Thrombotic events in systemic lupus erythematosus. Its association with acquired and inherited thrombophilic defects.
Systemic lupus erythematosus (SLE) is characterised by increased venous and arterial thrombotic risk. Although antiphospholipid antibodies (APAs) have been shown to be related with thrombotic tendency in these patients, in more than 40% of them, thrombosis occurs without the presence of such antibodies. We analysed the association of venous and arterial thrombotic events with acquired (anticardiolipin antibodies (ACAs) and lupus anticoagulant (LA)) and inherited (antithrombin (AT), protein C (PC), protein S (PS) deficiencies, factor V Leiden and the prothrombin G20210A mutation), thrombophilic risk factors in 86 SLE patients and 89 healthy controls. Patients showed a higher significant percentage of ACAs titres IgG>41 GPL u/ml and LA than controls (P=0.009; P<0.001, respectively), although no differences in AT, PC, PS deficiencies, factor V Leiden and prothrombin G20210A mutation was observed (P>0.05). When patients with and without thrombosis were compared, those with thrombosis showed a statistically higher percentage of ACAs IgG>41 GPL u/ml and LA (P=0.048; P=0.001, respectively), OR 4.33; 95% CI 1.01-18.50 and OR 11.57; 95% CI 3.28-40.75, respectively. When venous and arterial thrombotic events were considered separately, the presence of LA constituted a risk factor for arterial thrombosis (P=0.010), OR 11.33; 95% CI 1.86-68.89, as well as for venous thrombosis (P=0.005), OR 10.15; 95% CI 2.12-48.64, while ACAs IgG>41 GPL u/ml on their own, were not associated with arterial or venous thrombosis (P=0.142, P=0.233, respectively). In addition inherited thrombophilic risk factors AT, PC, PS deficiencies, factor V Leiden and PT G20210A mutation do not seem to increase thrombotic risk in SLE patients.


Standardized protocols increase organ and tissue donation rates in the neurocritical care unit.
The authors tested the effect of uncoupling and removal of the treating physician from organ and tissue donation requests on consent rates for donation in the neurocritical care unit. After a neurointensivist-led policy change, consent rates increased from 23.1 to 36.5% (odds ratio = 1.9, p = 0.01), whereas there was no change in other hospital units. This supports such a policy change and shows a positive effect of a neurointensivist on organ and tissue procurement.


[Long term consequences of obstetrical anal sphincter injuries on sexual function].
Obstetrical anal sphincter injuries (OASIS) can lead to sexual dysfunction. Literature is poor concerning long-term consequences of OASIS on female sexuality. The objective of this paper is to clarify long-term consequences of OASIS on sexual function. Dyspareunia and lubrication troubles are constantly reported based on articles reviewed in literature through Pubmed. Nevertheless, global sexual function seems not to be influenced by OASIS on a long-term basis. Therefore, sexual dysfunctions must be specifically analysed in women's follow-up after OASIS.


Genetic mutations influencing ovulation rate in sheep.
Ovulation rate in mammals is determined by a complex exchange of endocrine signals between the pituitary gland and the ovary, and by paracrine signals within ovarian follicles between the oocyte and its adjacent somatic cells. One approach to identifying factors regulating ovulation rate is to find mutations that influence the target phenotype and, in this context, sheep are proving to be remarkable experimental models. Recently, in three sheep families, namely Inverdale, Hanna and Booroola, the inherited mutation was mapped to a specific region of the sheep X chromosome (Inverdale, Hanna) or sheep chromosome 6 (Booroola) and in each, a point mutation was identified in genes from the bone morphogenetic protein (BMP) relatives of the transforming growth factor beta superfamily or their receptors. In Inverdale (I) and Hanna (H) sheep, separate point mutations were identified in the BMP15 gene corresponding to sites in the mature peptide coding region of the BMP15 growth factor (also known as growth differentiation factor 9B; GDF9B). Expression of the BMP15 gene was located exclusively in oocytes from the primary stage of follicular growth. There is a complete block of normal follicular development in females carrying two copies of the Inverdale mutation (II), two copies of the Hanna mutation (HH), or one copy of each mutation (HI). Increased ovulation rates are found in females with only one copy of either mutation (I+ or H+). In Booroola sheep, a point mutation was identified in the highly conserved intracellular serine threonine kinase signalling domain of the BMP-1B receptor. Within the ovary, this gene is expressed in oocytes in primordial and pre-antral follicles and in granulosa cells from the primary stage of growth as well as in corpora lutea. The effect of the Booroola mutation is additive for ovulation rate: animals with one copy of the mutation have an ovulation rate of 3 or 4, whereas those with two copies have an ovulation rate of between 5 and 14. Physiological studies of the above mutations demonstrate that the oocyte plays an active role with respect to its adjacent somatic cells during follicular development and support the hypothesis that the oocyte has a significant influence on the number of follicles that proceed to ovulation.


Solvent effects on the optical spectra and excited-state decay of triphenylamine-thiadiazole with hybridized local excitation and intramolecular charge transfer.
The triphenylamine-thiadiazole molecule (TPA-NZP) is a newly popular, highly efficient OLED fluorescent emitter with exciton utilization efficiency exceeding the upper limit of spin statistics (25%). In this work, the optical spectra and the radiative and nonradiative decay rate constants have been investigated theoretically for TPA-NZP in hexane, ethyl ether, tetrahydrofuran, and dimethylformamide solvents, in comparison with the gas phase. We observed the evolutions of the excited states from the hybridized local and charge-transfer (HLCT) character to complete intramolecular charge transfer (CT) character with the increase of the solvent polarities. It is found that upon increasing the solvent polarity, the amount of red shift in the absorption peak is much less than that of emission, resulting in breakdown of the mirror symmetry. This is because that 0-0 transition energy is red-shifted but the vibrational relaxation increases with the solvent polarity, leading to subtraction in absorption while addition in emission. The radiative decay rate constant is calculated to be almost independent of polarity. The nonradiative decay rate increases by almost one order of magnitude from that in nonpolar hexane to the strongly polarized dimethylformamide, which is attributed to the dual effects of the red shift in the gap and enhancement of the vibrational relaxation by solvent polarity.


Semiconservative replication in the quasispecies model.
This paper extends Eigen's quasispecies equations to account for the semiconservative nature of DNA replication. We solve the equations in the limit of infinite sequence length for the simplest case of a static, sharply peaked fitness landscape. We show that the error catastrophe occurs when micro, the product of sequence length and per base pair mismatch probability, exceeds 2 ln [2/ ( 1+1/k ) ], where k>1 is the first-order growth rate constant of the viable "master" sequence (with all other sequences having a first-order growth rate constant of 1 ). This is in contrast to the result of ln k for conservative replication. In particular, as k--> infinity, the error catastrophe is never reached for conservative replication, while for semiconservative replication the critical micro approaches 2 ln 2. Semiconservative replication is therefore considerably less robust than conservative replication to the effect of replication errors. We also show that the mean equilibrium fitness of a semiconservatively replicating system is given by k ( 2 e(-micro/2) -1 ) below the error catastrophe, in contrast to the standard result of k e(-micro) for conservative replication (derived by Kimura and Maruyama in 1966). From this result it is readily shown that semiconservative replication is necessary to account for the observation that, at sufficiently high mutagen concentrations, faster replicating cells will die more quickly than more slowly replicating cells. Thus, in contrast to Eigen's original model, the semiconservative quasispecies equations are able to provide a mathematical basis for explaining the efficacy of mutagens as chemotherapeutic agents.


The Thermodynamics of Anion Complexation to Nonpolar Pockets.
The interactions between nonpolar surfaces and polarizable anions lie in a gray area between the hydrophobic and Hofmeister effects. To assess the affinity of these interactions, NMR and ITC were used to probe the thermodynamics of eight anions binding to four different hosts whose pockets each consist primarily of hydrocarbon. Two classes of host were examined: cavitands and cyclodextrins. For all hosts, anion affinity was found to follow the Hofmeister series, with associations ranging from 1.6-5.7 kcal mol-1. Despite the fact that cavitand hosts 1 and 2 possess intrinsic negative electrostatic fields, it was determined that these more enveloping hosts generally bound anions more strongly. The observation that the four hosts each possess specific anion affinities that cannot be readily explained by their structures, points to the importance of counter cations and the solvation of the "empty" hosts, free guests, and host-guest complexes, in defining the affinity.


Altered levels of acid, basic, and neutral peptidase activity and expression in human clear cell renal cell carcinoma.
Peptides play important roles in cell regulation and signaling in many tissues and are regulated by peptidases, most of which are highly expressed in the kidney. Several peptide convertases have a function in different tumor stages, and some have been clearly characterized as diagnostic and prognostic markers for solid tumors, including renal cancer; however, little is known about their in vivo role in kidney tumors. The present study compares the activity of a range of peptidases in human tumor samples and nontumor tissue obtained from clear cell renal cell carcinoma (CCRCC) patients. To cover the complete spectrum and subcellular distribution of peptide-converting activity, acid, neutral, basic, and omega activities were selected. CCRCC displays a selective and restricted pattern of peptidase activities. Puromycin-sensitive aminopeptidase activity in the tumor increases [tumor (t) = 10,775 vs. nontumor (n) = 7,635 units of peptidase (UP)/mg protein; P < 0.05], whereas aminopeptidase N decreases (t = 6,664 vs. n = 33,381 UP/mg protein; P < 0.001). Aminopeptidase B activity of the particulate fraction in tumors decreases (t = 2,399 vs. n = 13,536 UP/mg protein; P < 0.001) compared with nontumor tissues, and aspartyl-aminopeptidase activity decreases significantly in CCRCC (t = 137 vs. n = 223 UP/mg protein; P < 0.05). Soluble and particulate pyroglutamyl peptidase I activities, aminopeptidase A activity, and soluble aminopeptidase B activity do not vary in renal cancer. The relative expression for the aforementioned peptidases, assayed using quantitative RT-PCR, increases in CCRCC for aminopeptidases B (1.5-fold) and A (19-fold), aspartyl-aminopeptidase (3.9-fold), puromycin-sensitive aminopeptidase (2.5-fold), and pyroglutamyl peptidase I (7.6-fold). Only aminopeptidase N expression decreases in tumors (1.3-fold). This peptidase activity profile in the neoplastic kidney suggests a specific role for the studied convertases and the possible involvement of an intracrine renin-angiotensin system in the pathogenesis of CCRCC.


Positron emission tomography imaging of novel AAV capsids maps rapid brain accumulation.
Adeno-associated viruses (AAVs) are typically single-stranded deoxyribonucleic acid (ssDNA) encapsulated within 25-nm protein capsids. Recently, tissue-specific AAV capsids (e.g. PHP.eB) have been shown to enhance brain delivery in rodents via the LY6A receptor on brain endothelial cells. Here, we create a non-invasive positron emission tomography (PET) methodology to track viruses. To provide the sensitivity required to track AAVs injected at picomolar levels, a unique multichelator construct labeled with a positron emitter (Cu-64, t1/2 = 12.7 h) is coupled to the viral capsid. We find that brain accumulation of the PHP.eB capsid 1) exceeds that reported in any previous PET study of brain uptake of targeted therapies and 2) is correlated with optical reporter gene transduction of the brain. The PHP.eB capsid brain endothelial receptor affinity is nearly 20-fold greater than that of AAV9. The results suggest that novel PET imaging techniques can be applied to inform and optimize capsid design.


Curcumin Promotes the Clearance of Listeria monocytogenes both In Vitro and In Vivo by Reducing Listeriolysin O Oligomers.
The pore-forming toxin listeriolysin O (LLO), an essential virulence factor that is secreted by Listeria monocytogenes (L. monocytogenes), is responsible for bacterial breaching at the phagosomal membranes and subsequent release into the cytoplasm; it cannot be recognized by the host immune system. The vital role that LLO plays in bacterial pathogenicity and evading host immune clearance makes this virulence a promising target for addressing L. monocytogenes infection. In this study, we hypothesized that curcumin, a polyphenol derived from turmeric that could effectively inhibit LLO pore-forming activity, might be useful in the prevention or treatment of L. monocytogenes infection. Thus, the in vitro protective effects of curcumin against L. monocytogenes infection by targeting LLO were assessed via hemolytic activity assays, cytotoxicity tests, intracellular growth assays, and confocal microscopy. Our results revealed that treating infected macrophages with curcumin can lead to a decrease in LLO-mediated bacteria phagosomal escape and limit the intracellular growth of L. monocytogenes. Moreover, results from animal experiments show that this natural compound effectively increases protection against bacterial infection and helps the host to clear the invading pathogen completely from an animal model, establishing it as a potent antagonist of L. monocytogenes. The results from our molecular modeling and mutational analysis demonstrated that curcumin directly engages with domains 2 and 4 of LLO, thereby decreasing the hemolytic activity of LLO by influencing its oligomerization. Taken together, these results suggest that, as an antitoxin agent, curcumin can be further developed into a novel therapy against L. monocytogenes infections by targeting LLO.


The Role of Parenting in Alcohol and Tobacco Use Among Latino Adolescents.
Parents can impact adolescent substance use, but it is unclear which substances are most affected. This study compared associations between parenting behaviors and alcohol and tobacco use to see if parenting was equally related to both behaviors. Alcohol and tobacco use data were collected from 252 Latino adolescents living along the San Diego-Tijuana border. Logistic regression was used to test parenting behaviors' impact. Parenting was protective against alcohol use, but not related to tobacco use. Substance using peers affected both alcohol and tobacco use. Alcohol prevention efforts among Latino adolescents should target parenting behaviors.


Does early surgery result in improved long-term survival compared to watchful waiting in patients with asymptomatic severe aortic regurgitation with preserved ejection fraction?
A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: In patients with asymptomatic severe aortic regurgitation with preserved ejection fraction, is early surgery superior to watchful waiting in terms of long-term survival? Altogether, 648 papers were found using the reported search, 3 of which represented the best evidence to answer the clinical question (all level III evidence). The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The 3 included studies comprised 469 patients. All 3 studies attempted to correct for potential baseline differences by different matching methods. As a result, a predominantly beneficial effect of early surgery on long-term survival in patients with severe asymptomatic AR and preserved LV function was observed, whereas none of the studies demonstrated a disadvantageous effect. Still, because many of the initially conservatively treated patients eventually proceed to surgery, longer term follow-up is warranted. Of note, older patients especially seem to adapt more poorly to chronic volume overload due to aortic regurgitation, making them potential candidates for a more aggressive approach. However, when a justified watchful waiting strategy is applied, close, extensive monitoring seems to be imperative, because the development of class I and II triggers seems to lead to improved survival.


Dysregulation of circRNA-0076906 and circRNA-0134944 is Correlated with Susceptibility to Osteoporosis and Osteoporotic Fracture in Postmenopausal Females from the Chinese Han Population.
Many circRNAs, such as circRNA-0076906 and circRNA-0134944, have been reported to participate in the pathogenesis of osteoporosis via sponging miRNAs in postmenopausal female patients. In this study, we aimed to study potential signaling pathways underlying the role of certain circRNAs, miRNAs and their target genes in the pathogenesis of osteoporotic fracture in postmenopausal females. Quantitative real-time PCR was performed to analyze the expression of circRNAs, miRNAs and their targets genes. Luciferase assays were carried out to explore the regulatory relationship between circ_0076906/miR-548i/OGN and circ_0134944/miR-630/TLR4. Osteoporosis and fracture were positively correlated to the expression of circ_0134944, miR-548i and TLR4, but negatively correlated to the expression of circ_0076906, miR-630 and OGN in the peripheral blood and bone tissue samples of postmenopausal women. Luciferase activities of wild-type circ_0076906 and OGN were inhibited by miR-548i, and the luciferase activities of wild-type circ_0134944 and TLR4 were suppressed by miR-630 in MG-63 and U-2 OS cells. Inhibition of circ_0076906 expression in MG-63 and U-2 OS cells activated the expression of miR-548i and inhibited the expression of OGN. Moreover, the overexpression of circ_0134944 in MG-63 and U-2 OS cells suppressed the expression of miR-630 and enhanced the expression of TLR4. This study implied that the dysregulation of circRNA-0076906 and circRNA-0134944 modulated their specific signaling and thus contributed to the severity of osteoporosis, increasing the risk of osteoporotic fracture.


Induced agitation in homogeneous bubbly flows at moderate particle Reynolds number.
We investigated the agitation induced in a liquid by quasimonodispersed spherical bubbles. For Re(p) about 10 and for void fractions ranging from 0.002 to 0.1, the axial velocity fluctuation probability density functions happen to be uniquely determined by the velocity variance. In addition, the variance experiences a rupture from a nonlinear to a quasilinear increase with the volumic concentration. It is shown that the presence of a deficit of neighbors in the wake of any test inclusion forces the screening of velocity disturbances at a finite distance X-of order Re(p)/alpha-and that the velocity variance does not depend on the system size when the later is large compared with X. Finally, the bubble-induced agitation happens to be much stronger for quasimonodispersed than for polydispersed size distributions because of the longer interaction duration between pairs in the former case.


Conventionally ligated versus self-ligating metal brackets--a comparative study.
The purpose of this study was to compare the frictional properties of four self-ligating metal brackets, Speed, Damon 2, In-Ovation, and Time, with those of three conventionally ligated metal brackets, Time, Victory Twin, and Discovery. The self-ligating Time bracket can also be used as a conventionally ligated bracket. Friction was tested 20 times for each bracket/wire combination using a Zwick testing machine with stainless steel wires in three different wire dimensions (0.017 x 0.025, 0.018 x 0.025, and 0.019 x 0.025 inches). All brackets had a 0.022 inch slot and the prescription of an upper first premolar. The data were statistically analysed with unsigned comparisons of all bracket/wire combinations using the Mann-Whitney U-test and the Games-Howell post hoc test. The results showed almost all brackets to have the lowest frictional force with a wire dimension of 0.018 x 0.025 inch. Friction of the self-ligating brackets using wire with a dimension of 0.018 x 0.025 inches was 45-48 per cent lower than with 0.017 x 0.025 and 0.019 x 0.025 inch wires. Friction of the conventionally ligated brackets showed a 14 per cent or less reduced friction with 0.018 x 0.025 inch wire compared with 0.017 x 0.025 and 0.019 x 0.025 inch wires. The self-ligating metal brackets showed lower frictional forces with a 0.018 x 0.025 inch wire than conventionally ligated brackets, whereas conventionally ligated brackets showed lower friction with 0.017 x 0.025 and 0.019 x 0.025 inch wire. Friction values vary with different bracket/archwire combinations and, therefore, the choice of a bracket system for treatment should consider the correct wire dimension to produce the lowest possible frictional forces.


[Bovine spongiform encephalopathy in Europe. Present and future].
Occurrence since 1986 and extension as an extended common source epidemic in United Kingdom of a new neurological bovine condition: bovine spongiform encephalopathy (BSE) initiated numerous epidemiological research actions in this country in order to discover the origin of this new disease, predict its evolution and implement control measures. In the same time epidemiological surveillance systems have been set up in several European countries leading to the identification of sporadic BSE cases in Ireland, Switzerland and France. In spite of the numerous informations published, a number of topics are not precisely known: identity and origin of BSE agent, influence of contaminated bovine genetics over disease development in contaminated bovine, infection incidence in herds where disease has been identified. As BSE is a member of the group of transmissible spongiform encephalopathies, concerns about foodborne transmission from cattle to human and inoculation of medicinal products containing bovine material and used for therapy or prevention in human beings or animals, has been expressed. The demonstration of iatrogenic transmission between human beings of Creutzfeld-Jakob disease has considerably influenced the implementation of measures to prevent the hypothetical risk for man to be infected by medicinal products or medical devises containing material of bovine origin.


Vibrational energy transfer between I2(B (3)Pi(0u)+, nu' = 21) and He at very low temperatures: impulsive versus complex formation mechanisms assisted by tunneling through the centrifugal barrier.
The temperature dependence of the state-to-state vibrational relaxation rate constant (k(nu)(21-Delta nu)) for collisions between I(2)(B,nu(')=21) and He at very low kinetic energies was studied. The fluorescence from I(2)(B,nu(')=21-Delta nu(')) with Delta nu(')=1-5 indicates that in the temperature range of 0.6-8.2 K these states are populated by only one collision with He. The behavior of k(nu)(21-Delta nu) with temperature can be divided into two groups. The group with quantum changes Delta nu(')=1-3 shows scattering resonances in the low temperature region, with a general monotonical decrease of the rate constant with temperature, suggesting the importance of van der Waals interactions. This behavior is supported by the calculation of the probability of tunneling through the centrifugal barriers. For collisions in which 4-5 quanta are lost in a single event, there are no evidences of scattering resonances and the values of the relaxation rate constants could be determined only at the highest temperatures of this study. This suggests that relaxation occurs via impulsive collisions. The branching ratios for each channel are also temperature dependent and this behavior also suggests that the energy transfer mechanism changes with Delta nu(').


Reconstruction of Single Image from Multiple Blurry Measured Images.
The problem of blind image recovery using multiple blurry images of the same scene is addressed in this paper. To perform blind deconvolution, which is also called blind image recovery, the blur kernel and image are represented by groups of sparse domains to exploit the local and nonlocal information such that a novel joint deblurring approach is conceived. In the proposed approach, the group sparse regularization on both the blur kernel and image is provided, where the sparse solution is promoted by -norm. In addition, the reweighted data fidelity is developed to further improve the recovery performance, where the weight is determined by the estimation error. Moreover, to reduce the undesirable noise effects in group sparse representation, distance measures are studied in the block matching process to find similar patches. In such a joint deblurring approach, a more sophisticated two-step interactive process is needed in which each step is solved by means of the well-known split Bregman iteration algorithm, which is generally used to efficiently solve the proposed joint deblurring problem. Finally, numerical studies, including synthetic and real images, demonstrate that the performance of this joint estimation algorithm is superior to the previous state-of-the-art algorithms in terms of both objective and subjective evaluation standards. The recovery results of real captured images using unmanned aerial vehicles are also provided to further validate the effectiveness of the proposed method.


Ultrasound in Infertility Setting: Optimal Strategy to Evaluate the Assessment of Tubal Patency.
Tubal patency is a key element in women who are undergoing assisted reproductive techniques (ART), in order to attempt or exclude intrauterine insemination (IUI) cycles. Amongst the different procedures that can be used, without resorting to laparoscopy that remains the gold standard, hystero-salpingo-contrast sonography (HyCoSy) is an acceptable, time-efficient, and well tolerated option; it can be performed with administration of saline and air simultaneously or alternately (air/saline-HyCoSy), or with some other contrast agents, like SonoVue (sulfur hexafluoride microbubbles). In this paper, we describe two different studies: in the first one, our aim is to compare the efficiency of air/saline-HyCoSy with HyCoSy performed with contrast media (SonoVue), considering hysterosalpingography (HSG) and laparoscopy (LPS) as reference tests; in the second one, we estimate the pregnancy rate of a cohort of infertile women selected to undergo IUI cycles after tubal bilateral patency demonstration with air/saline-HyCoSy, to understand if this technique can be used as an efficient screening procedure in a Reproductive Unit.


Measurements incompatible in quantum theory cannot be measured jointly in any other no-signaling theory.
It is well known that jointly measurable observables cannot lead to a violation of any Bell inequality--independent of the state and the measurements chosen at the other site. In this Letter we prove the converse: every pair of incompatible quantum observables enables the violation of a Bell inequality and therefore must remain incompatible within any other no-signaling theory. While in the case of von Neumann measurements it is sufficient to use the same pair of observables at both sites, general measurements can require different choices. The main result is obtained by showing that for arbitrary dimension the Clauser-Horne-Shimony-Holt inequality provides the Lagrangian dual of the characterization of joint measurability. This leads to a simple criterion for joint measurability beyond the known qubit case.


Characterization of hog kidney renin-binding protein: interconversion between monomeric and dimeric forms.
A radioimmunoassay for hog kidney renin-binding protein (RnBP) was developed. Using this assay method, we investigated the properties of hog kidney RnBP. The lower limit of detection was 24 fmol RnBP. The molecular weight of RnBP in hog kidney extract, as well as the purified RnBP, was estimated to be 65,000 by gel filtration on Ultrogel AcA 44. When the purified RnBP was treated with N-ethylmaleimide (NEM) or 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB), the molecular weight was reduced to 38,000. DTNB-treated RnBP was reconverted to the 65,000-dalton species with dithiothreitol. Cross-linked high molecular weight species of RnBP were produced by the reaction of native RnBP with dimethyl suberimidate, but formation of such species was much less with NEM-treated RnBP. These results suggest that the native RnBP exists as a dimeric form and dissociates to a monomeric form by sulfhydryl-alkylating or -oxidizing reagent. It was shown from analysis of amino acid composition of S-carboxymethylated RnBP and titration of sulfhydryl groups of native and NEM-treated RnBP with DTNB that native RnBP contained twelve cysteine residues and that three cysteine residues were alkylated by NEM under the conditions employed.


Fourier transform infrared and Raman microspectroscopy of materials in tissue.
Fourier transform infrared and Raman (FT-IR and FT-Raman) microspectroscopy were used to study materials found in human tissue. Individual cases involving cholesterol, calcium stearate, and a polystyrenesulfonate ion exchange resin demonstrate the utility of the spectroscopic data. Characteristic spectral bands for these materials were compared with those of authentic chemical species to confirm their identities. The role of vibrational spectroscopy in pathologic diagnoses is discussed.


Classifying Children with ADHD Based on Prefrontal Functional Near-infrared Spectroscopy Using Machine Learning.
: Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in children and adults characterized by cognitive and emotional self-control deficiencies. Previous functional near-infrared spectroscopy (fNIRS) studies found significant group differences between ADHD children and healthy controls during cognitive flexibility tasks in several brain regions. This study aims to apply a machine learning approach to identify medication-naive ADHD patients and healthy control (HC) groups using task-based fNIRS data. : fNIRS signals from 33 ADHD children and 39 HC during the Stroop task were analyzed. In addition, regularized linear discriminant analysis (RLDA) was used to identify ADHD individuals from healthy controls, and classification performance was evaluated. : We found that participants can be correctly classified in RLDA leave-one-out cross validation, with a sensitivity of 0.67, specificity of 0.93, and accuracy of 0.82. : RLDA using only fNIRS data can effectively discriminate children with ADHD from HC. This study suggests the potential utility of the fNIRS signal as a diagnostic biomarker for ADHD children.


Physical Activity, Obesity, and Hypertension among Adults in a Rapidly Urbanised City.
Few studies have explored the relationship between the level of physical activity and the occurrence or prevalence of obesity and hypertension among people residing in urbanised areas. A cross-sectional study involving a sample of 1,001 adults was conducted. Descriptive statistics were used to describe sociodemographic variables, physical activity levels, body mass index (BMI), and prevalence of hypertension. Logistic regression models were adopted to investigate the relationship between these factors. A total of 939 respondents who provided valid responses were included. Among them, 56.5% of the participants reported engaging in high levels of physical activity. However, 40.4% of the respondents were classified as overweight or obese, and 31.9% had diagnosed hypertension. After adjusting for sociodemographic factors, logistic regression analysis revealed that physical activity levels were negatively correlated with the prevalence of BMI (OR = 0.564, 95% CI: 0.352-0.905; OR = 0.583, 95% CI: 0.375-0.907) and hypertension (OR = 0.556, 95% CI: 0.348-0.888). Our study confirms recent evidence regarding the amount of physical activity that is associated with lower prevalence of obesity and hypertension in Pingshan District. Furthermore, different physical activities of various intensity levels had different effects on hypertension. Residents should be encouraged to engage in physical activities and maintain a healthy weight to improve their quality of life.


Metabolic engineering of Rhodopseudomonas palustris for the obligate reduction of n-butyrate to n-butanol.
Rhodopseudomonas palustris is a versatile microbe that encounters an innate redox imbalance while growing photoheterotrophically with reduced substrates. The resulting excess in reducing equivalents, together with ATP from photosynthesis, could be utilized to drive a wide range of bioconversions. The objective of this study was to genetically modify R. palustris to provide a pathway to reduce n-butyrate into n-butanol for maintaining redox balance. Here, we constructed and expressed a plasmid-based pathway for n-butanol production from Clostridium acetobutylicum ATCC 824 in R. palustris. We maintained the environmental conditions in such a way that this pathway functioned as the obligate route to re-oxidize excess reducing equivalents, resulting in an innate selection pressure. The engineered strain of R. palustris grew under otherwise restrictive redox conditions and achieved concentrations of 1.5 mM n-butanol at a production rate of 0.03 g L-1 day-1 and a selectivity (i.e., products compared to the consumed substrate) of close to 40%. Since the theoretical maximum selectivity is 45%, the engineered strain converted close to its maximum selectivity. The innate redox imbalance of R. palustris can be used to drive the reduction of n-butyrate into n-butanol after expression of a plasmid-based enzyme from a butanol-producing Clostridium strain.


Cognitive modeling, ecological psychology, and musical improvisation.
Understanding novelty and improvisation in music requires gathering insight from a variety of disciplines. One fruitful path for synthesizing these insights is via modeling. As such, my aim in this paper is to start building a bridge between traditional cognitive models and contemporary embodied and ecological approaches to cognitive science. To achieve this task, I offer a perspective on a model that would combine elements of ecological psychology (especially affordances) and the Learning Intelligent Decision Agent (LIDA) cognitive architecture. Jeff Pressing's cognitive model of musical improvisation will also be a central link between these elements. While some overlap between these three areas already exists, there are several points of tension between them, notably concerning the nature of perception and the function of artificial general intelligence modeling. I thus aim to alleviate the most worrisome concerns here, introduce several future research questions, and conclude with several points on how my account is part of a general theory, rather than merely a redescription of existent work.


Isolating and enhancing single-photon emitters for 1550 nm quantum light sources using double nanohole optical tweezers.
Single-photon sources are required for quantum technologies and can be created from individual atoms and atom-like defects. Erbium ions produce single photons at low-loss fiber optic wavelengths, but they have low emission rates, making them challenging to isolate reliably. Here, we tune the size of gold double nanoholes (DNHs) to enhance the emission of single erbium emitters, achieving 50× enhancement over rectangular apertures previously demonstrated. This produces enough enhancement to show emission from single nanocrystals at wavelengths not seen in our previous work, i.e., 400 and 1550 nm. We observe discrete levels of emission for nanocrystals with low numbers of emitters and demonstrate isolating single emitters. We describe how the trapping time is proportional to the enhancement factor for a given DNH structure, giving us an independent way to measure the enhancement. This shows a promising path to achieving single emitter sources at 1550 nm.


Effects of silicates from scaps of photovoltaic industries on powdery mildew of zucchini.
Silicon is the second most abundant element on earth's surface and its use can stimulate natural defense mechanisms in plants. The effect of silicate from scraps of photovoltaic industries against powdery mildew on zucchini (Cucurbita pepo) was evaluated under greenhouse conditions. Potted plants were inoculated with a spore suspension containing 1 x 10(5) cfu/ml. The following treatments have been carried out, 3 and 10 days after pathogen inoculation: chemical fungicide (propiconazole, TILT 25 EC, Syngenta); Bacillus subtilis (250 g/hl, Serenade, Intrachem); 1% and 0.1% sodium silicate (r = 1); 1% and 0.1% sodium silicate (r = 2); tap water as control. Disease incidence and severity were assessed 7, 14 and 21days after pathogen inoculation. Results showed that the application of 1% sodium silicate (r = 1) significantly reduced the powdery mildew to a level similar to chemical control. The other treatments, including Bacillus subtilis, reduced disease severity compared to water control, but were less efficient. The use of silicates from photovoltaic industries is a valid alternative for the control of powdery mildew on zucchini, in particular in organic farming. However, silicates might not be sufficient at higher disease incidence levels, and their use is more suitable within an integrated disease control strategy.


Dynamic changes in lipids and proteins of maternal, fetal, and pup blood and milk during perinatal development in CD and Wistar rats.
An understanding of the physiological factors that regulate perinatal dosimetry is essential to improve the ability of physiologically based (PB) pharmacokinetic (PK) models to predict chemical risks to children. However, the impact of changing maternal/offspring physiology on PK during gestation and lactation remains poorly understood. This research determined lipid and protein changes in blood, milk and amniotic fluid of CD and Wistar dams, fetuses and neonates to improve the precision of perinatal PBPK modeling. Samples were collected from time-mated CD dams, fetuses, and pups on gestation day (GD) 18 and 20 (sperm positive = GD 0) or lactation day 0 (day of birth), 1, 3, 5, 10, 15, and 20 (n > or = 5 per time point). Fewer time points were sampled in Wistar rats, which showed similar patterns to CDs. Relative to nonpregnant dams, maternal serum protein levels (albumin, total protein and globulin) each decreased by approximately 20% during late gestation, whereas maternal serum lipids (triglycerides, low density lipoproteins, and phospholipids) increased up to fourfold. These physiological changes can impact maternal PK of both protein-bound and lipophilic chemicals. During lactation, triglycerides in milk were greater than 100-fold higher than maternal serum, favoring the disposition of lipophilic chemicals into milk and potentially increasing neonatal rodent exposure during critical stages of postnatal development. Serum protein levels in pups were two- to threefold lower than adults at birth, which may increase the bioavailability of protein-bound compounds. These data will aid in the interpretation of perinatal toxicity studies and improve the accuracy of predictive perinatal PBPK models.


Measuring quality of life in theory and in practice: a dialogue between philosophical and psychological approaches.
Measuring quality of life is of concern to both philosophers and psychologists, yet the two disciplines typically approach the question in very different ways, ways so diverse that it may look as if they are engaged in such disparate activities that no dialogue between them is possible. In this paper we aim to construct the beginnings of a dialogue between the two disciplines which will show how they could serve each other and yet also show how, from the dialogue, difficult and previously unconsidered issues emerge for both sides.


Patent foramen ovale and ventricular septal defect closure.
Despite the growing recognition of the patent foramen ovale (PFO), particularly when associated with an atrial septal aneurysm, as risk factor for several disease manifestations (above all paradoxical embolism), the optimal treatment strategy for symptomatic patients remains controversial. Percutaneous PFO closure is a minimally invasive procedure which can be performed with high success and low morbidity. For secondary prevention of recurrent embolic events, it appears to be clinically at least as effective as oral anticoagulation. Ventricular septal defects (VSDs) are the most common congenital heart defects. Percutaneous VSD closure is more intricate than PFO closure. It is associated with a significant risk of both peri-interventional and mid-term complications. In suitable patients with congenital VSD, device closure may well be the preferred treatment both for muscular or perimembranous VSDs and for residual defects after surgical VSD closure. The risk of complete atrioventricular conduction block remains a concern in the perimembranous group. The history, technique and clinical role of percutaneous PFO and VSD closure are discussed, with emphasis on current problems and future developments.


SPring-8 in-vacuum undulator beam test at the ESRF.
Before the commissioning of SPring-8, the in-vacuum hybrid undulator developed at SPring-8 had been brought to the ESRF for the first beam test in the summer of 1996. The purpose of this test was to investigate the influence of the in-vacuum undulator on the beam and check its vacuum system. However, heating by the resistive wall impedance turned out to be a critical issue for the in-vacuum undulators.


The biomechanical analysis of bone strength: a method and its application to platycnemia.
Traditional methods of bone analysis (both metric and topographic) are restricted to external characters. Special distribution of material is, however, equally critical to an understanding of a bone's function. Dynamic testing to determine whole bone strength can only be performed on fresh specimens. Methods for the calculation of both bending and torsional strength of other specimens (such as preserved or fossil bones) are developed in this paper. In order to illustrate the methods, the functional significance of tibial shaft cross sectional variation is investigated.


Optimization of UV/H2O2 and ozone wastewater treatment by the experimental design methodology.
The objective of this study was to optimize UV/H2O2 and ozonation systems by means of an experimental design using as a response the efficiency of the operational conditions to remove the methylene blue (MB) dye. Two classes of experimental planning were used: the Doehlert matrix (DM) and the central composite design (CCD). The most important variables for each process were hydrogen peroxide concentration, the ratio of illuminated volume/total volume of the reactor and recirculation flow rate for UV/H2O2, and ozone flow rate, consumed ozone and MB concentration for the ozonation. The DM was more efficient in optimizing the systems, since it used a smaller number of experiments and achieved similar results when compared to the CCD. After optimization, the disinfection efficiency of the systems was tested with secondary effluent evaluating the inactivation of microbiological indicators, Escherichia coli and total coliforms, using the optimized and the worst condition previously obtained with MB removal as response. The inactivation efficiencies in the optimum conditions were about 99%, allowing an efficient disinfection as well as the production of an effluent with quality to be reused according to specific legislations, while at the worse conditions, the inactivation did not reach standards for reuse.


Models for governing relationships in healthcare organizations: Some empirical evidence.
Recently, most European countries have undergone integration processes through mergers and strategic alliances between healthcare organizations. The present paper examined three cases within the Italian National Health Service in order to determine how different organizations, within differing institutional contexts, govern an healthcare integration process. Furthermore, we explored the possibility that the governance mode, usually seen as alternatives (i.e., merger or alliance), could be considered as a separate step in the development of a more suitable integration process. Multiple case studies were used to compare different integration approaches. Specifically, three cases were considered, of which two were characterized by collaborative processes and the other by a merger. Semi-structured interviews were conducted with managers involved in the processes. Each case presents different governing modes, structures, and mechanisms for achieving integration. The role played by the institutional context also led to different results with unique advantages and disadvantages. Three main conclusions are discussed: (a) Alliances and mergers can be interpreted as different steps in a path leading to a better integration; (b) The alignment between institutional/political time horizon and the time needed for the organizations to achieve an integration process lead to a better integration;


Bispectral index is related to the spread of spinal sensory block in patients with combined spinal and general anaesthesia.
A relationship between the depth of sedation as measured by the bispectral index (BIS) and spinal sensory block height in patients with light to no additional sedation has been described previously. The present study was designed to investigate the hypothesis that BIS values closely correlate with the spread of spinal sensory block in patients deeply sedated with an i.v. target-controlled infusion of propofol. Subjects comprised 100 patients aged 20-64 yr and undergoing arthroscopic knee surgery. Patients were given spinal anaesthesia with bupivacaine 0.5% (3 ml). Propofol was administered to achieve a target effect-site concentration of 3.0 μg ml⁻¹. The relationship between the spinal sensory level at 15 min after spinal anaesthesia and BIS values during 1-5, 6-10, 11-15, and 16-20 min time intervals after the estimated effect-site concentration reached 3.0 μg ml⁻¹ was evaluated. The sensory level of spinal analgesia significantly and strongly correlated with BIS values during each time period after the estimated effect-site concentration remained at 3.0 μg ml⁻¹ (P<0.0001). The correlation coefficient values were 0.8 during 1-5 min, 0.844 during 6-10 min, 0.801 during 11-15 min, and 0.804 during 16-20 min time periods. We demonstrated that BIS values significantly correlate with the level of spinal sensory block under deep sedation with propofol. The depth of sedation induced by spinal anaesthesia depends on the spread of spinal sensory block.


Transition-metal-free formal decarboxylative coupling of α-oxocarboxylates with α-bromoketones under neutral conditions: a simple access to 1,3-diketones.
A transition-metal-free formal decarboxylative coupling reaction between α-oxocarboxylates and α-bromoketones to synthesize 1,3-diketone derivatives is presented. In this reaction, a broad scope of substrates can be employed, and neither a metal-based reagent nor an additional base is required. DFT calculations reveal that this reaction proceeds through a coupling followed by decarboxylation mechanism and the α-bromoketone unprecedentedly serves as a nucleophile under neutral conditions. The rate-determining step is an unusual hydrogen-bond-assisted enolate formation by thermolysis.


[Patient safety and quality of care].
Adverse effects related to health care are common and partly avoidable. We need to identify how and why adverse events occur and how system defects may contribute to their occurrence. Systems and processes can be designed to help prevent errors and decrease harm that occurs when they are not intercepted. Tactics to reduce errors and mitigate their adverse effects include reducing complexity and optimizing information processing. Implementation of information technology may offer great promise but the most important is to make an effort to promote a culture of safety.


Improved hardware and software for quick gas chromatography-olfactometry using CHARM and GC-"SNIF" analysis.
A multisniffing system has been developed to allow three panelists to simultaneously participate in a GC-olfactometric analysis. This device, associated with a computerized data treatment, allows shortening CHARM and GC-"SNIF' analyses to less than 1 week and less than 1 day, respectively. The program was developed as an extension of an existing commercial chromatography data system, as usual GC processing functions are suited to the treatment of olfactograms (plots of odor response versus GC elution time). Because of the improved algorithm, the consequences of gaps in coincident responses were minimized, and the systematic use of a panel improved the repeatability of CHARM olfactograms. Comparing both methods, GC-SNIF repeatability appears to be higher than that of CHARM, as the former method uses a larger panel, but in a shorter lapse of time.


Risk factors and outcome of nosocomial infections: results of a matched case-control study of ICU patients.
Intensive-care-unit (ICU) patients are at risk for both acquiring nosocomial infection and dying, and require a high level of therapy whether infection occurs or not. The objective of the present study was to precisely define the interrelationships between underlying disease, severity of illness, therapeutic activity, and nosocomial infections in ICU patients, and their respective influences on these patients' outcome. In a 10-bed medical ICU, we conducted a case-control study with matching for initial severity of illness, with daily monitoring of severity of illness and therapeutic activity scores, and with analysis of the contribution of nosocomial infections to patients' outcomes. Forty-one cases of patients who developed nosocomial infections during a 1-yr period were paired with 41 controls without nosocomial infection according to three criteria: age (+/- 5 yr), Acute Physiology and Chronic Health Evaluation II (APACHE II) score (+/- 5 points), and duration of exposure to risk. Successful matching was achieved for 118 of 123 (96%) variables. Neurologic failure on the third day after ICU admission was the sole independent risk factor for nosocomial infection (adjusted odds ratio [OR]: 1.34; 95% confidence interval [CI]: 1.09 to 1.64; p = 0.007). Unlike control patients, case patients showed no clinical improvement and required a high level of therapeutic activity between ICU admission and the day of infection. Mortality attributable to nosocomial infection was 44%. Excess length of stay and duration of antibiotic treatment attributable to nosocomial infection were 14 d and 10 d, respectively. Attributable therapeutic activity as measured with the Therapeutic Intervention Scoring System (TISS) and Omega score was 368 and 233 points, respectively. Such consequences were observed in patients who developed multiple infections. These findings suggest that a persistent high level of therapeutic activity and persistent impaired consciousness are risk factors for nosocomial infections in ICU patients. These infections are responsible for excess mortality, prolongation of stay, and excess therapeutic activity resulting in important cost overruns for health-care systems.


Bilateral Duane syndrome with bilateral congenital glaucoma.
Multiple ocular associations with Duane syndrome have been reported as summarized by DeRespinis et al. The most frequently noted include nystagmus, anisocoria, ptosis, optic nerve colobomas, and epibulbar dermoids. Less encountered abnormalities are optic nerve hypoplasia, heterochromia, and congenital cataract. To our knowledge, no reports of associated congenital glaucoma exist in the literature. We report a 10-year-old patient with bilateral Duane syndrome and bilateral congenital glaucoma who we have monitored for 7 months after birth.


Quantification of PARP Activity in Human Tissues: Ex Vivo Assays in Blood Cells and Immunohistochemistry in Human Biopsies.
Poly(ADP-ribosyl)ation of proteins is a posttranslational modification mediated by poly(ADP-ribose) polymerases (PARPs) that use NAD+ as substrate to form the negatively charged polymer of poly(ADP-ribose) (PAR). After DNA damage, PARP-1 is responsible for approximately 90% of the total cellular PARylation activity. Numerous studies showed activation of PARP-1 in various conditions associated with oxidative and nitrosative stress, such as ischemia-reperfusion injury, diabetes mellitus, and inflammation, and also proved the beneficial effects of PARP inhibitors. Several pharmacological inhibitors of PARP moved toward clinical testing for a variety of indications, including cardioprotection and malignant tumors, and in late 2014, olaparib became the first PARP inhibitor approved for human use for the therapy of ovarian cancer. These advances necessitate the detection of PARP activation in human tissues. In the present chapter, we review specific methods used to detect PARP activation in human circulating leukocytes and in human tissue sections.


Genetics and celiac disease: the importance of screening.
The prevalence of celiac disease (CD) is increasing. Despite an increased awareness and an improvement in diagnostic testing, the majority of individuals with CD remain undiagnosed. Currently, genetic testing in screening for CD is used only to exclude a diagnosis or reinforce a strong clinical suspicion. In this paper, we review the most current literature regarding genetic testing in CD. In response to important data revealing that an individual's HLA haplotype is one of the strongest known predictors of CD, we propose genetic screening for at-risk infants to stratify individuals based on genetic risk to ultimately create genetic specific screening algorithms.


The multi-PDZ domain protein-1 (MUPP-1) expression regulates cellular levels of the PALS-1/PATJ polarity complex.
MUPP-1 (multi-PDZ domain protein-1) and PATJ (PALS-1-associated tight junction protein) proteins are closely related scaffold proteins and bind to many common interactors including PALS-1 (protein associated with Lin seven) a member of the Crumbs complex. Our goal is to understand how MUPP-1 and PATJ and their interaction with PALS-1 are regulated in the same cells. We have shown that in MCF10A cells there are at least two different and co-existing complexes, PALS-1/MUPP-1 and PALS-1/PATJ. Surprisingly, MUPP-1 levels inversely correlated with PATJ protein levels by acting on the stabilization of the PATJ/PALS-1 complex. Upon MUPP-1 depletion, the increased amounts of PATJ are in part localized at the migrating front of MCF10A cells and are able to recruit more PAR3 (partition defective 3). All together these data indicate that a precise balance between MUPP-1 and PATJ is achieved in epithelial cells by regulating their association with PALS-1.


Kinetics of specific IgG antibodies for monitoring the effect of anti-Helicobacter pylori chemotherapy.
A total of 104 patients with recurrent duodenal ulcer were treated with either ranitidine plus amoxicillin plus metronidazole or ranitidine plus placebo. To study the effect of the eradication of Helicobacter pylori on the systemic immune response in an IgG ELISA, sera were drawn from all patients before the onset of therapy and at 6, 16 +/- 2, 32 +/- 2, and 60 +/- 2 weeks after therapy. In patients with eradication of the organism, a significant (P < .001) reduction of the specific IgG titer occurred. This was not observed in patients without bacterial eradication. If a titer reduction of > 50% was taken as an indicator for eradication of H. pylori, the sensitivity of the serologic test was 97.6%-99.7%. Its specificity increased with the interval to the onset of chemotherapy from 56.3% to 97.6%. Serologic tests are simple to perform and cause very little discomfort to the patient.


Early endoscopic retrograde cholangiopancreatography after laparoscopic cholecystectomy can strain the occurrence of trocar site hernia.
This study reports a 69-year-old, obese, female patient presenting with a biliary leakage after laparoscopic cholecystectomy for cholelithiasis. Closure of the umbilical trocar site had been neglected during the laparoscopic cholecystectomy. Early, on postoperative day five, endoscopic retrograde cholangiopancreatography (ERCP) requirement after laparoscopic cholecystectomy resolved the biliary leakage problem but resulted with a more complicated clinical picture with an intestinal obstruction and severe abdominal pain. Computed tomography revealed a strangulated hernia from the umbilical trocar site. Increased abdominal pressure during ERCP had strained the weak umbilical trocar site. Emergency surgical intervention through the umbilicus revealed an ischemic small bowel segment which was treated with resection and anastomosis. This report demonstrates that negligence of trocar site closure can result in very early herniation, particularly if an endoscopic intervention is required in the early postoperative period.


The 10-year results of a prospective trial of post-operative radiotherapy delivered in 3 fractions per week versus 2 fractions per week in breast carcinoma.
The 10-year results are presented of a prospective trial of 411 patients with breast carcinoma treated by mastectomy and post-operative radiotherapy given in either 2 or 3 fractions per week (i.e. a comparison of 6 fractions in 18 days with 12 fractions in 28 days). The early radiation effects on the normal tissues were similar and acceptable. The late skin changes in the chest wall (treated with 70 kV X rays) were progressive and by 10 years were slightly more marked with 6 fractions. Late subcutaneous fibrosis in the axilla (treated with cobalt-60 teletherapy), however, was much less in the 6-fraction group. Twelve fractions resulted in greater restriction of shoulder movement and an increased incidence of lymphoedema of the arm. Doses were selected on the basis of past clinical experience. The dose used to treat the axilla in 6 fractions was 35 Gy, 14.99% less than that predicted by NSD. The dose predicted by alpha:beta, using a value of 2 Gy for late reactions, is 38.14 Gy. Thus simple theory, which omits time, still predicts too high a dose for 6 fractions, although it is closer than NSD. In this trial, the 6-fraction technique showed an advantage over the 12-fraction technique. It was equally effective in controlling local recurrence and had fewer late sequelae. It was also convenient for patients and economic in the use of radiotherapy resources.


Differential effects of retinoids and inhibitors of ERK and p38 signaling on adipogenic and myogenic differentiation of P19 stem cells.
All-trans-retinoic acid (atRA) is an essential signaling molecule in embryonic development. It regulates cell differentiation by activating nuclear retinoic acid receptors (RAR) and retinoid-X receptors (RXR), which both control gene expression. In addition, atRA could act in the cytoplasm by modulating the activity of mitogen-activated protein kinases (MAPK) ERK and p38, which also have a role in cell differentiation. AtRA can induce the differentiation of P19 embryonic carcinoma stem cells into adipocytes, cardiomyocytes, and skeletal muscle cells, concurrently, in the same culture. We postulated that combinations of atRA, atRA analogs exhibiting selectivity for RAR or RXR, and inhibitors of ERK and p38 signaling (ERKi and p38i) could be used to favor one mesodermal fate over the others in the P19 model. In a first series of experiments, we replaced atRA by an agonist of RXR (LG100268) or RAR (TTNPB) to preferentially stimulate one group of receptors over the other. LG100268 was as adipogenic and myogenic as atRA, whereas TTNPB strongly induced adipogenesis, but not myogenesis. ERKi enhanced the myogenic action of atRA, and p38i increased both adipogenesis and myogenesis. In a second series of experiments, we combined atRA with an RAR or RXR antagonist (RARatg or RXRatg) to preferentially deactivate each receptor group in turn. The combinations atRA+RXRatg and atRA+RARatg, including or not ERKi, had similar mesodermal actions as atRA. In contrast, there was no myogenesis with atRA+RXRatg+p38i treatment, and there were no myogenesis and no adipogenesis with the atRA+RARatg+p38i combination. Overall, the results indicate that p38 has a role in mesodermal differentiation that depends on the retinoid context. Indeed, p38 in conjunction with RXR is important in myogenesis, and p38 and RAR in adipogenesis. Under the conditions tested, it was possible to stimulate adipogenesis with a block on myogenesis, whereas increased myogenesis was accompanied by adipogenesis.


Acing the Joint Commission Regulatory Visit: Running an Effective and Compliant Safety Program.
Ensuring the safety of patients and staff is a core effort of all health care organizations. Many regulatory agencies, from The Joint Commission to the Occupational Safety and Health Administration, provide policies and guidelines, with relevant metrics to be achieved. Data on safety can be obtained through a variety of mechanisms, including gemba walks, team discussion during safety huddles, audits, and individual employee entries in safety reporting systems. Data can be organized on a scorecard that provides an at-a-glance view of progress and early warning signs of practice drift. In this article, relevant policies are outlined, and instruction on how to achieve compliance with national patient safety goals and regulations that ensure staff safety and Joint Commission ever-readiness are described. Additional critical components of a safety program, such as department commitment, a just culture, and human factors engineering, are discussed. ©RSNA, 2018.


Pharmacological interventions for non-alcohol related fatty liver disease (NAFLD): an attempted network meta-analysis.
Non-alcohol related fatty liver disease (commonly called non-alcoholic fatty liver disease (NAFLD)) is liver steatosis in the absence of significant alcohol consumption, use of hepatotoxic medication, or other disorders affecting the liver such as hepatitis C virus infection, Wilson's disease, and starvation. NAFLD embraces the full spectrum of disease from pure steatosis (i.e. uncomplicated fatty liver) to non-alcoholic steatohepatitis (NASH), via NASH-cirrhosis to cirrhosis. The optimal pharmacological treatment for people with NAFLD remains uncertain. To assess the comparative benefits and harms of different pharmacological interventions in the treatment of NAFLD through a network meta-analysis and to generate rankings of the available pharmacological treatments according to their safety and efficacy. However, it was not possible to assess whether the potential effect modifiers were similar across different comparisons. Therefore, we did not perform the network meta-analysis, and instead, assessed the comparative benefits and harms of different interventions using standard Cochrane methodology. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.com to August 2016. We included only randomised clinical trials (irrespective of language, blinding, or publication status) in participants with NAFLD. We excluded trials which included participants who had previously undergone liver transplantation. We considered any of the various pharmacological interventions compared with each other or with placebo or no intervention. We calculated the odds ratio (OR) and rate ratio with 95% confidence intervals (CI) using both fixed-effect and random-effects models based on an available participant analysis with Review Manager. We assessed risk of bias according to the Cochrane risk of bias tool, controlled risk of random errors with Trial Sequential Analysis, and assessed the quality of the evidence using GRADE. We identified 77 trials including 6287 participants that met the inclusion criteria of this review. Forty-one trials (3829 participants) provided information for one or more outcomes. Only one trial was at low risk of bias in all domains. All other trials were at high risk of bias in one or more domains. Overall, all the evidence was very low quality. Thirty-five trials included only participants with non-alcohol related steatohepatitis (NASH) (based on biopsy confirmation). Five trials included only participants with diabetes mellitus; 14 trials included only participants without diabetes mellitus. The follow-up in the trials ranged from one month to 24 months.We present here only the comparisons of active intervention versus no intervention in which two or more trials reported at least one of the following outcomes: mortality at maximal follow-up, serious adverse events, and health-related quality of life, the outcomes that determine whether a treatment should be used. Antioxidants versus no interventionThere was no mortality in either group (87 participants; 1 trial; very low quality evidence). None of the participants developed serious adverse events in the trial which reported the proportion of people with serious adverse events (87 participants; 1 trial; very low quality evidence). There was no evidence of difference in the number of serious adverse events between antioxidants and no intervention (rate ratio 0.89, 95% CI 0.36 to 2.19; 254 participants; 2 trials; very low quality evidence). None of the trials reported health-related quality of life. Bile acids versus no interventionThere was no evidence of difference in mortality at maximal follow-up (OR 5.11, 95% CI 0.24 to 107.34; 659 participants; 4 trials; very low quality evidence), proportion of people with serious adverse events (OR 1.56, 95% CI 0.84 to 2.88; 404 participants; 3 trials; very low quality evidence), or the number of serious adverse events (rate ratio 1.01, 95% CI 0.66 to 1.54; 404 participants; 3 trials; very low quality evidence) between bile acids and no intervention. None of the trials reported health-related quality of life. Thiazolidinediones versus no interventionThere was no mortality in either group (74 participants; 1 trial; very low quality evidence). None of the participants developed serious adverse events in the two trials which reported the proportion of people with serious adverse events (194 participants; 2 trials; very low quality evidence). There was no evidence of difference in the number of serious adverse events between thiazolidinediones and no intervention (rate ratio 0.25, 95% CI 0.06 to 1.05; 357 participants; 3 trials; very low quality evidence). None of the trials reported health-related quality of life. Source of fundingTwenty-six trials were partially- or fully-funded by pharmaceutical companies that would benefit, based on the results of the trial. Twelve trials did not receive any additional funding or were funded by parties with no vested interest in the results. The source of funding was not provided in 39 trials. Due to the very low quality evidence, we are very uncertain about the effectiveness of pharmacological treatments for people with NAFLD including those with steatohepatitis. Further well-designed randomised clinical trials with sufficiently large sample sizes are necessary.


Porins of Haemophilus influenzae type b mutated in loop 3 and in loop 4.
Porin (341 amino acids; mass of 37,782 Da) in the outer membrane of Haemophilus influenzae type b (Hib) permits diffusion into the periplasm of small solutes up to a molecular mass of 1400 Da. Molecular modeling of Hib porin identified its structural similarities to OmpF of Escherichia coli and disclosed for Hib porin a shorter length of loop 3 and a longer length of loop 4. By site-directed mutagenesis of the porin gene ompP2, mutant porins were constructed to contain 6 or 12 amino acid deletions either in loop 3 or in surface-exposed loop 4. Wild type Hib porin and mutant porins were expressed in a nontypeable H. influenzae strain deleted for the ompP2 gene. The mutant porins were purified and reconstituted into planar bilayers, tested for channel formation and compared with wild type Hib porin. Mutant Haemophilus porin possessing a 6-amino acid deletion in loop 3 displayed a broad distribution of single channel conductance values, while deletion of 12 amino acids from the same loop destabilized the porin channel. By comparison, deletion of 6 or of 12 amino acids from loop 4 of Hib porin resulted in an increased single channel conductance (1.15 and 1.05 nanosiemens, respectively) compared with wild type Hib porin (0. 85 nanosiemens). The C3 epitope of the poliovirus VP1 capsid protein was inserted either into loop 3 or into loop 4 of Hib porin. By flow cytometry, the C3 epitope was detected as surface-exposed in strains expressing C3 insertion in loop 4; in strains expressing C3 insertion in loop 3, the epitope was inaccessible. We propose that loop 4 of Hib porin, although surface-accessible, is oriented toward the central axis of the pore and that deletions in this loop increase the single channel conductance by widening the pore entrance.


Preparation of core/shell and hollow nanostructures of cerium oxide by electrodeposition on a polystyrene sphere template.
Core/shell nanostructures of polystyrene (PS)/CeO2 have been prepared on conductive glass substrates by using a novel electrochemical route consisting of (i) the electrophoretic deposition of a PS sphere monolayer on the substrate and (ii) the following potentiostatic electrodeposition of CeO2 on the PS sphere template in Ce(NO3)3 aqueous solutions. The structural morphologies of the deposit changed drastically depending on the Ce(NO3)3 concentration; i.e., spherical and needlelike shells were deposited. The deposit was formed only on the PS sphere surface because of an interaction between cationic cerium species and a sulfate group that was immobilized on the PS sphere surface. The spherical shell layer was assigned as CeO2, and the needlelike shells were composed of Ce(OH)3 needles formed on the CeO2 layer surface, indicating that the deposit species changes from CeO2 to Ce(OH)3 during electrodeposition only in a 1 mM Ce3+ solution. Deposition of Ce(OH)3 would begin when electrogenerated hydrogen peroxide was consumed by decomposition under reductive conditions and could no longer oxidize Ce3+ ions. The corresponding CeO2 hollow shells were obtained by thermal elimination of the PS sphere core and transformation of Ce(OH)3 into CeO2 while keeping their original shapes.


Multiclass Learning With Partially Corrupted Labels.
Traditional classification systems rely heavily on sufficient training data with accurate labels. However, the quality of the collected data depends on the labelers, among which inexperienced labelers may exist and produce unexpected labels that may degrade the performance of a learning system. In this paper, we investigate the multiclass classification problem where a certain amount of training examples are randomly labeled. Specifically, we show that this issue can be formulated as a label noise problem. To perform multiclass classification, we employ the widely used importance reweighting strategy to enable the learning on noisy data to more closely reflect the results on noise-free data. We illustrate the applicability of this strategy to any surrogate loss functions and to different classification settings. The proportion of randomly labeled examples is proved to be upper bounded and can be estimated under a mild condition. The convergence analysis ensures the consistency of the learned classifier to the optimal classifier with respect to clean data. Two instantiations of the proposed strategy are also introduced. Experiments on synthetic and real data verify that our approach yields improvements over the traditional classifiers as well as the robust classifiers. Moreover, we empirically demonstrate that the proposed strategy is effective even on asymmetrically noisy data.


Development of a food-frequency questionnaire to measure the dietary calcium intake of adult Japanese women.
Assessing calcium intake is necessary for epidemiological studies on osteoporosis. This study was aimed at developing a valid food frequency questionnaire (FFQ) to estimate the dietary calcium intake of Japanese people. The FFQ contains 26 items, representing common sources of calcium. The respondents, 74 women aged 15 - 79 years living in Fukui city, whose dietary calcium intake was estimated at 638 +/- 306 (S.D.) mg based on a one-day weighted food record kept during the National Nutrition Survey of 1996, were asked to indicate their consumption frequency and usual portion size (large, medium, small) for each food item. Trained dieticians interviewed the subjects to confirm their answers to the FFQs. The mean calcium intake per day according to the FFQ (655 +/- 222 mg) did not differ significantly from that according to the one-day food record. The coefficient of correlation between these methods was 0.512, a statistically significant value. The calcium intake from dairy products showed a good correlation, r = 0.717. The coefficient of correlation between the values estimated based on two FFQ filled out three days apart was 0.900, showing good test-retest reliability. Therefore, this FFQ is valid and reliable in estimating dietary calcium intake for epidemiological studies.


SPECIATION AND FEATHER ORNAMENTATION IN BIRDS.
The hypothesis that sexual selection promotes speciation has rarely been tested. We identified 70 evolutionarily independent events of feather ornaments in birds. For each focal species we noted the number of ornamented and nonornamented species belonging to its genus and its number of subspecies, as well as its mating system and the extent of its geographic range. For purposes of comparison, we randomly chose a second, nonornamented species for which we obtained information on the number of subspecies, and in cases in which the nonornamented species was in the same genus, we chose a third, nonornamented species in a related genus and obtained the same information. We then noted the number of species in each genus and the difference in numbers of species, or species richness, between paired genera. For the genera of the focal ornamented species, we regressed number of ornamented species on number of nonornamented species and found a positive relationship. As number of species per genus rose, number of ornamented species per genus rose more rapidly, indicating that more speciose genera have a higher proportion of ornamented species than less speciose genera. We then took the deviations from this regression, the residual number of species, and regressed them on the differences in species richness between the paired genera. This relationship was positive indicating that ornamented genera with more than the expected number of ornamented species were more speciose with respect to their paired genera than were genera with fewer than the expected number of ornamented species. Finally, we compared the deviations from this regression, the residual number of ornamented species, with species' mating system and found a greater residual number of ornamented species among species whose mating system is associated with greater skew in male mating success and thus more intense sexual selection. Ornamented species had more subspecies than nonornamented species, even when controlling for geographic range, suggesting an association between subspeciation and ornaments.


Predicting pesticide residues in pod fruits with a modified peel-like uptake model: A green pea demonstration.
Peas are among the most popular leguminous plants, consumed by both humans and animals in large quantities. Pesticides are widely used globally to increase pea yield, and as a result, pesticide residues can be taken up by pea plants and bioaccumulate in their fruits, including peas and pods. However, there is a lack of modeling approaches available to predict residue concentrations in peas. To address this issue, a pod fruit model (specifically designed for neutral organic compounds) was proposed to simulate the bioaccumulation process of pesticide residues in pea plants, which was developed by modifying a peel-like uptake model. The simulation results, based on green pea as the modeling demonstration, reveal that moderately-lipophilic pesticides (i.e., log KOW around 3) have higher simulated concentrations in peas at harvest compared to hydrophilic (i.e., log KOW less than 0) or highly-lipophilic (i.e., log KOW over 5) pesticides, which is due to the enhanced uptake process of moderately-lipophilic compounds in the pod-pea system, such as their ability to penetrate the pod cuticle and be transported via phloem sap. The sensitivity test and variability analysis conducted in this study revealed that the degradation kinetics, including metabolism, hydrolysis, and photolysis, had a significant impact on moderately-lipophilic pesticides due to their high simulated concentrations in the pea plant. This can result in substantial loss of residue mass via degradation. The validation of the model demonstrated that the simulation results, specifically residue concentrations in the fruit, were consistent with the harvested data. However, some inconsistency was observed immediately after pesticide application, which could be attributed to plant growth dynamics and initial surface mass distributions. The proposed pod fruit model provides new insights into the bioaccumulation process of pesticide residues in pea plants and enables high-throughput simulations of residue concentrations at harvest. To enhance the performance of the pod fruit model, future research should consider plant growth dynamics, plant uptake of ionizable compounds, and initial mass distribution functions.


Urinary excretion of alpha 2 mu-globulin and albumin by adult male rats following treatment with nephrotoxic agents.
Nephrotoxic agents such as puromycin aminonucleoside (PAN) and sodium maleate (MAL) have been used to induce experimental glomerular proteinuria and tubular disease, respectively. Current studies show that PAN caused a massive loss of albumin in the urine while not affecting the excretion of the smaller, sex-dependent alpha 2 mu-globulin. On the other hand, MAL which inhibits the reabsorption of proteins, increased the loss of both alpha 2 mu and albumin. Both nephrotoxic agents increased the excretion of albumin when administered to female rats. MAL-induced proteinuria was used as a direct measure of the renal load for alpha 2 mu and albumin. Renal loads and excretion of alpha 2 mu and albumin were measured in male rats maintained on 0, 20, and 50% casein diets. On the protein-free diet, the excretion of both alpha 2 mu and albumin was reduced (less than 1 mg daily); their renal loads were almost totally reabsorbed. On a 50% casein diet the reabsorption of alpha 2 mu was reduced from a normal of 60% to 10% of the renal load. Thus the high protein diet increased the excretion of alpha 2 mu while having little effect on the excretion of albumin. We suggest that dietary protein exerts two levels of control on the excretion of protein in the urine of the adult male rat. Protein-deficient diets stimulate the general reabsorption of proteins thereby minimizing the excretion of alpha 2 mu and albumin. High protein diets appear to reduce selectively the reabsorption of alpha 2 mu-globulin, thereby increasing its excretion in the urine.


Clinical application of interventional embolization in tumor-associated hemorrhage.
Recently, the main clinical treatment methods for tumor-associated hemorrhage include systemic therapy, the application of hemostatic drugs, blood transfusion, symptomatic support therapy and endoscopic interventional hemostasis. Endoscopic hemostasis is performed mainly for patients with gastrointestinal bleeding, and the procedures include hardening of the blood vessels and the injection of hemostatic drugs. Surgical hemostasis methods mainly include the surgical ligation of bleeding blood vessels or tumor resection for hemostasis. Interventional hemostasis is a new hemostasis method. With the development of interventional radiology in recent years, transcatheter arterial embolization (TAE) can quickly detect and accurately embolize arterial blood vessels. It is the preferred treatment for present tumor-associated hemorrhages.


Adoptive T cell therapy: An overview of obstacles and opportunities.
The therapeutic potential of adoptive cell therapy (ACT) in cancer patients was first acknowledged 3 decades ago, but it was an esoteric approach at the time. In recent years, technological advancements have transformed ACT into a viable therapeutic option that can be curative in some patients. In fact, current ACT response rates are 80% to 90% for hematological malignancies and 30% for metastatic melanoma refractory to multiple lines of therapy. Although these results are encouraging, there is still much to be done to fulfill ACT's potential, specifically with regard to improving clinical efficacy, expanding clinical indications, reducing toxicity, and increasing production and cost-effectiveness. This review addresses the current major obstacles to ACT and presents potential solutions. Cancer 2017;123:2154-62. © 2017 American Cancer Society.


The course of tardive dyskinesia in newly treated psychogeriatric patients.
The author reports on the course of tardive dyskinesia in 10 newly treated psychogeriatric patients. Of the 5 whose medication was discontinued, 3 improved; TD continued unchanged in the other 5 patients whose neuroleptics were not discontinued. The author recommends that neuroleptics be discontinued whenever possible in this patient population.


Incidental discovery of radiopaque pills on abdominal CT in a patient with abdominal pain.
We present a case in which a young female ingested several tablets of an over-the-counter cough and cold remedy over the course of a week. Pill fragments were identifiable and incidentally discovered when a CT scan of the abdomen was performed to evaluate the cause of her abdominal pain. Discovery of radiopaque pills on diagnostic imaging studies warrants further history and appropriate testing to rule out a life-threatening ingestion.


Polymorphisms of the lipoprotein lipase gene are associated with atherosclerotic cerebral infarction in the Chinese.
Lipoprotein lipase (LPL), which plays an essential role in plasma lipoprotein metabolism and transportation, appears to be a risk factor for ischemic vascular diseases. Several studies have recently reported the presence of relationship between HindIII, PvuII, Ser447Ter (C-->G) polymorphisms of LPL and ischemic vascular diseases. We first studied the relationship between LPL polymorphisms and the risk of atherosclerotic cerebral infarction (CI) by detecting the frequencies of LPL HindIII, PvuII and Ser447Ter genotypes and combined genotypes in the Chinese. We recruited 185 CI patients, confirmed by cranial computed tomography or magnetic resonance imaging/angiography, or both, and 186 control subjects. Polymerase chain reaction-restriction fragment length polymorphisms technique was used to detect HindIII, PvuII and Ser447Ter polymorphisms of the LPL gene. The frequencies of the H+H+ genotype and H+ allele did not differ between CI and control groups. The frequencies of the P+P+ genotype and P+ allele gene were significantly higher in the CI group (P=0.040, P=0.015). The frequencies of CG+GG genotype and G allele were lower in the CI group (P<0.001, P<0.001). In the CI group, the individuals with P+P+ genotype had a significantly higher level of plasma triglyceride (TG) and a lower level of plasma high density lipoprotein cholesterol (HDL-c). CG+GG genotypes were correlated with significantly higher levels of plasma total cholesterol (TC), HDL-c and low density lipoprotein cholesterol (LDL-c) in the CI group. The frequencies of H+/C and P+/C combined genotypes were higher in the CI group than in controls (P<0.001, P<0.001). The frequency of H+/P+/C combined genotype was significantly higher in the CI group than in controls (P<0.001). Our study suggests that PvuII and Ser447Ter polymorphisms are associated with lipid profile and CI.


Transverse Anderson localization of surface plasmon polaritons.
We investigate the effect of disorder on the propagation of surface plasmon polaritons in arrays of evanescently coupled dielectric loaded surface plasmon polariton waveguides. Diagonal disorder is implemented by randomly varying the heights of the waveguides. Real-space as well as momentum-space images of the surface plasmon polariton intensity distribution in the waveguide arrays are recorded by leakage radiation microscopy. In real space, increasing disorder results in a transverse localization of surface plasmon polaritons. In the momentum distribution, we observe for the first time a disorder-induced transition from a continuous band to a set of discrete modes.


The PKD domain distinguishes the trafficking and amyloidogenic properties of the pigment cell protein PMEL and its homologue GPNMB.
Proteolytic fragments of the pigment cell-specific glycoprotein, PMEL, form the amyloid fibrillar matrix underlying melanins in melanosomes. The fibrils form within multivesicular endosomes to which PMEL is selectively sorted and that serve as melanosome precursors. GPNMB is a tissue-restricted glycoprotein with substantial sequence homology to PMEL, but no known function, and was proposed to localize to non-fibrillar domains of distinct melanosome subcompartments in melanocytes. Here we confirm that GPNMB localizes to compartments distinct from the PMEL-containing multivesicular premelanosomes or late endosomes in melanocytes and HeLa cells, respectively, and is largely absent from fibrils. Using domain swapping, the unique PMEL localization is ascribed to its polycystic kidney disease (PKD) domain, whereas the homologous PKD domain of GPNMB lacks apparent sorting function. The difference likely reflects extensive modification of the GPNMB PKD domain by N-glycosylation, nullifying its sorting function. These results reveal the molecular basis for the distinct trafficking and morphogenetic properties of PMEL and GPNMB and support a deterministic function of the PMEL PKD domain in both protein sorting and amyloidogenesis.


Assessment of oral health status among intellectually and physically disabled population in Chennai.
Oral health is an integral part of general health. In certain populations, especially among intellectually and physically disabled individuals, oral health is neglected. People with disabilities deserve the same opportunities for oral health and hygiene as those who are abled, but sadly dental care is the most common unmet health care need of the disabled people. The purpose of the study is to assess the oral health status and dental care utilization of people above 15 years with intellectual and physical disability in Chennai. A descriptive cross-sectional study was carried out to assess the dental caries experience, gingival status, prevalence of fluorosis and lesion, and dental service utilization among 132 intellectually and physically disabled people in Chennai. After obtaining the caregivers consent of the participants, oral health was assessed using the World Health Organization (WHO) proforma, 2013. Statistical analysis was done using Statistical Package for the Social Sciences Version 23. When DMFT indexes were examined with regard to sex, the mean DMFT was found to be higher for males with 1.453 ± 1.847 whereas females have 1.403 ± 1.73, and mean DMFT was found to be more for the 26-35 years age group with 2.3 ± 2.01. 81.8% of the population had no gingival bleeding whereas only 18.18% had gingival bleeding. With the obtained results, people with physical disability have a high mean DMFT compared with intellectual disability. The present study showed dental negligence among mentally disabled population where the parents, caretakers, and dentists are responsible.


RPS27a enhances EBV-encoded LMP1-mediated proliferation and invasion by stabilizing of LMP1.
Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) is an oncoviral protein that plays a pivotal role in EBV-induced oncogenic transformation. The function of LMP1 in EBV-induced oncogenesis has been well studied. However, the molecular mechanisms underlying LMP1 protein stability remain poorly understood. In this study, we found that ribosomal protein s27a (RPS27a) regulates LMP1 stability by a tandem affinity purification analysis. RPS27a interacts directly with LMP1 in vitro and in vivo. Furthermore, overexpression of RPS27a increases the half-life of LMP1 in 293T cells, whereas downregulation of RPS27a using lentiviral shRNA technology accelerates the decrease in LMP1 protein level in EBV-transformed B cells. We show that LMP1 ubiquitination via the proteasome is completely inhibited by overexpression of RPS27a. RPS27a also enhances LMP1-mediated proliferation and invasion, suggesting that RPS27a interacts with LMP1 and stabilizes it by suppressing proteasome-mediated ubiquitination. These results suggest that RSP27a could be a potential target in EBV-infected LMP1-positive cancer cells.


Granular cell tumor on larynx.
Granular cell tumors (GCTs) are uncommon neoplasm. They can originate in any part of the body. The most common sites of origin are in the head and neck, while the larynx is a relatively uncommon location. Patients affected with a laryngeal GCT typically present with persistent hoarseness, stridor, hemoptysis, dysphagia, and otalgia but, the tumor may be asymptomatic. Care must be taken to differentiate this lesion from others due to the presence of pseudo-epitheliomatous hyperplasia which overlies the GCT and may occasionally mimic squamous cell carcinoma. Therefore, a confirmative diagnosis should be made histopathologically and should be supported by immunohistochemical staining. These tumors are treated by complete surgical resection. Examining the complete removal of the tumor through securing a negative free margin is considered to be a consequential procedure. We experienced a 64-yr-old man with a laryngeal granular cell tumor involving the right true vocal cord. He was treated by surgical resection under a fine dissection laryngomicroscope. Here we present this case and a review of literature.


Toe component excision in postaxial polydactyly of the foot.
Polydactyly of the fifth toe is the most common congenital malformation of the forefoot, and no consensus has been reached as to which toe component should be excised or by which surgical technique. The purpose of this study was to evaluate the results of the operative treatment of postaxial polydactyly and to offer treatment guidelines. We retrospectively reviewed the details of 27 patients with postaxial polydactyly (36 feet) treated from September 2004 to March 2010. To select the dominant toe of postaxial polydactyly, we evaluated the morphological and radiological configurations. To excise the medial toe, we treated the polydactyly by dorsal rectangular flap and a full-thickness inguinal skin graft. To excise the lateral toe, we treated the polydactyly by racket-shape incision. Patient satisfaction indices were evaluated on the basis of responses to the PSQ-10 patient satisfaction questionnaire and clinical outcomes. Overall surgical outcomes were satisfactory with the exception of 2 cases of skin graft problems. Eighteen of the 36 reconstructed toes were smaller than the normal toes, but valgus deformity was observed in only 3 cases. The described medial toe excision technique and the devised toe selection algorithm were able to satisfy functional and cosmetic requirements.


RNA m6 A methylation regulates sorafenib resistance in liver cancer through FOXO3-mediated autophagy.
N6-methyladenosine (m6 A) is an abundant nucleotide modification in mRNA, known to regulate mRNA stability, splicing, and translation, but it is unclear whether it is also has a physiological role in the intratumoral microenvironment and cancer drug resistance. Here, we find that METTL3, a primary m6 A methyltransferase, is significantly down-regulated in human sorafenib-resistant hepatocellular carcinoma (HCC). Depletion of METTL3 under hypoxia promotes sorafenib resistance and expression of angiogenesis genes in cultured HCC cells and activates autophagy-associated pathways. Mechanistically, we have identified FOXO3 as a key downstream target of METTL3, with m6 A modification of the FOXO3 mRNA 3'-untranslated region increasing its stability through a YTHDF1-dependent mechanism. Analysis of clinical samples furthermore showed that METTL3 and FOXO3 levels are tightly correlated in HCC patients. In mouse xenograft models, METTL3 depletion significantly enhances sorafenib resistance of HCC by abolishing the identified METTL3-mediated FOXO3 mRNA stabilization, and overexpression of FOXO3 restores m6 A-dependent sorafenib sensitivity. Collectively, our work reveals a critical function for METTL3-mediated m6 A modification in the hypoxic tumor microenvironment and identifies FOXO3 as an important target of m6 A modification in the resistance of HCC to sorafenib therapy.


Neural networks in chemosystematic studies of Asteraceae: a classification based on a dichotomic approach.
This paper describes the application of artificial neural nets as an alternative and efficient method for the classification of botanical taxa based on chemical data (chemosystematics). A total of 28,000 botanical occurrences of chemical compounds isolated from the Asteraceae family were chosen from the literature, and grouped by chemical class for each species. Four tests were carried out to differentiate and classify different botanical taxa. The qualifying capacity of the artificial neural nets was dichotomically tested at different hierarchical levels of the family, such as subfamilies and groups of Heliantheae subtribes. Furthermore, two specific subtribes of the Heliantheae and two genera of one of these subtribes were also tested. In general, the artificial neural net gave rise to good results, with multiple-correlation values R>0.90. Hence, it was possible to differentiate the dichotomic character of the botanical taxa studied.


Spontaneous intracranial hypotension in a patient with Marfan's syndrome treated with epidural blood patch--a case report.
Spontaneous intracranial hypotension (SIH) is a well-defined clinical entity that is frequently misdiagnosed. We are reporting a case of 38 years old male who presented with severe headache and an episode of generalized tonic-clonic seizure. He was managed successfully with an epidural blood patch. Understanding of the characteristics, symptomatology, evaluation, treatment options, and prognosis is discussed.


Skin as the primary site of Hodgkin's disease: a case report of primary cutaneous Hodgkin's disease and review of its relationship with non-Hodgkin's lymphoma.
We report an elderly patient who presented with a single cutaneous nodule of primary cutaneous Hodgkin's disease (PCHD). Reed-Sternberg cells, expressing CD30 and CD15, but not leukocyte common antigen (CD45RB), were identified in the neoplastic cells. Southern blot analysis failed to detect T-cell receptor or immunoglobulin gene rearrangement. A work-up for systemic disease at the time of presentation was negative, supporting the diagnosis of PCHD. Nevertheless, 1 year later, the disease course was complicated by the development of nodal HD and nonHodgkin's lymphoma (NHL). This case report supports the existence of this rare, but distinct, cutaneous tumor.


Functional Spectroscopy Mapping of Pain Processing Cortical Areas During Non-painful Peripheral Electrical Stimulation of the Accessory Spinal Nerve.
Peripheral electrical stimulation (PES), which encompasses several techniques with heterogeneous physiological responses, has shown in some cases remarkable outcomes for pain treatment and clinical rehabilitation. However, results are still mixed, mainly because there is a lack of understanding regarding its neural mechanisms of action. In this study, we aimed to assess its effects by measuring cortical activation as indexed by functional near infrared spectroscopy (fNIRS). fNIRS is a functional optical imaging method to evaluate hemodynamic changes in oxygenated (HbO) and de-oxygenated (HbR) blood hemoglobin concentrations in cortical capillary networks that can be related to cortical activity. We hypothesized that non-painful PES of accessory spinal nerve (ASN) can promote cortical activation of sensorimotor cortex (SMC) and dorsolateral prefrontal cortex (DLPFC) pain processing cortical areas. Fifteen healthy volunteers received both active and sham ASN electrical stimulation in a crossover study. The hemodynamic cortical response to unilateral right ASN burst electrical stimulation with 10 Hz was measured by a 40-channel fNIRS system. The effect of ASN electrical stimulation over HbO concentration in cortical areas of interest (CAI) was observed through the activation of right-DLPFC (p = 0.025) and left-SMC (p = 0.042) in the active group but not in sham group. Regarding left-DLPFC (p = 0.610) and right-SMC (p = 0.174) there was no statistical difference between groups. As in non-invasive brain stimulation (NIBS) top-down modulation, bottom-up electrical stimulation to the ASN seems to activate the same critical cortical areas on pain pathways related to sensory-discriminative and affective-motivational pain dimensions. These results provide additional mechanistic evidence to develop and optimize the use of peripheral nerve electrical stimulation as a neuromodulatory tool (NCT03295370- www.clinicaltrials.gov).