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The efficacy of antibody responses is inherently linked to paratope diversity, as generated through V(D)J recombination and somatic hypermutation. Despite this, it is unclear how genetic diversification mechanisms evolved alongside codon optimality and affect antibody expression. Here, we analyze germline immunoglobulin (IG) genes, natural V(D)J repertoires, serum IgG, and monoclonal antibody (mAb) expression through the lens of codon optimality. Germline variable genes (IGV s) exhibit diverse optimality that is inversely related to mutability. Hypermutation deoptimizes heavy-chain (IGH) VDJ repertoires within human tonsils, bone marrow, lymph nodes (including SARS-CoV-2-specific clones), blood (HIV-1-specific clones), mice, and zebrafish. Analyses of mutation-affected codons show that targeting to complementarity-determining regions constrains deoptimization. Germline IGHV optimality correlates with serum variable fragment (VH) usage after influenza vaccination, while synonymous deoptimization attenuated mAb yield. These findings provide unanticipated insights into an antagonistic relationship between diversification mechanisms and codon optimality. Ultimately, the need for diversity takes precedence over that for the most optimal codon usage. [Display omitted] • Mutation potential antagonizes codon optimality within germline human IGV genes • Somatic hypermutation deoptimizes IGH VDJ sequences in humans, mice, and zebrafish • Mutational targeting to CDRs helps constrain deoptimization • Serum IgG-VH frequency reflects IGHV optimality, and deoptimization blunts mAb yield McGrath et al. investigate the evolutionary relationship between V(D)J mutability, somatic hypermutation, and codon optimality within immunoglobulin repertoires in order to gain a better understanding of how diversification mechanisms might impact antibody expression efficiency. [ABSTRACT FROM AUTHOR]

Lactation results in a number of physiological adaptations which exert direct effects on maternal health, some of which may confer both short and long term advantages for breast feeding mothers. Breast feeding in the early postpartum period promotes a more rapid return of the uterus to its prepregnant state through the actions of oxytocin. Breast feeding may also lead to a more rapid return to prepregnancy weight. Among studies that had good data on duration and intensity of lactation, the majority show a significant association between lactation and weight loss. However, there is no evidence that lactation prevents obesity. Lactation also affects glucose and lipid metabolism. The long term effects of these adaptations are unknown but may have implications for preventing subsequent development of diabetes and heart disease. Lactation delays the return of ovulation and significantly reduces fertility during the period of lactational amenorrhoea. This process is linked with feeding patterns and may therefore be affected by practices such as scheduled feedings and the timing of introduction of complementary foods. While the evidence from epidemiologic studies is mixed, several large studies have shown that extended lactation is associated with reduced risk of premenopausal breast, ovarian and endometrial cancers. Although bone mineralization declines during lactation, repletion takes place after weaning. As a result, breast feeding does not appear to cause long term depletion of bone nor does it increase risk of osteoporosis. Many of the physiological effects of lactation are dependent on the stimulation of the hypothalamic-pituitary axis and milk removal and thus may vary with infant feeding practices. Well controlled studies are needed that include detailed information regarding infant feeding practices in addition to the total duration of any breast feeding. Future feeding recommendations should reflect careful consideration of how such practices affect both infant and maternal health. [ABSTRACT FROM AUTHOR]

Abstract. School injuries occurring in a municipal school system during a 2-year period were reviewed to identify epidemiologic features of school injuries, to determine data requirements for ongoing injury surveillance, and to identify potential preventive strategies. Overall, 3,009 injuries were reported (2.82/100 students per year). Elementary school students had only a slightly higher rate (2.85) than secondary school students (2.78). However, the cause, nature, school location of injury, and body area injured formed distinct patterns in these two groups. Playgrounds were responsible for the highest overall and elementary school rates, whereas sports areas and classrooms had the highest rates among secondary school students. Falls were the most frequent cause of injury in elementary schools whereas, as expected, sports injuries were the most frequent cause among secondary school students. Contusions and abrasions of the head were the most frequent type of injury for both groups, although more common among elementary school students, whereas fractures, sprains, strains, and dislocations were more frequent among secondary school students. Although the proportion of severe injuries to secondary school students was slightly higher (39 v 35%), the rate of referral of students to a hospital or physicians among secondary school students (1.21 per 100 student-hours) was almost twice the rate of elementary school students (0.65 per 100 student-hours). Problems with definition of injury severity and the need to explore the social aspects of schools as a factor in injuries emerged as important considerations for future research. [ABSTRACT FROM AUTHOR]

The rapid evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants has emphasized the need to identify antibodies with broad neutralizing capabilities to inform future monoclonal therapies and vaccination strategies. Herein, we identified S728-1157, a broadly neutralizing antibody (bnAb) targeting the receptor-binding site (RBS) that was derived from an individual previously infected with WT SARS-CoV-2 prior to the spread of variants of concern (VOCs). S728-1157 demonstrated broad cross-neutralization of all dominant variants, including D614G, Beta, Delta, Kappa, Mu, and Omicron (BA.1/BA.2/BA.2.75/BA.4/BA.5/BL.1/XBB). Furthermore, S728-1157 protected hamsters against in vivo challenges with WT, Delta, and BA.1 viruses. Structural analysis showed that this antibody targets a class 1/RBS-A epitope in the receptor binding domain via multiple hydrophobic and polar interactions with its heavy chain complementarity determining region 3 (CDR-H3), in addition to common motifs in CDR-H1/CDR-H2 of class 1/RBS-A antibodies. Importantly, this epitope was more readily accessible in the open and prefusion state, or in the hexaproline (6P)-stabilized spike constructs, as compared with diproline (2P) constructs. Overall, S728-1157 demonstrates broad therapeutic potential and may inform target-driven vaccine designs against future SARS-CoV-2 variants. [ABSTRACT FROM AUTHOR]