Video-Based Anticipatory Guidance on Early Cognitive and Language Development in the First 6 Months: A Randomized Controlled Trial.

This randomized controlled trial showed that video-based anticipatory guidance implemented at well-child visits in the first 6 months increased knowledge of early cognitive and language development (P < .001), which in turn promoted cognitive growth fostering behaviors among parents of low socioeconomic status (95% CI 0.09-0.57). TRIAL REGISTRATION: ClinicalTrials.gov: NCT02812017.

Uncialamycin-based antibody-drug conjugates: Unique enediyne ADCs exhibiting bystander killing effect.

Antibody-drug conjugates (ADCs) have emerged as valuable targeted anticancer therapeutics with at least 11 approved therapies and over 80 advancing through clinical trials. Enediyne DNA-damaging payloads represented by the flagship of this family of antitumor agents, N-acetyl calicheamicin [Formula: see text], have a proven success track record. However, they pose a significant synthetic challenge in the development and optimization of linker drugs. We have recently reported a streamlined total synthesis of uncialamycin, another representative of the enediyne class of compounds, with compelling synthetic accessibility. Here we report the synthesis and evaluation of uncialamycin ADCs featuring a variety of cleavable and noncleavable linkers. We have discovered that uncialamycin ADCs display a strong bystander killing effect and are highly selective and cytotoxic in vitro and in vivo.

Social consequences and contexts of adverse childhood experiences.

Adverse childhood experiences' (ACEs) negative consequences on health, education, and life opportunities are often explained through the neurodevelopmental changes in a person's stress reactivity and coping, which contribute to the adoption of health-damaging and antisocial behaviors. However, such focus on the biological dimension eclipses the equally important social dimension of adversity, in particular, how adversities at home can influence association with peers who exhibit and can exacerbate negative behaviors like early and binge drinking, illegal drug use, and gang involvement. More than the consequences for peer formation, this study also investigates the contexts in which ACEs are most predictive. Using a longitudinal study of US youths who were adolescents in 2007 and young adults in 2017, I find that experiencing adversity predicted involvement in peers exhibiting negative behaviors. However, the consequences of ACEs are not similar for everyone and for every outcome: (1) In disadvantaged families where ACEs were most likely, experiencing adversity influenced having peers in gangs but not the other outcomes. (2) In the most advantaged families where ACEs were least likely, having an ACE only predicted adult peers' regular drug use. (3) In families who were in the middle, experiencing adversity predicted early and binge drinking among peers. Taken together, they suggest that complex social processes and environments operate in the negative effects of ACEs, and the present research suggests a method to investigate how ACEs' impact may differ according to one's social context.

Design, Synthesis, and Biological Evaluation of Tubulysin Analogues, Linker-Drugs, and Antibody-Drug Conjugates, Insights into Structure-Activity Relationships, and Tubulysin-Tubulin Binding Derived from X-ray Crystallographic Analysis.

Molecular design, synthesis, and biological evaluation of tubulysin analogues, linker-drugs, and antibody-drug conjugates are described. Among the new discoveries reported is the identification of new potent analogues within the tubulysin family that carry a C11 alkyl ether substituent, rather than the usual ester structural motif at that position, a fact that endows the former with higher plasma stability than that of the latter. Also described herein are X-ray crystallographic analysis studies of two tubulin-tubulysin complexes formed within the α/ß interface between two tubulin heterodimers and two highly potent tubulysin analogues, one of which exhibited a different binding mode to the one previously reported for tubulysin M. The X-ray crystallographic analysis-derived new insights into the binding modes of these tubulysin analogues explain their potencies and provide inspiration for further design, synthesis, and biological investigations within this class of antitumor agents. A number of these analogues were conjugated as payloads with appropriate linkers at different sites allowing their attachment onto targeting antibodies for cancer therapies. A number of such antibody-drug conjugates were constructed and tested, both in vivo and in vitro, leading to the identification of at least one promising ADC (Herceptin-LD3), warranting further investigations.

Evaluation of the quality of care of elderly patients with chronic and breakthrough pain treated with opioids: SAND study.

OBJECTIVE: The objective of this study was to evaluate the quality of care of elderly patients with treatment for chronic pain (CP) and breakthrough pain (BTP). METHODS: A cross-sectional observational study was conducted in 20 pain units, selecting patients aged 70 years or older with baseline controlled CP in treatment with opioids and a diagnosis of BTP. Patients were classified as first episode of BTP or patient in follow-up. The patients completed the SF-12 quality of life questionnaire, Brief Pain Inventory, Lattinen Index, and Edmonton Symptoms Assessment Scale. The patient's satisfaction with the treatment was evaluated through a visual analogue scale (VAS). RESULTS: A total of 199 patients were included with 67.7% women (132). There were 28.5% (55) attending the first visit for BTP and 71.5% (138) were on follow-up visits. On the physical component of the SF-12, 95% had a score below the mean for the Spanish general population and 44% had a score below the mean on the mental component. Worse scores were observed for women in the bodily pain dimension (p = .032) and in the overall physical component (p = .045). There were 62.9% (112) patients satisfied with the treatment for BTP. In the multivariate analysis, SF-12 physical component scores (p = .017) and patient's satisfaction with BTP treatment was better in follow-up visits (p = .031). CONCLUSIONS: All clinical parameters compared between first visit for the treatment of BTP and follow-up visits were improved, so the quality of care was also considered improved. Elderly women and non-oncologic patients were observed to be the population with worse symptom control.

First intercomparison among laboratories involved in COST Action-TU1301 "NORM4Building": Determination of natural radionuclides in ceramics.

This work describes the outcomes of the COST Action-TU1301 "NORM4Building" intercomparison on the determination of natural radioactivity in ceramics. Twenty-two laboratories involved in the intercomparison are evaluated for their performance using robust statistics. The reference values of 226Ra (214Bi and 214Pb) are determined to be 122 ± 11 Bq kg-1 and 124 ± 14 Bq kg-1, respectively and in secular equilibrium in the uranium chain while the reference values of 232Th (228Ac) is determined to be 61 ± 6 Bq kg-1 and that of 40K was determined to be 955 ± 40 Bq kg-1. Although the aim of the exercise was to determine the activity concentration of 226Ra, 232Th and 40K and evaluation of the "Activity Concentration Index", laboratories were asked to report complete characterization of natural radionuclides. The results of this exercise pointed out a good performance among laboratories since the percentage of the acceptable results were above 90% for the radionuclides of interest. Based on these results, considering the systematic rejection of the results reported from a few laboratories we emphasize the need for quality control procedures.

Radiofrequency for the Treatment of Lumbar Radicular Pain: Impact on Surgical Indications.

Study Design. Quasiexperimental study. Objective. To investigate whether radiofrequency treatment can preclude the need for spinal surgery in both the short term and long term. Background. Radiofrequency is commonly used to treat lumbosacral radicular pain. Only few studies have evaluated its effects on surgical indications. Methods. We conducted a quasiexperimental study of 43 patients who had been scheduled for spinal surgery. Radiofrequency was indicated for 25 patients. The primary endpoint was the decision of the patient to reject spinal surgery 1 month and 1 year after treatment (pulsed radiofrequency of dorsal root ganglion, 76%; conventional radiofrequency of the medial branch, 12%; combined technique, 12%). The primary endpoint was the decision of the patient to reject spinal surgery 1 month and 1 year after treatment. In addition, we also evaluated adverse effects, ODI, NRS. Results. We observed after treatment with radiofrequency 80% of patients rejected spinal surgery in the short term and 76% in the long term. We conclude that radiofrequency is a useful treatment strategy that can achieve very similar outcomes to spinal surgery. Patients also reported a very high level of satisfaction (84% satisfied/very satisfied). We also found that optimization of the electrical parameters of the radiofrequency improved the outcome of this technique.

Self-similar roughening of drying wet paper.

We studied the kinetic roughening dynamics of drying wet paper. The configurations of dry paper sheets are found to be self-similar, rater than self-affine. Accordingly, the paper roughening dynamics corresponds to the new class of anomalous kinetic roughening [J. J. Ramasco, J. M. López, and M. A. Rodríguez, Phys. Rev. Lett. 84, 2199 (2000)], characterized by the equal local and global roughness exponents zeta = alpha = 1 and the dynamic exponent z = 1.0+/-0.2, whereas the spectral roughness exponent alpha(s) > 1 is determined by the long-range correlations characterized by the fractal dimension of D crumpled sheet.

Intrinsically anomalous roughness of randomly crumpled thin sheets.

We study the effect of folding ridges on the scaling properties of randomly crumpled sheets of different kinds of paper in the folded and unfolded states. We found that the mean ridge length scales with the sheet size with the scaling exponent mu determined by the competition between bending and stretching deformations in the folded sheet. This scaling determines the mass fractal dimension of randomly folded balls D{M}=2/mu. We also found that surfaces of crumpled balls, as well as unfolded sheets, both display self-affine invariance with zeta=nu{ph}, if mu < or =nu{ph} , where nu{ph}=34 is the size exponent for crumpled phantom membrane, or both exhibit an intrinsically anomalous roughness characterized by the universal local roughness exponent zeta=0.72+/-0.04 and the material dependent global roughness exponent alpha=mu, when mu>nu{ph}. The physical implications of these findings are discussed.