[Relationship between tardive dyskinesia and the polymorphism of superoxide dismutase val9Ala and efficacy of Chaihu Taoren Capsules on it].
To investigate the relationship between efficacy of Chaihu Taoren Decoction (CTD) and the polymorphism of valine-alanine missense mutation of 9th codan (Val9Ala, T1183C) of superoxide dismutase (SOD) in patients with tardive dyskinesia (TD). Severity of TD was assessed by abnormal involuntary movement scale (AIMS), and the psychologic symptoms were rated by the positive and negative symptoms scale (PANSS). The sample size consisted of 119 patients with TD assigned to the TD group, 129 patients of chronic schizophrenia with the general condition matched strictly with that of the enrolled TD patients assigned to the non-TD group, and 148 healthy persons assigned to the normal group. The gene distribution rate of Val9Ala gene was analyzed using polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) analysis, and the therapeutic effect of CTD on 36 patients with TD was observed after 12 weeks treatment. There was no significant difference in genotype and allelic gene frequency of SOD Val9Ala among the TD, non-TD and normal groups (P > 0.05). Comparison of the AIMS score in TD patients with various Val9Ala genotypes showed that the difference of AIMS scores in patients with TT and CT genotype was not significant (P > 0.05), but CTD did show a better efficacy in TD patients with CT heterozygote than in those with TT homozygote (P < 0.05). The CTD could effectively relieve the symptoms of TD, its efficacy might be related with the genotype of SOD, and 9Ala is considered to be a protective factor for the susceptibility to TD.


Predicting the incidence of portosplenomesenteric vein thrombosis in patients with acute pancreatitis using classification and regression tree algorithm.
The accurate prediction of portosplenomesenteric vein thrombosis (PVT) in patients with acute pancreatitis(AP) is very important but may also be difficult because of our insufficient understanding of the characteristics of AP-induced PVT. The purpose of this study is to design a decision tree model that provides critical factors associated with PVT using an approach that makes use of classification and regression tree (CART) algorithm. The analysis included 353 patients with AP who were admitted between January 2011 and December 2015. CART model and logistic regression model were each applied to the same 50% of the sample to develop the predictive training models, and these models were tested on the remaining 50%. Statistical indexes were used to evaluate the value of the prediction in the 2 models. The predicted sensitivity, specificity, positive predictive value, negative predictive value, and accuracy by CART for PVT were 78.0%, 87.2%, 64.0%, 93.2%, and 85.2%, respectively. Significant differences could be found between the CART model and the logistic regression model in these parameters. There were significant differences between the CART and logistic regression models in these parameters (P<.05). When the CART model was used to identify PVT, the area under receiver operating characteristic curve was 0.803, which demonstrated better overall properties than the logistic regression model (area under the curve=0.696) (95% confidence interval, 0.603-0.812). The CART model based on serum amylase, d-dimer, Acute Physiology and Chronic Health Evaluation II, and prothrombin time is more likely to predict the occurrence of PVT induced by AP.


A meta-analysis of school-based smoking and alcohol use prevention programs.
Tobacco and alcohol use among adolescents continue at historically high rates, and school-based interventions designed to deter students from smoking and drinking are increasingly being implemented. This study reports a meta-analysis of 47 smoking and 29 alcohol school-based intervention programs published after 1970. Results indicate that, in general, smoking and alcohol interventions have equally modest effects on immediate behavioral outcomes. Smoking interventions, however, have been more successful than alcohol interventions at altering students' long term behavior. All of the alcohol programs and all but one of the smoking programs reviewed successfully increased knowledge regarding the risks of these behaviors. Attitude change appears to be more difficult to achieve. Twenty-nine of 33 smoking studies and only 19 of 31 alcohol studies successfully changed students' attitudes. Finally, the data indicate that for immediate smoking outcomes and long-term alcohol outcomes innovative interventions relying upon social reinforcement, social norms, and developmental behavioral models are more effective than traditional "awareness" programs designed to inform adolescents about the health risks associated with tobacco and alcohol use. The implications of these findings for future of school-based health promotion programs are discussed.


Molten globule state of equine beta-lactoglobulin.
The acid-unfolded state of equine beta-lactoglobulin was characterized by means of circular dichroism, nuclear magnetic resonance, analytical gel-filtration chromatography, and analytical centrifugation. The acid-unfolded state of equine beta-lactoglobulin has a substantial secondary structure as shown by the far-ultraviolet circular dichroism spectrum but lacks persistent tertiary packing of the side chains as indicated by the near-ultraviolet circular dichroism and nuclear magnetic resonance spectra. It is nearly as compact as the native conformation as shown by the gel filtration and sedimentation experiments, and it has the exposed hydrophobic surface as indicated by its tendency to aggregate. All of these characteristics indicate that the acid-unfolded state of equine beta-lactoglobulin is a molten globule state. The alpha helix content in the acid-unfolded state, which has been estimated from the circular dichroism spectrum, is larger than that in the native state, suggesting the presence of nonnative alpha helices in the molten globule state. This result suggests the generality of the intermediate with nonnative alpha helices during the folding of proteins having the beta-clam fold.


Motor cortex excitability does not increase during sustained cycling exercise to volitional exhaustion.
The excitability of the motor cortex increases as fatigue develops during sustained single-joint contractions, but there are no previous reports on how corticospinal excitability is affected by sustained locomotor exercise. Here we addressed this issue by measuring spinal and cortical excitability changes during sustained cycling exercise. Vastus lateralis (VL) and rectus femoris (RF) muscle responses to transcranial magnetic stimulation of the motor cortex (motor evoked potentials, MEPs) and electrical stimulation of the descending tracts (cervicomedullary evoked potentials, CMEPs) were recorded every 3 min from nine subjects during 30 min of cycling at 75% of maximum workload (W(max)), and every minute during subsequent exercise at 105% of W(max) until subjective task failure. Responses were also measured during nonfatiguing control bouts at 80% and 110% of W(max) prior to sustained exercise. There were no significant changes in MEPs or CMEPs (P > 0.05) during the sustained cycling exercise. These results suggest that, in contrast to sustained single-joint contractions, sustained cycling exercise does not increase the excitability of motor cortical neurons. The contrasting corticospinal responses to the two modes of exercise may be due to differences in their associated systemic physiological consequences.


Early-Career Autism Researchers Are Shifting Their Research Directions: Tragedy or Opportunity?
Early-career researchers (ECRs) are among the most creative, talented, and energetic researchers, and they play an important role in knowledge production and pushing scientific boundaries. Recent debates have implied that many early-career autism researchers are compelled to shift their areas of focus within autism research as a consequence of their work being scrutinized by the autistic and autism communities. In this Perspective, I draw on my own experience as an early-career autism researcher having recently pivoted my research focus to become more aligned with community priorities. I reflect on whether these putative shifts in research direction are, indeed, a tragedy, as has previously been suggested, or, in fact, an opportunity for autism researchers. I argue that pivoting in research is a demonstration of science adapting to the ever-evolving needs in society and changes in our understanding of neurodiversity, neurodivergence, and research methods. While disagreements between the autistic, autism, and research communities may well feel uncomfortable, these tensions also present an opportunity for us-as non-autistic autism researchers-to reflect and to act toward building trust with the community. I recommend three areas for reflections: the purpose of our research, our position of power, and the epistemic limits of our academic expertise. I end by encouraging ECRs to consider taking actions, however small, to lead the charge in improving practices in autism research.


Treatment of a Class II malocclusion with bilaterally impacted canines: a case report.
This article describes the treatment of a patient with a Class II malocclusion and bilaterally impacted canines using a Jasper jumper appliance. An unfavorable side effect of the appliance became a benefit as part of the treatment. Treatment objectives were to erupt the impacted canines, expand the decreased intermolar width, and obtain a well-balanced profile, with a Class I occlusion. The widening effect of this appliance on the maxillary molars was expected to help increase the intermolar distance. Favorable changes were noted, both in the occlusion and in the profile. Class I canine and molar relationships with ideal overjet and overbite were achieved. Overbite and overjet were decreased by a combination of retrusion and extrusion of the maxillary incisors, and protrusion and intrusion of the mandibular incisors. The maxillary canines were erupted successfully, with healthy gingival tissue. The crossbite in the right posterior segment was corrected as a result of the increase in the intermolar distance. The results gained were primarily dentoalveolar, rather than skeletal. There has been an improvement in the occlusion and esthetics.


Temperature dependence of ultrasonic propagation speed and attenuation in excised canine liver tissue measured using transmitted and reflected pulses.
Previous reported data from our laboratory demonstrated the temperature dependence of propagation speed and attenuation of canine tissue in vitro at discrete temperatures ranging from 25 to 95 degrees C. However, concerns were raised regarding heating the same tissue specimen over the entire temperature range, a process that may introduce irreversible and, presumably, cumulative tissue degradation. In this paper propagation speed and attenuation vs temperature are measured using multiple groups of samples, each group heated to a different temperature. Sample thicknesses are measured directly using a technique that uses both transmitted and reflected ultrasound pulses. Results obtained using 3 and 5 MHz center frequencies demonstrate a propagation speed elevation of around 20 m/s in the 22-60 degrees C range, and a decrease of 15 m/s in the 60-90 degrees C range, in agreement with previous results where the same specimens were subjected to the entire temperature range. However, sound speed results reported here are slightly higher than those reported previously, probably due to more accurate measurements of sample thickness in the present experiments. Results also demonstrate that while the propagation speed varies with temperature, it is not a function of tissue coagulation. In contrast, the attenuation coefficient depends on both tissue coagulation effects and temperature elevation.


Phosphatases XII. Isoenzymes of alkaline phosphatase and radionuclear investigation (85Sr) of patients with neoplastic affection of the skeleton.
In a group of 30 patients with neoplastic processes, 13 were found to have a significantly increased serum alkaline phosphatase activity. This finding correlated with the results of investigation with 85Sr in 7 patients, but owing to a concomitant hepatal symptomatology, it proved of differential diagnostic value in only one of them. On the other hand, the activity of bone isoenzyme of alkaline phosphatase was significantly altered in 15 patients. In 14 of them the increase in bone isoenzyme activity corresponded to an X-ray and a radionuclear finding of a tumor process in the bones. This activity was within the normal range of values in only one patient with a positive result of the 85Sr investigation. An agreement between the results of determination of bone isoenzyme activity of alkaline phosphatase and those of radionuclear investigations was found in 27 patients. In addition, a correlation was established between the increased activity of bone isoenzyme and that of intestinal isoenzyme of alkaline phosphatase. Enzyme investigation can be suitably utilized, alongside radionuclear examination, for early detection of a bone process.


Different functional roles for K+ channel subtypes in regulating small intestinal glucose and ion transport.
Although K+ channels are important in mediating the driving force for colonic ion transport, their role in small intestinal transport is poorly understood. To investigate this, small intestinal short circuit currents (Isc ) and HCO3 - secretion were measured in mice, and intracellular pH (pHi) was measured in small intestinal epithelial SCBN cells. The expression and location of Kv subtypes were verified by RT-PCR, western blotting and immunohistochemistry. Diabetic mice were also used to investigate the role of Kv subtypes in regulating intestinal glucose absorption. We found that KV7.1 is not involved in duodenal ion transport, while KCa3.1 selectively regulates duodenal Isc and HCO3 - secretion in a Ca2+-mediated but not cAMP-mediated manner. Blockade of KCa3.1 increased the rate of HCO3 - fluxes via cystic fibrosis transmembrane conductance regulator (CFTR) channels in SCBN cells. Jejunal Isc was significantly stimulated by glucose, but markedly inhibited by 4-aminopyridine (4-AP) and tetraethylammonium (TEA). Moreover, both Kv1.1 and Kv1.3 were expressed in jejunal mucosae. Finally, 4-AP significantly attenuated weight gain of normal and diabetic mice, and both 4-AP and TEA significantly lowered blood glucose of diabetic mice. This study not only examines the contribution of various K+ channel subtypes to small intestinal epithelial ion transport and glucose absorption, but also proposes a novel concept for developing specific K+ channel blockers to reduce weight gain and lower blood glucose in diabetes mellitus.


Single bouts of exercise selectively sustain attentional processes.
This study examined how single bouts of exercise may differentially modulate neuroelectric correlates of attentional orienting and processing. Using a within-participants design, ERPs and task performance were assessed in response to a perceptually challenging three-stimulus oddball task prior to and following a bout of exercise or seated rest during two separate, counterbalanced sessions. Findings revealed that, following a single bout of exercise, attentional processing was sustained relative to pretest whereas prolonged sitting resulted in attentional decrements. Focal attention resulting from attentional orienting, in contrast, does not appear to be sensitive to the influences of single bouts of physical activity. These findings suggest that acute exercise-induced changes in cognition do not originate from an overall modulation of attention but instead are specific to aspects of attentional processing.


Structure and Reactivity of Aromatic Radical Cations Generated by FeCl3.
This paper describes the isolation and characterization of an aromatic radical cation generated by FeCl3. X-ray crystallographic analysis and kinetic studies reveal the mechanism of the generation of aromatic radical cation. In the solid state, a tight ion-pair of a radical cation with FeCl4- is observed. Leveraging the efficient generation of the radical cation-FeCl4- ion pair, we explore a radical cation-induced cycloaddition of trans-anethole initiated by catalytic amount of FeCl3. Both [4+2] cycloaddition and [2+2] cycloaddition with a broad substrate scope are also described. Moreover, a 100 g-scale reaction is demonstrated with the use of 1 mol % of FeCl3 as a simple and a highly active initiator.


The optimal use of PET/CT in the management of lymphoma patients.
18F-fluoro-deoxyglucose positron emission tomography (PET)/computed tomography (CT) scans play an important role in the management of lymphoma patients. They are critical to accurately stage disease and assess its response to therapy. In addition, PET/CT scans enable precise target delineation for radiation therapy planning. In this review, we describe the use of PET/CT scans in lymphoma, with a focus on their role in staging disease, assessing response to therapy, predicting prognosis, and planning RT.


Genetic and Transcriptional Analyses of the Flagellar Gene Cluster in Actinoplanes missouriensis.
Actinoplanes missouriensis, a Gram-positive and soil-inhabiting bacterium, is a member of the rare actinomycetes. The filamentous cells produce sporangia, which contain hundreds of flagellated spores that can swim rapidly for a short period of time until they find niches for germination. These swimming cells are called zoospores, and the mechanism of this unique temporal flagellation has not been elucidated. Here, we report all of the flagellar genes in the bacterial genome and their expected function and contribution for flagellar morphogenesis. We identified a large flagellar gene cluster composed of 33 genes that encode the majority of proteins essential for assembling the functional flagella of Gram-positive bacteria. One noted exception to the cluster was the location of the fliQ gene, which was separated from the cluster. We examined the involvement of four genes in flagellar biosynthesis by gene disruption, fliQ, fliC, fliK, and lytA Furthermore, we performed a transcriptional analysis of the flagellar genes using RNA samples prepared from A. missouriensis grown on a sporangium-producing agar medium for 1, 3, 6, and 40 days. We demonstrated that the transcription of the flagellar genes was activated in conjunction with sporangium formation. Eleven transcriptional start points of the flagellar genes were determined using the rapid amplification of cDNA 5' ends (RACE) procedure, which revealed the highly conserved promoter sequence CTCA(N15-17)GCCGAA. This result suggests that a sigma factor is responsible for the transcription of all flagellar genes and that the flagellar structure assembles simultaneously. The biology of a zoospore is very interesting from the viewpoint of morphogenesis, survival strategy, and evolution. Here, we analyzed flagellar genes in A. missouriensis, which produces sporangia containing hundreds of flagellated spores each. Zoospores released from the sporangia swim for a short time before germination occurs. We identified a large flagellar gene cluster and an orphan flagellar gene (fliQ). These findings indicate that the zoospore flagellar components are typical of Gram-positive bacteria. However, the transcriptional analysis revealed that all flagellar genes are transcribed simultaneously during sporangium formation, a pattern differing from the orderly, regulated expression of flagellar genes in other bacteria, such as Salmonella and Escherichia coli These results suggest a novel regulatory mechanism for flagellar formation in A. missouriensis.


[The regulatory contours of correction of the pancreatic secretion].
It is offered to allocate three basic contours of regulation and self-regulation of pancreatic secretion: duodeno-pancreatoglandulary, hemato-pancreatoglandulary and ductulo-pancreatoglandulary, at which participation the correction of enzymatic structure of a secret of pancreas concerning permanent properties of duodenal chyme and variation of enzymatic spectrum of a secret in the postprandial period of secretion is carried out. In all three contours in quality of the regulatory factor acts actually a pancreatic secret and its components, and also condition of ductal hydrokinetics of a pancreatic secret. Is established, that the pancreatic secretion is provided with the large number of the functionally nonequipotential secretory-transport modules having certain determinants of their morpho-functional organization.


Controlled polymer grafting on single clay nanoplatelets.
We report on the controlled chemical grafting of well-defined polymer chains onto individual montmorillonite-type clay nanoplatelets and the direct visualization of the formed hybrid material at the nanoscale level. Our approach is based on the use of a surfactant mixture that contains varying proportions of hydroxyl-substituted alkylammonium and unsubstituted alkylammonium cations to exchange the initial Na(+) counterions of the natural montmorillonite. This allows for the exchange of Na(+) by a tunable amount of hydroxyl functions at the surface of the clays. Those functions are then derivatized into aluminum alkoxides in order to initiate the ring-opening polymerization of epsilon-caprolactone directly from the clay surface that was swollen in an organic solvent. Atomic force microscopy measurements on the resulting polymer-grafted nanoplatelets demonstrate the strong dependence of the coating of the individual clay particles with the composition of the surfactant mixture used for the cationic exchange. This allows for the generation of a range of morphologies varying from polymer islands distributed over the clay surface to homogeneous polymer layers thoroughly coating the platelets. Finally, the control that is achievable over the synthesis of this new family of organic-inorganic nanohybrid materials has been extended to the surface grafting of semicrystalline poly(epsilon-caprolactone)-poly(lactic acid) diblock copolymers with defined compositions.


Leukocyte reduction's role in the attenuation of infection risks among transfusion recipients.
Despite advances in the screening of donated blood for infectious agents, the risk of transmitting viral, bacterial, and protozoal infections, as well as newly emerging diseases, via transfusion persists. A complementary approach is leukocyte reduction (LR), the removal of leukocytes from donated blood by filtration. Published evidence, establishing the benefit of LR in reducing the risk of febrile nonhemolytic reactions, cytomegalovirus transmission, and human leukocyte antigen alloimmunization has led to its use for some time for the care of immunosuppressed and other individuals considered to be at high risk for such complications. Recent literature suggests that LR may be effective in reducing the risk of transmission of a number of additional transfusion-transmitted infectious agents, including herpesviruses, retroviruses, bacteria, protozoa, and prions. There is also evidence that LR may reduce the risk of transfusion-related immunomodulation, further contributing to protection against infections that would complicate treatment. With the mounting evidence of potential benefit, a number of countries, as well as many hospitals and blood centers in the United States, have adopted a policy of performing LR for all donated blood. Physicians who care for immunosuppressed patients and those who are responsible for institutional infection-control practices should remain informed of the growing body of literature on LR.


Correlation between the pharmacokinetics of oxindanac and inhibition of serum thromboxane B2 in calves.
The pharmacokinetics and pharmacodynamics of the non-steroidal antiinflammatory drug, oxindanac, were assessed simultaneously in calves after intravenous (i.v.) administration at dose rates of 0.5, 1, 2, 4 and 8 mg/kg. Plasma pharmacokinetic data were fitted to either two or three compartment open models. The elimination t1/2 was constant in the dose range 0.5 to 4 mg/kg (20.2-22.8 h) and shorter at 8 mg/kg (14.7 h). The pharmacodynamics of oxindanac were assessed by its inhibition of serum TxB2, an index of platelet cyclo-oxygenase activity. Plots of total plasma oxindanac concentration vs. inhibition of serum TxB2 fitted in all cases a sigmoidal Emax equation. There were no significant differences in the estimates for ED50 (1.6-1.9 micrograms/ml), Hill constant (1.3-2.7) or Emax between the doses used in the in vivo studies or when blood was spiked with oxindanac in vitro. Plots of inhibition of serum TxB2 vs. time were prepared from the pharmacokinetic model equations in each calf in combination with a single sigmoidal Emax plot generated in vitro. These data were not significantly different from the results produced in vivo. It is concluded that oxindanac causes reversible inhibition of platelet cyclo-oxygenase in calves. Its inhibition of serum TxB2 can be predicted from total plasma drug concentration, as described by a multicompartmental model, and sigmoidal Emax enzyme kinetics. It was not necessary to take into account factors such as drug equilibration between plasma and its target site, free vs. total drug concentration or chirality. This simple model may be useful for predicting the pharmacodynamics of oxindanac in other species.


Complete mitochondrial genome sequence of Grundulus bogotensis (Humboldt, 1821).
The Grundulus bogotensis is an Endangered fish in Colombia. In this study, we report the complete mitochondrial DNA sequences of G. bogotensis. The entire genome comprised 17.123 bases and a GC content of 39.84%. The mitogenome sequence of G. bogotensis would contribute to better understand population genetics, and evolution of this lineage. Molecule was deposited at the GenBank database under the accession number KM677190.


CD36 mediates the cardiovascular action of growth hormone-releasing peptides in the heart.
Growth hormone-releasing peptides (GHRPs) are known as potent growth hormone secretagogues whose actions are mediated by the ghrelin receptor, a G protein-coupled receptor cloned from pituitary libraries. Hexarelin, a hexapeptide of the GHRP family, has reported cardiovascular activity. To identify the molecular target mediating this activity, rat cardiac membranes were labeled with a radioactive photoactivatable derivative of hexarelin and purified using lectin affinity chromatography and preparative gel electrophoresis. A binding protein of M(r) 84 000 was identified. The N-terminal sequence determination of the deglycosylated protein was identical to rat CD36, a multifunctional glycoprotein, which was expressed in cardiomyocytes and microvascular endothelial cells. Activation of CD36 in perfused hearts by hexarelin was shown to elicit an increase in coronary perfusion pressure in a dose-dependent manner. This effect was lacking in hearts from CD36-null mice and hearts from spontaneous hypertensive rats genetically deficient in CD36. The coronary vasoconstrictive response correlated with expression of CD36 as assessed by immunoblotting and covalent binding with hexarelin. These data suggest that CD36 may mediate the coronary vasospasm seen in hypercholesterolemia and atherosclerosis.


Benzene-1,4-diboronic acid-4,4'-bipyridine-water (1/2/2).
In the presence of water, benzene-1,4-diboronic acid (1,4-bdba) and 4,4'-bipyridine (4,4'-bpy) form a cocrystal of composition (1,4-bdba)(4,4'-bpy)(2)(H(2)O)(2), in which the molecular components are organized in two, so far unknown, cyclophane-type hydrogen-bonding patterns. The asymmetric unit of the title compound, C(6)H(8)B(2)O(4).2C(10)H(8)N(2).2H(2)O, contains two 4,4'-bpy, two water molecules and two halves of 1,4-bdba molecules arranged around crystallographic inversion centers. The occurrence of O-H...O and O-H...N hydrogen bonds involving the water molecules and all O atoms of boronic acid gives rise to a two-dimensional hydrogen-bonded layer structure that develops parallel to the (01-4) plane. This supramolecular organization is reinforced by pi-pi interactions between symmetry-related 4,4'-bpy molecules.


Moral Features of the Therapeutic Relationship with Adults: Dignity, Trust, Autonomy, Vulnerability, and Resilience.
Using dignity as a foundational value of morality, this article defines trust, autonomy, vulnerability, and resilience in relational terms. A fictional narrative illustrates these attributes as well as solidarity and care, two core tenets of relational ethics. Medicine and rehabilitation are described as moral enterprises with respect for persons at the core of our professional obligations to patients-namely, duties of care, trustworthiness, and loyalty. Clinically, promoting autonomy, decreasing vulnerability, and fostering resilience are encouraged, with particular emphasis on avoiding words or actions (or inactions) that could cause patients to feel discouraged or depersonalized. In conclusion, the purpose of our work with persons with aphasia and other communication disorders is to help them live their lives as fully as possible, despite their life-changing losses. Viewing our therapeutic relationships with them in relational moral terms can enhance our work.


Antagonistic Interactions Between Microsaccades and Evidence Accumulation Processes During Decision Formation.
Despite their small size, microsaccades can impede stimulus detections if executed at inopportune times. Although it has been shown that microsaccades evoke both inhibitory and excitatory responses across different visual regions, their impact on the higher-level neural decision processes that bridge sensory responses to action selection has yet to be examined. Here, we show that when human observers monitor stimuli for subtle feature changes, the occurrence of microsaccades long after (up to 800 ms) change onset predicts slower reaction times and this is accounted for by momentary suppression of neural signals at each key stage of decision formation: visual evidence encoding, evidence accumulation, and motor preparation. Our data further reveal that, independent of the timing of the change events, the onset of neural decision formation coincides with a systematic inhibition of microsaccade production, persisting until the perceptual report is executed. Our combined behavioral and neural measures highlight antagonistic interactions between microsaccade occurrence and evidence accumulation during visual decision-making tasks.SIGNIFICANCE STATEMENT When fixating on a location in space, we frequently make tiny eye movements called microsaccades. In the present study, we show that these microsaccades impede our ability to make perceptual decisions about visual stimuli and this impediment specifically occurs via the disruption of several processing levels of the sensorimotor network: the encoding of visual evidence itself, the accumulation of visual evidence toward a response, and effector-selective motor preparation. Furthermore, we show that the production of microsaccades is inhibited during the perceptual decision, possibly as a counteractive measure to mitigate their negative effect on behavior in this context. The combined behavioral and neural measures used in this study provide strong and novel evidence for the interaction of fixational eye movements and the perceptual decision-making process.


Aeromedical Pediatric Burn Transportation: A Six-Year Review.
Aeromedical transportation has been shown to be a safe and efficient mode of transportation for critical care patients, including adult burn patients. Common flight concerns specific to the care of the burn patient are maintenance of intravenous lines and airway access, precision of ongoing fluid resuscitation, and effective treatment of hemodynamic instability. These concerns are particularly crucial when patients are transported by flight teams with limited burn experience. The purpose of this study was to review the safety and outcomes associated with 6 years of aeromedical pediatric burn transportation and to ascertain if differences exist when using a dedicated burn pediatric flight team versus a non-dedicated burn pediatric flight teams. Through a retrospective, IRB approved, chart review from January 2007 to January 2013, all aeromedical admissions were evaluated for demographic data, flight data, complications, and medical interventions. A total of 333 patients were transported by air, of which 282 transfers occurred during the first week of burn injury. In-flight complications occurred in <10% of patients and primarily involved airway and hemodynamic issues. There were no in-flight deaths. Patients transported by alternate teams were noted to be more hypothermic and hypotensive on admission (p < .001). Alternate teams were also noted to transfer older patients, spend less time with initial patient evaluation, and travelled shorter distances (p < .05). Aeromedical transportation of the pediatric burn patient is safe and associated with minimal complications. Communications with the transferring hospitals can facilitate transfer of the pediatric burn patient. When using alternate flight teams, particular attention should focus on resuscitation and maintenance of euthermia with large burn patients.


Influence of lithium on neutrophil granulocyte distribution and turnover.
In 10 psychiatric patients marrow granulocyte reserve, marginal granulocyte pool, granulocyte mobilization into skin chamber, serum lysozyme activity was estimated before and ten days after the lithium treatment. In all patients the peripheral neutrophil count rose significantly. The marrow granulocyte reserve did not change markedly. Moreover, the marginal granulocyte pool as expressed in percentages diminished. Serum lysozyme activity, total leukocyte mobilization, and blood granulocyte clearance remained unchanged. However, the serum lysozyme activity index fell significantly. The in vitro addition of lithium to the suspension of granulocytes obtained from healthy persons reduce the granulocyte adherence especially in concentrations similar to those induced in treated patients. Our findings suggest that lithium in vivo may diminish the granulocyte adherence resulting in the prolonged intravascular half-life time of the cells. Thus, the cell accumulation in the vascular bed seems to be the main reason for lithium induced granulocytosis rather than the intensification of marrow granulocyte system proliferation.


Abortion rights judgment: a ray of hope!
While granting a prisoner the right to abort her foetus, a recent Bombay High Court judgment recognised a woman's absolute right to abortion. This article discusses the judgment in detail and the bioethical debates over abortion rights. It deals with the restrictions imposed by the law not only on when the foetus can be aborted, but also who can get the abortion done and in what circumstances.


Fundamental investigation of foam flow in a liquid-filled Hele-Shaw cell.
The relative immobility of foam in porous media suppresses the formation of fingers during oil displacement leading to a more stable displacement which is desired in various processes such as Enhanced Oil Recovery (EOR) or soil remediation practices. Various parameters may influence the efficiency of foam-assisted oil displacement such as properties of oil, the permeability and heterogeneity of the porous medium and physical and chemical characteristics of foam. In the present work, we have conducted a comprehensive series of experiments using customised Hele-Shaw cells filled with either water or oil to describe the effects of foam quality, permeability of the cell as well as the injection rate on the apparent viscosity of foam which is required to investigate foam displacement. Our results reveal the significant impact of foam texture and bubble size on the foam apparent viscosity. Foams with smaller bubble sizes have a higher apparent viscosity. This statement only applies (strictly speaking) when the foam quality is constant. However, wet foams with smaller bubbles may have lower apparent viscosity compared to dry foams with larger bubbles. Furthermore, our results show the occurrence of more stable foam-water fronts as foam quality decreases. Besides, the complexity of oil displacement by foam as well as its destabilizing effects on foam displacement has been discussed. Our results extend the physical understanding of foam-assisted liquid displacement in Hele-Shaw cell which is a step towards understanding the foam flow behaviour in more complex systems such as porous media.


The biomechanical and clinical significance of the lumbar erector spinae flexion-relaxation phenomenon: a review of literature.
The aim of this study was to review the biomedical literature to ascertain the biomechanical and clinical significance of the lumbar erector spinae flexion-relaxation phenomenon (FRP). Index Medicus via PubMed, the Noble Science Library's e-journal archives, and the Manual Alternative and Natural Therapy Index System databases were searched using the same search terms. The presence of the FRP during trunk flexion represents myoelectric silence consistent with increased load sharing of the posterior discoligamentous passive structures. Passive contributions from erector spinae stretching during the flexion posture and active contributions from other muscles (quadratus lumborum and deep erector spinae among others) further assist in load sharing in the trunk flexion posture. A number of studies have shown differences in the FRP between patients with chronic low back pain and healthy individuals, and the reliability of the assessment. Persistent activation of the lumbar erector spinae musculature among patients with back pain may represent the body's attempt to stabilize injured or diseased spinal structures via reflexogenic ligamentomuscular activation thereby protecting them from further injury and avoiding pain. The myoelectric silencing of the erector spinae muscles in the trunk flexion posture is indicative of increased load sharing on passive structures, which tissues have been found to fail under excessive loading conditions and shown to be a source of low back pain. The studies that show differences in the presence of the FRP among patients and control subjects are encouraging for this type of clinical assessment and suggest that assessment of the FRP is a valuable objective clinical tool to aid in the diagnosis and treatment of patients with low back pain.


Possible role of vascular angiotensin converting enzyme in the genesis of hypertension.
This study was designed to evaluate changes in angiotensin converting enzyme (ACE) activity in 2-kidney, 1-clip renal hypertensive dogs. Blood pressure increased and remained elevated for eight months after partial clamping of the left renal artery. Plasma renin activity was increased for one month after surgery, but then returned to the pre-clamping level. SA-446, a potent ACE inhibitor, reduced blood pressure in 8 M-hypertensive dogs. Plasma ACE activities was not altered during the course of hypertension, but vascular ACE activities in the pulmonary and mesenteric arteries and the aorta were significantly increased in 8 M-hypertensive dogs. These results may indicate that ACE plays an important role in the maintenance of chronic phase of 2-kidney, 1-clip renal hypertension and that suppression of vascular ACE activities might be a mechanism underlying the hypotensive effect of ACE inhibitors.


Identification of SNPs in MITF associated with beak color of duck.
Introduction: Beak color-a pigment-related trait-is an important feature of duck breeds. Recently, little research has addressed genetic mechanism of the beak colors in poultry, whereas the process and the regulation factors of melanin deposition have been well described. Methods: To investigate the genetic mechanism of beak colors, we conducted an integrated analysis of genomic selection signatures to identify a candidate site associated with beak color. For this, we used black-billed (Yiyang I meat duck synthetic line H1, H2, H3&HF) and yellow-billed ducks (Cherry Valley ducks and white feather Putian black duck). Quantitative real-time PCR and genotyping approaches were used to verify the function of the candidate site. Results: We identified 3,895 windows containing 509 genes. After GO and KEGG enrichment analysis, nine genes were selected. Ultimately, MITF was selected by comparing the genomic differentiation (FST). After loci information selection, 41 extreme significantly different loci were selected, which are all located in intron regions of MITF and are in almost complete linkage disequilibrium. Subsequently, the site ASM874695v1:10:g.17814522T > A in MITF was selected as the marker site. Furthermore, we found that MITF expression is significantly higher in black-beaked ducks than in yellow-beaked ducks of the F2 generation (p < 0.01). After genotyping, most yellow-billed individuals are found with homozygous variant; at the same time, there are no birds with homozygous variant in black-billed populations, while the birds with homozygous and heterozygous variant share the same proportion. Conclusion: MITF plays a very critical role in the melanogenesis and melanin deposition of duck beaks, which can effectively affect the beak color. The MITF site, ASM874695v1:10:g.17814522T > A could be selected as a marker site for the duck beak color phenotype.


Prostate cancer metastases alter bone mineral and matrix composition independent of effects on bone architecture in mice--a quantitative study using microCT and Raman spectroscopy.
Prostate cancer is the most common primary tumor and the second leading cause of cancer-related deaths in men in the United States. Prostate cancer bone metastases are characterized by abnormal bone remodeling processes and result in a variety of skeletal morbidities. Prevention of skeletal complications is a crucial element in prostate cancer management. This study investigated prostate cancer-induced alterations in the molecular composition and morphological structure of metastasis-bearing bones in a mouse model of prostate cancer using Raman spectroscopy and micro-computed tomography (microCT). LNCaP C4-2B prostate cancer cells were injected into the right tibiae of 5-week old male SCID mice. Upon sacrifice at 8weeks post tumor inoculation, two out of the ten tumor-bearing tibiae showed only osteoblastic lesions in the radiographs, 4 osteolytic lesions only and 4 mixed with osteoblastic and osteolytic lesions. Carbonate substitution was significantly increased while there was a marked reduction in the level of collagen mineralization, mineral crystallinity, and carbonate:matrix ratio in the cortex of the intact tumor-bearing tibiae compared to contralateral controls. MicroCT analysis revealed a significant reduction in bone volume/total volume, trabecular number and trabecular thickness, as well as significant increase in bone surface/volume ratio in tibiae with osteolytic lesions, suggesting active bone remodeling and bone loss. None of the changes in bone compositional properties were correlated with lesion area from radiographs or the changes in bone architecture from microCT. This study indicates that LNCaP C4-2B prostate cancer metastases alter bone tissue composition independent of changes in architecture, and altered bone quality may be an important contributor to fracture risk in these patients. Raman spectroscopy may provide a new avenue of investigation into interactions between tumor and bone microenvironment.


Detection and drivers of exposure and effects of pharmaceuticals in higher vertebrates.
Pharmaceuticals are highly bioactive compounds now known to be widespread environmental contaminants. However, research regarding exposure and possible effects in non-target higher vertebrate wildlife remains scarce. The fate and behaviour of most pharmaceuticals entering our environment via numerous pathways remain poorly characterized, and hence our conception and understanding of the risks posed to wild animals is equally constrained. The recent decimation of Asian vulture populations owing to a pharmaceutical (diclofenac) offers a notable example, because the exposure route (livestock carcasses) and the acute toxicity observed were completely unexpected. This case not only highlights the need for further research, but also the wider requirement for more considered and comprehensive 'ecopharmacovigilance'. We discuss known and potential high risk sources and pathways in terrestrial and freshwater ecosystems where pharmaceutical exposure in higher vertebrate wildlife, principally birds and mammals, may occur. We examine whether approaches taken within existing surveillance schemes (that commonly target established classes of persistent or bioaccumulative contaminants) and the risk assessment approaches currently used for pesticides are relevant to pharmaceuticals, and we highlight where new approaches may be required to assess pharmaceutical-related risk.


Multiple kerato-acanthoma: a case report.
A case of multiple keratoacanthomas in a 36-year-old healthy seaman is presented. Four months prior to the onset of the disease the patient had been exposed to strong sunlight. Histopathological examination gave the diagnosis of keratoacanthoma.


Self-audit of lockout/tagout in manufacturing workplaces: A pilot study.
Occupational health and safety (OHS) self-auditing is a common practice in industrial workplaces. However, few audit instruments have been tested for inter-rater reliability and accuracy. A lockout/tagout (LOTO) self-audit checklist was developed for use in manufacturing enterprises. It was tested for inter-rater reliability and accuracy using responses of business self-auditors and external auditors. Inter-rater reliability at ten businesses was excellent (κ = 0.84). Business self-auditors had high (100%) accuracy in identifying elements of LOTO practice that were present as well those that were absent (81% accuracy). Reliability and accuracy increased further when problematic checklist questions were removed from the analysis. Results indicate that the LOTO self-audit checklist would be useful in manufacturing firms' efforts to assess and improve their LOTO programs. In addition, a reliable self-audit instrument removes the need for external auditors to visit worksites, thereby expanding capacity for outreach and intervention while minimizing costs.


Acute sciatica: an unusual presentation of extramedullary relapse of acute lymphoblastic leukemia.
A 10-year-old boy who had been treated for acute lymphoblastic leukemia presented with persistent numbness of the left big toe and progressive pain of the ipsilateral lower leg. He had received allogeneic bone marrow transplantation 3 months after a testicular relapse. He was in hematologic remission at admission but as progressive swelling of his left leg continued, bone marrow relapse developed. A muscle biopsy revealed leukemic infiltrates in the surrounding muscles of the left sciatic nerve, and swelling of the nerve was found on a magnetic resonance imaging scan. His symptoms/signs subsided soon after reinduction chemotherapy. Unfortunately, he didn't survive because of a fungal sepsis that developed during the neutropenic state. This case represents a rare neurologic complication of what is currently an uncommon presentation for relapse of acute lymphoblastic leukemia, with acute sciatica and without coexisting epidural or leptomeningeal leukemia.


Primary malignant bone tumors incidence, mortality, and trends in China from 2000 to 2015.
Primary malignant bone tumors are uncommon, and their epidemiological features are rarely reported. We aimed to study the incidence and death characteristics of bone tumors from 2000 to 2015. Population-based cancer registries submitted registry data to National Central Cancer Registry of China (NCCRC). The data collected from 501 local cancer registries in China were assessed using NCCRC screening methods and criteria. Incidence and mortality rates of primary bone tumor were stratified by age group, gender, and area. Age-standardized incidence and mortality rates were adjusted using the Chinese standard population in 2000 and Segi's world population. The annual percentage change (APC) in rate was calculated using the Joinpoint Regression Program. Data from 368 registries met quality control criteria, of which 134 and 234 were from urban and rural areas, respectively. The data covered 309,553,499 persons. The crude incidence, age-standardized incidence, and crude mortality rates were 1.77, 1.35, and 1.31 per 100,000, respectively. Incidence and mortality rates were higher in males than those in females; they showed downward trends, with declines of 2.2% and 4.8% per year, respectively, and the rates in urban areas were lower than those in rural areas. Significant declining trends were observed in urban areas. Stable trends were seen in rural areas during 2000 to 2007, followed by downward trends. Age-specific incidence and mortality rates showed stable trends in the age group of 0 to 19 years, and downward trends in the age group elder than 19 years. The incidence and mortality rates of primary malignant bone tumors in rural areas were higher compared to those in urban areas. Targeted prevention measures are required to monitor and control bone tumor incidence and improve the quality of life of affected patients. This research can provide a scientific basis for the prevention and control of bone tumors, as well as basic information for follow-up research.


Photocatalytic water reduction using a polymer coated carbon quantum dot sensitizer and a nickel nanoparticle catalyst.
Hydrogen gas is produced photocatalytically using 470 nm light, PVP-coated carbon quantum dots (CQDs) as the photosensitizer, and nickel nanoparticles (NiNPs) as the catalyst. The effect of the amount of polyvinylpyrrolidone (PVP) on the ability of the CQD/NiNP composites to catalyze proton reduction was studied. A maximum of 330 mmols H2/g CQD is produced using 68 μg ml-1 of CQDs and 6 μg ml-1 of NiNPs, with activity persisting for 4 h when 20 wt%-PVP-coated CQDs were used. The H2 production quantum yield under these conditions is 6%. It was found that composites having higher weight percent PVP had decreased rates of H2 production, but increased duration. Increasing the weight percent of PVP coating also increases the fluorescence quantum yield of CQDs. Fluorescence quenching titrations reveal that H2 production could occur by either a reductive or oxidative quenching mechanism. The nanomaterials, prepared using simple methods, are used as the photosensitizer and catalyst in the proton reduction system that operates using visible light.


Informed consent: does the consent process reflect the realities of current treatment, procedures, and side effects?
Quality in, quality out. The consent process can be complete and realistic or it can be a sham. The key is in whether physicians listen to parents' questions and answer them. It must be certain that information is given on what is happening, that the parent is told what could happen in the specific treatment involved, and that the information given is up-to-date. The law views each family as a unique entity with its own personal bundle of hopes, fears, and concerns, and views the consent process in the light of this subjective standard. Would the family consent to this treatment if it was disclosed that the treatment might result in sterility, mental dysfunction, or limb loss? Is there a risk that this child could become severely brain-damaged? Are there alternative treatments? A parent's decision as surrogate for a child can only be as good as the information that physicians provide.


[Effect of immunotherapy with recombinant allergen group 3 from dermatophagoides farinae in asthma mice].
To explore the effect of specific immunotherapy with major 3 group recombinant allergen rDer f 3 of Dermatophagoides farinae in murine asthma model. Forty BALB/c mice were randomly divided into 4 groups, namely PBS group (negative control), ovalbumin(0VA) group (positive control), rDerf3 allergen sensitization group (asthma group), and rDerf3 specific immunotherapy group(SIT group). The mice in asthma group and SIT group were injected intraperitoneally with purified rDer f 3 protein on days 0, 7 and 14, respectively, and rDer f 3 solution was inhalated from day 21 for 7 days. During the 25th-27th day, mice in SIT group were injected subcutaneously with 100 jg rDer f 3 allergen for 30 min before nasal inhalation. Mice in groups of PBS and OVA were treated with PBS and OVA, respectively. Twenty-four hours after the final challenge, all mice were sacrificed, the bronchoalveolar lavage fluid (BALF) was collected and the total number of white blood cells and the number of eosinophils were recorded. The levels of IL-5 and IFN-gamma in BALF and supernatant of cultured splenocytes were detected by ELISA, as well as the serum levels of specific IgE and IgG2, antibodies. Lung tissues were stained with haematoxylin and eosin for histological analysis. Compared with the asthma group, the rDer f 3-induced lung inflammation was significantly alleviated in SIT group. The total number of white blood cells [(7.03 +/- 1.38) x 10(8)/ml] in SIT group was considerably lower than that of OVA group [(22.11 +/- 3.70) x 10(8)/ml] and asthma group [(22.75 +/- 3.24) x 10(8)/ml] (P<0.01). The change trend of eosinophil leukocytes was similar with that of white blood cells. IL-5 levels in BALF [(108.20 +/- 11.02) pg/ml] and splenocyte culture supernatant [(98.34 +/- 13.06) pg/ml] in SIT group were significantly lower than that of OVA group [(182.04 +/- 13.94) pg/ml, (208.26 +/- 10.63) pg/ml] and asthma group [(195.33 +/- 15.33) pg/mL, (179.54 +/- 13.65) pg/ml] (P<0.01). Whereas, the level of IFN-gamma in BALF [(107.98 +/- 12.64) pg/ml] and supernatant of cultured splenocytes [(105.51 +/- 1.62) pg/ml] in SIT group was significantly higher than those of OVA group and asthma group (P<0.01). Compared with OVA group [(26.87 +/- 4.30) IU/ml] and asthma group [(35.25 +/- 8.84) IU/ml], a lower level of allergen-specific IgE [(9.12 +/- 3.78) IU/ml] and higher level of allergen-specific IgG2, [(38.52 +/- 6.33) microg/ml] were observed in SIT group (P<0.01). rDer f 3 allergen can reverse allergen-induced airway and lung inflammation in murine asthma model.


CORRELATION BETWEEN MAMMOGRAPHY DETECTED BREAST ARTERIAL CALCIFICATIONS AND LIFESTYLE RISK FACTORS.
The aim of the study was to investigate the association between some lifestyle-attributable risk factors of atherosclerosis, such as body mass index (BMI), oral contraceptives, hormone replacement therapy, smoking and alcohol consumption with breast arterial calcification (BAC) and its intensity on mammograms, and to assess the impact of these lifestyle risk factors on mammography findings of BAC. This prospective study included 300 women aged 47-69, i.e. a group of 149 women with BAC on mammograms and control group of 151 women without BAC. Self-reported BMI, use of oral contraceptives, hormone replacement therapy, smoking and alcohol consumption were recorded by medical interview. The presence of BAC and its intensity on mammography was compared according to the presence of high BMI and use of hormone therapy, smoking and alcohol consumption. The results showed the highest proportion of smokers (28.9%) in the group with mild BAC as compared with the groups without calcification (14.6%) and with intense calcification (12.1%). Women taking oral contraceptives had a higher level of calcified breast arteries but no significant between-group difference was found for high BMI, hormone therapy and alcohol consumption. Thus, study results showed the mammographic finding of BAC to be inadequate to identify women with some lifestyle-attributable risk factors such as BMI, hormone replacement therapy, smoking and alcohol consumption.


Biosensors for Studying Neuronal Proteostasis.
Cellular health depends on the integrity and functionality of the proteome. Each cell is equipped with a protein quality control machinery that maintains protein homeostasis (proteostasis) by helping proteins adopt and keep their native structure, and ensuring the degradation of damaged proteins. Postmitotic cells such as neurons are especially vulnerable to disturbances of proteostasis. Defects of protein quality control occur in aging and have been linked to several disorders, including neurodegenerative diseases. However, the exact nature and time course of such disturbances in the context of brain diseases remain poorly understood. Sensors that allow visualization and quantitative analysis of proteostasis capacity in neurons are essential for gaining a better understanding of disease mechanisms and for testing potential therapies. Here, I provide an overview of available biosensors for assessing the functionality of the neuronal proteostasis network, point out the advantages and limitations of different sensors, and outline their potential for biological discoveries and translational applications.


Regular surface layer of Azotobacter vinelandii.
Washing Azotobacter vinelandii UW1 with Burk buffer or heating cells at 42 degrees C exposed a regular surface layer which was effectively visualized by freeze-etch electron microscopy. This layer was composed of tetragonally arranged subunits separated by a center-to-center spacing of approximately 10 nm. Cells washed with distilled water to remove an acidic major outer membrane protein with a molecular weight of 65,000 did not possess the regular surface layer. This protein, designated the S protein, specifically reattached to the surface of distilled-water-washed cells in the presence of the divalent calcium, magnesium, strontium, or beryllium cations. All of these cations except beryllium supported reassembly of the S protein into a regular tetragonal array. Although the surface localization of the S protein has been demonstrated, radioiodination of exposed envelope proteins in whole cells did not confirm this. The labeling behavior of the S protein could be explained on the basis of varying accessibilities of different tyrosine residues to iodination.


Imaging studies in renal failure. Emphasis of selection and sequencing in the clinical evaluation.
The focus of this review will be on the current role of imaging studies in the clinical evaluation of patients with acute and chronic renal failure. We will stress the application of these studies in specific clinical settings in an effort to indicate the current value, and also to suggest fruitful areas for future clinical investigation. It is clear that imaging studies are an essential component in the evaluation of acute and chronic renal failure. Physicians who manage such patients must choose appropriately from a variety of available studies to obtain a maximal information with the least risk to their patients. This selection is influenced by local conditions, the most important among these being the experience and technical skill of those involved. Attention to detail is particularly important and it is critical that the studies be done at the appropriate time in the evaluation. There will be emphasis on the evolving role of imaging studies in evaluating these patients.


Characterization of a novel PERK kinase inhibitor with antitumor and antiangiogenic activity.
The unfolded protein response (UPR) is a signal transduction pathway that coordinates cellular adaptation to microenvironmental stresses that include hypoxia, nutrient deprivation, and change in redox status. These stress stimuli are common in many tumors and thus targeting components of the UPR signaling is an attractive therapeutic approach. We have identified a first-in-class, small molecule inhibitor of the eukaryotic initiation factor 2-alpha kinase 3 (EIF2AK3) or PERK, one of the three mediators of UPR signaling. GSK2656157 is an ATP-competitive inhibitor of PERK enzyme activity with an IC(50) of 0.9 nmol/L. It is highly selective for PERK with IC(50) values >100 nmol/L against a panel of 300 kinases. GSK2656157 inhibits PERK activity in cells with an IC(50) in the range of 10-30 nmol/L as shown by inhibition of stress-induced PERK autophosphorylation, eIF2α substrate phosphorylation, together with corresponding decreases in ATF4 and CAAT/enhancer binding protein homologous protein (CHOP) in multiple cell lines. Oral administration of GSK2656157 to mice shows a dose- and time-dependent pharmacodynamic response in pancreas as measured by PERK autophosphorylation. Twice daily dosing of GSK2656157 results in dose-dependent inhibition of multiple human tumor xenografts growth in mice. Altered amino acid metabolism, decreased blood vessel density, and vascular perfusion are potential mechanisms for the observed antitumor effect. However, despite its antitumor activity, given the on-target pharmacologic effects of PERK inhibition on pancreatic function, development of any PERK inhibitor in human subjects would need to be cautiously pursued in cancer patients.


[Novel treatment for prostate cancer targeting prostaglandins].
PGE2 is highly expressed in the prostate, associating with prostate cancer progression. Targeting downstream signaling pathways of PGE2 may represent an attractive new strategy for the treatment of prostate cancer. We have established a novel prostate cancer xenograft model, KUCaP-2. The expression of EP4, one of PGE2 receptors, was significantly up-regulated during the development of castration resistance. A specific EP4 antagonist, ONO-AE3-208, decelerated castration-resistant growth of KUCaP-2 tumors in vivo. Moreover, ONO-AE3-208 could in vitro inhibit the cell invasion and in vivo suppress the bone metastasis of prostate cancer cells. These results indicated that EP4 is a novel target for the treatment of metastatic castration resistant prostate cancer.


Domestic violence in pregnancy. A prevalence study.
To determine the extent of physical and psychological abuse of pregnant women in an Australian population. All women attending the public prenatal clinic of the Royal Women's Hospital (Brisbane) between 23 November and 18 December 1992 were interviewed and asked to complete a self-report questionnaire on their history of abuse. Of 1014 women eligible to enter the study, 301 (29.7%) reported a history of abuse. Fifty-nine (5.8%) had been abused during the pregnancy. The proportion of women admitting to abuse rose over the duration of pregnancy to 8.9% at 36 weeks. Medical treatment was sought for injuries related to domestic violence by 31% of those who reported abuse during the pregnancy. Marital status and education were both significantly associated with the prevalence of abuse. Domestic violence towards women may continue or be initiated during pregnancy. Because most women will not reveal details about their experience of violence in the home unless asked, a relationship history should be included at the first visit along with medical, obstetric and other histories.


[Viral genotypes in different infective processes].
This lecture includes three sections. Firstly, the concepts of genotype, subtype and quasi-specie are described. The appearance of virus is correlated with the evolution of the medical picture, and their resistance to antiviral agents. Secondly, the most modern genetical and molecular biology techniques, including DNA sequencing are studied. Thirdly, some examples of the investigation lines carried out at the Microbiology Department of the Granada Medicine School are explained, especially regarding to papillomavirus, hepatitis C virus, hepatitis G virus, virus associated to transfusions (TTV) and human immunodeficiency. The great transcendence that the genetical variability has to establish pathogeny and therapy control is emphasized.


AMPK inhibitor compound C suppresses cell proliferation by induction of apoptosis and autophagy in human colorectal cancer cells.
AMP-activated protein kinase (AMPK) is a main regulator of energy metabolism through the inhibition of biosynthetic pathways and enhancement of ATP-generating pathways. However, targeting AMPK as anti-tumor therapy remains controversial. In this study, we examined the effect of compound C, a small molecule inhibitor of AMPK, on the proliferation of several human colorectal cancer cell lines with diverse characteristics. Four human colorectal cancer cell lines (HCT116, DLD-1, SW480, and KM12C) were treated with compound C. Cell viability was determined by MTS assay. Cell cycle prolife was analyzed by flow cytometry. Acidic vesicular organelles were detected by acridine orange staining. Protein levels were measured by western blotting. Compound C inhibited the growth of four cell lines in a dose-dependent manner and caused G(2) /M arrest. Compound C increased sub-G(1) cell population and induced chromatin condensation and cleavage of PARP in HCT116 and KM12C cells, while it induced acidic vesicular formation and conversion of LC3-I to autophagosome-associated LC3-II in DLD-1 and SW480 cells. Survivin, an anti-apoptotic protein, was down-regulated in all cell lines treated with compound C. Compound C induces apoptotic or autophagic death in colorectal cancer cells and the preferred death mode is cell type-dependent.


Early response of C-reactive protein as a predictor of survival in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors.
Pretreatment C-reactive protein (CRP) has been shown to be an independent prognostic factor for metastatic renal cell carcinoma (mRCC) treated with tyrosine kinase inhibitors (TKIs). We further evaluated the early response of CRP after the initiation of TKIs. A total of 103 patients (80 men and 23 women) were treated with TKIs for mRCC from 2008-2013. Patients were divided into three groups according to their early CRP kinetics-patients whose baseline CRP levels were <10 mg/L (non-elevated), patients whose baseline CRP levels were ≥10 mg/L and had decreased by >20% at 4 weeks after the initiation of TKIs (early CRP responder), and the remaining patients (non-early CRP responder). The endpoints were progression-free survival (PFS) and overall survival (OS). The median follow-up period was 21 (interquartile range 10-34) months. The numbers of patients classified as non-elevated, early CRP responder, and non-early CRP responder were 62, 19, and 22, respectively. The 1-year PFS rates of patients in the non-elevated, early CRP responder, and non-early CRP responder groups were 50, 23, and 9.7%, respectively (p < 0.001). The 1-year OS rates of patients in these three groups were 79, 62, and 36%, respectively (p < 0.001). In multivariate analysis, the early CRP kinetics assessment was a significant independent factor for PFS and OS. Early CRP response at 4 weeks is predictive of survival for patients with mRCC treated with TKI.


Use of the Toric Surgical Marker to Aid in Intraoperative Plaque Placement for the USC Eye Physics Plaques to Treat Uveal Melanoma: A New Surgical Technique.
To describe a new surgical technique for intraoperative placement of Eye Physics (EP) plaques for uveal melanoma using a toric marker. A toric marker is designed for cataract surgery to align the axis of astigmatism; its use was modified in this protocol to mark the axis of suture coordinates as calculated by Plaque Simulator (PS) software. The toric marker can be used to localize suture coordinates, in degrees, during intraoperative plaque placement. Linear marking using the toric marker decreases potential inaccuracies associated with the surgeon estimating 'clock-hours' by dot placement. Use of the toric marker aided surgical placement of EP plaques. The EP planning protocol is now designed to display the suture coordinates either by clock-hours or degrees, per surgeon preference. Future research is necessary to determine whether routine use of the toric marker improves operative efficiency. [Ophthalmic Surg Lasers Imaging Retina. 2015;46:866-870.].


Corticobasal syndrome and primary progressive aphasia as manifestations of LRRK2 gene mutations.
Mutations in the LRRK2 gene are an important cause of familial and nonfamilial parkinsonism. Despite pleomorphic pathology, LRRK2 mutations are believed to manifest clinically as typical Parkinson disease (PD). However, most genetic screens have been limited to PD clinic populations. To clinically characterize LRRK2 mutations in cases recruited from a spectrum of neurodegenerative diseases. We screened for the common G2019S mutation and several additional previously reported LRRK2 mutations in 434 individuals. A total of 254 patients recruited from neurodegenerative disease clinics and 180 neurodegenerative disease autopsy cases from the University of Pennsylvania brain bank were evaluated. Eight cases were found to harbor a LRRK2 mutation. Among patients with a mutation, two presented with cognitive deficits leading to clinical diagnoses of corticobasal syndrome and primary progressive aphasia. The clinical presentation of LRRK2-associated neurodegenerative disease may be more heterogeneous than previously assumed.


Experimental Approaches for Improving the Assessment of Partner Violence.
Intimate partner violence (IPV) is a serious and widespread problem. Unfortunately, like many other private behaviors, self-report is one of the few practical means of assessing IPV. Despite its known limitations, few studies have examined methods for improving the assessment of IPV through self-report, particularly in research contexts. The current study examined implicit goal priming (IGP) and restricted response latencies (RRL), which have previously been used successfully to improve reporting of other types of sensitive information. Participants in the IGP condition engaged in a word-matching task intended to subliminally prime an honesty goal immediately before completing the IPV self-report measure. In the RRL condition, the amount of time participants were allotted to answer each question was restricted to 3 s. Using a pilot sample of 71 cohabiting/married couples, we currently provide experimental support for the utility of the IGP task for increasing the frequency of reported IPV, as well as agreement between self-reports and partner reports, particularly when used in conjunction with the RRL method. We found the strongest and most consistent effects for women's reports of severe IPV perpetration and victimization, which is important given the extreme nature of these forms of IPV and because they are frequently underreported by women. We also found evidence to support the use of these methods to enhance reporting of other forms of IPV and provide additional directions for future research.


Differential Effects of Iron, Zinc, and Copper on Dictyostelium discoideum Cell Growth and Resistance to Legionella pneumophila.
Iron, zinc, and copper play fundamental roles in eucaryotes and procaryotes, and their bioavailability regulates host-pathogen interactions. For intracellular pathogens, the source of metals is the cytoplasm of the host, which in turn manipulates intracellular metal traffic following pathogen recognition. It is established that iron is withheld from the pathogen-containing vacuole, whereas for copper and zinc the evidence is unclear. Most infection studies in mammals have concentrated on effects of metal deficiency/overloading at organismal level. Thus, zinc deficiency or supplementation correlate with high risk of respiratory tract infection or recovery from severe infection, respectively. Iron, zinc, and copper deficiency or overload affects lymphocyte proliferation/maturation, and thus the adaptive immune response. Whether they regulate innate immunity at macrophage level is open, except for iron. The early identification in a mouse mutant susceptible to mycobacterial infection of the iron transporter Nramp1 allowed dissecting Nramp1 role in phagocytes, from the social amoeba Dictyostelium to macrophages. Nramp1 regulates iron efflux from the phagosomes, thus starving pathogenic bacteria for iron. Similar studies for zinc or copper are scant, due to the large number of copper and zinc transporters. In Dictyostelium, zinc and copper transporters include 11 and 6 members, respectively. To assess the role of zinc or copper in Dictyostelium, cells were grown under conditions of metal depletion or excess and tested for resistance to Legionella pneumophila infection. Iron shortage or overload inhibited Dictyostelium cell growth within few generations. Surprisingly, zinc or copper depletion failed to affect growth. Zinc or copper overloading inhibited cell growth at, respectively, 50- or 500-fold the physiological concentration, suggesting very efficient control of their homeostasis, as confirmed by Inductively Coupled Plasma Mass Spectrometry quantification of cellular metals. Legionella infection was inhibited or enhanced in cells grown under iron shortage or overload, respectively, confirming a major role for iron in controlling resistance to pathogens. In contrast, zinc and copper depletion or excess during growth did not affect Legionella infection. Using Zinpyr-1 as fluorescent sensor, we show that zinc accumulates in endo-lysosomal vesicles, including phagosomes, and the contractile vacuole. Furthermore, we provide evidence for permeabilization of the Legionella-containing vacuole during bacterial proliferation.


Virtual reality surgical simulation for lower urinary tract endoscopy and procedures.
To provide a realistic experience of lower urinary tract endoscopic procedures, we have developed and continue to expand a computer-based surgical simulator that incorporates a surgical tool interface with anatomic detail and haptic feedback. Surface-based geometric data for the lower urinary tract were generated from the National Library of Medicine Visible Human dataset. The three-dimensional texture map of the surface geometry was developed from recorded endoscopic video procedures. Geometry and associated texture maps were rendered in real time using the Silicon Graphics Extreme Impacts program. The surgical interface device incorporated all normal ranges of motion and resistance that occur within an actual operative environment. The hands-on endoscopic device attached to the interface device was provided by Circon-ACMI, Inc. Urologic residents evaluated the program for correlation with actual endoscopic procedures. Texture-mapped digitized images provided a close anatomic similarity to actual videoendoscopic images. Virtual endoscopy of the lower urinary tract was reproducible and closely simulated actual visual and tactile endoscopic experience. Virtual reality surgical simulation is feasible for a variety of lower urinary tract procedures. This system coordinates visual perception with appropriate haptic feedback in both longitudinal and rotational axes. These types of procedures may be incorporated into future educational experiences for urologists to introduce new techniques and to provide documentation of surgical experience.


Timing of neural excitation in relation to basilar membrane motion in the basal region of the guinea pig cochlea during the presentation of low-frequency acoustic stimulation.
In spite of many studies concerning auditory nerve action potentials, the timing of neural excitation in relation to basilar membrane (BM) motion is still not well understood. In this study, therefore, BM vibrations in the basal region of the guinea pig cochlea were measured using a laser Doppler velocimeter, and action potentials in auditory nerve fibers were recorded by a conventional microelectrode technique. An attempt was then made to determine the relationship between BM motion and neural excitation in auditory nerve fibers. To obtain BM responses in the high-characteristic frequency (CF) region (18-22 kHz) and responses of auditory nerve fibers with high CFs (14-22 kHz), low-frequency stimuli (50-2000 Hz), frequencies of which were well below CFs, were presented at 60-100 dB SPL. The results indicated that neural excitation occurred when the BM was displaced toward the scala vestibuli. Moreover, the neural excitatory phase did not significantly vary with the fiber's CF between 14 and 22 kHz nor with the stimulus level between 60 and 100 dB SPL.


Matters of the heart: cardiovascular disease in U.S. women.
Cardiovascular disease is the leading cause of death in United States women and accounts for approximately 500,000 deaths annually. Over half of cardiovascular disease-related deaths in women result from coronary artery disease including acute coronary syndromes. This paper reviews gender specific issues in women as they relate to current cardiovascular disease epidemiology, trends in cardiovascular disease epidemiology, coronary artery disease detection, risk factor modification, and prevention of cardiovascular disease-related events.


Tuning the Packing Density of Gold Nanoparticles in Peptoid Nanosheets Prepared at the Oil-Water Interface.
Two-dimensional (2D) arrays of gold nanoparticles that can freely float in water are promising materials for solution-based plasmonic applications like sensing. To be effective sensors, it is critical to control the interparticle gap distance and thus the plasmonic properties of the 2D arrays. Here, we demonstrate excellent control over the interparticle gap distance in a family of freely floating gold nanoparticle-embedded peptoid nanosheets. Nanosheets are made via monolayer assembly and collapse at the oil-water interface, allowing for fine control over the solution nanoparticle concentration during assembly. We used surface pressure measurements to monitor the assembly of the peptoid, nanoparticle, and combined system at the oil-water interface to determine a workable range of nanosheet assembly conditions suitable for controlling the interparticle gap distances within the nanosheets. These measurements revealed that the extent of nanoparticle adsorption to the peptoid monolayer can be tuned by varying the bulk nanoparticle concentration, but the ability for the monolayer to collapse into nanosheets is compromised at high nanoparticle concentrations. Peptoid nanosheets were synthesized with varying bulk nanoparticle concentrations and analyzed using light microscopy and UV-visible spectroscopy. Based on the spectral shift of the localized surface plasmon resonance peaks for the nanoparticles in the nanosheets relative to those well dispersed in toluene, we estimate that we can access interparticle gap distances within the nanosheet interior between 2.9 ± 0.5 and 9 ± 2 nm. Our results suggest that the minimum interparticle distance achievable by this method is limited by the nanoparticle ligand length, and so has the potential to be further tuned by varying the ligand chemical structure. The ability to quantitatively control and monitor the assembly conditions by this method provide an opportunity to readily tune the optoelectronic properties of this new class of 2D nanomaterial, making it a promising platform for plasmonic-based sensing applications.


Cardiac gunshot injury: child with stable presentation and asymptomatic short-term follow-up.
A 2-year-old female child was brought to the emergency department after she was accidentally shot by her father, while cleaning his air rifle loaded with the pointed type 0.22 (5.5 mm) caliber pellet. The pellet hit the front of chest from a distance of about 10-15 m. On physical examination, it was found that there was entrance wound in right lower parasternal area but no exit wound. She was hemodynamically stable with normal auscultatory findings. Chest roentgenogram (Fig. 1) demonstrated a bullet overlying cardiac silhouette with no other findings. Two-dimensional transthoracic echocardiography (Figs, 2, 3, and movie clip 1) showed an echogenic density in the interventricular septum just beneath the insertion of tricuspid and mitral leaflets. The atrioventricular valves appear normal with no regurgitation. The biventricular function also appeared normal with no regional wall motion abnormalities. There was no pericardial effusion present. The echogenicity is most likely the pellet that punctured the chest wall and continued inward to lodge in the interventricular septum. Computed tomographic scan of the chest showed an intracardiac foreign body without other abnormalities. Up to 11 months, repeated scans have shown no changes. She will continue to receive ongoing follow-up to assess for late complications (migration, erosion, conduction, disturbance, etc.) To the best of our knowledge, she may be the youngest living patient having cardiac trauma with clinically stable presentation and asymptomatic short-term follow-up.


[Sleep habits of medical students, physicians and nurses regarding age, sex, shift work and caffein consumption].
The aim of this study was to evaluate sleep habits of nurses, medical students, and physicians and to explore whether they are influenced by age, sex, shift work, and caffeine consumption. The questionnaire was derived from the MEDSleep Survey. A total of 453 respondents were surveyed: second-year medical students (130); physicians at the postgraduate study program (68); specialists (162); nurses (93). Results of our study indicate that hours of sleep needed for feeling rested depends on age and gender. Younger respondents and women in the study need longer sleep to feel rested (7.5 hours and more) than older ones and males who need less than 7.5 hours of sleep. Among medical professionals a need for sleep differs related to work demands and work schedule. Nurses need more sleep than physicians (chi2 = 38.57, p < 0.001). Female nurses need more sleep for feeling rested than female physicians (chi2 = 18.18, p < 0.001), and sleep longer during the weeknights (chi2 = 33.78, p < 0.001) and weekends (chi2 = 28.06, p < 0.001). The respondents that consume caffeine have more trouble staying awake while listening to lectures or learning (chi2 = 9.37, p = 0.009), and while driving a car (chi2 = 14.56, p = 0.001). The results indicate that sleep habits are related to age, sex and caffeine consumption.


Anti-Inflammatory Effects of Campomanesia xanthocarpa Seed Extract Obtained from Supercritical CO2.
Campomanesia xanthocarpa is a plant species traditionally used in the treatment of diabetes, fever, hypercholesterolemia, obesity, and urinary tract diseases. The anti-inflammatory effects of C. xanthocarpa leaves in mice were already known. Nevertheless, studies on the anti-inflammatory activity of its seeds are still lacking. The aim of this study was to investigate the anti-inflammatory activity and acute toxicity of C. xanthocarpa seed extract, obtained from supercritical CO2 extraction (SCCO2) at 40°C and 250 bar, in mice. GC/MS analysis revealed that β-caryophyllene is the major compound present in the C. xanthocarpa SCCO2 extract. The extract (60 mg/kg, p.o.) significantly reduced the nociceptive behavior in the second phase of the formalin test and prevented the paw oedema induced by carrageenan up to 6 h after carrageenan injection. The extract (0.1-1 μg/mL) inhibited neutrophils migration induced by LPS from E. coli in vitro. This antichemostatic effect was comparable to the effect of indomethacin. Acute administration (2000 mg/kg, p.o.) of C. xanthocarpa SCCO2 extract caused no mice mortality, demonstrating that the extract is devoid of acute toxicity. These data suggest that C. xanthocarpa seeds present anti-inflammatory activity and represent a source of anti-inflammatory compounds.


Mutations in exons 3 and 7 resulting in truncated expression of human ATP6V1B1 gene showing structural variations contributing to poor substrate binding-causative reason for distal renal tubular acidosis with sensorineural deafness.
Distal renal tubular acidosis (dRTA) is an autosomal recessive syndrome results defect in either proximal tubule bicarbonate reabsorption or in distal tubule H(+) secretion and is characterized by severe hyperchloraemic metabolic acidosis in childhood. dRTA is associated with functional variations in the ATP6V1B1 gene encoding β1 subunit of H(+)-ATPase, key membrane transporters for net acid excretion of α-intercalated cells of medullary collecting ducts. In the present study, a 13-year-old male patient suffering with nephropathy and sensorineural deafness was reported in the Department of Nephrology. We predicted improper functioning of ATP6V1B1 gene could be the reason for diseased condition. Therefore, exons 3, 4, and 7 contributing active site of ATP6V1B1 gene was amplified and sequenced (Accession numbers: KF571726, KM222653). The obtained sequences were BLAST searched against the wild type ATP6V1B1 gene which showed novel mutations c.307 A > G, c.308 C > A, c.310 C > G, c.704 T > C, c.705 G > T, c.709 A > G, c.710 A > G, c.714 G > A, c.716 C > A, c.717delC, c.722 C > G, c.728insG, c.741insT, c.753G > C. These mutations resulted in the expression of truncated protein terminating at Lys 209. The mutated ATP6V1B1structure superimposed with wild type showed extensive variations with RMSD 1.336 Å and could not bind to substrate ADP leading to non-functional ATPase. These results conclusively explain these mutations in ATP6V1B1 gene resulted in structural changes causing accumulation of H(+) ions contributing to dRTA with sensorineural deafness.


[The correlation between the carotid artery plaque and the change of aldosterone level related indexes during captopril challenge test].
To investigate the correlation between the carotid artery plaque and the change of plasma aldosterone level related indexes during captopril challenge test. The patients with hypertension were enrolled as research objects and the captopril challenge test were carried out when they were hospitalized to screen the cause of hypertension. There were intact carotid artery duplex ultrasonography diagnostic data in them (83 cases). They were divided into the plaque group(57 cases) with carotid artery plaque and no plaque group( 26 cases) without carotid artery plaque according to the carotid artery duplex ultrasonography diagnostic data. The correlation between the carotid artery plaque and the changes of aldosterone concentration, renin activity and aldosterone to renin activity ratio(ARR) in two groups were analyzed. The detection rate of carotid artery plaque was 68.67%. Compare with no plaque group, the patients in plaque group were elder and the level of apolipoprotein A1,(APOA1) was lower (all P<0.05). The ARR difference value before and after captopril challenge test was lower ( P<0.05).The aldosterone difference value and the renin activity difference value before and after captopril challenge test were higher in plaque group (all P<0.05).The aldosterone difference value and the renin activity difference value were positive in plaque group and were negative in no plaque group. The difference value of the ARR was negative in plaque group and was positive in no plaque group. Logistic regression analysis showed that the age, the difference value of ARR and the aldosterone before and after captopril challenge test could be associated independently with carotid artery plaque occurrence after excluding gender difference and other factors. The detection rate of carotid artery plaque was high among hospitalized patients with hypertension, the difference value of ARR and the aldosterone before and after captopril challenge test could be associated independently with carotid artery plaque occurrence.


Dengue in renal transplant patients: a retrospective analysis.
We reviewed the impact of dengue in 27 renal transplant recipients (9 females and 18 males) at a mean of 63 (6-287) months after transplantation. Their mean age was 37+/-14 years and all were first transplantations (21 live donors, 6 deceased donors). Twenty-six were dengue fever cases and one had dengue hemorrhagic fever. Symptoms were: fever (100%), muscular pain (90%), malaise (75%), and headache (68%). Eight (29%) patients were admitted to hospital with one death. All other cases had full recovery. Mean serum creatinine before dengue was 1.4+/-0.6 mg/dL, increased to a mean peak of 1.9+/-1.2 mg/dL (P<0.001), and returned to baseline after recovery (1.6+/-0.82 mg/dL, P=NS). After a mean follow-up of 39+/-18 months, four patients lost their grafts due to chronic allograft nephropathy and four died, due to infectious causes not related to dengue. The first episode of dengue in transplanted patients resembled a flu-like syndrome, as in the general population. It did not cause long-term damage to either the patient or the graft.


Persistence of Nonceliac Wheat Sensitivity, Based on Long-term Follow-up.
We investigated how many patients with a diagnosis of nonceliac wheat sensitivity (NCWS) still experienced wheat sensitivity after a median follow-up time of 99 months. We collected data from 200 participants from a previous study of NCWS, performed between July and December 2016 in Italy; 148 of these individuals were still on a strict wheat-free diet. In total, 175 patients (88%) improved (had fewer symptoms) after a diagnosis of NCWS; 145 of 148 patients who adhered strictly to a gluten-free diet (98%) had reduced symptoms, compared with 30 of 52 patients who did not adhere to a gluten-free diet (58%) (P < .0001). Of the 22 patients who repeated the double-blind, placebo-controlled challenge, 20 reacted to wheat. We conclude that NCWS is a persistent condition. Clinicaltrials.gov registration number: NCT02823522.


Public Adoption of and Trust in the NHS COVID-19 Contact Tracing App in the United Kingdom: Quantitative Online Survey Study.
Digital contact tracing is employed to monitor and manage the spread of COVID-19. However, to be effective the system must be adopted by a substantial proportion of the population. Studies of mostly hypothetical contact tracing apps show generally high acceptance, but little is known about the drivers and barriers to adoption of deployed systems. The aim of this study was to investigate adoption of and attitudes toward the NHS (National Health Service) COVID-19 smartphone app, the digital contact tracing solution in the United Kingdom. An online survey based on the extended Technology Acceptance Model with the added factor of trust was carried out with a representative sample of the UK population. Statistical analysis showed adoption rates, attitudes toward and trust in the app, and compliance with self-isolation advice and highlighted differences for vulnerable populations (ie, older adults aged 65 years and over and members of Black, Asian, and minority ethnic [BAME] communities). A total of 1001 participants took part in the study. Around half of the participants who had heard of the NHS COVID-19 mobile phone app (490/963, 50.9%; 95% CI 47.8%-54.0%) had downloaded and kept the app, but more than one-third (345/963, 35.8%; 95% CI 32.8%-38.8%) either did not intend to download it or had deleted it. Significantly more BAME respondents than White respondents had deleted the app (16/115, 13.9%; 95% CI 11.8%-16.0%, vs 65/876, 7.4%; 95% CI 5.8%-9.0%), and significantly more older adults 65 years and over than those under 65 years did not intend to download it (44/127, 34.6%; 95% CI 31.7%-37.5%, vs 220/874, 25.2%; 95% CI 22.5%-27.9%). Broadly, one of the reasons for uptake was to help the NHS and other people, especially among older adults, although significantly fewer BAME participants agreed that they did so to help the NHS. Reported compliance with received notifications to self-isolate was high but was significantly lower than reported intended compliance without received notifications. Only one-fifth (136/699, 19.5%; 95% CI 17.0%-22.0%) of participants understood that the decision to send self-isolation notifications was automated by the app. There were a range of significantly more negative views among BAME participants, including lower trust in the NHS, while older adults were often significantly more positive. Respondents without the app reported significantly lower trust and more negative views toward the app and were less likely to report that they understood how the app works. While compliance on the part of the approximately 50% of participants who had the app was fairly high, there were issues surrounding trust and understanding that hindered adoption and, therefore, the effectiveness of digital contact tracing, particularly among BAME communities. This study highlights that more needs to be done to improve adoption among groups who are more vulnerable to the effects of the virus in order to enhance uptake and acceptance of contact tracing apps.


Contemporary changes in phenotypic variation, and the potential consequences for eco-evolutionary dynamics.
Most studies assessing rates of phenotypic change focus on population mean trait values, whereas a largely overlooked additional component is changes in population trait variation. Theoretically, eco-evolutionary dynamics mediated by such changes in trait variation could be as important as those mediated by changes in trait means. To date, however, no study has comprehensively summarised how phenotypic variation is changing in contemporary populations. Here, we explore four questions using a large database: How do changes in trait variances compare to changes in trait means? Do different human disturbances have different effects on trait variance? Do different trait types have different effects on changes in trait variance? Do studies that established a genetic basis for trait change show different patterns from those that did not? We find that changes in variation are typically small; yet we also see some very large changes associated with particular disturbances or trait types. We close by interpreting and discussing the implications of our findings in the context of eco-evolutionary studies.


[Is crystalloid cardioplegia still a valid technique for myocardial myocardial protection?].
The routine use of a cardioplegic solution for myocardial protection during the ischemic phase of cardiac surgery represents a great therapeutic advance. Two cardioplegic solutions are currently in use: crystalloid and blood solutions. As blood cardioplegia has been shown to offer superior myocardial protection, its use at present is widespread. We did a retrospective study to assess whether crystalloid cardioplegia might nevertheless continue to be useful. Forty patients with heart disease underwent surgery between March 1994 and March 1995, with the use of crystalloid cardioplegia (group A). Blood cardioplegia was used in 72 patients during the same period (group B). There were no significant differences in clinical (age, arterial hypertension, diabetes, chronic bronchial disease, severity of angina, severity of heart disease) or surgical (emergency, percent use of the internal thoracic artery, duration of extracorporeal circulation) variables. The percentage of patients with low ejection fraction was higher in group B as a result of preoperative selection. The mean number of grafts was higher in group B than in group A (3.5% and 2.5, respectively) (p < 0.01). Postoperative results (use of inotropics, counterpulsation balloon, creatine phosphokinase, perioperative myocardial infarction or hospital mortality) were not significantly different. The percent of supraventricular arrhythmias after surgery was higher in group A than in group B (20% and 5%, respectively) (p < 0.05) and lactic dehydrogenase level was lower in group A than in group B (472 and 572 mu/l, respectively) (p < 0.05). We believe that crystalloid cardioplegia continues to be a valid and effective myocardial protection technique in heart patients with preserved left ventricular systolic function.


[HIV infection in the Public Assistance Hospitals in Paris. Cross-sectional survey on a given day per trimester, a hospital indicator of morbidity].
Many patients with Acquired Immunodeficiency Syndrome (AIDS) and the other forms of human immunodeficiency virus infection are treated in the Assistance Publique hospitals of Paris (AP). A cross-sectional survey to be repeated on a given day of each trimester was designed to obtain rapidly and anonymously the number of inpatients treated. A questionnaire was sent to the head of every department treating acute inpatients, asking for the number of patients with AIDS, AIDS-related Complex, pre-AIDS... and asymptomatic carriers of HIV. In 1986, a regular increase was observed from 252 (139 AIDS patients) in March to 318 (170 AIDS patients) in December. On the average, approximately two-thirds of the AIDS patients were hospitalized in three hospitals; however, their number remained stable over the year so these three hospitals' proportion tended to decrease. An estimation of the annual number of inpatients with HIV infection was drawn from the mean of the cross-sectional survey's results. This survey makes it possible to evaluate on an almost continuous basis the impact of AIDS and related conditions on hospitalization figures.


Postsynaptic protein synthesis is required for presynaptic enhancement in persistent forms of long-term potentiation.
Long-term potentiation (LTP) in the hippocampus is a fundamental process underlying learning and memory in the brain. At CA3-CA1 synapses, three discrete forms of LTP (LTP1, 2, and 3) have been differentiated on the basis of their persistence, maintenance mechanisms, Ca(2+) signaling pathways, expression loci, and electrophysiological requirements. We previously showed that LTP2 and LTP3 involve a presynaptic expression component that is established in a translation-dependent manner. Here we investigate the locus of translation required for presynaptic expression. Neurotransmitter release rate was estimated via FM 1-43 destaining from CA3 terminals in hippocampal slices from male Wistar rats (6-8 weeks). Destaining was measured at sites making putative contact with CA1 dendritic processes in stratum radiatum that had been filled with a membrane impermeable translation inhibitor and a fluorescent indicator. Our results suggest that inhibition of postsynaptic translation eliminates the enhanced release ordinarily observed at 160 min post-LTP induction, and that this effect is limited to sites closely apposed to the filled postsynaptic cell. We conclude that postsynaptic translation is required for the presynaptic component of LTP2 and LTP3 expression. These data considerably strengthen the mechanistic separation of LTP1, 2, and 3 and provide evidence for an expanded repertoire of communication between synaptic elements.