Development and Performance Evaluation of a New Test Kit for Quantifying the Degree of DNA Fragmentation.

BACKGROUND: PCR-based genetic testing of agricultural products and foods is widely used for detecting various analytical targets such as genetically modified organisms and food allergens. However, it is difficult to obtain accurate genetic testing results from processed foods because DNA is fragmented by heat and pressure during food processing. Thus, we previously developed an analytical method to quantitatively evaluate the degree of DNA fragmentation for the purpose of QC of genetic testing for processed foods. OBJECTIVE: Our previous analytical method requires four PCR primer sets, resulting in high reagent costs and heavy analytical workloads. Therefore, we attempted to develop an easy-to-use test kit for quantifying the degree of DNA fragmentation and to evaluate its analytical performance. METHODS: To simplify the analysis procedure, we used only two primer sets. In addition, no-fragmentation control templates were prepared to obtain stable measurement results. The precision of the simplified analysis was evaluated through blind tests between laboratories. RESULTS: It was confirmed that plant species and extracted DNA concentrations had little effect on analysis with the newly developed test kit. In addition, the analytical values indicating the degree of DNA fragmentation exhibited small variability between laboratories. CONCLUSION: We confirmed the high practicality of the developed test kit. Because DNA fragmentation in cells is a universal phenomenon, we anticipate that the test kit will be used not only for QC of genetic testing but also for food testing, medical diagnostics, and other applications in a range of fields. HIGHLIGHTS: The newly developed test kit enables quantitative evaluation of the degree of DNA fragmentation in a simple manner.

Clinical characteristics of rheumatoid arthritis patients complicated with pulmonary nontuberculous mycobacterial disease: A cross-sectional case series study.

OBJECTIVES: Pulmonary nontuberculous mycobacterial disease (pNTM) is a common pulmonary complication of rheumatoid arthritis (RA), but their association has rarely been researched. We aimed to reveal the clinical characteristics of RA with pNTM. METHODS: Among all the RA patients who visited Tenri hospital from April 2017 to March 2018, we enrolled those fulfilling the 2007 ATS/IDSA diagnostic criteria of pNTM, and sex- and age- matched control group at a ratio of 1:5. Demographic characteristics were compared between the two groups. RESULTS: Among 865 RA patients, 35 (4.0%) patients were complicated with pNTM. RA patients with pNTM had significantly lower BMI and higher rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) positivity. Bronchiectasis was the most frequent lesion, followed by clusters of small nodules, patchy consolidation and cavity. Multivariable logistic regression analysis revealed bronchiectasis as a strong independent associated factor of pNTM. Treatment for pNTM was needed in 14 of the 35 (40%) RA patients with pNTM and sputum negative conversion was accomplished in 11 of the 14 cases (78.6%). CONCLUSIONS: RA patients with lower BMI, RF/ACPA positivity, and bronchiectasis were associated with pNTM. Treatment for pNTM may attain sputum negative conversion and radiological improvement in patients with RA.

Simple, Precise, and Less Biased GMO Quantification by Multiplexed Genetic Element-Specific Digital PCR.

BACKGROUND: To provide the consumer with choices of genetically modified organisms (GMO) or non-GMO, official food labeling systems were established in many countries. Because the threshold GMO content values were set to distinguish between "non-GMO" and "GMO" designations, GMO content quantification methods are required for ensuring the appropriateness of labeling. OBJECTIVE: As the number of GMOs is continuously increasing around the world, we set out to develop a low-cost, simple and less biased analytical strategy to cover all necessary detection targets. METHODS: Digital PCR methods are advantageous compared to the conventional quantitative real-time PCR methods. We developed a digital PCR-based GMO quantification method to evaluate the GMO content in maize grains. To minimize the analytical workload, we adopted multiplex digital PCR targeting the 35S promoter and the nopaline synthase terminator, which are genetic elements commonly introduced in many GMOs. RESULTS: Our method is significantly simpler and more precise than the conventional real-time PCR-based methods. Additionally, we found that this method enables quantification of the copy number of GMO DNA without double counting multiple elements (35S promoter and nopaline synthase terminator) tandemly placed in a recombinant DNA construct. CONCLUSION: This is the first report on the development of a genetically modified maize quantification method using a multiplexed genetic element-specific digital PCR method. The tandem effect we report here is quite useful for reducing the bias in the analytical results. HIGHLIGHTS: Multiplexed genetic element-specific digital PCR can simplify weight-based GMO quantification and thus should prove useful in light of the continuous increase in the number of GM events.

The diagnosis of early pneumoconiosis in dust-exposed workers: comparison of chest radiography and computed tomography.

BACKGROUND: Chest radiography (CR) is employed as the evaluation of pneumoconiosis; however, we sometimes encounter cases in which computed tomography (CT) is more effective in detecting subtle pathological changes or cases in which CR yields false-positive results. PURPOSE: To compare CR to CT in the diagnosis of early-stage pneumoconiosis. MATERIAL AND METHODS: CR and CT were performed for 132 workers with an occupational history of mining. We excluded 23 cases of arc-welder's lung. Five readers who were experienced chest radiologists or pulmonologists independently graded the pulmonary small opacities on CR of the remaining 109 cases. We then excluded 37 cases in which the CT data were not sufficient for grading. CT images of the remaining 72 cases were graded by the five readers. We also assessed the degree of pulmonary emphysema in those cases. RESULTS: The grade of profusion on CR (CR score) of all five readers was identical in only 5 of 109 cases (4.6%). The CR score coincided with that on CT in 40 of 72 cases (56%). The CT score was higher than that on CR in 13 cases (18%). On the other hand, the CT score was lower than that on CR in 19 cases (26%). The incidence of pulmonary emphysema was significantly higher in patients whose CR score was higher than their CT score. CONCLUSION: CT is more sensitive than CR in the evaluation of early-stage pneumoconiosis. In cases with emphysema, the CR score tends to be higher in comparison to that on CT.

Prediction of forced vital capacity with dynamic chest radiography in interstitial lung disease.

PURPOSE: The pulmonary function test (PFT) has played an essential role in diagnosing and managing interstitial lung disease (ILD) but has its contraindications and difficult conditions to perform. Therefore, the present study aimed to evaluate dynamic chest radiography (DCR) ability to predict forced vital capacity (FVC) and other PFT parameters of ILD patients. METHOD: The prospective observational study included 97 patients who underwent DCR at Tenri Hospital (Tenri, Japan) between June 2019 and April 2020. Twenty-five patients with stable disease status underwent DCR twice to evaluate test-retest reliability using the intraclass correlation coefficient. From the lung field areas measured by DCR, lung volumes at maximum inspiration (V.ins) and expiration (V.exp) were estimated. Correlation coefficients between the measured values of DCR and PFT parameters were calculated. Multilinear models for predicting FVC and other PFT parameters were developed. RESULTS: Intraclass correlation coefficients between first and second measurements of V.ins and V.exp were 0.94 (95% CI: 0.89-0.97, p < 0.001) and 0.88 (95% CI: 0.78-0.94, p < 0.001), respectively. The correlation coefficient between V.ins and FVC was 0.86 (95% CI: 0.79-0.90, p < 0.001). A multilinear model for predicting FVC was developed using V.ins, V.exp, age, sex, and body mass index as predictor variables, wherein the adjusted coefficient of determination was 0.814. CONCLUSIONS: Lung volumes measured by DCR correlated with the lung function of ILD patients. Prediction models with high predictive power and internal validity were developed, suggesting that DCR can predict FVC and other PFT parameters of ILD patients.

Characteristics of interstitial lung disease in patients from post-marketing data on metastatic breast cancer patients who received abemaciclib in Japan.

BACKGROUND: This study evaluated characteristics of patients treated with abemaciclib and diagnosed with interstitial lung disease (ILD), using 12-month post-marketing data from the real-world setting in Japan. METHODS: Spontaneous reports of adverse events in patients receiving abemaciclib were collected regularly from healthcare providers (HCPs) from November 30, 2018, to November 29, 2019. Detailed follow-up was requested on suspected ILD cases via questionnaires and/or interviews. Radiological images (when available) were reviewed by an ILD adjudication committee of specialists. The age distribution of patients prescribed abemaciclib in Japan was estimated based on insurance claims data. RESULTS: Of 4700 patients estimated to be exposed to abemaciclib, 82 cases of ILD were reported (46 serious, 13 fatal). Most (91%) had ≥ 1 symptom at diagnosis, commonly dyspnea/shortness of breath (59%), cough (44%), and/or fever (37%). The majority (68%) received steroid therapy (24 [56%] recovered/recovering; 5 [12%] not recovered; 13 [30%] deaths, 1 [2.3%] unknown). No specific imaging patterns or sites of predilection were identified, but a diffuse alveolar damage (DAD) pattern was observed at outcome in 3 of 4 evaluated fatal cases (16 in total evaluated). Features of fatal cases included advanced age, pre-existing interstitial change, and advanced Eastern Cooperative Oncology Group Performance Status. CONCLUSION: Advanced age and a DAD pattern were identified as potential risk factors for cases with poorer outcomes, as previously reported for drug-induced ILD. HCPs should consider the benefit-risk profile when prescribing abemaciclib, informing patients of risks and regularly monitoring treated patients to ensure early detection and treatment of ILD.

Prognostic value of chest computed tomography in community-acquired pneumonia patients.

BACKGROUND: Chest computed tomography (CT) is commonly used to diagnose pneumonia in Japan, but its usability in terms of prognostic predictability is not obvious. We modified CURB-65 (confusion, urea >7 mmol·L-1, respiratory rate ≥30 breaths·min-1, blood pressure <90 mmHg (systolic) ≤60 mmHg (diastolic), age ≥65 years) and A-DROP scores with CT information and evaluated their ability to predict mortality in community-acquired pneumonia patients. METHODS: This study was conducted using a prospective registry of the Adult Pneumonia Study Group - Japan. Of the 791 registry patients, 265 hospitalised patients with chest CT were evaluated. Chest CT-modified CURB-65 scores were developed with the first 30 study patients. The 30-day mortality predictability of CT-modified, chest radiography-modified and original CURB-65 scores were validated. RESULTS: In score development, infiltrates over four lobes and pleural effusion on CT added extra points to CURB-65 scores. The area under the curve for CT-modified CURB-65 scores was significantly higher than that of chest radiography-modified or original CURB-65 scores (both p<0.001). The optimal cut-off CT-modified CURB-65 score was ≥4 (positive-predictive value 80.8%; negative-predictive value 78.6%, for 30-day mortality). For sensitivity analyses, chest CT-modified A-DROP scores also demonstrated better prognostic value than did chest radiography-modified and original A-DROP scores. Poor physical status, chronic heart failure and multiple infiltration hampered chest radiography evaluation. CONCLUSION: Chest CT modification of CURB-65 or A-DROP scores improved the prognostic predictability relative to the unmodified scores. In particular, in patients with poor physical status or chronic heart failure, CT findings have a significant advantage. Therefore, CT can be used to enhance prognosis prediction.

Clinical and radiological features of immune checkpoint inhibitor-related pneumonitis in lung cancer and non-lung cancers.

OBJECTIVE: To investigate the clinical and radiological features of immune checkpoint inhibitor-related pneumonitis (ICI-P), a rare but serious pulmonary complication of cancer immunotherapy and to evaluate key differences between lung cancer (LC) and non-LC patients. METHODS: 247 patients (LC, n = 151) treated with ICI for malignancies were retrospectively screened in a single institute. The number of patients, history of other immune-related adverse events (irAE), the onset, serum KL-6 levels, and chest CT features (types of pneumonitis, symmetry, laterality, location) were recorded for the ICI-P population and compared for LC and non-LC groups. RESULTS: ICI-P was identified in 26 patients in total (LC, n = 19; non-LC, n = 7). The incidence of other irAE was significantly higher in ICI-P group (63%) compared with patients without ICI-P (34%) (p = 0.0056). An earlier onset of ICI-P was recorded in LC (78 days) compared to non-LC patients (186 days) (p = 0.0034). Serum KL-6 was significantly elevated only in the non-LC group when ICI-P was noticed (p = 0.029). Major CT findings of ICI-P, irrespective of primary disease, were organizing pneumonia pattern and ground glass opacities. LC patients commonly exhibited consolidation and traction bronchiectasis and were prone to asymmetrical shadows (p < 0.001). Non-LC patients were more likely to exhibit symmetrical infiltrations. A small fraction of both groups experienced relapse or moving patterns of ICI-P. CONCLUSION: ICI-P patients more often experienced other irAE prior to the development of ICI-P. The characteristics of ICI-P can differ in terms of the onset, KL-6 reliability, and chest CT findings between LC and non-LC patients. ADVANCES IN KNOWLEDGE: In ICI-P patients, a history of other irAE can be more frequently observed. Differences in disease onset and radiological patterns between LC and non-LC patients might be helpful to make a diagnosis of ICI-P; however, longitudinal observation of chest CT scans is advised to observe the pneumonitis activity irrespective of cancer types.

Progression of right ventricular dysfunction and predictors of mortality in patients with idiopathic interstitial pneumonias.

BACKGROUND: Few studies have examined the relationship between echocardiographic indices of right ventricular (RV) function and the severity of pulmonary disease, or their prognostic impact. We evaluated the RV function in patients with interstitial pneumonia and its prognostic impact at each stage of disease severity. METHOD: A total of 176 patients with idiopathic interstitial pneumonias (IIPs) were retrospectively enrolled and we evaluated RV function by transthoracic echocardiography. The severity of IIPs was graded according to the Goh score. The primary outcome was all-cause death. RESULTS: There were 55 patients in mild group (31%), 66 in moderate group (38%), and 55 in severe group (31%). Regarding RV function, RV free wall longitudinal strain and tricuspid annular plane systolic excursion (TAPSE) deteriorated with increasing severity of IIPs, but fractional area change (FAC) decreased significantly only in severe group. There were 64 all-cause deaths during the follow-up period (median 908 days). In moderate group, TAPSE [hazard ratio (HR): 0.85, 95% confidence interval (CI): 0.74-0.97, p=0.017], FAC (HR: 0.89, 95% CI: 0.83-0.96, p=0.001), and mean pulmonary artery pressure (PAP)/cardiac output (HR: 1.50, 95% CI: 1.08-2.09, p=0.015) were independent predictors of all-cause death, even after adjusting for age and log brain natriuretic peptide (BNP). On the other hand, not RV function or PAP but male sex and BNP level were associated with mortality in severe group. CONCLUSIONS: Among patients with IIPs, RV longitudinal function deteriorated with increasing severity of IIPs. Echocardiographic indices of RV function were independently associated with mortality in moderate-stage IIPs.

Laparoscopic surgery in patients with interstitial lung disease: A single-center retrospective observational cohort study.

INTRODUCTION: Laparoscopic surgery requiring longer operative times and artificial pneumoperitoneum may affect pulmonary function; its feasibility in patients with interstitial lung disease remains unknown. Therefore, we examined the feasibility of laparoscopic surgery in patients with interstitial lung disease. METHODS: We conducted a retrospective observational cohort study and examined the clinical data of patients with interstitial lung disease who had undergone abdominal surgery under general anesthesia. The primary end-point was the incidence of pulmonary complications. The secondary end-points were non-pulmonary complications and in-hospital mortality. RESULTS: Twenty-nine patients who had undergone abdominal surgery were diagnosed with interstitial lung disease after a review of their clinical and imaging records. Laparoscopic surgery and open surgery were performed in 11 and 18 patients, respectively. Acute exacerbation occurred in one (9%) patient in the laparoscopic group and three patients (17%) in the open group; all had undergone emergency surgery. Postoperative pneumonia did not occur in any patients. Non-pulmonary complications occurred in one patient (9%) in the laparoscopic group and two patients (11%) in the open group. One patient in each group died of acute exacerbation during hospitalization. CONCLUSION: Neither acute exacerbation nor pulmonary complications occurred after elective laparoscopic or open surgery in patients with interstitial lung disease. The risk of acute exacerbation after elective laparoscopic surgery may not be as high as that after elective thoracic surgery.

Inter-observer agreement in identifying traction bronchiectasis on computed tomography: its improvement with the use of the additional criteria for chronic fibrosing interstitial pneumonia.

PURPOSE: To assess inter-observer variability in identifying traction bronchiectasis on computed tomography (CT) using additional criteria for chronic fibrosing interstitial pneumonia. METHODS: Seven experts categorized CT image set representing 39 patients into three groups on the basis of the presence of traction bronchiectasis, using a three-point scale: 3-definitely/probably yes; 2-possibly yes; and 1-definitely/probably no. This scale served as a reference standard. The image set included cases of chronic fibrosing interstitial pneumonia, non-interstitial lung disease, and difficult-to-determine cases. Forty-eight observers similarly assessed the same image set, first according to the Fleischner Society definition, and second with additional criteria, in which traction bronchiectasis was observed exclusively in chronic fibrosing interstitial pneumonia. The agreement level between the reference standard and each observer's evaluation in each session was calculated using weighted kappa values which were compared between the two sessions using a paired t test. RESULTS: The mean weighted kappa value for all observers was significantly higher in the second reading session (mean 0.75) than in the first reading session (mean 0.62) (p < 0.001). CONCLUSION: Inter-observer agreement in identifying traction bronchiectasis improves when using the additional criteria which specify chronic fibrosing interstitial pneumonia as the underlying disease.

A case report of pulmonary Botrytis sp. infection in an apparently healthy individual.

BACKGROUND: Botrytis species are well known fungal pathogens of various plants but have not been reported as human pathogens, except as allergenic precipitants of asthma and hypersensitivity pneumonitis. CASE PRESENTATION: The asymptomatic patient was referred because of a nodule revealed by chest X-ray. Computed tomography (CT) showed a cavitary nodule in the right upper lobe of the lung. He underwent wedge resection of the nodule, which revealed necrotizing granulomas and a fungus ball containing Y-shaped filamentous fungi, which was confirmed histopathologically. Culture of the specimen yielded white to grayish cotton-like colonies with black sclerotia. We performed multilocus gene sequence analyses including three single-copy nuclear DNA genes encoding glyceraldehyde-3-phosphate dehydrogenase, heat-shock protein 60, and DNA-dependent RNA polymerase subunit II. The analyses revealed that the isolate was most similar to Botrytis elliptica. To date, the pulmonary Botrytis sp. infection has not recurred after lung resection and the patient did not require any additional medication. CONCLUSIONS: We report the first case of an immunocompetent patient with pulmonary Botrytis sp. infection, which has not recurred after lung resection without any additional medication. Precise evaluation is necessary for the diagnosis of pulmonary Botrytis infection because it is indistinguishable from other filamentous fungi both radiologically and by histopathology. The etiology and pathophysiology of pulmonary Botrytis infection remains unclear. Further accumulation and analysis of Botrytis cases is warranted.

Combined pulmonary fibrosis and emphysema with myeloperoxidase-antineutrophil cytoplasmic antibody positivity that resolved upon smoking cessation.

Myeloperoxidase antineutrophil cytoplasmic autoantibody (MPO-ANCA) is well-known as a serological marker for small-vessel vasculitis. However, when a smoker with interstitial lung disease (ILD) exhibits serum ANCA positivity without systemic vasculitis, diagnosis is a matter of debate; the relationship between smoking and ANCA is unknown. We report a case of combined pulmonary fibrosis and emphysema (CPFE) with elevated MPO-ANCA. Surgical lung biopsy showed emphysema and fibrotic interstitial pneumonia without vasculitis. The MPO-ANCA level decreased after smoking cessation, and no vasculitis or progression was observed during 3 years of follow-up. This suggested that smoking cessation was related to normalization of MPO-ANCA and corresponding disease activity.

Synthesis of 1,5-Anhydro-d-fructose derivatives and evaluation of their inflammasome inhibitors.

Synthesis of several 1,5-Anhydro-d-fructose (1,5-AF) derivatives to evaluate inhibitory activities of the inflammasome was carried out. Recently, 1,5-AF reported to suppress the inflammasome, although with only low activity. We focused on the hydration of 2-keto form of 1,5-AF and speculated that this hydration was the cause of low activity. Therefore, we synthesized some 1,5-AF derivatives that would not be able to form the dimer conformation and can be expected to have high activity against inflammasome, and then evaluated their inhibitory activities with respect to the NLRP3 inflammasome by using mouse bone marrow-derived macrophages and human THP-1 cells. As a result, some synthesized 2-keto form compounds had much higher inhibitory activities with respect to the NLRP3 inflammasome than did 1,5-AF.

Association of Focal Radiation Dose Adjusted on Cross Sections with Subsolid Nodule Visibility and Quantification on Computed Tomography Images Using AIDR 3D: Comparison Among Scanning at 84, 42, and 7 mAs.

RATIONALE AND OBJECTIVES: The objectives of this study were to compare the visibility and quantification of subsolid nodules (SSNs) on computed tomography (CT) using adaptive iterative dose reduction using three-dimensional processing between 7 and 42 mAs and to assess the association of size-specific dose estimate (SSDE) with relative measured value change between 7 and 84 mAs (RMVC7-84) and relative measured value change between 42 and 84 mAs (RMVC42-84). MATERIALS AND METHODS: As a Japanese multicenter research project (Area-detector Computed Tomography for the Investigation of Thoracic Diseases [ACTIve] study), 50 subjects underwent chest CT with 120 kV, 0.35 second per location and three tube currents: 240 mA (84 mAs), 120 mA (42 mAs), and 20 mA (7 mAs). Axial CT images were reconstructed using adaptive iterative dose reduction using three-dimensional processing. SSN visibility was assessed with three grades (1, obscure, to 3, definitely visible) using CT at 84 mAs as reference standard and compared between 7 and 42 mAs using t test. Dimension, mean CT density, and particular SSDE to the nodular center of 71 SSNs and volume of 58 SSNs (diameter >5 mm) were measured. Measured values (MVs) were compared using Wilcoxon signed-rank tests among CTs at three doses. Pearson correlation analyses were performed to assess the association of SSDE with RMVC7-84: 100 × (MV at 7 mAs - MV at 84 mAs)/MV at 84 mAs and RMVC42-84. RESULTS: SSN visibilities were similar between 7 and 42 mAs (2.76 ± 0.45 vs 2.78 ± 0.40) (P = .67). For larger SSNs (>8 mm), MVs were similar among CTs at three doses (P > .05). For smaller SSNs (<8 mm), dimensions and volumes on CT at 7 mAs were larger and the mean CT density was smaller than 42 and 84 mAs, and SSDE had mild negative correlations with RMVC7-84 (P < .05). CONCLUSIONS: Comparable quantification was demonstrated irrespective of doses for larger SSNs. For smaller SSNs, nodular exaggerating effect associated with decreased SSDE on CT at 7 mAs compared to 84 mAs could result in comparable visibilities to CT at 42 mAs.

Immunogenicity of simultaneous versus sequential administration of a 23-valent pneumococcal polysaccharide vaccine and a quadrivalent influenza vaccine in older individuals: A randomized, open-label, non-inferiority trial.

It is unclear whether simultaneous administration of a 23-valent pneumococcal polysaccharide vaccine (PPSV23) and a quadrivalent influenza vaccine (QIV) produces immunogenicity in older individuals. This study tested the hypothesis that the pneumococcal antibody response elicited by simultaneous administration of PPSV23 and QIV in older individuals is not inferior to that elicited by sequential administration of PPSV23 and QIV. We performed a single-center, randomized, open-label, non-inferiority trial comprising 162 adults aged ≥65 years randomly assigned to either the simultaneous (simultaneous injections of PPSV23 and QIV) or sequential (control; PPSV23 injected 2 weeks after QIV vaccination) groups. Pneumococcal immunoglobulin G (IgG) titers of serotypes 23F, 3, 4, 6B, 14, and 19A were assessed. The primary endpoint was the serotype 23F response rate (a ≥2-fold increase in IgG concentrations 4-6 weeks after PPSV23 vaccination). With the non-inferiority margin set at 20% fewer patients, the response rate of serotype 23F in the simultaneous group (77.8%) was not inferior to that of the sequential group (77.6%; difference, 0.1%; 90% confidence interval, -10.8% to 11.1%). None of the pneumococcal IgG serotype titers were significantly different between the groups 4-6 weeks after vaccination. Simultaneous administration did not show a significant decrease in seroprotection odds ratios for H1N1, H3N2, or B/Phuket influenza strains other than B/Texas. Additionally, simultaneous administration did not increase adverse reactions. Hence, simultaneous administration of PPSV23 and QIV shows an acceptable immunogenicity that is comparable to sequential administration without an increase in adverse reactions. (This study was registered with ClinicalTrials.gov [NCT02592486]).

Heterorhizy and fine root architecture of rabbiteye blueberry (Vaccinium virgatum) softwood-cuttings.

All fine root systems consist of individual fine roots. Individual roots have morphological, anatomical, and functional heterogeneity (heterorhizy). Heterorhizy plays crucial roles in plant ecosystems. However, in many species, the heterorhizy and fine root system architecture based on individual root units are unclear. This study investigated heterorhizy along the root system architecture of Vaccinium virgatum Ait (rabbiteye blueberry) softwood-cuttings (propagated from annual shoots in growing season) using protoxylem groups (PGs), a classification according to the number of protoxylem poles, as an indicator of individual root traits. Individual roots of rabbiteye blueberry varied from monarch to heptarch. The frequency of roots with larger number of PGs decreased but those with smaller number of PGs increased from adventitious roots toward lateral roots with different branching levels. This architecture were stable among cultivars, collecting position of the cuttings, or indole acetic acids treatment. Individual root sizes and secondary growth were positively correlated with the PGs. These results indicate that branching itself strongly and broadly controls individual root traits. The individual roots were classified into two types: monarch and diarch roots with small size and lacking secondary growth (thought to be hair roots in core Ericaceae) and triarch or more PG roots with large size and showing secondary growth. These heterogeneous individual roots responded differently to the experimental factors. In particular, elongation of the large roots significantly contributed to increased total root length. These results mean that heterorhizic plasticity is a determinant of root system development and heterorhizic variation exists even under practical cutting condition. In conclusion, we demonstrated heterorhizy of rabbieye blueberry cuttings based on the strong relationships of PG, individual root morphology and growth potential, and root system architecture. This study also supports strong connection between root morphology and functional roles intermediated by the PG.

Low-dose trimethoprim-sulfamethoxazole treatment for pneumocystis pneumonia in non-human immunodeficiency virus-infected immunocompromised patients: A single-center retrospective observational cohort study.

BACKGROUND/PURPOSE: The efficacy of low-dose trimethoprim-sulfamethoxazole (TMP-SMX) may be acceptable for the treatment of pneumocystis pneumonia (PCP) in non-human immunodeficiency virus (HIV)-infected patients, with a low incidence of adverse reactions. This study is aimed to evaluate the efficacy and safety of such a regimen for the treatment of non-HIV PCP. METHODS: We retrospectively enrolled 24 consecutive patients diagnosed with non-HIV PCP who were treated with low-dose TMP-SMX (TMP, 4-10 mg/kg/day; SMX, 20-50 mg/kg/day). Data of the conventional-dose treatment were used as reference. The primary endpoints were the 30- and 180-day survival rates from the day of treatment, and secondary endpoints were the incidence of each adverse reaction and dropout rate from the initial TMP-SMX regimen. The survival rate was estimated using the Kaplan-Meier method with 95% confidence interval (CI). RESULTS: The median age of patients was 72 years (54.2% men), and connective tissue disease was the most frequent underlying disease (66.7%) in the low-dose group. The 30- and 180-day survival rates were 95.8% (95% CI: 88.2-100.0%) and 91.0% (95% CI: 79.9%-100.0%), respectively, in the low-dose group and 69.0% (95% CI: 54.0%-88.0%) and 51.5% (95% CI: 36.1%-73.4%), respectively, in the conventional-dose group. The total adverse reaction rate was 58.3% in the low-dose group and 72.4% in the conventional-dose group. A total of 75.0% of patients in the low-dose group and 31.0% in the conventional-dose group completed treatment with the initial regimen. CONCLUSION: Low-dose TMP-SMX may be a treatment option for patients with non-HIV PCP.

Sub-solid Nodule Detection Performance on Reduced-dose Computed Tomography with Iterative Reduction: Comparison Between 20 mA (7 mAs) and 120 mA (42 mAs) Regarding Nodular Size and Characteristics and Association with Size-specific Dose Estimate.

RATIONALE AND OBJECTIVES: This study aimed to compare sub-solid nodule detection performances (SSNDP) on chest computed tomography (CT) with Adaptive Iterative Dose Reduction using Three Dimensional Processing (AIDR 3D) between 7 mAs (0.21 mSv) and 42 mAs (1.28 mSv) in total and in subgroups classified by nodular size, characteristics, and location, and analyze the association of SSNDP with size-specific dose estimate (SSDE). MATERIALS AND METHODS: As part of the Area-detector Computed Tomography for the Investigation of Thoracic Diseases Study, a Japanese multicenter research project, 68 subjects underwent chest CT with 120 kV, 0.35 seconds per rotation, and three tube currents: 240 mA (84 mAs), 120 mA (42 mAs), and 20 mA (7 mAs). The research committee of the study project outlined and approved our study protocols. The institutional review board of each institution approved this study. Axial 2-mm-thick CT images were reconstructed using AIDR 3D. Standard reference was determined by CT images at 84 mAs. Four radiologists recorded SSN presence by continuously distributed rating on CT at 7 mAs and 42 mAs. Receiver operating characteristic analysis was used to evaluate SSNDP at both doses in total and in subgroups classified by nodular longest diameter (LD) (≥5 mm), characteristics (pure and part-solid), and locations (ventral, intermediate, or dorsal; central or peripheral; and upper, middle, or lower). Detection sensitivity was compared among five groups of SSNs classified based on particular SSDE to nodule on CT with AIDR 3D at 7 mAs. RESULTS: Twenty-two part-solid and 86 pure SSNs were identified. For larger SSNs (LD ≥ 5 mm) as well as subgroups classified by nodular locations and part-solid nodules, SSNDP was similar in both methods (area under the receiver operating characteristics curve: 0.96 ± 0.02 in CT at 7 mAs and 0.97 ± 0.01 in CT at 42 mAs), with acceptable interobserver agreements in five locations. For larger SSNs (LD ≥ 5 mm), on CT at 42 mAs, no significant differences in detection sensitivity were found among the five groups classified by SSDE, whereas on CT with 7 mAs, four groups with SSDE of 0.65 or higher were superior in detection sensitivity to the other group, with SSDE less than 0.65 mGy. CONCLUSIONS: For SSNs with 5 mm or more in cases with normal range of body habitus, CT at 7 mAs was demonstrated to have comparable SSNDP to CT at 42 mAs regardless of nodular location and characteristics, and SSDE higher than 0.65 mGy is desirable to obtain sufficient SSNDP.

The long-term outcome of interstitial lung disease with anti-aminoacyl-tRNA synthetase antibodies.

RATIONALE: Anti-aminoacyl transfer RNA synthetase antibodies (anti-ARS) are a group of myositis-specific autoantibodies that are detected in the sera of patients with polymyositis and dermatomyositis (PM/DM) and also in those of patients with idiopathic interstitial pneumonias without any connective tissue disease (CTD), including PM/DM. Although we reported the clinical characteristics of interstitial lung disease with anti-ARS antibodies (ARS-ILD) with and without PM/DM, the long-term prognosis of ARS-ILD remains undetermined. As our previous studies revealed that ARS-ILD without PM/DM was similar to CTD-associated ILD, and that ARS-ILD with PM/DM was radiologically suggestive of a nonspecific interstitial pneumonia (NSIP) pathological pattern, we hypothesized that the prognosis of ARS-ILD might be distinct from that of idiopathic pulmonary fibrosis (IPF) without anti-ARS. OBJECTIVES: To elucidate the long-term outcome of ARS-ILD with and without PM/DM and compare it to that of IPF. METHODS: A two-center retrospective study was conducted. The study population comprised 36 patients with ARS-ILD (8 with PM, 12 with DM, and 16 without myositis throughout the course), 100 patients with IPF without anti-ARS, and 7 patients with NSIP without anti-ARS. The presence of anti-ARS was determined by RNA immunoprecipitation using the sera obtained at the time of diagnosis before specific treatment. MEASUREMENTS AND MAIN RESULTS: During the observational period (median 49 months; range, 1-114 months), 7 patients with ARS-ILD (19%; 3 with PM, 1 with DM, and 3 without PM/DM) and 51 patients with IPF (51%) died. Patients with ARS-ILD had better overall survival than those with IPF (log-rank test, P < 0.001) and similar survival compared to those with NSIP (log-rank test, P = 0.59). The prognosis for patients with ARS-ILD was similar between those with and without myositis (log-rank test, P = 0.91). At the median follow-up time of 76.5 months, 14 of the 36 patients with ARS-ILD had deteriorated. Both a decline in forced vital capacity or an initiation of long-term oxygen therapy during the course (odds ratio [OR], 5.34) and acute exacerbation (OR, 28.4) significantly increased the mortality risk. CONCLUSIONS: The long-term outcome of ARS-ILD was significantly better than that of IPF regardless of the presence or absence of myositis.