Inverse dynamic finite element-optimization modeling of the brain tumor mass-effect using a variable pressure boundary.
Statistical atlases of brain structure can potentially contribute in the surgical and radiotherapeutic treatment planning for the brain tumor patients. However, the current brain image-registration methods lack of accuracy when it comes to the mass-effect caused by tumor growth. Numerical simulations, such as finite element method (FEM), allow us to calculate the resultant pressure and deformation in the brain tissue due to tumor growth, and to predict the mass-effect. To date, however, the pressure boundary in the brain tissue due to tumor growth has been simply presented as a constant profile throughout the entire tumor outer surface that resulted in discrepancy between the patient imaging data and brain atlases. In this study, we employed a fully-coupled inverse dynamic FE-optimization method to estimate the resultant variable pressure boundary due to tumor resection surgery. To do that, magnetic resonance imaging data of two patients' pre- and post-tumor resection surgery were registered, segmented, volume-meshed, and prepared for fully-coupled inverse dynamic FE-optimization simulations. Two different pressure boundaries were defined on the brain cavity after tumor resection including: a) a constant pressure boundary and b) a variable pressure boundary. The inverse FE-optimization algorithm was used to find the optimum constant and variable pressure boundaries that result in the least distance between the surface-nodes of the post-surgery brain cavity and pre-surgery tumor. The results revealed that a variable pressure boundary causes a considerably lower mean percentage error compared to a constant pressure one; hence, it can more effectively address the realistic boundary in tumor resection surgery and predict the mass-effect. The proposed variable pressure boundary can be a robust tool that allows batch processing to register the brains with tumors to statistical atlases of normal brains and construction of brain tumor atlases. This approach is also computationally inexpensive and can be coupled to any FE software to run. The findings of this study have implications for not only predicting the accurate pressure boundary and mass-effect before tumor resection surgery, but also for predicting some clinical symptoms of brain cancers and presenting useful tools for APPLICATIONs in image-guided neurosurgery.


Quickly and efficiently remove multiple pesticides in tea infusions by low-cost carbonized bacterial cellulose.
Soaking tea leaves make tea consumers exposure to pesticide residues more easily. However, there are few studies on the removal of pesticides in tea infusions. Therefore, a low-cost carbonized bacterial cellulose material was prepared by direct calcination method, and used to remove multiple pesticides in tea infusions quickly and efficiently. CBC-350 has the best removal efficiency for 9 pesticides and then screened the best adsorption conditions. The adsorption isotherm experiment was carried out and indicated that the adsorption process was in consist with the Freundlich model. The thermodynamic parameters are also calculated. Moreover, the adsorption mechanism was discussed, which suggests that π-π interaction and hydrophobic action are the driving force during the adsorption process. Exhilaratingly, the CBC-350 also has excellent adsorption capacity compared to other adsorbents and can be reused at least five times.


4-Bromo-2-[({2-[(2-hy-droxy-eth-yl)amino]-eth-yl}imino)-meth-yl]phenol.
The new title Schiff base compound, C11H15BrN2O2, crystallizes in the monoclinic space group P21 with two independent mol-ecules in the asymmetric unit. It was prepared by the condensation reaction of 5-bromo-2-hy-droxy-benzaldehyde and amino-ethyl-ethano-lamine. There is an intra-molecular O-H⋯N hydrogen bond with an S(6) ring motif. Moreover, there are inter-molecular C-H⋯N, C-H⋯O and Br⋯O inter-actions in the crystal structure of the title compound.


Low vitamin D concentrations among indigenous Argentinean children living at high altitudes.
Hypovitaminosis D is an international problem; however, there is little information about its prevalence in apparently healthy Indian children living at high altitudes. To determine (i) the prevalence of hypovitaminosis D and (ii) the association of serum vitamin D with the risk factors for diabetes among Indian Koya children. A cross-sectional study of 290 (129 males) school children aged 10.7 ± 2.9 yr was performed. Anthropometric measures, blood pressure (BP), Tanner stages and serum levels of glucose, lipids, and insulin were measured. 25-hydroxyvitamin D [25(OH)D] was measured by radioimmunoassay (Dia Sorin). The prevalence of obesity was 3.4% (10), overweight 3.4% (10), normal weight 79.0% (229), and underweight 14.1 % (41) per CDC reference standards. Concentrations of [25(OH)D] were median 10 (range 8-13 ng/mL); 10 (3.4%) had insufficient vitamin D levels (20 to <30 ng/mL), 136 (46.9%) had deficient levels (10 to <20 ng/mL), 144 (49.7%) had severe deficiency (<10 ng/mL) and none had optimal levels (≥30 ng/mL). There was an inverse significant correlation between [25(OH)D] and age (r = 0.14), body mass index (BMI) (r = 0.16), waist circumference (r = 0.15), systolic BP (r = 0.19), hemoglobin (r = 0.19), glucose (r = 0.22), insulin (r = 0.13), and homeostasis model of assessment-insulin resistance (r = 0.16). Multiple linear regression analysis showed that 25(OH)D concentrations were significantly and inversely associated with glucose concentrations (β = -0.28; p = 0.02) adjusted for age, BMI, systolic BP, hemoglobin, and insulin. This study demonstrated a high prevalence of both 25(OH)D deficiency and insufficiency and an inverse association between 25(OH)D and glucose concentration in apparently healthy Koya Indian children. Further research is needed to confirm these findings.


Function and structure of lipid storage droplet protein 1 studied in lipoprotein complexes.
Triglycerides (TG) stored in lipid droplets (LDs) are the main energy reserve in all animals. The mechanism by which animals mobilize TG is complex and not fully understood. Several proteins surrounding the LDs have been implicated in TG homeostasis such as mammalian perilipin A and insect lipid storage proteins (Lsd). Most of the knowledge on LD-associated proteins comes from studies using cells or LDs leaving biochemical properties of these proteins uncharacterized. Here we describe the purification of recombinant Lsd1 and its reconstitution with lipids to form lipoprotein complexes suitable for functional and structural studies. Lsd1 in the lipid bound state is a predominately alpha-helical protein. Using lipoprotein complexes containing triolein it is shown that PKA mediated phosphorylation of Lsd1 promoted a 1.7-fold activation of the main fat body lipase demonstrating the direct link between Lsd1 phosphorylation and activation of lipolysis. Serine 20 was identified as the Lsd1-phosphorylation site triggering this effect.


A beta fibrillogenesis: kinetic parameters for fibril formation from congo red binding.
Using Scatchard analysis, we have formulated as a function of time and pH the relationship between the binding of Congo red to Alzheimer's beta-amyloid and the aggregation number (i.e., monomer concentration within fibrils) as defined by nucleation-dependent self-assembly. This provides a basis on which to determine the kinetic parameters for fibril formation from the observed concentration of bound Congo red.


A dose-response meta-analysis reveals an association between vitamin B12 and colorectal cancer risk.
The current meta-analysis evaluated the association between vitamin B12 intake and blood vitamin B12 level and colorectal cancer (CRC) risk. The PubMed and EMBASE databases were searched. A dose-response analysis was performed with generalized least squares regression, with the relative risk (RR) and 95 % CI as effect values. The meta-analysis included seventeen studies. A total of 10 601 patients. The non-linear dose-response relationship between total vitamin B12 intake and CRC risk was insignificant (P=0·690), but the relationship between dietary vitamin B12 intake and CRC risk was significant (P<0·001). Every 4·5 μg/d increment in total and dietary vitamin B12 intake was inversely associated with CRC risk (total intake: RR=0·963; 95 % CI 0·928, 0·999; dietary intake: RR=0·914; 95 % CI 0·856, 0·977). The inverse association between vitamin B12 intake and CRC risk was also significant when vitamin B12 intake was over a dosage threshold, enhancing the non-linear relationship. The non-linear dose-response relationship between blood vitamin B12 level and CRC risk was insignificant (P=0·219). There was an insignificant association between every 150 pmol/l increment in blood vitamin B12 level and CRC risk (RR=1·023; 95 % CI 0·881, 1·187). Our meta-analysis indicates that evidence supports the use of vitamin B12 for cancer prevention, especially among populations with high-dose vitamin B12 intake, and that the association between CRC risk and total vitamin B12 intake is stronger than between CRC risk and dietary vitamin B12 intake only.


Electrical neuroimaging reveals intensity-dependent activation of human cortical gustatory and somatosensory areas by electric taste.
To analyze the neural basis of electric taste we performed electrical neuroimaging analyses of event-related potentials (ERPs) recorded while participants received electrical pulses to the tongue. Pulses were presented at individual taste threshold to excite gustatory fibers selectively without concomitant excitation of trigeminal fibers and at high intensity evoking a prickling and, thus, activating trigeminal fibers. Sour, salty and metallic tastes were reported at both intensities while clear prickling was reported at high intensity only. ERPs exhibited augmented amplitudes and shorter latencies for high intensity. First activations of gustatory areas (bilateral anterior insula, medial orbitofrontal cortex) were observed at 70-80ms. Common somatosensory regions were more strongly, but not exclusively, activated at high intensity. Our data provide a comprehensive view on the dynamics of cortical processing of the gustatory and trigeminal portions of electric taste and suggest that gustatory and trigeminal afferents project to overlapping cortical areas.


Wavelength-dependent Optical Instability Mechanisms and Decay Kinetics in Amorphous Oxide Thin-Film Devices.
We present a study on decay kinetics for a recovery process depending on the light wavelength selected in optical instability measurements against amorphous In-Ga-Zn-O (a-IGZO) thin-film devices. To quantitatively analyze optically-induced instability behaviors, a stretched exponential function (SEF) and its inverse Laplace transform are employed for a time- and energy-dependent analysis, respectively. The analyzed results indicate that a shorter wavelength light activates electrons largely from the valence band while metastable states are deionized with the respective photon energy (hv). In contrast, a longer wavelength illumination is mainly activating trapped electrons at metastable states, e.g. oxygen defects. In particular, at 500 nm wavelength (hv ~ 2.5 eV), it shows an early persistency with a much higher activation energy. This also implies that the majority of metastable states remain ionized, thus the deionization energy >2.5 eV. However, the decay trend at 600 nm wavelength (hv ~ 2 eV) is found to be less persistent and lower current level compared to the case at 500 nm wavelength, suggesting the ionization energy of metastable states >2 eV. Finally, it is deduced that majority of oxygen defects before the illumination reside within the energy range between 2 eV and 2.5 eV from the conduction band edge.


Advancing Imaging to Enhance Surgery: From Image to Information Guidance.
Conventional magnetic resonance imaging (cMRI) has an established role as a crucial disease parameter in the multidisciplinary management of glioblastoma, guiding diagnosis, treatment planning, assessment, and follow-up. Yet, cMRI cannot provide adequate information regarding tissue heterogeneity and the infiltrative extent beyond the contrast enhancement. Advanced magnetic resonance imaging and PET and newer analytical methods are transforming images into data (radiomics) and providing noninvasive biomarkers of molecular features (radiogenomics), conveying enhanced information for improving decision making in surgery. This review analyzes the shift from image guidance to information guidance that is relevant for the surgical treatment of glioblastoma.


Impact of systemic dexamethasone dosage on docetaxel-induced oral mucositis in patients with breast cancer.
Oral mucositis (OM) is a common adverse effect of docetaxel-containing treatment. This study aimed to assess whether dexamethasone (DEX) dose-dependently attenuates docetaxel-induced OM and dysgeusia. We retrospectively analyzed medical records of patients with breast cancer receiving docetaxel-containing regimens at Hokkaido University Hospital between June 2015 and June 2022. The patients were divided into low-dose and high-dose groups (DEX 4 or 8 mg/day on days 2-4, respectively), and incidence of OM and dysgeusia, and risk factor(s) for OM incidence were evaluated. The incidence of all-grade OM in the first cycle was 57.8% in the low-dose group and 19.2% in the high-dose group (P = 0.0002), which met our primary endpoint. The incidence of OM in all treatment cycles was also significantly lowered by DEX-dose increase (P = 0.01). In contrast, the incidence of dysgeusia was similar between the two groups in the first and all cycles (P = 0.50 and P = 0.28, respectively). These results were also confirmed in a propensity score-matched population. Multivariate logistic regression analysis also suggested that lower DEX dosage was a singular risk factor for all-grade OM incidence. In conclusion, our study suggests that DEX dose-dependently reduces the incidence of OM in docetaxel-containing regimens for breast cancer treatment.


The effect of n-3 polyunsaturated fatty acids on lipids, haemostasis, neutrophil and monocyte chemotaxis in insulin-dependent diabetes mellitus.
Insulin-dependent diabetes mellitus (IDDM) is associated with an increased risk of coronary artery disease (CAD). There is some evidence that polyunsaturated fatty acids of the marine n-3 type (n-3 PUFA's) may offer protection against CAD. We have studied the effect of short-term dietary supplementation with n-3 PUFAs on lipids, haemostasis, neutrophil and monocyte chemotaxis in 10 patients with IDDM. The patients were given 4 g daily of n-3 PUFAs (fish oil) for 6 weeks and were investigated before and after the supplement. No significant effects on platelets or haemostasis were observed. High density lipoprotein (HDL)-cholesterol significantly increased, and triglycerides and the ratio of total cholesterol to HDL-cholesterol significantly decreased. Monocyte chemotaxis was unaltered, while neutrophil chemotaxis significantly increased after fish oil. The finding of an improvement in neutrophil chemotaxis after supplementation with n-3 PUFAs to patients with IDDM needs to be confirmed in future studies.


Analysis of tourism sustainability synthetic indicators. A case study of Aragon.
Tourism sustainability is a long-term exploration process of human beings seeking to coexist harmoniously with the ecological environment. The core of sustainable tourism development is to achieve the harmonious development of the economy, society, and environment. Aragon's rich tourism resources attract many tourists, and the local government has formulated a sustainable development strategy to develop tourism vigorously. This paper constructs a tool to assess the sustainable development of tourism in Aragon based on the theory of sustainable tourism development and related methods. It proposes the construction of synthetic indicators based on the environmental-social-economic triad model, identifies individual indicators suitable for the study of the region based on indicators that appear more frequently in related studies, and defines and evaluates these indicators. We construct the matrices by questionnaire and expert consultation method and find that environmental and social factors significantly impact sustainable development. The indicators are then standardized and weighted using hierarchical analysis to determine the level of sustainable development of the local tourism industry based on the standard for assessing sustainable tourism development. The steps and methods of constructing synthetic indicators proposed in this paper can guide future analysis of the strengths and weaknesses of tourism development in Aragon and similar areas under different conditions, as well as for the study of factors affecting tourism development, and provide targeted suggestions for improving the competitiveness of local tourism, taking into account regional tourism characteristics and actual conditions.


Evolution of Hemophilia Care in India.
Haemophilia is a high cost low volume disease. Being a relatively uncommon condition governments of the day are not very interested in developing comprehensive care for such a condition. Patient's society where such kind of patients come together under one umbrella and fight for their rights and proper management of the condition has important role to play in developing and helping to deliver high standards care in such a condition. Haemophilia Federation of India, a patient's organization played a stellar role in developing haemophilia care in this country and continues to do so today, present article explains how this organization engaged itself through local, national and international interaction in evolving haemophilia care in this country. The present description can act as a template for developing similar architecture of care for rare but difficult and costly to treat disorders'.


Comparison of different autophagic vacuoles with regard to ultrastructure, enzymatic composition, and degradation capacity--formation of crinosomes.
The number of rat liver autophagic vacuoles (AVs) was increased by separate injection of three different inhibitors--vinblastine, leupeptin, and chloroquine--of lysosomal protein degradation. The different mechanisms of action of the agents correlated to the ultrastructure of the AVs. Accumulation of the base chloroquine with ensuing influx of water into AVs caused a significant swelling. The leupeptin-induced AVs were processed into residual-body-like structures within a few hours of exposure in line with the presence of a leupeptinase in liver tissue. Vinblastine was the most efficient agent in increasing the occurrence of AVs. The effect of vinblastine lasted for the entire study period (36 hr) with continuous formation of nascent AVs. In addition, vinblastine caused the appearance of a subpopulation of AVs laden with VLDL particles. The term crinosomes was suggested for these hybrid organelles, since they seemed to evolve by fusion between secretory granules and lysosomes. In addition to sequestered cell organelles, the AVs harbored cytosolic enzyme activities (LDH and aldolase). Leupeptin was the only agent that caused a decrease in cathepsin B and L activities. Similarly, leupeptin impeded protein breakdown in isolated AVs, whereas vinblastine and chloroquine evoked an increase. In vivo, chloroquine and vinblastine block protein degradation. The reason for this discrepancy is probably that during in vivo exposure the substrate (cytoplasmic proteins) is built up in the AVs because degradation is retarded. Upon isolation of the AVs the inhibitor block is released, and proteolysis proceeds at enhanced rates over control due to excess of substrates. Leupeptin, on the other hand, caused a substantial inhibition of thiol proteinases; this block remained in the isolated AVs. Accordingly, leupeptin-induced AVs displayed decreased protein degradation following shorter exposure times. Later, when leupeptin was metabolized, catch-up proteolysis was noted. The differing mechanisms of action of the inhibitors were also apparent as regards lipid contents and lipolysis. Whereas chloroquine and vinblastine increased the amounts of cholesterol and triglycerides parallel to proteins, leupeptin had no such effect. Lipolysis proceeded at normal rate following leupeptin administration, which was not the case after vinblastine and chloroquine exposure. Leupeptin has no effect on acid lipases; therefore lipids do not accumulate in AVs of hepatocytes that are exposed to leupeptin.


Erratum: This Article Corrects: "Systemwide Clinical Ultrasound Program Development: An Expert Consensus Model".
[This corrects the article on p. 649 in vol. 19, PMID: 30013699.].


Reduction in surgical ischemic-reperfusion injury with adenosine and nitric oxide therapy.
Ischemia and reperfusion impair the inherent capacity of the heart to protect itself from related pathophysiologic events by reducing endogenous oxygen radical scavengers and inhibitors. However, other endogenously produced agents, notably adenosine and nitric oxide, are produced during ischemia, reperfusion, or both. These autacoids have several cardioprotection actions in common, particularly antineutrophil effects and inhibition of endothelial-neutrophil interactions, which are key initial steps in ischemic-reperfusion injury. Studies have shown that nitric oxide exerts cardioprotection primarily during reperfusion. Adenosine, on the other hand, protects the myocardium to some extent during both ischemia and reperfusion, thereby covering both periods during which myocardial injury may be sustained during a cardiac operation. Native adenosine or active analogues, or donors of nitric oxide, may be given before or in conjunction with cardioplegia solutions. However, these endogenous agents can also be pharmacologically recruited to provide a new potent therapeutic approach against surgical ischemic-reperfusion injury. This article reviews the cardioprotective effects of primarily endogenous nitric oxide and adenosine in both nonsurgical and surgical models of ischemia-reperfusion injury. Both adenosine and nitric oxide provide potent cardioprotection in surgical and nonsurgical models of ischemia-reperfusion. An important mechanism in this cardioprotection is attenuation of neutrophil-mediated damage.


Basic ingredients for mathematical modeling of tumor growth in vitro: cooperative effects and search for space.
Based on the literature data from HT-29 cell monolayers, we develop a model for its growth, analogous to an epidemic model, mixing local and global interactions. First, we propose and solve a deterministic equation for the progress of these colonies. Thus, we add a stochastic (local) interaction and simulate the evolution of an Eden-like aggregate by using dynamical Monte Carlo methods. The growth curves of both deterministic and stochastic models are in excellent agreement with the experimental observations. The waiting times distributions, generated via our stochastic model, allowed us to analyze the role of mesoscopic events. We obtain log-normal distributions in the initial stages of the growth and Gaussians at long times. We interpret these outcomes in the light of cellular division events: in the early stages, the phenomena are dependent each other in a multiplicative geometric-based process, and they are independent at long times. We conclude that the main ingredients for a good minimalist model of tumor growth, at mesoscopic level, are intrinsic cooperative mechanisms and competitive search for space.


Lessons from the anemia of prematurity.
In our view, three main lessons stem from consideration of the refractory early anemia of prematurity (REAP). These are: (1) Hemoglobin concentration is not enough to describe the anemia. (2) The REAP may be clinically very severe but is often easily missed. It interacts with and worsens other causes of anemia in preterm infants, such as blood losses. Its pathogenesis is multifactorial, but it is generally interrelated with short gestation and its other complications. (3) Prevention, prophylaxis, and if necessary, adequate management are very important.


Characterization of Spinal Cord Injury Patients for Arm Functional Restoration through Nerve Transfer.
Traumatic spinal cord injuries (tSCI) are common, often leaving patients irreparably debilitated. Therefore, novel strategies such as nerve transfers (NT) are needed for mitigating secondary SCI damage and improving function. Although different tSCI NT options exist, little is known about the epidemiological and injury-related aspects of this patient population. Here, we report such characteristics to better identify and understand the number and types of tSCI individuals who may benefit from NTs. Two peripheral nerve experts independently evaluated all adult tSCI individuals < 80 years old admitted with cervical tSCI (C1-T1) between 2005 and 2019 with documented tSCI severity using the ASIA Impairment Scale for suitability for NT (nerve donor with MRC strength ≥ 4/5 and recipient ≤ 2/5). Demographic, traumatic injury, and neurological injury variables were collected and analyzed. A total of 709 tSCI individuals were identified with 224 (32%) who met the selection criteria for participation based on their tSCI level (C1-T1). Of these, 108 (15% of all tSCIs and 48% of all cervical tSCIs) were deemed to be appropriate NT candidates. Due to recovery, 6 NT candidates initially deem appropriate no longer qualified by their last follow-up. Conversely, 19 individuals not initially considered appropriate then become eligible by their last follow-up. We found that a large proportion of individuals with cervical tSCI could potentially benefit from NTs. To our knowledge, this is the first study to detail the number of tSCI individuals that may qualify for NT from a large prospective database.


Machine learning methods revealed the roles of immune-metabolism related genes in immune infiltration, stemness, and prognosis of neuroblastoma.
Immunometabolism plays an important role in neuroblastoma (NB). However, the mechanism of immune-metabolism related genes (IMRGs) in NB remains unclear. This study aimed to explore the effects of IMRGs on the prognosis, immune infiltration and stemness of patients with NB using machine learning methods. R software (v4.2.1) was used to identify the differentially expressed IMRGs, and machine learning algorithm was used to screen the prognostic genes from IMRGs. Then we constructed a prognostic model and calculated the risk scores. The NB patients were grouped according to the prognosis scores. In addition, the genes most associated with the immune infiltration and stemness of NB were analyzed by weighted gene co-expression network analysis (WGCNA). There were 89 differentially expressed IMRGs between the MYCN amplification and the MYCN non-amplification group, among which CNR1, GNAI1, GLDC and ABCC4 were selected by machine learning algorithm to construct the prognosis model due to their better prediction effect. Both the K-M survival curve and the 5-year Receiver operating characteristic (ROC) curve indicated that the prognosis model could predict the prognosis of NB patients, and there was significant difference in immune infiltration between the two groups according to the median of risk score. We verified the effects of IMRGs on the prognosis, immune infiltration and stemness of NB. These findings could provide help for predicting prognosis and developing immunotherapy in NB.


Activity against drug resistant-tuberculosis strains of plants used in Mexican traditional medicine to treat tuberculosis and other respiratory diseases.
Tuberculosis (TB) kills about 3 million people per year worldwide. Furthermore, TB is an infectious disease associated with HIV patients, and there is a rise in multidrug-resistant TB (MDR-TB) cases around the world. There is a need for new anti-TB agents. The study evaluated the antimycobacterial activity of nine plants used in Mexican traditional medicine to treat tuberculosis and other respiratory diseases. Nasturtium officinale showed the best activity (MIC = 100 microg/mL) against the sensitive Mycobacterium tuberculosis. The following plants were active also but at 200 microg/mL: Citrus sinensis, Citrus aurantifolia, Foeniculum vulgare, Larrea tridentata, Musa acuminata and Olea europaea. Contrary to the above data, activity against drug-resistant variants of M. tuberculosis was more evident, e.g. N. officinale was the most potent (MIC < or = 100 microg/mL) against the four mono-resistant variants tested; F. vulgare and O. europaea were active against all the resistant variants (MICs < or = 100 microg/mL). The most susceptible variant was the isoniazid resistant, being inhibited by C. aurantifolia, C. sinensis and O. europaea (MIC = 25 microg/mL). These data point to the importance of biological testing of extracts against drug-resistant M. tuberculosis isolates, and the bioguided assay of these extracts for the identification of lead compounds against MDR-TB isolates.


Paraneoplastic Raynaud's phenomenon as sign of progression: a case report on a patient with breast cancer.
Paraneoplastic Raynaud's phenomenon is a rare complication occurring in patients with advanced cancer. We present a case of a patient with breast cancer and presenting with acrocyanosis evolving into necrosis as a paraneoplastic phenomenon in progressive breast cancer. Unless a multidisciplinary approach was taken, improvement of the symptoms was only seen with prostacyclin analogs, and cancer treatment needed to be changed because of rapidly progressing disease. Paraneoplastic Raynaud's phenomenon is a rare but severe presentation of advanced and progressive cancer. Treatment with intravenous prostacyclin analogs should be considered and a multidisciplinary approach is necessary.


Understanding the N-acylated homoserine lactones(AHLs)-based quorum sensing for the stability of aerobic granular sludge in the aspect of substrate hydrolysis enhancement.
Efficient substrate metabolism is the premise for stable operation of aerobic granular sludge and can be regulated by quorum sensing (QS). In this study, starch and acetate were selected to represent complex and simple substrates to provide comparable amount of metabolic energy for granules cultivation. Starch-fed granules were larger in size and contained higher EPS content than acetate-fed granules, though both granules exhibited similar substrate-degradation rates during sequencing batch reactor (SBR) cycle. Three N-acylhomoserine lactones (AHLs), including C8-HSL, 3OHC8-HSL and 3OHC12-HSL, were detected as dominant autoinducers in granules. They accumulated more in starch-fed granules than acetate-fed granules. The batch experiments were implemented to investigate QS regulation for granular stability in terms of substrate hydrolysis and transformation. The addition of three AHLs increased the activity of α-amylase, the main starch hydrolase, 4-6 times, significantly (p < 0.01) higher than the control treatment without AHLs amendment. While activity of dehydrogenase, the main simple substrate degradation enzyme, was increased only 1-2 times. Higher enzyme activity, especially α-amylase, significantly (p < 0.05) promoted the substrate-degradation rate (65 % than control group) and EPS yield in starch-fed system. Overall, QS can facilitate complex substrate uptake via hydrolysis enhancement and EPS secretion, which together promote sludge granulation and stability.


Phase II study of fulvestrant 250 mg/month in patients with recurrent or metastatic endometrial cancer: a study of the Arbeitsgemeinschaft Gynäkologische Onkologie.
The aim of this study is to evaluate the activity and toxicity of fulvestrant, a pure estrogen receptor antagonist in patients with advanced or recurrent endometrial cancer, expressing estrogen and/or progesterone receptors (ER/PR). Eligible patients with advanced or recurrent endometrial cancer not amenable to curative surgery and/or radiotherapy were treated with fulvestrant at a dose of 250 mg by IM injection every 4 weeks for at least 12 weeks. Therapy was continued until disease progression, death, intolerable side effects or end of study. Response was assessed in patients with at least one target lesion according to WHO-criteria. Thirty-five patients were enrolled in this study and received at least one injection of fulvestrant (intention to treat-population, ITT). Twenty six patients received the intended 3 injections of fulvestrant (per protocol population, PP). There was no complete response but 4 partial responses (11.4% ITT) and 8 stable diseases. The median time to progression was 2.3 months (ITT). Overall survival was 13.2 months (ITT). Treatment was well tolerated. Fulvestrant at a dose of 250 mg IM every 4 weeks has marginal activity and good tolerability in patients with ER and/or PR positive advanced or recurrent endometrial cancer. A loading dose strategy and the use of 500 mg/4 weeks might improve the efficacy of this treatment.


Nursing students' critical thinking disposition according to academic level and satisfaction with nursing.
The development of critical thinking dispositions has become an important issue in nursing education in Korea. Nursing colleges in Korea have developed teaching strategies and curricula that focus on developing critical thinking dispositions. It is an imperative step that evaluates the changing pattern and development of students' critical thinking dispositions. This study identified critical thinking dispositions of Korean nursing students according to academic level and satisfaction with nursing. A cross-sectional questionnaire survey was conducted among 1074 students in four colleges who completed the self-reported Critical Thinking Disposition Scale. Descriptive and univariate general linear model analyses were performed. The critical thinking disposition score increased according to academic level until junior year, after which it decreased in the senior year. Nursing students who were satisfied with nursing reported higher levels of critical thinking than those who were not satisfied or who responded neutrally. The critical thinking scores of nursing students not satisfied with nursing dropped greatly in the senior year. These results suggest the importance of targeting the development of curriculum and teaching methods for seniors and students who have a lower level of satisfaction with nursing to increase their critical thinking dispositions.


The role of intra-operative neuroelectrophysiological monitoring in single-level approach selective dorsal rhizotomy.
Selective dorsal rhizotomy via a single-level approach (SL-SDR) to treat spasticity 100% relies on the interpretation of results from the intra-operative neuroelectrophysiological monitoring. The current study is to investigate the role EMG interpretation plays during SL-SDR procedure with regard to the selection of nerve rootlets for partially sectioning in pediatric cases with spastic cerebral palsy (CP). A retrospective study was conducted in pediatric patients with spastic CP undergone our modified rhizotomy protocol-guided SL-SDR from May 2016 to Mar. 2019 in our hospital. Our study focused on intra-operative EMG interpretation and its correlation with pre-op evaluation results, and dorsal rootlet selection difference when data of our intra-operative EMG recordings interpreted using different rhizotomy protocols. Clinical and intra-operative neuroelectrophysiological monitoring data of a total of 318 consecutive cases were reviewed, which include 231 boys and 87 girls with 32 hemiplegias, 161 diplegias, and 125 quadriplegias. Age at the time of SL-SDR in those cases was between 3.0-14.0 (5.9 ± 1.9) years. The number of targeted muscle ranged from 2 to 8 over these cases (the muscle in lower limbs with its pre-op muscle tone ≥ 2 grade, Modified Ashworth scale). Among 21,728 nerve rootlets tested (68.3 ± 8.2/case), 6272 (28.9%) were identified sphincter related by our intra-operative neuromonitoring. In the rest of 15,456 (48.6 ± 7.6/case) nerve rootlets which neuromonitoring suggested associated with lower limbs, 11,009 were taken as the dorsal ones (34.6 ± 7.4/case). A total of 3370 (10.6 ± 4.7/case) rootlets matched our rhizotomy criteria with 3061 (9.6 ± 4.1/case) sectioned 50% and 309 (1.0 ± 1.0/case) cut 75%. The rhizotomy ratio (partially transected nerve rootlets/all dorsal rootlets associated with lower limbs in a particular case) was 15.8%, 22.3%, 33.4%, 41.8%, and 45.7% across cases with their pro-op GMFCS level from I to V, respectively. Rootlets required 75% cut had a tendency to increase as well in our cases with their pro-op GMFCS level from I to V, which comprising 1.5%, 4.8%, 8.5%, 14.1%, and 15.2% of all rootlets transected, respectively. The muscle tone of 2068 targeted muscles in these cases at the time of 3 weeks after the SL-SDR was revealed a significant decrease when compared to pre-op (1.7 ± 0.5 vs. 2.7 ± 0.6). Further investigation to compare our rootlet selection with the one guided by the traditional rhizotomy criteria using our intro-operative EMG recordings in 318 cases, revealed that the overlap ratio had a tendency to increase in cases when their pre-op GMFCS level increased (39.5%, 41.3%, 52.2%, 54.1%, and 62.8% in cases with levels I-V, respectively). While our modified rhizotomy protocol successfully identified 2-23 rootlets for sectioning in all of our 318 cases, the traditional rhizotomy protocol failed to distinguish any for cutting in about 20% of cases with their pre-op GMFCS levels I and II. The rhizotomy criteria fully rely on the EMG interpretation making intra-operative neuroelectrophysiological monitoring crucial when SDR is performed via a single-level approach. Our modified rhizotomy protocol is feasible, safe, and effective to guide SL-SDR to treat all types of spastic CP cases by decreasing muscle tone in particular spastic muscle groups in their lower limbs. Data of EMG responses during SL-SDR procedure and as well as the clinical outcomes based on their interpretation could help clinicians to further understand how neuronal circuits work in the spinal cord of these patients.


[Reflux esophagitis: operative method in adults: fundoplication (author's transl)].
When the indications for fundoplication are correctly applied and followed, the standard anterior wall method has been proved both clinically and experimentally to be the best antireflux operation; it offers excellent immediate and long-term results. It is debatable whether it should be combined with a vagotomy when the peptic element is excessive, for while this approach is undisputed in the presence of an ulcerated draining path, it calls for important considerations in its manner of execution. Gastropexy alone is an inadequate solution in all its technical modifications: We reserve it as the operation of choice for cases of paraesophageal volvulus of the stomach.


Extensive paraspinal abscess complicating tuberculous spondylitis in an adolescent with Pott kyphosis.
A 16-year-old girl who suffered from untreated tuberculosis spondylitis since childhood presented with marked Potts kyphotic deformity in adolescence. She had increasing shortness of breath and was admitted for investigation of right pleural effusion. On radiological examination, she was found to have extensive paraspinal abscesses, with the largest collection trapped within the kyphotic angulation in the thoracic region. The latter could only be appreciated with magnetic resonance (MR) imaging and had been overlooked in the initial computed tomography (CT).


Comparative genomic analysis of four multidrug-resistant isolates of Acinetobacter baumannii from Georgia.
This study reports the draft genomes of four newly isolated multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) isolates (0830, 0365, 4022, and 2846) from western Georgia to identify putative antimicrobial resistance genes (ARGs) and to determine the clonal subtypes of local clinical isolates. An Illumina MiSeq sequencer was used to perform whole-genome sequencing (WGS). The Vitek 2 automated system was used for microbial identification and antimicrobial resistance profiling. Taxonomical identification as A. baumannii was confirmed by WGS. In silico analyses resolved their ARG content and clonal relatedness using the Oxford (Oxf) and Pasteur (Pas) multi-locus sequence typing schemes. Isolates 0365 and 4022 displayed similar allelic profiles corresponding to ST944Oxf/ST78Pas. Isolate 2846 displayed a different allelic profile consistent with ST19Pas/IC 1 (International or European Clone I) and exhibited a novel Oxford ST that was designated as 1868. Isolate 0830 displayed the ST78Pas allelic profile, similar to isolates 0365 and 4022, and also possessed a single allelic mismatch in the gpi gene, resulting in an ST1104Oxf allele profile in the Oxford typing scheme. Circulating MDR A. baumannii exhibited genetic heterogeneity with variations in the structure and content of genomic A. baumannii resistance islands and encoded multiple putative ARGs. This report represents the first clonal subtype information and genomic characterization of MDR A. baumannii in Georgia and may inform future epidemiological investigations.


A simple and efficient purification of transduced cells by using green fluorescent protein gene as a selection marker.
Simple and efficient method for the selection of transduced cells would greatly facilitate the clinical utilization of retrovirus vectors. We developed a therapeutic bicistronic retrovirus vector for Gaucher disease, MFG-GC-GFP, which contains the human glucocerebrosidase (GC) gene and the green fluorescent protein (GFP) gene of the jellyfish Aequorea victoria as a vital selection marker, and investigated its applicability as gene therapy for Gaucher disease. A packaging cell line, GP + envAM12, was transfected with MFG-GC-GFP and, thus, produced a high titer recombinant virus (1.0 x 10(6) c.f.u./mL) in the culture supernatant. The expression level of GFP was correlated with the virus production in cells. The recombinant virus infected skin fibroblasts from a Gaucher patient and a sorted fraction of the cells expressing GFP by flow cytometry exhibited almost a six-fold higher activity of GC than normal fibroblasts. These data indicate that MFG-GC-GFP enables the one-step purification of a transduced fraction of target cells and is, therefore, considered to be a useful therapeutic vector for the experimental gene therapy of Gaucher disease.


Comparison of the effects of doxazosin and atenolol on target organ damage in adults with type 2 diabetes mellitus and hypertension in the CARDHIAC study: a 9-month, prospective, randomized, open-label, blinded-evaluation trial.
The CARDHIAC (CARduran en pacientes Diabéticos con HIpertensi'on Arterial no Controlada) trial examined the effects of doxazosin gastrointestinal therapeutic system (GITS) and atenolol on 3 separate measures of target-organ damage--left ventricular mass index (LVMI), carotid intima media thickness (IMT), and urinary albumin excretion (UAE)--in patients with type 2 diabetes mellitus and hypertension. This trial had a prospective, open-label, blinded-evaluation design and a duration of 9 months. Patients whose blood pressure (BP) was uncontrolled (systolic BP > or = 130 mm Hg and/or diastolic BP > or = 80 mm Hg) despite at least 1 month of treatment with a renin-angiotensin blocker and diuretic were randomly allocated to receive doxazosin GITS 4 mg or atenolol 50 mg once daily in addition to their existing treatment. Seated BP was measured at study visits at 1, 3, 6 and 9 months; if the BP goal was not achieved at any visit, the dose of doxazosin or atenolol was titrated upward to 8 or 100 mg, respectively. Treatment compliance (pill count) and adverse reactions were monitored at each visit. Each patient underwent echocardiography and Doppler ultrasonography at baseline and at the end of the study for evaluation of the change in LVMI. The change in carotid IMT was evaluated by carotid ultrasound examination at the same time points. UAE also was measured at baseline and the end of the study. Sixty patients (100% white; 51% female; mean [SD] age, 63.4 [7.5] years; body mass index, 28.2 [3.4] kg/m(2)) were randomized to receive doxazosin GITS (n=32) or atenolol (n=28). At baseline, mean BP was 150.2 (10.6)/90.1 (7.3) mm Hg in the doxazosin group and 153.1 (13.8)/92.3 (6.1) mm Hg in the atenolol group (P=NS). At the end of the study, BP had decreased by 10.1 (3.2)/5.2 (1.3) mm Hg in the doxazosin group and 12.2 (4.2)/6.3 (2.1) mm Hg in the atenolol group (both, P<0.001 vs baseline; P=NS between groups). Heart rate at the end of the study was 78(6) beats/min in the doxazosin group (P=NS vs baseline) and 66(7) beats/min in the atenolol group (P<0.01 vs baseline and between groups). LVMI decreased by 10.8 in the doxazosin group (P=0.001 vs baseline) and 4.2% in the atenolol group (P=NS vs baseline; P=0.03 between groups). The changes in carotid IMT and UAE were not statistically significant between groups. In this study in hypertensive patients with type 2 diabetes, LVMI was significantly decreased in doxazosin-treated patients relative to baseline and compared with atenolol-treated patients. The differences in carotid IMT and UAE were not statistically significant between groups.


Olmsted syndrome: report of a new case with unusual features.
Olmsted syndrome is a rare disorder characterized by the combination of periorificial keratotic plaques and bilateral palmoplantar keratoderma. New associated features continue to be reported. Olmsted syndrome in a female patient is particularly rare, and we report such a case having a haemangioma in addition to other features of the syndrome.


Epidemiological features of aplastic anaemia in Pakistan.
To complete the data on the demographic features of patients diagnosed to have aplastic anemia at a single institution over a 7.5 years period. Demographic information was retrieved from the patients medical records retrospectively as well as prospectively of those patients who presented with features of aplastic anaemia. Their diagnosis was confirmed by performing a complete blood count and bone marrow trephine. One hundred and forty four patients were diagnosed to have aplastic anemia; there were 106 males and 38 females. Their ages ranged from 2 to 75 years, with a median of 17 years, 112 (77.7%) patients were below the age of 30 years. Severe aplastic anemia (SAA) was seen in 74 (51.4%), very severe (VSAA) in 24 (16.7%) and non-severe aplastic anemia (NSAA) in 46 (31.9%) patients. No obvious cause could be established for 74.3%. Thirteen patients admitted using drugs known to cause AA and one was a radiographer (9%). Out of 44 patients tested, 7 (15.9%) were found to have either hepatitis B virus markers or antibody to hepatitis C at the time of diagnosis of AA. However it was difficult to establish a cause and effect relationship with either drugs or viruses. Aplastic anaemia is found to occur mostly in young males. The most common type was idiopathic severe aplastic anaemia.


Overview of Pharmacovigilance System in Vietnam: Lessons Learned in a Resource-Restricted Country.
Drug safety issues in developing countries are complex and sensitive, and health authorities cannot always simply implement decisions from developed countries because the health system, disease patterns, and lists of marketed drugs all differ. A system for proactive and effective surveillance of drugs in each nation is needed to identify and manage the exact drug-related problems faced by patients in these countries. Vietnam launched its university-based National Drug Information and Adverse Drug Reaction Monitoring Centre (NDIADRMC) in 2009, a significant step towards catching up with international trends. Although the center is still in its infancy and has limited resources, it has attained some achievements and largely met the minimum World Health Organization requirements for a functional pharmacovigilance center. The number of reports has increased rapidly, with some important signals generated from the national database leading to regulatory actions at a national level. In addition, this system can help detect drug-quality problems that are less common in developed countries. The success of the quantity and quality of reporting, risk assessment, and communication is still limited compared with more developed systems. A number of opportunities remain to enhance the system, particularly in risk communication and evaluation of the impact of pharmacovigilance, and to apply reporting outcomes to reduce drug-related risks throughout the country. More internal and external support is needed to develop a stronger and more comprehensive pharmacovigilance system.


Lessons Learned During the COVID-19 Pandemic in Central India: Overlooked Psychological and Social Determinants of Health.
The coronavirus disease 2019 (COVID-19) pandemic, which started in 2019, has created unprecedented public health problems, mental health crises, and economic and social problems. These effects have been studied by numerous researchers on the general population but none on hospitalized and discharged COVID-19 patients. To assess psychological and social problems among hospitalized and discharged COVID-19 patients. During lockdown and post-lockdown in India, we interviewed 500 COVID-19 patients admitted at our tertiary care center during their hospitalization and post-discharge period for psychological and social problems. The common psychological issues in hospitalized patients during lockdown were anxiety and misconceptions about COVID-19, while insomnia, anxiety, and frustration were common during the post-lockdown period. The typical social problems in hospitalized patients during the lockdown were containment-related issues, discrimination, longer wait for repeat COVID-19 tests, and boredom; whereas issues related to employment and financial matters were common during post-lockdown. Psychological problems comparatively decreased whereas social problems increased after discharge. Unrehearsed mitigation strategies at the beginning of the pandemic unknowingly led to various psychological and social problems. It was further aggravated by a lack of information and miscommunication.


Association of a polymorphism of the angiotensin I-converting enzyme gene with essential hypertension.
Angiotensin I-converting enzyme (ACE) is responsible for production of angiotensin II and breakdown of kinins, leading to increased blood pressure (BP). Furthermore, ACE inhibitors are effective antihypertensive agents. A 287 bp insertion/deletion polymorphism in intron 16 of the ACE gene (ACE) was examined by PCR in a cross-sectional study of 80 hypertensive (HT) and 93 normotensive (NT) subjects whose parents had a similar BP status at age greater than or equal to 50. The frequency of the insertion allele was 0.56 in HTs and 0.41 in NTs, and the difference between observed alleles in all subjects in each group was significant (chi 2 = 7.6, P less than 0.01). The data thus provide evidence in favour of an association of HT with a polymorphism at the ACE locus (17q23), so implicating this locus, and possibly a genetic variant of ACE itself, in human essential hypertension.


A rare case of primary tuberculosis in a solitary thyroid nodule.
Tuberculosis (TB) of the thyroid gland is extremely rare with fewer than 200 cases reported worldwide. We report a case of primary TB of the thyroid in a 73-year-old gentleman with no risk factors for TB, presenting with a painless right neck mass of one week's duration. A pre-operative ultrasound scan reported a solid-cystic, right TIRADS 5 nodule, and initial fine needle cytology showed granulomatous inflammation and was negative for AFB on Ziehl-Neelsen stain. A right hemithyroidectomy was done subsequently, and histology demonstrated necrotizing granulomatous inflammation, but TB-PCR detected Mycobacterium DNA. Primary TB of the thyroid is rare and can manifest in patients with no apparent risk factors for TB. Initial cytology may only yield granulomatous inflammation and surgery is needed to ascertain the exact cause of granulomatous inflammation and additional TB-PCR can help clinch the diagnosis.


Clinico-pathological study on macular mutant mouse.
The macular mutant mouse was clinically and pathologically examined. The hemizygotes began to show white fur color and curly whiskers around postnatal day 3, then seizures and ataxia around day 8, while the normal littermates did not. The hemizygotes also increased weight gradually from birth to day 9, but then showed weight loss and died around day 15 with severe emaciation. These clinical features resembled those in Menkes kinky hair disease. There were no pathological changes in the cerebral cortex in the hemizygotes on day 7. On day 10, two to three clear vacuoles began to appear in a few neurons in the cerebrum. These neurons with vacuoles increased gradually in number and degenerative neurons were also observed by day 14. Ultrastructurally, they corresponded to giant abnormal mitochondria with an electron-lucent matrix and short peripherally located cristae. Other abnormal mitochondria, which were characterized by an electron-dense matrix with tubular or vesicular cristae, were also observed in the cerebral cortical neurons.


Triglyceride assay using the ABA-50 and Boehringer Mannheim Triglyceride reagent kit.
1. A procedure for the assay of triglycerides on the ABA-50 is described. 2. The Boehringer Mannheim Triglyceride (Fully Enzymatic method) reagent kit has been evaluated with this method and was found to be satisfactory.


The Role of Imaging in Diagnosis and Monitoring of Large Vessel Vasculitis.
Technological advances and increased recognition of the prevalence and implications of large vessel vasculitis have led to robust research into various imaging techniques. Although there is still debate about which modality to choose in specific clinical scenarios, Ultrasound, PET/CT, MRI/A, and CT/A offer complementary information regarding diagnosis, disease activity, and vascular complication monitoring. Recognition of the strengths and limitations of each technique is important for appropriate application in clinical practice.


Computed tomography assessment of splenic size as a predictor of splenic weight and disease involvement in laparotomy staged Hodgkin's disease.
To evaluate how well splenic size predicts the risk of splenic Hodgkin's disease and to assess how accurately splenic dimensions on computerized tomographic scans predict spleen size and involvement by Hodgkin's disease. Splenic weights were obtained from laparotomies performed on 897 patients who presented with Hodgkin's disease and were compared with histologic involvement using logistic regression. Splenic dimensions were measured from preoperative computerized tomographic scans in 94 of these patients, and unidimensional splenic measurements [length (L), width (W), thickness (T)] and their products were compared with splenic weight at laparotomy using linear regression. Hodgkin's disease involved 42% of the spleens at laparotomy and 31% of those assessed by computerized tomography. Splenic weight averaged 198 +/- 5 g (range 40-2000 g). Weight and involvement were greater with "unfavorable" histologies (mixed cellularity, lymphocyte depletion, and unclassified Hodgkin's disease: 229 +/- 12 g; 62.7% involved) than with "favorable" histologies (nodular sclerosing, lymphocyte predominant, and interfollicular Hodgkin's disease: 191 +/- 5 g; 37.8% involved). Splenic weight was the strongest independent risk factor correlated with Hodgkin's disease in univariate and multivariate analyses in all patients and the only identifiable univariate risk factor among those with computerized tomographic scans. For most patients, however, splenic weight poorly predicted involvement: The probability of involvement never fell below 20% and exceeded 80% when splenic weight exceeded 270 g with unfavorable histologies or 685 g in favorable histologies. Spleens of average weight had a probability of involvement of 36% with favorable histologies, 70% with unfavorable histologies. Unidimensional measurements of the spleen on computed tomography correlated poorly with splenic weight, but their product correlated well (Correlation coefficients: L: 0.73; W: 0.65; T: 0.78; [0.344485 x L x W x T]: 0.94). Splenic weight is the strongest factor correlating with the risk of splenic involvement by Hodgkin's disease and can be accurately estimated from three-dimensional measurements on computed tomographic scans, but not from unidimensional measurements. However, splenic weight is not a sensitive predictor of involvement of the spleen by Hodgkin's disease. Therefore, treatment approaches to Hodgkin's disease must be based upon intermediate risks of splenic involvement for most clinically staged patients.


High yield of recombinant human Apolipoprotein A-I expressed in Pichia pastoris by using mixed-mode chromatography.
A vast majority of the cardioprotective properties exhibited by High-Density Lipoprotein (HDL) is mediated by its major protein component Apolipoprotein A-I (ApoA1). In order to develop a simplified bioprocess for producing recombinant human Apolipoprotein A-I (rhApoA1) in its near-native form, rhApoA1was expressed without the use of an affinity tag in view of its potential therapeutic applications. Expressed in Pichia pastoris at expression levels of 58.2 mg ApoA1 per litre of culture in a reproducible manner, the target protein was purified by mixed-mode chromatography using Capto™ MMC ligand with a purity and recovery of 84% and 68%, respectively. ApoA1 purification was scaled up to Mixed-mode Expanded Bed Adsorption chromatography to establish an 'on-line' process for the efficient capture of rhApoA1 directly from the P. pastoris expression broth. A polishing step using anion exchange chromatography enabled the recovery of ApoA1 up to 96% purity. Purified ApoA1 was identified and verified by RPLC-ESI-Q-TOF mass spectrometry. This two-step process would reduce processing times and therefore costs in comparison to the twelve-step procedure currently used for recovering rhApoA1 from P. pastoris.


The Impact of Surgical Practice on Oncological Outcomes in Robot-Assisted Radical Hysterectomy for Early-Stage Cervical Cancer, Spanish National Registry.
This study aimed to assess whether surgical practice had a significant impact on oncological outcomes among women who underwent robot-assisted radical hysterectomy for early-stage cervical cancer (≤IB1 or IIA1, FIGO 2009). The secondary objective was to audit the pre-surgical quality indicators (QI) proposed by the European Society of Gynaecological Oncology (ESGO). The top 5 of 10 centers in Spain and Portugal were included in the analysis. The hospitals were divided into group A (n = 118) and group B (n = 97), with recurrence rates of <10% and >10%, respectively. After balancing both groups using the propensity score, the ORs for all events were higher and statistically significant for group B (recurrences OR = 1.23, 95% CI = 1.13-1.15, p-value = 0.001; death OR = 1.10, 95% CI = 1.02-1.18, p-value = 0.012; disease-specific mortality ORr = 1.11, 95% CI = 1.04-1.19, p-value = 0.002). A higher surgical volume, higher participation in clinical trials, higher rate of MRI use for diagnosis, greater use of sentinel lymph node biopsies, and a favorable learning curve with low rates of early recurrences were observed among the centers with better oncological outcomes. These factors might have a significant impact on oncological outcomes not only after robot-assisted surgery, but also after laparoscopies and open surgeries in the treatment of cervical cancer.


Computer analysis of automated Edman degradation and amino acid analysis data.
Computer programs are described that allow facile analysis of data from a protein sequencer and amino acid analyzer. The sequencer program provides automated sequence interpretation while requiring minimal user interaction. The program serves as a powerful aid in deciphering mixture sequences and allows routine monitoring of sequencer performance. The computer program for amino acid analysis data provides the following calculations: mole percent, protein concentration and residues per mole with comparison between theoretical and calculated values. A plot of molecular weight versus deviation from integer values is calculated providing a measure of peptide or protein purity.


The Nd:YAG laser in neurological surgery.
The Nd:YAG laser has been applied in microneuro-surgery and has been found to be quite effective in removing had and hemorrhagic tumors such as meningiomas, tumors of the deep skull base, or tumors deep in the ventricle. Another indication for the use of the Nd:YAG laser is to open the thick sellar floor in transsphenoidal operations.


Well-Defined Mannosylated Polymer for Peptide Vaccine Delivery with Enhanced Antitumor Immunity.
Peptide-based cancer vaccines offer production and safety advantages but have had limited clinical success due to their intrinsic instability, rapid clearance, and low cellular uptake. Nanoparticle-based delivery vehicles can improve the in vivo stability and cellular uptake of peptide antigens. Here, a well-defined, self-assembling mannosylated polymer is developed for anticancer peptide antigen delivery. The amphiphilic polymer is prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization, and the peptide antigens are conjugated to the pH-sensitive hydrophobic block through the reversible disulfide linkage for selective release after cell entry. The polymer-peptide conjugates self-assemble into sub-100 nm micelles at physiological pH and dissociate at endosomal pH. The mannosylated micellar corona increases the accumulation of vaccine cargoes in the draining inguinal lymph nodes and facilitates nanoparticle uptake by professional antigen presenting cells. In vivo studies demonstrate that the mannosylated micelle formulation improves dendritic cell activation and enhances antigen-specific T cell responses, resulting in higher antitumor immunity in tumor-bearing mice compared to free peptide antigen. The mannosylated polymer is therefore a simple and promising platform for the delivery of peptide cancer vaccines.


Preparation, characterization and application of Aspergillus sp. xylanase immobilized on Eudragit S-100.
Aspergillus sp. 5 (strain 5) and Aspergillus sp. 44 (strain 44) produced xylanase (34.3 and 32.7 IU ml-1, respectively) with very low levels of cellulases when grown on 1% wheat bran medium. Xylanase was non-covalently immobilized on Eudragit S-100 for saccharification. The system retained 70 and 80% of strain 5 and strain 44 xylanase activity, respectively. On immobilization, optimum temperature of activity broadened between 50 and 60 degrees C as compared to 50 degrees C in the case of the free enzymes. No significant shift in the pH optima was observed on immobilization. However, immobilization increased enzyme stability mainly by decreasing the temperature sensitivity to the inactivation reaction. The K(m) values increased from 5.6 to 8.3 mg ml-1 for strain 5 xylanase and 7.0 to 9.0 mg ml-1 for strain 44 xylanase. Enzymatic saccharification of xylan and wheat bran was improved on xylanase immobilization. Immobilized xylanase from both the strains produced three times more sugar as compared to free xylanase. In repeated batch saccharification studies immobilized xylanase was recycled three times without loss of enzyme activity.


The Association of Harsh Parenting, Parent-Child Communication, and Parental Alcohol Use With Male Alcohol Use Into Emerging Adulthood.
This study investigates the association between mother and father harsh parenting, and parent-child communication, and parental alcohol use on males' alcohol use from early adolescence into emerging adulthood. Data come from the Iowa Youth and Families Project, a prospective 28-year longitudinal study of rural Midwestern youth and their families. Mother and father harsh parenting, parent-child communication, and alcohol use were assessed at time 1 when males were in early adolescence (13 years old, n = 215). Target male alcohol use was assessed at time 2 during late adolescence (18 and 19 years old, n = 206, 96% follow-up rate), and at time 3 in emerging adulthood (23 and 25 years old, n = 197, 92% follow-up rate). Results obtained from structural equation modeling using Mplus, version 7, statistical software indicated that father harsh parenting in early adolescence was directly associated with alcohol use in emerging adulthood. Mother communication was negatively associated while father alcohol use was positively associated with adolescent alcohol use in late adolescence and emerging adulthood. Alcohol use in late adolescence was significantly related to alcohol use in emerging adulthood. This study offers unique insights into how mother- and father-son dyads differ in communication and parenting styles, as well as how these associations influence adolescent male alcohol use continuing into emerging adulthood. Multiple informants utilized in the current study provide a more complex understanding of how each parent uniquely contributes to the role of their adolescent's alcohol use in late adolescence into emerging adulthood.


Addition polymerization of 1,1-dimesitylneopentylgermene: synthesis of a polygermene.
A new polymer with an alternating germanium-carbon backbone has been synthesized from 1,1-dimesitylneopentylgermene via addition polymerization using an anionic initiator.


Ethyl 3,4-bis-(acet-yloxy)-2-(4-meth-oxy-phen-yl)pyrrol-idine-1-carboxyl-ate.
The title pyrrolidine compound, C18H23NO7, is a tetra-substituted species in which the five-membered ring has a twisted conformation with the twist occurring in the C-C bond bearing the adjacent acet-yloxy substituents; the Cm-Ca-Ca-Cp torsion angle is -40.76 (18)° [m = methyl-ene, a = acet-yloxy and p = phen-yl]. The N atom, which is sp 2-hybridized [sum of bond angles = 359.4°], bears an ethyl-carboxyl-ate substitutent and is connected to a methyl-ene-C atom on one side and a carbon atom bearing a 4-meth-oxy-phenyl group on the other side. Minor disorder is noted in the ethyl-carboxyl-ate substituent as well as in one of the acet-yloxy groups; the major components of the disorder have site occupancies of 0.729 (9) and 0.62 (3), respectively. The most notable feature of the mol-ecular packing is the formation of helical, supra-molecular chains aligned along the b-axis direction whereby the carbonyl-O atom not involved in a disordered residue accepts C-H⋯O inter-actions from methyl-ene-H and two-C atom separated methine-H atoms to form a six-membered {⋯HCCCH⋯O} synthon.


Heterotopic submucosal gastric cysts: Report of two cases, one in association with carcinoma.
Two cases of heterotopic submucosal gastric cysts, one with a coexisting superficial spreading carcinoma, are described. This is an uncommon entity with which radiologists should be familiar. An association between such cysts and carcinoma has been predicated previously. The induction of submucosal gastric cysts in monkeys fed polychlorinated biphenyls is cited, and the potential significance of this observation with regard to such lesions in humans is discussed.


[Antioxidant activity in fungi degrading lignocellulose substrates].
Considerable differences in lignin degradation by fungi of two ecological groups have been revealed. Xylotrophs cause a twofold decrease in the molecular weight of lignin. The degrading activity of saprotrophs is insignificant. Xylotrophs demethoxylate and oxidize lignin more rapidly than saprotrophs, showing a higher level of antioxidant activity. As follows from the comparison of the degrading and antioxidative effects, measurement of the antioxidant activity can be used in screening of fungi for the ability to degrade lignocellulose substrates.


Cognitive predictors of medication adherence among middle-aged and older outpatients with schizophrenia.
Medication nonadherence presents a considerable problem in patients with schizophrenia. There are limited and conflicting data on the association of cognitive impairment with antipsychotic nonadherence. In this study, we evaluated the correlation of patients' scores on Mattis' Dementia Rating Scale (DRS; total and subscale scores) with scores on the Medication Management Ability Assessment (MMAA), a performance-based measure of medication management. Participants included 110 outpatients with schizophrenia or schizoaffective disorder. Each was evaluated using the MMAA role-play tasks and the DRS. Patients also completed the Drug Attitude Inventory (DAI), and the PANSS (Positive And Negative Syndrome Scale). Age, DAI score, and DRS scores were all correlated with MMAA performance. In a stepwise regression analysis, only DRS scores were predictive of MMAA performance. Among the DRS subscales, conceptualization and memory were the best statistical predictors of MMAA performance. Cognitive functions, especially conceptualization and memory, were the strongest patient-related predictors of his or her ability to manage medications, over and above the effects of age, gender, education level, symptom severity, and attitudes toward medications. These results suggest a need for intervention studies focused on improving, or at least compensating for, specific cognitive deficits such as those in memory and conceptualization among patients with schizophrenia in order to improve their ability to manage medications.


Blood-meal identification in phlebotomine sand flies (Diptera: Psychodidae) from Valle Hermoso, a high prevalence zone for cutaneous leishmaniasis in Ecuador.
Cutaneous leishmaniasis is a neglected tropical disease transmitted by phlebotomine sand flies of the genus Lutzomyia. In South America, cutaneous leishmaniasis is endemic in the majority of countries. There are no previous reports of phlebotomine sand fly host feeding sources in Ecuador. We identified blood meal sources for phlebotomine sand fly species in Valle Hermoso, a hyper endemic area for leishmaniasis in Ecuador. Phlebotomine sand fly collections were carried out during the dry and rainy seasons. PCR and multiplex PCR were performed from DNA extracted from the abdomens of blood-fed females to specifically identify the avian and mammalian blood meal sources. Avian-blood (77%), mammalian-blood (16%) and mixed avian-mammalian blood (7%) were found in the samples. At the species level, blood from chickens (35.5%), humans (2.8%), cows (2.8%) and dogs (1.9%) was specifically detected. Nyssomyia trapidoi was the most common species of Lutzomyia found that fed on birds. The present results may aid the development of effective strategies to control leishmaniasis in Ecuador.


Anti-inflammatory effects of vicenin-2 and scolymoside on polyphosphate-mediated vascular inflammatory responses.
Recent results indicate that polyphosphate (polyP) released by human endothelial cells can function as a pro-inflammatory mediator. Cyclopia subternata is a medicinal plant commonly used in traditional medicine to relieve pain in biological processes. This study was undertaken to investigate whether two structurally related active compounds found in C. subternata, namely vicenin-2 and scolymoside, can modulate polyP-mediated inflammatory responses in human umbilical vein endothelial cells (HUVECs) and in mice. The anti-inflammatory activities of vicenin-2 and scolymoside were determined by measuring permeability, leukocytes adhesion and migration, and activation of pro-inflammatory proteins in polyP-activated HUVECs and mice. In addition, the beneficial effects of vicenin-2 and scolymoside on survival rate in polyP-injected mice were determined. We found that vicenin-2 and scolymoside inhibits polyP-mediated barrier disruption, the expressions of cell adhesion molecules, and leukocyte to HUVEC adhesion/migration. Interestingly, polyP-induced NF-κB activation and the productions of TNF-α and IL-6 were inhibited by vicenin-2 and scolymoside in HUVECs. These anti-inflammatory functions of vicenin-2 and scolymoside were confirmed in polyP-injected mice. These results suggest that vicenin-2 and scolymoside have therapeutic potential for various systemic inflammatory diseases.


The role of spatial complexity in the perception of speech and pure tones in dichotic listening.
Ear advantages for CV syllables were determined for 28 right-handed individuals in a target monitoring dichotic task. In addition, ear dominance for dichotically presented tones was determined when the frequency difference of the two tones was small compared to the center frequency and when the frequency difference of the tones was larger. On all three tasks, subjects provided subjective separability ratings as measures of the spatial complexity of the dichotic stimuli. The results indicated a robust right ear advantage (REA) for the CV syllables and a left ear dominance on the two tone tasks, with a significant shift toward right ear dominance when the frequency difference of the tones was large. Although separability ratings for the group data indicated an increase in the perceived spatial separation of the components of the tone complex across the two tone tasks, the separability judgment ratings and the ear dominance scores were not correlated for either tone task. A significant correlation, however, was evidenced between the laterality measure for speech and the judgment of separability, indicating that a REA of increased magnitude is associated with more clearly localized and spatially separate speech sounds. Finally, the dominance scores on the two tone tasks were uncorrelated with the laterality measures of the speech task, whereas the scores on the tone tasks were highly correlated. The results suggest that spatial complexity does play a role in the emergence of the REA for speech. However, the failure to find a relationship between speech and nonspeech tasks suggest that all perceptual asymmetries observed with dichotic stimuli cannot be accounted for by a single theoretical explanation.


'Zap axotomy': localized fluorescent excitation of single dye-filled neurons induces growth by selective axotomy.
The response of populations of neurons to axotomy has traditionally been studied by crushing or sectioning whole nerve trunks. The present communication describes a technique by which single neurons can be reliably and selectively axotomized in the absence of damage to other axons and non-neuronal cells within the nerve. To obtain selective axotomy, identified neurons of the buccal ganglia of the snail, Helisoma, were first filled with fluorescent dye. Next, the preparation was positioned in a restricted beam of blue light using low light video fluorescence microscopy. Finally, the selected region of axon was briefly exposed to light levels normally employed for fluorescence microscopy. Shortly after irradiation of the identified neuron 5, antidromic action potentials no longer propagated past the region of exposure in the dye-filled cell, whereas adjacent axons were physiologically intact. Several days after exposure, profuse neurite outgrowth was observed from the proximal region of axon of neuron 5, but never in neighboring axons which were not filled with dye at the time of irradiation. When the axons of both neurons 5R and 5L were spot irradiated neurite outgrowth resulted in the formation of a novel electrical connection between these cells. These changes in growth and connectivity which were induced by selective axotomy of single axons were indistinguishable from the changes which are produced by crushing entire nerve trunks.


Carbon dioxide: an alternative to iodinated contrast media.
To study the use of carbon dioxide as a contrast medium for arteriography. Carbon dioxide was used as a contrast medium for intra-arterial digital subtraction lower limb angiography in 12 examinations on 11 patients. No complication was encountered and no significant changes occurred in the arterial pH, PaCO2 and PaO2. The quality of images as assessed by an independent observer was adequate for the majority of the vessels (77%). Carbon dioxide is a safe alternative in patients at an increased risk of adverse reaction to iodinated ionic or non-ionic contrast medium and is very cheap.


Effect of various prostaglandins on the metabolism of fructose by epididymal and ejaculated ram spermatozoa in vitro.
The effects of a number of prostaglandins on the metabolism of fructose by epididymal and ejaculated ram spermatozoa were investigated using conventional Warburg techniques. Spermatozoa from the two sources were collected concurrently during electrical stimulation; the epididymal spermatozoa were harvested via a cannula inserted chronically into one vas deferens and thus were free from exposure to the seminal prostaglandins. In general, the metabolism of fructose by the spermatozoa was little affected by a wide range of prostaglandins at a concentration of 20 micrograms/ml. Of the PGs present in semen, PGE2, PGE3 and PGF2alpha had no significant effects whereas PGE1 and PGF1alpha significantly increased lactate accumulation and the latter increased oxygen uptake, in both cases without significantly changing fructose utilization, fructose oxidized or CO2 production. Both 15-methyl-substituted PGE2 and PGF2alpha and their corresponding methyl esters failed to change fructose metabolism and it is unlikely therefore that the lack of response to PGE2 and PGF2alpha was due to their being metabolized by the spermatozoa during the incubation. Of a number of breakdown products tested, PGA1 and to a lesser extent PGA2 appeared to inhibit the Krebs tricarbocyclic acid cycle and 15-keto 13,14-dihydro-PGF2alpha appeared to stimulate it. In general, epididymal spermatozoa responded to the PGs in the same way as ejaculated spermatozoa. Thus we did not confirm a suggestion in the literature that spermatozoa have lowered sensitivity to PGs in vitro once they have been in contact with the PGs in seminal plasma.


AMMO-Prot: amine system project 3D-model finder.
Amines are biogenic amino acid derivatives, which play pleiotropic and very important yet complex roles in animal physiology. For many other relevant biomolecules, biochemical and molecular data are being accumulated, which need to be integrated in order to be effective in the advance of biological knowledge in the field. For this purpose, a multidisciplinary group has started an ontology-based system named the Amine System Project (ASP) for which amine-related information is the validation bench. In this paper, we describe the Ontology-Based Mediator developed in the Amine System Project (http://asp.uma.es) using the infrastructure of Semantic Directories, and how this system has been used to solve a case related to amine metabolism-related protein structures. This infrastructure is used to publish and manage not only ontologies and their relationships, but also metadata relating to the resources committed with the ontologies. The system developed is available at http://asp.uma.es/WebMediator.


Long term health and neurodevelopment in children exposed to antiepileptic drugs before birth.
To investigate the frequency of neonatal and later childhood morbidity in children exposed to antiepileptic drugs in utero. Retrospective population based study. Population of the Grampian region of Scotland. Mothers taking antiepileptic drugs in pregnancy between 1976 and 2000 were ascertained from hospital obstetric records and 149 (58% of those eligible) took part. They had 293 children whose health and neurodevelopment were assessed. Frequencies of neonatal withdrawal, congenital malformations, childhood onset medical problems, developmental delay, and behaviour disorders. Neonatal withdrawal was seen in 20% of those exposed to antiepileptic drugs. Congenital malformations occurred in 14% of exposed pregnancies, compared with 5% of non-exposed sibs, and developmental delay in 24% of exposed children, compared with 11% of non-exposed sibs. After excluding cases with a family history of developmental delay, 19% of exposed children and 3% of non-exposed sibs had developmental delay, 31% of exposed children had either major malformations or developmental delay, 52% of exposed children had facial dysmorphism compared with 25% of those not exposed, 31% of exposed children had childhood medical problems (13% of non-exposed sibs), and 20% had behaviour disorders (5% of non-exposed). Prenatal antiepileptic drug exposure in the setting of maternal epilepsy is associated with developmental delay and later childhood morbidity in addition to congenital malformation.


Retrospective Review of Reproductive Outcomes Comparing Vaginal Progesterone to Intramuscular Progesterone as Luteal Support in Frozen Embryo Transfer Cycles.
Recent literature suggests that progesterone in oil (PIO) is superior to vaginal progesterone (VP; Prometrium) for endometrial preparation in frozen embryo transfer cycles (FET), improving the live birth rate and reducing the rate of miscarriage. PIO has disadvantages including cost, pain, and stress of administration. The objective of this study was to evaluate whether VP is non-inferior to PIO for medicated FET cycles. We conducted a retrospective analysis comparing pregnancy, miscarriage, and live birth rates for PIO versus VP for medicated FET cycles, from 2017 to 2020 at a single fertility clinic. A total of 745 participants were included in the study; 438 received VP, and 307 received PIO. Univariate and multivariate binary and ordinal logistic regression analyses were performed to compare the rates of pregnancy, miscarriage, and live birth between VP and PIO. Our data demonstrated no difference between PIO and VP with respect to the rates of pregnancy (51% vs. 53%), miscarriage (20% vs. 18%), or live birth (31% vs. 34%) (all P > 0.05). For participants taking PIO, the odds of pregnancy were 0.93 [95% CI (0.70, 1.25), P = 0.65] that of participants on VP. In our single-centre experience, VP was non-inferior to PIO for endometrial preparation in FET cycles.


PDIA1 acts as master organizer of NOX1/NOX4 balance and phenotype response in vascular smooth muscle.
Changes in vascular smooth muscle cell (VSMC) phenotype underlie disease pathophysiology and are strongly regulated by NOX NADPH oxidases, with NOX1 favoring synthetic proliferative phenotype and NOX4 supporting differentiation. Growth factor-triggered NOX1 expression/activity strictly depends on the chaperone oxidoreductase protein disulfide isomerase-A1 (PDIA1). Intracellular PDIA1 is required for VSMC migration and cytoskeleton organization, while extracellular PDIA1 fine-tunes cytoskeletal mechanoadaptation and vascular remodeling. We hypothesized that PDIA1 orchestrates NOX1/NOX4 balance and VSMC phenotype. Using an inducible PDIA1 overexpression model in VSMC, we showed that early PDIA1 overexpression (for 24-48 h) increased NOX1 expression, hydrogen peroxide steady-state levels and spontaneous VSMC migration distances. Sustained PDIA1 overexpression for 72 h and 96 h supported high NOX1 levels while also increasing NOX4 expression and, remarkably, switched VSMC phenotype to differentiation. Differentiation was preceded by increased nuclear myocardin and serum response factor-response element activation, with no change in cell viability. Both NOX1 and hydrogen peroxide were necessary for later PDIA1-induced VSMC differentiation. In primary VSMC, PDIA1 knockdown decreased nuclear myocardin and increased the proliferating cell nuclear antigen expression. Newly-developed PDIA1-overexpressing mice (TgPDIA1) exhibited normal general and cardiovascular baseline phenotypes. However, in TgPDIA1 carotids, NOX1 was decreased while NOX4 and calponin expressions were enhanced, indicating overdifferentiation vs. normal carotids. Moreover, in a rabbit overdistension injury model during late vascular repair, PDIA1 silencing impaired VSMC redifferentiation and NOX1/NOX4 balance. Our results suggest a model in which PDIA1 acts as an upstream organizer of NOX1/NOX4 balance and related VSMC phenotype, accounting for baseline differentiation setpoint.


Toxicological consequences of Aroclor 1254 ingestion by female rhesus (Macaca mulatta) monkeys. Part 1A. Prebreeding phase: clinical health findings.
A group of 80 menstruating rhesus (Macaca mulatta) monkeys, with an average estimated age of 11.1 +/- 4.1 yr SD, were first randomly allocated to four similar test rooms (20 monkeys/room) and then randomly allocated to one of the five dose groups (four females/dose group/room). Each day, the females self-ingested capsules containing doses of 0, 5, 20, 40 or 80 micrograms Aroclor 1254/kg body weight. After 25 months of daily dosing, approximately 90% of the treated females attained a qualitative pharmacokinetic steady state with respect to the concentration of polychlorinated biphenyl in their adipose tissue. The test monkeys were monitored daily for health and menstrual status, as well as feed and water consumption. On a weekly basis, each female's body weight was determined and a detailed clinical examination was conducted. Minor treatment effects included a slight, but not statistically significant, decrease in feed and water consumption as well as a decreased feed conversion ratio and a slight increase in the duration of menses. Statistically significant, dose-related treatment effects included inflammation and/or prominence of the tarsal (Meibomian) glands, eye exudate, and various finger and toe nail changes. These results were found at doses lower than those previously reported for non-human primates.


Hemispheric asymmetry in memory for pictorial semantics in normal subjects.
Effects of presence versus absence of semantic organization in pictorial scenes were investigated in a memory hemi-field tachistoscopic paradigm in order to assess the hemispheric status of long-term semantic memory (LTSM). Forty normal subjects were asked to remember a series of pictorial scenes which were organized either in common configurations or were unorganized with respect to real-world configurations. Memory for these scenes was measured by hemi-field presentations of detail probes and whole scene probes. The results showed that there were no differences between the two visual fields in accuracy scores. Latency of positive responses showed that memory for the common/organized scenes was better in the left (LVF) than in the right visual field (RVF) and a dissociation between the two types of pictorial organization was present only in the LVF, with the slower latencies for unorganized scenes. The effect of probe-type was also different in the two visual fields: detail and whole scene probes were undifferentiated within the LVF but were differentiated in the RVF, with whole scenes remembered more quickly. The findings are discussed in terms of asymmetries in storage/retrieval of schemata in LTSM.


Effect of training on hormonal responses to exercise in competitive swimmers.
The effects of 9 weeks of training on responses of plasma hormones to swimming were studied in eight competitive swimmers who had not trained for several months. Two types of swimming tests were used: (1) 200 yd, a high intensity, exhausting type of exercise in which maximal effort was required both before and after training, and (2) 1000 yd, a pace type of exercise in which subjects swam as fast as possible prior to training and at the same rate after training. Plasma levels of glucagon increased and of insulin decreased during 1000 yd of swimming, but were not altered by 200 yd of swimming. No training effects were apparent in responses of plasma insulin and glucagon to these shortterm, high intensity exercise tests. During the 1000 yd swim, plasma adrenaline was 0.8 ng/ml before vs. 0.1 ng/ml after training. Plasma noradrenaline response decreased from 3.4 to 1.2 ng/ml as a result of training. In the 200 yd swim, adrenaline, but not noradrenaline, was lower after training.


Genetic markers in Libyan Jews.
Blood groups, serum proteins, and red-cell enzyme frequencies were determined on a random sample of 148 Libyan Jews now settled in Israel. Comparisons with data on Libyan non-Jews show significant differences in most systems, implying maintenance of a high degree of genetic isolation of the Jewish group from surrounding populations. The relative lack of the African component in their gene pool shows that they have interbred very little, if at all, with their negroid neighbours.


Glycoprotein IIb/IIIa blockade inhibits platelet-mediated force development and reduces gel elastic modulus.
The effects of GPIIb/IIIa blockade on clot retraction were studied utilizing an instrument which directly measures force produced by platelets. GPIIb/IIIa disruption by calcium chelation, and GPIIb/IIIa blockade by peptides and anti-GPIIb/IIIa antibodies were investigated. One mM EDTA suppressed ADP-induced platelet aggregation by 72% and reduced force developed at 1200 s by 33%. At 234 microM, the tetrapeptide Arg-Gly-Asp-Ser (RGDS) suppressed platelet aggregation by 74%, reduced force at 1200 s by 45% and reduced gel elastic modulus by 19%. At 10 microM, the peptide D-Arg-Gly-L-Asp-L-Try (D-RGDW) completely suppressed platelet aggregation, reduced force development by 38% and reduced gel elastic modulus by 29%. At 0.133 microM, monoclonal anti-GPIIIa antibody (AP-3) reduced force development by 74% and reduced gel modulus by 60%. Murine antiGPIIb/IIIa antibodies 10E5 and 7E3 markedly suppressed force development. At 0.133 microM, 10E5 reduced force by 89% and reduced gel modulus by 67%. At 0.053 microM, 7E3 completely stopped force development and reduced gel modulus by 46%. Platelet aggregation was blocked by 0.027 microM 7E3. Selective GPIIb blockade by antibodies did not affect force development. None of the agents studied altered fibrin structure as monitored by effects of fibrin mass/length ratios. Suppression of platelet aggregation occurred at inhibitor concentrations substantially lower than those required to suppress force development. Complete suppression of platelet aggregation did not assure inhibition of clot retraction probably due to profound platelet activation by thrombin.(ABSTRACT TRUNCATED AT 250 WORDS)


MicroRNA-495 inhibits proliferation of glioblastoma multiforme cells by downregulating cyclin-dependent kinase 6.
Glioblastoma multiforme (GBM) is the most aggressive type of glioma and carries the poorest chances of survival. There is therefore an urgent need to understand the mechanisms of glioma tumorigenesis and develop or improve therapeutics. The aim of this study was to assess the possible prognostic value of cyclin-dependent kinase 6 (CDK6) and the effects of microRNA-495 (miR-495) manipulation on CDK6 expression and cell survival in glioma cells. Analyses of clinical specimens from GBM patients were used. Expression of CDK6 was analyzed by real-time polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemistry. Expression of CDK6 was also analyzed after over-expression of miR-495 in T98 cells; both cell proliferation and RB phosphorylation were examined. Cell proliferation, cell cycle distribution, and RB phosphorylation were also examined after knockdown of CDK6 in U87-MG and T98 cells. Analyses of clinical specimens from GBM patients identified that CDK6 is significantly expressed in gliomas. CDK6 antigen expression was higher in tumor cores and margins than in adjacent normal brain tissues, and higher levels of CDK6 expression in the tumor margin correlated with decreased survival. Over-expression of miR-495 in T98 cells downregulated the expression of CDK6 and inhibited retinoblastoma phosphorylation, and knockdown of CDK6 in U87-MG and T98 cells by siRNAs resulted in cell cycle arrest at the G1/S transition and inhibition of cell proliferation. This study revealed miR-495 is down-regulated in glioma tissues. Furthermore, miR-495 regulated CDK6 expression and involved in glioma cell growth inhibition, which indicated the possible role of miR-495 in tumor progression.


Nasal mucosal blood flow after intranasal allergen challenge.
The nasal mucosal blood flow in patients with allergic rhinitis was determined at nasal allergen challenges with the 133Xenon washout method. Determinations were made in 12 subjects before and 15 minutes after challenge with diluent and increasing doses of allergen. The time course was followed in eight subjects by means of repeated measurements during 1 hour after a single allergen dose. Finally, the blood flow was measured after unilateral allergen challenge in the contralateral nasal cavity. A dose-dependent decrease in blood flow was found after nasal challenge with increasing doses of allergens, whereas challenge with diluent alone did not induce any changes. The highest allergen dose, which also induced pronounced nasal symptoms, resulted in a decrease in blood flow of 25% (p less than 0.001). The time-course study demonstrated a maximum decrease in blood flow 10 to 20 minutes after challenge and then a gradual return to baseline. Unilateral allergen challenge resulted in a decrease in blood flow in the contralateral, unchallenged nasal cavity, suggesting that part of the allergen-induced changes in blood flow were reflex mediated.


Supermacroporous chemically cross-linked poly(aspartic acid) hydrogels.
Chemically cross-linked poly(aspartic acid) (PASP) gels were prepared by a solid-liquid phase separation technique, cryogelation, to achieve a supermacroporous interconnected pore structure. The precursor polymer of PASP, polysuccinimide (PSI) was cross-linked below the freezing point of the solvent and the forming crystals acted as templates for the pores. Dimethyl sulfoxide was chosen as solvent instead of the more commonly used water. Thus larger temperatures could be utilized for the preparation and the drawback of increase in specific volume of water upon freezing could be eliminated. The morphology of the hydrogels was characterized by scanning electron microscopy and interconnectivity of the pores was proven by the small flow resistance of the gels. Compression tests also confirmed the interconnected porous structure and the complete re-swelling and shape recovery of the supermacroporous PASP hydrogels. The prepared hydrogels are of interest for several biomedical applications as scaffolding materials because of their cytocompatibility, controllable morphology and pH-responsive character.


UHRF1 Is a Novel Druggable Epigenetic Target in Malignant Pleural Mesothelioma.
Ubiquitin-like with plant homeodomain and ring finger domains 1 (UHRF1) encodes a master regulator of DNA methylation that has emerged as an epigenetic driver in human cancers. To date, no studies have evaluated UHRF1 expression in malignant pleural mesothelioma (MPM). This study was undertaken to explore the therapeutic potential of targeting UHRF1 in MPM. Microarray, real-time quantitative reverse transcription-polymerase chain reaction, immunoblot, and immunohistochemistry techniques were used to evaluate UHRF1 expression in normal mesothelial cells (NMCs) cultured with or without asbestos, MPM lines, normal pleura, and primary MPM specimens. The impact of UHRF1 expression on MPM patient survival was evaluated using two independent databases. RNA-sequencing, proliferation, invasion, and colony formation assays, and murine xenograft experiments were performed to evaluate gene expression and growth of MPM cells after biochemical or pharmacologic inhibition of UHRF1 expression. UHRF1 expression was significantly higher in MPM lines and specimens relative to NMC and normal pleura. Asbestos induced UHRF1 expression in NMC. The overexpression of UHRF1 was associated with decreased overall survival in patients with MPM. UHRF1 knockdown reversed genomewide DNA hypomethylation, and inhibited proliferation, invasion, and clonogenicity of MPM cells, and growth of MPM xenografts. These effects were phenocopied by the repurposed chemotherapeutic agent, mithramycin. Biochemical or pharmacologic up-regulation of p53 significantly reduced UHRF1 expression in MPM cells. RNA-sequencing experiments exhibited the pleiotropic effects of UHRF1 down-regulation and identified novel, clinically relevant biomarkers of UHRF1 expression in MPM. UHRF1 is an epigenetic driver in MPM. These findings support the efforts to target UHRF1 expression or activity for mesothelioma therapy.


Male-biased protein expression in primordial germ cells, identified through a comparative study of UAS vectors in Drosophila.
In Drosophila, three types of UAS vectors (UASt, UASp, and UASz) are currently available for use with the Gal4-UAS system. They have been used successfully in somatic cells and germline cells from ovaries. However, it remains unclear whether they are functional in the germline cells of embryos, larvae, and adult testes. In this study, we found that all three types of UAS vectors were functional in the germline cells of embryos and larvae and that the UASt and UASz vectors were active in the germline of the distal tip region in adult testes. Moreover, we observed that protein expression from the UAS vectors was male-biased in germline cells of late embryos, whereas their respective mRNA expression levels were not. Furthermore, O-propargyl-puromycin (OPP) staining revealed that protein synthesis was male-biased in these germline cells. In addition, GO terms related to translation and ribosomal maturation were significantly enriched in the male germline. These observations show that translational activity is higher in male than in female germline cells. Therefore, we propose that male-biased protein synthesis may be responsible for the sex differences observed in the early germline.


High performance flexible and antibacterial strain sensor based on silver‑carbon nanotubes coated cellulose/polyurethane nanofibrous membrane: Cellulose as reinforcing polymer blend and polydopamine as compatibilizer.
In this study, ethyl cellulose was used as the second-phase polymer blended with polyurethane to make nanofibrous membrane as antibacterial strain sensor. The results indicated that ethyl cellulose could regulate the morphology of polyurethane through strong hydrogen bonding, which observably enhanced the nanofiber uniformity of polyurethane. Furthermore, rigid cellulose also remarkably improved the mechanical strength and thermal stability of the nanofibrous membrane. After being coated with silver nanoparticles and carbon nanotubes assisted by polydopamine (PDA), the membrane with outstanding bacteria inhibition performance exhibited outstanding sensitivity toward external mechanical stretching, as well as real-time motion of human body parts. The conductive composite membrane possessed sensitive and regular resistance feedback to 100 cycles of varied human motions. The cellulose in the nanofiber structure ensured the shape recovery and longtime use stability of the membrane. This study proposed a novel thinking for the construction of high performance strain sensor by rational introduction of rigid polysaccharide into the polymer matrix.