Around 1.7 million children are estimated to live with HIV-1 worldwide, and about 160,000 infants are newly infected every year. Since adaptive immunity takes time to mature and develop in infants, and maternal antibodies provide limited antiviral activity, innate and intrinsic immunity against HIV-1 in the young is of critical importance. Intrinsic restriction factors are cellular proteins that effectively inhibit HIV-1 replication in vitro, but there is limited understanding of their role in vivo, and little to no data has been reported on the expression of host restriction factors in children. We hypothesized that restriction factor expression might be particularly important in children living with HIV-1 and correlate with disease progression. We analyzed gene expression of APOBEC3A, APOBEC3C, APOBEC3G, APOBEC3H, SAMHD1, ISG15, CDKN1A, MX2, TRIM5, and SLFN11 by qPCR in 121 samples of CD4+ T cells from vertically infected children living with HIV-1. Cell surface expression of BST-2/tetherin and markers of CD4+ T-cell activation were analyzed by flow cytometry. After adjusting for gender and age, BST-2/tetherin expression on CD4+ T cells showed significant positive correlation with viral load (P = 0.0006; ρ = 0.33), CD4+ T-cell activation (P < 0.0001; ρ = 0.53), CD8+ T-cell activation (P < 0.0001; ρ = 0.53), and a negative correlation with CD4+ T-cell counts (P = 0.0008; ρ = -0.33). The expression of SAMHD1 correlated negatively with markers of T-cell activation (P = 0.046; ρ = -0.22). These results suggest an important role of some restriction factors in the pathogenesis of HIV-1 in children.These results suggest an important role of some restriction factors in the pathogenesis of HIV-1 in children. While there have been studies in adults reporting discordant empiric antibiotic treatment associated with poor outcomes, this area is relatively unexplored in children and neonates despite evidence of increasing resistance to recommended first-line treatment regimens. Patient characteristics, antibiotic treatment, microbiology, and 30-day all-cause outcome from children <18 years with blood-culture-confirmed bacterial bloodstream infections (BSI) were collected anonymously using REDCap™ through the Global Antibiotic Prescribing and Resistance in Neonates and Children network from February 2016 to February 2017. Concordance of early empiric antibiotic treatment was determined using European Committee on Antimicrobial Susceptibility Testing interpretive guidelines. https://www.selleckchem.com/products/CP-690550.html The relationship between concordance of empiric regimen and 30-day mortality was investigated using multivariable regression. Four hundred fifty-two children with blood-culture-positive BSI receiving early empiric antibiotics were reported b-fold higher for patients receiving a discordant early empiric antibiotic regimen. The impact of improved concordance of early empiric treatment on mortality, particularly in critically ill patients, needs further evaluation. Antibacterial activity of ceftazidime-avibactam (CAZ-AVI) was evaluated against bacterial isolates from children in the United States with a urinary tract infection (UTI) or intra-abdominal infection (IAI) during the 2016-2019 International Network for Optimal Resistance Monitoring program. Prevalence of isolates and susceptibility to CAZ-AVI in pediatric and adult patients were compared. Bacterial isolates were collected from children with a UTI or IAI at 70 US medical centers from 2016 to 2019. The antimicrobial activity of CAZ-AVI and comparator agents was tested by broth microdilution methods. The most prevalent Enterobacterales pathogens in children with UTIs were Escherichia coli (62.5%), Klebsiella pneumoniae (12.1%) and Proteus mirabilis (6.2%). Minimum inhibitory concentration 90% values for CAZ-AVI against Enterobacterales (0.25 μg/mL) and Pseudomonas aeruginosa (4 μg/mL) were identical for children and adults. The most prevalent Enterobacterales pathogens in children with IAIs were E. coli (57.4%), K. pneumoniae (11.1%) and Enterobacter cloacae species complex (9.3%). All isolates of Enterobacterales from pediatric patients with UTI and IAI were susceptible to CAZ-AVI, including extended-spectrum β-lactamase phenotypes. Susceptibility of P. aeruginosa isolates to CAZ-AVI was 96.2% in children and 98.4% in adults with a UTI for IAI it was 100% and 97.2%, respectively. Contemporary UTI and IAI pathogens collected from US children from 2016 to 2019 exhibited similar prevalence and susceptibilities as isolates collected from adult patients. CAZ-AVI exhibited potent activity against these pathogens.Contemporary UTI and IAI pathogens collected from US children from 2016 to 2019 exhibited similar prevalence and susceptibilities as isolates collected from adult patients. CAZ-AVI exhibited potent activity against these pathogens. The purpose of this guideline is to assist specialists in Nuclear Medicine and Radionuclide Radiology in recommending, performing, interpreting and reporting the results of lacrimal scintigraphy (also known as Dacroscintigraphy). This guideline will assist individual departments to formulate their own local protocols. This does not aim to be prescriptive regarding technical aspects of individual camera acquisitions, which need to be developed in conjunction with the local experts in medical physics. There are numerous radiological techniques to assess the physiology of the lacrimal system. This guideline will describe the application of a drop of radiotracer into each eye and consecutive imaging to demonstrate the level of impaired drainage, with the possibility of quantifying such impairment. This guideline is a recent and updated version of a previously published guideline on the British Nuclear Medicine Society website in 2018 [1].The purpose of this guideline is to assist specialists in Nuclear Medicine and Radionuclide Radiology in recommending, performing, interpreting and reporting the results of lacrimal scintigraphy (also known as Dacroscintigraphy). This guideline will assist individual departments to formulate their own local protocols. This does not aim to be prescriptive regarding technical aspects of individual camera acquisitions, which need to be developed in conjunction with the local experts in medical physics. There are numerous radiological techniques to assess the physiology of the lacrimal system. This guideline will describe the application of a drop of radiotracer into each eye and consecutive imaging to demonstrate the level of impaired drainage, with the possibility of quantifying such impairment. This guideline is a recent and updated version of a previously published guideline on the British Nuclear Medicine Society website in 2018 [1]. |