A quality assessment of evidence-based guidelines for the prevention and management of ventilator-associated pneumonia: a systematic review.

BACKGROUND: Numerous evidence-based guidelines (EBGs) pertaining to ventilator-associated pneumonia (VAP) have been published by domestic and international organizations, but their qualities have not been reported. METHODS: A systematic search of the literature was performed up to July 2018 for relevant guidelines. Guidelines were eligible for inclusion if they incorporated recommendation statements for prevention and/or management in adults or children with VAP and were developed on a systematic evidence-based method. Four reviewers evaluated each guideline using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument, which comprises 23 items organized into six domains in addition to two overall items. RESULTS: Thirteen EBGs were identified for review. An overall high degree of agreement among reviewers was reached [intra-class correlation coefficient (ICC), 0.885; 95% CI, 0.862-0.905] during their review. The scores (mean, range) for the six AGREE domains were: scope and purpose (61%, 51-74%), stakeholder involvement (36%, 18-68%), rigor of development (41%, 22-59%), clarity and presentation (56%, 47-71%), applicability (38%, 21-59%) and editorial independence (50%, 0-77%). Only two EBGs (15.4%) were rated "recommended" for clinical practice. Approximately 86% of recommendations were based on moderate or low levels of evidence (levels B-D were 46.2%, 19.0%, and 21.2%, respectively). The recommendations for prevention and management of VAP were similar among the different EBGs. CONCLUSIONS: The overall quality of the identified EBGs pertaining to VAP was classified as moderate. The management of VAP varied by guideline. More high-quality evidence is needed to improve guideline recommendations.

Hantaan virus RNA load in patients having hemorrhagic fever with renal syndrome: correlation with disease severity.

To investigate the role of viral load in the pathogenesis of hemorrhagic fever with renal syndrome, the Hantaan virus RNA load in plasma from 101 patients was quantified, and the relationships between viral load and disease course, severity, and level of specific humoral immunity were analyzed. The viral load, detectable in 79 patients, ranged from 3.43 to 7.33 log10 copies/mL of plasma. In the early stage of disease, patients in severe/critical group were found to have higher viral loads than those in the mild/moderate group (5.90 vs 5.03 log10 copies/mL; P = .001), suggesting an association between Hantaan virus load and disease severity.

Identification of a novel B-cell epitope of Hantaan virus glycoprotein recognized by neutralizing 3D8 monoclonal antibody.

Hantaan virus (HTNV), a member of the family Bunyaviridae, is a major agent causing haemorrhagic fever with renal syndrome, a high-mortality-rate disease threatening approximately 150 000 people around the world yearly. The 3D8 mAb displays a neutralizing activity to HTNV infection. In this study, the B-cell epitopes of HTNV glycoproteins (GPs) were finely mapped by peptide scanning. A new B-cell epitope (882)GFLCPEFPGSFRKKC(896) of HTNV, which locates on Gc, has been screened out from a set of 15-mer synthesized peptides covering the full-length of HTNV-GPs. It has been shown by the alanine-scanning technique that (885)C, (893)R, (894)K, (895)K and (896)C are the key amino acids of the binding sites of the GPs. The implications of identifying a novel B-cell epitope for hantavirus immunology and vaccinology are discussed.

A novel middle-wavelength opsin (M-opsin) null-mutation in the retinal cone dysfunction rat.

The disease-causing gene which underlies a naturally occurring X-linked mutant cone dysfunction Sprague-Dawley rat model was investigated. Full-field electroretinogram (ERG) and simple sequence length polymorphism analyses were applied to 441-second filial generation rats that were derived from crossing a mutant rat and a Brown-Norway rat. After identifying a mutation mapping within the telomeric region of chromosome X, a candidate gene related to retinal cone function in this region was further screened using real-time PCR, immunohistochemistry and histological methods. The results showed that a G-to-T substitution at the splice acceptor site of intron 4 was present in the opsin 1, medium-wave sensitive (Opn1mw) gene, thereby causing down-regulated transcription and translation. These changes were consistent with abnormities seen in the ERG response. However, there was no significant histological change in the mutant rat retina. Therefore, we infer from this that the causative gene for the mutation is Opn1mw and consequently term this a middle-wavelength opsin cone dysfunction (MCD) rat model. The deficiency in vision of the MCD rat is similar to the color vision defects that occur in humans with a color vision defect but without recessive retinal degeneration. This rat model may be useful for understanding the mechanism that is responsible for color vision and for developing clinical therapies for several retinal dystrophies caused by cone opsin deficiencies.

A naturally-occurring mutation in Cacna1f in a rat model of congenital stationary night blindness.

PURPOSE: To identify the gene mutation responsible for a previously described rat model of X-linked congenital stationary night blindness (CSNB). METHODS: Rat orthologous genes for Nyx and Cacna1f were isolated from retina through rapid amplification the cDNA ends (RACE) and examined for mutations. Electroretinograms were used to identify affected animals. RESULTS: The rat Nyx cDNA spans 1,971 nucleotides and encodes a protein of 476 amino acids (GenBank: DQ393414). The rat Cacna1f cDNA spans 6,076 nucleotides and encodes a protein of 1,980 amino acids (GenBank: DQ393415). A c.2941C>T (p.R981Stop) mutation in Cacna1f was found in affected rats. Immunochemistry study showed labeling for rod bipolar and horizontal cells were reduced in affect retinas. For affected rats, b-wave and oscillatory potentials of scotopic ERG were absent, and b-wave of photopic ERG was clear but obviously reduced. CONCLUSIONS: The Cacna1f mutation identified in the rat model of CSNB was predicted to lead to a protein product that is shortened by 999 amino acids, indicating that this is a model for the incomplete subtype of human X-linked CSNB (CSNB2). This rat model will be useful for defining the pathophysiological properties of this human disorder.

[Analysis of pde6b mRNA sequences of Kunming mice and C57BL/6J mice].

AIM: To clone and sequence the phosphodiesterase 6 beta subunit (pde6b) gene of Kunming mice, and to compare it with counterpart sequences in the GenBank database. METHODS: The primers were designed covering the CDS region of the pde6b gene, and the corresponding fragments were amplified using RT-PCR. The fragments were cloned into plasmids, amplified in E.coli, and sequenced. Bioinformatics programs and online tools were used to analyze the sequences. RESULTS: The CDS of the pde6b gene of Kunming mice was cloned and sequenced. Compared with the inbred mice C57BL/6J, pde6b CDS sequence of Kunming mice was different in some points: a G-->A transition at +706, a C-->T transversion at +1149. The protein sequence was of little difference: only a glycine-->serine at +236. CONCLUSION: The pde6b CDS region of Kunming mice was successfully cloned. Pde6b sequences are of some level difference in different kinds of mice, but they are most conserved in protein level.