It takes two: The relative contributions of parent versus child-led regulatory behaviours on toddler vaccination pain.

BACKGROUND: Past research has established the important role of parent soothing in early childhood pain management. However, limited research has assessed children's own emerging emotion regulation strategies to reduce their pain during vaccination. The purpose of the current study was to understand the relative contributions of child-led emotion-regulation behaviours over and above parent regulatory behaviours and pre-needle distress. METHODS: Toddler-caregiver dyads were videotaped at their 12- and/or 18-month vaccinations. Videos were coded for pain-related behavioural distress, child-led regulatory behaviours (disengagement of attention, parent-focused behaviours, and physical self-soothing), and parent regulatory/soothing behaviours (distraction, physical comfort, rocking, verbal reassurance). Pre-needle distress, followed by parent regulatory behaviours, followed by child regulatory behaviours were used as hierarchical predictors of pain regulation. Two sets of models were estimated at each age, by incorporating parent and child regulatory behaviours at 1 min and 2 min post-needle, separately. RESULTS: At both ages, child-led parent-focused behaviours predicted less regulation. At 18 months, parent soothing behaviours (e.g. distraction, verbal reassurance, rocking) played a stronger role in regulation, however; the only behaviour that increased regulation was rocking. CONCLUSIONS: Measuring both parent and child regulatory behaviours was important for fully understanding pain-related distress regulation. Toddlers' use of parent-focused regulatory behaviours (e.g. proximity seeking) suggests that they signal to their parent directly when they are struggling to regulate post-needle. The only parent behaviour that supported this regulation was rocking at 18 months, suggesting a greater need to understand the sensitivity of parent behaviours post-needle. SIGNIFICANCE: To our knowledge, this is the first study to examine both parent and child regulatory behaviours following vaccination at different stages in toddlerhood. This investigation allows a deeper understanding of the dyadic nature of early childhood vaccination, as well as the evolving role of the parent through toddlerhood. Importantly, findings suggest that toddlers do not simply wait for their parents to respond to their pain post-needle and provide clear signals to show their need of support in regulation.

Association of clinical factors and recent anticancer therapy with COVID-19 severity among patients with cancer: a report from the COVID-19 and Cancer Consortium.

BACKGROUND: Patients with cancer may be at high risk of adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed a cohort of patients with cancer and coronavirus 2019 (COVID-19) reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies. PATIENTS AND METHODS: Patients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between 17 March and 18 November 2020 were included. The primary outcome was COVID-19 severity measured on an ordinal scale (uncomplicated, hospitalized, admitted to intensive care unit, mechanically ventilated, died within 30 days). Multivariable regression models included demographics, cancer status, anticancer therapy and timing, COVID-19-directed therapies, and laboratory measurements (among hospitalized patients). RESULTS: A total of 4966 patients were included (median age 66 years, 51% female, 50% non-Hispanic white); 2872 (58%) were hospitalized and 695 (14%) died; 61% had cancer that was present, diagnosed, or treated within the year prior to COVID-19 diagnosis. Older age, male sex, obesity, cardiovascular and pulmonary comorbidities, renal disease, diabetes mellitus, non-Hispanic black race, Hispanic ethnicity, worse Eastern Cooperative Oncology Group performance status, recent cytotoxic chemotherapy, and hematologic malignancy were associated with higher COVID-19 severity. Among hospitalized patients, low or high absolute lymphocyte count; high absolute neutrophil count; low platelet count; abnormal creatinine; troponin; lactate dehydrogenase; and C-reactive protein were associated with higher COVID-19 severity. Patients diagnosed early in the COVID-19 pandemic (January-April 2020) had worse outcomes than those diagnosed later. Specific anticancer therapies (e.g. R-CHOP, platinum combined with etoposide, and DNA methyltransferase inhibitors) were associated with high 30-day all-cause mortality. CONCLUSIONS: Clinical factors (e.g. older age, hematological malignancy, recent chemotherapy) and laboratory measurements were associated with poor outcomes among patients with cancer and COVID-19. Although further studies are needed, caution may be required in utilizing particular anticancer therapies. CLINICAL TRIAL IDENTIFIER: NCT04354701.

Disaggregating the distal, proximal, and time-varying effects of parent alcoholism on children's internalizing symptoms.

We tested whether children show greater internalizing symptoms when their parents are actively abusing alcohol. In an integrative data analysis, we combined observations over ages 2 through 17 from two longitudinal studies of children of alcoholic parents and matched controls recruited from the community. Using a mixed modeling approach, we tested whether children showed elevated mother- and child-reported internalizing symptoms (a) at the same time that parents showed alcohol-related consequences (time-varying effects), (b) if parents showed greater alcohol-related consequences during the study period (proximal effects), and (c) if parents had a lifetime diagnosis of alcoholism that predated the study period (distal effects). No support for time-varying effects was found; proximal effects of mothers' alcohol-related consequences on child-reported internalizing symptoms were found and distal effects of mother and father alcoholism predicted greater internalizing symptoms among children of alcoholic parents. Implications for the time-embedded relations between parent alcoholism and children's internalizing symptoms are discussed.

Self-association properties of monomeric insulin analogs under formulation conditions.

PURPOSE: The purpose of the current study was to investigate the effects of two important excipients, zinc and m-cresol, on the self-association properties of a series of monomeric insulin analogs. In this way, the effects on formulation behavior of individual amino acid substitutions in the C-terminal region of the insulin B-chain could be compared. METHODS: The self-association of ten insulin analogs was monitored by equilibrium and velocity analytical ultracentrifugation under three different conditions: (i) in neutral buffer alone; (ii) in neutral buffer containing zinc ion; and (iii) in neutral buffer containing both zinc ion and phenolic preservative (a typical condition for insulin formulations). The self-association properties of these analogs were compared to those of human insulin and the rapid-acting insulin analog Lys(B28)Pro(B29)-human insulin. RESULTS: The analogs in the current study exhibited a wide range of association properties when examined in neutral buffer alone or in neutral buffer containing zinc ion. However, all of these analogs had association properties similar to human insulin in the presence of both zinc and m-cresol. Under these formulation conditions each analog had an apparent sedimentation coefficient of s* = 2.9-3.1 S, which corresponds to the insulin hexamer. CONCLUSIONS: Analogs with changes in the B27-B29 region of human insulin form soluble hexamers in the presence of both zinc and m-cresol, and m-cresol binding overrides the otherwise destabilizing effects of these mutations on self assembly.

Modifications in the B10 and B26-30 regions of the B chain of human insulin alter affinity for the human IGF-I receptor more than for the insulin receptor.

Inversion of the natural sequence of the B chain of human insulin (HI) from ProB28LysB29 to LysB28ProB29 generates an insulin analogue with reduced tendency to self-associate. Since this substitution increases the homology of insulin to insulin-like growth factor-I (IGF-I), we have examined the affinity of a series of insulin analogues with the general modified structure XaaB28ProB29 HI for binding to both human placental insulin and IGF-I receptors. The XaaB28ProB29 HI series is approximately equipotent to HI in binding to the insulin receptor with the exception of when Xaa = Phe, Trp, Leu, Ile, and Gly (40-60% relative to HI). Substitution with basic residues in the B28 position increased the relative affinity to the IGF-I receptor approximately 1.5-2-fold (ArgB28ProB29 > OrnB28ProB29 = LysB28ProB29). Substitution with acidic residues reduced relative affinity for the IGF-I receptor approximately 2-fold (CyaB28ProB29 = GluB28ProB29 > AspB28ProB29). Combination of AspB10 substitution in conjunction with a modification in the B28-29 position (e.g. AspB10LysB28ProB29 HI) showed an additional 2-fold selective increase in affinity for the IGF-I receptor, suggesting that these two effects are additive. Addition of Arg residues at B31-32, on the backbone of either HI or AspB10 HI, increased affinity for the IGF-I receptor 10 and 28 fold, respectively, compared to HI, confirming the significance of enhanced positive charge at the C-terminal end of the insulin B-chain in increasing selectivity for the IGF-I receptor. This relative increase in IGF-I receptor affinity correlated largely, but not completely, with enhanced growth promoting activity in human mammary epithelial cells. In the case of LysB28ProB29 HI, growth activity correlated with dissociation kinetics from the insulin receptor which were shown to be identical with those of human insulin.