Comparison of leak fraction between the laryngeal mask airway and endotracheal tube during anesthesia: a single-center retrospective study.

The use of the laryngeal mask airway (LMA), which offers the benefits of ease in insertion and prevention of tracheal damage, is associated with a risk of flow leakage. This study analyzed our extensive database to compare leakage associated with the use of LMA and endotracheal tube (ETT). Adult patients who underwent chest wall, abdominal wall, inguinal region, limb, transurethral, or transvaginal surgery and received either LMA or ETT between January 2007 and March 2020 were included. The leak fraction was calculated as (inspiratory tidal volume-expiratory tidal volume)/(inspiratory tidal volume) × 100% every minute during intraoperative stable positive pressure ventilation. The median leak fraction was calculated for each case. The leak fraction in the LMA group demonstrated a left-skewed distribution with a larger proportion of excessive leak fraction. The leak fraction in the LMA group (median, 7.9%; interquartile range, 4.8-11.4%) was significantly lower than that in the ETT group (median, 9.1%; interquartile range: 5.5-12.4%; P < 0.001). This tendency was consistent across subgroups divided by sex, age, type of surgery, and ventilation mode. We propose that LMA provides leakage comparable to or less than ETT in most cases if stable positive pressure ventilation is achieved.

Quantitative relationship between anteriorization of alpha oscillations and level of general anesthesia.

A typical electroencephalogram (EEG) change induced by general anesthesia is anteriorization-disappearance of occipital alpha oscillations followed by the development of frontal alpha oscillations. Investigating the quantitative relationship between such a specific EEG change and the level of anesthesia has academic and clinical importance. We quantified the degree of anteriorization and investigated its detailed relationship with the level of anesthesia. We acquired 21-electrode EEG data and bispectral index (BIS) values of 50 patients undergoing surgery from before anesthesia induction until after patient arousal. For each epoch of a 10.24-s window with 1-s offsets, we calculated frontal alpha power [Formula: see text], occipital alpha power [Formula: see text], and their difference [Formula: see text] to quantify anteriorization. We calculated Spearman's rank correlation coefficients between these values and the BIS value. We used locally weighted regression to estimate [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text] at each BIS value. Thirty-six patients (26 females and 10 males aged 24-85 years) were analyzed. The 95% confidence intervals for the mean of Fisher transformations of Spearman's rank correlation coefficients between [Formula: see text], [Formula: see text], and [Formula: see text] and BIS value were [- 0.68, - 0.26], [0.02, 0.62], and [- 1.11, - 0.91], respectively. The change in [Formula: see text] and [Formula: see text] with BIS value showed different patterns by the type of anesthetic agent, whereas that in [Formula: see text] was more consistent with smaller individual variance. Anteriorization, quantified by the difference between frontal and occipital alpha powers, continuously developed in conjunction with general anesthesia. Quantifying anteriorization may provide an objective indicator of the level of anesthesia.

Quantitative evaluation of stress in Japanese anesthesiology residents based on heart rate variability and psychological testing.

Clinical anesthesiologists, particularly residents, work in stressful environments. However, evidence-based physiological and psychological tests to evaluate stress are still lacking. In this single-center study of 33 residents, we investigated the relationship between heart rate variability (HRV), which had the potential to screen residents' stress levels using Holter electrocardiography (ECG) and psychological mood as assessed by the Profile of Mood States (POMS) questionnaire. HRV analysis revealed 2 findings. Firstly, standard deviation of the average of 5-min normal-to-normal R-R intervals (SDANN) was significant lower than that of same-aged healthy volunteers (69.3 ± 27.9 vs. 137.0 ± 43.0 ms, P < 0.05), which indicated suppression of autonomic nervous system activity throughout their work. Secondly, at induction of anesthesia, significant higher low frequency/high frequency ratio (LF/HF ratio: 1.326 vs. 0.846; P < 0.05) and lower HF (3326 vs. 5967 ms2; P < 0.05) and lower standard deviation of normal-to-normal R-R intervals (SDNN: 50.5 vs. 79.4 ms; nervous system was suppressed at the induction of anesthesia: expected to be the most stressful period of their work. On the other hand, deviation scores of POMS questionnaire elucidated that all the residents were within normal range of psychological mood, and without any significant diurnal changes with respect to total mood disturbance deviation (TMD) scores (48 vs. 47; P = 0.368). HRV elucidated physiological stress among anesthesiology residents quantitatively by evaluating autonomic nervous activities, especially at induction of anesthesia. These changes in HRV could be observed regardless of psychological mood.

Temperature-dependent inotropic and lusitropic indices based on half-logistic time constants for four segmental phases in isovolumic left ventricular pressure-time curve in excised, cross-circulated canine heart.

Varying temperature affects cardiac systolic and diastolic function and the left ventricular (LV) pressure-time curve (PTC) waveform that includes information about LV inotropism and lusitropism. Our proposed half-logistic (h-L) time constants obtained by fitting using h-L functions for four segmental phases (Phases I-IV) in the isovolumic LV PTC are more useful indices for estimating LV inotropism and lusitropism during contraction and relaxation periods than the mono-exponential (m-E) time constants at normal temperature. In this study, we investigated whether the superiority of the goodness of h-L fits remained even at hypothermia and hyperthermia. Phases I-IV in the isovolumic LV PTCs in eight excised, cross-circulated canine hearts at 33, 36, and 38 °C were analyzed using h-L and m-E functions and the least-squares method. The h-L and m-E time constants for Phases I-IV significantly shortened with increasing temperature. Curve fitting using h-L functions was significantly better than that using m-E functions for Phases I-IV at all temperatures. Therefore, the superiority of the goodness of h-L fit vs. m-E fit remained at all temperatures. As LV inotropic and lusitropic indices, temperature-dependent h-L time constants could be more useful than m-E time constants for Phases I-IV.

Tracking of intertissue migration reveals the origins of tumor-infiltrating monocytes.

Myeloid cells such as monocytes and monocyte-derived macrophages promote tumor progression. Recent reports suggest that extramedullary hematopoiesis sustains a sizable reservoir of tumor-infiltrating monocytes in the spleen. However, the influence of the spleen on tumor development and the extent to which spleen monocytes populate the tumor relative to bone marrow (BM) monocytes remain controversial. Here, we used mice expressing the photoconvertible protein Kikume Green-Red to track the redistribution of monocytes from the BM and spleen, and mice expressing fluorescent ubiquitination-based cell-cycle indicator proteins to monitor active hematopoiesis in these tissues. In mice bearing late-stage tumors, the BM, besides being the major site of monocyte production, supplied the expansion of the spleen reservoir, replacing 9% of spleen monocytes every hour. Deployment of monocytes was equally rapid from the BM and the spleen. However, BM monocytes were younger than those in the spleen and were 2.7 times more likely to migrate into the tumor from the circulation. Partly as a result of this intrinsic difference in migration potential, spleen monocytes made only a minor contribution to the tumor-infiltrating monocyte population. At least 27% of tumor monocytes had traveled from the BM in the last 24 h, compared with only 2% from the spleen. These observations highlight the importance of the BM as the primary hematopoietic tissue and monocyte reservoir in tumor-bearing mice, despite the changes that occur in the spleen monocyte reservoir during tumor development.

Reliability of cardiac output measurements using LiDCOrapid™ and FloTrac/Vigileo™ across broad ranges of cardiac output values.

Knowing a patient's cardiac output (CO) could contribute to a safe, optimized hemodynamic control during surgery. Precise CO measurements can serve as a guide for resuscitation therapy, catecholamine use, differential diagnosis, and intervention during a hemodynamic crisis. Despite its invasiveness and intermittent nature, the thermodilution technique via a pulmonary artery catheter (PAC) remains the clinical gold standard for CO measurements. LiDCOrapid™ (LiDCO, London, UK) and FloTrac/Vigileo™ (Edwards Lifesciences, Irvine, CA) are less invasive continuous CO monitors that use arterial waveform analysis. Their calculations are based on arterial waveform characteristics and do not require calibration. Here, we evaluated LiDCOrapid™ and FloTrac/Vigileo™ during off-pump coronary artery bypass graft (OPCAB) and living-donor liver transplantation (LDLT) surgery. This observational, single-center study included 21 patients (11 OPCAB and 10 LDLT). We performed simultaneous measurements of CO at fixed sampling points during surgery using both devices (LiDCOrapid™ version 1.04-b222 and FloTrac/Vigileo™ version 3.02). The thermodilution technique via a PAC was used to obtain the benchmark data. LiDCOrapid™ and FloTrac/Vigileo™ were used in an uncalibrated fashion. We analyzed the measured cardiac index using a Bland-Altman analysis (the method of variance estimates recovery), a polar plot method (half-moon method), a 4-quadrant plot and compared the widths of the limits of agreement (LOA) using an F test. One OPCAB patient was excluded because of the use of an intra-aortic balloon pumping during surgery, and 20 patients (10 OPCAB and 10 LDLT) were ultimately analyzed. We obtained 149 triplet measurements with a wide range of cardiac index. For the FloTrac/Vigileo™, the bias and percentage error were -0.44 L/min/m2 and 74.4 %. For the LiDCOrapid™, the bias and percentage error were -0.38 L/min/m2 and 53.5 %. The polar plot method showed an angular bias (FloTrac/Vigileo™ vs. LiDCOrapid™: 6.6° vs. 5.8°, respectively) and radial limits of agreement (-63.9 to 77.1 vs. -41.6 to 53.1). A 4-quadrant plot was used to obtain concordance rates (FloTrac/Vigileo™ vs. PAC and LiDCOrapid™ vs. PAC: 84.0 and 92.4 %, respectively). We could compare CO measurement devices across broad ranges of CO and SVR using LDLT and OPCAB surgical patients. An F test revealed no significant difference in the widths of the LoA for both devices when sample sizes capable of detecting a more than two-fold difference were used. We found that both devices tended to underestimate the calculated CIs when the CIs were relatively high. These proportional bias produced large percentage errors in the present study.

Reduced supply of monocyte-derived macrophages leads to a transition from nodular to diffuse lesions and tissue cell activation in silica-induced pulmonary fibrosis in mice.

Pulmonary fibrosis (PF) is an intractable disorder with a poor prognosis. Lung macrophages have been reported to regulate both progression and remission of bleomycin-induced diffuse PF. However, it remains unclear how macrophages contribute to silica-induced progressive nodular PF and the associated tissue cell responses in vivo. We found that lack of monocyte-derived macrophages results in the formation of diffuse PF after silica instillation. We found that the proportion and the number of monocyte-derived macrophages were persistently higher in silica-induced progressive PF compared with bleomycin-induced PF. Surprisingly, in Ccr2(-/-) mice, in which monocyte-derived macrophage infiltration is impaired, silica administration induced diffuse PF with loose nodule formation and greater activation of tissue cells. In the diffuse lesions, the distribution of epithelial cells, distribution of myofibroblasts, and architecture of the basement membrane were disrupted. Consistent with the development of diffuse lesions, genes that were differentially expressed in CD45(-) tissue cells from the lung of wild-type and Ccr2(-/-) mice were highly enriched in human diffuse, progressive PF. In gene ontology network analyses, many of these genes were associated with tissue remodeling and included genes not previously associated with PF, such as Mmp14, Thbs2, and Fgfr4. Overall, these results indicate that monocyte-derived macrophages prevent transition from nodular to diffuse silica-induced PF, potentially by regulating tissue cell responses.

Half-Logistic Function Model for First Half of Descending Phase of Cardiomyocyte Cytoplasmic Ca(2+) Concentration ([Ca(2+)]i)-Time Curve (CaTCIII) in Isolated Aequorin-Injected Mouse Left Ventricular Papillary Muscle.

BACKGROUND: Myocardial contraction and relaxation are regulated by increases and decreases in cytoplasmic calcium concentration ([Ca(2+)]i). In previous studies, we found that a half-logistic (h-L) function, which represents a half-curve of a symmetrical sigmoid logistic function with a boundary at the inflection point, curve-fits the first half of the ascending phase and the second half of the descending phase of the [Ca(2+)]i transient curve better than a mono-exponential (m-E) function. In the present study, we investigated the potential application of an h-L function to analyse the first half of the descending phase of CaTC (CaTCIII). METHODS: The [Ca(2+)]i was measured using the Ca(2+)-sensitive aequorin, which was microinjected into 15 isolated mouse left ventricular (LV) papillary muscles. The observed CaTCIII data in the interval from the point corresponding to the peak [Ca(2+)]i to the point corresponding to dCa/dtmin was curve-fitted using the h-L and m-E function equations by the least-squares method. RESULTS: The mean correlation coefficient (r) values of the h-L and m-E function best curve-fits for 11 CaTCIIIs were 0.9986 and 0.9982, respectively. The Z transformation of h-L r (3.64 ± 0.45) was larger than that of m-E r (3.50 ± 0.33) (p < 0.05). CONCLUSIONS: The h-L function can evaluate most CaTCIIIs more accurately than the m-E function in isolated aequorin-injected mouse LV papillary muscle. The three calculated h-L parameters i.e., amplitude constant, time constant, and non-zero asymptote, are more reliable indices than m-E for evaluating the magnitude and time course of the change in the decrease in [Ca(2+)]i. KEY WORDS: Ca(2+) transient; Half-logistic amplitude constant; Half-logistic non-zero asymptote; Half-logistic time constant; Myocardial Ca(2+) handling.

Intracellular Ca(2+) Transient Phase II Can be Assessed by Half-Logistic Function Model in Isolated Aequorin-Injected Mouse Left Ventricular Papillary Muscle.

BACKGROUND: Myocardial contraction and relaxation are regulated by increases and decreases in intracellular cytoplasmic calcium (Ca(2+)) concentration ([Ca(2+)]i). In previous studies, we found that a half-logistic (h-L) function, which represents a half-curve of a symmetrical sigmoid logistic function with a boundary at the inflection point, curve-fits the first half of the ascending phase (CaTI) and the second half of the descending phase of the [Ca(2+)]i transient curve (CaTIV) better than a mono-exponential (m-E) function. In the present study, we investigated the potential application of an h-L function to the analysis of the second half of the ascending phase of the [Ca(2+)]i transient curve (CaTII). METHODS: The [Ca(2+)]i transient was measured using the Ca(2+)-sensitive photoprotein aequorin, which was microinjected into 15 isolated left ventricular (LV) papillary muscles of mice. The observed CaTII data during the time duration from the point corresponding to the maximum of the first-order time derivative of Ca(2+) concentration (dCa/dtmax) to the point corresponding to the peak Ca(2+) concentration was curve-fitted by the least-squares method using the h-L and m-E function equations. RESULTS: The mean correlation coefficient (r) values of the h-L and m-E curve-fits for CaTII were 0.9996 and 0.9984, respectively. The Z transformation of h-L r was larger than that of m-E r (p < 0.0001). H-L residual mean square (RMS) was smaller than m-E RMS (p < 0.001). CONCLUSIONS: The h-L function tracks the magnitudes and time courses of CaTII more accurately than the m-E function in isolated aequorin-injected mouse LV papillary muscle. Compared with the m-E time constant, the h-L time constant of CaTII is a more reliable index for evaluating the time duration of the change in the increase in [Ca(2+)]i during the combination of the middle part of the contraction process and the early part of the relaxation process. CaTII can be assessed by the h-L function model in cardiac muscles. The h-L approach may provide a more useful model for studying each process in myocardial Ca(2+) handling. KEY WORDS: Calcium handling; Calcium transient; Curve-fit; Half-Logistic function; Time constant.

Calcium-induced calcium release from the sarcoplasmic reticulum can be evaluated with a half-logistic function model in aequorin-injected cardiac muscles.

PURPOSE: Release of calcium (Ca(2+)) from the sarcoplasmic reticulum (SR) induced by Ca(2+) influx through voltage-dependent sarcolemmal L-type Ca(2+) channels (CICR) in cardiac muscle cells has been implicated as a potential target contributing to anesthetic-induced myocardial depression. In an earlier study, we found that (1) a half-logistic (h-L) function, which represents a half-curve of a sigmoid logistic function with a boundary at the inflection point, curve-fits the first half of the ascending phases of the isometric myocardial tension and isovolumic left ventricular (LV) pressure waveforms better than a mono-exponential (m-E) function and (2) the h-L time constants are useful as inotropic indices. We report here our investigation of the potential application of an h-L function to the analysis of the first half of the ascending phase of the Ca(2+) transient curve (faCaT) that precedes and initiates myocardial contraction and the increase in LV pressure. METHODS: Ca(2+) transients (CaT) were measured using the Ca(2+)-sensitive photoprotein aequorin, which was microinjected into seven isolated rabbit right ventricular and 15 isolated mouse LV papillary muscles. The faCaT data from the beginning of twitch stimulation to the maximum of the first-order time derivative of Ca(2+) concentration (dCa/dt(max)) was curve-fitted by the least-squares method using h-L and m-E function equations. RESULTS: The mean correlation coefficient (r) values of the h-L and m-E curve-fits for the faCaTs were 0.9740 and 0.9654 (P < 0.05) in the rabbit and 0.9895 and 0.9812 (P < 0.0001) in the mouse. CONCLUSION: The h-L curves tracked the amplitudes and time courses of the faCaTs in cardiac muscles more accurately than m-E functions. Based on this result, we suggest that the h-L time constant may be a more reliable index than the m-E time constant for evaluating the rate of CICR from the SR in myocardial Ca(2+) handling. The h-L approach may provide a more useful model for the study of CICR during the contraction process induced by anesthetic agents.

[Attenuation of phrenic nerve palsy associated with brachial plexus block by modified supra costal approach under fluoroscopic guidance].

BACKGROUND: Brachial plexus block (BPB) frequently accompanies phrenic nerve palsy (PNP). METHODS: Thirty six patients scheduled for upper-limb surgery were allocated to 2 groups; 14 patients undergoing BPB with the supra costal approach (i. e. placing the needle-tip at the middle of the 1st lib), and 22 patients undergoing BPB with the modified supra costal approach (i. e. placing the needle-tip in the visceral or dorsal area of the 1st lib). We evaluated analgesic effects of the block and changes in forced vital capacity (FVC). RESULTS: BPB with both approaches provided sufficient analgesia. After BPB with both approaches, a significant reductions in FVC was observed; however, the reduction after BPB with the modified supra costal approach was significantly lower than that with the supra costal approach. CONCLUSIONS: These results suggest that BPB with the modified supra costal approach provides sufficient analgesia with a significantly lower degree of PNP. We suppose that distribution of local anesthetics is altered by changing the location of the needle-tip on the 1st lib. Amounts of local anesthetics distributing around the phrenic nerve can be reduced by the modified supra costal approach, leading to the significantly less reduction in FVC after BPB.

[Evaluation of cardiac and myocardial inotropism and lusitropism using half-logistic curve-fitting].

Half-logistic (h-L) function, which is half of the sigmoidal, logistic function with a boundary at the inflection point, curve-fits the isovolumic relaxation left ventricular (LV) pressure curve from the minimum of the first order time derivative of pressure (dP/dt(min)), and the myocardial isometric relaxation tension curve from the minimum of the first order time derivative of tension (dF/dt(min)) superior to the conventional mono-exponential function. Recently, we found that h-L function could curve-fit the other partial curves. The isovolumic LV pressure curve in the excised, cross-circulated canine heart, was divided into four distinct phases with boundaries set at the maximum of dP/dt (dP/dt(max)), peak LV pressure, dP/dt(min), and LV end-diastolic pressure (LVEDP) resulting in the first phase from the point corresponding to QR on the electrocardiogram to dP/dt(max); the second phase from dP/dt(max) to the peak LV pressure; the third phase from the peak LV pressure to dP/dt(min); and the fourth phase from dP/dt(min) to LVEDP. Similarly, the isometric twitch tension curves in the mouse LV and rabbit right ventricular (RV) papillary muscles were divided into four distinct phases with boundaries set at the maximum of dF/dt (dF/dt(max)), peak tension, dF/dt(min), and resting tension resulting in the first phase from the point corresponding to twitch stimulation to dF/dt(max); the second phase from dF/dt(max) to the peak tension; the third phase from the peak tension to dF/dt(min); and the fourth phase from dF/dt(min) to resting tension. The h-L correlation coefficient (r) values for the sequential curves were larger than the m-E r values, respectively, and the h-L residual mean squares (RMS) were smaller than the m-E RMS values, respectively. The h-L time constants are indices which quantify cardiac and myocardial inotropism and lusitropism more accurately. We consider that the h-L approach also applies for evaluation of the isovolumic contraction phase and the isovolumic relaxation phase in the beating hearts.

[Efficacy of acetated-Ringer containing 10% dextran: evaluation in a rat model of acute normovolemic hemodilution].

BACKGROUND: In this study, we prepared acetated-Ringer containing 10% dextran, and evaluated its efficacy in a rat model of acute normovolemic hemodilution (ANH). METHODS: Under sevoflurane anesthesia, 21 rats (350-400 g) underwent ANH. In all rats 10 ml of blood was withdrawn, and they were infused with 10 ml of acetated-Ringer containing 10% dextran (Group-A, n = 11) or lactated-Ringer containing 10% dextran (Group-L, n = 10). For each rat, ANH procedure took 20 minutes. Hemodynamics and arterial blood gas data before and after ANH were compared. RESULTS: All results but for blood lactate level after ANH were comparable between the 2 groups. Blood lactate level was elevated in both groups after ANH; however, the elevation was significantly higher in Group-L. CONCLUSIONS: No differences in hemodynamics after ANH reveal that 2 plasma substitutes used in this study have almost the same quality in maintaining intravascular volume. Blood lactate level is generally recognized as an indicator of tissue hypoxia. A possible explanation for the significantly higher blood lactate level in Group-L after ANH is that exogenous overload of lactate as well as tissue hypoxia might have elevated blood lactate levels after ANH in this study. These results suggest the efficacy of acetated-Ringer containing 10% dextran.

Targeting FROUNT with disulfiram suppresses macrophage accumulation and its tumor-promoting properties.

Tumor-associated macrophages affect tumor progression and resistance to immune checkpoint therapy. Here, we identify the chemokine signal regulator FROUNT as a target to control tumor-associated macrophages. The low level FROUNT expression in patients with cancer correlates with better clinical outcomes. Frount-deficiency markedly reduces tumor progression and decreases macrophage tumor-promoting activity. FROUNT is highly expressed in macrophages, and its myeloid-specific deletion impairs tumor growth. Further, the anti-alcoholism drug disulfiram (DSF) acts as a potent inhibitor of FROUNT. DSF interferes with FROUNT-chemokine receptor interactions via direct binding to a specific site of the chemokine receptor-binding domain of FROUNT, leading to inhibition of macrophage responses. DSF monotherapy reduces tumor progression and decreases macrophage tumor-promoting activity, as seen in the case of Frount-deficiency. Moreover, co-treatment with DSF and an immune checkpoint antibody synergistically inhibits tumor growth. Thus, inhibition of FROUNT by DSF represents a promising strategy for macrophage-targeted cancer therapy.

[Curve-fit with hybrid logistic function for intracellular calcium transient].

As the left ventricular (LV) pressure curve and myocardial tension curve in heart are composed of contraction and relaxation processes, we have found that hybrid logistic (HL) function calculated as the difference between two logistic functions curve-fits better the isovolumic LV pressure curve and the isometric twitch tension curve than the conventional polynomial exponential and sinusoidal functions. Increase and decrease in intracellular Ca2+ concentration regulate myocardial contraction and relaxation. Recently, we reported that intracellular Ca2+ transient (CaT) curves measured using the calcium-sensitive bioluminescent protein, aequorin, were better curve-fitted by HL function compared to the polynomial exponential function in the isolated rabbit RV and mouse LV papillary muscles. We speculate that the first logistic component curve of HL fit represents the concentration of the Ca2+ inflow into the cytoplasmic space, the concentration of Ca2+ released from sarcoplasmic reticulum (SR), the concentration of Ca2+ binding to troponin C (TnC), and the attached number of cross-bridge (CB) and their time courses, and that the second logistic component curve of HL fit represents the concentration of Ca2+ sequestered into SR, the concentration of Ca2+ removal from the cytoplasmic space, the concentration of Ca2+ released from TnC, and the detached number of CB and their time courses. This HL approach for CaT curve may provide a more useful model for investigating Ca2+ handling, Ca(2+) -TnC interaction, and CB cycling.

Transcriptome network analysis identifies protective role of the LXR/SREBP-1c axis in murine pulmonary fibrosis.

Pulmonary fibrosis (PF) is an intractable disorder with a poor prognosis. Although lung fibroblasts play a central role in PF, the key regulatory molecules involved in this process remain unknown. To address this issue, we performed a time-course transcriptome analysis on lung fibroblasts of bleomycin- and silica-treated murine lungs. We found gene modules whose expression kinetics were associated with the progression of PF and human idiopathic PF (IPF). Upstream analysis of a transcriptome network helped in identifying 55 hub transcription factors that were highly connected with PF-associated gene modules. Of these hubs, the expression of Srebf1 decreased in line with progression of PF and human IPF, suggesting its suppressive role in fibroblast activation. Consistently, adoptive transfer and genetic modification studies revealed that the hub transcription factor SREBP-1c suppressed PF-associated gene expression changes in lung fibroblasts and PF pathology in vivo. Moreover, therapeutic pharmacological activation of LXR, an SREBP-1c activator, suppressed the Srebf1-dependent activation of fibroblasts and progression of PF. Thus, SREBP-1c acts as a protective hub of lung fibroblast activation in PF. Collectively, the findings of the current study may prove to be valuable in the development of effective therapeutic strategies for PF.

A mass conserved reaction-diffusion system captures properties of cell polarity.

Cell polarity is a general cellular process that can be seen in various cell types such as migrating neutrophils and Dictyostelium cells. The Rho small GTP(guanosine 5'-tri phosphate)ases have been shown to regulate cell polarity; however, its mechanism of emergence has yet to be clarified. We first developed a reaction-diffusion model of the Rho GTPases, which exhibits switch-like reversible response to a gradient of extracellular signals, exclusive accumulation of Cdc42 and Rac, or RhoA at the maximal or minimal intensity of the signal, respectively, and tracking of changes of a signal gradient by the polarized peak. The previous cell polarity models proposed by Subramanian and Narang show similar behaviors to our Rho GTPase model, despite the difference in molecular networks. This led us to compare these models, and we found that these models commonly share instability and a mass conservation of components. Based on these common properties, we developed conceptual models of a mass conserved reaction-diffusion system with diffusion-driven instability. These conceptual models retained similar behaviors of cell polarity in the Rho GTPase model. Using these models, we numerically and analytically found that multiple polarized peaks are unstable, resulting in a single stable peak (uniqueness of axis), and that sensitivity toward changes of a signal gradient is specifically restricted at the polarized peak (localized sensitivity). Although molecular networks may differ from one cell type to another, the behaviors of cell polarity in migrating cells seem similar, suggesting that there should be a fundamental principle. Thus, we propose that a mass conserved reaction-diffusion system with diffusion-driven instability is one of such principles of cell polarity.

[Curve-fits with hybrid logistic functions for isovolumic left ventricular pressure curve and isometric myocardial tension curve].

Non-linear regression and curve-fitting may contribute to resolution of the mechanism, summarise information, remove noise, allow speculation regarding unmeasured data, and separate the effects of multiple factors. The isovolumic left ventricular (LV) pressure curve and isometric myocardial tension curve have been curve-fit with polynomial expotential and sinusoidal functions. The isovolumic LV pressure curve and myocardial isometric tension curve are composed of contraction and relaxation processes. We have proposed that hybrid logistic (HL) functions, calculated as the difference between two logistic functions, fit better the isovolumic LV pressure curves at any LV volume, heart rate, and infused calcium (Ca2+) concentration in coronary artery in the excised, cross-circulated canine heart, and the isometric twitch tension curves at any muscle length and extracellular Ca2+ concentration in the ferret right ventricular (RV) papillary muscle. We suggest that the six HL parameters are useful to evaluate the contraction and relaxation processes in the heart and myocardium. This HL approach for the isovolumic LV pressure curves and the isometric twitch tension curves may provide a more useful model for speculating Ca2+ handling, Ca(2+) -Troponin C interaction, and cross-bridge cycling.

[Multiple linear regression analysis for predictability of the extent of spinal anesthesia by plain bupivacaine].

BACKGROUND: Predictability of the extent of spinal anesthesia by plain bupivacaine has been controversial. METHODS: Two hundred and twenty-eight patients undergoing elective surgery with spinal anesthesia were enrolled in this retrospective study. Using gender, age, height, body mass index (BMI), chosen spinal interspace for spinal tap (L2-3 or L3-4), and dose of plain bupivacaine as independent variables, we performed stepwise multiple linear regression analysis to examine predictability of the extent of sensory blockade produced by spinal anesthesia using plain bupivacaine. RESULTS: Following equation was obtained. Extent of sensory blockade = 14.9 + (male : 0.540, female: -0.540) -0.0774 x height + 0.124 x BMI + (L2-3 : 0.345, L3-4: -0.345): r2 = 0.0604. P values of gender, height and BMI were less than 0.05; however, r2 of each variable was very low. CONCLUSIONS: Results of this retrospective study imply the unpredictability of the extent of spinal anesthesia produced by plain bupivacaine.

[Assessment by logistic model of hemodynamic changes during general anesthesia].

The anesthesia induction with strong anesthetic agents generally reduces blood pressure. Cardiovascular agents used during anesthesia induce hemodynamic changes. The time courses of systolic (sBP) and diastolic blood pressure (dBP) and heart rate (HR) are expressed as sigmoidal curve. We have found that the hemodynamic changes can be precisely curve-fitted with a logistic function giving non-linear curve. The four parameters of the logistic function present the first asymptote, the last asymptote, the slope at the inflection point, and the time to the inflection point. Moreover, each logistic parameter is used for the effects of drug dose, age and sex differences of subjects on the hemodynamic change. In this review, we introduce the analyses with the logistic function for the changes in sBP, and dBP during preintubation period and HR, sBP, and dBP during infusion of landiolol hydrochloride, an ultra-short-acting beta1-adrenergic receptor blocking agent, which is used for subjects with tachycardia during general anesthesia. The logistic parameters are useful for assessing the hemodynamic response during general anesthesia. The assessment method of the hemodynamic change using the logistic model contributes much to the management of anesthesia.