Typical epidemiology of respiratory virus infections in a Brazilian slum.

Host population size, density, immune status, age structure, and contact rates are critical elements of virus epidemiology. Slum populations stand out from other settings and may present differences in the epidemiology of acute viral infections. We collected nasopharyngeal specimens from 282 children aged ≤5 years with acute respiratory tract infection (ARI) during 2005 to 2006 in one of the largest Brazilian slums. We conducted real-time reverse transcription-polymerase chain reaction (RT-PCR) for 16 respiratory viruses, nested RT-PCR-based typing of rhinoviruses (HRVs), and collected clinical symptoms. Viruses were common causes of respiratory disease; with ≥1 virus being detected in 65.2% of patients. We detected 15 different viruses during 1 year with a predominance of HRV (33.0%) and human respiratory syncytial virus (hRSV, 12.1%) infections, and a high rate of viral coinfections (28.3%). We observed seasonality of hRSV, HRV and human coronavirus infections, more severe symptoms in hRSV and influenza virus (FLU) infections and prolonged circulation of seven HRV clusters likely representing distinct serotypes according to genomic sequence distances. Potentially unusual findings included the absence of human metapneumovirus detections and lack of typical FLU seasonal patterns, which may be linked to the population size and density of the slum. Nonetheless, most epidemiological patterns were similar to other studies globally, suggesting surprising similarities of virus-associated ARI across highly diverse settings and a complex impact of population characteristics on respiratory virus epidemiology.

Mutagenesis Induced by Sub-Lethal Doses of Ciprofloxacin: Genotypic and Phenotypic Differences Between the Pseudomonas aeruginosa Strain PA14 and Clinical Isolates.

Bacterial resistance is a severe threat to global public health. Exposure to sub-lethal concentrations has been considered a major driver of mutagenesis leading to antibiotic resistance in clinical settings. Ciprofloxacin is broadly used to treat infections caused by Pseudomonas aeruginosa, whereas increased mutagenesis induced by sub-lethal concentrations of ciprofloxacin has been reported for the reference strain, PAO1, in vitro. In this study we report increased mutagenesis induced by sub-lethal concentrations of ciprofloxacin for another reference strain, PA14-UCBPP, and lower mutagenesis for clinical isolates when compared to the reference strain. This unexpected result may be associated with missense mutations in imuB and recX, involved in adaptive responses, and the presence of Pyocin S2, which were found in all clinical isolates but not in the reference strain genome. The genetic differences between clinical isolates of P. aeruginosa and the reference PA14-UCBPP, often used to study P. aeruginosa phenotypes in vitro, may be involved in reduced mutagenesis under sub-lethal concentrations of CIP, a scenario that should be further explored for the understanding of bacterial fitness in hospital environments. Moreover, we highlight the presence of a complete umuDC operon in a P. aeruginosa clinical isolate. Even though the presence of umuDC did not contribute to a significant increase in mutagenesis, it highlights the dynamic exchange of genetic material between bacterial species in the hospital environment.

Tropism of mesenchymal stem cell toward CD133+ stem cell of glioblastoma in vitro and promote tumor proliferation in vivo.

BACKGROUND: Previous studies have demonstrated remarkable tropism of mesenchymal stem cells (MSCs) toward malignant gliomas, making these cells a potential vehicle for delivery of therapeutic agents to disseminated glioblastoma (GBM) cells. However, the potential contribution of MSCs to tumor progression is a matter of concern. It has been suggested that CD133+ GBM stem cells secrete a variety of chemokines, including monocytes chemoattractant protein-1 (MCP-1/CCL2) and stromal cell-derived factor-1(SDF-1/CXCL12), which could act in this tropism. However, the role in the modulation of this tropism of the subpopulation of CD133+ cells, which initiate GBM and the mechanisms underlying the tropism of MSCs to CD133+ GBM cells and their effects on tumor development, remains poorly defined. METHODS/RESULTS: We found that isolated and cultured MSCs (human umbilical cord blood MSCs) express CCR2 and CXCR4, the respective receptors for MCP-1/CCL2 and SDF-1/CXCL12, and demonstrated, in vitro, that MCP-1/CCL2 and SDF-1/CXC12, secreted by CD133+ GBM cells from primary cell cultures, induce the migration of MSCs. In addition, we confirmed that after in vivo GBM tumor establishment, by stereotaxic implantation of the CD133+ GBM cells labeled with Qdots (705 nm), MSCs labeled with multimodal iron oxide nanoparticles (MION) conjugated to rhodamine-B (Rh-B) (MION-Rh), infused by caudal vein, were able to cross the blood-brain barrier of the animal and migrate to the tumor region. Evaluation GBM tumors histology showed that groups that received MSC demonstrated tumor development, glial invasiveness, and detection of a high number of cycling cells. CONCLUSIONS: Therefore, in this study, we validated the chemotactic effect of MCP-1/CCL2 and SDF-1/CXCL12 in mediating the migration of MSCs toward CD133+ GBM cells. However, we observed that, after infiltrating the tumor, MSCs promote tumor growth in vivo probably by release of exosomes. Thus, the use of these cells as a therapeutic carrier strategy to target GBM cells must be approached with caution.

Albuterol via metered-dose inhaler in children: Lower doses are effective, and higher doses are safe.

BACKGROUND: The ideal dosing of albuterol via metered-dose inhalers for acute childhood asthma is not well established. We hypothesized that greater doses of albuterol would result in less time in the hospital and lower admission rates. METHODS: This was a randomized controlled double-blind multicenter study, conducted in emergency rooms (ER). We included patients with 2-17 years old with moderate to severe acute asthma (Pediatric Respiratory Assessment Measure, PRAM, score ≥5). Dosages administered during the first hour included: 6 (up to 25 kg) or 12 puffs (>25 kg) in the control group and 9 (up to 15 kg), 12 (>15-20 kg), 15 (>20-25 kg), or 18 puffs (>25 kg) in the study group. Several efficacy (changes in PRAM score, pulse oximetry, and FEV1 , length of stay, and admission rates) and safety (albuterol plasma levels, heart rate, serum potassium, glucose and bicarbonate levels, EKG, and tremor rates) outcome measures were assessed. RESULTS: We included 119 patients with similar baseline conditions, and no significant differences were observed between groups in the length of stay (P = 0.48) or admission rate (P = 0.55). No significant differences were observed in FEV1 , PRAM score, and pulse oximetry changes after 1 hr and at discharge or admission. No significant differences were observed in safety outcomes between groups. CONCLUSIONS: Higher albuterol dosage regimens did not result in lower admission rate or shorter length of stay in the ER, but showed similar safety profile for children with moderate to severe acute asthma. Pediatr Pulmonol. 2016;51:1122-1130. © 2016 Wiley Periodicals, Inc.