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Detection of Helicobacter pylori urease antigen in saliva in patients with different gastric H. pylori status. Finding a simple, accurate, and noninvasive diagnosis method is a substantial challenge for the detection of Helicobacter pylori. The aim of the present study was to compare the presence of H. pylori urease antigen in saliva with the presence of this bacterium in gastric mucosa. Saliva samples and gastric biopsies were taken from 153 consenting Moroccan patients. Saliva samples were analyzed using an immunochromatographic test for urease antigen H. pylori detection. Thereafter, the gastric biopsies were analyzed by histology and polymerase chain reaction (PCR) to detect this bacterium. From a total of 153 recruited Moroccan patients, H. pylori was detected in 28 (18.30%), 87 (57.24%), and 69 (45.10%) cases by saliva test, histology, and PCR, respectively. A significant association was observed between the presence of H. pylori antigen in saliva and age. However, no association was found with sex, H. pylori virulence factors, gastric disease outcome, and density of the bacterium on the gastric mucosa. Considering that only 90 patients presented concordant results on H. pylori diagnosis (positive or negative) by both histology and PCR, the immunochromatographic test showed very low sensitivity (29.79%) and high specificity (90.70%). Of these two tests, the positive and negative predictive values were 77.78% and 54.17%, respectively. The accuracy of the test for salivary detection of urease antigen H. pylori was 58.89%. This study demonstrated a low detection rate of H. pylori antigens in saliva compared with the presence of this bacterium in gastric mucosa, suggesting that saliva cannot be used as a suitable sample for the diagnosis of H. pylori in our study population.

Infection Exposure is a Causal Factor in B-cell Precursor Acute Lymphoblastic Leukemia as a Result of Pax5-Inherited Susceptibility. Earlier in the past century, infections were regarded as the most likely cause of childhood B-cell precursor acute lymphoblastic leukemia (pB-ALL). However, there is a lack of relevant biologic evidence supporting this hypothesis. We present in vivo genetic evidence mechanistically connecting inherited susceptibility to pB-ALL and postnatal infections by showing that pB-ALL was initiated in Pax5 heterozygous mice only when they were exposed to common pathogens. Strikingly, these murine pB-ALLs closely resemble the human disease. Tumor exome sequencing revealed activating somatic, nonsynonymous mutations of Jak3 as a second hit. Transplantation experiments and deep sequencing suggest that inactivating mutations in Pax5 promote leukemogenesis by creating an aberrant progenitor compartment that is susceptible to malignant transformation through accumulation of secondary Jak3 mutations. Thus, treatment of Pax5(+/-) leukemic cells with specific JAK1/3 inhibitors resulted in increased apoptosis. These results uncover the causal role of infection in pB-ALL development. These results demonstrate that delayed infection exposure is a causal factor in pB-ALL. Therefore, these findings have critical implications for the understanding of the pathogenesis of leukemia and for the development of novel therapies for this disease.

Routine use of a higher order interpolator and bone algorithm in thoracic CT. This study was designed to evaluate the utility of the routine use of high spatial frequency algorithms and higher order helical interpolators for imaging lung parenchyma during routine thoracic CT. We evaluated 50 consecutive patients undergoing clinically indicated thoracic CT using the same imaging parameters and scanner. The helical volume was reconstructed three separate times using standard and higher order (180 degrees linear with double-sided lobes) interpolators and standard and high spatial frequency (bone) algorithms. The images were photographed and given to five separate readers who were kept unaware of the interpolator and algorithm and who were asked to evaluate simultaneously each patient's three sets of images for best, in-between, and worst images of the lung interstitium, pathology, and normal anatomy. All five readers rated the standard interpolator and algorithm images as the worst (p < .01). All five readers consistently rated the double-sided lobe interpolator and bone algorithm images as the best (p < .01). A second reconstruction of routine thoracic helical CT data using higher order helical interpolators and a bone algorithm significantly improves interstitial detail of lung parenchyma and overall visualization of normal anatomy and pathologic processes.

Language delay and behavioral/emotional problems in toddlers: findings from two developmental clinics. The association between language delay and behavior problems in toddlers was examined in 2 studies, 1 conducted in a developmental clinic in New Jersey (Study 1; N = 83) and the other conducted in a developmental clinic in New York (Study 2; N = 103). In both clinics, parents of 18- to 35-month-olds completed the Language Development Survey (LDS) and the Child Behavior Checklist/1.5-5 (CBCL). In Study 2, the Preschool Language Scale-Fourth Edition (PLS-4) was also administered. Neurodevelopmental delay (ND) and pervasive developmental disorder (PDD) symptoms were also assessed in both studies but were done so using different measures. In Study 1, LDS Vocabulary score and CBCL Total Problems, Internalizing, and Withdrawn scores were significantly correlated. However, when children with ND and/or suspected PDD were excluded, only the correlation between LDS Vocabulary and Withdrawn remained significant. In Study 2, only the correlation between LDS Vocabulary and Withdrawn approached significance. Children delayed in language on the PLS-4 had higher CBCL scores than typically developing toddlers only on the CBCL Withdrawn syndrome. Significant associations between language delays and behavior problems were not found in 2 samples of 18- to 35-month-olds when children with ND and PDD were excluded, except that toddlers with language delays appeared to show elevated social withdrawal relative to typically developing toddlers.

Growth inhibition and oxidative stress caused by four ionic liquids in Scenedesmus obliquus: Role of cations and anions. Ionic liquids (ILs) are widely used in various industrial applications. However, they are considered potential toxins in aquatic environments because of their physical stability and solubility. The growth inhibition and oxidative stress induced by four ionic liquids with different cations and anions on the green algae Scenedesmus obliquus was investigated in this study. The order of growth inhibition was 1‑hexyl‑3‑methylimidazolium nitrate ([HMIM]NO3) > 1‑hexyl‑3‑methylimidazolium chloride ([HMIM]Cl) > N‑hexyl‑3‑metylpyridinium bromide ([HMPy]Br) > N‑hexyl‑3‑metylpyridinium chloride ([HMPy]Cl). Imidazolium IL had a higher growth inhibition effect than pyridinium IL, nitrate IL and bromide IL had a higher effect than chloride IL. Reactive oxygen species (ROS) level in S. obliquus increased with increasing IL concentrations. Green fluorescence in [HMIM]Cl treated algae showed increased brightness compared to the [HMPy]Cl treatment, and [HMIM]NO3 treatment produced increased brightness compared to the [HMPy]Br treatment, suggesting that higher ROS levels were induced by [HMIM]Cl and [HMIM]NO3. Soluble protein, catalase (CAT), and superoxide dismutase (SOD) activities were stimulated at lower concentrations but were inhibited at higher concentrations. Regression analysis suggested that ROS level is the main index responsible for oxidative stress induced by the four ILs. The ILs induced oxidative damage on S. obliquus, and ROS in high concentration treatments could not be effectively removed by the antioxidant system, leading to oxidative damage and ultimately resulting in growth inhibition and cell death.

Med19 promotes breast cancer cell proliferation by regulating CBFA2T3/HEB expression. Mediator complex 19 (Med19) is a pivotal subunit of the Mediator complex, and its aberrant expression is involved in tumourigenesis. We aimed to explore the mechanism by which Med19 promotes the proliferation of breast cancer. Lentivirus-mediated inhibition of Med19, ectopic expression of Med19 and ectopic expression of core-binding factor subunit alpha 2 to translocation 3 (CBFA2T3) were applied in human breast cancer cell lines. Human breast cancer cell proliferation was determined using CCK8 and colony formation assays after lentivirus infection. The expression of Med19, CBFA2T3 and HEB was measured by real-time reverse transcription polymerase chain reaction and Western blotting. The correlation between Med19 and CBFA2T3 expression in tissue from 25 cases of human breast cancer was analysed. In this study, we demonstrate that cell proliferation and colony formation capacity were significantly inhibited after Med19 inhibition in vitro. The expression of CBFA2T3 was distinctly up-regulated in MDA-MB-231 and MCF-7 human breast cancer cells when Med19 was knocked down; however, the expression of HEB, which is targeted by CBFA2T3, was down-regulated. Meanwhile, ectopic expression of Med19 in BT-549 and Hs578T human breast cancer cells inhibited CBFA2T3 expression but enhanced HEB expression. The proliferation capacity of human breast cancer cells was increased when Med19 was overexpressed, but the effect of Med19 up-regulation could be reversed by CBFA2T3 overexpression. Furthermore, a negative correlation between Med19 and CBFA2T3 expression was demonstrated by Western blotting in human breast cancer tissue. These results suggest that Med19 promotes breast cancer cell proliferation and that this effect is associated with CBFA2T3 and HEB. These results provide new insights into the potential role of Med19 in the regulation of breast carcinogenesis, and Med19 may be a useful therapeutic target in breast cancer therapy.

Labral and cartilage abnormalities in young patients with hip pain: accuracy of 3-Tesla indirect MR arthrography. Assess the diagnostic accuracy of 3-T indirect magnetic resonance arthrography (iMRA) for hip cartilage and labral pathology detection using arthroscopy as the reference standard and compare it to the published performance of direct magnetic resonance arthrography (dMRA). Between 2009 and 2011, 290 patients suspected of having femoroacetabular impingement underwent iMRA. Our study group consisted of 41 of these patients (17 males, mean age 35 years; 24 females, mean age 33 years) who did not have a prior history of hip surgery and who subsequently underwent arthroscopy. Two experienced musculoskeletal radiologists separately evaluated the randomized and anonymized studies for the presence and quadrant location of labral and cartilage pathology. These recorded data were compared to arthroscopic reports. Forty-one patients had labral pathology, 34 patients had acetabular and 5 patients had femoral cartilage pathology at arthroscopy. Sensitivity, specificity, accuracy, negative- and positive-predictive values for labral lesion detection were respectively 98, 99, 99, 99 and 98 %; for acetabular cartilage lesion detection they were 69, 98, 89, 87 and 95 %; for femoral cartilage lesion detection they were 69, 95, 93 and 39 %. Sensitivities of iMRA by quadrant (anteroinferior, anterosuperior, posteroinferior, posterosuperior) for the labrum were 100.0, 95.0, NA and 85.7 %, for acetabular cartilage were NA, 58.8, NA and 39.5 % and for femoral cartilage were 50.0, 33.3, 75.0 and 75.0 %). NA indicates results not available because of the absence of findings in those quadrants. Specificities of iMRA by quadrant (anteroinferior, anterosuperior, posteroinferior, posterosuperior) for the labrum (95.0, 100.0, 95.1, 67.5 %), acetabular (100.0, 85.7, 92.6, 79.5 %) and femoral cartilage (100.0, 94.7, 96.2, 85.9 %). iMRA at 3 T is accurate in detecting labral pathology suggesting that it is a viable alternative to dMRA.

Translation of Inhaled Drug Optimization Strategies into Clinical Pharmacokinetics and Pharmacodynamics Using GSK2292767A, a Novel Inhaled Phosphoinositide 3-Kinase δ Inhibitor. This study describes the pharmacokinetic (PK) and pharmaco-dynamic (PD) profile of N-(5-(4-(5-(((2R,6S)-2,6-dimethylmorpholino)methyl)oxazol-2-yl)-1H-indazol-6-yl)-2-methoxypyridin-3-yl)methanesulfonamide (GSK2292767A), a novel low-solubility inhaled phosphoinositide 3-kinase delta (PI3Kδ) inhibitor developed as an alternative to 2-(6-(1H-indol-4-yl)-1H-indazol-4-yl)-5-((4-isopropylpiperazin-1-yl)methyl)oxazole (nemiralisib), which is a highly soluble inhaled inhibitor of PI3Kδ with a lung profile consistent with once-daily dosing. GSK2292767A has a similar in vitro cellular profile to nemiralisib and reduces eosinophilia in a murine PD model by 63% (n = 5, P < 0.05). To explore whether a low-soluble compound results in effective PI3Kδ inhibition in humans, a first time in human study was conducted with GSK2292767A in healthy volunteers who smoke. GSK2292767A was generally well tolerated, with headache being the most common reported adverse event. PD changes in induced sputum were measured in combination with drug concentrations in plasma from single (0.05-2 mg, n = 37), and 14-day repeat (2 mg, n = 12) doses of GSK2292767A. Trough bronchoalveolar lavage (BAL) for PK was taken after 14 days of repeat dosing. GSK2292767A displayed a linear increase in plasma exposure with dose, with marginal accumulation after 14 days. Induced sputum showed a 27% (90% confidence interval 15%, 37%) reduction in phosphatidylinositol-trisphosphate (the product of phosphoinositide 3-kinase activation) 3 hours after a single dose. Reduction was not maintained 24 hours after single or repeat dosing. BAL analysis confirmed the presence of GSK2292767A in lung at 24 hours, consistent with the preclinical lung retention profile. Despite good lung retention, target engagement was only present at 3 hours. This exposure-response disconnect is an important observation for future inhaled drug design strategies considering low solubility to drive lung retention.

Transient ileus associated with the use of mydriatics after screening for retinopathy of prematurity in a very low birth weight infant. Very low birth weight (VLBW) infants have ophthalmologic examinations for retinopathy of prematurity (ROP) prior to discharge, with appropriate follow-up and intervention where appropriate. Eye drops such as cylopentolate, tropicamide, and phenylephrine are used at different concentrations to provide proper pupil dilation for screening ROP. Topical instillation of eye drops may cause mild or severe ocular or systemic adverse effects. Early recognition of systemic toxicity after eye drop instillation is important. The authors present a case of a VLBW infant who developed significant abdominal symptoms (mimicking ileus) that were significant enough to discontinue oral feeding after ocular instillation of 0.5% tropicamide and 2.5% phenylephrine eye drops for routine examination of ROP. After structural and functional gastrointestinal disorders and sepsis were excluded, symptoms resolved completely after discontinuation of the drug. This report is thought to be the first in the medical literature to address 5% tropicamide and 2.5% phenylephrine eye drops, and the combination that may lead to serious complication after ROP examinations.

The TBP gene from Aspergillus nidulans-structure and expression in Saccharomyces cerevisiae. The genomic and cDNA copy of the TATA-binding protein (TBP) gene from the filamentous fungus Aspergillus nidulans have been cloned. The gene is interrupted by four introns, one of which is in the long 5' untranslated region of 615 bp. The transcription initiation site was established and the levels of mRNA were analysed under diverse growth conditions and found to vary severalfold. The gene encodes a protein of 268 amino acids composed of an N-terminal domain of 88 amino acids with no significant homology to other TBPs and a C-terminal domain of 180 amino acids with about 95% homology to other fungal TBPs. A cDNA clone under the yeast ADH1 promoter was able to substitute for the yeast TBP gene in vivo; however, the transformants obtained grew poorly at 35 degrees C and on galactose and glycerol at 30 degrees C, though they could grow in the presence of copper ions or aminotriazole at this temperature. This phenotype may be the result of altered function of A. nidulans TBP in certain yeast transcription activation pathways.

Humanized anti-CD271 monoclonal antibody exerts an anti-tumor effect by depleting cancer stem cells. CD271, known as a neurotrophin receptor, is expressed in various cancers such as hypopharyngeal cancer (HPC) and melanoma. We recently reported that CD271 is a cancer-stem-cell biomarker of HPC, and that its expression is essential for cancer-cell proliferation and is correlated with a poor prognosis in this disease. Here, to develop a therapeutic antibody to CD271, we established a humanized anti-CD271 monoclonal antibody (hCD271 mA b). hCD271 mA b bound to the cysteine-rich domain 1 (CRD1) of human CD271 with high affinity (KD = 1.697 × 10-9 M). In vitro, hCD271 mA b exerted antibody-dependent cell-mediated cytotoxicity (ADCC) activity against SP2/0-CD271 (human CD271-transduced mouse cell line). Treatment with hCD271 mA b also exerted anti-tumor activity in graft models of three cell lines (HPCM2 (patient-derived xenograft cell line of hypopharyngeal cancer), MeWo-Luc (melanoma cell line), and SP2/0-CD271) in mice, resulting in smaller tumors compared to controls and reduced numbers of CD271-positive cells. Collectively, these data suggest that an antibody targeting CD271 is a promising therapeutic strategy.

Trends in the incidence of childhood and adolescent cancer in Connecticut, 1935-1979. Trends in the incidence of childhood cancer in Connecticut are reported and analyzed for the period 1935-1979 by 5-year age groups (0-4, 5-9, 10-14, 15-19 years), using a log linear model method. A threefold increase (P less than .001) in the incidence of ALL in males 0-4 years of age was observed, with significant increases of smaller magnitude seen in males aged 5-9 and 15-19 and females aged 0-4 and 5-9. The incidence of central nervous system cancers also increased in several age groups for both sexes with the largest increase seen in males 0-4 years old. Significant increases in incidence of large magnitude were also observed for Hodgkin's disease, in males aged 15-19 years and females aged 10-19 years, for neuroblastoma in both sexes at ages 0-4 years, and for testis and ovarian cancer at ages 15-19 years. This study of trends in incidence of childhood cancers by 5-year age groups has revealed significant changes, which would not have been as apparent if broader age groups had been used. These results provide relevant data for investigating the etiology of cancer during infancy, childhood, and adolescence. Trends in Connecticut are compared with findings from other registries in the United States and other countries.

Structure and function of the type 3 deiodinase gene. Thyroid hormones (TH) are essential for normal growth and development in vertebrates, and are important for the maintenance of normal metabolic activity in most tissues of the body. Because the actions of TH result from the binding of 3,3',5'-triiodothyronine (T(3)) to specific nuclear receptors in the target cell, the extent of TH action in a given cell is dependent in part on the intracellular concentration of T(3). The type 3 deiodinase (D3) is a selenoenzyme that inactivates TH by catalyzing their conversion to biologically inactive metabolites. The findings that D3 activity is very high in the pregnant uterus and fetoplacental unit, and that D3-deficient mice exhibit deficits in growth, viability, and fertility strongly suggest that D3 plays an important role in development. The D3 gene (Dio3) is preferentially expressed from the paternally inherited allele and is associated with an overlapping gene transcribed from the opposite DNA strand (Dio3os). D3 mRNA expression and D3 activity are regulated by a number of hormones and growth factors as well as by genomic imprinting. Although some genomic structures appear to mediate some of these effects, many details concerning the function of the Dio3 gene are unresolved. These include the full characterization of the Dio3 and Dio3os genes, the elucidation of the mechanisms responsible for the developmental and tissue-specific patterns observed in Dio3 allelic expression, and the response of the genes to hormones and growth factors. Knowledge of these details will be important for understanding the physiologic function of an enzyme that appears to be critical for normal mammalian development.

Treatment of Kaposi's sarcoma with bleomycin. Two cases of Kaposi's sarcome that responded to bleomycin therapy are reported herein. The first case, resistant to various treatments, responded remarkably well after 240 mg of bleomycin was administered over a thirteen month period. The second case had rapidly progressive untreated Kaposi's sarcoma of six months's duration; a prompt response was obtained to an initial course of 105 mg of bleomycin.

Rapid and massive green fluorescent protein production leads to formation of protein Y-bodies in plant cells. Although high level of recombinant protein production can be achieved via transient expression in plant cells, the mechanism by which tolerance to the presence of recombinant protein is acquired remains unclear. Here we show that green fluorescent protein (GFP) encoded by an intron-optimized tobacco mosaic viral vector formed large membraneless GFP bodies called Y-bodies that demonstrated mainly perinuclear localization. The Y-bodies were heterogeneous in size, approaching the size of the cell nucleus. Experiments with extracted GFP and live cell imaging showed that Y-bodies included actively fluorescent, non-aggregated, tightly packed GFP molecules. The plant cells probably formed Y-bodies to exclude the recombinant protein from normal physiological turnover.

Wavelet transforms in the analysis of mechanical heart valve cavitation. Cavitation is known to cause blood element damage and may introduce gaseous emboli into the cerebral circulation, increasing the patient's risk of stroke. Discovering methods to reduce the intensity of cavitation induced by mechanical heart valves (MHVs) has long been an area of interest. A novel approach for analyzing MHV cavitation is presented. A wavelet denoising method is explored because currently used analytical techniques fail to suitably unmask the cavitation signal from other valve closing sounds and noise detected with a hydrophone. Wavelet functions are used to denoise the cavitation signal during MHV closure and rebound. The wavelet technique is applied to the signal produced by closure of a 29-mm Medtronic-Hall MHV in degassed water with a gas content of 5 ppm. Valve closing dynamics are investigated under loading conditions of 500, 2500, and 4500 mm Hg/s. The results display a marked improvement in the quantity and quality of information that can be extracted from acoustic cavitation signals using the wavelet technique compared to conventional analytical techniques. Time and frequency data indicate the likelihood and characteristics of cavitation formation under specified conditions. Using this wavelet technique we observe an improved signal-to-noise ratio, an enhanced time-dependent aspect, and the potential to minimize valve closing sounds, which disguise individual cavitation events. The overall goal of this work is to eventually link specific valves with characteristic waveforms or distinct types of cavitation, thus promoting improved valve designs.

Safe use of glucocorticoids. How to monitor patients taking these potent agents. Glucocorticoids reduce inflammation and combat stress. However, they are very powerful, and guidelines for their use must be followed to avoid such adverse effects as Cushing's syndrome and adrenal insufficiency. Whenever possible, physicians should consider alternative treatment strategies, because the consequences of steroid therapy may be worse than those of the disease being treated.

A new method for breath-to-breath determination of oxygen flux across the alveolar membrane. A new method for breath-to-breath determination of the oxygen flux across the alveolar membrane is described. The principle of the method is to integrate the product of oxygen concentration and flow in the respiratory gas over an interval, which covers a complete respiratory cycle. The result is corrected for the change in oxygen content of the lungs through a formula, which, in contrast to those used in other methods, is independent of the residual capacity of the lungs. The method was evaluated with respect to repeatability by repetitive measurement of oxygen flux in twenty volunteer subjects, and with respect to accuracy by comparing the measured oxygen fluxes with those obtained by the gas collection method. The coefficient of variation was found to be 8% and the breath to breath determinations were, on an average, 6% lower than those of the gas collection method.

Stimulation of the ferroxidase activity of ceruloplasmin during iron loading into ferritin. Ceruloplasmin purified from horse serum was rapidly reduced upon addition of increasing equivalents of ferrous iron, generating an electronically and conformationally distinct form. This form of ceruloplasmin was characterized by significant (80%) loss of EPR detectable type I and type II copper(II), complete loss of visible absorbance at 610 nm, as well as decreased hydrophobic surface area. The reduced form of ceruloplasmin slowly reduced molecular oxygen to complete its catalytic cycle. The presence of varied concentrations of apoferritin, but not apotransferrin, significantly enhanced the rate of ceruloplasmin oxidation. The magnitude of this stimulatory effect increased as the molar ratio of ceruloplasmin to apoferritin approached 1.0, shown previously to be the optimum ratio for loading iron into ferritin. The rate of ferrous iron oxidation by ceruloplasmin was significantly stimulated by the presence of apoferritin; however, apotransferrin had no effect. The length of time required for ceruloplasmin to oxidize all the iron and return to the native form of the enzyme was also affected by the concentration of iron. In addition, the rate of iron loading into ferritin was dependent upon ferrous iron concentration. These results provide evidence for the formation of a specific complex between the reduced form of ceruloplasmin and apoferritin and that reduction of ceruloplasmin by ferrous iron may be the signal for complex formation.

New noninvasive ultrasound techniques: can they predict liver cirrhosis? This study aimed to determine the threshold values and accuracy of 2 noninvasive techniques, contrast-enhanced ultrasound with maximum-intensity projection (MIP) imaging and ultrasound elastography, acoustic radiation force impulse (ARFI), to differentiate a normal from a cirrhotic liver. One hundred thirty-two patients were predicted clinically as having a normal liver (n = 60) or cirrhosis (n = 72). All had MIP liver vessel evaluation on an Acuson Sequoia and 90 of them had ARFI on an S2000 (Siemens, Mountain View, Calif). Two readers reviewed 4 parameters on MIP data and predicted cirrhosis (n = 65) or normal (n = 67) outcome. They were considered as having cirrhosis when more than 1 MIP parameter was positive. Acoustic radiation force impulse values above 1.36 m/s suggested cirrhosis. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic accuracy of the ARFI measurement and to extract the optimal cutoff value in the differentiation of a cirrhotic liver from a noncirrhotic liver. Sixty-four patients (64/65, 98.5%) with abnormal and 8 (8/59, 13.6%) with normal vessels on MIP imaging were clinically cirrhosis (P < 0.001). Forty-five patients (45/49, 91.8%) with abnormal ARFI (≥ 1.36 m/s) and 6 (6/41, 14.6%) with normal ARFI (<1.36 m/s) had a clinical cirrhotic liver (P < 0.001). Sensitivity and specificity of MIP of vessel morphology to predict cirrhosis were 89% (64/72) and 98% (59/60), respectively. Acoustic radiation force impulse showed a sensitivity of 88% (45/51) and a specificity of 90% (35/39), and the area under the receiver operating characteristic curve was 0.932, suggesting very good accuracy. The combination of ARFI and MIP showed increased sensitivity and specificity to 95.8% and 100%. Liver evaluation with MIP and ARFI contributes to a noninvasive prediction of cirrhosis.

A simple, selective, and sensitive gas chromatography-mass spectrometry method for the analysis of five process-related impurities in atenolol bulk drug and capsule formulations. An extremely sensitive and simple gas chromatography with mass spectrometry method was developed and completely validated for the analysis of five process-related impurities, viz., 4-hydroxy-l-phenylglycine, 4-hydroxyphenylacetonitrile, 4-hydroxyphenylacetic acid, methyl-4-hydroxyphenylacetate, and 2-[4-{(2RS)-2-hydroxy-3-[(1-methylethyl)amino]propoxy}phenyl]acetonitrile, in atenolol. The separation of impurities was accomplished on a BPX-5 column with dimensions of 50 m × 0.25 mm i.d. and 0.25 μm film thickness. The method validation was performed following International Conference on Harmonisation guidelines in which the method was capable to quantitate 4-hydroxy-l-phenylglycine, 4-hydroxyphenylacetonitrile, and 4-hydroxyphenylacetic acid at 0.3 ppm, and methyl-4-hydroxyphenylacetate and 2-[4-{(2RS)-2-hydroxy-3-[(1-methylethyl)amino]propoxy}phenyl]acetonitrile at 0.35 ppm with respect to 10 mg/mL of atenolol. The method was linear over the concentration range of 0.3-10 ppm for 4-hydroxy-l-phenylglycine, 4-hydroxyphenylacetonitrile, and 4-hydroxyphenylacetic acid, and 0.35-10 ppm for methyl-4-hydroxyphenylacetate and 2-[4-{(2RS)-2-hydroxy-3-[(1-methylethyl)amino]propoxy}phenyl]acetonitrile. The correlation coefficient in each case was found ≥0.998. The repeatability and recovery values were acceptable, and found between 89.38% and 105.60% for all five impurities under optimized operating conditions. The method developed here is simple, selective, and sensitive with apparently better resolution than the reported methods. Hence, the method is a straightforward and good quality control tool for the quantitation of selected impurities at trace concentrations in atenolol.

Hypocalcemia due to osteoblastic metastases and diminished parathyroid reserve in a patient with advanced breast cancer. Symptomatic hypocalcemia is an uncommon finding in patients with malignant tumors. A patient with advanced breast cancer is described, who developed severe hypocalcemia in the course of her disease. The hypocalcemia was caused by the combination of enhanced calcium need due to progression of osteoblastic metastases and diminished parathyroid reserve due to tumorous infiltration of the parathyroid glands.

Predicting Satisfaction for Unicompartmental Knee Arthroplasty Patients in an Asian Population. Despite renewed interest in unicompartmental knee arthroplasty (UKA), there is a paucity of published literature with regard to patient satisfaction after UKA within Asian populations. The purpose of this study is to identify characteristics and factors which may contribute to patient dissatisfaction after UKA in a multiracial Asian population. Seven hundred twenty-four UKAs were performed between January 2007 and April 2013. Preoperative and postoperative variables were prospectively captured, such as standardized knee scores, knee range of motion, and patient satisfaction scores. These variables were then analyzed with a multiple logistic regression model to determine statistically significant factors contributing to patients' satisfaction. Minimum duration of follow-up was 2 years, with an overall patient satisfaction rate of 92.2%. There was improvement in mean knee range of motion and across various standardized knee scores. Preoperative variables associated with patient dissatisfaction included a poorer preoperative Mental Component Summary, better preoperative knee extension, and better preoperative Oxford Knee Scores. Significant postoperative variables included better Oxford Knee Score at 6 months and Mental Component Summary at 2 years. Despite the impressive patient satisfaction rate of UKA in this Asian population, these findings suggest that there is a targeted group of patients with select preoperative factors who would benefit from preoperative counseling.

Sequential Temporal Dependencies in Associations Between Symptoms of Depression and Posttraumatic Stress Disorder: An Application of Bivariate Latent Difference Score Structural Equation Modeling. Depression and posttraumatic stress disorder (PTSD) are highly comorbid conditions that may arise following exposure to psychological trauma. This study examined their temporal sequencing and mutual influence using bivariate latent difference score structural equation modeling. Longitudinal data from 182 emergency room patients revealed level of depression symptom severity to be positively associated with changes in PTSD intrusion, avoidance, and hyperarousal over 3 time intervals, beginning shortly after the traumatic event. Higher scores on depression anticipated increases (or worsening) in PTSD symptom severity. The pattern of influence from PTSD symptom severity to change in depression symptom severity simply followed the general trend toward health and well-being. Results are discussed in terms of the dynamic interplay and associated mechanisms of posttrauma depression and PTSD symptom severity.

hTERT mRNA expression in urine as a useful diagnostic tool in bladder cancer. Comparison with cytology and NMP22 BladderCheck Test®. To study the relationship between quantitative mRNA determination (hTERT) in patients with bladder tumor, history of bladder tumor, and in subjects without a history of this neoplasia. A prospective randomized controlled study with 91 subjects included. The value of mRNA-hTERTN was determined in 63 patients with a history or suspicion of bladder tumor and in 28 controls. Urine samples were sent for evaluation of the mRNA level (hTERT), the cytological study and the NMP22 result. Differences were observed in mean hTERTN levels in each of the groups: tumor presence 21.33+/- 40.66, tumor history 2.16+/- 2.67, controls 0.9+/- 1, 75 (p<0.001). In patients with tumor, there was no difference in mean hTERTN levels between the different grades and stages, although there was a tendency: low grade tumor 9.04+/- 16.95, high grade 28.95+/- 48.36 (p=.069), stage Ta 10.33+/- 19.39, T1 17.88+/- 27.14, T2 54.8+/- 74.05 (p=.056). In addition, the sensitivity of hTERTN was superior to that of other test (76%), although specificity and positive and negative predictive values were better for cytology (94%, 88.4% and 72.3% respectively) and NMP22 (88%, 80.6% and 73.3% respectively). hTERTN mRNA levels in urine were higher in patients with bladder tumors compared to patients with a history of bladder tumor and with negative cystoscopy, as well as in the control group. This determination showed a higher diagnostic yield compared with the detection of NMP22 and urinary cytology.

Ovarian stimulation modulates steroid receptor expression and spheroid attachment in peri-implantation endometria: studies on natural and stimulated cycles. To compare the effect of high serum E(2) levels on endometrial steroid receptors in gonadotropin-stimulated cycles (hCG + 7) and natural cycles (LH + 7), and to study its effect on spheroid attachment. Observational. University hospital. Infertile patient with normal menstrual cycles undergoing IVF treatment. Gonadotropin stimulation and endometrial biopsy; trophoblast spheroid (embryo surrogate, Jeg-3)-endometrial cell (Ishikawa) coculture assay. Steroid receptor expression by quantitative polymerase chain reaction and immunohistochemistry; spheroid attachment rate. Endometrial biopsies from natural (n = 12) and stimulated (n = 23) cycles were obtained. The expression of estrogen receptor α (ERα) but not ERβ or progesterone receptor (PR) transcript was significantly reduced in stimulated cycles compared with natural cycles. Glucocorticoid receptor (GR) transcript was significantly increased in the excessive responders of the stimulated cycle. There was no difference in ERα immunoreactivity in endometrial stroma, but a higher immunoreactivity was seen in endometrial glands of stimulated cycles. The endometrium of stimulated cycles had a lower expression of PR protein in glands, but a higher expression in stroma. Although no GR protein was detected in glands, GR protein expression was significantly up-regulated in stroma of the stimulated cycles. Endometrial cells treated with high steroid concentrations had a reduced spheroid attachment rate compared with the controls. High serum E(2) level affects the expression of steroid receptors in the endometrial cells and suppresses spheroid attachment.

Successful gastrostomy tube weaning program using an intensive multidisciplinary team approach. The present study evaluated the effectiveness of a multidisciplinary intensive inpatient model for gastrostomy tube (GT) weaning. A retrospective chart review was completed on 30 GT-dependent children, ages 3.9 (±1.4) years, admitted to the inpatient feeding program (length of stay 19 days) from May 2009 to December 2011. Administered GT calories were decreased on admission by an average of 73% from home regimen. Patients were offered 3 meals and 2 to 3 snacks/day, including 3 intensive feeding therapy sessions (Monday to Friday), along with psychosocial support, nutrition guidance, and behavioral therapy. Daily calorie counts and weights were recorded. Patients returned for a postdischarge feeding evaluation at an average of 4 months and a clinic visit at 1 year. Data were analyzed using paired samples t tests. Before admission, patients received 69% (±25) of goal calories by GT and 22% (±19) of goal calories orally. During admission, average caloric intake by mouth as a percentage of goal increased during the course of weeks 1, 2, and 3 (68%, 77%, and 82%, respectively), with a statistically significant increase between weeks 1 and 2 (P = 0.001) and 1 and 3 (P = 0.011). At discharge, 90% had discontinued GT feedings. Average percent weight change during admission was 0.2% (±4). At 1 year follow-up, 83% remained successfully off GT feedings. Children who are GT dependent can be weaned off GT feedings during a 3-week admission using a multidisciplinary feeding model. The therapeutic gains were maintained at 1 year postdischarge.

Control of filamentation induced by femtosecond laser pulses propagating in air. Filamentation formed by self-focusing of intense laser pulses propagating in air is investigated. It is found that the position of filamentation can be controlled continuously by changing the laser power and divergence angle of the laser beam. An analytical model for the process is given.

Perfusion fixation for placental morphologic investigation. Fifty placentas were collected after vaginal delivery or cesarean section from normal and abnormal pregnancies and were fixed under different conditions of perfusion using a peristaltic roller pump. In each case a physiologic-heparin perfusate was used for less than 10 minutes, followed by a buffered solution of glutaraldehyde-formaldehyde. The best results were obtained with placentas from cesarean sections perfused immediately after delivery with a pressure maintained under 60 mm Hg. Placentas of this group were fixed within 30 minutes and electron microscopy demonstrated good preservation of cellular ultrastructure. Perfusion fixation could be performed up to 6 hours after delivery with satisfactory histologic results. In these cases, electron microscopy revealed ischemic changes 10 minutes after delivery and severe necrosis 1 hour after delivery. When the perfusion pressure was maintained over 60 mm Hg, diffuse damage of the villous morphology was observed. Histomorphometric analysis showed significant differences between terminal villi from nonperfused (immersed-fixed) placentas and perfused-fixed placentas. The mean barrier and trophoblastic thicknesses and the mean volume fraction of trophoblast were significantly (P less than .001) increased in the nonperfused group compared with the perfused group.

Transient neonatal zinc deficiency due to a new autosomal dominant mutation in gene SLC30A2 (ZnT-2). Transient neonatal zinc deficiency (TNZD) has a clinical presentation similar to that of acrodermatitis enteropathica but is caused by a low zinc concentration in maternal breast milk. TNZD becomes clinically evident during breastfeeding and is resolved by weaning and the introduction of complementary nutrition. We present a 4-month-old girl with TNZD due to a new autosomal dominant mutation (663delC) in the maternal SLC30A2 gene not previously described in the literature.

Nasal reconstruction of the leprosy nose using costal cartilage. Leprosy is a chronic granulomatous infection of the skin and peripheral nerves that often leads to gross deformation of the nasal skeleton and subsequent formation of a saddle-nose deformity. Reconstruction of the nose following Mycobacterium leprae infection has challenged surgeons for centuries. As a result, a number of different techniques have been attempted with varying outcomes. This article describes the case and surgical treatment of a 37-year old female who presented with a subtotal nasoseptal perforation and saddle-nose deformity secondary to previous infection with leprosy. Reconstruction was achieved via an open septorhinoplasty approach using autologous costal cartilage grafts, yielding a successful postoperative result.

The head impulse test as a predictor of videonystagmography caloric test lateralization according to the level of examiner experience: A prospective open-label study. We conducted a study to compare how well the head impulse test (HIT), without and with eye-movement recordings, would predict videonystagmographic (VNG) caloric test lateralization when performed by a resident and an experienced otoneurologist. This prospective, open-label, blinded study was conducted in an ambulatory tertiary care referral center. Our study population was made up of 60 patients-29 men and 31 women, aged 20 to 82 years (mean: 56.4 ± 11.4)-with peripheral vestibulopathy who underwent HIT and VNG caloric testing. The HIT was conducted in two protocols: HIT0 and HIT1. The HIT0 was performed with passive brisk movements of the patient's head from the 0° null position to 20° sideways, and the HIT1 was performed toward the center while the null position was a 20° head rotation to the right and to the left. Each protocol was carried out without video eye-movement recordings (HIT0 and HIT1) and with such recordings (rHIT0 and rHIT1). The primary outcome measures were (1) a comparison of the HIT's sensitivity and specificity when performed by the resident and by the experienced otoneurologist and (2) the ability of video-recorded HIT to predict VNG caloric test lateralization. The sensitivity and specificity obtained by the resident were 41 and 81%, respectively, for HIT0 and 41 and 90% for HIT1. The sensitivity and specificity obtained by the experienced otoneurologist were 18 and 89% for HIT0 and 32 and 85% for HIT1. Analysis of the recorded eye-movement clips of the HIT0 and HIT1 obtained by a second experienced otoneurologist found a sensitivity and specificity of 32 and 63% for rHIT0 and 33 and 82% for rHIT1. We conclude that the HIT yields high false-negative rates in predicting significant caloric lateralization. Analysis of the eye-movement recordings was no better than normal testing alone for detecting saccades. The experience of the examining physician had no impact on test performance characteristics.

Mechanistic insights into mode of action of a potent natural antagonist of orexin receptor-1 by means of high throughput screening and molecular dynamics simulations. Insomnia is one of the most common clinical problems being faced by people all over the world. It adversely affects the routine life of these patients giving rise to even other health issues like hypertension, diabetes, obesity, depression, heart attack, and stroke. Orexin receptor-1 (OX1R), a noteworthy drug target, when inhibited can promote sleepiness in people suffering from such conditions. OX1R is a G-protein coupled receptor which is conserved throughout the mammalian species and is located primarily in hypothalamus and locus coeruleus. The present study aims at identifying potent natural-origin inhibitors of OX1R capable of affecting the arousal and sleep pattern. In the present work, we have screened a large dataset of natural compounds against OX1R using high throughput screening and high precision docking approaches. Molecular dynamics simulations were carried out to study the dynamical behavior of the top scoring compound. We also provided mechanistic insights into the binding mode of action of this compound. The study provides evidence for consideration of this natural molecule as prospective lead in treatment of insomnia.

Characteristics and cost impact of severe odontogenic infections. The objective of this study was to retrospectively analyze the clinical presentation, surgical management, and cost implications of inpatients treated for odontogenic infections at a public tertiary care hospital. Specific analysis from 3 years of chart review included length of stay, cost of hospitalization, site of infection, number of infected spaces, microbiology profile, antibiotics administered, intensive care unit (ICU) stay, number of days intubated, comorbidities, number of operating room visits, imaging studies, and whether the patients received preadmission treatment. Multiple fascial spaces were involved in most of the infections. The average length of stay was 4.57 days and average time in the ICU was 3.1 days. Ninety percent of the patients had a coexisting medical comorbidity. The overall hospital costs totaled $749,382 averaging $17,842 per person. This study reveals a staggering cost burden on a public health care facility as a result of odontogenic infections.

[Psychosomatic diseases in urology]. As in other medical fields there also exist psychosomatic diseases in urology which appear in the form of functional disturbances. Besides alterations of the diuresis, mainly an irritable bladder, symptoms of enuresis, urinary retention and additionally symptoms of chronic prostatitis and disturbances of sexual potency. In order to explore the psychic etiology usually a psychiatric examination is necessary with the aim to start adequate treatment.

Differential effects of propofol, thiamylal and ketamine on the cricothyroid and posterior cricoarytenoid muscles of the canine larynx. To measure the electromyographic (EMG) responses of the phasic discharge in the cricothyroid (CT; a tensor muscle of the vocal folds) and the posterior cricoarytenoid (PCA; sole abductor muscle of the vocal folds) following intravenous infusion of propofol 1.0 mg.kg-1.min-1, thiamylal 1.0 mg.kg-1.min-1, or ketamine 0.5 mg.kg-1.min-1 for five minutes. Prospective, nonrandomized, controlled animal study. University research laboratory. Fifteen mongrel dogs, including three groups of five animals in each group. Under 0.2-0.3% halothane and oxygen anesthesia with spontaneous ventilation, phasic EMG activities of the CT and PCA muscles were recorded in an identical manner after the administration of each drug. Propofol infusion produced almost equal suppression of EMG activity of the CT and the PCA with time and three minutes after the start of infusion of propofol there was a significant depression of the phasic activities in the both muscles; EMG activity of the CT and the PCA was 33.8 +/- 21.2 and 36.6 +/- 22.9% (% of control, mean +/- SD) respectively P < 0.05). Thiamylal selectively reduced rhythmic discharges in the CT muscle during spontaneous breathing and significant depression of discharge in the CT muscle was observed three minutes after the drug (47.3 +/- 24.9%, P < 0.05). In contrast, both phasic EMG activities of the CT and the PCA were rhythmically active and the differential sensitivity between the CT and the PCA muscles was not observed after ketamine, even after ten minutes of administration. This study confirms a difference in sensitivity between the CT and the PCA muscles, demonstrating that the intrinsic laryngeal muscles do not behave similarly after the administration of conventional intravenous anaesthetic agents.

Utilization of evidence-based cardiovascular therapies and achievement of therapeutic goals in patients with peripheral artery disease. Patients with peripheral artery disease have a high risk of cardiovascular events and death. The rate of prescription of evidence-based cardiovascular therapies and the attainment of therapeutic goals in this population is suboptimal. There are no previous studies evaluating the rate of prescription of these therapies in our country. PERIFERICA is a cross-sectional study conducted from May to December 2009 in 440 outpatient clinics of general practitioners, internal medicine, cardiology, vascular surgery, endocrinology, and nephrology specialists throughout Spain. Subjects were included if they were aged ≥45 years and had peripheral artery disease and a blood sample obtained during the previous 6 months. Patients were excluded if they had coronary or cerebrovascular diseases. Clinical and anthropometric variables and blood analysis were obtained in all participants. In total, 4087 patients were included in the study (mean age, 68 years; 74% men). There was a high prevalence of diabetes (50%) and hypertension (90%); 79% of participants received lipid-lowering drugs (76% statins), 85.5% antihypertensive drugs (66% renin-angiotensin blockers) and 83% antithrombotics (75% antiplatelet drugs and 11% anticoagulants). In addition, 30% of subjects had a low-density lipoprotein cholesterol concentration n<100 mg/dL, 29.5% had optimal control of blood pressure, and 74.5% did not smoke. Only 8% had a good control of all of their cardiovascular risk factors. Although a high percentage of subjects with peripheral artery disease receives adequate treatment with evidence-based preventive therapies, the percentage of subjects with good control of all their risk factors is low.

Establishment of esophageal-like non-keratinized stratified epithelium using normal human bronchial epithelial cells. Current experimental models of esophageal epithelium in vitro suffer from either poor differentiation or complicated culture systems. We have established a model to study stratified squamous epithelium in vitro, which is very similar to esophageal epithelium in vivo. A stratified squamous multilayer epithelium was formed by seeding primary normal human bronchial epithelial (NHBE) cells onto collagen- and fibronectin-coated trans-well inserts and then cultivating the cells under air-liquid interface (ALI) conditions in the presence of growth factors and low levels of all-trans-retinoic acid. Trans-epithelial electrical resistance (TEER) measurements revealed the presence of a tight barrier, previously only achievable with esophageal biopsies mounted in Ussing chambers. Molecular markers for desmosomes, cornified envelope, tight junctions, and mature esophageal epithelium were upregulated in the differentiating culture in parallel with functional properties, such as decreased permeability and acid resistance and restoration. Acid exposure resulted in a decrease in TEER, but following 1-h recovery the TEER values were fully restored. Treatment with all-trans-retinoic acid decreased TEER and inhibited the recovery after acid challenge. PPAR-delta agonist treatment increased TEER, and this temporary increase in TEER was consistent with an increase in involucrin mRNA. Global gene expression analysis showed that ALI-differentiated NHBE cells had expression profiles more similar to epithelial biopsies from the esophageal tissue of healthy volunteers than to any other cell line. With respect to morphology, molecular markers, barrier properties, and acid resistance, this model presents a new way to investigate barrier properties and the possible effects of different agents on human esophagus-like epithelium.

Formation of gap and tight junctions between reaggregated blastomeres of the killifish, Fundulus. Blastomeres from eggs of the killifish, Fundulus, were mechanically dissociated and reaggregated by pelleting in a simple saline solution. Formation of gap and tight junctions was followed by electron microscopy of freeze-fracture replicas. Five to eight min after pelleting, neither new nor old junctions were observed. After 10-15 min, small gap junctions were found, but these were not associated with distinct formation plaques. Larger gap junctions were observed after 45 min, and the images were consistent with growth by accretion of intramembrane particles. In aggregates, after 20 min or more, tight junctions were much more commonly found than in intact blastulae, and it seemed likely that they were being formed by cells that were not doing so in the intact embryo. Initial stages consisted of short strands that appeared to grow in length. Also, more elaborate junctions were seen than occur in situ. Particle-free membrane often occurred near incomplete junctions, and large junctions like those in situ separated particle-rich from particle-free membrane. In this system, the formation of both gap and tight junctions occurs with shorter latency, and is more precisely timed, than heretofore described.

Preoperative cholangitis independently increases in-hospital mortality after combined major hepatic and bile duct resection for hilar cholangiocarcinoma. This study evaluated the impact of ductal bile bacteria (bactibilia or cholangitis) on the development of surgical site infection (SSI) or in-hospital mortality after resection for hilar cholangiocarcinoma. A retrospective analysis was conducted on 81 patients who underwent a combined major hepatic (hemihepatectomy or more extensive hepatectomy) and bile duct resection for hilar cholangiocarcinoma. Ductal bile was submitted for bacterial culture before or during the operation. The incidence of SSI was higher in patients with preoperative bactibilia (83%) than in patients without (52%; P = 0.008). Preoperative bactibilia was an independent variable associated with SSI (relative risk 9.003; P = 0.002). The incidence of in-hospital mortality was higher in patients with preoperative cholangitis (33%) than in patients without (6%; P = 0.009). Preoperative cholangitis was the only independent variable associated with in-hospital mortality (relative risk 9.115; P = 0.006). Preoperative cholangitis independently increases in-hospital mortality after combined major hepatic and bile duct resection for hilar cholangiocarcinoma, whereas preoperative bactibilia independently increases SSI.

[Chronic inflammatory demyelinating polyneuropathy: Diagnosis and therapeutic update]. Chronic inflammatory demyelinating polyradiculoneuropathies are acquired demyelinating neuropathies belonging to the group of autoimmune neuropathies. Since specific biological markers are present in less than 10% of cases, the diagnosis is based on the clinical and electrophysiological analysis of each patient. Furthermore, a decision-making algorithm ranking all other available paraclinical tools will guide the physician to the diagnosis of atypical forms. In nearly 80% of cases, these dysimmune neuropathies are responsive to first-line treatments, namely intravenous immunoglobulins, corticosteroids and plasma exchanges. A second line treatment may be proposed in case of no response, intolerance or inaccessibility to the three reference treatments. While some immunosuppressants or monoclonal antibodies can sometimes be very effective, there is currently no predictive marker or recommendation available to determine which treatment will be most appropriate for which patient.

[Design of stimulating agents of non-specific resistance system]. The paper briefly reviews a study on the design of drugs enhancing the body's nonspecific resistance to pathogenic agents. To examine the potential regulatory effects on cytokine function was a main trend. The interferon inductor ridostin, dsRNA of microbiological origin, cytokines, as well as the recombinant probiotic strain yielding interferon alpha-2 synthesis were used as a pharmacological agent. This was shown by using a wide range of experimental models wherein these preparations activated the components of the non-specific resistance system resulting in the host's increased capacity to eliminate invasive agents and transformed cells.

Strengthening capacity in developing countries for evidence-based public health: the data for decision-making project. Public health officials and the communities they serve need to: identify priority health problems; formulate effective health policies; respond to public health emergencies; select, implement, and evaluate cost-effective interventions to prevent and control disease and injury; and allocate human and financial resources. Despite agreement that rational, data-based decisions will lead to improved health outcomes, many public health decisions appear to be made intuitively or politically. During 1991-1996, the US Centers for Disease Control and Prevention implemented the US Agency for International Development funded Data for Decision-Making (DDM) Project. DDM goals were to: (a) strengthen the capacity of decision makers to identify data needs for solving problems and to interpret and use data appropriately for public health decisions; (b) enhance the capacity of technical advisors to provide valid, essential, and timely data to decision makers clearly and effectively; and (c) strengthen health information systems (HISs) to facilitate the collection, analysis, reporting, presentation, and use of data at local, district, regional, and national levels. Assessments were conducted to identify important health problems, problem-driven implementation plans with data-based solutions as objectives were developed, interdisciplinary, in-service training programs for mid-level policy makers, program managers, and technical advisors in applied epidemiology, management and leadership, communications, economic evaluation, and HISs were designed and implemented, national staff were trained in the refinement of HISs to improve access to essential data from multiple sources, and the effectiveness of the strategy was evaluated. This strategy was tested in Bolivia, Cameroon, Mexico, and the Philippines, where decentralization of health services led to a need to strengthen the capacity of policy makers and health officers at sub-national levels to use information more effectively. Results showed that the DDM strategy improved evidence-based public health. Subsequently, DDM concepts and practices have been institutionalized in participating countries and at CDC.

Acid-base treated vermiculite as high performance adsorbent: Insights into the mechanism of cationic dyes adsorption, regeneration, recyclability and stability studies. Additional treatment with NaOH of acid activated vermiculite results in even higher increase in the adsorption capacity in comparison to samples modified only in acidic solution (first step of activation) with respect to raw material. Optimization of treatment conditions and adsorption capacity for two cationic dyes (methylene blue (MB) and astrazon red (AR)), also as binary mixture, was evaluated. The capacity, based on column studies, increased from 48 ± 2 to 203 ± 4 mg g-1 in the case of methylene blue and from 51 ± 1 to 127 ± 2 mg g-1 in the case of astrazon red on starting and acid-base treated material, respectively. It was shown that adsorption mechanism changes for both cationic dyes after NaOH treatment and it results in decrease of adsorption rate. In binary mixtures methylene blue is bound stronger by adsorbent and astrazon red may be removed in initial stage of adsorption. Extensive studies on desorption/regeneration process proved high efficiency in recyclable use of all materials. Although cation exchange capacity decreases due to acid treatment, after base treatment exchange properties are used more efficiently. On the other hand, increased specific surface area has less significant contribution into the adsorption potential of studied materials. Obtained adsorbents worked efficiently in 7 adsorption-regeneration cycles and loss of adsorption capacity was observed only in two first cycles.

Spur cell anemia associated with extrahepatic biliary tract obstruction. Two patients with extrahepatic biliary obstruction developed spur cell hemolytic anemia. Hemolysis and erythrocyte morphology reverted to normal when the obstruction was relieved. During the hemolytic phase, one patient's plasma converted normal erythrocytes to spur cells and normal plasma converted the patient's spur cells to normal morphology. The spur cells were discovered only when the patients' blood was examined under phase microscopy. We suggest that spur cells may occur in association with biliary obstruction more frequently than previously suspected and that their presence may be uncovered using phase microscopy.

Application of APCD/DIBK extraction system in strongly acidic media: Determination of traces of copper and nickel in titanium metals by extraction-flame atomic-absorption spectrometry. Extraction of nickel in strongly acidic solution (0.01 approximately 8M hydrochloric acid) with ammonium 1-pyrrolidinecarbodithioate (APCD) into di-isobutyl ketone (DIBK) has been studied, and the APCD/DIBK system has been applied to simultaneous extraction and flame atomic-absorption spectrometric determination of trace amounts of copper and nickel in titanium metal. Nickel could be extracted with copper from strongly acidic solution such as up to 5M hydrochloric acid with APCD/DIBK system. The extraction from such a strongly acidic media made it possible to extract nickel with copper, since it did not require the addition of a large amount of the masking agent which prevents the hydrolysis of the matrix titanium and also prevents the extraction of nickel. Thus, they could be extracted directly from the titanium metal sample digested by concentrated hydrochloric acid with a small amount of tetrafluorohydroboric acid. Effect of coexistence of a large amount (at least 0.2 g) of iron on the extraction of both elements could be prevented by keeping most of the matrix titanium as Ti(III). With the method described here, mug/g levels of copper and nickel in titanium metal could be rapidly determined with good precision and accuracy.

Patient support and education for promoting adherence to highly active antiretroviral therapy for HIV/AIDS. Adherence to prescribed regimens is required to derive maximal benefit from many highly active antiretroviral therapy (HAART) regimens in people living with HIV/AIDS. To conduct a systematic review of the research literature on the effectiveness of patient support and education to improve adherence to HAART. A systematic search of electronic databases was performed from January 1996 to May 2005. Randomized controlled trials examining the effectiveness of patient support and education to improve adherence to HAART were considered for inclusion. Only those studies that measured adherence at a minimum of six weeks were included. Study selection, quality assessments and data abstraction were performed independently by two reviewers. Nineteen studies involving a total of 2,159 participants met criteria for inclusion. It was not possible to conduct a meta-analysis due to study heterogeneity with respect to populations, interventions, comparison groups, outcomes, and length of follow-up. Sample sizes ranged from 22 to 367. The populations studied ranged from general HIV-positive populations to studies focusing exclusively on children, women, Latinos, or adults with a history of alcohol dependence, to studies focusing almost exclusively on men. Study interventions included cognitive behavioral therapy, motivational interviewing, medication management strategies, and interventions indirectly targeting adherence, such as programs directed to reduce risky sexual behaviours. Ten studies demonstrated a beneficial effect of the intervention on adherence. We found that interventions targeting practical medication management skills, those administered to individuals vs groups, and those interventions delivered over 12 weeks or more were associated with improved adherence outcomes. We also found that interventions targeting marginalized populations such as women, Latinos, or patients with a past history of alcoholism were not successful at improving adherence. We were unable to determine whether effective adherence interventions were associated with improved virological or immunological outcomes. Most studies had several methodological shortcomings leaving them vulnerable to potential biases. We found evidence to support the effectiveness of patient support and education interventions intended to improve adherence to antiretroviral therapy. Interventions targeting practical medication management skills, those interventions administered to individuals vs groups, and those interventions delivered over 12 weeks or more were associated with improved adherence outcomes. There is a need for standardization and increased methodological rigour in the conduct of adherence trials.

Changes of cytokeratin filament organization in human and murine Mallory body-containing livers as revealed by a panel of monoclonal antibodies. Mallory bodies (MBs) are characteristics morphologic features of alcoholic hepatitis and can be produced in mouse hepatocytes by chronic griseofulvin (GF) intoxication. The formation of MBs, which share some immunological, biochemical, and ultrastructural features with cytokeratin (CK) filaments of normal liver, is accompanied by derangement and even loss of the CK cytoskeleton of hepatocytes ("empty cells") as revealed by immunofluorescence microscopy. To clarify whether this diminution or lack of CK-related staining of MB-containing hepatocytes was due to loss of CK filaments or changes in antigenicity or accessibility of antigenic determinants immunohistochemical studies using a battery of monoclonal and polyclonal CK antibodies were performed. It could be shown that all these antibodies directed against different CK polypeptide components and antigenic determinants of CKs revealed a highly reduced or even undetectable cytoplasmic CK meshwork in most cells with fully developed large MBs. In the light of our present knowledge of the organization of CK intermediate filaments, these results indicate that the phenomenon of the "empty cells" reflects a diminution of CK meshwork rather than altered antigenic determinants.

Characterization of Bacilli isolated from the confined environments of the Antarctic Concordia station and the International Space Station. Bacillus and related genera comprise opportunist and pathogen species that can threaten the health of a crew in confined stations required for long-term missions. In this study, 43 Bacilli from confined environments, that is, the Antarctic Concordia station and the International Space Station, were characterized in terms of virulence and plasmid exchange potentials. No specific virulence feature, such as the production of toxins or unusual antibiotic resistance, was detected. Most of the strains exhibited small or large plasmids, or both, some of which were related to the replicons of the Bacillus anthracis pXO1 and pXO2 virulence elements. One conjugative element, the capacity to mobilize and retromobilize small plasmids, was detected in a Bacillus cereus sensu lato isolate. Six out of 25 tested strains acquired foreign DNA by conjugation. Extremophilic bacteria were identified and exhibited the ability to grow at high pH and salt concentrations or at low temperatures. Finally, the clonal dispersion of an opportunist isolate was demonstrated in the Concordia station. Taken together, these results suggest that the virulence potential of the Bacillus isolates in confined environments tends to be low but genetic transfers could contribute to its capacity to spread.

Importance of mineral dust and anthropogenic pollutants mixing during a long-lasting high PM event over East Asia. A long-lasting high particulate matter (PM) concentration episode persisted over East Asia from May 24 to June 3, 2014. The Nested Air Quality Prediction Model System (NAQPMS) was used to investigate the mixing of dust and anthropogenic pollutants during this episode. Comparison of observations revealed that the NAQPMS successfully reproduced the time series PM2.5 and PM10 concentrations, as well as the nitrate and sulfate concentrations in fine (aerodynamic diameter ≤ 2.5 μm) and coarse mode (2.5 μm < aerodynamic diameter ≤ 10 μm). This episode originated from two dust events that occurred in the inland desert areas of Mongolia and China, and then the long-range transported dust and anthropogenic pollutants were trapped over the downwind region of East Asia for more than one week due to the blocked north Pacific subtropical high-pressure system over the east of Japan. The model results showed that mineral dust accounted for 53-83% of PM10, and 39-67% of PM2.5 over five cities in East Asia during this episode. Sensitivity analysis indicated that the Qingdao and Seoul regions experienced dust and pollution twice, by direct transport from the dust source region and from dust detoured over the Shanghai area. The results of the NAQPMS model confirmed the importance of dust heterogeneous reactions (HRs) over East Asia. Simulated dust NO3- concentrations accounted for 75% and 84% of total NO3- in fine and coarse mode, respectively, in Fukuoka, Japan. The horizontal distribution of model results revealed that the ratio of dust NO3-/dust concentration increased from about 1% over the Chinese land mass to a maximum of 8% and 6% respectively in fine and coarse mode over the ocean to the southeast of Japan, indicating that dust NO3- was mainly formed over the Yellow Sea and the East China Sea before reaching Japan.

Role of magnetic resonance imaging and scintigraphy in the diagnosis and follow-up of osteomyelitis in cat-scratch disease. Cat-scratch disease (CSD) is a self-limiting infectious disease characterised with lymphadenopathy in a patient with a history of cat contact. Cases of bone involvement in patients with CSD are rare. We reported a case of 11-year-old boy with prolonged intermittent fever, inguinal lymphadenopathy and osteomyelitis. He had a history of exposure to kittens. The physical examination revealed a febrile boy without an apparent site of infection except an enlarged inguinal lymph node. Its histopathology demonstrated granulomatous lesion with no presence of acid-fast bacilli. Serum titers for Bartonella henselae were positive. Multiple bone lesions were detected by skeletal scintigraphy. Magnetic resonance imaging (MRI) confirmed and characterised osteolytic masses. The oral combination of azithromycin and rifampicin were given for 6 weeks with a good clinical response. At follow-up, the boy was without symptoms or signs of the disease. Successive MRI controls showed gradual regression of the bone lesions together with significant decrease of acute-phase reactants. In conclusion, CSD should be considered in the differential diagnosis of osteomyelitis. MRI is more reliable for the characterisation, evaluation of soft-tissue extension and follow-up of the bone lesions than scintigraphy. However, the later method permits an overview of the multiple osseous lesions. Therefore, standard MRI equipment may not exclude bone scintigraphy. Both methods are required until whole-body MRI units become routine.

Using Google Analytics as a process evaluation method for Internet-delivered interventions: an example on sexual health. The study aimed to demonstrate the potential of Google Analytics as a process evaluation method for Internet-delivered interventions, using a website about sexual health as an example. This study reports visitors' behavior until 21 months after the release of the website (March 2009-December 2010). In total, there were 850 895 visitors with an average total visiting time (i.e. dose) of 5:07 min. Google Analytics provided data to answer three key questions in terms of process evaluation of an Internet-delivered intervention: (i) How do visitors behave?; (ii) Where do visitors come from? and (iii) What content are visitors exposed to? This real-life example demonstrated the potential of Google Analytics as a method to be used in a process evaluation of Internet-delivered interventions. This is highly relevant given the current expansion of these interventions within the field of health promotion.

Multiple sebaceous adenomas and internal malignant disease: a case report with chromosomal analysis. A case of multiple sebaceous adenomas associated with internal malignant disease is further documented. Thirteen similar cases reported in the literature are also reviewed. We support the thesis that this association represents a unique syndrome. It can be seen in both sexes and usually is manifested during the fifth and sixth decades. A family history of malignant disease was revealed among seven of the nine cases mentioned. Of the other skin lesions, keratoacanthoma is also frequently seen. The internal malignant tumors most commonly afflict the gastrointestinal tract, especially the large intestine. With proper treatment the internal tumors appear to be of a low degree of malignancy. However, these patients have a propensity to develop muliple visceral tumors and require periodic follow-up. Some patients develop skin tumors prior to the discovery of internal malignant disease, an event that offers some prognostic value. Chromosomal study of the cultured blood lymphocytes by the Giemsa banding technique failed to reveal any abnormality.

Pathways of energy metabolism required for phenotypic expression of nif+Kp genes in Escherichia coli. In E. coli K12 (F'nif+Kp) hybrids, electron-transport-dependent phosphorylation is not necessary for anaerobic nitrogen fixation, and substrate level phosphorylation can provide sufficient ATP from glucose for nitrogenase activity. The fumarate-reduction system, however, is essential in these hybrids for the transfer of electrons to nitrogenase. This system is probably also involved in maintaining the membrane in the energized state, thereby allowing nitrogen fixation to occur. The nitrate-reduction system, which can energize the membrane like the fumarate-reduction system, is not necessary for nitrogenase activity in the E. coli K12(F'nif+Kp) hybrids. However, two nitrate reductase genes, chlA, and chlB, are essential for inhibition of nitrogen fixation by nitrate. Moreover, nitrate inhibits nitrogenase activity and this inhibition is most probably effected through a regulator factor coded by chlA and chlB.

Effect of prenatal phenytoin administration on the fine structure of rat myocardium and aorta. Phenytoin (PHT) is an antiepileptic drug known to have teratogenic effects. The aim of this study was to examine the ultrastructure of the left ventricle, the left atrium, and the aorta of 3-month-old offspring and 4-month-old mother animals after oral PHT (150 mg/kg/day) administration to Wistar/DV rats on days 7-18 of gestation. Electron microscopy of the myocardium revealed a heterogeneous population of cardiomyocytes with conventional architecture, and hypoxia/ischemia-like subcellular changes. Cardiomyocytes of offspring hearts were more vulnerable to PHT administration compared with the mother animals. Atrial cardiomyocytes of both mother animals and offspring were less affected by PHT than the ventricular ones. In the myocardium, both interstitial fibrosis and injury of capillaries were noted. Electron microscopy of the aorta revealed a higher resistance of maternal endothelial and smooth muscle cells to PHT compared with offspring cells. Nuclei of endothelial and smooth muscle cells showed pronounced mitotic activity with one and/or two hyperactive nucleoli, more frequently observed in offspring. PHT administration resulted in aortic arteriogenesis in both offspring and mother animals. Interestingly, bundles of myocardial fibers consisting of ischemia-like altered cardiomyocytes with own capillary network were noted in off-spring aortic adventitia. These results are indicative of harmful effects of PHT on rat myocardium and aorta.

[The situation of emergency psychiatry in Germany]. The impact of psychiatric emergencies for the care of patients in preclinical emergency medicine, in emergency departments and in psychiatric hospitals has been underestimated for a long time. There is still insufficient knowledge and a need for further research. There are, however, sufficient reasons to assume that annually approximately 500,000 patients with a psychiatric emergency receive treatment from a preclinical emergency physician and another 1.5 million in emergency departments in Germany. Further, approximately 500,000 patients are admitted to psychiatric hospitals as an emergency. The most frequent reasons are intoxication, agitation, aggressiveness and suicidal ideation, posing a threat of self-harm to the patient or to other persons and evoking other life-threatening conditions. Emergency psychiatry also plays a role in collective injuries, such as mass disasters, catastrophes and rampage situations. There is some evidence that the number of psychiatric emergencies is increasing. Reasons are, among others, changes in the services provided for inpatient and outpatient treatment, a reduction in stabilizing psychosocial factors and a general increase in the utilization of emergency healthcare services.

Factors discriminating gymnasts by competitive level. This study examined the relationship between the performance level as evaluated by expert coaches and the results on a multidimensional test battery in female gymnastics. 4 coaches assigned 168 female gymnasts aged 6-8 years into 2 groups (Elite-level potential, n=103 and Sub-elite-level potential, n=65) based upon their technical evaluation of the gymnastics abilities on the 4 apparatus. Moreover, anthropometric, physical and coordinative characteristics were assessed. ANOVA with age as fixed factor revealed that results on all aforementioned characteristics, except body fat%, sit-and-reach, rope climbing and a motor coordination test, significantly improved with increasing age. MANCOVA with competitive level as fixed factor and age and maturity as covariates indicated that all gymnasts portrayed a similar athletic built (Wilks' lambda=0.95, F=2.20, p=0.071), but the elite-level potential gymnasts outperformed the less gifted gymnasts on all physical (Wilks' lambda=0.65, F=8.00, p<0.001) and coordinative variables (Wilks' lambda=0.79, F=22.10, p<0.001). Discriminant analysis revealed motor coordination to be the most important factor in discriminating between young female elite and sub-elite gymnasts. A test battery measuring multidimensional performance characteristics is valuable in addition to the coaches' technical judgment in the search of young gifted female gymnasts.

Metal-free radical 5-exo-dig cyclizations of phenol-linked 1,6-enynes for the synthesis of carbonylated benzofurans. A new metal-free radical 5-exo-dig cyclization of phenol-linked 1,6-enynes with O2, 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO), and tBuONO is described. With this general method, carbonylated benzofurans can be accessed through incorporation of two oxygen atoms into the product from O2 and TEMPO through dioxygen activation and oxidative cleavage of the N-O bond, respectively.

Alcohol risk drinking, quality of life and health state among patients treated at the Sobering Unit in the emergency department - One year follow-up study. To evaluate impacts of brief intervention on patients' alcohol risk drinking, quality of life and health state after treatment at the Sobering Unit in the emergency department at three months, six months, and one year follow-up. This was a quasi-experimental study without control group (one-year follow-up). Alcohol use of patients in emergency department (Sobering Unit) in specialized care in Finland (AUDIT-test), quality of life (EQ-5D-3L) and health state (EQ VAS) at baseline, three months, six months and one year following the brief intervention were analyzed with Wilcoxon Signed-Rank test. The patients' alcohol risk use decreased statistically significantly after the treatment period at the Sobering Unit. The patients' health-related quality of life did not change statistically significantly during three months following the treatment period, whereas a statistically significant increase took place after six months. Self-perceived health status improved statistically significantly between the treatment period and three- and six-month follow up time points. The study gave some suggestive evidence that a brief intervention could be effective for harmful drinkers or alcohol-dependent patients when used in an emergency department. The Sobering Unit in the emergency department is one solution to encourage patients to pay attention to their alcohol risk drinking.

New universal scaling laws of diffusion and Kolmogorov-Sinai entropy in simple liquids. A new universal scaling law relating the self-diffusivities of the components of a binary fluid mixture to their excess entropies is derived using mode coupling theory. These scaling laws yield numerical results, for a hard sphere as well as Lennard-Jones fluid mixtures, in excellent agreement with simulation results even at a low density region, where the empirical scaling laws of Dzugutov [Nature (London) 381, 137 (1996)]] and Hoyt, Asta, and Sadigh [Phys. Rev. Lett. 85, 594 (2001)]] fail completely. A new scaling law relating the Kolmogorov-Sinai entropy to the excess entropy is also obtained.

A review of Agent Orange and its associated oncologic risk of genitourinary cancers. Agent Orange is an herbicide sprayed widely in Vietnam that is linked to a variety of malignancies in as early as 1991.Since then, there has been concern for, and subsequent interest in studying, the potential connection between Agent Orange and other malignancies. In the past 2 decades, there have been significant changes in the opinion of the National Academy of Science regarding Agent Orange and certain genitourinary malignancies. Herein, we review the literature regarding the potential link between Agent Orange and various urological cancers, including prostate, bladder, testicular, and renal cancers.

New approach for evaluating the public health risk of living near a polluted river. Chemical, physical and microbial analyses were conducted in the Sarno River basin to obtain a comprehensive description of the overall quality of the water bodies. The collection period lasted 12 months, between 2005 and 2006, with high frequency of sampling and analysis. More than 6,000 analytical determinations were performed on samples collected at six sampling points along the Sarno River and two points each on tributaries Solofrana and Cavaiola. The results indicated the presence of inorganic contaminants, which, in most cases, were below the Italian State water quality thresholds. The organic contamination showed an increasing trend, with respect to previous determinations, thus demonstrating the major contribution of untreated urban wastewater to the overall pollution of the river. Moreover, this study was designed to explore the correlation between the presence of microbial indicators of fecal contamination in Sarno River and their presumable presence in the aerosol surrounding the river, thus pointing to the possible environmental hazard associated with the presence of pathogens in the air.

Temporal evolution of the ABO allele frequencies in the Canary Islands: the impact of the European colonization. The indigenous Canary Islands population suffered a strong cultural and genetic impact when they were colonized by Europeans in the fifteenth century. The molecular analysis of the ABO blood group gene on aboriginal and seventeenth to eighteenth century remains confirms the demographic history of the islands depicted by previous archaeological, anthropological, and genetic studies. ABO allele frequencies clearly related Canarian aborigines with North African Berber populations, its most probable source of origin, and is far related to Iberian and to the current population of the archipelago. The historical sample shows a congruent intermediate position testifying already a strong European influence that would go in augment since then to present times, affecting all the islands with the important exception of La Gomera.

The effects of season and stage of pregnancy on 25-hydroxy-vitamin D levels in pregnant women in Madrid. The influence of seasonal variations and gestation on 25(OH)D3 levels was studied in a group of women from Madrid, Spain, at different stages of pregnancy, during March and September. The objective was to observe the incidence of this climate and dietary factors. No variations were found in serum concentration of the metabolite throughout pregnancy in comparison with the controls, in either March or September. 25(OH)D3 values decreased after winter in both groups of women, although mean values were consistently higher than 16 ng/ml.

Polybrominated diphenyl ethers and polychlorinated biphenyls in mangrove sediments of Shantou, China: Occurrence, profiles, depth-distribution, and risk assessment. Surface and columnar sediments were collected from four mangrove Wetlands in Shantou coastal areas of South China to investigate the level, distribution, possible sources and ecotoxicological risks of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs). Total concentration of 14 PBDEs (∑14PBDEs) and 41 PCBs (∑41PCBs) varied from 0.61 to 180 ng/g and 42-636 pg/g dry weight (dw) in surface sediments, respectively. The concentration of PBDEs was much higher than that of PCBs. Compared with other mangrove Wetlands around the world, PCBs levels in the studied area were relatively low, while the concentrations of PBDE were at higher level. Decabromodiphenyl ether (BDE-209) was the predominant PBDEs homologue in all sediment samples, indicating the extensive use of deca-BDE in this area. Penta-CBs and hexa-CBs were the main homologues of PCBs. Spatial variations showed that the concentration of PBDEs might be mainly affected by anthropogenic activities in specific sites of this region, whereas dry and wet deposition might be an important input source of PCBs in this area. Although accurate sediment chronology was not available, higher concentrations of PBDEs and PCBs were still found in some deeper sediment layers, suggesting that new input quantity tends to decrease with the increase of control. Risk assessment showed that penta-BDEs and deca-BDE may have potential negative ecological effects on the ecological of Shantou mangrove sediments, while the effects of PCBs can be neglected.

Global impact of rotavirus vaccine introduction on rotavirus hospitalisations among children under 5 years of age, 2008-16: findings from the Global Rotavirus Surveillance Network. Rotavirus vaccine use in national immunisation programmes has led to declines in hospital admissions for rotavirus gastroenteritis among children; however, the global impact of rotavirus vaccine introduction has not been described using primary data. We describe the impact of rotavirus vaccine introduction on admissions for acute rotavirus gastroenteritis in primarily low-income and middle-income countries, using 9 years of data from the WHO-coordinated Global Rotavirus Surveillance Network (GRSN). Between Jan 1, 2008, and Dec 31, 2016, children younger than 5 years of age who were admitted to hospital with acute gastroenteritis were prospectively enrolled in GRSN sites. We included sites that enrolled children and collected stool specimens monthly and tested at least 100 specimens annually in the impact analysis, with a separate analysis taking into account site continuity. We compared proportions of acute gastroenteritis cases positive for rotavirus in the pre-vaccine and post-vaccine periods and calculated mean proportion changes for WHO regions, with 95% CIs; these findings were then compared with interrupted time series analyses. We did further sensitivity analyses to account for rotavirus vaccination coverage levels and sites that collected specimens for at least 11 months per year and tested at least 80 specimens per year. We also analysed the age distribution of rotavirus-positive cases before and after vaccine introduction. 403 140 children younger than 5 years of age admitted to hospital with acute gastroenteritis from 349 sites in 82 countries were enrolled over the study period, of whom 132 736 (32·9%) were positive for rotavirus. We included 305 789 children from 198 sites in 69 countries in the impact analysis. In countries that had not introduced rotavirus vaccine in their national immunisation programmes, rotavirus was detected in 38·0% (95% CI 4·8-73·4) of admissions for acute gastroenteritis annually whereas in those that have introduced the vaccine, rotavirus was detected in 23·0% (0·7-57·7) of admissions for acute gastroenteritis, showing a 39·6% (35·4-43·8) relative decline following introduction. Interrupted time series analyses confirmed these findings. Reductions by WHO regions ranged from 26·4% (15·0-37·8) in the Eastern Mediterranean Region to 55·2% (43·0-67·4) in the European Region and were sustained in nine countries (contributing up to 31 sites) for 6-10 years. The age distribution of children with rotavirus gastroenteritis shifted towards older children after rotavirus vaccine introduction. A significant and sustained reduction in the proportion of hospital admissions for acute gastroenteritis due to rotavirus was seen among children younger than 5 years in GRSN sites following rotavirus vaccine introduction. These findings highlight the need to incorporate rotavirus vaccines into immunisation programmes in countries that have not yet introduced them and underline the importance of high-quality surveillance. The GRSN receives funding from Gavi, the Vaccine Alliance and the US Centers for Disease Control and Prevention. No specific funding was provided for this Article.

Selective kainic acid lesions in cultured explants of rat hippocampus. The influence of the excitotoxin kainic acid (KA) on cultivated explants of rat hippocampus was investigated. Addition of 3 microM KA to the culture medium over 24-48 h induced a destruction of the pyramidal cells in the CA3 region, whereas the CA1 pyramidal cells and the granule cells were left undamaged. Higher concentrations (10-100 microM) of KA destroyed also the latter cell groups. The selectivity of the KA lesion at 3 microM was further indicated by the fact that the acetylcholinesterase-positive neurons in the hippocampus were not destroyed through KA administration and that the stereoisomer dihydrokainic acid was ineffective in inducing lesions. Application of tetrodotoxin did not protect the CA3 pyramidal cells from KA lesion, whereas gamma-glutamylaminomethylsulphonic acid (GAMS) only offered a very small, statistically not significant, protection. Baclofen protected the cultures slightly from KA lesions but not when added together with GAMS. Possible mechanisms responsible for the KA lesions in these cultures are discussed.

Estimated incidence of acute pulmonary embolism in a Korean hospital. Patients with acute pulmonary embolism (PE) were identified retrospectively from patients hospitalized during a 2-year period from 2005 to 2007. Among adult patients (≥20 years), the incidence of established acute PE was 88 (0.17%) of 50 882 in Dongsan Hospital. The incidence of acute PE at Dongsan Hospital was 26% lower than that at Henry Ford Hospital (P < .01). Among patients more than 50 years of age, PE was more frequent in women (0.32%; 95% CI, 0.24-0.4) than in men (0.15%; 95% CI, 0.1-0.21; P < .01). Among all patients with PE older than 20 years of age, 68 (0.21%) of 31 869 (95% CI, 0.17-0.26) were from the medical service and 18 (0.08%) of 23 139 (95% CI, 0.04-0.11; P < .01) were from the surgical service. The estimated incidence of PE in a university teaching hospital in Korea was 0.17%, it was about two thirds of that in North America.

Postoperative fracture of os calcis and treatment. The occurrence of fracture of the calcaneus after heel spur surgery can be a devastating complication requiring prompt treatment and strict patient compliance during the postoperative course. The literature contains little information regarding this type of injury. Several factors must be considered in assessing the etiology of the fracture, including injuries incurred, surgical procedures performed, and axial forces that have been applied to the calcaneus.

[Immediate cooling with water: emergency treatment of burns]. Experimental data have demonstrated that prolonged immediate cooling with cold water is the best first-aid treatment for burn injuries. However in France, this treatment is rarely applied; instead old, inefficient and aggravating methods are still very popular. Pediatricians must help to change this practice by recommending immediate cold water treatment for burns in children.

Human histocompatibility antigen associations in patients with chronic cutaneous lupus erythematosus. Increased frequency of certain human leukocyte antigens (HLA) has been reported in various subsets of patients with lupus erythematosus (LE). Specifically, HLA-B8 and HLA-DR3 have been associated with subacute cutaneous LE; HLA-DR3 or HLA-DR2 is found in mothers of infants with neonatal LE; and HLA-A1, HLA-B8, HLA-B15, and HLA-DR2 occur in patients with systemic LE. We typed twenty-two white and nineteen black patients with chronic cutaneous (discoid) LE (DLE) for the A, B, and DR loci of the HLA antigens. HLA-DRw6 was found in an increased proportion of our patients of both races compared with controls. HLA-B8 was found more frequently in white DLE patients than in white control subjects. Thus a genetic predisposition may be a factor that explains the variation in disease expression.

Evidence of a central role for p38 map kinase induction of tumor necrosis factor alpha in pancreatitis-associated pulmonary injury. Tumor necrosis factor alpha (TNF alpha) has been implicated as an important mediator in acute pancreatitis-associated adult respiratory distress syndrome, but the precise pathogenesis remains unclear. The purpose of this work was to clarify the role of TNF alpha that is produced within the lung parenchyma in the inducement of pancreatitis-related pulmonary injury and to examine 1 of the potential pathways leading to the production of pulmonary TNF alpha. Bile salt pancreatitis was induced in rats (n = 40) that were randomized to receive a p38 mitogen-activated protein (MAP) kinase inhibitor or vehicle. A separate group (n = 16) underwent sham operation. Pulmonary capillary permeability was determined with fluorescein isothiocyanate-labeled albumin and Evans blue dye, and lung histologic analysis was performed. TNF alpha protein was measured in bronchoalveolar lavage fluid, and p38 MAP kinase was activity determined by Western blot analysis. The induction of pancreatitis resulted in increased pulmonary capillary leakage and worsened histologic condition (P < .01 vs sham). Effective inhibition of p38 MAP kinase-induced TNF alpha production completely prevented pancreatitis-associated pulmonary injury (P < .01 vs vehicle). p38 MAP kinase-induced TNF alpha production plays a central role in the development of pulmonary dysfunction, which accompanies severe acute pancreatitis in this rodent model.

[Analysis of hemagglutination inhibition antibody level in patients with influenza A H1N1]. To understand the hemagglutination inhibition antibody level in patients with influenza A H1N1. Sera from 28 patients with influenza A H1N1 at different time points after illness onset were collected and measured by hemagglutination inhibition assay. The serum hemagglutination inhibition antibody titers at 1, 5, 15, 22, 37, 49 and 58 days after illness onset were 5.36, 9.39, 39.02, 57.99, 137.92, 55.19 and 57.99 respectively. The top geometric mean titer of hemagglutination inhibition antibody was 148.55. The antibody seroconversion rate and seroprotection rate were occurred in 96.4% (27/28) of patients. The patients with influenza A H1N1 have effective immune response.

Uncommon complication after revision hip surgery. Cauda equina syndrome is an uncommon complication of ankylosing spondylitis characterized by the slow and insidious development of severe neurologic impairment related to dural ectasia. This report describes a unique case of cauda equina syndrome in a patient with ankylosing spondylitis after hip revision surgery. A 70-year-old man with long-standing ankylosing spondylitis underwent standard hip revision surgery; combined spinal and general anesthesia was administered. Pain was controlled with intravenous opioids postoperatively (patient-controlled analgesia). As per routine protocol, on the first postoperative day, the patient remained supine on a hip abduction pillow; mobilization was initiated on the second postoperative day. On postoperative day 1, the patient had severe low back pain that was controlled with patient-controlled analgesia. On postoperative day 2, the Foley catheter was removed and the patient sat and dangled. Back pain persisted while supine; in addition, the patient noticed involuntary loss of urine. On postoperative day 3, the patient had below-the-knee numbness that progressed to saddle anesthesia and foot flexor and extensor weakness. An epidural hematoma was suspected and urgent magnetic resonance imaging was performed, which showed severe degenerative stenosis at the L4-L5 level (mainly by dense ligamentum flavum). An L4-L5 decompression and instrumented fusion was performed; intraoperatively, L4-L5 was found to be the sole mobile segment. The extension of the spine in the supine position that completely obliterated the spinal canal was considered the mechanism of cauda equina syndrome. The intensity of back pain is a good indicator of a severe spinal lesion; however, pain can be dampened by intravenous opioids. High suspicion is required in patients with preexisting spinal pathology, such as ankylosing spondylitis.

"Immunoperoxidase" an essential modality of immunohistochemistry. The immunoperoxide (IP) technique can be used for the detection of immune deposits in various tissue pathologies. This article focusses on the standardization of the reagents anti IgG, anti IgA and anti C3C which are used to target these immune deposits. Lymph node tissue was used as substrate for standardization of anti IgG and anti IgM. For anti IgA, intestine was used while for anti C3C kidney tissue rapidly proliferating glomerulo nephritis - RPGN was utilized. Sensitivity of the technique was found to be high. Also the results on paraffin section were excellent and could be interpreted using simple light microscope. It is concluded that once standardization is achieved, IP can be used as an essential modality in the detection of immune deposits in a wide variety of immunologically mediated dermatologic disorders.

Structural and functional changes relevant to maxillary arterial flow observed during computed tomography and nonselective digital subtraction angiography in cats with the mouth closed and opened. Some cats develop blindness during procedures with mouth gags, which possibly relates to maxillary arterial occlusion by opening the mouth. Our first aim was to use computed tomography (CT) to describe how vascular compression is possible based on morphologic differences between mouth positions. Our second aim was to use nonselective digital subtraction angiography to assess whether opening the mouth induces collateral circulation. Six healthy cats were examined. During CT, the maxillary artery coursed between the angular process of the mandible and the rostrolateral wall of the tympanic bulla. The median distance between these structures was shorter when the mouth was opened (left, 4.3 mm; right, 3.6 mm) vs. closed (left, 6.9 mm; right, 7.1 mm). Additionally, the distance was shorter on the side ipsilateral to the gag (P = 0.03). During nonselective angiography, with the mouth closed, there was strong sequential opacification of the external carotid arteries, maxillary arteries, maxillary retia mirabilia, cerebral arterial circle, and basilar artery. Additionally, there was uniform opacification of the cerebrum and cerebellum. With the mouth opened, opacification of the maxillary arteries (rostral to the angular processes) was reduced in all cats, the cerebral arterial circle and basilar artery had simultaneous opacification in four of six (67%) cats, and the cerebrum had reduced opacification compared to the cerebellum in four of six (67%). In conclusion, the maxillary arteries are situated such that they can be compressed when opening the mouth. Opening the mouth did not consistently induce collateral circulation sufficient to produce comparable cerebral opacification as when the mouth was closed.

Non-small-cell superior sulcus tumor: results of en bloc resection in fifty-six patients - non-small-cell pancoast. Various multidisciplinary approaches are taken in the treatment of superior sulcus tumors. The purpose of this study was to determine the outcome, long-term results, and factors associated with prolonged survival after administering different combined radiosurgical regimens in a single institution. Between 1986 and 2000, 56 patients (43 men, 13 women) with superior sulcus tumor and histology of non-small-cell lung cancer underwent surgical resection. There were four treatment groups: I - preoperative radiation and operation (n = 15); II - preoperative radiation, operation and postoperative radiation (n = 22); III - operation and postoperative radiation (n = 10) and IV - no radiotherapy (n = 9). Survival was calculated by the Kaplan-Meier method and prognostic factors were assessed for significance by log-rank test and Cox regression analysis. The five-year survival rate after complete resection and N0/1 was 34 %. Of the prognostic factors analyzed, the histology, type of irradiation regimen and Horner's syndrome did not influence survival. Completeness of resection and mediastinal lymph node involvement clearly influences survival in univariate analysis. Age, sex and TNM classification were found to be independent significant prognostic factors for survival following resection. With superior sulcus tumors, every attempt should be made to resect the tumor completely by en bloc chest-wall resection with lobectomy and systematic hilar and mediastinal lymph node dissection. Mediastinal exploration by routine mediastinoscopy is recommended for identification of patients with advanced nodal involvement. Long-term survival may be relative to care taken in patient selection and extent of the resection performed. No significant difference in survival of patients with different irradiation regimens could be demonstrated in this study.

Diabetes training of community health workers serving native Hawaiians and Pacific people. Training of community health workers (CHWs) serving Native Hawaiian and Pacific People about diabetes prevention, control, and management was identified as a priority in a needs assessment of health agencies in Hawaii. Principles from Community-Based Participatory Research provided a framework to develop and implement a 4-hour training curriculum. The curriculum developers incorporated teaching strategies shown to be effective with this population and included culturally relevant material. Nineteen health organizations participated in the training that reached 111 CHWs over a 3-year period. Based on comparison of pre- and post-diabetes knowledge test results, the training participants showed significant gain in diabetes knowledge. A culturally tailored diabetes education gives CHWs the relevant knowledge and tools to participate in the delivery of diabetes education to a minority group experiencing disparate health outcomes. A community-based method facilitated development of seminar content and delivery strategies.

Diversity of genotypes of hepatitis C virus in southern India. A second generation assay for antibody to hepatitis C virus (anti-HCV) was used to screen 78 southern Indian individuals with a high risk of infection. RT-PCR targeted at the 5' end untranslated region (5'UTR) of the HCV genome was used to evaluate evidence of viraemia in 32 anti-HCV positive sera. The PCR products amplified from the 5'UTR of the HCV genome from 24 patients were sequenced, revealing the existence of two distinct groups of sequences: 21 corresponded to HCV type 1 while the other three sequences had 95% to 99% identity to HCV type 3. Two of these three isolates had more than 90% nucleotide identity in the NS5 region to established 3b sequences whereas the other had less than 74% nucleotide identity to any of the published genotype 3 (3a, 3b, 3c, 3d, 3e and 3f) sequences. However, a search of the EMBL nucleotide database revealed 91% identity to the unpublished sequence of an isolate of HCV from Indonesia. We provide evidence that these two isolates may represent a novel subtype within genotype 3. Our data also suggest that HCV genotype 1 predominates over HCV genotype 3 in southern India.

Cadmium, copper, and zinc in rice produced in Java. Cadmium (Cd), copper (Cu) and zinc (Zn) contents in 116 polished and unpolished rice samples produced in the Java Islands of Indonesia were assessed as a base-line study of trace metals. Arithmetic means and one standard deviation were 0.040 +/- 0.042 ppm Cd, 2.93 +/- 1.11 ppm Cu, and 18.17 +/- 3.13 ppm Zn. Concentration ratio of Cd to Zn was 0.00220 +/- 0.00222. The correlation coefficients between the metals were low. The two highest samples of rice contained 0.27 and 0.34 ppm Cd. Using the fact that Indonesians consume about 300 g of rice, the daily intake of Cd would exceed the tolerable limit proposed by FAO/WHO and could cause slight chronic renal damage to the rice eaters. Soil type by suborder and rice variety gave little difference of the three metals content in rice. Rice samples from West Java, where major soil type by order is Ultisol, contained higher cadmium and zinc, and lower copper than those from East Java (Vertisol).

Expedited development of a high dose orally disintegrating metformin tablet enabled by sweet salt formation with acesulfame. Salt formation has been extensively used to improve drug properties, including solubility, stability and mechanical properties. A sweet salt of metformin with acesulfame, prepared though an anion exchange reaction, showed superior properties over the commercial hydrochloride salt. These included both remarkable improvement of taste and significant enhancement in tabletability, which is explained by the different crystal structures and lower hardness as measured by nanoindentation. The relationship among crystal structure, mechanical properties and tabletability was rationalized through an energy framework analysis. This approach led to the successful development of an orally disintegrating tablet product containing 60% of metformin-acesulfame salt by direct compaction.

CYBB Gene Mutation Detection in an Iranian Patient with Chronic Granulomatous Disease. In this study, we report a mutation in CYBB gene in a patient with X-CGD (diagnosed on the base of family history, NDT test, DHR 123 assay). Mutation in CYBB gene was detected using SSCP analysis (single-strand conformation polymorphism) followed by sequencing. During screening for mutations in the CYBB gene we observed 880 CT in exon 8. This mutation resulted in 290 ArgStop. We also observed a change (-270 CA) in the promoter region which needs further investigation.We would like to pursue this study by analyzing more X-CGD patients to find out the CYBB mutation spectrum in Iranian patients.

Mattress sutures to remove unwanted convexity and concavity of the nasal tip: 12-year follow-up. Nasal tip bulbosity, or convexity, has been one of the most difficult problems to correct during rhinoplasty. Excision of cartilage from the cephalic part of the lateral crus has helped. However, complete correction of the deformity is not always possible with this maneuver alone. Suture techniques have also helped to improve outcomes. Twelve years ago, the lateral crus mattress suture was introduced as a way of converting the lateral crus to a flat, straight segment with resultant correction of the convexity. Since then, this suture technique has been employed in most primary and some secondary rhinoplasties and has stood the test of time. We report our experience with this technique, including a slight modification to facilitate its application when the cartilage is unusually narrow or when the original technique is difficult to complete. In addition, the suture technique for the less concave lateral crura is redescribed. It, too, has withstood the test of time.

Cation Clustering in Intermetallics: The Modular Bonding Schemes of CaCu and Ca2Cu. Electropositive metals such as the alkaline earths or lanthanides are generally assumed to act largely as spectator cations in solid state compounds. In polar intermetallic phases, atoms of such elements are indeed often placed at the peripheries of anions or polyanionic fragments. However, they also show a pronounced tendency to cluster with each other in these peripheral regions in a manner suggestive of multicenter bonding. In this Article, we theoretically investigate the bonding schemes that underlie these cationic cluster arrangements, focusing on CaCu (whose two polymorphs are based on the intergrowth of the FeB- and CrB-types) and Ca2Cu (a Ca-intercalated derivative of CaCu). The structures of these phases are based on Cu zigzag chains embedded in matrices of Ca atoms arranged into increasingly well-developed fragments of closest-packed arrangements. Using reversed approximation Molecular Orbital (raMO) analysis, the Cu chains of both structures are revealed to be connected via nearly fully occupied Cu-Cu isolobal σ-bonds, such that the Cu atoms control 11.67 of the 13 and 15 electrons/formula unit of CaCu and Ca2Cu, respectively. Most of the remaining electrons are drawn to multicenter bonding functions in the Ca sublattices despite the availability of additional Cu 4p orbitals, indicating that the electronegativity difference between Ca and Cu is insufficient to achieve formal Cu oxidation states far beyond -1. The metallic nature of the Ca-based bonding subsystem is reflected in the raMO analysis by a plurality of resonance structures that can be generated from the occupied crystal orbitals. Across these bonding schemes, a separation of the electronic structure into largely self-contained Ca-Ca and Ca-Cu states is a consistent theme. This modularity in the bonding can be correlated to the ease with which this and related systems rearrange FeB- and CrB-type features, which may provide clues to identifying other intermetallic families with similar degrees of structural versatility.

Activation of caspase-3 and cleavage of Rb are associated with p16-mediated apoptosis in human non-small cell lung cancer cells. The p16 tumor suppressor gene is frequently inactivated in human cancer tissues and cell lines. We previously reported that wild-type p16 expression from an adenovirus vector (Adv/p16) induced p53-dependent apoptotic cell death in non-small cell lung cancer (NSCLC) cell lines. Here we show the potential mechanism of apoptosis induced by Adv/p16 infection. Infection of human NSCLC cell line A549, which carries the wild-type p53 gene, with Adv/p16 resulted in activation of caspase-3, accompanied by the cleavage of its substrate poly (ADP-ribose) polymerase (PARP), on day 3 of infection. The retinoblastoma (Rb) cell cycle regulator protein was also cleaved after activation of caspase-3; when the levels of Rb significantly diminished, apoptosis began. When A549 cells were pretreated with the caspase-inhibitory peptide N-acetyl-asp-Glu-Val-Asp-CHO (aldehyde) (Ac-DEVD-CHO), Adv/p16-mediated apoptosis and Rb cleavage were greatly inhibited. Furthermore, MDM2, a negative regulator of p53 expression was upregulated 3 days after Adv/p16 infection, and MDM2 was subsequently cleaved by caspase-3; MDM2 cleavage was inhibited by Ac-DEVD-CHO treatment. These data implied that cleavage of Rb, in addition to activation of caspase-3, represented a mechanism by which Adv/p16 induced apoptotic cell death in human NSCLC cells. Our results support the clinical relevance of Adv/p16 as a treatment for p16-null human NSCLC that express wild-type p53.

Phenolic profiles and antioxidant capacities of crude extracts and subsequent fractions from Potentilla fruticosa L. leaves. This work aimed to further investigate the phenolic profiles and antioxidant capacities of the crude extracts and the subsequent fractions of Potentilla fruticosa leaves. Result showed that P. fruticosa leaves contained high amounts for hyperoside, ellagic acid and (+)-catechin contents, and the highest amount being registered for hyperoside (17.67 mg g(-1)). Nine sub-fractions were obtained after column chromatographic separation. EF-3, EF-4, EF-5 and BF-2 presented higher values for their total phenolic or flavonoid, (+)-catechin, ellagic acid and hyperoside content. Besides, EF-3, EF-4, BF-2 and BF-3 showed significant in vitro antioxidant capacities and protective effects on Escherichia coli under peroxide stress. The correlation between chromatograms and antioxidant activity showed that (+)-catechin, ellagic acid and hyperoside may play crucial roles in the antioxidant capacities of P. fruticosa and could be used as chemical markers for its quality assessment. Moreover, this is the first time P. fruticosa leaves have been systematically studied.

Hypercoagulability and chronic atrial fibrillation: the role of markers of thrombin generation. We have studied 64 patients with congestive heart failure, half of them also with chronic nonvalvular atrial fibrillation (AF). Patients were also stratified according to a history of prior stroke. The generation of thrombin was investigated by means of the molecular markers prothrombin fragment 1 + 2 (F1 + 2) and thrombin-antithrombin III complex (TAT), because AF patients may have a hypercoagulable state. There was only a trend toward higher values of TAT and F1 + 2 for AF patients, while subjects with previous stroke (irrespective of AF) had increased levels of the markers of thrombin generation (TAT stroke+ 18.95 +/- 5.15 vs TAT stroke- 8.34 +/- 2.41; F1 + 2 stroke+ 2.22 +/- 0.29 vs F1 + 2 stroke- 1.32 +/- 0.12). The presence of spontaneous echo contrast (SEC) within left atrium was also investigated in 32 AF patients by transesophageal echocardiography. TAT were significantly higher in subjects (n = 11) with SEC (TAT sec+ 37.5 +/- 13.41 vs TAT sec- 8.7 +/- 2.51, p = 0.008). Finally, when we grouped into 1) those with both AF and stroke, 2) AF alone, 3) stroke alone and 4) sinus rhythm without stroke, levels of F1 + 2 were higher (and marginally higher TAT) in patients with AF and stroke than in those without stroke, revealing that there is a true clotting activation state in these subjects.

Hybrid III-nitride/organic semiconductor nanostructure with high efficiency nonradiative energy transfer for white light emitters. A novel hybrid inorganic/organic semiconductor nanostructure has been developed, leading to very efficient nonradiative resonant-energy-transfer (RET) between blue emitting InGaN/GaN multiple quantum wells (MQWs) and a yellow light emitting polymer. The utilization of InGaN/GaN nanorod arrays allows for both higher optical performance of InGaN blue emission and a minimized separation between the InGaN/GaN MQWs and the emitting polymer as a color conversion medium. A significant reduction in decay lifetime of the excitons in the InGaN/GaN MQWs of the hybrid structure has been observed as a result of the nonradiative RET from the nitride emitter to the yellow polymer. A detailed calculation has demonstrated that the efficiency of the nonradiative RET is as high as 73%. The hybrid structure exhibits an extremely fast nonradiative RET with a rate of 0.76 ns(-1), approximately three times higher than the InGaN/GaN MQW nonradiative decay rate of 0.26 ns(-1). It means that the RET dominates the nonradiative processes in the nitride quantum well structure, which can further enhance the overall device performance.

Cisplatin microcrystals suspended in oil--toxicity in mice. A new dosage format, cisplatin microcrystals suspended in oil (CDDP-oil), was developed for the treatment of peritoneal carcinomatoses. We studied the acute toxicity of CDDP-oil injected intraperitoneally in mice. The 50% lethal dose was 30.3 mg/kg (27.1-33.7 mg/kg at the 95% confidence level), which was 1.79 times that of a cisplatin aqueous solution (CDDP-sol) of 16.9 mg/kg (16.1-17.8 mg/kg at the 95% confidence level). There were no significant differences in the duration of the toxic effects and the toxic symptoms between these two dosage forms. However, the severity of weight loss in the group given CDDP-oil was less than the group given CDDP-sol.

Age- and ability-related differences in young readers' use of conjunctions. Two studies investigating young readers' use of conjunctions are reported. In Study One, 145 eight- to ten-year-olds completed one of two narrative cloze tasks in which different types of conjunction were deleted. Performance for additive conjunctions was not affected by age in this study, but older children were more likely to select the target conjunction than were younger children for temporal, causal, and adversative terms. Performance was superior in the cloze task in which they were given a restricted choice of responses (three vs. seven). In Study Two, 35 eight- and nine-year-old good and poor comprehenders completed the three-choice cloze task. The poor comprehenders were less likely to select the target terms in general. Sentence-level comprehension skills did not account for their poor performance. The results indicate that understanding of the semantic relations expressed by conjunctions is still developing long after these terms are used correctly in children's speech. The findings are discussed in relation to the role of conjunctions in text comprehension.

Interaction between smoking history and gene expression levels impacts survival of breast cancer patients. In contrast to studies focused on cigarette smoking and risk of breast cancer occurrence, this study explored the influence of smoking on breast cancer recurrence and progression. The goal was to evaluate the interaction between smoking history and gene expression levels on recurrence and overall survival of breast cancer patients. Multivariable Cox proportional hazards models were fitted for 48 cigarette smokers, 50 non-smokers, and the total population separately to determine which gene expressions and gene expression/cigarette usage interaction terms were significant in predicting overall and disease-free survival in breast cancer patients. Using methods similar to Andres et al. (BMC Cancer 13:326, 2013a; Horm Cancer 4:208-221, 2013b), multivariable analyses revealed CENPN, CETN1, CYP1A1, IRF2, LECT2, and NCOA1 to be important predictors for both breast carcinoma recurrence and mortality among smokers. Additionally, COMT was important for recurrence, and NAT1 and RIPK1 were important for mortality. In contrast, only IRF2, CETN1, and CYP1A1 were significant for disease recurrence and mortality among non-smokers, with NAT2 additionally significant for survival. Analysis of interaction between smoking status and gene expression values using the combined samples revealed significant interactions between smoking status and CYP1A1, LECT2, and CETN1. Signatures consisting of 7-8 genes were highly predictive for breast cancer recurrence and overall survival among smokers, with median C-index values of 0.8 and 0.73 for overall survival and recurrence, respectively. In contrast, median C-index values for non-smokers was only 0.59. Hence, significant interactions between gene expression and smoking status can play a key role in predicting breast cancer patient outcomes.

Platelet function and coagulation in patients with Wilson disease. Sixteen patients with Wilson disease (hepatolenticular degeneration) were studied from the hemostatic point of view, particularly with regard to platelet function. Five of the patients had a mild bleeding tendency that was characterized by easy bruising. Moderate thrombocytopenia was observed in three of the five bleeders and in two of the others. One bleeder was thrombocytotic and hyperfibrinogenemic. Bleeding times, platelet retention and prothrombin consumption were abnormal rarely. However, 15 of the 16 patients had some abnormality of platelet aggregation: one when adenosine diphosphate was added to platelet rich plasma, three when epinephrine was added, and the remainder when collagen was added. The collagen abnormalities were delayed or absent aggregation (five patients, four of whom were bleeders) and absence of a change of shape (12 of the 16 patients). Platelet aggregation was completely normal in only one patient.

Imaging and invasive techniques for diagnosis and treatment of surgical infections. Advances in imaging techniques have caused a radical change in the radiologic approach to the diagnosis and treatment of surgical infections. Review of the pertinent English-language literature. Ultrasonography (US) is a useful modality for the initial evaluation of intra-abdominal infection, whereas computed tomography (CT) often represents the modality of choice for definitive identification of the cause and extent of the infection. Both US and CT can be used to guide diagnostic fluid aspiration or drainage catheter placement. Fluoroscopy may be useful for diagnostic and interventional procedures in the biliary and urinary tracts, whereas magnetic resonance imaging plays a leading role in evaluating bone and soft tissue structures and the pancreatobiliary tree. The choice of imaging study must be individualized to the particular circumstances of the clinical situation, particularly whether image-guided therapy may be required in addition to diagnosis. Computed tomography is the most versatile for most clinical circumstances.

Experimental studies on the pathogenesis and prophylaxis of stroke in stroke-prone spontaneously hypertensive rats (SHR).(1) Quantitative estimation of cerebrovascular permeability. The cerebrovascular permeability quantitatively determined by the retention of 131I-human albumin in the perfused brains was increased in SHR, especially in stroke-prone SHR compared with normotensive Wistar-Kyoto, and confirmed the macroscopical or microscopical findings on the leakage into the brain or trypan blue or peroxidase injected intravenously 2 to 3 hours before sacrifice. The localization of increased vascular permeability in SHR corresponded to the predilection sites of cerebral hemorrhage or softening, which developed likely following the increased cerebrovascular permeability.

Molecular defects in haemophilia B: detection by direct restriction enzyme analysis. The common restriction fragment length polymorphisms (RFLPs) associated with the FIX gene: 5' BamH I, Dde I, BamH I (2), Taq I and 3' Hha I were absent or of low incidence in Southern Chinese and are therefore not useful for linkage analysis. No deletion was detected amongst seven consecutive unrelated haemophilia B patients, but one had an insertion of a 15 kb Pvu II fragment containing exon d. Using an alternate strategy of polymerase chain reaction (PCR) amplification and direct sequencing, the molecular defect in the other six patients was defined. The four novel mutations characterized were: nucleotide (nt) 6410 G----C (Gly12----Ala); nt 31261 delta T (stop codon 31 bp downstream); nt 31260 C----G (Thr380----Ser) and nt 31122 C----A (Ala34----Asp). Two patients had the same mutation at nt 6365, G----A (Arg-4----Gln), identical to one previously described in other ethnic groups, suggesting that this is a hotspot for mutation. Each of the mutations was found to affect an enzyme recognition site and could thus be identified by direct visualization of abnormal restriction fragments in amplified genomic DNA. This allows rapid and accurate DNA diagnosis of haemophilia B in an ethnic group which otherwise shows little or no polymorphism for the common RFLP sites.

The Nrf2-Keap1 defence pathway: role in protection against drug-induced toxicity. The metabolic biotransformation of xenobiotics to chemically reactive metabolites can, in some instances, underlie the pathogenesis of certain adverse drug reactions, due to the development of chemical or oxidative stress. In order to guard against such stresses, mammalian cells have evolved multi-faceted, highly-regulated defence systems, one of the most important being that which is regulated by the transcription factor Nrf2. Through regulating the expression of numerous cytoprotective genes, Nrf2 serves as a critical determinant of a cell's capacity to survive, or succumb, to a toxic insult. The aim of this review is to summarise our current understanding of the biochemistry that underlies the Nrf2 defence pathway, and highlight the important role of this transcription factor in the protection against drug-induced toxicity, primarily through the examination of recent investigations that have demonstrated an increased vulnerability to various toxins in animals lacking Nrf2.

Molecular typing of toxic shock syndrome toxin-1- and Enterotoxin A-producing methicillin-sensitive Staphylococcus aureus isolates from an outbreak in a neonatal intensive care unit. Outbreaks of Staphylococcus aureus are common in neonatal intensive care units (NICUs). Usually they are documented for methicillin-resistant strains, while reports involving methicillin-susceptible S. aureus (MSSA) strains are rare. In this study we report the epidemiological and molecular investigation of an MSSA outbreak in a NICU among preterm neonates. Infection control measures and interventions were commissioned by the Local Public Health Authority and supported by the Robert Koch Institute. To support epidemiological investigations molecular typing was done by spa-typing and Multilocus sequence typing; the relatedness of collected isolates was further elucidated by DNA SmaI-macrorestriction, microarray analysis and bacterial whole genome sequencing. A total of 213 neonates, 123 healthcare workers and 205 neonate parents were analyzed in the period November 2011 to November 2012. The outbreak strain was characterized as a MSSA spa-type t021, able to produce toxic shock syndrome toxin-1 and Enterotoxin A. We identified seventeen neonates (of which two died from toxic shock syndrome), four healthcare workers and three parents putatively involved in the outbreak. Whole-genome sequencing permitted to exclude unrelated cases from the outbreak and to discuss the role of healthcare workers as a reservoir of S. aureus on the NICU. Genome comparisons also indicated the presence of the respective clone on the ward months before the first colonized/infected neonates were detected.

The use of blood glucose/cerebrospinal fluid glucose ratio in the diagnosis of central nervous system infection in infants and children. The diagnosis of bacterial meningitis can be difficult nowadays when antibiotics are freely used in infants and children with fever due to infection, so that a positive smear or culture may be difficult to achieve. In areas where sophisticated methods of diagnosis may be hard to come by, the simple procedure of simultaneously estimating the blood and cerebrospinal fluid (CSF) glucose levels may be helpful in distinguishing bacterial meningitis from viral meningitis. 74 proven cases of bacterial meningitis and aseptic meningitis were investigated prior to treatment. There were 36 cases of bacterial meningitis and 38 cases of aseptic meningitis. The CSF glucose/plasma glucose ratio was calculated for each patient. The cases were divided into two groups; Group A with CSF glucose/plasma glucose ratio of (0.38-2.0) and Group B with CSF glucose/plasma glucose ratio of (0.1-0.35). In Group A, two out of 59 cases died while in Group B, nine out of 15 died (p < 0.01). 44 out of 59 in Group A recovered fully while only two out of 15 in Group B were cured (p < 0.01). It was also found that 54.2% in Group A were admitted in deep coma compared with 86.7% in Group B (p < 0.05) and 25.4% in Group A were admitted with seizures while 66.7% in Group B had convulsion (p < 0.01). Hence, a low CSF glucose/plasma glucose ratio was associated with a poor outcome. The mechanisms responsible for these findings are discussed especially with reference to the blood-brain barrier (BBB).(ABSTRACT TRUNCATED AT 250 WORDS)

Polymeric reagents with propane-1,3-dithiol functions and their precursors for supported organic syntheses Reliable completely odorless syntheses of soluble copolymeric reagents of styrene type containing propane-1,3-dithiol functions able to convert carbonyl compounds into 1,3-dithiane derivatives and to support other useful transformations are reported together with their progenitor copolymers containing benzenesulfonate or thioacetate groups perfectly stable in open air and suitable for unlimited storage. The effectiveness of the prepared reagents as tools for polymer-supported syntheses to produce ketones by aldehyde umpolung and alkylation is tested in the conversion of benzaldehyde to phenyl n-hexyl ketone starting from copolymers with different contents of active units and molecular weights. To facilitate the adaptation of the prepared soluble copolymeric reagents to other possible applications, a table of solvents and nonsolvents is presented.

Dissociation between the correlation of peritoneal and urine Kt/V with sodium and fluid removal: a possible explanation of their difference on patient survival. It has been shown that residual renal function but not peritoneal clearance predicted patients' survival in peritoneal dialysis therapy. In the present study, we tried to explore the potential causes resulting in the difference between residual renal function and peritoneal dialysis in continuous ambulatory peritoneal dialysis (CAPD) patients. A cross sectional study was performed during July and August 2003 to evaluate the dialysis adequacy in CAPD patients who were clinically stable and had daily urinary volume more than 100 ml. A total of 45 patients (male 27 and female 18) with an average ( +/- SD) age of 61.76 +/- 13.27 years were included in this study. The daily urinary volume and dialysate ultrafiltration volume were 570.33 +/- 395.47 ml and 726.09 +/- 454.01 ml, respectively. Peritoneal urea clearance (Kt/V) correlated significantly with the drained daily dialysate volume (r = 0.362, P < 0.01), but not with peritoneal net fluid removal (ultrafiltration) (r = 0.232, P > 0.05) and sodium removal (r = 0.139, P > 0.05). On the other hand, there were strong positive correlations between residual renal Kt/V and daily urine volume (r = 0.802, P < 0.001), as well as between residual renal Kt/V and urinary sodium removal (r = 0.670, P < 0.001). High residual renal Kt/Vurea represents both higher solute clearance and higher sodium and fluid removal, but higher peritoneal Kt/Vurea is not necessarily associated with better sodium and fluid removal. This dissociation might explain the differences on the survival of patients and peritoneal clearances.