Pilot validation of central line-associated bloodstream infection data in a voluntary surveillance system in Taiwan between October and December 2021.

Background: Central line-associated bloodstream infection (CLABSI) surveillance data are voluntarily submitted to the Taiwan Healthcare-associated Infection and Antimicrobial Resistance Surveillance (THAS) System. Validation of the CLABSI data is important to ensure the quality of surveillance data. We aimed to validate the CLABSI surveillance data reported to the THAS system. Methods: This study was a retrospective medical record review of patients with positive blood cultures admitted to the intensive care units (ICUs) of 13 participating hospitals between October and December 2021. An external validation team was convened to perform the validation process according to the standardised protocol and to record the reasons for misclassification. Discussion: During the study period, 688 patients with 1,238 positive blood cultures from 59 ICUs at 13 hospitals were evaluated. Among the 185 potential CLABSI events which met the THAS definition by either the external reviewers or the hospital reviewers, 24 (13.0%) events were identified by only the external reviewers, and six (3.2%) were identified by only the hospital reviewers, with an agreement rate of 83.8%. Using external reviewers as the gold standard, the pooled mean sensitivity and positive predictive value of CLABSI reporting were 86.6% (155/179) and 96.3% (155/161), respectively. Among the 37 misclassification episodes, missed case findings were the most common reason for misclassification (N=16, 43.2%). Conclusions: The CLABSI data reported to the THAS system are generally reliable. This study showed the need for ongoing validation processes and quality improvement to maintain the accuracy and validity of the surveillance data.

Association of early-onset Alzheimer's disease with germline-generated high affinity self-antigen load.

Self-antigen presentation outside the central nervous system has crucial role regarding self-proteins tolerance and autoimmunity, leading to neuroinflammation. Self-antigen with strong-binding affinity is considered to be pathogenic. We aim to investigate whether strong-binding affinity self-antigen load is associated with early/late-onset Alzheimer's disease (AD). A total of 54 AD samples (22 early-onset, 32 late-onset) underwent next-generation sequencing (NGS) for whole-exome sequencing. Genotypes of HLA class I genes and germline mutations were obtained for estimation of the binding affinity and number of self-antigens. For each patient, self-antigen load was estimated by adding up the number of self-antigens with strong-binding affinity. Self-antigen load of early-onset AD was significantly higher than late-onset AD (mean ± SD: 6115 ± 2430 vs 4373 ± 2492; p = 0.011). An appropriate cutoff value 2503 for dichotomizing self-antigen load was obtained by receiver operating characteristic (ROC) curve analysis. Patients were then dichotomized into high or low self-antigen load groups in the binary multivariate logistic regression analysis. Adjusted odds ratio of the high self-antigen load (>2503) was 14.22 (95% CI, 1.22-165.70; p = 0.034) after controlling other covariates including gender, education, ApoE status, and baseline CDR score. This is the first study using NGS to investigate germline mutations generated self-antigen load in AD. As strong-binding affinity self-antigen is considered to be pathogenic in neuroinflammation, our finding indicated that self-antigen load did have a role in the pathogenesis of AD owing to its association with neuroinflammation. This finding may also contribute to further research regarding disease mechanism and development of novel biomarkers or treatment.

Biosynthetic pathway for the epipolythiodioxopiperazine acetylaranotin in Aspergillus terreus revealed by genome-based deletion analysis.

Epipolythiodioxopiperazines (ETPs) are a class of fungal secondary metabolites derived from diketopiperazines. Acetylaranotin belongs to one structural subgroup of ETPs characterized by the presence of a seven-membered 4,5-dihydrooxepine ring. Defining the genes involved in acetylaranotin biosynthesis should provide a means to increase the production of these compounds and facilitate the engineering of second-generation molecules. The filamentous fungus Aspergillus terreus produces acetylaranotin and related natural products. Using targeted gene deletions, we have identified a cluster of nine genes (including one nonribosomal peptide synthetase gene, ataP) that is required for acetylaranotin biosynthesis. Chemical analysis of the wild-type and mutant strains enabled us to isolate 17 natural products from the acetylaranotin biosynthesis pathway. Nine of the compounds identified in this study are natural products that have not been reported previously. Our data have allowed us to propose a biosynthetic pathway for acetylaranotin and related natural products.

A potential for granulocyte-colony stimulating factor for use as a prophylactic agent for heatstroke in rats.

Heatstroke is a form of excessive hyperthermia associated with a systemic inflammatory response that leads to multi-organ dysfunction in which central nervous system disorders predominate. Herein we determined to ascertain whether heat-induced multi-organ dysfunction in rats could be attenuated by granulocyte-colony stimulating factor (G-CSF) preconditioning. Anesthetized rats were divided into 2 major groups and given vehicle solution (isotonic saline, 0.3 ml, subcutaneously) or G-CSF (50-200 µg/kg body weight in 0.3 ml normal saline, subcutaneously) daily and consecutively for 5 days before the start of thermal experiments. They were exposed to an ambient temperature of 43°C for 68 min to induce heatstroke. G-CSF preconditioning significantly prolonged the survival time in heatstroke rats in a dose-related way (82-98 min vs 127-243 min). The non-preconditioning heatstroke animals showed hyperthermia, arterial hypotension, increased serum levels of systemic inflammatory response molecules, increased hypothalamic apoptotic cell numbers as well as neuronal damage scores, and increased serum levels of renal and hepatic dysfunction indicators. These heatstroke syndromes could be significantly reduced by G-CSF preconditioning. Thus our results revealed a potential for G-CSF used as a prophylactic agent for heatstroke in rats.

Microcirculatory effect of different skin contacting pressures around the blood pressure.

We used laser Doppler flowmetry (LDF) and spectrum analysis to investigate the microcirculatory responses to pressure stimulation (PS) of the skin surface. A control group without PS applied, and four groups with different PS (20, 60, 100 and 160 mmHg in groups PS(20), PS(60), PS(100) and PS(160), respectively) were formed from seven volunteers. Each experiment involved recording a 20 min baseline and two effect data recorded at 0-20 and 50-70 min after stopping PS. The relative energy contribution (REC) in five frequency bands revealed by Morlet-wavelet transformation was calculated. At the pressed site, the dc component of the flux signal in the second effect increased significantly only in group PS(60) compared with the control values. The REC was significantly increased in a myogenic-related band in groups PS(60), PS(100) and PS(160), and was significantly decreased in a nerve-related band only in group PS(160). Different PS magnitudes compress vessels to different extents. The proposed vessel-pressing model-which is supported by the results of spectral analysis of flux signals-might help to elucidate the underlying mechanism. The study results indicate that an improved perfusion was sustained for the longest time when applying 60 mmHg PS. This might aid the development of techniques for improving skin microcirculatory perfusion.

Pathogenesis in Transgenic Mice Expressing Bovine Cellular Retinoic Acid-Binding Protein: (transgenic/retinoic acid/CRABP/pathogenesis).

Transgenic mice with ectopic expression of bovine CRABP under the control of the human metallotheionein IIA promoter have shown a variety of pathological consequences. Expression of the transgene has been detected in most of the tissues examined, including heart, lung, liver, spleen, kidney, intestine, testis, and ovary, except pancreas. Two independent lines have been able to produce normal non-transgenic F1 animals of both sexes but only female transgenic progenies. All of these F1 female transgenic animals derived from both lines are sterile, and the ovaries from these animals appear to be significantly smaller as compared to their non-transgenic littermates. Histopathological examinations have shown no maturing follicles in these transgenic ovaries in which abnormal cells have been observed. Another independent line has generated transgenic F1 animals which have been growing retardly. These animals all have small spleen and liver and have become very sick at the age of 4 to 5 weeks. Histopathological examinations on these transgenic progenies have shown hepatocytes to be reduced in the cytoplasmic portion in which glycogen is highly depleted. The spleen is poorly developed as no well organized germinal centers can be observed in the spleen sections of these transgenic animals.