The contribution of respiratory viral infections to the onset of asthma and atopy is controversial. In "high risk" children (n = 455) born into asthmatic/atopic families, we determined the relationship of exposures to common respiratory viruses and concomitant respiratory symptoms, and to subsequent possible asthma and atopy at ages 1 and 2 years. Frozen nasal specimens, obtained when children were 2 weeks, 4, 8, and 12 months old, underwent reverse transcription-polymerase chain reaction (RT-PCR) testing for parainfluenza virus (PIV), respiratory syncytial virus (RSV), and picornavirus (rhinovirus/enterovirus). Odds ratios of viral RT-PCR results to respiratory symptoms ("cold," rhinitis, cough, wheezing) and to possible asthma or atopy at 1 and 2 years of age were calculated. Positive viral RT-PCR was associated with increased odds of "cold" and cough; PIV and picornavirus were associated with rhinitis, and RSV was associated with wheezing. PIV was associated with increased odds of atopy at 1 year of age in the control group; PIV and RSV were associated with possible asthma at 2 years of age. We conclude that in high-risk children, viral exposures documented by RT-PCR are associated with respiratory symptoms, and exposures to PIV and RSV during the first year of life are associated with the initial onset of possible asthma.

Although most children survive B cell acute lymphoblastic leukemia (B-ALL), they frequently experience long-term, treatment-related health problems, including osteopenia and osteonecrosis. Because some children present with fractures at ALL diagnosis, we considered the possibility that leukemic B cells contribute directly to bone pathology. To identify potential mechanisms of B-ALL–driven bone destruction, we examined the p53−/−; Rag2−/−; Prkdcscid/scid triple mutant (TM) mice and p53−/−; Prkdcscid/scid double mutant (DM) mouse models of spontaneous B-ALL. In contrast to DM animals, leukemic TM mice displayed brittle bones, and the TM leukemic cells overexpressed Rankl, encoding receptor activator of nuclear factor κB ligand. RANKL is a key regulator of osteoclast differentiation and bone loss. Transfer of TM leukemic cells into immunodeficient recipient mice caused trabecular bone loss. To determine whether human B-ALL can exert similar effects, we evaluated primary human B-ALL blasts isolated at diagnosis for RANKL expression and their impact on bone pathology after their transplantation into NOD.Prkdcscid/scidIl2rgtm1Wjl/SzJ (NSG) recipient mice. Primary B-ALL cells conferred bone destruction evident in increased multinucleated osteoclasts, trabecular bone loss, destruction of the metaphyseal growth plate, and reduction in adipocyte mass in these patient-derived xenografts (PDXs). Treating PDX mice with the RANKL antagonist recombinant osteoprotegerin–Fc (rOPG-Fc) protected the bone from B-ALL–induced destruction even under conditions of heavy tumor burden. Our data demonstrate a critical role of the RANK-RANKL axis in causing B-ALL–mediated bone pathology and provide preclinical support for RANKL-targeted therapy trials to reduce acute and long-term bone destruction in these patients.

Echinocandins are first-line agents for treating severe invasive candidiasis. Glucan synthase gene (FKS1) mutations lead to echinocandin resistance but the role of enhanced chitin expression is not well recognized in clinical isolates. We report a case of bloodstream Candida albicans infection with both Fks1 hotspot mutation and elevated cell wall chitin.

The identified predictor variables are all quantifiable at the time of initial presentation, and these may help identify severe cases of diverticular bleeding requiring urgent management.

GS, the stimulatory heterotrimeric G protein, is an essential regulator of osteogenesis and bone turnover. To determine if increasing GαS in osteoblasts alters bone responses to hyperparathyroidism, we used a transgenic mouse line overexpressing GαS in osteoblasts (GS-Tg mice). Primary osteoblasts from GS-Tg mice showed increased basal and parathyroid hormone (PTH)-stimulated cAMP and greater responses to PTH than cells from WT mice. Skeletal responses to 2-week continuous PTH administration (cPTH) in female mice resulted in trabecular bone loss in WT mice but 74% and 34% increase in trabecular bone mass in long bones and vertebrae, respectively, in GS-Tg mice. Vertebral biomechanical strength was compromised by cPTH treatment in WT mice but not in GS-Tg. Increased peritrabecular fibrosis was greatly increased by cPTH in Gs-Tg compared to WT mice and corresponded with greater increases in Wnt pathway proteins in trabecular bone. Cortical bone responded negatively to cPTH in WT and Gs-Tg mice with large increases in porosity, decreased cortical thickness and compromised biomechanical properties. These results demonstrate that hyperparathyroidism can increase trabecular bone when GS expression and cAMP stimulation in osteoblasts are increased but this is not the case in cortical bone where increased GS expression exacerbates cortical bone loss.

Background-Research study participants with diverse characteristics produce the most generalizable outcomes, but recruiting heterogeneous samples is difficult.