[Risk of reactivation or exacerbation of an infectious disease during iatrogenic immunosuppression or immune reconstitution].
Drug induced immunosuppression increases the risk of infections, both occurring as reactivation of latent-infections and occurrence of recent opportunistic ones. Thus, a careful mandatory infection screening is needed before immunosuppressive drugs onset. In addition, immune reconstitution after immunosuppression cessation can be associated with acute worsening of the underlying infection leading to the immune reconstitution inflammatory syndrome that must be differenciated from infection recurrences, relapses or resistance to antiinfective agents.


Spotted fever group rickettsiae in Dermacentor variabilis from Cape Cod, Massachusetts.
Spotted fever group (SFG) rickettsiae were identified by indirect immunofluorescent antibody tests in 1.1% of 6,956 specimens of Dermacentor variabilis collected on Cape Cod, Massachusetts. Forty-one of 45 rickettsial isolates were serotyped as Rickettsia montana, one as Rickettsia rickettsii, and three were unidentified. Studies of canines and humans with clinical evidence of spotted fever, and of healthy dogs with antibody to SFG rickettsiae, indicated that exposure of the canine population to R. montana was common but that R. montana was not involved in the etiology of spotted fever.


Towards online spike sorting for high-density neural probes using discriminative template matching with suppression of interfering spikes.
The process of grouping neuronal spikes in an extracellular recording according to their neuronal sources, is generally referred to as spike sorting. Currently, the use of spike sorting is mainly limited to an offline usage, where spikes are sorted after the data acquisition has been completed. In this paper, we propose a discriminative template matching algorithm for threshold-based spike sorting on high-density extracellular data. Such threshold-based spike sorting has a low and deterministic algorithmic delay, allowing for fast online spike sorting. At its core, threshold-based spike sorting is driven by linear filters. The proposed discriminative template matching filter design algorithm optimizes the output signal-to-peak-interference ratio in a data-driven fashion, assuming the template of the target spike is available. The latter allows the filter to suppress the spikes of interfering neurons and to resolve spike overlap. The data-driven filter design algorithm requires only templates of the target neurons of interest, which can be retrieved, e.g. through a prior clustering on an initial recording. The proposed discriminative template matching filters are validated on in vivo ground truth data and are shown to provide single-unit activity with good accuracy using a simple thresholding operation on the filter outputs. The low algorithmic complexity allows for computationally cheap and fast spike sorting. Also the proposed filters are guaranteed to be stable and have a deterministic delay. These characteristics make the proposed filter design method a valuable building block for online spike sorting, thereby enabling unit activity-based real-time and closed-loop experiments for high-density neural recordings.


Determination of partition coefficients using 1 H NMR spectroscopy and time domain complete reduction to amplitude-frequency table (CRAFT) analysis.
We have developed a simple, direct and novel method for the determination of partition coefficients and partitioning behavior using 1 H NMR spectroscopy combined with time domain complete reduction to amplitude-frequency tables (CRAFT). After partitioning into water and 1-octanol using standard methods, aliquots from each layer are directly analyzed using either proton or selective excitation NMR experiments. Signal amplitudes for each compound from each layer are then extracted directly from the time domain data in an automated fashion and analyzed using the CRAFT software. From these amplitudes, log P and log D7.4 values can be calculated directly. Phase, baseline and internal standard issues, which can be problematic when Fourier transformed data are used, are unimportant when using time domain data. Furthermore, analytes can contain impurities because only a single resonance is examined and need not be UV active. Using this approach, we examined a variety of pharmaceutically relevant compounds and determined partition coefficients that are in excellent agreement with literature values. To demonstrate the utility of this approach, we also examined salicylic acid in more detail demonstrating an aggregation effect as a function of sample loading and partition coefficient behavior as a function of pH value. This method provides a valuable addition to the medicinal chemist toolbox for determining these important constants. Copyright © 2017 John Wiley & Sons, Ltd.


Regulations on nutrition in Indonesia and its relation to early childhood caries.
There is a close relationship between food and nutrition policies and oral health. The relationship between nutrition and dental problems has been widely discussed, including the major dental problem in children: early childhood caries (ECC). Health-oriented national policies are the main principles of public health welfare. This article is a policy brief that provide a review of the food and nutrition policies in Indonesia that may have a relationship with ECC. It is concluded that some policies support the efforts to prevent ECC however, other technical explanations are still needed for health workers and especially parents regarding its simple implementation in everyday life. Multisectoral approaches that includes health, nutrition and education are needed to address ECC.


Biodegradable stents as a platform to drug loading.
Despite technical and mechanical improvement in coronary stents the incidence of restenosis caused by in-stent neointimal hyperplasia remains high. Oral administration of numerous pharmacological agents has failed to reduce restenosis after coronary stenting in humans, possibly owing to insufficient local drug concentration. Therefore, drug-eluting stents were developed as a vehicle for local drug administration. The authors developed a new drug-eluting polymer stent that is made of poly-l-lactic acid polymer mixed with tranilast, an anti-allergic drug that inhibits the migration and proliferation of vascular smooth muscle cells induced by platelet-derived growth factor and transforming growth factor->1. Polymer stents might be superior to polymer-coated metallic stents as local drug delivery stents in terms of biodegradation and the amount of loaded drug. Drug-mixed polymer stents can be loaded with a larger amount of drug than can drug-coated metallic stents because the polymer stent struts can contain the drug. Clinical application is required to assess the safety and efficacy of drug-eluting polymer stents against stent restenosis.


Focus on phosphohistidine.
Phosphohistidine has been identified as an enzymic intermediate in numerous biochemical reactions and plays a functional role in many regulatory pathways. Unlike the phosphoester bond of its cousins (phosphoserine, phosphothreonine and phosphotyrosine), the phosphoramidate (P-N) bond of phosphohistidine has a high DeltaG degrees of hydrolysis and is unstable under acidic conditions. This acid-lability has meant that the study of protein histidine phosphorylation and the associated protein kinases has been slower to progress than other protein phosphorylation studies. Histidine phosphorylation is a crucial component of cell signalling in prokaryotes and lower eukaryotes. It is also now becoming widely reported in mammalian signalling pathways and implicated in certain human disease states. This review covers the chemistry of phosphohistidine in terms of its isomeric forms and chemical derivatives, how they can be synthesized, purified, identified and the relative stabilities of each of these forms. Furthermore, we highlight how this chemistry relates to the role of phosphohistidine in its various biological functions.


Use of a methylene blue azide medium for isolation of enterococci.
A methylene blue azide medium (MBA), developed by Schaedler, Dubos, and Costello to isolate enterococci from the gastrointestinal tract of animals, was evaluated. This was done by comparing the isolation of enterococci from feces and saliva on the medium. Fifty-two catalase-negative, gram-positive cocci from human feces isolated from MBA were classified as enterococci. All strains grew in S F, 6.5% NaCl, and streptomycin broths, and all fermented mannitol. The isolates were provisionally subdivided into Streptococcus faecalis and S. faecium groups. S. faecalis-like strains fermented glycerol and pyruvate aerobically and produced acid in Snyder's medium (initial pH, 4.8). The S. faecium group fermented raffinose. Among all strains, several tests were variable. These included growth at 45 C, in 0.1% tellurite and in methylene blue milk. Three methods were employed to isolate and identify enterococci from the oral cavity. Direct streaking of MBA with saliva failed to produce any growth on the medium. Two other methods, with the use of various selective broths to promote the recovery of oral enterococci, failed to produce any bacteria capable of growing on MBA. The MBA-isolated fecal strains and oral viridans streptococci were generally indistinguishable on Mitis-Salivarius and K F agars. In experiments with fecal material, no gram-negative bacilli were found among the isolates selected. The MBA medium was judged as a high selectivity-low yield medium, and may provide a means of separating fecal and nonfecal enterococci.


Ecallantide for the treatment of hereditary angiodema in adults.
Hereditary angioedema (HAE) is a clinical disorder characterized by a deficiency of C1 esterase inhibitor (C1-INH). HAE has traditionally been divided into two subtypes. Unique among the inherited deficiencies of the complement system, HAE Types I and II are inherited as an autosomal dominant disorder. The generation of an HAE attack is caused by the depletion and/or consumption of C1-inhibitor manifested as subcutaneous or submucosal edema of the upper airway, face, extremities, or gastrointestinal tract mediated by bradykinin. Attacks can be severe and potentially life-threatening, particularly with laryngeal involvement and treatment of acute attacks in the United States has been severely limited. In December 2009 the FDA approved ecallantide for the treatment of acute HAE attacks. Ecallantide is a small recombinant protein acting as a potent, specific and reversible inhibitor of plasma kallikrein which binds to plasma kallikrein blocking its binding site, directly inhibiting the conversion of high molecular weight kininogen to bradykinin. Administered subcutaneously, ecallantide was demonstrated in two clinical trials, EDEMA3 and EDEMA4, to decrease the length and severity of acute HAE attacks. Although there is a small risk for anaphylaxis, which limits home administration, ecallantide is a novel, safe, effective and alternative treatment for acute HAE attacks.


Developing a community-led SMS reporting tool for the rapid assessment of lymphatic filariasis morbidity burden: case studies from Malawi and Ghana.
Lymphoedema and hydrocoele are the two most common clinical manifestations of lymphatic filariasis (LF). In order to effectively target morbidity management strategies, more information is rapidly needed on morbidity burden across all endemic countries. The purpose of this study was to develop and test an SMS tool (MeasureSMS) which enables trained community-based health workers to report basic information on all cases they identified. The tool was trialled in Chikwawa district, Malawi and Ahanta West district, Ghana in 2014. Salaried health surveillance assistants (HSAs) identified and reported cases in Malawi whereas volunteer community health workers (CHWs) were used in Ghana. Health workers were trained in recognising lymphoedema and hydrocoeles and submitting individual case data using MeasureSMS, after which they undertook a LF morbidity survey. After the reporting period, a random sample of reported cases was visited by a physician to verify the health workers' diagnoses. The proportion of correctly diagnosed cases i.e. the positive predictive value (PPV) was then calculated. HSAs in Malawi successfully reported 256 unique cases by SMS from 107 communities (166 hydrocoele, 88 lymphoedema, 2 with both), resulting in an estimated adult prevalence of 17.7 per 10,000 and 33.0 per 10,000 for lymphoedema and hydrocoele respectively. In Ghana, despite being less experienced in using SMS, CHWs successfully reported 360 unique cases by SMS from 33 communities (169 hydrocoele, 185 lymphoedema, 6 with both), resulting in an estimated adult prevalence of 76.9 per 10,000 and 70.5 per 10,000 adults for lymphoedema and hydrocoele respectively. The verification exercise resulted in a PPV for lymphoedema and hydrocoele diagnosis of 90 % (n = 42, 95 % CI 76.5 - 96.9) and 92 % (n = 49, 95 % CI 79.5 - 97.4) in Malawi and 94 % (n = 34, 95 % CI 78.9 %-99.0 %) and 47 % (n = 59, 35.1 %-61.7 %) in Ghana, indicating that non-invasive methods for diagnosing hydrocoeles needed to be further emphasised. The study concludes that given the appropriate education and tools, community-based health workers are exceptionally well-placed to participate in quantifying LF morbidity burden, and other NTDs with observable symptoms. This concept has the potential to enable national programmes to more effectively monitor their community impact in an efficient, timely and cost-effective way.


Language Entails Linguistic Relativity.
This commentary addresses the challenge of linking an individual-grounded theory of concepts to a phenomenon that assumes conceptual conventions at population level (linguistic relativity). We distinguish I-concepts (individual, interior, imagistic) from L-concepts (linguistic, labeled, local) and see that quite different causal processes are often conflated under the term "concepts." I argue that the Grounded Cognition Model (GCM) entails linguistic relativity only to the extent that it imports L-concepts into its scope, which it can hardly avoid doing given that practitioners require language to coordinate around their theory and findings. I conclude that what entails linguistic relativity is not the GCM but language itself.


Tracking of a Fixed-Shape Moving Object Based on the Gradient Descent Method.
Tracking moving objects is one of the most promising yet the most challenging research areas pertaining to computer vision, pattern recognition and image processing. The challenges associated with object tracking range from problems pertaining to camera axis orientations to object occlusion. In addition, variations in remote scene environments add to the difficulties related to object tracking. All the mentioned challenges and problems pertaining to object tracking make the procedure computationally complex and time-consuming. In this paper, a stochastic gradient-based optimization technique has been used in conjunction with particle filters for object tracking. First, the object that needs to be tracked is detected using the Maximum Average Correlation Height (MACH) filter. The object of interest is detected based on the presence of a correlation peak and average similarity measure. The results of object detection are fed to the tracking routine. The gradient descent technique is employed for object tracking and is used to optimize the particle filters. The gradient descent technique allows particles to converge quickly, allowing less time for the object to be tracked. The results of the proposed algorithm are compared with similar state-of-the-art tracking algorithms on five datasets that include both artificial moving objects and humans to show that the gradient-based tracking algorithm provides better results, both in terms of accuracy and speed.


Evidence for multifactor regulation of the adrenocorticotropin secretory response to hemodynamic stimuli.
We have examined the contributions of corticotropin-releasing factor (CRF), arginine vasopressin (AVP), epinephrine, and oxytocin to the ACTH secretory responses to hemorrhage. The relative significance of each of these putative ACTH regulatory factors is undefined with respect to net ACTH secretion. Initially, the effects of selective systemic pharmacological blockade of individual factors on the ACTH response were examined. Immunoneutralization of CRF reduced resting ACTH levels below the detection limits of our RIA and abolished the secretory response to hemorrhage. Ganglionic blockade or treatment with a potent AVP antagonist reduced the ACTH secretory response by 55% and 38%, respectively. Further evidence for multifactor regulation of hemodynamically evoked alterations in ACTH secretion was obtained by measurement of the concentrations of these factors in the hypophysial portal circulation during hemorrhage. Immunoreactive CRF, AVP, oxytocin and epinephrine were present in the portal plasma at concentrations within a range shown to evoke ACTH secretion from cultured pituitary cells when presented alone or in combination. The concentrations of all of these were significantly elevated during hemorrhage. During atrial pulsation, a stimulus mimicking volume loading and associated with a reduction of systemic ACTH levels, we observed a significant decline in portal concentrations of immunoreactive AVP coupled with a nonsignificant trend toward reduced portal immunoreactive CRF levels. These observations are highly suggestive of multifactor regulatory control of ACTH secretion in response to hemodynamic stimuli.


Mitochondrial NADP+-Dependent Isocitrate Dehydrogenase Deficiency Exacerbates Mitochondrial and Cell Damage after Kidney Ischemia-Reperfusion Injury.
Mitochondrial NADP+-dependent isocitrate dehydrogenase (IDH2) catalyzes the oxidative decarboxylation of isocitrate to α-ketoglutarate, synthesizing NADPH, which is essential for mitochondrial redox balance. Ischemia-reperfusion (I/R) is one of most common causes of AKI. I/R disrupts the mitochondrial redox balance, resulting in oxidative damage to mitochondria and cells. Here, we investigated the role of IDH2 in I/R-induced AKI. I/R injury in mice led to the inactivation of IDH2 in kidney tubule cells. Idh2 gene deletion exacerbated the I/R-induced increase in plasma creatinine and BUN levels and the histologic evidence of tubule injury, and augmented the reduction of NADPH levels and the increase in oxidative stress observed in the kidney after I/R. Furthermore, Idh2 gene deletion exacerbated I/R-induced mitochondrial dysfunction and morphologic fragmentation, resulting in severe apoptosis in kidney tubule cells. In cultured mouse kidney proximal tubule cells, Idh2 gene downregulation enhanced the mitochondrial damage and apoptosis induced by treatment with hydrogen peroxide. This study demonstrates that Idh2 gene deletion exacerbates mitochondrial damage and tubular cell death via increased oxidative stress, suggesting that IDH2 is an important mitochondrial antioxidant enzyme that protects cells from I/R insult.


Predominant VH1-69 IgBCR Clones Show Higher Expression of CD5 in Heterogeneous Chronic Lymphocytic Leukemia Populations.
The immunoglobulin B cell receptor (IgBCR) expressed by chronic lymphocytic leukemia (CLL) B cells plays a pivotal role in tumorigenesis, supporting neoplastic transformation, survival, and expansion of tumor clones. We demonstrated that in the same patient, two or more CLL clones could coexist, recognized by the expression of different variable regions of the heavy chain of IgBCR, composing the antigen-binding site. In this regard, phage display screening could be considered the easier and most advantageous methodology for the identification of small peptide molecules able to mimic the natural antigen of the tumor IgBCRs. These molecules, properly functionalized, could be used as a probe to specifically identify and isolate single CLL subpopulations, for a deeper analysis in terms of drug resistance, phenotype, and gene expression. Furthermore, CLL cells express another surface membrane receptor, the CD5, which is commonly expressed by normal T cells. Piece of evidence supports a possible contribution of CD5 to the selection and maintenance of autoreactivity in B cells and the constitutive expression of CD5 on CLL cells could induce pro-survival stimuli. In this brief research report, we describe a peptide-based single-cell sorting using as bait the IgBCR of tumor cells; in the next step, we performed a quantitative analysis of CD5 expression by qRT-PCR related to the expressed IgBCR. Our approach could open a new perspective for the identification, isolation, and investigation of all subsets of IgBCR-related CLL clones, with particular attention to the more aggressive clones.


Analysis of the Influence of Pre-Pregnancy BMI and Weight Gain during Pregnancy on the Weight of Healthy Children during the First 2 Years of Life: A Prospective Study.
Increased pre-pregnancy maternal BMI (pBMI) and gestational weight gain (GWG) have been found to increase infants' birthweight and result in the programming of child weight and impact its later weight gain. To assess the impact of pBMI and GWG on the weight of children from birth to 2 years of age and over the duration of breastfeeding. Single Centre observational prospective longitudinal cohort study. Data were collected from medical records, and medical history. The analysis of multiple linear and mixed models was involved. 20% of females were overweight, while 13% were obese before the pregnancy. An overall model, including gender and smoking, indicated a significant impact of pBMI category on a child's birth mass (p = 0.01). The GWG category affected a child's birth weight (p = 0.018, Effect size 0.41). pBMI did not affect the breastfeeding duration. pBMI and GWG correlate with birth weight and weight in neonatal period, however they become insignificant in later childhood. Weight assessment methods among children aged up to two years of age require standardization. Maternal weight before the pregnancy nor the weight gain during the pregnancy do not influence the length of breastfeeding. The biggest limitation was the small sample size and the failure to account for weight gain per trimester of pregnancy. Further research on a larger population should be continued.


Machine learning reveals sequence-function relationships in family 7 glycoside hydrolases.
Family 7 glycoside hydrolases (GH7) are among the principal enzymes for cellulose degradation in nature and industrially. These enzymes are often bimodular, including a catalytic domain and carbohydrate-binding module (CBM) attached via a flexible linker, and exhibit an active site that binds cello-oligomers of up to ten glucosyl moieties. GH7 cellulases consist of two major subtypes: cellobiohydrolases (CBH) and endoglucanases (EG). Despite the critical importance of GH7 enzymes, there remain gaps in our understanding of how GH7 sequence and structure relate to function. Here, we employed machine learning to gain data-driven insights into relationships between sequence, structure, and function across the GH7 family. Machine-learning models, trained only on the number of residues in the active-site loops as features, were able to discriminate GH7 CBHs and EGs with up to 99% accuracy, demonstrating that the lengths of loops A4, B2, B3, and B4 strongly correlate with functional subtype across the GH7 family. Classification rules were derived such that specific residues at 42 different sequence positions each predicted the functional subtype with accuracies surpassing 87%. A random forest model trained on residues at 19 positions in the catalytic domain predicted the presence of a CBM with 89.5% accuracy. Our machine learning results recapitulate, as top-performing features, a substantial number of the sequence positions determined by previous experimental studies to play vital roles in GH7 activity. We surmise that the yet-to-be-explored sequence positions among the top-performing features also contribute to GH7 functional variation and may be exploited to understand and manipulate function.


Effects of Two Common Polymorphisms rs2910164 in miR-146a and rs11614913 in miR-196a2 on Gastric Cancer Susceptibility.
Background. Single nucleotide polymorphisms (SNPs) in genes encoding microRNAs may play important role in the development of gastric cancer. It has been reported that common SNPs rs2910164 in miR-146a and rs11614913 in miR-196a2 are associated with susceptibility to gastric cancer. The published results remain inconclusive or even controversial. A meta-analysis was conducted to quantitatively assess potential association between the two common SNPs and gastric cancer risk. Methods. A comprehensive literature search was performed in multiple internet-based electronic databases. Data from 12 eligible studies were extracted to estimate pooled odds ratios (ORs) and 95% confidence intervals (95% CI). Results. C allele of rs2910164 is associated with reduced gastric cancer risk in heterozygote model and dominant model whereas rs11614913 indicates no significant association. Subgroup analysis demonstrates that C allele of rs2910164 and rs11614913 may decrease susceptibility to diffuse type gastric cancer in dominant model and recessive model, respectively, while rs11614913 increased intestinal type gastric cancer in dominant model. Conclusion. SNPs rs2910164 and rs11614913 might have effect on gastric cancer risk in certain genetic models and specific types of cancer. Further well-designed studies should be considered to validate the potential effect.


Redox-responsive chemosensitive polyspermine delivers ursolic acid targeting to human breast tumor cells: The depletion of intracellular GSH contents arouses chemosensitizing effects.
Antitumor efficacy of ursolic acid (UA) is seriously limited due to its low hydrophilicity and needy bioavailability. To overcome these obstacles, chemosensitive polyspermine (CPSP) conjugated with UA and folic acid (FA) as a novel targeted prodrug was designed and successfully synthesized in this investigation. This prodrug not only showed high aqueous solubility, GSH-triggered degradation and good biocompatibility, but also exhibited better inhibition effect on the tumor cells proliferation in comparison with free UA. FA-CPSP-UA could down-regulate the generation of GSH and manifest excellent ability in enhancing antitumor efficacy. In addition, FA-CPSP-UA could inhibit the expression of MMP-9, which led to restricting MCF-7 cells migration. Taken together, the results indicated that FA-CPSP-UA, as a carrier, can efficiently deliver UA to folate receptor positive cancer cells and improve tumor therapy of UA by Chemosensitive effect.


The stochastic world of emerging viruses.
The acquisition of new hosts is a fundamental mechanism by which parasitic organisms expand their host range and perpetuate themselves on an evolutionary scale. Among pathogens, viruses, due to their speed of evolution, are particularly efficient in producing new emergence events. However, even though these phenomena are particularly important to the human species and therefore specifically studied, the processes of virus emergence in a new host species are very complex and difficult to comprehend in their entirety. In order to provide a structured framework for understanding emergence in a species (including humans), a comprehensive qualitative model is an indispensable cornerstone. This model explicitly describes all the stages necessary for a virus circulating in the wild to come to the crossing of the epidemic threshold. We have therefore developed a complete descriptive model explaining all the steps necessary for a virus circulating in host populations to emerge in a new species. This description of the parameters presiding over the emergence of a new virus allows us to understand their nature and importance in the emergence process.


In Vivo Dopamine Biosensor Based on Copper(I) Sulfide Functionalized Reduced Graphene Oxide Decorated Microelectrodes.
A novel dopamine biosensor based on carbon fiber microelectrodes (CFMEs) modified with copper(I) sulfide functionalized nanocomposites of the reduced graphene oxide (Cu2S/RGO) has been explored for the sensitive detection of dopamine and in vivo monitoring the neurotransmitters released by Drosophila's brain. The as-prepared Cu2S/RGO decorated microelectrodes were characterized by scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS), and cyclic voltammetry (CV). Our observations demonstrate that Cu2S/RGO-CFMEs exhibited excellent catalytic activity and high selectivity for dopamine with relatively low detection limit (24 nM), wide linear range (i.e., from 0.1-20 μM) and outstanding reproducibility. Furthermore, the as-prepared new dopamine biosensor with high sensitivity and good stability was readily used to detect the amount of dopamine in the brain of drosophila, indicating the potential and promising application in the in vivo measurement of neurotransmitters without other electrochemical interference such as histidine, ascorbic acid, uric acid, and others.


Visual selective attention and the effects of monetary rewards.
Outcomes of actions, in the form of rewards and punishments, are known to shape behavior. For example, an action followed by reward will be more readily elicited on subsequent encounters with the same stimuli and context -- a phenomenon known as the law of effect. These consequences of rewards (and punishments) are important because they reinforce adaptive behaviors at the expense of competing ones, thus increasing fitness of the organism in its environment. However, it is unknown whether similar influences regulate covert mental processes, such as visual selective attention. Visual selective attention allows privileged processing of task-relevant information, while inhibiting distracting contextual elements. Using variable monetary rewards as arbitrary feedback on performance, we tested whether acts of attentional selection, and in particular the resulting aftereffects, can be modulated by their consequences. Results show that the efficacy of visual selective attention can be sensibly adjusted by external feedback. Specifically, although lingering inhibition of distractors is robust after highly rewarded selections, it is eliminated after poorly rewarded selections. This powerful feature of visual selective attention provides attentive processes with both flexibility and self-regulation properties.


The validity of locus of control dimensions for Chicano populations.
The multidimensional locus of control literature supported the tenability of five factorial dimensions: a) luck/fate, b) leadership/success, c) academics, d) politics, and e) respect. Contending that the contradictory locus of control findings involving Chicano populations may be due to methodological inadequacies, the purpose of the present study was to empirically determine the appropriateness of the five categories for comparing Chicano and Anglo populations. This was done by factor analyzing the responses of 203 Anglo and 244 Chicano undergraduates to Rotter's (1966) 1-E scale separately, and then comparing the corresponding factor pairs by using Cliff's (1966) congruence procedure. The luck/fate and leadership/success factors show substantial invariance across the two samples, whereas the cultural equivalence of the remaining three factors is somewhat questionable. The findings are discussed in relation to current knowledge of cross-cultural differences between Anglo and Chicano populations.


Towards open data blockchain analytics: a Bitcoin perspective.
Bitcoin is the first implementation of a technology that has become known as a 'public permissionless' blockchain. Such systems allow public read/write access to an append-only blockchain database without the need for any mediating central authority. Instead, they guarantee access, security and protocol conformity through an elegant combination of cryptographic assurances and game theoretic economic incentives. Not until the advent of the Bitcoin blockchain has such a trusted, transparent, comprehensive and granular dataset of digital economic behaviours been available for public network analysis. In this article, by translating the cumbersome binary data structure of the Bitcoin blockchain into a high fidelity graph model, we demonstrate through various analyses the often overlooked social and econometric benefits of employing such a novel open data architecture. Specifically, we show: (i) how repeated patterns of transaction behaviours can be revealed to link user activity across the blockchain; (ii) how newly mined bitcoin can be associated to demonstrate individual accumulations of wealth; (iii) through application of the naïve quantity theory of money that Bitcoin's disinflationary properties can be revealed and measured; and (iv) how the user community can develop coordinated defences against repeated denial of service attacks on the network. Such public analyses of this open data are exemplary benefits unavailable to the closed data models of the 'private permissioned' distributed ledger architectures currently dominating enterprise-level blockchain development owing to existing issues of scalability, confidentiality and governance.


Children admitted to high security (special) hospital.
The Special Hospitals in England provide psychiatric treatment in high security. The aim of this study was to examine the demographics and background characteristics of children admitted to high security hospitals in England, using the special hospital case register. Forty-six children (the subject group) were admitted to a high security hospital under the MHA (1983) classification of disorder of mental illness and/or psychopathic disorder between 1983 and 1999, 33 (72%) of whom were male. A comparison group of adults was matched on sex, legal classification of detention and MHA 1983 classification of disorder. The children were admitted for a similar range of offences to those of the comparison group. However, the children had received convictions for criminal damage and violence at a significantly earlier age, they were more likely to have experienced a change in caregiver during their childhood, been placed in a children's home and were less likely to be living with a family member on their 16th birthday. Children admitted to special hospital experience a lot of disruption in their childhood and are extremely high users of multi-agency services as they grow up. Issues are raised regarding how to provide a developmentally sensitive service for children who require high security care.


Social priming modulates the neural response to ostracism: a new exploratory approach.
The present study sought to evaluate whether social priming modulates neural responses to ostracism, such that making arbitrary interpersonal decisions increases the experience of social exclusion more than making arbitrary physical decisions. This exploratory event-related potential (ERP) study utilized the Lunchroom task, in which adults (N = 28) first selected one of two options that included either interpersonal or physical descriptors. Participants then received ostracism outcome feedback within a lunchroom scenario in which they were either excluded (e.g. sitting alone) or included (e.g. surrounded by others). While the N2 component was sensitive to priming decision condition, only the P3 component discriminated between ostracism decisions. Further inspection of the neural sources indicated that the amygdala, anterior cingulate cortex, and superior temporal gyrus were more engaged for exclusion than inclusion conditions during both N2 and P3 temporal windows. Evaluation of temporal source dynamics suggest that the effects of ostracism are predominant between 250-500 ms and were larger following interpersonal than physical decisions. These results suggest that being ostracized evokes a larger neural response that is modulated following priming of the social brain.


Coxsackievirus and Adenovirus Receptor (CAR) Expression in Autopsy Tissues: Organ-Specific Patterns and Clinical Significance.
Coxsackievirus and adenovirus receptor (CAR) homologs have been identified in many species, and their proteins appeared to be highly conserved in evolution. While most of the human studies are about pathological conditions, the animal studies were more about the physiological and developmental functions of receptors. The expression of CAR is developmentally regulated, and its tissue localization is complex. Hence, we planned to study CAR expression in five different human organs at autopsy in different age groups. CAR expression was analyzed in the pituitary, heart, liver, pancreas, and kidney by immunohistochemistry, and CAR mRNA expression in the heart and pituitary by real-time PCR. In the current study, CAR expression was strong in cells of the anterior pituitary, hepatocytes, and bile ducts in the liver, acini, and pancreas and distal convoluted tubule/collecting duct in the kidney, with uniform expression in all age groups. We have noted high CAR expression in fetuses and infantile hearts, which get reduced drastically in adults due to its presumed developmental role in intrauterine life studied in animal models. In addition, the receptor was expressed in glomerular podocytes around the period of fetus viability (37 weeks) but not in early fetuses and adults. We have hypothesized that this intermittent expression could be responsible for the intercellular contact normally formed between the podocytes during the developmental phase. Pancreatic islets also showed increased expression after the emergence of the viability period but not in early fetuses and adults, which might be related to an increase in fetal insulin secretion at that particular age group.


Why do accident and emergency doctors request X-rays?
A prospective study was carried out to analyse all X-rays requested from the three accident and emergency departments in Sheffield during one week. There were 3253 patients examined, of which 1028 (31.6%) were X-rayed, 1251 sets of X-rays being performed. Few X-rays (4.5%) were requested for medico-legal reasons. Skull X-rays were studied in particular detail. Only 5 (4.5%) of 112 films were subsequently reported as abnormal by the radiologist. The accident and emergency doctor's ability to predict X-ray outcome was not very good, their false positive rate being high at 21% while their false negative rate was low at 5.5%. This indicates that the accident and emergency doctors tended to be over cautious to compensate for their lack of experience.


Docking performance of fragments and druglike compounds.
This paper addresses two questions of key interest to researchers working with protein-ligand docking methods: (i) Why is there such a large variation in docking performance between different test sets reported in the literature? (ii) Are fragments more difficult to dock than druglike compounds? To answer these, we construct a test set of in-house X-ray structures of protein-ligand complexes from drug discovery projects, half of which contain fragment ligands, the other half druglike ligands. We find that a key factor affecting docking performance is ligand efficiency (LE). High LE compounds are significantly easier to dock than low LE compounds, which we believe could explain the differences observed between test sets reported in the literature. There is no significant difference in docking performance between fragments and druglike compounds, but the reasons why dockings fail appear to be different.


What Arguments against COVID-19 Vaccines Run on Facebook in Poland: Content Analysis of Comments.
Social media allow anti-vaxxers to quickly spread misinformation and false statements. This situation may lead to an increase in vaccine hesitancy. We wanted to characterize what arguments against COVID-19 vaccines run on Facebook in Poland. We analyzed Facebook comments related to the five events of the introduction of COVID-19 vaccines-announcements of the efficacy of the Pfizer-BioNTech (09.11.2020), Moderna (16.11.2020), and AstraZeneca (23.11.2020) vaccines, registration of the Pfizer-BioNTech vaccine by the European Medicines Agency (21.12.2020), and the first vaccination in Poland (27.12.2020). We collected the comments from fanpages of the biggest Polish media and then established their main anti-vaccine themes. We found that the negative arguments about COVID-19 vaccines can be divided into 12 categories. Seven of them are universal and also apply to other vaccines but five are new and COVID-19' specific. The frequency of arguments from a given category varied over time. We also noticed that, while the comments were mostly negative, the reactions were positive. Created codebook of anti-vaccine COVID-19 arguments can be used to monitor the attitude of society towards COVID-19 vaccines. Real-time monitoring of social media is important because the popularity of certain arguments on Facebook changes rapidly over time.


[Digital technology in clinical surgery and rehabilitation].
This article is devoted to a very actual and insufficiently imagine in the literature theme - innovation and digital technologies in clinical surgery and rehabilitation. To schow posibilities of modern digital and information technologies in clinical practice based on the experience of the Pirogov Center. Analysis of experience in the application of innovative technologies, robotic surgery, intraoperative navigation computer, robotic systems in medical rehabilitation, integrated operating room, surgical video communication systems in service of those doing the Pirogov Center for the past 10 years. Shows the feasibility of the considered technologies in modern clinical practice clinics. The experience of the Pirogov Center indicates that the extensive use in clinical practice of modern health care facilities of the latest high-tech equipment in conjunction with the introduction of process automation and digital integrated technology management and medical-diagnostic activity is an essential reserve to increase the activity of providing specialized, including high-tech medical care, carrying out a variety of scientific and educational activities.


Bioethics in nephrology: guidelines for decision-making in Italy.
In 1998, the Italian Ministry of Health urged the Italian Society of Nephrology (SIN) to draft recommendations for uniform decision-making procedures in the field of dialysis. In accordance with the Ministry's specifications, at the time the Society approved diagnostic protocols regarding clinical questions, but without fully recognizing the multiple issues arising in complex medical situations where dialysis is likely to go on for a long time. The authors propose some guidelines for ethical conduct and their application, with special regard to medico-legal dilemmas, together with the principles of clinical guidelines that would further improve the "perceived quality" of chronic dialytic treatment.


Cognitive and psychological factors associated with early posttreatment functional outcomes in breast cancer survivors.
Breast cancer survivors experience cognitive difficulties following chemotherapy, yet the effects of these deficits on functional outcomes have not been systematically evaluated. This study assessed the relationships between postchemotherapy cognitive difficulties and functional outcomes. Forty-six women with breast cancer were seen at 1-month postchemotherapy; data were collected on cognitive functioning, psychological variables, and physical symptoms. Wilcoxon signed-rank analyses revealed cognitive deficits in executive functioning and verbal fluency. Subsequent regression analyses demonstrated that poorer executive functioning was associated with decreased productivity, community involvement, and social role functioning. Poorer quality of life was predicted by depression and reluctance to seek social support, but not cognitive functioning. These findings indicate that executive functioning deficits are associated with important functional outcomes among breast cancer survivors 1-month postchemotherapy. Thus, treatment efforts should focus on addressing cognitive, as well as psychological and physical, issues among cancer survivors.


Variation in genotype and higher virulence of a strain of Sporothrix schenckii causing disseminated cutaneous sporotrichosis.
Sporotrichosis is usually a localized, lymphocutaneous disease, but its disseminated type was rarely reported. The main objective of this study was to identify specific DNA sequence variation and virulence of a strain of Sporothrix schenckii isolated from the lesion of disseminated cutaneous sporotrichosis. We confirmed this strain to be S. schenckii by(®) tubulin and chitin synthase gene sequence analysis in addition to the routine mycological and partial ITS and NTS sequencing. We found a 10-bp deletion in the ribosomal NTS region of this strain, in reference to the sequence of control strains isolated from fixed cutaneous sporotrichosis. After inoculated into immunosuppressed mice, this strain caused more extensive system involvement and showed stronger virulence than the control strain isolated from a fixed cutaneous sporotrichosis. Our study thus suggests that different clinical manifestation of sporotrichosis may be associated with variation in genotype and virulence of the strain, independent of effects due to the immune status of the host.


Biobutanol Production from Crystalline Cellulose through Consolidated Bioprocessing.
Biobutanol production directly from lignocellulose, known as consolidated bioprocessing (CBP), is expected to be much less expensive than a process where hydrolytic enzyme production, cellulose saccharification, and microbial fermentation are accomplished separately. However, few microbes possess both cellulolytic and solventogenic properties in nature. Current research aims to endow cellulolytic microorganisms with butanol-producing ability or to set up microbial consortia for CBP. This review comprehensively details current achievements attempting to confer butanol-generating ability, not only to cellulolytic Clostridium strains but also to microbial consortia, to address and overcome major challenges in butanol production from cellulose. Recent advances in improving cellulosome activities within cellulolytic Clostridium strains are also emphasized.


Acquisition of protease resistance by prion proteins in scrapie-infected cells does not require asparagine-linked glycosylation.
The scrapie and cellular isoforms of the prion protein (PrPSc and PrPC) differ strikingly in a number of their biochemical and metabolic properties. The structural features underlying these differences are unknown, but they are thought to result from a posttranslational process. Both PrP isoforms contain complex type oligosaccharides, raising the possibility that differences in the asparagine-linked glycosylation account for the properties that distinguish PrPC and PrPSc. ScN2a and ScHaB cells in culture produce several PrP molecules with relative molecular masses of 26-35 kDa and proteinase K-resistant cores of 19-29 kDa. When the cells were treated with tunicamycin, this heterogeneity was eliminated and a single PrP species of 26 kDa was observed. Several hours after its synthesis, a fraction of this protein became insoluble in detergents and acquired a proteinase K-resistant core, thus displaying two of the biochemical hallmarks of PrPSc. Synthesis in the presence of tunicamycin restricted the proteinase K-resistant cores of PrP to a single species of 19 kDa. No proteinase K-resistant PrP was found in uninfected cells. Expression of a mutated PrP gene lacking both asparagine-linked glycosylation sites in ScN2a cells resulted in the synthesis of 19-kDa proteinase K-resistant PrP molecules. We conclude that asparagine-linked glycosylation is not essential for the synthesis of proteinase K-resistant PrP and that structural differences unrelated to asparagine-linked oligosaccharides must exist between PrPC and PrPSc. Whether unglycosylated PrPSc molecules are associated with scrapie prion infectivity remains to be established.


The role of the cingulate cortex as neural generator of the N200 and P300 in a tactile response inhibition task.
Both the N200 and P300, which are, for example, evoked by Go/Nogo or Stop-Signal tasks, have long been interpreted as indicators for inhibition processes. Such interpretations have recently been challenged, and interest in the exact neural generators of these brain responses is continuously growing. Using recent methodological advancements, source estimations for the N200 and P300 as evoked by a tactile response inhibition task were computed. Current density reconstructions were also calculated accounting for interindividual differences in head geometry by incorporating information from T1-weighted magnetic resonance images. To ease comparability with relevant paradigms, the task was designed to mimic important characteristics of both Go/Nogo and Stop-Signal tasks as prototypes for a larger set of paradigms probing response inhibition. A network of neural generators was revealed, which has previously been shown to act in concert with executive control processes and thus is in full agreement with observations from other modalities. Importantly, a spatial segregation of midcingulate sources was observed. Our experimental data indicate that a left anterior region of the midcingulate cortex (MCC) is a major neural generator of the N200, whereas the midcingulate generator of the P300 is located in the right posterior MCC. Analyses of the P300 also revealed several areas, which have previously been associated with motor functions, for example, the precentral region. Our data clearly suggest a neuroanatomical and therefore also functional dissociation of the N200 and P300, a finding that cannot easily be provided by other imaging techniques.


Brazil Nut (Bertholletia excelsa H.B.K) Retards Gastric Emptying and Modulates Enteric Glial Cells in a Dose-Dependent Manner.
The role of food and nutrients in the regulation of enteric glial cell functions is unclear. Some foods influence enteric neurophysiology and can affect glial cell functions that include regulation of the intestinal barrier, gastric emptying, and colonic transit. Brazil nuts are the most abundant natural source of selenium, unsaturated fatty acids, fibers, and polyphenols. The study investigated the effects of a Brazil nut-enriched diet on enteric glial cells and gastrointestinal transit. Two-month-old male Wistar rats were randomized to a standard diet (control group, CG), standard diet containing 5% (wt/wt) Brazil nut (BN5), and standard diet containing 10% (wt/wt) Brazil nut (BN10) (n = 9 per group). After eight weeks, the animals underwent constipation and gastric emptying tests to assess motility. Evaluations of colonic immunofluorescence staining for glial fibrillary acidic protein (GFAP) and myenteric ganglia area were performed. The BN5 group showed increased weight gain while the BN10 group did not (p < 0.0001). The BN10 group showed higher gastric residue amounts compared to the other groups (p = 0.0008). The colon exhibited an increase in GFAP immunoreactivity in the BN5 group compared to that in the other groups (p = 0.0016), and the BN10 group presented minor immunoreactivity compared to the CG (p = 0.04). The BN10 group presented a minor ganglia area compared to the CG (p = 0.0155). The Brazil nut-enriched diet modified the gastric residual, colonic GFAP immunoreactivity, and myenteric ganglia area after eight weeks in healthy male Wistar rats.


Transhilar passage in right graft live donor liver transplantation: intrahilar anatomy and its impact on operative strategy.
The passage through the hilar plate during right graft live donor liver transplantation (LDLT) can have dangerous consequences for both donors and recipients. The purpose of our study was to delineate hilar transection and biliary reconstruction strategies in right graft LDLT, with special consideration of central and peripheral hilar anatomical variants. A total of 71 consecutive donors underwent preoperative three-dimensional (3D) CT reconstructions and virtual 3D hepatectomies. A three-modal hilar passage strategy was applied, and its impact on operative strategy analyzed. In 68.4% of cases, type I and II anatomical configurations allowed for an en block hilar transection with simple anastomotic reconstructions. In 23.6% of cases, donors had "difficult" type II and types III/IV hilar bile duct anatomy that required stepwise hilar transections and complex graft biliary reconstructions. Morbidity rates for our early (A) and recent (B) experience periods were 67% and 39%, respectively. (1) Our two-level classification and 3D imaging technique allowed for donor-individualized transhilar passage. (2) A stepwise transhilar passage was favored in types III and IV inside the right-sided hilar corridor. (3) Reconstruction techniques showed no ameliorating effect on early/late biliary morbidity rates.


[The programme of managed ambulatory rehabilitation for patients after heart valve defect surgery].
THE AIM of our research was to evaluate the impact of 8-week comprehensive rehabilitation programme on circulatory parameters, left ventricular (LV) function and functional capacity of patients after aortal (ao) and mitral (mi) heart defect surgery. The rehabilitation programme was completed by 54 patients (exercising, RHB+) following valve defect surgery (13 women/41 men), aged 27-83 (56 +/- 16) years. The majority were patients with aortal (ao) stenosis (39), the remainder had a combined ao defect (7), ao regurgitation (3) or mitral (mi) regurgitation (5). Myocardial revascularisation was concomitantly performed in 18 patients. There were 18 patients in the control group (non-exercising, RHB-). Patients from both groups were assessed before and after the rehabilitation with exercise echocardiography and spiroergometry to the individual maximum. The intervention group underwent the managed rehabilitation programme. The control group exercised individually. Reduction of the heart rate (HR) values at rest and on exercise and of the systolic and diastolic blood pressure (sBP, dBP) was observed in the exercising group. However, these changes were not statistically significant. The systolic, diastolic and global LV function parameters showed improvement although, once again, not statistically significant. Highly significant improvement in exercise tolerance (1.41 W/kg before and 1.67 W/kg after, p < 0.01) and peak oxygen consumption (20.0 ml/min/kg before and 23.6 ml/min/kg after, p < 0.01) were observed in the exercising patients. Improvement in functional and aerobic capacity in the control group was not statistically significant. The resting and exercise parameters (SF, sBP, dBP) have not changed either. The ambulatory rehabilitation programme was associated with improvement in circulatory response to exercise together with reduction in resting and exercise SF, sBP a dBP values. Tendency towards improvement in systolic, diastolic and global LV function parameters was observed even though not statistically significant in our sample. Unlike control group, the exercising group showed significant increase in exercise tolerance and aerobic capacity (p < 0.01). Managed rehabilitation programme enabled evaluation of the outcomes of the surgery, better education of the patients and optimal adjustment ofpharmacotherapy, the anticoagulation treatment in particular. We did not observe any adverse reactions or other complications associated with the exercise.


Δ-Machine learning for quantum chemistry prediction of solution-phase molecular properties at the ground and excited states.
Due to the limitation of solvent models, quantum chemistry calculation of solution-phase molecular properties often deviates from experimental measurements. Recently, Δ-machine learning (Δ-ML) was shown to be a promising approach to correcting errors in the quantum chemistry calculation of solvated molecules. However, this approach's applicability to different molecular properties and its performance in various cases are still unknown. In this work, we tested the performance of Δ-ML in correcting redox potential and absorption energy calculations using four types of input descriptors and various ML methods. We sought to understand the dependence of Δ-ML performance on the property to predict the quantum chemistry method, the data set distribution/size, the type of input feature, and the feature selection techniques. We found that Δ-ML can effectively correct the errors in redox potentials calculated using density functional theory (DFT) and absorption energies calculated by time-dependent DFT. For both properties, the Δ-ML-corrected results showed less sensitivity to the DFT functional choice than the raw results. The optimal input descriptor depends on the property, regardless of the specific ML method used. The solvent-solute descriptor (SS) is the best for redox potential, whereas the combined molecular fingerprint (cFP) is the best for absorption energy. A detailed analysis of the feature space and the physical foundation of different descriptors well explained these observations. Feature selection did not further improve the Δ-ML performance. Finally, we analyzed the limitation of our Δ-ML solvent effect approach in data sets with molecules of varying degrees of electronic structure errors.


Early and Late Effects of Cardiac Resynchronization Therapy in Adult Congenital Heart Disease.
Background There are limited data about cardiac resynchronization therapy (CRT) in adult congenital heart disease. We aimed to assess early and late outcomes of CRT among patients with adult congenital heart disease. Methods and Results We retrospectively studied 54 patients with adult congenital heart disease (median age, 46 years; range, 18-73 years; 74% men) who received CRT implantation (biventricular paced >90%) between 2004 and 2017. Clinical and echocardiographic data were analyzed at baseline and early (mean±SD: 1.8±0.8 years) and late (4.7±0.8 years) follow-up after CRT. Compared with baseline, CRT was associated with significant improvement at early follow-up in New York Heart Association functional class, QRS duration, and cardiothoracic ratio (P<0.05 for all); improvement in New York Heart Association class was sustained at late follow-up. Among patients with a systemic left ventricle (LV; n=39), there was significant increase in LV ejection fraction and reduction in LV end-systolic volume at early and late follow-up (P<0.05 for both). For patients with a systemic right ventricle (n=15), there was a significant early but not late reduction in systemic right ventricular basal and longitudinal diameters. Eleven patients died, and 2 had heart transplantation unrelated to systemic ventricular morphological characteristics. Thirty-five patients (65%) responded positively to CRT, but only baseline QRS duration was predictive of a positive response. Conclusions CRT results in sustained improvement in functional class, systemic LV size, and function. Patients with a systemic LV and prolonged QRS duration, independent of QRS morphological characteristics, were most likely to respond to CRT.


Molecular identification of Borrelia crocidurae in a patient returning from Senegal.
Borrelia spp. are pathogens responsible for worldwide tickborne relapsing fever (TBRF). In West Africa, TBRF is due to a single species, Borrelia crocidurae, transmitted by the soft-body tick Ornithodoros sonrai. We report a case of B crocidurae infection in a French tourist in Senegal, diagnosed by molecular biology using 16S rDNA, flaB, and the 16S-23S intergenic spacer. We found six imported cases reported in travellers (since 1999). We review here clinical and molecular aspects and pathophysiology, and discuss diagnostic methods and therapeutic regimens. In the coming years, this emerging disease will be of concern to more and more travellers returning from disease-endemic regions. Thus, physicians must be aware of its presentation and diagnosis, since the spontaneous outcome can be severe, and a simple treatment is effective.


Clinical analysis of pipeline dredging agent poisoning: A case report.
Pipeline dredging agents are new household deep cleaning products used to dredge blockages in kitchen and bathroom pipeline caused by grease, hair, vegetable residue, paper cotton fibre, and other organic substances. Pipeline dredging agents are corrosive chemicals that can cause poisoning through corrosive damage to the digestive tract; however, this has not been reported clinically. Therefore, this report emphasises that oral pipeline dredging agent poisoning can cause corrosive damage to the digestive tract and may have serious health consequences. A 68-year-old man consumed liquor (200 mL) at approximately 13:00 on April 22, 2021. At approximately 16:00, his family found him unresponsive with blackened lips, blood spots in the corners of the mouth, and blood stains on the ground, as well as an empty bottle of a pipeline dredging agent. One hour later, he was admitted to the emergency department of a local hospital. Considering the empty bottle, he was suspected to have sustained severe corrosive damage to the digestive tract and was transferred to our department at 23:15 on April 22, 2021. He developed dysphagia and intermittent fever and experienced difficulty in opening his mouth throughout his hospital stay. The patient's condition gradually stabilised. However, he suddenly developed respiratory failure on day 12, and endotracheal intubation and ventilator-assisted ventilation were performed. However, the patient died after 1.5 h despite emergency rescue efforts. Pipeline dredging agents are highly corrosive and may cause corrosive damage to the digestive tract and asphyxia upon consumption.


Stage I testicular seminoma: para-aortic and iliac irradiation with reduced dose after orchiectomy.
Radiotherapy remains the treatment of choice for patients with stage I seminoma. The aim of this study is to report preliminary results of reduced dose radiotherapy to ipsilateral pelvic and para-aortic lymph nodes. Between February 1996 and December 2001, 53 patients with stage I testicular seminoma were treated with adjuvant radiotherapy after orchiectomy. The median age was 34 years (19-59 years). Four (7.5%) patients had a history of cryptorchidism. Eleven (20.8%) patients showed elevated beta-human chorionic gonadotropin. All patients had a radical inguinal orchiectomy and histopathological analysis yielded classic seminoma in 47 (88.7%), spermatocytic in 5 (9.4%) and anaplastic in 1 (1.9%) patients. A total of 19.6-20 Gy in 1.8- to 2-Gy daily fractions was administered to the para-aortic and ipsilateral iliac lymphatics. Median follow-up time was 42 months (12-77 months). One patient developed para-aortic lymph node recurrence at month 28 of the follow-up. Five-year overall and disease-free survivals were 100 and 98%, respectively. Only grade I-II of the Radiation Therapy Oncology Group acute gastrointestinal complications without any severe late toxicity was detected. Reduced dose radiotherapy seems to be as effective as higher doses in the management of stage I seminoma with an acceptable toxicity.


Effects of GRF with or without a SRIF antiserum on GH, IGF-1, thyroxin, cholecystokinin, gastrin and metabolite concentrations in growing rats.
This study was undertaken to examine the effects of increasing doses of rat somatocrinin (GRF) with or without a somatostatin antiserum (SS-ab) on serum hormone and metabolic concentrations, as well as serum and duodenal cholecystokinin (CCK) and antral gastrin concentrations. 24-day-old male Sprague-Dawley rats were injected twice daily s.c. (10:00 and 16:30) for 14 consecutive days with either saline or rat GRF (1-43) NH2 (4 and 20 micrograms/kg) in gelatin. Three other groups of animals received the same treatment in association with the SS-ab given i.p. every other day making up the 6 groups of 12 animals in a 2 x 3 factorial design experiment. GRF treatment increased circulating growth hormone (GH) concentrations in a dose-dependent manner, alone or in combination with the SS-ab; the SS-ab treatment alone or combined with GRF also increased GH concentrations. Total hypophyseal GH content was increased (P < 0.05) by the GRF treatment alone. Serum levels of IGF-1, acetoacetate, alpha 2 globulin and antral gastrin were all increased by the GRF treatment with plateaus observed for antral gastrin and serum IGF-1 levels at the intermediary dose of GRF. Serum concentrations of T4 were reduced at the 4 micrograms/kg dose of GRF. Serum concentrations of CCK were increased by the SS-ab treatment alone, an effect reversed by increasing doses of GRF. Rat GRF produced a dose-dependent increase and decrease of alpha 2 globulin and albumin, respectively. These data indicate that GRF, probably via its effect on GH release, influences gastrointestinal hormone levels which are implicated in gastrointestinal organ growth and digestive processes.


Microfluidic Organ-Chips and Stem Cell Models in the Fight Against COVID-19.
SARS-CoV-2, the virus underlying COVID-19, has now been recognized to cause multiorgan disease with a systemic effect on the host. To effectively combat SARS-CoV-2 and the subsequent development of COVID-19, it is critical to detect, monitor, and model viral pathogenesis. In this review, we discuss recent advancements in microfluidics, organ-on-a-chip, and human stem cell-derived models to study SARS-CoV-2 infection in the physiological organ microenvironment, together with their limitations. Microfluidic-based detection methods have greatly enhanced the rapidity, accessibility, and sensitivity of viral detection from patient samples. Engineered organ-on-a-chip models that recapitulate in vivo physiology have been developed for many organ systems to study viral pathology. Human stem cell-derived models have been utilized not only to model viral tropism and pathogenesis in a physiologically relevant context but also to screen for effective therapeutic compounds. The combination of all these platforms, along with future advancements, may aid to identify potential targets and develop novel strategies to counteract COVID-19 pathogenesis.


Increased osmotic fragility of erythrocytes in essential hypertension.
The correlation between hypertension and the osmotic fragility of erythrocytes was examined. High osmotic fragility of erythrocytes was observed in patients with essential hypertension and normotensive subjects with family history of hypertension, compared with normotensive controls without family history of hypertension. In patients with secondary hypertension, the osmotic fragility of erythrocytes was not significantly different from that of normotensive controls without family history of hypertension. The membrane fragility had no correlation with the level of blood pressure or dietary salt intake. Thus, the osmotic fragility of erythrocytes might reflect functional or structural abnormalities of cell membranes, and could be one of the genetic markers of the hypertensive predisposition.


Development of biological tissue-equivalent phantoms for optical imaging.
Optical characteristics of freshly isolated tissues depend on their color and composition. The surface backscattered profile, which account for the tissue compositional variation in fresh excised sheep's heart, lungs, bone and muscle, were measured by multi-probe reflectometer. Optical phantoms were prepared from paraffin wax by mixing a specific combination of wax color materials till the surface backscattered profile of these matched with that of the biological tissues. The optical parameters absorption coefficient (micro(a)), reduced scattering coefficient (micro(s)) and anisotropy factor (g) of these phantoms, are the same as that of biological tissues and are obtained by matching their surface backscattered profiles with that as simulated by Monte Carlo procedure. The maximum and minimum values of absorption coefficient are for the phantoms of lungs (1.0 cm(-1)) and muscle (0.02 cm(-1)), whereas, for scattering coefficient these values are for muscle (21.2 cm(-1)) and bone (13.08 cm(-1)).


Leukotriene B4 Receptors Are Necessary for the Stimulation of NLRP3 Inflammasome and IL-1β Synthesis in Neutrophil-Dominant Asthmatic Airway Inflammation.
The stimulation of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome and IL-1β synthesis are associated with chronic respiratory diseases such as neutrophil-dominant severe asthma. Leukotriene B4 (LTB4) is a principal chemoattractant molecule for neutrophil recruitment, and its receptors BLT1 and BLT2 have been suggested to contribute to neutrophil-dominant asthmatic airway inflammation. However, the relationship between BLT1/2 and NLRP3 in neutrophil-dominant asthmatic airway inflammation has not been previously studied. In the present study, we investigated whether BLT1/2 play any roles in stimulating the NLRP3 inflammasome and IL-1βsynthesis. The blockade of BLT1 or BLT2 clearly suppressed the stimulation of the NLRP3 inflammasome and IL-1β synthesis in house dust mite (HDM)/lipopolysaccharide (LPS)-induced neutrophilic airway inflammation. The enzymes 5-lipoxygenase and 12-lipoxygenase, which catalyze the synthesis of BLT1/2 ligands [LTB4, 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE), and 12-hydroxyheptadecatreinoic acid (12-HHT)], were also critically associated with the stimulation of NLRP3 and IL-1β synthesis. Together, our results suggest that the 5-/12-LOX-BLT1/2-linked cascade are necessary for the simulation of the NLRP3 inflammasome and IL-1β synthesis, thus contributing to HDM/LPS-induced neutrophil-dominant airway inflammation.


Multifactor Authentication for Smart Emergency Medical Response Transporters.
Securing telehealth IoT infrastructure is essential to provide high-level medical care and prevent cyberattacks. A vulnerable stage in IoT telehealth is while the patient is being transported to a healthcare facility, the transporter could be an ambulance or an air ambulance. In this paper, we propose a multifactor authentication scheme to secure the system when the patient is in transit to the healthcare facility. We apply this scheme to an ambulance, using physical unclonable functions (PUFs) embedded in the ambulance to facilitate authentication and secure key exchange. We validated the security of the proposed scheme using formal and informal security analysis. The analysis supports our claim that the proposed scheme protects against many types of attacks.


[Successful treatment with multidisciplinary therapy including low-dose chemoradiotherapy against metastatic recurrences of small cell carcinoma of the renal pelvis: a case report].
Primary small cell carcinoma of the renal pelvis is a rare and aggressive disease; reportedly, a mean survival is only 8 months. A 78 year-old woman with chronic kidney disease was referred to our hospital complaining of asymptomatic gross hematoturia. On imaging studies and voided urine cytology, diagnosis of right renal pelvic cancer (cT2N0M0) was made. She underwent total nephroureterectomy. Pathological diagnosis was small cell carcinoma, infiltrating into the renal parenchyma, with lymphovascular invasion. Post-operatively, hemodialysis was introduced. Five months after the operation, new lesions developed in the right adrenal gland, aortocaval lymph nodes and subcutaneous layer of the right back. The subcutaneous mass was surgically removed and low-dose chemoradiotherapy (sigma 45 Gy/25 Fr/32 d + cisplatin 10 mg/d for 2 d x 2) was given to the other lesions. Although the lesions regressed to CR, new small masses emerged in the muscle layers of the right flank 14 months after total nephroureterectomy. Low-dose chemoradiotherapy (sigma 40 Gy/20 Fr/29 d + cisplatin 10 mg/d for 2 d x 2) to these lesions successfully brought CR. She is alive without any evidence of disease at 3 years after total nephroureterectomy.


The control dilemma in eating behavior: influence of temptation cues in restrained versus unrestrained eaters.
The present research explored the effects of pre-exposure to temptation primes and dieting primes on food intake, goal accessibility and explicit automatic evaluations of food-enjoyment and dieting goals among restrained and unrestrained eaters. Participants (n= 166) were randomly assigned to three conditions: food-cue, dieting, or control, in which they were exposed to incidental presentation of gourmet, fashion or geographic magazines, respectively. Words related to the goals of dieting and/or food- enjoyment were presented in a computer decision task following the incidental presentation of gourmet, dieting, and geographic magazine photographs. The computer task and the presentation of food were counterbalanced. Participants' food intake was assessed in a taste-rating task. Restrained eaters ate more than did unrestrained eaters across the three conditions. Restrained eaters who were exposed to food cues ate more than did restrained eaters in the control condition and they evaluated the goal of dieting more negatively compared to restrained eaters in the other two conditions. These findings were inconsistent with 'Counteractive Self-Control Theory' but consistent with previous studies on the effects of food-cue exposure in restrained eaters.


Identification of a lacosamide binding protein using an affinity bait and chemical reporter strategy: 14-3-3 ζ.
We have advanced a useful strategy to elucidate binding partners of ligands (drugs) with modest binding affinity. Key to this strategy is attaching to the ligand an affinity bait (AB) and a chemical reporter (CR) group, where the AB irreversibly attaches the ligand to the receptor upon binding and the CR group is employed for receptor detection and isolation. We have tested this AB&CR strategy using lacosamide ((R)-1), a low-molecular-weight antiepileptic drug. We demonstrate that using a (R)-lacosamide AB&CR agent ((R)-2) 14-3-3 ζ in rodent brain soluble lysates is preferentially adducted, adduction is stereospecific with respect to the AB&CR agent, and adduction depends upon the presence of endogenous levels of the small molecule metabolite xanthine. Substitution of lacosamide AB agent ((R)-5) for (R)-2 led to the identification of the 14-3-3 ζ adduction site (K120) by mass spectrometry. Competition experiments using increasing amounts of (R)-1 in the presence of (R)-2 demonstrated that (R)-1 binds at or near the (R)-2 modification site on 14-3-3 ζ. Structure-activity studies of xanthine derivatives provided information concerning the likely binding interaction between this metabolite and recombinant 14-3-3 ζ. Documentation of the 14-3-3 ζ-xanthine interaction was obtained with isothermal calorimetry using xanthine and the xanthine analogue 1,7-dimethylxanthine.


Losartan in patients with type 2 diabetes and proteinuria: observations from the RENAAL Study.
Recently, the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) Study demonstrated the benefit of losartan in reducing renal outcomes in patients with type 2 diabetes and proteinuria. Additional questions concerning the reduction of proteinuria and its relationship to end-stage renal disease (ESRD) as well as cardio-renal outcomes and the safety and tolerability of losartan remain to be addressed. Three analyses were performed: (a) the impact of losartan on the relationship between the reduction of proteinuria and ESRD; (b) a time-to-event analysis of the cardio-renal composite endpoint of ESRD, myocardial infarction, stroke or all-cause death; and (c) additional analyses of adverse events, particularly in patients with serum creatinine >or=2.0 mg/dL. After adjusting the values for proteinuria over the entire study, the reduction of proteinuria accounted for approximately half of the treatment effect of losartan on the risk reduction for ESRD. In addition, losartan was associated with a 21% risk reduction for the composite cardio-renal outcome (P=0.003). The addition of losartan to a conventional antihypertensive regimen did not increase the overall incidence of adverse events, regardless of severity of renal impairment. Losartan significantly reduced the risk of cardiorenal outcomes and was well tolerated by patients, including those with serum creatinine levels >or=2.0 g/dL. In addition, although this study shows that the reduction of proteinuria does not completely explain the impact of intervention on outcomes such as ESRD, reduction of proteinuria must remain an important consideration when treating patients with type 2 diabetes and nephropathy. However, the reduction of outcomes such as ESRD should remain the goal of therapy when evaluating renal protection in this patient population.


Treatment of metastatic sialoblastoma with chemotherapy and surgery.
Tumors of the salivary gland are very uncommon in children. Sialoblastoma is a rare, aggressive, blastomatous, and potentially malignant congenital tumor. Distant metastases are rare. We present a case of sialoblastoma with lung metastases that developed in a 4-year-old girl adjacent to a congenital nevus in the left cheek. The tumor was inoperable at diagnosis but the largest of the pulmonary metastases was removed surgically. The patient responded well to chemotherapy and underwent surgical excision of the primary tumor, followed by three more courses of chemotherapy.


An automated approach to the classification of impact spatter and cast-off bloodstain patterns.
In the forensic discipline of bloodstain pattern analysis, it has been suggested that there is a blurred boundary between characterising the features of a bloodstain pattern and determining the mechanism(s) that led to its deposition. This study proposes that bloodstain pattern classification can become a distinct and logical process by implementing an automated approach. To do this, an automated bloodstain pattern recognition system was developed to enable the distinction of two types of spatter bloodstain patterns. First, global pattern features based on common bloodstain pattern properties were extracted from laboratory-generated impact spatter and cast-off bloodstain patterns. Following this, automated feature selection methods were used to identify the combination of features that best distinguished the two bloodstain pattern types. This eventually led to the training and testing of a Fisher quadratic discriminant classifier using separate subsets of the generated bloodstain patterns. When applied to the training dataset, a 100% classification precision resulted. An independent dataset comprising of bloodstain patterns generated on paint and wallpaper substrates were used to validate the performance of the classifier. An error rate of 2% was obtained when the classifier was applied to these bloodstain patterns. This automated bloodstain pattern recognition system offers considerable promise as an objective classification methodology which up to now, the discipline has lacked. With further refinement, including testing it over a wider range of bloodstain patterns, it could provide valuable quantitative data to support analysts in their task of classifying bloodstain patterns.


Long Non-Coding RNAs and the Innate Immune Response.
Innate immunity provides the initial defence against infection and it is now clear that long non-coding RNAs (lncRNAs) are important regulators of this response. Following activation of the innate response, we commonly see rapid induction of these lncRNAs and this is often mediated via the pro-inflammatory transcription factor, nuclear factor-κB (NF-κB). Knockdown studies have shown that lncRNAs tend to act in trans to regulate the expression of multiple inflammatory mediators and other responses. Mechanistically, many lncRNAs have demonstrated acting through heterogeneous nuclear ribonucleoproteins, complexes that are implicated chromatin re-modelling, transcription process and translation. In addition, these lncRNAs have also been shown to interact with multiple other proteins involved in the regulation of chromatin re-modelling, as well as those proteins involved in intracellular immune signalling, which include NF-κB. In this review, we will describe the evidence that supports this emerging role of lncRNA in the innate immune response.


On-road, in-use gaseous emission measurements by remote sensing of school buses equipped with diesel oxidation catalysts and diesel particulate filters.
A remote sensing device was used to obtain on-road and in-use gaseous emission measurements from three fleets of schools buses at two locations in Washington State. This paper reports each fleet's carbon monoxide (CO), hydrocarbon (HC), nitric oxide (NO), and nitrogen dioxide (NO2) mean data. The fleets represent current emission retrofit technologies, such as diesel particulate filters and diesel oxidation catalysts, and a control fleet. This study shows that CO and HC emissions decrease with the use of either retrofit technology when compared with control buses of the same initial emission standards. The CO and HC emission reductions are consistent with published U.S. Environmental Protection Agency verified values. The total oxides of nitrogen (NOx), NO, and the NO2/NOx ratio all increase with each retrofit technology when compared with control buses. As was expected, the diesel particulate filters emitted significantly higher levels of NO2 than the control fleet because of the intentional conversion of NO to NO2 by these systems. Most prior research suggests that NOx emissions are unaffected by the retrofits; however, these previous studies have not included measurements from retrofit devices on-road and after nearly 5 yr of use. Two 2006 model-year buses were also measured. These vehicles did not have retrofit devices but were built to more stringent new engine standards. Reductions in HCs and NOx were observed for these 2006 vehicles in comparison to other non-retrofit earlier model-year vehicles.


Is Activation the Active Ingredient of Transdiagnostic Therapies? A Randomized Clinical Trial of Behavioral Activation, Acceptance and Commitment Therapy, and Transdiagnostic Cognitive-Behavioral Therapy for Emotional Disorders.
Studying the usefulness of contextual and cognitive transdiagnostic therapies calls for an analysis of both their differential efficacy and their specificity when acting on the transdiagnostic conditions on which they focus. This controlled trial compares the post-treatment and 3- and 6-month follow-up effects of Behavioral Activation (BA), Acceptance and Commitment Therapy (ACT) and Cognitive-Behavioral Transdiagnostic Therapy (TD-CBT) on emotional symptomatology, and analyses the role played by Experiential Avoidance, Cognitive Fusion, Activation and Emotion Regulation in the clinical change. One hundred twenty-eight patients who fulfilled diagnostic criteria for anxiety and/or depression (intention-to-treat sample) were randomly assigned to three experimental group-treatment conditions (BA, n = 34; ACT, n = 27; TD-CBT n = 33) and one control group (WL, n = 34). Ninety-nine (77.34%) completed the treatment (per-protocol sample). In the post-treatment, all therapies reduced anxiety and depression symptomatology. In the follow-ups, the reduction in emotional symptomatology was greater in the condition which produced greater and more prolonged effects on Activation. Activation appears to be the principal condition in modifying all the transdiagnostic patterns and BA was the most efficacious and specific treatment. The trial was registered at ClinicalTrials.gov NCT04117464. Raw data are available online http://dx.doi.org/10.17632/krj3w2hfsj.1.


Safety, tolerability and humoral immune responses after intramuscular administration of a malaria DNA vaccine to healthy adult volunteers.
DNA-based vaccines are considered to be potentially revolutionary due to their ease of production, low cost, long shelf life, lack of requirement for a cold chain and ability to induce good T-cell responses. Twenty healthy adult volunteers were enrolled in a Phase I safety and tolerability clinical study of a DNA vaccine encoding a malaria antigen. Volunteers received 3 intramuscular injections of one of four different dosages (20, 100, 500 and 2500 microg) of the Plasmodium falciparum circumsporozoite protein (PfCSP) plasmid DNA at monthly intervals and were followed for up to twelve months. Local reactogenicity and systemic symptoms were few and mild. There were no severe or serious adverse events, clinically significant biochemical or hematologic changes, or detectable anti-dsDNA antibodies. Despite induction of excellent CTL responses, intramuscular DNA vaccination via needle injection failed to induce detectable antigen-specific antibodies in any of the volunteers.


Prevalence of salmonellae in cattle and in the environment on California dairies.
Milk samples were collected from all lactating cows on 60 dairies (mean number of cows/dairy, 584; range, 66 to 2,834) randomly selected from 701 California dairies enrolled in the Dairy Herd Improvement Association program. Samples were tested, by means of an ELISA, for antibodies against Salmonella serogroup B, C1, and D1 antigens (somatic antigens O1, 4, 6, 7, 9, 12). Blood samples were collected from all cows with positive results and tested for serologic evidence of exposure to salmonellae. Samples for bacteriologic culture (pooled feces from 20 randomly selected calves, swabs of wet areas and feces from calf pens and dairy hospital pens, drag swab sample from wastewater lagoon, and samples of feed components) were also collected from all 60 dairies. Seven (11.7%) of the 60 dairies each had 1 sample that yielded Salmonella organisms (3 S typhimurium, 1 S dublin, 1 nonmotile Group D salmonella, 1 S derby, and 1 S oranienberg). Five of the Salmonella isolates came from the hospital pens and 2 came from calf pens. Thirty-three dairies did not vaccinate cattle against salmonellosis, and of these, 24 (72.7%) had > or = 1 seropositive cow (titer > or = 200), and 20 (61%) had > or = 1 persistently seropositive cow (titer for each of 2 blood samples collected > or = 60 days apart was > or = 200). Of the 27 dairies that did vaccinate cows against salmonellosis, 24 (89%) had > or = 1 seropositive cow, and 21 (78%) had > or = 1 persistently seropositive cow.(ABSTRACT TRUNCATED AT 250 WORDS)


Divergent Synthesis of Stachyurin and Casuarinin Focusing on C-Glycosidic Bond Reactivity.
Stachyurin and casuarinin are ellagitannins, a class of polyphenols that exhibit various biological activities that have an impact on human health. Casuarinin is a stachyurin stereoisomer. These compounds contain the characteristic C-glycosidic bond between the open-chain d-glucose and the phenol aromatic ring. Therefore, chemical elucidation of the C-glycosidic bond reactivity is required to exploit their multiple bioactivities. This study developed a method for the divergent synthesis of stachyurin and casuarinin via the α-selective C-glycosylation as well as the β-selective introduction of the oxygen functional group, focusing on structural specificity. The proposed method applies to the syntheses of stachyurin and casuarinin analogues, thereby facilitating the utilisation of their beneficial bioactivities.


Pleomorphic (anaplastic) neuroblastoma in nude mice.
Two pleomorphic (anaplastic) neuroblastomas, from two children aged 1 and 6 years, were transplanted into nude mice. Two noteworthy observations were made. In one case, the transplanted tumor gave rise to a soft-tissue sarcoma. Moreover, in both cases hepatic metastases were associated with a striking modification of murine hepatocytes, resulting in hyperchromatic and dysplastic nuclei. The latter finding was particularly evident in the hepatic areas surrounding all metastases of pleomorphic (anaplastic) neuroblastoma cells.


Beyond faithful conduction: short-term dynamics, neuromodulation, and long-term regulation of spike propagation in the axon.
Most spiking neurons are divided into functional compartments: a dendritic input region, a soma, a site of action potential initiation, an axon trunk and its collaterals for propagation of action potentials, and distal arborizations and terminals carrying the output synapses. The axon trunk and lower order branches are probably the most neglected and are often assumed to do nothing more than faithfully conducting action potentials. Nevertheless, there are numerous reports of complex membrane properties in non-synaptic axonal regions, owing to the presence of a multitude of different ion channels. Many different types of sodium and potassium channels have been described in axons, as well as calcium transients and hyperpolarization-activated inward currents. The complex time- and voltage-dependence resulting from the properties of ion channels can lead to activity-dependent changes in spike shape and resting potential, affecting the temporal fidelity of spike conduction. Neural coding can be altered by activity-dependent changes in conduction velocity, spike failures, and ectopic spike initiation. This is true under normal physiological conditions, and relevant for a number of neuropathies that lead to abnormal excitability. In addition, a growing number of studies show that the axon trunk can express receptors to glutamate, GABA, acetylcholine or biogenic amines, changing the relative contribution of some channels to axonal excitability and therefore rendering the contribution of this compartment to neural coding conditional on the presence of neuromodulators. Long-term regulatory processes, both during development and in the context of activity-dependent plasticity may also affect axonal properties to an underappreciated extent.


Successful Infusion Therapy in Older Adults.
Older adults are a special patient population who require attention to a variety of issues and considerations related to infusion therapy. The need to alter practice approaches includes vascular access techniques and the administration of intravenous medications, fluids, and blood components. In addition, older adults will manifest very different signs and symptoms related to development of an infection in the body. This article reviews the normal physical changes that occur in their major body systems and discusses recommendations to accomplish successful venous access and correct administration of infusates.


Conservative aesthetic techniques for discoloured teeth: 1. The use of bleaching.
There is an increasing move towards more minimally invasive techniques in restorative dentistry. This series of two articles discusses conservative techniques for the treatment of discoloured teeth. A step-wise approach to treatment is promoted to encourage the most conservative solution to achieve satisfactory aesthetics. The first of these two articles will describe the use of bleaching, whilst part two will go on to describe microabrasion and the use of direct composite resin. Discoloured teeth are a common dental problem. Bleaching provides a simple conservative solution in many cases.


Reciprocal negative regulation of PDK1 and ASK1 signaling by direct interaction and phosphorylation.
Cell survival and death-inducing signals are tightly associated with each other, and the decision as to whether a cell survives or dies is determined by controlling the relationship between these signals. However, the mechanism underlying the reciprocal regulation of such signals remains unclear. In this study, we reveal a functional association between PDK1 (3-phosphoinositide-dependent protein kinase 1), a critical mediator of cell survival, and ASK1 (apoptosis signal-regulating kinase 1), an apoptotic stress-activated MAPKKK. The physical association between PDK1 and ASK1 is mediated through the pleckstrin homology domain of PDK1 and the C-terminal regulatory domain of ASK1 and is decreased by ASK1-activating stimuli, such as H(2)O(2), tumor necrosis factor alpha, thapsigargin, and ionomycin, as well as insulin, a PDK1 stimulator. Wild-type PDK1, but not kinase-dead PDK1, negatively regulates ASK1 activity by phosphorylating Ser(967), a binding site for 14-3-3 protein, on ASK1. PDK1 functionally suppresses ASK1-mediated AP-1 transactivation and H(2)O(2)-mediated apoptosis in a kinase-dependent manner. On the other hand, ASK1 has been shown to inhibit PDK1 functions, including PDK1-mediated regulation of apoptosis and cell growth, by phosphorylating PDK1 at Ser(394) and Ser(398), indicating that these putative phosphorylation sites are involved in the negative regulation of PDK1 activity. These results provide evidence that PDK1 and ASK1 directly interact and phosphorylate each other and act as negative regulators of their respective kinases in resting cells.


Phaeoacremonium parasiticum phaeohyphomycosis in a patient with systemic lupus erythematosus treated successfully with surgical debridement and voriconazole: A case report and review of the literature.
A 26-year old woman presented for evaluation of extensive edema, erythema, sinus tract formation and purulent drainage from the left lower extremity after trauma from a wooden object approximately three months prior. Skin biopsies and blood cultures revealed Phaeoacremonium parasiticum consistent with a diagnosis of phaeohyphomycosis. Despite hospitalization and initial treatment with several antifungals, including voriconazole, her infection progressed. Surgical debridement with split thickness skin grafting was performed. Subsequent clinical improvement allowed a transition from intravenous to oral voriconazole and discharge home. Seven months post presentation she remained on oral voriconazole with significant improvement and no clinical evidence of recurrence. This case illustrates an approach to management where aggressive debridement with split-thickness skin grafting and a prolonged course of intravenous and oral antifungals resulted in a good long-term outcome for the patient.


Characterization of RNA determinants recognized by the arginine- and proline-rich region of Us11, a herpes simplex virus type 1-encoded double-stranded RNA binding protein that prevents PKR activation.
The herpes simplex virus Us11 gene product inhibits activation of the cellular PKR kinase and associates with a limited number of unrelated viral and cellular RNA molecules via a carboxyl-terminal 68-amino-acid segment rich in arginine and proline. To characterize the determinants underlying the recognition of an RNA target by Us11, we employed an in vitro selection technique to isolate RNA ligands that bind Us11 with high affinity from a population of molecules containing an internal randomized segment. Binding of Us11 to these RNA ligands is specific and appears to occur preferentially on conformational isoforms that possess a higher-order structure. While the addition of unlabeled poly(I. C) reduced binding of Us11 to a selected radiolabeled RNA, single-stranded homopolymers were not effective competitors. Us11 directly associates with poly(I. C), and inclusion of an unlabeled selected RNA in the reaction reduces poly(I. C) binding, while single-stranded RNA homopolymers have no effect. Finally, Us11 binds to defined, double-stranded RNA (dsRNA) molecules that exhibit greater sequence complexity. Binding to these dsRNA perfect duplexes displays a striking dependence on length, as 39-bp or shorter duplexes do not bind efficiently. Furthermore, this interaction is specific for dsRNA as opposed to dsDNA, implying that the Us11 RNA binding domain can distinguish nucleic acid duplexes containing 2' hydroxyl groups from those that do not. These results establish that Us11 is a dsRNA binding protein. The arginine- and proline-rich Us11 RNA binding domain is unrelated to known dsRNA binding elements and thus constitutes a unique recognition motif that interacts with dsRNA. The ability of Us11 to bind dsRNA may be important for inhibiting activation of the cellular PKR kinase in response to dsRNA.


Prevalence of methicillin resistant Staphylococcus aureus (MRSA) in pigs and workers at abattoirs in Trinidad and Tobago.
Methicillin resistant Staphylococcus aureus (MRSA), a major cause of zoonotic infections, has emerged globally in livestock, particularly pigs. People with occupational contact with food producing animals are at high risk of colonization. The aim of this study was to determine the prevalence of MRSA in pigs and abattoir workers throughout Trinidad and Tobago as well as their resistance to other antimicrobial agents. Nasal and skin behind the ear swabs from pigs and nasal swabs from humans were enriched in Mueller Hinton broth with 6.5% sodium chloride, followed by phenol red mannitol broth with 75 mg/L aztreonam and 5 mg/L ceftizoxime. The enriched sample was then plated on both CHROMagar MRSA and Brilliance MRSA. All incubation was at 37ºC for approximately 24 h. Suspect MRSA isolates were confirmed as MRSA using the Penicillin-Binding Protein (PBP2a) test kit and polymerase chain reaction (PCR) to detect the mecA gene. Resistance of the S. aureus and MRSA isolates to 16 antimicrobial agents was determined using the disc diffusion method. Of the 929 pigs and 44 humans sampled, MRSA strains were isolated at a frequency of 0.9% (8/929) and 2.3% (1/44) respectively. All isolates exhibited resistance to one or more of the 16 antimicrobial agents. The study demonstrated that pigs and workers at slaughter houses in Trinidad and Tobago harbour multidrug resistance S. aureus and MRSA. This is of public health significance as occupational exposure of humans can lead to an increased risk of infection and therapeutic failure.