Multiple Intravitreal Liposomal Amphotericin B for a Case of Candida glabrata Endophthalmitis

We report a case of Candida glabrata endophthalmitis which was effectively treated by intravitreal liposomal amphotericin B (L-AMB) injection. A 72-year-old man was referred to our department for positive blood culture of Candida glabrata. First ophthalmologic examination revealed a chorioretinal lesion in left eye, and the patient was diagnosed as possible candida chorioretinitis. Despite systemic antifungal therapy, his chorioretinal lesion increased in both eyes and complicated by vitritis. Intravitreal administration of L-AMB was introduced for probable candida endophthalmitis. Finally, improvement of vitritis and regression of chorioretinal lesions were obtained by total of 9 times intravitreal injection. Our case suggests the safety and efficacy of intravitreal L-AMB injection for Candida glabrata endophthalmitis

Site‐specific methylation patterns of the GAL and GALR1/2 genes in head and neck cancer: Potential utility as biomarkers for prognosis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136246/1/mc22577.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136246/2/mc22577_am.pd

Validation of MALDI-TOF MS devices in reanalysis of unidentified pathogenic bacteria detected in blood cultures

In hospital microbial laboratories, morphological and biochemical analyses are performed to identify pathogenic microbes;however, these procedures lack rapidity and accuracy. Recently, Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) has been clinically utilized, and is expected to enable rapid and accurate microbial identification. We aimed to validate two MALDI-TOF MS devices available in Japan: the VITEK-MS (BioMérieux) and the Microflex LT (Bruker Daltonics). Clinically isolated bacteria, 100 samples in all, detected in blood cultures but incompletely identified by conventional procedures, were reanalyzed using the two devices. The VITEK-MS and Microflex LT, respectively, identified 49% (49/100) and 80% (80/100) of the tested bacteria at the species level, as well as 96% (96/100) and 95% (95/100) at the genus level. Among those reidentified strains, 26% (26/100) at the species level and 88% (88/100) at the genus level were concordant with each other, though three strains were unmatched. Moreover, four bacterial strains were unable to be identified using the VITEK-MS, versus five using the Microflex LT. MALDI-TOF MS devices can provide more rapid and accurate bacterial identification than ever before;however, the characteristics of each system were slightly different;therefore, it is necessary to understand the difference in performance of MALDI-TOF MS models

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Efficient Attenuation of Dextran Sulfate Sodium-Induced Colitis by Oral Administration of 5,6-Dihydroxy-8Z,11Z,14Z,17Z-eicosatetraenoic Acid in Mice

5,6-dihydroxy-8Z,11Z,14Z,17Z-eicosatetraenoic acid (5,6-DiHETE) is an eicosapentaenoic acid-derived newly discovered bioactive anti-inflammatory lipid mediator having diverse functions. Here, we assessed the potential of orally administered 5,6-DiHETE in promoting healing of dextran sulfate sodium (DSS)-induced colitis in mice. We measured the plasma concentrations of 5,6-DiHETE in untreated mice before and 0.5, 1, 3, and 6 h after its oral administration (150 or 600 μg/kg) in mice. Mice developed colitis by DSS (2% in drinking water for 4 days), and 5,6-DiHETE (150 or 600 μg/kg/day) was orally administered from day 9 to 14. Next, the faecal hardness and bleeding were assessed, and the dissected colons on day 14 via H&E staining. The plasma concentration of 5,6-DiHETE reached 25.05 or 44.79 ng/mL 0.5 h after the administration of 150 or 600 μg/kg, respectively, followed by a gradual decrease. The half-life of 5,6-DiHETE was estimated to be 1.25–1.63 h. Diarrhoea deteriorated after day 3 and peaked on day 5, followed by a gradual recovery. Histological assessment on day 14 showed DSS-mediated granulocyte infiltration, mucosal erosion, submucosal edema, and cryptal abscesses in mice. Oral administration of 150 or 600 μg/kg/day of 5,6-DiHETE accelerated the recovery from the DSS-induced diarrhoea and significantly ameliorated colon inflammation. The therapeutic effect of 600 μg/kg/day 5,6-DiHETE was slightly stronger than that by 150 μg/kg/day. Our study reveals attenuation of DSS-induced colitis in mice by the oral administration of 5,6-DiHETE dose-dependently, thereby suggesting a therapeutic potential of 5,6-DiHETE for inflammatory bowel disease

Effects of nitrogen and phosphorus fertilization on the ratio of activities of carbon-acquiring to nitrogen-acquiring enzymes in a primary lowland tropical rainforest in Borneo, Malaysia

Previous meta-analyses revealed that the ratio of activities of carbon (C)-acquiring enzyme to nitrogen (N)-acquiring enzymes in tropical forest ecosystems was nearly identical to those in other ecosystems, despite of the N-rich condition in tropical forests. This could be explained by microbes in tropical forest soils, which require a large amount of N to produce N-rich acid phosphatase (AP) for catalyzation of the organic form of phosphorus (P) and compensation for poor P availability in soils. Based on this idea, we hypothesized that experimental P fertilization would reduce the allocation to N-acquiring enzymes compared with that of C-acquiring enzymes, i.e. that it would increase the ratios of activities of -1,4-glucosidase (BG) to -1,4-acetylglucosaminidase (NAG) and leucine aminopeptidase (LAP). We tested this hypothesis using an experimental fertilization site with factorial N (100kg ha(-1)yr(-1)) and P (50kg ha(-1)yr(-1)) addition in a primary tropical lowland forest in Bornean Malaysia, where our earlier work demonstrated that P fertilization reduced AP activity. Contrary to our hypothesis, the BG:NAG and BG:(NAG +LAP) ratios were not altered by either N or P fertilizations. This result indicated that AP production was not a reason for the maintenance of a relatively high investment in N-acquiring enzyme at our study site. Rather, NAG and LAP production was likely driven by C acquisition, rather than N acquisition, as the target substrates contained C as well as N. This idea was supported by the fact that neither the BG:NAG ratio nor the BG:(NAG +LAP) ratio was elevated by N addition. We propose that the ratios of activities of BG to NAG and LAP do not necessarily indicate the ratio of C:N acquisition, at least in our N-rich tropical forest ecosystem