Sex Influences Age-Related Changes in Natural Antibodies and CD5+ B-1 Cells.

Natural Abs are primarily produced by B-1 cells and are essential for protection against Streptococcus pneumoniae The incidence and mortality rate for pneumococcal infection increases dramatically after age 65, disproportionately affecting males in both human and murine systems. To date, there is a significant gap in our understanding of the relationship among sex, aging, natural IgM efficacy, and the natural IgM repertoire. Our investigation demonstrates that the protective capacity of serum IgM against pneumococcal infection is maintained in IgM obtained from aged female mice but absent in IgM from aged male mice. To understand this difference in protective capacity, we examined serum Ig, discovering that the protective change was not associated with shifts in levels of phosphorylcholine (PC)- or pneumococcal capsular polysaccharide serotype 3-specific IgM. Interestingly, we observed that aged females have an increase in the total number of CD5+ B-1 cells, higher serum IL-5 levels, and a larger percentage of aged female CD5+ B-1 cells that express CD86 as compared with aged males. Furthermore, single-cell IgM repertoire analysis from peritoneal PC+, splenic PC+, and bone marrow CD5+ B-1 cell subsets demonstrated greater diversity with age and a higher level of germline status in female mice than previously observed in studies of aged male mice. Aged female CD5+ B-1 cells also expressed higher levels of transcripts associated with cell activity and self-renewal, such as Nanog and Hmga2 Taken together, these data indicate that females maintain a more diverse and active CD5+ B-1 cell pool and natural IgM repertoire, which has implications for sex-related susceptibility to infection and disease.

Academic Performance Following Sport-Related Concussions in Children and Adolescents: A Scoping Review.

Sport-related concussions (SRC) are an increasingly common concern in young athletes, with long-term cognitive, physiological, behavioral, and psychological adverse outcomes. An estimated 1.1 million to 1.9 million SRCs occur per year in children <18 years old in the United States. The post-concussive state has demonstrated consequences in several domains, including athletics and academics, although much more research has been conducted on the former. The objective of this scoping review was to ascertain findings from published studies on the effects of SRCs on academic performance and quality of life of young student athletes. A total of 175 articles were screened within the PubMed and CINAHL databases, along with a Google search. Fourteen papers fulfilled the inclusion criteria and were analyzed in the review. Quantitative and qualitative data were collated and demonstrated the heterogeneity with which, post-concussion academic performance outcomes were measured; only 4 of the 14 studies utilized formal academic metrics such as changes in grade point average (GPA) or examination scores. While the results overall did show statistically significant implications on academic performance decline after SRC, it is clear that there remains a paucity of research determining the consequences of SRCs on academic performance in the school environment. Further research is needed to better understand how to implement accommodations in the student's learning environment and guide return-to-learn protocols for student athletes following SRC.

Newborn screening and changing face of inborn errors of metabolism in the United States.

Newborn screening (NBS) in the United States helps each year diagnose, 1 in every 320 newborns (12,500 of the 4 million births), with a potentially severe or lethal condition prior to clinical symptoms manifestation. 10% of these are inborn errors of metabolism (IEM). Coordinated efforts of NBS program, primary care physicians, and metabolic centers can help with pre-symptomatic identification and interventions for such conditions to ameliorate or resolve associated morbidity and mortality. NBS in the United States is a successful public health program to improve short and long term health outcomes for newborns. Federal and State agencies provide the regulatory and funding framework to implement NBS programs, while professional societies provide medical guidelines to help identify and manage such conditions. However, each State independently organizes and administers its own NBS program. This article reviews the common NBS program workflow, federal regulatory framework, uniform screening panel recommendations, the testing processes and ethical considerations involved.

Group A Streptococcal M1 Protein Provides Resistance against the Antimicrobial Activity of Histones.

Histones are essential elements of chromatin structure and gene regulation in eukaryotes. An unexpected attribute of these nuclear proteins is their antimicrobial activity. A framework for histone release and function in host defense in vivo was revealed with the discovery of neutrophil extracellular traps, a specialized cell death process in which DNA-based structures containing histones are extruded to ensnare and kill bacteria. Investigating the susceptibility of various Gram-positive pathogens to histones, we found high-level resistance by one leading human pathogen, group A Streptococcus (GAS). A screen of isogenic mutants revealed that the highly surface-expressed M1 protein, a classical GAS virulence factor, was required for high-level histone resistance. Biochemical and microscopic analyses revealed that the N-terminal domain of M1 protein binds and inactivates histones before they reach their cell wall target of action. This finding illustrates a new pathogenic function for this classic GAS virulence factor, and highlights a potential innate immune evasion strategy that may be employed by other bacterial pathogens.