The mitochondrial transcription machinery genes are upregulated in acute myeloid leukemia and associated with poor clinical outcome.
Acute myeloid leukemia (AML) is characterized by rapid growth of abnormal blasts that overcrowd normal hematopoiesis. Defective mitochondrial biogenesis has been implicated in AML, which we believe is partly due to the deregulation of the mitochondrial transcription machinery (MTM) genes influencing the expression of mitochondrial genes. Here, we aim to characterize MTM gene upregulation in AML. Molecular and clinical patient data were retrieved from several public AML datasets. Kaplan-Meier survival curves were used to compare overall survival between patients, while Mann-Whitney U's non-parametric and Fisher's exact test were used for comparing continuous and categorical variables, respectively. The MTM genes TFB1M, TFB2M, TFAM, and POLRMT were upregulated in patients with AML compared with healthy donors. Upregulation of one or more of these genes was associated with higher percentage of peripheral blood blasts (P = 0.002), normal cytogenetic status (P = 0.027) and NPM1 mutations (P = 0.009). Additionally, patients with high expression of MTM genes (Z ≥ 1) had shorter median overall survival compared with low MTM gene expression (Z < 1) (months: 11.8 vs 24.1, P = 0.027; multivariate survival analysis Cox Proportional Hazards model, HR: 1.82 (1.22-2.70); p-value: 0.003). The mitochondrial transcriptional machinery is upregulated and associated with worse clinical outcome in patients with AML and may present a viable therapeutic target.


Microelectrode array recordings of cardiac action potentials as a high throughput method to evaluate pesticide toxicity.
The threat of environmental pollution, biological warfare agent dissemination and new diseases in recent decades has increased research into cell-based biosensors. The creation of this class of sensors could specifically aid the detection of toxic chemicals and their effects in the environment, such as pyrethroid pesticides. Pyrethroids are synthetic pesticides that have been used increasingly over the last decade to replace other pesticides like DDT. In this study we used a high-throughput method to detect pyrethroids by using multielectrode extracellular recordings from cardiac cells. The data from this cell-electrode hybrid system was compared to published results obtained with patch-clamp electrophysiology and also used as an alternative method to further understand pyrethroid effects. Our biosensor consisted of a confluent monolayer of cardiac myocytes cultured on microelectrode arrays (MEA) composed of 60 substrate-integrated electrodes. Spontaneous activity of these beating cells produced extracellular field potentials in the range of 100 microV to nearly 1200 microV with a beating frequency of 0.5-4 Hz. All of the tested pyrethroids; alpha-Cypermethrin, Tetramethrin and Tefluthrin, produced similar changes in the electrophysiological properties of the cardiac myocytes, namely reduced beating frequency and amplitude. The sensitivity of our toxin detection method was comparable to earlier patch-clamp studies, which indicates that, in specific applications, high-throughput extracellular methods can replace single-cell studies. Moreover, the similar effect of all three pyrethroids on the measured parameters suggests, that not only detection of the toxins but, their classification might also be possible with this method. Overall our results support the idea that whole cell biosensors might be viable alternatives when compared to current toxin detection methods.


Hybrid biofilm-membrane bioreactor (Bf-MBR) for minimization of bulk liquid-phase organic substances and its positive effect on membrane permeability.
Four biofilm membrane bioreactors (Bf-MBRs) with various fixed carrier volumes (C:M) were operated in parallel to investigate the effect of attached-growth mode biomass involvement to the change of liquid-phase organics characteristics and membrane permeability, by comparing with conventional MBR. The experiments displayed that C:M and co-existence of biofilm with suspended solids in Bf-MBRs resulted in slight difference in pollutants removal effectiveness, and in rather distinct biomass properties and bacterial activities. The membrane permeability and specific resistance of bulk suspension of Bf-MBRs related closely with the liquid-phase organic substance, including soluble microbial products (SMP) and biopolymer cluster (BPC). Compared with conventional MBR, Bf-MBR with proper C:M had a low total biomass content and food-chain, where biofilm formation and its dominance affected liquid-phase organics, especially through reducing their content and minimizing strongly and weakly hydrophobic components with small molecular weight, and thus to mitigate membrane fouling significantly.


Circadian rhythms in obsessive-compulsive disorder.
The etiopathology and neurobiology of obsessive-compulsive disorder (OCD) are not fully understood. As for altered circadian rhythms associated with OCD, hormonal dysregulation and a delayed sleep phase have come into the focus of research. The novel antidepressant agomelatine is able to resynchronize circadian rhythms and the augmentative administration of this compound has been shown to be of benefit in some OCD patients who are refractory to common forms of pharmacotherapy. Adjunctive chronotherapy might also enhance the outcome in treatment-refractory OCD. The present review summarises the findings regarding circadian abnormalities in OCD.


A Preliminary Study about the Potential Effects of Heavy Metals on the Human Male Reproductive Parameters in HIV-Infected Population in China.
Due to the inconsistent effects of human immunodeficiency virus (HIV) on the human male reproduction in previous studies and the impacts of environmental exposures, such as heavy metals, on male reproduction receiving little attention in HIV-infected population, the aim of present study was to investigate whether heavy metals have potential effects on reproductive parameters in HIV-infected men. The current study assessed the associations between semen quality or serum hormone and concentration of the three heavy metal toxicants (lead (Pb), cadmium (Cd), and zinc (Zn)) in seminal, urine, and serum, and 50 HIV-infected men were recruited in the present study. Concentrations of Pb, Cd, and Zn were measured in three fluids by graphite furnace atomic absorption spectrophotometer. Semen analyses were performed according to World Health Organization criteria. Serum samples were analyzed for follicle-stimulating hormone, luteinizing hormone, and testosterone. HIV RNA viral load was determined by HIV virus loads kit. Spearman's rank correlations were used for correlation analyses. The results showed that the concentrations of Pb, Cd, and Zn were significantly correlated with semen quality and serum hormone. HIV-1 virus loads were significantly associated with increased seminal Pb. However, HIV-1 virus loads were not statistically associated with semen quality and serum hormone. Our findings suggested that environmental heavy metals had potential effects on reproductive parameters in HIV-infected men in China.


Circuit and plasticity defects in the developing somatosensory cortex of FMR1 knock-out mice.
Silencing of the Fmr1 gene causes fragile X syndrome. Although defects in synaptic plasticity in the cerebral cortex have been linked to cognitive impairments in Fmr1 knock-out (ko) mice, the specific cortical circuits affected in the syndrome are unknown. Here, we investigated the development of excitatory projections in the barrel cortex of Fmr1 ko mice. In 2-week-old Fmr1 ko mice, a major ascending projection connecting layer 4 (L4) to L3 (L4-->L3), was defective in multiple and independent ways: its strength was reduced, caused by a lower connection probability; the axonal arbors of L4 cells were spatially diffuse in L2/3; the L4-->L3 projection did not show experience-dependent plasticity. By 3 weeks, the strength of the L4-->L3 projection was similar to that of wild type. Our data indicate that Fmr1 shapes sensory cortical circuits during a developmental critical period.


Are free fatty acids effective taste stimuli in humans? Presented at the symposium "The Taste for Fat: New Discoveries on the Role of Fat in Sensory Perception, Metabolism, Sensory Pleasure and Beyond" held at the iNstitute of Food Technologists 2011 Annual Meeting, New Orleans, LA, June 12, 2011.
The popularity of low- and reduced-fat foods has increased as consumers seek to decrease their energy consumption. Fat replacers may be used in fat-reduced products to maintain their sensory properties. However, these ingredients have been largely formulated to replicate nongustatory properties of fats to foods and have only achieved moderate success. There is increasing evidence that fats also activate the taste system and uniquely evoke responses that may influence product acceptance. Work supporting a taste component of fat has prompted questions about whether fat constitutes an additional "primary" or "basic" taste quality. This review briefly summarizes this evidence, focusing on human studies, when possible. Effective stimuli, possible receptors, and physiological changes due to oral fat exposure are discussed. Some studies suggest that there are fatty acid tasters and nontasters and if verified could have implications for targeted product development.


Treating hypertension in the elderly.
This article discusses various topics related to treating hypertension in the elderly, including pseudohypertension, systolic hypertension, characteristics of young and elderly hypertensive patients, diagnostic considerations in evaluating elderly hypertensive patients, and general therapeutic considerations.


Interaction between antidepressants and d-amphetamine on variable-interval performance.
Four experiments were carried out investigating the interactions between some antidepressant drugs (imipramine, desipramine, fluvoxamine, trazodone (4 and 8 mg/kg) and d-amphetamine (0.1-3.2 mg/kg) on operant behaviour maintained under a variable-interval 80-s schedule of sucrose reinforcement; each experiment employed 12 rats. d-Amphetamine exerted a dose-related suppressant effect on response rate. Imipramine and desipramine given alone had no effect on response rate, whereas fluvoxamine (both doses) and the higher dose of trazodone produced significant increases in response rate. Pretreatment with imipramine, desipiramine or fluvoxamine significantly potentiated the suppressant effect of d-amphetamine on responding; pretreatment with trazodone had no significant effect. The potentiating effect of imipramine and desipramine may be related to their well known uptake blocking actions. The fact that fluvoxamine, a selective inhibitor of 5-hydroxytryptamine (5HT) uptake, also potentiated the effect of d-amphetamine suggests that the suppressant effect of d-amphetamine on operant behaviour may involve 5HT as well as catecholamine release. The lack of effect of trazodone may reflect its failure to influence uptake mechanisms. On the basis of a formal model couched in terms of Herrnstein's (1970) equation, it is suggested that imipramine, desipramine and fluvoxamine may have enhanced d-amphetamine's ability to reduce response capacity; it is suggested that the data do not provide evidence for an interaction between the antidepressants and the putative "motivation-enhancing" effect of d-amphetamine.


Second German heavy-metal survey by means of mosses, and comparison of the first and second approach in Germany and other European countries.
This paper shows the geographic distribution in Germany of iron (Fe), nickel (Ni) and lead (Pb) analyzed in mosses in 1995/96 and compares it with the results of the 1990/91 pilot study within a European moss-monitoring programme. Other elements (As, Cd, Cr, Cu, Ti, V, Zn) are compared on basis of the overall element medians for Germany of the 1990/91 and 1995/96 survey. Samples of Pleurozium schreberi, Scleropodium purum, Hypnum cupressiforme and Hylocomium splendens were taken at a total of 1026 sites. In the 1995/96 monitoring campaign, 95% of the original sites of the 1990/91 study were resampled. The results from 1995/96 display local elevated values and many cases of areas affected by known sources of heavy-metal emissions. The industrialized and urban regions of Germany are shown up clearly by the 1995/96 moss-monitoring results: the Ruhr area, parts of Saarland and Baden-Württemberg, as well as areas in eastern Germany. Relatively low values for many elements were found in large areas of Lower Saxony and Bavaria. A comparison of the results of the 1990/91 and 1995/96 moss-monitoring programmes shows a fall in the concentration of the presented elements (except cadmium, copper and zinc) over the relevant period. Especially in the former GDR, chromium (Cr), iron (Fe), titanium (Ti) and vanadium (V) decreased significantly. This is, firstly, a reflection of the closure of and/or technological improvements to large power plants; secondly it is due to the fact that lignite has given way to other fuels. Vanadium (V) and nickel (Ni), typical constituents of crude oil, also show a decrease in the western part and thus document changes in the type of fuel consumed. The significant fall in lead concentration in 1995/96 as compared to 1990/91 in what used to be East and West Germany probably results from the increasing use of lead-free petrol. A comparison of the median values for 1990/91 and 1995/96 in mosses to the rate of emission of heavy metals in Germany for 1990 and 1995 shows similar trends in the case of elements such as arsenic (As), chromium (Cr), nickel (Ni), and lead (Pb). The comparison of the medians of the elements analyzed for 19 European countries indicates for most of the elements a general tendency to lower values in 1995, except for Lithuania, Netherlands, Portugal, Italy and United Kingdom.


High-frequency oscillatory ventilation with volume guarantee: a single-centre experience.
High-frequency oscillatory ventilation (HFOV) is widely used in neonatology. The Dräger Babylog VN500 ventilator offers volume-guaranteed HFOV (HFOV-VG) mode when the high-frequency tidal volume (VThf) to be delivered can be set. We investigated how HFOV-VG maintains VThf in the short and longer term and how it affects other ventilator parameters and blood gases. We downloaded ~3.2 million seconds (36.7 days) of ventilator data from 17 infants ventilated using HFOV-VG during clinical care with 1 Hz sampling rate. To process and analyse the data, we used the Python computer language. Overall, the median VThf was 1.93 mL/kg (IQR 1.64-2.45 mL/kg). The difference between set and delivered tidal volume was <0.2 mL/kg for 83% of time. In the individual recordings, the median VThf ranged between 1.44 and 3.31 mL/kg. During HFOV-VG, the VThf varied from 1 second to another, but it was very close to the target value when averaged over 5 min periods. After weight correction, the VThf or the diffusion coefficient of carbon dioxide (DCO2) showed weak inverse correlation with partial pressure of CO2(pCO2) (for VThf, r=-0.162, 95% CI -0.282 to -0.037, p=0.01). Uncorrected values showed no correlation. Of the 53 blood gas measurements taken when VThf was >2.5 mL/kg, there were only six (11%) with a pCO2 >8 kPa. During HFOV-VG, the tidal volume of oscillations varies in the short term but is maintained very close to the target over the longer term. VThf or DCO2 have poor correlation with CO2 levels but a volume of >2.5 mL/kg VThf is rarely needed.


Effect of ligamenta flava hypertrophy on lumbar disc herniation with contralateral symptoms and signs: a clinical and morphometric study.
The purpose of this study was to determine whether ligamentum flavum hypertrophy among disc herniated patients causes contralateral pain symptoms. For this reason we measured the thickness of the ligament in disc herniated patients with ipsilateral or contralateral symptoms. Two hundred disc herniated patients with ipsilateral symptoms as group I were compared with five disc herniated patients with only contralateral symptoms as group II. Ligamenta flava thicknesses and spinal canal diameters of both groups were measured on magnetic resonance imaging (MRI) with a micro-caliper. Both groups underwent surgery only on the disc herniated side. The total thicknesses of the ligamenta flava in group II was thicker than in group I. There was no spinal stenosis in either group and no significance difference between the groups. Statistically significant differences were found for both ipsilateral and contralateral thickness of the ligament flava in both groups. We also compared thickness of the ligamenta flava for each level of disc herniation in group I; ligamenta flava hypertrophy was more common at L3-L4 and L4-L5 levels of vertebrae in females. Aetiology of contralateral sciatica among disc herniated patients may be related to hypertrophy of the ligamenta flava, especially on the opposite side. Surgical approaches of the disc herniated side alone may be sufficient for a good outcome.


The C. elegans P4-ATPase TAT-1 regulates lysosome biogenesis and endocytosis.
P-type adenosine triphosphatases (ATPases) of the Drs2p family (P4-ATPases) are multipass transmembrane proteins required to generate and maintain phospholipid asymmetry in membrane bilayers. In Saccharomyces cerevisiae, several members of this family control distinct transport events within the endosomal and secretory pathways. Comparatively, little is known about the functions of P4-ATPases in multicellular organisms. In this study, we analyzed the role of the Caenorhabditis elegans Drs2p homologue transbilayer amphipath transporter (TAT)-1 in intracellular trafficking. tat-1 is expressed in many tissues including the intestine, the epidermis and the nervous system. In intestinal cells, tat-1 loss-of-function mutants accumulate large vacuoles of mixed endolysosomal identity positive for the lysosomal protein LMP-1. In addition, they lack the same class of storage granules as lmp-1 mutants, suggesting that part of the tat-1 phenotype might result from LMP-1 sequestration in an aberrant compartment. Epidermal cells mutant for tat-1 contain acidified giant hybrid multivesicular bodies probably corresponding to endolysosomal intermediate compartments or deficient lysosomes. Finally, TAT-1 is required for yolk uptake in oocytes and an early step of fluid-phase endocytosis in the intestine. Hence, TAT-1 is required at multiple steps of the endolysosomal pathway, at least in part by ensuring proper trafficking of cell-specific effector proteins.


Capsaicin-induced desensitization is prevented by capsazepine but not by ruthenium red in guinea pig bronchi.
In isolated guinea pig bronchi, the influence of ruthenium red, capsazepine and extracellular Ca2+ on capsaicin-induced desensitization was examined to investigate whether this desensitization was mediated via a specific receptor coupled with an ion channel. Pre-exposure of tissues to capsaicin (1, 3 or 10 microM) caused a dose-dependent desensitization to the second application of capsaicin. However, the contractile responses to exogenous tachykinins were not changed after pre-exposure of tissues to capsaicin. This capsaicin-induced desensitization was prevented by capsazepine (30 microM), but not by ruthenium red added to tissues 20 min before pretreatment with capsaicin (3 microM). While the excitatory contractile response to capsaicin was markedly reduced in the absence of extracellular Ca2+, the desensitization induced by capsaicin was not changed by the removal of extracellular Ca2+. In summary, the results from the present study suggest that in vitro functional desensitization induced by capsaicin in guinea pig bronchi may involve changes in the vanilloid receptor and occur through a ruthenium red-insensitive pathway.


The effect of the solvent on the film-forming parameters of hydroxypropyl-cellulose.
In pharmaceutical technology, film-forming agents are often applied in solution during the preparation of solid dosage forms. A wide range of polymers have already been examined, but many of the effects of the applied solvent on the properties of the film are still not fully known. The study of these phenomena might be of great help in the preparation of better films. In the present study, the frequently used polymer hydroxypropyl-cellulose was examined in water and ethanol. The latter solvent exhibits better wetting properties for this polymer. It was found that the use of ethanol enhanced the processibility because of the easier atomization and the shorter drying period. Properties characteristic of the chemical nature (wetting, surface free energy and thermal properties) and the physical behaviour (deformation process) of the poured films were studied. Relevant differences were detected only in the mechanical parameters. The sizes of the free volume holes in the differently prepared polymers were also determined, but this parameter proved irrelevant as concerns alterations of the breaking process. The explanation of the differences processibility of the films might be the different strengths of binding between the macromolecular chains. This phenomenon can also explain the different degrees of hydration of the polymer and the changes in the drying process.


Effects of high intravenous doses of dynorphin A(1-13) on tail flick latency and central nervous system histology in rats.
Dynorphin A(1-13) blocks opiate withdrawal in rats without producing dependence, and enhances analgesia in morphine-tolerant animals. Its potential use in humans is therefore of interest. Dynorphin A(1-13) has little toxicity when administered at modest doses IV but has been reported to cause hindlimb paralysis and necrosis of the spinal cord in rats, at the catheter tip, when administered intrathecally. To further evaluate its potential neurotoxicity, we administered dynorphin A(1-13) to rats at very high doses IV. Rats (n = 6-10 per group) received dynorphin A(1-13) as bolus IV doses of 5 mg/kg, or as continuous IV infusions of 40 mg/kg/day for 1 day, with saline controls. The appearance and behavior of all animals was normal. Tail flick latencies remained unchanged (p > 0.5). There were no histologic abnormalities of the spinal cord or brain when examined by light microscopy. Two additional groups received bolus injections of dynorphin A(1-13) 50 or 100 mg/kg IV. Animals receiving 50 mg/kg showed cutaneous flushing, labored respirations, and decreased spontaneous movement, which resolved within 10 min. Histology at 1 week was normal. All six animals receiving 100 mg/kg convulsed and died within minutes. Three animals that received dynorphin A(1-13) 40 mg/kg/day for 7 days had normal behavior and histology. We conclude that the previously observed neurotoxicity of intrathecally administered dynorphin A(1-13) is a local effect that does not occur when dynorphin A(1-13) is administered IV, even at very high doses.


Does the epiphyseal cartilage of the long bones have one or two ossification fronts?
Epiphyseal cartilage is hyaline cartilage tissue with a gelatinous texture, and it is responsible for the longitudinal growth of the long bones in birds and mammals. It is located between the epiphysis and the diaphysis. Epiphyseal cartilage also is called a growth plate or physis. It is protected by three bone components: the epiphysis, the bone bar of the perichondrial ring and the metaphysis. The epiphysis, which lies over the epiphyseal cartilage in the form a cupola, contains a juxtaposed bone plate that is near the epiphyseal cartilage and is in direct contact with the epiphyseal side of the epiphyseal cartilage. The germinal zone corresponds to a group of cells called chondrocytes. These chondrocytes belong to a group of chondral cells, which are distributed in rows and columns; this architecture is commonly known as a growth plate. The growth plate is responsible for endochondral bone growth. The aim of this study was to elucidate the causal relationship between the juxtaposed bone plate and epiphyseal cartilage in mammals. Our hypothesis is that cells from the germinal zone of the epiphyseal side of the epiphyseal cartilage are involved in forming a second ossification front that is responsible for the origin of the juxtaposed bone plate. We report the following: (a) The juxtaposed bone plate has a morphology and function that differs from that of the epiphyseal trabeculae; (b) on the epiphyseal edge of the epiphyseal cartilage, a new ossification front starts on the chondrocytes of the germinal area, which forms the juxtaposed bone plate. This ossification front is formed by chondrocytes from the germinal zone through a process of mineralisation and ossification, and (c) the process of mineralisation and ossification has a certain morphological analogy to the process of ossification in the metaphyseal cartilage of amphibians and differs from the endochondral ossification process in the metaphyseal side of the growth plate. The close relationship between the juxtaposed bone plate and the epiphyseal cartilage, in which the chondrocytes that migrate from the germinal area play an important role in the mineralisation and ossification process of the juxtaposed bone plate, supports the hypothesis of a new ossification front in the epiphyseal layer of the epiphyseal plate. This hypothesis has several implications: (a) epiphyseal cartilage is a morphological entity with two different ossification fronts and two different functions, (b) epiphyseal cartilage may be a morphological structure with three parts: perichondrial ring, metaphyseal ossification front or growth plate, and epiphyseal ossification front, (c) all disease (traumatic or dysplastic) that affects some of these parts can have an impact on the morphology of the epiphyseal region of the bone, (d) there is a certain analogy between metaphyseal cartilage in amphibians and mammalian epiphyseal cartilage, although the former is not responsible for bone growth, (e) comparative histological and anatomy studies are also warranted, to shed light on the phylogenetic study of epiphyseal cartilage throughout the changes that occur in the animal species.


Engineering a new-to-nature cascade for phosphate-dependent formate to formaldehyde conversion in vitro and in vivo.
Formate can be envisioned at the core of a carbon-neutral bioeconomy, where it is produced from CO2 by (electro-)chemical means and converted into value-added products by enzymatic cascades or engineered microbes. A key step in expanding synthetic formate assimilation is its thermodynamically challenging reduction to formaldehyde. Here, we develop a two-enzyme route in which formate is activated to formyl phosphate and subsequently reduced to formaldehyde. Exploiting the promiscuity of acetate kinase and N-acetyl-γ-glutamyl phosphate reductase, we demonstrate this phosphate (Pi)-based route in vitro and in vivo. We further engineer a formyl phosphate reductase variant with improved formyl phosphate conversion in vivo by suppressing cross-talk with native metabolism and interface the Pi route with a recently developed formaldehyde assimilation pathway to enable C2 compound formation from formate as the sole carbon source in Escherichia coli. The Pi route therefore offers a potent tool in expanding the landscape of synthetic formate assimilation.


[A case of sustained cholestasis caused by acute A viral hepatitis in Dubin-Johnson syndrome].
Dubin-Johnson syndrome is a rare clinical entity. It shows intermittent symptoms such as chronic or intermittent jaundice, abdominal pain, weakness, nausea, vomiting, anorexia and diarrhea. Symptoms are precipitated or aggravated by pregnancy, alcoholism, surgical procedures and intercurrent disease. Chronic idiopathic jaundice is typical of Dubin-Johnson syndrome and its prognosis is good. We describe a case of prolonged cholestasis for more than 10 months caused by acute A viral hepatitis in a patient with Dubin-Johnson syndrome. It is a first report of cholestasis complicated by acute A viral hepatitis in a patient with Dubin-Johnson syndrome.


Neuronal correlates of strategic cooperation in monkeys.
We recorded neural activity in male monkeys playing a variant of the game 'chicken' in which they made decisions to cooperate or not cooperate to obtain rewards of different sizes. Neurons in the middle superior temporal sulcus (mSTS)-previously implicated in social perception-signaled strategic information, including payoffs, intentions of the other player, reward outcomes and predictions about the other player. Moreover, a subpopulation of mSTS neurons selectively signaled cooperatively obtained rewards. Neurons in the anterior cingulate gyrus, previously implicated in vicarious reinforcement and empathy, carried less information about strategic variables, especially cooperative reward. Strategic signals were not reducible to perceptual information about the other player or motor contingencies. These findings suggest that the capacity to compute models of other agents has deep roots in the strategic social behavior of primates and that the anterior cingulate gyrus and the mSTS support these computations.


Tracking drivers' minds: Continuous evaluation of mental load and cognitive processing in a realistic driving simulator scenario by means of the EEG.
Driving safety strongly depends on the driver's mental states and attention to the driving situation. Previous studies demonstrate a clear relationship between EEG measures and mental states, such as alertness and drowsiness, but often only map their mental state for a longer period of time. In this driving simulation study, we exploit the high temporal resolution of the EEG to capture fine-grained modulations in cognitive processes occurring before and after eye activity in the form of saccades, fixations, and eye blinks. A total of 15 subjects drove through an approximately 50-km course consisting of highway, country road, and urban passages. Based on the ratio of brain oscillatory alpha and theta activity, the total distance was classified into 10-m-long sections with low, medium, and high task loads. Blink-evoked and fixation-evoked event-related potentials, spectral perturbations, and lateralizations were analyzed as neuro-cognitive correlates of cognition and attention. Depending on EEG-based estimation of task load, these measures showed distinct patterns associated with driving behavior parameters such as speed and steering acceleration and represent a temporally highly resolved image of specific cognitive processes during driving. In future applications, combinations of these EEG measures could form the basis for driver warning systems which increase overall driving safety by considering rapid fluctuations in driver's attention and mental states.


Utility and limitations of patient-adjusted D-dimer cut-off levels for diagnosis of venous thromboembolism-A systematic review and meta-analysis.
To systematically assess test performance of patient-adapted D-dimer cut-offs for the diagnosis of venous thromboembolism (VTE). Systematic review and analysis of articles published in PubMed, Embase, ClinicalTrials.gov, and Cochrane Library databases. Investigations assessing patient-adjusted D-dimer thresholds for the exclusion of VTE were included. A hierarchical summary receiver operating characteristic model was used to assess diagnostic accuracy. Risk of bias was assessed by Quality Assessment of Diagnostic Accuracy Studies 2 score. A total of 68 studies involving 141,880 patients met the inclusion criteria. The standard cut-off revealed a sensitivity of 0.99 (95% confidence interval [CI] 0.98-0.99) and specificity of 0.23 (95% CI 0.16-0.31). Sensitivity was comparable to the standard cut-off for age-adjustment (0.97 [95% CI 0.96-0.98]) and YEARS algorithm (0.98 [95% CI 0.91-1.00]) but lower for pretest probability (PTP)-adjusted (0.95 [95% CI 0.89-0.98) and COVID-19-adapted thresholds (0.93 [95% CI 0.82-0.98]). Specificity was significantly higher across all adjustment strategies (age: 0.43 [95% CI 0.36-0.50]; PTP: 0.63 [95% CI 0.51-0.73]; YEARS algorithm: 0.65 [95% CI 0.39-0.84]; and COVID-19: 0.51 [95% CI 0.40-0.63]). The YEARS algorithm provided the best negative likelihood ratio (0.03 [95% CI 0.01-0.15]), followed by age-adjusted (both 0.07 [95% CI 0.05-0.09]), PTP (0.08 [95% CI 0.04-0.17), and COVID-19-adjusted thresholds (0.13 [95% CI 0.05-0.32]). This study indicates that adjustment of D-dimer thresholds to patient-specific factors is safe and embodies considerable potential for reduction of imaging. However, robustness, safety, and efficiency vary considerably among different adjustment strategies with a high degree of heterogeneity.


The hazard of acute epiglottitis.
This report is based on a 3 1/2 year's study of 33 cases of acute epiglottitis with 3 child deaths. Suspicion of acute epiglottitis in children with respiratory distress is always an indication for rapid direct laryngoscopy under general anaesthesia with intubation, and preparation for tracheotomy and bronchoscopy. Should the diagnosis of acute epiglottitis not be excluded during this procedure, then a free airway should be ensured by endotracheal intubation, even in cases of apparently less severe character, where the procedure would seem to be more prophylactic than therapeutic. Intubation is often very difficult. It is concluded that the patient should be received at the hospital by an E.N.T.--anaesthetic team conversant with the treatment of this potential killer.


Disappointment and frustration, but long-term satisfaction: patient experiences undergoing treatment for a chronic Achilles tendon rupture-a qualitative study.
Delayed treatment of Achilles tendon ruptures is generally due to either misdiagnosis or patient delay. When the treatment is delayed more than 4 weeks, the rupture is defined as "chronic", and almost always requires more invasive surgery and longer rehabilitation time compared with acute Achilles tendon ruptures. There is insufficient knowledge of patient experiences of sustaining and recovering from a chronic Achilles tendon rupture. To evaluate patients' experiences of suffering a chronic Achilles tendon rupture, semi-structured group interviews were conducted 4-6 years after surgical treatment using a semi-structured interview guide. The data were analyzed using qualitative content analysis described by Graneheim and Lundman. The experiences of ten patients (65 ± 14 years, 7 males and 3 females) were summarized into four main categories: (1) "The injury", where the patients described immediate functional impairments, following either traumatic or non-traumatic injury mechanisms that were misinterpreted by themselves or the health-care system; (2) "The diagnosis", where the patients expressed relief in receiving the diagnosis, but also disappointment and/or frustration related to the prior misdiagnosis and delay; (3) "The treatment", where the patients expressed high expectations, consistent satisfaction with the surgical treatment, and addressed the importance of the physical therapist having the right expertise; and (4) "The outcomes", where the patients expressed an overall satisfaction with the long-term outcome and no obvious limitations in physical activity, although some fear of re-injury emerged. An Achilles tendon rupture can occur during both major and minor trauma and be misinterpreted by both the assessing health-care professional as well as the patient themselves. Surgical treatment and postoperative rehabilitation for chronic Achilles tendon rupture results in overall patient satisfaction in terms of the long-term outcomes. We emphasize the need for increased awareness of the occurrence of Achilles tendon rupture in patients with an atypical patient history.


Serological evidence that activation of ubiquitous human herpesvirus-6 (HHV-6) plays a role in chronic idiopathic/spontaneous urticaria (CIU).
Acute infection with viral pathogens in the herpesviridae family can trigger acute urticaria, and reactivation of herpesviridae is associated with cutaneous urticarial-like syndromes such as drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DRESS). Reactivation of latent herpesviridae has not been studied systematically in chronic idiopathic/spontaneous urticaria (CIU). This review proposes that CIU is an inflammatory disorder with autoimmune features (termed 'CVU' for chronic viral urticaria), based on serology consistent with the hypothesis that reactivation of a latent herpesvirus or -viruses may play a role in CIU. Serology obtained from a cohort of omalizumab (Xolair)-dependent patients with severe CIU was consistent with previous HHV-6 infection, persistent viral gene expression and replication. CIU patients also exhibited serological evidence of increased immune response to HHV-4 (Epstein-Barr virus, or EBV) but not all CIU patients were infected with EBV. These observations, combined with case reports of CIU response to anti-viral therapy, suggest that HHV-6, possibly interacting with HHV-4 in cutaneous tissues, is a candidate for further prospective study as a co-factor in CIU.


Mode of [14C] 2-deoxy-D-glucose uptake into retrosplenial cortex and other memory-related structures of the monkey during a delayed response.
Physiological studies on the monkey retrosplenial (RS) cortex have been few, and its functional role remains to be investigated. In the present study, activity of the RS cortex was investigated using radioactive 2-DG while the monkey was performing a visual tracking task with a delay (a delayed-response task) for 45 minutes. A remarkable increase in 2-DG uptake was observed equally in the left as well as in the right RS cortex. The anterior nucleus of the thalamus also showed increased 2-DG uptake. In addition, other memory-related structures (prefrontal cortex, dorsomedial nucleus of the thalamus, amygdala and hippocampus) showed a similar increase in 2-DG uptake compared to control monkeys, though their respective absolute values were different from one another. Since the RS cortex receives afferents from the anterior nucleus of the thalamus, which is one of the main nuclei of the Papez circuit, it is assumed that the RS cortex is important in memory function. Therefore, the remarkable increase in 2-DG uptake in the present study could reflect some aspects of memory or learning processes required to perform the delayed response.


Nobloedischia rasnitsyni, a new genus and species of Oedischiidae (Orthoptera) from the Lower Permian Wellington Formation of Oklahoma, USA.
Nobloedischia rasnitsynigen. et sp. n. (Oedischiidae) is described from the Lower Permian Wellington Formation of Noble County, Oklahoma. The genus is similar to both Petrelcana (Oedischiidae: Mezenoedischiinae) and Oedischia (Oedischiidae: Oedischiinae) and is left unplaced at the subfamily level. The new species is the twelfth Orthoptera species and the fourth species of Oedischiidae from these deposits.


Depression and anxiety in epilepsy: the association with demographic and seizure-related variables.
Depression and anxiety are common psychiatric symptoms in patients with epilepsy, exerting a profound negative effect on health-related quality of life. Several issues, however, pertaining to their association with psychosocial, seizure-related and medication factors, remain controversial. Accordingly, the present study was designed to investigate the association of interictal mood disorders with various demographic and seizure-related variables in patients with newly-diagnosed and chronic epilepsy. We investigated 201 patients with epilepsy (51.2% males, mean age 33.2 +/- 10.0 years, range 16-60) with a mean disease duration of 13.9 +/- 9.5 years. Depression and anxiety were assessed in the interictal state with the Beck Depression Inventory, 21-item version (BDI-21) and the state and trait subscales of the State-Trait Anxiety Inventory (STAI-S and STAI-T), respectively. The association of mood disorders with various variables was investigated with simple and multiple linear regression analyses. High seizure frequency and symptomatic focal epilepsy (SFE) were independent determinants of depression, together accounting for 12.4% of the variation of the BDI-21. The STAI-S index was significantly associated with the type of epilepsy syndrome (SFE). Finally, high seizure frequency, SFE and female gender were independent determinants of trait anxiety accounting for 14.7% of the variation of the STAI-T. Our results confirm the prevailing view that depression and anxiety are common psychological disorders in epileptics. It is additionally concluded that female gender, high seizure frequency and a symptomatic epilepsy syndrome are independent risk factors for the development of anxiety and/or depression.


Effect of p27Kip1 inhibition on proliferation of bovine corneal endothelial cells by RNA interference.
Three plasmids (pGenesil-P1, pGenesil-P2, pGenesil-P3) with different p27Kip1-shRNA sequences were designed and synthesized. Their effects on the proliferation of bovine corneal endothelial cells (bCEC) were investigated. Plasmid expressing irrelevant shRNA with a random combination was used as negative control (pGenesil-HK). The recombination of four plamids was confirmed by restrictive enzyme digestion and sequence analysis. The expression of mRNA and protein of p27Kip1 was detected by RT-PCR and Western blotting after stable transfection. The expressions of p27Kip1 mRNA and p27Kip1 protein of pGenesil-P1 group, pGenesil-P2 group and pGenesil-P3 group were all lower than those in the pGenesil-HK group and the blank group (non-transfected group). pGenesil-P3 had the strongest inhibitory effect and was selected for the next steps. The proliferation rates of the pGenesil-P3 group, the pGenesil-HK group and the blank group were assessed by MTT. The influence of shRNA-p27Kip1 on bCEC cell cycle was detected by flow cytometry (FCM). Compared with the control groups, the proliferation rate of the pGenesil-P3 group was increased significantly, and the ratio of S-phase also increased. It is concluded that shRNA-p27Kip1 could down-regulate the expression of p27Kip1 effectively and increase the proliferation of bCEC. RNA interference (RNAi) may be an effective means to promote the proliferation of CEC.


von Willebrand factor links primary hemostasis to innate immunity.
The plasma multimeric glycoprotein von Willebrand factor (VWF) plays a critical role in primary hemostasis by tethering platelets to exposed collagen at sites of vascular injury. Recent studies have identified additional biological roles for VWF, and in particular suggest that VWF may play an important role in regulating inflammatory responses. However, the molecular mechanisms through which VWF exerts its immuno-modulatory effects remain poorly understood. In this study, we report that VWF binding to macrophages triggers downstream MAP kinase signaling, NF-κB activation and production of pro-inflammatory cytokines and chemokines. In addition, VWF binding also drives macrophage M1 polarization and shifts macrophage metabolism towards glycolysis in a p38-dependent manner. Cumulatively, our findings define an important biological role for VWF in modulating macrophage function, and thereby establish a novel link between primary hemostasis and innate immunity.


Role of airway epithelial cells in development of asthma and allergic rhinitis.
Asthma and allergic rhinitis frequently coexist in the same patient. There is a similarity and variation as well as potential relationship between asthma and allergic rhinitis. There is an increasing evidence to suggest a major involvement of airway epithelial cells in the pathogenesis of asthma and allergic rhinitis. The present review describes the importance of the airway epithelial cell in the development of allergic airway diseases, its role as the primary airway defense against exposure of the airway and lung to inflammatory stimuli and antigens and as an important player through activation of epithelial Toll-like receptors (TLRs) to provide an important link between innate immunity and allergic disease. Additionally, airway epithelial cells can act as inflammatory promoters capable of directing dendritic cells (DCs) towards a T helper 2 (Th2) response, and as active producers of several inflammatory/anti-inflammatory mediators. It is hypothesized that airway epithelial cells may play as both inflammatory initiator and immuno-pathological feedback regulation between allergic rhinitis and asthma via release of systemic inflammatory mediators. Thus, airway epithelial cells may be valuable therapeutic targets for discovery and development of new drugs and/or new therapeutic strategies to treat asthma and allergic rhinitis.


Chromosomal polymorphisms and susceptibility to menstrual disorders: a retrospective analysis of 24,578 women.
To evaluate the association between the polymorphic variants of chromosomes and menstrual disorders. The data from our previous retrospective, single-center cohort study were re-analyzed. Women with regular menstruation were included as controls. Women with menstrual cycle abnormalities were subgrouped according to reproductive causes. The frequency of chromosomal polymorphisms was compared between groups. Regression analysis was used to adjust for potential confounding variables. A total of 24,578 women composed of 8062 women with regular cycles as the control group and 16,516 women as the menstrual cycle irregularity group were included. When compared with the control group, the incidence of chromosomal polymorphisms in the total menstrual cycle irregularity group, Polycystic ovary syndrome group, and Primary ovarian insufficiency group were significantly higher (4.49% versus 5.34%, P = 0.004, 4.49% versus 5.35%, P = 0.018 and 4.49% versus 5.94%, P = 0.002, respectively). The incidences of inv(9) in the Primary ovarian insufficiency group were significantly higher than that in the control individuals (1.0% versus 1.6%, P = 0.024). Logistic regression analysis showed an effect of chromosomal polymorphisms on menstrual cycle irregularity (OR: 1.62, 95% CI: 1.234-2.187, P = 0.007; adjusted OR: 1.46, 95% CI: 1.153-1.819, P < 0.001). The result demonstrated an effect of chromosomal polymorphisms on the Primary ovarian insufficiency group (OR: 2.52, 95% CI: 1.307-5.177, P < 0.001; adjusted OR: 2.61, 95% CI: 1.371-4.605, P < 0.001). The study suggests chromosomal polymorphisms adversely affect female menstrual cycle irregularity.


Surgical and prosthetic management of a complex edentulous patient for fabrication of complete dentures.
Fabrication of well-fitting complete dentures becomes a challenge in the presence of epulis fissuratum in the maxilla or severely resorbed alveolar tissue in the mandible. This clinical report describes the surgical and prosthetic treatment of a patient who presented with both problems. The neutral zone technique was used to improve the stability of the mandibular complete denture. Both dentures were fabricated prior to surgical excision of the epulis fissuratum and inserted immediately following the surgery.


Determination of the site-specific and isoform-specific glycosylation in human plasma-derived antithrombin by IEF and capillary HPLC-ESI-MS/MS.
The glycan structures of the major and more than ten minor populated isoforms of antithrombin (AT) were determined after separation of the isoforms by IEF using IPG strips. The bands excised from the gel were reduced, derivatized by iodoacetamide and submitted to tryptic digestion. The digest was analyzed by RP-HPLC-ESI-MS equipped with a quadrupole ion-trap mass analyzer. MS/MS experiments allowed establishing the monosaccharide compositions in the glycopeptides. For the major isoform of alpha-AT four identical biantennary glycans with two terminal sialic acids (SA) each, a total of eight SA, were found in full agreement with the literature. In the IEF-band containing this major isoform (pI 5.18) a further, much less abundant, isoform was detected showing a fucosylation on the glycan attached to Asn155 but being of otherwise identical structure as described above. The isoforms with pI 5.10 were found to include one triantennary glycan, all antennas carrying terminal SA. The occurrence of triantennary structure is site specific, involving the peptides with Asn(135) and Asn(155), alternately. At pI 5.24 we found those four isoforms that carry the glycans like the main-isoform of alpha-AT but missing one terminal SA. There was no site specificity found for the mono-sialo structure. The isoform at pI 5.31 is the major isoform of beta-AT containing three identical biantennary structures being fully sialylated. No isoforms (above 0.5% abundance) with two glycans only or three glycans other than beta-AT were detected. Fucosylation was found in the main isoform with an abundance of about 5%, and as expected with all the other isoforms with a comparable abundance.


Multiplex SuperSelective PCR Assays for the Detection and Quantitation of Rare Somatic Mutations in Liquid Biopsies.
SuperSelective primers, by virtue of their unique design, enable the simultaneous identification and quantitation of inherited reference genes and rare somatic mutations in routine multiplex PCR assays, while virtually eliminating signals from abundant wild-type sequences closely related to the target mutations. These assays are sensitive, specific, rapid, and low cost, and can be performed in widely available spectrofluorometric thermal cyclers. Herein, we provide examples of SuperSelective PCR assays that target eight different somatic EGFR mutations, irrespective of whether they occur in the same codon, occur at separate sites within the same exon, or involve deletions. In addition, we provide examples of SuperSelective PCR assays that detect specific EGFR mutations in circulating tumor DNA present in the plasma of liquid biopsies obtained from patients with non-small-cell lung cancer. The results suggest that multiplex SuperSelective PCR assays may enable the choice, and subsequent modification, of effective targeted therapies for the treatment of an individual's cancer, utilizing frequent noninvasive liquid biopsies.


MicroRNA-34a Suppresses Autophagy in Alveolar Type II Epithelial Cells in Acute Lung Injury by Inhibiting FoxO3 Expression.
Excessive autophagic activity of alveolar type II epithelial (AT-II) cells is one of the main causes of acute lung injury (ALI); however, the underlying molecular mechanism remains to be determined. The microRNAs (miRNAs) are involved with autophagy in many diseases. The objective of this study was therefore to investigate the relationship between the miRNA expression and the autophagic activity of the AT-II cells in the pathogenesis of ALI and its molecular mechanism. A mouse model of ALI and AT-II cell injury was induced using lipopolysaccharide (LPS) in vivo and in vitro, and the expression of miR-34a and the autophagy-related proteins LC3 II/I and p62 were determined. Moreover, the autophagic activity was investigated after miR-34a overexpression and inhibition. The effects of miR-34a on its target gene, FoxO3, in regulating autophagic activity in AT-II cells were also determined. LPS induced autophagic activity and increased the expression of miR-34a in lung tissues and in AT-II cells. The in vitro results showed that the upregulation of miR-34a suppressed, whereas the inhibition of miR-34a promoted, autophagy in AT-II cells. Moreover, miR-34a could directly bind to the 3'-untranslated region of the autophagy-related gene, FoxO3, to decrease its expression. In addition, the knockdown of FoxO3 expression inhibited the autophagic activity in AT-II cells. Together, this study suggested that miR-34a might suppress the excessive autophagic activity in AT-II cells via targeting FoxO3 to reduce the damage of LPS-induced ALI.


Acute aortic thrombosis causing sudden paraplegia in a patient with known thoraco-lumbar spinal metastasis: the diagnostic usefulness of magnetic resonance imaging.
Diagnosis and treatment of acute aortic thrombosis utilizing magnetic resonance imaging is reported. The patient had known thoracolumbar spinal metastases and sudden onset paraplegia. MRI critically shortened the time to emergent surgery and obviated the need for two invasive tests (myelogram and angiogram).


An advanced deep learning method to detect and classify diabetic retinopathy based on color fundus images.
In this article, we present a computerized system for the analysis and assessment of diabetic retinopathy (DR) based on retinal fundus photographs. DR is a chronic ophthalmic disease and a major reason for blindness in people with diabetes. Consistent examination and prompt diagnosis are the vital approaches to control DR. With the aim of enhancing the reliability of DR diagnosis, we utilized the deep learning model called You Only Look Once V3 (YOLO V3) to recognize and classify DR from retinal images. The DR was classified into five major stages: normal, mild, moderate, severe, and proliferative. We evaluated the performance of the YOLO V3 algorithm based on color fundus images. We have achieved high precision and sensitivity on the train and test data for the DR classification and mean average precision (mAP) is calculated on DR lesion detection. The results indicate that the suggested model distinguishes all phases of DR and performs better than existing models in terms of accuracy and implementation time.


[The UniSpacer™: correcting varus malalignment in medial gonarthrosis. Preliminary results].
While options for operative treatment of leg axis varus malalignment in patients with medial gonarthrosis include several established procedures, such as unicompartmental knee arthroplasty (UKA), total knee arthroplasty (TKA), or high tibial osteotomy (HTO), so far there has been little focus on a less invasive option introduced more recently: the UniSpacer™ implant, a modern, self-centering, metallic interpositional device for the knee. This study evaluates whether alignment correction can be achieved by UniSpacer™ arthroplasty as well as alignment change in the first 5 postoperative years is evaluated. Antero-posterior long leg stance radiographs of 15 legs were digitally analyzed to assess alignment change: two relevant angles and the deviation of the mechanical axis of the leg were analyzed before and after surgery. Additionally, the change of the postoperative alignment was determined one and five years postoperatively. Analyzing the mechanical tibiofemoral angle, a significant leg axis correction was achieved, with a mean valgus change of 4.7±1.9°; a varus change occurred in the first postoperative year, while there was no significant further change of alignment seen five years after surgery. The UniSpacer™ corrects malalignment in patients with medial gonarthrosis; however, a likely postoperative change in alignment due to implant adaptation to the joint must be considered before implantation.


The relationship between induced and spontaneous autoantibodies in MRL mice: the role of Ly-1 B cells?
The murine response to bromelain-treated mouse red blood cells (BrMRBC) is derived from Ly-1 B cells. It has been proposed that this B-cell subset produces a variety of other autoantibodies and is elevated in autoimmune mouse strains. We have studied the ability of MRL lpr/lpr and the non-autoimmune congenic MRL +/+ mice to make autoantibodies to BrMRBC and immunoglobulin (rheumatoid factors, RF). Following lipopolysaccharide (LPS) stimulation we found the numbers of autologous plaque-forming cells (PFC) to be low in both lpr and MRL +/+ mice, suggesting low Ly-1 B-cell numbers. This observation is consistent with the view that Ly-1 B cells in the mouse may not give rise to pathologically relevant RF.


Disordered eating and complexities of cultural origin: a focus on Jews from Muslim countries.
A dearth of data concerning eating problems among adult women from diverse cultural origins leaves substantial knowledge gaps and constrains evidence-based interventions. To examine prevalence and predictors of disordered eating behaviors (DEB) among adult Jewish women (21+) from distinct cultural origins. Community-based study includes 175 Israelis born to parents from Muslim countries (aka Sephardic) and 108 second generation Israelis mostly of European ancestry. DEB assessed with DSM-IV related symptoms. Hierarchical regressions examine influence of weight, self-criticism and psychological distress on DEB severity. Despite similar exposure to Israel's westernized norms, substantial group differences emerge. Considerably lower rate of DEB found among respondents of Sephardic origin (11.4%, 19.4%, p<.05); regressions reveal dissimilar patterns of clinical predictors. Community cohesiveness and deeply-rooted cultural and religious traditions may be protective for Israelis of Sephardic origin. Additional research is needed to clarify cultural influences and enhance culturally sensitive interventions for multicultural populations.


RAPD and SCAR markers as potential tools for detection of milk origin in dairy products: Adulterant sheep breeds in Serra da Estrela cheese production.
Serra da Estrela Protected Designation of Origin (PDO) cheese is the most famous Portuguese cheese and has a high commercial value. However, the adulteration of production with cheaper/lower-quality milks from non-autochthones ovine breeds compromises the quality of the final product and undervalues the original PDO cheese. A Randomly Amplified Polymorphic DNA (RAPD) method was developed for efficient detection of adulterant breeds in milk mixtures used for fraudulent production of this cheese. Furthermore, Sequence Characterized Amplified Region (SCAR) markers were designed envisioning the detection of milk adulteration in processed dairy foods. The RAPD-SCAR technique is here described, for the first time, to be potentially useful for detection of milk origin in dairy products. In this sense, our findings will play an important role on the valorization of Serra da Estrela cheese, as well as on other high-quality dairy products prone to adulteration, contributing to the further development of the dairy industry.


Cytoprotective effect of TRK-100, a prostacyclin analogue, against chemical injuries in cultured human vascular endothelial cells.
We studied the cytoprotective effect of TRK-100, a chemically stable analogue of prostacyclin (PGI2), in the cultured human endothelial cells from umbilical vein. TRK-100 (10 and 100 nM) stimulated significantly proliferation of endothelial cells but did not affect PGI2 production in endothelial cells. Exposure of cultured endothelial cells to homocysteine (2.5 mM) or glucose (50 mM) caused concentration-dependent cytotoxicity, as evidenced by a decrease in number of viable cells. When endothelial cells were treated with TRK-100 simultaneously or prior to, but not after, exposure to injury substances, decreases in viable cell were significantly suppressed. The protective effect of TRK-100 against homocysteine-induced cytotoxicity also appeared in endothelial cells treated with acetylsalicylic acid, suggesting that endogenous PGI2 did not involve in the protective effect of TRK-100.


[Study on extraction process for the icariin of hugu capsule with ultrasonic technology].
To study the best ultrasonic technology of the extraction of icariin of Hugu capsule. Used the content of icariin as index, orthogonal experiment was carried out to investigate 4 influential factors as follows: the ultrasonic power (A), the ultrasonic frequency (B), the material fluid ratio (C), the time (D). The best extraction conditions were as follows: the ultrasonic power was 120 W, the ultrasonic frequency was 28 KHz, solid-liquid ratio of 1 : 35, the extraction time was 10 min. Optimization of extracting process is simple, quick and low energy consumption. Under these conditions, the extraction of icariin is 1.8 times higher than that of the traditional extraction method.


Changes in the composition of plasma lipoproteins in the chronic uremic rat.
The effect of chronic renal failure on the lipid and apolipoprotein concentrations of plasma, very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), low density lipoproteins (LDL) and high density lipoproteins (HDL) was studied in an experimental uremic rat model. Control rats were sham-operated and were divided into adlibitum-fed and pair-fed groups. The rats were studied (after an overnight fast) 32 days after the onset of uremia. The uremic rats had a 4-fold increase in plasma urea nitrogen and creatinine. The pair-fed and ad-lib-fed controls had similar levels of plasma urea nitrogen and lipid profiles. In the uremic rats, plasma triglyceride (TG) levels were increased 3.8-fold due to increased TG in the VLDL, IDL and HDL fractions. Their 2-3-fold increase in plasma free cholesterol (FC), esterified cholesterol (EC) and phospholipids (PL) were due to FC, EC and PL increases in VLDL, IDL, LDL and HDL. Their increase in plasma apo B (x 2.4) and apo E (x 1.5) were due to increases in VLDL, IDL and LDL. Their plasma apo A-I increased 2.4 fold due to increases in the LDL and HDL fractions. Uremic rats also had increases in the FC/PL molar ratio in VLDL, IDL and LDL. In their LDL, the apo B/total cholesterol (TC), apo B/PL and apo B/apo E molar ratios were decreased. In their HDL, the apo E/TC and apo E/PL molar ratios were decreased and the apo A-I/apo E molar ratio was increased. In conclusion, chronic uremia causes both quantitative changes in the levels and qualitative changes in the composition of the plasma lipoprotein particles. These results are compatible with the decreased hepatic lipase activities and impairment of remnant clearance observed in human chronic renal failure.


Combining Charge-Transfer Pathways to Achieve Unique Thermally Activated Delayed Fluorescence Emitters for High-Performance Solution-Processed, Non-doped Blue OLEDs.
Two efficient blue thermally activated delayed fluorescence compounds, B-oCz and B-oTC, composed of ortho-donor (D)-acceptor (A) arrangement were designed and synthesized. The significant intramolecular D-A interactions induce a combined charge transfer pathway and thus achieve small ΔEST and high efficiencies. The concentration quenching can be effectively inhibited in films of these compounds. The blue non-doped organic light emitting diodes (OLEDs) based on B-oTC prepared from solution processes shows record-high external quantum efficiency (EQE) of 19.1 %.


Process of adaptation to Spanish of the Temperament Evaluation of Memphis, Pisa, Paris and San Diego Scale. Self applied version (TEMPS-A).
Investigation of the predisposing factors for affective disorders has shown that measures to assess affective temperament are necessary. The TEMPS-A is a self-evaluation measure to assess four affective temperaments (hyperthymic, depressive, cyclothymic and irritable) and anxious temperament. The TEMPS-A questionnaire version that includes 110 questions has been adapted following the translation-backtranslation methodology, including two translations to Spanish and the classification of equivalence to English by an independent author. The study results indicated that a satisfactory translation was obtained, as indicated by the validation of equivalence by the bilingual consultant. All the items showed a perfect (A) or satisfactory equivalence (B). The TEMPS-A, Spanish version, is an understandable questionnaire that is equivalent to the original version in English, that allows for the evaluation of affective temperaments.


Human telomeric C-strand tetraplexes.
Telomeric C-strand sequences form non-Watson-Crick base-paired structures in supercoiled plasmids and in oligonucleotides at low pH. Here we examine oligonucleotides composed of 2 or 4 repeats of the human telomeric C-strand sequence d(CCCTAA)n. At low pH, the 2-repeat molecule forms a dimer which exhibits H1'-H1' nuclear Overhauser effects (NOEs) between stacked CC+ base pairs. These NOEs are characteristic of the i-motif, which is a tetraplex composed of two intercalated CC+ duplexes. The 4-repeat molecule forms an intramolecular monomeric structure at low pH, suggesting that four contiguous cytosine tracts fold into a CC+ intercalated tetraplex. These unusual structures may be relevant to the formation of guanine tetraplexes by complementary G-rich sequences. They may also provide a general mechanism for self-recognition by nucleic acids.


Smart Scheduling (SMASCH): multi-appointment scheduling system for longitudinal clinical research studies.
Facilitate the multi-appointment scheduling problems (MASPs) characteristic of longitudinal clinical research studies. Additional goals include: reducing management time, optimizing clinical resources, and securing personally identifiable information. Following a model view controller architecture, we developed a web-based tool written in Python 3. Smart Scheduling (SMASCH) system facilitates clinical research and integrated care programs in Luxembourg, providing features to better manage MASPs and speed up management tasks. It is available both as a Linux package and Docker image (https://smasch.pages.uni.lu). The long-term requirements of longitudinal clinical research studies justify the employment of flexible and well-maintained frameworks and libraries through an iterative software life-cycle suited to respond to rapidly changing scenarios. SMASCH is a free and open-source scheduling system for clinical studies able to satisfy recent data regulations providing features for better data accountability. Better scheduling systems can help optimize several metrics that ultimately affect the success of clinical studies.


In vivo tissue pharmacokinetics by fluorine magnetic resonance spectroscopy: a study of liver and muscle disposition of fleroxacin in humans.
Magnetic resonance spectroscopy of fluorine (19F) has been used to noninvasively study the in vivo pharmacokinetics of a model drug, fleroxacin (a fluoroquinolone antibiotic agent), in healthy human subjects. After oral administration, fleroxacin was detected in 19F magnetic resonance spectra from both liver and calf muscle and four magnetic resonance examinations were undertaken during a 24-hour period. By combining plasma analysis by high performance liquid chromatography with the magnetic resonance data, the following pharmacokinetic parameters (mean values) were obtained: tmax, 1.4, 4.6, and 5.6 hours in liver, plasma, and muscle, respectively; Cmax, 53, about 250, and about 60 mumol/L in plasma, liver, and muscle, respectively; t1/2, 4.4 hours (fast phase) and 10.8 hours (slow phase) in liver and 14.2 hours in plasma. The study documents for the first time the potential use of 19F magnetic resonance spectroscopy to noninvasively observe the time-related changes of a fluorine-containing drug in human tissues after oral administration.


Physiology-Based Treatment of Myoclonus.
Myoclonus can cause significant disability for patients. Myoclonus has a strikingly diverse array of underlying etiologies, clinical presentations, and pathophysiological mechanisms. Treatment of myoclonus is vital to improving the quality of life of patients with these disorders. The optimal treatment strategy for myoclonus is best determined based upon careful evaluation and consideration of the underlying etiology and neurophysiological classification. Electrophysiological testing including EEG (electroencephalogram) and EMG (electromyogram) data is helpful in determining the neurophysiological classification of myoclonus. The neurophysiological subtypes of myoclonus include cortical, cortical-subcortical, subcortical-nonsegmental, segmental, and peripheral. Levetiracetam, valproic acid, and clonazepam are often used to treat cortical myoclonus. In cortical-subcortical myoclonus, treatment of myoclonic seizures is prioritized, valproic acid being the mainstay of therapy. Subcortical-nonsegmental myoclonus may be treated with clonazepam, though numerous agents have been used depending on the etiology. Segmental and peripheral myoclonus are often resistant to treatment, but anticonvulsants and botulinum toxin injections may be of utility depending upon the case. Pharmacological treatments are often hampered by scarce evidence-based knowledge, adverse effects, and variable efficacy of medications.


Impact of the first surge of the coronavirus disease pandemic on general thoracic surgery practices in Kanagawa: a questionnaire survey by the Kanagawa General Thoracic Surgical Study Group.
The first surge in severe acute respiratory syndrome coronavirus 2 infection had a significant impact on health care institutions. Understanding how the pandemic affected general thoracic surgery would provide valuable data for establishing a health care protocol for upcoming surges. A questionnaire survey on coronavirus disease-related patient statistics and health care was conducted between February 2020 and June 2020 across 14 facilities affiliated with the Kanagawa General Thoracic Surgery Study Group. The average number of newly referred patients from February to June 2020 was 65% of that during the same period in 2019. Six facilities placed restrictions on medical care services, among which four restricted surgeries. At all institutions and those placed on surgical restriction, the total number of surgeries under general anesthesia was 92% and 78%, the total number of primary lung cancers was 94% and 86%, and the total number of surgeries for pneumothorax was 71% and 77% of that in the preceding year, respectively. Infection control and insufficient resources of the medical material were the most influential factors impacting the medical institutions' decision to restrict the services provided. Restrictions on surgery had a significant impact on the care provided by general thoracic surgery departments. To avoid patient inconvenience, establishing a collaborative system that refers patients to operational medical institutions in case of medical treatment restrictions may be useful.


Bacterial adhesion to antibiotic-loaded guided tissue regeneration membranes - a scanning electron microscopy study.
Bacterial contamination of sites undergoing guided tissue regeneration (GTR) therapy may reduce the efficiency of periodontal regeneration. This study compared bacterial adhesion onto various GTR membranes incorporated with antibiotics. Three barrier membranes, including expanded polytetrafluoroethylene (ePTFE) membrane, collagen membrane, and glycolide fiber membrane, were loaded with tetracycline or amoxicillin. The adhesion of Streptococcus mutans and Aggregatibacter actinomycetemcomitans onto the GTR membranes with or without antibiotics was analyzed using the scanning electron microscopy (SEM) analysis. The SEM analysis showed no apparent alteration in the physical structure of the membranes loaded with antibiotics. Both S. mutans and A. actinomycetemcomitans attached best on the collagen membranes, followed by the ePTFE membranes, and then the glycolide fiber membranes without antibiotics. Moreover, higher numbers of bacteria were observed on the fibril areas than on the laminar areas of the ePTFE membranes. The amounts of attached bacteria on the GTR membranes increased after longer incubation. Incorporation of tetracycline or amoxicillin greatly reduced the adhesion of S. mutans and A. actinomycetemcomitans onto all of the GTR membranes examined. Incorporation of tetracycline or amoxicillin greatly reduced adhesion of S. mutans or A. actinomycetemcomitans on the ePTFE, glycolide fiber, or collagen membranes. This finding indicates that it is valuable and effective to use the antibiotic-loaded GTR membranes for periodontal regeneration therapy.


Neurons from fetal rat brain in a new cell culture system: a multidisciplinary analysis.
A new culture system for cells from the mammalian brain was developed by a modification of a previously established technique. This modification involved the use of fluorodeoxyuridine and adult horse serum. The cultures contained large, easily visualized neurons both isolated from other neurons and in networks of varying complexity. These cells were large enough to permit reliable intracellular electrophysiologic recording and were often sufficiently dispersed to allow examination of membrane responses to iontophoretically applied neurotransmitter candidates. Many responses characteristic of central neurons in situ were seen, including evoked and spontaneous action potentials, complex patterns of inhibitory and excitatory post-synaptic potentials, and neurotransmitter-induced membrane responses. These preparations were examined by phase contrast microscopy, by light microscopy after silver impregnation and by Nomarski interference optics. Total choline acetyltransferase (CAT) activity was little changed and specific activity was increased in the new culture system as compared with the earilier system. Conditions which gave the highest specific activity of CAT also provided the best cultures from the standpoint of electrophysiologic and morphologic analysis. This new approach will allow, in culture, detailed multidisciplinary analyses of individual neurons and small networks of neurons from the mammalian brain.


Diet and melanoma. An exploratory case-control study.
This population-based case-control study contrasted nutrient intakes of 41 women with cutaneous malignant melanoma to those of 297 women sampled from the same community (Brisbane, Australia). Diet was assessed by a comprehensive food frequency questionnaire. The strong inverse relation we observed between high intakes of polyunsaturated fatty acids and melanoma (P < 0.01) adds sufficient weight to prior findings for this persisting causal hypothesis to be abandoned. A relatively strong association with alcohol was observed: Women drinking 20 g or more (two or more drinks) daily had 2.5 (odds ratio) times the risk of melanoma as nondrinkers (95% confidence interval, 0.87 to 7.4). However, previous data are inconsistent. With regard to potential protective factors, our data fit with prior speculation that antioxidants (beta-carotene and vitamin E), zinc, and iron warrant further investigation. The nonsignificant (P = 0.18) 40% reduction in risk seen for those eating the most fish (> or = 15 g daily versus < 5 g) suggests the effects of marine oils and omega-3 fatty acids may deserve specific attention.


A case of significantly increased mitral regurgitation early after atrial septal defect closure.
We report a rare case in which mitral regurgitation (MR) was exacerbated to a severe level early after atrial septal defect (ASD) closure, even though the female patient had preoperatively mild MR and mild changes in mitral valve (MV) and sinus rhythm. The mechanism of increased MR was considered as poor coaptation and tethering of the MV due to the restricted motion of the posterior leaflet in addition to geometric changes of the left ventricle (LV) after ASD closure.


Interaction of histamine H1-and H2-receptor antagonists with histamine uptake and metabolism by guinea-pig isolated atrium and mouse neoplastic mast cells cells in vitro.
1. Burimamide, metiamide, chlorpheniramine, triprolidine and cocaine, were tested as inhibitors of histamine uptake and metabolism in the guinea-pig atrium and in mouse neoplastic mast cells. 2. Cocaine did not affect the uptake and metabolism of histamine, either in the atrium or in the mast cells. All the antihistamines tested blocked the uptake and metabolism of histamine in both preparations. The order of potency was burimamide greater than chlorpheniramine greater than triprolidine greater than metiamide in the atrium; and burimamide greater than metiamide greater than triprolidine greater than chlorpheniramine, in the mase cells. 3. Comparison of the present results with the antihistamine activity of these blocking agents suggests that no correlation exists between the receptor blocking activity and the ability of these substances to act as inhibitors of histamine uptake and metabolism.


Group B Streptococcus in Pregnancy.
To decrease risk of early-onset neonatal sepsis from group B streptococcus (GBS), pregnant patients should undergo screening between 36 0/7 and 37 6/7 weeks' gestation. Patients with a positive vaginal-rectal culture, GBS bacteriuria , or history of newborn with GBS disease should receive intrapartum antibiotic prophylaxis (IAP) with an agent targeting GBS. If GBS status is unknown at time of labor, IAP should be administered in cases of preterm birth, rupture of membranes for >18 hours, or intrapartum fever. The antibiotic of choice is intravenous penicillin; alternatives should be considered in cases of penicillin allergy depending on allergy severity.


Structure-based Inhibitor Design for the Intrinsically Disordered Protein c-Myc.
Intrinsically disordered proteins (IDPs) are associated with various diseases and have been proposed as promising drug targets. However, conventional structure-based approaches cannot be applied directly to IDPs, due to their lack of ordered structures. Here, we describe a novel computational approach to virtually screen for compounds that can simultaneously bind to different IDP conformations. The test system used c-Myc, an oncoprotein containing a disordered basic helix-loop-helix-leucine zipper (bHLH-LZ) domain that adopts a helical conformation upon binding to Myc-associated factor X (Max). For the virtual screen, we used three binding pockets in representative conformations of c-Myc370-409, which is part of the disordered bHLH-LZ domain. Seven compounds were found to directly bind c-Myc370-409 in vitro, and four inhibited the growth of the c-Myc-overexpressing cells by affecting cell cycle progression. Our approach of IDP conformation sampling, binding site identification, and virtual screening for compounds that can bind to multiple conformations provides a useful strategy for structure-based drug discovery targeting IDPs.


Preparation and Luminescent Property of the Self-Assembled Nanoscale Network Systems Combined Tetracyanoplatinate(II) and Copper(II)-Polyaza Complexes.
Complexes 1 and 2 were obtained by the reaction of [Cu(L1)](ClO4)2 (1) or [Cu(L2)](ClO4)2 (2) (L1 = 8-acetyl-1,3,6,8,10,13,15-heptaazatricyclo[220.127.116.11,15]octadecane, L2 = 3,7-bis(2-aminoethyl)- 1,3,5,7-tetraazabicyclo[3.3.l]decane) with K2[Pt(CN)4] in water. The X-ray crystal structures show that the geometry around Cu(II) ions of 1 and 2 adopts a square-pyramid. Their one-dimensional and two-dimensional structures are constructed by the intermolecular hydrogen bonding between the macrocyclic ligand and anionic complex ions or water molecules and Pt-Pt interaction. They show luminescent property and luminescence quantum yields are 0.341 and 0.187 for 1 and 2 in solid, respectively.


Investigating extracellular in situ EGFR structure and conformational changes using FRET microscopy.
The crystallographic structures of functional fragments of ErbBs have provided excellent insights into the geometry of growth factor binding and receptor dimerization. By placing together receptor fragments to build structural models of entire receptors, we expect to understand how these enzymes are allosterically regulated; however, several predictions from these models are inconsistent with experimental evidence from cells. The opening of this gap underlines the need to investigate intact ErbBs by combining cellular and structural studies into a full picture.


A potent human monoclonal antibody with pan-neutralizing activities directly dislocates S trimer of SARS-CoV-2 through binding both up and down forms of RBD.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel coronavirus disease (COVID-19). The neutralizing monoclonal antibodies (mAbs) targeting the receptor-binding domain (RBD) of SARS-CoV-2 are among the most promising strategies to prevent and treat COVID-19. However, SARS-CoV-2 variants of concern (VOCs) profoundly reduced the efficacies of most of mAbs and vaccines approved for clinical use. Herein, we demonstrated mAb 35B5 efficiently neutralizes both wild-type (WT) SARS-CoV-2 and VOCs, including B.1.617.2 (delta) variant, in vitro and in vivo. Cryo-electron microscopy (cryo-EM) revealed that 35B5 neutralizes SARS-CoV-2 by targeting a unique epitope that avoids the prevailing mutation sites on RBD identified in circulating VOCs, providing the molecular basis for its pan-neutralizing efficacy. The 35B5-binding epitope could also be exploited for the rational design of a universal SARS-CoV-2 vaccine.


Development of Multifunctional Fluorescent-Magnetic Nanoprobes for Selective Capturing and Multicolor Imaging of Heterogeneous Circulating Tumor Cells.
Circulating tumor cells (CTC) are highly heterogeneous in nature due to epithelial-mesenchymal transition (EMT), which is the major obstacle for CTC analysis via "liquid biopsy". This article reports the development of a new class of multifunctional fluorescent-magnetic multicolor nanoprobes for targeted capturing and accurate identification of heterogeneous CTC. A facile design approach for the synthesis and characterization of bioconjugated multifunctonal nanoprobes that exhibit excellent magnetic properties and emit very bright and photostable multicolor fluorescence at red, green, and blue under 380 nm excitation is reported. Experimental data presented show that the multifunctional multicolor nanoprobes can be used for targeted capture and multicolor fluorescence mapping of heterogeneous CTC and can distinguish targeted CTC from nontargeted cells.


The effect of bilirubin on long-term mortality in patients with chronic total coronary occlusion.
We intended to investigate the association of bilirubin with total mortality in patients with chronic total coronary occlusion (CTO). We included 172 patients who underwent coronary angiography due to stable angina pectoris and had CTO. We checked the viability of patients after 9 years of follow-up. Direct bilirubin levels were significantly lower in the non-viable group. We revealed age (OR = 1.045, 95% C.I: 1.009‒1.083; p = 0.015) and direct bilirubin concentrations (OR = 0.029, 95% C.I: 0.002‒0.435; p = 0.029) as independent predictors of mortality. Direct bilirubin value of > 0.2 mg/dL was associated with decreased mortality with a sensitivity of 85 %, and a specificity of 46 %. Serum direct bilirubin concentrations independently predict total mortality in patients with chronic total occlusion over 9 years of follow-up (Tab. 1, Fig. 2, Ref. 23).


High-accuracy wearable detection of freezing of gait in Parkinson's disease based on pseudo-multimodal features.
Freezing of gait (FoG) is a serious symptom of Parkinson's disease and prompt detection of FoG is crucial for fall prevention. Although multimodal data combining electroencephalography (EEG) benefit accurate FoG detection, the preparation, acquisition, and analysis of EEG signals are time-consuming and costly, which impedes the application of multimodal information in FoG detection. This work proposes a wearable FoG detection method that merges multimodal information from acceleration and EEG while avoiding the acquisition of real EEG data. A proxy measurement (PM) model based on long-short-term-memory (LSTM) network was proposed to measure EEG features from accelerations, and pseudo-multimodal features, i.e., pseudo-EEG and acceleration, could be extracted using a highly wearable inertial sensor for FoG detection. Based on a self-collected FoG dataset, the performance of different feature combinations were compared in terms of subject-dependent and cross-subject settings. In both settings, pseudo-multimodal features achieved the most promising performance, with a geometric mean of 91.0 ± 5.0% in subject-dependent setting and 91.0 ± 3.5% in cross-subject setting. Our study suggests that wearable FoG detection can be enhanced through leveraging cross-modal information fusion. The new method provides a promising path for multimodal information fusion and the long-term monitoring of FoG in living environments.


Hypopyon uveitis-a rare presentation of intraocular tuberculosis.
Intraocular TB is usually known to present as granulomatous uveitis and presence of hypopyon is extremely rare. The authors describe a case of intraocular tuberculosis presenting as hypopyon uveitis. Case report. A 40-year-old immunosuppressed woman presented with acute granulomatous uveitis with hypopyon and cervical lymphadenopathy. She underwent aqueous tap for polymerase chain reaction, lymph node biopsy, and PET scan. Molecular diagnostic procedures provided a definite diagnosis of ocular tuberculosis. Antitubercular treatment and steroids led to improvement. Intraocular TB can present as hypopyon uveitis and a high index of suspicion is needed, especially in the endemic areas.


Concentration-dependent toxicokinetics of novel PFOS alternatives and their chronic combined toxicity in adult zebrafish.
The increasing use of perfluorooctanesulfonate (PFOS) alternatives has led to their release into the aquatic environment. This study sought to determine the effects of exposure concentration on the toxicokinetics of PFOS and its alternatives, including perfluorobutanesulfonic acid (PFBS), perfluorohexanesulfonic acid (PFHxS), chlorinated polyfluorinated ether sulfonate (F-53B) and sodium p-perfluorous nonenoxybenzenesulfonate (OBS) in adult zebrafish by exposure to mixtures of the five per- and polyfluoroalkyl substances (PFAS) at 1, 10, and 100 ng/mL for 28-day, followed by a 14-day depuration. PFAS predominantly accumulated in the blood and liver, and the bioconcentration factor (BCF) decreased in the order of F-53B > PFOS > OBS ≫ PFHxS > PFBS in whole-fish homogenates. The uptake rate constants and BCF of the short-chain PFAS (≤C6) positively correlated with increasing exposure concentration, while the long-chain PFAS (≥C8) exhibited a pattern of first increasing and then decreasing. A consistent increase in the elimination rate constants of short- and long-chain PFAS was observed with increasing exposure concentration. All PFAS form tight conformations with ZSA and ZL-FABP via hydrogen bonding as revealed by molecular docking analysis. Furthermore, chronic combined exposure to PFAS induced the occurrence of vacuolation and oxidative stress in the zebrafish liver. Our findings uniquely inform the concentration-dependent bioconcentration potential and health risks to aquatic organisms of these PFOS alternatives in the environment.


Association between epilepsy and headache.
Similar clinical characteristics of epilepsy and migraine and the prevalence of their comorbidity have been investigated for years. The present study investigated the relationship between epilepsy and headache. A total of 420 epilepsy patients, who visited epilepsy outpatient clinic within 6-month period between January 2016 and June 2016, were questioned whether they have headache. Age, gender, duration of epilepsy, type of seizures, and temporal relationship of headache with seizure were investigated in the patients with headache. Headache was detected in 111 (26%) of 420 epilepsy patients. The prevalence of migraine was 15%. When the temporal relationship of headache with seizure was evaluated, interictal headache was found to be the most common type with a percentage of 74.8%. No significant difference was determined between the patients with migraine and non-migraine headache in terms of age, gender, duration of epilepsy, age at the onset of epilepsy, type of seizure, and electroencephalography findings. The prevalence of interictal headache was statistically significantly higher in migraine patients as compared to that of non-migraine patients (p < 0.001); however, the prevalence of preictal headache and the prevalence of postictal headache were significantly lower (p = 0.001 and p < 0.001, respectively). The prevalence of headache and the prevalence of migraine, which are considered to be pathogenetically linked to epilepsy, were not different in epilepsy patients as compared to that of the general population. Different outcomes and percentages in other studies suggest that pathogenesis of headache is multifactorial and that different diagnostic criteria might have been taken into consideration.


Narrative interviewing.
Introduction Narrative interviews place the people being interviewed at the heart of a research study. They are a means of collecting people's own stories about their experiences of health and illness. Narrative interviews can help researchers to better understand people's experiences and behaviours. Narratives may come closer to representing the context and integrity of people's lives than more quantitative means of research. Methodology Researchers using narrative interview techniques do not set out with a fixed agenda, rather they tend to let the interviewee control the direction, content and pace of the interview. The paper describes the interview process and the suggested approach to analysis of narrative interviews, We draw on the example from a study that used series of narrative interviews about people's experiences of taking antidepressants. Limitations Some people may find it particularly challenging to tell their story to a researcher in this way rather than be asked a series of questions like in a television or radio interview. Narrative research like all qualitative research does not set out to be generalisable and may only involve a small set of interviews.


Intercalation of cyclic imides in kaolinite.
The intercalation of two cyclic imides, succinimide and glutarimide, in the interlayer spaces of kaolinite was obtained from a "soft guest-displacement method" by displacing previously intercalated guest molecules. The dimethyl sulfoxide (DMSO)-kaolinite preintercalate was particularly efficient for that purpose. The intercalation exchange was done from a concentrated aqueous solution of the cyclic imides, at ambient temperature, in a relatively short time. Complete displacement of DMSO by the cyclic imides was confirmed by the results of several independent characterizations, including XRD, TG/DTA, FTIR, and (13)C MAS NMR analyses including dipolar dephasing experiments. The imide intercalates are two dimensionally constrained in the kaolinite interlayer spaces, and are structurally organized in a flattened configuration with their cycle roughly parallel to the ab plane of the kaolinite layers. Elemental analysis gives the following compositions: Al(2)Si(2)O(5)(OH)(4)(C(4)H(5)NO(2))(0.65) and Al(2)Si(2)O(5)(OH)(4)(C(5)H(7)NO(2))(0.49), respectively for succinimide and glutarimide. The results of the TG/DTA analyses showed enhanced thermal stabilities of the imide intercalates compared with the starting materials. The intercalation process from the aqueous solution is reversible: in prolonged contact with water, the imide molecules are released, resulting in the rebuilding of the kaolinite structure. These results demonstrate the potential use of kaolinite as a slow-releasing agent for molecules structurally related to the cyclic imides of this study.


Erythrocyte intracellular Mg(2+) concentration as an index of recognition and memory.
Magnesium (Mg(2+)) plays an important role in the neural system, and yet scarcely any research has quantitatively analyzed the link between endogenous Mg(2+) level and memory. Using our original technique, we measured erythrocyte intracellular ionized Mg(2+) concentration (RBC [Mg(2+)]i), which linearly correlated to recognition and spatial memory in normal aging rats. In the brain, RBC [Mg(2+)]i significantly correlated to hippocampus extracellular fluid Mg(2+) concentration, and further correlated to hippocampal synapse density. Elevation of Mg(2+) intake in aged rats demonstrated an association between RBC [Mg(2+)]i increase and memory recovery. The therapeutic effect of Mg(2+) administration was inversely correlated to individual basal RBC [Mg(2+)]i. In summary, we provide a method to measure RBC [Mg(2+)]i, an ideal indicator of body Mg(2+) level. RBC [Mg(2+)]i represents rodent memory performance in our study, and might further serve as a potential biomarker for clinical differential diagnosis and precise treatment of Mg(2+)-deficiency-associated memory decline during aging.


Sudden cardiac death and the role of medical therapy.
Sudden cardiac death (SCD) accounts for more than 300,000 deaths annually in the United States. The goal of medical therapy in patients considered to be at high risk (coronary artery disease, post myocardial infarction, structural heart disease and congestive heart failure) involves treating the disease state as well prevention of potentially lethal arrhythmias. Treatment with angiotensin receptor inhibitors, beta blockers and statins has been shown to improve survival in this high risk group. The use of anti-arrhythmic drugs has been studied and found to lack efficacy and has potential for adverse effects. The role of omega-3 fatty acids in preventing sudden death continues to evolve.


Chiral anthracene and anthrone templates as stereocontrolling elements in Diels-Alder/retro Diels-Alder sequences.
The development of chiral anthracene templates for use in Diels-Alder/retro Diels-Alder sequences is described. A summary of past results and new progress is reported.


Strategies for efficient numerical implementation of hybrid multi-scale agent-based models to describe biological systems.
Biologically related processes operate across multiple spatiotemporal scales. For computational modeling methodologies to mimic this biological complexity, individual scale models must be linked in ways that allow for dynamic exchange of information across scales. A powerful methodology is to combine a discrete modeling approach, agent-based models (ABMs), with continuum models to form hybrid models. Hybrid multi-scale ABMs have been used to simulate emergent responses of biological systems. Here, we review two aspects of hybrid multi-scale ABMs: linking individual scale models and efficiently solving the resulting model. We discuss the computational choices associated with aspects of linking individual scale models while simultaneously maintaining model tractability. We demonstrate implementations of existing numerical methods in the context of hybrid multi-scale ABMs. Using an example model describing Mycobacterium tuberculosis infection, we show relative computational speeds of various combinations of numerical methods. Efficient linking and solution of hybrid multi-scale ABMs is key to model portability, modularity, and their use in understanding biological phenomena at a systems level.


UDP-glucuronosyltransferases: a family of detoxifying enzymes.
Glucuronidation is an important process in the metabolism of xenobiotic and endogenous substances leading to enhancement of excretion of these compounds from the body. A multigene family encodes a number of UDP-glucuronosyltransferase enzymes which catalyse this route of metabolism. Recent advances in biochemical and molecular biological approaches, reviewed here by Thomas Tephly and Brian Burchell, have given new insight into the function and structure of UDP-glucuronosyltransferases. These proteins have surprising similarities and yet appear to be capable of conjugating a remarkable number of different chemicals.


Aortic annular abscess complicating prosthetic valve endocarditis with group G streptococcus: detection during life with transesophageal echocardiography.
Infection with group G streptococcus is an unusual but virulent cause of endocarditis. Aortitis and abscess formation due to this organism have been described in one previous report, but only at necropsy. We present here a patient with group G streptococcal endocarditis and aortic annular abscess diagnosed during life by transesophageal echocardiography, leading to successful surgical intervention.


Low doses and lifecycle exposure of waterborne antidepressants in zebrafish model: A survey on sperm traits, reproductive behaviours, and transcriptome responses.
Venlafaxine and citalopram have been commonly found in surface water and may disrupt fish reproduction, yet the long-term impact and the underlying mechanism are largely unknown. Here, zebrafish were exposed to 0.1-100 μg/L venlafaxine and citalopram for their entire life cycle from embryo to adult, respectively. After exposure for 180 days, the lowest observable effective concentration (LOEC) of venlafaxine and citalopram to significantly reduce the mean number of egg production in adults were 10 and 1 μg/L, respectively, whereas the fertilization rate displayed no significant changes. Further, we investigated the impacts of venlafaxine and citalopram in a reproductive context, including sperm quality and reproductive behaviour. In contrast, venlafaxine and citalopram exposure did not affect sperm quality but caused a reduction of reproductive behaviour (e.g., mating duration and mating interval) of adults exposed to 1-10 μg/L of the antidepressant. Transcriptomic profiling of the whole ovary revealed that lifecycle venlafaxine and citalopram exposure significantly affected the Na+/Cl- dependent neurotransmitter transporters signaling. Moreover, immune system-mediated ovarian regeneration and creatine metabolism regulated energy metabolism were proposed as the novel mechanism in the observed effects. Taken together, our results highlight the risk of lifecycle venlafaxine and citalopram exposure to fish reproduction and provide novel perspectives for unveiling the mechanism of female reproductive dysfunction.


Integrins as receptors for extracellular matrix proteins in human cornea.
Extracellular matrix (ECM) proteins form distinct protein families that play a role during tissue maturation, wound healing and maintenance of tissue architecture. Recent studies show that there are tissue type-specific variations in their expression. ECM proteins function by complexing with each other and also by interacting with their cellular receptors, called integrins. Integrins are heterodimeric membrane glycoproteins that are partly cell type-specifically expressed in human tissues. Like other stratified epithelia, corneal epithelium expresses alpha 2 beta 1, alpha 3 beta 1, alpha 6 beta 1, 4, and alpha v beta 1 integrins that mediate attachment to the basement membrane and cell-cell interactions.