An accumulating body of evidence suggests that the endocannabinoid system plays a significant role in pathophysiological processes and impacts disease severity. Here we investigate the possible role of a cannabinoid receptor type 2 (CB2) functional variant in determining disease severity and the potential pharmacological therapeutic effects of CB2 activation in viral respiratory infection. The common missense variant (CAA/CGG; Q63R) of the gene-encoding CB2 receptor (CNR2) was evaluated in 90 inpatient and 90 outpatient children with acute respiratory tract infection (ARTI). The frequency distribution of respiratory syncytial virus (RSV)-the main cause of severe cases of bronchiolitis and pneumonia in children-was studied in all collected samples. The mechanism through which CB2 affects clinical outcomes in case of RSV infection was studied in Balb/c mice model using AM630 as a CB2 antagonist. The potential therapeutic effect of CB2 activation during RSV infection was studied using a selective agonist, JWH133. The CB2 Q63R variation was associated with increased risk of hospitalization in children with ARTI. Children carrying the QQ genotype were more prone to developing severe ARTI (OR = 3.275, 95% CI: 1.221–8.705; p = 0.019). Of all the children enrolled in the study, 83 patients (46.1%) were found positive for RSV infection. The associated risk of developing severe ARTI following RSV infection increased more than two-fold in children carrying the Q allele (OR = 2.148, 95% CI: 1.092–4.224; p = 0.026). In mice, the blockade of CB2 by AM630 during RSV infection enhanced the influx of BAL cells and production of cytokines/chemokines while exaggerating lung pathology. CB2 activation by JWH133 reduces the influx of BAL cells and production of cytokines/chemokines while alleviating lung pathology. Collectively, CB2 is associated with RSV severity during infancy and may serve as a therapeutic target in RSV infection through the alleviation of virus-associated immunopathology.
Cytomegalovirus (CMV) disease in pediatric acute lymphoblastic leukemia in the nontransplant setting is very rare. We report our experience with 4 such cases, and review the literature (n=12). The median age at diagnosis was 10 years and 50% of patients were males. Among the 11 cases with available information at the time of diagnosis, CMV disease occurred during maintenance therapy in 10 patients. Fever was present in 9 cases. CMV disease manifested as retinitis in 6, hepatosplenic disease in 3, pneumonitis in 1, and hemophagocytic lymphohistiocytosis in 1 patient. One patient had both CMV retinitis and CMV-related hemophagocytic lymphohistiocytosis. Four of the 7 patients with retinitis complained of visual disturbance at diagnosis. CMV viremia was present in 10 patients. Three patients had at least 1 relapse and developed permanent visual defects, and 1 patient developed recurrent retinal detachment. In conclusion, prolonged immunosuppression is the major etiology and retinitis is the most common manifestation of CMV disease. As a significant number of patients with retinitis are asymptomatic, early diagnosis and treatment is important to prevent permanent visual loss.
BackgroundAntimicrobial stewardship program (ASP) is a distinguished method to improve the prescription and efficacy of antibiotics.AimThe efficacy of ASP and conventional methods was compared to measure the effectiveness of meropenem (MPM) and vancomycin (VMN) antibiotics in pediatric patients.DesignIn an interventional quasi-experimental study, 135 children admitted in Children’s Hospital affiliated to University of Medical Sciences in time periods of 2014–2015 and 2015–2016 were assessed.MethodsThe conventional and ASP methods in 2014–2015 and 2015–2016 were respectively utilized to provide the best antimicrobial therapy of MPM and VMN antibiotics in patient children. The data of mortality rate (MR), antibiotic prescription (AP), antibiotic dose (ADe), antibiotic duration (ADn), length of hospital stay (LOHS), and blood cultures (BCs) were compared across the years using the Chi square, independent t test, and Fisher’s exact test.ResultsThe levels of MR, AP, ADe, ADn, LOHS, and positive BCs using the ASP method in 2015–2016 were significantly lower those of in 2014–2015 using the conventional one (p < 0.05).ConclusionsThe ASP method versus conventional one with a better efficacy can be employed as an antibiotic administration guide for MPM and VMN in the therapy of patients in community-based hospitals.
These findings provide useful information for future surveillance in association with prevention programs. Subsequently, surveillance should be focused on high-risk patients in intensive care unit and/or who have undergone surgery and invasive procedures.
Viral gastroenteritis is a major public health problem worldwide. In Iran, very limited studies have been performed with regard to the epidemiology of noroviruses. This study aimed to evaluate the prevalence and molecular epidemiology of GII noroviruses in hospitalized children less than 5 years of age with acute gastroenteritis (AGE). A total of 210 stool specimens were collected from Ali Asghar Children's Hospital and Bahrami Children's Hospital in Tehran, from June 2015 to June 2016. The samples were screened by real-time RT-PCR for genogroup II (GII). Positive samples were genotyped by semi-nested PCR followed by Sanger sequencing and phylogenetic analysis. Norovirus was identified in 36 (17.1%) of 210 specimens. Based on genetic analysis of RdRp and capsid sequences, the strains were clustered into eight RdRp-capsid genotypes: GII.P4-GII.4 Sydney_2012 (41.7%), GII.Pe-GII.4 Sydney_2012 (30.6%), GII.P21-GII.3 (13.9%), GII.P16-GII.4 Sydney_2012 (2.8%), GII.P16-GII.12 (2.8%), GII.P2-GII.4 Sydney_2012 (2.8%), GII.P7-GII.7 (2.8%) and GII.P2-GII.2 (2.8%). We determined several different co-circulating norovirus genotypes in children < 5 years of age with AGE in our hospital in Tehran, Iran. Continued molecular surveillance of noroviruses, including typing of both RdRp and capsid genes, is important for monitoring emerging strains in our continued efforts to reduce the overall burden of norovirus disease.
To our knowledge this is the first published report of nosocomial outbreak of ESBL-producing K. pneumoniae in children in Iran. Although the epidemiology of nosocomial infections with ESBL-producing organisms has not yet been explored in depth in Iran, our findings suggest that ESBL-producing organisms are already an established public health threat in our country.
Background: The association between the use of antibiotics and bacterial resistance has obviously been established and it seems to be a significant problem for public health. It is clear that irrational use and high rates of antibiotic prescription are associated with increased bacterial resistance. As antibiotics are the class of drugs commonly prescribed in neonatal and Neonatal Intensive Care Unit (NICU) wards, neonates are at high risk of opportunistic or nosocomial infections due to prolonged hospitalization and immunosuppressed condition. Objectives: It is essential for antibiotic prescription patterns to be evaluated periodically for rational use. Therefore, the present study was carried out to identify the prescribing patterns of antibiotics in neonatal and NICU wards of 17 different Iranian hospitals. Methods: The study was done during 1 calendar week between January and February 2014. All in-patients admitted to the NICU and neonatal units of 17 Hospitals in 15 Iranian cities were included. Relevant data of all neonates receiving an antibiotic at 8 am on the day of the study was collected by trained members of the study team; age of the patients, type and number of administered antibiotics, route of administration, underlying disease, and indication for use were documented.
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