Perry disease, a rare autosomal dominant neurodegenerative disorder, is characterized by parkinsonism, depression or apathy, unexpected weight loss, and central hypoventilation. Genetic analyses have ...revealed a strong association between point mutations in the dynactin I gene (DCTN1) coding p150glued and Perry disease. Although previous reports have suggested a critical role of p150glued aggregation in Perry disease pathology, whether and how p150glued mutations affect protein aggregation is not fully understood. In this study, we comprehensively investigated the intracellular distribution of the p150glued mutants in HEK293T cells. We further assessed the effect of co-overexpression of the wild-type p150glued protein with mutants on the formation of mutant aggregates. Notably, overexpression of p150glued mutants identified in healthy controls, which is also associated with amyotrophic lateral sclerosis, showed a thread-like cytoplasmic distribution, similar to the wild-type p150glued. In contrast, p150glued mutants in Perry disease and motor neuron disease caused aggregation. In addition, the co-overexpression of the wild-type protein with p150glued mutants in Perry disease suppressed aggregate formation. In contrast, the p150glued aggregation of motor neuron disease mutants was less affected by the wild-type p150glued. Further investigation of the mechanism of aggregate formation, contents of the aggregates, and biological mechanisms of Perry disease could help develop novel therapeutics.
Microbial flora in several organs of HIV-infected individuals have been characterized; however, the palatine tonsil bacteriome and mycobiome and their relationship with each other remain unclear. ...Determining the palatine tonsil microbiome may provide a better understanding of the pathogenesis of oral and systemic complications in HIV-infected individuals. We conducted a cross-sectional study to characterize the palatine tonsil microbiome in HIV-infected individuals.
Palatine tonsillar swabs were collected from 46 HIV-infected and 20 HIV-uninfected individuals. The bacteriome and mycobiome were analyzed by amplicon sequencing using Illumina MiSeq. The palatine tonsil bacteriome of the HIV-infected individuals differed from that of HIV-uninfected individuals in terms of the decreased relative abundances of the commensal genera Neisseria and Haemophilus. At the species level, the relative abundances and presence of Capnocytophaga ochracea, Neisseria cinerea, and Selenomonas noxia were higher in the HIV-infected group than those in the HIV-uninfected group. In contrast, fungal diversity and composition did not differ significantly between the two groups. Microbial intercorrelation analysis revealed that Candida and Neisseria were negatively correlated with each other in the HIV-infected group. HIV immune status did not influence the palatine tonsil microbiome in the HIV-infected individuals.
HIV-infected individuals exhibit dysbiotic changes in their palatine tonsil bacteriome, independent of immunological status.
Abstract Pathogen identification is important for proper diagnosis and optimal treatment of infective endocarditis (IE). Blood and valve cultures are the gold standard for detecting pathogens ...responsible for IE. However, these tests only detect culturable pathogens, and have low sensitivity, especially in patients previously treated with antibiotics. Culture-negative IE is still a major clinical problem and a diagnostic challenge. Recently, metagenomic analysis using next generation sequencing has been used to detect pathogens directly from clinical samples. However, there are very few reports of the use of metagenomic analysis for pathogen identification in culture-negative IE cases and the usefulness of this new method is unknown. Here, we report a case of successful pathogen detection with metagenomic analysis in a patient of culture-negative IE. The patient underwent valve replacement surgery and received antibiotics for 5 weeks and survived. Using metagenomic analysis of resected vegetation, we detected Abiotrophia defectiva , which is often associated with culture-negative IE due to its fastidious growth. This method may be useful for pathogen identification in future cases of culture-negative IE.
The bioactivities of commensal duodenal microbiota greatly influence the biofunction of hosts. We investigated the role of Helicobacter pylori infection in extra-gastroduodenal diseases by ...determining the impact of H. pylori infection on the duodenal microbiota. We sequenced 16 S rRNA genes in samples aspirated from the descending duodenum of 47 (male, 20; female, 27) individuals who were screened for gastric cancer. Samples were analysed using 16 S rRNA gene amplicon sequencing, and the LEFSe and Kyoto Encyclopaedia of Genes and Genomes methods were used to determine whether the duodenal microflora and microbial biofunctions were affected using H. pylori infection.
Thirteen and 34 participants tested positive and negative for H. pylori, respectively. We identified 1,404 bacterial operational taxonomic units from 23 phyla and 253 genera. H. pylori infection changed the relative mean abundance of three phyla (Proteobacteria, Actinobacteria, and TM7) and ten genera (Neisseria, Rothia, TM7-3, Leptotrichia, Lachnospiraceae, Megasphaera, F16, Moryella, Filifactor, and Paludibacter). Microbiota features were significantly influenced in H. pylori-positive participants by 12 taxa mostly classified as Gammaproteobacteria. Microbial functional annotation revealed that H. pylori significantly affected 12 microbial metabolic pathways.
H. pylori disrupted normal bacterial communities in the duodenum and changed the biofunctions of commensal microbiota primarily by upregulating specific metabolic pathways. Such upregulation may be involved in the onset of diseases associated with H. pylori infection.
At room temperature, pure Co has a hexagonal close-packed (HCP) structure. When several percent of Fe is doped into a Co crystal, it changes to the face-centered cubic (FCC) structure. However, it is ...not clear why the FCC structure in the FexCo1−x system is so stable even with small amounts of Fe concentration. Therefore, we carried out X-ray fluorescence holography (XFH) on a Fe0.08Co0.92 single crystal to visualize the three-dimensional atomic images around both Fe and Co atoms. The intensities of the reconstructed images by XFH around Fe atoms at both 100 and 300 K are inversely proportional to the distance from the Fe emitter, and those at 100 K were always higher than those at 300 K due to the suppression of the thermal vibrations of atoms. However, the image intensities around Co did not increase by cooling unlike those around Fe. In particular, the distance dependence of the atomic image intensities at 100 K are roughly constant up to 0.8 nm. This suggests that the lattice around Co, i.e., matrix crystal lattice of Fe0.08Co0.92, is more distorted than that around dopant Fe.
β-Hemolytic streptococci occasionally cause severe infections such as necrotizing fasciitis and streptococcal toxic shock syndrome (STSS). Here, we conducted a prospective study to investigate the ...production of cytokines and chemokines in patients with STSS to explore its pathogenesis in survivors and fatal cases.
From January 2013 through August 2015, all culture results from normally sterile sites were prospectively followed and screened for STSS. Clinical characteristics of the patients with STSS were evaluated and compared between survivors and fatal cases. Serum samples were collected on admission for quantification of various cytokines and chemokines. Bacterial strains were categorized by Lancefield grouping and analyzed for the emm type, and presence of speA, speB, speC, and speF.
Fifteen patients received diagnosis of STSS. The median age of the patients was 60-year-old, and the mortality rate was 40% despite intensive treatment. Nine strains were categorized as group A, two belonged to group G, and four to group B. Group A contained various emm genotypes. Unexpectedly, potent proinflammatory cytokine levels such as TNF-α and IL-1β were not significantly elevated, and comparison with surviving patients showed that IL-6, IL-8, and MCP-1 levels were significantly decreased and creatine kinase level was significantly elevated in fatally ill cases.
Our results indicate that reduced production of proinflammatory cytokines and chemokines may be involved in STSS pathogenesis and critical for prognosis of patients with STSS.
Abstract Introduction Presenteeism is a condition in which an employee is unable to perform adequately due to physical or mental health problems despite being present at work. Although the previous ...study has shown that presenteeism is associated with near misses, the limitations are that it is a cross-sectional study and the subjects are limited to first responders. This study aims to investigate the relationship between presenteeism and occupational accidents. Methods The study design was a prospective cohort study with a baseline survey in March 2022 and a follow-up survey one year later. The independent variable was presenteeism at baseline using WHO-HPQ, classified into four categories. The outcome was the occurrence of occupational accidents from baseline to follow-up. We examined the relationship between presenteeism and occupational accidents using logistic regression analysis. This study was approved by the Ethics Committee of UOEH. Results Among 16,629 workers, presenteeism was “0-50%” (n=5,490); “60-70%” (n=5,235); “80%” (n=3,711); and “90-100%” (n=2,193). The odds ratios of each group were 1.46 (95%CI, 1.21-1.77), 1.13 (0.93-1.37), and 1.13 (0.92-1.39), respectively, compared to “90-100%”. Discussion Presenteeism may have reduced concentration and judgment, which in turn increased the risk of occupational accidents. The countermeasure for presenteeism may be effective in reducing the risk of occupational accidents. Conclusion Presenteeism was associated with the occurrence of occupational accidents.
Abstract Introduction Self-rated health is a subjective assessment of one’s own health status. The previous studies have shown that it is an antecedent factor of mortality, morbidity and falls in ...older people. However, the relationship between self-rated health and the occurrence of occupational accidents is not clear. This study aims to investigate the relationship between self-rated health and occupational accidents. Methods The study design was a prospective cohort study with a baseline survey in March 2022 and a follow-up survey one year later. The independent variable was self-rated health at baseline, classified into five categories. The dependent variable was the occurrence of occupational accidents from baseline to follow-up, classified into two categories: “none” and “more than once”. We examined the relationship between self-rated health and occupational accidents using logistic regression analysis. This study was approved by the Ethics Committee of UOEH. Results Among 16,629 workers, self-rated health was “bad/very bad” (n=662); “rather bad” (n=2,507); “rather good” (n=6,564); “good” (n=5,399); and “very good” (n=1,497). Compared to “bad/very bad” group, the odds ratios of each group were 0.69 (95%CI, 0.56-0.86), 0.40 (0.33-0.49), 0.29 (0.24-0.36), and 0.29 (0.22-0.38), respectively. Discussion The lower self-rated health, the more likely the worker was to have an occupational accident. This may be because physical and psychological problems cause a decline in workers’ ability to concentrate and make good decisions, leading to unsafe actions. The results of this study suggest the need for comprehensive measures to prevent occupational accidents, including the health status of workers. Conclusion Self-rated health influences the occurrence of occupational accidents.
We have developed instruments for magnetic neutron holography (MNH) using polarized white neutrons to investigate the local magnetic structures of magnetic alloys. We chose the 3He spin filter method ...as the neutron polarizer to polarize neutrons over a wide wavelength range of up to a few 100 meV. We developed a magnet device to saturate the magnetizations of ferromagnetic samples, and instruments to transport polarized neutrons from a 3He spin filter to the MNH sample. The neutron polarization, Pn, at the beginning of the MNH experiments was confirmed to be 0.46, which is feasible for MNH. Using the developed instruments, we obtained preliminary results for the room-temperature ferromagnetic alloy Fe0.08Co0.92. Technical problems encountered in the experiments and ways to overcome them are discussed. Based on these results, we believe that MNH that use polarized neutrons is promising.
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