Meningoencephalomyelitis Caused by Brucella Canis: A Case Report and Literature Review.

Human brucellosis, one of the most common zoonoses worldwide, is rare in Japan. Brucella canis is the specific pathogen of human brucellosis carried by dogs. According to an epidemiological study of B. canis infection in Japan, B. canis is the specific pathogen of human brucellosis in dogs. We herein report a rare case of meningoencephalomyelitis caused by B. canis in a 68-year-old Japanese man. Neurobrucellosis was diagnosed based on a serum tube agglutination test and abnormal cerebrospinal fluid findings. The patient was started on targeted treatment with a combination of doxycycline and streptomycin. Although extremely rare, neurobrucellosis should be considered in patients with a fever of unknown origin and unexplained neurological symptoms.

Stereoselective protecting-group-free synthesis of alkyl glycosides using dibenzyloxy triazine type glycosyl donors.

Chemical O-glycosylation is a key step for the synthesis of sugar-containing molecules such as glycolipids. However, traditional carbohydrate chemistry is characterized by extensive use of protective groups, resulting in laborious manipulations and poor atom economy. Here, we present a protecting-group-free glycosylation strategy employing dibenzyloxy-1,3,5-triazin-2-yl glycosides (DBT-glycosides) as glycosyl donors. The DBT-glycosyl donors could be prepared directly through an alkaline nucleophilic substitution from unprotected sugars in aqueous media. The O-glycosylation of alcohols by using DBT-glycosyl donors has been carried out under mild hydrogenolytic conditions, affording the corresponding alkyl glycosides stereo-selectively in good yields.

Pharmacokinetic/pharmacodynamic analysis of vancomycin in patients with Enterococcus faecium bacteraemia: a retrospective cohort study.

OBJECTIVES: The trough concentration of vancomycin and the area under the concentration-time curve (AUC)/minimum inhibitory concentration (MIC) ratio are crucial in determining vancomycin efficacy against methicillin-resistant Staphylococcus aureus. However, the use of similar pharmacokinetic principles in determining antibiotic efficacy against other gram-positive cocci is lacking. We performed a pharmacokinetic/pharmacodynamic analysis (association of target trough concentration values and AUC/MIC with therapeutic outcome) of vancomycin in patients with Enterococcus faecium bacteraemia. METHODS: Between January 2014 and December 2021 we performed a retrospective cohort study of patients with E. faecium bacteraemia treated with vancomycin. Patients who received renal replacement therapy or had chronic kidney disease were excluded. Clinical failure, the primary outcome, was defined as a composite of 30-day all-cause mortality, vancomycin-susceptible infection requiring change of treatment, and/or recurrence. AUC24 was estimated using a Bayesian estimation approach based on an individual vancomycin trough concentration. The MIC for vancomycin was determined using a standardised agar dilution method. Additionally, classification was used to identify the vancomycin AUC24/MIC ratio associated with clinical failure. RESULTS: Of the 151 patients identified, 69 were enrolled. All MICs of vancomycin for E. faecium were ≤1.0 µg/mL. The AUC24 and AUC24/MIC ratio were not significantly different between the clinical failure group and the clinical success group (432±123 µg/mL/hour vs 488±92 µg/mL/hour; p=0.075). However, 7 of 12 patients (58.3%) in the clinical failure group and 49 of 57 patients (86.0%) in the clinical success group had a vancomycin AUC24/MIC ratio ≥389 (p=0.041). No significant association between trough concentration or AUC24 ≥600 µg/mL×hour and acute kidney injury was observed (p=0.365 and p=0.487, respectively). CONCLUSION: The AUC24/MIC ratio is associated with the clinical outcome of vancomycin administration in E. faecium bacteraemia. In Japan, where vancomycin-resistant enterococcal infection is rare, empirical therapy with a target AUC24 ≥389 should be recommended.

Clinical Features of Acute Ischemic Stroke Patients with Hypoesthesia as an Initial Symptom.

This study aimed to evaluate the clinical characteristics of acute ischemic stroke (AIS) patients who experienced hypoesthesia as the initial symptom. We retrospectively analyzed the medical records of 176 hospitalized AIS patients who met our inclusion and exclusion criteria and evaluated their clinical features and MRI findings. Among this cohort, 20 (11%) patients presented with hypoesthesia as the initial symptom. MRI scans of these 20 patients identified lesions in the thalamus or pontine tegmentum in 14 and brain lesions at other sites in 6. The 20 hypoesthesia patients had higher systolic (p = 0.031) and diastolic blood pressure (p = 0.037) on admission, and a higher rate of small-vessel occlusion (p < 0.001) than patients without hypoesthesia. The patients with hypoesthesia had a significantly shorter average hospital stay (p = 0.007) but did not differ significantly from those without hypoesthesia in National Institutes of Health Stroke Scale scores on admission (p = 0.182) or the modified Rankin Scale scores for neurologic disability on discharge (p = 0.319). In the patients with acute onset hypoesthesia, high blood pressure, and neurological deficits were more likely to be due to AIS than other causes. Since most of the lesions in AIS patients with hypoesthesia as the initial symptom were found to be small, we recommend performing MRI scans with such patients to confirm AIS.

Post-Stroke Pneumonia in Real-World Practice: Background, Microbiological Examination, and Treatment.

Post-stroke pneumonia (PSP) has an impact on acute ischemic stroke (AIS). Although predictive scores for PSP have been developed, it is occasionally difficult to predict. Clarifying how PSP was treated after its onset in clinical practice is important. Admitted patients with AIS over a 2-year period were retrospectively reviewed. Of 281 patients with AIS, 24 (8.5%) developed PSP. The integer-based pneumonia risk score was higher in patients with PSP. The onset of PSP was frequently seen up to the 4th day of hospitalization. Of patients with PSP, sputum examination yielded Geckler 4 or 5 in only 8.3%. Angiotensin-converting enzyme inhibitor (ACE-I) was more frequently administered to patients with PSP; however, all these cases were started with ACE-I following PSP onset. Nasogastric tubes (NGTs) were inserted in 16 of the patients with PSP, of whom 11 were inserted following PSP onset. Multivariate analysis showed that PSP onset was a poor prognostic factor independent of the female sex, urinary tract infection, and National Institutes of Health Stroke Scale. PSP treatment would benefit from the administration of antimicrobials and ACE-I, as well as NGT insertion. To select effective agents for PSP and evaluate the indications for NGT insertion, further case studies are needed.

Use of the FilmArray® Meningitis/Encephalitis panel to detect pathogenic microorganisms in cerebrospinal fluid specimens: a single-center retrospective study.

OBJECTIVE: Meningitis and encephalitis are neurological emergencies requiring rapid diagnosis and treatment. The performance of the FilmArray® Meningitis/Encephalitis (ME) panel, a multiplex polymerase chain reaction test, and conventional methods for diagnosing meningitis and encephalitis was compared. METHODS: This retrospective study assessed 20 patients diagnosed with meningitis or encephalitis according to clinical symptoms and laboratory examination findings between January 2018 and December 2019. The results of the FilmArray® ME panel were compared with those of conventional methods. RESULTS: Pathogens were identified in 11 (55%) patients using the FilmArray® ME panel and in nine (45%) patients using conventional methods. The test identified herpes simplex virus type 1 in two patients, herpes simplex virus type 2 in one, varicella-zoster virus in four, Streptococcus pneumoniae in three, and Cryptococcus neoformans in one. Furthermore, additional pathogens were detected (n = 1, S. pneumoniae and n = 1, varicella-zoster virus). The median times to pathogen identification were 2 hours using the FilmArray® ME panel and 96 hours with conventional methods. CONCLUSIONS: The sensitivity of the FilmArray® ME panel for rapidly detecting the most common pathogens was similar to that of conventional methods. Hence, this method could decrease the time to definitive diagnosis and treatment initiation.

[Cryptococcal Meningitis with Inadequate Response to Antifungal Therapy or Drug-Induced Side Effects That Make It Difficult to Continue Treatment: Eleven Clinical Issues in Medical Practice].

Cryptococcal meningoencephalitis is mainly caused by Cryptococcus neoformans and accounts for 90% of fungal meningitis cases in Japan. Cryptococcal meningoencephalitis is a rare disease, and similar to tuberculosis meningitis. It often exhibits subacute or chronic progression symptoms such as headache, fever, coma, personality changes, and memory disturbance. Cryptococcal meningoencephalitis often develops in immunosuppressed hosts, but can sometimes occur in healthy individuals, and the mortality rate is 10-25%, indicating a poor prognosis. For the treatment of cryptococcal meningoencephalitis, introduction therapy using a combination of liposomal amphotericin B and flucytosine is recommended. However, in practice, cryptococcal meningoencephalitis is refractory and often requires prolonged treatment; therefore, it is the most difficult to treat among the central nervous system infections. We discuss the following 11 issues: I. Sustainability of first-line treatments, II. Treatment options in case of decreased renal function, III. Association with increased intracranial pressure IV. Causes of visual impairment, V. Necessary steps when symptoms/laboratory findings worsen during antifungal treatment, VI. Cerebral infarction, VII. Difficulty in controlling underlying and comorbid diseases, VIII. Indications for lumbar and ventricular drainage (Ommaya reservoir placement), IX. Pros and cons of concomitant use of corticosteroids, X. Treatment evaluation index: usefulness of head MRI, and XI. Determining the end of treatment and the need for preventive medication.

Locked-in Syndrome Due to Meningovascular Syphilis: A Case Report and Literature Review.

We herein report a 46-year-old man presenting with locked-in syndrome secondary to meningovascular syphilis. Brain magnetic resonance imaging (MRI) demonstrated multiple acute infarctions in the left ventromedial pons, right basis pontis, and left basal ganglia. His locked-in syndrome was hypothesized to have been caused by thrombosis of the small paramedian branches of the basilar artery due to syphilitic arteritis. This is a unique case of bilateral ventromedial pontine infarction caused by meningovascular syphilis that presented as locked-in syndrome. Meningovascular syphilis should be included in the differential diagnosis of uncommon stroke, particularly in young men.

Living-Cell Diffracted X-ray Tracking Analysis Confirmed Internal Salt Bridge Is Critical for Ligand-Induced Twisting Motion of Serotonin Receptors.

Serotonin receptors play important roles in neuronal excitation, emotion, platelet aggregation, and vasoconstriction. The serotonin receptor subtype 2A (5-HT2AR) is a Gq-coupled GPCR, which activate phospholipase C. Although the structures and functions of 5-HT2ARs have been well studied, little has been known about their real-time dynamics. In this study, we analyzed the intramolecular motion of the 5-HT2AR in living cells using the diffracted X-ray tracking (DXT) technique. The DXT is a very precise single-molecular analytical technique, which tracks diffraction spots from the gold nanocrystals labeled on the protein surface. Trajectory analysis provides insight into protein dynamics. The 5-HT2ARs were transiently expressed in HEK 293 cells, and the gold nanocrystals were attached to the N-terminal introduced FLAG-tag via anti-FLAG antibodies. The motions were recorded with a frame rate of 100 µs per frame. A lifetime filtering technique demonstrated that the unliganded receptors contain high mobility population with clockwise twisting. This rotation was, however, abolished by either a full agonist α-methylserotonin or an inverse agonist ketanserin. Mutation analysis revealed that the "ionic lock" between the DRY motif in the third transmembrane segment and a negatively charged residue of the sixth transmembrane segment is essential for the torsional motion at the N-terminus of the receptor.

Tilting and rotational motions of silver halide crystal with diffracted X-ray blinking.

The dynamic properties of crystalline materials are important for understanding their local environment or individual single-grain motions. A new time-resolved observation method is required for use in many fields of investigation. Here, we developed in situ diffracted X-ray blinking to monitor high-resolution diffraction patterns from single-crystal grains with a 50 ms time resolution. The diffraction spots of single grains of silver halides and silver moved in the θ and χ directions during the photolysis chemical reaction. The movements of the spots represent tilting and rotational motions. The time trajectory of the diffraction intensity reflecting those motions was analysed by using single-pixel autocorrelation function (sp-ACF). Single-pixel ACF analysis revealed significant differences in the distributions of the ACF decay constants between silver halides, suggesting that the motions of single grains are different between them. The rotational diffusion coefficients for silver halides were estimated to be accurate at the level of approximately 0.1 to 0.3 pm2/s. Furthermore, newly formed silver grains on silver halides correlated with their ACF decay constants. Our high-resolution atomic scale measurement-sp-ACF analysis of diffraction patterns of individual grains-is useful for evaluating physical properties that are broadly applicable in physics, chemistry, and materials science.

A Case of High Altitude Cerebral Edema With a Prolonged Motivational Deficit.

We report a case of prolonged motivational deficit as a sequela of high altitude cerebral edema (HACE), the most severe form of neuropsychiatric dysfunction arising from traveling to high altitude. Magnetic resonance imaging of the brain showed hyperintense lesions in the globi pallidi bilaterally on T2-weighted images. Single-photon emission computed tomography showed hypoperfusion in dorsolateral and orbital prefrontal cortices bilaterally and in the anterior cingulate cortex. This case suggests that a prolonged motivational deficit can occur in patients with HACE. The case may also suggest that HACE can cause network disturbances between the prefrontal cortex and the globi pallidi.

Ruptured long intramedullary spinal cord abscess successfully treated with antibiotic treatment.

Intramedullary spinal cord abscess (ISCA) is an extremely rare infection of the central nervous system. We report a 17-year old man with ISCA that suggested rupture confirmed by magnetic resonance imaging (MRI). The patient presented with meningeal signs, severe paraplegia, sensory impairment with a sensory level, and urinary retention. The cerebrospinal fluid (CSF) study showed pleocytosis with polymorphonuclear cells and a decreased glucose level suggesting bacterial meningitis. Computed tomography showed maxillary sinusitis and a lower respiratory tract infection. Spinal MRI showed an ISCA from Th5 to Th12. Part of the abscess seemed to have ruptured into the medullary cavity. Streptococcus intermedius was cultured from CSF, sputum, and the maxillary sinus abscess. It appeared that Streptococcus intermedius transferred from the respiratory tract to the spinal cord hematogenously, formed the ISCA, and the ISCA ruptured. The patient was treated with ampicillin, vancomycin, and meropenem. After 56 days of treatment, he could walk with a walker. In the present case, the MRI findings were helpful for early diagnosis and follow-up of the pathogenic condition. Although the present case suggested rupture of ISCA, he recovered with antibiotic therapy alone. This suggested earlier diagnosis with MRI and aggressive antibiotic therapy appear to be critical factors that determine the prognosis of patients with ISCA.

X-ray-based living-cell motion analysis of individual serotonin receptors.

G protein-coupled receptors (GPCRs) are seven-transmembrane proteins, which transmit extracellular signals inside cells via activating G proteins. GPCRs are involved in a wide variety of physiological functions, such as signal sensing, immune system processes, and neurotransmission. Although the structures and functions of GPCRs have been well studied, little has been known about their real-time dynamics on live cells. In this study, we used Diffracted X-ray Tracking (DXT) and Diffracted X-ray Blinking (DXB) techniques for analysis. These methods are very precise single-molecular analytical techniques that elucidate protein dynamics by analyzing the diffraction spots from the gold nanocrystals labeled on the protein surface. DXT tracks diffraction spot movements, whereas DXB analyzes continuation of signals by calculating the autocorrelation function of each pixel from the recorded data. Serotonin receptor subtype 2A (5-HT2A receptors) were transiently expressed on HEK 293 cells, and the gold nanocrystals were attached to the N-terminally introduced FLAG-tag via anti-FLAG antibodies. Fast- and mid-range motions were recorded by DXT with 100µs and 1.25 ms/frame rate, respectively. Slow-range motion was obtained using the DXB method with 100 ms/frame rate. An agonist interestingly suppressed the fluctuations of 5-HT2A receptors at the microsecond-ranged fast measurement. On the contrary, the motion was enhanced by the agonist in the hundred-millisecond-ranged slow time scale. These dual-natured data may suggest that we succeeded in extracting different modes of receptor's motion on live cells; microsecond ranged fluctuation on the cell membrane, and millisecond-ranged dynamic movement comprising interactions with intracellular signaling molecules.

Coaxial semi-dipole antenna microwave feeding on electron cyclotron resonance multicharged ion source.

How to produce multicharged ions efficiently on an electron cyclotron resonance ion source (ECRIS) has been investigated at Osaka University. Notably, in recent years, we have focused on heating by new resonance superimposing to electron cyclotron resonance (ECR) plasma. To evaluate its efficiency, we need to know the maximum efficiency of heating with ECR alone, and then, further optimization of ECR heating is required. In consideration of wave propagation, we installed the coaxial semi-dipole antenna on the mirror end along the geometrical axis of the vacuum chamber. We aim at exciting the strength of right-hand polarization (RHP) waves for efficient ECR because RHP waves give rise to ECR. We measure plasma parameters by Langmuir probes and charge state distributions (CSDs) of the extracted ion beams and investigate their qualitative tendencies to incident microwave powers and pressures. We compare the qualitative trend of ion beams and their CSD on microwave power in the case of both the microwave feeding system by the coaxial semi-dipole antenna and that by the rod antenna. Differences between the microwave feeding system before improving and then after upgrading are made clear.

Improving transport and optimizing deceleration of ion beams from electron cyclotron resonance multicharged ion sources.

Electron cyclotron resonance ion sources (ECRISs) are widely applied for ion beam applications, e.g., plasma processing, cancer therapy, and ion engine of an artificial satellite. In our ECRIS, we aim at producing and extracting various ion beams from this device, in particular, Xeq+ ion beams at low energy. In the aerospace engineering field, there are problems of accumulated damages on various component materials caused by low energy of Xe ions from the engine. There are not enough experimental sputtering data for satellite materials at the Xeq+ in the low energy region. Then, we are trying to investigate the sputtering yield experimentally by irradiating the low energy Xe ion beams. To perform this experiment, it is necessary to acquire a certain amount of beam current with low energy. Then, we generate the low energy ion beams by the following steps: First, the ion beams are extracted from the ECRIS at high voltage. Next, these are transported to an ion beam irradiation system (IBIS). Finally, the ion beams are decelerated by the deceleration voltage in the IBIS. We adjusted the beamline. We measure the characteristics of the transport efficiency and decelerated ion beam currents. In this paper, we describe the experimental setup using an existing ECRIS for decelerated heavy ion beams and the results of decelerated ion beam currents.

Upper hybrid resonance heating experiments by X-mode microwaves on electron cyclotron resonance ion source.

We have considered the accessibility condition of electromagnetic and electrostatic waves propagating in an electron cyclotron resonance (ECR) ion source (ECRIS) plasma and then investigated experimentally their correspondence relationships with production of multicharged ions. It has been clarified that there exists an efficient configuration of ECR zones for producing multicharged ion beams and has been suggested that a new resonance, i.e., upper hybrid resonance (UHR), must have occurred. We have been trying to perform advanced experiments with 4-6 GHz X-mode microwaves to the 2.45 GHz ECRIS plasma, and we have succeeded in enhancing the production of multicharged ions by launching X-mode microwaves of these bands. Furthermore, at the same time, we have observed sharp increases in electron energy distribution functions in the ECRIS plasma by means of probe methods. It has been concluded that the UHRs must have occurred when applying multiplex microwaves with their frequencies away from those frequencies for ECR in the ECRIS. In this paper, we will describe in brief the theoretical background and the results of these new experiments.

Improving multipole magnets and background vacuum conditions on electron cyclotron resonance ion sources.

Electron cyclotron resonance ion sources (ECRISs) are used in various fields such as accelerator physics, engineering, cancer therapy, and ion engines in the satellite. We are aiming to improve the production of multicharged ions efficiently at the point of view from the length of multipole magnets and vacuum conditions in the ECRIS. The diameter of the connection pipe between the main chamber and diffusion pump was made larger to improve vacuum conductance. Moreover, the length of multipole magnets with the direction along the geometrical axis in the ECRIS was extended. The effects of these improvements are investigated experimentally to measure the pressure in the vacuum chamber, beam intensity, charge state distributions of extracted ion beams, and plasma parameters. The purity of extracted ion beams and magnetic confinement have been enhanced. These results are expected to have positive effects on the production of various species and synthesized ion beams, e.g., production of iron endohedral fullerene in the future experiments in the ECRIS.

Nationwide survey of influenza-associated acute encephalopathy in Japanese adults.

BACKGROUND: Knowledge of adult patients with influenza-associated acute encephalopathy (IAE) is limited. We conducted a detailed survey to investigate the prevalence, clinical features, associated outcomes, and prognostic factors in adult IAE patients. METHOD: A nationwide questionnaire on IAE patients was sent to the departments of Internal Medicine, Neurology, Neurosurgery, and Emergency and Critical Care at all hospitals with ≥200 beds in Japan. RESULTS: 118 patients were diagnosed with IAE during the 2013/14 to 2015/16 influenza seasons, and the estimated annual incidence of IAE in Japanese adults was 0.98/1000,000 population. 44 patients were subsequently enrolled in the detailed study. 93% of patients exhibited disturbance of consciousness. Convulsions and delirious behavior were present in 26% and 40% of patients, respectively. 65% of patients received pulse corticosteroid therapy with methylprednisolone and 21% of patients received intravenous gamma-globulin therapy. 63% of patients achieved a good recovery, but 7% died. Multiple logistic regression analysis revealed that plasma glucose level demonstrated a statistically significant association with poor outcome. CONCLUSION: This nationwide survey provided data for the annual incidence and clinical features of IAE in Japanese adults. Hyperglycemia was indicated as an independent predictor of poor prognosis in IAE patients and reflected systemic hypercytokinemia in IAE pathogenesis.

[Dementia in Patients with Central Nervous System Mycosis].

Central nervous system (CNS) mycosis is a potentially life-threatening but treatable neurological emergency. CNS mycoses progress slowly and are sometimes difficult to distinguish from dementia. Though most patients with CNS mycosis have an underlying disease, such as human immunodeficiency virus (HIV) infection, cancer, diabetes mellitus, and/or use of immunosuppressants, cryptococcosis can occur in non-immunosuppressed persons. One of the major difficulties in accurate diagnosis is to detect the pathogen in patients' cerebrospinal fluid (CSF) cultures. Thus, the clinical diagnosis is often made by combining circumstantial evidence, including mononuclear cell-dominant pleocytosis with low glucose and protein elevation in the CSF, as well as positive results from an antigen-based assay and a (1-3)-beta-D-glucan assay using plasma and/or CSF. Polymerase chain reaction (PCR)-based diagnostics, which are not performed as routine examinations and are mostly performed as part of academic research in Japan, are sensitive tools for the early diagnosis of CNS mycosis. Mognetic resonance imaging (MRI) is useful to assess the complications of fungal meningitis, such as abscess, infarction, and hydrocephalus. Clinicians should realize the advantages and disadvantages of these diagnostic tools. Early and accurate diagnosis, including identification of the particular fungal species, enables optimal antifungal treatment that produces good outcomes in patients with CNS mycosis.