Changes in the Messenger RNA Expression of Toll-Like Receptors 2 and 4 in Healthy Infants According to Age.

BACKGROUND: Toll-like receptors (TLRs) are potentially useful indicators of several pediatric disease states. Here, we explore the mechanisms by which inflammation is regulated by interactions between microbiota and the host. Little data are available regarding the expression of TLRs in postnatal healthy infants. TLR 2 and TLR4 are extracellular TLRs that act as innate immune receptors by recognizing a wide range of endogenous ligands and microorganisms. METHODS: The aim of this study was to use real-time polymerase chain reaction to investigate the expression of the messenger RNAs (mRNAs) of TLR2 and TLR4 in blood samples obtained from healthy full-term infants and toddlers. RESULTS: We analyzed the mRNA expression levels of TLRs in 88 healthy term children separated according to age. The median expression level of TLR2 was 1.49 ± 1.10 arbitrary units (AU) (n = 25) in infants younger than 3 months, 0.67 ± 0.72 AU (n = 25) in infants aged between 3 and 12 months, and 0.03 ± 0.02 AU (n= 38) in infants older than 12 months. The median expression level of TLR4 was 1.25 ± 0.79 AU (n = 25) in infants younger than 3 months, 0.75 ± 0.54 AU (n = 25) in infants aged 3 to 12 months, and 0.44 ± 0.28 AU (n = 38) in infants older than 12 months. There was difference in the mRNA expression level of TLR2 and TLR4 between infants aged 0 to 3 and 3 to 12 months and those aged more than 1 year (p < 0.0001 and p < 0.0001, respectively) CONCLUSION: We found that the expression levels of TLR2 and TLR4 were associated with age. In particular, we observed that their expression increased during the suckling period and then clearly decreased once the infants reached 1 year of age (p < 0.001). These findings could be related to microbial colonization and the immune system.

Incidence of ultrasound-detected asymptomatic long-term central vein catheter-related thrombosis and fibrin sheath in cancer patients.

BACKGROUND: Most central venous catheter (CVC)-related deep vein thromboses (DVT) are asymptomatic and their incidence and clinical relevance are still under debate. Data on CVC-related fibrin sheaths are scarce. We investigated the incidence of asymptomatic DVT and fibrin sheaths in cancer patients with long-term CVC implantation who underwent Doppler ultrasound surveillance at 1, 6, and 12 months after implantation. Effects of low-weight molecular heparin (LWMH) therapy on DVT and fibrin sheaths were also analyzed. MATERIAL AND METHODS: This prospective study was performed on a large cohort (n = 400) of patients with cancer aged >18 requiring long-term CVC implantation for chemotherapy infusion. CVC was implanted by a trained qualified staff, according to standardized protocol in a specific surgery. Patients underwent ultrasound examination at 1 and 6 months after CVC implantation to detect 'early' (1 month) and 'late' (6 months) asymptomatic DVT or fibrin sheaths incidence. Sixty-nine patients underwent US examination also 12 months after CVC implantation. RESULTS: The incidence of CVC-related thrombosis was 0.10 events per 1000 catheter days. Anticoagulation therapy with LWMH resolved 50% of DVT, but no CVC needed removing. Incidence of new onset fibrin sheaths was 0.71 events per 1000 catheter days. Fibrin sheaths resolution occurred independently of LWMH therapy. DISCUSSION: The incidence of asymptomatic DVT in our patients with long-term CVC is very low and does not represent per se an indication for removal of functioning CVC in patients with cancer. Fibrin sheaths are frequent (13%) and never associated with CVC dysfunction. CONCLUSION: Asymptomatic DVT and fibrin sheaths do not represent per se an indication for removal of functioning CVC in cancer patients who need central vein access.

Peripheral Blood and Nasopharyngeal Swab MiRNA-155 Expression in Infants with Respiratory Syncytial Virus Infection.

INTRODUCTION: MicroRNA (miR) 155 has been implicated in the regulation of innate and adaptive immunity as well as antiviral responses, but its role during respiratory syncytial virus (RSV) infections is not known. The objective of this study was to investigate the expression of miR-155 using pharyngeal swabs and peripheral blood in infants with RSV infection and uninfected controls. METHODS: A prospective age-matched study was conducted in primary care in Torino from 1 August 2018 to 31 January 2020. We enrolled 66 subjects, 29 of them patients with RSV infection and 37 age-matched uninfected controls, and collected pharyngeal swabs and peripheral blood in order to assess miR-155 expression with real-time stem-loop-TaqMan real-time PCR. RESULTS: The data show that there is no correlation between pharyngeal swabs and peripheral blood with respect to miR-155 expression. The 1/ΔCq miR-155 expression levels in throat swabs in RSV bronchiolitis patients and healthy controls were 0.19 ± 0.11 and 0.21 ± 0.09, respectively, and were not significantly different between healthy controls and bronchiolitis (p = 0.8414). In the peripheral blood, miR-155 levels were higher than those of healthy control subjects: 0.1 ± 0.013 and 0.09 ± 0.0007, respectively; p = 0.0002. DISCUSSION: Our data provide evidence that miR-155 expression is higher in peripheral blood during RSV infection but not in swabs. This difference in the timing of sample recruitment could explain the differences obtained in the results; miR-155 activation is probably only assessable in the very early stages of infection in the swab and remains visible for longer in the blood. New investigations are needed in order to clarify whether the miR-155 expression in swabs can be influenced by different stages of virus disease of infants.

Assessment of interferon gamma and indoleamine 2,3-dioxygenase 1 analysis during respiratory syncytial virus infection in infants in Italy: an observational case-control study.

OBJECTIVES: The aim of this study was to measure interferon gamma (IFN-γ) and indoleamine 2,3-dioxygenase 1 (IDO1) values in the White blood cells of infants during respiratory tract infections and to compare these with healthy age-matched controls. DESIGN: This was a prospective, observational case-control study conducted in 2019-2020. SETTING: The study took place at Regina Margherita Children's Hospital, Turin, Italy. PARTICIPANTS: The study comprised 63 infants, including 26 patients hospitalised for bronchiolitis due to a respiratory syncytial virus (RSV) infection and 37 age-matched controls. The inclusion criteria included a positive RSV test for an infant with bronchiolitis. METHODS: We collected peripheral blood and measured the relative quantification of messenger RNA (mRNA) expression of IFN-γ and IDO1 with TaqMan real-time PCR amplification. The data were collected on the first day of admission. RESULTS: The mean age of the 26 patients with RSV bronchiolitis (53.8% female) was 85 (9-346) days when they were admitted to the hospital. Their mean gestational age at birth was 38 weeks and their mean birth weight was 3100 (2780-3730) g. The expression of IFN-γ was significantly reduced in patients with bronchiolitis RSV compared with healthy controls (p=0.0132). However, there was no significant difference between the two groups when the IDO1 mRNA expression values in their WCC were measured (p=0.0642). CONCLUSION: Our findings did not clarify whether IDO1 expression was related to the early stage of the disease or to the young age of the infants. The data provide evidence that IFN-γ was significantly reduced in infants with bronchiolitis due to RSV, compared with age-matched healthy controls, but the IDO1 was not different. New investigations that focus on subjects infected with RSV at different stages of infancy would help to clarify whether IDO1 expression can be related to age.

Lactobacillus reuteri DSM 17938 Probiotics May Increase CC-Chemokine Receptor 7 Expression in Infants Treated With for Colic.

Aim: Studies have shown that Lactobacilli reuteri probiotics can affect cells that play a key role in the immune system. This in vivo Italian study investigated how Lactobacillus reuteri DSM 17938 influenced CC-chemokine receptor 7 (CCR7) and interleukin 10 (IL-10) in breastfed colicky infants. Methods: Our University hospital in Turin recruited 50 healthy outpatients, at a median age of approximately 1 month, from September 2017 to August 2018. They were randomized to daily Lactobacillus reuteri DSM17938 (1 × 108 cfu) or a placebo for 28 days from recruitment. We collected peripheral blood and evaluated the expression of CCR7 messenger ribonucleic acid using the real-time TaqMan reverse transcription polymerase chain reaction method at baseline and after the study period. Results: We found increased expression of CC-chemokine receptor 7 in infants treated with the probiotic, but not the controls (p < 0.0026). No differences were observed for interleukin 10 after the study period in either group. At baseline, daily crying time was comparable in the probiotic and control groups: 341 (25) vs. 337 (29) min., respectively (p = 0.450). After 28 days, daily mean crying time decrease statistically in the probiotic group: 78 (23) vs. 232 (31), respectively (p < 0.001). Conclusion: The increase in CC-chemokine receptor 7 might have been a response to probiotic treatment. As a relatively small sample was used to conduct this study, our research needs to be replicated in different settings, and over time, to produce comparable findings.

Mother and Infant Body Mass Index, Breast Milk Leptin and Their Serum Leptin Values.

PURPOSE: This study investigates correlations between mother and infant Body Mass Index (BMI), their serum leptin values and breast milk leptin concentration in early infancy. SUBJECTS AND METHODS: We determined serum leptin values in 58 healthy infants and leptin values in their mothers' breast milk, using radioimmunoassay (RIA). Infant and maternal anthropometrics were measured. RESULTS: Median leptin concentration was 3.9 ng/mL (interquartile range (IQR): 2.75) in infant serum, 4.27 ng/mL (IQR: 5.62) in maternal serum and 0.89 ng/mL (IQR: 1.32) in breast milk. Median maternal BMI and weight were 24 kg/m² (IQR: 4.41) and 64 kg (IQR: 15). Median infant BMI was 15.80 kg/cm² (IQR: 4.02), while average weight was 5.130 kg (IQR: 1.627). Infants serum leptin values positively correlated with infants' BMI (p = 0.001; r = 0.213) and breast milk leptin (p = 0.03; r = 0.285). Maternal serum leptin values positively correlated with maternal BMI (p = 0.000, r = 0.449) and breast milk leptin ones (p = 0.026; r = 0.322). CONCLUSION: Breast milk leptin and maternal BMI could influence infant serum leptin values. Further studies are needed to better elucidate the role of genetics and environment on infant leptin production and risk of obesity later in life.