Drastically Progressive Ethambutol-induced Optic Neuropathy after Withdrawal of Ethambutol: A Case Report and Literature Review

Ethambutol-induced optic neuropathy (EON) is a well-known complication, although low-dose ethambutol seldom causes EON. An 85-year-old man with non-tuberculous mycobacterial lung disease was taking antibiotics, including low-dose ethambutol. On day 85 of treatment, the diagnosis of EON was made. Despite prior discontinuation, his best corrected visual acuity drastically deteriorated from 20/17 (right eye) and 20/20 (left eye) to 20/330 (right eye) and 20/1,000 (left eye) within 3 weeks, and this symptom did not resolve. To our knowledge, there have been no reported cases with drastically progressing and irreversible EON even after the withdrawal of low-dose and short-term ethambutol.     

Bacterial concentration and composition in liquid baby formula and a baby drink consumed with an artificial nipple

ObjectivesTo clarify the characteristics and growth of bacteria that may infiltrate liquid baby formula during feeding and after storage for more than 3 h, the transfer of oral bacteria through artificial nipples, and bacterial survival in liquid baby formula and a baby drink were examined immediately after drinking and after storage at 4 °C for 12 h and 24 h.MethodsThirteen human subjects (aged 19–24 years) were asked to drink approximately 50 mL of liquid baby formula and a baby drink, via the artificial nipple of a baby bottle. Samples of the remaining liquid after storage at 4 °C for 12 h and 24 h were inoculated onto blood agar plates and incubated anaerobically at 37 °C for 7 days. Genomic DNA was extracted from individual colonies, and the bacterial species were identified by 16S rRNA gene sequencing.ResultsThe mean concentrations of bacteria in the liquid baby formula were (2.6 ± 2.8) × 10⁴ and (4.1 ± 6.6) × 10⁴ colony-forming unit/mL after storage at 4 °C for 12 h and 24 h, respectively. Streptococcus (43.2%), Veillonella (9.3%), and Schaalia (8.2%) species were recovered from the remaining liquid baby formula after storage at 4 °C for 12 h. In contrast, no bacteria were detected in the remaining baby drink after storage at 37 °C for 24 h.ConclusionsThe levels of bacteria immediately after drinking and after storage at 4 °C for 12 h or 24 h were similar, suggesting that remaining liquid baby formula may be preserved safely in a refrigerator for more than 3 h.     

Relationship between paraspinal muscle cross-sectional area and relative proprioceptive weighting ratio of older persons with lumbar spondylosis

[Purpose] The purpose of this study was to examine the relationship between the paraspinal muscle cross-sectional area and the relative proprioceptive weighting ratio during local vibratory stimulation of older persons with lumbar spondylosis in an upright position. [Subjects] In all, 74 older persons hospitalized for lumbar spondylosis were included. [Methods] We measured the relative proprioceptive weighting ratio of postural sway using a Wii board while vibratory stimulations of 30, 60, or 240 Hz were applied to the subjects’ paraspinal or gastrocnemius muscles. Back strength, abdominal muscle strength, and erector spinae muscle (L1/L2, L4/L5) and lumbar multifidus (L1/L2, L4/L5) cross-sectional areas were evaluated. [Results] The erector spinae muscle (L1/L2) cross-sectional area was associated with the relative proprioceptive weighting ratio during 60Hz stimulation. [Conclusion] These findings show that the relative proprioceptive weighting ratio compared to the erector spinae muscle (L1/L2) cross-sectional area under 60Hz proprioceptive stimulation might be a good indicator of trunk proprioceptive sensitivity.Key words: Relative proprioceptive weighting ratio, Erector spinae muscle cross-sectional area, Older persons with lumbar spondylosis     

Analysis of oral microbiota in Japanese oral cancer patients using 16S rRNA sequencing

ObjectivesIt is important to determine the cause of increasing oral cancer occurrence and mortality rates in Japan, because the mortality rate has recently decreased in other developed countries. The impact of microbiota in carcinogenesis, especially in the digestive tract has been reported. This study aimed to clarify the relationship between oral cancer and oral microbiota in Japanese patients.MethodsDNA was extracted from salivary samples of 60 oral cancer patients and 80 non-cancer individuals as controls. We performed metagenomic analysis using 16S rRNA amplicon sequencing. Statistical analysis in this study was performed using R (version 3.5.0).ResultsOral cancer patients showed higher α-diversity compared to the control group, and the β-diversity between the two groups differed significantly. Further, there was a significant difference in the abundance ratio of bacterial genera between the two groups. Peptostreptococcus, Fusobacterium, Alloprevotella, and Capnocytophaga were more abundant in the cancer group compared to the control, whereas Rothia and Haemophilus were less abundant (p < 0.01). A negative correlation in the microbiota composition was confirmed between the operational taxonomic units (OTU) of genus Rothia and T-stage progression using the TNM classification method. We performed logistic regression analysis to investigate the impact factor for the oral cancer group, and the result showed that Chao 1 index and sex are statistically significant variables.ConclusionsIn this study, we observed an increased bacterial diversity in oral cancer patients and found distribution changes for some bacteria.     

Spontaneous atrial fibrillation initiated by tyramine in canine atria with increased sympathetic nerve sprouting

Sympathetic Activation and Atrial Fibrillation. Background: Chronic left ventricular myocardial infarction (LVMI) promotes atrial and pulmonary veins (PV) sympathetic nerve sprouting. Objectives: To test the hypothesis that sympathetic stimulation with tyramine initiates atrial fibrillation (AF) by early afterdepolarization (EAD)‐mediated triggered activity at the left atrial PV (LAPV) junction. Methods: LVMI was created in 6 dogs and 6 dogs served as controls. Six to 8 weeks later the activation pattern of the isolated LAPV was optically mapped using dual voltage and intracellular Ca⁺² (Ca_i²⁺)‐sensitive epifluorescent dyes before and after tyramine (5 μM) perfusion. Results: Tyramine initiated spontaneous AF in 5 of 6 atria but none in the control group (P < 0.01). The AF was initiated by late phase 3 EAD‐mediated triggered activity that arose from the LAPV junction causing functional conduction block in LA, reentry, and AF. The AF was subsequently maintained by mixed reentrant and focal mechanisms. The EADs arose during the late phase 3, when the Ca_i²⁺ level was 64 ± 12% of the peak systolic Ca_i²⁺ transient amplitude, a property caused by tyramine's simultaneous shortening of the action potential duration and lengthening of the Ca_i²⁺ transient duration in the LVMI group but not in the control. Tyrosine hydroxylase and growth associated protein 43 positive nerve sprouts were significantly increased in the sinus node, LAA, and the LSPV in the LVMI group compared to control (P < 0.01). Conclusions: Increased atrial sympathetic nerve sprouts after LVMI makes the LAPV junction susceptible to late phase 3 EAD‐mediated triggered and AF during sympathetic stimulation with tyramine.     

Computational study on the polymerization reaction of d-aminopeptidase for the synthesis of d-peptides

Almost all natural proteins are composed exclusively of l-amino acids, and this chirality influences their properties, functions, and selectivity. Proteases can recognize proteins composed of l-amino acids but display lower selectivity for their stereoisomers, d-amino acids. Taking this as an advantage, d-amino acids can be used to develop polypeptides or biobased materials with higher biostability. Chemoenzymatic peptide synthesis is a technique that uses proteases as biocatalysts to synthesize polypeptides, and d-stereospecific proteases can be used to synthesize polypeptides incorporating d-amino acids. However, engineered proteases with modified catalytic activities are required to allow the incorporation of d-amino acids with increased efficiency. To understand the stereospecificity presented by proteases and their involvement in polymerization reactions, we studied d-aminopeptidase. This enzyme displays the ability to efficiently synthesize poly d-alanine-based peptides under mild conditions. To elucidate the mechanisms involved in the unique specificity of d-aminopeptidase, we performed quantum mechanics/molecular mechanics simulations of its polymerization reaction and determined the energy barriers presented by the chiral substrates. The enzyme faces higher activation barriers for the acylation and aminolysis reactions with the l-stereoisomer than with the d-substrate (10.7 and 17.7 kcal mol⁻¹ higher, respectively). The simulation results suggest that changes in the interaction of the substrate with Asn155 influence the stereospecificity of the polymerization reaction.

We studied the molecular mechanism of d-aminopeptidase for the synthesis of polypeptides incorporating d-amino acids.     

Perfusion with carbon monoxide does not affect extracellular glutamate in dialysates of the hippocampus of freely moving mice

Carbon monoxide (CO) produces several neurological effects, including cognitive, mood, and behavioral disturbance. Glutamate is thought to play a particularly important role in learning and memory. Thus, the present study was aimed at investigating the local effect of CO on the glutamate level in the hippocampus of mice using in vivo reverse microdialysis. Mice were perfused with Ringer’s solution (control) or CO (60–125?μM) in Ringer’s solution into the hippocampus via microdialysis probe. Dialysate samples were collected every 20?min, and then analyzed with high-performance liquid chromatography coupled to an electrochemical detector. The result revealed that the perfusion with CO had no significant effect on glutamate levels (p?=?0.316) as compared to the control group. This finding does not support a local CO rise as the cause of the increased glutamate level in the hippocampus of mice.