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Affinity maturation increases antigen-binding affinity and specificity of antibodies by somatic hypermutation. Various monoclonal antibodies against (4-hydroxy-3-nitrophenyl)acetyl (NP) were obtained during affinity maturation. Among them, highly matured anti-NP antibodies, such as E11 and E3, possess Cys96 H and Cys100 H in the complementarity-determining region 3 of the heavy chain, which would form a disulfide bond. In this study, we evaluated the effects of disulfide bonds on antigen binding by generating single-chain Fv (scFv) antibodies of E11 and its mutants, E11_C96K H /C100E H and E11_C96K H /C100Q H , and determined their antigen-binding thermodynamics and kinetics. The binding affinities of the Cys mutants were lower than that of E11 scFv, indicating that the disulfide bond contributed to antigen binding, especially for stable complex formation. This was also supported by the decreased affinity of E11 scFv in the presence of a reducing agent. The crystal structures of NP-free and NP-bound E11 scFvs were determined at high resolution, showing the existence of a disulfide bond between Cys96 H and Cys100 H , and the antigen recognition mechanism, which could be compared with those of other anti-NP antibodies, such as germline-type N1G9 and matured-type C6, as reported previously. These structures could explain the molecular basis of changes in antigen-binding affinity and thermal stability in the absence or presence of antigens. Small-angle X-ray scattering further showed a local conformational change in E11 scFv upon antigen binding in solution., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Transplant recipients (TRs) are at high risk for severe coronavirus disease 2019 (COVID-19). Neutralizing monoclonal antibodies (mAbs) are used for treating mild-to-moderate COVID-19. However, reports comparing the efficacy of COVID-19 treatment without/with mAbs in TRs are limited. We assessed the efficacy of casirivimab/imdevimab against mild-to-moderate COVID-19 in TRs., Methods: Forty-one patients were retrospectively evaluated. The duration until defervescence, oxygen (O 2 ) requirement ≥5 L, and neutralizing antibody levels were compared in TRs with COVID-19 without/with casirivimab/imdevimab., Results: Casirivimab/imdevimab was correlated with shorter duration until defervescence and non-requirement of O 2  ≥ 5 L in TRs with COVID-19 [mean: without/with: 6 vs. 2; P = 0.0002, hazard ratio (HR) = 0.3333, 95% confidence interval (CI) = 0.1763-0.6301; 15 vs. 8; P < 0.0001, HR = 0.5333, 95% CI = 0.2878-0.9883; P = 0.0377, HR = 0.1502, 95% CI = 0.02511-0.8980]. Casirivimab/imdevimab was associated with early defervescence after adjusting for sex and age (P = 0.013, HR = 0.412, 95% CI = 0.205-0.826). The antibody levels between patients without/with casirivimab/imdevimab on the day of hospitalization were not significantly different (P = 0.1055), including 13 TRs with vaccination. Antibody levels were higher in patients with casirivimab/imdevimab at 3-5 days after hospitalization than in those without, at 7-9 days after hospitalization (P < 0.0001, mean, without/with: 414.9/40000 AU/mL)., Conclusion: Casirivimab/imdevimab was effective and increased the neutralizing antibody in TRs with mild-to-moderate COVID-19, it may contribute toward preventing the progression., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The conversion of agricultural waste into high-value carbon products has been an attractive area in waste management strategy. This study highlighted the synthesis and effectiveness of green pea peels (GPP), green pea biochar (GPBC), and nano-ferromagnetic green pea biochar (NFGPBC) by the ferrous/ferric co-precipitation synthesis method for eliminating cationic dyes molecules from solutions. The morphological, physicochemical, and structural properties of GPP, GPBC, and NFGPBC were approved by Scanning Electron Microscopy (SEM), Transmission Emission Microscopy (TEM), Energy Dispersive X-ray (EDX), Bruneau Emmett Teller (BET), Fourier Transform Infrared spectroscopy (FTIR), and X-ray Diffraction (XRD) techniques. Vibrating Sample Magnetometry (VSM) analysis confirmed the NFGPBC magnetization performance. The capacity of each adsorbent for methylene blue removal was evaluated at various parameters of material dosage (50-250 mg/150 mL), pH (2-12), initial concentration (50-250 mg/L), contact time (0-90 min) and temperature (20-60 °C). The three developed adsorbent materials GPP, GPBC, and NFGPBC, possessed reasonable BET surface areas of 0.6836, 372.54, and 147.88 m 2 g -1, and the corresponding monolayer adsorption capacities of 163.93, 217.40, and 175.44 mg/g, respectively. The superior performances of GPBC and NFGPBC were due to their increased surface area compared with the parent green pea peels (GPP). The results from adsorption kinetics studies of all prepared materials were pseudo-second-order and Elovich kinetics models. The thermodynamic parameters exhibited MB sorption's favorability, spontaneity, and endothermic nature. The NFGPBC material experienced Vander Waal forces, electrostatic interaction, hydrogen bonding, and hydrophobic interactions as predominant modes of the solid-liquid interaction. The regeneration, recycling, and reusability of the synthesized GPP, GPBC, and NFGPBC performed at five adsorption cycles revealed that NFGPBC demonstrated excellent cyclical performances attaining a minimum 8.9% loss in capacity due to paramagnetic properties. Thus, NFGPBC is a green, efficient, and eco-friendly material recommended for large-scale production and application in wastewater., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Diagnostic imaging modalities to evaluate the three-dimensional distribution of thoracodorsal artery perforators (TDAPs) are lacking. In this study, TDAPs were visualized and characterized using photoacoustic imaging., Material and Methods: In this study, 34 sites in the lateral chest wall of 18 individuals were analyzed. The region extending 5 cm ventral and 5 cm dorsal to the lateral edge of the latissimus dorsi (LD) and 5-15 cm from the posterior axillary fold was scanned using photoacoustic imaging. The largest perforator closest to the edge of the LD was characterized. The location of the stem portion and the orientation of the longest cutaneous branch of the perforator were described. The relationship between the maximal depth of delineation on photoacoustic images and the depth of the deep fascia was assessed., Results: On average, 2.6 perforators (range, 1-5 perforators) were visualized in the region of interest. The distribution of the TDAP stem portion was similar to that in previous studies. Cutaneous branches were preferentially oriented in a medial-caudal direction. The length of delineated cutaneous branches varied (range, 7-78 mm) depending on the thickness of the subcutaneous layer. Vessels under the LD were observed when the subcutaneous layer was thin., Conclusion: Photoacoustic imaging can successfully visualize TDAPs in three dimensions. Visualization of TDAPs varied by the thickness of the subcutaneous layer. A thin deep fascia of the LD might be a cause of deep laser penetration., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest in association with the present study. The author(s) used a photoacoustic imaging system made by Canon Inc., Tokyo, Japan., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Exogenous lipoid pneumonia (ELP) develops when lipid-containing substances enter the airways through aspiration or inhalation and incite an inflammatory response. The diagnosis of ELP often is difficult because findings may be nonspecific. The clinical course of ELP has not been well characterized., Research Question: What are the presenting clinicoradiologic features of ELP, its causative agents, and clinical course?, Study Design and Methods: We searched the Mayo Clinic electronic medical records for patients diagnosed with ELP between 1998 and 2020. Inclusion diagnostic criteria were: (1) lipoid pneumonia (LP) on histopathologic examination, (2) lipid-laden macrophages in BAL fluid, or (3) fatty attenuation of parenchymal opacities on chest CT imaging. Additionally, all patients were required to have a clinician diagnosis of LP in the absence of conditions known to cause endogenous LP., Results: Thirty-four patients were identified. Mean age was 71 years, with no sex predominance; one-half were asymptomatic. The diagnosis was confirmed by lung biopsy (including three lobectomies for suspected malignancy) in 71% of patients, CT scan in 24% of patients, and BAL in 5% of patients. Most patients manifested bilateral parenchymal opacities that commonly involved the lower lobes; fatty attenuation was identifiable in only 41% of patients. A causative substance was identified in 79% of patients, in most cases after the diagnosis was established. Over a median follow-up of 1.2 years, only 20% of patients with chronic respiratory symptoms improved, whereas 50% worsened. Over a median follow-up interval of 1 year, CT scan abnormalities improved or resolved in 33% of patients and progressed in 39% of patients. Patients who deteriorated were older, with a higher prevalence of GI disorders than those who remained stable or improved., Interpretation: ELP often is asymptomatic and may not manifest fatty attenuation on chest CT imaging. Clinical and radiologic abnormalities persist or worsen in most affected patients, even when the causative agent is discontinued., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Interleukin 15 receptor (IL-15R) is a transmembrane signalling protein consisting of 3 subsets: α, β (IL-15Rβ), and γ (γ c ). IL-2 and IL-15 share the signalling domains IL-15Rβ and γ c , although they bind to intrinsic α-subsets and non-signalling domains. Additionally, IL-2 and IL-15 play different roles; therefore, there have been many observations of the dynamic behaviours of IL-15R, which are linked to physiological functions. For more practical discrimination between IL-2 and IL-15, a study was designed and carried out in which α-subsets were removed and a cytoplasmic inhibitor was applied to create a simplified environment in which secondary signalling molecules were reduced. We also applied a new measurement method, diffracted X-ray blinking (DXB), to achieve higher accuracy (<0.01 Å). The dynamics of IL-2 binding (confined motion, max range = 0.71 Å) and IL-15 binding (normal motion) in live natural killer cells were different. We also confirmed. that DXB was a suitable method to quantitatively evaluate the transmembrane protein dynamics of inner/outer live cell membranes by labeling the extracellular domain since the measurements were dependent on the cytosolic environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Right ventricular (RV) dysfunction in sepsis and septic shock has been infrequently studied and has uncertain prognostic significance., Research Question: Does RV function impact mortality in sepsis and septic shock?, Study Design and Methods: We reviewed the published literature from January 1999 to April 2020 for studies evaluating adult patients with sepsis and septic shock. Study definition of RV dysfunction was used to classify patients. The primary outcome was all-cause mortality divided into short-term mortality (ICU stay, hospital stay, or mortality ≤30 days) and long-term mortality (>30 days). Effect estimates from the individual studies were extracted and combined, using the random-effects, generic inverse variance method of DerSimonian and Laird., Results: Ten studies, 1,373 patients, were included; RV dysfunction was noted in 477 (34.7%). RV dysfunction was variably classified as decreased RV systolic motion, high RV/left ventricular ratio and decreased RV ejection fraction. Septic shock, ARDS, and mechanical ventilation were noted in 82.0%, 27.5%, and 78.4% of the population, respectively. Patients with RV dysfunction had lower rates of mechanical ventilation (71.9% vs 81.9%; P < .001), higher rates of acute hemodialysis (38.1% vs 22.4%; P = .04), but comparable rates of septic shock and ARDS. Studies showed moderate (I 2  = 58%) and low (I 2  = 49%) heterogeneity for short-term and long-term mortality, respectively. RV dysfunction was associated with higher short-term (pooled OR, 2.42; 95%CI, 1.52-3.85; P = .0002) (10 studies) and long-term (pooled OR, 2.26; 95%CI, 1.29-3.95; P = .004) (4 studies) mortality., Interpretation: In this meta-analysis of observational studies, RV dysfunction was associated with higher short-term and long-term mortality in sepsis and septic shock., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

G protein-coupled receptors (GPCRs) are seven-transmembrane proteins, which transmit extracellular signals inside cells via activating G proteins. GPCRs are involved in a wide variety of physiological functions, such as signal sensing, immune system processes, and neurotransmission. Although the structures and functions of GPCRs have been well studied, little has been known about their real-time dynamics on live cells. In this study, we used Diffracted X-ray Tracking (DXT) and Diffracted X-ray Blinking (DXB) techniques for analysis. These methods are very precise single-molecular analytical techniques that elucidate protein dynamics by analyzing the diffraction spots from the gold nanocrystals labeled on the protein surface. DXT tracks diffraction spot movements, whereas DXB analyzes continuation of signals by calculating the autocorrelation function of each pixel from the recorded data. Serotonin receptor subtype 2A (5-HT 2A receptors) were transiently expressed on HEK 293 cells, and the gold nanocrystals were attached to the N-terminally introduced FLAG-tag via anti-FLAG antibodies. Fast- and mid-range motions were recorded by DXT with 100μs and 1.25 ms/frame rate, respectively. Slow-range motion was obtained using the DXB method with 100 ms/frame rate. An agonist interestingly suppressed the fluctuations of 5-HT 2A receptors at the microsecond-ranged fast measurement. On the contrary, the motion was enhanced by the agonist in the hundred-millisecond-ranged slow time scale. These dual-natured data may suggest that we succeeded in extracting different modes of receptor's motion on live cells; microsecond ranged fluctuation on the cell membrane, and millisecond-ranged dynamic movement comprising interactions with intracellular signaling molecules., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Recent clinical trials' findings have revealed the therapeutic noninferiority of direct oral anticoagulant (DOAC) to standard therapy with vitamin K antagonist (VKA) in patients with pulmonary thromboembolism (PTE). However, few studies have quantitatively analyzed thrombus reduction in the pulmonary artery., Methods: This observational study included 38 symptomatic PTE patients with stable hemodynamics. All patients received an intravenous heparin bolus followed by continual heparin injections immediately after the PTE diagnosis. The heparin was discontinued after edoxaban therapy began in the DOAC group (n = 22) or after the therapeutic range for the prothrombin time-international normalized ratio was achieved in the VKA group (n = 16). The thrombus volumes in the pulmonary arteries were quantitatively analyzed using contrast-enhanced computed tomography scans, and they were compared at baseline and at 2 weeks after admission., Results: The pulmonary thrombus volumes declined in the VKA and DOAC groups from 7.9 to 4.2 cm 3 (P = 0.048) and from 7.1 to 3.7 cm 3 (P < 0.01), respectively, and the thrombus reduction rates did not differ significantly between the groups (-34% vs. -64%, respectively; P = 0.38). The fibrinogenolysis parameter changes during the14 days after admission were similar in both groups. Compared with the VKAgroup, the average hospital stay was 9days shorter in the DOAC group. There were no in-hospital deaths, and 1 case experienced major bleeding in the VKA group., Conclusions: In relation to pulmonary artery thrombus volume reduction, DOAC monotherapy for PTE may be comparable with standard therapy involving VKAs., (Copyright © 2020 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Background: The effects of high-sensitivity C-reactive protein (hs-CRP) levels on clinical outcomes in chronic-phase acute coronary syndrome (ACS) patients undergoing aggressive lipid-lowering therapy remain unclear. We examined the effects of hs-CRP levels on the prognosis of ACS patients who underwent aggressive lipid-lowering therapy and determined treatment targets for hs-CRP value., Methods: This post-hoc sub-analysis of a prospective randomized control trial (HIJ-PROPER) included 1734 ACS patients with dyslipidemia, who were divided into hs-CRP quartiles after 3 months of treatment. Primary endpoints were combined all-cause death, non-fatal myocardial infarction, non-fatal stroke, unstable angina, and ischemia-driven coronary revascularization. Secondary endpoint was all-cause death., Results: The median follow-up period was 3.7 years. Overall, 1415 patients were evaluated retrospectively. No significant among-group differences were noted in low-density lipoprotein cholesterol (LDL-C) levels over time (p = 0.44). Kaplan-Meier analyses revealed that the incidence of the primary and secondary endpoints was significantly higher in the highest hs-CRP group than in the other groups [hazard ratio (HR) = 1.52, 95% confidence interval (CI) = 1.16-2.00, p < 0.01; HR = 5.30, 95% CI = 2.47-11.32, p < 0.01, respectively]. The cut-off hs-CRP level to predict all-cause death was 0.74 mg/L (receiver operating characteristic curve: sensitivity: 68%, specificity: 62%). Multivariate analyses revealed that hs-CRP ≥0.74 mg/L　at 3 months was correlated with an increased risk of all-cause death (adjusted HR = 3.68, 95% CI = 2.22-6.10, p < 0.01)., Conclusion: Elevated hs-CRP levels independently predicted a worse prognosis, regardless of LDL-C levels, suggesting that interventions against elevated inflammatory responses plus intensive lipid-lowering therapy and coronary revascularization are encouraging options for secondary prevention in ACS patients., Trial Registration: This trial is registered with the UMIN Clinical Trials Registry number UMIN000002742. Trial name: Proper level of lipid lowering with pitavastatin and ezetimibe in acute coronary syndrome (HIJ-PROPER) URL: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr-view.cgi?recptno=R000003334., (Copyright © 2019 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Deltoid ligament injuries account for 5.1% to 15.8% of ankle sprains and occur with concomitant lateral ankle sprains. The anterior tibiotalar ligament (ATTL), located within the deep layer of the deltoid ligament complex, connects the talus and the tibia on the medial side of the ankle and controls ankle eversion and rotation. If conservative treatment for chronic medial ankle instability after an ankle sprain fails, ATTL repair or reconstruction might be necessary. Arthroscopic reconstruction techniques of the lateral ankle ligaments recently have been reported. Here, we describe arthroscopic reconstruction of the ATTL using a free tendon graft (ARATTL). This technique is less invasive than other treatments and results in a more stable medial ankle joint., (© 2020 by the Arthroscopy Association of North America. Published by Elsevier.)

The lateral talocalcaneal ligament (LTCL) connects the talus and calcaneus on the lateral side of the hindfoot. Although its function remains has not yet been clearly elucidated, the LTCL is thought to be important for the stabilization of the subtalar joint. Ankle sprains often include not only the talocrural joint but also the subtalar joint; therefore, LTCL injuries occur at a certain rate. Moreover, surgeons often encounter and reluctantly dissect the LTCL during arthroscopic anterior talofibular ligament (ATFL) and calcaneofibular ligament (CFL) reconstruction because the LTCL connects to the ATFL at the talus in 42% of people and connects to the CFL at the calcaneus in 18% of people. As a result, LTCL reconstruction might be necessary for those patients. We describe the arthroscopic reconstruction technique of the ATFL, LTCL, and CFL using a triangle-shaped tendon graft (ALC-triangle). This technique provides a possible advantage of an anatomical and stable talocrural joint and subtalar joint., (© 2019 by the Arthroscopy Association of North America. Published by Elsevier.)

Arthroscopic techniques for anterior talofibular ligament (ATFL) repair and reconstruction have been developed in recent years. We simultaneously performed anatomical arthroscopic ATFL repair and reconstruction using a free tendon graft. The ATFL remnant is carefully dissected only at the footprint of the superior limb of the ATFL, and a bone tunnel is created on each side of the fibula and talus. A soft suture anchor with 2 sets of threads is inserted into the fibular tunnel. One set of threads is used to grab the ATFL remnant via a lasso-loop technique, whereas the other set of threads is used to introduce the ATFL graft. The graft is first fixed with a screw in the talar tunnel. Subsequently, the ATFL remnant and the graft are tightened simultaneously by pulling the 2 sets of suture anchor threads at the fibular tunnel and are fixed with a screw. This technique provides the possible advantages of remnant preservation and promotion of load sharing by the repaired ATFL remnant and the reconstructed ATFL graft., (© 2019 by the Arthroscopy Association of North America. Published by Elsevier.)

Case Presentation: A 40-year-old male subject employed as a grocery store manager presented to a pulmonary clinic with a dry cough and progressive dyspnea of 1 year duration. The patient was previously an avid cyclist and first noted his dyspnea when he was unable to bike as far as before. Bilateral interstitial lung infiltrates were recently noted on chest radiography. At the time of presentation, he could no longer cycle due to dyspnea. The patient's medical history was significant for albinism and severe visual impairment. He had no family history of albinism or pulmonary disorders. He had never smoked, drank alcohol only occasionally, and had no significant environmental exposures., (Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Previous structural analyses have shown that R2R3, the minimum unit of the DNA-binding domain of the transcriptional factor c-Myb, is largely flexible in solution, and changes to a more rigid structure upon DNA binding. In this study, we evaluated the structural dynamics using the diffracted X-ray tracking method, in correlation with DNA-binding abilities under different salt conditions, and compared them with the previous results. The resultant curve of the mean square angular displacements (MSD) clearly showed that the flexibility of R2R3 was decreased upon DNA binding, and the DNA-binding energies determined using the angular diffusion coefficients were in good agreement with those determined using isothermal titration calorimetry. The results of the MSD curves also indicate that the translational length reduces by approximately half upon DNA binding., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background and Aims: We aimed to examine the effect of serum sitosterol, a cholesterol absorption marker, on clinical outcomes in acute coronary syndrome patients with dyslipidaemia., Methods: This is a sub-analysis of the HIJ-PROPER trial that assesses the effect of aggressive low-density lipoprotein cholesterol (LDL-C) lowering treatment with pitavastatin + ezetimibe in 1734 acute coronary syndrome (ACS) patients with dyslipidaemia. Patients were divided into two groups based on sitosterol level at enrolment (cut-off value was 2.2 μg/mL; a median of baseline sitosterol level), and clinical outcomes were examined., Results: The mean LDL-C level after 3 years in the low sitosterol group was 84.8 ± 20.1 mg/dL with pitavastatin-monotherapy and 64.6 ± 20.3 mg/dL with pitavastatin + ezetimibe, while corresponding values in the high sitosterol group were 91.0 ± 22.9 mg/dL and 71.1 ± 23.3 mg/dL, respectively. In the high sitosterol group, the Kaplan-Meier event rate for the primary endpoint at 3 years was 26.0% in the pitavastatin + ezetimibe group, as compared with 34.3% in the pitavastatin-monotherapy group (hazard ratio, 0.71; 95% confidence interval, 0.56-0.91; p = 0.006, p-value for interaction = 0.010). However, in the low sitosterol group, there was no significant reduction of the primary endpoint by pitavastatin + ezetimibe therapy., Conclusions: Aggressive lipid-lowering treatment with ezetimibe had a positive effect on clinical outcomes in the high sitosterol subset of ACS patients with dyslipidaemia, but not in the low sitosterol subset. This effect was independent of LDL-C reduction and suggests that sitosterol measurement on admission in ACS patients might contribute to a "personalised" lipid-lowering approach., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Contrast-induced nephropathy is a complication following coronary angiography and percutaneous coronary intervention. Because contrast-induced nephropathy is a predictor of long-term mortality in patients with ischemic heart disease undergoing percutaneous coronary intervention, preventive strategies are required. We assessed the effects of periprocedural oxygenation on contrast-induced nephropathy among patients with pre-existing renal dysfunction., Methods: A total of 200 consecutive patients with impaired renal function (estimated glomerular filtration < 60 ml/min per 1.73 m 2 ) undergoing elective cardiovascular angiography were randomly assigned to an oxygenation treatment (n = 100) or control group (n = 100). In oxygenation treatment, pure oxygen (2 L/min) was administered for 10 minutes before exposure to contrast medium. The primary endpoint was the incidence of contrast-induced nephropathy, defined as a ≥ 25% increase in serum creatinine levels from baseline within 48 hours of exposure., Results: In the oxygenation treatment group, partial pressure of arterial oxygen was higher (135 ± 25 mm Hg vs. 84 ± 10 mm Hg, P  < 0.001); contrast-induced nephropathy incidence was lower (1% vs. 8%, odds ratio [OR] = 0.12, 95% confidence interval [CI] = 0.01-0.95, P  = 0.02); and partial pressure of arterial carbon dioxide and bicarbonate base lactate levels were similar compared with those in the control group. Upon univariate analysis, excess and absence of oxygenation treatment (OR = 9.18, CI = 1.13-74.86, P  = 0.03) and anemia (OR = 4.30, CI = 1.04-17.78, P  = 0.04) were shown to be associated with contrast-induced nephropathy incidence., Conclusion: Oxygenation, a simple, nonpharmacological strategy, may be beneficial when using contrast media in patients with impaired renal function from noninvasive angiography to emergency catheterization.

Neuropeptide Y (NPY) has been found to play a critical role in various mental functions as a neurotransmitter and is involved in the development of schizophrenia, a particularly intractable psychiatric disease whose precise etiology remains unknown. Recent molecular biological investigations have identified several candidate genes which may be associated with this disease, including disrupted-in-schizophrenia 1 (DISC1). The role of DISC1 would involve neurogenesis and neuronal migration. However, the functional consequences of this gene defect have not yet been fully clarified in neuronal systems. In the present study, to clarify the neuropathological changes associated with the function of DISC1, we explored how DISC1 dysfunction can induce abnormalities in the NPY neuronal network in the central nervous system. We performed immunohistochemical analyses (including the observation of the distribution and density) of prefrontal cortex specimens from DISC1-knockout (KO) mice, which are considered to be a novel animal model of schizophrenia. We then evaluated the number and size of NPY-immunoreactive (NPY-IR) neurons and the length of NPY-IR fibers. The number of NPY-IR neurons and the length of the fibers were decreased in the prefrontal cortex of DISC1-KO mice. The decrease was particularly prominent in the superficial regions, and the distribution of NPY-IR neurons differed between wild-type and DISC1-KO mice. However, the size of the neurons in the cortices of the DISC1-KO and wild-type mice did not differ markedly. Our findings suggest that dysfunction of DISC1 may lead to the alteration of NPY neurons and neurotransmission issues in NPY-containing neuron systems, which seem to play important roles in both the mental function and neuronal development. DISC1 dysfunction may be involved in the pathogenesis of schizophrenia through the impairment of the NPY neuronal network., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Stent expansion remains one of the most important predictors of restenosis and subacute thrombosis, even with the use of drug-eluting stents. This study was designed to clarify the impact of lesion preparation on final stent expansion., Methods: Sixty-six consecutive patients were included in this trial, and ultimately 52 enrolled non-calcified de novo lesions were randomly assigned to undergo single predilation with either a semi-compliant scoring balloon or a semi-compliant conventional balloon. Lesions were treated with a single 2.5- to 3.0-mm cobalt-chromium everolimus-eluting stent under optical coherence tomography (OCT) guidance without post-stenting dilation. Stent expansion was defined as the ratio of OCT-measured minimum stent area to the predicted stent area., Results: Stent expansion was significantly higher after predilation by a scoring balloon (68.0% vs. 62.1%, p=0.017) with similar stent lumen eccentricity (0.84 vs. 0.80, p=0.18). Intimal disruption was induced significantly more frequently (68.0% vs. 38.4%, p=0.035) and was more extensive in the scoring group (122° vs. 65°, p=0.038). Lesions with intimal disruption after predilation achieved significantly higher stent expansion than that without it (67.7% vs. 61.6%, p=0.023). One case in the conventional group required target lesion revascularization; however, any other adverse clinical events including death, myocardial infarction, and stent thrombosis were not observed up to 9months after PCI in both groups., Conclusions: In this randomized study, pretreatment with a scoring balloon enhanced stent expansion partly through induction of intimal disruption., Clinical Trial Registration: URL: http://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000014176., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Protein structure dynamics are critical for understanding structure-function relationships. An antibody can recognize its antigen, and can evolve toward the immunogen to increase binding strength, in a process referred to as affinity maturation. In this study, a single-chain Fv (scFv) antibody against (4-hydroxy-3-nitrophenyl)acetyl, derived from affinity matured type, C6, was designed to comprise the variable regions of light and heavy chains connected by a (GGGGS)3 linker peptide. This scFv was expressed in Escherichia coli in the insoluble fraction, solubilized in the presence of urea, and refolded by stepwise dialysis. The correctly refolded scFv was purified, and its structural, physical, and functional properties were analyzed using analytical ultracentrifugation, circular dichroism spectrometry, differential scanning calorimetry, and surface plasmon resonance biosensor. Thermal stability of C6 scFv increased greatly upon antigen binding, due to favorable enthalpic contributions. Antigen binding kinetics were comparable to those of the intact C6 antibody. Structural dynamics were analyzed using the diffracted X-ray tracking method, showing that fluctuations were suppressed upon antigen binding. The antigen binding energy determined from the angular diffusion coefficients was in good agreement with that calculated from the kinetics analysis, indicating that the fluctuations detected at single-molecule level are well reflected by antigen binding events., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Xenobiotic transporters play key roles in disposition of certain therapeutic agents, although limited information is available on their roles other than pharmacokinetic issues. Here, suppressive effect of multispecific organic cation transporter OCTN1/SLC22A4 on liver fibrosis was proposed in liver injury models. After injection of hepatotoxins such as dimethylnitrosamine (DMN) or concanavalin A, hepatic fibrosis, and oxidative stress, evaluated in terms of Sirius red and 4-hydroxy-2-nonenal staining, respectively, were more severe in liver of octn1/slc22a4 gene knockout (octn1(-/-)) mice than that in wild-type mice. DMN treatment markedly increased α-smooth muscle actin and F4/80, markers of activated stellate and Kupffer cells, respectively, in liver of octn1(-/-), but had less effect in wild-type mice. Thus, octn1/slc22a4 gene deletion results in more severe hepatic fibrosis, oxidative stress, and inflammation. DMN-treated wild-type mice showed increased Octn1 staining and hepatic concentration of its food-derived antioxidant ergothioneine (ERGO). The upregulated Octn1 was co-localized with α-smooth muscle actin. Functional expression of Octn1 was demonstrated in activated human hepatic stellate cell lines, LI90 and LX-2. Provision of ERGO-rich feed ameliorated DMN-induced liver fibrosis and oxidative stress. Overall, Octn1 is upregulated in activated stellate cells, resulting in increased delivery of its substrate antioxidant ERGO and a protective effect against liver fibrosis., (Copyright © 2016. Published by Elsevier Inc.)

Background: Pathogenic causes of acute hypoxemic respiratory failure (AHRF) can be difficult to identify at early clinical presentation. We evaluated the diagnostic utility of combined cardiac and thoracic critical care ultrasonography (CCUS)., Methods: Adult patients in the ICU were prospectively enrolled from January through September 2010 with a Pao2/Fio2 ratio < 300 on arterial blood gas (ABG) analysis within 6 h of a new hypoxemic event or the ICU admission. Focused cardiac and thoracic CCUS was conducted within 6 h of ABG testing. Causes of AHRF were categorized into cardiogenic pulmonary edema (CPE), ARDS, and miscellaneous causes after reviewing the hospitalization course in electronic medical records., Results: One hundred thirty-four patients were enrolled (median Pao2/Fio2 ratio, 191; interquartile range, 122-253). Fifty-nine patients (44%) received a diagnosis of CPE; 42 (31%), ARDS; and 33 (25%), miscellaneous cause. Analysis of CCUS findings showed that a low B-line ratio (proportion of chest zones with positive B-lines relative to all zones examined) was predictive of miscellaneous cause vs CPE or ARDS (receiver operating characteristic area under the curve [AUC], 0.82; 95% CI, 0.75-0.88). For further differentiation of CPE from ARDS, left-sided pleural effusion (> 20 mm), moderately or severely decreased left ventricular function, and a large inferior vena cava minimal diameter (> 23 mm) were predictive of CPE (AUC, 0.79; 95% CI, 0.70-0.87)., Conclusions: Combined cardiac and thoracic CCUS assists in early bedside differential diagnosis of ARDS, CPE, and other causes of AHRF.

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are often used to treat inflammation, pain, and fever, but no criterion standard exists for the management of postoperative pain following spinal surgery. In the present study, we compared the analgesic efficacy of loxoprofen sodium (loxoprofen) and celecoxib for the management of postoperative pain following spinal surgery., Methods: One-hundred forty-one patients (mean age 62.2 years) were randomly assigned to two groups before spinal surgery: a loxoprofen group (n = 73, 180 mg/day) and a celecoxib group (n = 68, 200 mg/day). The drugs were administered from 1 day until 7 days after surgery. A numeric rating scale (NRS) was used to evaluate pain at nine predefined times every day and the findings were compared between the two groups. Laboratory data and adverse events were also recorded., Results: There was no significant difference in the maximum and mean NRS scores on each day between loxoprofen and celecoxib, suggesting a comparable analgesic effect for these two NSAIDs. Greater improvement in the NRS score between preadministration (baseline) and 30 min or 2 h after administration was obtained for loxoprofen. This tendency was shown for both slight (NRS score <5 at baseline) and severe pain (NRS score ≥ 5 at baseline). Loxoprofen was discontinued in one patient on day 4 because of renal dysfunction. Celecoxib was discontinued in one patient on day 2 at the patient's request., Conclusions: Both loxoprofen sodium and celecoxib were well tolerated for the relief of acute postoperative pain after spinal surgery. A single administration of loxoprofen showed superior and rapid effectiveness compared with celecoxib for both slight and severe postoperative pain.

Thoracentesis is considered a relatively safe and well-established procedure commonly done at the bedside with minimal risk of complication. Thoracentesis-related hemothorax is uncommon; however, it may be life-threatening. We describe a case of a 19-year-old woman with persistent fever and pleural effusion, in which thoracentesis resulted in tension hemothorax due to intercostal artery laceration. It is important for proceduralists to understand not only the tortuosity of the intercostal artery covering 25% to 50% of the intercostal space, but also the presence of traversing collateral arteries. Herein, we discuss the potential benefit of vascular ultrasonography with color Doppler during thoracentesis, with the goal of avoiding vessel injury and hemorrhage.

Chaperonins are ubiquitous molecular chaperones with the subunit molecular mass of 60kDa. They exist as double-ring oligomers with central cavities. An ATP-dependent conformational change of the cavity induces the folding of an unfolded protein that is captured in the cavity. In the group I chaperonins, which are present in eubacteria and eukaryotic organelles, inter-ring communication takes important role for the reaction cycle. However, there has been limited study on the inter-ring communication in the group II chaperonins that exist in archaea and the eukaryotic cytosol. In this study, we have constructed the asymmetric ring complex of a group II chaperonin using circular permutated covalent mutants. Although one ring of the asymmetric ring complex lacks ATPase or ATP binding activity, the other wild-type ring undergoes an ATP-dependent conformational change and maintains protein-folding activity. The results clearly demonstrate that inter-ring communication is dispensable in the reaction cycle of group II chaperonins., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Paracentesis has been considered a relatively safe procedure; however, hemorrhagic complications do occur and can be fatal, especially in the context of coagulopathy. We describe the case of a 47-year-old man with coagulopathy secondary to end-stage liver disease, whose hospital course was complicated by paracentesis-related hemoperitoneum leading to abdominal compartment syndrome. Emergent laparotomy revealed left inferior epigastric artery laceration caused by paracentesis. Despite operative control of bleeding, postoperatively, the patient developed severe metabolic acidosis, disseminated intravascular coagulation, and ultimately died from complications of hemorrhagic shock. Understanding key anatomic structures is essential for patient safety in the setting of paracentesis. While recognizing the lack of clinical studies demonstrating the effectiveness of ultrasonography use in paracentesis, we discuss the benefit of bedside abdominal ultrasonography to locate ascites and avoid intraabdominal structures, as well as vascular ultrasonography, during needle insertion to avoid abdominal wall vessels.

We describe a 29-year-old woman who presented with chronic pleuropericarditis complicated by lung entrapment and constrictive pericarditis. Pleural biopsy performed during the decortication procedure revealed fibrinous pleuritis with lymphoplasmacytic inflammation including IgG4-positive plasma cells. The patient responded favorably to corticosteroid therapy with resolution of pleural effusion and constrictive physiology. To our knowledge, this is the first reported case of IgG4-related systemic disease manifesting as lung entrapment and constrictive pericarditis.

The antagonism of CXC-chemokine receptor 4 (CXCR4) with AMD3100 improves cardiac performance after myocardial infarction by augmenting the recruitment of endothelial progenitor cells (EPCs) from the bone marrow to the regenerating vasculature. We investigated whether AMD3100 may accelerate diabetes-impaired wound healing through a similar mechanism. Skin wounds were made on the backs of leptin receptor-deficient mice and treated with AMD3100 or saline. Fourteen days after treatment, wound closure was significantly more complete in AMD3100-treated mice (AMD3100: 87.0 ± 2.6%, saline: 33.1 ± 1.8%; P<0.0001) and was accompanied by greater collagen fiber formation, capillary density, smooth muscle-containing vessel density, and monocyte/macrophage infiltration. On day 7 after treatment, AMD3100 was associated with higher circulating EPC and macrophage counts, and with significantly upregulated mRNA levels of stromal cell-derived factor 1 and platelet-derived growth factor B in the wound bed. AMD3100 also promoted macrophage proliferation and phagocytosis and the migration and proliferation of diabetic mouse primary dermal fibroblasts and 3T3 fibroblasts, which express very little CXCR4. In conclusion, a single topical application of AMD3100 promoted wound healing in diabetic mice by increasing cytokine production, mobilizing bone marrow EPCs, and enhancing the activity of fibroblasts and monocytes/macrophages, thereby increasing both angiogenesis and vasculogenesis. Not all of the AMD3100-mediated effects evolved through CXCR4 antagonism.

Atmospheric microwave air plasma was used to treat asbestos-like microfiber particles that had two types of ceramic fiber and one type of stainless fiber. The treated particles were characterized via scanning electron microscopy (SEM) and X-ray diffraction (XRD). The experiment results showed that one type of ceramic fiber (Alumina:Silica=1:1) and the stainless fiber were spheroidized, but the other type of ceramic fiber (Alumina:Silica=7:3) was not. The conversion of the fibers was investigated by calculating the equivalent diameter, the aspect ratio, and the fiber content ratio. The fiber content ratio in various conditions showed values near zero. The relationship between the normalized fiber vanishing rate and the energy needed to melt the particles completely per unit surface area of projected particles, which is defined as η, was examined and seen to indicate that the normalized fiber vanishing rate decreased rapidly with the increase in η. Finally, some preliminary experiments for pure asbestos were conducted, and the analysis via XRD and phase-contrast microscopy (PCM) showed the availability of the plasma treatment., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: The purpose of this study was to evaluate the effectiveness of a simulation-based workshop with ultrasonography instruction in reducing mechanical complications associated with central venous catheter (CVC) insertion., Methods: A single-center prospective cohort study was conducted in the medical ICU and respiratory step-down unit of an urban teaching hospital. Fifty-six medical house staff members were trained prior to their rotations over a 6-month period. The data on mechanical complication rates after the implementation of the workshop were compared with previous experience when no structured educational program existed., Results: There were 334 procedures in the preeducation period compared to 402 procedures in the posteducation period. The overall complication rate, including placement failure, in the preeducation and posteducation period was 32.9% and 22.9%, respectively (P < .01). Placement failure rate decreased from 22.8% to 16.2% (P = .02), and arterial punctures decreased from 4.2% to 1.5% (P = .03). Ultrasonography usage increased from 3.0% to 61.4% (P < .01). Multivariate analysis demonstrated that interns were more likely to cause overall mechanical complications compared with fellows and attending physicians in the preeducation period (P = .02); however, this trend was not observed in the posteducation period. Catheter site and ultrasonography usage significantly affected the overall complication rate in both periods, and ultrasound-guided femoral CVC was the safest procedure in the posteducation period., Conclusions: Implementation of a prerotational workshop significantly improved the safety of CVC insertion, especially for CVCs placed by inexperienced operators. We suggest that simulation-based training with ultrasonography instruction should be conducted if house staff members are responsible for CVC placement.

Objective: Our purpose was to establish a technique to reduce residual artifacts after transcranial magnetic stimulation (TMS) from electroencephalographic (EEG) signals., Methods: We investigated the effects of coil direction and stimulus intensity on residual artifacts in an artificial circuit, and tested whether or not the size of the circuit area affects the residual artifact (the model study). Based on the results, the optimization by rearranging the electrode's lead wire was tested on the human scalp (the human study)., Results: The residual artifact after TMS was dependent on the direction of the figure-of-eight coil, and on the artificial circuit area size., Conclusions: In accordance with the model study, the scalp EEG shows that TMS-induced artifacts can be reduced dramatically before the amplifier input stages in TMS-EEG experiments by a step-wise procedure rearranging the lead wires relative to the fixed coil orientation., Significance: Our technique makes it possible to significantly reduce the residual artifacts from recordings of short-latency TMS-evoked potentials., (Copyright © 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Diffuse neurofibrillary tangles with calcification (DNTC) is a relatively rare presenile dementia that clinically shows overlapping symptoms of Alzheimer's disease and frontotemporal lobar degeneration (FTLD). DNTC is pathologically characterized by localized temporal or frontotemporal atrophy with massive neurofibrillary tangles, neuropil threads and Fahr's-type calcification without senile plaques. We tried to clarify the molecular basis of DNTC by immunohistochemically examining the appearance and distribution of accumulated alpha-synuclein (aSyn) and TAR DNA-binding protein of 43kDa (TDP-43) in the brains of 10 Japanese autopsy cases. We also investigated the clinically characteristic symptoms from the clinical charts and previous reports, and the correlations with neuropathological findings. The characteristic symptoms were evaluated using the Neuropsychiatric Inventory Questionnaire (NPI-Q). As a result, we confirmed the high frequency of neuronal cytoplasmic accumulation of aSyn (80%) and phosphorylated TDP-43 (90%) in DNTC cases. There was a significant correlation between some selected items of NPI-Q scores and the severity of the limbic TDP-43 pathology. The pathology of DNTC included TDP-43 and aSyn pathology with high frequency. These abnormal accumulations of TDP-43 might be involved in the pathological process of DNTC, having a close relationship to the FTLD-like psychiatric symptoms during the clinical course., (Copyright © 2010 Elsevier B.V. All rights reserved.)

The exact pathophysiology of schizophrenia is unknown despite intensive scientific studies using molecular biology, psychopharmacology, neuropathology, etc. It is thought that neurodevelopmental failures such as neuronal network incompetence and the inappropriate formation of neurons affect the neurotransmitters. Several animal models have been created to investigate the etiology of this disease. In this study, we investigated the expression of vesicle monoamine transporter 2 (VMAT2), which has a significant role in neurotransmission, in the hippocampal formation in 1-phenylcyclohexylpiperazine (PCP)-treated mice using immunohistochemical staining technique to clarify neuronal abnormalities. PCP-treated mice are thought to be one of novel animal models for schizophrenia. The expression of VMAT2 in the hippocampal formation was significantly reduced overall in the PCP-treated mice compared to that in control (saline-treated) mice, also these reductions were observed throughout the brain. These facts implied that the pathophysiology of this disease involves abnormal monoaminergic transmission through VMAT2, despite PCP was the N-methyl-d-aspartate (NMDA) receptor antagonist that might induce glutamatergic abnormality. Since insufficient or excess release of neurotransmitter might alter neurochemical function and neurotransmission, VMAT2 might be an important target for biological research in psychiatric disease including schizophrenia., (2010 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.)

Recent studies of the gliding bacteria Mycoplasma mobile have identified a family of proteins called the Gli family which was considered to be involved in this novel and yet fairly unknown motility system. The 349kDa protein called Gli349 was successfully isolated and purified from the bacteria, and electron microscopy imaging and antibody experiments led to the hypothesis that it acts as the "leg" of M. mobile, responsible for attachment to the substrate as well as for gliding motility. However, more precise evidence of the molecular shape and function of this protein was required to asses this theory any further. In this study, an atomic force microscope (AFM) was used both as an imaging and a force measurement device to provide new information about Gli349 and its role in gliding motility. AFM images of the protein were obtained revealing a complex structure with both rigid and flexible parts, consistent with previous electron micrographs of the protein. Single-molecular force spectroscopy experiments were also performed, revealing that Gli349 is able to specifically bind to sialyllactose molecules and withstand unbinding forces around 70pN. These findings strongly support the idea that Gli349 is the "leg" protein of M. mobile, responsible for binding and also most probably force generation during gliding motility., (Copyright 2009 Elsevier Inc. All rights reserved.)

We have developed a method to detect specific proteins with a high sensitivity using a gel electrophoresis method and force measurement of atomic force microscopy (AFM). Biotinylated proteins were separated by electrophoresis and fixed with cross-linking chemicals on the gel, followed by direct force measurement between the biotinylated proteins on the gel and a streptavidin-modified tip of an AFM cantilever. We were able to achieve a high enough sensitivity to detect the picogram order of the biotinylated proteins by evaluating the frequency of the interaction force larger than 100pN in the force profile, which corresponds to the rupture force of interaction between streptavidin and biotin.

Introduction: Quality of information available over the Internet has been a cause for concern. Our goal was to evaluate the quality of information available on lung cancer in the United States and Japan and assess the differences between the two., Methods: We conducted a prospective, observational Web review by searching the word "lung cancer" in Japanese and English, using Google Japan (Google-J), Google United States (Google-U), and Yahoo Japan (Yahoo-J). The first 50 Web sites displayed were evaluated from the ethical perspective and for the validity of the information. The administrator of each Web site was also investigated., Results: Ethical policies were generally well described in the Web sites displayed by Google-U but less well so in the sites displayed by Google-J and Yahoo-J. The differences in the validity of the information available was more striking, in that 80% of the Web sites generated by Google-U described the most appropriate treatment methods, whereas less than 50% of the Web sites displayed by Google-J and Yahoo-J recommended the standard therapy, and more than 10% advertised alternative therapy. Nonprofit organizations and public institutions were the primary Web site administrators in the United States, whereas commercial or personal Web sites were more frequent in Japan., Conclusion: Differences in the quality of information on lung cancer available over the Internet were apparent between Japan and the United States. The reasons for such differences might be tracked to the administrators of the Web sites. Nonprofit organizations and public institutions are the up-and-coming Web site administrators for relaying reliable medical information.

In this study, we measured the structural properties of "blue membrane", which is specific formation of a purple membrane (PM) upon acid titration or removal of cations, by the force curve measurement mode of an atomic force microscopy. The PM fragments were immobilized on a glass substrate and force curve measurements were carried out on the fragments under neutral (pH 7.2) and acidic (pH 2.4) condition. The results revealed that peak positions of the unfolding spectra obtained under acidic condition were shifted to the shorter extension region than those at neutral pH and that the relative position of only the first peak was changed by about 5nm. These results suggest the possibility that the specific secondary structure is formed at the site from its C-terminus to helices F in acidified PM.

We developed a method to measure the rupture forces between antibody and antigen by atomic force microscopy (AFM). Previous studies have reported that in the measurement of antibody-antigen interaction using AFM, the specific intermolecular forces are often obscured by nonspecific adhesive binding forces between antibody immobilized cantilever and substrate surfaces on which antigen or nonantigen are fixed. Here, we examined whether detergent and nonreactive protein, which have been widely used to reduce nonspecific background signals in ordinary immunoassay and immunoblotting, could reduce the nonspecific forces in the AFM measurement. The results showed that, in the presence of both nonreactive protein and detergent, the rupture forces between anti-ferritin antibodies immobilized on a tip of cantilever and ferritin (antigen) on the substrate could be successfully measured, distinguishing from nonspecific adhesive forces. In addition, we found that approach/retraction velocity of the AFM cantilever was also important in the reduction of nonspecific adhesion. These insights will contribute to the detection of specific molecules at nanometer scale region and the investigation of intermolecular interaction by the use of AFM.

We report two cases of a rapidly progressive fatal overwhelming pneumococcal infection. Patient 1 was a 67-year-old man with a 24-h history of fever and malaise and was transferred to our department. He was severely ill, tachypneic, and felt a chill. A purpuric discoloration with ecchymosis of the skin was noted over the body. The chest X-ray findings demonstrated thickening of the bronchovascular bundle in the right lower lung field, which later revealed the presence of bronchopneumonia. Laboratory studies revealed the presence of metabolic acidosis and disseminated intravascular coagulation. After presentation, rapid deterioration occurred followed by cardiopulmonary arrest. Despite cardiopulmonary resuscitation, the patient died only 3 h after presentation. The isolates from the patient's blood revealed penicillin-susceptible Streptococcus pneumoniae, serotype 4. Patient 2 was a 30-year-old woman with a prior history of uneventful pregnancies was transferred to our department with a 2-day history of fever, nausea, headache, and malaise. Although she was in the 19th week of pregnancy at the time, she suffered a miscarriage just prior to admission. Upon presentation to our department, she demonstrated unstable vital signs, diminished consciousness, anuria, and icterus. Purpuric discoloration with ecchymosis of the skin was noted in over most of her body, including the distal extremities. The chest X-ray findings were close to normal. Initial laboratory studies revealed the presence of severe metabolic acidosis and disseminated intravascular coagulation with multiple organ failure. Despite aggressive cardiopulmonary support, normal neurological responses disappeared on the 2nd day following admission and the patient died on the 16th day after admission. The patient's isolates from blood and vaginal swabs both later revealed penicillin-susceptible Streptococcus pneumoniae, serotype 12F. The presentation of rapidly progressive septic shock should raise the treating physician's suspicion of overwhelming pneumococcal infection, which has limited management options.

Objectives: The incidence of contrast-induced nephropathy (CIN) after coronary angiography and the prognostic value in patients with acute myocardial infarction remains to be determined. This study investigated the frequency, predictors of CIN, and the prognostic significance of CIN in acute myocardial infarction patients undergoing emergent coronary angiography., Methods: This study included 132 consecutive acute myocardial infarction patients undergoing emergent coronary angiography within 24 hr after the onset between January 1999 and June 2001. The serum creatinine concentration was measured on admission and at 48 hr after contrast medium exposure. CIN was defined as an increase in serum creatinine from the baseline > or = 0.5 mg/dl or > or = 25% at 48 hr after emergent coronary angiography. The patient characteristics, and in-hospital and long-term mortality were compared between the CIN and non-CIN groups., Results: CIN occurred in 15 patients (11.4%) after emergent coronary angiography. The predictor of CIN development was preexisting renal impairment (serum creatinine concentration > or = 1.2 mg/dl on presentation; 21.9% vs 8.0%, odds ratio 3.22, 95% confidence interval 1.07-9.74, p = 0.04). In-hospital mortality was significantly higher in the CIN group than in the non-CIN group (13.3% vs 1.7%; odds ratio 8.85, 95% confidence interval 1.15-68.2, p = 0.01). The long-term mortality (mean follow-up period of 40 months) was also higher in the CIN group (26.7% vs 8.6%; hazard ratio 3.91, 95% confidence interval 1.21-12.5, p = 0.02)., Conclusions: CIN was an independent predictor of both in-hospital and long-term mortality in acute myocardial infarction patients undergoing emergent coronary angiography. Preexisting renal insufficiency was associated with subsequent CIN.

Objective: To investigate the effects of loading and unloading of the lower limb joints on the soleus H-reflex in standing humans., Methods: H-reflexes were elicited in the soleus muscle in subjects standing on a force platform in a water tank under the following loading conditions of the ankle and knee joints: control condition; reduced loads of -10 and -20 N; imposed loads of 10 and 20 N. The joint loading was altered by changing the combinations of buoys and weights attached to the lower limb segments, while total body weight was kept constant., Results: As the ankle- or knee-joint load was reduced, the H-reflex was significantly enhanced compared to that under the control condition. In contrast, the H-reflex was decreased as the ankle- or knee-joint load was increased. In both cases, similar levels of background activity were recorded., Conclusions: The present results suggest that joint afferents might mediate the suppression of the soleus H-reflex in standing humans. However, the identification of the receptors and/or the mechanisms cannot be addressed under the current experimental set up., Significance: The results of this study give some basic insights into reflex control in an upright posture.

Background: It remains unclear whether circadian variation (CV) of cardiac autonomic nervous activity (CANA) is preserved in patients with chronic heart failure (CHF) as in healthy subjects. We have demonstrated that CANA in CHF patients is largely affected by patient recumbent position., Methods: We studied eight mild to moderate CHF patients and eight age, sex-matched healthy subjects. Each subject underwent 24-h ambulatory ECG monitoring. One channel was used to record the CM5 lead, and another to record the signal of patient position from a newly developed, small-sized detector. By using spectral analysis of heart rate variability, frequency-domain measures were calculated. Normalized high-frequency (HF: 0.15-0.40 Hz) power was used as an index of vagal activity and the low frequency (LF: 0.04-0.15 Hz)/HF power ratio was used as an index of sympathovagal balance. These indexes in the same recumbent position were compared between night (2:00-4:00 a.m.) and morning (6:00-8:00 a.m.)., Results: In healthy subjects, a definite CV of CANA was observed in each recumbent position. In patients with CHF, in each position, normalized HF power was lower in the morning than at night, whereas LF/HF was higher in the morning than at night. Thus, CANA in CHF patients is influenced not only by patient position but also by the time of day., Conclusion: CV of CANA in mild to moderate CHF patients is well preserved when taking patient position into consideration.