Apoptosis Inhibitor of Macrophages Contributes to the Chronicity of Mycobacterium avium Infection by Promoting Foamy Macrophage Formation.

In Mycobacterium avium infections, macrophages play a critical role in the host defense response. Apoptosis inhibitor of macrophage (AIM), also known as CD5L, may represent a novel supportive therapy against various diseases, including metabolic syndrome and infectious diseases. The mechanisms of AIM include modulating lipid metabolism in macrophages and other host cells. We investigated the role of AIM in M. avium infections in vitro and in vivo. In a mouse model of M. avium pneumonia, foamy macrophages were induced 6 wk after infection. The bacteria localized in these macrophages. Flow cytometric analysis also confirmed that the percentage of CD11chighMHCclassIIhigh interstitial and alveolar macrophages, a cell surface marker defined as foamy macrophages, increased significantly after infection. AIM in alveolar lavage fluid and serum gradually increased after infection. Administration of recombinant AIM significantly increased the number of bacteria in the lungs of mice, accompanied by the induction of inflammatory cytokine and iNOS expression. In mouse bone marrow-derived macrophages, the mRNA expression of AIM after M. avium infection and the amount of AIM in the supernatant increased prior to the increase in intracellular bacteria. Infected cells treated with anti-AIM Abs had fewer bacteria and a higher percentage of apoptosis-positive cells than infected cells treated with isotype control Abs. Finally, AIM in the sera of patients with M. avium-pulmonary disease was measured and was significantly higher than in healthy volunteers. This suggests that AIM production is enhanced in M. avium-infected macrophages, increasing macrophage resistance to apoptosis and providing a possible site for bacterial growth.

Deep convolutional neural network for differentiating between sarcoidosis and lymphoma based on [18F]FDG maximum-intensity projection images.

OBJECTIVES: To compare the [18F]FDG PET/CT findings of untreated sarcoidosis and malignant lymphoma (ML) and develop convolutional neural network (CNN) models to differentiate between these diseases using maximum intensity projection (MIP) [18F]FDG PET images. METHODS: We retrospectively collected data on consecutive patients newly diagnosed with sarcoidosis and ML who underwent [18F]FDG PET/CT before treatment. Two nuclear radiologists reviewed the images. CNN models were created using MIP PET images and evaluated with k-fold cross-validation. The points of interest were visualized using gradient-weighted class activation mapping (Grad-CAM). RESULTS: A total of 56 patients with sarcoidosis and 62 patients with ML were included. Patients with sarcoidosis had more prominent FDG accumulation in the mediastinal lymph nodes and lung lesions, while those with ML had more prominent accumulation in the cervical lymph nodes (all p < 0.001). For the mediastinal lymph nodes, sarcoidosis patients had significant FDG accumulation in the level 2, 4, 7, and 10 lymph nodes (all p < 0.01). Otherwise, the accumulation in ML patients tended to be in the level 1 lymph nodes (p = 0.08). The CNN model using frontal and lateral MIP images achieved an average accuracy of 0.890 (95% CI: 0.804-0.977), a sensitivity of 0.898 (95% CI: 0.782-1.000), a specificity of 0.907 (95% CI: 0.799-1.000), and an area under the curve of 0.963 (95% CI: 0.899-1.000). Grad-CAM showed that the model focused on the sites of abnormal FDG accumulation. CONCLUSIONS: CNN models based on differences in FDG accumulation sites archive high performance in differentiating between sarcoidosis and ML. CLINICAL RELEVANCE STATEMENT: We developed a CNN model using MIP images of [18F]FDG PET/CT to distinguish between sarcoidosis and malignant lymphoma. It achieved high performance and could be useful in diagnosing diseases with involvement across organs and lymph nodes. KEY POINTS: • There are differences in FDG distribution when comparing whole-body [18F]FDG PET/CT findings in patients with sarcoidosis and malignant lymphoma before treatment. • Convolutional neural networks, a type of deep learning technique, trained with maximum-intensity projection PET images from two angles showed high performance. • A deep learning model that utilizes differences in FDG distribution may be helpful in differentiating between diseases with lesions that are characteristically widespread among organs and lymph nodes.

Predictive Value of Vancomycin AUC24/MIC Ratio for 30-day Mortality in Patients with Severe or Complicated Methicillin-Resistant Staphylococcus aureus Infections: A Multicenter Retrospective Study.

BACKGROUND: Although vancomycin is typically employed against methicillin-resistant Staphylococcus aureus (MRSA) infections, the optimal ratio of 24-h area under the concentration-time curve to minimum inhibitory concentration (AUC24/MIC) for severe or complicated infections lacks clear guideline recommendations. This study aimed to determine the target AUC24/MIC ratio associated with treatment outcomes of infections treated with vancomycin. METHODS: This retrospective multicenter cohort study included adult patients receiving ≥ 5 days of vancomycin for severe/complicated MRSA infections (e.g., osteoarticular, pulmonary, endocarditis, etc.) between January 2018 and December 2023. The primary outcome was 30-day mortality, with secondary outcomes including clinical success, microbiological eradication, and nephrotoxicity. Receiver operating characteristic (ROC) curve analysis was used to identify the AUC24/MIC cutoff for 30-day mortality. Multivariate regression analysis was used to determine association between AUC24/MIC and outcomes. RESULTS: This study included 82 patients. ROC identified a target AUC24/MIC of ≥ 505 for 30-day mortality. The overall 30-day mortality rate (22.0%) was significantly higher for below average AUC24/MIC cutoff (34.1%) than for above AUC24/MIC cutoff group (9.8%). Multivariate analysis confirmed AUC24/MIC of < 505 as an independent predictor (adjusted odds ratio, 5.001; 95% confidence interval, 1.335-18.75). The clinical success rate differed significantly between below- and above-cutoff groups, whereas microbiological eradication tended to favor the above-cutoff group. The nephrotoxicity rates were comparable between groups. CONCLUSIONS: In treating severe/complicated MRSA infections, vancomycin AUC24/MIC ratio ≥ 505 was independently associated with favorable 30-day mortality. Given the retrospective nature of this study, further prospective studies are essential to confirm the reliability of the target AUC24/MIC ratios.

Prognostic Impact of Reduced Left Ventricular Ejection Fraction After Endovascular Therapy for Lower Extremities.

BACKGROUND: The mechanism underlying a poor prognosis in patients with lower-extremity artery disease (LEAD) with heart failure is unknown. We examined the prognostic impact of the left ventricular ejection fraction (LVEF) in patients with LEAD who underwent endovascular therapy (EVT).Methods and Results: From August 2014 to August 2016, 2,180 patients with LEAD (mean age, 73.2 years; male, 71.9%) underwent EVT and were stratified into low-LVEF (LVEF <40%; n=234, 10.7%) and not-low LVEF groups. In the low- vs. not-low LVEF groups, there was a higher prevalence of heart failure (i.e., history of heart failure hospitalization or New York Heart Association functional class III or IV symptoms) (44.0% vs. 8.3%, respectively), diabetes mellitus, chronic kidney disease, below-the-knee lesion, critical limb ischemia, and incidence of major cardiovascular and cerebrovascular events (MACCEs) and major adverse limb events (MALEs) (P<0.001, all). Low LVEF independently predicted MACCEs (hazard ratio: 2.23, 95% confidence interval: 1.63-3.03; P<0.001) and MALEs (hazard ratio: 1.85, 95% confidence interval: 1.15-2.96; P=0.011), regardless of heart failure (P value for interaction: MACCEs: 0.27; MALEs: 0.52). CONCLUSIONS: Low LVEF, but not symptomatic heart failure, increased the incidence of MACCEs and MALEs. Intensive cardiac dysfunction management may improve LEAD prognosis after EVT.

Relapsing bronchopneumonia due to community-associated methicillin-resistant Staphylococcus aureus: a case report.

BACKGROUND: The emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has increased the incidence of community-onset MRSA infection. Respiratory tract infections caused by MRSA has been noted for their severity; however, repeated relapses that require extended antibiotic therapy are rare. CASE PRESENTATION: We report a case of relapsing bronchopneumonia caused by CA-MRSA in a 56-year-old man. The patient responded to antibiotics, but repeatedly relapsed after stopping treatment. MRSA was consistently isolated from airway specimens during each relapse. Extended oral antibiotic treatment with trimethoprim/sulfamethoxazole (TMP/SMX) for 6 months achieved infection control. Whole-genome sequencing of the isolated strain revealed that the causative agent was sequence type (ST)1/staphylococcal cassette chromosome mec (SCCmec) type IVa, a clone that is rapidly increasing in Japan. DISCUSSION AND CONCLUSIONS: This patient had an unusual course of MRSA bronchopneumonia with repeated relapses. Although the choice of antibiotics for long-term use in MRSA respiratory tract infections has not been well established, TMP/SMX was effective and well tolerated for long-term therapy in this case. The clinical course of infections related to the rapid emerging clone, ST1/SCCmec type IVa warrants further attention.

A case of refractory disseminated subcutaneous abscess with intrahousehold transmission by a USA300-LV-like strain of PVL-positive community-acquired MRSA clone.

A 44-year-old man with hypertension and dyslipidemia presented with pain in the buttocks. The patient was diagnosed with perianal ischiorectal fossa abscesses and cellulitis. He was subsequently diagnosed with a perineal subcutaneous abscess after a week, a right lower leg impetigo after a month, right periorchitis, a scrotal abscess, and Fournier's gangrene after two months. The patient was treated with various antimicrobials and underwent incisional drainage. Methicillin-resistant Staphylococcus aureus (MRSA) was detected in all draining specimens. Her daughter and son, who lived with the patient, presented with subcutaneous abscesses caused by MRSA. Suspecting repeated infections and household infections by virulent types of MRSA, such as PVL-positive strains, we performed genetic analyses of his and his son's strains. The results showed that the genotype and toxin gene profiles [ST8/t008/SCCmec type IVc/Panton-Valentine leucocidin (PVL) (+)/arginine catabolic mobile element (ACME) (-)] of both strains matched. single nucleotide polymorphism (SNP) analysis confirmed genetic homology between the two, concluding that home transmission by the same clone had occurred. In addition, the strain in this case differed from USA300 [ST8/t008/SCCmec type IVa/PVL (+) ACME (+)], which is a PVL-positive MRSA worldwide, including Japan, and its genetic profile matches that of USA300-LV, which is detected mainly in South America. Furthermore, SNP analysis showed that this strain is similar to USA300-LV/J (derived from USA300-LV) detected on Ishigaki Island, Okinawa Prefecture, Japan. This is the first report of refractory infections and household transmission of USA300-LV/J. Therefore, it is necessary to closely monitor both the USA300 and the USA300-LV.

Assessing the discriminability of PCR-based open reading frame typing versus single-nucleotide polymorphism analysis via draft whole-genome sequencing of methicillin-resistant Staphylococcus aureus in nosocomial transmission analysis.

Phylogenetic analysis based on single-nucleotide polymorphism (SNP)-based through whole-genome sequencing is recognized as the standard method for probing nosocomial transmission. However, the application of WGS is constrained by the high cost of equipment and the need for diverse analysis tools, which limits its widespread use in clinical laboratory settings. In Japan, the prevalent use of PCR-based open reading frame typing (POT) for tracing methicillin-resistant Staphylococcus aureus (MRSA) transmission routes is attributed to its simplicity and ease of use. Although POT's discriminatory power is considered insufficient for nosocomial transmission analysis, conclusive data supporting this notion is lacking. This study assessed the discriminatory capabilities of SNP analysis and POT across 64 clinical MRSA strains. All 21 MRSA strains of ST5/SCCmec IIa, having more than 16 SNPs, demonstrated distinct clones. Conversely, two strains shared the same POT number and were identified as group A. Among the 12 MRSA strains of ST8/SCCmec IVl with over nine SNPs, five fell into POT group B, and five into POT group C. All four MRSA strains of ST8/SCCmec IVa were classified into POT group D, although they included strains with more than 30 SNPs. Among the 27 MRSA strains of ST1/SCCmec IVa, 14 were classified into POT group E. However, except for two clusters (each comprising two or three strains), all had SNP counts >10 (Fig. 1-D). SNP analysis of MRSA in CC1/SCCmec IV showed that several strains had the same number of SNPs in POT number (106-183-37), even among bacteria with >100 SNPs, indicating POT's limited use in detailed nosocomial transmission analysis.

Ponatinib-Related Vasospastic Angina.

Tyrosine kinase inhibitors (TKIs) are essential drugs for chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. Cardiovascular or arteriothrombotic adverse events have been reported in patients treated with TKIs. We report 3 cases of Ponatinib-related vasospastic angina, in which prophylactic administration of nitrates or calcium channel blockers was effective.

Pseudomonas otitidis bacteremia in an immunocompromised patient with cellulitis: case report and literature review.

BACKGROUND: Pseudomonas otitidis belongs to the genus Pseudomonas and causes various infections, including ear, skin, and soft tissue infections. P. otitidis has a unique susceptibility profile, being susceptible to penicillins and cephalosporins but resistant to carbapenems, due to the production of the metallo-ß-lactamase called POM-1. This revealed genetic similarities with Pseudomonas aeruginosa, which can sometimes lead to misidentification. CASE PRESENTATION: We report the case of a 70-year-old Japanese male who developed cellulitis and bacteremia during chemotherapy for multiple myeloma. He was initially treated with meropenem, but blood culture later revealed gram-negative bacilli identified as P. otitidis using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). Carbapenem resistance was predicted from previous reports; therefore, we switched to dual therapy with levofloxacin and cefepime, and favorable treatment results were obtained. CONCLUSION: This is the first reported case of P. otitidis cellulitis and bacteremia in an immunocompromised patient. Carbapenems are typically used in immunocompromised patients and P. otitidis is often resistant to it. However, its biochemical properties are similar to those of Pseudomonas aeruginosa; therefore, its accurate identification is critical. In the present study, we rapidly identified P. otitidis using MALDI-TOF MS and switched from carbapenems to an appropriate antimicrobial therapy, resulting in a successful outcome.

Prognostic impact of atrial fibrillation on the outcomes of peripheral artery disease according to preoperative symptoms for endovascular revascularization.

Peripheral artery disease (PAD) and atrial fibrillation (AF) are associated with major cardiovascular and cerebrovascular events (MACCE). However, outcomes stratified according to the preoperative symptoms of PAD in patients with AF have not been sufficiently investigated. This was a retrospective study of prospectively collected data pertaining to 2237 patients (1179 patients with intermittent claudication [IC] and 1058 patients with critical limb-threatening ischemia [CLTI]) who underwent endovascular therapy at 34 hospitals between August 2014 and August 2016. AF was present in 91 (7.7%) patients with IC and 150 (14.2%) patients with CLTI. In the CLTI group, patients with AF had a higher event rate of MACCE and all-cause death than those without AF (1-year rates of freedom from MACCE: 0.66 and 0.81 in patients with and without AF, respectively, p < 0.001). In contrast, in the IC group, there was no statistically significant difference in the rates of MACCE between patients with and without AF. In the Cox multivariate analysis, AF was a significant predictor of MACCE in patients with CLTI but not in patients with IC, even after adjusting for covariates. The impact of AF on the outcome of patients with PAD was greater in those with CLTI. Further studies are needed to clarify the possible mechanisms underlying these differences.

Differences in major limb outcomes by indication for lower extremity endovascular revascularization in patients receiving hemodialysis.

The incidence of lower extremity artery disease (LEAD) in patient receiving hemodialysis is remarkably higher than the general population. The treatment strategy and prognosis for LEAD patients differs depending on whether a patient has intermittent claudication (IC) or critical limb-threatening ischemia (CLTI). However, the distinction between the prognosis in HD-dependent patients with IC and CLTI has not been fully elucidated. This study is to determine whether indication of PAD has a distinct impact on major adverse cardiovascular and cerebrovascular events (MACCE) and limb events in patients receiving hemodialysis. The current study included 2321 prospectively enrolled patients from the Tokyo taMA peripheral vascular intervention research ComraDE registry (UMIN-CTR no. UMIN000015100) between September 2014 and December 2016. Out of the enrolled patients, 1644 were not receiving hemodialysis (non-HD patients) and 603 were receiving hemodialysis (HD patients). A composite of all-cause death, myocardial infarction, and stroke events defined as MACCE; while limb events were defined as a composite of unscheduled major amputation, unscheduled major lower limb surgery, acute limb ischemia, unscheduled endovascular treatment, and target lesion revascularization. Propensity score matching was applied among the non-HD and HD patients, in whole group, IC subgroup, and CLTI subgroup. Kaplan-Meier analysis was used for the analysis of outcomes for the whole group, IC subgroup, and the CLTI subgroup. CLTI accounted for 75.5% of the HD patients, whereas IC was 63.4% in the non-HD patients. The HD patients exhibited more frequent below-the-knee lesions than those in the non-HD patients in both IC (p = 0.01) and CLTI (p < 0.001) subgroups. Overall, HD patients exhibited a significantly higher rate of MACCE at 24 months. This trend was similar for limb events in whole group and CLTI subgroup. In contrast, no significant differences in outcomes for limb events were found in IC subgroup. Although, prognosis after EVT in HD patients were significantly worse than non-HD patients, comparable outcome with non-HD patients was observed in the patients treated for IC. Clinical trial registration: This study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR No. UMIN000015100).

Comparison of the incidence of depression before and after endovascular treatment in patients with lower limb peripheral artery disease.

Depression is a chronic illness that affects mood, physical health, and overall vitality and quality of life. Depression has been associated with an increased risk of all-cause and cardiovascular mortality among patients with peripheral arterial disease (PAD). Therefore, this study aimed to compare the incidence of depression before and after endovascular treatment in patients with lower limb PAD. This is an important clinical issue considering the worldwide increase in PAD with the aging population and the known negative impact of depression on recovery. This was a retrospective sub-analysis of data from the Tokyo Peripheral Vascular Intervention Study using the TOMA-CODE registry. The presence and extent of depressive symptoms were evaluated using the patient health questionnaire (PHQ-9), with a depressive tendency score of ≥ 5. The PHQ-9 score was evaluated before endovascular treatment (EVT) and at 4 (± 1) weeks after EVT. The study population consisted of 87 patients who completed the PHQ-9 before EVT, with 76 completing the post-EVT PHQ-9. Of these 76, 19 had a pre-EVT score ≥ 5. Overall, there was no difference in the pre- and post-EVT scores (P = 0.091). There was no significant change in the 19 patients with a pre-EVT score ≥ 5 (mean 9.2 ± 4.4); however, there was a tendency to improve in the pre- to post-EVT score (mean, 6.9 ± 5.2; P = 0.059). Diabetes was a significant negative factor for pre- to post-EVT score improvement (P = 0.023). Overall, symptoms of depression showed the tendency to improve at 30 days post-EVT. However, diabetes was associated with lower improvement in symptoms.

Time-Dependent Controlled Release of Ferulic Acid from Surface-Modified Hollow Nanoporous Silica Particles.

Release of ferulic acid from surface-functionalized hollow nanoporous silica particles (HNSPs) was investigated in deionized water (DI water) and in ethanol. The host material, an HNSP, was synthesized in the presence of polymer and surfactant templates, and the pore as well as the surface were modified with either pentyltriethoxysilane (PTS) or octyltriethoxysilane (OTS) through silane coupling reactions. The inner hollow space occupied a volume of ~45% of the whole HNSP with a 2.54 nm pore channel in the wall. The pore size was estimated to decrease to 1.5 nm and 0.5 nm via the PTS and OTS functionalization, respectively. The encapsulation efficiencies of the HNSP (25 wt%), PTS-functionalized HNSP (PTS-HNSP, 22 wt%) and OTS-functionalized HNSP (OST-HNSP, 25 wt%) toward ferulic acid were similar, while the %release in DI water and ethanol varied following HNSP > PTS-HNSP > OTS-HNSP. Release kinetic analyses with Korsmeyer-Peppas fitting suggested a trade-off relationship between the solvent's ability to access the HNSP and the affinity of ferulic acid to the surface, allowing us to understand the solvent's controlled release rate and mechanism.

Wetting dynamics of viscoelastic solid films.

We study the wetting phenomena of a soft viscoelastic solid film on a smooth and flat substrate. A poly-dimethylsiloxane (PDMS) rubber film is suspended from a stage at both ends, and the wetting behavior of the film against a glass substrate is observed while lowering the stage at a constant velocity. We find that the dynamics of the rubber-glass-air contact lines vary with the lowering velocity of the stage. When the stage velocity is sufficiently low, the film wets the substrate smoothly and the contact lines are straight throughout. Consequently, the contact line velocity is proportional to the lowering velocity. As the stage velocity is increased, the contact line velocity reaches a maximum at the critical stage velocity and then subsequently decreases. The contact lines are wavy and sensitive to the defects above the critical velocity, resulting in the trapping of air bubbles at the interface. We reproduce the wetting behavior using a simple numerical model, assuming an upper limit for the contact line velocity. The wetting behavior observed in our experiments is attributed to the transition in the in-plane stress state from tensile to compressive along the film, leading to buckling of the film above the critical stage velocity. Our results suggest the existence and importance of the maximum wetting velocity for viscoelastic solids.

Independent Predictors of Major Adverse Cardiovascular Events at 3 Years after Aortoiliac Stent Implantation.

PURPOSE: To identify the risk factors for major adverse cardiovascular events (MACEs) in real-world practice for symptomatic peripheral artery disease in Japan. MATERIALS AND METHODS: Data on Japanese patients (N = 880) from the Observational Prospective Multicenter Registry Study on Outcomes of Peripheral Arterial Disease Patients Treated by Angioplasty Therapy for Aortoiliac Artery who underwent de novo aortoiliac stent placement. The 3-year risk of incident MACEs was investigated. RESULTS: The median age of the patients was 72.6 years (range, 34-97 years), and 83.1% of the patients were men. The patients had the following conditions: smoking (35.6%), hypertension (94.1%), dyslipidemia (81.7%), diabetes (48.0%), renal failure on dialysis (12.6%), myocardial infarction (12.7%), stroke (15.8%), and chronic limb-threatening ischemia (7.1%). Femoropopliteal lesions were present in 38.8% of the limbs with aortoiliac lesions. The 3-year rate of freedom from MACEs was 89.1%. Baseline characteristics, such as age, renal failure on dialysis, myocardial infarction, stroke, and femoropopliteal lesions, were independently associated with the risk of incident MACEs. When the study population was stratified according to these risk factors, the rate of MACEs was highest in patients with at least 3 risk factors (32.9% at 3 years). CONCLUSIONS: The 3-year rate of freedom from MACEs was reported. Baseline characteristics, such as age, renal failure on dialysis, myocardial infarction, stroke, and femoropopliteal lesions, are independent risk factors for MACEs after aortoiliac stent placement.

Invasive pectoral abscess and costal osteomyelitis with bloodstream infection caused by methicillin-resistant Staphylococcus aureus after nasal septoplasty in an immunocompetent adult patient.

There are few reports of multilocus sequence type (ST) 5/staphylococcal cassette chromosome (SCC) mec type IVc/toxic shock syndrome toxin (TSST)-1- positive methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections. We report a case of community-onset MRSA (CO-MRSA) bloodstream infection in a healthy 41-year-old Japanese man after nasal septoplasty, followed by pectoral abscess and costal osteomyelitis. The patient presented with right anterior chest pain and fever. After admission, MRSA was isolated from two sets of blood cultures, and vancomycin was administered. On the fifth day, contrast-enhanced computed tomography (CT) scan and contrast-enhanced magnetic resonance imaging (MRI) scan showed an abscess in the right anterior chest to the right subpleural region. The dosage of vancomycin (4 g/day) did not reach the effective blood concentration; therefore, there was a switch to daptomycin. On the 23rd day, contrast-enhanced MRI revealed osteomyelitis of the right first rib, and as a result, linezolid was initiated. Two weeks later, contrast-enhanced CT of the chest showed improvement in the abscess. The patient was treated for 6 weeks during hospitalization and then switched to minocycline for 10 weeks. Molecular characterization of this isolate showed that it was ST5/SCCmec type IVc/TSST-1-positive/Panton-Valentine leucocidin (PVL)-negative. PVL-negative CO-MRSA can lead to hematogenous osteomyelitis and abscess even if the patient is immunocompetent, and if isolated from blood cultures, it is important to repeat imaging studies, even if the initial imaging studies were normal. It is possible that this strain contributes to the pathogenesis of invasive CO-MRSA, but further case accumulation is needed.

National survey of physicians in Japan regarding their use of diagnostic tests for legionellosis.

INTRODUCTION: Bacterial culture remains the gold standard for the diagnosis of legionellosis. However, past reports indicate that most physicians use the urinary antigen test (UAT) alone. Combining it with other tests is important, especially in patients with negative UAT results. The aim of this study was to investigate the current situation of legionellosis diagnostics and clarify the issues that need to be addressed. METHODS: Between March 1, 2021 and April 30, 2021, a questionnaire survey was conducted in an anonymous manner among physicians working in Japan. Questionnaires were generated on a website and asked questions in a multiple-choice format. RESULTS: Valid responses were received from 309 physicians during the study period. Most (92.9%) physicians reported using UAT as the initial test for patients suspected of having legionellosis, and <10% reported using other tests (e.g., culture, nucleic acid amplification test [NAAT], Gimenez staining, and serum antibody titer measurement [ATM]). When the initial test result was negative, 63% of physicians reported not conducting additional tests. Even when they chose to run additional tests, at most 27.8%, 23.6%, 12.3%, and 10.4% of all physicians used NAAT, culture, Gimenez staining, and serum ATM, respectively. The major reasons for not using tests other than UAT were "unavailability in the medical facility," "long turn-around time," and "difficult to collect sputum." CONCLUSIONS: The present survey revealed that most physicians in Japan used UAT alone for diagnosing legionellosis. Eliminating barriers to creating a reasonable environment and edification of physicians are needed to improve the current situation.

Characteristics of gene expression in frozen shoulder.

BACKGROUND: Severe frozen shoulder (FS) is often resistant to treatment and can thus result in long-term functional impairment. However, its etiology remains unknown. We hypothesized that gene expression of FS would vary by synovial location. METHODS: The synovial tissues of patients with FS were collected prospectively and analyzed for the expression of 19 genes. Synovial tissues from patients with rotator cuff tear (RCT) or shoulder instability (SI) were also analyzed as controls. A total of 10 samples were analyzed from each group. The specimens were arthroscopically taken from three different locations: rotator interval (RI), axillary recess (AX), and subacromial bursa (SAB). Total RNA was extracted from the collected tissues and was analyzed by real-time polymerase chain reaction for the following genes: matrix metalloproteinases (MMPs); tissue inhibitors of metalloproteinases (TIMPs); inflammatory cytokines (IL1B, TNF, and IL6); type I and II procollagen (COL1A1 and COL2A1); growth factors (IGF1 and TGFB1); neural factors (NGF and NGFR); SOX9; and ACTA2. RESULTS: Site-specific analysis showed that MMP13, IL-6, SOX9, and COL1A1 were increased in all three sites. Four genes (MMP3, MMP9, COL2A1, and NGFR) were increased in the AX, MMP3 in the RI, and NGFR in the SAB were increased in the FS group than in the RCT and SI groups. In the FS group, there was a correlation between the expression of genes related to chondrogenesis (MMP2, IGF1, SOX9, COL2A1, NGF, and NGFR) or fibrosis (MMP9, TGFB1, and COL1A1). CONCLUSION: The expression levels of numerous MMPs, pro-inflammatory cytokines, and collagen-related genes were increased in the FS group, suggesting that catabolic and anabolic changes have simultaneously occurred. In addition, genes related to chondrogenesis or fibrosis were highly expressed in the FS group, which might have affected the range of motion limitation of the shoulder. Compared to RI and SAB, the AX was the most common site of increased expression in FS. Analyzing the lower region of the shoulder joint may lead to the elucidation of the pathogenesis of FS.

Photoinduced movement: how photoirradiation induced the movements of matter.

Pioneered by the success on active transport of ions across membranes in 1980 using the regulation of the binding properties of crown ethers with covalently linked photoisomerizable units, extensive studies on the movements by using varied interactions between moving objects and environments have been reported. Photoinduced movements of various objects ranging from molecules, polymers to microscopic particles were discussed from the aspects of the driving for the movements, materials design to achieve the movements and systems design to see and to utilize the movements are summarized in this review.

Photochemical Consideration in the Interactions between Blood Proteins and Layered Inorganic Materials.

Interactions between layered double hydroxide (LDH) nanomaterials and plasma proteins according to their particle size and surface charge were evaluated. The LDHs with different particle size (150, 350 and 2000 nm) were prepared by adjusting hydrothermal treatment and urea hydrolysis and subsequent organic coating with citrate, malite and serite was applied to control the surface charge (ζ-potential: -15, 6 and 36 mV). Adsorption isotherms and Stern-Volmer plots for fluorescence quenching indicated that the human blood plasma had weak interactions toward all the types of LDHs. The adsorption isotherms did not show significant differences in the size and surface charges, while the fluorescence quenching ratio increased with the increase in the surface charge, implying that electrostatic interaction played a major role in their interactions. The fluorescence quenching of three types of plasma proteins (human serum albumin, γ-globulin and fibrinogen) by the surface charge-controlled LDHs suggested that the proteins adsorbed on the LDHs with a single layer and additional proteins were weakly adsorbed to surround the LDHs with adsorbed proteins. It was concluded that the LDH nanomaterials are fairly compatible for blood components due to the protein corona while the electrostatic interaction can affect their interaction with the proteins.