Effects of Altering Physiologically Relevant Cholesterol Levels and Media Types on Porin Gene Expression in Klebsiella pneumoniae and the Resulting Impact on Antibiotic Resistance

Klebsiella pneumoniae is a Gram-negative, non-motile bacterium belonging to the Enterobacteriaceae family. K. pneumoniae is a rising threat in the clinical setting, as there has been a large increase in the presence of antibiotic resistant isolates. While much research is conducted on laboratory and clinical strains of bacteria, not much is known regarding the impact that human physiology can have on bacterial gene expression, and in response, to antibiotic susceptibility. The goal of this study is to determine if physiologically relevant cholesterol levels and media types impact porin gene expression and antibiotic resistance in K. pneumoniae. To accomplish this, quantitative-PCR and minimum inhibitory concentration assays were utilized. The results of this study indicate that physiologically relevant levels of cholesterol and media types can have several significant effects on porin gene expression and on antibiotic resistance. Firstly, laboratory strain K. pneumoniae was more impacted by changes in cholesterol than clinical strain K. pneumoniae regarding changes to antibiotic susceptibility; however, expression varied largely across all cholesterol concentrations and genes. Secondly, gene expression was downregulated for all six tested genes in the physiologic media compared to the laboratory media; also, the physiologic media often had significantly lower antibiotic susceptibility than the laboratory media. Lastly, it was found that surfactant can have significant effects on both gene expression and antibiotic susceptibility analyses. The results indicate that physiological conditions can impact gene expression and antibiotic susceptibility. Hence, careful consideration should be given to experiments designed to mimic physiological conditions

Preschooler's Developmental Profiles and School-Readiness in a Low-Income Canadian City: A Cross-Sectional Survey

A joint initiative between community and public health stakeholders in a low-income Canadian city was created to describe the developmental profiles of children aged 2–5 years. A two-phase, cross-sectional design was used. Children’s development was assessed using an online screening procedure. Those at risk of delays were invited for a school-readiness face-to-face brief assessment. Descriptive and exploratory analyses were conducted. In Phase 1, 223 families were screened; 100 children were at risk of delays (45%); 13% were at risk in 3 developmental domains; 26% were at risk in the fine motor domain. Risk of delay was associated with parental concerns, accessing more healthcare professionals, and using fewer public health/community programs. Lower incomes, and not attending day care showed trends towards an increased risk of delay. In Phase 2, 49 children were assessed; 69% were at risk of school-readiness delays; 22% had potential motor delays; 37% were at risk in the social domain. This study found a higher proportion of children at risk of delay than typically reported. Creating community partnerships could help identify all children needing developmental and school-readiness support. More research is needed to ensure these community-based partnerships are integrated into health/community programs responding to children’s needs and parental concerns

Concert recording 2015-10-17

[Track 01]. Morris dance / William Kraft -- [Track 02]. Sonata for timpani. I ; [Track 03]. III / John Beck -- [Track 04]. Rhapsody in blue / George Gershwin ; arranged by Linda Maxey -- [Track 05]. Fractalia / Owen Clayton Condon -- [Track 06]. Jump in the line / De Leon ; Bell ; Oller ; Samuel ; arranged by Jennifer Duerden

Reporting on invasive lobular breast cancer in clinical trials: a systematic review

Invasive lobular breast cancer (ILC) differs from invasive breast cancer of no special type in many ways. Evidence on treatment efficacy for ILC is, however, lacking. We studied the degree of documentation and representation of ILC in phase III/IV clinical trials for novel breast cancer treatments. Trials were identified on Pubmed and clinicaltrials.gov. Inclusion/exclusion criteria were reviewed for requirements on histological subtype and tumor measurability. Documentation of ILC was assessed and ILC inclusion rate, central pathology and subgroup analyses were evaluated. Inclusion restrictions concerning tumor measurability were found in 39/93 manuscripts. Inclusion rates for ILC were documented in 13/93 manuscripts and varied between 2.0 and 26.0%. No central pathology for ILC was reported and 3/13 manuscripts had ILC sub-analyses. ILC is largely disregarded in most trials with poor representation and documentation. The current inclusion criteria using RECIST v1.1, fall short in recognizing the unique non-measurable metastatic infiltration of ILC

Latitude dictates plant diversity effects on instream decomposition

Running waters contribute substantially to global carbon fluxes through decomposition of terrestrial plant litter by aquatic microorganisms and detritivores. Diversity of this litter may influence instream decomposition globally in ways that are not yet understood. We investigated latitudinal differences in decomposition of litter mixtures of low and high functional diversity in 40 streams on 6 continents and spanning 113 degrees of latitude. Despite important variability in our dataset, we found latitudinal differences in the effect of litter functional diversity on decomposition, which we explained as evolutionary adaptations of litter-consuming detritivores to resource availability. Specifically, a balanced diet effect appears to operate at lower latitudes versus a resource concentration effect at higher latitudes. The latitudinal pattern indicates that loss of plant functional diversity will have different consequences on carbon fluxes across the globe, with greater repercussions likely at low latitudes

Preschoolers’ Developmental Profiles and School-Readiness in a Low-Income Canadian City: A Cross-Sectional Survey

A joint initiative between community and public health stakeholders in a low-income Canadian city was created to describe the developmental profiles of children aged 2–5 years. A two-phase, cross-sectional design was used. Children’s development was assessed using an online screening procedure. Those at risk of delays were invited for a school-readiness face-to-face brief assessment. Descriptive and exploratory analyses were conducted. In Phase 1, 223 families were screened; 100 children were at risk of delays (45%); 13% were at risk in ≥3 developmental domains; 26% were at risk in the fine motor domain. Risk of delay was associated with parental concerns, accessing more healthcare professionals, and using fewer public health/community programs. Lower incomes, and not attending day care showed trends towards an increased risk of delay. In Phase 2, 49 children were assessed; 69% were at risk of school-readiness delays; 22% had potential motor delays; 37% were at risk in the social domain. This study found a higher proportion of children at risk of delay than typically reported. Creating community partnerships could help identify all children needing developmental and school-readiness support. More research is needed to ensure these community-based partnerships are integrated into health/community programs responding to children’s needs and parental concerns

Phylogeny, morphology, virulence, ecology, and host range of Ordospora pajunii (Ordosporidae), a microsporidian symbiont of Daphnia spp.

The impacts of microsporidia on host individuals are frequently subtle and can be context dependent. A key example of the latter comes from a recently discovered microsporidian symbiont of Daphnia, the net impact of which was found to shift from negative to positive based on environmental context. Given this, we hypothesized low baseline virulence of the microsporidian; here, we investigated the impact of infection on hosts in controlled conditions and the absence of other stressors. We also investigated its phylogenetic position, ecology, and host range. The genetic data indicate that the symbiont is Ordospora pajunii, a newly described microsporidian parasite of Daphnia. We show that O. pajunii infection damages the gut, causing infected epithelial cells to lose microvilli and then rupture. The prevalence of this microsporidian could be high (up to 100% in the lab and 77% of adults in the field). Its overall virulence was low in most cases, but some genotypes suffered reduced survival and/or reproduction. Susceptibility and virulence were strongly host-genotype dependent. We found that North American O. pajunii were able to infect multiple Daphnia species, including the European species Daphnia longispina, as well as Ceriodaphnia spp. Given the low, often undetectable virulence of this microsporidian and potentially far-reaching consequences of infections for the host when interacting with other pathogens or food, this Daphnia-O. pajunii symbiosis emerges as a valuable system for studying the mechanisms of context-dependent shifts between mutualism and parasitism, as well as for understanding how symbionts might alter host interactions with resources.ImportanceThe net outcome of symbiosis depends on the costs and benefits to each partner. Those can be context dependent, driving the potential for an interaction to change between parasitism and mutualism. Understanding the baseline fitness impact in an interaction can help us understand those shifts; for an organism that is generally parasitic, it should be easier for it to become a mutualist if its baseline virulence is relatively low. Recently, a microsporidian was found to become beneficial to its Daphnia hosts in certain ecological contexts, but little was known about the symbiont (including its species identity). Here, we identify it as the microsporidium Ordospora pajunii. Despite the parasitic nature of microsporidia, we found O. pajunii to be, at most, mildly virulent; this helps explain why it can shift toward mutualism in certain ecological contexts and helps establish O. pajunii is a valuable model for investigating shifts along the mutualism-parasitism continuum

Researching COVID to enhance recovery (RECOVER) pediatric study protocol: Rationale, objectives and design.

IMPORTANCE: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or Long COVID) in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults. OBSERVATIONS: We describe the protocol for the Pediatric Observational Cohort Study of the NIHs REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of four cohorts that comprise RECOVER-Pediatrics: 1) a de novo RECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study (n = 10,000). The de novo cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n = 6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n = 6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n = 600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science. CONCLUSIONS AND RELEVANCE: RECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions. CLINICAL TRIALS.GOV IDENTIFIER: Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011