Activation of mammalian tyrosinase by ferrous ions.
Kinetic experiments are reported showing that mammalian tyrosinase from B16 mouse melanoma is significantly activated by catalytic amounts of ferrous ions. Monitoring of tyrosine oxidation by both dopachrome formation and oxygen consumption showed that ferrous ions at micromolar concentrations induce a marked enzymatic activity with 0.01 U/ml of highly purified tyrosinase, whereas no detectable reaction occurs in the absence of metal over a sufficiently prolonged period of time. The extent of the activating effect, which is specific for the reduced form of iron, is proportional to the concentration of the added metal with a typical saturation profile, no further effect being observed beyond a threshold value. Changing the buffer system from phosphate to hepes or tris results in a marked decrease of the Fe2(+)-induced activation. Scavengers of active oxygen species, such as superoxide dismutase, catalase, formate and mannitol have no detectable effect on the tyrosinase activity. These results are accounted for in terms of an activation mechanism involving reduction of the cupric ions at the active site of the resting enzyme.


Twice-a-day treatment in the radiotherapeutic management of malignant mixed tumor of the parotid gland: A case report.
A patient with a 2,300 gm malignant mixed tumor of the parotid gland had recurrence 19 days post surgery. The recurrent mass failed to respond to daily fractions of 200 rad conventional irradiation four times per week and actually increased in size. A superfractionation scheme was substituted, employing twice-a-day 200 rad at 4-5½ hours intervals three times a week for 2½ weeks. At the completion of treatment, there was a 50 percent regression of the recurrent tumor mass and a 100 percent regression two weeks post irradiation. A protocol using a twice-a-day treatment is discussed.


Repeatability of i.Profiler for measuring wavefront aberrations in healthy eyes.
To evaluate the repeatability of wavefront aberration measurements and the correlation between corneal aberration and pupil size in normal eyes using a wavefront-based autorefractor (i.ProfilerPlus; Carl Zeiss Vision, Germany). A prospective cross-sectional study. Wavefront aberrations, including spherical aberration (SA) (Z40), coma (Z3-1, Z31), trefoil (Z3-3, Z33) and total higher-order aberrations (tHOA), were measured at different pupil diameters. The repeatability was evaluated using one-way ANOVA method, and statistical indicators including within-subject standard deviation (Sw), test-retest repeatability (TRT), and intra-class correlation coefficient (ICC). The correlations between corneal aberrations and pupil sizes were evaluated by Pearson correlation analysis. A total of 96 healthy young volunteers were enrolled. Corneal and ocular higher-order aberrations (HOA) measured by i.Profiler showed Sw < 0.01 μm, TRT < 0.10 μm, ICC > 0.90. There was a linear positive correlation between the corneal HOA and pupil size. The correlation coefficient between SA and tHOA was the largest (r = 0.996, P < 0.001). The measurements of wavefront aberrations by i.Profiler are highly repeatable. Corneal HOA was significantly dependent on pupil size. SA was the most influential aberration for visual quality in this study.


In situ pore formation in a polymer matrix by differential polymer degradation.
A new approach for the in situ formation of porosity in a matrix based on differential polymer degradation has been studied. This approach exploits the differences in polymer properties such as molecular weight, hydrophilicity (hydrophobicity), and degradation to induce preferential degradation of one phase in a biphasic polymer system. Biphasic polymer systems polymers derived from alpha-hydroxy acids and poly(anhydrides), which vary in their erosion characteristics (surface vs. bulk) and hydrophobicities were studied. In addition to examining the generality of the approach, potential advantages of such systems in the context of tissue engineering and drug delivery are briefly discussed.


Reduction of dioxin-like toxicity in effluents by additional wastewater treatment and related effects in fish.
Efficiency of advanced wastewater treatment technologies to reduce micropollutants which mediate dioxin-like toxicity was investigated. Technologies compared included ozonation, powdered activated carbon and granular activated carbon. In addition to chemical analyses in samples of effluents, surface waters, sediments, and fish, (1) dioxin-like potentials were measured in paired samples of effluents, surface waters, and sediments by use of an in vitro biotest (reporter gene assay) and (2) dioxin-like effects were investigated in exposed fish by use of in vivo activity of the mixed-function, monooxygenase enzyme, ethoxyresorufin O-deethylase (EROD) in liver. All advanced technologies studied, based on degradation or adsorption, significantly reduced dioxin-like potentials in samples and resulted in lesser EROD activity in livers of fish. Results of in vitro and in vivo biological responses were not clearly related to quantification of targeted analytes by use of instrumental analyses.


Study of aflatoxin B1 production by Aspergillus parasiticus in bee pollen of Greek origin.
Aflatoxin B1 (AFB1) is a carcinogenic metabolite produced by certain Aspergillus species such as A. parasiticus and A. flavus. The beneficial properties of bee pollen have transformed this commodity into an increasingly frequent component of the human diet. As bee pollen is a substrate on which aflatoxigenic fungi can grow, AFB1 production is likely. In the present study, we describe a method for aflatoxin B1 determination in bee pollen utilising high pressure liquid chromatography (HPLC) with a fluorescence detector (FD). The recovery factor of the method was found to be 111% (RSD% 1.61), while the detection limit (LOD) was 0.08 ng AFB1/g. An additional aim of this study was to investigate the growth of A. parasiticus and AFB1 production in bee pollen. Results indicated that no mycelial growth was observed and no AFB1 was detected in bee pollen samples containing natural microbiota throughout the entire observation period (20 days). In contrast, AFB1 production in treated bee pollen samples (15 g pollen/flask) inoculated with A. parasiticus was significantly higher (p ≤ 0.05) compared to control samples (treated but not inoculated) throughout the entire incubation period, while no mycelial growth was apparent. Maximum production was observed on the 12th day (79.29 ng AFB1/flask and 32.44 ng AFB1/flask for inoculated and non-inoculated bee pollen, respectively). As a result, AFB1 production in bee pollen is likely even following a minor contamination, which could occur randomly.


National survey in the United Kingdom of prophylaxis of deep vein thrombosis for patients with fracture of the neck of the femur.
Thromboprophylaxis continues to be a contentious issue because of a lack of clear answers to pertinent questions. Hence, a survey is helpful in identifying current practices. A national survey in the UK in January 2004 investigated the use of thromboprophylaxis following fracture of the neck of the femur. Responses from 723/1648 (44%) orthopaedic consultants to a postal questionnaire showed that 623 (86%) regularly undertook trauma surgery and 625 (87%) had protocols for prophylaxis of deep venous thrombosis. In all, 555 (89%) consultants followed these protocols routinely and, of these, 276 (50%) regularly used both chemical and mechanical prophylaxis, 235 (42%) used chemoprophylaxis only and 44 (8%) used mechanical prophylaxis only. Among consultants using chemoprophylaxis, 238 (46%) used low-molecular-weight heparin, 148 (30%) used aspirin, 75 (15%) used low-molecular-weight heparin and aspirin, 35 (6%) used unfractionated heparin and 15 (3%) used warfarin. However, 68 (11%) did not use any thromboprophylaxis at all for patients with fractured neck of the femur.


[The problem of the terminology of "diffuse neurodermatitis--atopic dermatitis" in the work of the expert physician].
The problem in terminology, regarding diffuse neurodermatitis or atopic dermatitis, is discussed from a viewpoint of an expert physician evaluating the health status of certain patients populations. The author advocates A. A. Kalamkarian and V. A. Samsonov's view point, for it permits expert evaluation of the subjects' health status from a universal clinical and methodological standpoint.


Dermoscopy of Common Inflammatory Disorders.
In addition to its "traditional" application for the early diagnosis of melanoma and nonmelanoma skin cancers, dermoscopy gains appreciation in fields beyond dermato-oncology. Nowadays, dermoscopy has been established as a reliable adjunctive tool to the everyday clinical practice of general dermatology. Morphology and distribution of vascular structures, background colors, follicular abnormalities, and the presence of scales are important features that should be evaluated. Clinical examination remains the undoubted mainstay of diagnosis in inflammatory and infectious diseases.


Isolation and quantification of HIV from lymph nodes.
This chapter describes a standardized microculture technique adapted from a peripheral blood mononuclear cells (PBMC) microculture assay to isolate and quantify HIV from lymph nodes. This quantitative lymph node microculture estimates the number of infectious cells per million lymph node mononuclear cells. The assay, as described below, is performed in two 24-well tissue culture plates using six fivefold dilutions. Each sample of patient cells is cocultivated with phytohemagglutinin-stimulated normal donor PBMC for 21 d. The supernatant from each well is assayed for HIV p24 antigen production by the standard HIV p24 enzyme-linked immunosorbent assay (ELISA). HIV-1 infectious titers are expressed as tissue culture infective dose (TCID50/10(6) cells) according to Reed and Muench.


The effect of cyproheptadine on insulin biosynthesis.
The effect of a potent antiserotonin-antihistaminic compound, cyproheptadine (CPH) on insulin biosynthesis was studied in pancreatic islets isolated from CPH-treated rats. Though insulin content of islets was markedly reduced in CPH-treated rats, the incorporation of radiolabeled leucine into proinsulin and insulin fractions was not affected with respect to the rate and amount. It is concluded that CPH may deplete insulin content of the islets through causing the leakage of insulin.


The timing of cyclophosphamide therapy in tumor-bearing rats affects the resistance to tumor challenge in survivors.
Cyclophosphamide given to rats 2 or 5 days after an injection of Yoshida ascites sarcoma cured approximately the same proportion of animals, but the resistance to a subsequent tumor challenge was found only in rats treated with the drug 5 days after tumor injection.


Multiple poor sleep characteristics and metabolic abnormalities consistent with metabolic syndrome among white, black, and Hispanic/Latina women: modification by menopausal status.
Poor sleep is a potential risk factor for metabolic syndrome (MetS), and its relationship with MetS may vary by race/ethnicity and menopausal status among women. We used Sister Study enrollment data from 2003 to 2009 to investigate the cross-sectional associations between multiple subjective sleep characteristics and having ≥ 3 prevalent metabolic abnormalities consistent with MetS among white, black, and Hispanic/Latina women. Self-reported sleep characteristics included average sleep duration (short [< 7 h] vs. recommended [7-9 h]), sleep debt (≥ 2-h difference between shortest and longest sleep duration, napping ≥ 3 times/week, and insomnia symptoms (difficulty falling or staying asleep). We used Poisson regression with robust variance to estimate adjusted prevalence ratios (PRs) and 95% confidence intervals (CIs) to compare MetS prevalence between women with poor sleep (e.g., short sleep, sleep debt, frequent napping, or insomnia symptoms [all yes vs. no]) and non-poor sleep within menopausal status categories (premenopausal or postmenopausal). We adjusted for sociodemographic characteristics, mental health, and health behaviors. Among 38,007 eligible women (13,988 premenopausal, 24,019 postmenopausal), mean age was 55 ± 8.8 years, racial/ethnic composition was 86.63% white, 8.53% black, and 4.84% Hispanic/Latina, and 12% had MetS. Associations between certain poor sleep characteristics [i.e., short sleep (PRpremenopausal = 1.23 [95% CI 1.06-1.42], PRpostmenopausal = 1.09 [1.02-1.16], pshort sleep*menopause = 0.0070) and insomnia symptoms (PRpremenopausal = 1.21 [1.05-1.41], PRpostmenopausal = 1.11 [1.05-1.18], pinsomnia symptoms*menopause = 0.035)] and prevalent MetS were stronger among premenopausal compared to postmenopausal women, but did not vary by race/ethnicity. Associations between concurrent short sleep/insomnia symptoms and MetS were stronger among white and Hispanic/Latina postmenopausal women compared to their black counterparts. Menopausal status and race/ethnicity did not modify positive associations for other poor sleep characteristics. Poor sleep was positively associated with MetS prevalence. Associations between individual poor sleep characteristics (i.e., short sleep, insomnia symptoms) were stronger among premenopausal compared to postmenopausal women but did not vary by race/ethnicity.


Structural features of diverse ligands influencing binding affinities to estrogen alpha and estrogen beta receptors. Part I: Molecular descriptors calculated from minimal energy conformation of isolated ligands.
We report a neural network modeling approach combined with genetic algorithm for prediction of experimental binding affinity to human Estrogen Receptor alpha and beta (ER-alpha and ER-beta) of a diverse set of chemicals. The counterpropagation artificial neural network is used as a modeling method. Structural features of ligands having the strongest influence to the binding affinities were investigated. The molecular descriptors have been selected in the variable selection procedure based on the genetic algorithm (GA). The 3D descriptors of molecular structures were calculated for the minimal energy conformation of isolated ligands. All the optimized models were tested by an internal and an external set of compounds. The models served for classification and prediction of binding affinities. The optimized models were 100% correct in the classification part, where the active molecules were separated from the inactive ones. The best predictive model of active molecules was assessed with the internal test set yielding the error in prediction RMS = 0.12, while the predictions for the external test set contain some outliers, which are ascribed to the incompatibility of individual compounds concerning the structural domain of our model. The influence of the receptor on the conformation of the ligands in the ligand-protein complex is described and discussed in the accompanying paper.


Epistatic effect of C-reactive protein (CRP) single nucleotide polymorphism (SNP) +1059 and interleukin-1B SNP +3954 on CRP concentration in healthy male blood donors.
Baseline C-reactive protein (CRP) concentrations are indicative of persons prone to cardiovascular diseases and are about 40-50% heritable. We have previously shown that interleukin (IL)-1B +3954 allele T is associated with lower CRP concentration. In this study, we aimed to examine the effect of this polymorphism together with the CRP +1059 gene polymorphism on baseline CRP concentrations, and genotyped 336 healthy blood donors for CRP +1059 (G-->C) and IL-1B +3954 (C-->T) polymorphisms. In men, the carriers of the CRP +1059 C-allele had significantly lower CRP values than GG homozygotes (0.66 versus 0.43 mg l(-1), up to -35%, P = 0.009). No significant difference was found in women. When the data were stratified for both of these polymorphisms in men, CRP +1059 GG homozygotes had low CRP concentrations only if they were allele-T carriers of IL-1B +3954 simultaneously (0.93 versus 0.50 mg l(-1), P = 0.013). Genotype CRP +1059 GG/IL-1B +3954 CC was associated with an almost 3-fold risk of a higher baseline CRP value [odds ratio (OR) 2.84 (CI 1.03-6.07)]. Thus, both IL-1B +3954 (C-->T) and CRP +1059 (G-->C) polymorphisms influence baseline CRP values and act independently of each other in male subjects. These polymorphisms might be predictive markers of persons prone to cardiovascular diseases.


Carcinomas of the urinary bladder in a 4-chloro-o-toluidine cohort.
In an historical mortality study, conducted on a cohort of 335 male employees in 4-chloro-o-toluidine (4-COT) production and processing plants, no deaths due to cancer of the urinary bladder had been identified. However, after completion of this study, urothelial carcinomas were recorded in eight of the employees, two of whom have died in the meantime (as of December 1986). All eight persons had been employed in the 4-COT production plant before improvements in industrial hygiene were introduced in 1970 (a subcohort of 116 men). This presumably higher level of exposure to monocyclic arylamines lasted for 14.0 years (median), and the total exposure time (before and after 1970) in the 4-COT plant was 25.5 years (median). The standardized incidence rate for urothelial carcinomas in the 4-COT subcohort was 73 times higher than expected and was comparable with the results obtained for polycyclic arylamines, which have been identified as human carcinogenic agents. On the basis of our results as association may be postulated between occupational exposure to 4-COT and carcinomas of the urinary bladder observed among production workers.


Comparison of E-Test, disk diffusion and a modified CLSI broth microdilution (M 38-A) method for in vitro testing of itraconazole, fluconazole and voriconazole against dermatophytes.
We compared two agar-based methods, the E-test and the disk diffusion method with the Clinical Laboratory Standards Institute (CLSI) reference broth microdilution method (CLSI M38-A; MD). Forty six dermatophytes strains including 30 Trichophyton mentagrophytes, 8 T. rubrum and 8 M. gypseum were tested against three antifungal agents, i.e., fluconazole (FLC), itraconazole (ITC) and voriconazole (VRC). The level of agreement between the E-test and MD (+/-2 dilutions) was 45.6% for fluconazole, 19.5% for itraconazole and 52.1% for voriconazole. The results obtained with disk diffusion had low correlation with the results obtained by the CLSI broth microdilution reference method with azoles.


Does feeding effort of Tengmalm's owls reflect offspring survival prospects in cyclic food conditions?
In an environment fluctuating in a predicatable manner with wide among-year variation in offspring mortality, fitness is largely influenced by the timing of reproductive investment. In vole-eating nocturnal Tengmalm's owls (Aegolius funereus), within-cycle variation in 1st-year survival of owlets is 3-fold as estimated by the recruitment probability of an offspring. It increases from the peak through the low to the increase phase of the vole cycle. We recorded prey delivery rates of males during a 3-year vole cycle using 4 h continuous recording at night. Males brought significantly more prey items per offspring in a low-vole year than in the increase and peak vole years. In the early night (10 p.m.-12 p.m.), males fed their families equally in the increase and peak vole years, whereas in the late night (0.01-2.00 a.m.) males reduced their feeding rate in the peak year but not in other years. Both prey number and prey mass per offspring were larger in the low and increase vole years than in the peak year, though in the peak phase food is most abundant. We suggest that feeding effort of site-tenacious, long-lived (mean lifespan 3.5 years) male owls culminates in the increase rather than in the peak phase of the vole cycle, because offspring survive better in the former phase.


Hierarchical micro/nanostructured silver hollow fiber boosts electroreduction of carbon dioxide.
Efficient conversion of CO2 to commodity chemicals by sustainable way is of great significance for achieving carbon neutrality. Although considerable progress has been made in CO2 utilization, highly efficient CO2 conversion with high space velocity under mild conditions remains a challenge. Here, we report a hierarchical micro/nanostructured silver hollow fiber electrode that reduces CO2 to CO with a faradaic efficiency of 93% and a current density of 1.26 A · cm-2 at a potential of -0.83 V vs. RHE. Exceeding 50% conversions of as high as 31,000 mL · gcat-1 · h-1 CO2 are achieved at ambient temperature and pressure. Electrochemical results and time-resolved operando Raman spectra demonstrate that enhanced three-phase interface reactions and oriented mass transfers synergistically boost CO production.


Isomer-selective thermal activation of methane in the gas phase by [HMO]+ and [M(OH)]+ (M=Ti and V).
Methane scrabble: To have the right elements is sometimes just not sufficient, as shown by [M(OH)](+) (M=Ti, V), which do not react with methane. However, reshuffling of the "tiles" to [HMO](+) changes the reactions behavior completely, leading to the first example of C-H bond activation of methane by an early first-row transition-metal cation.


The high-affinity choline transporter CHT1 is regulated by the ubiquitin ligase Nedd4-2.
The high-affinity choline transporter (CHT1), which is specifically expressed in cholinergic neurons, constitutes a rate-limiting step for acetylcholine synthesis. We have found that the exogenous ubiquitin ligase Nedd4-2 interacts with CHT1 expressed in HEK293 cells decreasing the amount of cell surface CHT1 by approximately 40%, and that small interfering RNA for endogenous Nedd4-2 enhances the choline uptake activity by CHT1 in HEK293 cells. These results indicate that Nedd4-2-mediated ubiquitination regulates the cell surface expression of CHT1 in cultured cells and suggest a possibility that treatments or drugs which inhibit the interaction between CHT1 and Nedd4-2 might be useful for diseases involving decrease in acetylcholine level such as Alzheimer's disease.


Influence of varying concentrations of TiO2 nanoparticles and engine speed on the performance and emissions of diesel engine operated on waste cooking oil biodiesel blends using response surface methodology.
For a few decades now fast depleting fossil fuels has been a major challenge. Fast expanding population and increased rate of urbanization has increased energy demand. This makes the current scenario worse. Fossil fuels' emissions are another challenge. Apart from fossil fuel emissions, the untreated disposal of waste cooking oil presents another environment's sustainability challenge. The treatment of waste cooking oil as fuel presents a tangible solution to challenge. In this research article, impact of the engine speed and the concentration of titanium dioxide (TiO2) nanoparticles (NPs) in diesel-biodiesel blended fuels on the engine's performance. The emission characteristics of a single-cylinder four-stroke diesel engine has also been examined. TiO2 NPs were produced by a sol-gel methodology. The diesel-biodiesel combination was fortified with TiO2 NPs at 40, 80 and 120 ppm. These mixtures were used to power the diesel engine, which was then run at 1150, 1400, 1650, 1900 and 2150 RPM. Interaction between engine speeds and nanoparticle concentrations and investigation of their combined effect on engine performance and emissions was done using response surface methodology. The minimum BSFC of 0.33994 kg/kWh and maximum BTE of 25.90% were found for B30 + 120 ppm biodiesel blend at 2150 rpm as compared to all other tested fuels. The emissions including CO and HC emissions were recorded as 25.61486 kg/kWh and 0.05289kg/kWh respectively at 2150 rpm for B30 + 120 ppm biodiesel blend while NOx on the contrary side exhibits a slight escalation with increasing engine speed and nanoparticles concentration. The findings of the experiments demonstrated that adding TiO2 nanoparticles to diesel-biodiesel blends is an effective way to enhance the performance of diesel engines while simultaneously reducing the emissions. It was also discovered that the mathematical model that was built can efficiently estimate the performance of the engine and the emission levels.


Fundamental insights into autosomal dominant polycystic kidney disease from human-based cell models.
Several animal- and human-derived models are used in autosomal dominant polycystic kidney disease (ADPKD) research to gain insight in the disease mechanism. However, a consistent correlation between animal and human ADPKD models is lacking. Therefore, established human-derived models are relevant to affirm research results and translate findings into a clinical set-up. In this review, we give an extensive overview of the existing human-based cell models. We discuss their source (urine, nephrectomy and stem cell), immortalisation procedures, genetic engineering, kidney segmental origin and characterisation with nephron segment markers. We summarise the most studied pathways and lessons learned from these different ADPKD models. Finally, we issue recommendations for the derivation of human-derived cell lines and for experimental set-ups with these cell lines.


Single plane cineangiographic study of normal left ventricular volumes in human subjects.
Single plane cine angiographic estimation of left ventricular volumes in 10 Indian subjects with no evidence of left ventricular disease was carried out. The figures obtained were end diastolic volume 72.43+/-10.27 ml/M2, endsystolic volume 26.82+/-7.46 ml/M2, stroke volume 45.61+/-12.23ml/M2, ejection faction 62.30+/-10.90%. These values compare well with those already reported in literature from Western countries. No study in Indian subjects was available for comparison so far.


Living-related donor nephrectomy by eleventh rib intraperitoneal extrapleural incision.
Living-related kidney transplants continue to yield the best results. The two primary approaches for living-related donor nephrectomy are the intraperitoneal and extraperitoneal operations. We herein describe a series of 8 cases in which an eleventh rib intraperitoneal extrapleural incision was used for living-related donor nephrectomy. The advantages of the operation in terms of improved ability to manage vascular anomalies is described. No complication has been encountered.


Helicobacter pylori prevalence in diabetes mellitus patients with dyspeptic symptoms and its relationship to glycemic control and late complications.
There are contradictory reports on Helicobacter pylori prevalence and its relationship to late complications of diabetes mellitus (DM). The aim of this study was to determine the prevalence of H. pylori infection in type 2 DM patients and to evaluate the relationship between H. pylori infection and the glycemic control, late complications. A total of 141 type 2 DM patients and 142 nondiabetic subjects with upper gastrointestinal symptoms were enrolled in the study. All patients underwent upper gastrointestinal endoscopy with biopsy specimens obtained from gastric antrum and corpus. H. pylori status was evaluated in each patient by both the rapid urease test and histopathological examination. Plasma glucose, HbA1c, microalbuminuria in 24 h collected urine, electroneuromyography, and fundoscopic examinations were performed in all subjects. The prevalence of H. pylori infection was 61.7% and 58.5%, respectively, among type 2 diabetic patients and nondiabetic controls and was not statistically significant (P = 0.577). The duration of diabetes, fasting blood glucose and haemoglobin A1c levels, nephropathy and retinopathy prevalence did not differ significantly between the two groups (diabetics versus nondiabetics). There was no late complication in 60.3% of the type 2 diabetic patients as compared to at least one late complication in the remainders. A statistically significant correlation was found between H. pylori infection and the presence of neuropathy (P = 0.021). The prevalence of H. pylori infection did not differ significantly between the diabetic patients and nondiabetic controls. Interestingly, diabetics with H. pylori infection had a higher incidence of neuropathy, although there was no association between the duration and regulation of diabetes, retinopathy, nephropathy and H. pylori status.


Multivariate models of brain volume for identification of children and adolescents with fetal alcohol spectrum disorder.
Magnetic resonance imaging (MRI) studies of fetal alcohol spectrum disorder (FASD) have shown reductions of brain volume associated with prenatal exposure to alcohol. Previous studies consider regional brain volumes independently but ignore potential relationships across numerous structures. This study aims to (a) identify a multivariate model based on regional brain volume that discriminates children/adolescents with FASD versus healthy controls, and (b) determine if FASD classification performance can be increased by building classification models separately for each sex. Three-dimensional T1-weighted MRI from two independent childhood/adolescent datasets were used for training (79 FASD, aged 5.7-18.9 years, 35 males; 81 controls, aged 5.8-18.5 years, 32 males) and testing (67 FASD, aged 6.0-19.6 years, 38 males; 74 controls, aged 5.2-19.5 years, 42 males) a classification model. Using FreeSurfer, 87 regional brain volumes were extracted for each subject and were used as input into a support vector machine generating a classification model from the training data. The model performed moderately well on the test data with accuracy 77%, sensitivity 64%, and specificity 88%. Regions that contributed heavily to prediction in this model included temporal lobe and subcortical gray matter. Further investigation of two separate models for males and females showed slightly decreased accuracy compared to the model including all subjects (male accuracy 70%; female accuracy 67%), but had different regional contributions suggesting sex differences. This work demonstrates the potential of multivariate analysis of brain volumes for discriminating children/adolescents with FASD and provides indication of the most affected regions.


miRNAGE-34 induces cardiac damAGE.
Small non-coding microRNAs (miRNAs, miRs) regulate gene expression in virtually all cells, and they have been implicated in cardiovascular disease and aging. In a paper recently published in Nature, miR-34a was identified as an aging-associated apoptotic and overall damaging factor for the heart.


[Fibrinolytic treatment with urokinase of post acute phlebothromboses (author's transl)].
Standardised urokinase-heparin treatment was administered to 32 patients one to six weeks after deep-vein thrombosis. Treatment generally continued over 7-14 days. Complete recanalisation occurred in six, partial in 18 patients. In eight patients there was no evidence of thrombolysis in the phlebogram.


Simultaneous nitrification-denitrification and membrane fouling alleviation in a submerged biofilm membrane bioreactor with coupling of sponge and biodegradable PBS carrier.
Simultaneous nitrification-denitrification (SND) was achieved in submerged biofilm membrane bioreactor (SBF-MBR) treating low carbon/nitrogen (C/N) ratio wastewater. A novel bio-carrier coupling of sponge and biodegradable poly(butanediol succinate) (PBS) was applied as external carbon source and biofilm carrier. Result represented that NH4+-N and total nitrogen removal efficiencies were high of 99.1% and 94.3% in the SBF-MBR. Protein (PN) contents from SND-biofilm were reduced by 10.5% and 44.3% in TB-EPS and LB-EPS, while polysaccharides (PS) were reduced by 45.8% and 34.8%, respectively. 3D-EEM spectra indicated that protein-like, humic acid-like and fulvic acid-like substances were the main components in EPS and their peak intensities were reduced. Additionally, membrane fouling of SBF-MBR was improved after the achievement of biofilm. Microbial community analysis showed that Simplicispira, Thauera, Desulfovibrio, Dechlorobacter and Acinetobacter were dominant genus, which indicated co-existence of nitrifying bacteria, heterotrophic denitrifiers and aerobic denitrifiers in the SBF-MBR.


Positron emission tomography for radiation treatment planning.
To evaluate the impact of positron emission tomography (PET) on target volume delineation for radiation treatment planning. The data of the literature concerning the use of PET in target volume delineation are summarized. The following points are discussed for each tumor entity: biological background for the PET investigation, sensitivity and specificity of PET (with different tracers) in comparison to computed tomography (CT) and magnetic resonance imaging (MRI) and impact of PET on target volume definition. New PET tracers, which could visualize biological pathways, such as hypoxia, proliferation, angiogenesis, apoptosis and gene expression patterns, will also be discussed. The results of clinical studies on the integration of PET in target volume definition for lung, head-and-neck, genitourinary and brain tumors were analyzed. Fluorodeoxyglucose-(FDG-)PET has a significant impact on GTV (gross tumor volume) and PTV (planning target volume) delineation in lung cancer and can detect lymph node involvement and differentiate malignant tissue from atelectasis. In head-and-neck cancer, the value of FDG-PET for radiation treatment planning is still under investigation. For example, FDG-PET could be superior to CT and MRI in the detection of lymph node metastases and unknown primary cancer and in the differentiation of viable tumor tissue after treatment. Therefore, it might play an important role in GTV definition and sparing of normal tissue. Choline PET and acetate PET are promising tracers in the diagnosis of prostate cancer, but their validity in local tumor demarcation, lymph node diagnosis and detection of recurrence has to be defined in future clinical trials. FDG-PET seems to be particularly valuable in lymph node status definition in cervical cancer. In high-grade gliomas and meningiomas, methionine PET helps to define the GTV and differentiate tumor from normal tissue. For other entities like gastrointestinal cancer, lymphomas, sarcomas, etc., the data of the literature are yet insufficient. The imaging of hypoxia, cell proliferation, angiogenesis, apoptosis and gene expression leads to the identification of different areas of a biologically heterogeneous tumor mass that can individually be targeted using intensity modulated radiotherapy (IMRT). In addition, a biological dose distribution can be generated, the socalled dose painting. However, systematic experimental and clinical trials are necessary to validate this hypothesis. Regarding treatment planning in radiotherapy, PET offers advantages in terms of tumor delineation and the description of biological processes. To define the real impact of this investigation in radiation treatment planning, subsequent experimental, clinical and cost-benefit analyses are required.


Impacts of Road Deicing Application on Sodium and Chloride Concentrations in Philadelphia Region Drinking Water.
Historical application of roadway deicing agents (e.g., road salt and brines) has led to an increase in sodium and chloride concentrations in surface water over time. Numerous studies have explored the impacts of road salt on freshwater aquatic organisms such as amphibians and benthic macroinvertebrates; however, the public health risk associated with consuming drinking water with elevated sodium has been largely unexplored in the literature. Yet, sodium ingestion, primarily through diet, has been linked to adverse human health conditions, such as hypertension. This study documents weekly sodium and chloride concentrations in municipal tap water from three municipalities within the Philadelphia metropolitan area during winter 2018-2019 (November through March). A late winter peak in sodium and chloride concentrations was observed for all three municipalities immediately following successive snow events coupled with daily high temperatures above 0°C. Among municipalities, mean and peak sodium and chloride concentrations were associated with relatively higher development in upstream areas. Observed sodium concentrations ranged from 1 to 6.4x the USEPA recommended guideline of 20 mg/L for individuals restricted to a total sodium intake of 500 mg/day. Additionally, the contribution of sodium ingestion from water consumption to the recommended daily sodium intake limits for adults ranged from 3.5% to 18.8% for non-restricted and 4.2%-33.3% for "low salt" (i.e., <1,500 mg/day) diets, respectively. The study results coupled with a records review for 40 U.S. municipalities in snow affected regions indicate the need for real-time communication between water utilities and the general public regarding sodium exposure risk during winter months.


In vitro toxicity of particulate matter emissions from residential pellet combustion.
Particulate matter emissions (PM10) from the combustion, in a residential stove, of two commercial brands of certified (ENplus A1) pellets, a non-certified brand and laboratory made pellets of acacia were tested for their ability to induce ecotoxic, cytotoxic, and mutagenic responses in unicellular organisms and a human cell line. Ecotoxicity was evaluated through the Vibrio fischeri bioluminescence inhibition assay. Moreover, cytotoxicity was assessed at two time points (24- and 48-hr) through two complementary techniques in order to evaluate the cellular metabolic activity and membrane integrity of human lung epithelial cells A549. The Ames test using two Salmonella typhimurium strains (TA100 and TA98) was employed to assess the mutagenic potential of the polycyclic aromatic hydrocarbon fraction extracted from the PM10 samples. Results obtained with the bioluminescent bacteria indicated that only particles from the combustion of acacia pellets were toxic. All samples induced impairment on the A549 cells metabolic activity, while no significant release of lactate dehydrogenase was recorded. PM10 emissions from acacia pellets were the most cytotoxic, while samples from both certified pellets evoked significant cytotoxicity at lower doses. Cytotoxicity time-dependency was only observed for PM10 from the combustion of acacia pellets and one of the brands of certified pellets. Mutagenic activity was not detected in both S. typhimurium strains. This study emphasises the role of the raw material for pellet manufacturing on the toxicological profile of PM emissions. Alternative raw materials should be deeply investigated before their use in pelletisation and combustion in residential appliances.


Leaving Las Vegas: Exposure to Las Vegas and risk of suicide.
Residents of Las Vegas, Nevada have much higher suicide rates than residents of other metropolitan counties in the USA. Whether the risk of suicide among visitors to Las Vegas is also significantly elevated has been difficult to assess because person-time denominator information is not available. We used a case-control design to examine the association between exposure to Las Vegas and risk of suicide expressed as mortality odds ratios. We conceptualized four different types of potential suicide risk with respect to Las Vegas: (1) risk of suicide among usual residents of Las Vegas ("chronic risk"), (2) risk of suicide among temporary visitors to Las Vegas ("acute risk"), (3) risk of suicide among Las Vegas residents visiting elsewhere ("leaving Las Vegas risk"), and (4) risk of suicide among travelers in general ("traveler risk"). Controlling for age, gender, marital status, and year effects, the odds of suicide among Las Vegas residents was at least 50% greater than among residents elsewhere in each of the three decades we observed. Visitors to Las Vegas were at double the risk compared to those who stayed in their home county. Leaving Las Vegas was associated with a greater than 20% reduction in risk for suicide. Traveling to Las Vegas is associated with a twofold increase in risk compared to traveling elsewhere. We discuss three possible theoretical frameworks to help explain our observed results: ecological effects, whereby social factors unique to Las Vegas, or uniquely amplified in Las Vegas, result in increased risk to both residents and visitors; selection effects whereby those predisposed to suicide disproportionately choose Las Vegas to reside in and visit; and contagion effects, whereby high numbers of suicides tend to lead to even greater numbers over time, as people emulate the suicides of others. We compare our empirical evidence for each of the effects with existing sociological and historical scholarship on Las Vegas.


Costs and Effects of School-Based Licensed Practical Nurses on Elementary Student Attendance and Chronic Absenteeism.
Despite increasing reliance on licensed practical nurses (LPNs) to provide health services in schools, we do not know whether this is a cost-effective prevention strategy against student absenteeism. Therefore, we evaluated the costs and effectiveness of an LPN-based school nursing program for improving attendance and chronic absenteeism at a large, urban school district in the southeastern USA. We first identified a matched set of 46 elementary schools (23 nurse, 23 no-nurse) by using an optimal multilevel matching algorithm based on student- and school-level characteristics. We then conducted a cost-effectiveness analysis on the matched set, using the ingredients method to estimate societal costs and multilevel regression to estimate effects. The results indicated that despite substantial incremental costs of $68,228 per school, the presence of a full-time LPN was associated with at best negligible improvements, and at worst slight disimprovements, in attendance and chronic absenteeism. We recommend a careful review of the theory of change for LPN-based school nursing programs to clarify the specific inputs and activities that are expected to lead to improved student outcomes. Education agencies should develop explicit assignment, training, monitoring, and auditing plans to ensure LPNs are equitably distributed and that their activities are aligned with the theory of change. Education agencies should also explore whether expanded Medicaid billing can reduce their share of the nursing cost burden.


Unveiling the need of interactions for social N400s and supporting the N400 inhibition hypothesis.
When participants (Pps) are presented with stimuli in the presence of another person, they may consider that person's perspective. Indeed, five recent ERP studies show that the amplitudes of their N400s are increased. The two most recent ones reveal that these social-N400 increases occur even when instructions do not require a focus on the other's perspective. These increases also happen when Pps know that this other person has the same stimulus information as they have. However, in all these works, Pps could see the other person. Here, we tested whether the interaction occurring with this sight is important or whether these social N400 increases also occur when the other person is seated a bit behind Pps, who are aware of it. All had to decide whether the word ending short stories was coherent, incoherent, or equivocal. No social N400 increase was observed: N400s elicited by those words in Pps who were with a confederate (n = 50) were similar to those of Pps who were alone (n = 51). On the other hand, equivocal endings did not elicit larger N400s than coherent ones but triggered larger late posterior positivities (LPPs), like in previous studies. The discussion focuses on the circumstances in which perspective-taking occurs and on the functional significance of the N400 and the LPP.


Angiographic visualization of a right gastroepiploic artery-left circumflex coronary artery graft.
A 41-year-old man who underwent coronary artery bypass grafting using a gastroepiploic artery graft to the left circumflex coronary artery is reported. Subselective angiography of the right gastroepiploic artery using a steerable guidewire and coaxial catheter system is described.


Peri-implant evaluation of osseointegrated implants subjected to orthodontic forces: results after three years of functional loading.
The objective of this study was to clinically and radiographically assess the peri-implant conditions of implants used as orthodontic anchorage. Two groups were studied: 1) a test group in which osseointegrated implants were used as orthodontic anchorage, with the application of 200-cN force; and 2) a control group in which implants were not subjected to orthodontic force, but supported a screw-retained prosthesis. Clinical evaluations were performed three, six and nine months after prosthesis installation and 1- and 3-year follow-up examinations. Intraoral periapical radiographs were obtained 30 days after surgical implant placement, at the time of prosthesis installation, and one, two and three years thereafter. The results were compared by Kruskal-Wallis test. There was no statistically significant difference in clinical probing depth (p = 0.1078) or mesial and distal crestal bone resorption (p = 0.1832) during the study period. After three years of follow-up, the mean probing depth was 2.21 mm for the control group and 2.39 mm for the test group. The implants of the control group showed a mean distance between the bone crest and implant shoulder of 2.39 mm, whereas the implants used as orthodontic anchorage showed a mean distance of 2.58 mm at the distal site. Results suggest that the use of stable intraoral orthodontic anchorage did not compromise the health of peri-implant tissues or the longevity of the implant.


Interferon research: impact on understanding transcriptional control.
Celebrations are certainly in order for the 50th anniversary of the Isaacs/Lindenmann discovery of interferon as a secreted substance of probable cellular origin that conferred resistance to at least four viruses of distinctly different character--influenza, Sendai, Newcastle's disease, and vaccinia. Personal pride, excusable, I hope, leads me to recall also that following the trail of how interferon works its magic led 15 years ago this year to the discovery of the STATs and their activation by the Jak kinases. These later findings were stimulated by and in turn further stimulated an ever deepening interest in how transcription figured in changing cell behavior. Here are presented some further reflections on these topics.


Acinetobacter community-acquired pneumonia in a healthy child.
Acinetobacter is involved in a variety of infectious diseases primarily associated with healthcare. Recently there has been increasing evidence of the important role these pathogens play in community acquired infections. We report on the case of a previously healthy child, aged 28 months, admitted for fever, cough and pain on the left side of the chest, which on radiographic examination corresponded to a lower lobe necrotizing pneumonia. After detailed diagnostic work-up, community acquired Acinetobacter lwoffii pneumonia was diagnosed. The child had frequently shared respiratory equipment with elderly relatives with chronic obstructive pulmonary disease. As there were no other apparent risk factors, it could be assumed that the sharing of the equipment was the source of infection. The authors wish to draw attention to this possibility, that a necrotising community-acquired pneumonia due to Acinetobacter lwoffii can occur in a previously healthy child and to the dangers of inappropriate use and poor sterilisation of nebulisers. This case is a warning of the dangers that these bacteria may pose in the future in a community setting.


Endonuclease activation during apoptosis: the role of cytosolic Ca2+ and pH.
An axiom of apoptosis is that increases in cytosolic Ca2+ activate a Ca2+/Mg(2+)-dependent endonuclease. However, when HL-60 human promyelocytic leukemia cells were incubated with the Ca2+ ionophore ionomycin in varied extracellular Ca2+, DNA digestion was independent of extracellular Ca2+. Under these conditions, intracellular Ca2+ concentrations did not correlate with the observed DNA digestion. In contrast, intracellular acidification correlated well with DNA digestion. These data indicate that increased intracellular Ca2+ is not the primary signal for endonuclease activation in all forms of apoptosis, but that intracellular acidification may be involved. The observed intracellular acidification is consistent with the involvement of deoxyribonuclease II in apoptosis.


Brain temperature measured by 1H-magnetic resonance spectroscopy in acute and subacute carbon monoxide poisoning.
Brain temperature (BT) is associated with the balance between cerebral blood flow and metabolism according to the "heat-removal" theory. The present study investigated whether BT is abnormally altered in acute and subacute CO-poisoned patients by using (1)H-magnetic resonance spectroscopy (MRS). Eight adult CO-poisoned patients underwent 3-T magnetic resonance imaging in the acute and subacute phases after CO exposure. MRS was performed on deep cerebral white matter in the centrum semiovale, and MRS-based BT was estimated by the chemical shift difference between water and the N-acetyl aspartate signal. We defined the mean BT + 1.96 standard deviations of the BT in 15 healthy controls as the cutoff value for abnormal BT increases (p < 0.05) in CO-poisoned patients. BT of CO-poisoned patients in both the acute and subacute phases was significantly higher than that of the healthy control group. However, BT in the subacute phase was significantly lower than in the acute phase. On the other hand, no significant difference in body temperature was observed between acute and subacute CO-poisoned patients. BT weakly correlated with body temperature, but this correlation was not statistically significant (rho = 0.304, p = 0.2909). The present results suggest that BT in CO-poisoned patients is abnormally high in the acute phase and remains abnormal in the subacute phase. BT alteration in these patients may be associated with brain perfusion and metabolism rather than other factors such as systemic inflammation and body temperature.


Adaptive gene profiling of Mycobacterium tuberculosis during sub-lethal kanamycin exposure.
Resistance to anti-tuberculosis drugs is a formidable obstacle to effective tuberculosis (TB) treatment and prevention globally. New forms of multidrug, extensive drug and total drug resistance Mycobacterium tuberculosis (Mtb) causing a serious threat to human as well as animal's population. Mtb shows diverse adaptability under stress conditions especially antibiotic treatment, however underlying physiological mechanism remained elusive. In present study, we investigated Mtb's response and adaptation with reference to gene expression during sub-lethal kanamycin exposure. Mtb were cultured under sub-lethal drug and control conditions, where half were sub-cultured every 3-days to observe serial adaptation under same conditions and the remaining were subjected to RNA-seq. We identified 98 up-regulated and 198 down-regulated responsive genes compared to control through differential analysis, of which Ra1750 and Ra3160 were the most responsive genes. In adaptive analysis, we found Ra1750, Ra3160, Ra3161, Ra3893 and Ra2492 up-regulation at early stage and gradually showed low expression levels at the later stages of drug exposure. The adaptive expression of Ra1750, Ra3160 and Ra3161 were further confirmed by real time qPCR. These results suggested that these genes contributed in Mtb's physiological adaptation during sub-lethal kanamycin exposure. Our findings may aid to edify these potential targets for drug development against drug resistance tuberculosis.


Increased allergic and asthmatic risks in children residing in industrial areas by surveying the pre-inflammatory (IgE, IL-4 and IL-13) biomarkers.
Toxic metal(loid)s can lead to high damages on human. This work was conducted to investigate the levels of metal(loid)s in PM2.5 and a total of 123 male children's (aged 6-9 years) blood chosen from different areas in Ahvaz and their association with the pre-inflammatory (Immunoglobulin E and cytokines: IgE, IL-4 and IL-13) responses in serum cells. Six metal(loid)s (arsenic, cadmium, chromium, mercury, nickel and lead) in three regions including industrial (Padad), vehicle traffic (Golestan) and reference (Kianpars) areas were studied. Results showed the concentrations of As, Cr, Cd, Ni and Hg in the ambient air of industrial area (Padad) (P < 0.001), and Pb in vehicle traffic area (Golestan) were higher (p < 0.001). Moreover, the mean levels of IgE (mean = 146.44 pg/200landa, P < 0.003), IL-4 (mean = 548.23 pg/200landa, P < 0.001) and IL-13 (mean = 53.21 pg/200landa, P < 0.001) in Padad were higher than Golestan and Kianpars. Our results suggest that living in industrial areas leads to accelerated synthesis of IgE, IL-4 and IL-13 in blood. The spatial distribution of children's serum IgE, IL-4 and IL-13 concentrations showed an abnormal increase of 240 to 400 pg/200landa for IgE, 950 to 1400 pg/200landa for IL-4 and 90 to 128 pg/200landa for IL-13. Our results indicate children in the industrial area are prone to asthma, allergy, miRNA mutation, and other chronic diseases.


Epigallocatechin-3-gallate inhibits proliferation and induces apoptosis in odontogenic keratocyst keratinocytes.
The aim of this study was to investigate the effects of epigallocatechin-3-gallate on the proliferation and apoptosis of odontogenic keratocyst (OKC) keratinocytes in vitro. Keratinocytes isolated from the epithelial lining of the OKC were cultured in keratinocyte serum-free medium and identified by CK10, CK14, pan-cytokeratin and vimentin immunofluorescence staining. The cells were exposed to EGCG at different concentrations, and proliferation inhibition was measured by cell counting kit 8 assay. Cell cycle and apoptosis were assessed by flow cytometry, and expression of the WNT signalling pathway-related proteins FZD3 and JNK3 was detected by quantitative real-time PCR and Western blotting. Human oral keratinocytes (HOKs) were used as the control. The OKC keratinocytes were successfully cultured. The primary cells were tile-like and expressed the epithelial biomarkers CK10, CK14 and pan-cytokeratin. Epigallocatechin-3-gallate inhibited cell proliferation in a dose- and time-dependent manner, arrested cell cycle in the G1 phase and induced apoptosis of OKC keratinocytes. FZD3 and JNK3 were overexpressed in OKC keratinocytes compared with HOKs and were downregulated by epigallocatechin-3-gallate treatment. Epigallocatechin-3-gallate inhibited proliferation and induced apoptosis in OKC keratinocytes, possibly by suppressing the WNT/JNK signalling pathway. It may thus be potentially used for OKC treatment.


Organ donation after assisted death: Is it more or less ethically-problematic than donation after circulatory death?
A provocative question has emerged since the Supreme Court of Canada's decision on assisted dying: Should Canadians who request, and are granted, an assisted death be considered a legitimate source of transplantable organs? A related question is addressed in this paper: is controlled organ donation after assisted death (cDAD) more or less ethically-problematic than standard, controlled organ donation after circulatory determination of death (cDCDD)? Controversial, ethics-related dimensions of cDCD that are of relevance to this research question are explored, and morally-relevant distinctions between cDAD and cDCD are identified. In addition, a set of morally-relevant advantages of one practice over the other is uncovered, and a few potential, theoretical issues specifically related to cDAD practice are articulated. Despite these concerns, the analysis suggests a counterintuitive conclusion: cDAD is, overall, less ethically-problematic than cDCDD. The former practice better respects the autonomy interests of the potential donor, and a claim regarding irreversibility of cessation of the donor's circulatory function in the cDAD context can be supported. Further, with cDAD, there is no possibility that the donor will have negative sensory experiences during organ procurement surgery. Although the development of appropriate policy-decision and regulatory approaches in this domain will be complex and challenging, the comparative ethical analysis of these two organ donation practices has the potential to constructively inform the deliberations of relevant stakeholders, resource persons and decision makers.


Effects of human growth hormone on immune functions: in vitro studies on cells of normal and growth hormone-deficient children.
We have studied the in vitro effects of human growth hormone on cell surface markers and mitogenic responses of peripheral blood lymphocytes (PBL) of normal and growth hormone-deficient children before, during and after treatment with growth hormone. Growth hormone resulted in a decrease in B cell expression but it did not affect expression of T cell subsets. Growth hormone depressed the proliferation of PBL of normal and untreated growth hormone-deficient children. The proliferative responses to phytohemagglutinin (PHA) versus PHA with growth hormone were not statistically different, though the responses of most normal and on treatment children were diminished by the addition of growth hormone. PBL derived from growth hormone-deficient children during treatment with human growth hormone exhibited significantly greater spontaneous proliferation then the PBL of normal children. Growth hormone further significantly enhanced their proliferation. PHA and PHA with growth hormone resulted in significantly greater proliferation of these patients' PBL when compared to those of normal children. We demonstrated that human growth hormone had substantial in vitro effects on immune functions. These effects, some of which depend on the treatment status of the children, may need to be considered in the clinical use of human growth hormone.


Dosimetric and clinical impact of 3D vs. 2D planning in palliative radiotherapy for bone metastases.
The incorporation of three-dimensional (3D) planning for the treatment of bone metastases has been embraced in many North American practices with assumed superior tumor targeting, sparing of normal structures, and improvement in patient outcomes. The goal of our project was to evaluate the dosimetric and clinical impact of 3D vs. two-dimensional (2D) planning for patients who require simple palliative radiotherapy techniques (≤ 2 beams) for bone metastases. Patients undergoing palliative radiation therapy for bone metastases were eligible. The study oncologists first documented the intended treatment target, defined the treatment target/field using digital radiographs (2D), followed by using full 3D planning computerized tomography volumetric datasets. Treatment plans were compared dosimetrically, and patient-reported outcomes (pain, fatigue, anorexia, and nausea) were compared against a historical cohort treated with 2D plans. Eighty-five patients were enrolled in the study group. Review of the 3D datasets led to changes in the target area of interest in 44/85 (52 %) of cases, of which 21/85 (25 %) were clinically significant. 3D plans resulted in superior target coverage and normal tissue sparing. There was no significant difference in patient-reported outcomes however. 3D radiotherapy planning resulted in superior treatment plans but we were unable to demonstrate a significant benefit in clinical outcomes. Prospective study designs are needed to describe the contemporary expectation of palliative radiotherapy for bone metastases in the modern era of 3D planning.


Successful treatment of niclosamide- and praziquantel-resistant beef tapeworm infection with nitazoxanide.
Beef tapeworm (Taenia saginata) infection is acquired by eating inadequately cooked beef that contains the larvae or cysticerci of T. saginata. Niclosamide and praziquantel have proved effective for its treatment but treatment failures are well known. We report herein the results of nitazoxanide therapy. A prospective study was conducted in 18 children and 34 adults to assess the efficacy and safety of nitazoxanide in the treatment of niclosamide- and praziquantel-resistant T. saginata infection. Nitazoxanide was administered twice daily for 3 days in 500-mg doses for those aged over 14 years and at 20mg/kg body weight/day in children aged 5-14 years. Post-treatment follow-up was undertaken at 1, 2, 4, 8, and 12 weeks for fecal samples for proglottides, and to check the presence, number, and viability of Taenia eggs. Nitazoxanide cured 51 of 52 (98.1%) patients. Mild side effects occurred in seven patients, which resolved spontaneously. There were no abnormalities in laboratory parameters. Nitazoxanide is a safe, effective, inexpensive, and well-tolerated drug for the treatment of niclosamide- and praziquantel-resistant beef tapeworm infection.


Synthesis of mycothiol, 1D-1-O-(2-[N-acetyl-L-cysteinyl]amino-2-deoxy-alpha-D-glucopyranosyl)-myo-inositol, principal low molecular mass thiol in the actinomycetes.
Members of the actinomycetes produce 1D-1-O-(2-[N-acetyl-L-cysteinyl]amino-2-deoxy-alpha-D-glucopyranosyl)-myo-inositol or mycothiol 1 as principal low molecular mass thiol. Chemical synthesis of a biosynthetic precursor of mycothiol, the pseudodisaccharide 1D-1-O-(2-amino-2-deoxy-alpha-D-glucopyranosyl)-myo-inositol 13 was achieved by the following steps: (1) Enantioselective synthesis gave the glycosyl acceptors (-)-2,3,4,5,6-penta-O-acetyl-D-myo-inositol D-7 and the corresponding L-isomer L-7. (2) Condensation of D-7 and L-7 with the glycosyl donor 3,4,6-tri-O-acetyl-2-deoxy-2-(2,4-dinitrophenylamino)-alpha-D-glucopyranosylbromide afforded the corresponding alpha and beta anomeric products, which could be resolved by silica gel chromatography. (3) Deprotection of these by hydrolysis using an anion exchange resin gave 1D- and 1L-1-O-(2-amino-2-deoxy-alpha-D-glucopyranosyl)-myo-inositol 13 and 15 and the corresponding beta-coupled anomers 14 and 16. Only 13, and to a much lesser extent 15, were used by enzymes present in an ammonium sulphate fraction of a cellfree extract of Mycobacterium smegmatis for the enzymatic synthesis of mycothiol. In the absence of acetyl-SCoA, the immediate biosynthetic precursor of 1, desacetylmycothiol, was the major product.


Impact Total Psoas Volume on Short- and Long-Term Outcomes in Patients Undergoing Curative Resection for Pancreatic Adenocarcinoma: a New Tool to Assess Sarcopenia.
While sarcopenia is typically defined using total psoas area (TPA), characterizing sarcopenia using only a single axial cross-sectional image may be inadequate. We sought to evaluate total psoas volume (TPV) as a new tool to define sarcopenia and compare patient outcomes relative to TPA and TPV. Sarcopenia was assessed in 763 patients who underwent pancreatectomy for pancreatic adenocarcinoma between 1996 and 2014. It was defined as the TPA and TPV in the lowest sex-specific quartile. The impact of sarcopenia defined by TPA and TPV on overall morbidity and mortality was assessed using multivariable analysis. Median TPA and TPV were both lower in women versus men (both P < 0.001). TPA identified 192 (25.1%) patients as sarcopenic, while TPV identified 152 patients (19.9%). Three hundred sixty-nine (48.4%) patients experienced a postoperative complication. While TPA-sarcopenia was not associated with higher risk of postoperative complications (OR 1.06; P = 0.72), sarcopenia defined by TPV was associated with morbidity (OR 1.79; P = 0.002). On multivariable analysis, TPV-sarcopenia remained independently associated with an increased risk of postoperative complications (OR 1.69; P = 0.006), as well as long-term survival (HR 1.46; P = 0.006). The use of TPV to define sarcopenia was associated with both short- and long-term outcomes following resection of pancreatic cancer. Assessment of the entire volume of the psoas muscle (TPV) may be a better means to define sarcopenia rather than a single axial image.


High concentrations of glucose induce synthesis of argpyrimidine in retinal endothelial cells.
To determine if high concentrations of glucose applied to cultured bovine retinal endothelial cells (BRE cells) would result in production of intracellular methylglyoxal (MG), and consequently, the synthesis of MG-derived advanced glycation end products (AGEs). BRE cells were incubated with 30 mM D-glucose or 30 mM L-glucose for 7 days. Cells incubated with medium that had 5-mM glucose served as controls. Cells were lysed and the lysate was centrifuged to get a supernatant and a pellet fraction. We measured argpyrimidine, a MG-derived fluorescent AGE in the two fractions by a competitive ELISA using a monoclonal antibody. BRE cells incubated with 30 mM D-glucose produced significantly higher (P < 0.05) levels of intracellular MG than control cells or cells incubated with 30 mM L-glucose. Incubation with 30 mM D-glucose significantly (P < 0.05) enhanced the synthesis of argpyrimidine in both supernatant and pellet fractions when compared to control cells. Immunofluorescence studies confirmed results obtained by ELISA and showed higher levels of argpyrimidine in cells incubated with 30 mM D-glucose. These results suggest that MG-mediated protein modification can occur in elevated glucose, and might contribute to endothelial cell changes associated with diabetic retinopathy.


A novel ultrasonic aerosol generator.
An ultrasonic aerosol generator constructed from a domestic humidifier is described which has been used to produce liquid aerosols for physiological investigations. The instrument was constructed from a Pifco domestic humidifier modified to include an energy guide to direct the oscillations of the transducer through the coupling water, which would normally be aerosolized, onto a small membrane based sample chamber containing the liquid to be aerosolized. The size distribution of the aerosol produced was found to be between 2 and 6 mm, optimum for diffuse intrapulmonary deposition. Up to 4 ml/min of aqueous liquid was used; however the sample chamber could be made small enough to contain economic amounts of expensive material to administer by inhalation. The instrument has proved to be reliable over a period of three years.


In vitro fracture testing of submicron diameter collagen fibril specimens.
Mechanical testing of collagenous tissues at different length scales will provide improved understanding of the mechanical behavior of structures such as skin, tendon, and bone, and also guide the development of multiscale mechanical models. Using a microelectromechanical-systems (MEMS) platform, stress-strain response curves up to failure of type I collagen fibril specimens isolated from the dermis of sea cucumbers were obtained in vitro. A majority of the fibril specimens showed brittle fracture. Some displayed linear behavior up to failure, while others displayed some nonlinearity. The fibril specimens showed an elastic modulus of 470 ± 410 MPa, a fracture strength of 230 ± 160 MPa, and a fracture strain of 80% ± 44%. The fibril specimens displayed significantly lower elastic modulus in vitro than previously measured in air. Fracture strength/strain obtained in vitro and in air are both significantly larger than those obtained in vacuo, indicating that the difference arises from the lack of intrafibrillar water molecules produced by vacuum drying. Furthermore, fracture strength/strain of fibril specimens were different from those reported for collagenous tissues of higher hierarchical levels, indicating the importance of obtaining these properties at the fibrillar level for multiscale modeling.


Alpha-fetoprotein concentrations in sera from epileptic patients with immunodeficiency.
The alpha-fetoprotein serum concentration was determined by radioimmunoassay in 22 epileptic patients treated with phenytoin. The concentration was normal in all of the patients. The IgA concentration in serum was below 0.20 g/l in 15 of the patients and normal in 7 (0.60-3.30 g/l). IgG and IgM concentrations were normal. The total number of lymphocytes was significantly reduced in the epileptic patients compared to healthy controls, while the relative percentage of various mononuclear blood cell sub-populations did not differ between the patients and the controls. The response to PHA stimulation was lower in the patients than in the controls for all PHA concentrations tested, the differences, however, were not significant at a 5% level. The results indicate that alpha-fetoprotein does not participate in the pathogenesis of the immune disturbances observed in patients with epilepsy.


Comparing cytotoxicity and efficacy of miltefosine and standard antimicrobial agents against Acanthamoeba trophozoites and cyst forms: An in vitro study.
Acanthamoeba keratitis (AK) is an eye disease often occurring in contact lens wearers. AK treatment is prolonged and requires multiple drugs, which can lead to adverse effects. Our study aimed to compare the in vitro activities and safety of Miltefosine with that of conventional antimicrobial agents used to treat AK. Acanthamoeba castellanii genotype T4 was obtained from a patient with keratitis and subjected to in vitro susceptibility testing with various antimicrobial agents, including Chlorhexidine (CHX), Pentamidine isethionate (PI)Polyhexamethylene biguanide (PHMB), and Miltefosine to assess their efficacy against Acanthamoeba trophozoites and cyst. The cytotoxicity of the agents was evaluated in Vero cells, and their selectivity indexes (SI) were calculated. Chlorhexidine exhibited the highest amoebicidal activity with the highest selectivity index against the trophozoite and cyst, ranging from 1.17 to 8.35. The selectivity index of PHMB is slightly comparable to Chlorhexidine, exhibiting significant anti-Acanthamoeba activity. On the other hand, Pentamidine isethionate and Miltefosine displayed low SI among the compounds. Pentamidine isethionate was effective at high concentrations, which was toxic. Miltefosine exhibited the lowest cytotoxicity; nevertheless, due to the lowest anti-Acanthamoeba activity presented a low selectivity against the parasite. Further studies on more clinical samples and prolonged incubation time should be done to investigate the effectiveness and toxicity of drugs in both in vitro and in vivo conditions.


Alterations and clinical relevance of gut microbiota in patients with Peutz-Jeghers syndrome: A prospective study.
In this case-control study we aimed to investigate the intestinal microbiota profile of patients with Peutz-Jeghers syndrome (PJS) and its association with polyp growth. Thirty-two PJS patients and 35 healthy controls were enrolled. Fecal samples of all participants were collected for gut microbiota analysis via 16S rRNA gene (regions V3-V4) sequencing. SPSS version 22.0 and R software version 3.1.0 were used for the statistical analysis. The richness was comparable, while the overall structure of the gut microbiota differed significantly between the PJS and control groups (weighted UniFrac, P = 0.001; unweighted UniFrac, P = 0.008). Significantly different abundances of two phyla, seven families, and 18 genera as well as twenty-nine differentially enriched functional modules (false discovery rate, P < 0.05) between the two groups were identified. Morganella was positively associated with the median number of polyps (JPN; r = 0.96, P < 0.001) and number of newly discovered polyps in the jejunum between two recent endoscopic resections (JPNG; r = 0.78, P = 0.04). Desulfovibrio was positively associated with JPNG (r = 0.87, P = 0.01). Blautia was negatively associated with the median maximum size of polyps in the jejunum (JPS). Anaerostipes was negatively associated with JPN, JPNG and JPS. Clostridium XVIII and Fusicatenibacter were negatively associated with JPN and JPS, respectively. We found remarkably different gut microbiota of patients with PJS compared to healthy individuals and associations between specific fecal bacteria and clinical features of PJS. These findings may provide a new perspective for the management of PJS in clinical practice.


Superior pedicle reduction mammoplasty: A multivariable analysis of 1306 patients. Risk factors for complications and development of a predictive score.
Breast reduction surgery for hypertrophy is one of the most commonly performed procedures in plastic surgery. This surgery exposes patients to complications well documented in the literature. The objective of this study is therefore to identify the risk factors in order to establish an estimate of the risk of developing complications. We propose the first predictive score of postoperative complications including continuous preoperative variables like Body Mass Index (BMI) and Supra Sternal Notch - Nipple Distance (SSN:N). 1306 patients were analyzed. Multivariable logistic regression showed three independent risk factors : active smoking (OR 6.10 [4.23; 8.78] p < 0.0001), BMI (OR 1.16 [1.11; 1.22] p < 0.0001), SSN:N (OR 1.14 [1.08; 1.21] p < 0.0001). The Rennes Plastic Surgery Score estimating occurrence of postoperative complications was determined, integrating regression coefficient of each risk factor. Active smoking, BMI and SSN:N distance are independent preoperative risk factors for the occurrence of breast reduction complications. The Rennes Plastic Surgery Score including the continuous values of BMI and SSN:N allows us to provide to our patients a reliable estimate of the risk of occurrence of these complications. Lesser-quality prospective cohort or comparative study; retrospective cohort or comparative study; or untreated controls from a randomized controlled trial.


Cellular localization of angiotensinogen gene expression in brown adipose tissue and mesentery: quantification of messenger ribonucleic acid abundance using hybridization in situ.
The cellular localization of angiotensinogen messenger RNA (mRNA) in rat atria, aorta, and mesentery was studied using hybridization in situ. Angiotensinogen mRNA was identified in periatrial and periaortic brown adipocytes and in fibroblast-like cells of periaortic connective tissue and mesentery. Angiotensinogen gene expression in brown adipose tissue was confirmed by both Northern blot analysis and cell-free translation of RNA extracted from brown adipose tissue. For control rats, the level of angiotensinogen mRNA of brown adipose tissue, quantitated by Northern blot analysis, was 5% of the level in liver and showed a 12-fold increase in response to treatment with the combination of dexamethasone, ethynylestradiol, and T3. Comparison of the relative amounts of angiotensinogen mRNA detected by hybridization in situ in liver and brown adipose tissue, with the amounts determined by Northern blot analysis, revealed that hybridization in situ detected mRNA in brown adipose tissue with higher efficiency than in liver. These results suggest a role for angiotensinogen gene expression in brown adipose tissue function. In addition, these studies show that tissue-specific factors may modify the efficiency of detection of tissue mRNA using hybridization in situ.


Heavy metal exposure linked to metabolic syndrome in Korean male firefighters: FRESH cohort cross-sectional analysis.
This study aimed to identify the relationship between blood lead and Cadmium (Cd) concentrations and metabolic syndromes (MetS), including its components (central obesity, hypertriglyceridemia, low high-density lioioritein, hypertension, and hyperglycemia) among Korean firefighters. A total of 965 firefighters of the Enhancement of Safety and Health cohort were analyzed in this study. MetS was defined according to the 2005 revised National Cholesterol Education Program-Adult Treatment Panel III criteria and the Korean Society for the Study of Obesity criteria for waist circumference. The collected data were analyzed using a logistic regression model. Of the 965 participants, 190 (19.7%) had MetS. After adjusting for age, body mass index, smoking, drinking, exercise, shift duty, and main duty position, the Cd level was significantly associated with an increased risk of MetS in the Korean firefighter population (odds ratio [OR] = 1.62, 95% confidence interval [CI] 1.07, 2.46). This association was significant among non-smokers and ex-smokers (OR = 1.58, 95% CI 1.03, 2.43), non-drinkers and ex-drinkers (OR = 1.77, 95% CI 1.06, 2.94), firefighters aged 40 year or older (OR = 1.77, 95% CI 1.10, 2.86), and office administrators (OR = 3.85, 95% CI 1.42, 10.39). This outcome suggests that exposure to Cd is likely to increase risk of MetS among firefighters.


Illness perception of adolescents with allergic conditions under specialist care.
Our understanding of how adolescents perceive and cope with their allergic condition/s is limited. This study used the Brief Illness Perception Questionnaire (BIPQ) in a group of adolescents with allergies and correlates the findings with demographic and clinical conditions. In this retrospective questionnaire-based study, we analysed 100 valid questionnaires from adolescents (11-18 years) attending our service after receiving management and treatment for their allergic condition/s. The overall BIPQ score was 4.8 (IQR 3.6-5.6). The highest item-related scores were for "timeline" (illness duration) followed by "concern." The lowest scores were found for "coherence/understanding," demonstrating that adolescents do not perceive that they have a sound understanding of their condition/s. We found a significant difference in the overall BIPQ scores between the genders and in the emotional representation score, with females showing a highest score. Older adolescents reported a more chronic perception of the allergic disease/s. Our results suggest that a better understanding and support of the allergic condition/s in adolescents, particularly in females, are likely an important target for intervention intended to improve their quality of life. BIPQ can be used as adjunct to routine allergy clinic appointments for further exploration of the wider impact of allergies on adolescents' lives.


Pre-referral stabilization and compliance with WHO guidelines for trauma care among adult patients referred to an urban emergency department of a tertiary referral hospital in Tanzania.
The outcomes of trauma are considered to be time dependent. Efficient and timely pre-referral stabilization of trauma patients has been shown to impact survival. Tanzania has no formal pre-hospital or trauma system. World Health Organisation has provided a set of standards for initial stabilization of trauma patients according to the level of the hospitals. We aimed to describe pre-referral stabilization provided to adult trauma patient referred to the national referral hospital and compliance with World Health Organisation guidelines. This prospective observational cross-sectional study was conducted at the Emergency Medicine Department of Muhimbili National Hospital (EMD-MNH), between July 2017 and December 2017. Eligible patients were adults with head injury and extremity injury ≥18 years who were referred from a peripheral hospital and had a referral note. Research assistant enrolled patients using structured case report form clinical information, and initial stabilization received at the referring hospital. Primary outcome was the proportion of patients who had initial stabilization performed according to World Health Organisation recommendation. We enrolled 368 (29% of eligible patients), the median age was 34 years (Interquartile range 26-44 years), and 281 (76%) were male. Overall 69% of referred patients arrived at the EMD more than 24 h after injury. Of those enrolled, 50 (13.6%) patients had received at least one stabilization intervention prior to transfer to MNH. Among 206 patients with extremity injuries, splinting was inadequate or missing in all cases; No patients with head injury received cervical spine protection. Among patients referred from a health center, 26.9% received an initial stabilization, while stabilization procedures were administered to 13.2% of those from district hospitals, and 10% of those from regional hospitals. In this urban public emergency department in Tanzania, majority of trauma patients were referred from lower health facilities after 24-h of injury. Most did not receive initial trauma stabilization as recommended by the World Health Organisation guidelines. Future studies should identify barriers to pre-referral stabilization of adult trauma patients.


Calcium currents in rat cerebellar Purkinje cells maintained in culture.
Calcium permeabilities were examined in large cerebellar neurons maintained in culture, and morphologically identified as Purkinje cells. When cells were supplied with a Dulbecco Minimum Eagle's Medium with 10% horse serum added (5-10 days), somatic recordings revealed complex spikes and these were shown to be generated by Na and Ca components, the Na one being tetrodotoxin-sensitive. At the dendritic level, Ca currents were better resolved than at the soma. In dendrites, Ca entry was shown to occur through at least two distinct currents. The first was a low-threshold transient current (elicited above -60 mV from a holding potential of -80 mV) which was reduced by almost 30% by 50 microM cadmium. The second was a high-threshold current (above -20 mV) which gave rise to (1) a transient component exhibiting a steady-state inactivation and so requiring holding potentials at -80 mV, and (2) a sustained component. Both components were suppressed by 50 microns cadmium. We measured a total Ca current at the dendritic level reaching values of up to 1 nA. In another culture medium (Leibovitz medium) known to allow expression of three types of calcium currents in nodose cells we observed the development of the dendritic tree of Purkinje cells but with no simultaneous expression of the high-threshold Ca current.


The effect of leptin on maturing porcine oocytes is dependent on glucose concentration.
Increased body weight is often accompanied by increased circulating levels of leptin and glucose, which alters glucose metabolism in various tissues, including perhaps the oocyte. Alteration of glucose metabolism impacts oocyte function and may contribute to the subfertility often associated with obese individuals. The objective of this study was to determine the effect of leptin (0, 10, and 100 ng/ml) on the oocyte and cumulus cells during in vitro maturation under differing glucose concentrations. We examined the effects of leptin on oocyte maturation, blastocyst development, and/or gene expression in oocytes and cumulus cells (IRS1, IGF1, PPARγ, IL6, GLUT1) in a physiological glucose (2 mM) and high glucose (50 mM) environment. We also evaluated the effect of leptin on glucose metabolism via glycolysis and the pentose phosphate pathway. In a physiological glucose environment, leptin did not have an influence on oocyte maturation, blastocyst development, or oocyte gene expression. Expression of GLUT1 in cumulus cells was downregulated with 100 ng/ml leptin treatment, but did not affect oocyte glucose metabolism. In a high glucose environment, oocyte maturation and glycolysis were decreased, but in the presence of 100 ng/ml leptin, these parameters were improved to levels similar to control. This effect is potentially mediated by an upregulation of oocyte IRS1 and a correction of cumulus cell IGF1 expression. The present study demonstrates that in a physiological glucose concentration, leptin plays a negligible role in oocyte function. However, leptin appears to modulate the deleterious impact of a high glucose environment on oocyte function.


Optimization of the differentiation and quantification of high-Z nanoparticles incorporated in medical devices for CT-guided interventions.
Material differentiation has been made possible using dual-energy computed tomography (DECT), in which the unique, energy-dependent attenuating characteristics of materials can provide new diagnostic information. One promising application is the clinical integration of biodegradable polymers as temporary implantable medical devices impregnated with high-atomic number (high-Z) materials. The purpose of this study was to explore the incorporation of high atomic number (high-Z) contrast materials in a bioresorbable inferior vena cava filter for advanced CT-based monitoring of its location and differentiating from surrounding materials. Imaging optimization and calibration studies were performed using a body phantom. The dual-energy CT (DECT) ratios for iron, zirconium, barium, gadolinium, ytterbium, tantalum, tungsten, gold, and bismuth were generated for peak kilovoltage combinations of 80/150Sn, 90/150Sn, and 100/150Sn kVp in dual-source CT via linear regression of the CT numbers at low and high energies. A secondary calibration of the material map to the nominal material concentration was generated to correct for use of materials other than iodine. CT number was calibrated to the material concentration based on single-energy CT (SECT) with additional filtration (150Sn kVp). These quantification methods were applied to monitoring of biodegradable inferior vena cava filters (IVCFs) made of braided poly(p-dioxanone) sutures infused with ultrasmall bismuth nanoparticles (BiNPs) implanted in an adult domestic pig. Qualitative material differentiation was optimal for high-Z (>73) contrast agents in DECT. However, quantification became nonlinear and inaccurate as the K-edge of the material increased. Using the high-energy (150Sn kVp) data component as a SECT scan, the linearity of quantification curves was maintained with lower limits of detection than with DECT. Among the materials tested, bismuth had optimal differentiation from iodine in DECT while maintaining increased contrast in high-energy SECT for quantification (11.5% error). Coating the IVCF with BiNPs resulted in markedly greater radiopacity (maximum CT number, 2028 HU) than that of an uncoated IVCF (maximum CT number, 127 HU). Using DECT imaging and processing, the BiNP-IVCF could be clearly differentiated from iodine contrast injected into the inferior vena cava of the pig. These findings may improve widespread integration of medical devices incorporated with high-Z materials into the clinic, where technical success, possible complications, and device integrity can be assessed intraoperatively and postoperatively via DECT imaging.


Spicing up the menu: evidence of fruit feeding in Galago moholi.
The African lesser bushbaby, Galago moholi, is described as a food specialist, feeding exclusively on small arthropods and gum primarily from Acacia karroo trees. We studied a population of G. moholi in a highly fragmented habitat in the southernmost part of its natural distributional range in South Africa. In this habitat, we opportunistically observed bushbabies feeding on fruits of the winter fruiting tree, Pappea capensis. Plot counts of tree composition revealed that although the dominant tree species in the area belonged to the genus Acacia, A. karroo trees were widely absent and gum could only be found in small quantities on other Acacia species. The analysis of P. capensis fruits showed high levels of protein, fat, and energy content, making the fruits a potentially important food source for G. moholi during winter when insect availability is low. Our observation is the first documented case of fruit feeding in G. moholi, suggesting that the species is not a food specialist as previously reported but can supplement its diet with fruit when available.


Deviated nose: Physiological and pathological changes of the nasal cavity.
Deviated nose is highly challenging in rhinoplasty since the surgeon should consider both aesthetic and functional aspects of the nose. Deviated nose correction is surgically complex, and a thorough understanding of the mechanical and physiological changes of intranasal structures, including the septum and turbinates, is necessary for functional improvement.


Localization and subcellular distribution of smg p25A, a ras p21-like GTP-binding protein, in rat brain.
We have made a monoclonal antibody which specifically recognizes smg p25A among many ras p21/ras p21-like GTP-binding proteins thus far purified from bovine brain membranes. By use of this antibody, we have investigated the localization and subcellular distribution of smg p25A in rat brain by light and electron microscopic immunocytochemistry and by immunoblotting. By light microscopic immunocytochemistry, specific immunoreactivity is widely distributed, most abundant in neuropil, weak in neuronal somata, and absent from white matter. By electron microscopic immunocytochemistry, intense labeling is demonstrated on most of the synapses and concentrated in the presynaptic area where synaptic vesicles are observed. Presynaptic plasma membranes are weakly labeled but mitochondria, postsynaptic plasma membranes, and postsynaptic densities are unlabeled. In subcellular fractionation analysis of cerebrum, about one-fifth of smg p25A is found in the soluble cytosol fraction and the rest is found in the particulate fraction. About half of the particulate-bound smg p25A is recovered in the P2 fraction containing synaptosomes, mitochondria, and myelin, among which a major portion of smg p25A is recovered in the synaptosomal fraction. In the synaptosomal fraction, smg p25A is concentrated about 8-fold in the fraction containing synaptic vesicles and about 3-fold in the fraction containing synaptic plasma membranes compared with the original homogenate. smg p25A is present at a low level in the fraction containing synaptosomal soluble substances but almost absent from the fractions containing intrasynaptosomal mitochondria or post-synaptic densities. These results suggest that smg p25A plays important roles in the regulation of synaptic functions such as exo-endocytotic recycling of synaptic vesicles during neurotransmitter release.


Endoscopic management of a spontaneous rectus sheath hematoma causing bladder perforation.
Rarely pelvic hemorrhage events can lead to bladder perforation. We present a 48-year-old female who developed a spontaneous rectal sheath hematoma which perforated her bladder. Her case was monitored with serial MRI imaging and managed with two endoscopic clot resections which demonstrated new epithelialization of the bladder wall across the hematoma point of entry. We conclude that the bladder has an impressive potential to heal and select cases of symptomatic invasive bladder hematomas may be monitored with serial imaging and managed endoscopically.


Should progesterone on the human chorionic gonadotropin day still be measured?
To evaluate in our setting whether there is currently a level of P on the hCG day (P-hCG) predictive of no pregnancy. Observational study of prospectively collected data of the P-hCG levels of stimulated IVF cycles. In vitro fertilization unit. All cycles of IVF/intracytoplasmic sperm injection with fresh embryo transfer performed between January 2009 and March 2014. None. Pregnancy rate. Clinical pregnancy rate per ET was 38.7% and live birth rate was 29.1%. The P-hCG concentration was positively correlated to E2 on the hCG day, and the number of oocytes was negatively correlated to age. Progesterone on hCG day was higher among agonist- compared with antagonist-treated patients (mean ± SD: 1.13 ± 0.69 ng/mL vs. 0.97 ± 0.50 ng/mL) and among recombinant FSH compared with recombinant FSH + hMG stimulation (mean ± SD: 1.11 ± 0.58 ng/mL vs. 0.94 ± 0.50 ng/mL). Pregnancy rate was positively associated with the number of oocytes. There was no correlation between P-hCG value and pregnancy rate, overall or according to the type of treatment. In our setting there is no P-hCG value differentiating a good from a poor cycle success rate. NCT02323347.


Discovering phonetic coherence in acoustic patterns.
Despite spectral and temporal discontinuities in the speech signal, listeners normally report coherent phonetic patterns corresponding to the phonemes of a language that they know. What is the basis for the internal coherence of phonetic segments? According to one account, listeners achieve coherence by extracting and integrating discrete cues; according to another, coherence arises automatically from general principles of auditory form perception; according to a third, listeners perceive speech patterns as coherent because they are the acoustic consequences of coordinated articulatory gestures in a familiar language. We tested these accounts in three experiments by training listeners to hear a continuum of three-tone, modulated sine wave patterns, modeled after a minimal pair contrast between three-formant synthetic speech syllables, either as distorted speech signals carrying a phonetic contrast (speech listeners) or as distorted musical chords carrying a nonspeech auditory contrast (music listeners). The music listeners could neither integrate the sine wave patterns nor perceive their auditory coherence to arrive at consistent, categorical percepts, whereas the speech listeners judged the patterns as speech almost as reliably as the synthetic syllables on which they were modeled. The outcome is consistent with the hypothesis that listeners perceive the phonetic coherence of a speech signal by recognizing acoustic patterns that reflect the coordinated articulatory gestures from which they arose.


Interaction of a spirooxazine dye with latex and its photochromic efficiency on cellulosic paper.
Spirooxazine (SO) is a class of important photochromic dyes for many applications, such as anti-counterfeiting printing, reversible memory photo devices and optical switching elements in molecular electronics. Since these dyes are expensive, improving their coloration efficiency in response to photo stimuli is of practical importance. In this study, a spirooxazine dye, 1,3-dihydro-1,3,3-trimethylspiro[2H-indole-2,3'-[3H]naphtha[2,1-b][1,4]oxazine], was dispersed into the substrate of a polystyrene acrylic latex emulsion to obtain a stable photochromic dye loaded latex. The photochromic latex was then applied on cellulose paper, and its coloration efficiency was significantly higher than the control (without the latex). Transmission electron microscope (TEM) observation revealed that the spirooxazine dye was well dispersed into the matrix of the latex particles, which functioned as a carrier/dispersant for the photochromic dye. Other results, including color stability, and fatigue resistance, were also discussed.


Impairment of microsomal calcium sequestration activity upon superoxide dismutase depletion in rat liver.
We have studied the Ca2+-accumulation activity of microsomal vesicles isolated from the liver of rats held for from 2 to 8 weeks on a copper-deficient diet. With this treatment that deeply modifies fatty acid composition, microsomal membranes show progressively lower Ca2+ sequestration. The activity can be fully restored upon physiological copper supply to the depleted animals. The determination of kinetic parameters of microsomal Ca2+ uptake shows that copper deficiency affects mainly the apparent velocity, leaving unaffected the apparent affinity of the pump for Ca2+. Many similarities were found between this model and the Morris hepatomas with different growth rate. The data support the hypothesis that the oxidative stress imposed on the cell by the loss of superoxide dismutase can influence many cell features, with different implications in the regulation of several biological and biochemical functions.


Modification of the cysteamine side chain of thienamycin. II.
A new type of thienamycin derivatives (3a-3j, 4a, 4b), having a monothioacetal or a thioacetal side chain at the C-2 position was prepared, and the susceptibility to renal dehydropeptidase-1 (DHP-1) and the antimicrobial activity of these compounds were determined. The structure-activity relationships of these derivatives are also discussed.


Effect of fascial Manipulation® on reaction time.
This study aimed to investigate the effects of fascial manipulation (FM) on muscle force and electrical activity. Sixty healthy adult participants were randomly assigned to the FM intervention group (FM group; n = 20), static stretching intervention group (SS group; n = 20), and control group (C group; n = 20). The FM group underwent FM for the right brachial fascia (antecubitus) for 210 s. The SS group underwent static stretching of the right biceps brachii for 210 s. The C group was supine for 210 s. Participants were asked to flex the right elbow joint as quickly as possible after a light signal appeared during three sessions (before, immediately after, and 1 week after the intervention). During each session, the muscle activity of the right biceps brachii and bending force of the right elbow joint were measured. We calculated the reaction time (RT), pre-motor time (PMT), motor time (MT), time to peak force (TPF), and time to peak activity (TPA) from these measurements. The RT, MT, TPA, and TPF of the FM group were significantly shorter immediately after or 1 week after the intervention compared with those before the intervention. The RT, MT, TPA, and TPF of the FM group were significantly shorter than those of the SS group or C group immediately after or 1 week after the intervention. FM improved RT, MT, TPA, and TPA, and the effects lasted for 1 week. Both mechanical and neurological factors may contribute to improvements in motor performance after FM.


Exploring the involvement of TASK-1 in the control of isolated rat right atrium function from healthy animals and an experimental model of monocrotaline-induced pulmonary hypertension.
The TASK-1 channel belongs to the two-pore domain potassium channel family. It is expressed in several cells of the heart, including the right atrial (RA) cardiomyocytes and the sinus node, and TASK-1 channel has been implicated in the pathogenesis of atrial arrhythmias (AA). Thus, using the rat model of monocrotaline-induced pulmonary hypertension (MCT-PH), we explored the involvement of TASK-1 in AA. Four-week-old male Wistar rats were injected with 50 mg/kg of MCT to induce MCT-PH and isolated RA function was studied 14 days later. Additionally, isolated RA from six-week-old male Wistar rats were used to explore the ability of ML365, a selective blocker of TASK-1, to modulate RA function. The hearts developed right atrial and ventricular hypertrophy, inflammatory infiltrate and the surface ECG demonstrated increased P wave duration and QT interval, which are markers of MCT-PH. The isolated RA from the MCT animals showed enhanced chronotropism, faster contraction and relaxation kinetics, and a higher sensibility to extracellular acidification. However, the addition of ML365 to extracellular media was not able to restore the phenotype. Using a burst pacing protocol, the RA from MCT animals were more susceptible to develop AA, and simultaneous administration of carbachol and ML365 enhanced AA, suggesting the involvement of TASK-1 in AA induced by MCT. TASK-1 does not play a key role in the chronotropism and inotropism of healthy and diseased RA; however, it may play a role in AA in the MCT-PH model.