Genetic variations of toll-like receptors: Impact on susceptibility, severity and prognosis of bacterial meningitis.

Bacterial meningitis (BM) is a serious infectious disease of the central nervous system，which is mainly caused by Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Group B Streptococcus and Listeria monocytogenes. Throughout the world, BM has become one of the most lethal diseases that commonly occurs in children. Toll like receptors (TLRs) are one of the most important immune defense lines in infectious diseases, and play an essential role in host defense. Accumulating evidence shows that genetic variations in TLRs are associated with host responses in BM. This review aims to summarize the role of different TLRs and their genetic variations in the susceptibility, severity and prognosis of BM and discuss the identified risk factors for better treatment and improvement of the course and outcome of BM.

Effectiveness of the Close Collaboration with Parents intervention on parent-infant closeness in NICU.

BACKGROUND: Parent-infant closeness during hospital care of newborns has many benefits for both infants and parents. We developed an educational intervention for neonatal staff, Close Collaboration with Parents, to increase parent-infant closeness during hospital care. The aim of this study was to evaluate the effectiveness of the intervention on parent-infant closeness in nine hospitals in Finland. METHODS: Parents of hospitalized infants were recruited in the hospitals during 3-month periods before and after the Close Collaboration with Parents intervention. The data were collected using daily Closeness diaries. Mothers and fathers separately filled in the time they spent in the hospital and the time of skin-to-skin contact with their infant during each hospital care day until discharge. Statistical analyses were done using a linear model with covariates. RESULTS: Diaries were kept before and after the intervention by a total of 170 and 129 mothers and 126 and 84 fathers, respectively. Either parent was present on average 453 min per day before the intervention and 620 min after the intervention in the neonatal unit. In the adjusted model, the increase was 99 min per day (p = 0.0007). The infants were in skin-to-skin contact on average 76 min per day before the intervention and 114 min after the intervention. In the adjusted model, skin-to-skin contact increased by 24 min per day (p = 0.0405). CONCLUSION: The Close Collaboration with Parents intervention increased parents' presence and skin-to-skin contact in nine hospitals. This study suggests that parent-infant closeness may be one mediating factor explaining benefits of parenting interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT04635150 . Retrospectively registered.

Filovirus VP24 Proteins Differentially Regulate RIG-I and MDA5-Dependent Type I and III Interferon Promoter Activation.

Filovirus family consists of highly pathogenic viruses that have caused fatal outbreaks especially in many African countries. Previously, research focus has been on Ebola, Sudan and Marburg viruses leaving other filoviruses less well studied. Filoviruses, in general, pose a significant global threat since they are highly virulent and potentially transmissible between humans causing sporadic infections and local or widespread epidemics. Filoviruses have the ability to downregulate innate immunity, and especially viral protein 24 (VP24), VP35 and VP40 have variably been shown to interfere with interferon (IFN) gene expression and signaling. Here we systematically analyzed the ability of VP24 proteins of nine filovirus family members to interfere with retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated antigen 5 (MDA5) induced IFN-ß and IFN-λ1 promoter activation. All VP24 proteins were localized both in the cell cytoplasm and nucleus in variable amounts. VP24 proteins of Zaire and Sudan ebolaviruses, Lloviu, Taï Forest, Reston, Marburg and Bundibugyo viruses (EBOV, SUDV, LLOV, TAFV, RESTV, MARV and BDBV, respectively) were found to inhibit both RIG-I and MDA5 stimulated IFN-ß and IFN-λ1 promoter activation. The inhibition takes place downstream of interferon regulatory factor 3 phosphorylation suggesting the inhibition to occur in the nucleus. VP24 proteins of Mengla (MLAV) or Bombali viruses (BOMV) did not inhibit IFN-ß or IFN-λ1 promoter activation. Six ebolavirus VP24s and Lloviu VP24 bound tightly, whereas MARV and MLAV VP24s bound weakly, to importin α5, the subtype that regulates the nuclear import of STAT complexes. MARV and MLAV VP24 binding to importin α5 was very weak. Our data provides new information on the innate immune inhibitory mechanisms of filovirus VP24 proteins, which may contribute to the pathogenesis of filovirus infections.