Macrophages as targets for inhibition by cyclosporine.
In order to understand the mechanism of immunosuppression by cyclosporine, its effects on macrophage-mediated antigen-specific T cell activation (IL-2 production) were studied in vitro. While cyclosporine (CsA) present during the macrophage-T cell coculture inhibited antigen presentation effectively, pretreatment (2 hr) of macrophages with the drug also caused marked inhibition regardless of the antigen concentration and order of drug/antigen addition. Pretreatment of T cells caused only modest inhibition. With macrophage pretreatment, the structural analog cyclosporine-G had the same inhibitory activity as cyclosporine (cyclosporine-A), whereas dihydro-cyclosporine-D and cyclosporine-H were inactive. Cyclosporine demonstrated saturable binding to macrophages suggesting the existence of CsA-binding sites. A 50% inhibition of IL-2 production was achieved with 10(-6) M CsA and 60-70% of the binding sites were occupied at this concentration. CsA-treated macrophages did not release inhibitory material and the drug did not appear to be transferred from the macrophages to the T cells during the coculture. Although antigen-specific T cells could bind to drug-treated macrophages, they did not produce IL-2. Collectively, these results suggest that CsA has a direct effect on macrophages that subsequently interferes with IL-2 production at a stage following T cell antigen recognition.


Independent effects of Alzheimer's disease on neuropsychological functioning.
A new analytical procedure, single common factor analysis, was carried out on the data from a relatively large sample of normals (n = 101) and patients with Alzheimer's disease (AD; n = 180) to examine the extent to which there were independent effects of disease status on different neuropsychological variables. This technique uses structural equation methods to determine what all of the variables have in common, and then controls this common factor when examining the relationship between diagnostic group and each individual test variable. To the extent that AD represents the sum of independent breakdowns of different information processing domains, then there should be sets of variables that have weak or nonexistent links to the other variables. However, the results revealed that a large proportion of the AD-related effects on test scores was shared and was not independent of the AD-related effects on other variables.


Repeat associated small RNAs vary among parents and following hybridization in maize.
Small RNAs (sRNAs) are hypothesized to contribute to hybrid vigor because they maintain genome integrity, contribute to genetic diversity, and control gene expression. We used Illumina sequencing to assess how sRNA populations vary between two maize inbred lines (B73 and Mo17) and their hybrid. We sampled sRNAs from the seedling shoot apex and the developing ear, two rapidly growing tissues that program the greater growth of maize hybrids. We found that parental differences in siRNAs primarily originate from repeat regions. Although the maize genome contains greater number and complexity of repeats compared with Arabidopsis or rice, we confirmed that, like these simpler plant genomes, 24-nt siRNAs whose abundance differs between maize parents also show a trend of down-regulation following hybridization. Surprisingly, hybrid vigor is fully maintained when 24-nt siRNAs are globally reduced by mutation of the RNA-dependent RNA polymerase 2 encoded by modifier of paramutation1 (mop1). We also discovered that 21-22-nt siRNAs derived from a number of distinct retrotransposon families differentially accumulate between B73 and Mo17 as well as their hybrid. Thus, maize possesses a unique source of genetic variation for regulating transposons and genes at a genomic scale, which may contribute to its high degree of observed heterosis.


Severe acute pancreatitis: Clinical course and management.
Severe acute pancreatitis (SAP) develops in about 25% of patients with acute pancreatitis (AP). Severity of AP is linked to the presence of systemic organ dysfunctions and/or necrotizing pancreatitis pathomorphologically. Risk factors determining independently the outcome of SAP are early multi-organ failure, infection of necrosis and extended necrosis (>50%). Up to one third of patients with necrotizing pancreatitis develop in the late course infection of necroses. Morbidity of SAP is biphasic, in the first week strongly related to early and persistence of organ or multi-organ dysfunction. Clinical sepsis caused by infected necrosis leading to multi-organ failure syndrome (MOFS) occurs in the later course after the first week. To predict sepsis, MOFS or deaths in the first 48-72 h, the highest predictive accuracy has been objectified for procalcitonin and IL-8; the Sepsis-Related Organ Failure Assessment (SOFA)-score predicts the outcome in the first 48 h, and provides a daily assessment of treatment response with a high positive predictive value. Contrast-enhanced CT provides the highest diagnostic accuracy for necrotizing pancreatitis when performed after the first week of disease. Patients who suffer early organ dysfunctions or at risk of developing a severe disease require early intensive care treatment. Early vigorous intravenous fluid replacement is of foremost importance. The goal is to decrease the hematocrit or restore normal cardiocirculatory functions. Antibiotic prophylaxis has not been shown as an effective preventive treatment. Early enteral feeding is based on a high level of evidence, resulting in a reduction of local and systemic infection. Patients suffering infected necrosis causing clinical sepsis, pancreatic abscess or surgical acute abdomen are candidates for early intervention. Hospital mortality of SAP after interventional or surgical debridement has decreased in high volume centers to below 20%.


Metabolic and cardiovascular responses during aquatic exercise in water at different temperatures in older adults.
The aim of this study was to investigate the physiological responses during upper-body aquatic exercises in older adults with different pool temperatures. Eleven older men (aged 65 years and older) underwent 2 identical aquatic exercise sessions that consisted of 3 upper-body exercises using progressive intensities (30, 35, and 40 metronome beat · min(- 1)) on separate visits. Water temperatures for the visits were 28°C (cold water [CW]) and 36°C (hot water [HW]), and water depth ranged from 1.2 m to 1.4 m. Measurements for heart rate (HR), blood pressure (BP), oxygen consumption (VO2), and rate of perceived exertion (RPE) were compared between the CW and HW conditions. The comparison between temperatures showed a higher HR response during exercise in HW, particularly when participants exercised at the highest intensities. During a 30-min postexercise period in resting conditions, HR was statistically significantly higher for the HW condition compared with the CW condition, with a large effect size (15.9%, d = 1.23). Systolic and diastolic BPs were found to be lower for the HW condition ( - 7.2%, d = - 0.60; - 10.1%, d = - 0.65), while VO2 and RPE showed no differences. The effect size between double products (HR · systolic BP) for the 2 conditions was small (CW = 8,649 ± 1,287, HW = 9,340 ± 1,672; d = 0.36), suggesting similar myocardial oxygen requirements. This study showed that HR response was higher in an HW condition for older men. Warmer environments may add additional stressors to the body, which may impact training strategies and should be considered when estimating the effort of performing aquatic exercise.


Prognostic biomarkers correlated with immune infiltration in non-small cell lung cancer.
Lung cancer is the leading cause of cancer-related mortality in men and women globally. Non-small cell lung cancer (NSCLC) is the most prevalent subtype, accounting for 85-90% of all cancers. Although there have been dramatic advances in therapeutic approaches in recent decades, the recurrence and metastasis rates of NSCLC are as high as 30-40% with the 5-year overall survival rate being less than 15%. Therefore, it is necessary to explore the pathogenesis of NSCLC at the genetic level and identify prognostic biomarkers and novel therapeutic targets. Here, we aimed to identify mutated genes with high frequencies in Chinese NSCLC patients using next-generation sequencing and to investigate their relationships with the tumor mutation burden (TMB) and tumor immune microenvironment. A total of 110 NSCLC patients were enrolled to profile the genetic variations. Mutations in EGFR (62.37%), TP53 (61.29%), LRP1B (13.98%), FAT1 (12.90%), KMT2D (11.83%), CREBBP (10.75%), and RB1 (9.68%) were most prevalent. TP53, LRP1B, KMT2D, and CREBBP mutations were all significantly associated with high TMB (P < 0.05 or P < 0.01). The infiltrating levels of immune cells and immune molecules were enriched significantly in the LRP1B mutation group. LRP1B mutations significantly correlated with stimulating and inhibitory immunoregulators. Gene set enrichment analysis revealed that cell cycle, the Notch signaling pathway, the insulin signaling pathway, and the mTOR signaling pathway are related to LRP1B mutations in the immune system. LRP1B mutations may be of clinical importance in enhancing the anti-tumor immune response and may be a promising biomarker for predicting immunotherapy responsiveness.


Selective Removal of Aminoquinoline Auxiliary by IBX Oxidation.
8-Aminoquinoline (AQ) is a widely used bidentate auxiliary in metal-catalyzed directed C-H functionalization reactions. Herein, we report an efficient and chemoselective method to convert various N-quinolyl carboxamides to primary amides with the treatment of a stoichiometric amount of 2-iodoxybenzoic acid oxidant or the combination of a catalytic amount of 2-iodobenzoic acid and Oxone co-oxidant in mixed solvents of H2O and HFIP. Its unique compatibility with the Phth-protected α-amino acid (αAA) substrates enhances the overall synthetic utility of the AQ-directed palladium-catalyzed C-H functionalization strategy for synthesis of complex αAAs.


Abnormal brain scan with subacute extradural haematomas.
Four patients are described with proven subacute extradural haematomas, each with an abnormal cerebral scan of diagnostic assistance. A possible mechanism of production of the subacute extradural haematoma is discussed, and appears to be similar to the mechanism involved in the subacute subdural haematoma. The means by which the abnormal scan results in such cases is also examined, from which it appears that non-specific meningeal membrane inflammatory reaction surrounding the haematoma is significant.


Effect of hydrogen peroxide on antioxidant enzyme activities in Saccharomyces cerevisiae is strain-specific.
The effect of hydrogen peroxide on the survival and activity of antioxidant and associated enzymes in Saccharomyces cerevisiae has been studied. A difference found in the response of wild-type yeast strains treated with hydrogen peroxide was probably related to the different protective effects of antioxidant enzymes in these strains. Exposure of wild-type YPH250 cells to 0.25 mM H(2)O(2) for 30 min increased activities of catalase and superoxide dismutase (SOD) by 3.4- and 2-fold, respectively. However, no activation of catalase in the EG103 strain, as well as of SOD in the YPH98 and EG103 wild strains was detected, which was in parallel to lower survival of these strains under oxidative stress. There is a strong positive correlation (R(2) = 0.95) between activities of catalase and SOD in YPH250 cells treated with different concentrations of hydrogen peroxide. It is conceivable that catalase would protect SOD against inactivation caused by oxidative stress and vice versa. Finally, yeast cell treatment with hydrogen peroxide can lead to either a H(2)O(2)-induced increase in activities of antioxidant and associated enzymes or their decrease depending on the H(2)O(20 concentration used or the yeast strain specificity.


Epidemiology and public health at CDC.
Epidemiology is the study of the distribution and determinants of health-related states or events in specified populations and the application of this study to control health problems. However, in public health, the terms "field epidemiology" and "applied epidemiology"--which emphasize use of results in public health settings--define the practice of epidemiology at CDC. Epidemiology has been characterized as the basic science of public health, and its practice at CDC has shaped the agency's development and will contribute to its future success.


Theoretical Modeling and Inverse Analysis of Thermal Conductivity of Skeletons in SiO2 Nano-Insulation Materials.
With the developments in high-performance nano-insulation material technology, theoretical studies on the heat transfer mechanisms in these materials have been conducted. However, the conductivity of nanometer-sized skeletons is still unclear. It is necessary to clarify the thermal conductivity of nanometer-sized solid skeletons in order to better understand the heat transfer mechanisms in nano-insulation materials. In the present study, a theoretical model for the thermal conductivity of nanometer-sized skeletons in nano-insulation materials is presented based upon the meso-structure of the material and the equation of phonon transfer. The size effect in thermal conductivity of the nanometer-sized particles is studied numerically, and the thermal conductivity is theoretically obtained. At the same time, a reverse method is established for the thermal conductivity of nanometer-sized particles based on the method of particle swarm optimization (PSO). The skeleton thermal conductivity for a specific nano-insulation material with a density of 110 kg/m3 and porosity of 0.94 is identified based upon experimental data from literature. Comparison results show that the theoretical conductivity of nanometer-sized skeletons and the identified results give the values of 0.145 and 0.124 W/(m K), respectively, clearly revealing obvious an size effect in the thermal conductivity of nanometer-sized skeletons.


Ordered vacancy distribution in 2/1 mullite: a superspace model.
A mullite single crystal with composition Al4.84Si1.16O9.58 (2) exhibiting sharp satellite reflections was investigated by means of X-ray diffraction. For the refinement of a superspace model in the superspace group Pbam(α0½)0ss different scale factors for main and satellite reflections were used in order to describe an ordered mullite structure embedded in a disordered polymorph. The ordered fraction of the mullite sample exhibits a completely ordered vacancy distribution and can be described as a block structure of vacancy blocks (VBs) that alternate with vacancy-free blocks (VFBs) along a and c. The incommensurate nature of mullite originates from a modulation of the block size, which depends on the composition. The displacive modulation is analyzed with respect to the vacancy distribution and a possible Al/Si ordering scheme is derived, although the measurement itself is not sensitive to the Al/Si distribution. An idealized, commensurate approximation for 2/1 mullite is also presented. Comparison of the ordered superspace model with different preceding models reconciles many key investigations of the last decades with partly contradicting conclusions, where mullite was usually treated as either ordered or disordered instead of considering simultaneously different states of order.


Effect of Therapeutic Ultrasound on Calcaneal Tendon Heating and Extensibility in Dogs.
Objective: To (1) characterize the warming pattern of canine calcaneal tendons during and after four different therapeutic ultrasound (US) treatment protocols, and (2) to quantify changes in tarsal flexion immediately after therapeutic US treatment, and following return to baseline temperature. Design: A prospective, crossover, experimental study. Animals: Ten adult hound-type breed dogs. Procedure: Therapeutic ultrasound (3.3 MHz) was applied to one calcaneal tendon of anesthetized dogs using four different settings applied in random fashion (1.5 and 1.0 W/cm2 continuous, and 1.5 and 1.0 W/cm2 pulsed US) while the temperature of the tendon was recorded by a thermistor needle. The contralateral tendon was used to compare extensibility of the treated soft tissues by measuring changes in tarsal joint flexion before, immediately after, and 5-min after continuous US treatment at 1.5 W/cm2 for 10 min. Results: The greatest increase in tendon temperature occurred with continuous US at 1.5 W/cm2. Pulsed US resulted in minimal tendon heating. Most of the increase in tissue temperature occurred within the first 3 min of US application. Tarsal flexion increased significantly following US treatment; however, it returned to near baseline within 5 min after US was discontinued. Conclusion and Clinical Relevance: Continuous US of the calcaneal tendon at 1.5 W/cm2 resulted in the greatest increase in tissue temperature while maintaining a safe range of tissue temperature increase. Tendon heating and heat dissipation were slightly different from what has been reported for muscle. Our results suggest that 3.3 MHz US applied to tendon for >3 min may not provide additional tissue temperature increase. Therapeutic US resulted in increased tarsal flexion, however the change was only transitory. Therefore, stretching exercises should be performed during and immediately after US.


Activation of Rac1 GTPase by nanoparticulate structures in human macrophages.
Inflammatory activation of alveolar macrophages by ambient particles can be facilitated via Toll-like receptors (TLR). The action of TLR agonists and antagonists has been reported to depend on the formation of nanoparticulate structures. Aim of the present study was to identify the signaling pathways induced by nanoparticulate structures in human macrophages, which might be critical for inflammatory cell activation. Studies were performed in primary human alveolar macrophages or in differentiated THP-1 macrophages. Silica nanoparticles were prepared by Stöber synthesis and characterized by dynamic light scattering and scanning electron microscopy. Mycobacterial DNA was isolated from Mycobacterium bovis BCG, and nanoparticle formation was assessed by atomic force microscopy and dynamic light scattering. Actin polymerization was measured by phalloidin-TRITC staining, and cell activation was determined by reverse transcription quantitative PCR analysis, L929 cytotoxicity assay (cytokine induction), and pull-down assays (Rho GTPases). In contrast to immune stimulatory sequence ISS 1018, BCG DNA spontaneously formed nanoparticulate structures and induced actin polymerization as did synthetic silica nanoparticles. Co-incubation with silica nanoparticles amplified the responsiveness of macrophages toward the TLR9 ligand ISS 1018. The activation of Rac1 was induced by silica nanoparticles as well as BCG DNA and is suggested as the critical signaling event inducing both cytoskeleton changes as well as inflammatory cell activation. Nanoparticles can induce signaling pathways, which amplify an inflammatory response in macrophages.


[Microscopic changes in the ligated and resected stumps of the uterine vessels during abdominal hysterectomy (author's transl)].
30 stumps of the uterine vessels during abdominal hysterectomy were excised with the ligature 10 to 20 minutes after the original ligature. Inspite of the ligature the most important mechanism of hemostasis is an occlusive thrombosis in the lumen of the vessels. In this process damage of the wall of the vessel and the endothelium is very important.


In silico Prediction on the PI3K/AKT/mTOR Pathway of the Antiproliferative Effect of O. joconostle in Breast Cancer Models.
The search for new cancer treatments from traditional medicine involves developing studies to understand at the molecular level different cell signaling pathways involved in cancer development. In this work, we present a model of the PI3K/Akt/mTOR pathway, which plays a key role in cell cycle regulation and is related to cell survival, proliferation, and growth in cancer, as well as resistance to antitumor therapies, so finding drugs that act on this pathway is ideal to propose a new adjuvant treatment. The aim of this work was to model, simulate and predict in silico using the Big Data-Cellulat platform the possible targets in the PI3K/Akt/mTOR pathway on which the Opuntia joconostle extract acts, as well as to indicate the concentration range to be used to find the mean lethal dose in in vitro experiments on breast cancer cells. The in silico results show that, in a cancer cell, the activation of JAK and STAT, as well as PI3K and Akt is related to the effect of cell proliferation, angiogenesis, and inhibition of apoptosis, and that the extract of O. joconostle has an antiproliferative effect on breast cancer cells by inhibiting cell proliferation, regulating the cell cycle and inhibiting apoptosis through this signaling pathway. In vitro it was demonstrated that the extract shows an antiproliferative effect, causing the arrest of cells in the G2/M phase of the cell cycle. Therefore, it is concluded that the use of in silico tools is a valuable method to perform virtual experiments and discover new treatments. The use of this type of model supports in vitro experimentation, reducing the costs and number of experiments in the real laboratory.


Predictive analytics in smart healthcare for child mortality prediction using a machine learning approach.
In developing countries, child health and restraining under-five child mortality are one of the fundamental concerns. UNICEF adopted sustainable development goal 3 (SDG3) to reduce the under-five child mortality rate globally to 25 deaths per 1,000 live births. The under-five mortality rate is 69 deaths per 1,000 live child-births in Pakistan as reported by the Demographic and Health Survey (2018). Predictive analytics has the power to transform the healthcare industry, personalizing care for every individual. Pakistan Demographic Health Survey (2017-2018), the publicly available dataset, is used in this study and multiple imputation methods are adopted for the treatment of missing values. The information gain, a feature selection method, ranked the information-rich features and examine their impact on child mortality prediction. The synthetic minority over-sampling method (SMOTE) balanced the training dataset, and four supervised machine learning classifiers have been used, namely the decision tree classifier, random forest classifier, naive Bayes classifier, and extreme gradient boosting classifier. For comparative analysis, accuracy, precision, recall, and F1-score have been used. Eventually, a predictive analytics framework is built that predicts whether the child is alive or dead. The number under-five children in a household, preceding birth interval, family members, mother age, age of mother at first birth, antenatal care visits, breastfeeding, child size at birth, and place of delivery were found to be critical risk factors for child mortality. The random forest classifier performed efficiently and predicted under-five child mortality with accuracy (93.8%), precision (0.964), recall (0.971), and F1-score (0.967). The findings could greatly assist child health intervention programs in decision-making.


INDUCED BIOSYNTHESIS OF ALPHA-AMYLASE BY GROWING CULTURES OF BACILLUS STEAROTHERMOPHILUS.
Welker, N. E. (Western Reserve University, Cleveland, Ohio), and L. Leon Campbell. Induced biosynthesis of alpha-amylase by growing cultures of Bacillus stearothermophilus. J. Bacteriol. 86:1196-1201. 1963.-The maximal differential rate (K) of alpha-amylase synthesis was usually two to three times that of the sucrose control culture, over an inducer concentration range of 5 x 10(-4) to 1 x 10(-3)m. With maltotetraose, higher concentrations decreased the K value, whereas higher concentrations of maltose were needed to obtain maximal K values. Glucose, in concentrations from 10(-5) to 10(-2)m, had no effect on the differential rate of enzyme synthesis. Cultures growing on maltotriose, maltotetraose, maltopentaose, and maltohexaose exhibited the same growth rate (k) and differential rate of alpha-amylase synthesis over a concentration range of 2.92 x 10(-4) to 1.46 x 10(-2)m. Growth of cultures in various concentrations of pure maltose revealed that with concentrations of maltose ranging from 2.92 x 10(-3) to 1.46 x 10(-2)m the K value for alpha-amylase production increased 18-fold. The amount of maltose utilized, during the growth period, at each concentration of maltose, was constant. Diauxic type growth was observed when maltose was used in addition to another carbon source (i.e., glucose, glycerol, fructose, or sucrose). Maltose was not utilized until the other carbon source had been metabolized. Phenyl-, methyl-, and ethyl-alpha-d-glucoside and methyl-beta-d-maltoside were good inducers of alpha-amylase and would not serve as a carbon source in a chemically defined medium supplemented with 0.1% casein hydrolysate. These compounds were therefore gratuitous inducers of alpha-amylase. Isomaltose, panose, butyl-alpha-d-glucoside, and methyl-alpha-d-maltotetraoside were not effective as inducers of alpha-amylase. Fructose had an inhibitory effect on constitutive (41%) and inducible (55%) alpha-amylase formation; glucose had no effect.


Enumerating bone marrow blasts from nonerythroid cellularity improves outcome prediction in myelodysplastic syndromes and permits a better definition of the intermediate risk category of the Revised International Prognostic Scoring System (IPSS-R).
The Revised International Prognostic Scoring System (IPSS-R) has been recognized as the score with the best outcome prediction capability in MDS, but this brought new concerns about the accurate prognostication of patients classified into the intermediate risk category. The correct enumeration of blasts is essential in prognostication of MDS. Recent data evidenced that considering blasts from nonerythroid cellularity (NECs) improves outcome prediction in the context of IPSS and WHO classification. We assessed the percentage of blasts from total nucleated cells (TNCs) and NECs in 3924 MDS patients from the GESMD, 498 of whom were MDS with erythroid predominance (MDS-E). We assessed if calculating IPSS-R by enumerating blasts from NECs improves prognostication of MDS. Twenty-four percent of patients classified into the intermediate category were reclassified into higher-risk categories and showed shorter overall survival (OS) and time to AML evolution than those who remained into the intermediate one. Likewise, a better distribution of patients was observed, since lower-risk patients showed longer survivals than previously whereas higher-risk ones maintained the outcome expected in this poor prognostic group (median OS < 20 months). Furthermore, our approach was particularly useful for detecting patients at risk of dying with AML. Regarding MDS-E, 51% patients classified into the intermediate category were reclassified into higher-risk ones and showed shorter OS and time to AML. In this subgroup of MDS, IPSS-R was capable of splitting our series in five groups with significant differences in OS only when blasts were assessed from NECs. In conclusion, our easy-applicable approach improves prognostic assessment of MDS patients.


Ultrasound-Assisted Extraction, Followed by Gas Chromatography-Mass Spectrometry for the Simultaneous Quantification of Ethinyl Estradiol and Drospirenone in Contraceptive Formulations.
Contraceptive tablets typically contain a combination of two synthetic versions of an estrogen and a progestogen, which work together to inhibit the ovulation process. An accurate and precise quantification of these components is essential for contraceptive producers. In this study, we have developed the first gas chromatography-mass spectrometry (GC-MS) method for the simultaneous quantification of 17α-ethinyl estradiol (EE) and drospirenone (DP) in contraceptive formulations. Under the final working conditions, analytes were extracted from the solid by ultrasound-assisted extraction (15 min) in methanol. The resulting suspension was diluted in ethyl acetate, subjected to centrifugation and, finally, the supernatant was directly injected into the GC-MS system. No derivatization reagents were utilized. To correct for instrumental variations, calibration was performed using the internal standard method, with cholesterol as the internal standard. A good linearity was achieved throughout the calibration range for both EE (3-12 µg mL-1) and DP (300-1200 µg mL-1), with R2 values exceeding 0.99. Trueness, assessed in terms of percentages of recovery, was also found to be satisfactory for both analytes, with recovery rates of 106 ± 8% for EE and 93 ± 9% for DP. Furthermore, intra-day and inter-day precision studies yielded relative standard deviation values below 6% for both analytes. In terms of sensitivity, the instrumental limits of detection were 0.25 µg mL-1 for EE and 6.6 µg mL-1 for DP, and the instrumental limits of quantification 0.82 µg mL-1 for EE and 22 µg mL-1 for DP. The method was successfully applied to the analysis of contraceptive tablets from three different pharmaceutical companies. No differences were observed between the measured and the declared amount of active principle per tablet, demonstrating the applicability of the procedure. In addition, a stability study conducted on both the standards and sample extracts demonstrated that they can be stored at room temperature for a minimum period of seven days.


Reproducibility of postprocessing of quantitative CT perfusion maps.
The purpose of this study was to assess interobserver and intraobserver variability in evaluation of the reproducibility of quantitative data obtained in semiautomated postprocessing of CT perfusion data sets by observers of different levels of skill and experience and in fully automated postprocessing. Twenty CT perfusion data sets were postprocessed by a neuroradiologist using an automated postprocessing program and by five observers (neuroradiology attending, neurology attending, radiology resident, senior and junior CT technologists) who received a brief training session in use of software for semiautomated postprocessing. For assessment of intraobserver variability, each observer repeated postprocessing of 10 CT perfusion data sets. Standard regions of interest were placed on identical locations for each observer's cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) maps of three brain regions: an ischemia-infarct region, normal cortical gray matter, and white matter. The variability in mean quantitative values of CBF, CBV, and MTT was 2.5-9.5% among all observers. Greater variability (20.4%) was introduced with the automated program. High correlation was found among all possible pairings of observers (r = 0.87-0.99). Low correlation was observed between automated postprocessing and postprocessing by all observers. Intraobserver variability in quantitative CT perfusion data ranged from 0.29% to 10.8%. High intraobserver correlation (r = 0.91-0.99) was found for the observers. Quantitative CBF, CBV, and MTT data obtained from postprocessing of CT perfusion data sets are reproducible among observers with varying levels of skill and experience. Observer interaction with the software is an important component for correct identification of user-defined parameters. Establishing a uniform and standard postprocessing technique is essential for maintaining good reproducibility.


Sex-related differences of urethane and sodium valproate effects on Ki-67 expression in urethane-induced lung tumors of mice.
The aim of the present study was to evaluate sex differences in tumorigenesis by assessing the number of Ki-67-positive cells [Ki-67(+)] in urethane-induced mice lung tumors and the effect of sodium valproate (NaVP) in BALB/c mice. Gonad-intact and gonadectomized female and male mice were divided into the following groups: i) Treated with urethane, ii) treated with urethane and NaVP and iii) gonad-intact or gonadectomized control. Urethane (total 50 mg/mouse) was injected intraperitoneally. The NaVP 0.4% solution was administered orally for 6 months. Histologically, lung tumors were divided into adenomas and adenocarcinomas and assessed immunohistochemically using antibodies against Ki-67. The Ki-67(+) was calculated per one mm2 of a tumor. In adenomas, Ki-67(+) in the urethane-treated gonad-intact males was significantly higher than in females (P=0.001) and in castrated males (P<0.01); Ki-67(+) in adenomas of the urethane-treated gonad-intact males was significantly higher than in urethane-NaVP-treated ones (P<0.04). No significant differences were found in analogous female groups. In adenocarcinomas, Ki-67(+) in urethane-treated gonad-intact males was significantly higher than in females and gonadectomized mice of both sexes (P<0.001), and in ovariectomized females was significantly higher than in ovary-intact group (P=0.01). A significantly higher number of Ki-67(+) cells were observed in gonad-intact adenocarcinomas of the urethane-NaVP-treated females compared with the urethane-treated ones (P<0.001). Comparing between urethane-NaVP-treated gonadectomized males and females in adenocarcinomas, determined that Ki-67(+) was significantly lower in females (P=0.005). In adenocarcinomas, Ki-67(+) in urethane-NaVP-treated gonadectomized males and females was significantly lower than in gonad-intact mice of the same sex (P<0.001). In summary, gonadectomy with NaVP treatment decreased Ki-67(+) in adenocarcinomas for mice of both sexes. The results of the present study indicate sex-related differences in mice lung tumorigenesis, and a sex-related effect of NaVP on progression in urethane-induced BALB/c mice lung tumors.


Electrochemical detection of single molecules.
The electrochemical behavior of a single molecule can be observed by trapping a small volume of a dilute solution of the electroactive species between an ultramicroelectrode tip with a diameter of approximately 15 nanometers and a conductive substrate. A scanning electrochemical microscope was used to adjust the tip-substrate distance ( approximately 10 nanometers), and the oxidation of [(trimethylammonio)methyl] ferrocene (Cp(2)FeTMA(+)) to Cp(2)FeTMA(2+) was carried out. The response was stochastic, and anodic current peaks were observed as the molecule moved into and out of the electrode-substrate gap. Similar experiments were performed with a solution containing two redox species, ferrocene carboxylate (Cp(2)FeCOO(-)) and Os(bpy)(3)(2+) (bpy is 2,2'-bipyridyl).


Familial vasculitides: granulomatosis with polyangitis and microscopic polyangitis in two brothers with differing anti-neutrophil cytoplasm antibody specificity.
Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is a group of rare autoimmune diseases. Although the aetiology of AAV is uncertain, it is likely that genetic and environmental factors contribute. We report the unusual case of two brothers presenting with AAV with differing clinical pictures and differing ANCA specificity. There is a recently identified difference in genetic risk factors associated with ANCA specificity, making it surprising that first-degree relatives develop AAV with differing clinical and serological features. Our report illustrates the complex aetiology of AAV and suggests that further research on the interaction of genetic and environmental factors is needed.


[Current status of smoking and passive smoking among aged 45 to 65 years old females in five cities of China].
To investigate the current status of smoking and passive smoking among Chinese females to provide evidence for related strategy development. Data from 32 720 women aged 45-65 years old who participated in the 2008 to 2010 Chinese Multi-center Women Breast Cancer Screening Project, were used to analyze the prevalence rates of smoking/heavy smoking, daily smoking, smoking cessation, successful smoking cessation, passive smoking, etc. A total of 913 females, accounted for 2.8% of all the women in the study, had reported the history of smoking. There were significant differences seen regarding the prevalence rates of smoking in different regions (Beijing, 2.8%; Tianjin, 5.9%; Nanchang, 1.7%; Feicheng, 0.9%; Shenyang, 1.8%). The prevalence rates of current smoking, daily smoking, and heavy smoking were 1.8%, 1.0% and 0.2%, respectively. The prevalence rates of smoking and current smoking increased with age but not the prevalence rates of daily smoking and heavy smoking. Among the smokers, the median initiation age of smoking, the median daily cigarette per day, and median year of smoking were 30 years old, 10 cigarette, and 16 years, respectively. And the prevalence rates of smoking cessation and successful smoking cessation were 19.1% and 8.2%. The prevalence rate of passive smoking was 45.7% (12 730/27 874). After combing the number of smokers and the number of passive smokers, the total exposure rate to tobacco was 41.8% (13 670/32 720). There was a relatively low level of smoking among Chinese females, so as the rate of smoking cessation. However, passive smoking presented a relatively high level among Chinese females.


The elastolytic properties of subtilisin GX from alkalophilic Bacillus sp. strain 6644 provides a means of differentiation from other subtilisins.
A serine protease exhibiting high activity in alkaline media was purified from alkalophilic Bacillus strain GX6644. The enzyme, subtilisin GX, has a molecular weight of 25,000 and a pI greater than 9.5. The protease exhibited high elastolytic activity, but unlike most elastin hydrolyzing enzymes, elastin hydrolysis and binding were not inhibited by 0.1 M NaCl. The elastolytic properties of subtilisin GX together with its specificity toward amino acid phenyl esters functionally distinguishes this protease from other subtilisins. However, comparisons of the available amino-terminal sequence of subtilisin GX with subtilisins from alkalophilic and neutrophilic Bacillus species revealed extensive homology.


A framework and themes for social network intervention.
This paper is concerned with the development and application of social network concepts in clinical practice. A framework of network levels and sets for ordering data and observations is proposed; the phenomenon of truncated networks is considered and two emphases in network intervention (gathering and connecting forms) are proposed to conceptualize network characteristics and practice that follows from such characteristics. A number of current examples of network practice are placed within the framework, and several advantages of utilizing a network perspective as a complement to existing models of family therapy are noted.


Severity of fatigue in people with rheumatoid arthritis, psoriatic arthritis and spondyloarthritis - Results of a cross-sectional study.
Despite improvements in treatment for rheumatoid arthritis (RA), psoriatic arthritis (PsA) and spondyloarthritis (axSpA), several key unmet needs remain, such as fatigue. The objective of this study was to describe the severity of fatigue, disease characteristics and socioeconomic factors in people with RA, PsA and axSpA. The study was designed as a cross-sectional survey collecting patient characteristics such as disease characteristics, socioeconomic factors and fatigue in people with RA, PsA and axSpA in Denmark. Respondents were consecutively recruited for the study over a six-month period in 2018 via routine visits to outpatient rheumatology clinics. Study nurses collected information on diagnosis, current disease-related treatment and disease activity from medical journals. People were invited to complete a questionnaire related to socioeconomic factors and containing the FACIT-Fatigue subscale. Descriptive statistics were analyzed using SAS. We invited 633 people to participate, and 488 (77%) completed the questionnaire. Women constituted 62% of respondents, and the mean age was 53.5 years. Respondents had on average been diagnosed between 11 and 15 years ago. Overall, 79% had no changes to their disease-related treatment during the past year, and the average disease activity as indicated by DAS28 for RA and PsA was 2.48 and 2.36, respectively, and BASDAI for axSpA was 28.40. Fatigue was present in all three diagnoses (mean: 34.31). The mean fatigue score varied from respondents answering that they suffered from no or little fatigue (mean: 45.48) to extreme fatigue (mean: 10.11). Analyses demonstrated that the respondents were not considerably different from nonrespondents, and the study population is considered representative compared with Danish RA and axSpA patients in the Danish National Rheumatology Registry, the DANBIO database. We found that the majority of the study population were fatigued (61%). They had low disease activity and few disease-related treatment changes.


A case of acquired stuttering resulting from left parietal infarction.
Acquired stuttering is uncommon, and is reported anecdotally after head injury and cerebrovascular diseases. Although this entity is described to occur in lesions of dominant hemisphere, it is rarely shown to occur in non-dominant hemispheric and subcortical lesions, too. Therefore we described a case with this rare syndrome and we discussed the possible mechanisms, lesion locations and medical treatment of stuttering according to previous reports. A 61-year-old right-handed man with sudden onset of right hemiparesia and stuttering without aphasia is reported. There was a circumscribed cortical infarction in the left parietal cortex on computerized tomography (CT) and magnetic resonance imaging (MRI) showed a recent infarct. Single photon emission computed tomography (SPECT) images evidenced perfusion abnormalities in the same region. He never stuttered before and has no family history of stuttering. He has been maintained on antiaggregant and paroxetine treatment. A rare presentation of stroke associated with stuttering is reported and the treatment of stuttering with paroxetine is discussed.


Incidentally detected renal angiomyolipoma with tumour thrombus into the inferior vena cava.
A right-renal angiomyolipoma with tumour thrombus into the inferior vena cava was incidentally detected. This is the ninth published case of its type and the second incidental case. Presence of a thrombus does not imply invasive disease, but the tumour then is often bigger than 6 cm and radical surgery is mandatory.


Does biased gene conversion influence polymorphism in the circumsporozoite protein-encoding gene of Plasmodium vivax?
Variation between North Korean and Latin American isolates in the circumsporozoite (CS) protein encoding gene of the human malaria parasite Plasmodium vivax was studied. Polymorphic positions are confined to the central tandemly repeated sequences. Nucleotide substitutions in the tandem repeats produce variants; these substituted positions within the repeat array tend to be conserved between genes. The North Korean CS gene has a short insertion after the repeats encoding a 4-amino acid repeat (Ala-Gly-Gly-Asn) not found in the New World P. vivax genes. This sequence is found both flanking and within the tandem repeats of the CS genes of several strains of the Southeast Asian simian malaria parasite, Plasmodium cynomolgi. The intraspecific conservation of positions of variants within tandem repeat arrays and the interspecific conservation of probably ancestral repeat motifs at the end of these arrays are consistent with the occurrence of nonreciprocal genetic exchanges between the tandem repeats of these genes. However, a striking asymmetry in strand nucleotide composition within the tandem repeats of all CS genes leads us to suggest that biased correction of heteroduplexes formed during recombination plays a role in the evolution of these genes.


Effects of testosterone propionate upon the sexual and aggressive behavior of adult male marmosets (Callithrix jacchus) castrated as neonates.
In New World monkeys of the family Callitrichidae (marmosets and tamarins), females frequently give birth to dizygotic twins. Twins share a placental circulation throughout fetal development and are hemopoietic chimeras. Despite this, there is no masculinization (freemartinism) in females which develop next to a male co-twin. It has been suggested that the organizing effects of testicular androgen upon sexual differentiation of the brain occur mainly during early postnatal development in male callitrichids, rather than in utero. However, this report demonstrates activation of masculine copulatory behavior by testosterone propionate (TP) administered to adult male marmosets (N = 8) which were castrated in infancy (between Days 1-7). Effects of neonatal castration upon aggressive behavior during pair tests with females (high frequencies of aggression) and intact adult males (low frequencies of aggression) were also reversed by TP treatment in adulthood. While early postnatal androgen secretion plays an important role in behavioral development in marmosets, it appears that a substantial degree of neural sexual differentiation occurs in utero in males of this callitrichid species.


Radiomics of Patients with Locally Advanced Rectal Cancer: Effect of Preprocessing on Features Estimation from Computed Tomography Imaging.
The purpose of this study was to investigate the effect of image preprocessing on radiomic features estimation from computed tomography (CT) imaging of locally advanced rectal cancer (LARC). CT images of 20 patients with LARC were used to estimate 105 radiomic features of 7 classes (shape, first-order, GLCM, GLDM, GLRLM, GLSZM, and NGTDM). Radiomic features were estimated for 6 different isotropic resampling voxel sizes, using 10 interpolation algorithms (at fixed bin width) and 6 different bin widths (at fixed interpolation algorithm). The intraclass correlation coefficient (ICC) and the coefficient of variation (CV) were calculated to assess the variability in radiomic features estimation due to preprocessing. A repeated measures correlation analysis was performed to assess any linear correlation between radiomic feature estimate and resampling voxel size or bin width. Reproducibility of radiomic feature estimate, when assessed through ICC analysis, was nominally excellent (ICC > 0.9) for shape features, good (0.75 < ICC ≤ 0.9) or moderate (0.5 < ICC ≤ 0.75) for first-order features, and moderate or poor (0 ≤ ICC ≤ 0.5) for textural features. A number of radiomic features characterized by good or excellent reproducibility in terms of ICC showed however median CV values greater than 15%. For most textural features, a significant (p < 0.05) correlation between their estimate and resampling voxel size or bin width was found. In CT imaging of patients with LARC, the estimate of textural features, as well as of first-order features to a lesser extent, is appreciably biased by preprocessing. Accordingly, this should be taken into account when planning clinical or research studies, as well as when comparing results from different studies and performing multicenter studies.


Renal anaemia: recent developments, innovative approaches and future directions for improved management.
The morbidity, mortality and economic burden of chronic kidney disease (CKD) and associated anaemia are substantial. With the increasing numbers of patients who are likely to be affected in the future, approaches are required to improve anaemia management without increasing the burden on health-care professionals. A multidisciplinary approach to treatment, where early initiation of erythropoiesis-stimulating agents (ESA) is encouraged, may improve patient outcomes. Recent studies also suggest that the early use of iron therapy in patients with CKD not on dialysis may be associated with beneficial effects on haemoglobin levels. Another strategy to reduce the burden on health-care providers is to simplify anaemia management by extending the administration interval of ESA. Indeed, recent studies have explored the efficacy of extending the administration interval of ESA in clinical practice in CKD patients on dialysis and not on dialysis. The ability to maintain haemoglobin levels within guideline ranges at extended administration intervals may improve patient care and reduce the workload of health-care providers.


Deep learning for computational biology.
Technological advances in genomics and imaging have led to an explosion of molecular and cellular profiling data from large numbers of samples. This rapid increase in biological data dimension and acquisition rate is challenging conventional analysis strategies. Modern machine learning methods, such as deep learning, promise to leverage very large data sets for finding hidden structure within them, and for making accurate predictions. In this review, we discuss applications of this new breed of analysis approaches in regulatory genomics and cellular imaging. We provide background of what deep learning is, and the settings in which it can be successfully applied to derive biological insights. In addition to presenting specific applications and providing tips for practical use, we also highlight possible pitfalls and limitations to guide computational biologists when and how to make the most use of this new technology.


Infant feeding styles: barriers and opportunities for good nutrition in India.
India has the lion's share of malnourished children in the world. Poverty and social exclusion contribute to this rate of malnutrition, but care practices also play a role. Breastfeeding is rarely exclusive, sanitation tends to be limited, complementary feeding often begins late, and the quantities are small. In the past, government programs have focused on the supply of food rather than caring practices. A research agenda will include both operational research on the nutrition programs, and formative and intervention research to improve caring practices, particularly those around infant and young child feeding.


A comparison of the efficacy of metronidazole vaginal gel and Myrtus (Myrtus communis) extract combination and metronidazole vaginal gel alone in the treatment of recurrent bacterial vaginosis.
Due to the high incidence of bacterial vaginosis (BV) and its resistance to chemical medications and considering the anti-bacterial and anti-fungal effects of Myrtus communis, the present study aimed to compare the therapeutic effects of the vaginal gel of M. communis 2% (in metronidazole base) with metronidazole vaginal gel 0.75% alone on BV. This research was a randomized controlled clinical trial conducted on 80 women of 18-40 years old with BV. Patients were divided into two groups of 40 women. Diagnostic criteria were Amsel's criteria and Gram staining. The first group received vaginal gel of metronidazole plus M. communis 2% and the second group received metronidazole vaginal gel alone for five consecutive nights. Therapeutic effects and Amsel's criteria were assessed after one week. Finally, the data were analyzed by SPSS 16 using t-test and Chi square tests. There was a significant difference in the therapeutic response between the two groups. The results demonstrated that the combination of metronidazole and M. communis had a higher efficiency (p<0.05). The patients receiving M. communis in metronidazole gel base did not experience any recurrent BV, but 30% of patients taking metronidazole alone faced recurrent BV after three weeks of follow up. Findings of the study suggested that adding M. communis extract to metronidazole increases the efficiency of BV treatment.


UV resonance Raman study of TrpZip2 and related peptides: π-π interactions of tryptophan.
Aromatic interactions are important stabilizing forces in proteins but are difficult to detect in the absence of high-resolution structures. Ultraviolet resonance Raman spectroscopy is used to probe the vibrational signatures of aromatic interactions in TrpZip2, a synthetic β-hairpin peptide that is stabilized by edge-to-face and face-to-face tryptophan π-π interactions. The vibrational markers of isolated edge-to-face π-π interactions are investigated in the related β-hairpin peptide W2W11. The bands that comprise the Fermi doublet exhibit systematic shifts in position and intensity for TrpZip2 and W2W11 relative to the model peptide, W2W9, which does not form aromatic interactions. Additionally, hypochromism of the Bb absorption band of tryptophan in TrpZip2 leads to a decrease in the relative Raman cross-sections of Bb-coupled Raman bands. These results reveal spectral markers for stabilizing tryptophan π-π interactions and indicate that ultraviolet resonance Raman may be an important tool for the characterization of these biological forces.


Through the magnifying glass: Underlying literacy deficits and remediation potential in childhood apraxia of speech.
Interactions among psycholinguistic deficits and literacy difficulties in childhood apraxia of speech (CAS) have been inadequately studied. Comparisons with other disorders (Specific Language Impairment (SLI) and phonological dyslexia) and the possibility of reading remediation in CAS warrant further research. This case study describes the speech, language, cognitive, and literacy deficits and therapy gains in a girl aged 11;6 with severe CAS and borderline IQ. A comprehensive assessment of literacy-related cognitive skills, including phonological memory and working memory capacity, language, speech production and reading skills, was administered. Treatment from 6;0 to 11;6 targeted speech sounds, oral sequencing, phonological awareness (PA), speech-print connections, syllabic structure, and real and non-word decoding. Phonological memory was similar to that of children with SLI, but working memory was significantly worse. Unlike children with phonological dyslexia, our participant demonstrated relative strength in letter-sound correspondence rules. Despite deficits, she made progress in literacy with intensive long-term intervention. Results suggest that the underlying cognitive-linguistic profile of children with CAS may differ from those of children with SLI or dyslexia. Our results also show that long-term intensive intervention promotes acquisition of adequate literacy skills even in a child with a severe motor speech disorder and borderline IQ.


An Approach to Developing Local Climate Change Environmental Public Health Indicators in a Rural District.
Climate change represents a significant and growing threat to population health. Rural areas face unique challenges, such as high rates of vulnerable populations; economic uncertainty due to their reliance on industries that are vulnerable to climate change; less resilient infrastructure; and lower levels of access to community and emergency services than urban areas. This article fills a gap in public health practice by developing climate and health environmental public health indicators for a local public health department in a rural area. We adapted the National Environmental Public Health Tracking Network's framework for climate and health indicators to a seven-county health department in Western Kentucky. Using a three-step review process, we identified primary climate-related environmental public health hazards for the region (extreme heat, drought, and flooding) and a suite of related exposure, health outcome, population vulnerability, and environmental vulnerability indicators. Indicators that performed more poorly at the county level than at the state and national level were defined as "high vulnerability." Six to eight high vulnerability indicators were identified for each county. The local health department plans to use the results to enhance three key areas of existing services: epidemiology, public health preparedness, and community health assessment.


Chip fractures of the mandibular condyle.
Four patients suffered from trauma of the temporomandibular (TM) joints. They were examined by routine x-ray procedures. The x-ray films failed to demonstrate a chip fracture of the head of the mandibular condyle. A coronal computed tomographic (CT) view established the fracture shortly after the trauma in three patients. These patients improved clinically after physiotherapy. The fourth patient was retrospectively diagnosed as having a chip fracture of the mandibular head. She underwent CT scan 10 months posttrauma , and ankylosis of the TM joint was established. The mechanism and the clinical symptoms of this injury, which have not been previously described, are reported in this article.


Dengue virus transmission from live donor liver graft.
Arboviral transmission through transplanted organs is rare. We report a highly probable case of dengue viral transmission during live donor liver transplantation. Fever with severe thrombocytopenia was observed in the donor and recipient within 6 and 9 days after transplantation, respectively. Dengue diagnosis was confirmed by testing blood and explant tissue from the donor and recipient using dengue-specific NAT (nucleic acid testing) and serology. Serology indicated the donor had secondary dengue infection that ran a mild course. However, the dengue illness in the recipient was severe and deteriorated rapidly, eventually proving fatal. The recipient's explant liver tissue tested negative for viral RNA indicative of a pretransplant naïve status. The prM-Envelope gene sequence analysis of the donor and recipient viral RNA identified a similar serotype (DENV1) with almost 100% sequence identity in the envelope region. Molecular phylogenetic analysis of donor and recipient viral envelope sequences with regional and local dengue strains further confirmed their molecular similarity, suggesting a probable donor-to-recipient transmission via organ transplantation. Screening of living donors for dengue virus may be considered in endemic regions.


Body composition and susceptibility to type 2 diabetes: an evolutionary perspective.
Type 2 diabetes is rapidly increasing in prevalence worldwide, in concert with epidemics of obesity and sedentary behavior that are themselves tracking economic development. Within this broad pattern, susceptibility to diabetes varies substantially in association with ethnicity and nutritional exposures through the life-course. An evolutionary perspective may help understand why humans are so prone to this condition in modern environments, and why this risk is unequally distributed. A simple conceptual model treats diabetes risk as the function of two interacting traits, namely 'metabolic capacity' which promotes glucose homeostasis, and 'metabolic load' which challenges glucose homoeostasis. This conceptual model helps understand how long-term and more recent trends in body composition can be considered to have shaped variability in diabetes risk. Hominin evolution appears to have continued a broader trend evident in primates, towards lower levels of muscularity. In addition, hominins developed higher levels of body fatness, especially in females in relative terms. These traits most likely evolved as part of a broader reorganization of human life history traits in response to growing levels of ecological instability, enabling both survival during tough periods and reproduction during bountiful periods. Since the emergence of Homo sapiens, populations have diverged in body composition in association with geographical setting and local ecological stresses. These long-term trends in both metabolic capacity and adiposity help explain the overall susceptibility of humans to diabetes in ways that are similar to, and exacerbated by, the effects of nutritional exposures during the life-course.


Pilot study of the air-Q intubating laryngeal airway in clinical use.
The air-Q Intubating Laryngeal Airway (ILA) is a newly introduced extraglottic airway device. In this pilot study, we evaluated its use as a routine airway device during positive pressure ventilation. Ease of endotracheal intubation through the device was also assessed. Fifty-nine ASA I and II patients undergoing elective surgery received an air-Q ILA and an endotracheal tube where indicated. Insertion, ventilation and intubation characteristics were noted, as well as throat morbidity and occurrence of adverse events. An air-Q ILA was successfully inserted in 100% of patients. Mean leak pressure was 19 +/- 5 cmH2O. Endotracheal intubation was indicated in 19 patients and successful in 58% on the first attempt and 74% in total. Ten percent of the study patients were noted to have dysphagia. One patient was diagnosed with bilateral lingual nerve injury but made a complete recovery in four weeks. The air-Q ILA is an adequate extraglottic airway device in terms of insertion and ventilation. However the proposed advantage of ease of endotracheal intubation requires further investigation.


Emergence and maintenance of menopause in humans: A game theory model.
Menopause, the permanent cessation of ovulation, occurs in women well before the end of their expected life span. Several adaptive hypotheses have been proposed to solve this evolutionary puzzle, each based on a possible fitness benefit derived from an early reproductive senescence, but no consensus has emerged. The construction of a game theory model allowed us to jointly study the main adaptive hypotheses in emergence and maintenance of menopause. Four classical hypotheses on the benefits of menopause were considered (decreased maternal mortality, increased grandmothering, decreased conflict over reproductive resources between older and younger females, and changes in their relatedness) plus a fifth one derived from a possible pleiotropic trade-off. Interestingly, the conditions for the emergence of menopause are more restrictive than those for its maintenance due to the social and familial changes induced by the occurrence of non-reproductive older women.


Expanding the feruloyl esterase gene family of Aspergillus niger by characterization of a feruloyl esterase, FaeC.
A feruloyl esterase (FAE) from Aspergillus niger N402, FaeC was heterologously produced in Pichia pastoris X-33 in a yield of 10mg/L. FaeC was most active at pH 7.0 and 50°C, and showed broad substrate specificity and catalyzed the hydrolysis of methyl 3,4-dimethoxycinnamate, ethyl ferulate, methyl ferulate, methyl p-coumarate, ethyl coumarate, methyl sinapate, and methyl caffeate. The enzyme released both ferulic acid and p-coumaric acid from wheat arabinoxylan and sugar beet pectin (up to 3mg/g polysaccharide), and acted synergistically with a commercial xylanase increasing the release of ferulic acid up to six-fold. The expression of faeC increased over time in the presence of feruloylated polysaccharides. Cinnamic, syringic, caffeic, vanillic and ferulic acid induced the expression of faeC. Overall expression of faeC was very low in all tested conditions, compared to two other A. niger FAE encoding genes, faeA and faeB. Our data showed that the fae genes responded differently towards the feruloylated polysaccharides and tested monomeric phenolic compounds suggesting that the corresponding FAE isoenzymes may target different substrates in a complementary manner. This may increase the efficiency of the degradation of diverse plant biomass.


Ambient pressure thermal desorption ionization mass spectrometry for the analysis of substances of forensic interest.
The large backlog of forensic samples needing chemical analysis requires new tools with high specificity, throughput, and reliability. Mass spectrometric techniques have the specificity and reliability necessary for identification, but often require sample preparation before analysis. The growth of ambient pressure ionization techniques has the capability to reduce the need for lengthy preparation. This report presents one possible technique, ambient pressure thermal desorption ionization mass spectrometry, which could prove to be useful to the forensic science community. Example mass spectra for several explosive compounds and illicit drugs obtained from liquid and bulk samples with almost no sample preparation are presented. The use of the technique for quantitative analysis is also addressed.


Imaging of Conductive Hearing Loss With a Normal Tympanic Membrane.
This article presents an approach to imaging conductive hearing loss in patients with normal tympanic membranes and discusses entities that should be checked as the radiologist evaluates this potentially complicated issue. Conductive hearing loss in a patient with a normal tympanic membrane is a complicated condition that requires a careful imaging approach. Imaging should focus on otosclerosis, and possible mimics and potential surgical considerations should be evaluated. The radiologist should examine the ossicular chain and the round window and keep in mind that a defect in the superior semicircular canal can disturb the hydraulic integrity of the labyrinth.


Host-sensitized luminescence properties in CaNb2O6:Ln(3+) (Ln(3+) = Eu(3+)/Tb(3+)/Dy(3+)/Sm(3+)) phosphors with abundant colors.
A series of Ln(3+) (Ln(3+) = Eu(3+)/Tb(3+)/Dy(3+)/Sm(3+)) ion doped CaNb2O6 (CNO) phosphors have been prepared via the conventional high-temperature solid-state reaction route. The X-ray diffraction (XRD) and structure refinement, diffuse reflection, photoluminescence (PL), and fluorescent decay curves were used to characterize the as-prepared samples. Under UV radiation, the CNO host present a broad emission band from about 355 to 605 nm centered around 460 nm originating from the NbO6 octahedral groups, which has spectral overlaps with the excitation of f-f transitions of Eu(3+)/Tb(3+)/Dy(3+)/Sm(3+) in CNO:Eu(3+)/Tb(3+)/Dy(3+)/Sm(3+) samples. They show both host emission and respective emission lines derived from the characteristic f-f transitions of activators, which present different emission colors owing to the energy transfer from the NbO6 group in the host to Eu(3+)/Tb(3+)/Dy(3+)/Sm(3+) with increasing activator concentrations. The decreases of decay lifetimes of host emissions in CNO:Eu(3+)/Tb(3+)/Dy(3+)/Sm(3+) demonstrate the energy transfer from the hosts to Eu(3+)/Tb(3+)/Dy(3+)/Sm(3+). The energy transfer mechanisms in CNO:Eu(3+)/Tb(3+)/Dy(3+) phosphors have been determined to be a resonant type via dipole-dipole mechanisms. For CNO:Sm(3+), the metal-metal charge transfer transition (MMCT) might contribute to the different variations of decay lifetimes and emission intensity from CNO:Eu(3+)/Tb(3+)/Dy(3+) samples. The best quantum efficiency is 71.2% for CNO:0.01/0.02Dy(3+). The PL properties of as-prepared materials indicate the promising application in UV-pumped white-emitting lighting diodes field.


Lichen sclerosus. A review.
Lichen sclerosus is a chronic inflammatory skin condition that can cause substantial physical and psychological morbidity. It most commonly affects women in the anogenital region, but may affect any area of skin in either sex at any age. Not only does it cause itching and soreness, but also urinary and sexual problems. There is an increased risk of developing squamous cell carcinoma in the genital area in both female and male sufferers, thus long term follow-up may be justified. The aetiology of Lichen sclerosus is unknown but genetic factors play a role, and chronic infection had been postulated but not proven. The association with autoimmune disease is also well recognized. The mainstay of treatment for genital lichen sclerosus is potent topical steroid. Surgery may be required only to relieve the effect of scarring. Current research to understand the pathogenesis of disease may allow us to target specific intervention in the future.


Small polarons in dry DNA.
We report ab initio calculations for positively charged fragments of dry poly(dC)-poly(dG) DNA, with up to 4 C-G pairs. We find a strong hole-lattice coupling and clear evidence for the formation of small polarons. The largest geometry distortions occur in only one or two base pairs. They involve the stretching of weak bonds within each base pair, increasing the distance of positive hydrogens, and decreasing that of negative oxygens, to the region in which the hole localizes. We obtain an energy of approximately 0.30 eV for the polaron formation, nearly independent of the chain size. From it, we can estimate an activation energy for polaron hopping of approximately 0.15 eV, consistent with the available experimental value.


[The relationship between blood alcohol level and head injury].
Alcoholic intoxication and a traumatic intracranial lesion have many features in common. It is important for a doctor not to make an incorrect diagnosis between these two conditions, but it is difficult in some cases. The effect of alcohol on the conscious level may complicate the assessment of patients and make it more difficult to recognize the development of complications such as intracranial hematoma. The most immediate and correct diagnosis can be obtained by estimating the amount of alcohol in a patient's blood although it is often difficult in the usual emergency departments in Japan. To try to throw some light on this question, we decided to attempt both clinical and laboratory diagnosis of alcohol ingestion. In 68 adult patients who had head injuries with conscious disturbance admitted to our ward at night, alcohol levels in their blood were estimated by gas chromatography, during the past 24 months. At the same time clinical examinations for the diagnosis of drunkenness were made: on admission, it was recorded whether all patients had white or red conjunctiva, whether speech was clear or slurred, whether there was a distinctive smell on their breath, and whether coordination was good or poor. Of 68 patients (63 male, 5 female), 7 had no alcohol in their blood and 61 had positive alcohol results. The mean blood alcohol level was 233 +/- 130 mg/dl. Clinical diagnosis of alcohol ingestion; The amount of alcohol in the blood correlated highly with the strength of the smell on their breath and of conjunctival injection (p less than 0.001), on the other hand, did not correlate with the speech disturbance, skillfullness of coordination and level of consciousness.(ABSTRACT TRUNCATED AT 250 WORDS)


High levels of incidental physical activity are positively associated with cognition and EEG activity in aging.
High levels of physical activity seem to positively influence health and cognition across the lifespan. Several studies have found that aerobic exercise enhances cognition and likely prevents cognitive decline in the elderly. Nevertheless, the association of incidental physical activity (IPA) with health and cognition during aging has not been studied. Thus, the aim of this study was to evaluate the association of IPA level with cognitive functions and resting electroencephalogram (EEG) in healthy old participants. Participants (n = 97) with normal scores on psychometric and neuropsychological tests and normal values in blood analyses were included. A cluster analysis based on the scores of the Yale Physical Activity Scale (YPAS) allowed the formation of two groups: active, with high levels of IPA, and passive, with low levels of IPA. Eyes-closed resting EEG was recorded from the participants; the fast Fourier transform was used offline to calculate absolute power (AP), relative power (RP), and mean frequency (MF) measures. There were no differences in socioeconomic status, cognitive reserve, general cognitive status, or lipid and TSH profiles between the groups. The results of cognitive tests revealed significant differences in the performance variables of the WAIS scores (p = .015), with advantages for the active group. The resting EEG exhibited significantly slower activity involving the frontal, central, and temporal regions in the passive group (p < .05). Specifically, higher delta RP (F7, T3), lower delta MF (F4, C4, T4, T6, Fz, Cz), higher theta AP (C4), higher theta RP (F4, C4, T3, Fz), lower alpha AP (F3, F7, T3), lower alpha RP (F7), and lower total MF (F3, F7, T3, T5, Fz) were found. Altogether, these results suggest that IPA induces a neuroprotective effect, which is reflected both in behavioral and electrophysiological variables during aging.


Effect of soybean protein on serological response, non-specific defense mechanisms, growth, and protein utilization in rainbow trout.
Rainbow trout (Oncorhynchus mykiss) were fed chemically and immunologically defined diets containing either a low-temperature fish meal or soybean preparations containing high (SBM) or low levels of the globular antigenic proteins glycinin (G) and beta-conglycinin (BC) for 26 weeks. While trout fed both soybean preparations exhibited poorer growth than those fed fish meal, those fed the soya diet with high levels of G and BC showed the most significant growth diminution, elevated feed conversion and impaired utilization of dietary protein. Changes in intestinal morphology were also observed in fish fed the SBM diet, coinciding with the inferior nutritional performance. Several serologic and non-specific immune defense mechanisms were monitored. Cell counts showed increased leukocyte cell numbers as well as increased concentrations of plasma protein and immunoglobulin in the soya-fed fish. Increased neutrophil, monocyte and macrophage activity, as assessed by several oxidative radical production and phagocytic index assays, were higher in the soya-fed fish, possibly indicating an inflammatory or hypersensitivity response. The results of this study suggest that antigenic soya protein affects non-specific defense mechanisms, growth performance, and protein utilization in rainbow trout. Furthermore, it would appear that dietary sensitivity can be overcome by process removal of this immunologically characterized antigen in soybean protein. Serological and immunological assessments appear to be very useful criteria for evaluating various protein sources for fishes.


Fusobacterium necrophorum infection associated with portal vein thrombosis.
This report describes a patient without obvious upper respiratory tract or gastrointestinal infection who developed portal vein thrombosis secondary to Fusobacterium necrophorum septicaemia. The patient responded well to systemic antibiotic therapy. The implications of F. necrophorum infection caudal to the head are discussed.


[Tyrosine kinase inhibitor therapy discontinuation for chronic myelogenous leukemia to achieve clinical cure: current status and future perspectives].
Tyrosine kinase inhibitors (TKIs) markedly improve the prognosis of patients with chronic myelogenous leukemia (CML) by potentially helping to achieve a deep molecular response (DMR). In many clinical trials, beginning with the French Stop Imatinib (STIM1) trial, approximately 40%-60% patients with chronic CML who sustained a long DMR could discontinue TKI therapy and achieve long-term treatment-free remission (TFR). These trials have proposed many predictive factors for successful TKI therapy discontinuation, including deeper molecular response, longer duration of DMR and lack of TKI resistance prior to the discontinuation, and greater numbers of natural killer (NK) cells during the discontinuation. However, further investigations are necessary because only 20%-30% patients with chronic CML could achieve TFR. Recent studies have suggested that the recovery and reconstitution of immune effector cells against CML, including NK cells, and the elimination of CML cells using aberrant clones that are resistant to TKI are crucial for successfully achieving DMR and subsequent TFR. CML stem cells are not sensitive to TKI and could potentially interfere with TFR. Therefore, therapies targeting CML stem cells are being investigated, and the results are highly anticipated.


Distinct DNA methylomes of human placentas between pre-eclampsia and gestational diabetes mellitus.
The placenta acts not only as a conduit of nutrient and waste exchange between mother and developing fetus but also functions as a regulator of the intrauterine environment. Pre-eclampsia (PE) and gestational diabetes mellitus (GDM) are leading causes of complications during pregnancy. Pathophysiologies show that they are associated with one another. Epigenetics provides a link between environmental factors that have previously been linked to poor pregnancy outcomes and fetal programming. The present study investigated genome-wide DNA methylation changes in PE and GDM compared with control subjects through DNA methylation microarray. We found that the methylation patterns of placentas from PE and GDM women were similar; 64.4% of the annotated genes with differential methylation presented concordant changes between PE and GDM patients. Significantly, the same functional processes were affected by PE and GDM, with cell adhesion and cell differentiation being the most populated clusters and including genes related to carbohydrate metabolism and lipid metabolism. Our work showed that of DNA methylation patterns in human placentas are reliably and significantly associated with PE and GDM. DNA methylation status in the human placenta can function as a marker for the intrauterine environment and potentially play a functional role in PE and GDM development.


The risk of minor depression before age 65: results from a community survey.
Data from a general population survey of psychiatric disorder in Camberwell were used to calculate the risk of a CATEGO-defined depressive episode before the age of 65, using a modification of Strömgren's method. Current depression was defined as cases within the relevant categories of the CATEGO program and at threshold level or above on the Index of Definition (Wing et al. 1978). A past history of depression was elicited using key symptoms such as persistent tearfulness and depressed mood, already enquired after in the course of the PSE, to identify potential episodes, followed by questions to determine accessory symptoms, duration, and degree of social impairment. Clinical judgement was then used to decide whether the disturbance constituted a significant depressive episode. Risk under one set of assumptions was 46% for men and 72% for women. Using another method based on (untenably) conservative assumptions, it became 16% and 30% respectively. The status and implications of these high values are discussed, particularly for genetic studies.


Interleukin 2 activates a receptor-associated protein kinase.
The interleukin 2 (IL 2) receptor complex has been shown to consist of at least two IL 2 binding molecules, one of 55 to 57 kd (gp57Tac) and one of 75 to 78 kd apparent m.w. The data presented here indicate that a protein of m.w. 78,000 (pp78) co-immunoprecipitates with gp57Tac when a monoclonal antibody against gp57Tac is used. The 78 kd molecule is phosphorylated in vitro within the immune complex only in the presence of exogenously added IL 2, whereas the 57 kd molecule is phosphorylated equally in the presence or absence of IL 2. Phosphorylation in vitro of pp78 was demonstrated in extracts of human peripheral blood T cells (PBL-T) and the human T cell line Jurkat, but not in extracts of the human macrophage line U937 or the murine T cell line 2.8.2. Metabolic phosphorylation in intact cells reflects results observed in vitro; both pp78 and gp57Tac are phosphorylated in PBL-T and Jurkat, but not in U937. These data demonstrate that the IL 2 receptor complex contains an IL 2 responsive protein kinase activity and may signal the cell through a phosphorylation event.


Cloning and characterization of five cDNAs encoding peritrophin-A domains from the cat flea, Ctenocephalides felis.
Five cDNAs encoding peritrophin-A domains were identified as expressed sequence tags (ESTs) from flea hindgut and Malpighian tubule (HMT) cDNA libraries. The full-length cDNAs for each were subsequently isolated and sequenced. Three of the encoded proteins were similar to published peritrophin sequences, and thus were called "peritrophin-like", or PL1, PL2, and PL3. The other two sequences had similarity to both mucin and peritrophin proteins, and were called "mucin/peritrophin-like", or MPL1 and MPL2. The predicted protein sequences encoded by these cDNAs all contained a signal sequence and one or more peritrophin-A domains, which have been shown in other proteins to bind chitin. Aside from the peritrophin-A domains, the sequences shared little or no similarity to each other or to other proteins in the GenBank non-redundant database. The predicted protein sequences were variable in size, ranging in length from 81 to 453 amino acids. The two MPL proteins contained putative N-linked and O-linked glycosylation sites, including a region of seven nearly perfect tandem repeats in the MPL1 protein sequence. Northern blot analysis of different flea lifestages and fed adult timepoints showed distinct mRNA expression patterns for each gene, although all five transcripts were primarily or exclusively detected in the HMT tissues in adults. The PL1 protein was detected by immuno-blot in soluble and insoluble protein extracts from unfed and fed adult fleas. The PL1 protein from the insoluble fractions appeared to be approximately 1 kDa larger than the PL1 protein from the soluble protein fractions. Immunohistochemistry performed on flea thin sections revealed that the PL1 protein was detected in the Malpighian tubules, hindgut, rectum, and trachea. Unpurified native PL1 protein from both soluble and insoluble protein fractions was tested for chitin-binding activity but did not bind to chitin under the conditions tested. These results show that the flea peritrophin-like proteins may have biological functions that are distinct from the peritrophic matrix and from the binding of chitin.


Hybrid neural network approaches to predict drug-target binding affinity for drug repurposing: screening for potential leads for Alzheimer's disease.
Alzheimer's disease (AD) is a neurodegenerative disease that primarily affects elderly individuals. Recent studies have found that sigma-1 receptor (S1R) agonists can maintain endoplasmic reticulum stress homeostasis, reduce neuronal apoptosis, and enhance mitochondrial function and autophagy, making S1R a target for AD therapy. Traditional experimental methods are costly and inefficient, and rapid and accurate prediction methods need to be developed, while drug repurposing provides new ways and options for AD treatment. In this paper, we propose HNNDTA, a hybrid neural network for drug-target affinity (DTA) prediction, to facilitate drug repurposing for AD treatment. The study combines protein-protein interaction (PPI) network analysis, the HNNDTA model, and molecular docking to identify potential leads for AD. The HNNDTA model was constructed using 13 drug encoding networks and 9 target encoding networks with 2506 FDA-approved drugs as the candidate drug library for S1R and related proteins. Seven potential drugs were identified using network pharmacology and DTA prediction results of the HNNDTA model. Molecular docking simulations were further performed using the AutoDock Vina tool to screen haloperidol and bromperidol as lead compounds for AD treatment. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) evaluation results indicated that both compounds had good pharmacokinetic properties and were virtually non-toxic. The study proposes a new approach to computer-aided drug design that is faster and more economical, and can improve hit rates for new drug compounds. The results of this study provide new lead compounds for AD treatment, which may be effective due to their multi-target action. HNNDTA is freely available at https://github.com/lizhj39/HNNDTA.


Using organizational change strategies to guide peer support technician implementation in the Veterans Administration.
The Veterans Administration (VA) mental health system is in the process of hiring "Peer Support Technicians" or PSTs-individuals in recovery from serious mental illnesses hired as clinical team members. The purpose of this article is to demonstrate an implementation process that has potential to improve the deployment of the Peer Support Technicians to existing clinical teams within the VA. As part of a larger randomized trial called PEers Enhancing Recovery (PEER), research staff collaboratively planned the deployment of PSTs with three case management teams serving those with serious mental illnesses. Clinical staff received significant opportunity to participate in defining the PST role. PEER staff took extensive notes during planning meetings about the discussions held and decisions made about the PST role. PEER and clinical staff discussed and came to a consensus on several elements that comprise the PST job including goals for employing PSTs, desired characteristics of PSTs, job duties, training to be provided to PSTs, PST access to medical records, supervision, boundaries, confidentiality, how PSTs are to discuss their mental illness with veterans, and a sick leave policy. It is critical to solicit and use input from team providers and leaders when establishing PST services. This approach using input and solicitation can be a model to implement a wide range of clinical interventions in which existing providers and teams will be asked to do something new.


Identification of an alternatively spliced variant of Ca2+-promoted Ras inactivator as a possible regulator of RANKL shedding.
The receptor activator of NF-kappaB ligand (RANKL), a critical regulator of osteoclastogenesis, is synthesized as a membrane-anchored protein and cleaved into a soluble form by ectodomain shedding. We developed an assay system to identify molecules regulating the RANKL shedding. Using this system, we found that a splice variant of Ca2+-promoted Ras inactivator (CAPRI), deltaCAPRI, which is expressed in primary osteoblasts, promoted the RANKL shedding. The wild type CAPRI is a member of the Ras GTPase-activating protein (GAP) family and suppresses Ca2+-dependent Ras activation, whereas deltaCAPRI, which lacks one exon in the GAP-related domain, activated the Ras pathway. Overexpression of deltaCAPRI or a constitutive active form of Ras up-regulated the expression level of matrix-metalloproteinase 14 (MMP14), which directly cleaves the ectodomain of RANKL, whereas Erk activation by expressing the constitutive active Mek1 did not affect the MMP14 expression or RANKL shedding. These results suggest that deltaCAPRI is a possible regulator of RANKL shedding by modulating MMP14 expression through Ras signaling cascades other than the Erk pathway.


Hypertension control with daily dialysis.
Hypertension is present in 60-90% of patients on maintenance hemodialysis (HD) and it is an important cause of cardiovascular (CV) mortality and morbidity. Frequent and prolonged HD has been uniformly shown to control hypertension in end-stage renal disease (ESRD) patients more effectively than conventional HD. The etiology of hypertension is predominantly volume dependent, but in a subset of patients increased renin, sympathetic overactivity, and endothelial dysfunction may play a role. Intradialytic hypotension precludes attainment of dry weight and hence optimal control of hypertension in conventional HD is challenging. Frequent and prolonged dialysis with gentle and persistent ultrafiltration allows time for refilling of the intravascular compartment and permits normalization of extracellular volume. It is also possible that intensive dialysis enables removal of pressor molecules and improves endothelial function. Improved blood pressure control translates into regression of left ventricular hypertrophy in patients on daily HD. Thus prolonged and frequent dialysis permits better control of hypertension via volume and volume-independent mechanisms and also improves cardiac geometry.


Spiral laminar flow in arteries?
Spiral blood-flow patterns in infrainguinal blood-vessels were observed at angioscopy in 54 patients who underwent peripheral vascular reconstruction; the endoluminal surface had spiral folds in 51 of 75 arteries examined. Spiral flow patterns, congruous with inherent endoluminal anatomical features, might more accurately represent blood-flow in infrainguinal arteries than current models of laminar flow.


The Alonissos Study: Cross-Sectional Study of the Healthcare Access and User Satisfaction in the Community of a Non-Profit-Line Greek Island.
Healthcare access and a high quality of the provided services to healthcare users are fundamental human rights according to the Alma Ata Declaration of 1978. Although 45 years have passed since then, health inequalities still exist, not only among countries but also within populations of the same country. For example, several small Greek islands have only a small Primary Healthcare Center in order to provide healthcare services to the insular population. In the current study, we investigated the level of self-reported overall, dental and mental health status and the level of satisfaction regarding the access to and the quality of the healthcare services provided by the Primary Healthcare center of Alonissos, along with registering the requirements for transportation to the mainland in order to receive such services. In this questionnaire-based cross-sectional study, 235 inhabitants of the remote Greek island of Alonissos that accounts for nearly 9% of the population participated (115 males and 120 females). The self-reported overall health status was reported to be moderate to very poor at a percentage of 31.49%, and the results were similar for dental and self-reported mental health status. Although nearly 60% of the participants reported very good/good quality of the healthcare provision, only 37.45% reported that the access to healthcare was very good/good, while around 94% had at least one visit to the mainland in order to receive proper healthcare services. Strategies for improving access to healthcare services need to be placed in remote Greek islands like Alonissos.


Reactive lymphoid hyperplasia of the liver mimicking hepatocellular carcinoma: a case report.
Reactive lymphoid hyperplasia (RLH) of the liver is an extremely rare benign lesion, which is often misdiagnosed as a malignant liver tumour. We present the case of a 69-year-old man with an incidental liver tumour revealed on the ultrasonography of the kidney-urinary bladder system for benign prostatic hyperplasia. Hepatocyte-specific contrast (gadoxetate disodium) magnetic resonance imaging revealed a round 6-mm lesion, which was hypointense on T1-weighted images, slightly hyperintense on T2-weighted images and highly intense on diffusion-weighted images. Other findings included arterial hyperintensity, venous and delayed hypointensity and a defect in liver segment 6. The patient was diagnosed with hepatocellular carcinoma; laparoscopic partial hepatectomy was performed. Intraoperatively, a 7-mm greyish white solid nodule was observed. In conclusion, it may be difficult to distinguish RLH from other malignant liver tumours. However, it should be considered as a differential diagnosis for small liver lesions in young, female patients without liver cirrhosis.


Simulation-Guided 3D Nanomanufacturing via Focused Electron Beam Induced Deposition.
Focused electron beam induced deposition (FEBID) is one of the few techniques that enables direct-write synthesis of free-standing 3D nanostructures. While the fabrication of simple architectures such as vertical or curving nanowires has been achieved by simple trial and error, processing complex 3D structures is not tractable with this approach. In part, this is due to the dynamic interplay between electron-solid interactions and the transient spatial distribution of absorbed precursor molecules on the solid surface. Here, we demonstrate the ability to controllably deposit 3D lattice structures at the micro/nanoscale, which have received recent interest owing to superior mechanical and optical properties. A hybrid Monte Carlo-continuum simulation is briefly overviewed, and subsequently FEBID experiments and simulations are directly compared. Finally, a 3D computer-aided design (CAD) program is introduced, which generates the beam parameters necessary for FEBID by both simulation and experiment. Using this approach, we demonstrate the fabrication of various 3D lattice structures using Pt-, Au-, and W-based precursors.


[Erythrocyte elongation with 10% dextran 40,000: comparison of 2 substances].
A dosage-effect-study with two 10% dextrans 40,000 was carried out in 12 venous blood samples of healthy men aged from 21 to 45 years. Dextran A (trade name: Dextran 40,000 "Ebewe") and Dextran B (trade name: "Rheomacrodex") were added in dosages of 0.5 to 10 mg/ml whole blood and the elongation-index of erythrocytes at shearrate 50/sec was determined. From 1 mg up to 10 mg/ml the elongation-index in Dextran B showed a stronger decrease than in Dextran A. Under the highest dosage the difference was about 20%. So it was possible to show that in spite of identical molecular weight there are different effects on deformability of erythrocytes. This should be taken into account for parenteral treatment.


Surgery for meningioma in the elderly and long-term survival: comparison with an age- and sex-matched general population and with younger patients.
OBJECTIVE The purpose of this study was to compare long-term prognosis after meningioma surgery in elderly and younger patients as well as to compare survival of elderly patients with surgically treated meningioma to survival rates for the general population. METHODS Five hundred meningioma patients (median follow-up 90 months) who underwent surgery between 1994 and 2009 were subdivided into "elderly" (age ≥ 65 years, n = 162) and "younger" (age < 65 years, n = 338) groups for uni- and multivariate analyses. Mortality was compared with rates for the age- and sex-matched general population. RESULTS The median age at diagnosis was 71 in the elderly group and 51 years in the younger group. Sex, intracranial tumor location, grade of resection, radiotherapy, and histopathological subtypes were similar in the 2 groups. High-grade (WHO Grades II and III) and spinal tumors were more common in older patients than in younger patients (15% vs 8%, p = 0.017, and 12% vs 4%, p = 0.001, respectively). The progression-free interval (PFI) was similar in the 2 groups, whereas mortality at 3 months after surgery was higher and median overall survival (OS) was shorter in older patients (7%, 191 months) than in younger patients (1%, median not reached; HR 4.9, 95% CI 2.75-8.74; p < 0.001). Otherwise, the median OS in elderly patients did not differ from the anticipated general life expectancy (HR 1.03, 95% CI 0.70-1.50; p = 0.886). Within the older patient group, PFI was lower in patients with high-grade meningiomas (HR 24.74, 95% CI 4.23-144.66; p < 0.001) and after subtotal resection (HR 10.57, 95% CI 2.23-50.05; p = 0.003). Although extent of resection was independent of perioperative mortality, the median OS was longer after gross-total resection than after subtotal resection (HR 2.7, 95% CI 1.09-6.69; p = 0.032). CONCLUSIONS Elderly patients with surgically treated meningioma do not suffer from impaired survival compared with the age-matched general population, and their PFI is similar to that of younger meningioma patients. These data help mitigate fears concerning surgical treatment of elderly patients in an aging society.


Derivation of a monoclonal antibody that detects an Ia antigen encoded by 2 complementing I-subregions.
A monoclonal antibody designated A303, which reacts with Ia antigens controlled by the complementation of 2 distinct I-subregion genes, is described. Complementation of both I-A and I-EC subregion gene products is necessary for the cytotoxic, direct and 125I-protein A-amplified indirect cell binding, and immunoprecipitation activities of A303. Positive prototype strains of independent origin include H-2k,p, whereas A303-negative haplotypes include H-2b,d,f,r,s,u. Seven recombinant strains, H-2ap5,as1,h4,i3,i5,t3,t4 representing intra I-region cross-over events between positive and negative haplotypes are A303 negative. Trans complementation occurs between the I-Ak allele and the I-EdCd, I-EkCk and I-EkCd alleles, respectively. Analysis of F1 heterozygotes suggests that A303-binding activity is also controlled by gene-dose effects. Thus, the activity of A303 is formally equivalent to a system of coupled complementation previously described for Ir and Is genes.


Post-operative arm morbidity and quality of life. Results of the ALMANAC randomised trial comparing sentinel node biopsy with standard axillary treatment in the management of patients with early breast cancer.
This study is the first large prospective RCT of sentinel node biopsy (SNB) compared with standard axillary treatment (level I-III axillary lymph node dissection or four node sampling), which includes comprehensive and repeated quality of life (QOL) assessments over 18 months. Patients (n = 829) completed the Functional Assessment of Cancer Therapy - Breast (FACT-B+4) and the Spielberger State/Trait Anxiety Inventory (STAI) at baseline (pre-surgery) and at 1, 3, 6, 12, and 18 months post-surgery. There were significant differences between treatment groups favouring the SNB group throughout the 18 months assessment. Patients in the standard treatment group showed a greater decline in Trial Outcome Index (TOI) scores (physical well-being, functional well-being and breast cancer concerns subscales in FACT-B+4) and recovered more slowly than patients in the SNB group (p < 0.01). The change in total FACT-B+4 scores (measuring global QOL) closely resembled the TOI results. 18 months post-surgery approximately twice as many patients in the standard group compared with the SNB group reported substantial arm swelling (14% versus 7%) (p = 0.002) or numbness (19% versus 8.7%) (p < 0.001). Despite the uncertainty about undergoing a relatively new procedure and the possible need for further surgery, there was no evidence of increased anxiety amongst patients randomised to SNB (p > 0.05). For 6 months post-surgery younger patients reported less favourable QOL scores (p < 0.001) and greater levels of anxiety (p < 0.01). In view of the benefits regarding arm functioning and quality of life, the data from this randomised study support the use of SNB in patients with clinically node negative breast cancer.