe the performance and result of blood cultures. RESULTS: Overall, 1315 children investigated for appendicitis were reviewed. Seven hundred fifty (57.0%) were girls, the average age was 11.7 years (SD, 4.0). Blood cultures were obtained in 288 (21.9%) of 1315 patients. Of the 11 (3.8%) cultures that were positive, only 1 (0.35%) was a true positive. Young age, high triage acuity, and presence of fever were associated with the acquisition of cultures (P < 0.001 for all). The proportion of children undergoing appendectomy and the negative appendectomy rate was similar between those with and without blood culture (P = 0.10 and P = 0.96, respectively). CONCLUSIONS: True-positive blood cultures are very rare in children presenting to the ED with suspected appendicitis. Given the potential for false-positive cultures and the social/economic implications of initial testing/retesting of false positives, the use of routine blood cultures for children with suspected appendicitis is not supported.