Neurotoxic effects of intrathecal magnesium sulphate.
To assess the potential neurotoxic effects at the ultrastructural level of magnesium sulfate administered intrathecally as a single or multi-dose. Our study was conducted with 24 Sprague-Dawley rats that weighed 250-300 g. After a 4-hour fast, the rats were given 10 mg.kg(-1) xylazine chloride intraperitoneal and then randomly allocated into three groups. Group I (n=8) received 0.9% normal saline, Group II (n = 8) was given one intrathecal injection of 0.02 mL of 15% magnesium sulphate, and Group III (n = 8) was given 0.02 mL of 15% magnesium sulphate once a day for seven days. The injections were given within 0.40 × 50 mm from the lumbar area. After seven days, the animals were sacrificed under anesthesia with an aortic injection of 10% formaldehyde and their tissues were fixed. The medulla spinalis was then examined and histopathologically evaluated under an electron microscope. The Kruskal-Wallis test was used for statistical evaluation. A value of p < .05 was considered to be statistically significant. Significant neurodegeneration was detected in rats given single or repeated magnesium sulphate injections compared to the control group. The histopathological evaluation score of this group was also high. Based on electron microscopic examination, we found that intrathecal magnesium sulphate administration induced neurodegeneration.


[Solid-phase immunoenzyme analysis of apoprotein A-1].
The authors have optimized indirect solid-phase enzyme immunoassay for measuring human blood serum apoA-1. Immunochemical identification of the obtained apoA-1 and specific antibodies has been carried out, working regimens for the components and conjugates employed have been selected. Relationship between the method of preliminary treatment of the serum and the completeness of detected apoA-1 antigenic determinants is demonstrated. Normal blood serum apoA-1 level is 1.06 +/- 0.1 g/l in females and 1.05 +/- 0.1 g/l in male subjects.


Selective C-C coupling at a Pt(iv) centre: 100% preference for sp2-sp3 over sp3-sp3.
The oxidative addition of three different organic halides RX to the non-symmetric platinum(ii) mer coordinated dicyclometallated C^N^C complex 1 yielded short-lived six-coordinate platinum(iv) complexes 2(R) (R = Me, allyl, Bn), with the incoming groups trans across the platinum centre. A spontaneous reductive coupling reaction then occurred with, in each case, a completely chemoselective sp2-sp3 coupling, and exclusively gave R-3, with the newly introduced R group bonded to the previously cyclometallated aryl ring. Following a recyclometallation reaction, the oxidative addition/reductive elimination cycle was repeated and gave the same selectivity. A one-pot route to doubly alkylating the aryl ring was developed. The observed selectivity might have been predicted on the normal basis of a steric barrier associated with non-flat sp3 hybridised groups, but we suggest that it arises from the stereochemistry at the metal, and the orientation of the ligands.


Serum N-Acetylneuraminic Acid Is Associated with Atrial Fibrillation and Left Atrial Enlargement.
Recent studies have indicated that N-acetylneuraminic acid (Neu5Ac) plays a key role in severe coronary artery diseases, involving RhoA signaling pathway activation, which is critically involved in cardiac fibrosis. There is convincing evidence from many studies that left atrium fibrosis is involved in the pathophysiology of AF. Therefore, we speculated that Neu5Ac may be associated with atrial fibrillation (AF) and involved in the development of AF. This study aims to investigate the clinical relationship between Neu5Ac and AF and left atrial enlargement. Forty-five patients with AF (AF group) and forty-five patients with non-AF (control group) matched for age, sex, and hospitalization date were recruited for our study. Plasma concentrations of Neu5Ac from peripheral venous blood were analyzed using enzyme-linked immunosorbent assay (ELISA). The baseline characteristics, plasma level of Neu5Ac, and echocardiographic characteristics were evaluated. The plasma level of Neu5Ac was significantly higher in the AF group than in the control group (107.66 ± 47.50 vs 77.87 ± 39.09 ng/ml; P < 0.05); the left atrial diameters were positively correlated with the plasma Neu5Ac level (R = 0.255; P < 0.05). The plasma Neu5Ac level (R = 0.368; P < 0.05) and the left atrial diameters (R = 0.402; P < 0.05) were positively correlated with AF history times. Neu5Ac (odds ratio 1.018, 95% CI 1.003-1.032; P < 0.05) and the left atrial diameter (odds ratio 1.142, 95% CI 1.020-1.280; P < 0.05) were independent risk factors for AF in multivariate regression analysis. Serum Neu5Ac is associated with atrial fibrillation, and the mechanism may involve left atrial enlargement.


Comparison of 2% hydroxypropyl methylcellulose and 1% sodium hyaluronate in implant surgery.
We conducted a prospective randomized clinical trial of 2% hydroxypropyl methylcellulose and 1% sodium hyaluronate (Healon) in routine extracapsular cataract surgery with implantation of a posterior chamber intraocular lens. Of the 84 patients 40 received methylcellulose and 44 received sodium hyaluronate. There was no statistically significant difference in endothelial-cell loss or induced cellular polymegathism between the two groups. The intraocular pressure before and after surgery was similar in the two groups, as was the visual acuity 8 weeks after surgery. The results suggest that 2% hydroxypropyl methylcellulose is a safe and effective alternative to 1% sodium hyaluronate in routine implant surgery.


Whole-Genome Sequences of 14 Strains of Bradyrhizobium canariense and 1 Strain of Bradyrhizobium japonicum Isolated from Lupinus spp. in Algeria.
We report here the whole-genome sequences of 14 strains of Bradyrhizobium canariense, isolated from root nodules of Lupinus microanthus and Lupinus angustifolius, and 1 strain of Bradyrhizobium japonicum isolated from root nodules from Lupinus angustifolius in Algeria. These sequences add to the known diversity of this agronomically important genus.


Strontium and lead isotope analyses for determining the geographic origins of grains.
A rapid determination method of (87)Sr/(86)Sr and Pb isotope ((204)Pb, (206)Pb, (207)Pb, and (208)Pb) ratios was applied to determining the geographic origin of grain crops. This new method is more economical in terms of both time and cost compared to conventional methods. We used samples of barley (n = 321), rice (n = 111), and wheat (n = 93) grown in various countries. (87)Sr/(86)Sr versus Sr concentration plots for the barley and wheat showed differences between products from Australia and those from other countries. Graphs of the Pb isotope ratios, comprising 15 two-dimensional plots, gave rise to a particular distribution for each country of production. The presented method showed promise for determining the production countries of grains by using the isotope ratios of Sr and Pb.


Morphometric evaluation of posterior funiculus nerve fibers in relation to aging.
We morphologically evaluated the size of axons in the posterior funiculus in different age groups and examined the changes due to aging. In the past, such studies have been conducted at the cervical spinal cord (C6) level, and a decrease in the size and number of axons due to aging has been noted. The current study was conducted at the lower lumbar spinal cord (L2) level.


Spontaneous Intracranial Hemorrhage Associated With an Intracranial Meningioma.
Spontaneous intracranial hemorrhage associated with an intracranial meningioma is rare, with a reported incidence of below 2.4% of all meningiomas. Such cases are described with a cause subdural with intratumoral hemorrhage, which is a challenge for patients and healthcare professionals because it can occur spontaneously without other pathological antecedents. We describe the case of a 55-year-old woman with subdural hemorrhage over the frontoparietal region of the right hemisphere associated with a meningioma, generating a mass effect and shifting the third ventricle and lateral ventricle. Therefore, urgent surgical treatment was decided. A tumor lesion was found with apoplexy, soft consistency, and violaceous color with abundant vascularity in the lesion's center, suggesting a probable angiomatous meningioma. The histopathological evaluation confirmed meningothelial hemorrhagic meningioma grade I, according to the World Health Organization grading. This article discusses the causes, risk factors, diagnosis, and surgical treatment for hemorrhage associated with intracranial meningioma.


Collision-induced hyper-Rayleigh spectrum of H(2)-Ar gas mixture.
The collision-induced hyper-Rayleigh (CIHR) spectra of the gaseous H(2)-Ar mixture are discussed in the binary regime on the basis of our ab initio computed H(2)-Ar collision-induced (CI) first dipole hyperpolarizability tensor Deltabeta(R). A method for the computation of the spherical, rotationally adapted components Deltabeta(lambdaL) ((s,K))(R) of Deltabeta(R) needed for spectroscopic line shape analysis is proposed. Both the vector and the septor parts of the H(2)-Ar CIHR spectrum are evaluated at room (T=295 K) temperature. The spectra are calculated assuming the full quantum computations based on the Schrodinger equation of the relative translational motion of H(2)-Ar as well as semiclassical methods (classical trajectory approach and Birnbaum-Cohen model translational profiles). The H(2)-Ar pair CIHR septor spectrum has been found stronger than the vector one.


[The construction of Thermotoga maritima endoglucanase Cel12B fused with CBD and the characterization of chimeric enzyme].
Thermotoga maritima is strictly anaerobic and extremely thermophilic bacteria. The endoglucanase found in T. maritima showed extremely high thermostability and considerable potential in industrial application. Endoglucanase (Tm) Cel12B is extracellular enzyme. Tm Cel12B did not contain a cellulose-binding domain (CBD)and lacked activity on crystalline cellulose. Tm XynA is composed of catalytic domain (CD) and cellulose-binding domain (CBD). As such, the gene of CBD from Tm XynA was fused at the carboxyl-terminus of Tm Cel12B and recombinant plasmid pET-20b- Cel 12B- CBD was obtained. The recombinant plasmid pET-20b- Cel 12 B- CBD was transformed to E. coli JM109 (DE3), induced by IPTG. The properties of chimeric enzyme were determined. The chimeric enzyme displayed pH activity and stability profiles similar to those of parental enzyme with optimal pH 5.8. The optimal activity of the chimera was observed at 100 degrees C and the enzyme kept 87% of original enzyme activity after incubated at 90 degrees C for 2h. A notable feature on substrate specificity is that the chimeric enzyme has the capacity to hydrolases crystalline cellulose.


Comparison of two surrogate estimates of insulin resistance to predict cardiovascular disease in apparently healthy individuals.
Insulin resistance is associated with a cluster of abnormalities that increase cardiovascular disease (CVD). Several indices have been proposed to identify individuals who are insulin resistant, and thereby at increased CVD risk. The aim of this study was to compare the abilities of 3 indices to accomplish that goal: 1) plasma triglyceride × glucose index (TG × G); 2) plasma triglyceride/high-density lipoprotein cholesterol ratio (TG/HDL-C); and 3) Metabolic Syndrome (MetS). In a population sample of 723 individuals (486 women and 237 men, 50 ± 16 and 51 ± 16 years old, respectively), baseline demographic and metabolic variables known to increase CVD risk and incident CVD were compared among individuals defined as high vs. low risk by: TG × G; TG/HDL-C; or MetS. CVD risk profiles appeared comparable in high risk subjects, irrespective of criteria. Crude incidence of CVD events was increased in high risk subjects: 12.2 vs. 5.3% subjects/10 years, p = 0.005 defined by TG/HDL-C; 13.4 vs. 5.3% subjects/10 years, p = 0.002 defined by TG × G; and 13.4% vs. 4.5% of subjects/10 years, p < 0.001 in subjects with the MetS. The area under the ROC curves to predict CVD were similar, 0.66 vs. 0.67 for TG/HDL-C and TG × G, respectively. However, when adjusted by age, sex and multiple covariates, hazard ratios for incident CVD were significantly increased in high risk patients classified by either TG/HDL-C ratio (2.18, p = 0.021) or MetS (1.93, p = 0.037), but not by TG × G index (1.72, p = 0.087). Although the 3 indices identify CVD risk comparably, the TG × G index seems somewhat less effective at predicting CVD.


Evidence that the GCN2 protein kinase regulates reinitiation by yeast ribosomes.
The yeast gene GCN4 produces an mRNA that has a long 5' 'untranslated' region containing four small open reading frames (ORFs) preceding the protein coding frame. This configuration suppresses the rate by which GCN4 protein is synthesized. However, translational derepression of the GCN4 mRNA occurs when yeast cells are grown under conditions of amino acid limitation. Such translational derepression requires the GCN2 protein kinase and the presence of the 5' most proximal ORF. In this study we show that a functional coupling between the translation of the first ORF and the amount of the GCN2 protein is responsible for the translational derepression of the GCN4 mRNA. Our evidence suggests that this coupling involves an increase in the ability of 40S ribosomal subunits that have translated the first frame to resume scanning and reinitiate translation at a downstream AUG independently of the base sequence in the intervening region.


Palliation of recurrent myxofibrosarcoma with radiotherapy and hyperthermia.
Soft tissue sarcomas are rare biologically and histologically heterogeneous neoplasms that may arise throughout the body. The preferred treatment is total resection with a sufficient margin. Radiotherapy with or without chemotherapy offers another treatment option, but its effectiveness is limited. Hyperthermia, a treatment method that heats tumour tissue by exposing the target tissues to conductive heat sources or non-ionising radiation, is known to enhance the effect of radiotherapy. We report a case of an elderly man with a second recurrent myxofibrosarcoma in the left groin, who responded well to radiotherapy in combination with hyperthermia. This combination treatment was effective in maintaining the patient's quality of life during his remaining years.


Tobacco control in New Zealand from 1945 to 1961.
The 1945 to 1961 period was characterised by a significant increase in the international scientific knowledge of the health risks of smoking. Despite this, there was relatively little response by the New Zealand Government, the New Zealand medical profession and other local agencies. Specific tobacco control activities were virtually limited to some episodic and low profile publicity measures, and an incidental increase in tobacco taxation. This limited response may have partly been due to the slow diffusion of the health risk information to health professionals in this country and the presence of other more obvious health concerns (such as polio epidemics). Other reasons may have been the absence of a New Zealand research base, the lack of focused advocacy groups, political wariness about using tobacco taxation, a minimalist approach by government to product safety regulation and the major extent to which smoking was normalised within New Zealand society. Britain and the US led to further research. Reports linking lung cancer to smoking were published in 1950 by Doll and Hill in Britain, and by Wynder and Graham in the US. As a result of subsequent prospective studies, the American Cancer Society and the British Medical Research Council produced in 1954, independent reports that death rates were higher for cigarette smokers. A number of further studies on smoking and health were published in Britain and the US during the 1950s (e.g. by Doll and Hill in 1954), and the Medical Research Council and the United States Surgeon General gave further strong warnings. However, the unease of some parts of the medical world with the new science of epidemiology was reflected in the confusion by public and politicians over the conclusiveness of the evidence. Nevertheless, by the late 1950s there was evidence of declining tobacco consumption amongst US doctors, partly at least because of concern about health risks such as lung cancer.


Succinylcholine-induced fasciculations in denervated rat muscles as measured using 31P-NMR spectroscopy: the effect of pretreatment with dantrolene or vecuronium.
We have previously demonstrated by 31P nuclear magnetic resonance (NMR) that succinylcholine (SCh) induces metabolic changes in denervated muscle. To specify those changes, we attempted to inhibit them using two different kinds of drugs, dantrolene and vecuronium. Three weeks after unilateral sciatic nerve section, 75 male Wistar rats were randomly assigned to one of the following 5 groups: (1) non-pretreated normal muscle group; (2) non-pretreated denervated muscle group; (3) denervated muscle group pretreated with a low dose of vecuronium (0.02 mg.kg(-1)); (4) denervated muscle group pretreated with a high dose of vecuronium (0.2 mg.kg(-1)); (5) denervated muscle group pretreated with dantrolene (2 mg.kg(-1)). The change of the inorganic phosphate/phosphocreatine (Pi/PCr) ratio of each muscle was measured by 31P-NMR before and after SCh (1 mg.kg(-1)) administration and the corresponding peak amplitude of the electromyograms (EMG) was determined. The high dose of vecuronium totally inhibited SCh-induced fasciculation on EMG (100%-->2%). In this group, though the Pi/PCr ratio significantly increased 10 min after SCh, the peak after 5 min disappeared. The inhibition with dantrolene was about the same order of magnitude as with the low dose of vecuronium (35%:21%). However, the increase in the Pi/PCr only lasted about 10 min, in contrast to the other drugs. Our findings indicate that the Pi/PCr increases 5 and 10 min after SCh, respectively, as a result of two different processes. The first peak is caused by an excessive energy consumption in response to excessive muscle contraction. This in turn triggers the second peak, caused by breakdown of glycogen, initiated by an increased Ca2+ concentration.


3D synaptic organization of layer III of the human anterior cingulate and temporopolar cortex.
The human anterior cingulate and temporopolar cortices have been proposed as highly connected nodes involved in high-order cognitive functions, but their synaptic organization is still basically unknown due to the difficulties involved in studying the human brain. Using Focused Ion Beam/Scanning Electron Microscopy (FIB/SEM) to study the synaptic organization of the human brain obtained with a short post-mortem delay allows excellent results to be obtained. We have used this technology to analyze layer III of the anterior cingulate cortex (Brodmann area 24) and the temporopolar cortex, including the temporal pole (Brodmann area 38 ventral and dorsal) and anterior middle temporal gyrus (Brodmann area 21). Our results, based on 6695 synaptic junctions fully reconstructed in 3D, revealed that Brodmann areas 24, 21 and ventral area 38 showed similar synaptic density and synaptic size, whereas dorsal area 38 displayed the highest synaptic density and the smallest synaptic size. However, the proportion of the different types of synapses (excitatory and inhibitory), the postsynaptic targets, and the shapes of excitatory and inhibitory synapses were similar, regardless of the region examined. These observations indicate that certain aspects of the synaptic organization are rather homogeneous, whereas others show specific variations across cortical regions.


Increased beta-actin expression in an invasive moloney sarcoma virus-transformed MDCK cell variant concentrates to the tips of multiple pseudopodia.
An invasive variant of Moloney sarcoma virus-transformed MDCK cells (MSV-MDCK-INV), which was isolated by the repeated selection of cells that successfully traversed a Matrigel-coated filter, exhibits increased motile ability and presents an elongated cell shape and numerous pseudopodia. Although stress fibers are present in both MDCK and MSV-MDCK cells, MSV-MDCK-INV cells contain no stress fibers and exhibit a dense concentration of actin at the tips of pseudopodia. Relative to both MDCK and MSV-MDCK cells, the MSV-MDCK-INV cells exhibit increased expression of beta-actin and redistribution of beta-actin to the tips of pseudopodia. These actin concentrations are enriched in both F- and G-actin and, thus, represent dynamic regions of actin cytoskeleton remodeling. The acquisition of invasive properties by epithelial transformants is, therefore, associated with the increased expression of beta-actin and its concentration in actin-rich domains, which may drive pseudopodial extension and facilitate tumor cell invasion.


Relationship between CTLA-4 and CD28 molecule expression on T lymphocytes and stimulating and blocking autoantibodies to the TSH-receptor in children with Graves' disease.
The present study was performed to elucidate the relationship between CTLA-4/CD28 molecules and stimulating (TSAb) and blocking (TBAb) antibodies to the TSH-receptor (TSH-R) in Graves' disease. CD28 and CD152 (CTLA-4) are glycoprotein molecules which provide a potent costimulatory signal for T-cell activation and proliferation via interactions with their ligands, B7.1/B7.2 molecules, which are present on the surface of antigen-presenting cells. The aim of the study was to estimate the expression of cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4, CD152), CD28, B7.1 (CD80), and B7.2 (CD86) molecules on peripheral blood cells in patients with Graves' disease (GD) (n = 55, mean age 15.5 +/- 5.1 years) and nontoxic nodular goiter (NTNG) (n = 55, mean age 15.2 +/- 4.5 years), in comparison with sex and age-matched healthy control subjects (n = 55, mean age 15.2 +/- 3.9 years). The expression of the costimulatory molecules on mononuclear cells was analyzed by three-color flow cytometry using a Coulter EPICS XL cytometer. Detection of TSAb and TBAb to the TSH-R using JPO9 CHO cells in unfractionated serum was measured by a highly sensitive commercial radioimmunoassay. When compared with healthy control subjects and euthyroid patients with GD, untreated patients with GD showed a significant increase of CD152+ (p < 0.001, p < 0.001) and CD28+ (p < 0.01, NS) T lymphocytes, respectively. After 6-12 months of methimazole therapy, the percentage of these cells in the peripheral blood of hyperthyroid patients returned to normal values. In addition, patients with GD showed an increase in the percentage of both B7.1 (3.8%) and B7.2 (18.4%) molecules on activated monocytes, compared to patients with NTNG (0.5% p < 0.05, 2.5% p < 0.01, respectively) and healthy control subjects (0.2% p < 0.05, 0.8% p < 0.003, respectively). In patients with untreated GD there was a statistically significant positive correlation between the expression of CTLA-4 on the surface of peripheral blood T cells and the index of TSAb antibodies (R = 0.54, p < 0.001) as well as a negative correlation with TBAb antibody titer (R = -0.58, p < 0.001). However, no such correlations were noted with regard to CD28 and anti-TPO, anti-TG, and TRAb antibodies. We conclude that changes in the expression of costimulatory molecules on the surface of peripheral blood T cells and their significant relationship with the level of antithyroid antibodies indicate an involvement of these molecules in the pathogenesis of GD.


Diapering, diaper technology, and diaper area skin health.
Disposable diapers are the most common diaper care practice in Western societies today, and their use continues to increase globally. Improvements in disposable diaper technology have helped to reduce the prevalence and severity of diaper dermatitis (DD) over the course of the last few decades. This article reviews how changes in disposable diaper technology interact with the various etiological factors in DD, thus helping to improve overall diaper area skin health for children around the world.


Quantitative determination of bioactive 4-hydroxy-α-tetralone, tetralone-4-O-β-D-glucopyranoside and ellagic acid in Ammannia baccifera (Linn.) by reversed-phase high-performance liquid chromatography.
Ammannia baccifera is an important component of various Chinese herbal formulations for which a rapid, simple, sensitive, gradient and reproducible reversed-phase high-performance liquid chromatographic method has been developed for the quantitative estimation of its bioactive constituents, 4-hydroxy-α-tetralone (4H), tetralone-4-O-β-D-glucopyranoside (T4) and ellagic acid (EA). The chromatographic separation of samples was performed on a Chromatopak Peerless C18 (250 × 4.6 mm i.d., 5 µm) column by gradient elution with 0.1% trifluoroacetic acid in water and methanol at a flow rate of 0.6 mL/min, a column temperature at 25°C and ultraviolet detection at λ 254 nm. The limit of detection (LOD) and limit of quantification (LOQ) were 1.51 and 5.06 µg/mL for EA, 0.70 and 2.33 µg/mL for T4 and 0.22 and 0.73 µg/mL for 4H, respectively. Good results were achieved with respect to linearity (r(2) > 0.999), repeatability (relative standard deviation ≤ 1.73%) and recovery (99.06-100.76%). The method was validated for linearity, accuracy, repeatability, LOQ and LOD. The method is simple, accurate and precise and was successfully applied to the analysis of these three analytes in five different leaf and root samples of A. baccifera; the method may be recommended for routine quality control analysis of various Chinese herbal formulations containing A. baccifera.


Evaluation of volatile compounds, phenolic acids, antioxidant potential and DFT study of essential oils from different parts of Araucaria columnaris (G. Forst.) Hook. from India.
This study is aimed to investigate the aroma composition, phenolic acid, antioxidant activities and computational analysis of essential oils of five different parts of A. columnaris (G. Forst.) Hook. from India. The essential oils were obtained from the fresh root, stem, leaves, bark, and branch of A. columnaris by hydro-distillation using a Clevenger apparatus: the volatile composition was examined by GC-MS; the phenolic acid quantification by RP-HPLC-DAD and the estimation of antioxidant potential by TAC, FRAP, CUPRAC, MCA, DRSC, and NOSC assays. Total 136 chemical compounds i.e. root-60, stem-55, leaves-50, bark-55 and branch-42 were identified in essential oils by GC-MS and major constituents were β-pinene, terpinolene, 2-nonanone, pinocarveol, trans-verbenol, dihydrocarvone, dodecane, thymol, isolongifolene, α-copaene, α-gurjunene, β-caryophyllene, isoledene, γ-muurolene, γ-cadinene, etc. The five phenolic acid contents were determined by RP-HPLC-DAD with AR: 91-99%, LOD: 0.010269-0.119857 mg/g and LOQ: 0.039553-0.003388 mg/g. The Density Functional Theory (DFT) study was carried out on the main phytochemicals present in essential oils of A. columnaris in a manner to support the experimental results and give detailed of antioxidants and reactivity parameters. The results suggested that the essential oils of A. columnaris have high antioxidant potential due to the presence of phenolic acids and aroma compositions.


Kinematic analysis of spinal fusions.
Two cases with clinical suspicion of incompletely healed anterior fusion between L5 and S1 were examined by means of a roentgen stereophotogrammetric method. In both cases a pseudarthrosis was found. The method makes it possible to disclose rotations and translations between veretebrae with an accuracy of about 0.2degree and 30-120 mum, respectively.


EPA and DHA in blood cell membranes from acute coronary syndrome patients and controls.
Increased blood levels of the omega-3 fatty acids (FA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been inversely associated with risk for sudden cardiac death, but their relationship with acute coronary syndromes (ACS) is unclear. We hypothesized that the EPA+DHA content of blood cell membranes, as a percent of total FAs, is reduced in ACS patients relative to matched controls. We measured the content of EPA+DHA in 768 ACS patients and 768 age-, sex- and race-matched controls. The association with ACS case status of blood cell EPA+DHA [both by a 1 unit change and by category (low, <4%; intermediate 4.1-7.9%; and high, > or =8%)] was assessed using multivariate conditional logistic regression models adjusting for matching variables and smoking status, alcohol use, diabetes, body mass index, serum lipids, education, family history of coronary artery disease, personal histories of myocardial infarction and hypertension, and statin, aspirin, and other antiplatelet drug use. The combined groups had a mean age of 61+/-12 years, 66% were male, and 92% were Caucasian. The EPA+DHA content was 20% lower in cases than controls (3.4+/-1.6 vs. 4.25+/-2.0%, p<0.001). The multivariable-adjusted odds for case status was 0.77 (95% CI 0.70 to 0.85, p<0.001) for a 1 unit increase in EPA+DHA content. Compared with the lowest EPA+DHA group, the odds ratio for an ACS event was 0.58 (95% CI 0.42-0.80), in the intermediate EPA+DHA group and was 0.31 (95% CI 0.14-0.67; p for trend <0.0001) in the highest EPA+DHA group. Odds for ACS case status increased incrementally as the EPA+DHA content decreased suggesting that low EPA+DHA may be associated with increased risk for ACS.


Ocular biometric parameters of mild hyperopia to mild myopia children aged 6-14 years from Wenzhou optometry center: A cross-sectional study.
Myopia is the most common visual disorder in school-aged children and adolescents worldwide. This study aimed to explore the ocular biometric characteristics of children aged 6-14 years from the Wenzhou optometry center and to determine the relationship between spherical equivalent refraction (SER) and macular pigment optical density (MPOD). Participants underwent a full-scale ophthalmic examination anteriorly and posteriorly. Relevant parameters were documented, such as axial length (AL), anterior chamber depth (ACD), SER and lens thickness (LT), corneal curvature radius (CCR), and MPOD. Lens power (LP) was calculated using Bennett's formula. Shapiro-Wilk tests and histograms were used to check the normality of the distribution of refractive and ocular biometric parameters. Scatter diagrams were adopted to analyze the relationships between refraction and parameters of ocular biometry. Multiple linear regression models were employed to fit the associated factors of AL, AL/CCR, and LP. A total of 902 mild hyperopia to mild myopia (+3.00 D ≤ SE ≤ -3.00 D) children aged 6-14 years were included. The mean age of participants was 10.03 ± 2.47 years, and the prevalence of mild hyperopia, emmetropia, and myopia was 5.65, 27.05, and 67.30%, respectively. The prevalence of mild myopia increased from 30.53% at 6 years of age to 93.62% at 14 years of age. Overall, AL, ACD, and AL/CCR increased, but LP declined from 6 to 14 years of age, whereas CCR and MPOD remained stable. An increase of 1 mm in AL was associated with -0.69 D of myopic change. A unit increase in AL/CCR was associated with -7.87 D in SER. As for the SER variance, AL explained 30.5% and AL/CCR explained 51.1%, whereas AL/CCR and LP accounted for 59.2%. In this work, we have studied the distributions of ocular biometric characteristics of mild hyperopia to mild myopia children from the perspective of an optometry center rather than a sampling survey. In addition, we found that children from the optometry center had a slower progression toward myopia than those from previous sampling surveys, which was an informative finding for future myopia prevention. In addition, we have made a correlation analysis between the macular pigment optical density and spherical equivalent refraction. Though, no correlation was found.


Different mechanisms of contralateral- or ipsilateral-acupuncture to modulate the brain activity in patients with unilateral chronic shoulder pain: a pilot fMRI study.
Chronic shoulder pain (CSP) is a common disease causing pain and functional limitation, which is highly prevalent and has substantial negative effects on the quality of life. Acupuncture has gained popularity and has been accepted gradually by many countries because it can successfully treat patients with chronic pain, but the specific brain mechanisms under acupuncture treatment for CSP remain unclear. Therefore, in this study, we aimed to 1) compare the clinical effects between acupuncture at the contralateral and ipsilateral Tiaokou (ST 38) point in patients with unilateral shoulder pain and 2) explore how contralateral- and ipsilateral-acupuncture modulates the regional homogeneity (ReHo) of patients with CSP. This was a pilot functional magnetic resonance imaging (fMRI) trial. Twenty-four patients with CSP were recruited and randomized to the contralateral acupuncture group (contra-group) and the ipsilateral acupuncture group (ipsi-group). All patients completed resting-state functional magnetic resonance imaging (fMRI) scans before and after acupuncture treatment. Shoulder pain intensity (visual analog scale [VAS]) and shoulder joint function (Constant-Murley score [CMS]) were used to evaluate clinical efficiency of treatment. ReHo was used to assess resting-state brain activity. We found clinical improvement in decreasing pain intensity and increasing shoulder function in both groups, and the mean objective shoulder functional improvement in contra-group was better than that in ipsi-group (p = 0.010). Interestingly, the brain mechanism of contra-acupuncture at ST 38 was distinguishable from ipsi-acupuncture regarding ReHo values. Anterior cingulate cortex (ACC) may play a direct role in the regulation of brain by the contralateral acupuncture at ST 38 in patients with shoulder pain. On the contrary, the pathway of brainstem-thalamus-cortex may be likely to work in mechanism of acupuncture at ipsilateral ST 38. Our results indicate that the clinical effects and brain mechanisms are different between the stimulation given at contralateral and ipsilateral acupoints in patients with CSP and imply that the selection of either contralateral or ipsilateral acupuncture therapy to treat some chronic pain conditions is necessary.


Pancreatic beta cell changes induced by cyproheptadine in vitro.
The effect of cyproheptadine on the structure and function of rat pancreatic beta cells was studied in vitro by culturing isolated islets in media containing the drug (0.5 mM). After 8 days in culture the ultrastructure of islet cells maintained in control media appeared well preserved, being similar to the previously reported for islets kept in long term organ culture. In contrast beta cells from islets incubated in media containing cyproheptadine appeared degranulated and the rough endoplasmic reticulum showed cisternal dilation and vacuole formation. These vacuoles were filled with an electron-dense granular material and their surface was usually studded with ribosomes. These lesions are identical with those produced by the administration of cyproheptadine to rats in vivo. In addition to these findings, increased numbers of lysosomes and myeloid bodies were observed in both alpha and beta cells. Compared with that of the controls, the 24-hour basal insulin secretion of islets cultured in the presence of cyproheptadine was significantly reduced from the 4th day of the study onwards. It is thus concluded that cyproheptadine has direct effects on the morphology and function of the rat pancreatic beta cell.


Characteristics of Pseudomonas corneal infection related to orthokeratology.
To describe a Pseudomonas aeruginosa corneal infection resulting from orthokeratology. Case report. A 17-year-old boy wearing orthokeratology (OK) lenses was referred to our clinic because of redness in his right eye in spite of his usage of ofloxacin (OFLX) eye drops. An excavated paracentral corneal ulcer with an immune ring and hypopyon was observed. It was positioned under the paracentral steeper portion of the optic of the OK lens. Culture of the lens solution revealed P. aeruginosa. The patient was treated with topical OFLX and cefmenoxime (CMX) plus intravenous and subconjunctival injections of cefozopran (CZOP), successfully. The antibiotic susceptibility of P. aeruginosa by the disk diffusion susceptibility test was reduced under moderately hypoxic conditions. Glycocalyx slime was formed on the OK lens in vitro by P. aeruginosa isolated from the case. Changes in P. aeruginosa susceptibility to antibiotics under moderately hypoxic conditions and glycocalyx slime formation might affect the features of OK lens-associated infections.


Iridium-catalyzed Synthesis of Saturated N-Heterocycles from Aldehydes and SnAP Reagents with Continuous Flow Photochemistry.
Commercially available tin amine protocol (SnAP) reagents provide a simple approach to the synthesis of a wide variety of saturated N-heterocycles from aldehydes. In this report, we disclose that the copper(II) promoter and hexafluoroisopropanol can be replaced by photocatalytic conditions using Ir[dF(CF3)ppy]2(dtbbpy)PF6 in CH3CN. Continuous flow photochemical conditions provide a clean, scalable approach to valuable products including morpholines, piperazines, thiomorpholines, diazepanes, and oxazepanes from aldehyde starting materials.


[A case of vesicosigmoidal fistula].
The clinical course of a case of vesicosigmoidal fistula is presented. The patient, a 76-year-old woman, became aware of terminal micturition pain and pollakisuria in February, 1985. She was first treated under the diagnosis of cystitis to be relieved of her subjective symptoms, although there was no improvement of pyuria. She also began to feel lower abdominal pain on April 3, 1985. After various examinations including intravenous pyelography, enteroclysis and cystoscopy the diagnosis of vesicosigmoidal fistula originating from sigmoid diverticulitis was established. Careful observation at operation revealed remarkable adhesion among the sigmoid colon, bladder, uterus and left ovary. The sigmoid colon, was resected followed by end-to-end anastomosis. Because of considerably extensive inflammatory changes over the mucosal membrane of the bladder, the hole of fistula on the vesical wall was simply closed from outside of the bladder without performing partial cystectomy. Histological examination only demonstrated non-specific inflammatory changes without evidence of malignancy. She had a favorable progress postoperatively.


Selective expression of class II E alpha d gene in transgenic mice.
Class II genes of the MHC must be expressed by APC for activation of CD4+ T cells and efficient delivery of T cell help to B lymphocytes. Class II genes have restricted tissue expression and are under complex regulation. By using various deletion constructs of the class II E alpha d gene in transgenic mice we have mapped different 5' flanking regions which control E alpha d gene expression in distinct cell types. We demonstrate dissociate expression of E alpha d within the macrophage lineage as well as within the B cell lineage, and present evidence for a repressive element operative in B cells and macrophages. We describe the generation of novel transgenic lines with limited constitutive and inducible E alpha mRNA and I-E protein.


Review of effective advanced cardiac life support training using experiential learning.
This paper examines issues of contention regarding current practices and suggests the application of the experiential theory of learning (incorporating reflective practice) to advanced cardiac life support (ACLS) training. The need for formalized training in cardiopulmonary resuscitation (CPR) and ACLS is well documented. However, the effectiveness of traditional training programmes has not been firmly established. The question still remains - how to best ensure transfer of learning enabling learners to apply classroom knowledge successfully in the clinical setting. It is argued that educators can no longer rely on traditional teaching methods and more effective learner-centred education techniques are required. A review of available literature regarding ACLS training has been conducted for this discussion. MEDLINE, CINAHL, OVID, Expanded Academic and Proquest were searched using textwords. English-language articles related to CPR and ACLS practices and also experiential learning were reviewed. Additional references were also reviewed from the bibliographies and from citation searches on key articles. Articles related to CPR/ACLS and experiential learning practices published within the last 10 years were reviewed. There is evidence that past ACLS training programmes have proven inconsistent and inadequate, with numerous studies reporting trainees have poor retention; and, therefore, ineffective ACLS skills as a result. The reviewed literature demonstrates that the need for effective ACLS training is clear. Increasing numbers of critically ill patients in hospitals means that it has never been more important to ensure the competence of healthcare professionals. Training must give learners a chance to pull together all aspects of ACLS and the use of experiential learning has the potential to achieve this aim. It is argued that providing training designed and implemented using experimental learning enhances learning through critical thinking and reflection, and subsequently should improve ACLS outcomes.


Severer lupus erythematosus-like skin lesions in MRL/lpr mice with homozygous Kitwsh/wsh mutation.
To clarify the roles of mast cells (MCs) on the pathogenesis of lupus erythematosus (LE)-like skin lesions on MRL/lpr mice. MRL/lpr mice were mated with C57BL/6-Kitwsh/wsh mice and the heterozygous F1 mice were 10 times backcrossed with the parental MRL/lpr to generate MRL/lpr-Kitwsh/wsh mice. MC-deficient MRL/lpr-Kitwsh/wsh mice were compared with MRL/lpr-Kit+/+ and MRL/lpr-Kitwsh/+ mice with intact MCs. MRL/lpr-Kitwsh/wsh mice developed skin lesions without infiltrating MCs. As similar skin lesions on MRL/lpr-Kit+/+ mice and MRL/lpr-Kitwsh/+ mice contain comparable number of MCs, these mice were collectively analyzed as MRL/lpr mice with MCs. Compared with MRL/lpr mice with MCs, skin lesions developed earlier and showed consistently higher severity, with significantly higher mRNA expressions of many inflammatory cytokines in the dorsal skin on MRL/lpr mice without MCs. Furthermore, survival rate was significantly lower in MRL/lpr mice without MCs. The number of infiltrating MCs significantly increased in association with the severity of skin lesions in MRL/lpr mice with MCs. These results demonstrated that MCs are infiltrated to suppress the progression of LE-like skin lesions in MRL/lpr mice.


Developmental toxicity of cryptotanshinone on the early-life stage of zebrafish development.
Cryptotanshinone (Cry) has multiple potential functions in treating different diseases. Most studies on Cry focus on its pharmacological effects and mechanisms, but toxicological reports on Cry are rare. Zebrafish is used as a model organism in drug development as it saves costs and time. This work aimed to investigate the toxicity of Cry on zebrafish. Results showed that growth retardation, pericardial edema, and scoliosis occurred when zebrafish embryos were exposed to Cry, indicating its teratogenic effects. Cell apoptosis was observed in the brainstem area of embryos using acridine orange staining, and qPCR showed that caspase-3 was increased in Cry-exposed embryos. The results of locomotor activity and touched-evoke escape reaction experiments showed that Cry significantly reduced the swimming speed and escape reaction time of larvae.


Zinc(II) and copper(II) binding to serum albumin. A comparative study of dog, bovine, and human albumin.
Metal binding strategies employing low molecular weight chelators and equilibrium dialysis were used to investigate several unresolved aspects of zinc and copper binding to serum albumin. Direct measurement of histidine binding to bovine serum albumin when the histidine is presented either as a metal-chelate or alone provides no evidence for an albumin-metal-histidine ternary complex. Using previously determined intrinsic constants for Zn(II) and Cu(II), we have measured zinc binding to bovine serum albumin in the presence of saturating amounts of copper. The results of these experiments unambiguously show that zinc and copper bind at separate noninteracting sites on this protein. The intrinsic constants for zinc and copper binding to dog serum albumin have been determined. Contrary to previous reports, we find that dog serum albumin has a specific high affinity site for copper, log10K 10.17 for Cu(II) compared to 6.85 for Zn(II) at the separate site.


Digestibility and dietary quality of nonacetylated and acetylated Vicia faba proteins in maintenance. Studies on 15N-labelled adult rats.
N digestibility and the dietary quality of a Vicia faba protein isolate as well as of two protein fractions from this isolate, acetylated and nonacetylated, were estimated in 15N-labelled adult rats. For reference, whole egg, casein and wheat were studied. The diets were fed at maintenance energy intake level. Daily metabolic fecal nitrogen estimated by an isotopic method was 5 mg/100 g body weight in animals receiving whole egg, casein, or Vicia faba proteins. When wheat was included in the diet metabolic fecal nitrogen was increased to 140% of this value. True N digestibility of reference proteins was 91-92% and of Vicia faba proteins 95-97%. Protein quality for maintenance was high and similar for all proteins. Acetylation affected neither N digestibility nor protein quality under maintenance conditions.


[Soluble CD40 ligand in systemic lupus erythematosus: link with atherosclerotic vascular affection].
To evaluate clinical implications of pCD40L as a marker of atherosclerotic vascular affection in systemic lupus erythematosus (SLE). The examination of 132 females (mean age 35 years, SLE duration 96 months) assessed classic factors of atherosclerosis risk (AR), total coronary risk (TCR), detected subclinical atherosclerosis with ultrasonic scanning of the carotid arteries. Serum level of pCD40L was measured with enzyme immunoassay (EL4). Concentration of pCD40L in SLE patients was higher than in the control group (7.1 +/- 4.9 and 5.8 +/- 3.1 ng/ml, respectively) but the difference was insignificant (p > 0.05). Upper limit of normal value (M + 2SD) for pCD40L was 12 ng/ml. Elevation of pCD40L level was seen in 21% of SLE patients. Clinical manifestations of atherosclerosis risk were seen in 13% SLE patients, subclinical in 19 and 17% (increased intima-media thickness and atherosclerotic plaques, respectively). No correlations were found between pCD40L level and atherosclerotic symptoms. The pCD40L level was higher in SLE patients with the plaques than in those without them (p = 0.005). A positive correlation exists between a pCD40L concentration and maximal intima-media thickness (r = 0.2; p = 0.02), total cholersterol (r = 0.3; p = 0.002), LDLP cholesterol (r = 0.3; p = 0.004), LDLP cholesterol (r = 0.2; p = 0.04) and age of the patients (r = 0.2; p = 0.03). In patients with TCR > 20% a pCD40L was significantly higher than in patients with TCR < 20% (p = 0.01). Elevated pCD40L level is a marker of atherosclerotic affection of the vessels, has an important clinical role for predicting risk of cardiovascular diseases in SLE and elicidation of the role of activation of cell immunity in development of atherosclerosis in this disease.


A Novel Curative Treatment Strategy for Patients with Lower Grade Rectal Gastrointestinal Stromal Tumor: Chemoreduction Combined with Transanal Endoscopic Microsurgery.
A multimodal treatment has been applied for patients with rectal gastrointestinal stromal tumor (GIST) that represents 5% of the total localization. Meanwhile, transanal endoscopic microsurgery (TEM) offers a minimally invasive method for full-thickness tumor excision with negative margins and low morbidity. We report the single most extensive analysis of data from China to evaluate the feasibility and safety of the procedure combined with neoadjuvant imatinib therapy to treat patients with rectal GISTs. All the clinical data were obtained for patients who underwent the procedure in our hospital from February 2008 to May 2015, and the data were retrospectively analyzed. Full-thickness excision by TEM was performed on 25 patients with rectal GIST by using primary surgical excision, 8 of whom had received perioperative chemotherapy after histopathological confirmation under the care of medical oncologists. No obvious postoperative complications were observed. The average tumor downsizing ratio was 14.5%, which apparently enabled oversized tumors to be resected by TEM. The comparative risk did not increase during or after the procedure. We did not observe recurrence or metastasis in any of the 25 patients during the median 3-year follow-up period after the procedures. The perioperative imatinib treatment effectively allowed oversized rectal GIST tumors to be resected by TEM, and the procedures did not exhibit an increased risk. Exclusively, the TEM procedure with alternative neoadjuvant imatinib therapy is a feasible and safe modality for treating patients with rectal GISTs.


Effects of captopril on atherosclerosis in cynomolgus monkeys.
A study was performed to investigate if oral dosing of captopril could influence the development of atherosclerosis in cholesterol-fed cynomolgus monkeys. Twenty-four monkeys were divided into four groups: (a) a control group given a normal monkey diet and placebo medication; (b) a high cholesterol group given a high cholesterol diet and placebo medication; (c) a low-dose captopril group given the cholesterol diet and 25 mg/kg of captopril twice daily; and (d) a high-dose captopril group given the cholesterol diet and 50 mg/kg of captopril twice daily. The doses of captopril used in this study did not change the levels of total serum cholesterol, high-density lipoprotein (HDL), or triglycerides. The total cholesterol/HDL ratio was also unaffected by captopril. The animals were killed after 6 months of treatment. The progression of atherosclerosis was assessed by gross pathology, histopathology, and biochemical methods. The results showed a significantly reduced progression of arterial lesions in monkeys given captopril; the effects of captopril were most evident in the coronary arteries, which were practically free from atherosclerosis in captopril-treated animals.


Allometric study on the relationship between the growth of ovarian follicles and oocytes in domestic cats.
The relationship between the growth of preantral and antral follicles and that of their oocytes in ovaries of domestic cats (Felis catus) was analyzed. Eight hundred and five pairs of follicles and oocytes from the ovaries of 51 female cats were collected, and only healthy and fresh follicles and oocytes with or without zona pellucida were used in this study. Immediately after collection, the diameters of follicles and their oocytes were measured. The relationship of the follicle diameter to the oocyte diameter was applied to four regression models and statistically analyzed. The best fitting model was found to be a hyperbolic regression (the coefficient of determination was 0.976 between the follicles and their oocytes with a zona pellucida, y=184x/(x+0.0738); the coefficient of determination was 0.983 between the follicles and their oocytes without a zona pellucida, y=122x/(x+0.0301)). The differentiated equations for the hyperbolic curves in the oocytes with or without a zona pellucida and the follicles were found to be y'=13.6/(x+0.0738)² and y'=3.67/(x+0.0301)², where y and x were the diameters of the oocytes (μm) and follicles (mm), respectively. When follicles grew to a size larger than 0.4 mm in diameter, the growth rates of their oocytes calculated by the differentiation equations showed an asymptotic depression around zero. Thus, it was suggested that when the follicles grew to a size larger than 0.4 mm in diameter, their oocytes reached full size and ceased to grow and that the zona pellucida stopped growing when the diameter of the follicles reached 0.3 mm in domestic cats.


Persistent caruncular hyperemia revealing unsuspected orbital foreign body.
A peculiar case of a 13-years-old child with persistent caruncular hyperemia following trauma to the right eye with a tree branch which didn't improved after several days of oral and intravenous antibiotic therapy. Closer examination revealed organic foreign body that was not evident on initial evaluation, computerized tomography with and without contrast nor on magnetic resonance imaging. After removal of the organic foreign body symptoms resolved.


Cultural Neuroscience.
Cultural neuroscience issues from the apparently incompatible combination of neuroscience and cultural psychology. A brief literature sampling suggests, instead, several preliminary topics that demonstrate proof of possibilities: cultural differences in both lower-level processes (e.g. perception, number representation) and higher-order processes (e.g. inferring others' emotions, contemplating the self) are beginning to shed new light on both culture and cognition. Candidates for future cultural neuroscience research include cultural variations in the default (resting) network, which may be social; regulation and inhibition of feelings, thoughts, and actions; prejudice and dehumanization; and neural signatures of fundamental warmth and competence judgments.


Spirometra erinacei / S. erinaceieuropaei in a feral cat in Manawatu with chronic intermittent diarrhoea.
A feral cat captured in the Manawatu region of New Zealand was treated for worms and fleas, and kept confined in a metabolic cage. It showed good appetite and weight gain but had intermittent watery, yellow diarrhoea. Clinical examination under sedation was unremarkable and routine blood tests showed no significant abnormalities. The cat was negative for feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV). Different canned cat foods did not alter the course of the diarrhoea, and the cat was euthanised 6 months after capture. At necropsy, two sections of adult Spirometra tapeworms were found in the jejunum and typical Spirometra eggs were found in colonic contents. Molecular identification of the parasite was undertaken, using the cytochrome-c oxidase subunit-1 gene (cox1) sequence. Chronic intermittent diarrhoea associated with Spirometra erinacei / S. erinaceieuropaei infection. Spirometra has not been reported in New Zealand before but has been associated with gastrointestinal disease in cats in other parts of the world. It requires species targeted treatment to be eliminated effectively, and is zoonotic. Diagnosis could be difficult for clinicians who are not familiar with the parasite and its life cycle.


Spontaneous chronic subdural hematoma in young adult: the role of missing coagulation facto.
Chronic subdural hematoma (CSDH) is typically in elderly and rarely in young people. To prevent complications and re-bleeding after surgical treatment of CSDH it is important to assess the risk factors as coagulation disorders especially in young patients (below 65 years) with no history of head trauma, alcohol abuse or anticoagulant therapy. This study consists of 16 patients (12 males, 4 females) with age ranging from 27 to 59 years (median 48,25 years) operated for CSDH. All patients are submitted to routine coagulation parameters pre-operatively and complete screening for unknown coagulation deficit in the follow-up. Factor VII was altered in 6 out of 16 patients and one patient had the alteration of the Von Willebrand factor. Recurrence occurred in 4 out of 16 patients and all of these patients were positive for factor VII deficiency. Three pts were in therapy with ASA. No patients were alcoholists or suffered from hematological disease. In this study we documented that the decreased activity of VII factor may play a role in the pathophysiology and recurrence of spontaneous CSDH in young adults. We suggest that for young patients aged under 65 y.o. suffered from CSDH the screening of coagulation factors is useful to planning a safely and correct surgical therapy.


The irradiated epidermis inhibits newt limb regeneration by preventing blastema growth. A histological study.
It has been established that X-ray irradiation localized to a forelimb or entire irradiation of premetamorphic Pleurodeles larvae prevented limb regeneration. Transplantation of non-irradiated skin, dermis or muscle to limb stumps of locally irradiated newts was sufficient to allow a blastema to develop. Transplantation of the same tissues to limb stumps of entirely irradiated newts yielded different results with the different graft types. Skin graft allowed a normal blastema to be established but dermis or muscle grafts did not. In order to define more precisely the role played by the epidermis in the establishment of a blastema, and in the growth of a regenerate, different combinations of limb tissues, either irradiated or not, were carried out at the level of amputated limb stumps. At four different times (8-10 days; 13-15 days; 20-23 days; 30 days or more) after amputation the stumps were examined in histological longitudinal sections to study the first events of regeneration, that is dedifferentiation and growth. Dedifferentiation occurred in both normal and irradiated tissues of mesodermal origin. The healthy mesenchymal cells began dividing and formed a growing blastema only when associated with a non-irradiated epidermis. Healthy mesenchymal cells covered with an irradiated epidermis exhibited a few mitoses after dedifferentiation, but the mitotic figures became rarer and rarer until the animals died. The lack of dense accumulation of blastemal cells in such limb stumps suggested that the healthy epidermis allows the mesenchymal cells to divide actively to constitute a growing blastema. Hence, X-ray irradiation seems to be responsible for the loss of such an epidermal mitogenic influence on the underlying mesenchymal cells.


Variation in management of intra-abdominal abscesses in children with Crohn's disease.
Complications of Crohn's disease may include intra-abdominal abscesses, which often result in hospitalization, surgery, and increased cost. There is a paucity of primary research and practice guidelines regarding optimal management in children. The study objective was to assess the current standard of care in an effort to define best practices and identify priority areas for additional research. The web-based survey was approved by the Institutional Review Board and North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. We examined preferences in imaging, drainage, anti-tumor necrosis factor-α therapy, and antibiotic use. We assessed for associations between provider level of experience and management strategies. A total of 248 of 1608 North American Society for Pediatric Gastroenterology, Hepatology and Nutrition members responded. Of them, 64% were male, 87% practiced in the United States, and 74% practiced in an academic setting. Approximately 26% cared for >50 patients with Crohn's disease and 25% were in practice for >20 years. For initial imaging, computed tomography was chosen by 52%, followed by magnetic resonance imaging (26%) and ultrasound (21%), and upon reassessment computed tomography was chosen by 13%, magnetic resonance imaging by 33%, and ultrasound by 47%. About 77% recommended percutaneous drainage, whereas 21% would only do so if antibiotics were unsuccessful, and 2% proceed to immediate surgery. If a fistula was demonstrated, 70% planned medical therapy followed by surgical resection; only 30% planned surgical resection if no fistula was present. Approximately 55% would consider infliximab before surgery. There were no clinically significant associations between treatment strategies and practitioner experience. There is considerable variation in diagnostic and therapeutic interventions in the management of intra-abdominal abscesses, which was not explained by practitioner experience.


Manipulation of rat litter size during suckling influences cortical spreading depression after weaning and at adulthood.
Nutritional conditions early in life constitute one environmental factor that can influence brain electrophysiological features. Cortical spreading depression (SD) is a brain electrophysiological phenomenon that can be altered by the early nutritional status of organism. SD-velocity changes were presently studied in young (30-40 days old) and adult (90-120 days) rats suckled in litters formed by 3, 6, or 12 pups (called respectively small (S), medium (M) and large (L) litters). Body weights and SD propagation velocities in the 3 groups varied, respectively in an inverse and direct way, in relation to the litter sizes. The present investigation provides the first systematic description of the effectiveness of favorable and unfavorable lactation conditions (respectively suckling in S and L litters) in altering cortical SD-propagation. The results confirm previous evidence in favor of permanent or at least long-lasting SD-changes associated to the prevailing nutritional status during the period of fast brain development.


Lighting programs for male and female meat quails (Coturnix coturnix) raised in equatorial region.
The aim of the present study was to evaluate the effect of lighting programs for male and female meat quails raised in an equatorial region on performance and carcass traits. A total of 1,500 sexed quails (Coturnix coturnix) was distributed in a completely randomized design in a 2 × 3 factorial arrangement, with 2 sexes (male and female) and 3 lighting programs (natural, intermittent, and continuous) with 5 replicates of 50 birds. The lighting programs were applied in the period from 7 to 49 d of age, being natural (12 h and 30 min of natural light and 11 h and 30 min of dark), intermittent (12 h and 30 min of natural light and 5 h and 30 min of artificial light, alternating lighting periods with one h and 06 min and periods of darkness with one h and 12 min), and continuous (23 h of natural + artificial light and one h of dark). Regardless of lighting program, female quails were heavier than males, and birds subjected to natural light weighed less than those exposed to continuous and intermittent lighting programs. Quails exposed to intermittent and continuous light presented higher weight gain and feed intake, and worse feed conversion ratio compared to birds under a natural light regimen. It is concluded that in an equatorial region, it is possible to use a lighting program with only natural light for raising male and female meat quails from 7 to 49 d of age.


The ischiatic region: normal and MRI anatomy.
The aim of this study was to describe the anatomy correlated to the normal magnetic resonance imaging (MRI) images of the proximal thigh region and the ischial tuberosity. MRI coronal and axial sequences were obtained from 20 asymptomatic volunteers (10 male and 10 female) aged 20 to 38 years (mean age: 28 years), and then they were compared with 2 anatomical dissections and 7 cryosections of 6 cadaver thighs. The anatomical specimens were directly correlated with MRI scans. From the comparison it could be seen how the axial MRI sequences well outlined the sciatic nerve, usually observed oval in shape with moderate signal intensity, and thus easily detectable from other surrounding organs. Other structures were also identified by axial images: the ischial tuberosity, the proximal origin of the hamstring muscles arising from the ischium and the related bursae, the gluteus maximus and its bursa, the quadratus femoris and its inconstant bursa, a triangular adipose body and vessels. Coronal scans also showed well the hamstring muscles, both in length and thickness. Both MRI images and cadaver dissections showed the ischial tuberosity as an interesting intersection area that could be delimited as follows: on the dorsal border the gluteus maximus and its bursa, on the dorso-medial side the hamstring muscle origin, and on the antero-lateral side the quadratus femoris muscle with its inconstant bursa and the ischial tuberosity. These anatomical and MRI descriptions are very useful to give a contribution to the right explanation of sciatic symptoms caused by those sports specifically overloading the hamstring muscles. Frequently, in fact, in these athletes a sciatic syndrome arise drawing the physician's attention to the lumbosacral joint or to the sciatic nerve course near the piriformis muscle. Another very important site where the sciatic symptoms can rise, indeed, could also be found in the hamstring muscle region, where the nerve run under the gluteus maximus beside the ischiatic bone. Athletes who manifest notorious muscle overload in this anatomical region usually show sciatic pain symptoms that are not to be related with pathologies of the lumbosacral junction nor to relationships of the sciatic nerve with the piriformis muscle but rather to relationships that this nerve acquires with either gluteal muscles as well as with muscles of the underneath ischiatic region.


Identification of regulatory elements in the Cyp19 proximal promoter in rat luteal cells.
The cytochrome P450 aromatase (Cyp19) gene encodes an enzyme of crucial importance in the synthesis of estradiol. Estradiol is luteotropic in the rat. In this species, luteal Cyp19 expression increases progressively during pregnancy and falls before parturition. The mechanisms that control these changes are unknown. Using gel shift assays, we sought to identify the promoter regions that control Cyp19 expression in the rat corpus luteum (CL). The Cyp19 promoter contains a cAMP response element-like sequence (CLS), two nuclear receptor elements half sites (NREs), a GATA binding site, a Yin Yang-1 (YY1) response element, and an activation protein 3 (AP3) binding site. Nuclear extracts were obtained from CL of rats on days 4, 15, and 23 of pregnancy and from the ovaries of immature rats treated with vehicle or a hormone that induces Cyp19 expression in the follicles. CLS was active in immature ovaries but inactive in the CL of pregnant rats, whereas binding to NREs and GATA was observed in both tissues. YY1 was inactive in all samples tested. In the CL, AP3 binding was higher on day 15 of pregnancy when compared with day 4 and day 23 but it was absent in ovaries of immature rats, whereas luteinization increased AP3 binding activity. Mutation of the AP3 site blunted the stimulation of Cyp19 promoter activity in granulosa cells. Our results indicate that CLS is active only in follicles; whereas in the CL, binding to the GATA, NRE, and AP3 sites associates with changes in Cyp19 expression, suggesting that they control Cyp19 promoter activity in luteal cells.


Performance Enhancement of Pedestrian Navigation Systems Based on Low-Cost Foot-Mounted MEMS-IMU/Ultrasonic Sensor.
The pedestrian navigation system (PNS) based on inertial navigation system-extended Kalman filter-zero velocity update (INS-EKF-ZUPT or IEZ) is widely used in complex environments without external infrastructure owing to its characteristics of autonomy and continuity. IEZ, however, suffers from performance degradation caused by the dynamic change of process noise statistics and heading estimation errors. The main goal of this study is to effectively improve the accuracy and robustness of pedestrian localization based on the integration of the low-cost foot-mounted microelectromechanical system inertial measurement unit (MEMS-IMU) and ultrasonic sensor. The proposed solution has two main components: (1) the fuzzy inference system (FIS) is exploited to generate the adaptive factor for extended Kalman filter (EKF) after addressing the mismatch between statistical sample covariance of innovation and the theoretical one, and the fuzzy adaptive EKF (FAEKF) based on the MEMS-IMU/ultrasonic sensor for pedestrians was proposed. Accordingly, the adaptive factor is applied to correct process noise covariance that accurately reflects previous state estimations. (2) A straight motion heading update (SMHU) algorithm is developed to detect whether a straight walk happens and to revise errors in heading if the ultrasonic sensor detects the distance between the foot and reflection point of the wall. The experimental results show that horizontal positioning error is less than 2% of the total travelled distance (TTD) in different environments, which is the same order of positioning error compared with other works using high-end MEMS-IMU. It is concluded that the proposed approach can achieve high performance for PNS in terms of accuracy and robustness.


Differences and similarities in false interpretations by AI CAD and radiologists in screening mammography.
We aimed to evaluate the false interpretations between artificial intelligence (AI) and radiologists in screening mammography to get a better understanding of how the distribution of diagnostic mistakes might change when moving from entirely radiologist-driven to AI-integrated breast cancer screening. This retrospective case-control study was based on a mammography screening cohort from 2008 to 2015. The final study population included screening examinations for 714 women diagnosed with breast cancer and 8029 randomly selected healthy controls. Oversampling of controls was applied to attain a similar cancer proportion as in the source screening cohort. We examined how false-positive (FP) and false-negative (FN) assessments by AI, the first reader (RAD 1) and the second reader (RAD 2), were associated with age, density, tumor histology and cancer invasiveness in a single- and double-reader setting. For each reader, the FN assessments were distributed between low- and high-density females with 53 (42%) and 72 (58%) for AI; 59 (36%) and 104 (64%) for RAD 1 and 47 (36%) and 84 (64%) for RAD 2. The corresponding numbers for FP assessments were 1820 (47%) and 2016 (53%) for AI; 1568 (46%) and 1834 (54%) for RAD 1 and 1190 (43%) and 1610 (58%) for RAD 2. For ductal cancer, the FN assessments were 79 (77%) for AI CAD; with 120 (83%) for RAD 1 and with 96 (16%) for RAD 2. For the double-reading simulation, the FP assessments were distributed between younger and older females with 2828 (2.5%) and 1554 (1.4%) for RAD 1 + RAD 2; 3850 (3.4%) and 2940 (2.6%) for AI+RAD 1 and 3430 (3%) and 2772 (2.5%) for AI+RAD 2. The most pronounced decrease in FN assessments was noted for females over the age of 55 and for high density-women. In conclusion, AI could have an important complementary role when combined with radiologists to increase sensitivity for high-density and older females. Our results highlight the potential impact of integrating AI in breast cancer screening, particularly to improve interpretation accuracy. The use of AI could enhance screening outcomes for high-density and older females.


Season- and herbivore-dependent competition and facilitation in a semiarid savanna.
Empirical and theoretical evidence suggests that facilitation between plants, when it occurs, is more likely during periods of abiotic stress, while competition predominates under more moderate conditions. Therefore, one might expect the relative importance of competition vs. facilitation to vary seasonally in ecosystems characterized by pronounced dry (abiotically stressful) and wet (benign) seasons. Herbivory also varies seasonally and can affect the net outcome of plant-plant interactions, but the interactive effects of seasonality and herbivory on the competition-facilitation balance are not known. I experimentally manipulated neighboring plants and herbivory during wet and dry periods for two species of grass: Cynodon plectostachyus and Pennisetum stramineum, in the semiarid Laikipia District of Kenya. These experiments indicate that Pennisetum was competitively dominant during the wet season and that it responded negatively to grazing, especially during the dry season. Cynodon showed more complex season- and herbivore-dependent responses. Cynodon experienced facilitation that was simultaneously dependent on presence of herbivores and on dry season. During the wet season Cynodon experienced net competition. These results illustrate how herbivory and seasonality can interact in complex ways to shift species-species competition-facilitation balance. Additionally, because Cynodon and Pennisetum are key players in a local successional process, these results indicate that herbivory can affect the direction and pace of succession.


Nitrate-dependent shoot sodium accumulation and osmotic functions of sodium in Arabidopsis under saline conditions.
Improving crop plants to be productive in saline soils or under irrigation with saline water would be an important technological advance in overcoming the food and freshwater crises that threaten the world population. However, even if the transformation of a glycophyte into a plant that thrives under seawater irrigation was biologically feasible, current knowledge about Na+ effects would be insufficient to support this technical advance. Intriguingly, crucial details about Na+ uptake and its function in the plant have not yet been well established. We here propose that under saline conditions two nitrate-dependent transport systems in series that take up and load Na+ into the xylem constitute the major pathway for the accumulation of Na+ in Arabidopsis shoots; this pathway can also function with chloride at high concentrations. In nrt1.1 nitrate transport mutants, plant Na+ accumulation was partially defective, which suggests that NRT1.1 either partially mediates or modulates the nitrate-dependent Na+ transport. Arabidopsis plants exposed to an osmotic potential of -1.0 MPa (400 mOsm) for 24 h showed high water loss and wilting in sorbitol or Na/MES, where Na+ could not be accumulated. In contrast, in NaCl the plants that accumulated Na+ lost a low amount of water, and only suffered transitory wilting. We discuss that in Arabidopsis plants exposed to high NaCl concentrations, root Na+ uptake and tissue accumulation fulfil the primary function of osmotic adjustment, even if these processes lead to long-term toxicity.


Exclusive skeletal muscle correction does not modulate dystrophic heart disease in the aged mdx model of Duchenne cardiomyopathy.
Duchenne muscular dystrophy (DMD) is characterized by severe degeneration and necrosis of both skeletal and cardiac muscle. While many experimental therapies have shown great promise in treating skeletal muscle disease, an effective therapy for Duchenne cardiomyopathy remains a challenge in large animal models and human patients. The current views on cardiac consequences of skeletal muscle-centered therapy are controversial. Studies performed in young adult mdx mice (a mild DMD mouse model) have yielded opposing results. Since mdx mice do not develop dystrophic cardiomyopathy until ≥21 months of age, we reasoned that old mdx mice may represent a better model to assess the impact of skeletal muscle rescue on dystrophic heart disease. Here, we aged skeletal muscle-specific micro-dystrophin transgenic mdx mice to 23 months and examined the cardiac phenotype. As expected, transgenic mdx mice had minimal skeletal muscle disease and they also outperformed original mdx mice on treadmill running. On cardiac examination, the dystrophin-null heart of transgenic mdx mice displayed severe cardiomyopathy matching that of non-transgenic mdx mice. Specifically, both the strains showed similar heart fibrosis and cardiac function deterioration in systole and diastole. Cardiac output and ejection fraction were also equally compromised. Our results suggest that skeletal muscle rescue neither aggravates nor alleviates cardiomyopathy in aged mdx mice. These findings underscore the importance of treating both skeletal and cardiac muscles in DMD therapy.


Gas-Phase Interaction of Anions with Polyisobutylenes: Collision-Induced Dissociation Study and Quantum Chemical Modeling.
The gas-phase interaction of anions including fluoride, chloride, bromide, iodide, ethyl sulfate, chlorate, and nitrate with polyisobutylene (PIB) derivatives was studied using collision-induced dissociation (CID). The gas-phase adducts of anions with PIBs ([PIB + anion](-)) were generated from the electrosprayed solution of PIBs in the presence of the corresponding anions. The so-formed adducts subjected to CID showed a loss of anion at different characteristic collision energies, thus allowing the study of the strength of interaction between the anions and nonpolar PIBs having different end-groups. The values of characteristic collision energies (the energy needed to obtain 50% fragmentation) obtained by CID experiments correlated linearly with the binding enthalpies between the anion and PIB, as determined by density functional theory calculations. In the case of halide ions, the critical energies for dissociation, that is, the binding enthalpies for [PIB + anion](-) adducts, increased in the order of I(-) < Br(-) < Cl(-) < F(-). Furthermore, it was found that the binding enthalpies for the adducts formed with halide ions decreased approximately with the square radius of the halide ion, suggesting that the strength of interaction is mainly determined by the "surface" charge density of the halide ion. In addition, the characteristic collision energy versus the number of isobutylene units revealed a linear dependence.


The increase in positively charged residues in cecropin D-like Galleria mellonella favors its interaction with membrane models that imitate bacterial membranes.
A comparative study of three synthetic peptides, namely neutral Cecropin D-like G. mellonella (WT) and two cationic peptides derived from its sequence, ΔM1 (+5) and ΔM2 (+9) is reported in this work. The influence of charge on the interactions between peptides and membranes and its effect on phase were studied by calorimetric assays. Differential scanning calorimetry (DSC) showed that ΔM2 peptide showed the strongest effect when the membrane contained phosphatidylcholine (PC) and phosphatidylglycerol (PG), increasing membrane fluidization. Fourier transform infrared spectroscopy (FTIR) was used to determine lipid segregation in the presence of peptides. When WT and ΔM1 bound to model membrane containing PG and PC (1:1 molar ratio) a separation of both lipids was observed. Meanwhile, ΔM2 peptide also induced a demixing of PG-peptide rich domains separated from PC. FTIR experiments also suggested that the presence of ΔM1 and ΔM2 peptides increased lipid carbonyl group hydration in DMPG membrane fluid phase, However, hydration at the interface level in fluid phase was notably increased in the presence of WT and ΔM1 peptides in DMPC/DMPG. Overall the increase in positively charged residues favors the interaction of the peptides with the negatively charged membrane and its perturbation.


Modulation of multidrug resistance P-glycoprotein 1 (ABCB1) expression in human heart by hereditary polymorphisms.
Variable expression of the ABC-type multidrug resistance membrane protein P-glycoprotein (P-gp, MDR1, ABCB1) in human heart is a potential modulator of drug effects or drug-induced cardiotoxicity. Expression of P-gp is known to be affected by single nucleotide polymorphisms in the MDR1 gene. Therefore, genotype-dependent expression of P-gp could be an important modulator of action of cardiac drugs. Heart tissue (auriculum) from 51 patients undergoing coronary artery bypass graft surgery was screened for genotype-dependent P-gp expression. P-gp was identified by immunoblotting and localized using immunohistochemistry. MDR1 mRNA was quantified by real-time PCR and immunohistochemistry and related to the MDR1 genotypes G2677T/A (Ala893Ser/Thr) and C3435T. MDR1/18S rRNA mRNA copy numbers in heart auriculum were 3.48 +/- 2.25 x 10(-6) compared to 4.56 +/- 0.58 x 10(-6) in non-failing ventricular samples studied before. While the exon 26 C3435T genotype did not influence MDR1 mRNA expression, we found significantly elevated MDR1 mRNA expression in 10 patients carrying the exon 21 2677 AT or TT genotype as compared to 12 patients carrying the GG-variant with intermediate MDR1 mRNA expression in 29 heterozygous samples. P-gp was detected in the endothelial wall. Quantitative immunohistochemistry of protein expression, however, did not reveal significant influence of the studied SNPs. The present study based on auricular samples suggests that genetic factors play a rather limited role in modulating P-gp expression in human heart. Therefore, the substantial interindividual variability in cardiac P-gp expression is likely related to environmental or disease related factors.


Optical Efficacy of Titanium Nitride-Coated Abutment Material on Soft Tissue Discoloration: A Spectrophotometric In Vitro Analysis.
The objective of this investigation was to assess the extent of mucosal discoloration caused by different CAD/CAM abutment materials and to determine the influence of mucosa thickness on the subsequent color, with a particular focus on titanium nitride. In a pig maxilla, a trapdoor-shaped mucosa flap was prepared unilaterally. Several CAD/CAM abutment materials were used to assess a number of clinical scenarios. Varying mucosa thicknesses were simulated by connective tissue grafts harvested at the contralateral side of the palate, resulting in layer thicknesses of 1.5, 2, and 3 mm. Titanium (Ti), zirconia (ZrO2), and titanium nitride (TiN) served as test specimens with and without ceramic veneering. Color differences (ΔE) and deviations in brightness (L), chroma (C), and hue (H) were determined spectrophotometrically, comparing the measured value of the native tissue and the results obtained with different materials at varying mucosa thicknesses. All tested specimens caused a mucosa discoloration in comparison to the native tissue, diminishing with increasing mucosa thickness. The use of TiN demonstrated the least mucosa discoloration in thin soft tissue of 1.5 mm, with a mean ΔE value of 1.93 (P = .004). While ZrO2 revealed a comparable ΔE value of 2.13 (P = .022) at a tissue thickness of 1.5 mm, Ti showed the highest mucosa discoloration above the visibility threshold of ΔE = 3.1, with a mean ΔE value of 4.07 (P = .002). Ceramic veneering of the Ti samples led to a considerable reduction in soft tissue discoloration, with a resulting ΔE value of 2.2. The veneering of TiN and ZrO2 samples with porcelain, on the other hand, had no noticeable effect on the mucosa color. CAD/CAM abutment materials cause an adverse soft tissue color shift that decreases with increasing mucosa thickness. In thin peri-implant mucosa, titanium nitride and zirconia lead to the least discoloration. Due to their positive optical properties and mechanical superiority compared with ceramic abutments, gold-hue titanium nitride-coated CAD/CAM abutments could be a clinical alternative in cases of thin peri-implant mucosa.


Impact of uneven sample morphology on mass resolving power in linear MALDI-TOF mass spectrometry: A comprehensive theoretical investigation.
This work discusses the correlation between the mass resolving power of matrix-assisted laser desorption/ionization time-of-flight mass analyzers and extraction condition with an uneven sample morphology. Previous theoretical calculations show that the optimum extraction condition for flat samples involves an ideal ion source design and extraction delay. A general expression of spectral feature takes into account ion initial velocity, and extraction delay is derived in the current study. The new expression extends the comprehensive calculation to uneven sample surfaces and above 90% Maxell-Boltzmann initial velocity distribution of ions to account for imperfect ionization condition. Calculation shows that the impact of uneven sample surface or initial spatial spread of ions is negligible when the extraction delay is away from the ideal value. When the extraction delay approaches the optimum value, the flight-time topology shows a characteristic curve shape, and the time-domain mass spectral feature broadens with an increase in initial spatial spread of ions. For protonated 2,5-dihydroxybenzoic acid, the mass resolving power obtained from a sample of 3-μm surface roughness is approximately 3.3 times lower than that of flat samples. For ions of m/z 3000 coexpanded with 2,5-dihydroxybenzoic acid, the mass resolving power in the 3-μm surface roughness case only reduces roughly 7%. Comprehensive calculations also show that the mass resolving power of lighter ions is more sensitive to the accuracy of the extraction delay than heavier ions.


A regioselective synthesis of 7-methyl juglone and its derivatives.
7-Methyl juglone as a naturally occurring naphthoquinone showed striking antibacterial, antifungal, antivirus and anticancer activity. Its derivatives had also been characterized as key intermediates in the preparation of natural naphthoquinones and anthraquinones. Herein, we reported a regioselective synthesis of 7-methyl juglone via the construction of fused polycyclic systems. The key steps of the strategy involved Stobbe condensation of 2,5-dimethoxy benzaldehyde with diethyl succinate, intramolecular cyclization, reduction, acid-facilitated debenzylation and further cerium(IV) ammonium nitrate-mediated oxidation. Compared with the reported methods employing Birch conditions in liquid ammonia or Friedel-Crafts cycloacylation with melting heat of aluminum salts, the reaction conditions in the new synthetic route were milder and suitable for large scale preparations. In addition, all of the starting materials in the synthesis were readily available. It has great implications for the design and synthesis of structurally asymmetric naphthoquinones derivatives.


MYOCARDIAL OXYGENATION DURING ACUTE NORMOVOLEMIC HEMODILUTION: IMPACT OF HYPOCAPNIC ALKALOSIS.
Increases in myocardial blood flow preserve myocardial oxygenation during moderate acute normovolemic hemodilution. Hypocapnic alkalosis (HA) is known to cause coronary vasoconstriction and increase hemoglobin-oxygen affinity. We evaluated whether these effects would compromise myocardial oxygenation during hemodilution. Eighteen anesthetized dogs were studied. Myocardial blood flow (MBF) was measured with radioactive microspheres. Arterial and coronary sinus samples were analyzed for oxygen content and plasma lactate. Myocardial oxygen supply, oxygen uptake, and lactate uptake were calculated. HA (PaCO2, 23 ± 2 (SD); pHa, 7.56 ± 0.03) was induced by removal of dead space tubing at baseline (n = 8) and during hemodilution (n = 10), with hematocrit at 43 ± 4% and 19 ± 2%, respectively. Hemodilution during normocapnia caused decreases in arterial oxygen content (19.9 ± 2.4 to 9.3 ± 1.2 ml/100; P < 0.05) and the coronary arteriovenous 02 difference (13.0 ± 3.0 to 6.4 ± 0.9 ml/100ml; P < 0.05). MBF increased (52 ± 12 to 111 ± 36 ml/min/100g; P < 0.05) to maintain myocardial oxygen supply and oxygen uptake. Myocardial lactate uptake increased (31 ± 19 to 68 ± 35 µeq/min/100g; P < 0.05). At normal hematocrit, HA decreased MBF (57 ± 18 to 45 ± 10 ml/min/100; P < 0.05), implying vasoconstriction, accompanied by decreased myocardial oxygen supply. These myocardial effects of HA were not apparent during hemodilution. HA did not alter myocardial lactate uptake during hemodilution. When HA was induced during hemodilution, its ability to cause coronary vasoconstriction was lost, and myocardial oxygenation remained well preserved.


Cell cycle reentry and cell proliferation as candidates for the seizure predispositions in the hippocampus of EL mouse brain.
We have recently found that there was DNA fragmentation without cell loss in the hippocampus in EL mice, an epileptic mutant. Neurotrophic factors are also expressed at high levels during the early developmental stages. In the present study, we used EL mice to examine how altered cyclin and the corresponding cyclin dependent kinase (CDK) family are related to cell proliferation during development and during epileptogenesis. Developmental changes of cyclin family and corresponding CDK family (cyclin D/CDK-4, cyclin E/CDK-2, cyclin A/CDK-2, cyclin A/CDK-1, cyclin B/CDK-1) were examined by Western blotting in the hippocampus of EL mice and in nonepileptic control animals (DDY mice). In addition, we attempted to quantify cell proliferation during this period. The developmental changes in cell proliferation were determined by using systemic injections of Bromo-deoxyUridine (BrdU) to label dividing cells. As compared with the control DDY mice, EL mice show an upregulation of cell cycle specific Cyclins/CDKs during early developmental stages suggesting that reentry into the cell cycle is enhanced prior to the onset of seizure activity, possibly due to the abundance of neurotrophic factors. These results show that Cyclins/CDKs are activated during early stages of development in an epileptic animal, before the mouse exhibits seizures. These results suggest that reentry of cells into the cell cycle, with consequent cell proliferation in the hippocampus, contribute to the seizure predispositions of EL mice.


A high-temperature environmental chamber for nuclear-resonant Bragg scattering studies.
A compact environmental chamber with a furnace operating in the range from room temperature to about 900 K has been built for a high-temperature nuclear-resonant Bragg scattering study. The compact size (75 mm diameter and 70 mm depth) allows an external magnetic field to be applied from outside permanent Nd-Fe-B alloy magnets; a magnetic field up to 1000 G has been obtained. The chamber can be mounted on a precise theta-2theta goniometer so that in situ observations of X-ray diffraction from a single crystal can be carried out. The temperature is measured by two thermocouples placed at the top and back of the sample and controlled by a PID controller. The temperature fluctuation of the chamber is less than +/-1 K.


Gonadal differentiation in frogs exposed to estrogenic and antiestrogenic compounds.
Exposure of amphibians to endocrine disrupting compounds (EDCs) may alter differentiation of gonads, especially when exposures begin during early life stages. Gonadal differentiation was observed in leopard frogs (Rana pipiens) and wood frogs (Rana sylvatica) exposed as tadpoles to estrogenic (estradiol, ethinylestradiol, nonylphenol) and antiestrogenic compounds (an aromatase inhibitor, flavone, and an antiestrogen, ICI 182780). Exposure to all compounds at micrograms/L concentrations altered gonadal differentiation in some animals by inducing either complete feminization or an intersex condition, and altered testicular tubule morphology, increased germ cell maturation (vitellogenesis), and oocyte atresia. Comparisons between the two species indicate that R. pipiens are more susceptible to sex reversal and development of intersex gonads. However, R. sylvatica also showed alterations to testicular morphology, germ cell maturation, and ooctye atresia. These laboratory results indicate that amphibians could be susceptible to altered gonadal differentiation and development when exposed to estrogenic and antiestrogenic compounds in aquatic environments, such as those impacted by agricultural, industrial, and municipal runoff.


Voltage adjustment improves rigidity and tremor in Parkinson's disease patients receiving deep brain stimulation.
Deep brain stimulation of the subthalamic nucleus is recognized as the most effective treatment for moderate and advanced Parkinson's disease. Programming of the stimulation parameters is important for maintaining the efficacy of deep brain stimulation. Voltage is considered to be the most effective programming parameter. The present study is a retrospective analysis of six patients with Parkinson's disease (four men and two women, aged 37-65 years), who underwent bilateral deep brain stimulation of the subthalamic nucleus at the First Affiliated Hospital of Sun Yat-sen University, China, and who subsequently adjusted only the stimulation voltage. We evaluated motor symptom severity using the Unified Parkinson's Disease Rating Scale Part III, symptom progression using the Hoehn and Yahr scale, and the levodopa equivalent daily dose, before surgery and 1 and 2 years after surgery. The 2-year follow-up results show that rigidity and tremor improved, and clinical symptoms were reduced, while pulse width was maintained at 60 μs and frequency at 130 Hz. Voltage adjustment alone is particularly suitable for patients who cannot tolerate multiparameter program adjustment. Levodopa equivalent daily dose was markedly reduced 1 and 2 years after surgery compared with baseline. Our results confirm that rigidity, tremor and bradykinesia can be best alleviated by voltage adjustment. The trial was registered at ClinicalTrials.gov (identifier: NCT01934881).


Action and location of neuropeptide tyrosine (Y) on hippocampal neurons of the rat in slice preparations.
The action of bath applied NPY (1-1,000 nM) was investigated on hippocampal slices of the rat with extra- and intracellular recording. Neuropeptide Y (NPY) at 10-1,000 nM caused a concentration-dependent, long-lasting reduction of excitatory postsynaptic potentials (EPSPs) in the hippocampal subfield CA1 and the area dentata, and an even stronger reduction of population spikes. Paired pulse experiments with low intensity, stimulation-evoked PSPs showed a marked increase in facilitation in the presence of NPY, indicating a presynaptic action. Spontaneous burst firing of CA1 pyramidal cells in low calcium, high magnesium medium was reduced, indicating a partially postsynaptic inhibitory action of NPY on their dendrites. Intracellular recording from CA1 somata during NPY administration revealed a reduction of the amplitudes of excitatory-inhibitory postsynaptic potential (EPSP-IPSP) sequences in the absence of changes in membrane potential and conductance. Accommodation of firing during long depolarizing pulses and afterhyperpolarizations were unchanged. The innervation pattern of NPY immunoreactive fibers in the same regions was studied in slices adjacent to the ones used for electrophysiology by using antisera against NPY and light and electron microscopy. There is a dense innervation of CA1 by NPY-immunoreactive axons and terminals, particularly in the stratum moleculare. NPY-immunoreactive neurons are present in the stratum oriens and pyramidale. The NPY labeled axons of the stratum moleculare participate in numerous synaptic contacts with the smaller dendritic elements in this layer, many of which belong to pyramidal neurons. These observations provide evidence for a dendritic NPY-immunoreactive innervation of CA1 neurons, which is in keeping with the electrophysiological effects of NPY on pyramidal neurons.(ABSTRACT TRUNCATED AT 250 WORDS)


First Report of Hb Limassol [β8(A5)Lys→Asn; HBB: c.27G>C] from Odisha, India.
In this short report, we describe the clinical presentation of a rare hemoglobin (Hb) variant, Hb Limassol [β8(A5)Lys→Asn; HBB: c.27G>C] with a faster electrophoretic mobility than Hb A and that elutes in the P3 window on cation exchange high performance liquid chromatography (HPLC). This sequence variation at codon 8 (AAG>AAC) of the HBB gene was found in the four heterozygous cases, all of whom were clinically asymptomatic.


Femtosecond excited-state dynamics of 4-nitrophenyl pyrrolidinemethanol: evidence of twisted intramolecular charge transfer and intersystem crossing involving the nitro group.
Ultrafast excited-state relaxation dynamics of a nonlinear optical (NLO) dye, (S)-(-)-1-(4-nitrophenyl)-2-pyrrolidinemethanol (NPP), was carried out under the regime of femtosecond fluorescence up-conversion measurements in augmentation with quantum chemical calculations. The primary concern was to trace the relaxation pathways which guide the depletion of the first singlet excited state upon photoexcitation, in such a way that it is virtually nonfluorescent. Ground- and excited-state (singlet and triplet) potential energy surfaces were calculated as a function of the -NO(2) torsional coordinate, which revealed the perpendicular orientation of -NO(2) in the excited state relative to the planar ground-state conformation. The fluorescence transients in the femtosecond regime show biexponential decay behavior. The first time component of a few hundred femtoseconds was ascribed to the ultrafast twisted intramolecular charge transfer (TICT). The occurrence of charge transfer (CT) is substantiated by the large dipole moment change during excitation. The construction of intensity- and area-normalized time-resolved emission spectra (TRES and TRANES) of NPP in acetonitrile exhibited a two-state emission on behalf of decay of the locally excited (LE) state and rise of the CT state with a Stokes shift of 2000 cm(-1) over a time scale of 1 ps. The second time component of a few picoseconds is attributed to the intersystem crossing (isc). In highly polar solvents both the processes occur on a much faster time scale compared to that in nonpolar solvents, credited to the differential stability of energy states in different polarity solvents. The shape of frontier molecular orbitals in the excited state dictates the shift of electron density from the phenyl ring to the -NO(2) group and is attributed to the charge-transfer process taking place in the molecule. The viscosity dependence of relaxation dynamics augments the proposition of considering the -NO(2) group torsional motion as the main excited-state relaxation coordinate.


Critics denounce Bush's proposed budget for HIV prevention and care.
AIDS Drug Assistance Programs in several states already have to put HIV-infected people on waiting lists to receive life-saving antiretroviral drugs because of budget shortfalls, and AIDS advocates say this problem will continue through 2002 and 2003 unless Congress provides a financial boost to HIV programs. Activists also say the United States will never achieve its goal of reducing new HIV infection rates by 50% within the next few years unless prevention spending is increased.