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Objective To evaluate the usefulness of biomarkers to predict the evolution of patients suspected of systemic lupus erythematosus (SLE), designated as probable SLE (pSLE), into classifiable SLE according to the American College of Rheumatology (ACR) classification criteria. Methods Patients suspected of SLE were enrolled by lupus experts if they fulfilled three ACR criteria for SLE and were followed for approximately 1‐3 years to evaluate transition into ACR‐classifiable SLE. Individual cell‐bound complement activation products (CB‐CAPs), serum complement proteins (C3 and C4), and autoantibodies were measured by flow cytometry, turbidimetry, and enzyme‐linked immunosorbent assay, respectively. Blood levels of hydroxychloroquine (HCQ) were measured by mass spectrometry. A multianalyte assay panel (MAP), which includes CB‐CAPs, was also evaluated. A MAP of greater than 0.8 reflected the optimal cutoff for transition to SLE. Time to fulfillment of ACR criteria was evaluated by Kaplan‐Meier analysis and Cox proportional hazards model. Results Of the 92 patients with pSLE enrolled, 74 had one or two follow‐up visits 9‐35 months after enrollment for a total of 128 follow‐up visits. Overall, 28 patients with pSLE (30.4%) transitioned to ACR‐classifiable SLE, including 16 (57%) in the first year and 12 (43%) afterwards. A MAP score of greater than 0.8 at enrollment predicted transition to classifiable SLE during the follow‐up period (hazard ratio = 2.72; P = 0.012), whereas individual biomarkers or fulfillment of Systemic Lupus International Collaborating Clinics criteria did not. HCQ therapy was not associated with the prevention of transition to SLE. Conclusion Approximately one‐third of patients with pSLE transitioned within the study period. MAP of greater than 0.8 predicted disease evolution into classifiable SLE.

Abstract In bacteria, evolution of resistance to one antibiotic is frequently associated with increased resistance (cross‐resistance) or increased susceptibility (collateral sensitivity) to other antibiotics. Cross‐resistance and collateral sensitivity are typically evaluated at the minimum inhibitory concentration (MIC). However, these susceptibility changes are not well characterized with respect to the mutant prevention concentration (MPC), the antibiotic concentration that prevents a single‐step mutation from occurring. We measured the MIC and the MPC for Staphylococcus epidermidis and 14 single‐drug resistant strains against seven antibiotics. We found that the MIC and the MPC were positively correlated but that this correlation weakened if cross‐resistance did not evolve. If any type of resistance did evolve, the range of concentrations between the MIC and the MPC tended to shift right and widen. Similar patterns of cross‐resistance and collateral sensitivity were observed at the MIC and MPC levels, though more symmetry was observed at the MIC level. Whole‐genome sequencing revealed mutations in both known‐target and nontarget genes. Moving forward, examining both the MIC and the MPC may lead to better predictions of evolutionary trajectories in antibiotic‐resistant bacteria.

Background: This study assessed the co-occurrence of cognitive problems and difficult temperament characteristics in children aged 3 to 5 years exhibiting aggressive behavior., Methods: Thirty-one children with high ratings on the Aggressive Behavior subscale of the Achenbach Child Behavior Checklist or Teacher Report Form were recruited from a school district-based clinic. Cognitive ability and temperament were assessed with the Differential Ability Scales and the Carey Temperament Scales Behavioral Styles Questionnaire, respectively. Cluster analysis was applied to these variables., Results: Three prominent groups of children sharing cognitive and temperament characteristics emerged. The first, comprising 41.9% of the sample, demonstrated low adaptability, low persistence, high activity, negative mood, and low rhythmicity, along with borderline-deficient cognitive scores. The second (38.7%) demonstrated low adaptability, low persistence, high activity, and negative mood, along with average cognitive scores. The third (19.4%) demonstrated essentially midrange temperament characteristics and average cognitive scores. All 3 groups shared temperamental tendencies toward a higher threshold of response. Most children in the sample also had significant sleep disturbances (54.5%), other health problems (63.6%), and/or suspected developmental problems (54.5%)., Conclusions: The widespread presence of sleep, health, cognitive, temperament, and developmental problems in this sample supports the involvement of medical and developmental health experts in teams evaluating young children who present with high levels of aggressive behavior. The diverse nature of cognitive-temperament profiles in this sample also suggests a need to assess cognitive ability and temperament in young, aggressive children to provide individualized interventions.

The selectivity of protein extraction by reversed micellar solutions can be improved by the addition of affinity cosurfactants bearing ligands which bind strongly to the target protein. The interactions between cosurfactant and protein, as well as the interfacial activity of both the free cosurfactant and the protein-cosurfactant complex, were accounted for in a model of the affinity-partitioning process. The aqueous phase dissociation constant was used to describe the protein-ligand interactions. The interfacial partition coefficient for several cosurfactant families varied with tail length according to the well-established hydrophobic effect. Control studies with alkylated chymotrypsin showed that when longer hydrophobic tails are irreversibly attached to the protein, the protein partitions more strongly to the reversed micellar phase. In contrast, for reversible protein-cosurfactant binding, the model predicts a maximum in protein uptake when the cosurfactant tail length is varied; the decrease at longer tail lengths is due to the lowered aqueous phase concentration of affinity cosurfactant, resulting in the formation of fewer protein-cosurfactant complexes. This behavior was confirmed experimentally., ((c) 1993 John Wiley & Sons, Inc.)

Affinity cosurfactants, consisting of hydrophilic ligands derivatized with hydrophobic tails, increase the efficiency of selective protein recoveries using reversed micelles by extending the operating range of pH and salt concentration over which an extraction can be performed. Three different affinity cosurfactant-protein pairs have been used to demonstrate the principles of this extractive technique: (i) concanavalin A, a lectin, was extracted with the addition of octyl glucoside; (ii) natural amphiphiles, such as lecithin, were used to extract myelin basic protein, a membrane-associated protein known to recognize and bind the phosphatidylcholine headgroup; and (iii) alkyl boronic acids were used to extract chymotrypsin. The enhancement in protein transfer correlated with the binding strength of the free ligand and protein in aqueous solution. Several control studies confirmed the biospecificity of the interactions of protein and affinity cosurfactant., ((c) 1993 John Wiley & Sons, Inc.)