Asthma attacks: Patients who survived paraquat poisoning.
A patient who survived acute paraquat (PQ) poisoning for more than 5 years was followed up in the emergency room. The patient had recurrent coughing and wheezing one month after discharge. Re-examination of chest CT showed increased dual lung texture. Spirometry suggested severe ventilatory dysfunction while bronchial dilation test was positive. The serum IgE level was significantly high. It is considered that patients with acute PQ poisoning may develop asthma in the long term.


[The domestic inhalation of the smoke from firewood and of other biological materials. A risk for the development of respiratory diseases].
A high proportion of the world population, especially in developing countries, is exposed to indoor pollutants produced by inefficient biomass stoves. The levels of pollutants, including toxins and carcinogens in the kitchen are usually very high. This potential pathogenic exposure has been scarcely studied. The exposure to biomass smoke has been associated to chronic bronchitis and chronic airflow obstruction in adults and to acute respiratory infections in children. At the National Institute of Pulmonary Diseases in Mexico, we have observed the entire spectrum of diseases associated with tobacco in people who never smoked and who were exposed to wood smoke. Women exposed to wood smoke had a five-fold risk of chronic bronchitis and chronic airflow obstruction, as compared to the non-exposed, according to a recent case-control study done at our Institute. The indoor levels of suspended particles smaller than 10 microns were frequently above 1,000 micrograms/m3 in a rural community in the state of Mexico. This information supports a causal role for biomass smoke for the genesis of several respiratory diseases, representing a potentially public health problem.


Heart and spleen "twin grafts" in rats: IV. Influence of donor spleen cell mass on allograft survival.
Heart and spleen twin grafts from LEW to ACI rats may survive permanently, whereas those grafted from ACI to LEW rats do not. This strain difference in graft acceptance was analyzed quantitatively by transplanting one to three ACI spleens into LEW rats in order to compensate for the relatively small size of ACI spleens (Fig. 1). Under these conditions permanent graft survival was not observed in LEW recipients. However, during host splenectomy 3 days after transplantation, a nonimmunological factor was observed. The transplanted ACI spleens showed congestion and infarctions, while in the LEW to ACI transplant model the LEW spleens did not. This observation could be explained by the size of the vascular pedicle in ACI spleens. Although no problem was encountered immediately after completing the anastomoses, allogeneic spleens react by increasing in size, to such an extent that their size exceeds the capacity of the smaller vascular pedicle in ACI rats and results in congestion. Hence, the concept is formulated that early compromise of hemodynamics on a nonimmunological base may determine the fate of ACI spleen graft before immunological factors have a chance to become effective.


Salivary secretory IgA concentration and dental caries in children with Down syndrome.
To evaluate the relationship between salivary secretory immunoglobulin A (sIgA) concentration and dental caries in children with Down syndrome (DS) and compare it with findings in non-DS children. The sample comprised 61 DS children and 52 non-DS children, aged 6 to 14 years. Caries experience, plaque index (PI), and gingival bleeding index (GBI) were recorded. Saliva samples were collected from all children. Total salivary sIgA concentrations were determined using an enzymatic assay method. Caries experience in primary and permanent dentitions were similar in DS and non-DS children. However, PI and GBI values were significantly lower in DS compared to non-DS children. DS children had higher salivary sIgA concentrations compared to non-DS children. No difference in sIgA concentration was observed between children with and without caries experience in either group. DS children have higher salivary sIgA concentrations than non-DS children. However, this finding did not correlate with caries experience in the study population.


Photocatalytic activity of TiO2 nanotubes doped with Ag nanoparticles.
TiO2 nanotubes formed on the surface of commercially pure titanium were prepared by anodizing processing and were then heat-treated. The silver doping was processed with different molar concentration of AgNO3 aqueous solution. The silver-doped TiO2 nanotubes were characterized using field emission scanning electron microscopy, ultraviolet visible near-infrared spectrophotometer and ampere-volts (I-V) curve system. The 20-100 nm Ag nanoparticles were well doped atop, inside, and between the nanotubes. The I-V curve of the TiO2 nanotubes increased with heat treatment temperature. The silver-doped TiO2 nanotubes with anatase plus rutile phases had better photocatalytic activity.


Sulfate recognition by a hexaaza cryptand receptor.
A hexamine macrobicycle with pyrrolyl spacers was evaluated as an anion receptor in its protonated forms. The protonation constants of the receptor, as well as its association constants with Cl(-), NO3(-), AcO(-), ClO4(-), H2PO4(-), and SO4(2-) were determined by potentiometry at 298.2 ± 0.1 K in H2O-MeOH (50 : 50 v/v) and at an ionic strength of 0.10 ± 0.01 M in KTsO. These studies revealed that the Hnpyrr(n+) receptor has a very high effective association constant value for the SO4(2-) at pH 4.0 (log Keff = 6.42), and it is selective for the uptake of this anion in the presence of the other studied anionic substrates. In particular, the receptor showed very high SO4(2-)/NO3(-) selectivity. Using the indicator-displacement approach the receptor is able to signal the presence of sulfate by a change of color. Single crystal X-ray diffraction determination of [(H6pyrr)(SO4)(H2O)3](SO4)2·9.3H2O revealed the presence of one sulfate anion inside the receptor cavity and showed that the encapsulation of the anion is favored by an array of nine hydrogen bonding interactions, including N-HO, C-HO and water-mediated ones.


Trends in kidney transplantation in Australia and New Zealand, 1993-2004.
We hypothesize that transplant outcome in Australia and New Zealand has improved despite more unfavorable transplant characteristics. Data from the Australia and New Zealand Dialysis and Transplant registry was used to examine this hypothesis. All adult kidney-only transplants from January 1993 to December 2004 in Australia or New Zealand were followed-up until death or December 2005. Outcomes were adjusted for covariates in multivariate models, with transplant year modeled as a continuous variable. Altogether 6764 patients were included. There were proportionately more live donor and primary transplants, older donors and recipients, and higher recipient body mass index, waiting time, and human leukocyte antigen mismatch in recent cohorts. Death-censored graft loss decreased (adjusted hazard ratio: 0.92 [0.90-0.95] per year, P<0.001). This trend was seen at both 0-1 and 1-5 years posttransplant, and was mainly for immune-mediated graft losses. Patient survival improved only in New Zealand, and only for the first posttransplant year (adjusted odds ratio: 0.88 [0.82-0.95] per year, P=0.001). Cardiovascular deaths decreased while infection or cancer deaths were unchanged. Adjusted delayed graft function rates were unchanged. The acute rejection incidence at 6 months decreased (adjusted odds ratio: 0.88 [0.85-0.90] per year, P<0.001). One and 3-year graft function significantly improved, even after adjusting for rejection. All outcomes did not vary by expanded donor criteria status. Graft survival and function have improved in recent years, but long-term patient survival remains unchanged. With longer follow-up, the improvement in rejection rates and graft function may lead to further improvements in long-term graft survival and potentially better patient survival.


[Treatment of femoral neck fractures with compressed screw and sartorius bone flap in youth or middle age].
To study the application and the curative effect of compressed screw and sartorius bone flap in treating femoral neck fractures in youth or middle age. From February 1996 to December 2004, 86 patients with femoral neck fracture were treated by open reduction compressed screw and sartorius bone flap, aging from 21 to 49 years. Fracture was caused by traffic accident in 35 cases, fall from height in 27 cases and fall in 24 cases. According to Garden classification, 23 cases were type II, 25 cases were type III, and 15 cases were type IV. We analyzed fracture healing and evaluate function by observation of the postoperative X-ray films. Of the 86 patients, 62 were followed up 6 months to 7 years (2 years and 5 months on average). According to Weijie's criterion for nonunion and necrosis of femoral head, nonunion occurred in 4 cases; the healing rate of fracture was 93.5%. In healed patients, necrosis of femoral head occurred in 7 cases (11.3%) after 3 years. The results of hip joint function evaluation were excellent in 44 cases, good in 8 cases, fair in 6 cases and poor in 4 cases; and the excellent and good rate was 83.9%. Compressed screw and sartorius bone flap was simple and effective for femoral neck fractures in youth or middle age.


Origins of elasticity in intermediate filament networks.
Intermediate filaments are common structural elements found in abundance in all metazoan cells, where they form networks that contribute to the elasticity. Here, we report measurements of the linear and nonlinear viscoelasticity of networks of two distinct intermediate filaments, vimentin and neurofilaments. Both exhibit predominantly elastic behavior with strong nonlinear strain stiffening. We demonstrate that divalent ions behave as effective cross-linkers for both networks, and that the elasticity of these networks is consistent with the theory for that of semiflexible polymers.


Room for one more? A review of the literature on 'inappropriate' admissions to hospital for older people in the English NHS.
This paper reports the findings of a review of the literature on emergency admissions to hospital for older people in the UK, undertaken between May and June 2014 at the Health Services Management Centre, University of Birmingham. This review sought to explore: the rate of in/appropriate emergency admissions of older people in the UK; the way this is defined in the literature; solutions proposed to reduce the rate of inappropriate admissions; and the methodological issues which particular definitions of 'inappropriateness' raise. The extent to which a patient perspective is included in these definitions of inappropriateness was also noted, given patient involvement is such a key policy priority in other areas of health policy. Despite long-standing policy debates, relatively little research has been published on formal rates of 'inappropriate' emergency hospital admissions for older people in the UK NHS in recent years. What has been produced indicates varying rates of in/appropriateness, inconsistent ways of defining appropriateness and a lack of focus on the possible solutions to address the problem. Significantly, patient perspectives are lacking, and we would suggest that this is a key factor in fully understanding how to prevent avoidable admissions. With an ageing population, significant financial challenges and a potentially fragmented health and social care system, the issue of the appropriateness of emergency admission is a pressing one which requires further research, greater focus on the experiences of older people and their families, and more nuanced contextual and evidence-based responses.


Divergent Hemogen genes of teleosts and mammals share conserved roles in erythropoiesis: analysis using transgenic and mutant zebrafish.
Hemogen is a vertebrate transcription factor that performs important functions in erythropoiesis and testicular development and may contribute to neoplasia. Here we identify zebrafish Hemogen and show that it is considerably smaller (∼22 kDa) than its human ortholog (∼55 kDa), a striking difference that is explained by an underlying modular structure. We demonstrate that Hemogens are largely composed of 21-25 amino acid repeats, some of which may function as transactivation domains (TADs). Hemogen expression in embryonic and adult zebrafish is detected in hematopoietic, renal, neural and gonadal tissues. Using Tol2- and CRISPR/Cas9-generated transgenic zebrafish, we show that Hemogen expression is controlled by two Gata1-dependent regulatory sequences that act alone and together to control spatial and temporal expression during development. Partial depletion of Hemogen in embryos by morpholino knockdown reduces the number of erythrocytes in circulation. CRISPR/Cas9-generated zebrafish lines containing either a frameshift mutation or an in-frame deletion in a putative, C-terminal TAD display anemia and embryonic tail defects. This work expands our understanding of Hemogen and provides mutant zebrafish lines for future study of the mechanism of this important transcription factor.


E-Beam Irradiation for Improving the Microbiological Quality of Smoked Duck Meat with Minimum Effects on Physicochemical Properties During Storage.
This study was performed to evaluate the effect of different doses (0, 1.5, 3, and 4.5 kGy) of e-beam irradiation on the quality parameters (pH, Hunter's parameter, and heme pigment) and stability qualifiers (peroxide value [POV], thiobarbituric acid reactive substances [TBARSs], and total volatile basic nitrogen [TVBN]) of smoked duck meat during 40 d of storage under vacuum packaging at 4 °C. The initial populations of total bacteria (7.81 log CFU/g) and coliforms (5.68 log CFU/g) were reduced by approximately 2 to 5 log cycles with respect to irradiation doses. The results showed that pH, myoglobin, met-myoglobin, L* , a* , and b* showed significant differences with respect to different doses and storage intervals; a* and b* did not vary significantly because of storage. Higher pH was found in samples treated with 4.5 kGy at 40 d, while the minimum was observed in nonirradiated samples at day 0 of storage. Higher POV (2.31 ± 0.03 meq peroxide/kg) and TBARS (5.24 ± 0.03 mg MDA/kg) values were found in 4.5 kGy-treated smoked meat at 40 d and the lowest was reported in 0 kGy-treated meat at initiation of storage (0 d). However, irradiation suppressed TVBN during storage and higher TVBN (7.09 ± 0.32 mg/100 mL) was found in duck meat treated with 0 kGy at 40 d. The electronic nose (e-nose) effectively distinguished flavor profiles during the different storage intervals. The results showed that different sensory attributes did not vary significantly with respect to the dose of irradiation. We conclude that low dose of e-beam irradiation and vacuum packaging is beneficial for safety and shelf life extension without affecting the sensory characteristics of smoked duck meat.


Intramedullary Fibular Fixation in One-Stage Ankle Fracture Surgery With Soft Tissue Damage: A Study of 19 Cases.
This study investigates the efficacy of one-stage surgical intramedullary fibular fixation in managing ankle fractures with associated soft tissue damage. Ankle fractures, often encountered, can lead to complications when coupled with soft tissue injury. Traditional plate and screw fixation can exacerbate infection risks and reduce wound healing. To address this, a minimally invasive approach employing intramedullary fixation of the fibula has been proposed. This retrospective analysis, conducted between 2019 and 2021, explores cases of intramedullary fibular fixation for ankle fractures with stage 2-3 soft tissue injuries. A total of 19 patients were included in the study. The procedure involved either ulna intramedullary nails or locking screws. Results indicate that the approach led to successful union (100%), one superficial infection (5.26%), and no complication was observed. While limitations include the retrospective nature and small sample size, this study contributes valuable insights into the use of intramedullary fibular fixation in one-stage surgery for ankle fractures with concurrent soft tissue damage.


Observations on seminal vesicle dynamics in an in vivo rat model.
To gain understanding of the seminal vesicle as a muscular organ, seminal vesicle compliance and contractile properties were quantified with an in vivo, microsurgical rat model. Microsurgical dissection was performed on anesthetized rats to enable simultaneous organ filling and monitoring of intraluminal pressures. The reliability and reproducibility of post-ganglionic hypogastric nerve-induced ipsilateral (4 rats) and bilateral (5 rats) seminal vesicle contractile responses were assessed during repeated nerve stimulation. Seminal vesicle resting compliance was assessed during a constant saline infusion (10 rats). Functional performance curves were obtained at fixed fill-volumes by measuring organ contraction after nerve stimulation (4 rats). A reproducible seminal vesicle contractile response was obtained with a nerve stimulation interval > 15 minutes. Bilateral seminal vesicle responses were observed with unilateral nerve stimulation. The resting organ compliance curve with saline filling exhibited a characteristic, triphasic response. Functional performance studies revealed that contractile performance improves as the fill-volume increases until the distensibility limit of the organ is reached. A reliable, in vivo, rat model of seminal vesicle organ compliance and contractility is described. The seminal vesicle is a highly contractile, compliant smooth muscular organ with dynamic properties analogous to that of the urinary bladder. This experimental system may allow for the investigation of pharmacologic and other physiological influences on in vivo organ activity.


Introducing Human Mandible Identification [(hu)MANid]: A Free, Web-Based GUI to Classify Human Mandibles.
Statistical programs have revolutionized the way in which forensic anthropologists conduct casework by allowing practitioners to use computationally complex analytics at the click of a button. Importantly, the products of these statistical programs are reproducible and contain measures of error or uncertainty, thereby strengthening conclusions. This paper is an introduction to (hu)MANid, a free, web-based application that uses linear and mixture discriminant function analyses to classify human mandibles into one of many worldwide and/or periodic reference groups. The mechanics, development, and use of the application will be discussed. Further, the program was tested against other software to compare model performances and classifications. Total correct classifications among the test cases and programs were identical. Ten mandibles were tested using both statistical procedures. Mixture discriminant analysis improved classification by an average of 9.3% and correctly identified three more mandibles than LDA. Therefore, we believe (hu)MANid will be an asset to the anthropological community.


A cystic fibrosis patient homozygous for the nonsense mutation R553X.
A cystic fibrosis patient homozygous for the nonsense mutation R553X was identified by mutation screening and the genotype confirmed by DNA sequencing. This patient, the only one described to date who is homozygous for this stop codon in exon 11 of the CFTR gene, is moderately severely affected. Clinical and molecular findings are presented.


By-catch of grey seals (Halichoerus grypus) in Baltic fisheries--a Bayesian analysis of interview survey.
Baltic seals are recovering after a population decline. The increasing seal stocks cause notable damage to fisheries in the Baltic Sea, with an unknown number of seals drowning in fishing gear every year. Thus, sustainable seal management requires updated knowledge of the by-catch of seals--the number of specimens that die in fishing gear. We analyse the by-catch of grey seals (Halichoerus grypus) in Finland, Sweden, and Estonia in 2012. We collect data with interviews (35 in Finland, 54 in Sweden, and 72 in Estonia) and analyse them with a hierarchical Bayesian model. The model accounts for variability in seal abundance, seal mortality and fishing effort in different sub-areas of the Baltic Sea and allows us to predict the by-catch in areas where interview data was not available. We provide a detailed description of the survey design and interview methods, and discuss different factors affecting fishermen's motivation to report by-catch and how this may affect the results. Our analysis shows that the total yearly by-catch by trap and gill nets in Finland, Sweden and Estonia is, with 90% probability, more than 1240 but less than 2860; and the posterior median and mean of the total by-catch are 1550 and 1880 seals, respectively. Trap nets make about 88% of the total by-catch. However, results also indicate that in one of the sub-areas of this study, fishermen may have underreported their by-catch. Taking the possible underreporting into account the posterior mean of the total by-catch is between 2180 and 2380. The by-catch in our study area is likely to represent at least 90% of the total yearly grey seal by-catch in the Baltic Sea.


BiFC for protein-protein interactions and protein topology: discussing an integrative approach for an old technique.
BiFC (Bimolecular Fluorescence Complementation) is one of the most widely used techniques to study protein-protein interactions as well as protein topology in living cells. This method allows the visualization of protein interactions or the analysis of their topology in the cell compartments where the proteins belong, without changing their chemical properties, as often occurs after mixing the content of different cellular compartments in cell extracts. Several laboratories use this method because it is relatively easy to perform; however, sometimes a positive protein-protein interaction BiFC signal (i.e., reconstitution of fluorescence of interacting protein pairs) does not necessarily mean that the tested proteins are actually interacting in vivo in a specific way. Here we describe the BiFC approach for assessing protein-protein interactions and for establishing protein topology and we discuss how to best perform this method to avoid false positive results when studying protein interactions in plant cells.


MIG1-dependent and MIG1-independent regulation of GAL gene expression in Saccharomyces cerevisiae: role of Imp2p.
Imp2p (Yil154c) is a transcriptional activator involved in glucose derepression of the maltose, galactose and raffinose utilization pathways and in resistance to thermal, oxidative or osmotic stress. We analysed the role of Imp2 in the regulation of GAL genes. Imp2 was shown to have a positive effect on glucose derepression of Leloir pathway genes and their activator gene GAL4. The effect of Imp2 on galactose metabolism was shown to be partially dependent on Mig1p. The Mig1-independent role depends on Nrg1p. However, disruption of both MIG1 and NRG1 only partially relieves the glucose repression of GAL genes in the Deltaimp2 mutant, indicating that Imp2 must also have other function(s). Moreover, the interaction between IMP2 and GAL6/BLH1, a recently isolated gene involved in the regulation of GAL genes that shares with Imp2 the ability to protect cells from the glycopeptide bleomycin, was also analysed. The results suggest a major role of Imp2 in a GAL6-independent pathway.


The Critical Role Played by the Catalytic Moiety in the Early-Time Photodynamics of Hydrogen-Generating Bimetallic Photocatalysts.
The effect of the catalytic moiety on the early-time photodynamics of Ru/M (M=Pt or Pd) bimetallic photocatalysts is studied by ultrafast transient absorption spectroscopy. In comparison to the Ru/Pd photocatalyst described earlier, the Ru/Pt analogue shows complex excited-state dynamics with three distinct kinetic components ranging from sub-ps to 10(2) ps, requiring a more sophisticated photophysical model than that developed earlier for the Ru/Pd complex. In the Pu/Pt photocatalyst, an additional lower-lying excited state is proposed to quench the hot higher-lying triplet metal-to-ligand charge-transfer states. Furthermore, a strong excitation wavelength dependence on the population of excited states is observed for both the Ru/Pt and Ru/Pd complexes, indicating a non-equilibrated distribution even on the 10(2) ps timescale. These insights shed light on the significant impact of the catalytic moiety on the fundamental early-time photophysics of Ru-based photocatalysts.


Previous task experience in metacognitive experience.
This study examined the sources of differences in the correlations among metacognitive experiences and between metacognitive experiences with performance. Task experience was treated as the source of differences. 70 Japanese undergraduate students solved two tasks, one similar to those experienced (experienced task) and the other one barely experienced previously (task not experienced). Correlations among metacognitive experiences showed outcomes of the experienced task supported findings from Efklides' laboratory, and those from a task not experienced were consistent with those of Akama and Yamauchi. The nature of metacognitive experiences in problem-solving is discussed.


Is selenium deficiency an important risk factor for chronic graft nephropathy? A pilot study.
Lipid peroxidation by free radicals is a key step in the development of atherosclerosis. Chronic graft nephropathy (CGN) is a common cause of allograft failure and shares many histologic features with atherosclerosis. Although hyperlipidemia is a common finding in renal transplant recipients, not all patients develop CGN. We hypothesized that the degree of damage sustained is related to recipient antioxidant status and that only those who are antioxidant deficient succumb to free radical attack and develop CGN. We aimed to determine the antioxidant profiles of patients with biopsy-proven CGN and to compare their profiles to transplant patients with good renal function. Plasma selenium and vitamin A and E concentrations were measured in 10 patients with CGN and 10 contemporaneous, sex-matched patients with normal renal graft function, who received the same immunosuppressive therapy. Patients with CGN had significantly lower plasma selenium concentrations compared with those with normal renal allograft function (P<0.05). There were no significant differences in plasma vitamin A or E concentrations between the two groups. There was no difference in the prevalence of any of the immunologic or nonimmunologic risk factors: human leukocyte antigen mismatches, panel-reactive antibody status, number of rejection episodes, cold ischemic time, hyperlipidemia, hypertension, diabetes, and cytomegalovirus infection between the two groups. Patients with CGN have evidence of selenium deficiency, suggesting that impaired antioxidant status may contribute to the development of CGN.


Targeting needs of the underserved: current programs in Tennessee.
Health care needs of indigents are a major force driving the need for health care reform in the U.S. Governor McWherter of Tennessee and his Administration have highlighted the need for available, affordable, and accessible health care services for all Tennesseans and especially for the medically indigent. This paper describes programs developed and implemented during the McWherter administration. These programs include community health agencies, placement of health care providers in underserved areas, increasing the number of citizens served by the Medicaid program, coordination of high-risk prenatal and child care to year one, and special demonstration projects in various African-American communities. Major reform is needed at the national level. In the meantime, the McWherter Administration will continue to develop new and innovative ways to increase the availability, accessibility, and affordability of health services in Tennessee.


Neuropathy with predominant small fiber involvement associated with abnormal anti-MAG titer.
We describe a patient with painful neuropathy associated with an abnormal anti-MAG titer in which predominant involvement of intra-epidermal nerve fiber was documented. Electrophysiological studies revealed low-borderline amplitude of sensory and compound motor action potentials registering from lower limbs and normal conduction velocity. Sural nerve biopsy disclosed only a slight loss of myelinated fiber. Skin biopsy performed at the proximal thigh and at the distal leg was consistent with a non-length-dependent small fiber neuropathy. It is likely that in this case anti-MAG antibodies played a role in the pathogenesis of small fiber neuropathy.


Fecal microbiome and volatile organic compound metabolome in obese humans with nonalcoholic fatty liver disease.
The histopathology of nonalcoholic fatty liver disease (NAFLD) is similar to that of alcoholic liver disease. Colonic bacteria are a source of many metabolic products, including ethanol and other volatile organic compounds (VOC) that may have toxic effects on the human host after intestinal absorption and delivery to the liver via the portal vein. Recent data suggest that the composition of the gut microbiota in obese human beings is different from that of healthy-weight individuals. The aim of this study was to compare the colonic microbiome and VOC metabolome of obese NAFLD patients (n = 30) with healthy controls (n = 30). Multitag pyrosequencing was used to characterize the fecal microbiota. Fecal VOC profiles were measured by gas chromatography-mass spectrometry. There were statistically significant differences in liver biochemistry and metabolic parameters in NAFLD. Deep sequencing of the fecal microbiome revealed over-representation of Lactobacillus species and selected members of phylum Firmicutes (Lachnospiraceae; genera, Dorea, Robinsoniella, and Roseburia) in NAFLD patients, which was statistically significant. One member of phylum Firmicutes was under-represented significantly in the fecal microbiome of NAFLD patients (Ruminococcaceae; genus, Oscillibacter). Fecal VOC profiles of the 2 patient groups were different, with a significant increase in fecal ester compounds observed in NAFLD patients. A significant increase in fecal ester VOC is associated with compositional shifts in the microbiome of obese NAFLD patients. These novel bacterial metabolomic and metagenomic factors are implicated in the etiology and complications of obesity.


Adjunctive pharmacologic treatment for elective stenting of the extracranial carotid arteries.
Endovascular stenting of the extracranial carotid arteries is a viable treatment option to carotid endarterectomy in selected patients. Patients undergoing this procedure must be treated with aspirin 325 mg at least 24 hours prior to the procedure and clopidogrel 75 mg oral, three to five days prior to the procedure (or 300 mg at least six hours prior to stenting). During the intervention, heparin is given to maintain an activated clotting time of at least 300 seconds. Although there are theoretical advantages on the use of a platelet IIb/IIIa inhibitor, their routine use during elective carotid stenting is not recommended until their clinical benefits have been clearly demonstrated in this patient population. Hemodynamic instability during balloon inflation and stent deployment should be treated with intravenous fluids, atropine, and an alpha agonist such as neosynephrine. All the oral antihypertensive must be discontinued after the procedure and if there is persistence of hypotension making discontinuation of neosynephrine difficult, an oral alpha agonist such as midodrine (2.5 to 5 mg two to three times daily) is helpful. In the majority of patients this medication can be tapered off three to five days following stenting.


Optimization of ultrasonic-assisted extraction of phenolic antioxidants from Malus baccata (Linn.) Borkh. using response surface methodology.
In this study, the optimum extraction conditions for maximum recovery of the content of total phenolics (TPC) and total antioxidant abilities were analyzed for Malus baccata (Linn.) Borkh. using response surface methodology. The effects of ethanol percentage (X1 ,%), ultrasonic power (X2 , W) and extraction temperature (X3 , °C) on the total phenolic content (Y1 ) and antioxidant ability (Y2 ) were evaluated. A second-order polynomial model produced a satisfactory fitting of the experimental data with regard to total phenolic content (R(2) = 0.9942, P < 0.0001) and antioxidant ability (R(2) = 0.9966, P < 0.0001). The optimized conditions were ethanol concentration of 61.0%, ultrasonic power of 308.6 W, extraction temperature of 51.1°C for TPC and 60.5%, 311.4 W, 51.6°C for antioxidant ability, the predicted values agreed well with the experimental values. Results implied that the major phenolic compounds in obtained extracts as chlorogenic acid, quercetin-3-gal/glu, quercetin-3-xyl/ara, phloretin-2-xyloside, quercetin-3- rhamnoside, and phloridzin.


Effects of a procaine preparation (Gerovital H3) in hospitalized geriatric patients: a double-blind study.
The effects of Gerovital H3 (a specially stabilized form of procaine hydrochloride) on geriatric psychiatric patients were assessed in a double-blind study at Bronx State Hospital. The mean age of the subjects was 73 years and the average rating for the severity of organic symptoms was "moderate." During the first six weeks of study, the patients were each given a 5-ml injection of either Gerovital or placebo (saline) intramuscularly three times a week. This dosage was doubled to 10 ml per injection during the second six weeks. Nine Gerovital and 10 control subjects completed the first six weeks; and 6 Gerovital and 7 control subjects completed the entire 12-week study. Objective rating scales were used to evaluate patients on measures of interpersonal functioning, cognitive ability, psychiatric symptoms, and urine and blood chemical findings. All subjects were assessed before treatment and at six weeks and twelve weeks of the study. Side effects were recorded at two-week intervals. On most measures the variability between subjects was quite large, whereas differences between average scores for the two groups usually were small The few significant differences showed no systematic pattern and would be expected to occur by chance alone when so many statistical comparisons are made. The overall results of this double-blind study strongly indicated that, among these hospitalized geriatric patients with organic symptoms, Gerovital H3 had no ameliorative effect on either psychologic or physiologic functioning.


Stereoselective preparation of key intermediates for the synthesis of iso-, neuro- and phyto-prostane family members: inaugural asymmetric synthesis of 17-E2c-dihomo- and 17-F2c-dihomo-isoprostanes.
A practical methodology for the synthesis of key intermediates for isoprostane, neuroprostane and dihomo-isoprostane preparation has been described. The key strategy involved a three stage C-12 stereocenter inversion of the configuration of a Corey lactone, commercially available in an enantiopure form. The key intermediate was then used to prepare 17-E2c-dihomo-isoprostane and 17-F2c-dihomo-isoprostane.


Chicken Egg Shell Membrane Associated Proteins and Peptides.
Egg shells are poultry industry byproducts with potential for use in various biological and agricultural applications. We have been interested in the membranes underlying the calcareous shell as a feed supplement, which showed potential to improve immunity and performance of post hatch poultry. Therefore, to determine their protein and peptide profiles, we extracted the egg shell membranes (ESM) from fresh unfertilized eggs with methanol and guanidine hydrochloride (GdHCl) to obtain soluble proteins for analysis by mass spectrometry. The methanol extract was subjected to matrix-assisted laser desorption ionization (MALDI), electrospray ionization (ESI), high-performance reverse phase liquid chromatographic separation (HPLC), and tandem mass spectrometry (MS/MS) to determine its peptide and protein profiles. The GdHCl extract was subjected to ESI-HPLC-MS/MS following trypsin digestion of reduced/alkylated proteins. Nine proteins from the methanol extract and >275 proteins from the GdHCl extract were tentatively identified. The results suggested the presence of several abundant proteins from egg whites, such as ovoalbumin, ovotransferrin, and lysozyme as well as many others associated with antimicrobial, biomechanical, cytoskeletal organizational, cell signaling, and enzyme activities. Collagens, keratin, agrin, and laminin were some of the structural proteins present in the ESM. The methanol-soluble fraction contained several clusterin peptides and defensins, particularly, two isoforms of gallin. The ratios of the two isoforms of gallin differed between the membranes obtained from brown and white eggs. The high abundance of several antimicrobial, immunomodulatory, and other bioactive proteins in the ESM along with its potential to entrap various microbes and antigens may make it a suitable vehicle for oral immunization of post hatch poultry and improve their disease resistance.


Multiparametric deoxyribonucleic acid and cell cycle analysis of breast carcinomas by flow cytometry. Clinicopathologic correlations.
Using intact ethanol-fixed cytokeratin monoclonal (CAM 5.2) and propidium iodide dual-stained cells, we have performed two-color multiparametric flow cytometric (FCM) DNA analysis and S-phase fraction (SPF) determination on 165 mechanically dissociated breast carcinomas. Sixty-seven patients were axillary node positive, 33 patients node negative; 59 had biopsy only and in 8, FCM was performed on tissue from metastatic lesions. Overall, 62% of the tumors contained aneuploid cell populations. Abnormal cellular DNA content (aneuploidy) was significantly correlated with high nuclear grade (p less than 0.001), lack of estrogen receptors (p less than 0.001), presence of vascular invasion (p less than 0.04), high histologic grade (p less than 0.04), and tumor size (p less than 0.03) but not with patient age (p greater than 0.07) or axillary node status (p greater than 0.50). SPF values derived from ungated histograms had a positively skewed frequency distribution (range 2 to 30%, N = 152) with an overall median of 11% (diploid, 8.9%; aneuploid, 15.7%). Higher SPF values were significantly correlated with aneuploidy (p less than 0.001), presence of necrosis (p less than 0.001), lack of estrogen receptor (p less than 0.0001), high nuclear grade (p less than 0.001), vascular invasion (p less than 0.003), tumor size (p less than 0.006), and high histologic grade (p less than .004) but not the presence of lymph node metastases (p greater than 0.56). Mean SPF values were significantly higher when calculated from cytokeratin gated DNA histograms (14.1% versus 11.5%, p less than 0.001), probably due to exclusion of contaminating stromal/inflammatory cells; and significantly lower when calculated from debris subtracted histograms (7.8% versus 11.4%). Cytokeratin gated and debris subtracted SPF values both had a greater degree of correlation than ungated values with clinicopathologic factors of known prognostic significance.(ABSTRACT TRUNCATED AT 250 WORDS)


A case of synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome with isolated lesions of the thoracic spine.
We report a case of isolated lesions of the thoracic spine attributed to synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. A 55-year-old woman who suffered from 6 months of back pain had vertebral osteomyelitis on magnetic resonance imaging (MRI). There were no laboratory findings suggestive of infection, malignancy, or autoimmune disease. Radiography, computed tomography (CT), and MRI of the thoracic spine showed mixed lesions of sclerosis and erosion, whereas bone scintigraphy did not show accumulation at any site except the thoracic spine. No lesions in the anterior chest wall or sacroiliac joints were apparent from CT and MRI. No lesions other than at the thoracic spine were observed. As the isolated lesions of the thoracic spine were considered not to have resulted from infection, malignancy, or autoimmune disease, the patient was referred to our department for differential diagnosis. Given that isolated sterile hyperostosis/osteitis among adults is included in the modified diagnostic criteria for SAPHO syndrome, we suspected that the mixed lesions of sclerosis and erosion of the thoracic spine in this case may reflect SAPHO syndrome with chronic non-bacterial osteitis (CNO) of the thoracic spine. Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) was initiated and led to alleviation of her back pain, although the thoracic spine lesions remained on the 6-month MRI. Based on the CNO of the thoracic spine and the rapid response to NSAIDs, the final diagnosis was SAPHO syndrome with isolated lesions of the thoracic spine.


Differentiating medulloblastoma in adults.
We present two cases of medulloblastoma in adults patients showing extensive astrocytic differentiation. In one case, there was synchronous oligodendroglial differentiation, both changes appearing after treatment with radiotherapy. The possible role of radiotherapy in the differentiation is discussed.


Changes in clinical research in anaesthesia and intensive care from 1974-2004.
The purpose was to identify how the quality of anaesthesia research has improved from articles published in Anaesthesia and Intensive Care over 25 years. Original papers were included during the periods 1974-1978 and 2000-2004. Each article was classified according to principal research designs and the two five-year periods were compared. All interventional trials were evaluated according to the following a priori criteria: author number; ethics approval; informed consent; competing financial interest; eligibility criteria; sample size calculation; method of randomization; patients accounted for; blind assessment of outcome; adverse outcomes; statistical method stated; type I error; type II error; and anaesthetic department of origin. Comparisons of above criteria were made between the two groups using chi-square test or Fischer's exact test. Two-hundred-and-ninety-two articles were reviewed in 1974-1978 and 529 articles were reviewed in 2000-2004. Animal/laboratory articles decreased from 17.47% to 12.28% (P=0.05). Review articles decreased from 34.35% to 10.4% (P<0.0001). Descriptive trials increased from 28.4% to 52.72% (P<0.0001). Interventional trials increased from 18.84% to 22.31% (P=0.269). Uncontrolled clinical trials decreased from 27.27% to 12.71%, non-randomized controlled trials decreased from 50.91% to 7.63%, and randomized controlled trials increased from 21.82% to 79.66% (P<0.0001). All interventional trials criteria improved and were statistically significant except competing financial interest, method of randomization, patients accounted for; and type II error The quality of anaesthetic research has improved in Anaesthesia and Intensive Care over the past 30 years. However; there is still room for improvement.


Interleukin-6 Treatment Results in GLUT4 Translocation and AMPK Phosphorylation in Neuronal SH-SY5Y Cells.
Interleukin-6 (IL-6) is a pleiotropic cytokine that can be released from the brain during prolonged exercise. In peripheral tissues, exercise induced IL-6 can result in GLUT4 translocation and increased glucose uptake through AMPK activation. GLUT4 is expressed in the brain and can be recruited to axonal plasma membranes with neuronal activity through AMPK activation. The aim of this study is to examine if IL-6 treatment: (1) results in AMPK activation in neuronal cells, (2) increases the activation of proteins involved in GLUT4 translocation, and (3) increases neuronal glucose uptake. Retinoic acid was used to differentiate SH-SY5Y neuronal cells. Treatment with 100 nM of insulin increased the phosphorylation of Akt and AS160 (p < 0.05). Treatment with 20 ng/mL of IL-6 resulted in the phosphorylation of STAT3 at Tyr705 (p ≤ 0.05) as well as AS160 (p < 0.05). Fluorescent Glut4GFP imaging revealed treatment with 20ng/mL of IL-6 resulted in a significant mobilization towards the plasma membrane after 5 min until 30 min. There was no difference in GLUT4 mobilization between the insulin and IL-6 treated groups. Importantly, IL-6 treatment increased glucose uptake. Our findings demonstrate that IL-6 and insulin can phosphorylate AS160 via different signaling pathways (AMPK and PI3K/Akt, respectively) and promote GLUT4 translocation towards the neuronal plasma membrane, resulting in increased neuronal glucose uptake in SH-SY5Y cells.


[Effects of methyl mercuric chloride on growth inhibition and the cell membrane of Tetrahymena].
The effects of methylmercuric chloride (MMC) on the growth and cell membrane of the ciliate protozoan Tetrahymena pyriformis GL were studied. The compositions of fatty acids in the cell membrane lipids, which were extracted from cells cultured in medium containing MMC at 30 and 20 degrees C, were examined. As compared with control cells, 30 degrees C-cells were richer in saturated fatty acids than 20 degrees C-cell, indicating that the cell membrane of 30 degrees C-cells was rigid and that that of 20 degrees C-cells was mobile. When MMC was added to the culture media, the amount of unsaturated fatty acid in the cell membrane tended to decrease, resulting in an increase of rigidity of the cell membrane. When ergosterol was added to the media, the cell membrane became more rigid, and lipids were richer in saturated fatty acids. Ergosterol contributed to reduce the composition change due to addition of MMC to the media.


Bacterial and fungal ventilator associated pneumonia in critically ill COVID-19 patients during the second wave.
The pandemic of coronavirus disease (COVID-19) has caused huge number of patients admitted to intensive care units (ICUs) in a critical need to mechanical ventilation. Ventilator associated pneumonia (VAP) has been noticed as a common complication in these patients with unfavorable outcomes. The current study aimed to assess bacterial and fungal VAP in COVID-19 patients admitted to ICUs during the second wave and to identify the possible risk factors. Respiratory samples were collected from 197 critically ill COVID-19 patients under mechanical ventilation. Bacterial and fungal superinfections were diagnosed by microbiological cultures with subsequent antimicrobial susceptibility testing of the isolates using available kits. All specimens 197/197 (100%) were positive for bacterial infections, while fungal elements were detected in 134/197 (68%) of specimens. The most frequently isolated bacteria were pan drug resistant (PDR) Klebsiella pneumoniae (41.1%), followed by multi drug resistant (MDR) Acinetobacter baumannii (27.4%). On the other hand, Candida species represented the most frequently isolated fungi (75.4%) followed by molds including Aspergillus (16.4%) and Mucor (8.2%) species. Possible risk factors for fungal VAP included underlying diabetes mellitus (95% confidence interval [CI] 1.09-3.31; p = 0.02), chest disease (95% CI 1.01-3.32; p = 0.05), hypothyroidism (95% CI 1.01-4.78; p = 0.05), and longer duration of mechanical ventilation (p < 0.001). Furthermore, all patients 134/134 (100%) who developed fungal VAP, were already under treatment with corticosteroids and Tocilizumab. Bacterial and fungal VAP in critically ill COVID-19 patients is a serious problem in the current pandemic. Urgent and strategic steps to keep it under control are compulsory.


Association of Low Serum Bilirubin Concentrations and Promoter Variations in the UGT1A1 and HMOX1 Genes with Type 2 Diabetes Mellitus in the Czech Population.
Bilirubin has potent biological beneficial effects, protecting against atherosclerosis, obesity, and metabolic syndrome. The aim of this study was to assess serum bilirubin concentrations and (TA)n and (GT)n microsatellite variations in the promoter regions of the UGT1A1 and HMOX1 genes, respectively, in patients with type 2 diabetes mellitus (T2DM). The study was carried out in 220 patients with T2DM and 231 healthy control subjects, in whom standard biochemical tests were performed. The (TA)n and (GT)n dinucleotide variations were determined by means of fragment (size-based) analysis using an automated capillary DNA sequencer. Compared to controls, both male and female patients with T2DM had lower serum bilirubin concentrations (9.9 vs. 12.9 μmol/L, and 9.0 vs. 10.6 μmol/L, in men and women, respectively, p < 0.001). Phenotypic Gilbert syndrome was much less prevalent in T2DM patients, as was the frequency of the (TA)7/7UGT1A1 genotype in male T2DM patients. (GT)nHMOX1 genetic variations did not differ between diabetic patients and controls. Our results demonstrate that the manifestation of T2DM is associated with lower serum bilirubin concentrations. Consumption of bilirubin due to increased oxidative stress associated with T2DM seems to be the main explanation, although (TA)n repeat variations in UGT1A1 partially contribute to this phenomenon.


[Molecular analysis on the capsid gene and 3' untranslation region of three Getah viruses isolated in China].
To compare the molecular characteristics of the Capsid gene and 3' untranslation region (3'UTR) of Getah viruses (GETV) isolated in Hainan Province and Hebei Province of China,the viral RNAs were extracted from M1(Hainan), HB0215-3 and HB0234(Hebei) virus stocks. Capsid gene segments and 3' UTR segments from three strains of Chinese GETV were obtained by RT-PCR and then sequenced. The obtained nucleotide sequences were analyzed using the Clustal X(1.8), DNASTAR, MAGA3.1 programs. The full-length Capsid gene of the 3 strains of Chinese GETV were comprised of 801, 804 and 804 nucleotides each, encoding the protein of 267,268 and 268 amino acids each. Sequencing of Capsid gene fragments showed that two strains of Hebei isolates were identical and had homology of 97.6% at nucleotide level and 97.8% at amino acids level with M1. Their homologies when compared with strains isolated from other countries were also high at nucleotide levels (95.4%-99.6%). The 3'UTR from the three strains were comprised of 411, 401 and 401 nucleotides each, and had found specific deletion of 10 nt at position 44-54 and two specific nucleotide sites that was T at position 64 and C at position 148. GETV isolated in China presented relation of the year of virus isolation with the phylogenesis distance when compared with the other GETV strains and comprised a genetically highly conserved group.


Sub-1min separation in sequential injection chromatography for determination of synthetic water-soluble dyes in pharmaceutical formulation.
Sequential Injection Chromatography (SIC) evolved from fast and automated non-separation Sequential Injection Analysis (SIA) into chromatographic separation method for multi-element analysis. However, the speed of the measurement (sample throughput) is due to chromatography significantly reduced. In this paper, a sub-1min separation using medium polar cyano monolithic column (5mm×4.6mm) resulted in fast and green separation with sample throughput comparable with non-separation flow methods The separation of three synthetic water-soluble dyes (sunset yellow FCF, carmoisine and green S) was in a gradient elution mode (0.02% ammonium acetate, pH 6.7 - water) with flow rate of 3.0mLmin-1 corresponding with sample throughput of 30h-1. Spectrophotometric detection wavelengths were set to 480, 516 and 630nm and 10Hz data collection rate. The performance of the separation was described and discussed (peak capacities 3.48-7.67, peak symmetries 1.72-1.84 and resolutions 1.42-1.88). The method was represented by validation parameters: LODs of 0.15-0.35mgL-1, LOQs of 0.50-1.25mgL-1, calibration ranges 0.50-150.00mgL-1 (r>0.998) and repeatability at 10.0mgL-1 of RSD≤0.98% (n=6). The method was used for determination of the dyes in "forest berries" colored pharmaceutical cough-cold formulation. The sample matrix - pharmaceuticals and excipients were not interfering with vis determination because of no retention in the separation column and colorless nature. The results proved the concept of fast and green chromatography approach using very short medium polar monolithic column in SIC.


Prevalence of arrhythmias and conduction disturbances in large population-based samples of children.
The aim of our study is to provide data on the prevalence of disturbances of rhythm in the general population of children. Accurate estimates of true prevalence of such disturbances of rhythm from large samples are mandatory if we are to interpret properly electrocardiographic abnormalities. We analysed prevalence of disturbances of rhythm in a population of 152,322, comprised of 71,855 elementary school students, 36,692 males and 35,163 females, aged from 5 to 6 years, and 80,467 students of junior high school, 41,842 males and 38,625 females, aged from 12 to 13 years. We analysed the prevalence of premature atrial and ventricular contractions, first, second and third degree atrioventricular block, incomplete and complete right bundle branch block, Wolff-Parkinson-White syndrome, and prolongation of the QT interval. The prevalence of disturbances of rhythm in total rose with age, being found in 1.25% of elementary school students and 2.32% of junior high school students, and was higher in males than females, at 2.00% as opposed to 1.38%, both values being statistically significant at a level of less than 0.0001. Prevalences of all types of rhythmic disturbances were higher in junior high school students than elementary school students (p < 0.0001). Premature atrial and ventricular contractions and prolongation of the QT interval were higher in female than male students, at percentages of 0.089, 0.497, and 0.02 for males, and 0.123, 0.534 and 0.027 in females (p < 0.0001). In contrast, incomplete and complete right bundle branch blocks were higher in males than females, at 0.983% and 0.083% in males versus 0.410% and 0.161% in females (p < 0.0001). Disturbances of rhythm increased with age, and conduction disturbances were higher in male students than female, although premature atrial and ventricular contractions and prolongation of the QT interval were more frequent in female. These data may be useful for future comparative studies of disturbance of rhythm in children.


Quantifying the relative contribution of hydrogen bonding and hydrophobic environments, and coordinating groups, in the zinc(II)-water acidity by synthetic modelling chemistry.
Ligands derived from the tripodal N4 ligand tris(pyridylmethyl)amine ((pyCH2)3N, tpa) of general formula (6-RNHpyCH2)nN(CH2py)(3-n)(R = H, n= 1-3 L(1-3); R = neopentyl, n= 1-3 L'(1-3)) were used to elucidate and quantify the magnitude of the effects exerted by hydrogen bonding and hydrophobic environments in the zinc-water acidity of their complexes. The pKa of the zinc-bound water molecule of [(L(1-3))Zn(OH2)]2+ and [(L'(1-3))Zn(OH2)]2+ 1'-3' was determined by potentiometric pH titrations in water (1-3) or water-ethanol (1:1) (1'-3'). The zinc(II) water acidity gradually increases as the number of -NH2 hydrogen bonding groups adjacent to the water molecule increases. Thus, the zinc-bound water of [(L3)Zn(OH2)]2+ and [(tpa)Zn(OH2)]2+ deprotonate with pKa values of 6.0 and 8.0, respectively. The pKa of the water molecule, however, is only raised from 8.0 in [(tpa)Zn(OH2)]2+ to 9.1 in [(bpg)Zn(OH2)]+ (bpa =(pyCH2)2N(CH2COO-)). Moreover, the acidity of the zinc-bound water of several of the five-coordinate zinc(II) complexes with the hydrogen bonding groups is greater than that of four-coordinate [((12)aneN3)Zn(OH2)]2+ (pKa = 7.0). This result shows that the magnitude of the effect exerted by the hydrogen bonding groups can be larger than that induced by changing one neutral by one anionic ligand, and/or even by changing the coordination number of the zinc(II) centre. The X-ray structure of [(L'2)Zn(OH)]ClO4 2' and [(L'3)Zn(OH)]ClO4.CH3CN 3'.CH3CN is reported, and show the neopentylamino groups forming N-H...O hydrogen bonds with the zinc-bound hydroxide. Although, which have hydrogen bonding and hydrophobic groups, have a zinc-bound water more acidic than [(tpa)Zn(OH2)]2+, their pKa is not always lower than that of 1-3. This result suggests that a hydrogen bonding microenvironment may be more effective than a hydrophobic one to increase the zinc-water acidity.


Chemopreventive effects of Panax notoginseng and its major constituents on SW480 human colorectal cancer cells.
In this study, we evaluated the effects of Panax notoginseng root extract (NGRE) and its major constituents on SW480 human colorectal cancer cells. We used high performance liquid chromatography to determine the contents of major saponins in NGRE. The anti-proliferative effects were evaluated by the cell counting method, and concentration-related anti-proliferative effects were observed. At 1.0 mg/ml, NGRE inhibited cell growth by 85.8% (P<0.01), probably linked to the higher concentration of ginsenosides Rb1 and Rg1. The pharmacologic activities of notoginsenoside R1 and ginsenosides Rg1 and Rb1 on the cells were antiproliferative. We tested the effects of NGRE on DNA synthesis by measuring [3H]-thymidine incorporation. NGRE induced cell apoptosis at 0.5 and 1 mg/ml. Two-day treatment with 300 microM of notoginsenoside R1, ginsenosides Rg1 and Rb1 increased cell apoptosis significantly. Cell cycle and cyclin A assay showed that NGRE arrested cells in the synthesis phase and increased the expression of cyclin A remarkably. NGRE also enhanced the actions of two chemotherapeutic agents, 5-fluorouracil and irinotecan. Cell growth decreased more with the combined treatment of NGRE and 5-fluorouracil (or irinotecan) than with the chemotherapy agent applied alone, suggesting that notoginseng can reduce the dose of 5-fluorouracil (or irinotecan) needed to achieve desired effects. Further in vivo and human trials are warranted to test whether notoginseng is a valuable chemo-adjuvant with clinical validity.


Differential gene expression in multilocus isozyme systmes of the developing green sunfish.
The patterns of expression of eight multilocous isozyme systems were investigated in the differentiated adult tissues and the early embryonic stages (0-210 hours after fertilization) of the green sunfish, Lepomis cyanellus. Enzymes encoded by approximately 23 gene loci were resolved by starch-gel electrophoresis and detected by specific histochemical staining. The developmental patterns of these isozyme systems appear to be the result of the diffential expression of the multiple gene loci. Isozymic forms of glucoseophosphate isomerase (GPI-A2), malate dehydrogenase (MDH-A2), and creatine kinase (CK-C2) were present in most differentiated tissues, in the unfertilized eggs, and in all stages of embryonic development. Closely homologous forms of these isozymes (GPI-B2, MDH-B2, and CK-A2) were expressed predominantly in skeletal muscle and were first detected at around the time of hatching (38-42 hours). The similar temporal and spatial patterns of gene expressions for the GPI, LDH, MDH, and CK loci suggest that the duplicates loci encoding enzymes, diverged in their regulation to patterns of differential gene expression which are similar for each enzyme system.


Hypoxia-induced apoptosis in human cells with normal p53 status and function, without any alteration in the nuclear protein level.
We have studied hypoxia-induced inactivation of cells from three established human cell lines with different p53 status. Hypoxia was found to induce apoptosis in cells expressing wild-type p53 (MCF-7 cells), but not in cells where p53 is either mutated (T-47D cells), or abrogated by expression of the HPV18 E6 oncoprotein (NHIK 3025 cells). Apoptosis was demonstrated by DNA fragmentation, using agarose gel electrophoresis of DNA and DNA nick end labeling (TUNEL). We demonstrate that extremely hypoxic conditions (< 4 ppm O2) do not cause any change of expression in the p53 protein level in these three cell lines. In addition, the localization of p53 in MCF-7 cells was found exclusively in the nucleus in only some of the cells both under aerobic and hypoxic conditions. Furthermore, no correlation was found between the p53-expression level and whether or not a cell underwent apoptosis. Flow cytometric TUNEL analysis of MCF-7 cells revealed that initiation of apoptosis occurred in all phases of the cell cycle, although predominantly for cells in S phase. Apoptosis was observed only during a limited time window (i.e., approximately 10 to approximately 24 h) after the onset of extreme hypoxia. While 66% of the MCF-7 cells lost their ability to form visible colonies following 15 h exposure to extreme hypoxia, only approximately 28% were induced to apoptosis, suggesting that approximately 38% were inactivated by other death processes. Commitment to apoptotic cell death was observed in MCF-7 cells even for oxygen concentrations as high as 5000 ppm. Our present results indicate that the p53 status in these three tumor cell lines does not have any major influence on cell's survival following exposure to extremely hypoxic conditions, whereas following moderate hypoxia, cells expressing functional p53 enhanced their susceptibility to cell death. Taken together, although these results suggest that functional p53 might play a role in the induction of apoptosis during hypoxia, other factors seem to be equally important.


A highly sensitive and selective fluorescent probe for fluoride anions based on intramolecular charge transfer.
Currently, there is a great need to develop methods for the selective detection of fluoride anions (F(-) ) owing to their toxicity in the environment and biological function in living systems. In this study, we developed a new fluorescent probe (probe 1) employing a Si-O bond as a highly selective recognition receptor for detecting F(-) via intramolecular charge transfer. Probe 1 could detect F(-) quantitatively using the turn-on fluorescence spectroscopy method with excellent sensitivity in the range of 4-38 μM and a detection limit of 0.26 μM; the detection time was < 17 min. We anticipate that probe 1 would be used widely to monitor F(-) in the environment. Copyright © 2015 John Wiley & Sons, Ltd.


A new report of Nocardiopsis valliformis strain OT1 from alkaline Lonar crater of India and its use in synthesis of silver nanoparticles with special reference to evaluation of antibacterial activity and cytotoxicity.
The authors report the biological synthesis of silver nanoparticles (AgNPs) by alkaliphilic actinobacterium Nocardiopsis valliformis OT1 strain isolated for the first time from Lonar crater, India. The primary detection of silver NPs formation was made by colour change from colourless to dark brown and confirmed by UV-Vis spectrum of AgNPs at 423 nm, specific for AgNPs. Further, AgNPs were characterized by nanoparticle tracking analysis, Zeta sizer, Fourier transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM) analyses. FTIR analysis showed the presence of proteins as capping agent. TEM analysis revealed the formation of spherical and polydispersed AgNPs within the size range of 5-50 nm. The antimicrobial activity of silver nanoparticles against Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus and Bacillus subtilis was evaluated. The AgNPs showed the maximum antibacterial activity against B. subtilis (Gram positive) and the minimum against E. coli (Gram negative). The minimal inhibitory concentration values of AgNPs for the tested bacteria were found to be in the range of 30-80 µg/mL. The AgNPs demonstrated higher antibacterial activity against all the bacteria tested as compared with the commercially available antibiotics. The cytotoxicity of biosynthesized AgNPs against in vitro human cervical cancer cell line (HeLa) demonstrated a dose-response activity. The IC50 value was found to be 100 µg/mL of AgNPs against cancer HeLa cell line.


Cardiovascular effects of novel antipsychotic medications.
This article reviews current knowledge of cardiovascular effects and drug interactions of the most commonly used novel antipsychotics, including clozapine and the atypical antipsychotics. The literature was reviewed through MEDLINE and PSYCINFO searches of articles published from 1980 to 2001. Materials were located using search terms such as antipsychotics and atypical antipsychotics, matched with the terms cardiovascular disease, coronary artery disease, cardiac risk factor, cardiovascular effects, and cardiac effects. Individual drug names were also searched and their 2001 package inserts were reviewed. Drug compendiums from 1998 to 2001 and some psychopharmacology texts were also used for this review. This article focuses on direct cardiovascular effects of these medications and the most common interactions between the antipsychotic and cardiovascular medications.


Differential expression of ceruloplasmin isoforms in the cerebrospinal fluid of amyotrophic lateral sclerosis patients.
Amyotrophic lateral sclerosis (ALS) a fatal degenerative disease that selectively affects motor neurons, likely results from a complex interplay among oxidative injury, excitotoxic stimulation, protein aggregation and genetic factors. Ceruloplasmin (Cp) protein is a ferroxidase that oxidizes toxic ferrous iron to its nontoxic ferric form, protecting the central nervous system (CNS) from iron deposition. Cp is thus considered as one of the main systems dedicated to the protection of the CNS from oxidative stress damage. We investigated Cp protein behaviour in the cerebrospinal fluid (CSF) of ALS patients of recent onset. An increased expression of Cp was observed in ALS (n = 16) compared to two control groups (healthy subjects, n = 11 and peripheral neuropathy patients, n = 10). 2-DE analysis revealed a differential expression of Cp isoforms in ALS patients compared to controls. ALS samples showed an increase in the relative abundance of more basic Cp forms, corresponding to the nonsialylated proteins. Despite the increase in protein expression, ferroxidase activity evaluated in the CSF of ALS patients was comparable to that of the controls, indicating a Cp functional impairment. Ceruloplasmin isoforms profile may be proposed as disease feature that could provide insight into the molecular mechanisms of ALS pathogenesis.


Analysis of noise barrier overlap gaps.
Sound propagation through the gap produced by two parallel vertical barriers with overlapped ends is formulated for traffic noise sources. The analysis identifies both source and receiver regions according to the mechanisms that influence noise propagation in the vicinity of an overlap gap. A method to account for the contributions from the various source regions for a given receiver location is described. The derived method can be implemented using various equations for sound propagation. The results of using equations approved by the United States Federal Highway Administration for traffic noise propagation are given. Uncalibrated predictions are compared with field measurements for up to 30 receiver positions from each of four overlap gaps. The relative importance of contributions from reflected rays to the noise levels at receiver positions is given. The analysis confirms the initial hypothesis that a commonly used strategy of overlapping barriers by an amount equal to two or three times the overlap width is useful for controlling line-of-sight propagation but ignores the substantial effect of reflections.


Double free-flap for a bimalleolar defect of lower leg and ankle.
Double free-flaps are necessary when tissue cover cannot be sufficed with a single flap. The other factors to be considered when using two free flaps for resurfacing of distal limb defects are the availability of more than one recipient vessel, the risk of distal limb ischaemia and the donor site morbidity of double flap harvest. If these factors are adequately addressed, double free-flaps can be safely executed for resurfacing distal limb defects with minimal morbidity. We report the simultaneous harvest and transfer of the anterolateral and anteromedial thigh flaps inset and vascularised as double free-flaps to resurface a large bimalleolar defect in a 14-year-old boy with no additional morbidity as compared to that of a single free tissue transfer.


Nrf2 protects human alveolar epithelial cells against injury induced by influenza A virus.
Influenza A virus (IAV) infection primarily targets respiratory epithelial cells and produces clinical outcomes ranging from mild upper respiratory infection to severe pneumonia. Recent studies have shown the importance of lung antioxidant defense systems against injury by IAV. Nuclear factor-erythroid 2 related factor 2 (Nrf2) activates the majority of antioxidant genes. Alveolar type II (ATII) cells and alveolar macrophages (AM) were isolated from human lungs not suitable for transplantation and donated for medical research. In some studies ATII cells were transdifferentiated to alveolar type I-like (ATI-like) cells. Alveolar epithelial cells were infected with A/PR/8/34 (PR8) virus. We analyzed PR8 virus production, influenza A nucleoprotein levels, ROS generation and expression of antiviral genes. Immunocytofluorescence was used to determine Nrf2 translocation and western blotting to detect Nrf2, HO-1 and caspase 1 and 3 cleavage. We also analyzed ingestion of PR8 virus infected apoptotic ATII cells by AM, cytokine levels by ELISA, glutathione levels, necrosis and apoptosis by TUNEL assay. Moreover, we determined the critical importance of Nrf2 using adenovirus Nrf2 (AdNrf2) or Nrf2 siRNA to overexpress or knockdown Nrf2, respectively. We found that IAV induced oxidative stress, cytotoxicity and apoptosis in ATI-like and ATII cells. We also found that AM can ingest PR8 virus-induced apoptotic ATII cells (efferocytosis) but not viable cells, whereas ATII cells did not ingest these apoptotic cells. PR8 virus increased ROS production, Nrf2, HO-1, Mx1 and OAS1 expression and Nrf2 translocation to the nucleus. Nrf2 knockdown with siRNA sensitized ATI-like cells and ATII cells to injury induced by IAV and overexpression of Nrf2 with AdNrf2 protected these cells. Furthermore, Nrf2 overexpression followed by infection with PR8 virus decreased virus replication, influenza A nucleoprotein expression, antiviral response and oxidative stress. However, AdNrf2 did not increase IFN-λ1 (IL-29) levels. Our results indicate that IAV induces alveolar epithelial injury and that Nrf2 protects these cells from the cytopathic effects of IAV likely by increasing the expression of antioxidant genes. Identifying the pathways involved in protecting cells from injury during influenza infection may be particularly important for developing new therapeutic strategies.


Seasonal and dietary effects on Vitamin D deficiencies detected in wild boar from mid-western Spain.
Vitamin D (VitD) is involved in important mammalian physiological mechanisms, such as Ca-P metabolism, bone development and immunological response. VitD deficiencies are frequently detected in domestic animals and related to various health problems (e.g., rickets, bone deformation). However, knowledge about the status of VitD in wildlife species, such as the wild boar, is scarce. The aims of this work were to explore VitD status in wild boar populations from mid-western Spain and to elucidate the influence of daylight exposure and food supplementation in levels of VitD. Serum concentration of VitD (measured as 25-hydroxivitaminD) was assessed in 276 wild boar from 27 game estates located in mid-western Spain using a commercial ELISA kit. In 19 out of 27 estates, the staff supplied a specific VitD-enriched food (2,000 UI/Kg) ad libitum throughout the year, while in the remaining estates (8), no food was supplied. Blood samples were extracted from hunted animals (198) between October and February of hunting seasons 2016/2017 and 2017/2018, and from live wild boar (78) that were captured, sampled and released (March-September of 2017). The percentage of animals with VitD deficiency (<20 ng/ml), VitD insufficiency (20-30 ng/ml) and VitD sufficiency (>30 ng/ml) was estimated, and the relationship of these levels to factors like sex, age and season was assessed using chi-square tests. Furthermore, associations between daylight exposure and supplemental food with VitD levels were explored using linear models. Of the studied wild boar population, 82.2% showed a VitD deficiency or insufficiency. VitD deficiencies were more frequent in animals sampled in winter and spring. Furthermore, levels of VitD positively correlated with daylight exposure and supplemental food intake. Ad libitum supplementation with VitD-enriched food was insufficient to prevent VitD deficiencies in wild boar from November to April, probably because food consumption is lower during this period.


Effect of chronic blockade of angiotensin II-receptor subtypes on aortic compliance in rats with myocardial infarction.
This study was undertaken to investigate changes in aortic geometry and compliance after long-term blockade of angiotensin receptors type 1 (AT1) and AT2 receptors under basal conditions and after myocardial infarction (MI). Sham-operated (sham) or MI rats received either no treatment, AT1 antagonist GR138950C (GR; 2 mg/kg/day i.v.), or AT2 antagonist PD123319 (PD; 3 mg/kg/day s.c.). After 3 weeks, mean arterial blood pressure (MAP) was measured. Thoracic aorta diastolic diameter (D[dia]), compliance coefficient (CC), and distensibility coefficient (DC) were determined noninvasively in anesthetized rats by using ultrasound and wall tracking. After the rats were killed, histologic measurements were made on aortic cross sections. In sham rats, MAP was reduced by GR treatment (76 +/- 6 vs. 106 +/- 5 mm Hg), but not by PD. D(dia) was reduced in both GR-treated (1.74 +/- 0.08 vs. 2.09 +/- 0.05 mm) and PD-treated (1.83 +/- 0.05 vs. 2.09 +/- 0.05 mm) sham rats. CC and DC were not modified by either treatment. Although media cross-sectional area was not affected by either GR or PD treatment in sham rats, media thickness and media/lumen ratio were increased in both cases. Induction of MI had no effect on aortic structure, geometry, or mechanics; however, treatment with either GR or PD improved DC versus untreated MI rats. We conclude that AT1 and AT2 receptors are involved in angiotensin II-mediated effects on aortic geometry and mechanics under both basal conditions and after MI. Whereas blockade of AT1 receptors most likely influences vascular properties through a depressor mechanism, AT2 receptors induce pressure-independent remodeling.


Some historical reflections on the neural control of locomotion.
Thought on the neural control of locomotion dates back to antiquity. In this article, however, the focus is more recent by starting with some major 17th century concepts, which were developed by René Descartes, a French philosopher; Thomas Willis, an English anatomist; and Giovanni Borelli, an Italian physiologist and physicist. Each relied on his personal expertise to theorize on the organization and control of movements. The 18th and early 19th centuries saw work on both the central and peripheral control of movement: the former most notably by Johann Unzer, Marie Jean-Pierre Flourens and Julien-Jean-César Legallois, and the latter by Unzer, Jirí Procháska and many others. Next in the 19th century, neurologists used human locomotion as a precise tool for characterizing motor pathologies: e.g., Guillaume Duchenne de Boulogne's description of locomotor ataxia. Jean-Martin Charcot considered motor control to be organized at two levels of the central nervous system: the cerebral cortex and the spinal cord. Maurice Philippson's defined the dog's step cycle and considered that locomotion used both central and reflex mechanisms. Charles Sherrington explained that locomotor control was usually thought to consist of a succession of peripheral reflexes (e.g., the stepping reflexes). Thomas Graham Brown's then contemporary evidence for the spinal origin of locomotor rhythmicity languished in obscurity until the early 1960s. By then the stage was set for an international assault on the neural control of locomotion, which featured research conducted on both invertebrate and vertebrate animal models. These contributions have progressively became more integrated and interactive, with current work emphasizing that locomotor control involves a seamless integration between central locomotor networks and peripheral feedback.


The effect of pneumatic balloon dilatation on gastric emptying in patients with achalasia.
Achalasia is a disease that characterized by relaxation hazard of lower esophageal sphincter. In patients with achalasia, it's known that gastric emptying time is delayed. In this study we aimed to evaluate the difference between the gastric emptying time before and after pneumatic balloon dilatation. Nine achalasia patients (7 female, mean age 51.5 +/- 13.1, range 36-71 year) that were diagnosed as clinically, radiologically and manometrically were enrolled into the study. In all patients, before and after pneumatic dilatation, gastric emptying time was measured with radionuclide method after eating a solid meal. In severely effected patients labeled egg was passed to stomach by a nasogastric tube. One hour after observing initial gastric activity, irradiation was detected dynamically. Radionuclide emptying time before (T1/2) dilatation was a mean of 301.9 +/- 64.7, and after dilatation 221.7 +/- 370.8 minute (p=0.018). As a result, elongation in gastric emptying time in patients with achalasia significantly decreases after effective pneumatic balloon dilatation.


Pathophysiology of food-induced anaphylaxis.
Food-induced anaphylaxis is a steadily increasing problem in westernized countries and now represents the leading cause of anaphylaxis in the outpatient setting, particularly in children. Much of our knowledge of the pathophysiology of food-induced anaphylaxis comes from animal studies. Food anaphylaxis in humans is thought to be entirely IgE mediated. Several features appear to be unique to these reactions; factors such as exercise can lower the "threshold" for anaphylaxis in certain susceptible individuals. Different methods of thermal processing can modify the allergenicity of food proteins. Alteration of stomach pH can allow for incomplete digestion of food proteins, leading to increased absorption of intact food allergens. Low serum platelet-activating factor acetylhydrolase may predispose to fatal food-induced anaphylaxis. With a greater understanding of the pathophysiology of food-induced anaphylaxis, novel approaches not only to identify those at risk, but to treat and ultimately prevent food-induced anaphylaxis, are on the horizon.


NON-INVASIVE PREDICTORS FOR THE PRESENCE, GRADE AND RISK OF BLEEDING FROM ESOPHAGEAL VARICES IN PATIENTS WITH POST-HEPATITIC CIRRHOSIS.
Variceal bleeding is the last step of a chain of events initiatedby an increase in portal pressure, followed by the development and progressive dilation ofvarices until these finally rupture and bleed. The ideal method to diagnose portal hypertension should be accurate, noninvasive, objective, and reproducible. The study evaluated the predictive value of two non-invasive parameters for the diagnosis of esophageal varices (EV): 1-Right liver lobe diameter/serum albumin ratios (RLLD/S. albumin), and 2-Platelet count/splenic bipolar diameter ratios (Platelets count/SBPD). This study included eighty Egyptian patients with post-hepatitic cirrhosis (45 males and 35 females). They underwent laboratory ultrasono-graphic and endoscopic examinations within one week. RLLD/S. albumin and Platelets count/SBPD ratios were calculated. The results showed that EV were not detected by upper digestive endoscopy in 25%, while grade I of EV was found in 17.5%, grade II in 17.5%, grade III in 20%, & grade IV in 20%. RLLD/S. albumin concentration ratio diagnosed the varices at cut off value of 3.43 with 95% sensitivity and 80% specificity. Also, it was positively correlated with grading of E.V, when this ratio increased the grading of E.V increases and vice versa. Besides, it predicted bleeding from E.V. at cut off value of 5.096 with 63% sensitivity and 73% specificity. Platelet count/SBPD ratio predicted the presence of varices at cut off value 1847 with 95% sensitivity and 93% specificity, and negatively correlated with grading of EV, when this ratio decreased grading of E.V increase and vice versa. It also predicted bleeding from E.V. at cut off value of 4809 with 50% sensitivity and 93% specificity.


Using CT and cholangiography to diagnose biliary tract carcinoma complicating primary sclerosing cholangitis.
The objective of our study was to determine the value of CT and cholangiography for diagnosing biliary tract carcinoma complicating primary sclerosing cholangitis. One hundred thirteen abdominal CT examinations and cholangiograms in 45 patients with primary sclerosing cholangitis, including 18 patients with established biliary tract carcinoma, were analyzed for tumor. Four radiologists who were unaware of the presence or absence of carcinoma rated each study as to the probability of malignancy. Receiver operating characteristic curve analysis was used to assess the diagnostic performance of CT and cholangiography, the value of imaging signs, and the degree of inter-observer variation in interpretation. Sensitivity and specificity values were calculated. CT outperformed cholangiography in the detection of carcinoma. The average area under the receiver operating characteristic curve was 0.82 for CT and 0.57 for cholangiography (p = 0.003). Sensitivity and specificity for detecting carcinoma using CT were good, with average values of 82% and 80%, respectively. Average sensitivity and specificity for cholangiography were 54% and 53%, respectively. The most reliable sign of tumor on CT was a discrete mass. Progressive biliary dilatation on sequential studies was the most useful sign on cholangiography. Interobserver agreement assessed using the Cronbach alpha was fair for cholangiography and good for CT. CT provides good sensitivity and specificity and significantly outperforms cholangiography in detecting biliary tract carcinoma complicating primary sclerosing cholangitis. Despite limitations, CT and cholangiography provide useful information not otherwise available in the treatment of patients with primary sclerosing cholangitis.


Is schizophrenia universal?
The question whether schizophrenia occurs in similar forms in different populations and cultures was first raised by Kraepelin at the turn of the century. However, methodological difficulties have impeded for decades the development of comparative cross-cultural research, and it was not until the 1960s that investigations of the kind Kraepelin envisaged became feasible. A major role in launching multi-centre clinical and epidemiological studies of schizophrenia in over 20 countries in different parts of the world has been played by the World Health Organization. The WHO studies have demonstrated that: (I) syndromes of schizophrenia occur in all cultures and geographical areas investigated; (II) their rate of incidence is very similar in the different populations; (III) the course and prognosis of schizophrenia is extremely variable, but outcome is significantly better in the developing countries. These findings have fundamental implications for the conceptualization of schizophrenia and for designing strategies of new research.


Tbx4 function during hindlimb development reveals a mechanism that explains the origins of proximal limb defects.
We dissect genetically a gene regulatory network that involves the transcription factors Tbx4, Pitx1 and Isl1 acting cooperatively to establish the hindlimb bud, and identify key differences in the pathways that initiate formation of the hindlimb and forelimb. Using live image analysis of murine limb mesenchyme cells undergoing chondrogenesis in micromass culture, we distinguish a series of changes in cellular behaviours and cohesiveness that are required for chondrogenic precursors to undergo differentiation. Furthermore, we provide evidence that the proximal hindlimb defects observed in Tbx4 mutant mice result from a failure in the early differentiation step of chondroprogenitors into chondrocytes, providing an explanation for the origins of proximally biased limb defects.


Nanoparticle-Based Therapy in Genomics.
In the modern era, humankind is making daily progress through industrialization. As various types of diseases are prevailing worldwide, scientists are using many approaches to manage these diseases, such as gene therapy. A nanoparticle (NP)-based approach is an example of a modern method used to address several pathologies. This modern therapeutic approach aims not only at safely transferring the drug of choice to the site of interest in a biological system but also at ensuring the biocompatibility of these NPs. Hence, various coating methodologies are being employed to avoid NP toxicity as well as immunoreactivity. This short review covers the latest approaches and advances in this biomedical field. Among nanomaterials, gold NPs (GNPs) are comprehensively employed as a diagnostic tool for the treatment and management of diseases such as cancer.


TLR4 contributes to disease-inducing mechanisms resulting in central nervous system autoimmune disease.
Environmental factors strongly influence the development of autoimmune diseases, including multiple sclerosis. Despite this clear association, the mechanisms through which environment mediates its effects on disease are poorly understood. Pertussis toxin (PTX) functions as a surrogate for environmental factors to induce animal models of autoimmunity, such as experimental autoimmune encephalomyelitis. Although very little is known about the molecular mechanisms behind its function in disease development, PTX has been hypothesized to facilitate immune cell entry to the CNS by increasing permeability across the blood-brain barrier. Using intravital microscopy of the murine cerebromicrovasculature, we demonstrate that PTX alone induces the recruitment of leukocytes and of active T cells to the CNS. P-selectin expression was induced by PTX, and leukocyte/endothelial interactions could be blocked with a P-selectin-blocking Ab. P-selectin blockade also prevented PTX-induced increase in permeability across the blood-brain barrier. Therefore, permeability is a secondary result of recruitment, rather than the primary mechanism by which PTX induces disease. Most importantly, we show that PTX induces intracellular signals through TLR4, a receptor intimately associated with innate immune mechanisms. We demonstrate that PTX-induced leukocyte recruitment is dependent on TLR4 and give evidence that the disease-inducing mechanisms initiated by PTX are also at least partly dependent on TLR4. We propose that this innate immune pathway is a novel mechanism through which environment can initiate autoimmune disease of the CNS.


Enhancing pediatric safety: using simulation to assess radiology resident preparedness for anaphylaxis from intravenous contrast media.
To prospectively develop and test a simulation model for assessing radiology resident preparedness for pediatric life-threatening events in the radiology environment. This study was institutional review board approved. Nineteen radiology residents (10 men, nine women; mean age, 28.5 years) participated in two simulated contrast material reaction scenarios: one with and one without resuscitation aids available. Each resident examined and managed two mannequins-simulating a 1-2-year-old patient and an 8-9-year-old patient-for type, sequence, dose, and administration route for any intervention, including administering medication, calling a code team, and providing oxygen. The time to order each intervention was documented. Resident responses (time to order intervention, appropriateness of intervention, and intervention route) were evaluated. The paired t test was used to compare the time to intervention between the resuscitation-aid-available and resuscitation-aid-not-available scenarios and between the scenario performed first and the scenario performed second. The McNemar test was performed to compare the percentage of appropriate interventions between the two resuscitation aid scenarios. The average time to call the code team was shorter when no resuscitation aids were available than when resuscitation aids were available (98 vs 149 seconds, P=.08). The average times to request oxygen and epinephrine were shorter when resuscitation aids were available (40 vs 89 seconds to request oxygen, P=.016; 121 vs 163 seconds to request epinephrine, P=.21). Appropriate medication dosing was not significantly different between the two scenarios. In only five of the 38 simulated scenarios was calling the code team the first intervention. The correct sequence of interventions (calling code team, providing oxygen, and then providing epinephrine) was performed by only one resident in one scenario. Only five residents recognized that they were encountering a contrast material reaction. Simulation training for radiology residents is valuable and suggests that resident preparedness for pediatric anaphylaxis from intravenous contrast media is insufficient. Clear step-by-step resuscitation aids are needed in the radiology environment.


Age-Related Decline in the Variation of Dynamic Functional Connectivity: A Resting State Analysis.
Normal aging is typically characterized by abnormal resting-state functional connectivity (FC), including decreasing connectivity within networks and increasing connectivity between networks, under the assumption that the FC over the scan time was stationary. In fact, the resting-state FC has been shown in recent years to vary over time even within minutes, thus showing the great potential of intrinsic interactions and organization of the brain. In this article, we assumed that the dynamic FC consisted of an intrinsic dynamic balance in the resting brain and was altered with increasing age. Two groups of individuals (N = 36, ages 20-25 for the young group; N = 32, ages 60-85 for the senior group) were recruited from the public data of the Nathan Kline Institute. Phase randomization was first used to examine the reliability of the dynamic FC. Next, the variation in the dynamic FC and the energy ratio of the dynamic FC fluctuations within a higher frequency band were calculated and further checked for differences between groups by non-parametric permutation tests. The results robustly showed modularization of the dynamic FC variation, which declined with aging; moreover, the FC variation of the inter-network connections, which mainly consisted of the frontal-parietal network-associated and occipital-associated connections, decreased. In addition, a higher energy ratio in the higher FC fluctuation frequency band was observed in the senior group, which indicated the frequency interactions in the FC fluctuations. These results highly supported the basis of abnormality and compensation in the aging brain and might provide new insights into both aging and relevant compensatory mechanisms.


ROS Scavenging and Anti-Wrinkle Effects of Clitocybin A Isolated from the Mycelium of the Mushroom Clitocybe aurantiaca.
Clitocybin A, an isoindolinone from Clitocybe aurantiaca, was investigated to assess its anti-wrinkle properties, through reactive oxygen species (ROS)-scavenging and elastase inhibitory activities, procollagen synthesis, and matrix metalloproteinase-1 (MMP-1) expression, in human primary dermal fibroblast-neonatal (HDF-N) cells. Clitocybin A exhibited no significant cytotoxicity up to 10 ppm in HDF-N cells, with cell viability and cell proliferation activity greater than 94.6% and 91.9%, respectively. Strong and concentration-dependent ROS radical scavenging activities of clitocybin A were observed following irradiation with UVB at 30 mJ/cm2. Furthermore, clitocybin A treatment of cells at 0.1, 1, and 10 ppm exhibited decreased elastase activity, in a concentration-dependent manner, by 1.97%, 6.6%, and 8.31%, respectively, versus the control group. The effects of clitocybin A on procollagen synthesis and MMP-1 expression were investigated. Clitocybin A treatment of cells at 1, 5, and 10 ppm increased procollagen synthesis, by 67.9%, 74.4%, and 112.9%, respectively, versus the control group. At these concentrations, MMP-1 expression decreased significantly following UV irradiation. Together, these findings suggest that clitocybin A may be an effective ingredient for use in anti-wrinkle cosmetic products.


Plasma polychlorinated biphenyls (PCB) levels of workers in a transformer recycling company, their family members, and employees of surrounding companies.
In spring 2010, high internal exposures (up to 236 μg/L plasma) for the sum of indicator polychlorinated biphenyls (PCB) were discovered in workers in a transformer recycling company in Germany, where PCB-contaminated material was not handled according to proper occupational hygiene. The release of PCB from this company raised growing concerns regarding possible adverse human health effects correlated with this exposure. This provided a basis for a large biological monitoring study in order to examine the internal exposure to PCB in individuals working in that recycling company, their family members, and relatives, as well as subjects working or living in the surroundings of this company. Blood samples from 116 individuals (formerly) employed in the transformer recycling company and 45 direct relatives of these persons were obtained. Further, blood samples of 190 subjects working in close vicinity of the recycling plant, 277 persons working in the larger area, and 41 residents of the area were investigated. Plasma samples were analyzed for the 6 indicator PCB (PCB 28, 52, 101, 138, 153, 180) and 12 dioxin-like PCB using gas chromatography/mass spectroscopy (GC/MS; limit of detection [LOD] at 0.01 μg/L). Median concentrations (maximum) for the sum of the 6 indicator PCB in blood of the employees, their relatives, individuals working in close vicinity, persons working in the larger area, and the residents were 3.68 (236.3), 1.86 (22.8), 1.34 (22.9), 1.19 (6.42), and 0.85 (7.22) μg/L plasma, respectively. The (former) employees of the transformer recycling plant partly showed the highest plasma PCB levels determined thus far in Germany. Even family members displayed highly elevated levels of PCB in blood due to contaminations of their homes by laundering of contaminated clothes. Vicinity to the recycling plant including reported contact with possibly contaminated scrap was the main contributor to the PCB levels of the workers of the surrounding companies. Residents of the area did not show significantly elevated blood PCB levels compared to the general population. Our biomonitoring results served as a basis for individual risk communication and successful risk management.


Effect of ferric nitrilotriacetate on rostral mesencephalic cells.
After murine fetal cells from the rostral mesencephalic tegmentum were isolated, prepared, and cultured; neuronal and glial cells in primary mixed cell cultures were exposed to ferric nitrilotriacetate (Fe-NTA) at varying concentrations. Studies were performed at 23 days in culture after 14 day exposure to Fe-NTA. In addition to morphologic studies, biochemical assays including specific [3H]flunitrazepam (FLU) binding, clonazepam (CLO)-displaceable [3H]-FLU binding, Ro5-4864-displaceable [3H]-FLU binding, [3H]-FLU binding, [3H]dopamine (DA) uptake, [3H]haloperidol (HAL) binding, [3H]spiperone (SP) binding, glutamine synthetase activity (GS), and protein determinations were performed. The data demonstrate that chelated ferric iron has an adverse effect on these cells. The data also demonstrate that increasing concentrations of Fe-NTA resulted in massive neuronal dropout leaving the culture population virtually all glial; however, the specific binding of [3H]HAL and [3H]SP increased. There was a concomitant decrease in both glutamine synthetase activity and overall protein content. The mechanism of enhancement in the presence of Fe-NTA of [3H]HAL and [3H]SP binding is unknown and may be unique, but may be related to the known increase in D2 receptor ligand affinity in the presence of other multivalent cations (Ca2+ and Mg2+).


The change of synovial fluid proteome in rabbit surgery-induced model of knee osteoarthritis.
The aims of this study were to explore the change of synovial fluid (SF) proteome in a knee osteoarthritis (KOA) rabbit model, and to provide a new target for the treatment of knee osteoarthritis at the proteomic level. Sixteen New Zealand rabbits were randomly and equally divided into two groups. Group A rabbits were subjected to right anterior cruciate ligament transection (ACLT), while group B rabbits were subjected to sham ACLT. Six weeks later, the proteomes of knee joint SF from group A and B rabbits were analyzed using a label-free quantitative proteomic analysis method. We extracted 944 relevant items from GO BlastGO2 for the 23 proteins differentially expressed between the two groups. The final annotation results were 23 protein sequences annotated by 462 GO items. According to the KEGG gene database of rabbit protein sequences, as well as annotation of the KO numbers of homologous/similar proteins to the relevant 64 KEGG pathways, we extracted the sequences of 16 significantly differently expressed proteins among the relevant 64 KEGG messages/metabolism pathways. These included adiponectin, pyruvate kinase, bisphosphoglycerate mutase, HtpG/heat shock proteins, hemoglobin subunit alpha-1 2, VCP (CDC48), 14-3-3 protein beta/theta/zeta, and ferritin heavy chain, whose levels were decreased in group A. The other proteins were fibrinogen alpha/beta/gamma chain, carboxylesterase 2, paraoxonase/arylesterase 1, apolipoprotein A-I, immunoglobulin heavy chain, and transferrin, whose levels were increased in group B. The identified differentially expressed proteins indicate the change of SF proteomic expression in KOA and may provide protein targets for treating this condition.


Disseminating nutrition research findings to health professionals.
Good nutrition is the basis of good health and poor nutrition is directly linked with certain illnesses, such as heart disease. A great deal of research on nutrition is carried out every year, but little may actually be read by health staff. A project aimed at ensuring that the latest information reaches those who need it is now running in 24 European countries.