Plantar Flexor Muscle Activity and Fascicle Behavior in Gastrocnemius Medialis During Running in Highly Cushioned Shoes With Carbon-Fiber Plates.

The purposes of this study were to clarify the electromyography (EMG) of plantar flexors and to analyze the fascicle and tendon behaviors of the gastrocnemius medialis (GM) during running in the carbon-fiber plate embedded in thicker midsole racing shoes, such as the Nike ZoomX Vaporfly (VF) and traditional racing shoes (TRAD). We compared the fascicle and series elastic element behavior of the GM and EMG of the lower limb muscles during running (14 km/h, 45 s) in athletes wearing VF or TRAD. GM EMGs in the push-off phase were approximately 50% lower in athletes wearing VF than in TRAD. Although the series elastic element behavior and/or mean fascicle-shortening velocity during the entire stance phase were not significantly different between VF and TRAD, a significant difference was found in both the mean EMG and integral EMG of the GM during the push-off phase. EMG of the gastrocnemius lateralis (GL) during the first half of the push-off phase was significantly different between VF and TRAD. Present results suggest that VF facilitates running propulsion, resulting in a decrease in GM and GL EMGs at a given running velocity during the push-off phase, leading to a reduction in metabolic cost.

[PROBLEMS ASSOCIATED WITH THE DIAGNOSIS OF PROLONGED/CHRONIC COUGH IN CLINICAL SETTINGS].

BACKGROUND: Many patients visit primary care clinics or local hospitals with a complaint of prolonged/chronic cough. Among the different types of chronic cough, cough variant asthma (CVA) and postinfectious cough may be the most common types, and their differential diagnosis is difficult. Some physicians tend to prescribe inhaled corticosteroids before establishing a definitive diagnosis. METHODS: We retrospectively investigated useful findings for diagnosis in 77 patients with a complaint of prolonged/ chronic cough to detect meaningful findings for differential diagnosis and to identify problems associated with diagnosis in clinical practice. RESULTS: CVA was diagnosed in 39 patients, and postinfectious cough was diagnosed in 19. Compared with postinfectious cough, CVA was associated with significant characteristics such as "diurnal variation of symptoms," "response to inhalation of short acting ß2 agonist (SABA)," and "recurrent episodes of symptoms." CVA was associated with high FeNO levels as well, and high FeNO levels were specific to CVA. However, these useful characteristics were not significant in the patients who had been prescribed ICS before visiting our hospital. CONCLUSIONS: Medical examination and determination of FeNO levels are useful for the differential diagnosis of prolonged/chronic cough, before treatment with ICS.

Overexpression of microRNA-155 suppresses chemokine expression induced by Interleukin-13 in BEAS-2B human bronchial epithelial cells.

BACKGROUND: MicroRNAs are non-coding small RNAs that regulate expression of target genes by binding to 3' untranslated regions. In this study, we used bronchial epithelial cells to investigate in vitro the role of the microRNA miR-155 in the expression of chemokines associated with airway inflammation. miR-155 has previously been reported to regulate allergic inflammation. METHODS: BEAS-2B bronchial epithelial cells were cultured and transfected with mimic or inhibitor oligonucleotides to overexpress or downregulate miR-155, as confirmed by real-time PCR. Cells were then stimulated with tumor necrosis factor-alpha, interleukin-13 (IL-13), and a double stranded RNA that binds Toll-like receptor 3. Expression and secretion of the chemokines CCL5, CCL11, CCL26, CXCL8, and CXCL10 were then quantified by real-time PCR and ELISA, respectively. Phosphorylation of signal transducer and activator of transcription 6 (STAT6), a target of the IL-13 receptor, was analyzed by ELISA. RESULTS: miR-155 overexpression significantly suppressed IL-13-induced secretion of CCL11 and CCL26. These effects were specific, and were not observed for other chemokines, nor in cells with downregulated miR-155. miR-155 overexpression also suppressed CCL11 and CCL26 mRNA, but did not affect expression of the IL-13 receptor or phosphorylation of STAT6. CONCLUSIONS: miR-155 specifically inhibits IL-13-induced expression of eosinophilic chemokines CCL11 and CCL26 in bronchial epithelial cells, even though the 3'-untranslated region of these genes do not contain a consensus binding site for miR-155.

Analysis of OXA23 and AmpCß-Lactamase Genes in Clinically Isolated Multidrug-Resistant Acinetobacter baumannii Clonal Complex 92.

Multidrug-resistant Acinetobacter baumannii, which is resistant to carbapenems, amino glycosides, and fluoroquinolones, was isolated from the wound of an outpatient. We performed Multi Locus Sequence Typing and analyzed the structures of the AmpC ß-lactamase and OXA23 carbapenemase genes. This strain was assigned as ST451, a member of clonal complex 92, by its MLST scheme. The structures of ISAba1-AmpC ß-lactamase and ISAba1-OXA23 carbapenemase were revealed and the major globally prevalent clone of carbapenem-resistant A. baumannii was identified.

Clinical features and outcomes of aspiration pneumonia compared with non-aspiration pneumonia: a retrospective cohort study.

Pneumonia is a leading cause of death among elderly patients. Although aspiration pneumonia (AP) commonly occurs with aging, its clinical features and outcomes are still uncertain. The aims of this study were to describe the clinical features and outcomes of AP and to assess whether presence of AP affects clinical outcomes in patients with community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP). We retrospectively analyzed patients with CAP and HCAP hospitalized in our institution in Japan from October 2010 to March 2012. We compared clinical features and outcomes between AP and non-AP, and investigated risk factors for recurrence of pneumonia and death. Of 214 consecutive patients, 100 (46.7%) were diagnosed as having aspiration pneumonia. These patients were older and had lower body mass index, more comorbidities, and poorer Eastern Cooperative Oncology Group performance status (ECOG PS) than the patients with non-AP. Patients with AP had more severe disease, required longer hospital stays, and had a frequent recurrence rate of pneumonia and higher mortality. In multivariate analyses, AP, age, and ECOG PS were related to recurrence of pneumonia, and the prognostic factors were CURB-65 score and ECOG PS. AP was not a significant indicator for prognosis but was the strongest risk factor for recurrence of pneumonia. Clinical background and outcomes including recurrence and mortality of AP were obviously different from those of non-AP; therefore AP should be considered as a distinct subtype of pneumonia, and it is important to prevent the recurrence of pneumonia in the patients with AP.

Antimicrobial Stewardship Program for Patients in the Hematological Department Receiving Carbapenem Therapy: A Single-Center and Interrupted Time Series Analysis.

As antibiotic resistance has become a global problem, the intervention of an antimicrobial stewardship team (AST) is warranted. In hematological disorders, infectious complications are crucial owing to abnormal neutrophil function and decreased cell-mediated immunity. Despite the widespread implementation of AST intervention, the effectiveness of stewardship practices for immunocompromised patients remains uncertain. We determined the effect of AST interventions on carbapenem therapy in the department of hematology. Patients admitted to the department and undergoing carbapenem therapy were enrolled. We compared carbapenem use between the pre-AST (April 2016-March 2018) and post-AST (April 2018-March 2021) periods. Factors associated with long-term carbapenem therapy were investigated. Overall, 515 episodes of carbapenem therapy in 264 patients in the department were evaluated. According to the interrupted time series analysis, the number of days of therapy decreased with AST intervention (ß = -0.263, p = 0.011). In multivariate analysis, predictive factors associated with long-term carbapenem therapy (>8 days) were outpatient onset, chronic obstructive pulmonary disease, acute myeloid leukemia, multiple myeloma, and infection with resistant bacteria (such as extended spectrum ß-lactamases and AmpC) (95% confidence interval, 1.030-2.818, 1.067-66.667, 1.057-2.782, 0.168-0.742, and 1.382-5.750, respectively). The AST intervention reduced carbapenem use in patients with hematological disorders.

Leg stiffness during running in highly cushioned shoes with a carbon-fiber plate and traditional shoes.

BACKGROUND: Nike ZoomX Vaporfly (NVF) improves running economy and performance. The biomechanical mechanisms of these shoes are not fully understood, although thicker midsoles and carbon fiber plates are considered to play an important role in the spring-like leg characteristics during running. Leg stiffness (kleg) in the spring-mass model has been commonly used to investigate spring-like running mechanics during running. RESEARCH QUESTION: Does kleg during running differ between NVF and traditional (TRAD) shoes? METHODS: Eighteen male habitual forefoot and/or midfoot strike runners ran on a treadmill at 20 km/h with NVF and TRAD shoes, respectively. kleg, vertical oscillation of the center of mass (∆CoM), spatiotemporal parameters, and mechanical loading were determined. RESULTS: kleg was 4.8% lower in the NVF shoe condition than in the TRAD condition, although no significant difference was observed. ∆CoM was not significantly different between shoe conditions. Spatiotemporal parameters and mechanical loading were also not significantly different between shoe conditions. SIGNIFICANCE: The NVF shoe is well known as improving the running economy and running performance for the cause by characteristics of better spring function. Contrary to expectation, kleg and other parameters were not significantly different during running in the NVF compared to TRAD shoe at 20 km/h. These findings indicate that well-trained runners' spring-like running mechanics would not alter even if wearing the NVF shoes.

Effect of tocilizumab treatment in mildly-obese patients with coronavirus disease 2019: a case series.

Background: The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an increasingly widespread international medical problem. Several randomized trials and observational studies in patients with COVID-19 have been performed. However, the standard treatment strategy has not yet been established. The purpose of this study is to report effect of tocilizumab treatment combined with remdesivir, dexamethasone, and heparin on obese Japanese patients with COVID-19. Tocilizumab is a monoclonal antibody against the interleukin-6 (IL-6) receptor. Obesity, characterized by systemic enlarged adipocytes, promotes proinflammatory cytokine expression in adipose tissue. More specifically, obesity induces detrimental adipocytokine production including tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and IL-6. In addition, its production in the adipose tissue is associated with body mass index (BMI) and adipocyte size. IL-6 can promote inflammation not only in the adipose tissues but also in endothelial cells and triggers systemic inflammation. Methods: A cross-sectional observational study was conducted. The study sample consisted of 96 patients between August 2020 and January 2021 at Showa University Fujigaoka Hospital. Results: Overall, 56.3% (54 of 96) were administered with remdesivir, 54.2% (52 of 96) with dexamethasone, 19.8% (19 of 96) with anticoagulant therapy with heparin. Of the patients, nine were administered tocilizumab with remdesivir, dexamethasone, and heparin. The current study indicated that single-dose treatment of tocilizumab in combination with remdesivir, dexamethasone, and heparin is beneficial for obese Japanese patients with COVID-19. Conclusions: We believe that the severity of obesity is related to the anti-IL-6 treatment sensitivity in patients with COVID-19.

Combination of anti-glycopeptidolipid-core IgA antibody and clinical features for diagnosing potential nontuberculous mycobacterium pulmonary disease in routine practice.

BACKGROUND: The anti-Mycobacterium avium complex (MAC) antibody test measures levels of IgA antibody against the glycopeptidolipid (GPL) core in the bacterial cell walls and is a useful clinical indicator of nontuberculous mycobacterium pulmonary disease (NTM-PD). However, it is not currently possible to diagnose the disease using anti-MAC antibodies alone. OBJECTIVES: The study aim was to assess the efficacy of the combination of anti-MAC antibodies and clinical findings for diagnosing potential NTM-PD. METHODS: This cross-sectional study included 938 patients tested using the anti-MAC antibody. NTM-PD was diagnosed by multiple positive cultures of the same species in sputum samples. Multivariate logistic regression models were used to identify the clinical factors related to NTM-PD. RESULTS: Overall, 19.6% (184/938) of participants were diagnosed with NTM-PD. In multivariate analysis, positive anti-MAC antibodies, low body mass index, absence of malignancy, and cavity-forming lung lesions were significantly associated with NTM-PD at diagnosis. The positive rates of the anti-MAC antibody test were 79.4% (135/170) for MAC and 55.6% (5/9) for Mycobacterium abscessus complex, respectively. CONCLUSIONS: Bronchoscopic examinations should be performed especially in certain types of individuals from whom sputum samples cannot be obtained. Anti-MAC antibodies are also positive in patients other than those harboring MAC, but the rate may be low because of the different components in GPLs.

Tracking the dynamics of individual gut microbiome of sea cucumber Apostichopus japonicus during gut regeneration.

Sea cucumbers possess the remarkable capacity to regenerate their body parts or organs. Regeneration of host organs and/or body parts involves reconstruction of the host associated microbiota, however, the dynamics and contribution of microbiota to the regeneration process are largely unknown due to a lack of experimental models. To track the dynamics of individual gut microbiomes during gut regeneration, both caged mariculture and laboratory isolator systems of sea cucumbers (Apostichopus japonicus) were developed and longitudinal meta16S analyses were performed. Under natural environmental conditions in the caged mariculture system, both bacterial and eukaryotic communities in sea cucumbers' guts appeared to be reconstructed within 4 months after evisceration. Using the laboratory isolator, which can trace daily dynamics, we found that fecal microbiota collected before evisceration were clearly different from those collected after evisceration. We also identified eight key bacteria, belonging to Alteromonadaceae, Rhodobacteraceae, Oceanospirillaceae and family-unassigned Gammaproteobacteria, suggesting that these bacteria might interact with the host during the gut regeneration process. Six of the eight key bacteria were isolated for further bioassay using the isolator developed in this study to test whether these isolates affect gut regeneration.

PCR amplification of the erm(41) gene can be used to predict the sensitivity of Mycobacterium abscessus complex strains to clarithromycin.

A worldwide increase in the Mycobacterium abscessus (M. abscessus) complex has been observed. Therefore, the aim of the present study was to investigate the diversity of the rrl and erm(41) genes, both of which are associated with macrolide sensitivity in the M. abscessus complex. The current study also examined the efficacy of mass spectrometry as an alternative to molecular testing to classify subspecies of the M. abscessus complex. A total of 14 strains of the M. abscessus complex were obtained, and based on conventional analyses using housekeeping genes, 57% were determined to be M. abscessus subsp. abscessus, 43% were M. abscessus subsp. massiliense, and none were identified as M. abscessus subsp. bolletii. However, depending on the strain, it was not always possible to distinguish between the subspecies by mass spectrometry. Consequently, PCR products for the rrl and erm(41) genes were directly sequenced. Overall, 7.1% of the strains were identified to have a rrl mutation, and 92.9% carried a T at position 28 of erm(41). Results presented here suggest that the principal cause of treatment failure for M. abscessus complex infections is inducible macrolide resistance encoded by the erm(41) gene. From a strictly pragmatic standpoint, the phenotypic function of a putative erm(41) gene is the most important piece of information required by clinicians in order to prescribe an effective treatment. Although PCR amplification of erm(41) is not sufficient to differentiate between the M. abscessus complex subspecies, PCR can be easily and efficiently used to predict the sensitivity of members of the M. abscessus complex to clarithromycin.

Impact of the interferon-γ release assay and glomerular filtration rate on the estimation of active tuberculosis risk before bronchoscopic examinations: a retrospective pilot study.

BACKGROUND: Bronchoscopic examinations are vital to diagnose pulmonary diseases. However, as coughing is triggered during and after the procedure, it is imperative to take measures against nosocomial infections, especially for airborne infections like tuberculosis (TB). The interferon-γ release assay (IGRA) has recently been established as a method to evaluate the infection status of TB. We aimed to ascertain the efficacy of IGRA and clinical findings in estimating the prevalence of active TB before bronchoscopy. METHODS: We obtained IGRA results from 136 inpatients using a QuantiFERON-TB Gold In-Tube test. Bronchoscopy samples were cultured in Mycobacteria Growth indicator tubes and 2% Ogawa solid medium. We evaluated the adjusted effects of multiple clinical variables on active TB status using a logistic regression model. In addition, multiple variables were converted into a decision tree to predict active TB. RESULTS: Five (3.7%) patients were diagnosed with culture-positive TB, two of whom were simultaneously diagnosed with non-small-cell lung carcinoma or small-cell lung carcinoma. The multivariate analysis suggested the probability of predicting active TB using the IGRA [odds ratio (OR), 72.7; 95% confidence interval (CI), 3.169-1668; P=0.007] and decreased estimated glomerular filtration rate (eGFR) (OR, 0.937; 95% CI, 0.882-0.996; P=0.038) in patients undergoing bronchoscopy. A decision tree validated the use of these two variables to predict active TB. CONCLUSIONS: IGRA test results are useful for predicting active TB before bronchoscopy. This strategy could identify patients who require antibiotic therapy to prevent TB or who are in the active phase of TB.

Repeated selective enrichment process of sediment microbiota occurred in sea cucumber guts.

Deposit-feeding sea cucumbers repeat ingestion of sediments and excretion of faeces daily and consequently increase bacterial abundance in sediments and promote organic matter mineralization. Such ecological roles are expected to be collaborative activities of sea cucumbers and the gut microbiota. Here, we performed a spatiotemporally broad 16S rRNA gene analysis using 109 samples from sea cucumber faeces and habitat sediments to explore potential contribution of their gut microbiota to the ecological roles. Most operational taxonomic units (OTUs) observed in the faecal samples were shared with the sediment samples, nevertheless faecal and sediment microbiota differed from each other in UniFrac analysis. Lower bacterial diversity and increased relative abundance of specific OTUs in the faecal microbiota strongly suggest selective enrichment of ingested sediment microbiota in their guts. Interestingly, representative faecal OTUs were more abundant in sea cucumber-populated sediments than in un-inhabited sediments, indicating bacteria selectively enriched in the guts were spread on ambient sediments via faeces. Moreover, the predicted microbial community metabolic potential showed a higher abundance of genes related to carbohydrate and xenobiotics metabolisms in faeces than in sediments. Our study suggests the repeated selective enrichment transforms ambient sediment microbial communities and maintains the host's ecological roles by promoting organic matter mineralization.

SCCmec typing of PVL-positive community-acquired Staphylococcus aureus (CA-MRSA) at a Japanese hospital.

The epidemiology of Panton-Valentine leukocidin (PVL)-positive MRSA in community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) was examined. Three hundred and forty-two CA-MRSA strains that were susceptible to imipenem and cefazolin were isolated from 1107 samples (intravenous catheter, blood, sputum, urine, skin, wound, and pharynx) from outpatients at Showa University Hospital in Japan between September 2009 and March 2017. The PVL gene was detected in 46 of 342 CA-MRSA strains, accounting for 13.5%. The type of SCCmec was determined by detection of each SCCmec-specific region, class complex, and ccr. SCCmec type IV comprised 33 strains, type V comprised 5 strains, type VII comprised 4 strains, and the unclassified type comprised 4 strains. Among the type IV strains, subtype IVa was dominant, comprising 23 of 33 strains, and the remaining 10 strains were of varying subtypes. The SCCmec type III-specific region, CZ049, was amplified in 2 type V strains, 4 type VII strains, and 4 unclassified strains. In 4 unclassified strains, CZ049 and ccr5 were detected, but neither the SCCmec-specific region nor class complex was detected. The PVL-positive rate was lower than that in Western countries. The SCCmec types of PVL-positive CA-MRSA strains were found to vary, indicating a diverse spreading route.

Individual Apostichopus japonicus fecal microbiome reveals a link with polyhydroxybutyrate producers in host growth gaps.

Gut microbiome shapes various aspects of a host's physiology, but these functions in aquatic animal hosts have yet to be fully investigated. The sea cucumber Apostichopus japonicus Selenka is one such example. The large growth gap in their body size has delayed the development of intensive aquaculture, nevertheless the species is in urgent need of conservation. To understand possible contributions of the gut microbiome to its host's growth, individual fecal microbiome comparisons were performed. High-throughput 16S rRNA sequencing revealed significantly different microbiota in larger and smaller individuals; Rhodobacterales in particular was the most significantly abundant bacterial group in the larger specimens. Further shotgun metagenome of representative samples revealed a significant abundance of microbiome retaining polyhydroxybutyrate (PHB) metabolism genes in the largest individual. The PHB metabolism reads were potentially derived from Rhodobacterales. These results imply a possible link between microbial PHB producers and potential growth promotion in Deuterostomia marine invertebrates.

The First Temporal and Spatial Assessment of Vibrio Diversity of the Surrounding Seawater of Coral Reefs in Ishigaki, Japan.

Coral reefs perform a major role in regulating marine biodiversity and serve as hotspot for highly dynamic and diverse microbiomes as holobionts. Corals around Ishigaki, however, are at risk due to tremendous stressors including elevation of seawater temperature, eutrophication and so on. However, no information is currently available on how Vibrio diversity fluctuates spatially and temporally due to environmental determinants in Ishigaki coral reef ecosystems. The aim of this study is to elucidate spatiotemporal Vibrio diversity dynamic at both community and population levels and to assess the environmental drivers correlated to Vibrio abundance and diversity. The Vibrio community identified based on pyrH gene phylogeny of 685 isolates from seawater directly connecting to Ishigaki coral holobionts consisted of 22 known and 12 potential novel Vibrionaceae species. The most prominent species were V. hyugaensis, V. owensii and V. harveyi followed by V. maritimus/V. variabillis, V. campbellii, V. coralliilyticus, and Photobacterium rosenbergii. The Vibrio community fluctuations, assessed by PCoA with UniFrac distance and clustering with Euclidiean distance were varied less not only by year but also by site. Interestingly, significant positive correlation was observed between rising seawater temperature and the abundance of V. campbellii (r = 0.62; P < 0.05) whereas the opposite was observed for V. owensii (r = -0.58; P < 0.05) and the C6 group of V. hyugaensis (r = -0.62; P < 0.05). AdaptML-based microhabitat differentiation revealed that V. harveyi, V. campbellii, P. rosenbergii, and V. coralliilyticus populations were less-ecologically distinctive whereas V. astriarenae and V. ishigakensis were ecologically diverse. This knowledge could be important clue for the future actions of coral conservation.

Acquired resistance L747S mutation in an epidermal growth factor receptor-tyrosine kinase inhibitor-naïve patient: A report of three cases.

The purpose of the present study was to report cases of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-naïve patients carrying a mutation associated with acquired resistance to the drug. Gene alterations in 77 lung carcinoma patients were analyzed by collecting and studying curette lavage fluid at the time of diagnosis. PCRs were performed to amplify mutation hotspot regions in EGFR genes. The PCR products were direct-sequenced and the mutations confirmed by resequencing using different primers. Case 1 was a 78-year-old Japanese male diagnosed with stage IB lung adenocarcinoma who was found to have two EGFR mutations, G719S and L747S. Case 2 was a 73-year-old Japanese male diagnosed with stage IV squamous cell lung carcinoma and bone metastasis who had the EGFR mutation, L747S. Case 3 was an 82-year-old Japanese male diagnosed with hyponatremia due to inappropriate secretion of antidiuretic hormone and stage IIIB small cell lung carcinoma (SCLC) who had the EGFR mutation, L747S. Thus, the EGFR mutation L747S associated with acquired EGFR-TKI resistance was detected in two non-small cell lung carcinoma (NSCLC) patients and one SCLC patient, none of whom had ever received EGFR-TKI. The patients were current smokers with stages at diagnosis ranging from IB to IV, and their initial tumors contained resistant clones carrying L747S. L747S may be associated with primary resistance. To the best of our knowledge, this study is the first report of an EGFR mutation associated with resistance to EGFR-TKI in SCLC patients. The early detection of EGFR-TKI resistance mutations may be beneficial in making treatment decisions for lung carcinoma patients, including those with SCLC.

Azacitidine-induced pneumonitis in a patient with myelodysplastic syndrome: first case report in Japan.

A 74-year-old Japanese man with myelodysplastic syndrome (MDS) received chemotherapy with azacitidine. From the second day after starting the administration, he complained of fever, cough and shortness of breath. Chest roentgenography and computed tomography showed consolidations and ground-glass opacities. His symptoms grew from worse to life-threatening. We diagnosed him with azacitidine-induced pneumonitis and began administering corticosteroids. Thereafter, his symptoms and radiographic abnormalities improved. Azacitidine is a hypomethylating agent that improves the survival of MDS patients. Although this drug is commonly well tolerated and rarely causes severe lung injury, it is important to consider the potentially serious adverse effects of azacitidine-induced pneumonitis.