Unexpectedly strong binding of a large metal ion (Bi3+) to human serum transferrin.
Large metal ions (>0.9 A ionic radius) have previously been found to bind only weakly to human serum transferrin (hTF, 80 kDa), presumably because the interdomain cleft cannot close around the metal and synergistic anion. Surprisingly, therefore, we report that Bi3+ (ionic radius 1.03 A), a metal ion widely used in anti-ulcer drugs, binds strongly to both the N- and C-lobes with log K1* = 19.42 and log K2* = 18.58 (10 mM Hepes, 5 mM bicarbonate, 310 K). The uptake of Bi3+ by apo-hTF from bismuth citrate complexes is very slow (hours), whereas that from bismuth nitrilotriacetate is rapid (minutes). Evidence from absorption and NMR spectroscopy is presented to show that Bi3+ binds to the specific Fe3+ binding sites along with carbonate as the synergistic anion. Under the conditions used, preferential binding of Bi3+ to the C-lobe of hTF is observed. Linear free energy relationships show that there is a strong correlation between the strength of binding of Bi3+ and Fe3+ to a wide variety of ligands which include transferrin. Therefore we conclude that the strength of metal ion binding to transferrin is determined more by the ligand donor set than by the size of the ion.


Diffusion coefficients and local structure in basic molten fluorides: in situ NMR measurements and molecular dynamics simulations.
The local structure and the dynamics of molten LiF-KF mixtures have been studied by nuclear magnetic resonance (NMR) and molecular dynamics simulations. We have measured and calculated the self-diffusion coefficients of fluorine, lithium and potassium across the full composition range around the liquidus temperature and at 1123 K. Close to the liquidus temperature, D(F), D(Li) and D(K) change with composition in a way that mimics the phase diagram shape. At 1123 K D(F), D(Li) and D(K) depend linearly on the LiF molar fraction. These results show that the composition affects the self-diffusion of anions and cations more weakly than the temperature. The activation energy for diffusion was also determined and its value can be correlated with the strength of the anion-cation interaction in molten fluoride salts.


Acute Cauda Equina Syndrome Caused by Epidural Steroid Injection in the Setting of a Spinal Dural Arteriovenous Fistula.
We present a case of acute cauda equina syndrome caused by an epidural steroid injection in the setting of a previously undiagnosed spinal dural arteriovenous fistula (SDAVF). Our patient was a 61-year-old man who presented to the emergency department with low back pain, inability to walk, paresthesias of his bilateral lower extremities, bowel and bladder incontinence, and saddle anesthesia. Physical examination revealed weakness and decreased sensation of the lower extremities as well as poor rectal tone and urinary retention. Magnetic resonance imaging (MRI) revealed evidence of spinal cord edema in the T9-10 region and a probable SDAVF with secondary distal thoracic cord ischemia. This case highlights the importance of prompt recognition of cauda equina syndrome in the emergency department, expedient imaging, and efficient transfers of care, which allowed this patient to quickly undergo necessary surgery that led to an almost complete recovery. It also highlights the importance of recognizing subtle changes on lumbar MRI.


[In-vitro plaque accumulation on different filling materials].
The influence of the surface roughness of dental filling materials as well as of specific properties of materials on plaque accumulation was to be tested in a comparative study for various materials (Degulor S, Amalcap SAS, Visio Dispers, Ketak-Fil, CuproDur, Harvard Cement) was to be tested in a comparative investigation. For this purpose, the different materials were placed in a Streptococcus mutans NCTC 10449 culture medium containing sucrose, and incubated for three days at 37 degree C. Following this, the specific accumulation of polysaccharides formed outside of cells (plaque) was subjected to gravimetric analysis. Filling materials that take a high polish (Degulor S, Amalcap SAS, Visio Dispers) accumulated only 25 to 50% as much plaque as did cements. Within the group of cements there were also differences (up to 40%) in spite of similar surface roughness. These differences are presumably due to properties specific to the materials. In preliminary examinations of the products named, antibacterial effects were registered in three cases (Degulor S, Harvard Cement and Cupro-Dur--inhibiting areola between 1 and 7.5 mm).


The kinetics of interferon clearance in mice: comparison of mouse and human interferon.
Mice were injected with three kinds of interferon, i.e., mouse, human leucocyte and human fibroblast interferon, and the kinetics of their clearance from the blood was compared. After intravenous injection, mouse interferon was cleared very rapidly with an initial half life to two to three minutes, while both types of human interferon were cleared rather slowly with a corresponding value of about 20 minutes. When mouse interferon was injected intramuscularly or intraperitoneally, only very low levels of interferon activity were detected in the serum, and the recovery did not exceed 1% at any time. In contrast, both types of human interferon gave appreciable levels of activity in the serum upon injection by the same routes, and the levels remained stable during the observation period. The recovery of human interferon in the blood was about 10-fold that of mouse interferon. Mouse interferon was not inactivated in vitro by incubation with normal mouse serum. Our results suggest the validity of using homologous interferon for studies on the kinetics of interferon clearance in experimental animals.


Evaluation of corneal biomechanical properties modification after small incision lenticule extraction using Scheimpflug-based noncontact tonometer.
To quantify the effect of small incision lenticule extraction (SMILE) on the corneal biomechanics using Scheimpflug noncontact tonometer (Corvis ST). Twenty eyes of twenty patients, evaluated as eligible for surgery, with high myopia and/or moderate myopic astigmatism, underwent small incision lenticule extraction (SMILE). All patients underwent Corvis ST preoperatively and postoperatively after 1 week, and 1 and 3 months to observe alterations of corneal biomechanical properties. The main outcome measures were Deformation Amplitude, 1st-AT, and 2nd-AT. The relationship between the amount of stroma removed and the percentage variation of the measured parameters from baseline was evaluated with generalized linear model from each time point. For completeness also intraocular pressure (IOP), central corneal thickness (CCT), and their variations after surgery were evaluated. The ratio between the amount of removed refractive error and, respectively, changes of Deformation Amplitude, 1st-AT, and 2nd-AT were significantly modified at the 1st week after surgery (P = 0.005; P = 0.001; P = 0.024). At 1 and 3 months these values did not show statistically significant alterations. Intraocular pressure and central corneal thickness showed statistically significant changes during follow-up. No significant modifications in biomechanical properties were observed after SMILE so this procedure could induce only minimal transient alterations of corneal biomechanics.


Pearls, tips, and tricks for use of the Nidek OPD-Scan and FinalFit software.
Nidek's FinalFit/NAVEX is likely the most comprehensive customized ablation platform currently available. This software/laser platform offers a full range of customized ablation treatments from aspheric ablation, topography-based, and (entire eye) aberrometry-based custom ablation. With the plethora of options available, a surgeon can treat a full spectrum of cases, ranging from primary eyes to highly aberrated eyes and those requiring retreatments due to previous refractive surgery. As with any new indication or surgical technique, a learning curve is involved and one should proceed step-by-step and carefully monitor his/her initial results.


Facile Synthesis of Methylsilsesquioxane Aerogels with Uniform Mesopores by Microwave Drying.
Methylsilsesquioxane (MSQ) aerogels with uniform mesopores were facilely prepared via a sol⁻gel process followed by microwave drying with methyltrimethoxysilane (MTMS) as a precursor, hydrochloric acid (HCl) as a catalyst, water and methanol as solvents, hexadecyltrimethylammonium chloride (CTAC) as a surfactant and template, and propylene oxide (PO) as a gelation agent. The microstructure, chemical composition, and pore structures of the resultant MSQ aerogels were investigated in detail to achieve controllable preparation of MSQ aerogels, and the thermal stability of MSQ aerogels was also analyzed. The gelation agent, catalyst, solvent, and microwave power have important roles related to the pore structures of MSQ aerogels. Meanwhile, the microwave drying method was found to not only have a remarkable effect on improving production efficiency, but also to be conducive to avoiding the collapse of pore structure (especially micropores) during drying. The resulting MSQ aerogel microwave-dried at 500 W possessed a specific surface area up to 821 m²/g and a mesopore size of 20 nm, and displayed good thermal stability.


Protura of Italy, with a key to species and their distribution.
The Italian Protura were studied basing on 5103 specimens from 198 sampling areas, along with bibliographic data from 49 collecting sites. 17 out of the 20 Italian regions are covered. As a result, 40 species have been identified (belonging to 8 genera and 4 families), 6 of which are new records for the Italian fauna.A key to the Italian species is reported, followed by a series of distribution maps and brief remarks for some of them. A preliminary biogeographical overview allowed us to delineate the chorological categories of these species, 10 of which are actually known only in Italy. The comparison with the species richness known for some best studied Central and Eastern European Countries leads us to speculate that widening our research, Italian Protura check-list will be much implemented.


Creatine kinase activity decrease with short-term freezing.
Freezing of serum samples at -30 degrees C without protective agents is the simplest and least expensive method of storage in serum banks. We investigated the stability of creatine kinase (CK) in human sera after freezer storage under such conditions for 24 h (n = 30) or for 2 or 4 weeks (n = 99). CK activity was measured in fresh sera and compared to matched thawed sera after freezer storage at the designated time intervals. The enzyme's median activity decreased significantly after 24 h, 2 weeks, and 4 weeks of freezer storage by 2.6, 5.9, and 8.3%, respectively (p < 0.0001, r = 0.99). Sex or high CK initial values had no significant effect on these results. We conclude that freezer storage of serum at -30 degrees C, even for short periods, causes a steady and significant decline in CK activity. These results should be taken into consideration when analyzing CK activity in frozen sera for research or clinical purposes.


Phytophthora gallica sp. nov., a new species from rhizosphere soil of declining oak and reed stands in France and Germany.
A non-papillate, slow-growing Phytophthora species, which could not be assigned to any existing taxon, was isolated from rhizosphere soil of a declining oak in Northeast France, and from the rhizosphere of Phragmites australis at Lake Constance in south-west Germany in 1998 and 2004, respectively. We describe this species, previously informally designated Phytophthora taxon 'G', as Phytophthora gallica sp. nov. Morphology, growth rates, and pathogenicity against cuttings of riparian tree species and leaves of reed are described and compared with those of morphologically and phylogenetically similar Phytophthora species. P. gallica produces colonies with limited aerial mycelium and variable growth patterns. Gametangia are not formed in single or mixed cultures with tester strains of known mating types. P. gallica produces globose and elongated irregular chlamydospores, of which a high proportion is abortive. In water culture irregular hyphal swellings and non-papillate persistent sporangia are formed abundantly. P. gallica is moderately aggressive to Alnus glutinosa and Fagus sylvatica, weakly aggressive to Quercus robur and Salix alba and non-pathogenic to Fraxinus excelsior and Phragmites australis. According to ITS and mtDNA sequence data P. gallica belongs to a distinct Phytophthora clade, with P. boehmeriae and P. kernoviae being the closest relatives. The origin of P. gallica and its ecological role in wet ecosystems remain unclear.


Patterns of muscle coordination vary with stride frequency during weight assisted treadmill walking.
Partial body weight-supported treadmill training is an approach for gait rehabilitation. Variables such as stepping frequency and the amount of body weight support are key parameters manipulated during training. The purpose of this study was to quantify the extent to which body weight support and stride frequency contribute and interact to produce the coordination patterns of the leg muscles. Principal components analysis was used to provide insight into the interaction effects of these factors on electromyographical (EMG) activity during treadmill locomotion. Eight healthy subjects walked on a treadmill at 15 different combinations of weight support (0%, 20%, 40%, 60%, 100%), and stride frequency (0.40, 0.49, 0.57 Hz). Treadmill walking was performed with the Lokomat robotic gait orthosis to constrain leg kinematics. Surface EMG data were collected from several lower limb muscles. Results indicate that much of the variance in EMG activity during treadmill locomotion can be attributed to the mechanics of the locomotor task imposed by the level of body weight support and stride frequency. We also showed that body weight support and stride frequency interact in different ways to affect muscle coordination patterns. EMG coordination patterns are similar between conditions of high levels of body weight support and faster stride frequencies vs. lower levels of body weight support and slower stride frequency. Our data suggest that the interaction of body weight support and stride frequency should be taken into consideration for optimizing motor output during locomotor training.


Color Correction of Stained Tissue Section Images by Histogram Transfer According to Control Images.
To present a color correction method by histogram transfer depending upon control tissue image (CTI) differences, and subsequently evaluate its performance. Images from colon and placenta sections stained by anti-CD34 were used as CTI and/ or sample tissue images (STIs). In total, 36 slides were stained: 1 according to standard procedure and 35 with some variation in the durations or dilutions used for the staining process. For hematoxylin and eosin (20 slides) and Van Gieson (20 slides) stains, colonic mucosa and liver tissues were used. Digital images without normalization were taken by a CCD camera connected to a light microscope and stored on a computer. A software tool was developed in order to find the histogram difference between 2 CTIs and transfer the difference to the STI for achieving a corrected STI (corSTI). sSTI (1 image) and STI and corSTI (for each image) were semiquantitatively scored by 2 observers in blind fashion, and the STI and corSTI scores were compared with the sSTI score. Total optic density (TOD) and median optic density (MOD) and intensity were also calculated by the software. The STI semiquantitative score was equal to the sSTI in 23.5% of the image; this improved to 76.35% when the corSTI was compared to the sSTI. The concordance of TOD and intensity values of CD34-stained placenta images, as well as TOD and MOD values of H&E-stained colonic mucosa images, with the values calculated for the sSTI, increased following image correction. These results suggest that histogram transfer depending upon CTIs may be a valuable tool for color correction of tissue section images.


A model of the gastric gland ejection cycle: low ejection fractions require reduction of the glandular dead space.
This paper was inspired by the reported results of authors from Uppsala and Lund that gastric glands in rats rhythmically contract 3-7 cycles per minute and develop luminal pressures more than 10 mmHg. To ensure that pepsinogen is not retained in the acid-rich section of the gland, ejection fractions would need to be more than 50% of the gland volume. We have tried to calculate the ejection fraction of such contractions. Dimensions of human gastric glands were measured on the fresh frozen samples of macroscopically and histologically normal gastric mucosa. In total, 18 specimens (from nine persons) were measured under the microscope. The density of glands was 135 +/- 11 (mean +/- S.D.) glands per mm( 2) of gastric mucosa. A typical gastric gland is a tubular structure 1.2 +/- 0.22 mm long and 0.03-0.05 mm wide. We have used 1 mm for length and 0.03 mm for the gland diameter to calculate that each gland approximates a volume of 707 pl, suggesting that the total glandular volume for 15 million glands reaches 10.6 ml. Further calculations based on one to five contractions per minute on an average and on the total volume of gastric glands of 10 ml showed that only ejection fractions less than 10% deliver daily volumes less than 3 l. The presented model of the gastric gland activity is based on the idea that the low ejection fractions require a reduction of the glandular dead space. The reduced luminal pressure during the gland relaxation might cause backflux of hydrophobic viscoelastic mucus through the gland aperture. Repeated glandular contractions and relaxations would move the mucus all the way to the gland bottom, filling the gland cavity below the neck with an axial semisolid mucous cylinder. This filling would reduce the gland dead space. During contractions, the gland would eject mainly the peripheral, the more liquid part of its content. The decreasing luminal pressure in the relaxing gland would pull the outlet mucus inside, protecting gland apertures from the gastric juice.


Medicinal chemistry of 2,2,4-substituted morpholines.
We have designed a number of 2-hydroxy (alkoxy)-2-aryl-4-alkyl-(5,6-alkyl)-morpholines with interesting biological activities, i.e. sympathomimetic, analgesic, drug metabolizing enzyme modulating ability, antioxidant potential, anti-inflammatory and anti-dyslipidemic properties. They are synthesised by reaction of the proper 2-aminoethanol with aryl-bromomethyl-ketone. The intermediate hydroxyaminoketone is spontaneously cyclised to form the tetrahydro-1,4-oxazine ring. The produced 2-hydroxy substituted morpholines form the 2-alkoxy derivatives. The 2-hydroxy or 2-alkoxy-1,4-oxazine derivatives can lose water or alcohol, to give styrene-type products. The conditions for oxazine ring formation and water or alcohol abstraction are investigated. Ionisation constants and partition coefficients have been determined and related to structure and activity. The biological activities of these compounds are quite interesting: The 2-phenyl analogues acquire the structural requirements for sympathomimetic amines, and present a structure related to the pethidine-type analgesics. Indeed, they show central dopaminergic and analgesic, antagonized by naloxone, activities. They also affect drug metabolising enzymes. The 2- phenyl and especially the 2-biphenyl derivatives are good antioxidants, also possessing anti-inflammatory and immunomodulating action. The later class of compounds reduces remarkably plasma triglycerides, total cholesterol and LDL-cholesterol in hyperlipidemic rats. Since NO plays a multiple role in atheromatosis and inflammation, some 2-nitroxy-alkoxy derivatives are synthesized and their NO-liberating ability assessed. These nitric esters are also found to be potent hypolipidemic-hypocholesterolemic agents. In a mechanism elucidation attempt, it is indicated that these derivatives may act as squalene synthase inhibitors.


Ocular Complications of Diabetes and Therapeutic Approaches.
Diabetes mellitus (DM) is a metabolic disease defined by elevated blood glucose (BG). DM is a global epidemic and the prevalence is anticipated to continue to increase. The ocular complications of DM negatively impact the quality of life and carry an extremely high economic burden. While systemic control of BG can slow the ocular complications they cannot stop them, especially if clinical symptoms are already present. With the advances in biodegradable polymers, implantable ocular devices can slowly release medication to stop, and in some cases reverse, diabetic complications in the eye. In this review we discuss the ocular complications associated with DM, the treatments available with a focus on localized treatments, and what promising treatments are on the horizon.


[Change and consistency in nuptiality in Mexico].
The author uses census data to analyze recent trends in nuptiality in Mexico. She notes that "the fact that census data include both married and common-law couples enables...[questions] to be answered at the same time as it allows one to trace the development of the main indexes of marriage rates from 1930 to 1990. Differences between the sexes are established to provide a fuller analysis and a distinction is made between changes experienced by common-law and married couples." (SUMMARY IN ENG)


Quantification of epithelial cells in coculture with fibroblasts by fluorescence image analysis.
To demonstrate that senescent fibroblasts stimulate the proliferation and neoplastic transformation of premalignant epithelial cells (Krtolica et al.: Proc Natl Acad Sci USA 98:12072-12077, 2001), we developed methods to quantify the proliferation of epithelial cells cocultured with fibroblasts. We stained epithelial-fibroblast cocultures with the fluorescent DNA-intercalating dye 4,6-diamidino-2-phenylindole (DAPI), or expressed green fluorescent protein (GFP) in the epithelial cells, and then cultured them with fibroblasts. The cocultures were photographed under an inverted microscope with appropriate filters, and the fluorescent images were captured with a digital camera. We modified an image analysis program to selectively recognize the smaller, more intensely fluorescent epithelial cell nuclei in DAPI-stained cultures and used the program to quantify areas with DAPI fluorescence generated by epithelial nuclei or GFP fluorescence generated by epithelial cells in each field. Analysis of the image areas with DAPI and GFP fluorescences produced nearly identical quantification of epithelial cells in coculture with fibroblasts. We confirmed these results by manual counting. In addition, GFP labeling permitted kinetic studies of the same coculture over multiple time points. The image analysis-based quantification method we describe here is an easy and reliable way to monitor cells in coculture and should be useful for a variety of cell biological studies.


Functional expression of the endogenous Thy-1 gene and the transfected murine Thy-1.2 gene in rat basophilic leukemia cells.
An interaction of MRC OX7 monoclonal antibody with Thy-1.1 antigen of rat peritoneal and pleural mast cells has been previously shown to induce rat mast cell activation (L. Dráberová, Eur. J. Immunol. 1989, 19: 1715). In the present study we analyzed the expression and function of the Thy-1 antigen in rat basophilic leukemia cells, clone RBL-2H3. Two RBL-2H3-derived cell lines with stable expression of murine Thy-1.2 antigen, after transfection of a genomic clone of murine Thy-1.2 or Thy-1.2 cDNA under the control of simian virus 40 promoter, were also analyzed. Direct radioantibody binding assays, indirect immunofluorescence studies and flow cytometry analyses revealed that both endogenous Thy-1.1 and transfected murine Thy-1.2 gene products were expressed on the surface of the cells under study. Analysis of the distribution of the Thy-1 antigen in situ in cells grown attached to tissue culture vessels located the Thy-1 predominantly in regions of cell-cell contacts. Incubation of RBL-2H3 cells with Thy-1.1-specific antibodies, or of the transfected cells with both Thy-1.1- and Thy-1.2-specific antibodies, induced a rapid early increase in the concentration of intracellular free calcium [( Ca2+]i) released from internal stores. Sustained increase of [Ca2+]i required the presence of Ca2+ in the extracellular medium. The increase in [Ca2+]i was followed by histamine release from the target cells. The combined data indicate that RBL-derived cells can be used as a useful model system for analysis of Thy-1 antigen-mediated activation of rat mast cells.


Selective killing of cholinergic neurons by microglial activation in basal forebrain mixed neuronal/glial cultures.
Microglia activation by lipopolysaccharides (LPS) significantly decreased choline acetyltransferase-immunopositive (ChAT+) neuron number and ChAT activity in rat primary basal forebrain mixed neuronal/glial cultures. The number of non-cholinergic (ChAT(-)) neurons was unaffected. LPS induced nitric oxide synthase (NOS) in microglia, increased the media level of the NO metabolite nitrite, and the NOS inhibitor Ng-nitro-L-arginine methylester (NAME) protected the ChAT+ neurons from LPS. The combination of beta-amyloid peptide (1-42) and interferon-gamma (INF-gamma) also increased the media nitrite level and decreased ChAT+ neuron number. Cholinergic neurons are lost early in the course of Alzheimer's disease, and the enhanced sensitivity of these neurons to microglial activation in mixed neuronal/glial culture may be useful for modeling Alzheimer's disease and developing therapeutic strategies to combat this disease.


Metabolic Effects of a Hydrophobic Alginate Derivative and Tetrahydrolipstatin in Rats Fed a Diet Supplemented with Palm Fat and Cholesterol.
The effects of octadecylamide of alginic acid (amidated alginate) and tetrahydrolipstatin on serum and hepatic cholesterol, and the faecal output of fat and sterols, were investigated in rats. Amidated alginate is a sorbent of lipids, tetrahydrolipstatin is an inhibitor of pancreatic lipase. Rats were fed diets containing cholesterol and palm fat at 10 and 70 g/kg, respectively. Palm fat was provided by coconut meal. Amidated alginate at 40 g/kg diet significantly decreased serum total cholesterol, low-density lipoprotein and hepatic cholesterol, and hepatic lipids and increased the faecal output of fat and coprostanol. Tetrahydrolipstatin at 300 mg/kg diet significantly decreased low-density lipoprotein cholesterol and hepatic lipids and increased the faecal output of fat. The intake of feed was not significantly influenced; however, the weight gains in rats fed amidated alginate were lower than in rats of the control group. Both amidated alginate and tetrahydrolipstatin modified the fatty acid profile in excreta lipids. Concentrations of saturated fatty acids were decreased and those of unsaturated fatty acids increased. Despite different modes of action, amidated alginate and tetrahydrolipstatin were equally efficient in removing the dietary fat from the body.


Contrasting effects of historical contingency on phenotypic and genomic trajectories during a two-step evolution experiment with bacteria.
The impact of historical contingency, i.e. the past evolutionary history of a population, on further adaptation is mostly unknown at both the phenotypic and genomic levels. We addressed this question using a two-step evolution experiment. First, replicate populations of Escherichia coli were propagated in four different environmental conditions for 1000 generations. Then, all replicate populations were transferred and propagated for further 1000 generations to a single new environment. Using this two-step experimental evolution strategy, we investigated, at both the phenotypic and genomic levels, whether and how adaptation in the initial historical environments impacted evolutionary trajectories in a new environment. We showed that both the growth rate and fitness of the evolved populations obtained after the second step of evolution were contingent upon past evolutionary history. In contrast however, the genes that were modified during the second step of evolution were independent from the previous history of the populations. Our work suggests that historical contingency affects phenotypic adaptation to a new environment. This was however not reflected at the genomic level implying complex relationships between environmental factors and the genotype-to-phenotype map.


Individual sarcomere lengths in whole muscle fibers and optimal fiber length computation.
Estimation of muscle fiber optimum length is typically accomplished using either laser diffraction or by counting the number of sarcomeres in a portion of the muscle fiber, measuring the distance that encompasses those sarcomeres and dividing by the number of sarcomeres to obtain an average sarcomere length. If the sarcomeres are not uniformly distributed, either of these techniques could produce errors when estimating optimum lengths. The purposes of this study were: to describe new software that automatically analyzes digital images of skeletal muscle fibers to measure individual sarcomere lengths; and to use this software to measure individual sarcomere lengths along complete muscle fibers to examine the influence of computing whole muscle fiber properties from portions of the fiber. Six complete muscle fibers were imaged using a digital camera attached to a microscope. The images were then processed to achieve the best resolution possible, individual sarcomeres along the image were detected, and each individual sarcomere length was measured. The software accuracy was compared with that of manual measurement and was found to be as accurate. In addition, the time to measure individual sarcomere lengths was greatly reduced using the software compared with manual measurement. The arrangement of individual sarcomere lengths demonstrated long-range correlations, which indicates problems in assuming only a portion of a fiber can be used to determine whole fiber properties. This study has provided evidence on the number of sarcomeres which must be analyzed to infer the properties of whole muscles.


[Mid-term results of heart valve replacement with 2 types of pericardial heterograft. Apropos of 208 cases].
Medium-term results of valve replacement with a pericardial bioprosthesis were analysed in 141 patients receiving an Ionescu-Shiley aortic prosthesis and in 67 patients receiving a Mitroflow aortic (42), mitral (21) or double mitro-aortic (4) bioprostheses. There were 8 deaths in the operative (5.7%) and medium term (56 months) follow-up periods in the Ionescu group and a cumulative survival of 625 patient-years. There were 16 late deaths, 8 of cardiac origin. The 8 year survival and good functional results rates were 71% and 53% respectively. The linear rates of thrombo-embolism, endocarditis, reoperation, valvular dysfunction and regurgitation were 3.5, 1.1, 2.6, 2.7 and 6.1% patient-years. The corresponding figures in the Mitroflow bioprostheses were 0.5, 1.0, 3.1, 3.1 and 5.6% patient-years, but the average follow-up was shorter (36 months) with a cumulative survival of 195 patient-years. These results underline the frequency of primary valve dysfunction the mechanisms of which are: early tear in areas of high mechanical stress and late calcification. However, the hemodynamic profiles of this type of prosthesis are better than those of porcine bioprostheses which make them a valuable alternative in elderly patients operated for calcific aortic stenosis with a small aortic ring.


Determinants of breastfeeding initiation in Ireland.
Ireland continues to rank among countries with the lowest breastfeeding initiation rates. National and regional studies also show that few women in Ireland who initiate exclusive breastfeeding continue to breastfeed for the recommended 6 months. To assess the rate of exclusive and partial breastfeeding in Ireland at three time periods: birth to 48 h, 3-4 months following birth, and when the infant was 6-7 months old. A longitudinal national cohort survey of 2527 mothers. Findings show that just 56 % (n = 1002) of mothers initiated breastfeeding at birth and, at 48 h, 42 % (n = 1064) of women were exclusively breastfeeding their babies. At 6-7 months, only 2.4 % of the 2527 mothers who took part, reported exclusive breastfeeding. Irish women were less likely to initiate breastfeeding (52.6 %) compared with Polish (82.2 %), British (64.5 %), and other nationalities (74.6 %). Multivariate analysis also revealed significant relationships between initiation and socio-economic variables, with mothers' health insurance status being of particular importance. The results highlight the necessity to support the initiation and maintenance of breastfeeding in Ireland, in order to reduce rates of infant morbidity.


Consumers of 4-chloro-2-methylphenoxyacetic acid from agricultural soil and drilosphere harbor cadA, r/sdpA, and tfdA-like gene encoding oxygenases.
Microbial degradation of 2-methyl-4-chlorophenoxyacetic acid (MCPA) in soil is enhanced by earthworms and initiated by tfdA-like, cadA and r/sdpA gene encoding oxygenases. Copy numbers of such genes increased during MCPA degradation in soil, and MCPA stimulated transcription of tfdA-like and r/sdpA genes up to 4×. Transcription of cadA was detected in the presence of MCPA only. DNA stable isotope probing after consumption of 0.6-0.8 mg 13C-MCPA gdw -1 in oxic microcosms indicated diverse labeled oxygenase genes in bulk soil, burrow walls, and cast. 9, 6, and 3 operational taxonomic units of tfdA-like, cadA, and r/sdpA genes, respectively, were labeled and affiliated with group 2 Alphaproteobacteria including Bradyrhizobia and group 1 class III Betaproteobacteria. New genes encoding putative MCPA degrading oxygenases were identified. Diversity of labeled OTUs tended to be lower for cast than for bulk soil. The collective data indicate (1) hitherto unknown active MCPA degraders and/or oxygenase genes in soil; (2) that multiple oxygenases are associated with MCPA degradation in soil at the same time; (3) that earthworms impact the capability of MCPA degraders in soil to respond to MCPA; and (4) the collective data enable a more in-depth analysis of MCPA degrader communities in soil by future structural gene-based experimental strategies.


Mode of grasp, materials, and grooved chopstick tip on gripping performance and evaluation.
This study evaluated the effects of the mode of grasping, chopstick materials, and the groove of the chopstick-tip on gripping performance of 32 participants, among whom 16 were accustomed to using chopsticks with a pliers-grasping mode and the other 16 with a scissors-grasping mode. Based on a random sequence, 8 kinds of chopsticks with different combinations (materials: bamboo, wood, plastic, and stainless steel, with and without grooves in the chopstick-tip) were used to carry out the action of gripping two different objects (peanuts and longan). The time to finish gripping 50 pieces of peanut and longan, the number which fell on the table when gripping, the subjective effort and the subjective preference were measures of efficiency of pinching for 8 kinds of chopsticks. Analysis showed that chopstick materials significantly affect time of gripping. The large object (such as longan) could be gripped more easily with the pliers-grasping mode or gripped with the grooved chopstick-tip. However, for small objects (such as peanuts), there was no significant difference in performance whether the chopstick-tip was grooved or not. A combination of bamboo chopsticks with grooved tips used with a pliers-grasping seem preferrable for more favorable gripping performance.


Evaluation of outcome and prognostic factors in patients of glioblastoma multiforme: A single institution experience.
We present retrospective analysis of patients of glioblastoma multiforme (GBM) and discuss clinical characteristics, various treatment protocols, survival outcomes, and prognostic factors influencing survival. From January 2002 to June 2009, 439 patients of GBM were registered in our department. The median age of patients was 50 years, 66.1% were males, and 75% underwent complete or near-total excision. We evaluated those 360 patients who received radiotherapy (RT). Radiotherapy schedule was selected depending upon pre-RT Karnofsky Performance Status (KPS). Patients with KPS < 70 (Group I, n = 48) were planned for RT dose of 30-35 Gy in 10-15 fractions, and patients with KPS ≥ 70 (Group II, n = 312) were planned for 60 Gy in 30 fractions. In group I, six patients and in group II, 89 patients received some form of chemotherapy (lomustine or temozolomide). Statistical analysis was done using Statistical Package for Social Sciences, version 12.0. Overall survival (OS) was calculated using Kaplan-Meier method, and prognostic factors were determined by log rank test. The Cox proportional hazards model was used for multivariate analysis. The median follow-up was 7.53 months. The median and 2-year survival rates were 6.33 months and 2.24% for group I and 7.97 months and 8.21% for group II patients, respectively (P = 0.001). In multivariate analysis, site of tumor (central vs. others; P = 0.006), location of tumor (parietal lobe vs. others; P = 0.003), RT dose (<60 Gy vs. 60 Gy; P = 0.0001), and use of some form of chemotherapy (P = 0.0001) were independent prognostic factors for survival. In patients with GBM, OS and prognosis remains dismal. Whenever possible, we should use concurrent and/or adjuvant chemotherapy to maximize the benefits of post-operative radiotherapy. Patients with poor performance status may be considered for hypofractionated RT schedules, which have similar median survival rates as conventional RT.


Soluble Receptor for Glycation End-products Concentration Increases Following the Treatment of Severe Diabetic Ketoacidosis
To determine the time relationships of soluble receptor for glycation end-products (sRAGE), [a decoy of the advanced glycation end-products (AGE)-RAGE axis] and D-lactate, (a metabolite of methylglyoxal) in the inflammatory response to diabetic ketoacidosis (DKA). Sixteen children and adolescents with type 1 diabetes (T1D) had blood samples obtained, 6-12 hours into treatment, at three weeks and three months post start of treatment. sRAGE and D-lactate concentrations at three months were considered baseline. Expression of RAGE was investigated in the myocardium of a newly diagnosed and untreated young person with fatal T1D/DKA. sRAGE 6-12 hours after the start of treatment was 39% lower than the values at two weeks (p=0.0036) and at three months (p=0.0023) post treatment. D-lactate was higher during treatment than at three weeks (p=0.04) and at three months (p=0.035). sRAGE concentration was decreased during treatment, compared to concentrations at two weeks and three months after treatment. The increased D-lactate during treatment was in keeping with the known increase in dicarbonyls at this time. The finding of RAGE expression in a young myocardium prior to DKA treatment suggested cardiovascular inflammation pre-treatment and at a young age.


Preparing the care relationship: a welcoming tool in health units.
This study aimed to identify and analyze aspects regarding the preparation for the worker-user relationship in a primary health care unit in a city in the state of São Paulo-Brazil, from the perspective of welcoming. The health work process is the theoretical basis of the study; participant observation and semi-structured interviews were used as data collection techniques, and thematic analysis in the analysis stage. For the welcoming to be processed, there is a 'moment' of preparation for the worker, the physical environment and the relationships present at work so that users are welcomed, in which the users' needs are sometimes disregarded. Despite the difficulties in terms of resource availability, especially in the public sector, when preparing the service/user and worker/user relationships, one should consider the aspects associated to a more human, welcoming relationship, since it is during live work, in this intersection, that care quality is established.


Brugada syndrome with SCN5A mutations exhibits more pronounced electrophysiological defects and more severe prognosis: A meta-analysis.
Whether the presence of SCN5A mutation is a predictor of BrS risk remains controversial, and patient selection bias may have weakened previous findings. Therefore, we performed this study to clarify the clinical characteristics and outcomes of BrS probands with SCN5A mutations. We systematically retrieved eligible studies published through October 2018. A total of 17 studies enrolling 1780 BrS patients were included. Overall, our results found that compared with BrS patients without SCN5A mutations, patients with SCN5A mutations exhibited a younger age at the onset of symptoms and higher rate of the spontaneous type-1 electrocardiogram pattern, more pronounced conduction or repolarization abnormalities, and increased atrial vulnerability. In addition, the presence of SCN5A mutations was associated with an elevated risk of major arrhythmic events in both Asian (odds ratio [OR] = 1.82, 95% confidence interval [CI] 1.07-3.11; P = .03) and Caucasian (OR = 2.24, 95% CI 1.02-4.90; P = .04) populations. In conclusions, patients with SCN5A mutations exhibit more pronounced electrophysiological defects and more severe prognosis. Clinicians should be cautious when utilizing genetic testing for risk stratification or treatment guidance before determining whether the causal relationship regarding SCN5A mutation status is an independent predictor of risk.


Abuse among Portuguese older people at a time of economic crisis recovery: findings from the Harmed study.
This study aimed to assess the prevalence of abuse against Portuguese older people after an economic crisis and to assess how it has influenced health. A cross-sectional study was carried out including 677 older adults (≥60 years) during 2017. Results show that overall, 23.9% of older people reported being a victim of abuse in the last 12 months. The prevalence of psychological abuse was 19.9%, financial abuse 5.8%, physical abuse 2.5% and sexual abuse 1.9%. Older people who report abuse were more likely to have perceived insufficient income and low social support. The abuse was also significantly associated with poor health status and depressive symptoms. Even in an auspicious period, more than a fifth of older people experiences abuse which is associated with social and health vulnerabilities. These results support that an investment should be made in terms of policies toward an age-friendly environment.


Characteristics of physicians targeted by the pharmaceutical industry to participate in e-detailing.
Electronic detailing (e-detailing) has been introduced in the last few years by the pharmaceutical industry as a new communication channel through which to promote pharmaceutical products to physicians. E-detailing involves using digital technology, such as Internet, video conferencing, and interactive voice response, by which drug companies target their marketing efforts toward specific physicians with pinpoint accuracy. A mail survey of 671 Iowa physicians was used to gather information about the physician characteristics and practice setting characteristics of those who are usually targeted by pharmaceutical companies to participate in e-detailing. A model is developed and tested to explain firms' targeting strategy for targeting physicians for e-detailing.


Chlamydiosis in pen-raised bobwhite quail (Colinus virginianus) and chukar partridge (Alectoris chukar) with high mortality.
In a flock of 12,000 bobwhite quail (Colinus virginianus) and 7200 chukar partridge (Alectoris chukar), the owner had 100% morbidity and 40%-50% mortality in birds between the ages of 2 and 4 wk. Affected birds were stunted and anorexic and had yellow/green diarrhea. Two- and 4-wk-old birds submitted for necropsy all had slight nasal discharge. Histopathologic examination revealed mild (bobwhite) to severe (chukar) rhinitis. Immunohistochemistry was positive for Chlamydia psittaci in all birds. Chlamydia psittaci organisms were demonstrated histopathologically in hematoxylin and eosin and Gimenez-stained slides. Management sanitation and treatment with chlortetracycline stopped further excessive losses. The owners were also infected. Treatment by their local physician with tetracycline alleviated symptoms.


Synaptic membrane G proteins are complexed with tubulin in situ.
The G proteins G S and Gi1 appear to be capable of binding to tubulin specifically, and it has been suggested that such binding results in G protein activation via direct transfer of GTP. This study was undertaken to demonstrate that consequences of G protein activation by tubulin, i.e., stimulation or inhibition of adenyl cyclase, were dependent on the G proteins expressed as well as unique aspects of the membrane or cytoskeleton in a given cell type. Membranes from rat C6 glioma cells, which express G s alpha but not G i alpha 1, responded to the addition of tubulin with a stable activation of adenyl cyclase. Conversely, membranes from rat cerebral cortex, which contain both G s and G i 1, responded to exogenous tubulin with a stable inhibition of adenyl cyclase. Unlike C6 membranes, cerebral cortex membranes are richly endowed with tubulin, and antitubulin antibodies immunoprecipitated complexes of tubulin and G i 1 and G s from detergent extracts of these membranes. Nearly 90% of the G s alpha from Triton X-114 extracts coimmunoprecipitated with tubulin, suggesting that these proteins exist as a complex in the synaptic membrane. Such complexes may provide the framework for a G protein-cytoskeleton link that participates in the modulation of cellular signal transduction.


Solidarity in medicine: the role of medical students and young doctors.
The descriptions of medical caring and of highly technical specialism and science utilize different vocabularies and language. Medical caring has an ancient glossary of words, gestures, and behavior which is rapidly being transformed by specialization and advances in the technology of communication. The technologic capabilities of intensive care have, for example, exceeded the human life span and forced redefinition of the meaning of being olive. There are risks for the contemporary profession as linguistic and technical evolution proceed at a faster pace than the evolution of human health and illth. The accentuation and acceleration of generational disparity between the young and the old diminishes the solidarity of the profession and the quality of care that it provides.


Southwestern internal medicine conference: growth hormone--aging and osteoporosis.
Until recently, the use of growth hormone (GH) has been confined to the treatment of GH-deficient children. The advent of GH produced by recombinant DNA technology has increased the availability of GH. The increased availability of GH has made possible studies of the physiology and the possible therapeutic role of this hormone and its mediator insulin-like growth factor. One area where GH may play a therapeutic role is in the treatment of osteoporosis. This review will briefly summarize normal GH physiology and discuss age-related changes in GH and insulin-like growth factor 1 (IGF-1) axis and how they may relate to age-related physiologic changes. Evidence for and against a possible therapeutic role for GH/IGF-1 in the treatment of age-related (senile) osteoporosis will be discussed.


Onset of auditory deprivation.
The purpose of this investigation was to study further the assertion that auditory function deteriorates in the unaided ear of individuals with sensorineural hearing loss (SNHL) who receive monaural hearing aid fittings. The word recognition scores (WRSs) of 77 monaurally and 65 binaurally fitted subjects with symmetric bilateral SNHL were examined at 1, 3, and 5 years post hearing aid fitting. The deterioration in auditory function was defined as a significant change in the WRSs for Northwestern University Auditory Test No. 6 (NU-6) materials in the unaided ear of individuals fitted with a monaural hearing aid arrangement. Analyses of the data indicate that 25 percent of the monaurally fitted subjects experienced a significant change in the WRSs of their unaided ears, whereas only 6 percent of the binaurally fitted subjects experienced a significant change in the WRSs of either ear. Auditory function does deteriorate in the unaided ears of individuals with SNHL who receive monaural hearing aid fittings. Moreover, the decline in auditory function of the unaided ear does not result from a decrease in hearing sensitivity.


Prevention of early complications following total hip replacement.
Total hip arthroplasty (THA) has been quoted as "the operation of the century", owing to its efficacy and the substantial improvements evidenced with respect to functional patient outcomes and quality of life. However, early postoperative complications are often inevitable, hence it is imperative to take every step to prevent them and minimise morbidity and mortality. This manuscript focuses on the most common early complications following THA, namely venous thromboembolism (VTE), prosthetic joint infection, periprosthetic fracture, instability, and leg length inequality. It aims to outline effective risk stratification strategies and prevention measures that could apply to the wider Orthopaedic community.


Impact of a clinical decision support tool targeting QT-prolonging medications.
To evaluate the impact of a newly implemented clinical decision support (CDS) tool targeting QT interval-prolonging medications on order verification and provider interventions. A multicenter, retrospective quasi-experimental study was conducted to evaluate provider response to CDS alerts triggered during ordering of QT-prolonging medications for adult patients. The primary outcome was the proportion of orders triggering QTc alerts that were continued without intervention during a specified preimplementation phase (n = 49) and during a postimplementation phase (n = 100). Patient risk factors for QTc prolongation, provider alert response, and interventions to reduce the risk of QTc-associated adverse events were evaluated. The rate of order continuation without intervention was 82% in the preimplementation phase and 37% in the postimplementation phase, representing an 55% reduction in continued verified orders following implementation of the QT-focused CDS tool. Most alerts were initially responded to by the prescriber, with pharmacist intervention needed in only 33% of cases. There were no significant differences in patient QTc-related risk factors between the 2 study groups (P = 0.11); the postimplementation group had a higher proportion of patients using at least 2 QTc-prolonging medications (48%, compared to 26% in the preimplementation group; P = 0.02). Implementation of the CDS tool was associated with a reduction in the proportion of orders continued without intervention in patients at high risk for QTc-related adverse events.


The theory of spin noise spectroscopy: a review.
Direct measurements of spin fluctuations are becoming the mainstream approach for studies of complex condensed matter, molecular, nuclear, and atomic systems. This review covers recent progress in the field of optical spin noise spectroscopy (SNS) with an additional goal to establish an introduction into its theoretical foundations. Various theoretical techniques that have been recently used to interpret results of SNS measurements are explained alongside examples of their applications.


Selective cytotoxicity mechanisms and biodistribution of diamond nanoparticles on the skin cancer in C57 mouse.
The cytotoxicity of diamond nanoparticles (DNs) to various cell lines has been on focus by numerous scientists. The cellular toxicity system of DNs has not been fully understood or explained in skin cancer, at this point. This research was carried out to discover and reveal the potential impacts of DNs on the secluded brain, heart, liver, kidney, and skin in addition to evaluation of their cytotoxicity mechanism under test conditions. Their biological activities, for example cell viability, the level of reactive oxygen species (ROS), lipid peroxidation, cytochrome c release and Apoptosis/Necrosis were evaluated. Additionally, the bio-distribution of these nanomaterials in tissues was examined in the C57 mouse. Relying on the findings of the investigation, DNs were found to increase the ROS level, Malondialdehyde (MDA) content, release of cytochrome c, and cell death in skin significantly compared to other groups. In the C57 mouse, DNs were observed to have accumulated in skin tissue more intensively than they did in other organs. The present study presents for the proof that DNs can completely induce cell death signaling in skin cancer without bringing about a high cytotoxicity in other tissues. Results suggest that DNs can be valuable in recognition of skin cancer.


Sodium Tanshinone IIA Silate Exerts Microcirculation Protective Effects against Spinal Cord Injury In Vitro and In Vivo.
Spinal cord microcirculation involves functioning endothelial cells at the blood spinal cord barrier (BSCB) and maintains normal functioning of spinal cord neurons, axons, and glial cells. Protection of both the function and integrity of endothelial cells as well as the prevention of BSCB disruption may be a strong strategy for the treatment of spinal cord injury (SCI) cases. Sodium Tanshinone IIA silate (STS) is used for the treatment of coronary heart disease and improves microcirculation. Whether STS exhibits protective effects for SCI microcirculation is not yet clear. The purpose of this study is to investigate the protective effects of STS on oxygen-glucose deprivation- (OGD-) induced injury of spinal cord endothelial cells (SCMECs) in vitro and to explore effects on BSCB and neurovascular protection in vivo. SCMECs were treated with various concentrations of STS (1 μM, 3 μM, and 10 μM) for 24 h with or without OGD-induction. Cell viability, tube formation, migration, and expression of Notch signaling pathway components were evaluated. Histopathological evaluation (H&E), Nissl staining, BSCB permeability, and the expression levels of von Willebrand Factor (vWF), CD31, NeuN, and Notch signaling pathway components were analyzed. STS was found to improve SCMEC functions and reduce inflammatory mediators after OGD. STS also relieved histopathological damage, increased zonula occludens-1 (ZO-1), inhibited BSCB permeability, rescued microvessels, protected motor neuromas, and improved functional recovery in a SCI model. Moreover, we uncovered that the Notch signaling pathway plays an important role during these processes. These results indicated that STS protects microcirculation in SCI, which may be used as a therapeutic strategy for SCI in the future.


[Study on rhGM-CSF as adjuvant in revaccination among adults of non-and hyporesponders to hepatitis B vaccine].
To investigate the effect of recombinant human granulocyte macrophage colony stimulating factor (rhGM-CSF) as adjuvant on immune response in adults of non-and hyporesponders to hepatitis B vaccine. Those who were once immunized with recombined yeast gene hepatitis B vaccine more than one standard scheme in two years and negative for hepatitis B markers were randomly sorted as group A and group B. 33 adults of group A were given hepatitis B vaccine 10 microg each time. The immune procedure was 0, 1 and 6 month. 34 adults of group B were given rhGM-CSF 300 microg for the first day, then 10 microg each time for routine immune. The blood samples were collected before the first injection and in 1, 2 and 8 months (T1, T2, T8) following the first injection to test Anti-HBs. Anti-HBs positive conversion rates of group A and B at T8 was 39.39% and 64.71% respectively (P = 0.038). Anti-HBs levels of group B at T1, T2, T8 were (113.85 +/- 198.56) mIU/ml, (312.40 +/- 349.44) mIU/ml, (427.74 +/- 411.58) mIU/ml (P = 0.001). There was significant difference between group A and B in T8 Anti-HBs levels (P = 0.010). Better immune response was found in the group of rhGM-CSF with hepatitis B vaccine. So rhGM-CSF can induce the immune respond to hepatitis B vaccine.


Confronting difficult decisions.
Medical technology has given clinicians the means to sustain life past the time when such actions are prudent or wise. The existence of such technology does not always mandate its use. The decision to withhold or withdraw treatment must be based on diagnosis, prognosis, and the patient's wishes. Given the relationship between PAs, physicians, and patients, PAs are in a unique position to assist in the decision-making process. Continuation of care is an important consideration even when a specific therapy is withheld or withdrawn.


Psychological mechanisms in hyperactivity: II. The role of genetic factors.
The main aim of this study was to combine two research approaches to hyperactivity: the behaviour genetic approach and the testing of psychological theories of hyperactivity. For a sample of 268 twin pairs aged 7-11 years we obtained ratings on the Conners' scales from both teachers (CTRS-28) and parents (CPRS-48). Forty-six hyperactive twin pairs (pairs in which at least one twin was pervasively hyperactive) and 47 control twin pairs were assessed on a psychological test battery. Confirming findings from previous twin studies, a substantial proportion of the variance in hyperactivity considered as a dimension was due to genetic effects. There was significant evidence of genetic effects also on extreme hyperactivity, although the present group heritability estimates were somewhat lower than those reported in most previous studies. We investigated the possibility that the psychological mechanisms we reported to be associated with hyperactivity (Kuntsi, Oosterlaan, & Stevenson, 2001) share common genetic factors with hyperactive behaviour. The data produced significant evidence of such shared genetic effects only on hyperactivity and the variability of reaction times. Given that the high variability in speed of responding would indicate a state-regulation problem, this is the psychological mechanism that could possibly be the "link" between genetic effects and hyperactive behaviour.


First example of solid-state luminescent borasiloxane-based chiral helices assembled through N-B bonds.
The reaction between differently substituted borasiloxanes and 2,5-bis(3-pyridylethynyl)thiophene provided the first example of luminescent borasiloxane-based chiral helices held together by N-B bonds. The starting building blocks and the helices were fully characterized, and the nature of the N-B bond rationalized by means of theoretical calculations.


Circadian and daily rhythms of melatonin in the blood and pineal gland of free-running and entrained Syrian hamsters.
The aim of this study was to develop a radioimmunoassay for the measurement of endogenous circulating melatonin concentrations in the Syrian hamster, and then to determine the effect of various photic manipulations upon this endocrine signal. In experiment 1, pineal-intact or pinealectomized adult male Syrian hamsters, housed under a long photoperiod (LD; 16 h light:8 h darkness) for 2 weeks, were then either maintained on LD or transferred to a short photoperiod (SD; 8 h light:16 h darkness) for a further 8 weeks. The profile of serum melatonin concentrations was determined from blood samples taken by cardiac puncture at intervals over a 24-h period. Radioimmunoassay revealed that daytime concentrations were at or below the limit of sensitivity of the assay (< or = 50 pmol/l). Under both photoperiods, the concentration of melatonin in the serum of pineal-intact animals rose 4-5 h after the onset of darkness, and the peak amplitude of the melatonin rhythm was not significantly different between the SD- or LD-housed animals (200-250 pmol/l). Premature exposure of animals to light during the dark phase of LD caused a precipitous decline in circulating concentrations to daytime values within 15 min and they remained there for several hours. In animals which experienced an uninterrupted night on either LD or SD, the most striking difference in the rhythm of endogenous melatonin secretion was the duration. Animals housed under LD had high levels until the start of the light period, a peak duration of 3.7 h.(ABSTRACT TRUNCATED AT 250 WORDS)


Applying holistic review practices to a Combined Baccalaureate/Medical Degree Program: Reflections on lessons learned.
Despite the implementation of holistic review in the medical school application process, there is little information about how this can be utilized in Combined Baccalaureate/Medical Degree pipeline programs, especially since many programs offer reserved spots to their students in the medical school. Implementing holistic review in a Combined Baccalaureate/Medical Degree program and intentionally structuring it to align with the medical school mission and admissions practices and processes, can improve the diversification of the physician workforce, contribute to more primary care doctors, and promote in-state practice. Utilizing the medical school admissions by-laws, committee structure, shared training, and educational processes, we successfully engrained in our committee members the values and mission alignment to select the best applicants to fulfill the medical school mission using holistic review. To our knowledge, no other program has written about how holistic review is used in Combined Baccalaureate/Medical Degree programs and how it contributes to program outcomes. The Combined Baccalaureate/Medical Degree Program is a partnership between the undergraduate College of Arts and Sciences and the School of Medicine. The Combined Baccalaureate/Medical Degree admissions committee is a subcommittee of the School of Medicine admissions committee but has a separate membership. Hence, the holistic admissions process for the program mirrors the School of Medicine admissions process. To determine the outcome of this process, we analyzed practice specialty, practice location, gender, race and ethnicity of program alumni. To date, the Combined Baccalaureate/Medical Degree holistic admissions processes have supported the medical school mission, "…To meet the physician workforce needs of the state by selection of students who are likely to train in specialty areas of need and to remain in or return to the areas of our state needing physicians." This implementation has resulted in 75% (37/49) of our practicing alumni selecting a primary care specialty, and 69% (34/49) practicing in the state. In addition, 55% (27/49) identify as Underrepresented in Medicine. We observed that having an intentional structured alignment in place allowed for implementation of holistic practices in the Combined Baccalaureate/Medical Degree admissions process. The high retention rates and specialty of graduates from the Combined Baccalaureate/Medical Degree Program support our intentional efforts to diversify our admissions committees and align the Combined Baccalaureate/Medical Degree program's holistic review admissions process with our School of Medicine mission and admissions practices and processes, as key strategies to reach our diversity-related goals.


Pattern and outcome of management of Fournier's gangrene in a resource-constraint setting.
Fournier's gangrene (FG) is a necrotizing fasciitis of the external genitalia and perineum but may involve upper thigh and anterior abdominal wall. This is a retrospective study of 47 patients managed for FG at Usmanu Danfodiyo University Teaching Hospital from January 2001 to June 2017. Data were entered into a semi-structured pro forma and analyzed using SPSS version 20.0. The mean age of the patients was 42.7 ± 19.4 years, with age range of 7 weeks to 72 years. All the patients were male. The patients had underlying urologic conditions in 27.6%, 15.0% were postoperative, 4.2% had anorectal diseases, 10.6% had medical conditions, and 42.6% were idiopathic. After resuscitation, all the patients had serial debridement, Hypertonic saline bath, broad spectrum antibiotics and wound dressing. The wound healed by secondary intention in 34.0% and 32.3% of the patients had wound closure ± skin graft. The treatment was successful in 68.0% of the patients, 15.0% left against medical advice, and 17.0% died of severe sepsis. FG mainly affects men with existing urologic conditions in our environment. Aggressive debridement, hypertonic saline sitz bath, broad-spectrum antibiotics, and appropriate wound care are associated with good outcome.


Segregation Phenomena in Size-Selected Bimetallic CuNi Nanoparticle Catalysts.
Surface segregation, restructuring, and sintering phenomena in size-selected copper-nickel nanoparticles (NPs) supported on silicon dioxide substrates were systematically investigated as a function of temperature, chemical state, and reactive gas environment. Using near-ambient pressure (NAP-XPS) and ultrahigh vacuum X-ray photoelectron spectroscopy (XPS), we showed that nickel tends to segregate to the surface of the NPs at elevated temperatures in oxygen- or hydrogen-containing atmospheres. It was found that the NP pretreatment, gaseous environment, and oxide formation free energy are the main driving forces of the restructuring and segregation trends observed, overshadowing the role of the surface free energy. The depth profile of the elemental composition of the particles was determined under operando CO2 hydrogenation conditions by varying the energy of the X-ray beam. The temperature dependence of the chemical state of the two metals was systematically studied, revealing the high stability of nickel oxides on the NPs and the important role of high valence oxidation states in the segregation behavior. Atomic force microscopy (AFM) studies revealed a remarkable stability of the NPs against sintering at temperatures as high as 700 °C. The results provide new insights into the complex interplay of the various factors which affect alloy formation and segregation phenomena in bimetallic NP systems, often in ways different from those previously known for their bulk counterparts. This leads to new routes for tuning the surface composition of nanocatalysts, for example, through plasma and annealing pretreatments.


Total hip arthroplasty in the young adult.
The durability of cemented and hybrid total hip arthroplasty in the young adult was evaluated. A consecutive series of primary cemented total hip arthroplasties performed between 1970 and 1976, and a consecutive series of primary hybrid total hip arthroplasties performed between 1986 and 1991, were evaluated for revision and radiographic loosening of the components. All patients were younger than 50 years of age at the time of surgery and all surgery was performed by one surgeon. At minimum 20 years followup of the cemented group (93 hips in 69 patients) 22% of hips (21 hips) were revised for aseptic loosening (5% of femoral components, five hips, and 19% of acetabular components, 18 hips). At 5- to 10-year followup of the hybrid group (45 hips in 37 patients) 18% of hips (eight hips) were revised for aseptic loosening (18% of femoral components, eight hips, and 0% of acetabular components, 0 hips). Although the cemented femoral component used in the hybrid series showed a marked increase in revision and loosening compared with the cemented series, the excellent fixation obtained with uncemented acetabular components has encouraged the authors to continue the use of hybrid fixation in the young adult. However, the femoral component has been modified to incorporate a polished surface finish and a stem geometry similar to the Charnley flat back prosthesis used in the cemented series.


Microscale physiological and ecological studies of aquatic cyanobacteria: macroscale implications.
Cyanobacteria have had a profound and unparalleled biogeochemical impact on the earth's biosphere. As the first oxygenic phototrophs, cyanobacteria were responsible for the transition from anaerobic to aerobic life. Ironically, molecular oxygen (O2) is inhibitory to critical components of cyanobacterial metabolism, including photosynthesis and nitrogen fixation. Cyanobacteria have developed a great variety of biochemical, structural, and biotic adaptations ensuring optimal growth and proliferation in diverse oxic environments to counter this difficult situation. Structurally, cyanobacteria reveal remarkable diversity, including the formation of highly differentiated, O2-deplete cells (heterocysts), multicellularity as trichomes, and aggregates, that, among N2-fixing genera, facilitate division of labor between aerobic and anaerobic processes. Cyanobacteria enjoy unique consortial and symbiotic associations with other microorganisms, higher plants, and animals, in which O2 consumption is closely coupled in time and space to its production. Because as prokaryotes they are devoid of O2-consuming organelles (e.g., mitochondria), cyanobacteria have developed alternative strategies for locally protecting O2-sensitive processes, including consortial relationships with other microorganisms. Specific organic compounds released by cyanobacteria are capable of chemotactically attracting bacterial consorts, which in turn attach to the host cyanobacteria, consume O2, and recycle inorganic nutrients within the cyanobacterial "phycosphere." Multicellularity and aggregation lead to localized O2 gradients and hypoxic/anoxic microzones in which O2-sensitive processes can coexist. Microscale partitioning of O2-producing and O2-inhibited processes promotes contiguous and effective metabolite and nutrient exchange between these processes in oxygenated waters, representing a bulk of the world's oceanic and freshwater ecosystems.


The influence of 5-aminosalicylic acid on the progression of colorectal adenomas via the β-catenin signaling pathway.
Surveillance colonoscopy is an important strategy for prevention of colorectal cancer. 5-aminosalicylate (ASA) (mesalazine) is discussed as a chemopreventive agent as it reduces the cancer risk in ulcerative colitis patients. The current study analyses the effect of 5-ASA on Wnt/β-catenin signaling in vitro and in vivo in colon epithelial cells. The effect of 5-ASA was determined using a β-catenin/T-cell factor (TCF)-reporter assay and by western blotting in cultured colon cancer cells. Formalin fixed paraffin embedded material from 227 polyps removed from a subgroup of 56 patients, who participated in a randomized placebo-controlled 3-year prevention trial with 5-ASA was evaluated according to histomorphological characteristics and expression of β-catenin and target genes Cox2, cyclin D1 and E-cadherin as well as ornithine decarboxylase (ODC). Patients were grouped into a low-risk and a high-risk group according to the number of adenomas at initial colonoscopy. ß-catenin/TCF signaling activity was significantly reduced by 5-ASA treatment possibly through a reduction in ß-catenin levels. Moreover, 5-ASA significantly reduced ß-catenin levels and nuclear localization in patients' adenomas. In addition, 5-ASA also significantly changed expression of the downstream targets Cox2, cyclin D1 and E-cadherin, correlating with ß-catenin status. Moreover, 5-ASA significantly reduced levels of ODC in vivo. Expression of p53 was unaltered by the 5-ASA treatment. Our study shows a significant in vitro and long-term in vivo effect of 5-ASA on ß-catenin signaling as a key signaling pathway in the development of colorectal adenoma. Therefore, we suggest the use of 5-ASA as a promising drug for prevention of sporadic colorectal carcinoma.


Sensing and Responding to Hypersaline Conditions and the HOG Signal Transduction Pathway in Fungi Isolated from Hypersaline Environments: Hortaea werneckii and Wallemia ichthyophaga.
Sensing and responding to changes in NaCl concentration in hypersaline environments is vital for cell survival. In this paper, we identified and characterized key components of the high-osmolarity glycerol (HOG) signal transduction pathway, which is crucial in sensing hypersaline conditions in the extremely halotolerant black yeast Hortaea werneckii and in the obligate halophilic fungus Wallemia ichthyophaga. Both organisms were isolated from solar salterns, their predominating ecological niche. The identified components included homologous proteins of both branches involved in sensing high osmolarity (SHO1 and SLN1) and the homologues of mitogen-activated protein kinase module (MAPKKK Ste11, MAPKK Pbs2, and MAPK Hog1). Functional complementation of the identified gene products in S. cerevisiae mutant strains revealed some of their functions. Structural protein analysis demonstrated important structural differences in the HOG pathway components between halotolerant/halophilic fungi isolated from solar salterns, salt-sensitive S. cerevisiae, the extremely salt-tolerant H. werneckii, and halophilic W. ichthyophaga. Known and novel gene targets of MAP kinase Hog1 were uncovered particularly in halotolerant H. werneckii. Molecular studies of many salt-responsive proteins confirm unique and novel mechanisms of adaptation to changes in salt concentration.


Fam3c modulates osteogenic cell differentiation and affects bone volume and cortical bone mineral density.
Fam3c, a cytokine-like growth factor, has been suggested to have a role in epithelial-to-mesenchymal transition (EMT), tumor growth and metastasis. A single-nucleotide polymorphism affecting bone mineral density has been found in the first intron of the Fam3c gene in a study analyzing an Asian population cohort. Other independent studies on different population cohorts have found the fam3c locus to be associated with bone mineral density and fractures. In order to investigate the role of Fam3c in bone biology, we have generated a Fam3c knock-out (KO) mouse strain. The Fam3c KO mice were found to have normal appearance, behavior and fertility, but small changes in bone morphology and content were also observed. Micro-CT analysis of tibiae of the female mice revealed decreased number of trabeculae. In male mice the changes in the bone phenotype were smaller, but hematological changes were observed. Furthermore, there was a negative correlation between body weight and tibial trabecular and cortical bone volume in the male KO mice. There was a small increase in cortical bone mineral density, but in the lateral direction of tibiae the breaking strength was reduced. Fam3c KO bone marrow cells showed accelerated osteogenic differentiation and mineralization in vitro. The reduced number of bone trabeculae in Fam3c KO mice and the stimulated osteogenic differentiation indicate a role for Fam3c in osteoblast differentiation and bone homeostasis.


Deconstruction of complex protein signaling switches: a roadmap toward engineering higher-order gene regulators.
The control of gene expression is an important tool for metabolic engineering, the design of synthetic gene networks, gene-function analysis, and protein manufacturing. The most successful approaches to date are based on modulating messenger RNA (mRNA) synthesis via their inducible coupling to transcriptional effectors, which requires biosensing functionality. A hallmark of biological sensing is the conversion of an exogenous signal, usually a small molecule or environmental cue such as a protein-ligand interaction, into a useful output or response. One of the most utilized regulatory proteins is the lactose repressor (LacI). In this review we will (1) explore the mechanochemical structure-function relationship of LacI; (2) discuss how the physical attributes of LacI can be leveraged to identify and understand other regulatory proteins; (3) investigate the designability (tunability) of LacI; (4) discuss the potential of the modular design of novel regulatory proteins, fashioned after the topology and mechanochemical properties of LacI. WIREs Nanomed Nanobiotechnol 2017, 9:e1461. doi: 10.1002/wnan.1461 For further resources related to this article, please visit the WIREs website.


[Pulmonary hypertension--some problems resolved. More remain to be solved].
Pulmonary hypertension especially arterial and idiopathic is still a poorly understood disease often affecting young adults and leading to right ventricular overload, failure and death due to low cardiac output. Justification for new, aggressive, costly but effective methods of pharmacological and interventional treatment of pulmonary hypertension require precise, repeatedly performed prognostic assessment. This is currently provided not only by repeated right heart catheterization but mostly by exercise testing as well as non-invasive techniques such as echo-Doppler and biochemical myocyte markers including B-type natriuretic peptide and cardiac troponin. Such methods should allow better timing of atrial septostomy and listing for lung transplantation.


Some Lives Matter: The Dirty Little Secret of the U.S. Health Care System.
Our health care system in the United States reflects the inequities that are part of the larger society, which is why our system for financing access to needed and effective health care is so complicated and unfair.


Pulmonary functions and associated risk factors among school teachers in a selected Nigerian population.
Objective. This study aimed to determine pulmonary functions and associated risk factors among school teachers. Methods. This cross-sectional ex-post facto study included 121 participants (20 males and 101 females). The setting for this study included 11 private schools and eight government schools. Participants were recruited using non-probability sampling techniques. Subjective data were collected using a self-administered asthma questionnaire. A spirometer was used for measuring pulmonary function values and data were analyzed using descriptive statistics and one-way analysis of variance for inferential statistics. The α level was set at 0.05. Results. Age, gender, duration of employment, type of school, school level taught, type of teaching board, working hours per day, previous occupation, usage of carpet and usage of rugs were significantly associated with the forced vital capacity prediction (p = 0.000, 0.010, 0.000, 0.032, 0.013, 0.000, 0.027, 0.000, 0.000 and 0.041, respectively). Also, the forced expiratory volume in 1 s and the peak expiratory flow were statistically different with alcohol consumption (p = 0.015) and place of residence (p = 0.004), respectively. Conclusion. Teachers using chalkboards are at increased risk of developing occupationally related pulmonary impairments. Hence, there is a need to shift from routine chalkboards to whiteboards.


Cowden's syndrome diagnosed through oral lesions: A case report.
Cowden's syndrome (CS), also known as multiple hamartoma syndrome, is a rare autosomal dominant genodermatosis first described in 1963. It has a high penetrance in both sexes and variable phenotypes. Its origin is a PTEN (phosphatase and tensin homologue) gene mutation and affects multiple organs of endodermal, ectodermal, and mesodermal origin, resulting in the development of hamartomatous mucocutaneus lesions and an increased risk for malignancies in breast, thyroid, endometrium, kidney, colon, rectum, among other organs. The diagnosis of CS is based mainly on clinical findings and oral cavity manifestations are frequent, occurring in 80-90% of patients. This include oral and labial papillomatous papules that usually precede the development of malignant tumours. Here, we report a case of a 58-years-old male with a presumptive diagnosis of multiple "pseudofibromas" in the oral cavity that was diagnosed with CS by a dental surgeon through the identification of extra and intraoral lesions, demonstrating the importance of awareness of this entity in the dental community to improve its early diagnosis, which is vital for the early detection and treatment of malignancies. Key words:Cowden's Syndrome, Multiple Hamartoma Syndrome, PTEN Hamartoma Tumor Syndrome, Papillomatous papules.


Taxol biosynthesis: differential transformations of taxadien-5 alpha-ol and its acetate ester by cytochrome P450 hydroxylases from Taxus suspension cells.
The biosynthesis of the diterpenoid antineoplastic drug Taxol in Taxus species involves the cyclization of the ubiquitous isoprenoid intermediate geranylgeranyl diphosphate to taxa-4(5),11(12)-diene followed by cytochrome P450-mediated hydroxylation (with allylic rearrangement) of this olefin precursor to taxa-4(20),11(12)-dien-5 alpha-ol, and further oxygenation and acylation reactions. Based on the abundances of naturally occurring taxoids, the subsequent order of oxygenation of the taxane core is considered to occur at C10, then C2 and C9, followed by C13, and finally C7 and C1. Circumstantial evidence suggests that the acetylation of taxadien-5 alpha-ol may constitute the third specific step of Taxol biosynthesis. To determine whether taxadienol or the corresponding acetate ester serves as the direct precursor of subsequent oxygenation reactions, microsomal preparations isolated from induced Taxus cells and optimized for cytochrome P450 catalysis were incubated with each potential substrate. Both taxadienol and taxadienyl acetate were oxygenated to the level of a diol and to higher polyols at comparable rates by cytochrome P450 enzymes of the microsomal preparation. Preparative-scale incubation allowed the isolation of sufficient quantities of the diol derived from taxadienol to permit the NMR-based structural elucidation of this metabolite as taxa-4(20),11(12)-dien-5 alpha,13 alpha-diol, which may represent an alternate route of taxoid metabolism in induced cells. GC-MS-based structural definition of the diol monoacetate derived in microsomes from taxadienyl acetate confirmed this metabolite as taxa-4(20),11(12)-dien-5 alpha-acetoxy-10 beta-ol, thereby indicating that acetylation at C5 of taxadienol precedes the cytochrome P450-mediated insertion of the C10-beta-hydroxyl group of Taxol.


Measuring vascular permeability in mice.
Noninvasive techniques have been developed for the assessment of vascular parameters, including vascular permeability, in normal and diseased tissues of mice. In this protocol, mice are injected with an appropriate fluorescent tracer. The effective average vascular permeability (P) of a region of vessels is measured by single-photon microscopy. Additionally, the vascular permeability of individual vessel segments within ~600 µm of a tumor/window interface is measured by multiphoton laser-scanning microscopy (MPLSM).


Clinical Performance of Nonvitamin K Antagonist Oral Anticoagulants in Real-World Obese Patients with Atrial Fibrillation.
The prevalence of both atrial fibrillation (AF) and obesity has steadily increased. Nonvitamin K antagonist oral anticoagulants (NOACs) have been shown to be more effective and safer than vitamin K antagonists (VKAs) for long-term stroke prevention in patients with nonvalvular AF. There are still limited data in the literature regarding performance of NOACs in obese patients with AF in the "real world." The aim of our study was to compare the safety and effectiveness of NOACs versus well-controlled VKA therapy in obese AF patients in a "real-world" setting. Here, we have considered patients with AF and obesity (body mass index [BMI] > 30 kg/m2) on NOAC or VKA therapy included in the multicenter Atrial Fibrillation Research Database (NCT03760874). The occurrence of major bleedings (MBs) and thromboembolic events (composite of ischemic stroke, transient ischemic attack, and systemic embolism) was respectively considered primary safety and effectiveness outcomes. We identified 1,047 AF patients with obesity who received NOAC (n = 272) or VKA (n = 775) treatment. After propensity score matching analysis, 248 NOAC and 496 VKA recipients with similar clinical characteristics, including BMI (34.8 ± 3.4 in NOAC vs. 35.1 ± 3.8 in the VKA group; p = 0.50), were evaluated. The mean follow-up was 39 ± 7 months. The incidence rate of thromboembolic events was 1.10 per 100 person-years (0.67 in NOAC vs. 1.28 in the VKA group; hazard ratio [HR]: 0.52; 95% confidence interval [CI]: 0.22-1.22; p = 0.19). The incidence rate of MB was 1.9 per 100 person-years (1.1 in NOAC vs. 2.28 in the VKA group; HR: 0.46; 95% CI: 0.24-0.88; p = 0.04). The incidence rate of intracranial hemorrhage was 0.4 per 100 person-years (0.27 in NOAC vs. 0.47 in the VKA group; HR: 0.57; 95% CI: 0.12-2.73; p = 0.48). A positive net clinical benefit (NCB) of NOACs over VKAs was found (+0.91). Presence of anemia (HR: 1.75; p = 0.003) and concomitant use of antiplatelet drugs (HR: 2.41; p = 0.001) were found to be independent predictors of MB; moreover, age (HR: 1.65; p = 0.003) was an independent predictor of thromboembolic events. Our data support the hypothesis of safe and effective use of NOACs in patients with AF and obesity, justified by a statistically significant lower incidence of MB and a favorable NCB over VKAs.


Interactions mediating bacterial translocation in the immature intestine.
Systemic disease caused by transmucosal passage of enterovirulent bacteria and toxins from the gut lumen into the mesenteric lymph nodes (MLN) is reviewed, with particular concern for bacterial interactions in the developing gut of premature newborns. Anaerobic bacteria are rarely observed to translocate to the MLN. Bifidobacterial strains have been tested for their abilities to adhere to enterocyte-like Caco-2 cells in culture. We have investigated the inhibitory effect of adherent human bifidobacterial strains against colonization by a number of diarrheagenic bacteria (Escherichia coli O157; Salmonella typhimurium) and viruses (murine and rhesus rotavirus), in various in vitro and in vivo models. The phagocytic cell (macrophage) may be a key factor in bacterial translocation (BT). Human breast milk contains abundant bioactive substances (immunologic, nutritional) that provide protective effects through inhibition of bacterial overgrowth and BT. New biotherapeutic therapies that stimulate beneficial anaerobic microflora (Lactobacillus, Bifidobacterium) are promising avenues of research to combat BT in disease treatment.


Inferring Phenotypic Trait Evolution on Large Trees With Many Incomplete Measurements.
Comparative biologists are often interested in inferring covariation between multiple biological traits sampled across numerous related taxa. To properly study these relationships, we must control for the shared evolutionary history of the taxa to avoid spurious inference. An additional challenge arises as obtaining a full suite of measurements becomes increasingly difficult with increasing taxa. This generally necessitates data imputation or integration, and existing control techniques typically scale poorly as the number of taxa increases. We propose an inference technique that integrates out missing measurements analytically and scales linearly with the number of taxa by using a post-order traversal algorithm under a multivariate Brownian diffusion (MBD) model to characterize trait evolution. We further exploit this technique to extend the MBD model to account for sampling error or non-heritable residual variance. We test these methods to examine mammalian life history traits, prokaryotic genomic and phenotypic traits, and HIV infection traits. We find computational efficiency increases that top two orders-of-magnitude over current best practices. While we focus on the utility of this algorithm in phylogenetic comparative methods, our approach generalizes to solve long-standing challenges in computing the likelihood for matrix-normal and multivariate normal distributions with missing data at scale.


Wide-area assessment of topographical and meteorological effects on sound propagation by time-domain modeling.
Noise mapping with a three-dimensional finite-difference time-domain (FDTD) model over larger areas suffers from its high computational demand. This study shows that an FDTD model in combination with a meteorological model can be used for at least qualitative assessments of topographical and meteorological effects on sound propagation in domains of even some kilometers extension. This is achieved by restricting the acoustical simulations to low frequencies which allow the use of a rather large numerical grid spacing.


Development of a new irrigation sucker for microneurosurgery--technical note.
A new irrigation sucker (Delta Irrigation Sucker) was designed for microneurosurgery. The Delta Irrigation Sucker has a unique trigonal pyramid-shape thumb piece, providing a very stable grip. Irrigation is achieved easily by pushing a small button just behind the pressure-regulating pore. Stable hold of the sucker and easy handling of the irrigation button enable irrigation without unsteadiness of the sucker. The Delta Irrigation Sucker is available in six sizes, with diameters from 1.5 mm to 4.0 mm at 0.5 mm intervals. Irrigation force is provided by a pressure bag, and a normal sterile transfusion set can be used as the irrigation circuit. The Delta Irrigation Sucker was used in 20 cases of clipping for ruptured cerebral aneurysm, five cases of tumor resection, and three cases of anterior clinoidectomy and opening of the internal auditory meatus. Subarachnoid clot was easily removed and the bleeding points were easily confirmed. Irrigation, controlled by natural finger movement, did not cause unsteadiness of the sucker.


Inflammation-associated regulation of RGS in astrocytes and putative implication in neuropathic pain.
Regulators of G-protein signaling (RGS) are major physiological modulators of G-protein-coupled receptors (GPCR) signaling. Several GPCRs expressed in both neurons and astrocytes participate in the central control of pain processing, and the reduced efficacy of analgesics in neuropathic pain conditions may rely on alterations in RGS function. The expression and the regulation of RGS in astrocytes is poorly documented, and we herein hypothesized that neuroinflammation which is commonly observed in neuropathic pain could influence RGS expression in astrocytes. In a validated model of neuropathic pain, the spared nerve injury (SNI), the regulation of RGS2, RGS3, RGS4, and RGS7 messenger RNA (mRNA) was examined up to 3 weeks after the lesion. Changes in the expression of the same RGS were also studied in cultured astrocytes exposed to defined activation protocols or to inflammatory cytokines. We evidenced a differential regulation of these RGS in the lumbar spinal cord of animals undergoing SNI. In particular, RGS3 appeared upregulated at early stages after the lesion whereas expression of RGS2 and RGS4 was decreased at later stages. Decrease in RGS7 expression was already observed after 3 days and outlasted until 21 days after the lesion. In cultured astrocytes, we observed that changes in the culture conditions distinctly influenced the constitutive expression of these RGS. Also, brief exposures (4 to 8 h) to either interleukin-1β, interleukin-6, or tumor necrosis factor α caused rapid changes in the mRNA levels of the RGS, which however did not strictly recapitulate the regulations observed in the spinal cord of lesioned animals. Longer exposure (48 h) to inflammatory cytokines barely influenced RGS expression, confirming the rapid but transient regulation of these cell signaling modulators. Changes in the environment of astrocytes mimicking the inflammation observed in the model of neuropathic pain can affect RGS expression. Considering the role of astrocytes in the onset and progression of neuropathic pain, we propose that the inflammation-mediated modulation of RGS in astrocytes constitutes an adaptive mechanism in a context of neuroinflammation and may participate in the regulation of nociception.


Effects of cytoskeletal perturbation on the sensitivity of Ehrlich ascites tumor cell surface membranes to mechanical trauma.
Evidence presented previously indicated that shape changes in circulating cancer cells within the microvasculature may lead to rapid, lethal rupture of the cell surface membranes, thereby contributing to the inefficiency of this phase of hematogenous metastasis. As the cytoskeleton is known to regulate cell shape and, in at least some cases, to be attached to the surface membrane, we have determined whether or not it plays a role in inhibiting lethal, deformation-associated, mechanically induced surface membrane trauma. Thus, Ehrlich ascites tumor (EAT) cells were treated with different cytoskeleton-perturbing agents, and their susceptibility to filtration trauma on passage through Nuclepore membranes was determined. In contrast to the involvement of the cytoskeleton in nonlethal cell deformation, agents which disrupt intracellular networks of microtubules, microfilaments and intermediate filaments had little or no direct effect on EAT cell susceptibility to rapid, mechanically induced, lethal trauma.


Neutrophil glutamine deficiency in relation to genotype in children with cystic fibrosis.
Pulmonary disease in cystic fibrosis (CF) is characterized by a chronic neutrophil-dominated inflammation of lung tissue. Inasmuch as some amino acids (AA) play a pivotal role in various aspects of neutrophil metabolism, the aim of this study was to investigate a possible alteration of neutrophil AA metabolism and to evaluate its relation (if any) with the genotype. We performed plasma and neutrophil AA analysis in 26 CF patients with known genotype, 10 patients with non-CF bronchiectasis, and 20 normal subjects. The CF group showed a significant decrease of free intracellular neutrophil glutamine (Gln) content compared with controls and the non-CF bronchiectasis group. In the latter group, levels of neutrophil Gln were significantly lower compared with the controls. Amino acid plasma concentration in non-CF bronchiectasis showed a decrease of Gln and taurine compared with controls. Neutrophil Gln content showed values significantly lower in CF patients with severe mutations (class I, II, and III mutations) compared with mild mutations (class IV and V mutations). Results of our study add further evidence for intrinsic neutrophil alterations that could play an important role in the pathogenesis of chronic pulmonary disease in CF patients.


Steroid rosacea in prepubertal children.
To examine clinical associations, family history of rosacea, and response to treatment in prepubertal children with steroid rosacea. Retrospective case-series evaluation of children younger than 13 years with steroid rosacea seen over an 8-year period (1991-1998). Ambulatory care university hospital. Referral patients from pediatricians serving a population of 3.4 million. Abrupt cessation of topical corticosteroid use and initiation of treatment with oral erythromycin stearate for 4 weeks. Age at onset, class of topical corticosteroid used, family history of rosacea, location of lesions, treatment, and weeks to clearing. We evaluated 106 (46 boys and 60 girls) who developed steroid rosacea. Preceding steroids used were predominantly (54% of children) class 7 agents including 1% hydrocortisone and over-the-counter hydrocortisone preparations. Only 3% of children had used superpotent (class 1) topical corticosteroids. The mean age at onset was 7.04 years (range, 6 months to 13 years). Twenty-nine children were younger than 3 years. A family history of rosacea was found for 20% of the children. After abruptly stopping topical steroid use and starting treatment with oral erythromycin, 86% of children had complete clearing within 4 weeks and 100% by 8 weeks. Clearing within 3 weeks was observed in 22% of children. Abrupt discontinuation of topical corticosteroids and institution of oral antibiotics resulted in clearing within 4 weeks. This finding does not support the concept that prepubertal children with steroid rosacea need to continue low-strength steroids in a gradual withdrawal strategy. This conclusion is supported by the finding that 54% developed the steroid rosacea while being treated with the lowest-strength (class 7) topical corticosteroids. Even over-the-counter hydrocortisone preparations induced steroid rosacea in susceptible children. Susceptibility may be genetic as 20% of children had a first-degree relative with rosacea.


Evaluation of the Ability of Miltefosine Associated with Topical GM-CSF in Modulating the Immune Response of Patients with Cutaneous Leishmaniasis.
Cutaneous leishmaniasis (CL) due to L. braziliensis is associated with an exaggerated inflammatory response and tissue damage. Miltefosine is more effective than pentavalent antimony (Sbv) in the treatment of CL, and here, we evaluate the ability of Sbv, miltefosine, and GM-CSF administered intravenously, orally, or topically, respectively, to modify the immune response. Patients were treated with miltefosine plus GM-CSF, miltefosine plus placebo, or Sbv. Mononuclear cells were stimulated with soluble Leishmania antigen (SLA) on day 0 and day 15 of therapy, and cytokine levels were determined in supernatants by ELISA. The lymphocyte proliferation and oxidative burst were evaluated by flow cytometry, and the degree of infection and Leishmania killing by optical microscopy. Proliferation of CD4+ T cells were enhanced in patients using miltefosine and in CD8+ T cells when GM-CSF was associated. Enhancement in the oxidative burst occurred in the miltefosine plus GM-CSF group on day 15 of therapy. Moreover, the number of L. braziliensis in infected monocytes on day 15 as well as the percentage of infected cells was lower after 48- and 72-hour culture in cells from patients treated with miltefosine plus GM-CSF. In addition to the ability of miltefosine to kill Leishmania, the changes in the immune response caused by miltefosine and GM-CSF may increase the cure rate of CL patients using these drugs.


Increased expression of CD4 molecules on Jurkat cells mediated by human immunodeficiency virus tat protein.
The tat gene of the human immunodeficiency virus, tat-III, when introduced into T-lymphoblastoid Jurkat cells by a Moloney retroviral recombinant DNA vector expressed high levels of the functional tat protein as measured by the chloramphenicol acetyltransferase assay. Immunofluorescence analysis with CD4-specific monoclonal antibodies demonstrated that the cell surface levels of the CD4 antigen were increased by 5- to 10-fold in the tat-III-infected Jurkat cells. Cellular cytoplasmic RNA analysis indicated that the enhanced CD4 expression was mediated at the mRNA level. Our findings suggest that the single expression of the human immunodeficiency virus tat protein in the absence of the other viral proteins causes an upregulation of CD4 gene expression on helper T cells, although infection of these cells by the virus, thus expressing all the viral gene products including tat, is known to downregulate CD4 antigen expression.