Nutritional screening for risk prediction in patients scheduled for abdominal operations.
Increased risks related to surgery might reflect the nutritional status of some patients. Such a group might benefit from perioperative nutritional support. The purpose of this study was to identify the relative importance of nutritional risk screening along with established medical, anaesthetic and surgical predictors of postoperative morbidity and mortality. This prospective observational study enrolled consecutive eligible patients scheduled for elective abdominal operations. Data were collected on nutritional variables (body mass index, weight loss, food intake), age, sex, type and extent of operation, underlying disease, American Society of Anesthesiologists grade and co-morbidities. A modified composite nutritional screening tool (Nutritional Risk Screening, NRS 2002) currently recommended by European guidelines was used. Relative complication rates were calculated with multiple logistic regression and cumulative proportional odds models. Some 653 patients were enrolled of whom 132 (20.2 per cent) sustained one or more postoperative complications. The frequency of this event increased significantly with a lower food intake before hospital admission. No other individual or composite nutritional variable provided comparable or better risk prediction (including NRS 2002). Other factors significantly associated with severe postoperative complications were ASA grade, male sex, underlying disease, extent of surgical procedure and volume of transfused red cell concentrates. In abdominal surgery, preoperative investigation of feeding habits may be sufficient to identify patients at increased risk of complications. Nutritional risk alone, however, is not sufficient to predict individual risk of complications reliably.


Genes adopt non-optimal codon usage to generate cell cycle-dependent oscillations in protein levels.
The cell cycle is a temporal program that regulates DNA synthesis and cell division. When we compared the codon usage of cell cycle-regulated genes with that of other genes, we discovered that there is a significant preference for non-optimal codons. Moreover, genes encoding proteins that cycle at the protein level exhibit non-optimal codon preferences. Remarkably, cell cycle-regulated genes expressed in different phases display different codon preferences. Here, we show empirically that transfer RNA (tRNA) expression is indeed highest in the G2 phase of the cell cycle, consistent with the non-optimal codon usage of genes expressed at this time, and lowest toward the end of G1, reflecting the optimal codon usage of G1 genes. Accordingly, protein levels of human glycyl-, threonyl-, and glutamyl-prolyl tRNA synthetases were found to oscillate, peaking in G2/M phase. In light of our findings, we propose that non-optimal (wobbly) matching codons influence protein synthesis during the cell cycle. We describe a new mathematical model that shows how codon usage can give rise to cell-cycle regulation. In summary, our data indicate that cells exploit wobbling to generate cell cycle-dependent dynamics of proteins.


Induction of apoptosis by aryl-substituted diamines: role of aromatic group substituents and distance between nitrogens.
A series of aromatic substituted diamines was synthesized and characterized for their cytotoxic profiles against human breast and prostate tumor cell lines. Following a structure function analysis of the effects of changes of the benzyl substituents and the distance between amino groups the most potent analogues were analyzed biologically and were shown to induce apoptosis. These compounds do not induce the enzyme SSAT or deplete intracellular polyamine levels, mechanisms demonstrated by other cytotoxic polyamine analogues.


A Generative Model to Synthesize EEG Data for Epileptic Seizure Prediction.
Scarcity of good quality electroencephalography (EEG) data is one of the roadblocks for accurate seizure prediction. This work proposes a deep convolutional generative adversarial network (DCGAN) to generate synthetic EEG data. Another objective of our study is to use transfer-learning (TL) for evaluating the performance of four well-known deep-learning (DL) models to predict epileptic seizure. We proposed an algorithm that generate synthetic data using DCGAN trained on real EEG data in a patient-specific manner. We validate quality of generated data using one-class SVM and a new proposal namely convolutional epileptic seizure predictor (CESP). We evaluate performance of VGG16, VGG19, ResNet50, and Inceptionv3 trained on augmented data using TL with average time of 10 min between true prediction and seizure onset samples. The CESP model achieves sensitivity of 78.11% and 88.21%, and false prediction rate of 0.27/h and 0.14/h for training on synthesized and testing on real Epilepsyecosystem and CHB-MIT datasets, respectively. Using TL and augmented data, Inceptionv3 achieved highest accuracy with sensitivity of 90.03% and 0.03 FPR/h. With the proposed data augmentation method prediction results of CESP model and Inceptionv3 increased by 4-5% as compared to state-of-the-art augmentation techniques. The performance of CESP shows that synthetic data acquired association between features and labels very well and by using the augmented data CESP predicted better than chance level for both datasets. The proposed DCGAN can be used to generate synthetic data to increase the prediction performance and to overcome good quality data scarcity issue.


Association of deoxyribonuclease I with the pointed ends of actin filaments in human red blood cell membrane skeletons.
We have characterized the interaction of bovine pancreatic deoxyribonuclease I (DNase I) with the filamentous (F-)actin of red cell membrane skeletons stabilized with phalloidin. The hydrolysis of [3H]DNA was used to assay DNase I. We found that DNase I bound to a homogenous class of approximately equal to 2.4 X 10(4) sites/skeleton with an association rate constant of approximately 1 X 10(6) M-1 S-1 and a KD of 1.9 X 10(-9) M at 20 degrees C. Phalloidin lowered the dissociation constant by approximately 1 order of magnitude. The DNase I which sedimented with the skeletons was catalytically inactive but could be reactivated by dissociation from the actin. Actin and DNA bound to DNase I in a mutually exclusive fashion without formation of a ternary complex. Phalloidin-treated red cell F-actin resembled rabbit muscle G-actin in all respects tested. Since the DNase I binding capacity of the skeletons corresponded to the number of actin protofilaments previously estimated by other methods, it seemed likely that the enzyme binding site was confined to one end of the filament. We confirmed this premise by showing that elongating the red cell filaments with rabbit muscle actin monomers did not appreciably add to their capacity to bind or inhibit DNase I. Saturation of skeletons with cytochalasin D or gelsolin, avid ligands for the barbed end of actin filaments, did not reduce their binding of DNase I. Furthermore, neither cytochalasin D nor DNase I alone blocked all of the sites for addition of monomeric pyrene-labeled rabbit muscle G-actin to phalloidin-treated skeletons; however, a combination of the two agents did so. In the presence of phalloidin, the polymerization of 300 nM pyrenyl actin on nuclei constructed from 5 nM gelsolin and 25 nM rabbit muscle G-actin was completely inhibited by 35 nM DNase I but not by 35 nM cytochalasin D. We conclude that DNase I associates uniquely with and caps the pointed (slow-growing or negative) end of F-actin. These results imply that the amino-terminal, DNase I-binding domain of the actin protomer is oriented toward the pointed end and is buried along the length of the actin filament.


Exponential decay of between-month spatial dissimilarity congruence of phytoplankton communities in relation to phosphorus in a highland eutrophic lake.
Phytoplankton species composition has long been recognized to be structured by environmental filtering, but our knowledge of patterns of spatial dissimilarity congruence between the phytoplankton community and environmental divers is rather limited. Specifically, a study on whether there are specific temporal properties that could be more related to spatial dissimilarity remains to be seen. We examined the extent to how spatial dissimilarity changed with seasonal succession by measuring β-diversity in phytoplankton communities in Lake Erhai (from January 2012 to December 2014 at 15 sampling sites) as a function of different period conditions (high-density period and low-density period). We found that congruences of spatial dissimilarity in algal communities over time were neither stable in time nor showed a seasonal pattern. The spatial dissimilarity congruence between the phytoplankton community and dissolved inorganic phosphorus (DIP) concentration followed exponential decay patterns, and this congruence was led by algal cell density. This result implies that species and functions of phytoplankton are specialized, and DIP concentration drastically increases in high-density periods than in low-density periods. This means that DIP enrichment is related to the loss of algal diversity and functions and the increase of algal biomass in eutrophic lakes.


Neighborhood Socioeconomic Status and Identification of Patients With CKD Using Electronic Health Records.
Screening for chronic kidney disease (CKD) is recommended for patients with diabetes and hypertension as stated by the respective professional societies. However, CKD, a silent disease usually detected at later stages, is associated with low socioeconomic status (SES). We assessed whether adding census tract SES status to the standard screening approach improves our ability to identify patients with CKD. Screening test analysis. Electronic health records (EHR) of 256,162 patients seen at a health care system in the 7-county Minneapolis/St. Paul area and linked census tract data. The first quartile of census tract SES (median value of owner-occupied housing units <$165,200; average household income <$35,935; percentage of residents >25 years of age with a bachelor's degree or higher <20.4%), hypertension, and diabetes. CKD (eGFR <60 mL/min/1.73 m2, or urinary albumin-creatinine ratio >30mg/g, or urinary protein-creatinine ratio >150mg/g, or urinary analysis [albuminuria] >30 mg/d). Sensitivity, specificity, and number needed to screen (NNS) to detect CKD if we screened patients who had hypertension and/or diabetes and/or who lived in low-SES tracts (belonging to the first quartile of any of the 3 measures of tract SES) versus the standard approach. CKD was prevalent in 13% of our cohort. Sensitivity, specificity, and NNS of detecting CKD after adding tract SES to the screening approach were 67% (95% CI, 66.2%-67.2%), 61% (95% CI, 61.1%-61.5%), and 5, respectively. With the standard approach, sensitivity of detecting CKD was 60% (95% CI, 59.4%-60.4%), specificity was 73% (95% CI, 72.4%-72.7%), and NNS was 4. One health care system and selection bias. Leveraging patients' addresses from the EHR and adding tract-level SES to the standard screening approach modestly increases the sensitivity of detecting patients with CKD at a cost of decreased specificity. Identifying further factors that improve CKD detection at an early stage are needed to slow the progression of CKD and prevent cardiovascular complications.


Isolation of Corynebacterium group D2 from clinical specimens.
A total of 38 strains of Corynebacterium Group D2 isolated from clinical specimens in Belgian laboratories were characterized by pronounced urease activity, inability to acidify sugars and to reduce nitrates and multiresistance to antibiotics. Two strains were involved in clinical diseases. The organisms were found to have a more opportunistic than pathogenic behaviour.


Effects of vitamin E on the toxicity of oxidized LDL on endothelial cells in vitro in smokers vs nonsmokers on diets rich in fish.
To clarify whether supplementation of vitamin E can alter the low density lipoprotein (LDL) oxidation properties and thereby affect endothelial cell function and prostacyclin production in smokers compared to nonsmokers on diets rich in fish in a pilot study. The LDL of six smokers and six nonsmokers on habitual high fish diet was isolated before and after an 8-week supplementation of vitamin E (800 IU/day). LDL was oxidized by incubation with CuSO4. Cytotoxicity of LDL oxidized to different degrees on endothelial cells was investigated in vitro in these two groups. Helsinki University Central Hospital; Institute of Biomedicine, Pharmacology, University of Helsinki. At baseline, the rate of oxidation was higher in nonsmokers than in smokers. The lag phase increased significantly after the supplementation of vitamin E both in smokers and nonsmokers. Native LDL dose dependently tended to reduce the viability of endothelial cells in vitro more markedly when isolated from smokers than from nonsmokers. Vitamin E supplementation had no beneficial effect on the cytotoxicity of oxidized LDLs in endothelial cell culture. On the other hand, simultaneous administration of Trolox, the water-soluble analogue of vitamin E, attenuated the LDL cytotoxicity on endothelial cells. The vitamin E supplementation to LDL donors attenuated the increase in prostacyclin production both in smokers and nonsmokers. Supplementation of LDL donors (healthy male volunteers on habitual fish diet) with vitamin E increased the lag phase of LDL oxidation, but, on the other hand, did not influence in vitro cytotoxicity of LDL, or prostacyclin production.


Pronounced Seasonal Changes in the Movement Ecology of a Highly Gregarious Central-Place Forager, the African Straw-Coloured Fruit Bat (Eidolon helvum).
Straw-coloured fruit bats (Eidolon helvum) migrate over vast distances across the African continent, probably following seasonal bursts of resource availability. This causes enormous fluctuations in population size, which in turn may influence the bats' impact on local ecosystems. We studied the movement ecology of this central-place forager with state-of-the-art GPS/acceleration loggers and concurrently monitored the seasonal fluctuation of the colony in Accra, Ghana. Habitat use on the landscape scale was assessed with remote sensing data as well as ground-truthing of foraging areas. During the wet season population low (~ 4000 individuals), bats foraged locally (3.5-36.7 km) in urban areas with low tree cover. Major food sources during this period were fruits of introduced trees. Foraging distances almost tripled (24.1-87.9 km) during the dry season population peak (~ 150,000 individuals), but this was not compensated for by reduced resting periods. Dry season foraging areas were random with regard to urban footprint and tree cover, and food consisted almost exclusively of nectar and pollen of native trees. Our study suggests that straw-coloured fruit bats disperse seeds in the range of hundreds of meters up to dozens of kilometres, and pollinate trees for up to 88 km. Straw-coloured fruit bats forage over much larger distances compared to most other Old World fruit bats, thus providing vital ecosystem services across extensive landscapes. We recommend increased efforts aimed at maintaining E. helvum populations throughout Africa since their keystone role in various ecosystems is likely to increase due to the escalating loss of other seed dispersers as well as continued urbanization and habitat fragmentation.


The underlying characteristics of sleep behavior and its relationship to sleep-related cognitions: a latent class analysis of college students in Wuhu city, China.
The aim of this study was to gain insight into the sleep quality of college students and related factors from a new perspective by using Latent Class Analysis (LCA). A total of 1,288 college students from four universities in Wuhu city participated in the study. LCA was used to identify the classes of sleep behaviors. Differences in class membership related to selected research factors were examined using multinomial logistic regression analysis.Four distinct classes of behaviors were identified: (1) good sleep (Class 1, 31.8%), (2) prolonged sleep latency (Class 2, 49.1%), (3) sleep disturbances and daytime dysfunction (Class 3, 6.8%), (4) multiple poor sleep behavior (Class 4, 12.3%). The latent classes of sleep behavior were correlated with the DBAS-16 total score (rs = -0.109, P < 0.001). Learning pressure and mental state during the day could affect overall sleep (Class 2, Class 3 and Class 4), and female students were at higher risk of severe sleep problems (Class 3 and Class 4), while bedtime exercised could improve mild sleep problems (Class 2). The sleep behavior of college students in Wuhu city has obvious class heterogeneity, and different influencingfactors may affect sleep to varying degrees. In addition, our research provides a basis for targeted intervnetion in college student's sleep. .


Agonism of free fatty acid receptors 1 and 4 generates peptide YY-mediated inhibitory responses in mouse colon.
Free fatty acid receptors FFA1 and FFA4 are located on enteroendocrine L cells with the highest gastrointestinal (GI) expression in descending colon. Their activation causes the release of glucagon-like peptide 1 and peptide YY (PYY) from L cells. Additionally, FFA1 agonism releases insulin from pancreatic β cells. As these receptors are modulators of nutrient-stimulated glucose regulation, the aim of this study was to compare the pharmacology of commercially available agonists (TUG424, TUG891, GW9508) with proven selective agonists (JTT, TAK-875, AZ423, Metabolex-36) in mice. Mouse mucosa was mounted in Ussing chambers, voltage-clamped and the resultant short-circuit current (Isc ) was recorded continuously. Pretreatments included antagonists of FFA1, Y1 or Y2 receptors. Glucose sensitivity was investigated by mannitol replacement apically, and colonic and upper GI transit was assessed in vitro and in vivo. FFA1 and FFA4 agonism required glucose and reduced Isc in a PYY-Y1 receptor-dependent manner. The novel compounds were more potent than GW9508. The FFA1 antagonists (GW1100 and ANT825) blocked FFA1 activity only and revealed FFA1 tonic activity. The FFA4 agonist, Metabolex-36, slowed colonic transit in vitro but increased small intestinal transit in vivo. The selective FFA1 and FFA4 agonists were more potent at reducing Isc than GW9508, a dual FFA1 and FFA4 agonist. A paracrine epithelial mechanism involving PYY-stimulated Y1 receptors mediated their responses, which were glucose sensitive, potentially limiting hypoglycaemia. ANT825 revealed tonic activity and the possibility of endogenous FFA1 ligands causing PYY release. Finally, FFA4 agonism induced regional differences in transit.


Evaluating the probability of CRISPR-based gene drive contaminating another species.
The probability D that a given clustered regularly interspaced short palindromic repeats (CRISPR)-based gene drive element contaminates another, nontarget species can be estimated by the following Drive Risk Assessment Quantitative Estimate (DRAQUE) Equation: D = h y b + t r a n s f × e x p r e s s × c u t × f l a n k × i m m u n e × n o n e x t i n c t with hyb = probability of hybridization between the target species and a nontarget species; transf = probability of horizontal transfer of a piece of DNA containing the gene drive cassette from the target species to a nontarget species (with no hybridization); express = probability that the Cas9 and guide RNA genes are expressed; cut = probability that the CRISPR-guide RNA recognizes and cuts at a DNA site in the new host; flank = probability that the gene drive cassette inserts at the cut site; immune = probability that the immune system does not reject Cas9-expressing cells; nonextinct = probability of invasion of the drive within the population. We discuss and estimate each of the seven parameters of the equation, with particular emphasis on possible transfers within insects, and between rodents and humans. We conclude from current data that the probability of a gene drive cassette to contaminate another species is not insignificant. We propose strategies to reduce this risk and call for more work on estimating all the parameters of the formula.


Reflections on the classification of yeasts for different end-users in biotechnology, ecology, and medicine.
The approach to yeast identification has significantly changed in just a few decades due to the rapid increase in basic biological knowledge, increased interest in the practical applications and biodiversity of this important microbial group, and enormous technological advances. While some conventional methods can still be validly applied, many molecular techniques have been developed that allow for strain classification on all taxonomic levels. A critical evaluation of the actual scope of each identification procedure will in the end determine the most appropriate use of the many protocols now available. Nonetheless, the oldest tool of microbiology, the microscope, is still a fundamental accessory for studies involving yeast biology, biodiversity and taxonomy.


If 'atypical' neuroleptics did not exist, it wouldn't be necessary to invent them: perverse incentives in drug development, research, marketing and clinical practice.
Perverse incentives in drug development, research, marketing and clinical usage can be illustrated by considering the example of the so-called 'atypical' neuroleptics which have grown to become a standard - indeed expanding - part of psychiatric practice despite their probable inferiority to older sedative agents. There is now ample evidence to suggest that neuroleptics (aka. anti-psychotics and major tranquillizers) are dangerous drugs, and patients' exposure to them should be minimized wherever possible. This clinical imperative applies whether neuroleptics are of the traditional type or atypical variety, albeit for different reasons since the traditional agents are neurotoxic, while atypicals are mainly metabolic poisons. Usage of traditional neuroleptics seems indeed to be declining progressively, but the opposite seems to be happening for 'atypicals', and new indications for these drugs are being promoted. Yet the atypical neuroleptics are a category of pharmaceuticals which are close to being un-necessary since there are safer, cheaper and pleasanter substitutes, such as benzodiazepines and the sedative antihistamines (e.g. promethazine). If 'atypical' neuroleptics did not exist, it would not be necessary to invent them. Analysis of how such expensive, dangerous and inferior drugs as the 'atypicals' have nevertheless come to dominate clinical practice casts light on the perverse incentives which now motivate the pharmaceutical industry in an era of massive state regulation. The lack of positive incentives to deploy off-patent drugs is longstanding, but there is a new disincentive in the widespread but erroneous belief that only randomized controlled trials (RCTs) can provide valid 'evidence' of effectiveness. Consequently, those who control RCTs now control clinical practice. It sometimes makes commercial sense to develop and market new drugs that are inferior to existing agents, since new drugs are patent-protected and can be promoted on the back of a mass of new RCTs funded and 'owned' by the pharmaceutical corporations. The current regulatory and patenting situation, therefore, requires major reform if drug efficacy and patient safety are to become higher priorities. Given that psychiatric practice is apparently 'locked-in' to prescribing atypicals, and if (as seems likely) most informed individuals would wish to avoid neuroleptics for themselves and their loved-ones except as a last resort; then in the short-term it may be wise for patients and their families to explore the possibilities of increased self-management of psychiatric problems using over-the-counter drugs, such as the sedative antihistamines. In the long-term, there need to be legal reforms to change the regulatory and commercial framework of incentives relating to drug development. These might include new forms of short-term re-patenting of old drugs.


Lipocalin2 enhances the matrix metalloproteinase-9 activity and invasion of extravillous trophoblasts under hypoxia.
The invasion of extravillous trophoblasts (EVTs) to the decidua and spiral arteries in early pregnancy is a crucial step for a successful pregnancy; however, its mechanisms are not fully understood. Lipocalin2 (LCN2), a multifunctional secretory protein known as neutrophil gelatinase-associated lipocalin (NGAL), reportedly enhanced invasiveness via the activation of matrix metalloproteinase-9 (MMP-9) in several cancer cells. In this study, the expression and function of LCN2 in early placenta were analyzed. Early placental tissues between 7 and 10 weeks of gestation were obtained from normal pregnant women who underwent elective termination. The expression of LCN2 was examined using immunostaining and RT-PCR. EVTs isolated from these placental tissues and a choriocarcinoma cell line (JAR) were used to investigate the effects of LCN2 on proliferation, invasion potential, and MMP-9 activity under hypoxia using a WST-1 assay, Matrigel invasion assay, and gelatin gel zymography, respectively. The immunohistochemical expression of LCN2 was observed in the cytoplasm of EVTs, cytotrophoblasts and the decidua, but not in syncytiotrophoblasts. The addition of recombinant LCN2 did not affect proliferation, but enhanced the invasiveness (500 ng/mL, p < 0.01) and MMP-9 activity of primary cultured EVTs and JAR in a dose-dependent manner. Silencing LCN2 using shRNA reduced the invasiveness (p < 0.01) and MMP-9 activity of JAR. In addition, the hypoxic condition (2% O₂) increased LCN2 expression (p < 0.01), MMP-9 activity, and invasive ability (p < 0.01). LCN2 was involved in the invasiveness of EVTs, especially under hypoxia, via increased MMP-9 activity.


Contingency Horizon: on Private Events and the Analysis of Behavior.
Skinner's radical behaviorism incorporates private events as biologically based phenomena that may play a functional role with respect to other (overt) behavioral phenomena. Skinner proposed four types of contingencies, here collectively termed the contingency horizon, which enable certain functional relations between private events and verbal behavior. The adequacy and necessity of this position has met renewed challenges from Rachlin's teleological behaviorism and Baum's molar behaviorism, both of which argue that all "mental" phenomena and terminology may be explained by overt behavior and environment-behavior contingencies extended in time. A number of lines of evidence are presented in making a case for the functional characteristics of private events, including published research from behavior analysis and general experimental psychology, as well as verbal behavior from a participant in the debate. An integrated perspective is offered that involves a multiscaled analysis of interacting public behaviors and private events.


Sesamin reduces acute hepatic injury induced by lead coupled with lipopolysaccharide.
In this study, we investigated the potential anti-inflammatory and antioxidative effects of sesamin on acute liver injury. Lead (Pb) causes oxidative damage and enhances the effects of low-dose lipopolysaccharide (LPS), inducing acute hepatic injury in rats. Male Sprague-Dawley rats were given intraperitoneal injections of Pb acetate (5 mg/kg) and LPS (50 μg/kg) to induce liver injury, and we tested the effects of oral administration of sesamin (10 mg/kg) on liver damage. To assess the extent of acute hepatic injury in the rats, we measured the anti-inflammatory and antioxidant markers and relevant signaling pathways: serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), C-reactive protein (CRP), reactive oxygen species (ROS), tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, nitric oxide (NO), and cyclooxygenase-2 (COX-2), inducible NO synthase (iNOS) levels, mitogen-activated protein kinases (MAPKs), c-Fos, and GADD45β. Sesamin significantly decreased the serum AST, ALT, and CRP levels in the rat model. In the Pb and LPS-stressed rats, sesamin administration reduced the serum levels of TNF-α, IL-1, IL-6, NO, and ROS generation, and liver tissue expressions of c-Jun N-terminal kinase (JNK), p38 MAPK, GADD45β, COX-2, and iNOS. Collectively, these results demonstrate that sesamin is associated with antioxidant and anti-inflammatory activity. The observed effect of scavenging of ROS and NO and inhibiting the production of proinflammatory cytokines may be achieved through the suppression of COX-2, iNOS, and MAPK pathways in the acute hepatic injury rats.


Incorporation of gypsum waste in ceramic block production: Proposal for a minimal battery of tests to evaluate technical and environmental viability of this recycling process.
Civil engineering-related construction and demolition debris is an important source of waste disposed of in municipal solid waste landfills. After clay materials, gypsum waste is the second largest contributor to the residential construction waste stream. As demand for sustainable building practices grows, interest in recovering gypsum waste from construction and demolition debris is increasing, but there is a lack of standardized tests to evaluate the technical and environmental viability of this solid waste recycling process. By recycling gypsum waste, natural deposits of gypsum might be conserved and high amounts of the waste by-product could be reused in the civil construction industry. In this context, this paper investigates a physical property (i.e., resistance to axial compression), the chemical composition and the ecotoxicological potential of ceramic blocks constructed with different proportions of clay, cement and gypsum waste, and assesses the feasibility of using a minimal battery of tests to evaluate the viability of this recycling process. Consideration of the results for the resistance to axial compression tests together with production costs revealed that the best formulation was 35% of plastic clay, 35% of non-plastic clay, 10% of Portland cement and 20% of gypsum waste, which showed a mean resistance of 4.64MPa. Energy dispersive X-ray spectrometry showed calcium and sulfur to be the main elements, while quartz, gypsum, ettringite and nacrite were the main crystalline compounds found in this formulation. Ecotoxicity tests showed that leachate from this formulation is weakly toxic toward daphnids and bacteria (EC(20%)=69.0 and 75.0, respectively), while for algae and fish the leachate samples were not toxic at the EC(50%) level. Overall, these results show that the addition of 20% of gypsum waste to the ceramic blocks could provide a viable substitute for clay in the ceramics industry and the tests applied in this study proved to be a useful tool for the technical and environmental evaluation of this recycling process, bacterial and daphnid tests being more sensitive than algae and fish tests.


Fragile X syndrome in Japanese patients with infantile autism.
Forty-seven patients (39 boys and 8 girls) with infantile autism whose clinical symptoms had matched the diagnostic criteria of DSM III were studied cytogenetically for the occurrence of fragile X [fra(X)] syndrome. The existence of fra(X) chromosome in these patients was screened first by culturing peripheral blood lymphocytes in a medium in which folic acid was absent; the fra(X) chromosome then was confirmed by reculturing in another medium to which 5-fluoro-2'-deoxyuridine was added for the last 24 hours of culture. Fra(X) chromosome was found in 2 of 39 male patients, but in none of the female patients; the 2 patients are siblings. Thus, fra(X) syndrome occurs in 2.6% (1/38) in this study population of male autistic children. The frequencies of fra(X) expression in the older brother with mild mental retardation, in the more severely retarded younger brother, and in their mother were 3-5%, 17-20%, and 9-3%, respectively. Of the two methods used in the present study, the method employing 5-fluoro-2'-deoxyuridine tended to be more sensitive to fra(X) chromosome detection, especially for a suspected carrier.


Massive Esophageal Variceal Bleeding as a Rare Complication of Sickle Cell Anemia.
A 24-year-old man with sickle cell anemia presented with fatigue, dark stool, and coffee ground emesis. He was found to have large esophageal varices and experienced massive variceal hemorrhage in the hospital. The varices were caused by diffuse splanchnic venous thrombosis, and his only risk factor for hypercoagulability was sickle cell anemia. Splanchnic venous thrombosis due to sickle cell anemia is exceedingly rare.


Genetic Evidence for Colletotrichum gloeosporioides Transmission Between the Invasive Plant Ageratina adenophora and Co-occurring Neighbor Plants.
To understand the disease-mediated invasion of exotic plants and the potential risk of disease transmission in local ecosystems, it is necessary to characterize population genetic structure and spatio-temporal dynamics of fungal community associated with both invasive and co-occurring plants. In this study, multiple genes were used to characterize the genetic diversity of 165 strains of Colletotrichum gloeosporioides species complex (CGSC) isolated from healthy leaves and symptomatic leaves of invasive plant Ageratina adenophora, as well as symptomatic leaves of its neighbor plants from eleven geographic sites in China. The data showed that these CGSC strains had a high genetic diversity in each geographic site (all Hd > 0.67 and Pi > 0.01). Haplotype diversity and nucleotide diversity varied greatly in individual gene locus: gs had the highest haplotype diversity (Hd = 0.8972), gapdh had the highest nucleotide diversity (Pi = 0.0705), and ITS had the lowest nucleotide diversity (Pi = 0.0074). Haplotypes were not clustered by geographic site, invasive age, or isolation source. AMOVA revealed that the genetic variation was mainly from within-populations, regardless of geographic or isolation origin. Both AMOVA and neutrality tests indicated these CGSC strains occurred gene exchange among geographic populations but did not experience population expansion along with A. adenophora invasion progress. Our data indicated that A. adenophora primarily accumulated these CGSC fungi in the introduced range, suggesting a high frequency of CGSC transmission between A. adenophora and co-occurring neighbor plants. This study is valuable for understanding the disease-mediated plant invasion and the potential risk of disease transmission driven by exotic plants in local ecosystems.


The lower the expectations in controlling the symptoms of advanced cancer patients, the better the clinical response.
The aim of this study was to compare patients' global impression (PGI) and the achievement of personalised symptom goal response (PSGR), after a comprehensive palliative care treatment in advanced cancer patients having high (HPSG) and low symptom goals (LPSG). Advanced cancer patients admitted to palliative care units rated symptoms intensity by the Edmonton Symptom Assessment Score (ESAS) at admission and then after one week of comprehensive palliative care treatment. For each symptom, patients were divided into two groups, according to their patient symptom goal (PSG): ≥4 (HPSG), and 0-2 (LPSG). PGI and PSGR were evaluated after one week of palliative care. The Memorial Delirium Assessment Scale (MDAS) was assessed at admission. After one week of palliative care, changes in ESAS items were significantly larger in the HPSG group. HPSG patients had a better PGI and reached their target more frequently than LPSG patients for pain, weakness, and poor well-being. LPSG patients were more likely to obtain their target for appetite and insomnia. HPSG patients were more likely to have a lower Karnofsky, a lower educational level, older age, or higher MDAS values for the different ESAS items. Advanced cancer patients with low expectations (HPSG) were more likely to achieve their PSGR after a comprehensive palliative care treatment, reporting also a better PGI for some leading symptoms such as pain, weakness, and poor well-being. More fragile patients seem to have lower expectations and to be more likely to be satisfied.


Testing for mutagens in an aluminium plant. The results of Salmonella typhimurium tests on expectorates from exposed workers.
Methanol extracts of hydrolyzed expectorate samples from workers in a Söderberg potroom were evaluated by the Salmonella reversion assay. The expectorates from exposed workers--mostly from smokers, but also to a certain extent from nonsmokers--were mutagenic; however, the control samples from both smokers and nonsmokers were not. The positive results produced by the expectorate samples from the exposed smokers suggest a synergistic relationship between exposure to air pollution of the working atmosphere and smoking.


Signaling pathway of globo-series glycosphingolipids and β1,3-galactosyltransferase V (β3GalT5) in breast cancer.
The globo-series glycosphingolipids (GSLs) SSEA3, SSEA4, and Globo-H specifically expressed on cancer cells are found to correlate with tumor progression and metastasis, but the functional roles of these GSLs and the key enzyme β1,3-galactosyltransferase V (β3GalT5) that converts Gb4 to SSEA3 remain largely unclear. Here we show that the expression of β3GalT5 significantly correlates with tumor progression and poor survival in patients, and the globo-series GSLs in breast cancer cells form a complex in membrane lipid raft with caveolin-1 (CAV1) and focal adhesion kinase (FAK) which then interact with AKT and receptor-interacting protein kinase (RIP), respectively. Knockdown of β3GalT5 disrupts the complex and induces apoptosis through dissociation of RIP from the complex to interact with the Fas death domain (FADD) and trigger the Fas-dependent pathway. This finding provides a link between SSEA3/SSEA4/Globo-H and the FAK/CAV1/AKT/RIP complex in tumor progression and apoptosis and suggests a direction for the treatment of breast cancer, as demonstrated by the combined use of antibodies against Globo-H and SSEA4.


Age-dependent increases in oxidative damage to DNA, lipids, and proteins in human skeletal muscle.
A role for oxidative damage in normal aging is supported by studies in experimental animals, but there is limited evidence in man. We examined markers of oxidative damage to DNA, lipids, and proteins in 66 muscle biopsy specimens from humans aged 25 to 93 years. There were age-dependent increases in 8-hydroxy-2-deoxyguanosine (OH8dG), a marker of oxidative damage to DNA, in malondialdehyde (MDA), a marker of lipid peroxidation, and to a lesser extent in protein carbonyl groups, a marker of protein oxidation. The increases in OH8dG were significantly correlated with increases in MDA. These results provide evidence for a role of oxidative damage in human aging which may contribute to age-dependent losses of muscle strength and stamina.


Biaryl ureas as potent and orally efficacious melanin concentrating hormone receptor 1 antagonists for the treatment of obesity.
Herein, we report a small molecule MCH-R1 antagonist which demonstrates oral efficacy in chronic rodent models. Substituted phenyl biaryl urea derivatives were synthesized and evaluated as MCH-R1 antagonists for the treatment of obesity. The structure-activity relationship studies in this series resulted in identification of urea 1 as a potent and selective MCH-R1 antagonist. Compound 1 exhibited oral efficacy in chronic (28 d) rodent models at 3-30 mpk showing significant reduction in food intake and weight gain relative to controls.


[The e(y)3 gene codes for SAYP, an evolutionary conserved protein that is essential for ontogeny].
Enhancers of yellow (e(y)) is a group of genetically and functionally related genes. The proteins encoded by these genes are involved in transcription regulation. The e(y)3 gene under study codes for an ubiquitous nuclear protein, termed SAYP, which has homologs in various multicellular organisms. SAYP contains an AT-hook domain, two PHD domains, and a new evolutionarily conserved domain. SAYP mutants die during embryonic development. The weak e(y)ul mutation causes multiple malformations. The potent e(y)EMSl mutation causes embryonic death, implicating SAYP in early development.


B cell linker protein (BLNK) is a regulator of Met receptor signaling and trafficking in non-small cell lung cancer.
Met is an oncogene aberrantly activated in multiple cancers. Therefore, to better understand Met biology and its role in disease we applied the Mammalian Membrane Two-Hybrid (MaMTH) to generate a targeted interactome map of its interactions with human SH2/PTB-domain-containing proteins. We identified thirty interaction partners, including sixteen that were previously unreported. Non-small cell lung cancer (NSCLC)-focused functional characterization of a Met-interacting protein, BLNK, revealed that BLNK is a positive regulator of Met signaling, and modulates localization, including ligand-dependent trafficking of Met in NSCLC cell lines. Furthermore, the interaction between Met and GRB2 is increased in the presence of BLNK, and the constitutive interaction between BLNK and GRB2 is increased in the presence of active Met. Tumor phenotypical assays uncovered roles for BLNK in anchorage-independent growth and chemotaxis of NSCLC cell lines. Cumulatively, this study provides a Met-interactome and delineates a role for BLNK in regulating Met biology in NSCLC context.


Toll like receptor 2 agonists lipoteichoic acid and peptidoglycan are able to enhance antigen specific IFNγ release in whole blood during recall antigen responses.
Interferon gamma release assays (IGRA) have been developed to support the diagnosis of diseases like tuberculosis, which lack robust serological test systems. IGRAs focus on cellular immunity especially memory T cells and thus complement serological testing. However, the low frequency of antigen-specific memory T cells in peripheral blood limits IFNγ production to minute amounts and constitutes a major challenge for downstream test systems. We hypothesized that certain toll like receptor (TLR) agonists might enhance IFNγ production in IGRAs after antigen challenge without inducing background cytokine production. In addition, we investigated the potential use of IL2 release after TLR agonist application as another surrogate marker in cytokine release assays. 176 healthy controls (HC) were tested for IFNγ- and IL2-secretion in whole blood in the presence of different TLR agonists with and without antigen challenge by ELISA. The selected TLR agonists were lipopolysaccharide (LPS ≙ TLR4), lipoteichoic acid (LTA ≙ TLR2), peptidoglycan (PGN ≙ TLR2), zymosan (Zym ≙ TLR2 and 6), polyinosinic-polycytidylic acid (Poly I:C ≙ TLR3), flagellin (Fla ≙ TLR5), R848 (≙TLR7 and 8), loxoribine (Lox ≙ TLR7) and bropirimine (Bro ≙ TLR7). TLR2 agonists LTA and PGN increased IFNγ secretion after antigen challenge nearly twofold (740 vs. 443 pg/ml for LTA and 969 vs. 469 pg/ml for PGN, respectively) without eliciting higher background expression. TLR3 agonist Poly(I:C) and TLR5 agonist Fla also induced a twofold increase in IFNγ synthesis (2.230 vs. 1.085 pg/ml for Poly(I:C) and 518 vs. 278 pg/ml for Fla, respectively), but background expression was slightly increased (114 vs. 7 pg/ml for Poly(I:C) and 47 vs. 12 pg/ml for Fla, respectively). IL2 production was not increased after antigen challenge in the presence of LTA, PGN, Poly(I:C) or Fla. The agonists LPS, Zym, R848, Lox and Bro did not raise cytokine synthesis after antigen challenge or they generated high levels of cytokines by themselves. Of all tested agonists TLR2-specific LTA and PGN met the requirements to increase IFNγ synthesis in whole blood after challenge with recall antigens without heightening basal cytokine levels alone. Thus, they constitute a potential costimulating reagent for IGRAs. IL2 did not show any potential as a surrogate marker in cytokine release assays in combination with TLR agonists.


Patent strategies in molecular diversity.
The patentability of combinatorial libraries is examined, requirement by requirement. In general, combinatorial libraries can be patented, as long as the library meets the statutory criteria of utility, novelty, and non-obviousness, and the application meets the standards of enablement, best mode, and written description. Licensing and alternatives to patenting are also considered, along with potential problems unique to combinatorial chemistry agreements.


Additive roles for MCP-1 and MCP-3 in CCR2-mediated recruitment of inflammatory monocytes during Listeria monocytogenes infection.
Chemokine receptor-mediated recruitment of inflammatory cells is essential for innate immune defense against microbial infection. Recruitment of Ly6C(high) inflammatory monocytes from bone marrow to sites of microbial infection is dependent on CCR2, a chemokine receptor that responds to MCP-1 and MCP-3. Although CCR2(-/-) mice are markedly more susceptible to Listeria monocytogenes infection than are wild-type mice, MCP-1(-/-) mice have an intermediate phenotype, suggesting that other CCR2 ligands contribute to antimicrobial defense. Herein, we show that L. monocytogenes infection rapidly induces MCP-3 in tissue culture macrophages and in serum, spleen, liver, and kidney following in vivo infection. Only cytosol invasive L. monocytogenes induce MCP-3, suggesting that cytosolic innate immune detection mechanisms trigger chemokine production. MCP-3(-/-) mice clear bacteria less effectively from the spleen than do wild-type mice, a defect that correlates with diminished inflammatory monocyte recruitment. MCP-3(-/-) mice have significantly fewer Ly6C(high) monocytes in the spleen and bloodstream, and increased monocyte numbers in bone marrow. MCP-3(-/-) mice, like MCP-1(-/-) mice, have fewer TNF- and inducible NO synthase-producing dendritic cells (Tip-DCs) in the spleen following L. monocytogenes infection. Our data demonstrate that MCP-3 and MCP-1 provide parallel contributions to CCR2-mediated inflammatory monocyte recruitment and that both chemokines are required for optimal innate immune defense against L. monocytogenes infection.


Spin-dependent electron transmission through bacteriorhodopsin embedded in purple membrane.
Spin-dependent photoelectron transmission and spin-dependent electrochemical studies were conducted on purple membrane containing bacteriorhodopsin (bR) deposited on gold, aluminum/aluminum-oxide, and nickel substrates. The result indicates spin selectivity in electron transmission through the membrane. Although the chiral bR occupies only about 10% of the volume of the membrane, the spin polarization found is on the order of 15%. The electrochemical studies indicate a strong dependence of the conduction on the protein's structure. Denaturation of the protein causes a sharp drop in the conduction through the membrane.


Cell-mediated immunity to antigens associated with murine sarcoma virus-induced tumors: augmentation of cytolytic T lymphocyte activity by successive specific and nonspecific stimulation in vitro.
It has been shown previously that lymphoid cells from mice which have rejected a tumor induced by the Moloney sarcoma virus-leukemia virus (MSV-MLV) complex develop high levels of specific H-2-restricted cytolytic T lymphocyte (CTL) activity after in vitro stimulation with syngeneic, irradiated MLV-induced lymphoma cells in mixed leukocyte-tumor cell cultures (MLTC). Attempts to further increase lytic activity by restimulating long-term MLTC cells with syngeneic, irradiated lymphoma cells have met but with limited success. This report shows that, in contrast to the lack of increased activity observed after specific stimulation with lymphoma cells, nonspecific stimulation of long-term MLTC cells either with supernatants from secondary mixed leukocyte cultures (2 degrees MLC SN) or with supernatants from concanavalin A-stimulated spleen cells leads, on a per cell basis, to a further 5 to 10-fold increase in CTL activity. The stimulatory activity of 2 degrees MLC SN is due to a factor(s) of apparent mol. wt. of 25,000 to 40,000. The activity of the CTL populations formed under these conditions is at least 100-fold higher against syngeneic as compared to allogeneic MLV-induced or unrelated tumor cells.


A study on the independence of egocentric and allocentric neglect.
Currently there seems to be consensus that visuospatial neglect may involve egocentric and allocentric symptoms. However, the relation between the two is still discussed and models have been proposed based on the high correlation between allocentric and egocentric neglect symptoms. To analyze the relation between these two kinds of symptoms we developed a new paradigm. In contrast to previous paradigms, we varied the extension of the search field and we added centered reference targets to evaluate egocentric effects independent from allocentric effects. Patients with exclusively left-sided neglect (n = 15) and left-sided visual field deficit (VFD) (n = 9) were included. Right brain damaged patients (n = 15) and a healthy control (n = 15) acted as control groups. The results revealed egocentric inattention in VFD patients. Neglect patients suffered from egocentric and allocentric neglect, but we found no interaction between both kinds of impairments in the sense of a monotonous additive or multiplicative increase going from right to left in terms of egocentric and allocentric coordinates. On the contrary, at the outmost left allocentric and egocentric positions, the number of omissions did not increase, unlike in outmost right and centered positions. In conclusion, our experiment shows that egocentric and allocentric neglect can be clearly dissociated in neglect patients and do not interact. Inclusion of neglect patients with a VFD may lead to an artificial interaction between egocentric and allocentric symptoms and this may explain the differences with results of previous studies.


Photoelectron diffraction from laser-aligned molecules with X-ray free-electron laser pulses.
We report on the measurement of deep inner-shell 2p X-ray photoelectron diffraction (XPD) patterns from laser-aligned I2 molecules using X-ray free-electron laser (XFEL) pulses. The XPD patterns of the I2 molecules, aligned parallel to the polarization vector of the XFEL, were well matched with our theoretical calculations. Further, we propose a criterion for applying our molecular-structure-determination methodology to the experimental XPD data. In turn, we have demonstrated that this approach is a significant step toward the time-resolved imaging of molecular structures.


Computational Method to Obtain the Lifetime of Electrons for Polycrystalline Silicon Solar Cells.
Limitations in the calculation of the lifetime of electrons experimentally give a way to calculate the lifetime of the electrons inside the grains of the polycrystalline silicon solar cells through modelling. A theoretical model to calculate the same has been reported here for the first time. Dependency of the solar cell parameters on the lifetime of electrons have been employed to do the calculation. The proposed model has been validated by using the experimentally reported values for calculation.


Evidence for coexistence of serotonin and noradrenaline in sympathetic nerves supplying brain vessels of guinea pig.
Nerve fibers containing 5-hydroxytryptamine (5-HT) were demonstrated immunohistochemically in the wall of pial vessels associated with the circle of Willis in the guinea pig. The fibers formed a network structure which was more dense in the rostral part of the arterial circle and its branches than in the caudal part. The 5-HT immunoreactive fibers disappeared in all arteries studied after bilateral superior cervical ganglionectomy, and unilateral ganglionectomy eliminated the 5-HT immunoreactivity in the ipsilateral part of the middle cerebral, posterior cerebral and superior cerebellar arteries. Decentralization of the superior cervical ganglion had no effect on the perivascular nerve plexus. Subsequent staining with dopamine-beta-hydroxylase (DBH) antiserum following elution of the first antibody revealed that 5-HT was present in the noradrenergic nerve fibers. Small intensive fluorescent cells with positive immunoreaction for 5-HT and DBH, respectively, were located in clusters within the ganglion, which showed no immunohistochemical evidence for the presence of serotonergic neurons. It is concluded that 5-HT is probably not synthesized in truly serotonergic fibers but rather taken up and stored together with noradrenaline in cerebrovascular sympathetic nerves originating in the superior cervical ganglia.


The treatment of choroidal neovascularisation with intravitreal injections of bevacizumab (Avastin).
Although bevacizumab (Avastin) has only been approved for the treatment of colorectal carcinoma, many reports have shown that its intravitreal administration against choroidal neovascularisation (CNV) leads to a stabilisation or even a regression of the pathological neovessels, and thus to a positive evolution of visual acuity. From April 2006 to July 2007, the CNV of different aetiologies were treated with intravitreal injections of bevacizumab (1.25 mg in 0.05 mL) in 300 patients with an average age of 75, 78 years. Fluorescein angiography and optical coherence tomography were used for the diagnosis and for the checks which were carried out every twelve weeks. The intravitreal injections were performed every six weeks until the macular findings were considered to be dry. The visual acuity was checked using an ETDRS chart. In all the groups considered the visual acuity was stabilised or improved on an average with + 4.44 ETDRS letters after 3.04 injections. During the follow-up six cardiovascular diseases were diagnosed and in one case a patient died. No ocular complications were reported after 1036 injections. The results clearly show that the intravitreal injections of bevacizumab are effective, safe and cost-effective. However, further randomised studies are needed to confirm the duration of the effect, as well as the good ocular and systemic tolerability of the drug.


A NADH dehydrogenase subunit gene is co-transcribed with the abnormal Petunia mitochondrial gene associated with cytoplasmic male sterility.
DNA sequence analysis 3' to the Petunia S-pcf coding region has resulted in the identification of an open reading frame similar to mammalian mitochondrial genes for subunit 3 of the NADH dehydrogenase complex (nad3). Both the abnormal fused gene S-pcf and S-nad3 fall within the mitochondrial DNA region previously shown to be associated with cytoplasmic male sterility (CMS). The S-nad3 sequence, co-transcribed with S-pcf, is present in only one copy within the Petunia CMS genome. A homologous transcribed sequence from the mitochondrial genome of a fertile Petunia line has been identified. The coding region of the two genes are identical and they share homology for at least 800 bp downstream. The genes diverge 117 bp upstream of the nad3 start codon. Transcripts of the S-pcf/S-nad3 transcripts are similar in tissues of a fertility-restored line and a CMS line.


Skin of color in dermatopathology: does color matter?
Skin of color (SoC) remains an understudied and under taught area of dermatology despite its rising importance. Race and ethnicity play a particularly important role in dermatology as skin pigmentation can affect the manifestation and presentation of many common dermatoses. With this review, we seek to review pertinent differences in SoC histology, as well as highlight the histopathology of conditions more common in SoC and address inherent bias that may affect accurate dermatopathology sign out.


How to reduce Domestic Violence against married women? a mixed methods study from rural Tamil Nadu.
Despite government legislations for protection of women, domestic violence (DV) continues to remain as a public health problem in India. Objectives 1. To find out the prevalence of various types of self-reported DV among married women of 18-45 years of age and to identify its social determinants and their help-seeking behavior. 2. To understand the solutions from key informants' point of view. It was a sequential explanatory mixed methods study design, which consisted of quantitative (Survey) followed by qualitative (Interviews) phase. A representative sample of 360 married women was chosen by two-stage cluster sampling from villages in Tamil Nadu, South India. The female investigator conducted the survey by house to house visit. Post-survey, six key informant interviews were conducted to explore the solutions and suggestions from experts' point of view. Bivariate and multivariate regression analysis was carried out to identify the significant predictors of DV. Manual content analysis of qualitative data was done. The overall prevalence of spousal DV was 49.5% [95% CI: 44.3-54.6] in the last one year. In multivariate analysis, two factors namely 'current alcoholism in husband' and 'controlling behavior of husband' were found to be the significant predictors of DV. In order to prevent alcoholism in husband, the key informants suggested deaddiction services and measures to limit access to alcohol. Furthermore, to prevent controlling behavior of husband, the key informants suggested women's empowerment, employment, helplines, responsible parenting, social change in dowry practice and gender equality. The prevalence of spousal DV was found to be high. Current alcohol consumption and controlling behavior of the husband were the important determinants of domestic violence. Key informants suggested interprofessional approach consisting of deaddiction services, women empowerment and strengthening of family life to address the problem of DV.


A pathway to greater meaning in life and well-being for senior executives beset by anti-meaning.
Although work is a significant source of meaning for most people, the role of senior executive generates different meaning and well-being complexities than those experienced or faced by general employees. This study explored how meaning and anti-meaning components affect senior executives' experiences of meaning in life and well-being. The findings enabled devising a pathway to enhance senior executives' net experiences of meaning in life and well-being. A cross-sectional, semi-structured interview study design was used to gather rich qualitative data. Eight participants from southern and eastern Africa, who had held the position of chief executive officer or managing director for at least five years, were interviewed. The findings demonstrated that senior executives' work roles provide a significant source of meaning. However, the roles are accompanied by unavoidable anti-meanings, which are likely to generate additional anti-meanings if not tempered sufficiently, thus reducing the net meaning experienced. From the findings, a practical pathway was devised to assist top executives to deal with the bipolar relationship between meaning and anti-meaning. Consulting and counseling practitioners can utilize the pathway to guide, support, and counsel senior executives towards improved meaning, temper anti-meaning and improve well-being.


[Effect of Helicobacter pylori-encoded CagA on biological behavior of gastric adenocarcinoma cells in vitro].
To investigate the effect of Helicobacter pylori-encoded CagA on biological behavior of gastric adenocarcinoma AGS cells. With experiment-control system of the wild-type CagA positive strain and isogenic CagA negative mutant strain of Helicobacter pyroli (Hp) were used as control and experimental groups, respectively. The cell contact, migration and invasion were examined by light and electron microscopy and invasion assay. The AGS cells infected by Hp strain with positive wild-type CagA showed more severely changed tight junction, wider intercellular space, loss of cell contacts, and higher migrating and invasive ability. Hp CagA may lead to loss of cell contacting and higher migrating and invading ability of gastic cells, and accelerates the malignant progress of tumor.


Identification of key pathways and genes in nasopharyngeal carcinoma based on WGCNA.
We aim to identify the potential genes and signaling pathways associated with the nasopharyngeal carcinoma (NPC) prognosis using Weighted Gene Co-Expression Network Analysis (WGCNA). Gene Expression Omnibus (GEO) query was utilized to download two NPC mRNA microarray data. WGCNA was conducted on differentially expressed genes (DEGs) to obtain tumor-associated gene modules. Genes in core modules were intersected with DEGs for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis. GSE102349 dataset was devoted to identifying prognostic hub genes by survival analysis and the results were confirmed by quantitative polymerase chain reaction (qPCR). Co-expression networks were built, and we detected 12 gene modules. The Brown module and Magenta module were extremely associated with NPC samples. GO functional analysis and KEGG pathway analysis was carried out to the genes in the Brown and Magenta modules. Our data indicated that DEGs in Brown module and Magenta module were correlated with the biological regulation, metabolic process, reproduction, and cellular proliferation. Twenty-six hub genes were obtained and were considered to be closely related to NPC. GSE102349 dataset was devoted to identifying prognostic hub genes by survival analysis. The expression of IL33, MPP3 and SLC16A7 in GSE102349 dataset was significantly correlated with the progression-free survival (PFS). The results of qPCR indicated a strong correlation between SLC16A7 expression and the overall survival (OS). WGCNA contributed to the detection of gene modules and identification of hub genes and crucial genes. These crucial genes might be potential targets for pharmaceutic therapies with potential clinical significance.


Human parainfluenza virus type 3: analysis of the cytoplasmic tail and transmembrane anchor of the hemagglutinin-neuraminidase protein in promoting cell fusion.
The role of the cytoplasmic tail and transmembrane anchor of the human parainfluenza virus type 3 (HPIV3) hemagglutinin-neuraminidase (HN) glycoprotein in promoting cell fusion was investigated. A series of amino terminal deletion mutants (d10, d20, d27, d31, d40, d44, and d73) were compared for processing, cell surface expression, and maintenance of their biological attributes by recombinant expression of mutant genes using a plasmid vector (pcDL-SR alpha-296) in CV-1 and HeLa cells. To determine the fusion promoting activity (FPA) of the various mutant proteins, a simple assay was developed which quantified the fusion of two different HeLa cell types. One of the cell types, HeLa-tat, constitutively expressed the human immunodeficiency virus type I (HIV-1) tat protein from a Moloney murine leukemia virus long terminal repeat (LTR), while the second cell type, HeLa beta-gal, contained a reporter gene, beta-galactosidase, under the control of an HIV1-LTR. Fusion of mixed HeLa cell monolayers (50:50, HeLa-tat: HeLa beta-gal), following transfection with appropriate plasmids, resulted in transactivation of the reporter gene which was then measured by direct staining of cells or using cell lysates with appropriate substrates. Cell fusion was observed only when both the HPIV3 F and functional HN proteins were both co-transfected into cells. Of the seven deletion mutants examined, only d10, d20, d27 and d31 were expressed to significant levels on the cell surface and only these four mutant proteins maintained FPA. Compared with the wt HN at 48 h post transfection, d10 and d20 had enhanced FPA (119% and 158%, respectively), while d27 and d31 were diminished (74% and > 4%, respectively). Analysis of protein expression suggested that the reason for the increase in FPA of the mutant proteins was that the levels of protein expressed at the cell surface was twofold or threefold higher for d10 and d20, respectively, compared to the wt HN.


Treatment with methimazole in a 3-year-old male with thyroid hormone resistance.
Thyroid hormone resistance syndromes are disorders in which there is decreased end-organ responsiveness to thyroid hormone. Patients typically present with elevated levels of thyroxine and triiodothyronine with a normal or increased serum thyroid-stimulating hormone concentration. Clinical features are variable, and there are no guidelines regarding treatment. The patient was noted to have tachycardia at 6 months of age. He had persistently elevated free thyroxine and normal/mildly elevated thyroid-stimulating hormone for the first 2 years of life. At age 2 years, he was noted to have sinus tachycardia, a mildly enlarged thyroid, hyperactive behavior, subtle developmental delay, and poor weight gain. The patient has a previously described de novo mutation in the thyroid hormone receptor-β gene. He was started on methimazole (0.3-0.5 mg/kg/day) at age 3 years to treat his symptoms. With medication, weight gain, sleep, behavior, and tachycardia improved. Linear growth has remained appropriate for age. Heart rate is in the upper normal range and his thyroid has become more enlarged. Methimazole has improved thyrotoxic symptoms in a 3-year-old male with thyroid hormone resistance. The use of methimazole should be considered in certain patients.


The centrosome cycle: Centriole biogenesis, duplication and inherent asymmetries.
Centrosomes are microtubule-organizing centres of animal cells. They influence the morphology of the microtubule cytoskeleton, function as the base for the primary cilium and serve as a nexus for important signalling pathways. At the core of a typical centrosome are two cylindrical microtubule-based structures termed centrioles, which recruit a matrix of associated pericentriolar material. Cells begin the cell cycle with exactly one centrosome, and the duplication of centrioles is constrained such that it occurs only once per cell cycle and at a specific site in the cell. As a result of this duplication mechanism, the two centrioles differ in age and maturity, and thus have different functions; for example, the older of the two centrioles can initiate the formation of a ciliary axoneme. We discuss spatial aspects of the centrosome duplication cycle, the mechanism of centriole assembly and the possible consequences of the inherent asymmetry of centrioles and centrosomes.


On the use of EMG-ratios to assess the coordination of back muscles.
Electromyographic (EMG) amplitude ratios (EMG-ratios) have been proposed to assess back muscle coordination in chronic low back pain patients to avoid the normalization of EMG using maximal contractions. The aim of this study was to test the relevance of this type of EMG analysis. Healthy subjects (44 men and 13 women) and patients with chronic low back pain (57 men) performed three 7s static ramp extension contractions ranging from 0% to 100% of the maximal voluntary contraction while standing in a static dynamometer. A subgroup of 20 healthy men also performed 5s step contractions at 10%, 20%, 40%, 60% and 80% of the maximal voluntary contraction. Finally, to assess reliability, another subgroup (n=20 healthy and 20 men with chronic low back pain) performed the protocol three times, on different days. Surface EMG signals were collected from four pairs of back muscles and subcutaneous tissue thickness was measured at the corresponding electrode sites. EMG amplitude values were computed at each 5% force level from 10% to 80% of the maximal voluntary contraction. Then, EMG-ratios were computed between different electrode sites and averaged bilaterally. All EMG-ratios were affected by the force level and the contraction type (ramp vs step contractions). Statistically significant Pearson's correlations (r=-0.38 to -0.57) were obtained between some EMG-ratios and their corresponding subcutaneous tissue thickness ratios. The reliability of the EMG-ratio variables ranged from moderate to excellent (intra-class correlation coefficients between 0.50 and 0.91). Comparisons between 12 men and 13 women and between 24 healthy men and 57 men with chronic low back pain showed that EMG-ratios were sensitive to sex but not to pain status. Multivariate analyses applied on the EMG-ratios identified clusters of subjects but none of the main clinical variables were able to clearly characterize these clusters. Overall, even though additional research is warranted to further substantiate some important psychometric characteristics of the EMG-ratios as well as their biomechanical and clinical significance, these results support their use for assessing the coordination patterns of back muscles, provided that confounding variables such as the force level, the contraction type, and subcutaneous tissue thickness are accounted for.


Structure-based design and synthesis of 2,4-diaminopyrimidines as EGFR L858R/T790M selective inhibitors for NSCLC.
Mutated epidermal growth factor receptor (EGFR) is a major driver of non-small cell lung cancer (NSCLC). The EGFRT790M secondary mutation has become a leading cause of clinically-acquired resistance to gefitinib and erlotinib. Herein, we present a structure-based design approach to increase the potency and selectivity of the previously reported reversible EGFR inhibitor 7, at the kinase and cellular levels. Three-step structure-activity relationship exploration led to promising compounds 19e and 19h with unique chemical structure and binding mode from the other third-generation tyrosine kinase inhibitors. In a human NSCLC xenograft model, 19e and 19h exhibited dose-dependent tumor growth suppression without toxicity. These selective inhibitors are promising drug candidates for EGFRT790M-driven NSCLC.


Client-centeredness of Finnish and Estonian nursing students and the support from nursing education to develop it. Students' self-evaluation.
The purpose of this comparative study is to describe the differences between Finnish and Estonian students evaluations about their client-centeredness and educational support they received to develop it. Client-centeredness has many positive effects on the quality and effectiveness of care. However, some deficiencies have been identified in the client-centeredness of nursing staff. Research on the subject has been limited, and we lack knowledge of graduating students' competence in client-centeredness and the support of their education to develop it. The sample consisted of 390 undergraduate nursing students, 195 from Finland and 195 from Estonia. The data were collected in 2009 using the structured five-point scale questionnaire. The questionnaire was designed to measure students' client-centeredness and the educational support they received from nursing education. The data were analyzed by the PASW Statistics 18-programme using descriptive statistics, Kolmogorov-Smirnov test and Mann-Whitney U-test. Predominantly, students in both countries evaluated their level of client-centeredness high. The Estonian students generally evaluated their client-centeredness higher compared to the Finnish students. The same applied to support provided by nursing education. The greatest differences were related to education and particularly theoretical teaching. In Estonia, students' client-centeredness manifested itself more in politeness and willingness to serve clients, whereas respecting the clients' values was emphasized in Finland. Students' requisites, referred here as knowledge, skills and abilities to implement client-centered nursing, for client-centeredness had deficiencies, and the support from education was also the weakest regarding these aspects. In future, education on development of nursing activities, acquisition of knowledge and services provided by health care as well as legislation should be enhanced, since these areas proved the most difficult for the students.


Dynamic chromatin accessibility during nutritional iron overload reveals a BMP6-independent induction of cell cycle genes.
Iron is essential to organism physiology as it participates in numerous biological processes including oxygen transport, respiration, and erythropoiesis. Although iron is critical to physiology, excess iron is toxic to cells and tissues due to generation of reactive oxygen species. Therefore, well-kept iron homeostasis is a mainstay of proper cell and organ function. Iron overload disorders, caused by nutritional or genetic factors, contribute to many pathologies such as diabetes, non-alcoholic steatohepatitis and hepatocellular carcinoma. The liver is not only vulnerable to the effects of iron overload, it is also the major organ controlling iron homeostasis. During iron overload, Bone Morphogenic Protein (BMP) levels increase and initiate a hepatic response aimed at lowering iron levels. The transcriptional effects of iron overload are not well-characterized and the underlining enhancer regulation is uncharted. Here, we profiled the liver's transcriptome and chromatin accessibility following nutritional iron overload. We found marked changes in gene expression and enhancer accessibility following iron overload. Surprisingly, 16% of genes induced following iron overload participate in propagating the cell cycle. Induction of cell cycle genes was independent of BMP. Genome-wide enhancer landscape profiling revealed hundreds of enhancers with altered activity following iron overload. Characterization of transcription factor motifs and footprints in iron-regulated enhancers showed a role for the Activator Protein 1 (AP-1) transcription factor in promoting cell cycle-related transcription. In summary, we found that the transcriptional program at play during iron overload is bifurcated in which BMP signaling controls iron homeostasis genes while an AP-1-driven program controls cell cycle genes.


Practical suggestions for successful immunoenzyme double-staining experiments.
Many methodologies exist to perform an immunoenzyme double staining. Hence, the practical problem arises as to which of these methods is optimal for one's own experimental design. A process of selection is described which is derived from our own practical experience. First, a general strategy is outlined for the handling of tissue sections to be used for multiple staining methods. Secondly, the selection of an appropriate immunoenzyme double-staining concept is made using a flow chart. Thereafter we give criteria for the definitive selection of an immunoenzyme double-staining protocol based on the characteristics of the tissue or cell type under study. Particular attention is given to the selection of appropriate detection systems, applying enzymes or gold particles, and good contrasting colour combinations. The problems of visualizing co-localization using immunoenzyme double staining are dealt with, and suggestions are made to adapt the method, if necessary, in order to optimize it.


Loss of factor XIIIa in pig dermis during tissue expansion.
Considerable evidence suggests that factor XIIIa, a blood coagulation factor, also functions in tissue repair, and specifically in the dynamic process of fibroplasia. On the other hand, the dynamic process of tissue expansion would require a loosening of the dermis, the opposite of fibroplasia. We examined the effects of tissue expansion on the expression of factor XIIIa in pig skin. Standard immunohistochemical procedures were used coupled with a rabbit antibody to factor XIIIa. In this report, we demonstrate that the normal expression of factor XIIIa in pig dermis is completely inhibited at the apex overlying the tissue expander. Factor XIIIa inhibition during expansion supports the thesis that this substance is important in the production and maintenance of fibroplasia.


Normal and neoplastic Langerhans cells: phenotypic comparison with other types of macrophages.
The antigenic properties of normal epidermal Langerhans cells and their neoplastic counterparts (histiocytosis X cells) were compared with those of other types of macrophages, by immunohistochemical staining of skin and lymph node biopsies with a panel of mono-clonal antibodies. The phenotype of Langerhans cells, histiocytosis X cells, dermal macrophages and interdigitating reticulum cells were similar (HLA-DR+, OKT 6+/-, Leu3+/-, C3-receptor-, Ig-complex-, R4/23-, MO2-), and differed markedly from those of follicular dendritic cells (HLA-DR-, OKT6-, Leu3-, C3 receptor+, Ig+, R4/23+, MO2-, and histiocytic reticulum cells (HLA-DR+/-, OKT6-, Leu3+/-, C3-receptor+, Ig-complex+, R4/23-, MO2+/-). This indicates that Langerhans cells are related to the interdigitating reticulum cells found in the T cell areas of lymphoid organs, and demonstrates that Langerhans cells do not express C3b, C3bi or C3d receptor molecules. Our data also emphasise that the Leu3 antigen is not restricted to cells of the T cell lineage.


A Cost-Benefit Analysis of Medical Scribes and Electronic Medical Record System in an Academic Urology Clinic.
Electronic medical records have introduced an additional level of complexity to the patient-provider encounter and medical scribes may offer a solution. We examined how a medical scribe system could support an academic urology clinic. To assess the financial feasibility of this model, we analyzed the additional costs associated with adding medical scribes and we discuss the potential benefits of this system. We measured total patient wait and interaction times with staff, and estimated the additional staff required to maintain an increased patient load if medical scribes were introduced. We then calculated the average revenue per patient during the most recent 9 months of data to estimate the minimum increase in the number of patient visits needed to offset the additional staffing needs. Mean ± SD total wait time was 23 minutes 28 seconds ± 13 minutes 4 seconds. Average monthly expenses would increase by $17,452.50 for 6 additional staff members, including 1 nursing assistant, 1 patient service specialist, 1 nurse and 3 scribes. There was an average of 666 monthly office visits and average net revenue to the department was $107.78 per patient visit. The increase in the number of patient visits required to break even would be 162 additional patients per month, representing a 24.3% increase. Additional downstream revenue was considered. A medical scribe system in the example of an academic urology clinic setting could increase patient flow and decrease the burden on medical providers by reducing computer charting. This model is only financially prudent if the increased expenses are offset by additional revenue from increased patient visits.


Measuring outcome after discharge from hospital for the elderly--a conceptual and empirical investigation.
Despite the fact that the elderly are a major client group of the hospital service, there has been comparatively little investigation of outcome for this client group after discharge. In this paper the difficulties in recording outcome for the elderly are discussed, using the example of a survey based in Wales. A 4% random sample of patients aged 65 years and over discharged from NHS non-psychiatric hospitals in Wales during 1981 were sent a postal questionnaire 3 months after discharge. Response rates of over 80% were achieved. Outcome after discharge was measured by 3 indices: mortality, physical disability, and patients' own assessments of their health status and rehabilitation. Of survivors, 35% were more disabled than before admission, and 43% did not feel that they were fully rehabilitated. All measures of outcome were strongly inter-correlated and demonstrate a clear trend to deteriorate with increased time after discharge. Interpretation of these results remains difficult until measures of cost and benefit are developed. Without these it is not possible to determine if the results reported are better (or worse) than would be expected given the level of resources involved.


Association study of semaphorin 5A with risk of Parkinson's disease in a Chinese Han population.
Parkinson's disease (PD) is a common neurodegenerative disorder with genetic risk factors. Semaphorin 5A (SEMA5A) was recognized as a risk factor for PD through high resolution whole genome association study by Maraganore et al. We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay to check two single nucleotide polymorphisms (SNPs) within SEMA5A in 340 PD patients and 222 PD free cases of Chinese Han ancestry and tested by gene sequencing. We found that the SEMA5A variant genotype (allele) of rs7702187 and rs3798097 had no association with the risk of PD in our sample. The AC haplotype was associated with a significant increased risk of PD and the AT haplotype showed an associated decreased risk of PD compared with the most common haplotype TC. Our findings suggested that haplotypes of SEMA5A may be involved in PD risk in the Chinese Han population.


Cerebrospinal fluid immune complexes in multiple sclerosis.
Using a C1q binding test, immune complexes have been detected in one half of cerebrospinal fluid samples from patients with multiple sclerosis. These results provide additional evidence for the participation of an immune reaction in the disease process.


Evaluating pituitary adenomas using national research databases: systematic review of the quality of reporting based on the STROBE scale.
The use of national research databases has become more prevalent for studying various neurosurgical diseases. Despite the advantages of using large databases to glean clinical insight, variation remains in the methodology and reporting among studies. Using STROBE and RECORD guidelines, we evaluated the quality of reporting of the database literature investigating surgical management of benign pituitary adenomas. In this systematic review of the PubMed/MEDLINE database, we identified studies employing large national research databases of patients who underwent surgery for benign pituitary adenoma. We evaluated each of these studies using the STROBE-RECORD reporting guideline criteria to assess their quality. A total of 42 studies from 2003 to 2020 were identified for inclusion. The two raters demonstrated a κ = 0.228 with 84% overall agreement. Commonly underreported criteria included bias (discussed in 56% of studies), main result reporting (70%), subgroup analysis (69%), generalizability (68%), and funding (57%). These factors, in addition to the data sources/measurement criteria, also had the largest discrepancies between reviewers. About 20% of administrative database reviews did not accurately address bias or control for confounding variables. We found frequent underreporting of crucial information and criteria that can be challenging to identify may limit large database studies of pituitary adenomas. Improved reporting of certain criteria is critical to optimize reader understanding of large database studies. This would allow better dissemination and implementation of study findings, especially as the use of these research tools increases.


From sequence to phenotype: reverse genetics in Drosophila melanogaster.
There has been a long history of innovation and development of tools for gene discovery and genetic analysis in Drosophila melanogaster. This includes methods to induce mutations and to screen for those mutations that disrupt specific processes, methods to map mutations genetically and physically, and methods to clone and characterize genes at the molecular level. Modern genetics also requires techniques to do the reverse to disrupt the functions of specific genes, the sequences of which are already known. This is the process referred to as reverse genetics. During recent years, some valuable new methods for conducting reverse genetics in Drosophila have been developed.


The short- and long-term effects of cognitive behavioral therapy on the glycemic control of diabetic patients: a systematic review and meta-analysis.
Glycemic control is an important issue in the treatment of diabetic patients. However, traditional methods, such as medication (the usual treatment), have limitations. Cognitive behavioral therapy (CBT) might be a useful option to help control the glycemic condition. The effects can be revealed by systemic review or meta-analysis of randomized clinical trials (RCT). A systematic search and a meta-analysis for the RCT were done of the short- and long-term effects of CBT on the glycemic control of diabetic patients in a comparison with the usual treatment. Nineteen RCT studies and 3,885 diabetic patients were enrolled in this meta-analysis. Subgroup analyses of types 1 and 2 diabetes and individual and group CBT were also performed. Patients treated with CBT showed no significant difference in HbA1c when compared to the usual treatment within six months. However, CBT was more effective in reducing HbA1c when compared to usual treatment with at least six months of treatment duration [standardized mean difference: -0.44 (95% confidence interval (CI): -0.63 ~ -0.25), Z = 4.49]. Subgroup analysis of type 1 and 2 diabetic patients supported a long-term effect of CBT on glycemic control [standardized mean difference: -0.85 (95% CI: -1.19 ~ -0.10), Z = 2.23, standardized mean difference: -0.33 (95% CI:-0.47 ~ -0.19), Z = 4.52, respectively]. CBT would be a useful option for improving the glycemic control of diabetic patients undergoing long-term treatment. The advantages of the long-term effects of CBT should be considered by clinicians and staff.


Aldehyde-methacrylate-hyaluronan profited hydrogel system integrating aligned and viscoelastic cues for neurogenesis.
Either oriented architecture or viscoelasticity is pivotal to neurogenesis, thus, native neural extracellular matrix derived-hyaluronan hydrogels with nano-orientation and viscoelasticity recapitulated might be instructive for neurogenesis, however it is still unexploited. Herein, based on aldehyde-methacrylate difunctionalized hyaluronan, by integrating imine kinetic modulation and microfluidic biofabrication, we construct a hydrogel system with orthogonal viscoelasticity and nano-topography. We then find the positive synergy effects of matrix nano-orientation and viscoelasticity not only on neurites outgrowth and elongation of neural cells, but also on neuronal differentiation of stem cells. Moreover, by implanting viscoelastic and nano-aligned hydrogels into lesion sites, we demonstrate the enhanced repair of spinal cord injury, including ameliorated pathological microenvironment, facilitated endogenous neurogenesis and functional axons regeneration as well as motor function restoration. This work supplies universal platform for preparing neuronal inducing hyaluronan-based hydrogels which might serve as promising therapeutic strategies for nerve injury.


An improved particle swarm optimization algorithm for reliability problems.
An improved particle swarm optimization (IPSO) algorithm is proposed to solve reliability problems in this paper. The IPSO designs two position updating strategies: In the early iterations, each particle flies and searches according to its own best experience with a large probability; in the late iterations, each particle flies and searches according to the fling experience of the most successful particle with a large probability. In addition, the IPSO introduces a mutation operator after position updating, which can not only prevent the IPSO from trapping into the local optimum, but also enhances its space developing ability. Experimental results show that the proposed algorithm has stronger convergence and stability than the other four particle swarm optimization algorithms on solving reliability problems, and that the solutions obtained by the IPSO are better than the previously reported best-known solutions in the recent literature.


Biomechanical properties of artificial bones made by Sawbones: A review.
Biomedical engineers and physicists frequently use human or animal bone for orthopaedic biomechanics research because they are excellent approximations of living bone. But, there are drawbacks to biological bone, like degradation over time, ethical concerns, high financial costs, inter-specimen variability, storage requirements, supplier sourcing, transportation rules, etc. Consequently, since the late 1980s, the Sawbones® company has been one of the world's largest suppliers of artificial bones for biomechanical testing that counteract many disadvantages of biological bone. There have been many published reports using these bone analogs for research on joint replacement, bone fracture fixation, spine surgery, etc. But, there exists no prior review paper on these artificial bones that gives a comprehensive and in-depth look at the numerical data of interest to biomedical engineers and physicists. Thus, this paper critically reviews 25 years of English-language studies on the biomechanical properties of these artificial bones that (a) characterized unknown or unreported values, (b) validated them against biological bone, and/or (c) optimized different design parameters. This survey of data, advantages, disadvantages, and knowledge gaps will hopefully be useful to biomedical engineers and physicists in developing mechanical testing protocols and computational finite element models.


Ghrelin-producing cells exist as two types of cells, closed- and opened-type cells, in the rat gastrointestinal tract.
Ghrelin was recently isolated from the rat stomach as an endogenous ligand for the growth-hormone secretagogue receptor (GHS-R) and is known to exist in the gastrointestinal tract and hypothalamus. In this study, we investigated in detail the distribution and morphologic characteristics of ghrelin-containing cells (ghrelin cells) in the gastrointestinal tract by immunohistochemistry and in situ hybridization. Ghrelin cells were found to be localized in the mucous membrane of the stomach, duodenum, ileum, cecum and colon but not in myenteric plexus, and they can be classified into open- and closed-type cells. The greatest number of ghrelin cells was found in the stomach, and it was found that the number of the opened-type cells gradually increased in the direction from stomach to the lower gastrointestinal tract. These results suggest that the two types of ghrelin cells may be distinctly regulated and play different physiological roles in various regions of the gastrointestinal tract.


Topical or no anaesthesia for external urethral sphincterotomy in neurogenic vesical dysfunction due to spinal injury.
Considerable controversy exists regarding the ideal anaesthetic coverage for external urethral sphincterotomy in spinal injury patients with detrusor-sphincter dyssynergia. From this preliminary experience on 34 patients in whom this procedure was indicated and then attempted under topical (urethral instillation of 20 ml of 2 per cent Lignocaine jelly) or no anaesthesia, we are encouraged into believing that these patients may not require general or regional anaesthesia for this operation.


Influence of different storage temperatures on the mechanical properties of NiTi, Cu-NiTi and SS orthodontic archwires: An in vitro study.
Due to their exceptional temperature sensitivity, the mechanical properties of Nickel-titanium and Copper Nickel-titanium wires may be influenced by their storage temperature. This in turn may have clinical implications and may also affect the outcomes. This study analyzed the influence of storage temperatures on the mechanical properties of orthodontic wires in a laboratory setting. Stainless steel (SS), Nickel-Titanium (NiTi), and three variants of Copper-NiTi (Cu-NiTi 27°C, 35°C and 40°C), 0.017×0.025 inches in size were analysed using a three-point bending test in a pre-heated chamber at 36°C. The orthodontic wires were stored for twenty-four hours before the mechanical testing at four different temperatures (5°, 22°, 36° and 60°C). The obtained results showed that the mechanical forces exerted by 27°C Copper-NiTi exhibit the most stable behaviour after having been stored at different temperatures, whereas 35°C Copper-NiTi showed the highest variability. As to be expected, Stainless steel shows no changes in its bending mechanical properties. Furthermore, the results of this investigation reflect the importance of controlling the storage temperature of orthodontic NiTi and Copper-NiTi wires tested in a research environment in order to avoid unexpected bias.


Investigations on the clonality of isolates of Pasteurella gallinarum obtained from turkeys in Germany.
Pasteurella gallinarum has been considered an opportunistic pathogen rather than a primary pathogen for chickens. As P. gallinarum has been found to have a high genotypic diversity, one would expect a polyclonal distribution among isolates from different farms if this organism is a secondary invader. The aims of this investigation were to genetically characterize isolates obtained from outbreaks affecting several turkey farms to confirm the existence of the infection in turkeys and to investigate the genetic relationship between isolates from affected farms. A total of 17 isolates from 14 outbreaks of respiratory disease in Germany were subjected to extended phenotypic and genotypic characterization. All isolates were of the same phenotype, typical of P. gallinarum. Ribotyping of three isolates using either HpaII or HindIII showed that they had identical profiles and indicated that the isolates all originated from the same clone. Comparison with HpaII ribotypes from a previous study showed that the pattern was identical to that obtained with isolates from a Zimbabwean outbreak in chickens during 1999 to 2000. Restriction endonuclease analysis typing of 14 isolates from all 14 farms showed that they had identical profiles but these differed from those obtained with isolates from the Zimbabwean outbreak. Sequencing of the 16S rRNA gene and sequence comparisons with other Pasteurellaceae confirmed their classification as P. gallinarum. Identification of the same clone of P. gallinarum from 14 outbreaks of acute respiratory disease in turkeys within a time period of 2 months suggests a common source of infection, and that P. gallinarum probably played a primary role rather than a secondary role in the outbreaks.


Comparison of equations for dosing of medications in renal impairment.
The aim of this study is to determine the concordance among the Cockcroft-Gault, the Modification of Diet in Renal Disease and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in hypothetical dosing of renally cleared medications. A total of 2163 patients prescribed at least one of the 31 renally cleared drugs under review were included in the study. Kidney function was estimated using the three equations. We compared actual prescribed dosages of the same drug with recommended dosages based on the kidney function as calculated by each of the equations and applying dosing recommendations in the Australian Medicines Handbook. There was a significant difference in the kidney function values estimated from the three equations (P < 0.001). Despite the good overall agreement in renal drug dosing, we found selected but potentially important discrepancies among the doses rendered from the equations. The CKD-EPI equation non-normalized for body surface area had a greater rate of concordance with the Cockcroft-Gault equation than the Modification of Diet in Renal Disease equation for renal drug dosing. There is need for a long-term multi-centre study in a diverse population to define the clinical effects of the discrepancies among the equations for drug dosing. Given the greater concordance of the non-normalized CKD-EPI equation with the Cockcroft-Gault equation for dosing, the recommendation by Kidney Health Australia and the United States National Kidney Disease Education Program that 'dosing based on either eCrCl or an eGFR with body surface area normalization removed are acceptable' seems suitable and practicable for the purpose of dosing of non-critical drugs in the primary care setting.


Meconium proteases and antiproteases as a potential source of biomarkers for the assessment of the intrauterine environment of the fetus.
A protease-antiprotease balance is required to maintain the homeostasis of the intrauterine environment in which the fetus develops. Proteases and antiproteases accumulate in meconium exclusively during intrauterine life and are excreted after birth. Proteomic analysis was used to investigate the protein composition in pooled 50 serial meconium portions from 10 neonates. The UniProt, BRENDA and MEROPS databases were the sources of information used to classify the meconium proteases and antiproteases among 946 proteins identified in meconium. A total of 265 enzymatic proteins and 33 protein inhibitors were identified in the meconium. The six main enzyme groups represented in the meconium were oxidoreductases (n = 44), transferases (n = 62), hydrolases (n = 137), lyases (n = 10), isomerases (n = 7) and ligases (n = 5). Six protease families were distinguished: serine (n = 28, 41.2% of all proteases), metallo (n = 23, 33.8%), cysteine (n = 10, 14.7%), aspartic (n = 4, 5.9%), theorine (n = 2, 2.9%) and mixed (n = 1, 1.5%) proteases. The well-characterized meconium-based biomarker panel of proteases and their inhibitors may be a source of important information for use in diagnosing fetal disorders and predicting postnatal health and development. The differences in the composition and function between individual meconium proteases and antiproteases confirm their association with numerous metabolic processes characteristic of the intrauterine environment.