Pediatric Cellulitis: A Red-Hot Concern

Cellulitis and other skin and soft tissue infections are a common reason for children to seek care, both in the primary care setting and the emergency department. Cellulitis is a common skin and soft-tissue infection that is usually caused by streptococci bacteria or, less commonly, Staphylococcus aureus. Most children recover quickly from cellulitis, but a small subset will require hospitalization. Practitioners need to be skilled in the diagnosis and treatment of cellulitis, including recognition of the need for inpatient treatment. However, diagnosis of cellulitis, and exclusion of complicated or other more serious infections, can be challenging. Management of these infections has also been highly variable, resulting in some difficulty identifying the ideal treatment regimen. The goal is to use the antibiotic with the narrowest spectrum for the shortest duration necessary to provide clinical improvement. Research to identify the best treatment for pediatric cellulitis will be important moving forward

COVID-19 and hereditary spherocytosis: A recipe for hemolysis

We describe a patient infected with COVID-19 in the setting of a known chronic illness, HS, and the resulting presentation and medical complications

Gulls as Sources of Environmental Contamination by Colistin-resistant Bacteria

In 2015, the mcr-1 gene was discovered in Escherichia coli in domestic swine in China that conferred resistance to colistin, an antibiotic of last resort used in treating multi-drug resistant bacterial infections in humans. Since then, mcr-1 was found in other human and animal populations, including wild gulls. Because gulls could disseminate the mcr-1 gene, we conducted an experiment to assess whether gulls are readily colonized with mcr-1 positive E. coli, their shedding patterns, transmission among conspecifics, and environmental deposition. Shedding of mcr-1 E. coli by small gull flocks followed a lognormal curve and gulls shed one strain \u3e101 log10 CFU/g in their feces for 16.4 days, which persisted in the environment for 29.3 days. Because gulls are mobile and can shed antimicrobial-resistant bacteria for extended periods, gulls may facilitate transmission of mcr-1 positive E. coli to humans and livestock through fecal contamination of water, public areas and agricultural operations

Testing of an oral dosing technique for double-crested cormorants, \u3ci\u3ePhalacocorax auritus\u3c/i\u3e, laughing gulls, \u3ci\u3eLeucophaeus atricilla\u3c/i\u3e, homing pigeons, \u3ci\u3eColumba livia\u3c/i\u3e, and western sandpipers, \u3ci\u3eCalidris mauri\u3c/i\u3e, with artificially weather MC252 oil

Scoping studies were designed to determine if double-crested cormorants (Phalacocorax auritus), laughing gulls (Leucophaues atricilla), homing pigeons (Columba livia) and western sandpipers (Calidris mauri) that were gavaged with a mixture of artificially weathered MC252 oil and food for either a single day or 4–5 consecutive days showed signs of oil toxicity. Where volume allowed, samples were collected for hematology, plasma protein electrophoresis, clinical chemistry and electrolytes, oxidative stress and organ weigh changes. Double-crested cormorants, laughing gulls and western sandpipers all excreted oil within 30 min of dose, while pigeons regurgitated within less than one hour of dosing. There were species differences in the effectiveness of the dosing technique, with double-crested cormorants having the greatest number of responsive endpoints at the completion of the trial. Statistically significant changes in packed cell volume, white cell counts, alkaline phosphatase, alanine aminotransferase, creatine phosphokinase, gamma glutamyl transferase, uric acid, chloride, sodium, potassium, calcium, total glutathione, glutathione disulfide, reduced glutathione, spleen and liver weights were measured in double-crested cormorants. Homing pigeons had statistically significant changes in creatine phosphokinase, total glutathione, glutathione disulfide, reduced glutathione and Trolox equivalents. Laughing gulls exhibited statistically significant decreases in spleen and kidney weight, and no changes were observed in any measurement endpoints tested in western sandpipers

Multivariate discovery and replication of five novel loci associated with Immunoglobulin G <i>N</i>-glycosylation

Multivariate analysis methods can uncover the relationship between phenotypic measures characterised by modern omic techniques. Here the authors conduct a multivariate GWAS on IgG N-glycosylation phenotypes and identify 5 novel loci enriched in immune system genes

ZRANB3 is an African-specific type 2 diabetes locus associated with beta-cell mass and insulin response

Abstract: Genome analysis of diverse human populations has contributed to the identification of novel genomic loci for diseases of major clinical and public health impact. Here, we report a genome-wide analysis of type 2 diabetes (T2D) in sub-Saharan Africans, an understudied ancestral group. We analyze ~18 million autosomal SNPs in 5,231 individuals from Nigeria, Ghana and Kenya. We identify a previously-unreported genome-wide significant locus: ZRANB3 (Zinc Finger RANBP2-Type Containing 3, lead SNP p = 2.831 × 10−9). Knockdown or genomic knockout of the zebrafish ortholog results in reduction in pancreatic β-cell number which we demonstrate to be due to increased apoptosis in islets. siRNA transfection of murine Zranb3 in MIN6 β-cells results in impaired insulin secretion in response to high glucose, implicating Zranb3 in β-cell functional response to high glucose conditions. We also show transferability in our study of 32 established T2D loci. Our findings advance understanding of the genetics of T2D in non-European ancestry populations

HIV Evolution in Early Infection: Selection Pressures, Patterns of Insertion and Deletion, and the Impact of APOBEC

The pattern of viral diversification in newly infected individuals provides information about the host environment and immune responses typically experienced by the newly transmitted virus. For example, sites that tend to evolve rapidly across multiple early-infection patients could be involved in enabling escape from common early immune responses, could represent adaptation for rapid growth in a newly infected host, or could represent reversion from less fit forms of the virus that were selected for immune escape in previous hosts. Here we investigated the diversification of HIV-1 env coding sequences in 81 very early B subtype infections previously shown to have resulted from transmission or expansion of single viruses (n = 78) or two closely related viruses (n = 3). In these cases, the sequence of the infecting virus can be estimated accurately, enabling inference of both the direction of substitutions as well as distinction between insertion and deletion events. By integrating information across multiple acutely infected hosts, we find evidence of adaptive evolution of HIV-1 env and identify a subset of codon sites that diversified more rapidly than can be explained by a model of neutral evolution. Of 24 such rapidly diversifying sites, 14 were either i) clustered and embedded in CTL epitopes that were verified experimentally or predicted based on the individual's HLA or ii) in a nucleotide context indicative of APOBEC-mediated G-to-A substitutions, despite having excluded heavily hypermutated sequences prior to the analysis. In several cases, a rapidly evolving site was embedded both in an APOBEC motif and in a CTL epitope, suggesting that APOBEC may facilitate early immune escape. Ten rapidly diversifying sites could not be explained by CTL escape or APOBEC hypermutation, including the most frequently mutated site, in the fusion peptide of gp41. We also examined the distribution, extent, and sequence context of insertions and deletions, and we provide evidence that the length variation seen in hypervariable loop regions of the envelope glycoprotein is a consequence of selection and not of mutational hotspots. Our results provide a detailed view of the process of diversification of HIV-1 following transmission, highlighting the role of CTL escape and hypermutation in shaping viral evolution during the establishment of new infections