Experience Using Ustekinumab in Pediatric Patients With Medically Refractory Crohn Disease.

Introduction: Ustekinumab (UST), a human monoclonal antibody against interleukin-12 and 23, is approved to treat adult patients with psoriasis or Crohn disease (CD). Outcomes data for off-label use in pediatric patients with CD are limited.

Aim: We conducted a retrospective cohort study to analyze the long-term efficacy of UST, including dose adjustments, in the treatment of pediatric patients with medically refractory CD.

Non-catalytic ubiquitin binding by A20 prevents psoriatic arthritis-like disease and inflammation.

A20 is an anti-inflammatory protein that is strongly linked to human disease. Here, we find that mice expressing three distinct targeted mutations of A20's zinc finger 7 (ZF7) ubiquitin-binding motif uniformly developed digit arthritis with features common to psoriatic arthritis, while mice expressing point mutations in A20's OTU or ZF4 motifs did not exhibit this phenotype. Arthritis in A20 mice required T cells and MyD88, was exquisitely sensitive to tumor necrosis factor and interleukin-17A, and persisted in germ-free conditions.

Experience with corrective surgery for postburn contractures in Mumbai, India.

Postburn contracture is a source of significant morbidity in India, even though its occurrence can be reduced significantly by comprehensive postburn injury care, including surgical intervention. This study investigates whether limited access to initial medical care after burn injury has been associated with increased contracture formation among lower socioeconomic class patients in Mumbai, India. During a surgical mission in Mumbai, India, patients presenting with functionally debilitating burn contractures and minimal income were surveyed for initial care received immediately after burn injury.

Comic books can educate children about burn safety in developing countries.

Burns in developing countries account for significant morbidity and many occur within the pediatric population. This study investigates whether a comic book can increase burn awareness in primary school age children, both domestically and abroad. Based on demographic data regarding pediatric burns in developing nations, a comic book was developed to educate primary school age children on key risk factors regarding burn safety, including teaching children to not touch active stoves, not to light fireworks without supervision, and to "stop, drop, and roll" after burn injury.

Systemic signals regulate ageing and rejuvenation of blood stem cell niches.

Ageing in multicellular organisms typically involves a progressive decline in cell replacement and repair processes, resulting in several physiological deficiencies, including inefficient muscle repair, reduced bone mass, and dysregulation of blood formation (haematopoiesis). Although defects in tissue-resident stem cells clearly contribute to these phenotypes, it is unclear to what extent they reflect stem cell intrinsic alterations or age-related changes in the stem cell supportive microenvironment, or niche. Here, using complementary in vivo and in vitro heterochronic models, we show that age-associated changes in stem cell supportive niche cells deregulate normal haematopoiesis by causing haematopoietic stem cell dysfunction.

The transcription factor EGR1 controls both the proliferation and localization of hematopoietic stem cells.

EGR1 is a member of the immediate early response transcription factor family and functions in cell growth, development, and stress responses in many tissues. Here we report an additional role for EGR1 in regulating homeostasis of hematopoietic stem cells (HSCs). HSCs normally express Egr1 at high levels, but dramatically downregulate its expression when induced to divide and migrate.