Risk Factors for Poor Outcome or Death in Young Children With Respiratory Syncytial Virus-Associated Acute Lower Respiratory Tract Infection: A Systematic Review and Meta-Analysis.

BACKGROUND: Respiratory syncytial virus (RSV)-associated acute lower respiratory tract infection (RSV-ALRTI) constitutes a substantial disease burden in young children. We aimed to identify all studies investigating the risk factors for RSV-ALRTI poor outcome or death in young children. METHODS: We carried out a systematic literature review across 7 databases with data from studies published from January 1995 to December 2019. We defined poor outcome as need for prolonged hospital stay, oxygen supplementation, mechanical ventilation, or intensive care unit admission. The quality of all eligible studies was assessed according to modified Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria. We conducted meta-analyses to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for individual risk factors. RESULTS: We identified 27 eligible studies, which investigated 20 risk factors for RSV-ALRTI poor outcome and/or death in children <5 years old, compared with children with RSV-ALRTI who did not have poor outcome or who did not die. Among the risk factors, 6 were significantly associated with RSV-ALRTI poor outcome: any comorbid condition (OR, 2.69; 95% CI, 1.89-3.83), congenital heart disease (3.40; 2.14-5.40), prematurity with gestational age (GA) <37 weeks (1.75 (1.31-2.36), prematurity with GA ≤32 weeks (2.68; 1.43-5.04), age <3 months (4.91; 1.64-14.71), and age <6 months (2.02; 1.73-2.35). The meta-estimate ORs for all risk factors other than age <3 months were based on studies using multivariable analysis. For death, only prematurity with GA <37 weeks had a significant meta-estimated OR-3.81 (95% CI, 1.68-8.63)-based on univariable analysis. CONCLUSIONS: This study represents a comprehensive report of the association between various risk factors and RSV-ALRTI poor outcome or death in young children. More research should be carried out to elucidate risk factors associated with poor outcome or death using multivariable analysis.

Preparation and characterization of pectin/hydroxyethyl cellulose/clay/TiO2 bionanocomposite films for microbial pathogen removal from contaminated water.

Some of conventional wastewater disinfectants can have a harmful influence on the environment as well as human health. The aim of this investigation was synthesis and characterizes ecofriendly pectin/hydroxyethyl cellulose (HEC)/clay and pectin/HEC/clay incorporated with titanium dioxide nanoparticles (TiO2NPs) and use the prepared bionanocomposite as microbial disinfectants for real wastewater. Pectin/HEC/clay and pectin/HEC/clay/TiO2 bionanocomposite were characterized by various methods including X-ray diffraction (XRD), scanning electron microscope (SEM), and Fourier-transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA). Mechanical properties and water vapor permeability (WVP) were carried out. The results of SEM showed that, the prepared bionanocomposite had a smooth surface. Additionally, TiO2 nanoparticles to the pectin/HEC/clay composites may lead to changes in the FTIR spectrum. The intensity of XRD peaks indicated that, TiO2NPs was small size crystallite. TGA illustrated that pectin has moderate thermal stability, while HEC generally exhibits good thermal stability. The TEM showed that, TiO2 nanoparticles have diameters <25 nm. On the other hand, antimicrobial activities of pectin/HEC/clay against Escherichia coli (E. coli), Staphylococcus aureus and Candida albicans have been enhanced by adding TiO2NPs. The minimum inhibitory concentration (MIC) of pectin/HEC/clay/TiO2 against E. coli was 200 mg/mL. Moreover, complete eradication of E. coli, Salmonella and Candida spp. from real wastewater was observed by using pectin/HEC/clay/TiO2 bionanocomposite. Finally, it can be concluded that, the synthesized bionanocomposite is environmentally friendly and considered an excellent disinfectant matter for removal of the microbial pathogens from wastewater to safely reuse.

Human HPSE2 gene transfer ameliorates bladder pathophysiology in a mutant mouse model of urofacial syndrome.

Rare early-onset lower urinary tract disorders include defects of functional maturation of the bladder. Current treatments do not target the primary pathobiology of these diseases. Some have a monogenic basis, such as urofacial, or Ochoa, syndrome (UFS). Here, the bladder does not empty fully because of incomplete relaxation of its outflow tract, and subsequent urosepsis can cause kidney failure. UFS is associated with biallelic variants of HPSE2, encoding heparanase-2. This protein is detected in pelvic ganglia, autonomic relay stations that innervate the bladder and control voiding. Bladder outflow tracts of Hpse2 mutant mice display impaired neurogenic relaxation. We hypothesized that HPSE2 gene transfer soon after birth would ameliorate this defect and explored an adeno-associated viral (AAV) vector-based approach. AAV9/HPSE2, carrying human HPSE2 driven by CAG, was administered intravenously into neonatal mice. In the third postnatal week, transgene transduction and expression were sought, and ex vivo myography was undertaken to measure bladder function. In mice administered AAV9/HPSE2, the viral genome was detected in pelvic ganglia. Human HPSE2 was expressed and heparanase-2 became detectable in pelvic ganglia of treated mutant mice. On autopsy, wild-type mice had empty bladders, whereas bladders were uniformly distended in mutant mice, a defect ameliorated by AAV9/HPSE2 treatment. Therapeutically, AAV9/HPSE2 significantly ameliorated impaired neurogenic relaxation of Hpse2 mutant bladder outflow tracts. Impaired neurogenic contractility of mutant detrusor smooth muscle was also significantly improved. These results constitute first steps towards curing UFS, a clinically devastating genetic disease featuring a bladder autonomic neuropathy.