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Background and Objective: Weight and muscle loss are predictors of poor outcomes in chronic obstructive pulmonary disease. However, to our knowledge, no study has investigated the predictors of longitudinal weight loss or its composition from functional and morphological perspectives. Methods: This longitudinal observational study with a median follow‐up period of 5 years (range: 3.0–5.8 years) included patients with COPD and ever‐smokers at risk of COPD. Using chest computed tomography (CT) images, airway and emphysematous lesions were assessed as the square root of the wall area of a hypothetical airway with an internal perimeter of 10 mm (√Aaw at Pi10) and the percentage of low attenuation volume (LAV%). Muscle mass was estimated using cross‐sectional areas (CSAs) of the pectoralis and erector spinae muscles, and fat mass was estimated using the subcutaneous fat thickness at the level of the 8th rib measured using chest CT images. Statistical analyses were performed using the linear mixed‐effects models. Results: In total, 114 patients were enrolled. Their body mass index remained stable during the study period while body weight and muscle CSA decreased over time and the subcutaneous fat thickness increased. Reduced forced expiratory volume in 1 s and peak expiratory flow (PEF) at baseline predicted the future decline in muscle CSA. Conclusion: Severe airflow limitation predicted future muscle wasting in patients with COPD and ever‐smokers at risk of COPD. Airflow limitation with a PEF slightly below 90% of the predicted value may require intervention to prevent future muscle loss. [ABSTRACT FROM AUTHOR]

This paper examines the employment impact of British Columbia's revenue-neutral carbon tax implemented in 2008. While all industries appear to benefit from the redistributed tax revenues, the most carbon-intensive and trade-sensitive industries see employment fall with the tax, while clean service industries see employment rise. By aggregating across industries I find the BC carbon tax generated, on average, a small but statistically significant 0.74 percent annual increases in employment over the 2007–2013 period. This paper provides initial evidence showing how a revenue-neutral carbon tax may not adversely affect employment. [ABSTRACT FROM AUTHOR]

Abstract: Recent studies have suggested a possible involvement of abnormal tau in some retinal degenerative diseases. The common view in these studies is that these retinal diseases share the mechanism of tau-mediated degenerative diseases in brain and that information about these brain diseases may be directly applied to explain these retinal diseases. Here we collectively examine this view by revealing three basic characteristics of tau in the rod outer segment (ROS) of bovine retinal photoreceptors, i.e., its isoforms, its phosphorylation mode and its interaction with microtubules, and by comparing them with those of brain tau. We find that ROS contains at least four isoforms: three are identical to those in brain and one is unique in ROS. All ROS isoforms, like brain isoforms, are modified with multiple phosphate molecules; however, ROS isoforms show their own specific phosphorylation pattern, and these phosphorylation patterns appear not to be identical to those of brain tau. Interestingly, some ROS isoforms, under the normal conditions, are phosphorylated at the sites identical to those in Alzheimer's patient isoforms. Surprisingly, a large portion of ROS isoforms tightly associates with a membranous component(s) other than microtubules, and this association is independent of their phosphorylation states. These observations strongly suggest that tau plays various roles in ROS and that some of these functions may not be comparable to those of brain tau. We believe that knowledge about tau in the entire retinal network and/or its individual cells are also essential for elucidation of tau-mediated retinal diseases, if any. [Copyright &y& Elsevier]

Retinal photoreceptor phosphodiesterase (PDE6), a key enzyme for phototransduction, consists of a catalytic subunit complex (Pαβ) and two inhibitory subunits (Pγs). Pαβ has two noncatalytic cGMP-binding sites. Here, using bovine PDE preparations, we show the role of these cGMP-binding sites in PDE regulation. Pαβγγ and its transducin-activated form, Pαβγ, contain two and one cGMP, respectively. Only Pαβγ shows [H]cGMP binding with a K∼ 50 n and Pγ inhibits the [H]cGMP binding. Binding of cGMP to Pαβγ is suppressed during its formation, implying that cGMP binding is not involved in Pαβγγ activation. Once bound to Pαβγ, [H]cGMP is not dissociated even in the presence of a 1000-fold excess of unlabeled cGMP, binding of cGMP changes the apparent Stokes' radius of Pαβγ, and the amount of [H]cGMP-bound Pαβγ trapped by a filter is spontaneously increased during its incubation. These results suggest that Pαβγ slowly changes its conformation after cGMP binding, i.e. after formation of Pαβγ containing two cGMPs. Binding of Pγ greatly shortens the time to detect the increase in the filter-trapped level of [H]cGMP-bound Pαβγ, but alters neither the level nor its Stokes' radius. These results suggest that Pγ accelerates the conformational change, but does not add another change. These observations are consistent with the view that Pαβγ changes its conformation during its deactivation and that the binding of cGMP and Pγ is crucial for this change. These observations also imply that Pαβγγ changes its conformation during its activation and that release of Pγ and cGMP is essential for this change. Pαβγ slowly changes its conformation after cGMP binding, i.e., after formation of Pαβγ containing two cGMPs. Binding of Pγ accelerates the conformational change caused by cGMP, but does not add another change. Pαβγ changes its conformation during its inactivation and that the binding of cGMP and Pγ is crucial for this change. [ABSTRACT FROM AUTHOR]

This paper introduces a methodology for neural net- work global optimization. The aim is the simultaneous optimization of multilayer perceptron (MLP) network weights and architectures, in order to generate topologies with few connections and high classification performance for any data sets. The approach combines the advantages of simulated annealing, tabu search and the backpropagation training algorithm in order to generate an automatic process for producing networks with high classification performance and low complexity. Experimental results obtained with four classification problems and one prediction problem has shown to be better than those obtained by the most commonly used optimization techniques. [ABSTRACT FROM AUTHOR]

We have recently shown that activation of retinal guanylate cyclase (retGC) by GC-activating proteins (GCAPs) is much stronger than that previously reported and that preincubation of photoreceptor outer segment homogenates with ATP or its analogue, adenylyl imidodiphosphate (AMP-PNP), is required for the strong activation [Yamazaki, A., Yu, H., Yamazaki, M., Honkawa, H., Matsuura, I., Usukura, J., and Yamazaki, R. K. (2003) J. Biol. Chem. 278, 33150–33160]. Here we show that illuminated rhodopsin is essential for development of the AMP-PNP incubation effect. This was demonstrated by illumination of dark homogenates and treatments of illuminated homogenates with 11-cis-retinal and hydroxylamine prior to the AMP-PNP incubation and by measurement of the GCAP2 concentration required for 50% activation. We also found that the AMP-PNP incubation effect was not altered by addition of guanosine 5′-O-(3-thiotriphosphate), indicating that transducin activation is not required. It is concluded that illuminated rhodopsin is involved in retGC activation in two ways: to initiate the ATP incubation effect for preparation of retGC activation as shown here and to reduce the Ca2+ concentrations through cGMP phosphodiesterase activation as already known. These two signal pathways may be activated in a parallel and perhaps proportional manner and finally converge for strong activation of retGC by Ca2+-free GCAPs. [ABSTRACT FROM AUTHOR]

It has been believed that retinal guanylyl cyclase (retGC), a key enzyme in the cGMP recovery to the dark state, is solely activated by guanylyl cyclase-activating proteins (GCAPs) in a Ca[sup 2+]-sensitive manner. However, a question has arisen as to whether the observed GCAP stimulation of retGC is sufficient to account for the cGMP recovery because the stimulated activity measured in vitro is less than the light/GTP-activated cGMP phosphodiesterase activity. Here we report that the retGC activation by GCAPs is larger than previously reported and that a preincubation with adenine nucleotide is essential for the large activation. Under certain conditions, ATP is two times more effective than adenylyl imidodiphosphate (AMP-PNP), a hydrolysis-resistant ATP analog; however, this study mainly used AMP-PNP to focus on the role of adenine nucleotide binding to retGC. When photoreceptor outer segment homogenates are preincubated with AMP-PNP (EC[sub 50] = 0.65 ± 0.20 mM), GCAP2 enhanced the retGC activity 10-13 times over the control rate. Without AMP-PNP, GCAP2 stimulated the control activity only 3-4-fold as in previous reports. The large activation is due to a GCAP2-dependent increase in V[sub max] without an alteration of retGC affinity for GCAP2 (EC[sub 50] = 47.9 ± 2.7 nM). GCAP1 stimulated retGC activity in a similar fashion but with lower affinity (EC[sub 50] = 308 nM). In the AMP-PNP preincubation, low Ca[sup 2+] concentrations are not required, and retGC exists as a monomeric form. This large activation is accomplished through enhanced action of GCAPs as shown by Ca[sup 2+] inhibition of the activity (IC[sub 50] = 178 nM). We propose that retGC is activated by a two-step mechanism: a conformational change by ATP binding to its kinase homology domain under high Ca[sup 2+] concentrations that allows large enhancement of GCAP activation under low Ca[sup 2+] concentrations. [ABSTRACT FROM AUTHOR]

This paper presents an approach of using Simulated Annealing and Tabu Search for the simultaneous optimization of neural network architectures and weights. The problem considered is the odor recognition in an artificial nose. Both methods have produced networks with high classification performance and low complexity. Generalization has been improved by using the backpropagation algorithm for fine tuning. The combination of simple and traditional search methods has shown to be very suitable for generating compact and efficient networks. [ABSTRACT FROM AUTHOR]

This study investigated the pore distributions in water-saturated Ca-montmorillonite using 1H nuclear magnetic resonance (NMR) measurements for various dry densities (0.8–1.6 g/cm 3) and porewater salinity conditions (deionized water, 0.1 and 1 M CaCl 2) at a temperature range of 233–303 K. The volume fractions of the interlayer pore and the non-interlayer pore in the compacted Ca-montmorillonite were quantified by NMR relaxometry. At a lower Ca-montmorillonite density (0.8 g/cm 3), the volume fraction of the 3-HL-dominated interlayer pore was close to 20%, while that of the non-interlayer pore was higher (> 80%) than that in Na-montmorillonite. For the higher density (1.4 g/cm 3), the volume fraction of the interlayer pore in both Ca- and Na-montmorillonite seemed to be more than 90% close to the total porosity. This comparison showed that the main factor affecting the pore distribution in the compacted Ca- and Na-montmorillonite is density. Meanwhile, the effect of the porewater salinity is relatively smaller. The effect of the interlayer cations is also relatively smaller at the higher density. The established method based on NMR relaxometry is expected to provide structural parameters for a realistic modeling of mass transport in water-saturated compacted clay. • NMR relaxometry and X-ray diffractometry were applied to compacted clay. • The pore distribution was insensitive to salinity for higher compacted clay. • The effect of the interlayer cations type was small for higher compacted clay. • The main factor affecting the porewater was density. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the usefulness of deep learning image reconstruction (DLIR) to improve the image quality of dual-energy computed tomography (DECT) of the abdomen, compared to hybrid iterative reconstruction (IR). Methods: This study included 40 patients who underwent contrast-enhanced DECT of the abdomen. Virtual monochromatic 40-, 50-, and 70-keV and iodine density images were reconstructed using three reconstruction algorithms, including hybrid IR (ASiR-V50%) and DLIR (TrueFidelity) at medium- and high-strength level (DLIR-M and DLIR-H, respectively). The standard deviation of attenuation in liver parenchyma was measured as image noise. The contrast-to-noise ratio (CNR) for the portal vein on portal venous phase CT was calculated. The vessel conspicuity and overall image quality were graded on a 5-point scale ranging from 1 (poor) to 5 (excellent). The comparative scale of lesion conspicuity in 47 abdominal solid lesions was evaluated on a 5-point scale ranging from 0 (best) to −4 (markedly inferior). Results: The image noise of virtual monochromatic 40-, 50 -, and 70-keV and iodine density images was significantly decreased by DLIR compared to hybrid IR (p < 0.0001). The CNR was significantly higher in DLIR-H and DLIR-M than in hybrid IR (p < 0.0001). The vessel conspicuity and overall image quality scores were also significantly greater in DLIR-H and DLIR-M than in hybrid IR (p < 0.05). The lesion conspicuity scores for DLIR-M and DLIR-H were significantly higher than those for hybrid IR in the virtual monochromatic image of all energy levels (p ≤ 0.001). Conclusions: DLIR improves vessel conspicuity, CNR, and lesion conspicuity of virtual monochromatic and iodine density images in abdominal contrast-enhanced DECT, compared to hybrid IR. Key Points: • Deep learning image reconstruction (DLIR) is useful for reducing image noise and improving the CNR of visual monochromatic 40-, 50-, and 70-keV images in dual-energy CT. • DLIR can improve lesion conspicuity of abdominal solid lesions on virtual monochromatic images compared to hybrid iterative reconstruction. • DLIR can also be applied to iodine density maps and significantly improves their image quality. [ABSTRACT FROM AUTHOR]

Whether inflammatory biomarkers including procalcitonin (PCT) and C-reactive protein (CRP) are useful for predicting prognosis in nursing and healthcare-associated pneumonia (NHCAP) is unknown. The aim of the present study was to investigate the utility of serial PCT and CRP measurements for predicting prognosis and treatment efficacy for hospitalized NHCAP patients. This prospective, observational, cohort study enrolled consecutive NHCAP patients hospitalized at Kurashiki Central Hospital from October 2010 to September 2017. PCT and CRP were measured twice, once on admission and again within 48–72 h after admission. The primary outcome was 30-day all-cause mortality, and the secondary outcome was initial treatment failure. A total of 299 patients were included. The 30-day mortality rate was 8.4% (25/299), and the initial treatment failure rate was 15.4% (46/299). On multivariate analysis, performance status [odds ratio (OR) (95% confidence interval (CI)): 2.25 (1.34–3.77), P = 0.002], temperature [OR (95%CI): 0.53 (0.32–0.88), P = 0.02], heart rate [OR (95%CI): 1.03 (1.01–1.06), P = 0.007], albumin [OR (95%CI): 0.42 (0.18–0.95), P = 0.04], and blood urea nitrogen [OR (95%CI): 1.02 (1.00–1.05), P = 0.04] were significant prognostic factors, and CRP D3 [OR (95%CI): 1.07 (1.02–1.11), P = 0.003] and PSI [OR (95%CI): 1.01 (1.00–1.02), P = 0.01] were the predictors of initial treatment failure. Consecutive measurements of PCT and CRP were not significant predictors of 30-day mortality. Inflammatory biomarkers including PCT and CRP were not useful for predicting prognosis and treatment efficacy in NHCAP patients. We should carefully evaluate the patients' vital signs and comorbidities when managing NHCAP patients. [ABSTRACT FROM AUTHOR]

Introduction: Whether the sensitivity of the BinaxNOW Streptococcus pneumoniae urinary antigen test kit (BinaxNOW), adjusted by some variables including vital signs, laboratory examinations and pneumonia severity, has been decreasing is unknown. The aim of the present study was to investigate whether BinaxNOW sensitivity has decreased recently and to identify the predictors of the BinaxNOW result, including the time trend. Methods: This prospective cohort study enrolled consecutive patients with pneumococcal community-acquired pneumonia who were hospitalised at Kurashiki Central Hospital from January 2001 to December 2015. Pneumococcal community-acquired pneumonia was defined as positive blood or pleural effusion or sputum culture results. To evaluate the effect of the time trend for the sensitivity of BinaxNOW, time series regression analysis was performed. In addition, predictors of the BinaxNOW result were examined by multivariable analysis using variables such as sex, vital signs, blood tests such as C-reactive protein, albumin, blood urea nitrogen, creatinine, white blood cell count, haematocrit and platelets, antibiotic pre-treatment, bacteraemia, and pneumonia severity, in addition to time trend and seasonality. Results: A total of 446 patients were included. BinaxNOW sensitivity showed a significant, gradual decrease from 2001 (81.3%) to 2015 (48.7%). On multivariable analysis [odds ratio (95% confidence interval)], bacteraemia [2.516 (1.387–4.561), P = 0.002] was a predictor of a positive BinaxNOW result, whereas male sex [0.467 (0.296–0.736), P = 0.001], white blood cell count [0.959 (0.930–0.989), P = 0.008] and the time trend per year [0.900 (0.859–0.943), P < 0.001] were predictors of a negative BinaxNOW result. Conclusions: The sensitivity of BinaxNOW decreased over a 15-year period. We should be careful when interpreting BinaxNOW results in daily clinical practice, and the development of a new kit with good sensitivity is anticipated. Trial registration number: UMIN000004353. [ABSTRACT FROM AUTHOR]

Japan experienced a heavy rainfall event from June 28 to July 8, 2018, and many casualties were caused by both heavy rainfall and flooding. Few studies have investigated patients' characteristics and the causative pathogens of community-acquired pneumonia before and after heavy rainfall events. The aim of the present study was to evaluate the causative pathogens and clinical characteristics of hospitalized patients with community-acquired pneumonia before and after the heavy rainfall event using prospective cohort data. The study was divided into two periods: July to November 2013–2017 (before heavy rainfall) and July to November 2018 (after heavy rainfall). The patients' clinical characteristics and causative pathogens before and after the heavy rainfall were investigated. Regarding the causative pathogens, adjustments were made for precipitation and seasonal patterns. There were no significant differences in the number and clinical characteristics of patients before and after heavy rainfall. However, the frequency of Legionella pneumonia was significantly higher after than before the heavy rainfall event (8.9% vs 3.0%, P = 0.02) and remained significant after adjusting for precipitation and season. Three of 7 Legionella pneumonia patients engaged in reconstruction work and 2 Legionella pneumonia patients had soil exposure. An increased risk of Legionella pneumonia after not only rainfall and serious flooding, but also following recovery work or soil exposure should be considered. [ABSTRACT FROM AUTHOR]

Whether β-lactam and macrolide combination therapy reduces mortality in severe community-acquired pneumonia (SCAP) patients hospitalized in the intensive care unit (ICU) is controversial. The aim of the present study was to evaluate the usefulness of β-lactam and macrolide combination therapy for SCAP patients hospitalized in the ICU. A prospective, observational, cohort study of hospitalized pneumonia patients was performed. Hospitalized SCAP patients admitted to the ICU within 24 h between October 2010 and October 2017 were included for analysis. The primary outcome was 30-day mortality, and secondary outcomes were 14-day mortality and ICU mortality. Inverse probability of treatment weighting (IPTW) analysis as a propensity score analysis was used to reduce biases, including six covariates: age, sex, C-reactive protein, albumin, Pneumonia Severity Index score, and APACHE II score. A total of 78 patients were included, with 48 patients in the non-macrolide-containing β-lactam therapy group and 30 patients in the macrolide combination therapy group. β-lactam and macrolide combination therapy significantly decreased 30-day mortality (16.7% vs. 43.8%; P = 0.015) and 14-day mortality (6.7% vs. 31.3%; P = 0.020), but not ICU mortality (10% vs 27.1%, P = 0.08) compared with non-macrolide-containing β-lactam therapy. After adjusting by IPTW, macrolide combination therapy also decreased 30-day mortality (odds ratio, 0.29; 95%CI, 0.09–0.96; P = 0.04) and 14-day mortality (odds ratio, 0.19; 95%CI, 0.04–0.92; P = 0.04), but not ICU mortality (odds ratio, 0.34; 95%CI, 0.08–1.36; P = 0.13). Combination therapy with β-lactam and macrolides significantly improved the prognosis of SCAP patients hospitalized in the ICU compared with a non-macrolide-containing β-lactam regimen. [ABSTRACT FROM AUTHOR]

Abstract: Background: This study endeavored to clarify the location, frequency, and prognostic value of metastatic lymph nodes in the mediastinum among patients with left upper lung cancer who underwent complete dissection of the superior mediastinal lymph node through a median sternotomy. Methods: Forty-four patients with left upper lobe cancer underwent extended radical mediastinal nodal dissection (ERD), all of whom were analyzed in this retrospective study. The group comprised 12 females and 32 males, with ages ranging from 28 to 70 years (median age, 60 years). Mediastinal nodal status was assessed according to the systems of Mountain/Dresler 7 and Naruke 8. The clinicopathological records of each patient were examined for prognostic factors, including age, sex, histology, tumor size, c-N number, preoperative serum CEA level, metastatic stations and distribution of metastatic nodes according to Naruke''s system 8. The superior mediastinal lymph nodes which cannot be dissected through a left thoracotomy (bilateral #1 and #2, #3, right #3a, and right #4 according to Naruke''s map 8 were defined as extra-superior mediastinal nodes for left lung cancer (ESMD). Results: Fourteen patients had one or more metastases to mediastinal lymph nodes, among whom the most common metastatic station was the aortic nodes: 71.4% had metastasis to #5 or #6 (57.1% to #5 and 50% to #6). The next most common metastatic station was the left tracheobronchial nodes (42.8%). Metastasis to the ESMD occurred in 7 of the 44 study subjects (16%), representing a 50% rate of occurrence (7/14) among those with mediastinal nodal involvement. Univariate analysis found that CN factor and aortic nodal involvement (#5, #6) were significant predictive factors for ESMD metastasis. Multivariate analysis determined that only aortic nodal involvement was significant (p =0.008). Furthermore, ESMD metastasis was rare (5.8%) in the absence of aortic node metastasis. The overall survival rate at 5 years was 50% among the patients without ESMD metastasis. However, the survival rate was 32% at 3 years and 0% at 5 years among the seven patients with ESMD metastasis. Conclusions: The aortic lymph node is the most common site of metastasis from left upper lobe cancer. Multivariate analysis demonstrated that aortic nodal involvement was a significant predictive factor for ESMD metastasis. Based upon the rates of metastasis and the post-operative prognosis in our study patients, dissection of aortic nodes and left tracheobronchial nodes may be important for patients with left upper lobe cancer. Whether ESMD dissection has a beneficial effect on prognosis remains controversial. [Copyright &y& Elsevier]

The usefulness of existing pneumonia severity indices for predicting mortality in nursing and healthcare-associated pneumonia (NHCAP) is unclear. This study compared the usefulness of existing pneumonia severity indices for predicting mortality in NHCAP and community-acquired pneumonia (CAP). Consecutive hospitalized pneumonia patients including NHCAP and CAP patients were prospectively enrolled between October 2010 and November 2017. Admission pneumonia severity was assessed using CURB-65, Pneumonia Severity Index (PSI), A-DROP, Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) severe pneumonia criteria, and I-ROAD. The primary outcome was 30-day mortality. The discriminatory ability of each severity index was evaluated by receiver operating characteristic curve analysis. Overall, 828 patients had NHCAP, and 1330 patients had CAP. Thirty-day mortality was 12.8% and 5.6% in NHCAP and CAP patients, respectively. The area under the curve of PSI (0.717, 95% confidence interval 0.673–0.761) was the highest among all pneumonia severity indices, with significant differences compared with CURB-65 (0.651, 95% confidence interval 0.598–0.705, P = 0.02) and IDSA/ATS severe pneumonia criteria (0.659, 95% confidence interval 0.612–0.707, P = 0.03). The predictive abilities for 30-day mortality of the pneumonia severity indices, excluding PSI and I-ROAD, were significantly inferior for NHCAP than for CAP. PSI may be the most useful pneumonia severity score for predicting mortality in NHCAP. However, the predictive ability for mortality of each pneumonia severity score was worse for NHCAP than for CAP; therefore, the prognostic factors in NHCAP need to be identified for better management of NHCAP patients. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the usefulness of inflammatory biomarkers such as white blood cell (WBC) count, C-reactive protein (CRP) and procalcitonin (PCT) for differentiating cryptogenic organising pneumonia (COP) from community-acquired pneumonia (CAP). Methods: COP patients hospitalised in Kurashiki Central Hospital between January 2010 and December 2017 whose WBC counts and CRP and PCT levels were measured were investigated retrospectively, and their results were compared with those of hospitalised CAP patients who were prospectively enrolled between October 2010 and November 2017. Definite COP was defined by specific histopathological findings, and possible COP was defined as a consolidation shadow on chest computed tomography and lymphocyte dominance in bronchoalveolar lavage fluid in the absence of specific histopathological findings or lung specimens. The discriminatory abilities of WBC counts, CRP and PCT were evaluated by receiver operating characteristic (ROC) curve analysis. Results: There were 56 patients in the entire COP group, 35 (61.4%) with definite COP, and 914 CAP patients. All three biomarkers were significantly lower in COP than in CAP. The AUC value of PCT in all COP patients was 0.79, significantly higher than of both CRP (AUC 0.59, p < 0.001) and WBC (AUC 0.69, p = 0.048). In definite COP patients, the AUC value of PCT was 0.79, which was also significantly higher than of both WBC (AUC 0.64, p = 0.006) and CRP (AUC 0.64, p = 0.001). Conclusions: PCT is a more useful biomarker for differentiating COP from CAP than WBC count or CRP. However, PCT should be used as an adjunct to clinical presentation and radiological findings. [ABSTRACT FROM AUTHOR]

Background: Quick Sepsis-related Organ Failure Assessment (qSOFA) is a new screening system for sepsis. The prognostic performance of qSOFA for patients with suspected infections outside the intensive care unit (ICU) is similar to that of full SOFA; however, its performance for community-acquired pneumonia (CAP) has not yet been evaluated in detail. The objectives of the present study were to compare the prognostic performance of qSOFA with existing pneumonia severity scores, such as CURB-65 (confusion, blood urea nitrogen > 19 mg/dL, respiratory rate ≥ 30/min, systolic blood pressure < 90 mmHg, or diastolic blood pressure ≤ 60 mmHg, age ≥ 65 years) and the pneumonia severity index (PSI), and examine its usefulness for predicting mortality and ICU admission in patients with CAP of high severity and mortality that requires hospitalization. Methods: We performed a secondary analysis of data from a prospective observational study of adult patients who were admitted to our hospital between October 2010 and June 2016. We compared the prognostic performance of qSOFA, CURB-65, and PSI for predicting in-hospital mortality and ICU admission using the C statistics. Results: The median age of the 1045 enrolled patients was 77 (68–83) years, and 71.4% were males. The in-hospital mortality and ICU admission rates of the entire cohort were 6.1 and 7.9%, respectively. All scores were significantly higher in non-survivors and ICU admission patients than in survivors and non-ICU admission patients (p < 0.001). The C statistics of qSOFA for predicting in-hospital mortality was 0.69 (95% CI 0.63–0.75), and no significant differences were observed between CURB-65 (C statistics, 0.75; 95% CI 0.69–0.81) and PSI (C statistics, 0.74; 95% CI 0.69–0.80). The C statistics of qSOFA for predicting ICU admission was 0.76 (95% CI 0.71–0.80), and no significant differences were noted between CURB-65 (C statistics, 0.73; 95% CI 0.67–0.79) and PSI (C statistics, 0.72; 95% CI 0.66–0.78). Conclusions: Regarding hospitalized CAP, the prognostic performance of qSOFA for in-hospital mortality and ICU admission was not significantly different from those of CURB-65 and PSI. qSOFA only requires a few items and vital signs, and, thus, may be particularly useful for emergency department or non-respiratory specialists. [ABSTRACT FROM AUTHOR]

Background and objective This study aimed to investigate the usefulness of procalcitonin-guided therapy in hospitalized community-acquired pneumonia patients to reduce antibiotic duration and costs without worsening prognosis. Methods 352 hospitalized community-acquired pneumonia patients in an observational cohort study in which procalcitonin was measured three times serially, on admission (Day 1) and 2–3 days (Day 3) and 6–8 days (Day 7) after admission, between October 2010 and February 2016 were reviewed retrospectively. Antibiotics could be stopped if Day 7 procalcitonin was <0.25 ng mL −1 or ≤10% of the higher value of procalcitonin on Day 1 or 3. Antibiotic duration and costs and recurrence and mortality rates were evaluated in mild to moderate or severe pneumonia by theoretical procalcitonin guidance for community-acquired pneumonia treatment. Results Using theoretical procalcitonin guidance, antibiotic duration could be reduced from 12.6 to 8.6 days ( P < 0.001), while costs could be reduced from 45,833 to 38,952 yen ( P = 0.005). Among the patients in whom theoretical procalcitonin guidance could be adopted, recurrence rates (5.6% vs. 8.1%, P = 0.15) and mortality rates (0% vs. 5.1%, P = 0.07) did not worsen between the group having the same antibiotic durations as with theoretical procalcitonin guidance in actual practice (N = 71) and the group having durations more than 2 days longer in actual practice than in theoretical procalcitonin guidance (N = 198). There was no significant difference in pneumonia severity using A-DROP, CURB-65, and PSI between two groups. Conclusions Procalcitonin-guided therapy may be useful in hospitalized community-acquired pneumonia patients to reduce antibiotic duration and costs without worsening the prognosis. [ABSTRACT FROM AUTHOR]

Rationale The new acronym, PES pathogens ( Pseudomonas aeruginosa , Enterobacteriaceae extended-spectrum beta-lactamase-positive, and methicillin-resistant Staphylococcus aureus ), was recently proposed to identify drug-resistant pathogens associated with community-acquired pneumonia. Objectives To evaluate the risk factors for antimicrobial-resistant pathogens in immunocompetent patients with pneumonia and to validate the role of PES pathogens. Methods A retrospective analysis of a prospective observational study of immunocompetent patients with pneumonia between March 2009 and June 2015 was conducted. We clarified the risk factors for PES pathogens. Results Of the total 1559 patients, an etiological diagnosis was made in 705 (45.2%) patients. PES pathogens were identified in 51 (7.2%) patients, with 53 PES pathogens ( P. aeruginosa, 34; ESBL-positive Enterobacteriaceae , 6; and MRSA, 13). Patients with PES pathogens had tendencies toward initial treatment failure, readmission within 30 days, and a prolonged hospital stay. Using multivariate analysis, female sex (adjusted odds ratio [AOR] 1.998, 95% confidence interval [CI] 1.047–3.810), admission within 90 days (AOR 2.827, 95% CI 1.250–6.397), poor performance status (AOR 2.380, 95% CI 1.047–5.413), and enteral feeding (AOR 5.808, 95% CI 1.813–18.613) were independent risk factors for infection with PES pathogens. The area under the receiver operating characteristics curve for the risk factors was 0.66 (95% CI 0.577–0.744). Conclusions We believe the definition of PES pathogens is an appropriate description of drug-resistant pathogens associated with pneumonia in immunocompetent patients. The frequency of PES pathogens is quite low. However, recognition is critical because they can cause refractory pneumonia and different antimicrobial treatment is required. [ABSTRACT FROM AUTHOR]

Extracorporeal membrane oxygenation (ECMO) is widely used for circulatory support in pediatric cardiac patients with low cardiac output and hypoxemia. We retrospectively evaluated the efficacy of ECMO support for respiratory and heart failure in infants and children. From April 2002 to February 2011, 14 patients aged 19 days to 20 years old (average 44 months), with body weight 2.6 kg to 71 kg (median 14.1 kg), underwent ECMO support for failing cardiac function, hypoxemia, and low cardiac output syndrome. In 12 patients, ECMO was introduced after operation for congenital heart disease (four with complete repair including Fontan circulation, and eight with palliative repair). In one patient, ECMO was introduced after partial pulmonary resection for congenital cystic adenomatoid malformation because of respiratory failure. ECMO was introduced in a patient with severe heart failure caused by fulminant myocarditis. Patients' demographics, duration of extracorporeal membrane oxygenation, additional support, and outcomes were analyzed. Ten patients (71%) were successfully weaned from ECMO, and eight patients (57%) were discharged from the hospital. The mean duration of ECMO support was 332 h (range 11-2030 h). Although management of the ECMO circuit, including anticoagulation (activated clotting time: 150-250), was conducted following the institutional practice guidelines, it was difficult to control the bleeding. Seven patients required renal replacement therapy during ECMO support using peritoneal dialysis or continuous hemodiafiltration. Five patients had additional operative procedures: systemic-pulmonary shunt in two, bidirectional Glenn takedown with right modified Blalock-Taussig shunt, total cavopulmonary connection takedown, and redo ECMO in one patient each. The patient who had the longest ECMO support for respiratory failure due to acute respiratory distress syndrome after lung surgery was successfully weaned from ECMO because high-frequency oscillation (HFO) improved respiratory function. ECMO for heart and respiratory failure in infants and children is effective and allows time for recovery of cardiac dysfunction and acute hypoxic insult. The long-term ECMO support for over 2000 h was very rare, but it was possible to wean this patient from ECMO using HFO. [ABSTRACT FROM AUTHOR]

• Targeted therapy for UAT-positive pneumococcal CAP was low rate. • Identification of GPDC was positive predictive factor of targeted therapy. • Aspiration and severe pneumonia were negative predictive factors. • Targeted therapy for UAT-positive pneumococcal CAP did not have worse outcomes. The aim of the present study was to investigate the predictors of targeted therapy (TT) for pneumococcal community-acquired pneumonia (PCAP) with a positive urinary antigen test (UAT) and compare the outcomes with those of nontargeted therapy. This prospective cohort study enrolled consecutive PCAP patients with a positive UAT who were hospitalized at Kurashiki Central Hospital from October 2010 to November 2019. A total of 286 patients were included. Of them, 56 patients (19.6%) were included in the TT group. On multivariate analysis, identification of Gram-positive diplococci by Gram stain (OR [95% CI]: 2.46 [1.32–4.63]) was a positive predictor, whereas aspiration pneumonia (0.17 [0.03–0.59]) and CURB-65 score (0.59 [0.42–0.81]) were negative predictors of TT. Initial treatment failure and 30-day mortality were not significantly different. The UAT is not used enough for TT, and TT for PCAP did not have worse outcomes. [ABSTRACT FROM AUTHOR]

Abstract: ATP bound to retinal guanylate cyclase (retGC)/membranes prior to the assay (pre-binding effect) and during the assay (direct effect) further enhances retGC activity stimulated by GC-activating proteins (GCAPs). Here we investigate differences between these two effects. We found that the pre-binding effect, but not the direct effect, was absent in membranes pre-washed with Mg2+-free hypotonic buffers, that the pre-binding effect, but not the direct effect, was strictly limited to GCAP-stimulated retGC activity, and that these two effects were independent and additive rather than being synergistic. Pre-incubation with amiloride enhanced GCAP2-activated retGC activity in a manner similar to that by ATP pre-binding; however, amiloride did not directly stimulate the retGC activity. These results indicate that these two effects are mechanistically different. Levels of retGC activation by these effects and conditions required for these effects indicate that only the mechanism involving ATP pre-binding is physiologically relevant to retGC activation. [Copyright &y& Elsevier]

Background: Right upper lobectomy with right cervical and bilateral mediastinal lymph node dissection via a median approach was performed for non-small cell lung cancer. Methods: From 1995 to 2003, 48 patients aged ≤ 70 years underwent resection of cancer in the right upper lobe, including 26 with N0, four with N1 and 18 with N2 disease. Results: Metastases to the right cervical, highest mediastinal, pretracheal and bilateral tracheobronchial lymph nodes were frequent. There were no operative or hospital deaths. Preoperative accuracy of N-factor diagnosis was only 35.4%. The overall 5-year survival rate was 58.8%. The rate for C-N2 disease ( n = 18) was 42.6%, and the rate for p-N2 disease ( n = 7) and p-N3 disease ( n = 13) was 57.1% and 0%, respectively, using the Kaplan−Meier method. Conclusions: Patients without N3 disease have a good prognosis, and extended and systematic radical lymphadenectomy via median sternotomy improves the staging, and possibly the prognosis of pure N2 disease. [ABSTRACT FROM AUTHOR]

Cyclic GMP phosphodiesterase (PDE6) in rod photoreceptors, a key enzyme in vertebrate phototransduction, consists of two homologous catalytic subunits (Pα and Pβ) and two identical regulatory subunits (Pγs). Pγ regulates the PDE activity through its direct interaction with transducin. Here, using electron microscopy and image analysis of single particles, we show the three-dimensional organization of the basic form of bovine PDE, Pαβγγ, and compare its average image with those of Pγ-released PDE. The structure of Pαβγγ appears to be a flattened bell-shape, with dimensions of 150×108×60 A˚, and with a handle-like protrusion attached to the top of the structure. Except for the protrusion, the organization consists of two homologous structures arranged side by side, with each structure having three distinct regions, showing pseudo twofold symmetry. These characteristics are consistent with a model in which the overall structure of Pαβγγ is determined by hetero-dimerization of Pα and Pβ, with each subunit consisting of one catalytic and two GAF regions. A comparison of the average image of Pαβγγ with those of Pγ-released PDE suggests that Pγ release does not affect the overall structure of Pαβ, and that the Pαβ C-terminus, but not Pγ, is a determinant for the Pαβ orientation on carbon-coated grids. These observations suggest that the basic structure of PDE does not change during its regulation, which implies that Pαβ is regulated by its regional interaction with Pγ. [Copyright &y& Elsevier]

Investigates phosphorylation of Pgamma by camp-dependent protein kinase and its functional effect on the Pgamma interaction with Palphabeta or Talpha in vitro. Examination of the functionally of Pgamma; Information on previous studies on phosphorylation; Methods and materials used to carry out the investigation.

Two guanylate-cyclase-activating proteins (GCAP) encoded by a tail-to-tail gene array have been characterized in the mammalian retina. Using frog retina as a model, we obtained evidence for the presence of a photoreceptor Ca2+-binding protein closely related to GCAP. This protein (206 amino acids) does not stimulate guanylate cyclase (GC) in low [Ca2+], but inhibits GC in high [Ca2+], and is therefore termed guanylate-cyclase-inhibitory protein (GCIP). Sequence analysis indicates that GCIP and GCAP1 and GCAP2 have diverged substantially, but conserved domains present in all vertebrate GCAP are present in GCIP. Moreover, partial characterization of the GCIP gene showed that the positions of two introns in the GCIP gene are identical to positions of corresponding introns of the mammalian GCAP gene array. As to the major differences between GCIP and GCAP, the fourth EF hand Ca2+-binding motif of GCIP is disabled for Ca2+ binding, and GCIP does not stimulate GC. Monoclonal and polyclonal antibodies raised against recombinant GCIP identified high levels of GCIP in the inner segments, somata and synaptic terminals of frog cone photoreceptors. The results suggest that GCIP is a Ca2+-binding protein of the GCAP/recoverin subfamily. Its localization in frog cones closely resembles that of GC in mammalian cones. GCIP inhibits GC at high free [Ca2+], competing with GCAP1 and GCAP2 for GC regulatory sites. [ABSTRACT FROM AUTHOR]

Whether macrolide combination therapy reduces the mortality of patients with severe community-acquired pneumonia (CAP) hospitalized in the non-intensive care unit (ICU) remains unclear. Therefore, we investigated the efficacy of adding azithromycin to β-lactam antibiotics for such patients. This prospective cohort study enrolled consecutive patients with CAP hospitalized in the non-ICU between October 2010 and November 2016. The 30-day mortality between β-lactam and azithromycin combination therapy and β-lactam monotherapy was compared in patients classified as mild to moderate and severe according to the CURB-65, Pneumonia Severity Index (PSI), and Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) criteria. Inverse probability of treatment weighting (IPTW) analysis was used to reduce biases. Based on the CURB-65 and PSI, combination therapy did not significantly reduce the 30-day mortality in either group (179 patients in the combination group, 952 in the monotherapy group). However, based on the IDSA/ATS criteria, combination therapy significantly reduced the 30-day mortality in patients with severe (odds ratio [OR] 0.12, 95% confidence interval [CI] 0.007–0.57), but not non-severe pneumonia (OR 1.85, 95% CI 0.51–5.40); these results were similar after IPTW analysis. Azithromycin combination therapy significantly reduced the mortality of patients with severe CAP who met the IDSA/ATS criteria. [ABSTRACT FROM AUTHOR]