Association of Hemometabolic Trajectory and Mortality: Insights From the Cardiogenic Shock Working Group Registry.

Cardiogenic shock (CS) is a hemodynamic syndrome that can progress to systemic metabolic derangements and end-organ dysfunction. Prior studies have reported hemodynamic parameters at the time of admission to be associated with mortality but hemodynamic trajectories in CS have not been well described. We studied the association between hemodynamic profiles and their trajectories and in-hospital mortality in patients with CS due to heart failure (HF-CS) and acute myocardial infarction (MI-CS). Using data from the large multicenter Cardiogenic Shock Working Group (CSWG) registry, we analyzed hemodynamic data obtained at the time of pulmonary artery catheter (PAC) insertion (dataset at baseline) and at PAC removal or death (dataset at final time point). Univariable regression analyses for prediction of in-hospital mortality were conducted for baseline and final hemodynamic values, as well as the interval change (delta-P). Data was further analyzed based on CS etiology and survival status. A total of 2260 patients with PAC data were included (70% male, age 61 ± 14 years, 61% HF-CS, 27% MI-CS). In-hospital mortality was higher in the MI-CS group (40.1%) compared with HF-CS (22.4%, P < .01). In the HF-CS cohort, survivors exhibited lower right atrial pressure (RAP), pulmonary artery pressure (PAP), cardiac output/index (CO/CI), lactate, and higher blood pressure (BP) than nonsurvivors at baseline. In this cohort, during hospitalization, improvement in metabolic (aspartate transaminase, lactate), BP, hemodynamic (RAP, pulmonary artery pulsatility index [PAPi], pulmonary artery compliance for right-sided profile and CO/CI for left-sided profile), had association with survival. In the MI-CS cohort, a lower systolic BP and higher PAP at baseline were associated with odds of death. Improvement in metabolic (lactate), BP, hemodynamic (RAP, PAPi for right-sided profile and CO/CI for left-sided profile) were associated with survival. In a large contemporary CS registry, hemodynamic trajectories had a strong association with short-term outcomes in both cohorts. These findings suggest the clinical importance of timing and monitoring hemodynamic trajectories to tailor management in patients with CS.

Pulmonary Artery Catheter Use and Risk of In-hospital Death in Heart Failure Cardiogenic Shock.

BACKGROUND: Pulmonary artery catheters (PACs) are increasingly used to guide management decisions in cardiogenic shock (CS). The goal of this study was to determine if PAC use was associated with a lower risk of in-hospital mortality in CS owing to acute heart failure (HF-CS). METHODS AND RESULTS: This multicenter, retrospective, observational study included patients with CS hospitalized between 2019 and 2021 at 15 US hospitals participating in the Cardiogenic Shock Working Group registry. The primary end point was in-hospital mortality. Inverse probability of treatment-weighted logistic regression models were used to estimate odds ratios (ORs) and corresponding 95% confidence intervals (CI), accounting for multiple variables at admission. The association between the timing of PAC placement and in-hospital death was also analyzed. A total of 1055 patients with HF-CS were included, of whom 834 (79%) received a PAC during their hospitalization. In-hospital mortality risk for the cohort was 24.7% (n = 261). PAC use was associated with lower adjusted in-hospital mortality risk (22.2% vs 29.8%, OR 0.68, 95% CI 0.50-0.94). Similar associations were found across SCAI stages of shock, both at admission and at maximum SCAI stage during hospitalization. Early PAC use (≤6 hours of admission) was observed in 220 PAC recipients (26%) and associated with a lower adjusted risk of in-hospital mortality compared with delayed (≥48 hours) or no PAC use (17.3% vs 27.7%, OR 0.54, 95% CI 0.37-0.81). CONCLUSIONS: This observational study supports PAC use, because it was associated with decreased in-hospital mortality in HF-CS, especially if performed within 6 hours of hospital admission. CONDENSED ABSTRACT: An observational study from the Cardiogenic Shock Working Group registry of 1055 patients with HF-CS showed that pulmonary artery catheter (PAC) use was associated with a lower adjusted in-hospital mortality risk (22.2% vs 29.8%, odds ratio 0.68, 95% confidence interval 0.50-0.94) compared with outcomes in patients managed without PAC. Early PAC use (≤6 hours of admission) was associated with a lower adjusted risk of in-hospital mortality compared with delayed (≥48 hours) or no PAC use (17.3% vs 27.7%, odds ratio 0.54, 95% confidence interval 0.37-0.81).

Direct identification of mycobacteria from clinical specimens by multiplex real-time PCR.

AIMS: To directly identify clinically relevant mycobacteria from clinical specimens, we have developed a multiplex real-time PCR assay with hydrolysis probes that can identify 20 mycobacterial species. METHODS AND RESULTS: The assay was initially evaluated using 248 strains, including both reference strains and clinical isolates. Then, the assay was implemented according to a scheme in our laboratory. The scheme based on the clinical differences between the Mycobacterium tuberculosis complex (MTC) and nontuberculous mycobacteria (NTM) consisted of three stepwise PCRs. MTC and NTM were differentially detected in the step 1 PCR, and the NTM species were identified in the step 2 and step 3 PCRs. During a 2·5-year period, 1877 isolates of MTC (1142 directly recovered from clinical specimens) and 596 isolates of NTM (143 directly recovered from clinical specimens) were detected, and the species of 590 (99·0%) of the 596 NTM isolates were identified. CONCLUSIONS: Our experience shows that this is a new paradigm for rapidly and accurately identifying clinically relevant mycobacteria, in which a multiplex real-time PCR assay is directly applied to clinical specimens in a stepwise fashion. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first report of a multiplex real-time PCR assay for identifying clinically important mycobacterial species directly from clinical specimens and its application in a clinical microbiology laboratory.

Inactivation of pathogenic bacteria inoculated onto a Bacto™ agar model surface using TiO2-UVC photocatalysis, UVC and chlorine treatments.

AIMS: The aim of this study was to study inactivation of different pathogenic bacteria on agar model surface using TiO2-UV photocatalysis (TUVP). METHODS AND RESULTS: A unified food surface model was simulated using Bacto(™) agar, a routinely used microbial medium. The foodborne pathogenic bacteria Escherichia coli K12 (as a surrogate for E. coli O157:H7), Salmonella Typhimurium, Staphylococcus aureus and Listeria monocytogenes were inoculated onto the agar surface, followed by investigation of TUVP-assisted inactivation and morphological changes in bacterial cells. The TUVP process showed higher bacterial inactivation, particularly for Gram-negative bacteria, than UVC alone and a control (dark reaction). A TUVP treatment of 17·2 mW cm(-2) (30% lower than the UVC light intensity) reduced the microbial load on the agar surface by 4·5-6·0 log CFU cm(-2). UVC treatment of 23·7 mW cm(-2) caused 3·0-5·3 log CFU cm(-2) reduction. CONCLUSIONS: The use of agar model surface is effective for investigation of bacterial disinfection and TUVP is a promising nonthermal technique. SIGNIFICANCE AND IMPACT OF THE STUDY: The results showing effects of photocatalysis and other treatments for inactivation of bacterial pathogens on model surface can be useful for applying such processes for disinfection of fruit, vegetables and other similar surfaces.

Diblock and triblock copolymer thin films on a substrate with controlled selectivity.

Using self-consistent field theory (SCFT), morphology development in symmetric linear ABC triblock copolymer films on neutral and selective substrates has been studied, and it is compared with the triblock copolymer morphologies in bulk. In particular, the effects of the substrate preferable to B (interior) block on nanopattern formation of the copolymer films are of our central interest. Here, we report various nanopatterns with tunable square morphologies. The domain patterns are much more diverse than those parallel to the substrate with substrate selectivity for end-block or those vertical to the substrate without substrate selectivity. Furthermore, in order to figure out an economical and efficient way to fabricate useful passive pattern transfer layers, which have potential applications in microelectronic processes and ultrahigh density storage media, we propose a two-step strategy and scrutinize the conditions for generating square symmetries using cylinder-forming or lamella-forming AB diblock copolymers deposited on substrates created from ABC triblock copolymer films. It is found that a thinner film with weak incompatibility can produce square patterns.

Finite-N effects for ideal polymer chains near a flat impenetrable wall.

This paper addresses the statistical mechanics of ideal polymer chains next to a hard wall. The principal quantity of interest, from which all monomer densities can be calculated, is the partition function, G(N)(z) , for a chain of N discrete monomers with one end fixed a distance z from the wall. It is well accepted that in the limit of infinite N , G(N)(z) satisfies the diffusion equation with the Dirichlet boundary condition, G(N)(0) = 0, unless the wall possesses a sufficient attraction, in which case the Robin boundary condition, G(N)(0) = - xi G(N)(')(0), applies with a positive coefficient, xi. Here we investigate the leading N(-1/2) correction, Delta G (N)(z). Prior to the adsorption threshold, Delta G(N)(z) is found to involve two distinct parts: a Gaussian correction (for z approximately

Does isoflurane enhance rhinovirus replication and virus-induced cytokine secretion in airway epithelial cells?

BACKGROUND: There have been no previous studies regarding the effect of volatile anesthetics on human rhinovirus (RV) infection in airway epithelial cells of patients with an upper respiratory infection (URI). We have therefore evaluated in vitro the effect of isoflurane on RV infection in airway epithelial cells. METHODS: A549 cells and RV-infected A549 cells were treated with isoflurane for 2 or 4 h. Surface expression of intercellular adhesion molecule-1 (ICAM-1) was assessed by flow cytometry, and effects on the secretion of interleukin (IL)-6 and IL-8 were measured by ELISA. The effect on RV replication in the cells was determined by viral titer. RESULTS: Isoflurane treatment for 2 or 4 h had no significant effect on ICAM-1 expression and secretion of IL-6 and IL-8 in control cells. Isoflurane also had no significant additional effect on RV-induced ICAM-1 expression and secretion of IL-6 and IL-8. Viral titers were not significantly influenced by isoflurane. CONCLUSION: Isoflurane treatment showed no additional effects with RV on ICAM-1 expression, secretion of IL-6 and IL-8, and viral titer in A549 cells. These results suggest that isoflurane itself may not increase further RV infections, inflammations, and viral replication in patients with a viral URI.

The effects of dairy processes and storage on insulin-like growth factor-I (IGF-I) content in milk and in model IGF-I-fortified dairy products.

The effects of several dairy processes on insulin-like growth factor-I (IGF-I) concentrations in milk and the storage stability of IGF-I-fortified dairy products were examined. The IGF-I content in raw milk determined by radioimmunoassay was significantly changed by the strength of heat treatments. In commercial manufacture of whole milk dry powder, IGF-I concentration was not significantly changed. A significant reduction in IGF-I content was found as the result of fermentation with a commercial starter culture. The IGF-I content in fortified milk and dried milk powder exhibited no significant changes over the tested storage periods (12 d for milk, 4 wk for dried milk powder), but the IGF-I content in the yogurt decreased significantly during storage. The use of IGF-I was varied by lactic strains and was apparent in the viable cells. When IGF-I was encapsulated using the surface-reforming process, the remaining IGF-I content after fermentation was significantly higher compared with that of the untreated control. Therefore, enteric coating of IGF-I before fermentation might be an effective method for the prevention of IGF-I degradation during fermentation.

Early primary biliary cholangitis is characterised by brain abnormalities on cerebral magnetic resonance imaging.

BACKGROUND: Brain change can occur in primary biliary cholangitis (PBC), potentially as a result of cholestatic and/or inflammatory processes. This change is linked to systemic symptoms of fatigue and cognitive impairment. AIM: To identify whether brain change occurs early in PBC. If the change develops early and is progressive, it may explain the difficulty in treating these symptoms. METHODS: Early disease brain change was explored in 13 patients with newly diagnosed biopsy-proven precirrhotic PBC using magnetisation transfer, diffusion-weighted imaging and 1 H magnetic resonance spectroscopy. Results were compared to 17 healthy volunteers. RESULTS: Cerebral magnetisation transfer ratios were reduced in early PBC, compared to healthy volunteers, in the thalamus, putamen and head of caudate with no greater reduction in patients with greater symptom severity. Mean apparent diffusion coefficients were increased in the thalamus only. No 1 H magnetic resonance spectroscopy abnormalities were seen. Serum manganese levels were elevated in all PBC patients, but no relationship was seen with imaging or symptom parameters. There were no correlations between neuroimaging data, laboratory data, symptom severity scores or age. CONCLUSIONS: This is the first study to be performed in this precirrhotic patient population, and we have highlighted that neuroimaging changes are present at a much earlier stage than previously demonstrated. The neuroimaging abnormalities suggest that the brain changes seen in PBC occur early in the pathological process, even before significant liver damage has occurred. If such changes are linked to symptom pathogenesis, this could have important implications for the timing of second-line-therapy use.

Comparison of effects of angiotensin peptides in the regulation of clitoral cavernosum smooth muscle tone.

The isometric tension measurement and in vitro autoradiography were used in clitoral cavernosum smooth muscle (CSM). Angiotensin ANG III, ANG IV, ANG II and ANG I induced contractions in clitoral CSM strips. ANG III and ANG I- induced contraction was five times less active than ANG II, whereas ANG IV-induced contraction was 1181-fold less potent than ANG II. Contractile responses to ANG III, ANG IV, ANG II and ANG I were significantly inhibited by type 1 ANG II (AT 1) receptor antagonist Dup 753 but not by type 2 ANG II (AT2) receptor antagonist PD 123,319. Pre-treatment with Nomega-nitro-L-arginine methyl ester, nitric oxide (NO) synthase inhibitor accentuated force of contraction induced by ANG III, ANG IV and ANG II. Amastatin, an aminopeptidase inhibitor enhanced ANG III- and ANG IV-induced contractions. Specific binding sites for 125I-ANG II were found in the clitoral CSM. Specific binding of 125I-ANG II was displaced by unlabeled ANG peptides. This study suggests that the contractile responses to all four peptides of the ANG family are mediated via AT1 receptors but not AT2 receptors. Further, the rank order of potency of contraction was as follows, ANG II> ANG I>ANG III>ANG IV. It is also suggested that peptides of the ANG family have a cross-talk with the NO system and aminopeptidase is involved in the modulation of the tone of clitoral CSM by ANG III and ANG IV.

Okadaic acid-induced upregulation of nitrotyrosine and heme oxygenase-1 in rat cortical neuron cultures.

Hyperphosphorylation of tau is a characteristic feature of the neurodegenerative pathology in Alzheimer's disease (AD). Okadaic acid (OA) is currently used in models of AD research to increase the phosphorylation of tau. Using immunocytochemistry and fluorescent study, we found that markers of oxidative activity such as nitrotyrosine, c-jun, 2',7'-dichlorofluorescein diacetate (DCF), and heme oxygenase-1 (HO-1) were altered in OA-treated culture. Immunoreactivity of nitrotyrosine and c-jun, and DCF-oxidation were increased in degenerating neurons, while HO-1 expression was increased in astrocyte in response to OA. The data suggest that tau phosphorylation and oxidative damage be implicated in OA-induced neurodegeneration.

HLA-B51 and its allelic types in association with Behçet's disease and recurrent aphthous stomatitis in Korea.

OBJECTIVE: This case-control study was undertaken to evaluate the association of HLA-B51 antigen and its allelic types with Behçet's disease (BD) and with recurrent aphthous stomatitis (RAS), to investigate the degree of this association with diagnostic types and clinical variables of BD. METHODS: The DNA typing of HLA-B51 by nested PCR-SSP was performed in 61 patients with BD, 56 patients with RAS, and in 70 healthy controls. Also, blind quality control study was done to assess the accuracy of nested PCR-SSP in HLA-B51-positive and negative BD patients on the microlymphocytotoxicity. In addition, direct DNA sequencing analysis was carried out in HLA-B51-positive individuals. RESULTS: The outcome of nested PCR-SSP showed 100% concordance with those of the microlymphocytotoxicity. The prevalence of HLA-B51 in patients with BD was 55.7%, 16.1% in patients with RAS, and 15.7% in healthy controls. According to the diagnostic types of BD, all ten patients with complete BD had HLA-B51 antigen, and 47.1% in patients with incomplete BD (p = 0.002). In addition, the prevalence of HLA-B51 was statistically significant in patients with BD who had uveitis (p = 0.003) or erythema nodosum (p = 0.042). Direct DNA sequencing analysis revealed that the major allelic types in BD, RAS, and in healthy control were mostly HLA-B*51011. CONCLUSIONS: Compared to patients with RAS or healthy controls, prevalence of HLA-B51 in the Korean patients with BD was much higher. The BD patients with B51 seemed to be susceptible for manifesting uveitis, erythema nodosum, and the full-blown syndrome as complete BD. Therefore the presence of HLA-B51 antigen in BD patients would be a genetic marker for the severe disease. In addition, there was no difference on the major allelic types of HLA-B51 in BD, RAS, and in healthy control.

The prevalence of atopy and atopic diseases in Behçet's disease.

OBJECTIVE: The prevalence of Th-2 cell-mediated diseases, such as atopic diseases, has been noted to be low in Th-1 cell-mediated diseases. This study was undertaken to assess the prevalence of atopy and atopic diseases in Behçet's disease (BD), a Th-1 cell-mediated disease, and to investigate the clinical association between the atopy and the development of severe manifestations in BD. METHODS: We examined 70 consecutive BD patients and 113 controls without BD or other inflammatory rheumatic diseases. The cumulative history of severe manifestations in BD patients was investigated during the disease course. A skin prick test was performed in all the subjects, and atopy was defined as present when the size of one or more allergen-induced wheals was equal to or larger than that caused by histamine. Atopic diseases were defined as present when there were relevant responses for atopic diseases on the questionnaires in the subjects with atopy. In addition, serum IgE levels and peripheral blood eosinophil counts were measured. RESULTS: The prevalence of atopy and atopic diseases was significantly lower in BD patients than in controls. Other atopy parameters, such as serum IgE levels and peripheral blood eosinophil counts, were also significantly lower in BD patients when compared with controls. However, atopy, serum IgE levels, and peripheral blood eosinophil counts did not differ significantly between BD patients with and without severe manifestations. CONCLUSION: The prevalence of Th-2 cell-mediated conditions, such as atopy and atopic diseases, appeared to be lower in BD, a Th-1 cell-mediated disease. In addition, a Th-1 and Th-2 balance may not influence the development of severe manifestations in BD.

Electron trapping and acceleration across a parabolic plasma density profile.

It is known that as a laser wakefield passes through a downward density transition in a plasma some portion of the background electrons are trapped in the laser wakefield and the trapped electrons are accelerated to relativistic high energies over a very short distance. In this study, by using a two-dimensional (2D) particle-in-cell (PIC) simulation, we suggest an experimental scheme that can manipulate electron trapping and acceleration across a parabolic plasma density channel, which is easier to produce and more feasible to apply to the laser wakefield acceleration experiments. In this study, 2D PIC simulation results for the physical characteristics of the electron bunches that are emitted from the parabolic density plasma channel are reported in great detail.

Pachyonychia congenita associated with steatocystoma multiplex.

We present an unique case of pachyonychia congenita associated with steatocystoma multiplex. A 33-year-old Japanese man had thickening and gray-brown dicoloration of all nails and a large number of nodules or tumors over his entire skin. No palmar and plantar hyperkeratosis, leukokeratosis of the mucous membranes, or follicular keratosis were observed. Histology of these tumors revealed the typical features of steatocystoma multiplex.

Improvement of existing nightsoil treatment plant for nitrogen removal.

This study was performed to increase the treatment efficiency and to reduce operation and maintenance costs of the existing nightsoil treatment plant. The existing nightsoil plant was not established by the nitrogen removal process, and was operated ineffectively with deterioration of treatment efficiency rate, and according to the demand of many operators, the expenses of operation and maintenance have become excessive. Modified plant has been changed through two steps. The first step, liquid decayed tank using closed oxidation ditch is operated to increase retention time only for nitrification. The second step, modified liquid decayed tank including anoxic tank is operated, it has an excellent nitrogen removal rate. In first step, when HRT was increased from 10 days to 13 days in liquid decayed tank including aeration tank using closed oxidation ditch, TN concentration of effluent appeared below 51 mg/L less than discharge limit, 60 mg/L. In second step, when anoxic tank and oxic tank were installed, HRT has been increased to 13 days and 26 days, respectively. Then average TN concentration of effluent was detected less than 13 mg/L for over one year. The simple process modified the existing two processes resulted in the reduction of costs for operation and maintenance in the personnel, chemical, and filter change sphere.

Characteristics of the pulse wave in patients with chronic gastritis and the healthy in Korean medicine.

Chronic gastritis is a disease that occurs in one in every 10 persons in Korea. Endoscopic examination is needed to diagnose chronic gastritis in western medicine, but it causes patients pain, long period of examinations and financial burden. In KM (Korean Medicine), on the other hand, it can be known whether stomach is abnormal or not through a pulse diagnosis. The 'Guan' position of the right wrist is related to a stomach in KM. Thus, the pulse wave of the right-hand "Guan" of patients with chronic gastritis and the healthy were measured. Then, the diagnostic parameter and features to distinguish between the patients with chronic gastritis and the healthy were discovered. Through P-H curve, consequently, it can be concluded that the pulse waves of patients with chronic gastritis appear as a floating pulse, whereas the pulse waves of the healthy appear as a normal pulse.

Finite-stretching corrections to the Milner-Witten-Cates theory for polymer brushes.

This paper investigates finite-stretching corrections to the classical Milner-Witten-Cates theory for semi-dilute polymer brushes in a good solvent. The dominant correction to the free energy originates from an entropic repulsion caused by the impenetrability of the grafting surface, which produces a depletion of segments extending a distance mu proportional to L(-1) from the substrate, where L is the classical brush height. The next most important correction is associated with the translational entropy of the chain ends, which creates the well-known tail where a small population of chains extend beyond the classical brush height by a distance xi proportional to L(-1/3). The validity of these corrections is confirmed by quantitative comparison with numerical self-consistent field theory.

Cytoskeletal control of myogenesis: a desmin null mutation blocks the myogenic pathway during embryonic stem cell differentiation.

A differentiating system based on embryonic stem (ES) cell-derived embryoid bodies (EBs) which recapitulates the in vivo cardiac, skeletal, and smooth muscle myogenesis of mouse embryos was developed and used to investigate the effects of the disruption of the desmin gene on muscle cell differentiation. Wild-type, heterozygous, and homozygous cell lines with the mutated desmin allele were evaluated. Skeletal myogenesis was totally inhibited in desmin null mutant EBs, as manifested by the absence of myotube formation, contractility, and myoD, myogenin, myf5, and myosin heavy chain expression. Smooth muscle formation was also completely blocked in the absence of desmin. On the other hand, there were no obvious effects on cardiomyocyte differentiation in these desmin null mutant EBs. However, reduced desmin expression in EBs heterozygous for the desmin mutation leads to partial inhibition of cardiac muscle formation. These data suggest that in contrast to early cardiocyte differentiation, desmin is indispensable for skeletal and smooth muscle formation.