Colour doppler ultrasonography (CDU) in temporal arteries (TA) is useful for diagnosis and follow-up of giant cell arteritis (GCA).1 However, the usefulness of CDU in carotid arteries (CA) for follow-up of GCA is not fully understood. 2
Objectives
We investigated retrospectively relationship between clinical features and vessel wall thickness of TA and CA on CDU at baseline and during follow-up.
Methods
We recruited patients with newly diagnosed GCA in our hospital from January in 2004 to July in 2017. Among 35 patients, both of TA and CA were evaluated by CDU before and after treatment in 14 patients (four male and 10 female). Trained ultrasonographers and rheumatologists evaluated the CDU findings. Vessel wall thickness was evaluated at thickest portion of parietal or frontal ramus of TA, where biopsy was often performed. Intima-media thickness (IMT) of CA was also evaluated at thickest portion in each carotid artery.
Results
Average age was 73.2±11.3 years old. Follow-up periods after starting treatment were 244±149 weeks. All patients were diagnosed as GCA according to ACR criteria (1990) or temporal artery biopsy. Twelve patients were complicated with polymyalgia rheumatica (PMR) meeting EULAR/.ACR classification criteria (2012). All patients were treated with oral glucocorticoids (0.2 to 1.0 mg/kg prednisolone, 0.886 mg/kg on average). Immunosuppressants were added in four patients (methotrexate; n=3, tacrolimus; n=1). Aspirin was prescribed in nine patients. Eleven patients (78.6%) had circumferential hypoechoic vessel wall thickness (halo sign) of TA at baseline, and halo signs dissapeared in eight patients during follow-up. Average of vessel wall thickness significantly decreased from 0.665 mm to 0.311 mm (p=0.0016). The vessel wall thickness apparently increased in two patients out of three on clinical relapse, but it didn't increase in those who kept remission. Graphical changes consistent with vasculitis in CA were observed in six patients, who showed hypoechoic thick intima and media on ultrasound or integration of FDG on PET/CT. Average of IMT in CA decreased from 1.167 mm to 0.883 mm (p=0.090) during follow-up in patients with vasculitis on CA. IMT changed little in patients without vasculitis on CA. Improvement rate was significantly higher in CA-involved patients than in CA-non-involved patients (p=0.043). IMT increased during follow-up in two CA-non-involved patients. Difference in B/A between CA involved and non-involved: p=0.043 (Mann-Whitney U test)
Conclusions
CDU of temporal arteries is useful for follow-up of GCA. CDU of carotid arteries has limited usefulness only in CA-involved patients.
References
[1] Suelves AM, et al. Clin Ophthalmol. 2010; Nov 25;4:1383–4. [2] Hafner F, et al. Eur J Clin Invest2014; 44(3):249–256.
Epoxy fatty acids (EpFA), cytochrome P450(CYP)-mediated metabolites of polyunsaturated fatty acids (PUFA), have anti-inflammatory effects[1]. However, EpFA is quickly converted to an inactive form by the soluble epoxide hydrolase(sEH). In recent years, the efficacy of sEH inhibitors (sEHi) has been reported in a variety of diseases[2-4]. However, compared to ω-6 epoxides, such as epoxyeicosatirienioic acids (EET) derived from arachidonic acid (AA), there are few reports on ω-3 epoxides, epoxyeicosapentaenoic acid (EEQ) from eicosapentaenoic acid (EPA) and epoxydocosapentaenoic acids (EDP) from docosapentaenoic acid (DHA)5), and their effects on arthritis are not well understood.
Objectives
To investigate and compare the effects of ω-6 and ω-3 epoxides on inflammatory arthritis.
Methods
Collagen induced arthritis (CIA) were treated with three different diets (ω-6 PUFA rich, ω-3 PUFA rich, and Control) and two types of drinking solution, one containing sEHi and the other containing only polyethylene glycol as solvent control (total 6 groups, 8 mice each). Arthritis and pathological scores were evaluated, and feces were collected before the onset of arthritis (day 25) for intergroup comparative analysis of bacterial flora.
Results
In all the dietary groups, there was a tendency for arthritis scores to decrease with sEHi administration, but the incidence of arthritis, arthritis scores, and pathological scores decreased dramatically in the group fed with the ω-3 rich diet and sEHi combination. The groups fed the ω-6 rich diet and Control diet showed almost similar results. In the ω-3 rich diet and sEHi combination group, showed an increase in a certain specific bacterial strain.
Conclusion
ω-3 epoxides were found to be more effective in reducing arthritis, and changes in intestinal bacteria may have influenced this pathological change.
References
[1]Shi, Z. et al. CYP450 Epoxygenase Metabolites, Epoxyeicosatrienoic Acids, as Novel Anti-Inflammatory Mediators. Molecules 2022,27,3873 [2]Sandra, C. et al. Discovery and In Vivo Proof of Concept of a Highly Potent Dual Inhibitor of Soluble Epoxide Hydrolase and Acetylcholinesterase for the Treatment of Alzheimer's Disease. J.Med.Chem,2022,65,4909-4925 [3]Merce, P.et al. Soluble Epoxide Hydrolase Inhibition to Face Neuroinflammation in Parkinson's Disease: A New Therapeutic Strategy.Biomolecules 2020, 10, 703; doi:10.3390/biom10050703 [4]Rebecca, L.et al. Protection from hypertension in mice by the Mediterranean diet is mediated by nitro fatty acid inhibition of soluble epoxide hydrolase. PNAS,2014,22,111,8167-8172 [5]Yang, Y. et al. Differential Effects of 17,18-EEQ and 19,20-EDP Combined with Soluble Epoxide Hydrolase Inhibitor t-TUCB on Diet-Induced Obesity in Mice. Int. J. Mol. Sci. 2021,22,8267 g. Characters from table content including title and footnotes.
Abstract Background In many bacteria, intragenomic diversity in synonymous codon usage among genes has been reported. However, no quantitative attempt has been made to compare the diversity levels among different genomes. Here, we introduce a mean dissimilarity-based index ( D mean) for quantifying the level of diversity in synonymous codon usage among all genes within a genome. Results The application of D mean to 268 bacterial genomes shows that in bacteria with extremely biased genomic G+C compositions there is little diversity in synonymous codon usage among genes. Furthermore, our findings contradict previous reports. For example, a low level of diversity in codon usage among genes has been reported for Helicobacter pylori , but based on D mean, the diversity level of this species is higher than those of more than half of bacteria tested here. The discrepancies between our findings and previous reports are probably due to differences in the methods used for measuring codon usage diversity. Conclusion We recommend that D mean be used to measure the diversity level of codon usage among genes. This measure can be applied to other compositional features such as amino acid usage and dinucleotide relative abundance as a genomic signature.
ABSTRACT Objectives Specific human leukocyte antigen (HLA) haplotypes are associated with Behçet’s disease. Because the effects of HLA-A26 and its combination with HLA-B51 on organ involvement in Behçet’s disease have not been well demonstrated, we aimed to examine them. Methods This multicentre, cross-sectional, observational study enrolled patients with Behçet’s disease who visited Kyoto University Hospital between 2018 and 2021 or Kurashiki Central Hospital between 2006 and 2016 (n = 200). Disease severity was evaluated using the Krause score. Results Uveitis and gastrointestinal involvement were observed in 95/196 and 57/167 patients, respectively. The HLA alleles identified were HLA-B51 (n = 52/106), HLA-A26 (n = 25/88), and HLA-B51 and HLA-A26 (n = 6/88). In patients harbouring HLA-B51, the presence of HLA-A26 was associated with higher frequencies of uveitis (P = .03) and coexistence of uveitis and gastrointestinal involvement (P = .002) and higher Krause scores (P = .02). Furthermore, the presence of HLA-A26 was associated with a higher frequency of uveitis in patients with gastrointestinal involvement (P = .001) and gastrointestinal involvement in patients with uveitis (P = .001). Conclusions Since specific HLA haplotypes and their combinations are associated with organ involvement, both HLA-A and HLA-B haplotypes should be confirmed when screening for affected organs.
Retrotransposons have been generally known to integrate randomly into host genomes. Jurka (Proc. Natl. Acad. Sci. USA 94: 1872-1877, 1977), however, showed consensus sequence patterns at integration sites of certain mammalian retrotransposons, and suggested involvement of sequence specific enzymes that mediate integration. We have conducted comprehensive sequence analyses of 5' flanking regions of primate Alu elements. In contrast to the small but clean data set Jurka (1977) used, (1) larger number of samples were used, (2) wider region of 5' end of Alu elements was analyzed, and (3) comparisons were made among different subfamilies for comprehensive analyses in order to identify characteristic sequence pattern(s) preceding 5' end of Alu elements. The nucleotide occurrences at each position within 500 bases of 5' end of Alus were counted to obtain profiles. Information content at each nucleotide position in the same region was, then, computed. Distinctive difference in the nucleotide composition and information content values that divides the region into two was observed. The region between -20 and 5' end of Alu elements is found to be highly adenine-rich and shows significantly higher information content values compared to the rest of the region, implying the existence of certain characteristic sequence pattern in this region. Also, younger subfamilies of Alu elements show higher information content values than older subfamilies. This implies that certain characteristic sequence pattern already existed in the region between -20 and 5' end of Alu elements at the time of Alu integration, and accumulation of mutation in the course of time resulted in the less distinctive sequence pattern in older sequences. Frequencies of all possible triplets (total of 64) were measured in the same region in order to identify characteristic sequence pattern(s). Observation that frequencies of triplets aaa, taa and tta in the 5' flanking sequences were high is consistent with Jurka (1977). Frequencies of some other triplets such as gaa, caa, aac, ctt, gtt, atg, etc. which do not comprise the primary candidates for the nick site in Jurka (1977) also show significantly high frequencies.
We encountered a case of aspergillus granuloma in the cavernous sinus originating in the left sphenoid sinus. The patient was a 56-year-old woman who complained of visual loss and cavernous sinus syndrome on the left side. Hematological data were within normal limits. Bone CT showed evidence of bone destruction in the roof of the left sphenoid sinus. MR images with gadolinium demonstrated an enhanced heterogeneous mass extending from the left sphenoid sinus to the cavernous sinus and the orbital apex. Angiography showed occlusion of the left internal carotid artery. Dexamethasone was administered intravenously every day, because the patient was diagnosed as having Tolosa-Hunt syndrome (THS). However, dexamethasone was not effective. We carried out a biopsy of the mass from the sphenoid sinus, and findings showed aspergillosis. On the 19th day after initiation of fluconazole treatment, the patient lapsed into unconsciousness and presented left hemiparesis. T2-weighted MR images showed high intensity areas in the pons and the thalamus. The patient died two days later. An autopsy revealed edema and many infarctions throughout the brain. The cavernous sinus had been replaced completely with aspergillus granuloma. Furthermore, numerous hyphae of aspergillus had adhered to the inside of the basilar artery, and caused occlusions of arteries around the brain. This case indicated the difficulty of diagnosis of THS and the hazard of over-application of steroids. In this paper, we describe the clinical and pathological behavior of aspergillosis in the cavernous sinus.
Background: Protein-energy wasting, characterized by disordered body protein catabolism resulting from metabolic and nutritional derangements, is associated with adverse clinical outcomes in patients undergoing hemodialysis. Extended-hours hemodialysis (≥6 h per treatment session) offers both enhanced removal of uremic solutes and better fluid management, generally allowing more liberalized dietary protein and calorie intake. This study aimed to evaluate the difference in plasma metabolite profiles among patients receiving in-center daytime extended-hours hemodialysis and those receiving conventional hemodialysis. Methods: Pre-dialysis plasma samples were obtained from 188 patients on extended-hours hemodialysis (21.9 h/week) and 286 patients on conventional hemodialysis (12.1 h/week) in Japan in 2020 using capillary electrophoresis-mass spectrometry. Group differences were compared for 117 metabolites using Wilcoxon rank-sum tests with multiple comparisons and partial least squares discriminant analysis. Additionally, propensity score-adjusted multiple regression analyses were performed to evaluate group differences for known uremic toxins, branched-chain amino acids, and lactate-to-pyruvate ratio (a possible surrogate marker of mitochondrial dysfunction). Results: Significant differences were observed in 39 metabolites, largely consistent with the high variable importance for prediction in partial least squares discriminant analysis. Among known uremic toxins, uridine and hypoxanthine levels were significantly higher in the conventional hemodialysis group than in the extended-hours hemodialysis group, whereas trimethylamine N-oxide levels were higher in the extended-hours hemodialysis group than in the conventional hemodialysis group. Patients on extended-hours hemodialysis had higher levels of all branched-chain amino acids and a lower lactate-to-pyruvate ratio than those on conventional hemodialysis (significant difference of –8.6 [95% confidence interval, –9.8 to –7.4]). Conclusions: Extended-hours hemodialysis was associated with a more favorable plasma metabolic and amino acid profile; however, concentrations of most uremic toxins did not significantly differ from those of conventional hemodialysis.
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