Perception of built environmental factors and physical activity among adolescents in Nigeria.
Understanding environmental factors related to adolescents' physical activity can inform intervention for obesity control and prevention, but virtually no study has been conducted in the African region, where adolescents' physical inactivity and chronic diseases rates are rising. This study assessed associations between perceived built environmental variables and adolescents' physical activity (active transportation to school and leisure-time moderate-to- vigorous physical activity), and the moderating effects of neighborhood-level income on association between environmental variables and physical activity among Nigerian boys and girls. Participants were 1006 adolescents (12-19 years, 50.4% girls) randomly selected from 11 secondary schools in Maiduguri city, Nigeria. Physical activity and perceptions of environmental characteristics were assessed by validated self-report questionnaires. Separate gender-based, hierarchical multiple moderated linear regression analyses were used to examine the direct associations between the environmental perceptions and physical activity variables (active transportation and leisure-time MVPA; dependent variables), as well as the moderating effects of neighborhood-level income. Only in boys were direct associations and interaction effect of neighborhood-level income found. Access to destinations was positively associated with active transportation to school (β = 0.18; CI = 0.67, 2.24); while residential density (β = 0.10; CI = 0.01, 1.74) and availability/quality of infrastructures (β = 0.14; CI = 0.49, 2.68) were positively associated with leisure-time MVPA. Also, neighborhood-level income moderated the association between perceived safety and leisure-time MVPA, with more perceived safety related to less MVPA (β = -0.16; CI = -0.01, -0.70) in boys living in high SES neighborhood but marginally related to more MVPA (β = 0.11; CI = -0.04, 2.88, p = 0.06) in boys living in low SES neighborhood. Few environmental attributes were associated with adolescents' physical activity in Nigeria. Future studies are needed to determine the multidimensional correlates of physical activity that may be relevant for both adolescents' boys and girls in Nigeria.


Adverse impact of sexual dysfunction in chronic prostatitis/chronic pelvic pain syndrome.
To examine the prevalence, characteristics, and impact of sexual dysfunction in our primary care referral population. Participants seeking treatment for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) were recruited from general urology clinics. The subjects completed the National Institutes of Health-Chronic Prostatitis Symptom Index, International Index of Erectile Function-5, and selected questions from the University of Washington Symptom Score. Additional information on demographics and medical and treatment history were also obtained. Sexual dysfunction was defined as self-reported erectile dysfunction (ED) or ejaculatory difficulty, or both. Of 296 participants with CP/CPPS, 214 (72.3%) reported sexual dysfunction. The National Institutes of Health-Chronic Prostatitis Symptom Index total score averaged 22.5 +/- 6.9 for participants with sexual dysfunction compared with 20.4 +/- 7.8 for participants who did not report sexual dysfunction (P = 0.03). Of the 214 participants with sexual dysfunction, 54 (25.0%) complained of ED only, 71 (33.4%) complained of ejaculatory difficulties only, and 89 (41.6%) complained of both ED and ejaculatory difficulties. Men reporting both ED and ejaculatory difficulty reported worse CP/CPPS symptoms (analysis of variance, P = 0.042) and worse quality of life (analysis of variance, P = 0.006) than men without sexual dysfunction. Sexual dysfunction was reported by almost three quarters of patients with CP/CPPS. Patients with CP/CPPS and sexual dysfunction experienced substantially worse symptoms, particularly worse quality of life, than other patients with CP/CPPS. Sexual dysfunction merits consideration as an important aspect of CP/CPPS and a potential outcome measure.


[The immunomorphological changes in the duodenal mucosa in peptic ulcer].
Results of immunomorphological investigation of the duodenal tissue, taken for biopsy at the time of operative intervention for the duodenal ulcer in 23 patients, are presented. Lowering of IgA-synthesizing cells count in lamina propria of the duodenal mucosa was determined. Deposition of IgG and the C3 component in vessels, the enlargement of IgA-synthesizing cells confirms the presence of antigenic properties of affected duodenum and the participation of immunocomplex and autoimmune mechanisms in pathogenesis of the duodenal ulcer disease.


Anticoagulant and antiplatelet use in seniors with chronic subdural hematoma: Systematic review.
To address whether to restart older patients on anticoagulants or antiplatelet agents in the setting of a chronic subdural hematoma (cSDH). This is an update of a previous review (searched until July 2012). Medline, EMBASE, ISI Web of Knowledge, Google Scholar, PLOS, and the Cochrane Register for Systematic Reviews databases were searched from January 2012 to December 2016. Studies included older adults (those over 65 years) experiencing traumatic subdural hematoma or cSDH who were on anticoagulation or antiplatelet agents. Seven studies were included (mean age 72 years). Four out of 7 studies provided combined data on anticoagulants or antiplatelet use. Only one study found anticoagulant or antiplatelet agent use to be a significant factor for cSDH rebleeding. Two studies considered anticoagulant use only and both reported similar increased odds of rebleeding (odds ratio [OR] 1.75, 95% confidence interval [CI] 0.18-16.86; OR 2.7 95% CI 1.42-6.96). Antiplatelets were not found to be associated with rebleeding. Ideal timing to resume anticoagulants or antiplatelets was unclear. Anticoagulant medication was associated with increased rebleeding risk in older adults with cSDH. However, antiplatelet medication was not associated with increased risk of rebleeding.


Monitoring of the Sensitivity In Vivo of Plasmodium falciparum to Artemether-Lumefantrine in Mali.
In Mali, since 2007, artemether-lumefantrine has been the first choice against uncomplicated malaria. Despite its effectiveness, a rapid selection of markers of resistance to partner drugs has been documented. This work evaluated the treatment according to the World Health Organization's standard 28-day treatment method. The primary endpoint was the clinical and parasitological response corrected by a polymerase chain reaction. It was more than 99.9 percent, the proportion of patients with anemia significantly decrease compared to baseline (p < 0.001), and no serious events were recorded. Plasmodium falciparum remains sensitive to artemether-lumefantrine in Mali.


Quantification of human insulin-like growth factor-1 and qualitative detection of its analogues in plasma using liquid chromatography/electrospray ionisation tandem mass spectrometry.
Human insulin-like growth factor-1 (IGF-1) is a peptide hormone that acts as a mediator of most of the somatotropic effects of growth hormone (GH). Therefore, it is supposed to be a biomarker indicating GH abuse in sports as well as diseases associated with a change in IGF-1 plasma concentration. It can be applied locally by injection to increase total protein and DNA content in tissues such as skeletal muscle--a highly desirable effect in various sports disciplines. In order to improve its growth-promoting properties, the primary structure of IGF-1 has been modified, yielding analogues such as des(1-3)IGF-1 and LONGR3IGF-1, which show a considerably reduced affinity to the respective binding proteins in plasma and, thus, an increased bioavailability at target tissues. Due to their capability to enhance performance, IGF-1 and its analogues belong to the prohibited list of the World Anti-Doping Agency. Hence, it was necessary to develop a reliable assay for the quantification of human IGF-1 as well as the detection of its derivatives. Immunoaffinity isolation and purification from 60 microL of plasma followed by liquid chromatography/electrospray ionisation tandem mass spectrometry enabled the unequivocal determination of all target analytes. Diagnostic product ions were characterised utilising an Orbitrap mass spectrometer with high resolution/high accuracy properties and employed for triple quadrupole MS/MS analysis. The described assay provided lower limits of detection (LLODs) between 20 and 50 ng/mL, recovery rates between 34-43% and a precision <15% at the LLOD as well as higher concentration levels. In order to prove the applicability of the developed assay, human plasma samples were analysed and the results were compared with the values obtained from a commercially available immunoradiometric assay (IRMA). Four of six samples resulted in concentration ratios with good correlation between both assays, whereas the absolute concentrations were lower for the presented procedure.


Biomedical journals and databases in Russia and Russian language in the former Soviet Union and beyond.
In the 20th century, Russian biomedical science experienced a decline from the blossom of the early years to a drastic state. Through the first decades of the USSR, it was transformed to suit the ideological requirements of a totalitarian state and biased directives of communist leaders. Later, depressing economic conditions and isolation from the international research community further impeded its development. Contemporary Russia has inherited a system of medical education quite different from the west as well as counterproductive regulations for the allocation of research funding. The methodology of medical and epidemiological research in Russia is largely outdated. Epidemiology continues to focus on infectious disease and results of the best studies tend to be published in international periodicals. MEDLINE continues to be the best database to search for Russian biomedical publications, despite only a small proportion being indexed. The database of the Moscow Central Medical Library is the largest national database of medical periodicals, but does not provide abstracts and full subject heading codes, and it does not cover even the entire collection of the Library. New databases and catalogs (e.g. Panteleimon) that have appeared recently are incomplete and do not enable effective searching.


Intramolecular indicator displacement assay for anions: supramolecular sensor for glyphosate.
One of the well-known strategies for anion sensing is an indicator (dye) displacement assay. However, the disadvantage of the dye displacement assays is the low sensitivity due to the excess of the dye used. To overcome this setback, we have developed an "Intramolecular Indicator Displacement Assay (IIDA)". The IIDAs comprise a receptor and a spacer with an attached anionic chromophore in a single-molecule assembly. In the resting state, the environment-sensitive anionic chromophore is bound by the receptor, while the anionic substrate competes for binding into the receptor. The photophysical properties of the dye exhibit change in fluorescence when displaced by anions, which results in cross-reactive response. To illustrate the concept, we have prepared IID sensors 1 and 2. Here, the characterization of sensors and microtiter arrays comprising the IIDA are reported. The microtiter array including IID sensors 1 and 2 is capable of recognizing biological phosphates in water. The utility of the IIDA approach is demonstrated on sensing of a phosphonate herbicide glyphosate and other biologically important anions such as pyrophosphate in the presence of interferent sodium chloride.


Genetic and epigenetic insight into morphospecies in a reef coral.
Incongruence between conventional and molecular systematics has left the delineation of many species unresolved. Reef-building corals are no exception, with phenotypic plasticity among the most plausible explanations for alternative morphospecies. As potential molecular signatures of phenotypic plasticity, epigenetic processes may contribute to our understanding of morphospecies. We compared genetic and epigenetic variation in Caribbean branching Porites spp., testing the hypothesis that epigenetics-specifically, differential patterns of DNA methylation-play a role in alternative morphotypes of a group whose taxonomic status has been questioned. We used reduced representation genome sequencing to analyse over 1,000 single nucleotide polymorphisms and CpG sites in 27 samples of Porites spp. exhibiting a range of morphotypes from a variety of habitats in Belize. We found stronger evidence for genetic rather than epigenetic structuring, identifying three well-defined genetic groups. One of these groups exhibited significantly thicker branches, and branch thickness was a better predictor of genetic groups than depth, habitat or symbiont type. In contrast, no clear epigenetic patterns emerged with respect to phenotypic or habitat variables. While there was a weak positive correlation between pairwise genetic and epigenetic distance, two pairs of putative clones exhibited substantial epigenetic differences, suggesting a strong environmental effect. We speculate that epigenetic patterns are a complex mosaic reflecting diverse environmental histories superimposed over a relatively small heritable component. Given the role of genetics in branching Porites spp. morphospecies we were able to detect with genomewide sequencing, use of such techniques throughout the geographic range of these corals may help settle their phylogeny.


Retinal degeneration in experimental Creutzfeldt-Jakob disease.
Mice with experimental Creutzfeldt-Jakob disease (CJD) develop a progressive retinal degeneration after a prolonged incubation period. Sections of the eyes stained with hematoxylin and eosin revealed pathologic changes in the optic nerve and a marked degeneration of photoreceptor cell inner and outer segment areas. Both peripheral and central retina, normally 10 cells thick, were reduced to one photoreceptor cell or less in thickness. Ultrastructural analysis revealed total loss of outer segment and most inner segment elements. Only Müller cell microvilli and macrophages remained in the subretinal space. Macrophages were also visible in the remnant photoreceptor cell layer. The inner nuclear layer and pigment epithelial cell layers appeared normal. Müller cell hypertrophy was evident but was not accompanied by spongiform vacuolation. Several of the degenerative changes of the eye in mice with experimental Creutzfeldt-Jakob disease differ from those observed for scrapie in rodents. The pathologic similarities between the retinal degenerations occurring in mice with experimental Creutzfeldt-Jakob disease and those found in some forms of human retinal degeneration are provocative. These similarities raise the question whether or not other retinal degenerative diseases might be caused by infectious agents such as prions or slow viruses.


Circadian rhythm-associated lncRNA RP11-414H17.5 as a key therapeutic target in osteosarcoma affects the tumor immune microenvironment and enhances malignancy.
It has previously been proven that circadian rhythm disruption is associated with the incidence and deterioration of several tumors, which potentially leads to increased tumor susceptibility and a worse prognosis for tumor-bearing patients. However, their potential role in osteosarcoma has yet to be sufficiently investigated. Transcriptomic and clinical data of 84 osteosarcoma samples and 70 normal bone tissue samples were obtained from the TARGET and GTEx databases, circadian rhythm-related genes were obtained from Genecards, and circadian rhythm-related lncRNAs (CRLs) were obtained by Pearson correlation analysis, differential expression analysis, and protein-protein interaction (PPI) analysis. COX regression and LASSO regression were performed on the CRLs in order to construct a circadian rhythm-related prognostic prediction signature (CRPS). CRPS reliability was verified by Kaplan-Meier (KM), principal component analysis (PCA), nomogram, and receiver operating characteristic (ROC) curve. CRPS effects on the immune microenvironment of osteosarcoma were explored by enrichment analysis and immune infiltration analysis, and the effect of critical gene RP11-414H17.5 on osteosarcoma was experimentally verified. CRPS consisting of three CRLs was constructed and its area under the curve (AUC) values predicted that osteosarcoma prognosis reached 0.892 in the training group and 0.843 in the test group, with a p value of < 0.05 for the KM curve and stable performance across different clinical subgroups. PCA analysis found that CRPS could significantly distinguish between different risk subgroups, and exhibited excellent performance in the prediction of the immune microenvironment. The experiment verified that RP11-414H17.5 can promote metastasis and inhibit apoptosis of osteosarcoma cells. The study revealed that circadian rhythm plays a crucial role in osteosarcoma progression and identified the impact of the key gene RP11-414H17.5 on osteosarcoma, which provides novel insights into osteosarcoma diagnosis and therapy.


[The impact of polysialic acid (PSA) and polysialylated neural cell adhesion molecule (PSA-NCAM) on tumor and cell signaling pathways].
The neural cell adhesion molecule (NCAM), the member of the immunoglobulin superfamily, plays an important role in regulating cell adhesion and cell communication, particularly in nervous system wiring and plasticity. Polysialic acid, which is attached to NCAM on cell surface, is a prominent regulator of neural cell migration and differentiation during nervous system development. It has been demonstrated that PSA and PSA-NCAM were re-expressed in some malignant tumors. It was indicated that PSA and PSA-NCAM were tightly associated with cell adhesion, migration and invasion, and mediated tumor development and progression through certain cell signaling pathways. Here, we summarize the functional role of PSA, PSA-NCAM and related cell signaling pathways in tumor development, progression and prognostic.


Mechanisms of interaction among subinhibitory concentrations of antibiotics, human polymorphonuclear neutrophils, and gram-negative bacilli.
Our hypothesis was that pretreatment of bacteria with subinhibitory concentrations (sub-MICs) of antibiotics enhances the susceptibility of the organisms to killing by human polymorphonuclear neutrophils (PMNs). Our purpose was to study a variety of drugs with different mechanisms of action and to determine whether the mechanism and locus of action altered the sub-MIC effect. The following outcome measures were used: ingestion and killing of bacteria by PMNs, bacterial killing in the absence of phagosome formation, and binding requirements of the bacteria to PMNs. The antibiotics used were representative of a variety of classes, including beta-lactams (piperacillin and imipenem) and quinolones (ciprofloxacin). Bacterial uptake and killing were measured by using standard techniques, and results were analyzed by using the analysis-of-variance technique and Dunnett's t test. Pretreatment of Escherichia coli with all drugs showed significantly enhanced killing of bacteria by PMNs, which was independent of ingestion by the phagocytes. Even in the absence of phagosome formation, statistically significant killing persisted with piperacillin-pretreated bacteria but not with imipenem- or ciprofloxacin-pretreated organisms. The opsonization experiments showed that contact between bacteria and PMNs was necessary for killing to occur. The sub-MIC effect appears to be independent of the locus or mechanism of action of the antibiotic. It results in enhanced killing by PMNs which is independent of ingestion and also may persist even in the absence of phagosome formation. Killing is dependent upon specific contact between bacteria and an intact phagocyte.


The role of homocysteine, asymmetric dimethylarginine and nitric oxide in pre-eclampsia.
Nitric oxide (NO) contributes to vasodilatation that is observed during normal pregnancy. Hyperhomocysteinaemia (HHcy) is a vascular risk factor associated with placental microvascular diseases and pre-eclampsia. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of endothelial nitric oxide synthase (NOS) has been linked to endothelial dysfunction. Maternal ADMA has been reported to be higher in women with pre-eclampsia and HHcy leads to accumulation of ADMA. The aim of this presented study is to evaluate the alterations of plasma homocysteine, ADMA and NO levels in mild pre-eclampsia. A total of 40 pre-eclamptic women and 40 healthy controls were included into the study. Mean systolic and diastolic blood pressure, mean serum homocysteine and ADMA levels were significantly higher and NO level was lower in patients. Serum homocysteine, ADMA and NO levels found to be correlated among them and with blood pressure. In conclusion, we found that homocysteine and ADMA levels were increased and NO levels decreased in pre-eclampsia.


Effect of cutting depth during sugarcane (Saccharum spp. hybrid) harvest on root characteristics and yield.
Ratooning is an important cultivation practice in sugarcane production around the world, with underground buds on the remaining stalk acting as the source for establishment of a subsequent ratoon crop. However, the optimal depth of cutting during harvest in terms of yield and root growth remains unknown. We carried out a two-year field study to determine the effects of three cutting depths (0, 5 and 10 cm below the surface) ratoon cane root and yield. Results showed that cutting to a depth of 5 cm increased the root fresh weight and root volume by 21-59% and 41-127%, respectively, compared to cutting depths of 0 and 10 cm. Remarkably, cutting to a depth of 5 cm also had a significant effect on the development of fine roots, which is closely linked to cane yield. The effect was particularly noticeable in terms of two root traits, root volume and the surface area of roots with a diameter of 1.0-2.0mm, and root length and the number of root tips in roots with a diameter of 0-0.5mm. As a result, a cutting depth of 5 cm below the surface increased cane yield by 43 and 28% compared to depths of 0 and 10 cm below the surface, respectively. Overall, these findings suggest that a cutting depth of 5 cm is optimal in terms of sugarcane yield, largely due to the enhanced effect on root traits, especially the development of fine roots. These findings will help optimize sugarcane ratoon management and improve the ratoon cycle.


Distortion product otoacoustic emission test performance for a priori criteria and for multifrequency audiometric standards.
1) To describe distortion product otoacoustic emission (DPOAE) test performance when a priori response criteria are applied to a large set of DPOAE data. 2) To describe DPOAE test performance when multifrequency definitions of auditory function are used. 3) To determine DPOAE test performance when a single decision regarding auditory status is made for an ear, based on DPOAE data from several frequencies. 4) To compare univariate and multivariate test performance when multifrequency gold standard definitions and response criteria are applied to DPOAE data. DPOAE and audiometric data were analyzed from 1267 ears of 806 subjects. These data were evaluated for three different frequency combinations (2, 3, 4 kHz; 2, 3, 4, 6 kHz; 1.5, 2, 3, 4, 6 kHz). DPOAE data were collected for each of the f2 frequencies listed above, using primary levels (L1/L2) of 65/55 dB SPL and a primary ratio (f2/f1) of 1.22. Sensitivity and specificity were evaluated for signal to noise ratios (SNRs) of 3, 6, and 9 dB, which are in common clinical use. In addition, test performance was evaluated using clinical decision theory, following the convention we have used in previous reports on otoacoustic emission test performance. Both univariate and multivariate analyses techniques were applied to the data. In addition to evaluating DPOAE test performance for the case when audiometric and f2 frequency were equal, multifrequency gold standards and multifrequency criterion responses were evaluated. Three new gold standards were used to assess test performance: average pure-tone thresholds, extrema thresholds that took into account both the magnitude of the loss and the number of frequencies at which hearing loss existed, and a combination of the two. These new gold standards were applied to each of the three frequency groups described above. As expected, SNR criteria of 3, 6, and 9 dB never resulted in perfect DPOAE test performance. Even the most stringent of these criteria (9 dB SNR) did not result in a sensitivity of 100%. This result suggests that caution should be exercised in the interpretation of DPOAE test results when these a priori criteria are used clinically. Excellent test performance was achieved when auditory status was classified on the basis of the new gold standards and when either SNR or the output of multivariate logistic regressions (LRs) were used as criterion measures. Invariably, the LR resulted in superior test performance compared with what was achieved by the SNR. For SNR criteria of 3, 6, and 9 dB and (by definition) for the LR, specificity, in general, exceeded 80% and often was greater than 90%. Sensitivity, however, depended on the magnitude of hearing loss. Diagnostic errors, when they occurred, were more common for patients with mild hearing losses (21 to 40 dB HL); sensitivity approached 100% once the hearing loss exceeded 40 dB HL. The largest differences between test performance based on SNR or LR occurred for the ears with mild hearing loss, where the LR resulted in more accurate diagnoses. It should not be assumed that the use of a priori response criteria, such as SNRs of 3, 6, or 9 dB, will identify all ears with hearing loss. Test performance when multifrequency gold standards are used to define an ear as normal or impaired and when data from multiple f2 frequencies are used to make a diagnosis, resulted in excellent test performance, especially when the LR was used. When predicting auditory status with multifrequency gold standards, the LR resulted in relative operating characteristic curve areas of 0.95 or 0.96. An output from the LR can be selected that results in a specificity of 90% or better. When the loss exceeded 40 dB HL, the same output from the LR resulted in test sensitivity of nearly 100%. These were the best test results that were achieved. (ABSTRACT TRUNCATED)


[Acute Acalculous Cholecystitis Associated with Sunitinib Treatment for Renal Cell Carcinoma].
A 64-year-old man was treated with sunitinib as a first-line therapy for metastatic renal cell carcinoma. He was given oral sunitinib in cycles of 50 mg once daily for 2 weeks followed by a week off. During the 5th week of treatment right upper quadrant pain developed, but this resolved spontaneously during the 6th week (off treatment). However, on the 8th week of treatment, he was admitted to hospital because the acute right upper quadrant pain recurred with nausea, vomiting, and fever. Acute acalculous cholecystitis was then diagnosed by ultrasonography and CT. In addition, his laboratory findings indicated disseminated intravascular coagulation. Accordingly, sunitinib therapy was discontinued and broad-spectrum antibiotics initiated. He subsequently recovered after emergent percutaneous cholecystostomy. His Naranjo Adverse Drug Reaction Probability Scale score was 7, indicaing a probable association of the event with sunitinib. Suspicion of sunitinib-related acute cholecystitis is required, because, although uncommon, it can be life-threatening.


Vision, cognition, and walking stability in young adults.
Downward gazing is often observed when walking requires guidance. This gaze behavior is thought to promote walking stability through anticipatory stepping control. This study is part of an ongoing effort to investigate whether downward gazing also serves to enhance postural control, which can promote walking stability through a feedback/reactive mechanism. Since gaze behavior alone gives no indication as to what information is gathered and the functions it serves, we aimed to investigate the cognitive demands associated with downward gazing, as they are likely to differ between anticipatory and feedback use of visual input. To do so, we used a novel methodology to compromise walking stability in a manner that could not be resolved through modulation of stepping. Then, using interference methodology and neuroimaging, we tested for (1) interference related to dual tasking, and (2) changes in prefrontal activity. The novel methodology resulted in an increase in the time spent looking at the walking surface. Further, while some dual-task interference was observed, indicating that this gaze behavior is cognitively demanding, several gaze parameters pertaining to downward gazing and prefrontal activity correlated. These correlations revealed that a greater tendency to gaze onto the walking surface was associated with lower PFC activity, as is expected when sensory information is used through highly automatic, and useful, neural circuitry. These results, while not conclusive, do suggest that gazing onto the walking surface can be used for purposes other than anticipatory stepping control, bearing important motor-control and clinical implications.


Systematically evaluating DOTATATE and FDG as PET immuno-imaging tracers of cardiovascular inflammation.
In recent years, cardiovascular immuno-imaging by positron emission tomography (PET) has undergone tremendous progress in preclinical settings. Clinically, two approved PET tracers hold great potential for inflammation imaging in cardiovascular patients, namely FDG and DOTATATE. While the former is a widely applied metabolic tracer, DOTATATE is a relatively new PET tracer targeting the somatostatin receptor 2 (SST2). In the current study, we performed a detailed, head-to-head comparison of DOTATATE-based radiotracers and [18F]F-FDG in mouse and rabbit models of cardiovascular inflammation. For mouse experiments, we labeled DOTATATE with the long-lived isotope [64Cu]Cu to enable studying the tracer's mode of action by complementing in vivo PET/CT experiments with thorough ex vivo immunological analyses. For translational PET/MRI rabbit studies, we employed the more widely clinically used [68Ga]Ga-labeled DOTATATE, which was approved by the FDA in 2016. DOTATATE's pharmacokinetics and timed biodistribution were determined in control and atherosclerotic mice and rabbits by ex vivo gamma counting of blood and organs. Additionally, we performed in vivo PET/CT experiments in mice with atherosclerosis, mice subjected to myocardial infarction and control animals, using both [64Cu]Cu-DOTATATE and [18F]F-FDG. To evaluate differences in the tracers' cellular specificity, we performed ensuing ex vivo flow cytometry and gamma counting. In mice subjected to myocardial infarction, in vivo [64Cu]Cu-DOTATATE PET showed higher differential uptake between infarcted (SUVmax 1.3, IQR, 1.2-1.4, N = 4) and remote myocardium (SUVmax 0.7, IQR, 0.5-0.8, N = 4, p = 0.0286), and with respect to controls (SUVmax 0.6, IQR, 0.5-0.7, N = 4, p = 0.0286), than [18F]F-FDG PET. In atherosclerotic mice, [64Cu]Cu-DOTATATE PET aortic signal, but not [18F]F-FDG PET, was higher compared to controls (SUVmax 1.1, IQR, 0.9-1.3 and 0.5, IQR, 0.5-0.6, respectively, N = 4, p = 0.0286). In both models, [64Cu]Cu-DOTATATE demonstrated preferential accumulation in macrophages with respect to other myeloid cells, while [18F]F-FDG was taken up by macrophages and other leukocytes. In a translational PET/MRI study in atherosclerotic rabbits, we then compared [68Ga]Ga-DOTATATE and [18F]F-FDG for the assessment of aortic inflammation, combined with ex vivo radiometric assays and near-infrared imaging of macrophage burden. Rabbit experiments showed significantly higher aortic accumulation of both [68Ga]Ga-DOTATATE and [18F]F-FDG in atherosclerotic (SUVmax 0.415, IQR, 0.338-0.499, N = 32 and 0.446, IQR, 0.387-0.536, N = 27, respectively) compared to control animals (SUVmax 0.253, IQR, 0.197-0.285, p = 0.0002, N = 10 and 0.349, IQR, 0.299-0.423, p = 0.0159, N = 11, respectively). In conclusion, we present a detailed, head-to-head comparison of the novel SST2-specific tracer DOTATATE and the validated metabolic tracer [18F]F-FDG for the evaluation of inflammation in small animal models of cardiovascular disease. Our results support further investigations on the use of DOTATATE to assess cardiovascular inflammation as a complementary readout to the widely used [18F]F-FDG.


AS1411 alters the localization of a complex containing protein arginine methyltransferase 5 and nucleolin.
AS1411 is a quadruplex-forming oligonucleotide aptamer that targets nucleolin. It is currently in clinical trials as a treatment for various cancers. We have proposed that AS1411 inhibits cancer cell proliferation by affecting the activities of certain nucleolin-containing complexes. Here, we report that protein arginine methyltransferase 5 (PRMT5), an enzyme that catalyzes the formation of symmetrical dimethylarginine (sDMA), is a nucleolin-associated protein whose localization and activity are altered by AS1411. Levels of PRMT5 were found to be decreased in the nucleus of AS1411-treated DU145 human prostate cancer cells, but increased in the cytoplasm. These changes were dependent on nucleolin and were not observed in cells pretreated with nucleolin-specific small interfering RNA. Treatment with AS1411 altered levels of PRMT5 activity (assessed by sDMA levels) in accord with changes in its localization. In addition, our data indicate that nucleolin itself is a substrate for PRMT5 and that distribution of sDMA-modified nucleolin is altered by AS1411. Because histone arginine methylation by PRMT5 causes transcriptional repression, we also examined expression of selected PRMT5 target genes in AS1411-treated cells. For some genes, including cyclin E2 and tumor suppressor ST7, a significant up-regulation was noted, which corresponded with decreased PRMT5 association with the gene promoter. We conclude that nucleolin is a novel binding partner and substrate for PRMT5, and that AS1411 causes relocalization of the nucleolin-PRMT5 complex from the nucleus to the cytoplasm. Consequently, the nuclear activity of PRMT5 is decreased, leading to derepression of some PRMT5 target genes, which may contribute to the biological effects of AS1411.


Image-based computational simulation of flow dynamics in a giant intracranial aneurysm.
Blood flow dynamics are thought to play an important role in the pathogenesis and treatment of intracranial aneurysms; however, hemodynamic quantities of interest are difficult to measure in vivo. This study shows that computational fluid dynamics (CFD) combined with computed rotational angiography can provide such hemodynamic information in a patient-specific and prospective manner. A 58-year-old woman presented with partial right IIIrd cranial nerve palsy due to a giant carotid-posterior communicating artery aneurysm that was subsequently coiled. Computed rotational angiography provided high resolution volumetric image data from which the lumen geometry was extracted. This and a representative flow rate waveform were provided as boundary conditions for finite element CFD simulation of the 3D pulsatile velocity field. CFD analysis revealed high speed flow entering the aneurysm at the proximal and distal ends of the neck, promoting the formation of both persistent and transient vortices within the aneurysm sac. This produced dynamic patterns of elevated and oscillatory wall shear stresses distal to the neck and along the sidewalls of the aneurysm. These hemodynamic features were consistent with patterns of contrast agent wash-in during cine angiography and with the configuration of coil compaction observed at 6-month follow-up. Anatomic realism of lumen geometry and flow pulsatility is essential for elucidating the patient-specific nature of aneurysm hemodynamics. Such image-based CFD analysis may be used to provide key hemodynamic information for prospective studies of aneurysm growth and rupture or to predict the response of an individual aneurysm to therapeutic options.


Teacher self-efficacy and perceived autonomy: relations with teacher engagement, job satisfaction, and emotional exhaustion.
When studied separately, research shows that both teacher self-efficacy and teacher autonomy are associated with adaptive motivational and emotional outcomes. This study tested whether teacher self-efficacy and teacher autonomy are independently associated with engagement, job satisfaction, and emotional exhaustion. 2,569 Norwegian teachers in elementary school and middle school (719 men, 1,850 women; M age = 45.0 yr., SD = 11.5) were administered the Norwegian Teacher Self-Efficacy Scale, the Teacher Autonomy Scale, the Utrecht Work Engagement Scale, the Teacher Job Satisfaction Scale, and the Maslach Burnout Inventory. The analysis revealed that both teacher autonomy and self-efficacy were independent predictors of engagement, job satisfaction, and emotional exhaustion. This study suggests that autonomy or decision latitude works positively but through different processes for teachers with high and low mastery expectations.


Comparison of two bioassay techniques for assessing the acute toxicity of pesticides to chironomid larvae (Diptera: Chironomidae).
Two container and substrate combinations were compared to determine which provided optimal survival of larvae of Chironomus tepperi and Glyptotendipes paripes in the absence of toxicants. Unfed final-stage larvae of G. paripes survived significantly (P < 0.05) better in waxed paper cups with sand substrate (92.8% after 3 days) than in glass tubes with a shredded paper substrate (85.3%). Survival of larvae of C. tepperi over the same period did not differ significantly in the 2 systems. Larvae of C. tepperi were bioassayed against 3 insecticides (technical and formulated imidacloprid, chlorpyrifos, and betacypermethrin) with both container and substrate combinations. Median lethal concentration values (24 h) obtained with waxed cups with sand were 1.8 times higher on average than those obtained with glass tubes with shredded paper (range 1.13-2.65 times). To determine the cause of this variability, solid-phase microextraction was used to measure changes in chlorpyrifos availability over time in the 2 bioassay systems. Chlorpyrifos concentrations in the waxed cups and sand system fell from 7.50 to 3.36 microg/liter over 24 h, probably as a consequence of chemical adsorption to the waxed surfaces. Chlorpyrifos concentrations in the glass tubes and paper system remained unchanged over this period. Excluding substrates from the containers had only a minor effect on chlorpyrifos availability. These results demonstrate that the behaviors of both test organisms and toxicants within bioassay systems need to be understood if the data generated with different systems are to be compared. Understanding how toxicant availability is affected by different container and substrate types is particularly important where bioassays are conducted with nominal concentration values rather than analytically determined exposure concentrations.


State and parameter estimation for canonic models of neural oscillators.
We consider the problem of how to recover the state and parameter values of typical model neurons, such as Hindmarsh-Rose, FitzHugh-Nagumo, Morris-Lecar, from in-vitro measurements of membrane potentials. In control theory, in terms of observer design, model neurons qualify as locally observable. However, unlike most models traditionally addressed in control theory, no parameter-independent diffeomorphism exists, such that the original model equations can be transformed into adaptive canonic observer form. For a large class of model neurons, however, state and parameter reconstruction is possible nevertheless. We propose a method which, subject to mild conditions on the richness of the measured signal, allows model parameters and state variables to be reconstructed up to an equivalence class.


Dynamic and contact analysis of a bimodal ultrasonic motor.
A bimodal ultrasonic motor, which operates with only one power amplifier, uses two simultaneously excited modes to drive the rotor; a longitudinal mode and a flexural mode. The equations of motion describing the vibrations and contact behavior are derived by Hamilton's principle and the geometry constraint. The Lagrange multiplier method is used to treat the frictional contact problem. The finite element method and numerical integration scheme are used to simulate the dynamic responses of this system with and without contact. Some important factors are studied for the bimodal ultrasonic motor design. The factors include structure design, amplitude of input voltage, phase displacement, exciting frequency, and contact behavior.


Chemical contaminants in water and sediment near fish nesting sites in the Potomac River basin: determining potential exposures to smallmouth bass (Micropterus dolomieu).
The Potomac River basin is an area where a high prevalence of abnormalities such as testicular oocytes (TO), skin lesions, and mortality has been observed in smallmouth bass (SMB, Micropterus dolomieu). Previous research documented a variety of chemicals in regional streams, implicating chemical exposure as one plausible explanation for these biological effects. Six stream sites in the Potomac basin (and one out-of-basin reference site) were sampled to provide an assessment of chemicals in these streams. Potential early life-stage exposure to chemicals detected was assessed by collecting samples in and around SMB nesting areas. Target chemicals included those known to be associated with important agricultural and municipal wastewater sources in the Potomac basin. The prevalence and severity of TO in SMB were also measured to determine potential relations between chemistry and biological effects. A total of 39 chemicals were detected at least once in the discrete-water samples, with atrazine, caffeine, deethylatrazine, simazine, and iso-chlorotetracycline being most frequently detected. Of the most frequently detected chemicals, only caffeine was detected in water from the reference site. No biogenic hormones/sterols were detected in the discrete-water samples. In contrast, 100 chemicals (including six biogenic hormones/sterols) were found in a least one passive-water sample, with 25 being detected at all such samples. In addition, 46 chemicals (including seven biogenic hormones/sterols) were found in the bed-sediment samples, with caffeine, cholesterol, indole, para-cresol, and sitosterol detected in all such samples. The number of herbicides detected in discrete-water samples per site had a significant positive relation to TO(rank) (a nonparametric indicator of TO), with significant positive relations between TO(rank) and atrazine concentrations in discrete-water samples and to total hormone/sterol concentration in bed-sediment samples. Such significant correlations do not necessarily imply causation, as these chemical compositions and concentrations likely do not adequately reflect total SMB exposure history, particularly during critical life stages.


Carer distress in the general population: results from the Sydney Older Persons Study.
To assess distress in a sample of carers who were selected from a community survey rather than recruited via community-service agencies. A community survey was carried out on 630 people aged 75 or over living in Sydney, Australia. Informants nominated by these elderly people were divided into full carer (n = 21), partial carer (n = 187) and non-carer groups (n = 344). Informants completed the General Health Questionnaire (a continuous measure of psychiatric symptoms), the life satisfaction index (a measure of well-being) and the interpersonal bonding measure (a measure of quality of the relationship with the elderly person). Elderly participants had a medical examination, were assessed for disability and were questioned about use of services. Elderly people who had a full carer were more disabled and had more medical diagnoses. Full, but not partial, carers reported more psychiatric symptoms and lower life satisfaction. In multivariate analysis, the main determinant of carer distress was a relationship in which the carer felt controlled by the elderly person. When carers are selected from a population-based sample, only those who are full carers are more distressed. However, relationship factors are the most important determinant of distress.


Role of seed flow on the pattern and dynamics of pearl millet (Pennisetum glaucum [L.] R. Br.) genetic diversity assessed by AFLP markers: a study in south-western Niger.
We studied the regional genetic diversity and seed exchange dynamics of pearl millet landraces in south-western Niger. The genetic study was based on AFLP markers. We found significant genetic differentiation between landraces in different geographical areas of south-western Niger. However, the degree of differentiation was low insofar as only 1.9% of the total molecular diversity was due to regional differentiation, suggesting a relatively high gene flow. Anthropologic studies on farming practices have suggested that seed exchanges between farmers on a large geographical scale probably make a considerable contribution to this result. In order to test this hypothesis, the effects of seed exchange on the genetic diversity of landraces was analyzed on seed samples from two distant villages in contrasting areas of south-western Niger. Seeds imported by farmers into the southern village of Sina Koara did not differ significantly from locally grown landraces. By contrast, in the northern village of Alzou, several samples were genetically different from locally grown landraces and closer to southern accessions. These data suggest that the seed flow is preferentially from south to north, i.e. from an area with more favorable rainfall conditions. The potential consequences for the genetic diversity and adaptation of northern pearl millet landraces are discussed.


Chest pain in daily practice: occurrence, causes and management.
We assessed the occurrence and aetiology of chest pain in primary care practice. These features differ between primary and emergency care settings, where most previous studies have been performed. 59 GPs in western Switzerland recorded all consecutive cases presenting with chest pain. Clinical characteristics, laboratory tests and other investigations as well as the diagnoses remaining after 12 months of follow-up were systematically registered. Among 24,620 patients examined during a total duration of 300 weeks of observation, 672 (2.7%) presented with chest pain (52% female, mean age 55 +/- 19(SD)). Most cases, 442 (1.8%), presented new symptoms and in 356 (1.4%) it was the reason for consulting. Over 40 ailments were diagnosed: musculoskeletal chest pain (including chest wall syndrome) (49%), cardiovascular (16%), psychogenic (11%), respiratory (10%), digestive (8%), miscellaneous (2%) and without diagnosis (3%). The three most prevalent diseases were: chest wall syndrome (43%), coronary artery disease (12%) and anxiety (7%). Unstable angina (6), myocardial infarction (4) and pulmonary embolism (2) were uncommon (1.8%). Potentially serious conditions including cardiac, respiratory and neoplasic diseases accounted for 20% of cases. A large number of laboratory tests (42%), referral to a specialist (16%) or hospitalisation (5%) were performed. Twentyfive patients died during follow-up, of which twelve were for a reason directly associated with thoracic pain [cancer (7) and cardiac causes (5)]. Thoracic pain was present in 2.7% of primary care consultations. Chest wall syndrome pain was the main aetiology. Cardio - vascular emergencies were uncommon. However chest pain deserves full consideration because of the occurrence of potentially serious conditions.


Localized high concentration electrolytes decomposition under electron-rich environments.
Localized high concentration electrolytes have been proposed as an effective route to construct stable solid-electrolyte interphase (SEI) layers near Li-metal anodes. However, there is still a limited understanding of the decomposition mechanisms of electrolyte components during SEI formation. In this work, we investigate reactivities of lithium bis(fluorosulfonyl)imide (LiFSI, salt), 1,2-dimethoxyethane (DME, solvent), and tris(2,2,2-trifluoroethyl)orthoformate (TFEO, diluent) species in DME + TFEO mixed solvents and 1M LiFSI/DME/TFEO solutions. By supplying an excess of electrons into the simulation cell, LiFSI is initially reduced via a four-electron charge transfer reaction yielding F- and N(SO2)2 3-. The local solvation environment has little effect on the subsequent TFEO reaction, which typically requires 6 |e| to decompose into F-, HCOO-, CH2CF-, and -OCH2CF3. Besides, the TFEO dehydrogenation reaction mechanism under an attack of anions is also identified. Unlike salt and diluent, DME shows good stability with any excess of electrons. The energetics of most relevant reactions are characterized. Most reactions are thermodynamically favorable with low activation barriers.


Design of multi-target compounds as AChE, BACE1, and amyloid-β(1-42) oligomerization inhibitors: in silico and in vitro studies.
Despite great efforts to develop new therapeutic strategies against Alzheimer's disease (AD), the acetylcholinesterase inhibitors (AChEIs): donepezil, rivastigmine, and galantamine, have been used only as a palliative therapeutic approach. However, the pathogenesis of AD includes several factors such as cholinergic hypothesis, amyloid-β (Aβ) aggregation, and oxidative stress. For this reason, the design of compounds that target the genesis and progression of AD could offer a therapeutic benefit. We have designed a set of compounds (M-1 to M-5) with pharmacophore moieties to inhibit the release, aggregation, or toxicity of Aβ, act as AChEIs and have antioxidant properties. Once the compounds were designed, we analyzed their physicochemical parameters and performed docking studies to determine their affinity values for AChE, β-site amyloid-protein precursor cleaving enzyme 1 (BACE1), and the Aβ monomer. The best ligands, M-1 and M-4, were then synthesized, chemically characterized, and evaluated in vitro. The in vitro studies showed that these compounds inhibit AChE (M-1 Ki = 0.12 and M-4 Ki = 0.17 μM) and BACE1 (M-1 IC50 = 15.1 and M-4 IC50 = 15.4 nM). They also inhibit Aβ oligomerization and exhibit antioxidant activity. In addition, these compounds showed low cytotoxicity in microglial cells. For these reasons, they are promising for future use as drugs in AD mice transgenic models.


Impact of an Infectious Disease Specialist on an Antimicrobial Stewardship Program at a Resource-Limited, Non-Academic Community Hospital in Korea.
Implementing a successful antimicrobial stewardship program (ASP) is difficult for non-academic community (NAC) hospitals due to insufficient infrastructure. We evaluated the impact of an infectious disease specialist (IDS) on implementing an ASP in a resource-limited setting in Korea. A retrospective study was performed at a NAC hospital between June 2015 and August 2018. An IDS has led an ASP at the hospital since June 2017. We used an interrupted time series analysis to evaluate longitudinal effects of the IDS-led ASP on the amount of antibiotic use and incidence of multidrug-resistant organism (MDRO) acquisition. Total antibiotic use changed from 698.82 ± 74.41 to 602.09 ± 69.94 defined daily dose/1000 patient-days (PDs) after intervention. An immediate reduction in the use of carbapenems, glycopeptides, penicillins, and other antibiotics followed the IDS-led ASP. The 3rd/4th generation cephalosporins and carbapenems prescription rates decreased in slope after the intervention. Incidence of MDRO acquisition changed from 1.38, 0.78, and 0.21/1000 PDs to 1.06, 0.15, and 0.32/1000 PDs in methicillin-resistant Staphylococcus aureus, multidrug-resistant Acinetobacter baumannii, and multidrug-resistant Pseudomonas aeruginosa, respectively. The incidence of methicillin-resistant Staphylococcus aureus and multidrug-resistant Acinetobacter baumannii acquisition immediately decreased following intervention. An IDS can implement a successful ASP by reducing antibiotic consumption and MDRO acquisition at resource-limited NAC hospitals.


[Role of SH-groups in the pharmacology of the action of novurite and ethacrynic acid].
In experiments in vivo the mercuric diuretic, novurite, and ethacrynic acid in therapeutic doses (25 and 50 mg/kg, respectively) do not block the respiration and active transport of calcium in the kidney mitochondria. The diuretic effect of these substances is not prevented by cystein (50 mg/kg), the donator of sulphydryl groups. In vitro novurite (3 mM) and ethacrynic acid (1 mM) block the systems of ionic transport inthe kidney epithelium cells and in concentrations of 0.2 and 0.5 mM, respectively, disturb the oxygen uptake and oxidative phosphorylation in the kidney mitochondria. A preliminary administration of cystein (5 mM) into the incubation medium prevents these effects. Novurite and ethacrynic acid manifest the typical thyol toxins of general cell effect in doses considerably exceeding the therapeutic ones. A specific "kidneys" effect of these substances is not connected with their ability to block SH-group of biologically active substances.


Quantitative analysis of the water occupancy around the selectivity filter of a K+ channel in different gating modes.
Recovery in K(+) channels, that is, the transition from the inactivated nonconductive selectivity filter conformation toward the conductive conformation, occurs on a time scale of the order of seconds, which is astonishingly long, given that the structural differences among the filter conformations are faint (<1 Å). Computational studies and electrophysiological measurements suggested that buried water molecules bound behind the selectivity filter are at the origin of the slowness of recovery in K(+) channels. Using a combination of solid-state NMR spectroscopy (ssNMR) and long molecular dynamics simulations, we sketch a high-resolution map of the spatial and temporal distribution of water behind the selectivity filter of a membrane-embedded K(+) channel in two different gating modes. Our study demonstrates that buried water molecules with long residence times are spread all along the rear of the inactivated filter, which explains the recovery kinetics. In contrast, the same region of the structure appears to be dewetted when the selectivity filter is in the conductive state. Using proton-detected ssNMR on fully protonated channels, we demonstrate the presence of a pathway that allows for the interchange of buried and bulk water, as required for a functional influence of buried water on recovery and slow inactivation. Furthermore, we provide direct experimental evidence for the presence of additional ordered water molecules that surround the filter and that are modulated by the channel's gating mode.


High-frequency stimulation of the dorsolateral periaqueductal gray and ventromedial hypothalamus fails to inhibit panic-like behaviour.
Electrical stimulation of the dorsolateral periaqueductal gray (dlPAG) and one of its target structures, the ventromedial hypothalamus (VMH), produces a typical behaviour in rats consisting of vigorous running and jumping which is known as "escape behaviour". Escape behaviour in rodents closely mimics panic attacks in humans. Since electrical stimulation at higher frequencies generally inhibits the stimulated region, we tested in this study the hypothesis that deep brain stimulation (DBS) of the dlPAG and VMH at higher frequencies (> 100 Hz) would not induce escape behaviour. More specifically, we evaluated whether experimental DBS could be used to inhibit panic-like behaviour. Rats underwent implantation of DBS-electrodes at the level of the dlPAG and VMH and the effects of various stimulation parameters were assessed. In addition, we studied the neural activation pattern resulting from DBS of the dlPAG and VMH using c-Fos immunohistochemistry. We found that stimulation amplitude is the most important stimulation parameter in the induction of escape behaviour. Remarkably, stimulation frequency (1-300 Hz) had no effect on stimulation-induced escape behaviour and therefore it was not possible to prevent the induction of escape behaviour with higher frequencies. The neuronal activation pattern resulting from dlPAG and VMH DBS was similar. These findings suggest that DBS of the dlPAG and VMH induces panic-related behaviours even at higher frequencies.


Selective molecular transport through the protein shell of a bacterial microcompartment organelle.
Bacterial microcompartments are widespread prokaryotic organelles that have important and diverse roles ranging from carbon fixation to enteric pathogenesis. Current models for microcompartment function propose that their outer protein shell is selectively permeable to small molecules, but whether a protein shell can mediate selective permeability and how this occurs are unresolved questions. Here, biochemical and physiological studies of structure-guided mutants are used to show that the hexameric PduA shell protein of the 1,2-propanediol utilization (Pdu) microcompartment forms a selectively permeable pore tailored for the influx of 1,2-propanediol (the substrate of the Pdu microcompartment) while restricting the efflux of propionaldehyde, a toxic intermediate of 1,2-propanediol catabolism. Crystal structures of various PduA mutants provide a foundation for interpreting the observed biochemical and phenotypic data in terms of molecular diffusion across the shell. Overall, these studies provide a basis for understanding a class of selectively permeable channels formed by nonmembrane proteins.


Association between collapse and serum creatinine and electrolyte concentrations in marathon runners: a 9-year retrospective study.
Abnormal biochemical measurements have previously been described in runners following marathons. The incidence of plasma sodium levels outside the normal range has been reported as 31%, and the incidence of raised creatinine at 30%. This study describes the changes seen in electrolytes and creatinine in collapsed (2010-2019 events) and noncollapsed (during the 2019 event) runners during a UK marathon. Point-of-care sodium, potassium, urea and creatinine estimates were obtained from any collapsed runner treated by the medical team during the Brighton Marathons, as part of their clinical care, and laboratory measurements from control subjects. Results from 224 collapsed runners were available. Serum creatinine was greater than the normal range in 68.9%. About 6% of sodium results were below, and 3% above the normal range, with the lowest 132 mmol/l. Seventeen percent of potassium readings were above the normal range; the maximum result was 8.4 mmol/l, but 97% were below 6.0 mmol/l. In the control group, mean creatinine was significantly raised in both the collapse and control groups, with 55.4% meeting the criteria for acute kidney injury, but had resolved to baseline after 24 h. Sodium concentration but not the potassium was significantly raised after the race compared with baseline, but only 15% were outside the normal range. In this study, incidence of a raised creatinine was higher than previously reported. However, the significance of such a rise remains unclear with a similar rise seen in collapsed and noncollapsed runners, and resolution noted within 24 h. Abnormal sodium concentrations were observed infrequently, and severely abnormal results were not seen, potentially reflecting current advice to drink enough fluid to quench thirst.


Suitability of Paper-Based Substrates for Printed Electronics.
Flexible plastic substrates are widely used in printed electronics; however, they cause major climate impacts and pose sustainability challenges. In recent years, paper-based electronics has been studied to increase the recyclability and sustainability of printed electronics. The aim of this paper is to analyze the printability and performance of metal conductor layers on different paper-based substrates using both flexography and screen printing and to compare the achieved performance with that of plastic foils. In addition, the re-pulpability potential of the used paper-based substrates is evaluated. As compared to the common polyethylene terephthalate (PET) substrate, the layer conductivity on paper-based substrates was found to be improved with both the printing methods without having a large influence on the detail rendering. This means that a certain surface roughness and porosity is needed for the improved ink transfer and optimum ink behavior on the surface of the substrate. In the case of uncoated paper-based substrates, the conductivity and print quality decreased by preventing the formation of the proper and intimate ink-substrate contact during the ink transfer. Finally, the re-pulpability trials together with layer quality analysis detected very good, coated substrate candidates for paper-based printed electronics competing with or even outperforming the print quality on the reference PET foil.


In situ monitoring of mechanochemical MOF formation by NMR relaxation time correlation.
In this paper, we present a new approach to monitoring mechanochemical transformations, based on a magnetic resonance (MR) method in which relaxation time correlation maps are used to track the formation of the popular metal-organic framework (MOF) materials Zn-MOF-74 and ZIF-8. The two-dimensional (2D) relaxation correlation measurement employed yields a spectrum which visually and analytically identifies different 1H environments in the sample of interest. The measurement is well-suited to analyzing solid mixtures, and liquids, in complex systems. Application in this work to monitoring MOF formation shows changes in signal amplitudes, and their MR lifetime coordinates, within the 2D plots as the reaction progresses, confirming reaction completion. This new measurement provides a simple way to analyse solid-state reactions without dissolution, and there is a logical pathway to benchtop measurement with a new generation of permanent magnet-based MR instruments. The methodology described permits measurement in an MR compatible milling container, which may be directly transferred from the shaker assembly to the MR magnet for in situ measurement of the entire reaction mixture.


Endurance training improves responsiveness to insulin and modulates insulin signal transduction through the phosphatidylinositol 3-kinase/Akt-1 pathway.
Endurance training increases insulin-stimulated muscle glucose transport and leads to improved metabolic control in diabetic patients. To analyze the effects of endurance training on the early steps of insulin action in muscle of rats. Male rats submitted to daily swimming for 6 weeks were compared with sedentary controls. At the end of the training period, anesthetized animals received an intravenous (i.v.) injection of insulin and had a fragment of their gastrocnemius muscle excised for the experiments. Associations between insulin receptor, insulin receptor substrates (IRS)-1 and -2 and phosphatidylinositol 3-kinase (PI3-kinase) were analyzed by immunoprecipitation and immunoblotting. Akt-1 serine phosphorylation and specific protein quantification were detected by immunoblotting of total extracts, and IRS-1/IRS-2-associated PI3-kinase activity were determined by thin-layer chromatography. Insulin-induced phosphorylation of IRS-1 and IRS-2 increased respectively by 1.8-fold (P<0.05) and 1.5-fold (P<0.05), whereas their association with PI3-kinase increased by 2.3-fold (P<0.05) and 1.9-fold (P<0.05) in trained rats as compared with sedentary controls, respectively. The activity of PI3-kinase associated with IRS-1 and IRS-2 increased by 1.8-fold (P<0.05) and 1.7-fold (P<0.05) respectively, in trained rats as compared with their untrained counterparts. Serine phosphorylation of Akt-1/PKB increased 1.7-fold (P<0.05) in trained rats in response to insulin. These findings were accompanied by increased responsiveness to insulin as demonstrated by a reduced area under the curve for insulin during an i.v. glucose tolerance test, by increased glucose disappearance rate during an insulin tolerance test, and by increased expression of glucose transporter-4. The increased responsiveness to insulin induced by chronic exercise in rat skeletal muscle may result, at least in part, from the modulation of the insulin signaling pathway at different molecular levels.


ROTATION TECHNIQUE IN ELECTRON MICROSCOPY OF VIRUSES.
Some of the features revealed by the rotation technique of examining electron micrographs may be artifacts. To avoid misinterpretation, "rotated" photographs should be compared with originals. The criterion of reinforcement of structures in the "rotated" photographs is not enough, and it cannot be presumed that all the structures reinforced are actually present in the object under study. Further tests for radial symmetry in the arrangement of elements in a pattern should be made.


Immunization with irradiated tumour cells and specific lymphocyte cytotoxicity in malignant melanoma.
A microculture technique has been adapted to assay the cytotoxic properties of the lymphocytes from patients with malignant melanoma when cultured with their autologous tumour cells. In a series of patients with established melanoma specific autologous cytotoxicity was extremely uncommon, being detectable in only 3 out of the 22 cases studied. This cytotoxicity did not correlate with clinical staging of the disease but may well have been related to tumour volume. By autoimmunization of patients with an irradiated suspension of their own tumour cells the appearance of cytotoxic lymphocytes could be provoked in 5 out of the 12 patients studied. This cytotoxicity was detectable at the end of the first week after the autograft and disappeared by the third week. Cytotoxic lymphocytes did not correlate in any obvious way with the appearance of specific antitumour antibodies detected by immunofluorescence. So far there has been no evidence of a serum factor capable of blocking the lymphocyte cytotoxicity in these patients.The presence and possible significance of cytotoxic lymphocytes in patients with malignant disease is discussed.


Enriching Beneficial Microbial Diversity of Indoor Plants and Their Surrounding Built Environment With Biostimulants.
Microbial diversity is suggested as the key for plant and human health. However, how microbial diversity can be enriched is largely unknown but of great interest for health issues. Biostimulants offer the way to directly augment our main living areas by the healthy microbiome of indoor plants. Here, we investigated shifts of the microbiome on leaves of spider plants (Chlorophytum comosum) and its surrounding abiotic surfaces in the built environment after irrigation with a vermicompost-based biostimulant for 12 weeks. The biostimulant could not only promote plant growth, but changed the composition of the microbiome and abundance of intact microbial cells on plant leaves and even stronger on abiotic surfaces in close vicinity under constant conditions of the microclimate. Biostimulant treatments stabilized microbial diversity and resulted in an increase of Bacteroidetes and a surprising transient emerge of new phyla, e.g., Verrucomicrobia, Acidobacteria, and Thaumarchaeota. The proportion of potentially beneficial microorganisms like Brevibacillus, Actinoallomurus, Paenibacillus, Sphaerisporangium increased relatively; microbial diversity was stabilized, and the built environment became more plant-like. Detected metabolites like indole-3-acetic acid in the biostimulant were potentially contributed by species of Pseudomonas. Overall, effects of the biostimulant on the composition of the microbiome could be predicted with an accuracy of 87%. This study shows the potential of biostimulants not only for the plant itself, but also for other living holobionts like humans in the surrounding environment.


High Mobility Group Box-1 and Pro-inflammatory Cytokines Are Increased in Dogs After Trauma but Do Not Predict Survival.
Trauma is common in dogs and causes significant morbidity and mortality, but it remains challenging to predict the prognosis of dogs with traumatic injuries. This study aimed to quantify plasma high-mobility group box-1 (HMGB-1) and cytokine concentrations in dogs with moderate-to-severe trauma, and to evaluate the association between these biomarkers and the injury severity and survival to discharge. Using a prospective, observational case-control study design, 49 dogs with an animal trauma triage (ATT) score ≥3 were consecutively enrolled from 07/2015 to 10/2017 and followed to hospital discharge. Dogs <3 kg and those with pre-existing coagulopathies were excluded. Thirty three healthy control dogs were also enrolled. Illness and injury severity scores including the acute patient physiologic and laboratory evaluation (APPLE) were calculated using at-presentation data. Plasma HMGB-1 concentrations were measured by ELISA; concentrations of 13 cytokines were measured using multiplex bead-based assays and separately concentrations of 4 cytokines were measured using a multiplex canine-specific ELISA. All biomarkers were measured in duplicate. Mann-Whitney U tests were used to compare biomarker concentrations between groups and between survivors and non-survivors. Associations between biomarkers were evaluated using Spearman's correlation coefficients. Independent predictors of survival were identified using multivariable logistic regression. Alpha was set at 0.05. Plasma concentrations of HMGB-1, interleukin-6, C-X-C motif chemokine-8, keratinocyte chemoattractant-like, and C-C chemokine ligand-2 were significantly greater in injured dogs vs. controls (all P ≤ 0.011). In univariate analyses, HMGB-1 was significantly greater in non-survivors 46.67 ng/mL (8.94-84.73) compared to survivors 6.03 ng/mL (3.30-15.75), (P = 0.003). Neither HMGB-1 or the cytokines were associated with survival independent of illness severity as measured by the APPLE score, however.


[Differential diagnosis of several allergic and neurologic diseases].
An analysis of the disease clinical picture in 205 patients has shown that there are neurological diseases imitating allergy. These are: hypothalamo-diencephalic syndrome, asthenic neurosis, sympathetic truncitis, epilepsy, and cerebrovascular insufficiency in the vertebrobasilar basin. It is primarily the clinical symptoms which are criteria for differential diagnosis. In diagnosing the bronchospastic syndrome use can be also made of changes in catecholamine metabolism and the lymphocyte blast transformation test.


The Effect of Cranial Shape on Esthetic Self-Worth in Bald Men.
During the last 3 decades, the incidence of positional plagiocephaly and brachycephaly has increased. Treatment options are conservative and can include physiotherapy and molding helmet therapy. The decision to start therapy is based on patient history and subjective assessment of cranial shape by the physician and the parents. To determine the impact of these deformations on esthetic self-worth, as well as cranial shape, this study was conducted on a population of adult bald men.Participants were asked to fill in a questionnaire about the amount of comments received on cranial shape, as well as grade their general esthetic and grade craniofacial features using a visual analogue scale. The cranial proportions and symmetry were measured using plagiocephalometry.50 adult bald men were included in this study. The prevalence of nonsynostotic plagiocephaly was 12%; the prevalence of nonsynostotic brachycephaly was 0%. No significant correlation was found between plagiocephaly or brachycephaly, cranial circumference, width or length and amount of comments on cranial shape, cosmetic assessment of appearance or cosmetic assessment of cranial shape. On average, teeth and eyes were given the highest cosmetic value, eyebrows and chin were given the lowest scores.Cranial shape does not have a significant impact on the amount of comments received on cranial shape, nor the cosmetic assessment of either overall appearance or cranial shape in bald men. For bald men, eyes and teeth are more important craniofacial features in cosmetic assessment. There is no clear esthetic need to treat deviating cranial shape with helmet therapy in male patients.


Effect of different immunosuppressive schedules on recurrence-free survival after liver transplantation for hepatocellular carcinoma.
Tumor recurrence represents the main limitation of liver transplantation in patients with hepatocellular carcinoma (HCC) and can be favored by exposure to calcineurin inhibitors. We investigated the effect of an immunosuppressant schedule that minimizes the exposure to calcineurin inhibitors on patients transplanted for HCC to ascertain whether this can reduce the tumor recurrence rate. For this purpose, we conducted a matched-cohort study: 31 patients with HCC transplanted between 2004 and 2007 who received sirolimus as part of their immunosuppression (group A) were compared with a control group of 31 patients (group B) transplanted in the same period who had the same prognostic factors but were given standard immunosuppression based on tacrolimus. Three-year recurrence-free survival was 86% in group A and 56% in group B (P=0.04). Although the prevalence of microvascular invasion G3-G4 grading and alpha-fetoprotein more than 200 ng/mL was identical in the two groups, exposure to tacrolimus was significantly higher in patients of group B (median, 8.54; range, 5.5-13.5) in comparison with those of group A (median, 4.6; range, 1.8-9.1) (P=0.0001). By using sirolimus, exposure to calcineurin inhibitors can be minimized, reducing the risk of HCC recurrence.


[Laparoscopic single patient use instruments: expensive outsourcing of product quality?].
The supply of medical goods is an important critical success factor in German hospitals. One major managerial area in the procurement concerns the decision between single patient use (SPU) and multiple patient use (MPU) products. Especially laparoscopic instruments which are generally expensive are a field of interest for decision makers. Due to a lack of quantifiable factors describing the two different forms of supply alternatives with their effects on effectivity and efficiency of the procurement process and the final use are often not taken into account. Since it is expected that in the future more and more laparoscopic instruments will be needed there is a necessity for finding a concept allowing the identification of the "right" product. The Center for Hospital Management (CKM) has the aim to develop a corresponding approach but needs the help of the reader.


A review of disease-modifying therapies for MS: maximizing adherence and minimizing adverse events.
In a chronic disabling disorder such as multiple sclerosis (MS), adherence to treatment is of critical importance in maximizing benefits of therapy over the long term. Adverse events (AEs) are often cited by patients who discontinue therapy. Databases including Medline, CINAHL, and International Pharmaceutical Abstracts were searched for literature pertaining to adherence and AEs in MS published between January 1970 and August 2008. Clinical studies and case reports of AEs were included, as were papers that outlined factors that influence adherence. An advisory board with extensive experience in managing patients with MS developed guidelines to assist healthcare providers in maximizing adherence to disease-modifying therapy. Internally based factors such as self-image, and externally based factors such as AEs, may influence patients' willingness and ability to adhere to therapy. Management of AEs associated with disease-modifying therapies and other therapies is reviewed, including intramuscular and subcutaneous interferon beta (IFNbeta)-1a, IFNbeta-1b, glatiramer acetate, natalizumab, methylprednisolone, mitoxantrone, cyclophosphamide, methotrexate, azathioprine, and intravenous immunoglobulin. Effective management of MS is an ongoing, dynamic process that can enhance patients' adherence to therapy. Healthcare practitioners may address factors influencing adherence among patients with MS by managing treatment expectations, maintaining good communication with the patient, and managing AEs of treatment. Although the guidelines proposed herein originate from a single advisory board, it seems clear that by addressing patient concerns, healthcare practitioners can work with patients to enhance their ability to continue to adhere to their therapies and thereby gain the benefits of their treatment over the long term.


Using semi covert research to evaluate an emergency hormonal contraception service.
The aim of our study was to evaluate whether the patient group direction protocol for supply of emergency hormonal contraception was being adhered to, that pharmacists were undertaking their professional duties appropriately and to evaluate how women researchers felt that the service was being delivered. Semi covert research was used, two women researchers posed as clients seeking emergency contraception in a sample of participating community pharmacies. They used two rehearsed scenarios about unsafe sexual intercourse and missed doses of the oral contraceptive pill. All transactions were tape recorded and the recordings were used to produce the findings. The two women researchers posing as clients were also asked to record their feelings and experiences concerning the service on leaving the pharmacy. Adherence to the patient group direction protocol and women's perceptions of service provision. In both scenarios the protocol was largely adhered to and emergency contraception was supplied appropriately. The length of each consultation for both scenarios was between 10-15 min. The women reported that the pharmacists had been courteous, polite and non judgemental. The consultations were carried out in a private area or in the dispensary. The women had no concerns about confidentiality. Whilst there are clear limitations of this study in terms of the size of the sample, our results do highlight the fact that the PGD protocol was being utilised appropriately in most cases. In addition, neither woman reported any instances of judgmental or negative attitudes and commented favourably on the scope for discussion about emergency hormonal contraception and other important issues with the pharmacist.


Dense graphlet statistics of protein interaction and random networks.
Understanding evolutionary dynamics from a systemic point of view crucially depends on knowledge about how evolution affects size and structure of the organisms' functional building blocks (modules). It has been recently reported that statistics over sparse PPI graphlets can robustly monitor such evolutionary changes. However, there is abundant evidence that in PPI networks modules can be identified with highly interconnected (dense) and/or bipartite subgraphs. We count such dense graphlets in PPI networks by employing recently developed search strategies that render related inference problems tractable. We demonstrate that corresponding counting statistics differ significantly between prokaryotes and eukaryotes as well as between "real" PPI networks and scale free network emulators. We also prove that another class of emulators, the low-dimensional geometric random graphs (GRGs) cannot contain a specific type of motifs, complete bipartite graphs, which are abundant in PPI networks.


Establishment and application of bioassay- and molecular marker-based methods for monitoring fluvalinate resistance of Varroa mites.
The Varroa mite, Varroa destructor, is an ectoparasite that infests honey bees. The extensive use of acaricides, including fluvalinate, has led to the emergence of resistance in Varroa mite populations worldwide. This study's objective is to monitor fluvalinate resistance in field populations of Varroa mites in Korea through both bioassay-based and molecular marker-based methods. To achieve this, a residual contact vial (RCV) bioassay was established for on-site resistance monitoring. A diagnostic dose of 200 ppm was determined based on the bioassay using a putative susceptible population. In the RCV bioassay, early mortality evaluation was effective for accurately discriminating mites with the knockdown resistance (kdr) genotype, while late evaluation was useful for distinguishing mites with additional resistance factors. The RCV bioassay of 14 field mite populations collected in 2021 indicated potential resistance development in four populations. As an alternative approach, quantitative sequencing was employed to assess the frequency of the L925I/M mutation in the voltage-gated sodium channel (VGSC), associated with fluvalinate kdr trait. While the mutation was absent in 2020 Varroa mite populations, it emerged in 2021, increased in frequency in 2022, and became nearly widespread across the country by 2023. This recent emergence and rapid spread of fluvalinate resistance within a span of three years demonstrate the Varroa mite's significant potential for developing resistance. This situation further underscores the urgent need to replace fluvalinate with alternative acaricides. A few novel VGSC mutations potentially involved in resistance were identified. Potential factors driving the rapid expansion of resistance were further discussed.


Reverse Genetics System for Rift Valley Fever Virus.
Rift Valley fever virus (RVFV) is an important mosquito-borne virus that can cause severe disease manifestations in humans including ocular damage, vision loss, late-onset encephalitis, and hemorrhagic fever. In ruminants, RVFV can cause high mortality rates in young animals and high rates of abortion in pregnant animals resulting in an enormous negative impact on the economy of affected regions. To date, no licensed vaccines in humans or anti-RVFV therapeutics for animal or human use are available. The development of reverse genetics has facilitated the generation of recombinant infectious viruses that serve as powerful tools for investigating the molecular biology and pathogenesis of RVFV. Infectious recombinant RVFV can be rescued entirely from cDNAs containing predetermined mutations in their genomes to investigate virus-host interactions and mechanisms of pathogenesis and generate live-attenuated vaccines. In this chapter, we will describe the experimental procedures for the implementation of RVFV reverse genetics.


The effect of stimulus size on stereoscopic fusion limits and response criteria.
The stereoscopic fusion limit denotes the largest binocular disparity for which a single fused image is perceived. Several criteria can be employed when judging whether or not a stereoscopic display is fused, and this may be a factor contributing to a discrepancy in the literature. Schor, Wood, and Ogawa (1984 Vision Research, 24, 661-665) reported that fusion limits did not change as a function of bar width, while Roumes, Plantier, Menu, and Thorpe (1997 Human Factors, 39, 359-373) reported higher fusion limits for larger stimuli than for smaller stimuli. Our investigation suggests that differing criteria between the studies could contribute to this discrepancy. In experiment 1 we measured horizontal and vertical disparity fusion limits for thin bars and for the edge of an extended surface, allowing observers to use the criterion of either diplopia or rivalry when evaluating fusion for all stimuli. Fusion limits were equal for thin bars and extended surfaces in both horizontal and vertical disparity conditions. We next measured fusion limits for a range of bar widths and instructed observers to indicate which criterion they employed on each trial. Fusion limits were constant across all stimulus widths. However, there was a sharp change in criterion from diplopia to rivalry when the angular extent of the bar width exceeded about twice the fusion limit, expressed in angular terms. We conclude that stereoscopic fusion limits do not depend on stimulus size in this context, but the criterion for fusion does. Therefore, the criterion for fusion should be clearly defined in any study measuring stereoscopic fusion limits.


Simultaneous recording of pituitary oxytocin secretion and myometrial activity in oestrous mares exposed to various breeding stimuli.
The aim of this study was to investigate the effect of different breeding stimuli on uterine contractility and pituitary oxytocin release in five oestrous mares, in order to design better treatments for mares with defective physical uterine clearance mechanisms. Electrodes and strain gauges were implanted surgically on the uterine myometrium and myometrial activity was monitored with a Grass polygraph. A catheter was placed non-surgically in the intercavernous sinus of each oestrous mare to sample pituitary venous blood and a second catheter was placed in the jugular vein. Continuous sampling was performed for 2 h to determine the baseline value and during sequentially applied stimuli of: (i) stallion call; (ii) visual contact with a stallion; (iii) active teasing; and (iv) artificial insemination. No association was observed between uterine contraction and pituitary oxytocin release episodes during baseline recording. Exposure of the mares to any of the breeding stimuli was associated with rapid onset of myometrial contractions (P < 0.0001). The application of a stimulus significantly increased pituitary oxytocin release (P < 0.02) and contraction duration (P < 0.05), and the response to artificial insemination was greater than the responses to the other treatments (P < 0.05). The onset of oxytocin secretion was generally simultaneous with the increase in uterine contraction, rather than preceding it, and in some instances the responses were dissociated, making a cause and effect relationship less likely. In conclusion, interactions between stallions and mares are important components of the uterine clearance mechanism around the time of breeding. Knowledge of these physiological responses may be useful in designing therapeutic regimens for mares with endometritis due to defective uterine contractions.


Supporting operational decision making.
The collection and processing of information is a source of power. This fact is true especially in the health care industry. The apparent lack of information related to operational decisions in the health care industry is cause for concern. Data envelopment analysis (DEA) provides information regarding efficiency of resource utilization. This article reports on the use of DEA to measure relative technical efficiency of nursing units and the level of association between efficiency scores and the presence of selected operational characteristics. We found a statistically significant association between efficiency and two of the selected characteristics. Although nursing units are used to illustrate the application of the technique, DEA can be applied to any operational unit of a health care organization. However, we conclude that information systems and a minimum data set are essential to optimizing utilization of a such techniques.


Thiamine treatments alleviate aphid infestations in barley and pea.
Treatment of plants with thiamine (Vitamin B1) has before been shown to activate plant defence against microorganisms. Here, we have studied the effects of thiamine treatments of plants on aphid reproduction and behaviour. The work was mainly carried out with bird cherry-oat aphid (Rhopalosiphum padi L.) on barley (Hordeum vulgare L.). Aphid population growth and aphid acceptance on plants grown from seeds soaked in a 150μM thiamine solution were reduced to ca. 60% of that on control plants. R. padi life span and the total number of offspring were reduced on barley plants treated with thiamine. Healthy aphids and aphids infected with the R. padi virus were similarly affected. Spraying or addition of thiamine at 150μM to nutrient solutions likewise resulted in reduced aphid population growth to ca. 60%, as did plant exposure to thiamine odour at 4mM. Thiamine treatments resulted in reduced aphid population growth also when tested with grain aphid (Sitobion avenae F.) on barley and pea aphid (Acyrthosiphon pisum H.) on pea (Pisum sativum L.). There was no direct effect of thiamine on aphid reproduction or thiamine odour on aphid behaviour, as evaluated using artificial diets and by olfactometer tests, respectively. Two gene sequences regulated by salicylic acid showed higher transcript abundance and one gene sequence regulated by methyl jasmonate showed lower transcript abundance in thiamine-treated plants but not in control plants after aphid infestation. These results suggest that the aphid antibiosis and antixenosis effects may be related to priming of defence, but more studies are needed to explain the effects against aphids.


Gemcitabine and pemetrexed (Alimta) in thoracic cancers: present and future perspectives. Introduction and current controversies.
With more than 1 million new cases annually worldwide, lung cancer remains a major public health problem, and ongoing efforts against tobacco consumption will not modify this situation in the near future. Most patients with lung tumors have advanced disease at the time of presentation and are thus treated with palliative intent. Several new active cytotoxic agents (ie, gemcitabine, irinotecan, the taxanes, and vinorelbine) have emerged during the last decade, and in combination with cisplatin, offer response rates of 35% to 50% and median survival durations of 9 to 11 months. Nevertheless, the results remain disappointing in the majority of cases, and data on long-term survivors are still anecdotal. Several strategies might improve treatment efficacy: administering multidrug combinations to increase antitumor activity, ameliorating the tolerance of chemotherapy, treating patients at an earlier stage of their disease, and developing new agents. This article discusses these promising strategies and places them in proper perspective.


Cross-Validation and Development of Empirically Derived ADHD Assessment Strategies: Insights From the National Longitudinal Study of Adolescent Health (Add Health).
Objective: There is replicated evidence that individual ADHD symptoms differentially predict ADHD diagnostic status, and that non-Diagnostic and Statistical Manual of Mental Disorders (DSM)-based symptom algorithms are superior to DSM criteria for ruling in or ruling out ADHD. However, these findings have been limited to case-control samples, despite the need to replicate them in independent and more representative samples and to increase their generalizability. Method: We analyzed the base rates and psychometric properties of ADHD symptoms in the population-based National Longitudinal Study of Adolescent Health (Add Health; http://www.cpc.unc.edu/projects/addhealth ) sample, and evaluated the predictive utility of empirically derived ADHD symptoms against the DSM approach with respect to academic, health, and relational functional outcomes. The sample consisted of 11,247 (54% female) ethnically diverse (45% non-White) individuals who retrospectively self-reported the severity of their ADHD symptoms from 5 to 12 years. Results: Individual ADHD symptoms variably predicted ADHD status, and whereas most symptoms were most predictive when endorsed at the two highest severity levels in previous studies, symptoms in Add Health were often most predictive of ADHD when endorsed at the highest severity level. Conclusion: The divergence in optimal severity thresholds for ADHD symptoms potentially reflects the different symptom base rates in clinical versus population-based samples. The accuracy of the different classification approaches also suggested that different symptom algorithms may be superior to evaluate ADHD depending on the assessment setting.


Unresponsiveness of platelets lacking both Galpha(q) and Galpha(13). Implications for collagen-induced platelet activation.
The diffusible platelet stimuli ADP and thromboxane A(2) activate multiple G protein-mediated signaling pathways and function as important secondary mediators of platelet activation as they are released from activated platelets. Because they can also increase their own formation and release, their effects are amplified; eventually, all major G protein-mediated signaling pathways are activated. The multiple positive feedback mechanisms operating during platelet activation have obscured the exact analysis of the roles individual G protein-mediated signaling pathways play during the platelet activation process. In this report, we show that platelets lacking G(q) and G(13) are completely unresponsive to diffusible stimuli such as ADP, thromboxane A(2), or thrombin, even when applied at very high concentrations in combination, whereas all stimuli are able to induce platelet aggregation, shape change, and RhoA activation in platelets lacking only one Galpha subunit. This shows that G(q) or G(13) is required to induce some platelet activation, whereas the activation of G(i)-mediated signaling alone is not sufficient to induceactivation of mouse platelets. In addition, platelets lacking Galpha(q) and Galpha(13) adhered normally to collagen under high shearbut did not aggregate any more in response to collagen, indicating that collagen-induced platelet activation but not platelet adhesion requires intact G protein-mediated signaling pathways.


Characterizing graft distribution in maleic anhydride grafted polyethylene - GPC with IR and UV-detection.
As commodity plastics, polyolefins are in high demand and used in innumerable applications. An important reason for their success-story is their high versatility in terms of applications. The application range of polyolefins was significantly extended through the development of functionalization. A common functionalization for improving the compatibility of polyolefins with more polar polymers and surfaces is grafting with maleic anhydride. While maleic anhydride-grafted polyolefins have found widespread application, methods for their characterization remain rudimentary compared to the developments seen in the structural characterization of polyolefins in general. Herein, we propose two new approaches for determining the degree of functionalization as a function of the molar mass of maleic anhydride grafted polyolefins. On the one hand, the latest generation bandpass filter-based IR detectors are shown to be sensitive to the carbonyl moiety of MAH. After optimization of analysis conditions, the relation between MAH content and molar mass could be unraveled in an easily applicable approach suitable for routine analysis. On the other hand, the high reactivity of MAH was leveraged in a tagging approach. By imidization with a UV chromophore, MAH distribution can be assessed by HT-GPC-UV with significantly higher sensitivity compared to HT-GPC-IR.


Racial/ethnic differences in early detection of breast cancer: a study of 250,985 cases from the California Cancer Registry.
This study analyzed early breast cancer detection rates as a surrogate for breast cancer mortality rates. Stage at diagnosis was broken down by race/ethnicity and year of diagnosis for the cases of female breast cancer in the California Cancer Registry from 1988 to 2002. A quarter million cases of breast cancer in women > or =50 years of age recorded in the California Cancer Registry over the period 1988-2002 were classified as early (in situ and localized stages) or late (regional and distant stages). The increases in the percent of cases that were early were studied by 3-year periods over this interval. In addition to the total group, data were broken down by race/ethnicity. The 3-year periods were used to compensate for small numbers of cases in some of the nonwhite groups. The proportion of early stage female breast cancers reached a plateau at 70% in the mid-1990s. African American and Hispanic women's screening rates reached a plateau at a considerably lower rate. Only Pacific Islander/Asian American women demonstrated a sustained rise in the percent of early breast cancers detected through 2002, eventually nearing the rate of early detection set by white women. The plateaus observed suggest that focused interventions continue to be needed for all women, especially for African American and Hispanic women if the American Cancer Society's 2015 goals are to be achieved.


Development of Lobular Panniculitis Long After Completing the Personalized Peptide Vaccine Therapy.
BACKGROUND Personalized peptide vaccine therapy is regarded as a well-tolerated, safe and effective immunotherapy for patients with advanced cancers. Herein we report an exceptional case of a patient with advanced pancreatic cancer who developed delayed lobular panniculitis at sites corresponding to vaccine injections. CASE REPORT A 64-year-old Japanese female visited our clinic due to thirst and polydipsia; she was diagnosed as having type 2 diabetes. Simultaneously, she was diagnosed as having advanced pancreatic cancer; and a distal pancreatectomy and splenectomy were performed. Afterwards, she received adjuvant chemotherapy with titanium silicate-1 and personalized peptide vaccination using Montanide® ISA-51 by a subcutaneous injection to her abdomen over a total of 30 times. Thirteen months after the vaccine therapy had come to an end, lobular panniculitis appeared at the vaccination sites. At this point, corticosteroid was administered, resulting in significant improvement in the condition of the subcutaneous nodules. CONCLUSIONS This case report highlights the importance of careful patient explanation before initiation of cancer vaccine therapy about the possibilities of lobular panniculitis as an adverse event. It also highlights that it is important that physicians have a greater awareness of the possibility of panniculitis in patients with concerns regarding subcutaneous indurations even long after the end of peptide vaccine therapy.