From directive to practice: are pictorial warnings and plain packaging effective to reduce the tobacco addiction?
Tobacco packaging represents an important form of promotion of tobacco products and for this reason plain packaging (PP) can be considered an additional tobacco control measure. In Italy the current tobacco packaging is branded with textual warnings. The study investigated the perception of PP with textual warnings (PPTWs) and pictorial warnings (PPPWs) in Italy. Cross-sectional. The study was conducted on adults who were current, never and former smokers. The participants watched out three types of packages (current packaging, PPTWs and PPPWs) and eight pictorial warnings, and indicated which they considered the most effective ones to motivate smoking cessation or reduction and to prevent the onset. 1065 subjects were recruited. The PPPWs were considered the most effective in motivating to quit, reduce and prevent the smoking habits (ranged 83.4%-96.1%) in all tobacco users and age groups (≤40/>40 years) (P < 0.005). In general PP does not seem to be very effective in quitting for three-quarters of the smokers and 60% declared that they would have still started smoking with PP. The younger group believed less than the older one that PP gives a motivation to quit (29.4% vs 39.1%, P = 0.002). The pictures perceived as most effective in communicating the smoking effects were lung cancer and gangrene (about one-third of the sample). The textual warnings on tobacco products are a measure of control now outdated. Countries still using them should consider the idea of replace them with pictorial warnings that seem to be more effective. It is also desirable in the near future that these countries introduce the PPPWs.


Vitamin A augments collagen production by corneal endothelial cells.
When isolated confluent corneal endothelial cells were cultured in delipidized serum, a marked reduction in collagen production was observed. Supplementation of such cultures with vitamin A as either retinol or retinoic acid at concentrations of 10(-6)-10(-7) M was capable of significantly increasing collagen production. In addition, when cultured in normal (non-delipidized) serum, both retinol and retinoic acid were capable of further increasing collagen production by corneal endothelial cells. Such augmentation of collagen production was relatively specific as total protein synthesis was not altered to the same extent, nor was it merely a reflection of changes in total cell number, as such cell numbers were similar in all treatment groups.


Food selection and taste changes in humans after Roux-en-Y gastric bypass surgery: a direct-measures approach.
It has been suggested that the weight loss seen in individuals who receive Roux-en-Y gastric bypass surgery may be due, at least in part, to changes in patient food selection, and that this change may stem from effects of the operation on the sense of taste. In this review, we evaluate the literature examining postoperative changes in food intake and food choice. While some evidence suggests that gastric bypass leads to altered food selection and taste perceptions, a clear picture regarding these changes remains to be elucidated and is blurred by inconsistencies, which may be rooted in the diverse subject pools within and between studies as well as in the indirect measures used to assess ingestive behavior. We argue that complementing current assessment tools with more direct measures of intake, food selection, and taste-related behavior might help provide some clarity and also facilitate translation between findings from animal models, in which similar measures are available, and clinical research.


Foliar application of benzovindiflupyr shows non-fungicidal effects in wheat plants.
The fungicide benzovindiflupyr belongs to the class of succinate dehydrogenase inhibitors (SDHIs). Certain SDHIs have shown plant physiological effects, so-called secondary effects, that appeared to be related to the plant water status. Therefore, the effect of benzovindiflupyr on transpiration of leaves and whole wheat plants was studied under controlled conditions. Furthermore, wheat yield trials under controlled and natural drought stress in the field were conducted. Transpiration of detached wheat leaves was reduced by benzovindiflupyr in a dose-dependent manner. Similarly, whole-plant transpiration decreased for several days following application of this fungicide. In 16 field trials under drought stress conditions that were classified as disease-free, treatment of wheat plants at the flag leaf stage or at heading with benzovindiflupyr showed a grain yield increase (+5.2%; P ≤ 0.01) that was partially attributed to an increased thousand-grain weight. Water saving during pre-anthesis as a result of benzovindiflupyr application may be associated with better seed setting and filling under dry field conditions in wheat. The results of this research provide new insights into secondary effects of SDHIs that lead directly to yield improvements. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Tomato miR156-targeted SlSBP15 represses shoot branching by modulating hormone dynamics and interacting with GOBLET and BRANCHED1b.
The miRNA156 (miR156)/SQUAMOSA PROMOTER-BINDING PROTEIN-LIKE (SPL/SBP) regulatory hub is highly conserved among phylogenetically distinct species, but how it interconnects multiple pathways to converge to common integrators controlling shoot architecture is still unclear. Here, we demonstrated that the miR156/SlSBP15 node modulates tomato shoot branching by connecting multiple phytohormones with classical genetic pathways regulating both axillary bud development and outgrowth. miR156-overexpressing plants (156-OE) displayed high shoot branching, whereas plants overexpressing a miR156-resistant SlSBP15 allele (rSBP15) showed arrested shoot branching. Importantly, the rSBP15 allele was able to partially restore the wild-type shoot branching phenotype in the 156-OE background. rSBP15 plants have tiny axillary buds, and their activation is dependent on shoot apex-derived auxin transport inhibition. Hormonal measurements revealed that indole-3-acetic acid (IAA) and abscisic acid (ABA) concentrations were lower in 156-OE and higher in rSBP15 axillary buds, respectively. Genetic and molecular data indicated that SlSBP15 regulates axillary bud development and outgrowth by inhibiting auxin transport and GOBLET (GOB) activity, and by interacting with tomato BRANCHED1b (SlBRC1b) to control ABA levels within axillary buds. Collectively, our data provide a new mechanism by which the miR156/SPL/SBP hub regulates shoot branching, and suggest that modulating SlSBP15 activity might have potential applications in shaping tomato shoot architecture.


CT demonstration of extraocular muscle atrophy.
Two cases of CT-documented extraocular muscle atrophy are presented. Unilateral atrophy was observed in a patient with a lesion of the cavernous sinus. Atrophic extraocular muscles were noted bilaterally in a young woman with "ophthalmoplegia plus" (probable Kearns-Sayre syndrome).


Time resolved DNA occupancy dynamics during the respiratory oscillation uncover a global reset point in the yeast growth program.
The structural dynamics of chromatin have been implicated in the regulation of fundamental eukaryotic processes, such as DNA transcription, replication and repair. Although previous studies have revealed that the chromatin landscape, nucleosome remodeling and histone modification events are intimately tied into cellular energetics and redox state, few studies undertake defined time-resolved measurements of these state variables. Here, we use metabolically synchronous, continuously-grown yeast cultures to measure DNA occupancy and track global patterns with respect to the metabolic state of the culture. Combined with transcriptome analyses and ChIP-qPCR experiments, these paint an intriguing picture where genome-wide nucleosome focusing occurs during the recovery of energy charge, followed by clearance of the promoter regions and global transcriptional slow-down, thus indicating a nucleosome-mediated "reset point" for the cycle. The reset begins at the end of the catabolic and stress-response transcriptional programs and ends prior to the start of the anabolic and cell-growth transcriptional program, and the histones on genes from both the catabolic and anabolic superclusters are deacetylated.


[Retrograde degeneration of the neurons of the cerebellar nuclei after partial removal of the associative cerebral cortex].
Retrograde degeneration of the cerebellar nuclei cells has been studied after partial ablation of the associative parietal cerebral cortex in the cat. The material is stained after Nissl. Retrogradely degenerated and normal cells are counted. The "ghost-cells" in the cerebellar nuclei indicate that a direct axonal connection exists between some neurons and the cerebral cortex operated, while the cells that are at other stages of degeneration are, perhaps, connected with this part of the cortex by means of axonal collaterals.


Effects of substance P and shorter analogs on body temperature in the rat.
The thermoregulatory effects of intraperitoneally administered substance P (SP1-11) (250 micrograms/kg), or equimolar quantities of SP1-4 and SP5-11 were studied in conscious rats at an ambient temperature of 4 degrees C. SP1-11 produced hypothermia, whereas SP1-4 and SP5-11 had no influence. The hypothermic effect of SP1-11 was partially antagonized by naloxone. Thus, an opiate-dependent step seems to be involved in the action of SP1-11.


Progestogen Hypersensitivity: An Evidence-Based Approach to Diagnosis and Management in Clinical Practice.
Heterogeneous presentations of disease pose particular diagnostic and management challenges to the clinician. Progestogen hypersensitivity (PH) classically consists of hypersensitivity symptoms to endogenous progesterone during the luteal phase of the menstrual cycle. However, with the rise of assisted fertility and the exponential growth in the use of exogenous progestins for contraception, PH's prevalence and symptom heterogeneity have increased. In this article, we focus on the clinical approach to PH diagnosis with an emphasis on key elements of the history, physical, and testing modalities. We also review the current evidence for successful management and treatment across a broad range of patients.


Removal of extracellular deoxyribonucleic acid increases the permeability and mass transfer of anammox granular sludge with different sizes.
As a key component of extracellular polymeric substances (EPS), extracellular deoxyribonucleic acid (eDNA) acts as a bridge in maintaining the structural stability of granular sludge. However, its ability of carrying antibiotic resistance genes (ARGs) promotes the gene horizontal transfer, raising a high risk for human health. In this study, a series of batch tests were performed to elucidate the response of anammox granular sludge (AnGS) with different sizes (S-AnGS with diameters lower than 0.9 mm and L-AnGS with diameters of 0.9-2 mm) to the removal of eDNA and corresponding mechanism. The results showed that the highest bioactivity of S-AnGS and L-AnGS was achieved by adding DNase I, and the absolute abundance of hzsA in the systems also increased. The dominant microorganism in each sludge was Candidatus Kuenenia, which maintained a higher relative abundance of 24% in S-AnGS. Settling experiments demonstrated that the permeability of AnGS was positively correlated with the addition of DNase I. The permeability index of granular sludge, Г, rose by 58.54% in S-AnGS and 11.79% in L-AnGS. The absence of eDNA is conducive to the increase in the permeability and porosity of AnGS. Similarity in the functional genes and microbial communities of intracellular and extracellular DNA implied the occurrence of gene transmembrane transfer. The findings enrich our knowledge of eDNA in anammox granules and provide a guidance for the specific control of gene transfer through reducing eDNA.


Bacterial lipopolysaccharide potentiates type II collagen-induced arthritis in mice.
Collagen-induced arthritis (CIA) is an immunologically relevant animal model of human rheumatoid arthritis. Studies comparing the disease incidence in genetically susceptible male and female DBA/1LacJ mice demonstrated that under low density/low stress housing conditions, female mice had earlier onset (day 35) and higher disease incidence (25%) than the male mice (17% at day 49) when immunized with bovine type II collagen. A single subcutaneous or intraperitoneal injection of bacterial lipopolysaccharide (LPS) 17-24 days after collagen immunization greatly potentiated this standard CIA model in a dose related manner. 20-40 mug of LPS accelerated the onset of disease from day 35 to day 21 and exacerbated the clinical severity score from 0.27 to 2.00 at day 42. A similar administration of 6 mug of recombinant interleukin-beta produced a comparable potentiated CIA model. The acute phase protein, serum amyloid P (SAP), was elevated in the serum at day 26 to 440 mug ml(-1) for the LPS potentiated CIA mice compared to 65 mug ml(-1) in the non-potentiated immunized CIA mice. There was a significant correlation (r = 0.78) between SAP levels and disease expression in the LPS treated CIA mice. The rapidity and uniformity of disease expression in this LPS potentiated CIA model will allow more and different drugs to be evaluated with a smaller number of animals.


Structure-activity relationship studies of acridones as potential antipsoriatic agents. 2. Synthesis and antiproliferative activity of 10-substituted hydroxy-10H-acridin-9-ones against human keratinocyte growth.
A series of 10-substituted hydroxy-10H-acridin-9-ones were synthesized and studied as potential antipsoriatic agents. The antiproliferative activity of the novel derivatives, which can be considered as aza-analogues of the antipsoriatic drug anthralin, was determined using the human keratinocyte cell line HaCaT. Structure-activity relationships with respect to the nature of the N-substituent at the acridone scaffold were delineated. Release of lactate dehydrogenase (LDH) was used to exclude non-specific cytotoxic effects. As compared to anthralin, N-substitution of the acridone scaffold in the target compounds provided agents devoid of radical producing properties, which was documented by their ineffectiveness to interact with the free radical 2,2-diphenyl-1-picrylhydrazyl. This was in excellent agreement with the data obtained from the LDH assay in which the novel compounds did not induce membrane damage. Benzyl substitution at the 10-position yielded keratinocyte growth inhibitory activity in the low micromolar range. The most potent inhibitor of keratinocyte hyperproliferation was compound 8a having an N-methyl group and a 1,3-dihydroxy arrangement at the acridone scaffold, with an IC(50) value comparable to that of anthralin.


Modifiable factors to improve work-life balance for trauma surgeons.
A balance between work and life outside of work can be difficult for practicing physicians to achieve, especially for trauma surgeons. Work-life balance (WLB) has been associated with burnout and career changes. The specific aim of this study was to investigate factors associated with WLB for trauma surgeons. We hypothesized that trauma surgeons are dissatisfied with their WLB, and there are modifiable factors that can be adjusted to improve and maintain WLB. Survey study of AAST members including detailed questions regarding demographics, clinical practice, family, lifestyle, and emotional support. Primary outcome was WLB, while the secondary outcome was surgeon burnout. A total of 1,383 American Association for the Surgery of Trauma members received an email with the survey, and 291 (21%) completed the survey. There was a total of 125 members (43%) satisfied with their WLB, and 166 (57%) were not. Factors independently associated with satisfying WLB included hobbies (2.3 [1.1-4.7], p = 0.03), healthy diet (2.6 [1.2-4.4], p = 0.02), exercise (2.6 [1.3-5.1], p = 0.006), vacation weeks off (1.3 [1.0-1.6], p = 0.02), and fair compensation (2.6 [1.3-5.3], p = 0.008). Conversely, factors independently associated with a poor WLB included being midcareer (0.3 [0.2-0.7], p = 0.002), more work hours (0.4 [0.2-0.7], p = 0.006), fewer awake hours at home (0.2 [0.1-0.6], p = 0.002), and feeling that there is a better job (0.4 [0.2-0.9], p = 0.02]. Risk factors for burnout were the same as those for poor WLB. Only 43% of trauma surgeons surveyed were satisfied with their WLB, and 61% reported burnout. Modifiable factors independently associated with a satisfying WLB were related to lifestyle and fair compensation. Factors independently associated with poor WLB and suffering burnout were being midcareer, increased hours at work, decreased awake hours at home, and feeling that there was a better job for yourself. Many factors associated with trauma surgeon WLB are modifiable. Trauma surgeons, as well as trauma leaders, should focus on these modifiable factors to optimize WLB and minimize burnout. Care management, Level III.


Inability of insulin to maintain normal nerve function during high-frequency stimulation in diabetic rat tail nerves.
The effect of insulin on the response to long-term high-frequency stimulation (HFS = 143 Hz for 20 min) was studied in mixed tail nerves of acute streptozotocin-induced diabetic rats. In consecutive tests, untreated diabetic rats showed a significant decrease in nerve conduction velocity (NCV) and peak-to-peak amplitude (P-Pamp) and the depression of the P-Pamp during HFS was augmented. In contrast, NCV and P-Pamp in the insulin-treated rats were unchanged from the prediabetic state, but the depression of the P-Pamp during HFS reached the same degree as in untreated rats. This implies that although insulin treatment of acute experimental diabetes is able to preserve a normal NCV and P-Pamp in the resting state, it is unable to preserve normal nerve function under stress produced by HFS. Monitoring of the axon membrane functional capacity may have clinical implications in the control of peripheral neuropathies.


Quantitative morphologic study of intimal thickening at the human carotid bifurcation: II. The compensatory enlargement response and the role of the intima in tensile support.
Arteries enlarge where intimal plaques form, tending to preserve lumen cross sectional area but causing an increase in mural tangential tension due to the increase in radius. To characterize the compensatory enlargement process at the carotid bifurcation and to evaluate the possible contribution of intima thickening to mural tensile support during the enlarging process, we assessed the relationships among intimal thickening, artery size and estimated tensile stress at 9 sequential axial levels in 42 human carotid bifurcations obtained during post-mortem examinations of 36 adults with no clinical or anatomical evidence of cerebrovascular disease. Right and left bifurcations were available for 6 patients. The arteries were fixed under conditions of controlled pressure distention and histologic sections were prepared at 0.5 cm axial intervals. We determined vessel radius (r), intima thickness (IT), media thickness (MT), intima area (IA), lumen area (LuA) and the area encompassed by the internal elastic lamina (IELA), i.e. the lumen area if there were no intimal thickening. Although IT, IA and r were greatest in the proximal sinus region, there was a highly significant linear relationship between IA and IELA at each axial level; correlation coefficients ranged from 0.64 to 0.97 with P < 0.001 at each level. Stenosis (IA/IELA x 100) ranged from 10.8 +/- 8.0% at the common carotid level immediately proximal to the bifurcation angle to 22.3 +/- 17.9% at the level immediately distal to the angle, but LuA remained nearly constant at each level regardless of IA.(ABSTRACT TRUNCATED AT 250 WORDS)


Fractional Fourier transform pre-processing for neural networks and its application to object recognition.
This study investigates fractional Fourier transform pre-processing of input signals to neural networks. The fractional Fourier transform is a generalization of the ordinary Fourier transform with an order parameter a. Judicious choice of this parameter can lead to overall improvement of the neural network performance. As an illustrative example, we consider recognition and position estimation of different types of objects based on their sonar returns. Raw amplitude and time-of-flight patterns acquired from a real sonar system are processed, demonstrating reduced error in both recognition and position estimation of objects.


A soluble sustained-release ophthalmic delivery unit.
Four studies carried out in normal volunteers assessed the characteristics and acceptability of the matrix of a soluble sustained-release delivery system. Fourteen volunteers in the first study received crossover single applications of a rod- and oval-shaped soluble unit at 8 AM. Fifteen normal volunteers in the second study received soluble units at 9 PM in the inferior cul-de-sac. During the crossover phase, the units were placed into the superior cul-de-sac rather than the inferior cul-de-sac. In the third study, 15 normal volunteers received a rod-shaped unit in one eye and an oval-shaped insert in the opposite eye nightly for five successive nights. In Study 4, 24 normal volunteers subdivided into four groups of 12 eyes received an 18-mg rod, 24-mg rod, 18 mg-oval, or 24-mg oval unit at 9 PM. We concluded that the disappearance rate of these soluble units from the conjunctival sac depended on the size rather than shape and was not influenced by sleep. The soluble units were well tolerated.


Cholesterol and saturated fatty acids synergistically promote the malignant progression of prostate cancer.
The excessive accumulation of saturated fatty acids and cholesterol have been linked to prostate cancer (Pca). Here, we found that lipoproteins, apolipoproteins, triglycerides and free fatty acids are significantly higher in the peripheral blood of prostate cancer patients than in non-cancer patients. Furthermore, the expression of ACC1, FASN and HMGCR is significantly higher in prostate cancer tissues than that in non-cancer tissues, and positively correlated with the gleason score. Using genetically engineered mouse models, we found that in a mouse model of high grade prostatic intraneoplasia (HGPIN), a combination of fatty acid synthase (FASN) overexpression and cholesterol efflux pump (Abca1) knockout resulted in the progression of prostatic intraneoplasia (PIN) to invasive PCa with 100% penetrance, as well as an increase in prostate cancer stem cell (PCSC)population, accompanied by activation of PGE2 and TGF-β signaling pathway. Our study suggests that the steady rise in prostate cancer incidence and mortality among Chinese population during the last several decades may be attribute to a combinational effect of fatty acid and cholesterol, and reduction in dietary fat and cholesterol intake could slow down the progression from occult lesions to prostate cancer.


CNS Drug Development: Lessons Learned Part 3: Psychiatric and Central Nervous System Drugs Developed Over the Last Decade-Implications for the Field.
This column reviews the divergence between the approach to drug development in infectious disease, oncology, and immunology versus psychiatry. Between 2009 and 2016, 254 new drugs were approved. Of those, only 9 were for a psychiatric indication; another 5 were labeled to treat central nervous system disorders that are not considered psychiatric per se but are frequently found in individuals with psychiatric illnesses (eg, substantial weight gain). There were 2 additional new products for psychiatric indications that involved either a combination product (Contrave) or a prodrug for the production of aripiprazole (Aristada). The column discusses the reasons behind these different rates of development of psychiatric and/or central nervous system drugs compared with drugs in the areas of infectious disease, oncology, and immunology, and it predicts that this situation will change over the next century as we develop an improved understanding of the neurobiology underlying specific psychiatric illnesses.


Dangers of including outcome at baseline as a covariate in latent change score models: Results from simulations and empirical re-analyses.
Latent change score modeling is a type of structural equation modeling used for estimating change over time. Often change is regressed on the initial value of the outcome variable. However, similarly to other regression analyses, this procedure may be susceptible to regression to the mean. The present study employed simulations as well as re-analyses of previously published data, claimed to indicate reciprocal promoting effects of vocabulary and matrix reasoning on each other's longitudinal development. Both in simulations and empirical re-analyses, when adjusting for initial value on the outcome, latent change score modeling tended to indicate an effect of a predictor on the change in an outcome even when no change had taken place. Furthermore, analyses tended to indicate a paradoxical effect on change both forward and backward in time. We conclude that results from latent change score modeling are susceptible to regression to the mean when adjusting for the initial value on the outcome. Researchers are recommended not to regress change on the initial value included in the calculation of the change score when employing latent change score modeling but, instead, to define this parameter as a covariance.


Retracted: Expression and Relationship of Netrin-1, DCC, UNC5B, and VEGF in Villous Tissues of Patients with Delayed Abortion.
[This retracts the article DOI: 10.1155/2022/6283372.].


[Interrelationship of microsomal and mitochondrial systems for hydroxylating steroids from cattle adrenal cortex: effect of highly-purified components of the mitochondrial monoxygenase system on hydroxylation of steroids by microsomes].
The possibility of functioning of microsomal steroid hydroxylases in the adrenal cortex in the presence of the electron-transporting proteins in mitochondrial monooxygenase systems has been studied. It was found that adrenodoxin reductase stimulates both the 21- and 17 alpha-steroid hydroxylation activities in microsomes of the adrenal cortex with the same efficiency as does NADPH-dependent cytochrome P-450 reductase. Using cytochrome b5 and its specific antibody, an attempt has been made to investigate possible mechanisms of the stimulating effect of adrenodoxin reductase.


Pica in the mentally handicapped: a 15-year surgical perspective.
To review the general surgical management of mentally handicapped persons with pica. A study of hospital records and a review of the current literature. A community hospital. Thirty-five patients from a large institution for the mentally handicapped were treated for well-documented pica on 56 occasions at the Orillia Soldiers Memorial Hospital between 1976 and 1991. Endoscopy and laparotomy for the removal of foreign bodies or to close perforations. Fourteen (25%) cases of pica were managed by observation only, but 42 (75%) cases required surgical intervention. There were 34 laparotomies. The complication rate was 30% and the death rate 11%. Pica is a serious health risk for mentally handicapped patients. Diagnosis and postoperative care can be difficult. Pica should be suspected in mentally handicapped patients with gastrointestinal symptoms.


Macrorestriction analysis and antimicrobial susceptibility profiling of Salmonella enterica at a University Teaching Hospital, Kuala Lumpur.
The genetic diversity and antimicrobial resistance rates of clinical Salmonella isolates (2007-2008) at the University of Malaya Medical Centre, Kuala Lumpur, were investigated and the genetic diversity of the isolates was determined by pulsed-field gel electrophoresis (PFGE) and repetitive extragenic palindromic (REP)-PCR. XbaI-PFGE analysis generated 57 profiles (Dice coefficient, F=0.08-1.00), whereas REP-PCR using the REP primer generated only 35 (F=0.34-1.00). PFGE was therefore the more discriminative and reproducible method for assessing the genetic diversity of salmonellae. The antibiograms of 78 Salmonella isolates were assessed against 19 antimicrobials using the disk diffusion method. Twenty serotypes were identified, with the most common being S. Enteritidis (18%) followed by S. Typhimurium (14%), S. Paratyphi B var Java (9%), S. Weltevreden (9%), and S. Corvallis (9%). A total of 38 resistant profiles were defined, with 53.8% of the isolates being resistant to three or more antimicrobials. The highest resistance rates were observed for cephalothin (55.1%), tetracycline (47.4%), and nalidixic acid (35.9%). The presence of multidrug-resistant Salmonella strains is a cause for concern as it may limit the treatment of severe salmonellosis. One multidrug-resistant S. Enteritidis strain was a putative extended-spectrum beta-lactamase producer, based on a double disk diffusion analysis, and was resistant to ceftriaxone (MIC>32 microg/mL). The data generated by this study will contribute towards epidemiological monitoring and investigations of Salmonella infections in Malaysia.


Acute cocaine administration alters permeability of blood-brain barrier in freely-moving rats- Evidence using miniaturized fluorescence microscopy.
Cocaine has a variety of negative effects on the central nervous system, including reports of decreased barrier function of brain microvascular endothelial cells. However, few studies have directly shown the effects of cocaine on blood-brain barrier (BBB) function in vivo. The miniature integrated fluorescence microscope (i.e., miniscope) technology was used to visualize cocaine-induced changes in BBB permeability in awake, freely-moving rats. The miniscope was implanted in the prefrontal cortex of adult male rats. After recovery and acclimation, rats received an injection of cocaine (5-20 mg/kg ip) 15 minutes following iv infusion of sodium fluorescein, a low molecular weight tracer. Fluorescence intensity was recordedin vivo via the miniscope for 30 minutes or 24 hours post cocaine administration and served as an indicator of BBB permeability. Results demonstrate that cocaine increased the sodium fluorescein extravasation in brain microcirculation in a dose-dependent manner 30 minutes, but not 24 hours after administration. We report for the first time using direct visualization of brain microcirculation with the miniscope technology in awake, freely-moving rats, that acute cocaine administration produced a transient increase in the BBB permeability.


Validity and reproducibility of a laser fluorescence system for detecting the activity of white-spot lesions on free smooth surfaces in vivo.
The aim of the study was to determine the reproducibility and validity of DIAGNOdent in detecting active and arrested caries lesions on free smooth surfaces. Volunteers were selected from state schools of Piracicaba, São Paulo, Brazil. Overall, 220 lesions were clinically examined. Two specially trained ('calibrated') examiners performed both clinical and laser evaluations independently, and after a 1-week interval, the examinations were repeated. The intra-examiner agreement for the laser evaluation was substantial (kappa(ex1) = 0.79, kappa(ex2) = 0.71). There was almost perfect agreement between the two examiners for the clinical examination (kappa(ex1) = 0.95, kappa(ex2) = 0.85). The inter-examiner agreement showed substantial reproducibility (kappa = 0.77) for the laser examination and almost perfect agreement (kappa = 0.85) for the clinical evaluation. The validation criterion was the clinical examination of white spots, recorded as active or arrested. The sensitivity was 0.72 and the specificity was 0.73, which indicates that the DIAGNOdent was a good auxiliary method for detecting incipient caries lesions on free smooth surfaces. The utilization of both methods can improve the efficacy of caries diagnosis.


Quantitative assessment by flow cytometry of T-lymphocytes producing antigen-specific gamma-interferon in Brucella immune cattle.
Peripheral blood mononuclear cells (PBMC) isolated from cattle infected with Brucella secreted gamma-interferon (IFN-gamma) after antigen-specific stimulation with Brucellergene, which is a mixture of cytoplasmic proteins of rough Brucella melitensis B115. Following the depletion of the monocyte-macrophages from the PBMC, the enriched lymphocyte populations stimulated with Brucellergene did not produce IFN-gamma. Two-colour immunofluorescence staining of intracellular IFN-gamma and bovine cell surface molecules identified the cells producing IFN-gamma among the PBMC stimulated with Brucellergene. Moreover, this method could be used to estimate the number of T-cells specifically producing IFN-gamma. For a given animal, there is a significant correlation (p < 0.05) between the production of IFN measured by an ELISA of the supernatant of whole blood stimulated with Brucellergene and the number of T-cells producing IFN-gamma after in vitro stimulation with Brucellergene. The development of the immunofluorescence staining technique provides a new tool for analysing and for measuring the T-cell immune response in cattle.


A disiloxane-functionalized phosphonium-based ionic liquid as electrolyte for lithium-ion batteries.
A disiloxane-functionalized ionic liquid based on a phosphonium cation and a bis(trifluoromethylsulfonyl)imide (TFSI) anion was synthesized and characterized. This new ionic liquid electrolyte showed good stability with a lithium transition metal oxide cathode and a graphite anode in lithium ion cells.


Alignment of practices for data harmonization across multi-center cell therapy trials: a report from the Consortium for Pediatric Cellular Immunotherapy.
Immune effector cell (IEC) therapies have revolutionized our approach to relapsed B-cell malignancies, and interest in the investigational use of IECs is rapidly expanding into other diseases. Current challenges in the analysis of IEC therapies include small sample sizes, limited access to clinical trials and a paucity of predictive biomarkers of efficacy and toxicity associated with IEC therapies. Retrospective and prospective multi-center cell therapy trials can assist in overcoming these barriers through harmonization of clinical endpoints and correlative assays for immune monitoring, allowing additional cross-trial analysis to identify biomarkers of failure and success. The Consortium for Pediatric Cellular Immunotherapy (CPCI) offers a unique platform to address the aforementioned challenges by delivering cutting-edge cell and gene therapies for children through multi-center clinical trials. Here the authors discuss some of the important pre-analytic variables, such as biospecimen collection and initial processing procedures, that affect biomarker assays commonly used in IEC trials across participating CPCI sites. The authors review the recent literature and provide data to support recommendations for alignment and standardization of practices that can affect flow cytometry assays measuring immune effector function as well as interpretation of cytokine/chemokine data. The authors also identify critical gaps that often make parallel comparisons between trials difficult or impossible.


miR-21 and miR-145 cooperation in regulation of colon cancer stem cells.
Acquired drug resistance is one of the major reasons for failing cancer therapies. Although the reasons are not fully understood, they may be related to the presence of cancer stem cells (CSCs). We have reported that chemo-resistant (CR) colon cancer cells, highly enriched in CSCs, exhibit a marked up-regulation of miR-21 and that down-regulation of this miR renders the CR cells more susceptible to therapeutic regimens. However, the underlying molecular mechanism is poorly understood. The aim of this investigation is to unravel this mechanism. The levels of miR-145 and miR-21 were manipulated by transfection of mature, antago-miRs or pCMV/miR-145 expression plasmid. Quantitative RT-PCR or/and Western blots were performed to examine the expression of CD44, β-catenin, Sox-2, PDCD4, CK-20 and k-Ras. Colonosphere formation and SCID mice xenograft studies were performed to evaluate the tumorigenic properties of CSC-enriched colon CR cells. We investigated the role that microRNAs (miRs), specifically miR-21 and miR-145 play in regulating colon CSCs. We found the expression of miR-21 to be greatly increased and miR-145 decreased in CR colon cancer cells that are highly enriched in CSC, indicating a role for these miRNAs in regulating CSCs. In support of this, we found that whereas forced expression of miR-145 in colon cancer cells greatly inhibits CSCs and tumor growth, up-regulation of miR-21 causes an opposite phenomenon. In addition, administration of mature miR-145 or antagomir-21 (anti-sense miR-21) greatly suppresses the growth of colon cancer cell xenografts in SCID mice. This was associated with decreased expression of CD44, β-catenin, Sox-2 and induction of CK-20 indicating that administration of miR-145 or antagomir-21 decreases CSC proliferation and induces differentiation. In vitro studies further demonstrate that miR-21 negatively regulates miR-145 and vice versa. k-Ras appears to play critical role in regulation of this process, as evidenced by the fact that the absence of k-Ras in CR colon cancer cells increases miR-145 expression, suppresses miR-21, and interrupts the negative cooperation between miR-21 and miR-145. Our current observations suggest that miR-21, miR-145, and their networks play critical roles in regulating CSCs growth and/or differentiation in the colon cancer and progression of chemo-resistance.


Structural analysis of Mg2+ and Ca2+ binding to CaBP1, a neuron-specific regulator of calcium channels.
CaBP1 (calcium-binding protein 1) is a 19.4-kDa protein of the EF-hand superfamily that modulates the activity of Ca(2+) channels in the brain and retina. Here we present data from NMR, microcalorimetry, and other biophysical studies that characterize Ca(2+) binding, Mg(2+) binding, and structural properties of recombinant CaBP1 purified from Escherichia coli. Mg(2+) binds constitutively to CaBP1 at EF-1 with an apparent dissociation constant (K(d)) of 300 microm. Mg(2+) binding to CaBP1 is enthalpic (DeltaH = -3.725 kcal/mol) and promotes NMR spectral changes, indicative of a concerted Mg(2+)-induced conformational change. Ca(2+) binding to CaBP1 induces NMR spectral changes assigned to residues in EF-3 and EF-4, indicating localized Ca(2+)-induced conformational changes at these sites. Ca(2+) binds cooperatively to CaBP1 at EF-3 and EF-4 with an apparent K(d) of 2.5 microM and a Hill coefficient of 1.3. Ca(2+) binds to EF-1 with low affinity (K(d) >100 microM), and no Ca(2+) binding was detected at EF-2. In the absence of Mg(2+) and Ca(2+), CaBP1 forms a flexible molten globule-like structure. Mg(2+) and Ca(2+) induce distinct conformational changes resulting in protein dimerization and markedly increased folding stability. The unfolding temperatures are 53, 74, and 76 degrees C for apo-, Mg(2+)-bound, and Ca(2+)-bound CaBP1, respectively. Together, our results suggest that CaBP1 switches between structurally distinct Mg(2+)-bound and Ca(2+)-bound states in response to Ca(2+) signaling. Both conformational states may serve to modulate the activity of Ca(2+) channel targets.


Detection of a mesenchymal tumor responsible for hypophosphatemic osteomalacia using FDG-PET.
We report a case of oncogenic osteomalacia (OO) in a 71-year-old man. The tumor, which was localized in the left lower mandible, was not found by CT, MRI, or 111-indium octreotide scintigraphy but was easily detected by FDG-PET. The use of this technique in OO has never been reported.


The Minnesota Clinical Comparison and Assessment Project.
Efforts to quantify and improve the effectiveness and efficiency of health care services are critical to the health care system in the United States. Essential components of these efforts are clinician involvement and support and reliable clinical information systems. Organized medicine and the hospital industry in Minnesota have initiated and funded the Minnesota Clinical Comparison and Assessment Project (MCCAP) to begin to document, compare, and improve health care services. Through MCCAP, a forum, comprising leaders in the Minnesota health care community, oversees efforts to collaboratively identify and address quality of care. In addition, MCCAP will adapt guidelines for specific conditions/procedures, collect hospital-level data on clinical practices in the state relative to those conditions/procedures, and provide feedback so that physicians can evaluate their practice and modify it, if necessary, to improve quality of care.


Combining Optimized Particle Morphology with a Niobium-Based Coating for Long Cycling-Life, High-Voltage Lithium-Ion Batteries.
Morphologically optimized LiNi0.5 Mn1.5 O4 (LMNO-0) particles were treated with LiNbO3 to prepare a homogeneously coated material (LMNO-Nb) as cathode in batteries. Graphite/LMNO-Nb full cells present a twofold higher cycling life than cells assembled using uncoated LMNO-0 (graphite/LMNO-0 cell): Graphite/LMNO-0 cells achieve 80 % of the initial capacity after more than 300 cycles whereas for graphite/LMNO-Nb cells this is the case for more than 600 cycles. Impedance spectroscopy measurements reveal significantly lower film and charge-transfer resistances for graphite/LMNO-Nb cells than for graphite/LMNO-0 cells during cycling. Reduced resistances suggest slower aging related to film thickening and increase of charge-transfer resistances when using LMNO-Nb cathodes. Tests at 45 °C confirm the good electrochemical performance of the investigated graphite/LMNO cells while the cycling stability of full cells is considerably lowered under these conditions.


Robotic-enhanced biventricular resynchronization: an alternative to endovenous cardiac resynchronization therapy in chronic heart failure.
Cardiac resynchronization therapy (CRT) by pacing the left and right ventricles is an emerging option for treatment of severe heart failure with ventricular conduction disturbances. Stimulation through a coronary vein is currently the technique of choice to achieve left ventricular (LV) pacing. Unfortunately, this approach carries significant limitations and drawbacks. Therefore we explored robotic-enhanced thoracoscopic implantation of an epicardial lead as an alternative technique to stimulate the LV in cardiac resynchronization therapy. A total of 15 patients were included in this study. Right (atrial and ventricular) leads were implanted classically through the left subclavian vein. Robotic-enhanced thoracoscopy was then performed to implant the LV epicardial lead. Of the 15 patients, 13 underwent successful endoscopic robotic cardiac resynchronization therapy. Two patients underwent conversion to a small thoracotomy. No perioperative complication occurred in the patients who did not undergo conversion. Acute and chronic LV lead thresholds were satisfactory in all patients, improving over time. All were subjectively and objectively improved at 4 months. As compared with conventional methods, the procedural cost was not significantly affected. Based on this feasibility study, we believe that robotic LV epicardial lead implantation is a valuable option to achieve biventricular resynchronization therapy. It allows for more reproducible acute thresholds for LV pacing and sensing than does the percutaneous approach; enables fine tuning of the LV lead position, thus potentially providing optimal hemodynamic benefit; and avoids the pitfalls and limitations of the endovenous approach. Therefore it deserves further prospective studies to assess its place in the therapeutic armamentarium against heart failure.


Herpes simplex as a possibly occupational disease in dentists of the County of Aarhus, Denmark.
Among the 765 dentists of the County of Aarhus , Denmark, a total of 65% answered a questionnaire on possible herpes panaritium experience. Among the answers 3.8% were positive. Among these, 10 had circulating antibodies against herpes simplex virus. During the study a case of recurrence of a panaritium , which appeared to be a herpes simplex infection, occurred.


Determination of a reference range for whole blood serotonin in a pediatric population using high pressure liquid chromatography with electrochemical detection.
Whole blood serotonin (5HT) concentrations were measured in a group of children and adolescents to determine a reference range for this population. Blood was collected after at least a 6-hour fast, mixed with ascorbic acid and EDTA, and frozen at -70 degrees C until analysis. 5HT was determined by HPLC with electrochemical detection. Matrix-matched whole blood standards and controls were used to determine 5HT concentrations, and monitor performance of the assay. 5HT concentrations in boys ranged from 0.53 to 3.13 mumol/L (mean = 1.27, SD = 0.47) while the range for girls was 0.63 to 2.46 mumol/L (mean = 1.21, SD = 0.47). There was no significant difference in 5HT concentrations between boys and girls, nor was there any significant change in 5HT concentration with age. The nonparametric central 95 percent reference range for boys and girls was determined to be 0.64-2.45 mumol/L.


A monoclonal antibody recognizing selectively rat granulocytes.
In the present study, a murine monoclonal antibody, RK-4 (IgG1) specific for rat granulocytes and their precursors in blood and bone marrow is described. Results obtained by immunocytological and flowcytometry analysis showed this mAb to recognize selectively a surface antigen on neutrophils, eosinophils and basophils. Analysis of cryosections of various lymphatic and non-lymphatic organs demonstrates that this mouse antibody does not cross-react with any other structures. By flow cytometric analysis we found peripheral blood leukocytes to consist of about 15-20% granulocytes. RK-4 is therefore a valuable tool for studying differentiation and function of granulocytes under various conditions.


The role of dopamine released from distal and proximal dendrites of nigrostriatal dopaminergic neurons in the control of GABA transmission in the thalamic nucleus ventralis medialis in the cat.
Halothane-anaesthetized cats implanted with push-pull cannulae were used in this study. Amphetamine was applied in the pars reticulata or pars compacta of the substantia nigra in order to determine the role of dopamine released from distal or proximal dendrites of dopaminergic cells in the control of GABAergic transmission in the nucleus ventralis medialis of the thalamus. When applied for 30 min in either the pars reticulata or the pars compacta, amphetamine (10(-6) M) enhanced to a similar extent the local release of [3H]dopamine synthesized from [3H]tyrosine, these effects being seen mainly during the drug application. The amphetamine-evoked release of dopamine in the pars reticulata produced a long lasting reduction in the release of [3H]GABA synthesized from [3H]glutamine in the nucleus ventralis medialis as well as in the paralamellar zone of the nucleus ventralis lateralis. Opposite effects were observed when amphetamine (10(-6) M) was applied in the pars compacta. In complementary experiments, single unit recordings were made in the intermediate part of the pars reticulata, some of the cells being identified by antidromic activation from the nucleus ventralis medialis. Whether applied in the pars reticulata or pars compacta, amphetamine (10(-6) M, 10 min) evoked a reversible decrease in the firing rate of most recorded cells whether or not they were identified as projecting to the nucleus ventralis medialis. Therefore, the decreased release of [3H]GABA in the nucleus ventralis medialis seen following application of amphetamine in the pars reticulata of the substantia nigra could result from an inhibition of nigrothalamic GABAergic neurons. Since the nucleus ventralis medialis is also innervated by GABAergic neurons originating in the entopeduncular nucleus, single unit recordings were made from cells in this nucleus during the application of amphetamine (10(-6) M, 10 min) into the pars compacta of the substantia nigra, some of which were identified antidromically as projecting to the nucleus ventralis medialis. Most cells identified or not were found to be activated during this treatment. These results suggested that the increased release of [3H]GABA seen in the nucleus ventralis medialis following application of amphetamine in the pars compacta of the substantia nigra might be linked to the enhanced firing rate of entopeduncular-thalamic GABAergic neurons.


Design and Synthesis of Galactosylated Bifurcated Ligands with Nanomolar Affinity for Lectin LecA from Pseudomonas aeruginosa.
Lectin A (LecA) from Pseudomonas aeruginosa is an established virulence factor. Glycoclusters that target LecA and are able to compete with human glycoconjugates present on epithelial cells are promising candidates to treat P. aeruginosa infection. A family of 32 glycodendrimers of generation 0 and 1 based on a bifurcated bis-galactoside motif have been designed to interact with LecA. The influences both of the central multivalent core and of the aglycon of these glycodendrimers on their affinity toward LecA have been evaluated by use of a microarray technique, both qualitatively for rapid screening of the binding properties and also quantitatively (Kd ). This has led to high-affinity LecA ligands with Kd values in the low nanomolar range (Kd =22 nm for the best one).


Leucine-Rich Alpha-2-Glycoprotein as a non-invasive biomarker for pediatric acute appendicitis: a systematic review and meta-analysis.
The aim of this study was to analyze the diagnostic performance of Leucine-Rich Alpha-2-Glycoprotein (LRG1) in pediatric acute appendicitis (PAA). We conducted a systematic review of the literature in the main databases of medical bibliography. Two independent reviewers selected the articles and extracted relevant data. Methodological quality was assessed using the QUADAS2 index. A synthesis of the results, standardization of the metrics and 4 random-effect meta-analyses were performed. Eight studies with data from 712 participants (305 patients with confirmed diagnosis of PAA and 407 controls) were included in this review. The random-effect meta-analysis of serum LRG1 (PAA vs control) resulted in a significant mean difference (95% CI) of 46.76 μg/mL (29.26-64.26). The random-effect meta-analysis for unadjusted urinary LRG1 (PAA vs control) resulted in a significant mean difference (95% CI) of 0.61 μg/mL (0.30-0.93). The random-effect meta-analysis (PAA vs control) for urinary LRG1 adjusted for urinary creatinine resulted in a significant mean difference (95% CI) of 0.89 g/mol (0.11-1.66). Conlusion: Urinary LRG1 emerges as a potential non-invasive biomarker for the diagnosis of PAA. On the other hand, due to the high between-study heterogeneity, the results on serum LRG1 should be interpreted with caution. The only study that analyzed salivary LRG1 showed promising results. Further prospective studies are needed to confirm these findings. What is Known: • Pediatric acute appendicitis continues to be a pathology with a high rate of diagnostic error. • Invasive tests, although useful, are a source of stress for patients and their parents. What is New: • LRG1 emerges as a promising urinary and salivary biomarker for the noninvasive diagnosis of pediatric acute appendicitis.


Risk factors associated with mupirocin resistance in meticillin-resistant Staphylococcus aureus.
Implementation of meticillin-resistant Staphylococcus aureus (MRSA) decolonisation programmes has been increasing and the emergence of mupirocin resistance has been reported. However, the patient-level risk factors associated with mupirocin resistance are not clear. In this study, independent predictors of mupirocin resistance in MRSA among Providence Veterans Affairs Medical Center patients with MRSA-positive culture dates between 1 July 2004 and 30 June 2008 were identified using a frequency-matched case-control study. Forty cases (mupirocin-resistant) were matched on culture date quarter and year to 270 controls (mupirocin-susceptible). The adjusted conditional logistic regression model identified three significant independent predictors associated with mupirocin resistance in MRSA: (1) exposure to mupirocin in the year prior to the culture date [odds ratio (OR): 9.84; 95% confidence interval (CI): 2.93-33.09]; (2) Pseudomonas aeruginosa infection in the year before the culture-related admission (4.85; 1.20-19.61); and (3) cefepime use in the year prior to culture (2.80; 1.03-7.58). In sensitivity analyses, previous mupirocin exposure was associated with low-level [minimum inhibitory concentration (MIC) 8-128mg/L; 23 cases, 202 controls; OR: 6.32; 95% CI: 1.58-25.33] and high-level (MIC ≥256mg/L; 17 cases, 151 controls; OR: 11.18; 95% CI: 1.89-66.30) mupirocin resistance. To our knowledge, this is the first case-control study to reveal a strong association between previous mupirocin exposure and subsequent mupirocin resistance in MRSA, with demonstrated robustness in low- and high-level mupirocin resistance. Mupirocin susceptibility monitoring is critical for facilities instituting decolonisation with mupirocin as increased use may reduce effectiveness through resistance.


Genetic diversity of Hepatitis C Virus in Pakistan using Next Generation Sequencing.
In Pakistan, HCV disease is considered a major public health issue with about 10-17 million people suffering with this infection and rate is increasing every day without any hindrance. The currently available Pyrosequencing approach used to analyze complex viral genomes as it can determine minor variants. It is crucial to understand viral evolution and quasispecies diversity in complex viral strains. To assess genetic diversity in patients with HCV using Next Generation Sequencing (NGS) and compare nucleotide diversity of genotype 3a with respect to other genotypes. Intra-host viral diversity of HCV was determined using NGS from 13 chronically HCV infected individuals. NGS of three different regions (E2 (HVR1), NS3 and NS5B) of HCV-3a allowed for a comprehensive analysis of the viral population. Phylogenetic analysis of different HCV genes revealed great variability within the Pakistani population. The average nucleotide diversity for HVR1, NS3 and NS5B was 0.029, 0.011 and 0.010 respectively. Our findings clearly indicate that patient-2 greater quasispecies heterogeneity than other patients of same genotype-3a using phylogenetic and one step network analyses. Initially phylogenetic analysis of these three genes showed that genotype 3a samples have greater genetic diversity. However, no significant difference was determined when nucleotide variability of genotype 3a compared with other genotypes (1a, 1b, 2a & 4a).


A rapid method for evaluation of cell number and viability by flow cytometry.
A simple, rapid and reliable method has been developed for assessing the number and viability of cells, as well as cell size, in suspension culture by the use of flow cytometry. Propidium iodide exclusion is used for viability determination and fluorescent beads serve as an internal standard for cell enumeration. The main advantages of this method are its ability to handle a large number of samples with a high degree of precision and its specificity in detecting viable cells quantitatively in a heterogeneous culture of living and dead cells and debris. The method shows only a fraction of the variation found in the haemacytometer/trypan blue counting method due to its very low operator dependence. CHO - Chinese hamster ovary; FCS - Foetal calf serum; FS - Forward scatter light; MTT - 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide; NCS - newborn calf serum; PBS - Phosphate buffered saline; PI - Propidium iodide; SS - Side scatter light.


Signal integral for optimizing the timing of defibrillation.
The possibility of successful defibrillation decreases with an increased duration of ventricular fibrillation (VF). Futile electrical shocks are inversely correlated with myocardial contractile function and long-term survival. Previous studies have demonstrated that various ECG waveform analyses predict the success of defibrillation. This study investigated whether the absolute amplitude of pre-shock VF waveform is likely to predict the success of defibrillation. ECG recordings of 350 out-of-hospital cardiac arrest (OOHCA) patients were obtained from the automated external defibrillator (AED) and analyzed by the method of signal integral. Successful defibrillation was defined as organized rhythm with heart rate ≥40beat/min commencing within one min of post-shock period and persisting for a minimum of 30s. Signal integral was significantly greater in successful defibrillation than unsuccessful defibrillation (81.76±32.3mV vs. 34.9±15.33mV, p<0.001). The intersection of the sensitivity and specificity curve provided a threshold value of 51mV. The corresponding values of sensitivity, specificity, positive predictive and negative predictive values for successful defibrillation were 90%, 86%, 80% and 93%, respectively. The receiver operator curve further revealed that signal integral predicted the likelihood of successful defibrillation (area under the curve=0.949). Signal integral predicted successful electrical shocks on patients with ventricular fibrillation and have potential to optimize the timing of defibrillation and reduce the number of electrical shocks.


Generalized skeletal involvement of a hematopoietic tumor in a dog.
Generalized polyostotic osteolytic lesions were caused by stage-5 multicentric lymphosarcoma in a dog. Findings were unique, because tumors of bone marrow do not usually result in diffuse bony changes detectable radiographically.


Variants in the CYP2B6 3'UTR Alter In Vitro and In Vivo CYP2B6 Activity: Potential Role of MicroRNAs.
CYP2B6*6 and CYP2B6*18 are the most clinically important variants causing reduced CYP2B6 protein expression and activity. However, these variants do not account for all variability in CYP2B6 activity. Emerging evidence has shown that genetic variants in the 3'UTR may explain variable drug response by altering microRNA regulation. Five 3'UTR variants were associated with significantly altered efavirenz AUC0-48 (8-OH-EFV/EFV) ratios in healthy human volunteers. The rs70950385 (AG>CA) variant, predicted to create a microRNA binding site for miR-1275, was associated with a 33% decreased CYP2B6 activity among normal metabolizers (AG/AG vs. CA/CA (P < 0.05)). In vitro luciferase assays were used to confirm that the CA on the variant allele created a microRNA binding site causing an 11.3% decrease in activity compared to the AG allele when treated with miR-1275 (P = 0.0035). Our results show that a 3'UTR variant contributes to variability in CYP2B6 activity.


Prevalence of and risk factors for depressive and anxiety symptoms in a large sample of Chinese adolescents in the post-COVID-19 era.
Depressive and anxiety symptoms are widespread among adolescents today, creating a large social problem. However, few previous studies have addressed depression and anxiety among adolescents in Chinese cohorts. The aim of this study was to evaluate the prevalence of and risk factors for depressive and anxiety symptoms among Chinese middle school adolescent students in the post-COVID-19 era. A total of 22,380 middle school students from Jiangsu Province were surveyed online, and their general demographic data were collected. The Patient Health Questionnaire-9 (PHQ-9) was used to assess depressive symptoms, and the seven-item Generalized Anxiety Disorder (GAD-7) scale was used to measure anxiety symptoms. Of these participants (aged 12-17 years), 25.6% had depressive symptoms, 26.9% had anxiety symptoms, and 20.6% had a combination of depression and anxiety symptoms. The prevalence of depressive symptoms was higher in female adolescents (27.6%) than in male adolescents (23.7%; χ2 = 45.479, P = 0.000), and the proportion with anxiety symptoms was higher among female adolescents (28.6%) than among male adolescents (25.4%; χ2 = 29.390, P = 0.000). Furthermore, binary logistic regression analysis showed that gender, region, and parental relationship were significantly associated with depressive symptoms among adolescents, while age, gender, region, and parental relationship were significantly associated with anxiety symptoms. Our findings demonstrated that the prevalence of reported depressive and anxiety symptoms in Chinese adolescents are high. Female gender, urban region, and poor parental relationship may be risk factors for depressive and anxiety symptoms. Furthermore, policy makers, schools, and families need to pay more attention to the psychological health of adolescents, develop response plans and take early intervention measures to reduce the prevalence of adolescent depression and anxiety.


IRAK-4 inhibitors. Part 1: a series of amides.
The synthesis and profile of a series of amides are described. Some of these compounds were potent IRAK-4 inhibitors and two examples were evaluated in vivo.


The diadinoxanthin diatoxanthin cycle induces structural rearrangements of the isolated FCP antenna complexes of the pennate diatom Phaeodactylum tricornutum.
The study investigated the influence of the xanthophyll cycle pigments diadinoxanthin (DD) and diatoxanthin (Dt) on the spectroscopic characteristics, structure and protein composition of isolated fucoxanthin chlorophyll protein (FCP) complexes of the pennate diatom Phaeodactylum tricornutum. 77 K fluorescence emission spectra revealed that Dt-containing FCP complexes showed a characteristic long wavelength fluorescence emission at 700 nm at a pH-value of 5 whereas DD-enriched FCPs retained the typical 680 nm fluorescence emission maximum of isolated FCPs. The 700 nm emission in Dt-containing FCPs indicates an aggregation of antenna complexes and is a typical feature of the quenching site Q1 in recent models for non-photochemical fluorescence quenching (NPQ). A comparable long-wavelength fluorescence emission was found in FCP complexes prepared with either triton X-100 or n-dodecyl β-D-maltoside as detergent. A treatment of the FCP complexes at low pH-values in the presence of a high concentration of Mg(2+) ions showed that the extent of FCP aggregation which leads to the 700 nm fluorescence emission is different from the macro-aggregation of antenna complexes in higher plants. Protein analyses by mass spectrometry showed that the protein composition of the DD- and Dt-enriched FCP complexes was comparable. However, the Lhcf6 and Lhcr1 polypeptides were only found in Dt-enriched FCPs isolated with dodecyl maltoside whereas the Lhcf17 protein was only detected in DD-enriched FCPs prepared with triton. With respect to low pH-induced antenna aggregation it is important that the Lhcx1 protein was found in both DD- and Dt-enriched FCPs, albeit with only two peptides with confident scores.


Synthesis of exfoliated multilayer graphene and its putative interactions with SARS-CoV-2 virus investigated through computational studies.
Our work investigates the interaction of synthesized graphene with the SARS-CoV-2 virus using molecular docking and molecular dynamics (MD) simulation method. The layer dependent inhibitory effect of graphene nanosheets on spike receptor-binding domain of 6LZG, complexed with host receptor i.e. angiotensin-converting enzyme 2 (ACE2) of SARS-CoV-2 was investigated through computational study. Graphene sample was synthesized using mechanical exfoliation with shear stress and its mechanism of inhibition towards the SARS-CoV-2 virus was explored by molecular docking and molecular dynamics (MD) simulation method. The thermodynamics study for the free binding energy of graphene towards the SARS-CoV-2 virus was analyzed. The binding energy of graphene towards the virus increased with an increasing number of layers. It shows the highest affinity of -17.5 Kcal/mol in molecular docking while ΔGbinding is in the order of -28.01 ± 0.04 5 Kcal/mol for the seven-layers structure. The increase in carbon layers is associated with an increasing number of edge sp3 -type carbon, providing greater curvature, further increase the surface reactivity responsible for high binding efficiency. The MD simulation data reveals the high inhibition efficiency of the synthesized graphene towards SARS-CoV-2 virus which would help to design future in-vitro studies. The graphene system could find potential applications in personal protective equipment and diagnostic kits.Communicated by Ramaswamy H. Sarma.


Ecological factors that determine Ixodes ricinus tick burdens in the great tit (Parus major), an avian reservoir of Borrelia burgdorferi s.l.
Although bird-tick systems affect the human risk of tick-borne diseases, very little is known about the ecological factors that shape the spatio-temporal variation of tick infestations in terrestrial songbirds. We present a risk model that explains the levels of infestation of Ixodes ricinus, the main vector of Borrelia burgdorferi s.l., during the breeding season of the great tit (Parus major), one of Europe's most abundant avian reservoir hosts of B. burgdorferi s.l. Tit tick burden were modelled as a function of variables summarising vegetation, climate, proxies for mammal abundance and characteristics of individual birds and their nests. Tick loads were positively associated with the relative humidity prior to capture of the bird and the cover of bracken inside its territory. The number of cold winter days prior to the bird's breeding season showed a negative association with tick loads. None of the proxies for mammal abundance correlated with tick loads. Tick loads decreased with age in female tits, whereas they increased with age in male tits. Tick burdens in the parental tits were positively associated with their brood size and negatively correlated with the average nestling body weight. Possible mechanisms include: how tit foraging influences tick encounter rates, host tick resistance mechanisms and the environmental conditions that simultaneously affect tick exposure risk and brood characteristics. We believe this study provides the first detailed insights into the ecological factors that shape tick burden in a terrestrial songbird.


A body weight loss- and health-promoting gut microbiota is established after bariatric surgery in individuals with severe obesity.
Obesity has reached an epidemic level worldwide, and bariatric surgery (BS) has been proven to be the most efficient therapy to reduce severe obesity-related comorbidities. Given that the gut microbiota plays a causal role in obesity development and that surgery may alter the gut environment, investigating the impact of BS on the microbiota in the context of severe obesity is important. Although, alterations at the level of total gut bacteria, total gene content and total metabolite content have started to be disentangled, a clear deficit exists regarding the analysis of the active fraction of the microbiota, which is the fraction that is most reactive to the BS. Here, active gut microbiota and associated metabolic functions were evaluated using shotgun proteomics and metabolomics in 40 severely obese volunteers. Samples from each volunteer were obtained under basal conditions, after a short high protein and calorie-restricted diet, and 1 and 3 months after BS, including laparoscopic surgery through Roux-en-Y Gastric Bypass or Sleeve Gastrectomy. The results revealed for the first time the most active microbes and metabolic flux distribution pre- and post-surgery and deciphered main differences in the way sugars and short-fatty acids are metabolized, demonstrating that less energy-generating and anaerobic metabolism and detoxification mechanisms are promoted post-surgery. A comparison with non-obese proteome data further signified different ways to metabolize sugars and produce short chain fatty acids and deficiencies in proteins involved in iron transport and metabolism in severely obese individuals compared to lean individuals.


Controlling the Selectivity Patterns of Au-Catalyzed Cyclization-Migration Reactions.
As little as 2 mol % of (XPhos)AuNTf2 catalyzes the transformation of a broad range of o-acetylene-substituted styrenes into 1,2-dihydronaphthalenes. Our data suggests that this transformation occurs via a gold-stabilized cyclopropyl carbinyl cation, which triggers either a [1,2] carboxylate shift or a less favorable [1,2] aryl shift. The relative rates of these migrations can be controlled by the identity of the ligand or by stabilizing the mesomeric cation.


Irradiation of primary thalamic and brainstem tumors in a pediatric population. A 33-year experience.
A retrospective analysis of 70 pediatric patients (less than 16 years of age) with histologically proven or presumed primary neoplasms of the thalamus, hypothalamus, and brainstem, treated with combined surgery and postoperative radiotherapy or radiotherapy alone at the Washington University Medical Center from January 1950 through December 1983, is reported. Overall survival for all patients at 5 and 10 years was 34.9% and 32.7%, respectively. Follow-up of the 22 surviving patients ranged from 3.0 to 20.0 years (median, 10.6 years). Statistical analysis of multiple prognostic factors was performed. Prognostic factors found by single variate analysis to significantly influence survival were primary site of disease, extent of surgery, race, cranial nerve paresis at diagnosis, and dose of radiation. Factors evaluated but found to be insignificant were age at diagnosis, duration of symptoms before diagnosis, sex, and volume irradiated. Multivariate analysis revealed that only total radiation dose and race were of prognostic significance.


Taraxacum officinale extract shows antitumor effects on pediatric cancer cells and enhance mistletoe therapy.
While Taraxacum officinale (dandelion) extracts showed antitumor effects on adult cancer cells, effects on pediatric tumor cells as a single agent or in combination with mistletoe extracts are hitherto unknown. The anti-proliferative effects of an aqueous fermented Taraxacum officinale extract (Taraxacum) on a pediatric cancer cell line panel were assessed by cell viability assays (MTT). In two neuroblastoma cell lines, SH-SY5Y and Kelly, the effects on cell cycle distribution (PI staining), mitochondrial integrity (MitoTracker staining), invasion (Boyden chamber assay) and migration (Scratch-assay) as well as the synergistic effects of the co-treatment of Taraxacum and mistletoe preparations (Iscucin® Tiliae or Iscucin® Pini) were investigated. All tested cancer cell lines were more susceptible to Taraxacum than the normal human fibroblast cell line, NHDF-C. In neuroblastoma cell lines Taraxacum caused apoptosis and loss of mitochondrial integrity as well as an inhibition of invasion and migration. The simultaneous therapy of Taraxacum and the mistletoe extracts revealed synergistic effects. This preclinical data support the use of Taraxacum as a potential adjuvant application in pediatric oncology.


Dissociation constants of 4-acetoxy-piperidines and -thiacyclohexanes at the muscarinic receptor.
The dissociation constants (KA) and the relative intrinsic efficacies (e) of 4-acetoxy-piperidines and -thiacyclohexanes were determined on the guinea-pig isolated left atrium. The differences in the muscarinic potencies are associated with differences in affinities and efficacies, respectively.


Electric birefringence of DNA and chromatin. Influence of divalent cations.
The effects of divalent cations on the DNA and chromatin conformation have been investigated by electric birefringence and birefringence relaxation measurements at low and constant ionic strength (0.001). An important decrease of the intrinsic optical anisotropy of DNA has been found in the presence of Mn2+ and Cu2+, but not with Mg2+. A complex variation of the mean relaxation time with the ratio I/P of ion to DNA-phosphate molar concentration has been evidenced in the presence of Mn2+ and Cu2+, while the mean relaxation time monotonously decreased in the presence of Mg2+. These observations are interpreted in terms of a specific organization of DNA in a compact, rigid structure, in the presence of Mn2+ and Cu2+, and a non-specific coiling in the presence of Mg2+. Drastic conformational changes encountered by chromatin in the presence of Mg2+ and Mn2+ cations have also been evidenced through electric birefringence measurements. They are interpreted by the formation of a superhelical compact arrangement of nucleosome strings which yielded a reversal of the birefringence sign with respect to the negative anisotropy observed in the presence of Na+ ions. The removal of the histone H1 prevented the appearance of this quaternary structure. More extended fragments of the chromatin chain obtained by ECTHAM chromatography of sonicated chromatin could not afford such compact arrangements.


An experimental study of dendritic cells-mediated immunotherapy against intracranial gliomas in rats.
To investigate the effect of dendritic cells(DC) pulsed with apoptotic tumor cells for treatment of intracranial gliomas in rats. C6 glioma cells were injected into brain of Wistar rats under stereotactic monitor to establish an animal model of glioma. The precursors of DCs were isolated from bone marrow of rats, stimulated in vitro with recombinent rat granulocyte-macrophage colony-stimulating factor (rrGM-CSF) and interleukin-4 (rrIL-4). These DCs were then pulsed ex vivo with apoptotic C6 glioma cells induced by heating and subsequently injected subcutaneously into rats harboring intracranial C6 glioma. Rats were treated with five weekly subcutaneous injections of either control media, unpulsed DCs, or DCs pulsed with apoptotic tumor cells. The animals were followed for survival, volume of tumor by MRI, CD8 + T cells, cytotoxicity assay in vitro and proliferational function of lymphocytes in peripheral blood were determined by flow cytometry(FCM). The concentration of cytokines interferon-gamma (IFN-gamma) and interleukin-10(IL-10) were monitored through enzyme-linked immunosorbent assay(ELISA) using ELISAkit. Our results indicated that C6 glioma model rats treated with apoptotic tumor cells pulsed DCs prolonged survival, inhibited the tumor growth and increased the level of CD8 + T lymphocytes in peripheral blood comparing with control group. Cytotoxicity assay suggested that vaccination with these apoptotic cells pulsed DCs can induce cytotoxic T lymphocytes response against C6 tumor cells compared with control group. Furthermore, significantly enhanced IFN-gamma and reduced IL-10(even undetectable) were observed in peripheral blood of rats treated with pulsed-DCs. No evident autoimmune response were detected. Our data demonstrated that systemic vaccination with DCs pulsed with apoptotic cells is a safe and effective immunotherapy for intracranial glioma.


Nitrogen, phenolic acids, and other feeding cues for salt marsh detritivores.
A number of feeding cues determine the palatability of detritus to detritivorous invertebrates. In salt marsh detritus the feeding cues include flavor provided by phenolics such as ferulic acid, pH, salinity, and nitrogen content. We examined the feeding responses to each cue by using experimental manipulations where we changed concentrations of these chemical cues. The palatability of detritus of the salt marsh grass Spartina alterniflora to the detritivorous snail Melampus bidentatus is reduced by increases in ferulic acid in the detritus. The acidity of the acid is partly responsible for inhibition of feeding, but other flavors of the ferulic acid are the major factor. Changes in salinity makes detritus more or less palatable to different species of detritivores. Available nitrogen confers greater palatability to detritus.In the field the feeding cues are all present simultaneously, and detritivores feed based on a hierarchy of cues. For M. bidentatus the presence of sufficient available nitrogen overwhelms the response to ferulic acid, the second most important cue. Salinity and pH, although used as discriminatory cues by themselves, are located lower in the hierarchy than nitrogen and ferulic acid.As detritus ages in the marsh, nitrogen content changes. Similarly, detritus from eutrophied environments shows enhanced nitrogen content. The differences in palatability of new and old detritus, and from eutrophic and non-eutrophic environments, suggests that detritivores respond not to total nitrogen but rather to the availabel nitrogen fractions. The increase in lignin found in old and eutrophic detritus may increase the binding of available nitrogen, and hence reduce the palatability of detritus.


A Feasibility Pilot Study on the Use of Telemedicine for the Examination of the Knee Joint.
In times of a pandemic threat, such as COVID-19, and the need for reduced direct doctor-patient contact, internet-based telemedicine has attracted more and more attention as a surrogate service. Suspending the diagnosis and treatment of non-virus related diseases for longer periods of time is not a viable option since this would only exacerbate problems on the patient and national level. The need for alternative treatment modalities increased rather quickly. So far, telemedical applications have mainly focused on teleradiological diagnosis, follow-up and monitoring of psychiatric and internal diseases, as well as geriatric patient care. As far as these authors are aware, orthopaedic physical examination of the knee joint, including trauma work-up, has not been the subject of any studies to date. This feasibility study explores how video consultation can be designed and implemented in the context of history taking and physical examination in knee joint complaints. 21 patient actors (PA) with simulated complaints of the knee joint were examined individually for each diagnosis, first via video consultation and then directly by a specialist (SP). One PA group has a medical background, the other was made up of laypersons. The time was measured for both types of consultation. The physician documented the detected symptoms, the quality of implementation of the self-examination steps, and the derived diagnosis on an assessment form. After completion of both consultation sessions, the PAs were handed a questionnaire on the respective examination modality. With the video consultation the examination lasted 8.63 (± 2.5) minutes on average and with the regular consultation in person 5.63 (± 1.7) minutes (p < 0.001). For the group with medical background the examination lasted 7.67 (± 1.4) minutes on average, while for the lay group the video consultation took 9.7 (± 3.1) minutes (p = 0.049). With increased age, the video consultation was prolonged (p = 0.032; r = 0.47). The mean value for self-examination of leg axis, gait pattern and degrees of freedom was 9.32 (± 0.4) of 10 points. The following functional tests resulted in lower mean values (points): Payr 7.2 (± 2.3), Merke 5.9 (± 2.8), no-touch Lachmann 6.4 (± 2.7), gravity sign-recurvatum 6.7 (± 2.4). The mean grade by the PAs for the feasibility of self-examination was 2.43 (± 0.98) out of 5 points. The video consultation for musculoskeletal complaints of the knee joint allows exploratory remote examination and helps to minimise the number of patients in hospitals and practices. It takes longer for the physician to perform and does not permit functional testing for ligament injuries of the knee joint. In its present form, telemedical examination is not able to fully replace personal consultation.


Swiss doctors' attitudes towards end-of-life decisions and their determinants: a comparison of three language regions.
To investigate attitudes to end-of-life decisions, and the influence of cultural factors and of doctors' personal characteristics on these attitudes. As part of a European research project (EURELD), a study on attitudes towards medical end-of-life decisions was conducted among doctors in the German-, French- and Italian-speaking areas of Switzerland. A written questionnaire was sent to a random sample of nine different types of specialist; it presented 14 statements on end-of-life decisions and doctors were asked whether they agreed or disagreed with them. The response rate was 64%. 1360 questionnaires were studied. The results show general agreement with statements on the alleviation of pain and other symptoms with possible life-shortening effect, as well as on non-treatment decisions. The language region was a strong determinant of agreement on some attitudes towards end-of-life decisions. Agreement on the use of lethal drugs and alleviation of pain and other symptoms with possible life-shortening effect was higher among French-speaking than among German- and Italian-speaking doctors. For nontreatment decisions, agreement was higher in the German-speaking region than in the French- and Italian-speaking regions of the country. Italian-speaking doctors were strongly opposed to any kind of end-of-life decision. Religious believers and those who attended a larger number of terminal patients tended to disagree more often with end-of-life decisions than the other doctors. In end-of-life decision-making, Switzerland represents "Europe in miniature". The impact on end-of-life decisions of cultural factors and the number of terminal patients attended needs further consideration.


COVID-19 Government Response Event Dataset (CoronaNet v.1.0).
Governments worldwide have implemented countless policies in response to the COVID-19 pandemic. We present an initial public release of a large hand-coded dataset of over 13,000 such policy announcements across more than 195 countries. The dataset is updated daily, with a 5-day lag for validity checking. We document policies across numerous dimensions, including the type of policy, national versus subnational enforcement, the specific human group and geographical region targeted by the policy, and the time frame within which each policy is implemented. We further analyse the dataset using a Bayesian measurement model, which shows the quick acceleration of the adoption of costly policies across countries beginning in mid-March 2020 through 24 May 2020. We believe that these data will be instrumental for helping policymakers and researchers assess, among other objectives, how effective different policies are in addressing the spread and health outcomes of COVID-19.


Effect of resistance to third-generation cephalosporins on morbidity and mortality from bloodstream infections in Blantyre, Malawi: a prospective cohort study.
The burden of antimicrobial resistance is a major threat to global health; however, prospective clinical outcome data from Africa are scarce. In Malawi, third-generation cephalosporins are the antibiotics of choice in patients admitted to hospital despite a rapid proliferation of resistance to these drugs. We aimed to quantify the effect of resistance to third-generation cephalosporins on mortality and length of hospital stay among patients with bloodstream infections. We did a prospective cohort study of patients admitted to Queen Elizabeth Central Hospital in Blantyre, Malawi. Patients of all ages who had positive blood cultures for Enterobacterales were included, with the exception of those from the genus Salmonella, and were followed up for 180 days. We characterised blood culture isolates using whole-genome sequencing and used Cox regression models to estimate the effect of resistance to third-generation cephalosporins on length of hospital stay, in-hospital mortality, and survival. Between Jan 31, 2018, and Jan 13, 2020, we recruited 326 patients, from whom 220 (68%) of 326 isolates were resistant to third-generation cephalosporins. The case fatality proportion was 45% (99 of 220) in patients with bloodstream infections that were resistant to third-generation cephalosporins, and 34% (36 of 106) in patients with bloodstream infections that were sensitive to third-generation cephalosporins. Resistance to third-generation cephalosporins was associated with an increased probability of in-hospital mortality (hazard ratio [HR] 1·44, 95% CI 1·02-2·04), longer hospital stays (1·5 days, 1·0-2·0) and decreased probability of discharge alive (HR 0·31, 0·22-0·45). Whole-genome sequencing showed a high diversity of sequence types of both Escherichia coli and Klebsiella pneumoniae. Although isolates associated with death were distributed across clades, we identified three E coli clades (ST410, ST617, and ST648) that were isolated from 14 patients who all died. Resistance to third-generation cephalosporins is associated with increased mortality and longer hospital stays in patients with bloodstream infections in Malawi. These data show the urgent need for allocation of resources towards antimicrobial resistance mitigation strategies in Africa. Wellcome Trust and Wellcome Asia and Africa Programme.


Immunization of NMRI mice against virulent Toxoplasma gondii. Differing efficacy of eleven cyst-forming Toxoplasma strains.
Mice were infected with eleven cyst-forming Toxoplasma strains of varying virulence and challenged 1 month later with highly virulent BK strain parasites. The early cellular reaction in vivo was estimated by collecting the peritoneal exudates 24 h after challenge. This consisted of 54.34--77.61% lymphocytes and 0-8.88% infected macrophages in the eleven immunized groups in contrast to 27.17% lymphocytes and 18.64% infected macrophages in the control group. The peritoneal exudate 72 h after challenge comprised of 55.88-73.86% lymphocytes and 0-6.97% infected macrophages compared to 25.88% lymphocytes and 92% infected macrophages in the control group. Following the virulent challenge, deaths occurred in seven of the eleven groups immunized with live strains and ranged 5-42% at the end of a 6-week observation period. The most virulent of the Toxoplasma strains used - Alt and Gail - gave higher mortality while the least virulent ones - 558, 1070, K8 and KSU - were solidly resistant. The significantly different mortality obtained with strains Alt, Gail and Witting in a similar experiment performed at an interval of 7 months is discussed.


A developmental investigation of the other-race categorization advantage in a multiracial population: Contrasting social categorization and perceptual expertise accounts.
Most prior studies of the other-race categorization advantage have been conducted in predominantly monoracial societies. This limitation has left open the question of whether tendencies to more rapidly and accurately categorize other-race faces reflect social categorization (own-race vs. other-race) or perceptual expertise (frequent exposure vs. infrequent exposure). To address this question, we tested Malay and Malaysian Chinese children (9- and 10-year-olds) and adults on (a) own-race faces (i.e., Malay faces for Malay participants and Chinese faces for Malaysian Chinese participants), (b) high-frequency other-race faces (i.e., Chinese faces for Malay participants and Malay faces for Malaysian Chinese participants), and (c) low-frequency other-race faces (i.e., Caucasian faces). Whereas the other-race categorization advantage was in evidence in the accuracy data of Malay adults, other aspects of performance were supportive of either the social categorization or perceptual expertise accounts and were dependent on the race (Malay vs. Chinese) or age (child vs. adult) of the participants. Of particular significance is the finding that Malaysian Chinese children and adults categorized own-race Chinese faces more rapidly than high-frequency other-race Malay faces. Thus, in accord with a perceptual expertise account, the other-race categorization advantage seems to be more an advantage for racial categories of lesser experience regardless of whether these face categories are own-race or other-race.


Multienergy Computed Tomography Applications: Trauma.
Computed tomography (CT) plays an important role in trauma because imaging findings directly impact management. Advances in CT technology, specifically multienergy CT, have allowed for simultaneous acquisition of images at low and high kilovolt peaks. This technique allows for differentiation of materials given that materials have different absorption behaviors. Various multienergy CT postprocessing applications are helpful in the setting of trauma, including bone subtraction, virtual monoenergetic imaging, iodine-selective imaging, and virtual noncontrast imaging. These techniques have been applied from head to toe and have been used to improve image quality and increase conspicuity of injuries, which increases diagnostic confidence.


Soluble PD-L1 and B7-H4 serum levels during the course of physiological pregnancy.
The aim of this study was to evaluate the soluble programmed death-ligand (sPD-L1) and soluble B7-H4 (sB7-H4) serum concentration levels longitudinal throughout the three trimesters of uncomplicated pregnancies. METHOD OF THE STUDY: sPD-L1 and sB7-H4 levels were determined with enzyme-linked immunosorbent assay (ELISA). The patients (n = 26) were divided into three groups according to the pregnancy trimester. Among 26 women involved in the study 14 had longitudinal sB7-H4 and sPD-L1 measurements in each trimester of pregnancy. During the course of pregnancy, the sB7-H4 blood serum levels were significant higher in second trimester than in first and third trimester, whereas sPD-L1 levels increased significantly over the course of pregnancy. The highest serum levels of sPD-L1 in the third trimester suggest increasing suppression of maternal immunity throughout pregnancy, whereas elevated sB7-H4 concentration levels in second trimester suggests different profile of T-cell regulation in physiological pregnancy.


Exosomal circ-CACNG2 promotes cardiomyocyte apoptosis in multiple myeloma via modulating miR-197-3p/caspase3 axis.
Multiple myeloma (MM) secreted exosomes are essential in MM-related complications such as osteolytic bone lesions and renal failure, but their role and underlying mechanism in cardiac complications has not yet been clarified. Here, we investigated the effects of U266 (a MM cell line) exosomes (U266-exo) on regulating the viability, cell cycle, oxidative stress and apoptosis of H9C2 cells and the role of circ-CACNG2 in these effects. We found that U266-exo coculture significantly inhibited viability and promoted apoptosis of H9C2 cells, and serum exosomes of MM patients harbored high level of circ-CACNG2. The clinical data analyses indicated that circ-CACNG2 was an independent prognostic and diagnostic indicator of MM-related cardiac complications. Also, in vitro experiments showed that circ-CACNG2 inhibited viability and promoted apoptosis of H9C2 cells. RIPA, pull-down assays, dual-luciferase reporter assays, and RNA FISH assays revealed that miR-197-3p could bind to circ-CACNG2 and caspase3 directly. Rescue experiments proved that circ-CACNG2 can increase the expression of caspase3 by binding to and decreasing the expression of miR-197-3p. In conclusion, MM-exosomes could inhibit cardiomyocyte viability and promote apoptosis partially through circ-CACNG2/miR-197-3p/caspase3 axis.


Endothelin and ischaemic arrhythmias-antiarrhythmic or arrhythmogenic?
The aim of this study was to investigate the influence of endogenously released and exogenously applied endothelin-1 (ET-1) on ischaemia-induced arrhythmias. Ischaemia was induced in pentobarbitone-anaesthetised rats by ligation of a coronary artery for 30 min. To determine the role of endogenous ET-1 in ischaemic arrhythmias, either the ETA receptor antagonist BQ123 (50 micrograms/kg/min, i.v.; n = 10) or the ETB receptor antagonist PD161721 (0.1 or 1 mg/kg i.v.; n = 10 per group) was administered before the onset of ischaemia. To assess the influence of exogenous ET-1 on arrhythmias, ET-1 (1.6 nmol/kg i.v.) was administered 5 min before ischaemia in the absence (n = 12) or presence of BQ123 (n = 10) or PD161721 (n = 10). The total number of ventricular ectopic beats (VEB's) were counted and expressed as median (Q1-Q3) and the incidence of ventricular fibrillation (VF) and ventricular tachycardia (VT) in each group was determined. Mean arterial blood pressure (MABP) and heart rate (HR) were measured. In control animals (n = 20), the incidence of VF was 65% and the total VEB count was 2775 (1870-4041). Both BQ123 and the higher dose of PD161721 reduced the VEB count to 654 (348-1489; P < 0.05) and 782 (432-1153; P < 0.05) respectively. Only PD161721 reduced the incidence of VF (to 10%; P < 0.05). Administration of ET-1 reduced VEB's to 1530 (1204-2017); P < 0.05) and the incidence of VF to 17% (P < 0.05). Neither PD161721 nor BQ123 modified this antiarrhythmic effect of ET-1, but rather enhanced the reduction in arrhythmias. Before occlusion, ET-1 caused a transient fall in MABP (from 107 +/- 3 to 63 +/- 3 mmHg; P < 0.05). PD161721, but not BQ123, partially blocked this effect. Upon occlusion, MABP fell in control animals (from 106 +/- 4 to 67 +/- 4 mmHg at 1 min post-occlusion; P < 0.05). This was significantly attenuated by ET-1, although neither of the antagonists were able to block this effect of ET-1. ET-1 released endogenously during ischaemia is arrhythmogenic whereas exogenous application of ET-1 may, under certain conditions, be antiarrhythmic.


Diffuse reflectance of short-fiber-reinforced composites aligned by an electric field.
This study aims to characterize the translucency of aligned, short-fiber composites by determining the effects of filler particle orientation on the Kubelka-Munk absorption and scattering coefficients. Rectangular composite specimens (n = 3) were filled with very short E-glass fibers. The fibers were oriented random, perpendicular, and parallel to the surface normal using an alternating electric field of 0.75 kV/mm. Diffuse reflectances of the composites on white and black backings were acquired with a spectrophotometer. The Kubelka-Munk model was then employed to calculate absorption and scattering coefficients. The ordering of the reflectances on a white backing is neither the same nor the reverse of the reflectances on the black backing. The effects of orientation were different for the absorption and scattering coefficients. Orientation parallel to the average light flux notably decreases the amount of absorption, while perpendicular orientation appreciably increases the amount of scattering. Since orientation affects the absorption and scattering coefficients differently, the ordering of the reflectances may be different when the backing is varied. This is because the translucency is composed of two parameters (absorption and scattering) and cannot be adequately summarized with one parameter such as transmittance or reflectance. Therefore, the use of a diffuse reflectance model, such as Kubelka-Munk, is essential to a quantitative understanding of the translucency effects of filler orientation. Understanding how the filler orientation affects diffuse reflectance of composites will yield insight as to how the orientation of enamel rods affects the diffuse reflectance in teeth by analogy.


A simple and fast LC-MS/MS method for the routine measurement of cabozantinib, olaparib, palbociclib, pazopanib, sorafenib, sunitinib and its main active metabolite in human plasma.
Targeted therapies such as cabozantinib (CABO), pazopanib (PAZO), sorafenib (SORA), sunitinib (SUNI) and its main active metabolite N-desethyl-sunitinib (DST-SUNI), olaparib (OLA) and palbociclib (PALBO) display large pharmacokinetics variability impacting their responses in terms of efficacy or toxicity. For the monitoring of these drugs, an analytical method allowing to routinely measure their concentrations in human plasma is needed. Such a method has been developed and validated and is presented here. The chromatographic separation is achieved on a Zorbax Bonus-RP analytical column using an isocratic elution of 92% V/V of acetonitrile and 8% of water in 0.1% formic acid at a flow rate of 500 µl/min for 0.5 min and then 300 µl/min for 2 min. After a liquid-liquid extraction of plasma samples, a step of filtration is performed. This method was validated based on the EMA and French committee of accreditation guidelines. The analysis time is 2.5 min per run, and all analytes eluted within 0.53-1.61 min. The standard curves are linear over the range from 1 to 380 ng/ml for SUNI; from 4.3 to 450 ng/ml for DST-SUNI; from 6 to 1000 ng/ml for PALBO; from 75 to 5000 ng/ml for CABO, from 0.17 to 20 µg/ml for OLA; from 0.35 to 40 µg/ml for SORA and from 1.7 to 200 µg/ml for PAZO. The method also showed satisfactory results in terms precision (below 9.5% for within-run and below 13% for between-run) and accuracy (below 13.5% for within-run and below 14% for between-run). After sampling, all the compounds are stable in whole blood at ambient temperature at least for 6 h and plasma are stable for 48 h at ambient temperature or 4 °C. The method presented here allows to measure the concentrations of 7 targeted therapies in a routine setting. We moreover present here a method that is, to our knowledge, one of the first detailed method aimed at the measurement of palbociclib in human plasma in a routine setting, together with data useful for the management of samples in routine hospital practice.