Metarhodopsin I/metarhodopsin II transition triggers light-induced change in calcium binding at rod disk membranes.
The hypothesis of Yoshikami and Hagins that calcium ions act as diffusible transmitter molecules between the photochemistry of rhodopsin and the subsequent electrical events at the outer plasma membrane of rods initiated many investigations on light-stimulated calcium release in vertebrate photoreceptor cells (see refs 2, 3). Although it not seems firmly established that light has some effect on the redistribution of calcium in various disk preparations, reconstituted systems and intact rod outer segments, the physiological significance remained unclear. We previously reported a rapid, light-triggered calcium release from binding sites at the disk membrane in the presence of calcium ionophore A23187 (refs 3, 8). However, there is no evidence for rapid calcium release into the cytosol in the absence of ionophore. On fragmentation of intact rod outer segments, calcium release due to a light-requlated change of calcium binding appeared almost completely abolished. We describe here experiments with sonicated rod outer segments in which the previously observed loss of the calcium release capacity has been prevented. Calcium release in sonicated disks in the presence of A23187 kinetically follows the metarhodopsin I/metarhodopsin II transition (tau 1/2 = 10 ms, activation energy EA = 34 kcal mol-1), suggesting that calcium release is triggered by this photochemical transition.


Mechanisms of guanosine triphosphate hydrolysis by Ras and Ras-GAP proteins as rationalized by ab initio QM/MM simulations.
The hydrolysis reaction of guanosine triphosphate (GTP) by p21(ras) (Ras) has been modeled by using the ab initio type quantum mechanical-molecular mechanical simulations. Initial geometry configurations have been prompted by atomic coordinates of the crystal structure (PDBID: 1QRA) corresponding to the prehydrolysis state of Ras in complex with GTP. Multiple searches of minimum energy geometry configurations consistent with the hydrogen bond networks have been performed, resulting in a series of stationary points on the potential energy surface for reaction intermediates and transition states. It is shown that the minimum energy reaction path is consistent with an assumption of a two-step mechanism of GTP hydrolysis. At the first stage, a unified action of the nearest residues of Ras and the nearest water molecules results in a substantial spatial separation of the gamma-phosphate group of GTP from the rest of the molecule (GDP). This phase of hydrolysis process proceeds through the low barrier (16.7 kcal/mol) transition state TS1. At the second stage, the inorganic phosphate is formed in consequence of proton transfers mediated by two water molecules and assisted by the Gln61 residue from Ras. The highest transition state at this segment, TS3, is estimated to have an energy 7.5 kcal/mol above the enzyme-substrate complex. The results of simulations are compared to the previous findings for the GTP hydrolysis in the Ras-GAP (p21(ras)-p120(GAP)) protein complex. Conclusions of the modeling lead to a better understanding of the anticatalytic effect of cancer causing mutation of Gln61 from Ras, which has been debated in recent years.


Genetic and molecular characterization of myelodysplastic syndromes and related myeloid neoplasms.
Whole exome next generation sequencing systematically applied as a discovery tool in myelodysplastic syndromes (MDS) has led to the identification of a large number of novel mutations. Despite hundreds of patients studied, mutational saturation has not been reached and it is expected that new driver mutations will be discovered in this very heterogeneous condition. Serial samples and deep sequencing of the identified alterations has allowed for a dynamic/chronologic analysis of clonal architecture and identification of a subset of ancestral and secondary molecular lesions. Chromosomal gains and losses have been incorporated into the mutational analyses because they can either cooperate with mutations or produce a functional phenocopy. In addition to the search for somatic defects in MDS, similar discovery studies have been also performed to identify germ line mutations/alterations. Clinical analysis showed applicability of multiplexed somatic mutational panels that would complement current pathomorphologic diagnosis, allow for subclassification of nosologic entities, and enhance predictive power of current prognostic algorithms. Overall, comprehensive genomic analysis in MDS has revealed a tremendous heterogeneity of somatic lesions and their combinations further enhanced by the heterogeneity of clonal architecture and chromosomal lesions.


Identification, classification, and partial characterization of genes in humans and other vertebrates homologous to a fish membrane progestin receptor.
Recently we discovered a previously uncharacterized gene with the characteristics of a membrane progestin receptor (mPR) in a fish model, spotted seatrout. Here, we report the identification, cloning, and characteristics of other members of this hitherto unknown family of putative mPRs from several vertebrate species, including human, mouse, pig, Xenopus, zebrafish, and Fugu, with highly conserved nucleotide and deduced amino acid sequences and similar structures to the spotted seatrout mPR. The 13 vertebrate genes identified seem to belong to an unknown gene family. Phylogenetic analysis indicates these cDNAs comprise three distinct groups (named alpha, beta, and gamma) within this gene family. Structural analyses of the translated cDNAs suggest they encode membrane proteins with seven transmembrane domains. The transcript sizes of the human alpha, beta, and gamma putative mPR mRNAs varied from 2.8 to 5.8 kb and showed distinct distributions in reproductive, neural, kidney and intestinal tissues, respectively. Recombinant human alpha, gamma, and mouse beta proteins produced in an Escherichia coli expression system demonstrated high affinity (K(d) = 20-30 nM) saturable binding for progesterone. Further analysis of binding to the gamma-subtype revealed binding was specific for progestins and was displaceable, with rapid rates of association and dissociation (t(1/2) = 2-8 min). These results suggest this is a new family of steroid receptors unrelated to nuclear steroid receptors, but instead having characteristics of G protein-coupled receptors.


Hyaluronidase production by type B Pasteurella multocida from cases of hemorrhagic septicemia.
Seventy-four cultures of Pasteurella multocida representing all four capsular types, A, B, D, and C, from various animal species and diseases were examined for the production of hyaluronidase by two procedures. In one, hyaluronidase production was determined by the depolymerization of streptococcal capsular hyaluronic acid, and in the other, production was determined by degradation of sodium hyaluronidate in a solid culture medium. Hyaluronidase production was only demonstrated in the 13 type B cultures that had been recovered from cases of hemorrhagic septicemia.


Effect of antioxidants on oxidation during the production of whey fat concentrate.
Whey fat has a relatively high level of unsaturated fatty acids, and as such, whey products with a high fat content are vulnerable to oxidation. The purposes of the present study were to assess the oxidative development in whey fat concentrate (WFC) during production and investigate the effect of the addition of antioxidants. Green tea extract (GTE) or a mixture of ascorbyl palmitate and tocopherol (AP/TOC) were used, each in two concentrations. Samples were taken before and after pasteurization of WFC and after drying. The level of volatile oxidation products decreased during processing, while dityrosine concentrations increased during drying. GTE reduced oxidation in both unpasteurized and pasteurized WFC, while the effect of AP/TOC was nonsignificant. In the WFC powder, there was no significant effect of the antioxidants. In conclusion, results indicated that GTE was able to inhibit oxidation in WFC during production and that AP/TOC addition had no effect.


Synchronous neural oscillations and cognitive processes.
The central problem for cognitive neuroscience is to describe how cognitive processes arise from brain processes. This review summarizes the recent evidence that synchronous neural oscillations reveal much about the origin and nature of cognitive processes such as memory, attention and consciousness. Memory processes are most closely related to theta and gamma rhythms, whereas attention seems closely associated with alpha and gamma rhythms. Conscious awareness may arise from synchronous neural oscillations occurring globally throughout the brain rather than from the locally synchronous oscillations that occur when a sensory area encodes a stimulus. These associations between the dynamics of the brain and cognitive processes indicate progress towards a unified theory of brain and cognition.


Combined Optimized Effect of a Highly Self-Organized Nanosubstrate and an Electric Field on Osteoblast Bone Cells Activity.
The effect of an electric field within specific intensity limits on the activity of human cells has been previously investigated. However, there are a considerable number of factors that influence the in vitro development of cell populations. In biocompatibility studies, the nature of the substrate and its topography are decisive in osteoblasts bone cells development. Further on, electrical field stimulation may activate biochemical paths that contribute to a faster, more effective self-adjustment and proliferation of specific cell types on various nanosubstrates. Within the present research, an electrical stimulation device has been manufactured and optimum values of parameters that led to enhanced osteoblasts activity, with respect to the alkaline phosphatase and total protein levels, have been found. Homogeneous electric field distribution induced by a highly organized titanium dioxide nanotubes substrate had an optimum effect on cell response. Specific substrate topography in combination with appropriate electrical stimulation enhanced osteoblasts bone cells capacity to self-adjust the levels of their specific biomarkers. The findings are of importance in the future design and development of new advanced orthopaedic materials for hard tissue replacement.


Updates on the pathophysiology and management of acne rosacea.
There are many options for the treatment of acne rosacea, including topical and systemic therapies, laser and light-based therapies, and surgical procedures. A classification system for rosacea identifies 4 subtypes (ie, erythematotelangiectatic, papulopustular, phymatous, and ocular), which may help guide therapeutic decision making. Until recently, the pathophysiology of acne rosacea has been poorly understood and limited to descriptions of factors that exacerbate or improve this disorder. Recent molecular studies suggest that an altered innate immune response is involved in the pathogenesis of the vascular and inflammatory disease seen in patients with rosacea. These findings may help explain the benefits of current treatments and suggest new therapeutic strategies helpful for alleviating this disease. The goals of therapy include reduction of papules, pustules, erythema, physical discomfort, and an improvement in quality of life. Standard topical treatment agents include metronidazole, azelaic acid, and sodium sulfacetamide-sulfur. Second-line therapies include benzoyl peroxide, clindamycin, calcineurin inhibitors, and permethrin. There are also various systemic therapy options.


Structure of imidazole glycerol phosphate synthase from Thermus thermophilus HB8: open-closed conformational change and ammonia tunneling.
Imidazole glycerol phosphate synthase (IGPs) catalyzes the fifth step in the histidine biosynthetic pathway located at the branch point to de novo purine biosynthesis. IGPs is a multienzyme comprising glutaminase and synthase subunits. The glutaminase activity, which hydrolyzes glutamine to give ammonia, is coupled with substrate binding to the synthase subunit. The three-dimensional structure of the IGPs from Thermus thermophilus HB8 has been determined at 2.3 A resolution, and compared with the previously determined structures for the yeast and Thermotoga maritima enzymes. The structure of each subunit is similar to that of the corresponding domain in the yeast enzyme or subunit in the T. maritima enzyme. However, the overall structure is significantly different from the yeast and T. maritima enzymes, indicating that IGPs may change the relative orientation between the two subunits and close the glutaminase site upon glutamine binding. The putative ammonia tunnel, which carries nascent ammonia from glutaminase to the synthase site, has a closed gate comprising a cyclic salt bridge formed by four charged residues of the synthase subunit. The side chain of Lys100 in the cyclic salt bridge might change its side chain direction to form new interactions with the main chain carbonyl group of glutamine from the synthase subunit and the hydoxyl group of tyrosine from the glutaminase subunit, resulting in the opening of the gate for ammonia transfer.


Predictors of quality of life: a model based study.
In this study, predictors of quality of life (QOL) in psychiatric outpatients (n = 410) were investigated using the psychological stress model developed by Taylor and Aspinwall (Psychosocial Stress. Perspective on Structures, Theory, Life-Course and Methods. San Diego, CA: Academic Press, 1996; pp. 71-110). External resources, personal resources, stressors, appraisal of stressors, social support, coping, and QOL were assessed with several questionnaires. The complete original Taylor and Aspinwall model was tested with SEM analyses. These analyses were not able to explain the data adequately. Therefore, initially a more exploratory data analytic strategy was followed using a series of multiple regression analyses. These analyses only partially supported the Taylor and Aspinwall model. In fact, QOL was not predicted by coping, while all other antecedents affected QOL directly, explaining considerable amounts of QOL variance. As a next step, taking the outcomes of the regression analyses as point of departure, new SEM analyses were carried out, testing a modified model. This model, without coping, had an excellent fit. Consequently, modifications of the model are recommended concerning psychiatric outpatients when QOL is the psychosocial outcome measure.


Nestin expression associates with poor prognosis and triple negative phenotype in locally advanced (T4) breast cancer.
Nestin, an intermediate filament protein, has traditionally been noted for its importance as a neural stem cell marker. However, in recent years, expression of nestin has shown to be associated with general proliferation of progenitor cell populations within neoplasms. There is no reported study addressing nestin expression in T4 breast cancer patients. Thus, the aim of the present study was to investigate, through immunohistochemistry, the expression and distribution of nestin in T4 breast cancer, in order to determine its association with clinical and pathological parameters as well as with patients' outcome. Nestin was detectable in tumoral cells and in endothelial cells of blood microvessels, and it is significantly expressed in triple-negative and in inflammatory breast cancer (IBC) subgroups of T4 breast tumours. The Kaplan-Meier analysis showed that the presence of nestin in tumoral cells significantly predicted poor prognosis at 5-years survival (P=0.02) and with borderline significance at 10-years of survival (P=0.05) in T4 breast cancer patients. On the basis of these observations, we speculate that nestin expression may characterize tumours with an aggressive clinical behavior, suggesting that the presence of nestin in tumoral cells and vessels may be considered an important factor that leads to a poor prognosis. Further studies are awaited to define the biological role of nestin in the etiology of these subgroups of breast cancers.


Customization of stock eye prosthesis for a pediatric patient by a simplified technique.
The unfortunate loss or absence of an eye may be caused by congenital defect , irreparable trauma, tumor or blind eye. The role of the maxillofacial prosthodontist in fabricating an ocular prosthesis to restore facial symmetry and normal appearance for the anophthalmic patient becomes essential. A custom-made ocular prosthesis is an excellent alternative for the people who lose their eye especially in young age. It has acceptable fit, retention and esthetics but is technically difficult to fabricate. On the other hand the stock eye has compromised fit and poor esthetics. Our case report presents a simple technique of customization of stock eye prosthesis to provide accurate fit and acceptable esthetics. How to cite this article: Jurel SK, Talwar N, Chand P, Singh RD, Gupta DS. Customization of Stock Eye Prosthesis for a Pediatric Patient by a Simplified Technique. Int J Clin Pediatr Dent 2012;5(2):155-158.


Gekkonid lizards: average ages derived from tail-loss data.
Information on the rate of tail loss by autotomy, obtained from mark and recapture data, was used to estimate the average ages of adult individuals of the geckos Gehyra variegata and Heteronota binoei; the ages calculated were 4.4 and 1.9 years, respectively.


Diarrheagenic Escherichia coli pathotypes isolated from children with diarrhea in the Federal Capital Territory Abuja, Nigeria.
Escherichia coli are frequently isolated from diarrheic children in the Federal Capital Territory Abuja, Nigeria, but their virulent properties are not routinely evaluated. Therefore, the etiology of childhood diarrheal disease attributable to diarrheagenic Escherichia coli (DEC) in Abuja, Nigeria remains unknown. Stool specimens from 400 acute diarrheic children between 0 and 60 months of age were studied. E. coli strains isolated were evaluated by polymerase chain reaction (PCR) for nine virulence genes and HEp-2 cell adherence to detect and identify five distinct diarrheagenic E. coli categories. Diarrheagenic E.coli was detected in 51 (12.8%) of the diarrheic children. The observed DEC pathotypes were enteropathogenic E. coli (EPEC) in 18 (4.5%) children, enterotoxigenic E. coli (ETEC) in 16 (4.0%), enteroaggrative E. coli (EAEC) in 8 (2.0%), enterohaemorrhagic E. coli (EHEC) in 6 (1.5%), and enteroinvasive E. coli (EIEC) in 3 (0.8%). Four (1.0 %) EPEC strains with only the eae+ gene that adhered diffusely to HEp-2 cell were identified as atypical EPEC. All the DEC categories except atypical EPEC were identified in children between 6 and 12 months of age. This study underscores the need for routine evaluation of diarrheic children for virulence properties of infectious DEC. Atypical EPEC are emerging among the DEC pathotypes isolated from childhood acute gastroenteritis in Abuja, Nigeria.


Utility of different cardiovascular disease prediction models in rheumatoid arthritis.
Rheumatoid arthritis comes with a 30% higher probability for cardiovascular disease than the general population. Current guidelines advocate for early and aggressive primary prevention and treatment of risk factors in high-risk populations but this excess risk is under-addressed in RA in real life. This is mainly due to difficulties met in the correct risk evaluation. This study aims to underline the differences in results of the main cardiovascular risk screening models in the real life rheumatoid arthritis population. In a cross-sectional study, patients addressed to a tertiary care center in Romania for an biannual follow-up of rheumatoid arthritis and the ones who were considered free of any cardiovascular disease were assessed for subclinical atherosclerosis. Clinical, biological and carotidal ultrasound evaluations were performed. A number of cardiovascular disease prediction scores were performed and differences between tests were noted in regard to subclinical atherosclerosis as defined by the existence of carotid intima media thickness over 0,9 mm or carotid plaque. In a population of 29 Romanian rheumatoid arthritis patients free of cardiovascular disease, the performance of Framingham Risk Score, HeartSCORE, ARIC cardiovascular disease prediction score, Reynolds Risk Score, PROCAM risk score and Qrisk2 score were compared. All the scores under-diagnosed subclinical atherosclerosis. With an AUROC of 0,792, the SCORE model was the only one that could partially stratify patients in low, intermediate and high-risk categories. The use of the EULAR recommended modifier did not help to reclassify patients. The only score that showed a statistically significant prediction capacity for subclinical atherosclerosis in a Romanian rheumatoid arthritis population was SCORE. The additional calibration or the use of imaging techniques in CVD risk prediction for the intermediate risk category might be warranted.


Developmental expression of NCS-1 (frequenin), a regulator of Kv4 K+ channels, in mouse heart.
The channel proteins responsible for the cardiac transient outward K+ current (Ito) of human and rodent heart are composed, in part, of pore-forming Kv4.3 or Kv4.2 principal subunits. Recent reports implicate K+ channel interacting proteins (members of the neuronal Ca2+-binding protein family) as subunits of the Ito channel complex. We reported that another Ca2+-binding protein, frequenin [or neuronal calcium center protein-1 (NCS-1)], also functions as a Kv4 auxiliary subunit in the brain. By examining cardiac expression of NCS-1, the aim of this study was to examine the potential physiologic relevance of this protein as an additional regulator of cardiac Ito. Immunoblot analysis demonstrates NCS-1 protein to be expressed in adult mouse ventricle at levels comparable to that found in some brain regions. Cardiac NCS-1 protein expression levels are much higher in fetal and neonatal mouse hearts when compared with the adult. Immunocytochemical analysis of isolated neonatal mouse ventricular myocytes demonstrates co-localization of NCS-1 and Kv4.2 proteins at the sarcolemma. Given its high levels of expression in the heart, NCS-1 should be considered an important potential Kv4 regulatory subunit, particularly in the immature heart.


Automated Ex Situ Assays of Amyloid Formation on a Microfluidic Platform.
Increasingly prevalent neurodegenerative diseases are associated with the formation of nanoscale amyloid aggregates from normally soluble peptides and proteins. A widely used strategy for following the aggregation process and defining its kinetics involves the use of extrinsic dyes that undergo a spectral shift when bound to β-sheet-rich aggregates. An attractive route to carry out such studies is to perform ex situ assays, where the dye molecules are not present in the reaction mixture, but instead are only introduced into aliquots taken from the reaction at regular time intervals to avoid the possibility that the dye molecules interfere with the aggregation process. However, such ex situ measurements are time-consuming to perform, require large sample volumes, and do not provide for real-time observation of aggregation phenomena. To overcome these limitations, here we have designed and fabricated microfluidic devices that offer continuous and automated real-time ex situ tracking of the protein aggregation process. This device allows us to improve the time resolution of ex situ aggregation assays relative to conventional assays by more than one order of magnitude. The availability of an automated system for tracking the progress of protein aggregation reactions without the presence of marker molecules in the reaction mixtures opens up the possibility of routine noninvasive study of protein aggregation phenomena.


[Effects of beta-antagonists and beta 1-partial agonists on the pulmonary pressor response to 5-HT].
The effects of beta-antagonists (propranolol, pindolol, atenolol) and beta 1-partial agonists (xamoterol, denopamine) on the pulmonary circulation, and on the pressor response to 5-HT were investigated and compared with those of a beta-agonist, isoproterenol. These agents (at doses of 0.002-20 mg) were administrated into the isolated lung lobe perfusion system excised from mongrel dogs (7-12 kg in weight). Under standard conditions (mean pulmonary inflow pressure, 15 mmHg; mean outflow pressure, 5 mmHg), propranolol and atenolol had no effect on pulmonary vascular resistance (PVR) at the tested doses, but pindolol which has intrinsic sympathomimetic activity (ISA) and two beta 1-partial agonists significantly decreased PVR in a dose-dependent manner (each n = 7). Isoproterenol, up to a dose of 0.2 mg, markedly decreased PVR, but induced vasoconstriction in larger doses (n = 7). Propranolol and xamoterol similarly reduced the pressor response to 30 micrograms of 5-HT from a dose of 2 mg, and these inhibitory actions were greater than those of the other drugs. Pindolol and denopamine inhibited the 5-HT response in a dose of 20 mg, whereas atenolol only augmented the response in a dose-dependent manner. In conclusion, beta-antagonists with ISA (including beta 1-partial agonist activity) can dilate the pulmonary vessels in a dose-dependent manner, but not beta-antagonists without ISA. Furthermore, the 5-HT inhibitory effects caused by relatively large doses of beta-antagonists, except for atenolol, may be related to the 5-HT receptor blockade or other unknown mechanisms, including calcium influx or prostaglandin synthesis, but not to the beta-receptor blockade.


Changes in U.S. life expectancy.
In 1993 the expectation of life in the United States apparently declined slightly. Newborns could expect, on average, to live 75.4 years; for baby boys the figure was 72.0 years and for girls 78.7 years. Each of these values represents a decline of 0.3 years from the 1992 provisional expectancies prepared by the National Center for Health Statistics, and results in average future lifetime returning to the 1990-91 level. Last year's decrease in life expectation was primarily brought about by the considerable rise in the absolute number of deaths and the corresponding increase in mortality rates. Indications are that mortality increased from all major forms of death as well as from AIDS. It is estimated that there were 2,260,000 deaths in 1993 compared with the provisional count of 2,177,000 in 1992 and the final figure of 2,169,518 in 1991. Notwithstanding, projections indicate that expectation of life will continue to rise into the foreseeable future although occasional small declines are likely such as that reported for 1993.


Generation and characterization of a recombinant vesicular stomatitis virus expressing the glycoprotein of Borna disease virus.
Borna disease virus (BDV) is an enveloped virus with a nonsegmented negative-strand RNA genome whose organization is characteristic of mononegavirales. However, based on its unique genetics and biological features, BDV is considered to be the prototypic member of a new virus family, Bornaviridae, within the order Mononegavirales. BDV cell entry occurs via receptor-mediated endocytosis, a process initiated by the recognition of an as yet unidentified receptor at the cell surface by the BDV surface glycoprotein (G). The paucity of cell-free virus associated with BDV infection has hindered studies aimed at the elucidation of cellular receptors and detailed mechanisms involved in BDV cell entry. To overcome this problem, we generated and characterized a replication-competent recombinant vesicular stomatitis virus expressing BDV G (rVSVDeltaG*/BDVG). Cells infected with rVSVDeltaG*/BDVG produced high titers (10(7) PFU/ml) of cell-free virus progeny, but this virus exhibited a highly attenuated phenotype both in cell culture and in vivo. Attenuation of rVSVDeltaG*/BDVG was associated with a delayed kinetics of viral RNA replication and altered genome/N mRNA ratios compared to results for rVSVDeltaG*/VSVG. Likewise, incorporation of BDV G into virions appeared to be restricted despite its high levels of expression and efficient processing in rVSVDeltaG*/BDVG-infected cells. Notably, rVSVDeltaG*/BDVG recreated the cell tropism and entry pathway of bona fide BDV. Our results indicate that rVSVDeltaG*/BDVG represents a unique tool for the investigation of BDV G-mediated cell entry, as well as the roles of BDV G in host immune responses and pathogenesis associated with BDV infection.


Drosophila melanogaster p-glycoprotein: a membrane detoxification system toward polycyclic aromatic hydrocarbon pollutants.
Polycyclic aromatic hydrocarbons (PAHs) are well-known ubiquitous environmental contaminants. Permeability glycoprotein (P-gp) is a transmembrane detoxification efflux pump transporting various lipophilic xenobiotics, such as PAHs, out of the cells. The existence of a P-gp detoxification system inducible by PAHs was investigated in Drosophila melanogaster. Western blot experiments showed that D. melanogaster expressed a 140-kDa P-gp in S12 cells, embryos, and adult flies. Permeability glycoprotein was expressed in adult flies in the head, abdomen, and thorax and sublocalized in the sexual and olfactory organs. Flow cytometry experiments using Drosophila S12 cells in the presence of PAHs and target P-gp drug compounds revealed that Drosophila P-gp acted as an efflux detoxification pump. In Drosophila exposed to benzo[a]pyrene or to ambient air polluted by higher or lower PAH concentrations, P-gp expression was clearly showed a dose-dependent increase response. The P-gp induction was detected both in adult flies and in different fly parts, such as the head, thorax, and antennae. Drosophila P-gp acts as a membrane barrier against PAH pollutants.


[X-ray evaluation of pulp calcification in adult permanent teeth after pulpotomy].
To compare the clinical effects of pulpotomy with two kinds of calcium silicate materials, and to evaluate the formation of dentin bridge and pulp calcification after pulpotomy of adult permanent teeth. Patients who visited the General Department of Peking University School and Hospital of Stomatology from November 2017 to September 2019 and planned for pulpotomy on permanent premolars and molars with carious exposed pulp were selected. They were randomly divided into two groups. Bioceramic putty material iRoot BP (iRoot group, n=22) and mineral trioxide aggregate MTA (MTA group, n=21) were used as pulp capping agents, respectively. The patients were recalled after one year and two years. The clinical efficacy, dentin bridge index (DBI) and pulp calcification index (PCI) were recorded. Blinding method was used for the patients and evaluators. There was no significant difference in gender, mean age, dentition and tooth position between the two groups (P>0.05). Seven cases were lost during the first year (4 cases in iRoot group and 3 cases in MTA group). In the iRoot group, 1 case had transient sensitivity at the time of 1-year follow-up. The cure rate of the two groups was 100% at the time of 2-year follow-up. The proportion of dentin bridge formation was 38.9% one year after operation, 55.6% two years after operation. The proportion of partial or even complete disappearance of root canal image was 5.6% before operation, 38.9% and 55.6% one and two years after operation, respectively. The difference was statistically significant by rank sum test (P < 0.05). There was no significant difference in dentin bridge formation and pulp calcification between the two groups (P < 0.05). DBI and PCI after operation was as the same as those before operation (44.4% cases of DBI and 25% cases of PCI) or gradually increased (55.6% cases of DBI and 75% cases of PCI). Spearman's nonparametric correlation analysis showed that age was positively correlated with preoperative pulp calcification index (PCI0, P < 0.05), but not with the dentin bridge index (DBI1, DBI2), pulp calcification index (PCI1, PCI2) and the degree of change (DBI2 vs. DBI1, PCI1 vs. PCI0, PCI2 vs. PCI0) 1-year and 2-year after operation (P>0.05). According to this study, good clinical effects were obtained within 2-year after pulpotomy of adult permanent teeth with MTA and iRoot. In some cases, the root canal system had a tendency of calcification aggravation, and there was no statistical difference in the development of this trend between the two groups.


Systematic Review of Multi-Dimensional Vulnerabilities in the Himalayas.
The Himalayan region is a fragile high mountain landscape where the population experiences acute vulnerability within a complex coupled human-natural system due to environmental, social, and economic linkages. The lack of significant regional and spatial knowledge of multi-faceted vulnerabilities hinders any potential recommendations to address these vulnerabilities. We systematically reviewed the literature to recommend mitigation interventions based on the region's socio-economic and ecological vulnerability research to date. We applied the PRISMA (Preferred Reporting of Items for Systematic Review and Meta-Analysis) criteria to search for results from four comprehensive databases. For our assessment, we compiled a final sample (n = 59) of vulnerability research papers to examine the vulnerability types, spatial variation, assessment methodology, and significant drivers of change. Our study represented all Himalayan countries, namely, India, Nepal, Pakistan, China, and Bhutan. More than half of the vulnerability studies were conducted in the central Himalayan region, a quarter in the western Himalayas, and a few in the eastern Himalayas. Our review revealed that the primary drivers of change were climate change, land use/land cover, and glacial lake formation. The vulnerability assessments in the Himalayan region primarily used social science methods as compared to natural science methods. While the vulnerability studies seldom assessed mitigation interventions, our analysis identified fourteen recommendations. The recommended interventions mainly included policy interventions, livelihood improvement, and adaptation measures. This study emphasized that sustainable development requires cross-sectoral interventions to manage existing resources and mitigate the confronting vulnerabilities of the region.


Efficient hydrolysis of tuna oil by a surfactant-coated lipase in a two-phase system.
A surfactant-coated lipase (SCL) prepared by mixing Candida rugosa lipase with emulsifier in ethanol was used to hydrolyze tuna oil in a two-phase aqueous-organic system. Both enzyme (SCL) and substrate (tuna oil) were soluble in the organic phase, and the hydrolysis could occur with water molecules from the aqueous phase. This hydrolysis could promptly proceed compared to that catalyzed by native lipases which only occurred at the interface between the two phases. Michaelis-Menten kinetics in the two-phase reactions showed that the K(m) value of the SCL was half that of the native lipase, while the maximum velocity (V(max)) was 11.5 times higher. The hydrolysis method resulted in enrichment of n-3 polyunsaturated fatty acid (n-3 PUFA) content in glyceride mixtures from 26.4% to 49.8% and DHA from 19.1% to 38.9%. The SCL acted as an efficient hydrolytic catalyst for tuna oil.


Identification of protein-bound oligosaccharides on the surface of growth cones that bind to muscle cells.
In the accompanying paper (Gabel, Den, and Ambron, in press) it was shown that eight populations of glycopeptides are synthesized by single neurons of Aplysia californica. To see which glycopeptides might mediate interactions with target cells, we first identified glycopeptides that are transported selectively to synapses and growth cones. The giant neuron R2 was injected intrasomatically with 3H-glucosamine. Twenty-four hours later, 3H-glycopeptides in the axon and cell body were isolated and resolved by serial lectin affinity chromatography. Of the eight populations, the biantennary-type glycopeptides (GPbi) and those that bind to WGA (GPwga) were preferentially associated with rapidly transported glycoproteins. In contrast, the glycopeptide that consists of N-acetylglucosamine O-linked to ser/thr was mostly retained in the cell body. GPbi and GPwga were also preferentially transported to growth cones. Analyses of RUQ cells, exposed to 3H-glucosamine in vitro for 36 h showed an enrichment of GPbi and GPwga at the growth cone relative to the cell body. The disposition of the various glycopeptides in growing neurons was also examined using FITC lectins. FITC-coupled WGA, Vicia vellosa, and lentil lectin showed extensive staining of the cell body, but only WGA stained the growth cones. To investigate if GPwga interacts specifically with target cells, these glycopeptides were isolated from the neurons of 180 abdominal ganglia. GPwga, other Aplysia glycopeptides, and glycopeptides prepared from ovalbumin were coupled separately to fluorescent spheres. The spheres were then added to muscle cells isolated from the auricle of the heart, which is innervated by many neurons from the ganglion. While spheres coupled to GPwga bound to the muscle cell surface, the other glycopeptides did not. These results indicate that glycopeptides class GPwga, found among rapidly transported glycoproteins and on the growth cone surface, is able to bind to muscle cells and may therefore play some role in neuron-target interactions.


Insertion of molecular oxygen into a palladium-hydride bond: computational evidence for two nearly isoenergetic pathways.
The reaction of a palladiumII-hydride species with molecular oxygen to form palladiumII-hydroperoxide has been proposed as a key step in Pd-catalyzed aerobic oxidation reactions. We recently reported one of the first experimental precedents for such a step (Angew. Chem., Int. Ed. 2006, 45, 2904-2907). DFT calculations have been used to probe the mechanism for this reaction, which consists of formal insertion of O2 into the palladium-hydride bond of trans-(NHC)2Pd(H)OAc (NHC = N-heterocyclic carbene). Four different pathways were considered: (1) hydrogen atom abstraction (HAA) of the Pd-H bond by molecular oxygen, (2) reductive elimination of HX followed by oxygenation of Pd0 and protonolysis of the (eta2-peroxo)-PdII species, (3) oxygenation of palladiumII-hydride with subsequent reductive elimination of the O-H bond from an eta2-peroxo-PdIV center, and (4) formation of a cis-superoxide adduct of the palladium-hydride species followed by O-H bond formation via hydrogen atom migration. The calculations reveal that pathways 1 and 2 are preferred energetically, and both pathways exhibit very similar kinetic barriers. This result suggests that more than one pathway is possible for catalyst reoxidation in Pd-catalyzed aerobic oxidation reactions.


Discordance of physiological and biochemical response to smoking and to psychological stress.
Both smoking and psychological stress produce marked effects upon cardiovascular function, and several studies have demonstrated that in combination they produce additive or potentiating effects. More recently, it has been reported that individuals strongly reactive to psychological stress are also strongly reactive to nicotine. In an attempt to replicate and extend those findings, we examined reactivity to smoking and competitive mental arithmetic across several physiological and biochemical variables. Despite stable responding across mental arithmetic trials, we were unable to demonstrate significant correlations between reactivity to smoking and to a psychological stressor. We further observed that anxiety level, when low, was a poor predictor of desire to smoke and of withdrawal, whereas higher anxiety levels were more tightly linked to these measures. These findings have implications for the identification of individuals at risk of cardiovascular disease as well as for the design of smoking treatment and relapse prevention programs.


Augmentation of Pulmonary Perfusion by Conducted Effects of a Pulmonary Artery Ultrasound Catheter.
Ultrasound (US) generated by catheters used clinically for US-facilitated thrombolysis can release shear-dependent vasodilators from endothelial and red blood cells. We hypothesized that catheter-based US in the pulmonary artery (PA) decreases downstream vascular resistance and increases pulmonary blood flow. In rhesus macaques, a U.S. Food and Drug Administration-approved multi-element US catheter was placed in a pulmonary artery. Comprehensive echocardiography was performed (i) at baseline, (ii) during hypoxemia (12% FIO2) to increase pulmonary vascular resistance (PVR) and (c) 15 min after initiating US during hypoxemia. Reduced FIO2 produced intended reductions in oxygen saturation (69 ± 3%) and PaO2 (34 ± 5 mm Hg), yet on echocardiography, hypoxemia did not create the intended model, with only modest hypoxia-related increases in PA systolic pressure (24 ± 4 to 28 ± 4 mm Hg, p = 0.05) and no significant change in PVR or multiparametric right ventricular (RV) function. Although US did not further change total PVR, on 99mTc-macroalbumin aggregate single-photon-emission computed tomography imaging, lung perfusion was significantly higher in the lung ipsilateral to the US catheter versus the contralateral control lung (133 ± 48 cpm vs. 103 ± 43 × 103 cpm, p = 0.01). We conclude that PA catheter-based US increases regional lung perfusion, most likely from vasodilators that are conducted downstream.


Prediction of diabetes recurrence in women with class A1 (diet-treated) gestational diabetes.
We sought to evaluate the likelihood of recurrent diabetes in women with a prior history of diet-treated (class A(1)) gestational diabetes mellitus (GDM). In a retrospective cohort analysis, nulliparous women diagnosed based upon National Diabetes Data Group criteria with diet-treated GDM who had recurrent diabetes in a subsequent pregnancy were compared with those who did not have recurrent diabetes. The probability of recurrent diabetes was calculated using maternal age at first pregnancy, interpregnancy interval, and body mass index (BMI) during the subsequent pregnancy. Three hundred forty-four nulliparous women with diet-treated GDM had a subsequent delivery in our database. One hundred thirty-seven (40%) had recurrent diabetes. Women with a history of GDM were more likely to have recurrent diabetes if they were heavier (193 versus 173 lbs; P < 0.001; BMI 35.7 versus 32.2; P < 0.001) and waited longer between pregnancies (2.9 versus 2.4 years, P = 0.02). Age, interpregnancy interval, and BMI can be used to predict diabetes recurrence in pregnant women with a history of GDM.


The increasing incidence of mumps orchitis: a comprehensive review.
There has been a recent increase in mumps orchitis among pubertal and postpubertal males. These outbreaks can be attributed to a reduction in the uptake of measles-mumps-rubella (MMR) vaccine during the early to mid-1990 s in children who have now matured. The mumps virus is commonly associated with extra-salivary complications. Unvaccinated postpubertal males diagnosed with mumps virus frequently develop complications such as mumps orchitis. Therefore, it is important that urologists are familiar with the diagnosis, treatment and complications of this condition. Here we review the epidemiology, clinical presentation, diagnostic methods, treatment options and complications of mumps orchitis, as a complication of mumps virus, with particular emphasis on testicular atrophy, subfertility and infertility.


Extradural Clinoidectomy in Clinoidal Meningiomas: Analysis of the Surgical Technique and Evaluation of the Clinical Outcome.
The surgical treatment of clinoidal meningiomas is currently still discussed in the literature. Different surgical approaches have been proposed and evaluated, in multiple studies, in order to improve the surgical outcomes. The aim of this study is to evaluate the advantages of extradural clinoidectomy in the context of tumor removal radicality for visual function improvement. A retrospective analysis was performed on 74 patients-of which 26 patients with clinoidal meningiomas were in group III, according to Al Mefty classification-who underwent surgery at the Policlinico Umberto I Hospital between 2000 and 2019. Further, extradural clinoidectomy was performed on 15 patients (Group A), and 11 patients underwent the pterional approach only (Group B). Additionally, visual impairment was present in all 26 patients before surgery. Next, visual function assessment was performed on all patients, both in presurgery and postsurgery. Radiological follow up was performed at 3 and 6 months, and then every 12 months. Gross Total Resection (GTR) was achieved in 13/15 (86.7%) patients who underwent clinoidectomy, and in 4/11 (36.4%) patients who did not undergo clinoidectomy. Visual function improvement was achieved in 12/15 (80%) patients who underwent clinoidectomy and in 4 of 11 (36.4%) who did not undergo clinoidectomy. According to our study, extradural clinoidectomy is the most suitable method for facilitating the gross total resection of clinoidal meningiomas. Our experience and data suggest that a higher rate of total resection and, subsequently, the best visual outcomes are achieved. Extradural drilling via the anterior clinoid process reveals a wider surgical corridor for meticulous tumor resection.


Properties of Sweet Buttermilk Released from the Churning of Cream Separated from Sheep or Cow Milk or Sheep Cheese Whey: Effect of Heat Treatment and Storage of Cream.
The objective of the study was to compare the buttermilk released from the churning of sweet cream separated from sheep milk (BSM) or whey (BSW) with the buttermilk from sweet cow milk cream (BCM). Additional experimental factors were the heat treatment (68 °C for 10 or 30 min) and storage of cream (refrigeration or freezing). The composition of BSM was the most advantageous in terms of non-fat solids, protein-which was the most abundant solid component-casein, calcium and phosphorus contents. No significant differences were observed in the phospholipids (PL) content of BSM, BCM and BSW. Antioxidant potential and emulsion stability (ES) of BSM were the highest. The radical scavenging activity (RSA) of BSW was high opposite to chelating activity (CA). Some functional properties of BSW were similar to those of BSM and BCM. The freezing of cream affected the churning, the fat content, the soluble nitrogenous fraction at pH 4.6 (WSN) and some functional properties of buttermilk, but not in a consistent manner. The properties of BSM were marginally affected or unaffected by the use of frozen cream. The freezing of whey cream caused significant changes (p < 0.05) in the protein profile and the functional behaviour of BSW. Cream heat treatment affected the WSN of BSW opposite to its sweet cream counterparts.


Identification of the correct lumbar level using passive intersegmental motion testing.
This study aimed to assess the accuracy and agreement between examiners when attempting to identify a single lumbar spinal level using passive intersegmental motion testing, a technique commonly used by physical therapists. Thirty-five adults were examined independently by an experienced and a novice clinician. Each examiner was asked to identify and note the interspace between the fifth lumbar vertebra and the first sacral vertebra, and to mark it. The mark was invisible to the second clinician asked to identify the same lumbar interspace. The true level was then identified by fluoroscopic imaging and was correct in 54-57% of cases. Interobserver agreement was poor. A significant learning effect was found for the experienced examiner, with proportionately more correct levels identified during the second part of the study (79%) when compared to the first (31%). The results show that intersegmental motion testing is a relatively unreliable method of identifying the correct spinal level.


Automated external defibrillators and in-hospital cardiac arrest: patient survival and device performance at an Australian teaching hospital.
To evaluate the effect of automated external defibrillators (AEDs) on patient survival and to describe the performance of AEDs after in-hospital cardiac arrest. Prospectively collected data were analysed for cardiac arrests in the general patient care areas of a teaching hospital during the 3 years before and the 3 years after the deployment of AEDs. The association between availability of an AED and survival to hospital discharge was assessed using multivariate logistic regression. AED performance during automated management of the initial rhythms was assessed using information captured by the AEDs. There were 84 cardiac arrests in the AED period and 82 in the pre-AED period. Patient and event characteristics were similar in each period. The initial rhythm was shockable in 16% of cases. Return of spontaneous circulation was higher in the AED period (54% vs. 35%, P=0.02) but the proportion of hospital survivors in each period was similar (22% vs. 19%, P=0.56). The adjusted odds ratio for hospital survival when an AED was available was 1.22 (95% CI 0.53-2.84, P=0.64). An AED was applied in 77/84 (92%) possible cases. Median interruption to chest compressions was 12s (inter-quartile range 12-13). An automated shock was delivered in 8/13 (62%) possible cases. Availability of AEDs was not independently associated with hospital survival. Shockable presenting rhythms were not common and, in keeping with the manufacturer's specifications, the AEDs did not shock all potentially shockable rhythms. The hands-off time associated with automated rhythm management was considerable.


TCDD and a putative endogenous AhR ligand, ITE, elicit the same immediate changes in gene expression in mouse lung fibroblasts.
The aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor, mediates toxicity of several classes of xenobiotics and also has important physiological roles in differentiation, reproduction, and immunity, although the endogenous ligand(s) mediating these functions is/are as yet unidentified. One candidate endogenous ligand, 2-(1'H-indolo-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), is a potent AhR agonist in vitro, activates the murine AhR in vivo, but does not induce toxicity. We hypothesized that ITE and the toxic ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), may modify transcription of different sets of genes to account for their different toxicity. To test this hypothesis, primary mouse lung fibroblasts were exposed to 0.5muM ITE, 0.2nM TCDD, or vehicle for 4 h, and total gene expression was evaluated using microarrays. After this short-term and low-dose treatment, several hundred genes were changed significantly, and the response to ITE and TCDD was remarkably similar, both qualitatively and quantitatively. Induced gene sets included the expected battery of AhR-dependent xenobiotic-metabolizing enzymes, as well as several sets that reflect the inflammatory role of lung fibroblasts. Real time quantitative RT-qPCR assay of several selected genes confirmed these microarray data and further suggested that there may be kinetic differences in expression between ligands. These data suggest that ITE and TCDD elicit an analogous change in AhR conformation such that the initial transcription response is the same. Furthermore, if the difference in toxicity between TCDD and ITE is mediated by differences in gene expression, then it is likely that secondary changes enabled by the persistent TCDD, but not by the shorter lived ITE, are responsible.


TAEO-A Thermal Aware & Energy Optimized Routing Protocol for Wireless Body Area Networks.
Wireless Body Area Networks (WBANs) are in the spotlight of researchers and engineering industries due to many applications. Remote health monitoring for general as well as military purposes where tiny sensors are attached or implanted inside the skin of the body to sense the required attribute is particularly prominent. To seamlessly accomplish this procedure, there are various challenges, out of which temperature control to reduce thermal effects and optimum power consumption to reduce energy wastage are placed at the highest priority. Regular and consistent operation of a sensor node for a long-time result in a rising of the temperature of respective tissues, where it is attached or implanted. This temperature rise has harmful effects on human tissues, which may lead to the tissue damage. In this paper, a Temperate Aware and Energy Optimized (TAEO) routing protocol is proposed that not only deals with the thermal aspects and hot spot problem, but also extends the stability and lifetime of a network. Analytical simulations are conducted, and the results depict better performance in terms of the network lifetime, throughput, energy preservation, and temperature control with respect to state of the art WBAN protocols.


[RAEB in transformation in continuing complete remission by small doses of cytarabin].
Two patients with refractory anemia with excess of blasts in transformation having entered remission and in continuing complete remission with the small-dose cytarabine therapy (SDCA) are reported. SDCA was the only chemotherapy used in these two patients. Cytarabine was injected subcutaneously every 12 hours at doses 15 mg and 10 mg, respectively, in cases 1 and 2. Case 1, a 60-year-old woman, achieved remission after a 14-day course of SDCA. Thereafter, she received SDCA for seven consecutive days every month or every other months in the first year and every two or three months in subsequent years. Her remission has been maintained for 57 months. Case 2, a 76-year-old man, attained a remission after three courses of SDCA, each consisting of 16, 11 and 14 days, respectively. SDCA was then repeated every month for 6 consecutive days. He is still in remission after 33 months. Whereas SDCA caused severe bone marrow suppression during induction, it was well tolerated when given in remission without necessitating any supportive measure.


Mental health reform not always beneficial.
History is instructive even when the lessons learned cannot be easily transposed to a new time and place. The aim of this paper is to describe psychiatric reforms implemented one hundred years ago in Germany and how, contrary to their intention, they resulted, with changes in economics, politics and ideology, in disaster for psychiatric patients. The conclusion for our time is that the new and seemingly expedient need always to be questioned. If nothing else, the paper reviews an important era in the history of our profession.


A guideline for placement of an infra-acetabular screw based on anatomic landmarks via an intra-pelvic approach.
Due to demographic changes, more and more fracture patterns involving anterior acetabular structures occur. The infra-acetabular screw is seen a useful tool to increase stability in fixation of the acetabular cup. However, the exact position of this screw in relation to anatomic landmarks which are intra-operatively palpable via an intra-pelvic approach has not yet been determined. This biomorphometric experimental study references the ideal screw position of an infra-acetabular screw to anatomic landmarks palpable via an intra-pelvic approach. Therefore, we created a computer tomography-based 3D-model of 40 patients (20 women, 20 men) who received a computer tomography (CT) scan of the pelvis for any other reason than an acetabular fracture. The entry point of an ideal infra-acetabular was of high constancy. At mean, this point was 10.2 mm caudal and 10.4 mm medial of the ilio-pubic/ilio-pectineal eminence. This reference is independent of age, gender, or physical dimensions. However, we found gender-dependent differences for the angulation and the length of the screw. This study provides a comprehensive guideline to determine the ideal entry point for an infra-acetabular screw via an intra-pelvic approach. The entry point is located 10.2 mm caudal and 10.4 mm medial of the ilio-pubic/ilio-pectineal eminence. Clinical Trial Registry University of Regensburg Z-2017-0930-1 . Registered 04. Dec 2017.


Carbohydrate metabolism in Dictyostelium discoideum: II. Systems' analysis.
A transition model of carbohydrate metabolism during differentiation of Dictyostelium discoideum was described in Wright & Albe (1994, J. theor. Biol. 168, 231-241). From this base model, two steady-state models are derived in which concentration and flux are consistent with culmination (600 min) or young sorocarp (700 min) stages of development. These steady-state models are analyzed using metabolic control theory (MCT), and the summation property is met for metabolites, individual flux rates, and overall flux control coefficients. The MCT analyses show that flux control differs between the two stages. At culmination, cellulose synthetase is the major control point for overall pathway flux (C = 0.86) whereas at young sorocarp, glycogen phosphorylase is the major control point (C = 0.89). This is a reflection of the increased competition between the endproduct synthases, which are used to define overall pathway flux. Thus the specific metabolic state of the cells is important in assessing control distribution. The significance of this work in understanding the mechanisms controlling biochemical differentiation is discussed and related to the work of others in the field. For example, mutant analysis can reveal which enzymes are essential to differentiation (most are) but cannot reveal which enzymes are unique and/or rate-controlling.


[Diagnosis of choledochal cysts. The methodological value of imaging procedures].
For 10 cases in which we detected cysts in the choledochus ourselves comparing traditional radiological methods (infusion-cholegram, ERC, scintigraphy, barium meal examination, angiography) with recent imaging procedures (ultrasound, CT, NMR) the following sequence of procedures proved to be favorable: Screening methods are ultrasound and infusion-cholegram. CT and NMR furnish good presentations of the intra- and extrahepatic dilatations of the bile duct. ERC still represents the best methods for demonstration of an extrahepatic cyst of the choledochus. Hepato-biliary functional scintigraphy is performed as a supplement. Barium meal examination and coeliacography furnish a small diagnostic contribution only.


A biodegradable polyurethane dermal matrix in reconstruction of free flap donor sites: a pilot study.
We have developed a biodegradable temporizing matrix (BTM) capable of supporting secondary split-skin graft-take in animal studies. We report its first long-term implantation and use as a dermal scaffold in humans. This preliminary study assesses its ability to integrate, its ease of delamination, its ability to sustain split-skin graft in complex wounds, the degree of wound contraction, and ultimately the quality of the scar at 1 year postimplantation. Ten patients were recruited, each requiring elective free flap reconstruction. Free flap donor sites created were anterolateral thigh flaps, fibular osseocutaneous flaps, or radial/ulnar forearm (RF/UF) flaps. The BTM was implanted when the flap was detached from its donor site. Dressing changes were performed twice weekly. The time elapsed between implantation and delamination depended on the type of flap and thus the wound bed left. Once integrated, the BTMs were delaminated in theatre, and the surface of the "neodermis" was refreshed by dermabrasion, prior to application of a split-skin graft. The BTM integration occurred in all patients (100% in 6 patients, with 90%, 84%, 76%, and 60% integration in the remainder). Integrated BTM sustained successful graft-take in all patients. Complete take was marred in 2 patients, over areas of BTM that had not integrated and graft application was performed too early. The BTM can be applied into wounds in humans and can integrate, persist in the presence of infection, and sustain split-skin overgrafting, despite the trial group presenting with significant comorbidities.


Serum lipid profile in leprosy.
Serum lipids and lipoproteins were assessed in 40 patients of leprosy and 20 healthy controls (age & sex matched). The leprosy cases included 20 cases each of paucibacillary and multibacillary leprosy.


The efficiency of cell fusion-based reprogramming is affected by the somatic cell type and the in vitro age of somatic cells.
Cell fusion is one approach that has been used to demonstrate nuclear reprogramming of somatic cells to a pluripotent-like state and is a useful tool for screening factors involved in reprogramming. Recent cell fusion studies reported that the overexpression of Nanog and SalI could improve the efficiency of reprogramming, whereas AID was shown to be essential for DNA demethylation and initiation of reprogramming. The aim of this study was to investigate factors affecting the reprogramming efficiency following cell fusion. We conducted fusions of mouse embryonic stem cells (ESCs) with somatic cells carrying a GFP transgene under control of the Oct4 promoter (Oct4-GFP), which is normally repressed in nonpluripotent cells. The effect of somatic cell type on the reprogramming efficiency was investigated using Oct4-GFP expression as an indicator. Different somatic cell types were tested including mesenchymal stem cells (MSCs), adipose tissue-derived cells (ADCs), neural stem cells (NSCs), and these were compared with the mouse embryonic fibroblast (mEF) standard. The reprogramming efficiencies differed greatly, with mEFs (0.477 ± 0.003%) and MSCs (0.313 ± 0.003%) showing highest efficiencies while NSCs (0.023 ± 0.014%), and ADCs (0.006 ± 0.006%) had significantly lower reprogramming efficiencies (p < 0.05). The differences in the reprogramming efficiencies observed could be in part explained by the in vitro age of the somatic cells used. We demonstrated that the reprogramming efficiency of early passage mEFs was significantly higher compared with late passage mEFs (0.330 ± 0.166% vs. 0.021 ± 0.011%, p < 0.05), suggesting that senescence can affect reprogramming potential. In summary, this study shows that different somatic cell types do not have equivalent potential to be reprogrammed following fusion with ESCs. Furthermore, the in vitro age of somatic cells can also affect the reprogrammability of somatic cells. These findings constitute an important consideration for reprogramming studies.


Atypical anorexia nervosa: Implications of clinical features and BMI cutoffs.
Atypical anorexia nervosa (atypical AN) appears to be a heterogeneous disorder under the current diagnostic system. Though the body mass index (BMI) cutoff point of 18.5 kg/m2 is a criterion that distinguishes atypical AN from AN, the cutoff may not be universally applicable as the norms for BMI vary and can be affected by several factors, including cross-country differences and social determinants. It is unfortunate that we do not yet have reliable or widely available criteria other than BMI for the diagnosis of atypical AN. Additional relevant markers of atypical AN are needed in future diagnostic systems.


Antigenic and genetic characterization of a putative hybrid transferrin-binding protein B from Neisseria meningitidis.
The transferrin-binding protein Bs (TbpBs) from the bacterium Neisseria meningitidis have been divided into two families according to genetic and antigenic features. TbpB from meningococcal strain B385 showed a molecular mass similar to that exhibited by TbpBs belonging to the high molecular mass family of TbpBs. TbpB was recognized by immunoassay using a specific serum directed against the TbpB of the reference strain for this family (strain M982). It was also recognized by a serum elicited against the TbpB of the reference strain for the low molecular mass family (strain B16B6). The tbpB gene from strain B385 was cloned and sequenced. The highest degree of sequence homology was found to be with the TbpBs belonging to the high molecular mass family, although a region of 14 amino acids that is only present in the TbpB from strain B16B6 was also found. This report illustrates a TbpB that shows hybrid antigenic and genetic behaviour.


The Link that Lasts: A New Frontier in Supramolecular Block Copolymer Design.
Lasting link: A supramolecular linkage between two parts of an amphiphilic block copolymer was developed that is sufficiently strong to allow phase-separation-driven nanopatterning as well as chromatographic characterization. The link can also be severed in response to a solvent trigger signal. This powerful approach will open new avenues for the production of self-healing materials, triggered-release systems, and reversible surface designs.


Clubroot resistance gene Rcr6 in Brassica nigra resides in a genomic region homologous to chromosome A08 in B. rapa.
Clubroot, caused by Plasmodiophora brassicae Woronin, is a very important disease of Brassica species. Management of clubroot relies heavily on genetic resistance. In a cross of Brassica nigra lines PI 219576 (highly resistant, R) × CR2748 (highly susceptible, S) to clubroot, all F1 plants were resistant to clubroot. There was a 1:1 ratio of R:S in the BC1 and 3R:1S in the F2, which indicated that a single dominant gene controlled clubroot resistance in PI 219576. This gene was designated Rcr6. Mapping of Rcr6 was performed using genome sequencing information from A-genome of B. rapa and B-genome of B. nigra though bulked segregant RNA sequencing (BSR-Seq) and further mapping with Kompetitive Allele Specific PCR (KASP) analysis. Reads of R and S bulks from BSR-Seq were initially aligned onto B. rapa (A-genome; B. nigra has the B-genome) where Rcr6 was associated with chromosome A08. KASP analysis showed that Rcr6 was flanked by SNP markers homologous to the region of 14.8-15.4 Mb of chromosome A08. There were 190 genes annotated in this region, with five genes (Bra010552, Bra010588, Bra010589, Bra010590 and Bra010663) identified as encoding the toll-interleukin-1 receptor / nucleotide-binding site / leucine-rich-repeat (TIR-NBS-LRR; TNL) class of proteins. The reads from BSR-Seq were then aligned into a draft B-genome of B. nigra, where Rcr6 was mapped on chromosome B3. KASP analysis indicated that Rcr6 was located on chromosome B3 in a 0.5 Mb region from 6.1-6.6 Mb. Only one TNL gene homologous to the B. rapa gene Bra010663 was identified in the target region. This gene is a likely candidate for Rcr6. Subsequent analysis of the Rcr6 equivalent region based on a published B. nigra genome was performed. This gene is located into chromosome B7 of the published B-genome, homologous to BniB015819. Rcr6 was the first gene identified and mapped in the B-genome of Brassica species. It resides in a genomic region homologous to chromosome A08 of A-genome. Based on this finding, it could possibly integrate into A08 of B. napus using marker assisted selection with SNP markers tightly linked to Rcr6 developed in this study.


Histoplasmosis in solid organ transplant recipients: early diagnosis and treatment.
To present current knowledge about the epidemiology, clinical presentation, diagnosis and treatment of histoplasmosis in solid organ transplant (SOT) recipients. Histoplasmosis is rare in SOT patients, and most cases have been reported from large transplant centers in the Midwestern USA, where the fungus is endemic. Urine antigen testing and the chest computed tomography scan are emerging as especially useful diagnostic tools in the SOT population. Standard treatments include liposomal amphotericin b followed by itraconazole, but newer azoles (voriconazole and posaconazole) have good in-vitro activity and have been successfully used in some SOT cases. Clinical suspicion is essential to early recognition of histoplasmosis in SOT patients who often present with fever of unknown cause and pulmonary symptoms. Diagnosis is usually made by a combinatorial approach, including antigen tests, radiology and appropriate biopsies for culture and histology. Treatment with available antifungals is associated with more than 95% success.


Relaxation properties in a diffusive model of k-mers with constrained movements on a triangular lattice.
We study the relaxation process in a two-dimensional lattice gas model, based on the concept of geometrical frustration. In this model the particles are k-mers that can both randomly translate and rotate on the planar triangular lattice. In the absence of rotation, the diffusion of hard-core particles in crossed single-file systems is investigated. We monitor, for different densities, several quantities: mean-square displacement, the self-part of the van Hove correlation function, and the self-intermediate scattering function. We observe a considerable slowing of diffusion on a long-time scale when suppressing the rotational motion of k-mers; our system is subdiffusive at intermediate times between the initial transient and the long-time diffusive regime. We show that the self-part of the van Hove correlation function exhibits, as a function of particle displacement, a stretched exponential decay at intermediate times. The self-intermediate scattering function (SISF), displaying slower than exponential relaxation, suggests the existence of heterogeneous dynamics. For each value of density, the SISF is well described by the Kohlrausch-Williams-Watts law; the characteristic timescale τ(q(n)) is found to decrease with the wave vector q(n) according to a simple power law. Furthermore, the slowing of the dynamics with density ρ(0) is consistent with the scaling law 1/τ(q(n);ρ(0))∝(ρ(c)-ρ(0))(ϰ), with the same exponent ϰ=3.34±0.12 for all wave vectors q(n). The density ρ(c) is approximately equal to the closest packing limit, θ(CPL)≲1, for dimers on the two-dimensional triangular lattice. The self-diffusion coefficient D(s) scales with the same power-law exponent and critical density.


HPV vaccine, Twitter, and gay, bisexual and other men who have sex with men.
This study aimed to quantify human papillomavirus (HPV) vaccine Twitter messaging addressing gay, bisexual and other men who have sex with men (GB+MSM) and describes messaging by vaccine sentiment (attitudes towards vaccine) and characteristics (topic of messaging). Between August 2014 and July 2015, we collected 193 379 HPV-related tweets and classified them by vaccine sentiment and characteristics. We analysed a subsample of tweets containing the terms 'gay', 'bisexual' and 'MSM' (N = 2306), and analysed distributions of sentiment and characteristics using chi-square. HPV-related tweets containing GB+MSM terms occupied 1% of our sample. The subsample had a largely positive vaccine sentiment. However, a proportion of 'gay' and 'bisexual' tweets did not mention the vaccine, and a proportion of 'gay' and 'MSM' tweets had a negative sentiment. Topics varied by GB+MSM term-HPV risk messaging was prevalent in 'bisexual' (25%) tweets, and HPV transmission through sex/promiscuity messaging was prevalent in 'gay' (18%) tweets. Prevention/protection messaging was prevalent only in 'MSM' tweets (49%). Although HPV vaccine sentiment was positive in GB+MSM messaging, we identified deficits in the volume of GB+MSM messaging, a lack of focus on vaccination, and a proportion of negative tweets. While HPV vaccine promotion has historically focused on heterosexual HPV transmission, there are opportunities to shape vaccine uptake in GB+MSM through public health agenda setting using social media messaging that increases knowledge and minimizes HPV vaccine stigma. Social media-based HPV vaccine promotion should also address the identities of those at risk to bolster vaccine uptake and reduce the risk of HPV-attributable cancers.


Moisture sorption profiles and tensile strength of tableted phenobarbitone formulations.
The tensile strength of tablets made from phenobarbitone and sodium phenobarbitone formulations after storage at increasing ambient relative humidity has been investigated. The moisture sorption and desorption profiles of the formulations were analysed for three locations of moisture: monolayer adsorbed moisture, normally condensed moisture and absorbed moisture. Maxima in tensile strength occur at moisture distributions determined by the disintegrant used. The changes in tensile strength have been explained in terms of changes produced in the interparticle separation, the range of the interparticle forces and changes in the ratio of the binding to diffusional forces, acting on the water molecules which are on the particles' surface.


Prediction of Damage Accumulation Effect of Wood Structural Members under Long-Term Service: A Machine Learning Approach.
It is well known that wood structural members can stand a relatively heavy load in the short term but will gradually get weaker if the load is applied for a longer period. This phenomenon is caused by the damage accumulation effect in wood and should be appropriately considered during the design of timber structures. Although various formulation methods (also known as classical models) have been proposed to evaluate the damage accumulation effect in wood, the calibration of model parameters is very time-consuming. Our work proposes a novel method to deal with the damage accumulation effect in wood that involves the application of machine learning algorithms. The proposed algorithm considers a multi-objective optimization process with a combination of goodness-of-fit and complexity. Long-term experimental data of typical wood species are used for developing the machine learning based damage accumulation model. Compared with existing pre-formulated models, our model managed to reduce the complexity of the model structure and give sufficiently accurate and unbiased predictions. This study aims to provide a novel tool for evaluating the damage accumulation in wood structural members, and the proposed model can further support the life-cycle performance assessment of timber structures under long-term service scenarios.


Hemodynamic effects of inhibitors of the renin-angiotensin system.
To review the hemodynamic effects of the various classes of inhibitors of the renin-angiotensin system. DATA PRESENTATION: First, hemodynamic alterations related to inhibition of the renin-angiotensin system were defined. Second, some comparative studies on the various types of inhibitors were examined. Angiotensin converting enzyme (ACE) inhibitors have been well studied in both hypertension and heart failure and have been shown to produce both arteriolar and venous dilation. Renin inhibitors have been shown to achieve equipotent blood pressure reductions to those induced by ACE inhibitors in experimental studies; the mechanism of blood pressure reduction was related to a decrease in systemic resistance, without altering the heart rate or cardiac output. Angiotensin II antagonists are still being studied. It may be still too early to predict how useful the renin inhibitors and the angiotensin II antagonists will be for the therapy of cardiovascular diseases, compared with ACE inhibitors.


Islamic jurisprudential and ethical considerations of practicing medical procedures on nearly dead patients: Part I (The theoretical section).
End-of-life care and protection of the patient in the near-death moments are part of a patient's rights and the duties of the medical staff. As the beginning and end of human life are most sensitive moments, there are various religious rules associated with them. The ethical issues regarding practicing medical procedures on nearly dead patients are of particular complexity and are consistent with invaluable and profoundly religious recommendations. In addition, the purpose of medical training is to provide physicians with the knowledge and skills necessary to practice appropriately and within legal and ethical frameworks. Therefore, respecting patients' cultural and religious beliefs is an ethically accepted principle in the health systems of different countries and is the basis of respect for human dignity. The present study used a qualitative content analysis to explain how to practice medical procedures on a dying or nearly dead patient in accordance with Islamic jurisprudential rules. It was finally concluded that according to the Islamic jurisprudential rules of "authority", "no harm", "necessity", and "public interest", procedures performed on a dying patient could be used for training purposes under certain circumstances. Nevertheless, such activities should only be done with the patient's permission and provided they cause no unnecessary harassment, and they may take place in the absence of alternative methods.


Determining elemental composition using prompt gamma activation analysis.
Prompt gamma-ray spectra sometimes contain hundreds of characteristic peaks, and the masses of the sample components can be determined from dozens of gamma-ray peak areas, some of which are affected by spectral interferences. Reliable qualitative and quantitative analyses can only be performed by using a precisely calibrated detector system, an accurate spectroscopic data library, high-quality spectroscopy software, and a sophisticated method to convert raw data into chemical composition. This article describes the steps of the chemical analysis with prompt gamma activation analysis (PGAA). A complete data reduction method has been constructed that handles the large number of spectral peaks using statistical procedures, identifies the chemical components based on statistical criteria, and determines the sample composition with a least-squares fit of the masses calculated from the individual peaks. The calculation of the uncertainties as well as the detection and analytical limits are discussed in detail. The validation of the method is also presented. The method can also be used in the evaluation of the results of other spectroscopic techniques.


Characterization of lncRNAs involved in cold acclimation of zebrafish ZF4 cells.
Long non-coding RNAs (lncRNAs) are increasingly regarded as a key role in regulating diverse biological processes in various tissues and species. Although the cold responsive lncRNAs have been reported in plants, no data is available on screening and functional prediction of lncRNAs in cold acclimation in fish so far. Here we compared the expression profile of lncRNAs in cold acclimated zebrafish embryonic fibroblast cells (ZF4) cultured at 18°C for 30 days with that of cells cultured at 28°C as control by high-throughput sequencing. Totally 8,363 novel lncRNAs were identified. Including known and novel lncRNAs, there are 347 lncRNAs up-regulated and 342 lncRNAs down-regulated in cold acclimated cells. Among the differentially expressed lncRNAs, 74 and 61 were detected only in control cells or cold-acclimated cells, respectively. The Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analyses of adjacent genes to the differentially expressed lncRNAs showed that the enriched genes are involved in electron transport, cell adhesion, oxidation-reduction process, and so on. We also predicted the target genes of the differentially expressed lncRNAs by looking for interactions between lncRNAs and mRNAs, and constructed an interaction network. In summary, our genome-wide systematic identification and functional prediction of cold responsive lncRNAs in zebrafish cells suggests a crucial role of lincRNAs in cold acclimation in fish.


Randomized, double-blind, parallel groups, placebo-controlled study of efficacy and safety of Rynatan in the treatment of allergic rhinitis using an acute model.
We conducted a randomized, double-blind, parallel groups, placebo-controlled acute study of Rynatan (8 mg chlorpheniramine tannate, 25 mg pyrilamine tannate, 25 mg phenylephrine tannate) in 104 volunteers with allergic rhinitis. Subjects reported to City Park on a Saturday morning during the height of the grass pollen season in late spring and remained in the park for eight hours that day and on the following day. Cards were completed hourly to evaluate symptoms of allergic rhinitis and adverse experiences caused by therapy. The first three cards completed on Saturday morning were used to demonstrate that each subject had had at least minimal symptoms of allergic rhinitis and to determine baseline symptoms. Rynatan or placebo was given at noon and 7:30 PM that day and at 8:30 AM the next day. Subjects completed symptom cards hourly until 4:30 PM on Saturday, three cards that evening, and eight cards hourly the next day until 4:30 PM. The group receiving Rynatan had significantly more allergic rhinitis symptom relief than the placebo group (P = .003). More subjects in the Rynatan group (34/52) reported global symptom improvement than did subjects in the placebo group (18/52, P = .002). There were no significant severe adverse experiences and no statistically significant differences between treatment groups in incidence or severity of drowsiness, dizziness, jitteriness, headache, or nausea. We conclude that Rynatan is safe and effective in treating acute symptoms of allergic rhinitis in otherwise healthy adult subjects.


Dexamethasone attenuates kainate-induced AP-1 activation in rat brain.
The goal of this investigation was to determine if administration of the synthetic glucocorticoid dexamethasone modulates rat brain AP-1 DNA binding activity. Treatment with the selective excitatory amino acid agonist kainate was used to activate AP-1 formation. Kainate (12 mg/kg) administration induced a biphasic activation of AP-1 in rat cerebral cortex and hippocampus with maximal levels observed at 1.5 h and 4.5 h and lower levels at 3 h and 6 h. Kainate also induced biphasic increases in the concentrations of some of the AP-1 constituent proteins (immediate early gene protein products), with initial increases of c-Jun, Fos, and Jun B occurring at 1.5 h and secondary larger increases at 4.5 h, but the level of Jun D was not altered by kainate treatment. Pretreatment with dexamethasone (1 mg/kg) reduced AP-1 activity at both 1.5 h and 4.5 h after kainate administration in both brain regions. Dexamethasone pretreatment did not modify the concentrations of the AP-1 constituent proteins obtained after kainate administration except for a reduction of Jun B levels 1.5 h after kainate. These results demonstrate that elevated glucocorticoid levels reduce the stimulation by kainate of AP-1 activity in rat cortex and hippocampus without causing corresponding decreases in the levels of immediate early gene proteins. Binding of the activated glucocorticoid receptor to c-Jun or Fos is likely to contribute to the decreased AP-1 DNA binding activity following dexamethasone treatment.


The importance of diversity in cognitive neuroscience.
The vast majority of what is known about the neural underpinnings of human cognition comes from studies limited to racially, ethnically, and socioeconomically homogeneous samples. Furthermore, although most studies include both males and females in their samples, sex differences in patterns of brain activity and performance are rarely evaluated. We discuss recent research suggesting that one's socioeconomic status, race/ethnicity, and sex contribute to individual differences in neural structure, function, and related cognitive performance across a variety of cognitive domains. These studies make it clear that findings from decades of cognitive neuroscience research are likely not generalizable to a population that is much more diverse than the samples tested. We argue that these demographics cannot be ignored if we want to understand the neural substrates of human cognition for the diverse, general population. Cognitive neuroscience has been, and continues to be, used to inform education policy and clinical practice. We argue that greater diversity in cognitive neuroscience research is needed to improve reproducibility and to serve the treatment needs of a diverse population. We discuss the challenges to achieving this goal, including consideration of confounding and correlated variables, recruitment, necessary costs, and best practices for dealing with them.


Chlorine interactions with water ice studied by molecular beam techniques.
The kinetics of chlorine interactions with ice at temperatures between 103 and 165 K have been studied using molecular beam techniques. The Cl(2) trapping probability is found to be unity at thermal incident energies, and trapping is followed by rapid desorption. The residence time on the surface is less than 25 microg at temperatures above 135 K and approaches 1 s around 100 K. Rate constants for desorption are determined for temperatures below 135 K. The desorption kinetics follow the Arrhenius equation, and activation energies of 0.24 +/- 0.03 and 0.31 +/- 0.01 eV, with corresponding preexponential factors of 10(12.08+/-1.19) and 10(16.52+/-0.38) s(-1), are determined. At least two different Cl(2) binding sites are concluded to exist on the ice surface. The observed activation energies are likely to be the Cl(2)-ice binding energies for these states, and the Cl(2)-surface interactions are concluded to be stronger than earlier theoretical estimates. The surface coverage of Cl(2) on ice under stratospheric conditions is estimated to be negligible, in agreement with earlier work.


Application of PEG-Covered Non-Biodegradable Polyelectrolyte Microcapsules in the Crustacean Circulatory System on the Example of the Amphipod Eulimnogammarus verrucosus.
Layer-by-layer assembled microcapsules are promising carriers for the delivery of various pharmaceutical and sensing substances into specific organs of different animals, but their utility in vivo inside such an important group as crustaceans remains poorly explored. In the current study, we analyzed several significant aspects of the application of fluorescent microcapsules covered by polyethylene glycol (PEG) inside the crustacean circulatory system, using the example of the amphipod Eulimnogammarus verrucosus. In particular, we explored the distribution dynamics of visible microcapsules after injection into the main hemolymph vessel; analyzed the most significant features of E. verrucosus autofluorescence; monitored amphipod mortality and biochemical markers of stress response after microcapsule injection, as well as the healing of the injection wound; and finally, we studied the immune response to the microcapsules. The visibility of microcapsules decreased with time, however, the central hemolymph vessel was confirmed to be the most promising organ for detecting the spectral signal of implanted microencapsulated fluorescent probes. One million injected microcapsules (sufficient for detecting stable fluorescence during the first hours after injection) showed no toxicity for six weeks, but in vitro amphipod immune cells recognize the PEG-coated microcapsules as foreign bodies and try to isolate them by 12 h after contact.


Who owns what? Private ownership and the public interest in recombinant DNA technology in the 1970s.
This essay analyzes how academic institutions, government agencies, and the nascent biotech industry contested the legal ownership of recombinant DNA technology in the name of the public interest. It reconstructs the way a small but influential group of government officials and university research administrators introduced a new framework for the commercialization of academic research in the context of a national debate over scientific research's contributions to American economic prosperity and public health. They claimed that private ownership of inventions arising from public support would provide a powerful means to liberate biomedical discoveries for public benefit. This articulation of the causal link between private ownership and the public interest, it is argued, justified a new set of expectations about the use of research results arising from government or public support, in which commercialization became a new public obligation for academic researchers. By highlighting the broader economic and legal shifts that prompted the reconfiguration of the ownership of public knowledge in late twentieth-century American capitalism, the essay examines the threads of policy-informed legal ideas that came together to affirm private ownership of biomedical knowledge as germane to the public interest in the coming of age of biotechnology and genetic medicine.


Outcomes from an extended scope of practice speech-language pathology service for low risk ENT outpatients: A 5-year service review.
Purpose: Early evidence supports the safety and efficiency of extended scope speech-language pathology (SLP) clinics designed to manage low risk ear nose and throat (ENT) outpatient referrals, however long-term data is lacking. The aim of this study was to complete a 5-year audit of clinical outcomes, including rates of re-referral, for a SLP Allied Health Practitioner (SLP AHP) led dysphagia and dysphonia service within an Integrated Specialist ENT Service.Method: A retrospective audit was undertaken of all patients referred with non-urgent dysphonia and/or dysphagia symptoms over a 5-year period since establishment of the SLP AHP service. Clinical outcomes, rates and reasons for re-referral to the specialist ENT waiting list were investigated.Result: Of 616 patient referrals, 462 patients were seen by the SLP AHP service. Most (72%, n = 333) received all required management through the clinical model, with only 28% (n = 129) requiring additional ENT intervention, consistent with previously published data. Only 36 of the 616 (6%) were re-referred/re-presented within 12 months of first presentation, of which only 12 were referred for same condition as initial referral. No adverse outcomes were recorded on the clinical database during this 5-year period.Conclusion: Results provide further evidence that the SLP AHP service is a safe and efficient method for managing low risk ENT outpatient referrals.


Data-driven control of hydraulic servo actuator: An event-triggered adaptive dynamic programming approach.
Hydraulic servo actuators (HSAs) are often used in the industry in tasks that request great power, high accuracy and dynamic motion. It is well known that an HSA is a highly complex nonlinear system, and that the system parameters cannot be accurately determined due to various uncertainties, an inability to measure some parameters and disturbances. This paper considers an event-triggered learning control problem of the HSA with unknown dynamics based on adaptive dynamic programming (ADP) via output feedback. Due to increasing practical application of the control algorithm, a linear discrete model of HSA is considered and an online learning data driven controller is used, which is based on measured input and output data instead of unmeasurable states and unknown system parameters. Hence, the ADP-based data driven controller in this paper requires neither the knowledge of the HSA dynamics nor exosystem dynamics. Then, an event-based feedback strategy is introduced to the closed-loop system to save the communication resources and reduce the number of control updates. The convergence of the ADP-based control algorithm is also theoretically shown. Simulation results verify the feasibility and effectiveness of the proposed approach in solving the optimal control problem of HSAs.


Of Pandemics and Zombies: The Influence of Prior Concepts on COVID-19 Pandemic-Related Behaviors.
We use a concepts and categories research perspective to explore how prior conceptual knowledge influences thinking about a novel disease, namely COVID-19. We collected measures of how similar people thought COVID-19 was to several existing concepts that may have served as other possible comparison points for the pandemic. We also collected participants' self-reported engagement in pandemic-related behaviors. We found that thinking the COVID-19 pandemic was similar to other serious disease outbreaks predicted greater social distancing and mask-wearing, whereas likening COVID-19 to the seasonal flu predicted engaging in significantly fewer of these behaviors. Thinking of COVID-19 as similar to zombie apocalypse scenarios or moments of major societal upheaval predicted stocking-up behaviors, but not disease mitigation behaviors. These early category comparisons influenced behaviors over a six-month span of longitudinal data collection. Our findings suggest that early conceptual comparisons track with emergent disease categories over time and influence the behaviors people engage in related to the disease. Our research illustrates how early concept formation influences behaviors over time, and suggests ways for public health experts to communicate with the public about emergent diseases.


Extracellular Engrailed participates in the topographic guidance of retinal axons in vivo.
Engrailed transcription factors regulate the expression of guidance cues that pattern retinal axon terminals in the dorsal midbrain. They also act directly to guide axon growth in vitro. We show here that an extracellular En gradient exists in the tectum along the anterior-posterior axis. Neutralizing extracellular Engrailed in vivo with antibodies expressed in the tectum causes temporal axons to map aberrantly to the posterior tectum in chick and Xenopus. Furthermore, posterior membranes from wild-type tecta incubated with anti-Engrailed antibodies or posterior membranes from Engrailed-1 knockout mice exhibit diminished repulsive activity for temporal axons. Since EphrinAs play a major role in anterior-posterior mapping, we tested whether Engrailed cooperates with EphrinA5 in vitro. We find that Engrailed restores full repulsion to axons given subthreshold doses of EphrinA5. Collectively, our results indicate that extracellular Engrailed contributes to retinotectal mapping in vivo by modulating the sensitivity of growth cones to EphrinA.


Body composition is prognostic and predictive of ipilimumab activity in metastatic melanoma.
Body composition is minimally investigated in an immunotherapy era. Specific body composition signals such as myosteatosis may reflect aspects of patients' immunology and thereby their ability to respond to immunotherapies. Ipilimumab is a key checkpoint inhibitor in metastatic melanoma. As an antibody, it may also be more accurately dosed using body composition parameters rather than weight alone. This retrospective study aimed to investigate body composition-based dosing and outcomes. Pretreatment computed tomography images from metastatic melanoma, ipilimumab-treated patients from 2009 to 2014 were used to measure myosteatosis [skeletal muscle radiographic density or SMD, in Hounsfield units (HU)] and surface area (cm2 ) as previously described. Cut point analysis determined whether a level of ipilimumab dose and myosteatosis demonstrated differences in progression-free (PFS) and overall survival (OS). Secondary endpoints included objective response rates and toxicities. Of 121 identified, 97 patients were evaluable. Baseline demographics included 56 years median age, 60% male participants, and 23.7% with BRAF mutations. SMD analysis identified cut-offs of SMD < 42 in those with BMI < 25 kg/m2 and <20 HU in those with BMI ≥ 25 kg/m2 , respectively. Low SMD patients had poorer median PFS [2.4 vs. 2.7 months, hazard ratio (HR) 1.76, P = 0.008] and OS (5.4 vs. 17.5 months, HR 2.47, P = 0.001), which remained significant in multivariate modelling. High SMD patients had more immune-related adverse events, better objective response rates (17.9 vs. 3.3%, P = 0.051), and lower baseline neutrophil-to-lymphocyte ratio (21 vs. 39%, P = 0.049). Separately, patients receiving <2.03 mg/cm2 had improved median PFS (3.0 vs. 2.6 months, HR 1.88, P = 0.02) and OS (14.9 vs. 5.7 months, HR 1.98, P = 0.01). Low SMD and receiving >2.03 mg/cm2 are prognostic of poorer melanoma outcomes post ipilimumab. SMD may identify patients with flawed immunology and predict who may better respond to such therapy. Ipilimumab dosing by skeletal muscle index stands in contrast to weight-based dosing and may demonstrate a more accurate method of antibody dosing.


[Advances in study of macrophages in chemotherapy resistance of cancer].
As extremely important inflammatory cells in the tumor microenvironment, tumor-associated macrophages (TAMs) can secrete a variety of chemokines and cytokines, which play an important role in the occurrence of tumor growth and metastasis. Recent years, increasing studies have shown that macrophages are associated with tumor chemotherapy sensitivity. The chemical substances produced by macrophages affect the efficacy of chemotherapeutic agents. In addition, some chemotherapeutic agents have an effect on the recruitment and bioactivity of macrophages in the tumor issue, which influences the anti-tumor efficacy of chemotherapy drugs. In this review, we summarize the roles of macrophages in the chemotherapy resistance, including the regulatory mechanism and the strategy of targeting macrophages.


[Study of androgen receptor and phosphoglycerate kinase gene polymorphism in major cellular components of the so-called pulmonary sclerosing hemangioma].
To study the clonality of polygonal cells and surface cuboidal cells in the so-called pulmonary sclerosing hemangioma (PSH). 17 female surgically resected PSH were found. The polygonal cells and surface cuboidal cells of the 17 PSH cases were microdissected from routine hematoxylin and eosin-stained sections. Genomic DNA was extracted, pretreated through incubation with methylation-sensitive restrictive endonuclease HhaI or HpaII, and amplified by nested polymerase chain reaction for X chromosome-linked androgen receptor (AR) and phosphoglycerate kinase (PGK) genes. The length polymorphism of AR gene was demonstrated by denaturing polyacrylamide gel electrophoresis and silver staining. The PGK gene products were treated with Bst XI and resolved on agarose gel. Amongst the 17 female cases of PSH, 15 samples were successfully amplified for AR and PGK genes. The rates of polymorphism were 53% (8/15) and 27% (4/15) for AR and PGK genes respectively. Polygonal cells and surface cuboidal cells of 10 cases which were suitable for clonality study, showed the same loss of alleles (clonality ratio = 0) or unbalanced methylation pattern (clonality ratio < 0.25). The polygonal cells and surface cuboidal cells in PSH demonstrate patterns of monoclonal proliferation, indicating that both represent true neoplastic cells.