Manganese-enhanced magnetic resonance imaging detects activation of limbic structures in response to auditory stimuli of different frequencies.

PURPOSE: As we are exposed to stress on a daily basis, it is important to detect and treat stress during the subclinical period. However, methods to quantify and confirm stress are currently unavailable, and the detection of subclinical stressors is difficult. This study aimed to determine whether manganese-enhanced magnetic resonance imaging (MEMRI) could be used to assess stress in rat brains. METHODS: We exposed male Wistar/ST rats bred in a specific pathogen-free environment to ultrasound stimuli (22 kHz and 55 kHz) for 10 days and then assessed brain activities using MEMRI, the light/dark box test, and ΔFosB immunohistochemical staining. RESULTS: In the MEMRI assessments, exposure at 22 kHz activated the periaqueductal gray, while exposure at 55 kHz specifically enhanced activity in the nucleus accumbens core and the orbitofrontal cortex. The exploratory behavior of the 55-kHz group increased sharply, while that of the 22-kHz group showed a lower exploratory value. ΔFosB expression increased in the orbitofrontal cortex, nucleus accumbens, periaqueductal gray, and amygdaloid nucleus in the 22-kHz group. CONCLUSION: Ultrasound stimuli at 22 kHz suppressed weight gain in rats and excessive ΔFosB induction in the nucleus accumbens caused excessive sensitization of the neural circuit, thereby contributing to pathological behavior. We thus demonstrated that MEMRI can be useful to objectively assess the pathophysiology of stress-related disorders.

Dopamine transporter single-photon emission computed tomography-derived radiomics signature for detecting Parkinson's disease.

BACKGROUND: We hypothesised that the radiomics signature, which includes texture information of dopamine transporter single-photon emission computed tomography (DAT-SPECT) images for Parkinson's disease (PD), may assist semi-quantitative indices. Herein, we constructed a radiomics signature using DAT-SPECT-derived radiomics features that effectively discriminated PD from healthy individuals and evaluated its classification performance. RESULTS: We analysed 413 cases of both normal control (NC, n = 101) and PD (n = 312) groups from the Parkinson's Progression Markers Initiative database. Data were divided into the training and two test datasets with different SPECT manufacturers. DAT-SPECT images were spatially normalised to the Montreal Neurologic Institute space. We calculated 930 radiomics features, including intensity- and texture-based features in the caudate, putamen, and pallidum volumes of interest. The striatum uptake ratios (SURs) of the caudate, putamen, and pallidum were also calculated as conventional semi-quantification indices. The least absolute shrinkage and selection operator was used for feature selection and construction of the radiomics signature. The four classification models were constructed using a radiomics signature and/or semi-quantitative indicator. Furthermore, we compared the classification performance of the semi-quantitative indicator alone and the combination with the radiomics signature for the classification models. The receiver operating characteristics (ROC) analysis was used to evaluate the classification performance. The classification performance of SURputamen was higher than that of other semi-quantitative indicators. The radiomics signature resulted in a slightly increased area under the ROC curve (AUC) compared to SURputamen in each test dataset. When combined with SURputamen and radiomics signature, all classification models showed slightly higher AUCs than that of SURputamen alone. CONCLUSION: We constructed a DAT-SPECT image-derived radiomics signature. Performance analysis showed that the current radiomics signature would be helpful for the diagnosis of PD and has the potential to provide robust diagnostic performance.

The utility of using TACE-assisted software with CBCT in colonic diverticular bleeding without extravascular leakage.

The utility of three-dimensional (3D) imaging with cone-beam computed tomography (CBCT) during interventional radiology (IVR) in colonic diverticular bleeding was compared to that of contrast-enhanced computed tomography (CECT). Additionally, to identify the responsible vessels in the absence of extravascular leakage using digital subtraction angiography, we examined the detection rate using software conventionally applied to transcatheter arterial chemoembolization (TACE). The 3D images obtained by CECT before IVR did not clearly show the destroyed vessels, whereas the 3D images obtained by CBCT during IVR clearly depicted the peripheral vessels. The TACE-assisted software identified the responsible vessels with a high probability, even in cases without extravascular leakage. CBCT could delineate vascular positions more accurately than CECT. Moreover, 80% of the responsible vessels could be delineated using the software; however, caution should be exercised as results may differ depending on the positioning of the region of interest.

Sinobronchial Syndrome Patients with Suspected Non-Tuberculous Mycobacterium Infection Exacerbated by Exophiala dermatitidis Infection.

Background: Exophiala dermatitidis is an environmental black fungus that rarely causes respiratory infections, yet its pathophysiological features and treatment regimens have not been established. Case Series: Two cases of exacerbations of chronic bronchitis and sinusitis due to E. dermatitidis infection in Japan are presented. Both patients were women, and non-tuberculous Mycobacterium (NTM) infection was suspected based on chest radiological findings, but E. dermatitidis was detected from bronchial lavage fluid and nasal mucus, respectively. Both cases were successfully treated by antifungal agents such as liposomal amphotericin B, voriconazole, and itraconazole, but clarithromycin, rifampicin, ethambutol, and sitafloxacin for NTM were not effective. Conclusion: E. dermatitidis can become a respiratory pathogen, especially in patients with chronic sinobronchial syndrome.

ΔHR/ΔWR derived from CPET; A novel predictor of 'off' symptom in Parkinson's disease.

INTRODUCTION: Chronotropic incompetence (CI) is broadly defined as the inability of the heart to increase its rate commensurate with increased activity. In this study, we tried to clarify the link between CI and UPDRS part II (off-on), which was calculated by subtracting part II (on) from part II (off), in patients with Parkinson's disease (PD). METHODS: Thirty-six hospitalized patients were examined by using cardiopulmonary exercise testing (CPET) for exercise tolerance (ΔVO2/ΔWR and peak VO2/W) and the presence of CI (ΔHR/ΔWR), and using electrocardiogram for heart rate variability. RESULTS: We originally divided the patients into three groups; Group I (ΔHR/ΔWR x100 <15) (N = 3), Group II (15≥, <60) (N = 28), Group III (>60) (N = 5). Since Group I and III were significantly smaller and older than Group II, we focused and divided into two groups; Group II CI (+), the PD patients with CI (15≤ ΔHR/ΔWR x100 <35), and Group II CI (-), those patients without that (35≤ ΔHR/ΔWR x100 <60). ΔVO2/ΔWR and peak VO2/W in CI (+) patients was lower than CI (-) (P = 0.022 and P = 0.096, respectively). HF power (parasympathetic activity) tends to be decreased, whereas LF/HF ratio (sympathetic activity) was increased in CI (+) patients as compared with CI (-). The UPDRS part II (off-on) of CI (+) patients was significantly higher than CI (-) (P = 0.023). CONCLUSIONS: In PD patients, the difference between 'on' and 'off' in activities of daily living might be predicted by using ΔHR/ΔWR x100 obtained from CPET as an index.

Detection of Representative Mutant Strains and a Case of Prolonged Infection by SARS-CoV-2 with Spike 69/70 Deletion in Japan.

There is a concern that the spread of mutant strains of SARS-CoV-2 will increase the number of severe COVID-19 patients and weaken vaccine effectiveness in the world. The mutants of the spike region of SARS-CoV-2, such as N501Y, E484K, P681H, and deletion H69/V70 (del 69/70), were studied in 25 COVID-19 patients admitted from December 2020 to April 2021; there were no patients with N501Y and P681H, but nine patients had E484K alone. Their symptoms, laboratory data, and course of their disease were similar to those of the other patients with the non-mutant virus. One patient with del69/70 alone showed prolonged inflammation, viral excretion, and late exacerbation 18 days after onset. Del69/70 may be independently associated with evasion of immunity, as previously reported, and it is present in Japan.

Severe Pulmonary Mycobacterium abscessus Cases Due to Co-Infection with Other Microorganisms Well Treated by Clarithromycin and Sitafloxacin in Japan.

BACKGROUND: Mycobacterium abscessus frequently causes severe infections, yet its pathophysiological features and treatment regimens have not been established. CASE REPORT: We present five cases of severe pneumonia due to Mycobacterium abscessus infection in Japan. All cases were diabetic patients, with possible acceleration to pneumonia due to co-infection with other microorganisms. However, following a short period of hospitalization and combination therapy with intravenous imipenem/cilastatin and amikacin, all the cases were successfully treated as outpatients with oral clarithromycin and sitafloxacin. CONCLUSION: M. abscessus infections can become severe in the presence of diabetes mellitus and co-infection with other chronic infectious organisms. Sitafloxacin might be a key drug in the treatment of M. abscessus infection in future.

Dectin-2-mediated initiation of immune responses caused by influenza virus hemagglutinin.

Antigen-presenting cells express pattern recognition receptors (PRRs), which sense pathogen-associated molecular patterns from microorganisms and lead to the induction of inflammatory responses. C-type lectin receptors (CLRs), the representative PRRs, bind to microbial polysaccharides, among which Dectin-2 and Mincle recognize mannose-containing polysaccharides. Because influenza virus (IFV) hemagglutinin (HA) is rich in mannose polysaccharides, Dectin-2 or Mincle may contribute to the recognition of HA. In this study, we addressed the possible involvement of Dectin-2 and Mincle in the viral recognition and the initiation of cytokine production. Interleukin (IL)-12p40 and IL-6 production by bone marrow-derived dendritic cells (BM-DCs) upon stimulation with HA was significantly reduced in Dectin-2 knockout (KO) mice compared to wild-type (WT) mice whereas there was no difference between WT mice and Mincle KO mice. BM-DCs that were treated with Syk inhibitor resulted in a significant reduction of cytokine production upon stimulation with HA. The treatment of BM-DCs with methyl-α-D-mannopyranoside (ManP) also led to a significant reduction in cytokine production by BM-DCs that were stimulated with HA, except for the A/H1N1pdm09 subtype. IL-12p40 and IL-6 synthesis by BM-DCs was completely diminished upon stimulation with HA treated with concanavalin A (ConA)-bound sepharose beads. Finally, GFP expression was detected in reporter cells that were transfected with the Dectin-2 gene, but not with the Mincle gene, when stimulated with HA derived from the A/H3N2 subtype. These data suggested that Dectin-2 may be a key molecule as the sensor for IFV to initiate the immune response and regulate the pathogenesis of IFV infection.

Effect of CARD9 Deficiency on Neutrophil-Mediated Host Defense against Pulmonary Infection with Streptococcus pneumoniae.

Streptococcus pneumoniae is a major causative bacterium of community-acquired pneumonia. Dendritic cell-associated C-type lectin-2 (dectin-2), one of the C-type lectin receptors (CLRs), was previously reported to play a pivotal role in host defense against pneumococcal infection through regulating phagocytosis by neutrophils while not being involved in neutrophil accumulation. In the present study, to elucidate the possible contribution of other CLRs to neutrophil accumulation, we examined the role of caspase recruitment domain-containing protein 9 (CARD9), a common adaptor molecule for signal transduction triggered by CLRs, in neutrophilic inflammatory response against pneumococcal infection. Wild-type (WT), CARD9 knockout (KO), and dectin-2 KO mice were infected intratracheally with pneumococcus, and the infected lungs were histopathologically analyzed to assess neutrophil accumulation at 24 h postinfection. Bronchoalveolar lavage fluids (BALFs) were collected at the same time point to count the neutrophils and assess the production of inflammatory cytokines and chemokines. Neutrophil accumulation was significantly decreased in CARD9 KO mice, but not in dectin-2 KO mice. Tumor necrosis factor alpha (TNF-α), keratinocyte-derived chemokine (KC), and macrophage inflammatory protein-2 (MIP-2) production in BALFs were also attenuated in CARD9 KO mice, but not in dectin-2 KO mice. Production of TNF-α and KC by alveolar macrophages stimulated with pneumococcal culture supernatants was significantly attenuated in CARD9 KO mice, but not in dectin-2 KO mice, compared to that in each group's respective control mice. In addition, pneumococcus-infected CARD9 KO mice showed larger bacterial burdens in the lungs than did WT mice. These data indicate that CARD9 is required for neutrophil migration after pneumococcal infection, as well as inflammatory cytokine and chemokine production by alveolar macrophages, and suggest that a CLR distinct from dectin-2 may be involved in this response.

Limited Role of Mincle in the Host Defense against Infection with Cryptococcus deneoformans.

Cryptococcus deneoformans is an opportunistic fungal pathogen that frequently causes fatal meningoencephalitis in patients with impaired cell-mediated immune responses such as AIDS. Caspase-associated recruitment domain 9 (CARD9) plays a critical role in the host defense against cryptococcal infection, suggesting the involvement of one or more C-type lectin receptors (CLRs). In the present study, we analyzed the role of macrophage-inducible C-type lectin (Mincle), one of the CLRs, in the host defense against C. deneoformans infection. Mincle expression in the lungs of wild-type (WT) mice was increased in the early stage of cryptococcal infection in a CARD9-dependent manner. In Mincle gene-disrupted (Mincle KO) mice, the clearance of this fungus, pathological findings, Th1/Th2 response, and antimicrobial peptide production in the infected lungs were nearly comparable to those in WT mice. However, the production of interleukin-22 (IL-22), tumor necrosis factor alpha (TNF-α), and IL-6 and the expression of AhR were significantly decreased in the lungs of Mincle KO mice compared to those of WT mice. In in vitro experiments, TNF-α production by bone marrow-derived dendritic cells was significantly decreased in Mincle KO mice. In addition, the disrupted lysates of C. deneoformans, but not those of whole yeast cells, activated Mincle-triggered signaling in an assay with a nuclear factor of activated T cells (NFAT)-green fluorescent protein (GFP) reporter cells expressing this receptor. These results suggest that Mincle may be involved in the production of Th22-related cytokines at the early stage of cryptococcal infection, although its role may be limited in the host defense against infection with C. deneoformans.

Mycobacterium abscessus Associated Peritonitis with CAPD Successfully Treated Using a Linezolid and Tedizolid Containing Regimen Suggested Immunomodulatory Effects.

BACKGROUND Mycobacterium abscessus is one of the most important mycobacteria, but its associated peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD) appears relative rare, and the treatment regimen of the antibiotics are still unclear. CASE REPORT A 38-year-old female with chronic glomerulonephritis on CAPD who was diagnosed with M. abscessus-associated peritonitis. Symptoms exacerbated despite treatment with a 3-antibiotic regimen combining clarithromycin, imipenem/cilastatin (IPM/CS), and minocycline (MINO). However, after changing IPM/CS and MINO to linezolid (LZD), her condition and inflammation improved, and she was able to be maintained on oral tedizolid (TZD). CONCLUSIONS Oxazolidinones such as LZD and TZD might be candidate antibiotics for the treatment of M. abscessus-associated diseases with chronic renal failure due to their immunomodulatory effects and non-renal excretion.

Contrast-enhanced magnetic resonance imaging evidence for the role of astrocytic aquaporin-4 water channels in glymphatic influx and interstitial solute transport.

The present study aimed to confirm the hypothesis that aquaporin-4 water channels (AQP4) control solute transition into the brain parenchyma using image analysis of gadolinium-based contrast agents (GBCAs) dissolved in cerebrospinal fluid (CSF) on dynamic contrast-enhanced magnetic resonance imaging (dyMRI) in live rats. Ten male Wistar ST rats were included in the study. Whole-brain dyMRI was performed for approximately 120 min after intrathecal infusion of gadolinium tetraazacyclododecane tetraacetic acid (Gd-DOTA). TGN-020, a specific AQP4 inhibitor, was used to inhibit the function of AQP4 in one group of rats (TGN-020 group, n = 4). The dyMRI after Gd-DOTA infusion in the rat, who were not treated with TGN-020 (control group, n = 6) revealed marked contrast-enhancement over time based on the distribution of the GBCA in the lateral regions of the brain surface, the ventral regions, the regions adjacent to the subarachnoid space, and the deep subcortical region. In contrast, smaller signal enhancement of the same regions in the TGN-020 group indicated poor distribution of the GBCA, suggesting a physiological consequence of the AQP4 inhibition by TGN-020. In this study, a close relationship between the function of AQP4 and the solute dynamics in the CSF was revealed from the distribution pattern of GBCA visualized in dyMRI in the living rat brain by administration of AQP4-selective inhibitor. This finding suggests that AQP4 functions to drive a glymphatic influx to transition molecules dissolved in the CSF from the subarachnoid space into the extracellular space of the brain parenchyma.

Nonuniform sampling pitch acquisition method in myocardial single-photon emission computed tomography.

BACKGROUND: Single-photon emission computed tomography is a tomographic imaging method that acquires a projection image by rotating a gamma camera around by 380° or 180°. For myocardial single-photon emission computed tomography, 180° acquisition is common, but it has limitations including an incomplete reconstruction, which can distort the resulting image. It is possible to produce a complete reconstruction using 360° acquisition, but the testing time is long and is burdensome to patients. METHODS: The nonuniform sampling pitch acquisition (NUSPA) method devised in this study involves reducing the total sampling count using NUSPA that reduces the sampling pitch in the range in which the gamma cameras are closer to the myocardium (RAO45-LPO45) and increases it elsewhere. RESULTS AND CONCLUSION: The NUSPA-1 method based on a 6° sampling pitch had 20 views fewer than 360° acquisition. In addition, the NUSPA-2 method based on a 3.75° sampling pitch had 60 views fewer than 360° acquisition, considerably reducing the testing time. The acquired sinograms from the NUSPA methods were subjected to nonuniform rational B-spline surface interpolation processing, producing data with a uniform sampling pitch, after which image reconstruction was performed. The images after nonuniform rational B-spline interpolation for both the line sources and heart-liver phantom investigated in this study were not found to have the distortion observed from 180° acquisition or a count decrease at the center, resulting in image quality nearly equivalent to 360° acquisition. This method enabled a reduction in testing time without impacting image quality.

Hemodynamic-based Mapping of Neural Activity in Medetomidine-sedated Rats using a 1.5T Compact Magnetic Resonance Imaging System: A Preliminary Study.

The use of compact magnetic resonance (MR) systems for the neuroimaging of small animals is spreading. We investigated the potential of such systems in functional MR imaging (fMRI) of somatosensory cortex activity elicited by forepaw stimulation in medetomidine-sedated rats. Using a 1.5-tesla compact imager, we detected maximum activity with an electrophysiologically optimized frequency of 9 Hz in 3 appropriately sedated rats. With this compact system, we successfully mapped neural activity by combining optimum stimulation for a large hemodynamic response with appropriate anesthesia, thus demonstrating the utility of such systems in hemodynamic-based fMRI in preclinical and translational research.