Learning in brain-computer interface control evidenced by joint decomposition of brain and behavior.
Motor imagery-based brain-computer interfaces (BCIs) use an individual's ability to volitionally modulate localized brain activity, often as a therapy for motor dysfunction or to probe causal relations between brain activity and behavior. However, many individuals cannot learn to successfully modulate their brain activity, greatly limiting the efficacy of BCI for therapy and for basic scientific inquiry. Formal experiments designed to probe the nature of BCI learning have offered initial evidence that coherent activity across spatially distributed and functionally diverse cognitive systems is a hallmark of individuals who can successfully learn to control the BCI. However, little is known about how these distributed networks interact through time to support learning. Here, we address this gap in knowledge by constructing and applying a multimodal network approach to decipher brain-behavior relations in motor imagery-based brain-computer interface learning using magnetoencephalography. Specifically, we employ a minimally constrained matrix decomposition method - non-negative matrix factorization - to simultaneously identify regularized, covarying subgraphs of functional connectivity, to assess their similarity to task performance, and to detect their time-varying expression. We find that learning is marked by diffuse brain-behavior relations: good learners displayed many subgraphs whose temporal expression tracked performance. Individuals also displayed marked variation in the spatial properties of subgraphs such as the connectivity between the frontal lobe and the rest of the brain, and in the temporal properties of subgraphs such as the stage of learning at which they reached maximum expression. From these observations, we posit a conceptual model in which certain subgraphs support learning by modulating brain activity in sensors near regions important for sustaining attention. To test this model, we use tools that stipulate regional dynamics on a networked system (network control theory), and find that good learners display a single subgraph whose temporal expression tracked performance and whose architecture supports easy modulation of sensors located near brain regions important for attention. The nature of our contribution to the neuroscience of BCI learning is therefore both computational and theoretical; we first use a minimally-constrained, individual specific method of identifying mesoscale structure in dynamic brain activity to show how global connectivity and interactions between distributed networks supports BCI learning, and then we use a formal network model of control to lend theoretical support to the hypothesis that these identified subgraphs are well suited to modulate attention.


Primary and secondary relaxation process in plastically crystalline cyanocyclohexane studied by 2H nuclear magnetic resonance. I.
We study the main (α-) and secondary (β-) relaxation in the plastically crystalline (PC) phase of cyanocyclohexane by various 2H nuclear magnetic resonance (NMR) methods (line-shape, spin-lattice relaxation, stimulated echo, and two-dimensional spectra) above and below the glass transition temperature T(g) = 134 K. Our results regarding the α-process demonstrate that molecular motion is not governed by the symmetry of the lattice. Rather it is similar to the one reported for structural glass formers and can be modeled by a reorientation proceeding via a distribution of small and large angular jumps. A solid-echo line-shape analysis regarding the β-process below T(g) yields again very similar results when compared to those of the structural glass formers ethanol and toluene. Hence we cannot confirm an intramolecular origin for the β-process in cyanocyclohexane. The fast β-process in the PC phase allows for the first time a detailed 2H NMR study of the process also at T > T(g): an additional minimum in the spin-lattice relaxation time reflecting the β-process is found. Furthermore the solid-echo spectra show a distinct deviation from the rigid limit Pake pattern, which allows a direct determination of the temperature dependent spatial restriction of the process. In Part II of this work, a quantitative analysis is carried out, where we demonstrate that within the model of a "wobbling in a cone" the mean cone angle increases above T(g) and the corresponding relaxation strength is compared to dielectric results.


Exploiting Listener Gaze to Improve Situated Communication in Dynamic Virtual Environments.
Beyond the observation that both speakers and listeners rapidly inspect the visual targets of referring expressions, it has been argued that such gaze may constitute part of the communicative signal. In this study, we investigate whether a speaker may, in principle, exploit listener gaze to improve communicative success. In the context of a virtual environment where listeners follow computer-generated instructions, we provide two kinds of support for this claim. First, we show that listener gaze provides a reliable real-time index of understanding even in dynamic and complex environments, and on a per-utterance basis. Second, we show that a language generation system that uses listener gaze to provide rapid feedback improves overall task performance in comparison with two systems that do not use gaze. Aside from demonstrating the utility of listener gaze in situated communication, our findings open the door to new methods for developing and evaluating multi-modal models of situated interaction.


[The role of concha bullosa in nasal pathologies].
We investigated the relationship between the size of concha bullosa (CB) detected by coronal paranasal sinus computed tomography (CT) and the frequency of sinonasal symptoms. The study included 60 patients (39 females, 21 males; mean age 38.3 years; range 17 to 67 years) who had CB on CT scans and underwent endoscopic sinus surgery for symptoms of chronic sinusitis, nasal obstruction and/or headache. The patients were evaluated in three groups according to the ratio of the cross-section area of CB to that of the nasal cavity (NC); hence, group 1, 0-14%; group 2, 15-29%; and group 3, = or >30%. The relationship of CB/NC with clinical symptoms and nasal pathologies were examined. The presenting complaints were sinusitis in 28 (46.7%), nasal obstruction in 56 (93.3%), and headache in 36 (60%) patients. Concha bullosa was on the right side in 16 (26.7%), on the left side in 13 (21.7%), and bilateral in 31 patients (51.7%). Of 91 CB, 29 (31.9%) were in group 1, 43 (47.3%) were in group 2, and 19 (20.9%) were in group 3. The cross-section area of CB was greater than 1 cm2 in 25.6%, and less than 0.5 cm2 in 53.4%. The most common pathology accompanying CB was nasal septal deviation (n=36, 60%). The distribution of symptoms and accompanying pathologies was similar in the three groups. Our findings show that symptoms and accompanying pathologies do not differ in patients with varying sizes of CB.


Studies on the livestock of southern Darfur, Sudan. III. Production traits in sheep.
The results of an intensive 15 months' study of 10 flocks of indigenous sheep are recorded. Lambing rates approach 1.5 lambs per ewe per year, but a death rate of 23 per cent and an offtake of 27 per cent, means that flock numbers are probably slightly declining. Twins account for 14 per cent of all births but the death rate of twin lambs is almost twice that of single lambs up to 6 months of age. Increased productivity is therefore more likely to be achieved by improving the survival and growth rates of single lambs than by selection for twinning. The weighted average rate of lightweight gain for all surviving lambs is 82 g per day up to 1 year of age, and is better than that recorded for any other indigenous African sheep. Meat production per kg of breeding female, at 0.253 kg up to 6 months of age of the young, is almost six times the production of cattle under the same management and environmental conditions, but is inferior to that of goats.


Cervical thymic cysts.
A review of cervical thymus cysts and a case report are presented. This benign lesion was, as in most cases previously reported, situated laterally on the neck, deep to the anterior border of the sternocleidomastoid muscle and thus simulating a common branchial cyst preoperative.y. But unlike the latter most cases of cervical thymus cysts are recognised during childhood. They are believed to develop in remmants of thymic tissue which have failed to descend from the third branchial pouch into the mediastinum in the 6th to 8th week of embryonic life.


An illustrated key to and diagnoses of the species of Staphylinidae (Coleoptera) associated with decaying carcasses in Argentina.
A key to 24 Staphylinidae species associated with decaying carcasses in Argentina is presented, including diagnoses, illustrations, distributional and bionomical data for these species. This article provides a table of all species associated with carcasses, detailing the substrate from which they were collected and geographical distribution by province. All 24 Staphylinidae species recorded are grouped into three subfamilies: Aleocharinae (three species of Aleochara Gravenhorst and one species of Atheta Thomson), Oxytelinae (one species of Anotylus Thomson) and Staphylininae (18 species, two belonging to the tribe Xantholinini and 16 species belonging to the tribe Staphylinini). A discussion is presented on the potential forensic importance of some species collected on human and pig carcasses.


Effect of Photoperiod on Longevity, Food Consumption, and Reproduction of Holotrichia oblita (Coleoptera: Scarabaeidae).
Holotrichia oblita (Faldermann) (Coleoptera: Scarabaeidae) is a major soil insect pest that damages forest trees, crops, and lawns. Adults of H. oblita fly, forage, and mate at night but remain underground during the day. We studied the effect of photoperiod on H. oblita reproduction. H. oblita females laid more eggs at 8:16 (L:D) h and 0:24 (L:D) h than other photoperiods. As the scotophase increased, the preoviposition period decreased and the oviposition period increased. Female longevity exceeded that of males at all photoperiods, and both males and females at 0:24 (L:D) h had the shortest longevity. The number of eggs laid per female increased with increasing food consumption. Females at 8:16 (L:D) h had the greatest food consumption and laid the most eggs, while females at 24:0 (L:D) h had the lowest food consumption and laid few eggs. The food intake of adults increased gradually and decreased slowly after reaching a peak. Females began to lay eggs when their food consumption reached a maximum. These results indicate that a scotophase is necessary for the reproduction of H. oblita. A long scotophase promotes greater oviposition. The effect of photoperiod on reproduction is affected by food intake.


An explanatory model of preterm labor.
The purpose of this article is to describe women's explanatory model of their preterm labor (PTL) experiences. Fourteen young adult (20 to 23 years of age) women living in the southeast, who were hospitalized for the treatment of PTL, participated in this naturalistic study. Stress was the dominant theme that all participants used to explain what had precipitated PTL. All women described multiple stressors and chaos in their lives, which preceded their admission to the hospital for PTL. Meanings of PTL were intertwined with dysfunctional families and problematic relationships. All 9 women who delivered at term were able to find a friend or family member to provide support that allowed the women to relax and reduce the stress in their lives. In contrast, women who delivered preterm had no one in their lives that could provide help and support. Women's conceptualizations of PTL suggest that culturally appropriate interventions to reduce stress and mobilize support may help improve birth outcomes after an episode of PTL.


Corneal stromal cell growth on gelatin/chondroitin sulfate scaffolds modified at different NHS/EDC molar ratios.
A nanoscale modification strategy that can incorporate chondroitin sulfate (CS) into the cross-linked porous gelatin materials has previously been proposed to give superior performance for designed corneal keratocyte scaffolds. The purpose of this work was to further investigate the influence of carbodiimide chemistry on the characteristics and biofunctionalities of gelatin/CS scaffolds treated with varying N-hydroxysuccinimide (NHS)/1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride (EDC) molar ratios (0-1) at a constant EDC concentration of 10 mM. Results of Fourier transform infrared spectroscopy and dimethylmethylene blue assays consistently indicated that when the NHS to EDC molar ratio exceeds a critical level (i.e., 0.5), the efficiency of carbodiimide-mediated biomaterial modification is significantly reduced. With the optimum NHS/EDC molar ratio of 0.5, chemical treatment could achieve relatively high CS content in the gelatin scaffolds, thereby enhancing the water content, glucose permeation, and fibronectin adsorption. Live/Dead assays and interleukin-6 mRNA expression analyses demonstrated that all the test samples have good cytocompatibility without causing toxicity and inflammation. In the molar ratio range of NHS to EDC from 0 to 0.5, the cell adhesion ratio and proliferation activity on the chemically modified samples significantly increased, which is attributed to the increasing CS content. Additionally, the materials with highest CS content (0.143 ± 0.007 nmol/10 mg scaffold) showed the greatest stimulatory effect on the biosynthetic activity of cultivated keratocytes. These findings suggest that a positive correlation is noticed between the NHS to EDC molar ratio and the CS content in the biopolymer matrices, thereby greatly affecting the corneal stromal cell growth.


Blood transfusion utilization in hospitalized COVID-19 patients.
The acute respiratory illness designated coronavirus disease 2019 (COVID-19) was first reported in Wuhan, China, in December 2019 and caused a worldwide pandemic. Concerns arose about the impact of the COVID-19 pandemic on blood donations and potential significant blood transfusion needs in severely ill COVID-19 patients. Data on blood usage in hospitalized COVID-19 patients are scarce. We performed a retrospective observational study of blood component transfusions in the first 4 weeks of COVID-19 ward admissions. The study period began 14 days before the first COVID-19 cohort wards opened in our hospital in March 2020 and ended 28 days afterward. The number of patients and blood components transfused in the COVID-19 wards was tabulated. Transfusion rates of each blood component were compared in COVID-19 wards versus all other inpatient wards. COVID-19 wards opened with seven suspected patients and after 4 weeks had 305 cumulative COVID-19 admissions. Forty-one of 305 hospitalized COVID-19 patients (13.4%) received transfusions with 11.1% receiving red blood cells (RBCs), 1.6% platelets (PLTs), 1.0% plasma, and 1.0% cryoprecipitate (cryo). COVID-19 wards had significantly lower transfusion rates compared to non-COVID wards for RBCs (0.03 vs 0.08 units/patient-day), PLTs (0.003 vs 0.033), and plasma (0.002 vs 0.018; all p < 0.0001). Cryo rates were similar (0.008 vs 0.009, p = 0.6). Hospitalized COVID-19 patients required many fewer blood transfusions than other hospitalized patients. COVID-19 transfusion data will inform planning and preparation of blood resource utilization during the pandemic.


circRNA of AR-suppressed PABPC1 91 bp enhances the cytotoxicity of natural killer cells against hepatocellular carcinoma via upregulating UL16 binding protein 1.
Hepatocellular carcinoma (HCC) is a heterogeneous malignancy type with limited approaches for treatment. Additionally, inappropriate immune therapy indicates that the understanding the underlying mechanism of HCC is necessary. The aim of the present study was to investigate the influence of a novel circular RNA (circRNA), circRNA of AR-suppressed PABPC1 91 bp (CircARSP91), on immune surveillance induced by natural killer (NK) cells. An in vitro cell cytotoxicity assay was performed to determine the cytotoxicity of NK cells against HCC cells. A specific plasmid for circRNA overexpression was used to establish stable cell lines. Additionally, samples from patients with HCC were analyzed to determine the association between the present in vitro data and those of clinical settings. CircARSP91 could increase the susceptibility of HCC cells to NK cell cytotoxicity. Following screening multiple factors that could influence the activation of NK cells, it was determined that such a phenotype may be caused by upregulating UL16 binding protein 1 (ULBP1) expression in HCC cells at the mRNA and protein levels. Additionally, the data generated from patient samples significantly support a positive association between CircARSP91 and ULBP1. In conclusion, CircARSP91 could enhance innate immune surveillance by strengthening the cytotoxicity of NK cells, implying that circRNA may serve a role in tumor immunity.


[Effect of Chorei-to on spontaneous discharge of urinary stones after extracorporeal shock wave lithotripsy (ESWL)].
To enhance stone elimination following extracorporeal shock wave lithotripsy (ESWL), we administered Tsumura Chorei-to to 74 patients who underwent the procedure at Kinki University School of Medicine and Kanbara Hospital between July 1990 and March 1991. We established a control group of 75 patients without medication. There was no significant difference between the two groups in terms of gender, age, stone size (mostly less than 20 mm), and stone position. The mean number of days required for complete stone elimination was 16.0 days in the Chorei-to administration group being significantly shorter than the 21.5 days in the control group (p < 0.001). These findings suggested that Chorei-to effectively enhanced the spontaneous discharge of fragmented stones following ESWL.


MHC Class I Regulation: The Origin Perspective.
Viral-derived elements and non-coding RNAs that build up "junk DNA" allow for flexible and context-dependent gene expression. They are extremely dense in the MHC region, accounting for flexible expression of the MHC I, II, and III genes and adjusting the level of immune response to the environmental stimuli. This review brings forward the viral-mediated aspects of the origin and evolution of adaptive immunity and aims to link this perspective with the MHC class I regulation. The complex regulatory network behind MHC expression is largely controlled by virus-derived elements, both as binding sites for immune transcription factors and as sources of regulatory non-coding RNAs. These regulatory RNAs are imbalanced in cancer and associate with different tumor types, making them promising targets for diagnostic and therapeutic interventions.


Effect of ethylenediaminetetraacetic acid gel on the incidence of dentinal cracks caused by three novel nickel-titanium systems.
The aim of this study is to evaluate the incidence of crack formation while using Reciproc, WaveOne and Twisted File Adaptive with and without ethylenediaminetetraacetic acid (EDTA) gel. Seventy extracted mandibular premolars were included. The teeth were decoronated until roots of 16 mm were obtained. Samples were distributed into seven groups: group 1, no canal preparation (control); other groups were instrumented so; group 2, Reciproc; group 3, Reciproc + EDTA; group 4, WaveOne; group 5, WaveOne + EDTA; group 6, Twisted File Adaptive; group 7, Twisted File Adaptive + EDTA. Roots were horizontally sectioned from 3, 6 and 9 mm from apex and observed under stereomicroscope. The number and the incidence of cracks were recorded and statistically analysed with chi-squared and Kruskal-Wallis tests. Control group did not reveal any cracks. Crack formation with three novel Ni-Ti instruments was similar. Using EDTA gel did not reduce crack occurrence.


Stability of Boolean networks with generalized canalizing rules.
Boolean networks are discrete dynamical systems in which the state (0 or 1) of each node is updated at each time t to a state determined by the states at time t-1 of those nodes that have links to it. When these systems are used to model genetic control, the case of canalizing update rules is of particular interest. A canalizing rule is one for which a node state at time t is determined by the state at time t-1 of a single one of its inputs when that inputting node is in its canalizing state. Previous work on the order-disorder transition in Boolean networks considered complex, nonrandom network topology. In the current paper we extend this previous work to account for canalizing behavior.


Virtual rough samples to test 3D nanometer-scale scanning electron microscopy stereo photogrammetry.
The combination of scanning electron microscopy for high spatial resolution, images from multiple angles to provide 3D information, and commercially available stereo photogrammetry software for 3D reconstruction offers promise for nanometer-scale dimensional metrology in 3D. A method is described to test 3D photogrammetry software by the use of virtual samples-mathematical samples from which simulated images are made for use as inputs to the software under test. The virtual sample is constructed by wrapping a rough skin with any desired power spectral density around a smooth near-trapezoidal line with rounded top corners. Reconstruction is performed with images simulated from different angular viewpoints. The software's reconstructed 3D model is then compared to the known geometry of the virtual sample. Three commercial photogrammetry software packages were tested. Two of them produced results for line height and width that were within close to 1 nm of the correct values. All of the packages exhibited some difficulty in reconstructing details of the surface roughness.


Differential tropism of human herpesvirus 6 (HHV-6) variants and induction of latency by HHV-6A in oligodendrocytes.
Human herpesvirus 6 (HHV-6) is a ubiquitous beta -herpesvirus associated with a number of clinical disorders. Two closely but biologically distinct variants have been described. HHV-6 variant B causes the common childhood disease exhanthem subitum, and although the pathologic characteristics for HHV-6 variant A are less well defined, HHV-6A has been suggested to be more neurotropic. We studied the effect of both HHV-6 variants in an oligodendrocyte cell line (MO3.13). Infection of M03.13 was monitored by cytopathic effect (CPE), quantitative TaqMan PCR for viral DNA in cells and supernatant, reverse transcriptase-polymerase chain reaction (RT-PCR) to detect viral RNA, and indirect immunofluorescence (IFA) to detect viral protein expression. HHV-6A infection induced significantly more CPE than infection with HHV-6B. HHV-6B induced an abortive infection associated with a decrease of the initial viral DNA load over time, early RNA expression, and no expression of viral antigen. In contrast, infection with HHV-6A DNA persisted in cells for at least 62 days. During the acute phase of infection with HHV-6A, intracellular and extracellular viral load increased and cells expressed the viral protein IE-2 and gp116/54/64. No HHV-6A RNA or protein was expressed after 30 days post infection, suggesting that HHV-6A formed a latent infection. These studies provide in vitro support to the hypothesis that HHV-6 can actively infect oligodendrocytes. Our results suggest that HHV-6A and HHV-6B have different tropism in MO3.13 cells and that an initially active HHV-6A infection can develop latency. Differences between HHV-6A and -6B infection in different neural cell types may be associated with different neurological diseases.


Characterization of Vibrio cholerae protease activities with peptide digest analysis.
A simple method for the analysis of microbial proteases is described that was used to characterize the proteolytic activities of various Vibrio cholerae isolates. This method utilized the unique peptides generated from the degradation of a standard protein by proteases of various specificities. These peptides were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The unique patterns of peptides seen in gels can be used to type proteases according to their relative specificities. Culture supernatants of V. cholerae isolates from a variety of environmental and human sources were analyzed for the presence of a protease previously isolated and characterized in this laboratory from V. cholerae strain CA401. Supernatants from most isolates showing dimethyl casein proteolytic activity exhibited the presence of enzymes similar to the CA401 protease in their peptide digest patterns against bovine serum albumin and in their immunological reactivities. The probable widespread presence of this virulence-associated protease in V. cholerae isolates is discussed.


Maximizing the sensitivity of a screening questionnaire for determining Fragile X at-risk status.
Parents of 55 preschool and school-aged children with the FMR1 full mutation (fM) completed a brief screening questionnaire. Parents of 55 additional children, each of whom was individually matched for sex, age, and IQ to one of the 55 children with Fragile X syndrome, also completed a questionnaire. Items on the questionnaire concerned behavior, rather than physical features or family history, associated with Fragile X syndrome. Children with the fM were more likely than controls to be on prescription medication, to have poor eye contact, to be described as nervous or anxious, and to regularly engage in repetitive movements and/or repetitive speech. Moreover, children with the fM received higher total scores on the questionnaire than their matched controls. These results suggest that questions about behavior are useful in the diagnostic evaluation of Fragile X syndrome, especially in the absence of the recognizable physical features associated with this condition.


Liquid chromatography with mass spectrometry enantioseparation of pomalidomide on cyclodextrin-bonded chiral stationary phases and the elucidation of the chiral recognition mechanisms by NMR spectroscopy and molecular modeling.
A sensitive and validated liquid chromatography with mass spectrometry method was developed for the enantioseparation of the racemic mixture of pomalidomide, a novel, second-generation immunomodulatory drug, using β-cyclodextrin-bonded stationary phases. Four cyclodextrin columns (β-, hydroxypropyl-β-, carboxymethyl-β-, and sulfobutyl-β-cyclodextrin) were screened and the effects of eluent composition, flow rate, temperature, and organic modifier on enantioseparation were studied. Optimized parameters, offering baseline separation (resolution = 2.70 ± 0.02) were the following: β-cyclodextrin stationary phase, thermostatted at 15°C, and mobile phase consisting of methanol/0.1% acetic acid 10:90 v/v, delivered with 0.8 mL/min flow rate. For the optimized parameter at multiple reaction monitoring mode 274.1-201.0 transition with 20 eV collision energy and 100 V fragmentor voltage the limit of detection and limit of quantitation were 0.75 and 2.00 ng/mL, respectively. Since enantiopure standards were not available, elution order was determined upon comparison of the circular dichroism signals of the separated pomalidomide enantiomers with that of enantiopure thalidomide. The mechanisms underlying the chiral discrimination between the enantiomers were also investigated. Pomalidomide-β-cyclodextrin inclusion complex was characterized using nuclear magnetic resonance spectroscopy and molecular modeling. The thermodynamic aspects of chiral separation were also studied.


Obtaining a Panel of Cascade Promoter-5'-UTR Complexes in Escherichia coli.
A promoter is one of the most important and basic tools used to achieve diverse synthetic biology goals. Escherichia coli is one of the most commonly used model organisms in synthetic biology to produce useful target products and establish complicated regulation networks. During the fine-tuning of metabolic or regulation networks, the limited number of well-characterized inducible promoters has made implementing complicated strategies difficult. In this study, 104 native promoter-5'-UTR complexes (PUTR) from E. coli were screened and characterized based on a series of RNA-seq data. The strength of the 104 PUTRs varied from 0.007% to 4630% of that of the PBAD promoter in the transcriptional level and from 0.1% to 137% in the translational level. To further upregulate gene expression, a series of combinatorial PUTRs and cascade PUTRs were constructed by integrating strong transcriptional promoters with strong translational 5'-UTRs. Finally, two combinatorial PUTRs (PssrA-UTRrpsT and PdnaKJ-UTRrpsT) and two cascade PUTRs (PUTRssrA-PUTRinfC-rplT and PUTRalsRBACE-PUTRinfC-rplT) were identified as having the highest activity, with expression outputs of 170%, 137%, 409%, and 203% of that of the PBAD promoter, respectively. These engineered PUTRs are stable for the expression of different genes, such as the red fluorescence protein gene and the β-galactosidase gene. These results show that the PUTRs characterized and constructed in this study may be useful as a plug-and-play synthetic biology toolbox to achieve complicated metabolic engineering goals in fine-tuning metabolic networks to produce target products.


Volumetric assessment is superior to axial measurements in estimating the outcome of patients with acute uncomplicated type B aortic intramural haematoma.
Our goal was to investigate the accuracy of the two-dimensional and three-dimensional computed tomography imaging features in predicting the progression of acute uncomplicated type B aortic intramural haematoma (IMH). This study retrospectively screened 140 patients diagnosed with acute uncomplicated type B IMH in our institution from January 2015 to December 2020. Patients were classified as exhibiting progression (aortic dissection, aortic rupture, aneurysm formation, ulcer-like projection depth >10 mm or >10% increase in the initial thickness of the aortic wall) and regression (completely or partially reabsorbed haematoma) based on follow-up computed tomography. During the 11.4-month follow-up [interquartile range (IQR), 2.6-17.8], 55 patients had haematoma progression. The progression group had higher haematoma volume (HV) and total lesion volume [94.8 (IQR, 80.0-108.2) cm3 vs 40.3 (IQR, 30.8-57.9) cm3; 278.0 (IQR, 238.6-369.3) cm3 vs 197.3 (IQR, 152.8-235.9) cm3, both P < 0.001) and longer lesion length [43.2 (IQR, 37.5-46.7) cm vs 30.4 (IQR, 28.1-37.6) cm, P < 0.001)] than the regression group. According to the area under the curve, HV > 66 cm3 is the greatest risk factor for haematoma progression. In multivariable analysis, HV was a powerful independent predictive factor for type B IMH progression, with a hazard ratio of 17.9 (95% confidence interval, 5.5-58.7; P < 0.001). Volumetric parameters may help to predict disease progression more precisely for patients with acute uncomplicated type B IMH compared to standard axial measurements, which might optimize the initial treatment and follow-up protocol.


The Fractal Tapestry of Life: II Entailment of Fractional Oncology by Physiology Networks.
This is an essay advocating the efficacy of using the (noninteger) fractional calculus (FC) for the modeling of complex dynamical systems, specifically those pertaining to biomedical phenomena in general and oncological phenomena in particular. Herein we describe how the integer calculus (IC) is often incapable of describing what were historically thought to be simple linear phenomena such as Newton's law of cooling and Brownian motion. We demonstrate that even linear dynamical systems may be more accurately described by fractional rate equations (FREs) when the experimental datasets are inconsistent with models based on the IC. The Network Effect is introduced to explain how the collective dynamics of a complex network can transform a many-body noninear dynamical system modeled using the IC into a set of independent single-body fractional stochastic rate equations (FSREs). Note that this is not a mathematics paper, but rather a discussion focusing on the kinds of phenomena that have historically been approximately and improperly modeled using the IC and how a FC replacement of the model better explains the experimental results. This may be due to hidden effects that were not anticapated in the IC model, or to an effect that was acknowledged as possibly significant, but beyond the mathematical skills of the investigator to Incorporate into the original model. Whatever the reason we introduce the FRE used to describe mathematical oncology (MO) and review the quality of fit of such models to tumor growth data. The analytic results entailed in MO using ordinary diffusion as well as fractional diffusion are also briefly discussed. A connection is made between a time-dependent fractional-order derivative, technically called a distributed-order parameter, and the multifractality of time series, such that an observed multifractal time series can be modeled using a FRE with a distributed fractional-order derivative. This equivalence between multifractality and distributed fractional derivatives has not received the recognition in the applications literature we believe it warrants.


Transient infantile hypertriglyceridaemia due to homozygous mutation in GPD1 presenting in childhood with hepatic adenoma.
Hypertriglyceridaemia in infancy is usually secondary to underlying metabolic disorder which usually has a genetic basis unlike the adult population. One such recently described entity is transient infantile hypertriglyceridaemia (HTGTI). In this disorder, mutation in glycerol-3-phosphate (G3P) dehydrogenase gene leads to deficiency of G3P dehydrogenase resulting in hypertriglyceridaemia and hepatomegaly. Clinical features tend to improve with age but may develop fibrosis. Our patient presented in infancy with hypoglycaemia, hepatomegaly, high transaminases and hypertriglyceridaemia. Limited genetic test for glycogen storage disorder was negative and was kept under follow-up. On follow-up, he developed hepatic lesion and his hepatomegaly with hypertriglyceridaemia persisted. There are only a few cases reported worldwide and none has reported development of adenoma so far. This could be the first report of development of adenoma in transient HTGTI.


Clinical workflow and applicability of electrophysiological cardiovascular magnetic resonance-guided radiofrequency ablation of isthmus-dependent atrial flutter.
To determine safety and efficacy of electrophysiological cardiovascular magnetic resonance (EP-CMR)-guided radiofrequency (RF) ablation in patients with typical right atrial flutter in a routine clinical setting. Thirty patients with typical right atrial flutter underwent clinically indicated EP-CMR-guided cavotricuspid isthmus ablation. EP-CMR protocols included pre- and post-ablation CMR imaging (whole heart, T2-weighted, and early-/late-gadolinium enhancement) together with electroanatomic mapping of the right atrium. Coronary sinus cannulation time and total ablation procedure duration were used as performance measures to determine the learning experience of the EP-CMR interventionalist and for comparison with conventional, fluoroscopy-guided atrial flutter ablation. Procedural safety and success rates were evaluated at 1 week and 3 months follow-up. Safety and success rates of EP-CMR were similar to conventional flutter ablations (primary success rate, 93% vs. 100%; recurrence rate, 0% vs. 3%, respectively). EP-CMR procedure duration indicated a learning experience (first vs. last six patients, 54.2 ± 23.1 vs. 29.7 ± 20.0 min) and the minimum number of procedures needed to achieve a level of competency was n = 12. An isthmus angle <110° and the presence of pouch-like isthmus anatomy were indicative of significantly prolonged EP-CMR procedure duration. CMR-defined ablation lesion size was not associated with total RF-ablation time or RF-induced maximum temperature. In a routine clinical setting, EP-CMR demonstrated its safety and high efficacy for the treatment of typical right atrial flutter with performance and outcome measures similar to conventional, fluoroscopy-guided flutter ablation. Hence, EP-CMR represents a valid alternative to conventional right atrial flutter ablation.


Chimerism-based tolerance in organ transplantation: preclinical and clinical studies.
Induction of allograft tolerance has been considered the ultimate goal in organ transplantation. Although numerous protocols to induce allograft tolerance have been reported in mice, a chimerism-based approach through donor haematopoietic stem cell transplantation has been the only approach to date that induced allograft tolerance reproducibly following kidney transplantation in man. Renal allograft tolerance has been achieved by induction of either transient mixed chimerism or persistent full donor chimerism. Although the risk of rejection may be low in tolerance achieved via durable full donor chimerism, the development of graft-versus-host disease (GVHD) has limited the wider clinical application of this approach. In contrast, tolerance induced by transient mixed chimerism has not been associated with GVHD, but the risk of allograft rejection is more difficult to predict after the disappearance of haematopoietic chimerism. Current efforts are directed towards the development of more clinically feasible and reliable approaches to induce more durable mixed chimerism in order to widen the clinical applicability of these treatment regimens.


The association of garlic intake and cardiovascular risk factors: A systematic review and meta-analysis.
Garlic is a common cooking ingredient and used in traditional medicine in Asian countries. There is a growing attention on garlic due to its preventive characteristics in cardiovascular diseases (CVDs). Many studies have reviewed the association between garlic intake and CVDs; however, no consistent conclusions have been drawn. New clinical trials have also been conducted and could contribute to more solid statements. In order to systematically review the reliability of previous studies regarding the implication of garlic in the management of CVDs, we performed in-depth meta-analysis using the most up-to-date randomized clinical trials (RCTs) data with more systematic controls. According to the 22 studies included, the effects of garlic intake on lowering total cholesterol (TC) and low-density lipoprotein (LDL) are more noticeable with lower dosage and longer duration, especially in patients with CVDs. In addition, subgroup analysis indicated that appropriate diet intervention could be an important control factor that should be taken into consideration in any future study designs.


Ten commonly asked computer questions ... and answers. Part 1.
I hope that you have learned something from this article that will help you get through your next computer crisis. Remember that most computer problems are not your fault and they are not the end of the world. It stinks when your car breaks down, and it stinks when your PC crashes, but you will get through it. If your PC does crash, write down what you were doing when it crashed, any changes that were made, any software that was installed, and take a deep breath. You will be able to help get the problem solved quicker if you stay relaxed. Part 2 of this article, to be published in a future issue of Dentistry Today, will answer the next 5 commonly asked computer questions.


Unstable triplets and their mutational mechanism: size reduction of the CGG repeat vs. germline mosaicism in the fragile X syndrome.
The mechanism responsible for the characteristic expansion of the trinucleotide repeat involved in the pathogenesis of the fragile X syndrome is still largely unclear. Slipped strand mispairing (SSM) and similar DNA replication errors could determine both increases and decreases of the unit number in simple repetitive sequences. Actually, there have been a few reports of size reduction of the (CGG)n in parent-to-child transmission of the fragile X syndrome, which may help in understanding the mutational mechanism and may have practical implications for genetic counseling. We describe here 5 such cases from our series of fragile X patients and emphasize the possible role of SSM-like events in causing (CGG)n expansions and reductions. The possibility that some of these reductions are only apparent, resulting from parental germinal mosaicism is also considered.


Multi-Omics Analysis Reveals a Dependent Relationship Between Rumen Bacteria and Diet of Grass- and Grain-Fed Yaks.
Current information on the differences between rumen bacteria and metabolites of the grass-fed and grain-fed yaks is limited. Understanding the composition and alterations of rumen microbial metabolites is important to clarify its potential role in grass-fed and grain-fed systems. The aim of this research was to explore the influence of different production systems on the functional attributes and metabolites in the rumen microbiota of yak using genomics (Illumina MiSeq sequencing of the 16S rRNA gene) and untargeted metabolomics (UHPLC-QTOF-MS). Rumen samples were obtained from grass-fed (C), grain-fed for 3-month (G3), and grain-fed for 6-month yaks (G6). Results showed that the grain-fed yaks presented a lower rumen bacterial richness and diversity when compared to grass-fed yaks. Bacteroidota, Firmicutes, and Fibrobacterota were the main bacterial phyla. At the phylum and genus level, the grass-fed yaks significantly increased the abundance of Fibrobacterota and Fibrobacter (p < 0.05), respectively. The metabolomics analysis revealed that the metabolite profiles differed among the three groups. Compared with the grass-fed group, grain feeding significantly increased azelaic acid, hypoxanthine, uridine, L-phenylalanine, anserine, and decreased alpha-linolenic acid, adenine. Pathway enrichment analysis showed significant differences in metabolic pathways among all comparison groups, but the glycerophospholipid metabolism and alpha-linolenic acid metabolism pathway were common key metabolic pathways. This study showed that the combined analysis of microbiota and metabolites could distinguish different production systems and the fattening time of yaks, providing novel insights for us to understand the function of the rumen bacteria.


Prevalence and genetic characterization of toxin A variant strains of Clostridium difficile among adults and children with diarrhea in France.
Toxin A variant strains (toxin A-negative, toxin B-positive strains) of Clostridium difficile have been reported to be responsible for diarrhea or pseudomembranous colitis in humans. These strains lack parts of the repeating sequences of the toxin A gene (tcdA) and are toxin A negative by commercial enzyme immunoassays (EIA). Here, we report the prevalence of the toxin A variant strains in 334 patients with C. difficile-associated diarrhea in France. The repeating segment of the tcdA gene (1,200 bp) was amplified by PCR using the primers NK9 and NK11 (H. Kato et al., J. Clin. Microbiol. 36:2178-2182, 1998). In the case of amplified fragments of unexpected size, the entire tcdA gene was studied by PCRs A1, A2, and A3 (Rupnik et al., J. Clin. Microbiol. 36:2240-2247, 1998), and strains were characterized by serotyping, pulsed-field gel electrophoresis and PCR ribotyping. By PCR with primers NK9 and NK11, C. difficile variant strains were detected in 2.7% of patients. Several variant types were found. A deletion of approximately 1,700 bp was observed in six strains from five patients. These strains belonged to serotype F and were characterized by the same pulsotype and the same PCR ribotype. They were toxin A negative by EIA and exhibited an atypical cytopathic effect on MRC-5 cells. Two other tcdA variant types that exhibited a positive result for toxin A by EIA were identified: one from serotype H with a longer amplified fragment (insertion of 200 bp) and one with a deletion of 600 bp. Diagnosis of C. difficile-associated diseases would have been missed in five patients (1.5%) by laboratories that screen the stools only for the presence of toxin A. This result underlines the need for testing stool by the cytotoxicity assay in patients with a high suspicion of C. difficile-associated diarrhea but a negative immunoassay for toxin A.


Inducible TAP1 Negatively Regulates the Antiviral Innate Immune Response by Targeting the TAK1 Complex.
The innate immune response is critical for host defense and must be tightly controlled, but the molecular mechanisms responsible for its negative regulation are not yet completely understood. In this study, we report that transporter 1, ATP-binding cassette, subfamily B (TAP1), a virus-inducible endoplasmic reticulum-associated protein, negatively regulated the virus-triggered immune response. In this study, we observed upregulated expression of TAP1 following virus infection in human lung epithelial cells (A549), THP-1 monocytes, HeLa cells, and Vero cells. The overexpression of TAP1 enhanced virus replication by inhibiting the virus-triggered activation of NF-κB signaling and the production of IFNs, IFN-stimulated genes, and proinflammatory cytokines. TAP1 depletion had the opposite effect. In response to virus infection, TAP1 interacted with the TGF-β-activated kinase (TAK)1 complex and impaired the phosphorylation of TAK1, subsequently suppressing the phosphorylation of the IκB kinase complex and NF-κB inhibitor α (IκBα) as well as NF-κB nuclear translocation. Our findings collectively suggest that TAP1 plays a novel role in the negative regulation of virus-triggered NF-κB signaling and the innate immune response by targeting the TAK1 complex.


Size-selective catalytic activity of Pd nanoparticles encapsulated within end-group functionalized dendrimers.
The synthesis and size-selective catalytic activity of Pd nanoparticles encapsulated within dendrimers functionalized with different-sized end groups is described. We designed and synthesized a series of fourth-generation poly(amidoamine) dendrimers having various extents of steric crowding on their periphery. This was accomplished by reacting the terminal amine groups of these dendrimers with epoxyalkanes substituted with different-sized alkyl groups. The modified dendrimers were characterized by 1H NMR, 13C NMR, and matrix-assisted laser desorption ionization mass spectrometry. Nearly monodisperse (1.7 +/- 0.2 nm) Pd nanoparticles were encapsulated within the interior of these dendrimers, and the resulting composite catalysts were used for the hydrogenation of three alpha-allylic alcohols having different sizes. The results showed a clear correlation between the extent of steric crowding on the dendrimer surface and the turnover frequencies (TOFs) for the substrates: more steric crowding on the dendrimer surface led to lower TOFs.


Paradoxical effects of external modulation of inhibitory interneurons.
The neocortex, hippocampus, and several other brain regions contain populations of excitatory principal cells with recurrent connections and strong interactions with local inhibitory interneurons. To improve our understanding of the interactions among these cell types, we modeled the dynamic behavior of this type of network, including external inputs. A surprising finding was that increasing the direct external inhibitory input to the inhibitory interneurons, without directly affecting any other part of the network, can, in some circumstances, cause the interneurons to increase their firing rates. The main prerequisite for this paradoxical response to external input is that the recurrent connections among the excitatory cells are strong enough to make the excitatory network unstable when feedback inhibition is removed. Because this requirement is met in the neocortex and several regions of the hippocampus, these observations have important implications for understanding the responses of interneurons to a variety of pharmacological and electrical manipulations. The analysis can be extended to a scenario with periodically varying external input, where it predicts a systematic relationship between the phase shift and depth of modulation for each interneuron. This prediction was tested by recording from interneurons in the CA1 region of the rat hippocampus in vivo, and the results broadly confirmed the model. These findings have further implications for the function of inhibitory and neuromodulatory circuits, which can be tested experimentally.


Competition between dopamine, beta-receptor agonists and promethazine in Escherichia coli plasmid replication.
The substrates in the phenylalanine, metabolism play key roles in the physiological processes of bacteria. Promethazine affects the phenylalanine metabolism in Escherichia coli. The antibacterial and anti-plasmid actions of promethazine were prevented by phenylalanine, tyrosine, phenylpyruvic acid, phenylacetic acid, noradrenaline and dopamine in minimal medium. Isoproterenol (and phenoxybenzamine) reduced, while propranolol, oxyprenolol and alprenolol isomers enhanced the anti-plasmid effect of promethazine. Propranolol itself induced an anti-plasmid effect. The effects of beta-receptor agonists and antagonists on promethazine-induced anti-plasmid action serve as an indirect evidence of beta adrenergic like binding sites in E. coli. These binding sites are involved in the plasmid replication process and are connected with promethazine binding sites in bacteria.


Estrogen to antiestrogen with a single methylene group resulting in an unusual steroidal selective estrogen receptor modulator.
Selective estrogen receptor (ER) modulators (SERMs) are important therapeutic agents for breast cancer prevention and treatment. We have synthesized two analogs, E11-2,1 [methyl-(3,17beta-dihydroxyestra-1,3,5(10)-triene-11beta-yl)acetate] and E11-2,2 [ethyl-(3,17beta-dihydroxyestra-1,3,5(10)-triene-11beta-yl)acetate], the methyl and ethyl esters of an estradiol analog, substituted in the B ring at C-11beta with a carboxymethyl group. The shorter methyl ester, E11-2,1, has high ER affinity and high estrogenic potency in the Ishikawa estrogen cell bioassay, whereas the longer ethyl ester, E11-2,2, has even higher ER affinity, but little or no estrogenic activity. We found that this minor change of one methylene group transforms a potent estrogenic agonist into an antagonist in vitro with either ER alpha or beta. In the rat, E11-2,2 acts as a SERM in the uterus, where it inhibits estradiol-induced proliferation, and as an estrogen agonist in the liver and skeleton, where it decreases plasma cholesterol and increases bone growth. The characteristic feature of antiestrogens, including SERMs, is a long and polar side-chain that prevents agonist-induced conformation of helix 12 of ER. E11-2,2 with its short, nonpolar side-chain, lacks this critical structure, presenting the possibility that it might act through a unique mechanism.


Variability and resistance mutations in the hepatitis C virus NS3 protease in patients not treated with protease inhibitors.
The goal of treatment of chronic hepatitis C is to achieve a sustained virological response, which is defined as exhibiting undetectable hepatitis C virus (HCV) RNA levels in serum following therapy for at least six months. However, the current treatment is only effective in 50% of patients infected with HCV genotype 1, the most prevalent genotype in Brazil. Inhibitors of the serine protease non-structural protein 3 (NS3) have therefore been developed to improve the responses of HCV-infected patients. However, the emergence of drug-resistant variants has been the major obstacle to therapeutic success. The goal of this study was to evaluate the presence of resistance mutations and genetic polymorphisms in the NS3 genomic region of HCV from 37 patients infected with HCV genotype 1 had not been treated with protease inhibitors. Plasma viral RNA was used to amplify and sequence the HCV NS3 gene. The results indicate that the catalytic triad is conserved. A large number of substitutions were observed in codons 153, 40 and 91; the resistant variants T54A, T54S, V55A, R155K and A156T were also detected. This study shows that resistance mutations and genetic polymorphisms are present in the NS3 region of HCV in patients who have not been treated with protease inhibitors, data that are important in determining the efficiency of this new class of drugs in Brazil.


Digital image analysis of endoscopic ultrasonography is helpful in diagnosing gastric mesenchymal tumors.
Endoscopic ultrasonography (EUS) is a valuable imaging tool for evaluating subepithelial lesions in the stomach. However, there are few studies on differentiation between gastrointestinal stromal tumors (GISTs) and benign mesenchymal tumors, such as leiomyoma or schwannoma, with the use of EUS. In addition, there are limitations in the analysis of the characteristic features of such tumors due to poor interobserver agreement as a result of subjective interpretation of EUS images. Therefore, the aim of this study was to evaluate the role of digital image analysis in distinguishing the features of GISTs from those of benign mesenchymal tumors on EUS. We enrolled 65 patients with histopathologically proven gastric GIST, leiomyoma or schwannoma on surgically resected specimens who underwent EUS examination at our endoscopic unit from January 2007 to September 2010. After standardization of the EUS images, brightness values including the mean (Tmean), indicative of echogenicity, and the standard deviation (TSD), indicative of heterogeneity, in the tumors were analyzed. The Tmean and TSD were significantly higher in GIST than in leiomyoma and schwannoma (p < 0.001). However, there was no significant difference in the Tmean or TSD between benign and malignant GISTs. The sensitivity and specificity were almost optimized for differentiating GIST from leiomyoma or schwannoma when the critical values of Tmean and TSD were 65 and 75, respectively. The presence of at least 1 of these 2 findings in a given tumor resulted in a sensitivity of 94%, specificity of 80%, positive predictive value of 94%, negative predictive value of 80%, and accuracy of 90.8% for predicting GIST. Digital image analysis provides objective information on EUS images; thus, it can be useful in diagnosing gastric mesenchymal tumors.


A Rare Case of Sarcoidosis Presenting as an Isolated Breast Mass and Pain: A Case Report and Literature Review.
BACKGROUND Sarcoidosis is a benign systemic granulomatous disorder of unknown etiology that affects multiple organs. Patients diagnosed with sarcoidosis usually present with nonspecific symptoms: fatigue, fever, weight loss, and respiratory symptoms such as cough and dyspnea; 50% of the patients are asymptomatic at the time of diagnosis. In 90% of patients, sarcoidosis targets hilar and mediastinal lymph nodes. In rare cases, it presents solely in the breast with no other symptoms. The diagnosis is established based on compatible clinical and radiological findings and supported by histological evidence in 1 or more organs of non-caseating epithelioid cell granulomas in the absence of organisms or particles. CASE REPORT We herein present a unique case of a 27-year-old woman who presented with pain and swelling in her left breast. On examination, the left breast revealed multiple, firm-hard, and tender masses. Breast ultrasound showed large loculated focally dilated ducts with significant periductal vascularity and inflammation. Fine-needle aspiration (FNA) showed an inflammatory process with granulomatous formation. An ultrasound-guided core biopsy, which was histologically consistent with granulomatous mastitis, and elevated angiotensin-converting enzyme (ACE) levels confirmed a diagnosis of sarcoidosis. The patient was started on IV steroids followed by oral prednisolone and azathioprine. During treatment, the mass size decreased and the pain substantially improved. CONCLUSIONS It is important to consider sarcoidosis in a patient who presents with only pain and swelling in the breast to ensure early diagnosis and initiate treatment, improving the patient's overall prognosis.


Prediction of left ventricular dysfunction after device closure of patent ductus arteriosus: proposal for a new functional classification.
The aims of this study were to determine the incidence and correlates of left ventricular (LV) dysfunction amongst percutaneous patent ductus arteriosus (PDA) device closure patients, and to propose an indexed parameter for predicting LV dysfunction. In a retrospective cross-sectional analysis of 30 months duration, 447 patients who underwent PDA device closure were studied. The diameter of the PDA at the pulmonary artery end was measured in the angiograms in all patients and was indexed for their body surface area. The indexed PDA size was categorised into group A (1-2.9 mm/m², 35/447), B (3-5.9 mm/m², 254/447), C (6-8.9 mm/m², 66/447) and D (>9 mm/m², 35/447). Systolic LV function was evaluated using echocardiography at frequent intervals. Overall, 62.63% of the patients were female (280/447). At baseline, all 447 patients had normal LV function. LV dysfunction was seen in 102/447 (22.8%) patients with 2.8% in category A (1/35), 10.6% in category B (27/254), 34.1% in category C (42/123) and 91.4% in category D (32/35) after PDA device closure. Correlation of indexed PDA size and LV dysfunction was statistically significant (p<0.05). Accurate prediction of LV dysfunction is important in risk stratification, ICU management and counselling in PDA device closures. Indexed PDA size correlates well with post-procedural LV dysfunction. The authors propose a new classification of PDA utilising this accurate, reproducible and easy to perform parameter, which does not involve any extra cost, for risk stratification and early management in device closure of PDA.


[Comparison of topic mydriasis and mydriasis achieved by soaked cellulose in the conjunctival sac].
To compare mydriasis before the cataract surgery after the local application of mydriatics in to the conjunctival sac with mydriasis achieved using the mydriatic solution in soaked piece of cellulose applied in to the lower fornix. The same mydriatics (tropicamide 0.5 %, phenylephrine 10%, and homatropine 4 %) were used. In a prospective, non-randomized study the authors measured maximal artificial mydriasis in 100 patients (60 women, 40 men) in 100 eyes before the cataract surgery. The mean age of the patients was 70.17 years (range, 42 - 91 years). The patients were divided into two groups (A, B), each of 50 persons: In the group A, during the 10 - 15 minutes period, the mydriatics, tropicamide 0.5%, phenylephrine 10%, and homatropine 4%, were topically applied three times. In the patients of the B group, the conjunctival sac was anesthetized by oxybuprocaine 0.4%; and afterwards, a cut piece of cellulose (Kettenbach) soaked in to the mydriatics solution was applied for 30 - 40 minutes in to the conjunctival sac and the eyelids were taped together. The mydriatic solution was mixed by tropicamide 0.5%, phenylephrine 10%, and homatropine 4%, of equal doses. On the surgery table, before the operation, th soaked cellulose was removed, and thereafter the achieved preoperative horizontal size of the pupil was measured with caliper under the operation microscope. The achieved preoperative pupillary width in the group A and B were compared. The authors noticed also subjective symptoms and objective signs in both groups of patients. For statistical comparison of the average mydriasis between the A and B group of patients, the unpaired Student t test was used. As statistically significant we considered p < 0.05. The average mydriasis in the A group (mydriatic drops topically) was 7.84 +/- 0.99 mm. In the B group of patients (cut piece of cellulose soaked in to the mydriatics solution), the average mydriasis was 7.94 +/- 1.03 mm. The authors did not found significant difference in the diameters between the A and the B group of patients (p = 0.622; p > 0.05). In the B group of patients, subjective symptoms as well as objective signs appeared (burning sensation, sticking, pain, and corneal epithelium erosion); these problems were caused by the triangle shape and the size of the cut cellulose piece. Artificial preoperative mydriasis in patients in both our groups was very good. Topic classically introduced preoperative mydriasis has its stable place also in contemporary modern cataract surgery; the mydriasis achieved by soaked cellulose may save the nurses' time.


Labor induction in the patient with preterm premature rupture of membranes.
Preterm premature rupture of membranes (PPROM) affects up to one-third of all preterm births and confers serious maternal risks, including intra-amniotic infection, and an increased risk of neonatal complications, including respiratory distress and intraventricular hemorrhage. Management of PPROM is a highly individualized process that requires an accurate determination of gestational age and causal factors, as well as the balancing of maternal and fetal risks. In this review of the existing literature on induction of labor in PPROM, we examine the differences in appropriate management of patients with early (32 weeks 0 days to 33 weeks 6 days) and near term (34 weeks 0 days to 36 weeks 6 days) PPROM, and compare the safety and efficacy of available treatment options. This review of previous research findings provides general guidelines for clinical decision making and highlights the need for future research on management of PPROM.


Exploring the Impact of the "RUEU?" Game on Greek Students' Perceptions of and Attitudes to European Identity.
European identity is a complex, multi-faced and inherently imprecise concept relating to a range of socio-political and psychological factors. Addressing this topic in educational practice, particularly with respect to Higher Education students, constitutes a complex and open problem for research. This paper reports on an experimental study designed to explore the effectiveness of the educational game "RUEU?" in supporting university students in understanding the key socio-political issues regarding European identity. Quantitative data regarding Greek university students' (N = 92) attitudes to European identity, before and after playing the game, were collected. Students' performance of the game group (N = 46) was compared with that of a control group (N = 46) who explored the same issues about European identity through a tutor-guided discussion. The findings showed that both instructional interventions were effective but in different ways. The participants in the game-based group appeared more attached to the EU after the intervention and moved toward a more balanced description of their Greek and European identity. On the other hand, the students in the control group rated higher what "European identity" and being EU citizen means to them. The findings indicated the potential of game-based interventions to deliver not only academic content but also to promote students' reflection and influence them at an attitudinal and emotional level.


Breaking Bad: a case of Lactobacillus bacteremia and liver abscess.
We present a case of a 46-year-old Hispanic male with a past medical history significant for uncontrolled diabetes presenting with abdominal pain, nausea and vomiting and found to have Lactobacillus bacteremia and liver abscess. A PubMed and Clinical Key literature review of the other known cases of Lactobacillus liver abscess was performed. Through examination of previous case reports, the patient presented in this paper, and the associated risk factors of Lactobacillus liver abscess it is likely that the incidence of this rare condition will increase and would therefore be prudent to further study Lactobacillus as a pathogenic bacteria so that its complications may be better treated and prevented.


Hormonal effects of an induction dose of etomidate for patients undergoing urgent myocardial revascularization.
The use of etomidate for induction of anesthesia in patients requiring urgent coronary artery surgery provides good cardiovascular stability. However, long-term etomidate infusions may cause transient signs of adrenocortical suppression. The purpose of this study was to determine whether an induction bolus dose of etomidate would cause clinically relevant endocrine dysfunction in urgent coronary artery bypass patients. With institutional review board approval, 11 patients were prospectively randomized to a diazepam (control) or etomidate rapid sequence induction. The diazepam group (n=6; mean, 69 years) received 0.4 mg/kg of diazepam. The etomidate group (n=5; mean, 54 years) received 0.3 mg/kg of etomidate. Maintenance anesthesia included nitrous oxide, oxygen, pancuronium, and fentanyl in increments up to 32 microg/kg. Hemodynamics, cortisol, epinephrine, and norepinephrine were measured both intraoperatively and postoperatively. The only significant difference between the two groups in hemodynamic parameters was a higher heart rate in the etomidate group. Both agents adequately controlled the stress response to intubation as judged from the levels of epinephrine, norepinephrine. and cortisol. However, in both groups epinephrine and norepinephrine increased between intubation and removal of the aortic cross-clamp. Cortisol also increased from the time of cross-clamp removal to 12 and 24 hours post-bypass. During anesthesia and surgery in the pre-bypass period, there was a decrease in cortisol over time in the etomidate group, and there was an increase with diazepam. Thus, etomidate provided stable hemodynamics, possible mild intraoperative adrenocortical suppression, a depressed hormonal stress response to intubation, and a normal hormonal reaction to the later part of surgery and the postoperative period.


Chitosan hydrogel improves mesenchymal stem cell transplant survival and cardiac function following myocardial infarction in rats.
Myocardial infarction (MI) remains the leading cause of cardiovascular-associated mortality and morbidity. Improving the retention rate, survival and cardiomyocyte differentiation of mesenchymal stem cells (MSCs) is important in improving the treatment of patients with MI. In the present study, temperature-responsive chitosan hydrogel, an injectable scaffold, was used to deliver MSCs directly into the infarcted myocardium of rats following MI. Histopathology and immunohistochemical staining were used to evaluate cardiac cell survival and regeneration, and cardiac function was assessed using an echocardiograph. It was demonstrated that chitosan hydrogel increased graft size and cell retention in the ischemic heart, promoted MSCs to differentiate into cardiomyocytes and increased the effects of MSCs on neovasculature formation. Furthermore, chitosan hydrogel enhanced the effect of MSCs on the improvement of cardiac function and hemodynamics in the infarcted area of rats following MI. These findings suggest that chitosan hydrogel is an appropriate material to deliver MSCs into infarcted myocardium.


A pangenome approach-based loop-mediated isothermal amplification assay for the specific and early detection of Bordetella pertussis.
Despite widespread vaccination, Bordetella pertussis continues to cause pertussis infections worldwide, leaving infants at the highest risk of severe illness and death, while people around them are likely the main sources of infection and rapidly spread the disease. Rapid and less complex molecular testing for the specific and timely diagnosis of pertussis remains a challenge that could help to prevent the disease from worsening and prevent its transmission. We aimed to develop and validate a colorimetric loop-mediated isothermal amplification (LAMP) assay using a new target uvrD_2 informed by the pangenome for the specific and early detection of B. pertussis. Compared to that of multitarget quantitative polymerase chain reaction (multitarget qPCR) using a large clinical DNA specimen (n = 600), the diagnostic sensitivity and specificity of the uvrD_2 LAMP assay were 100.0% and 98.6%, respectively, with a 99.7% degree of agreement between the two assays. The novel colorimetric uvrD_2 LAMP assay is highly sensitive and specific for detecting B. pertussis DNA in nasopharyngeal swabs and showed similar diagnostic accuracy to complex and high-cost multitarget qPCR, but it is faster, simpler, and inexpensive, which makes it very helpful for the reliable and timely diagnosis of pertussis in primary health care and resource-limited settings.


A fast layout algorithm for protein interaction networks.
Graph drawing algorithms are often used for visualizing relational information, but a naive implementation of a graph drawing algorithm encounters real difficulties when drawing large-scale graphs such as protein interaction networks. We have developed a new, extremely fast layout algorithm for visualizing large-scale protein interaction networks in the three-dimensional space. The algorithm (1) first finds a layout of connected components of an entire network, (2) finds a global layout of nodes with respect to pivot nodes within a connected component and (3) refines the local layout of each connected component by first relocating midnodes with respect to their cutvertices and direct neighbors of the cutvertices and then by relocating all nodes with respect to their neighbors within distance 2. Advantages of this algorithm over classical graph drawing methods include: (1) it is an order of magnitude faster, (2) it can directly visualize data from protein interaction databases and (3) it provides several abstraction and comparison operations for effectively analyzing large-scale protein interaction networks. http://wilab.inha.ac.kr/interviewer/


The national burdens of rheumatoid arthritis and osteoarthritis in Japan: projections to the year 2010, with future changes in severity distribution.
Abstract We projected the national burdens of rheumatoid arthritis (RA) and osteoarthritis (OA) in Japan in the year 2010, together with future changes in severity distribution. The age-, sex-, and in/outpatient-specific prevalence rates of RA and OA from the 1999 National Patient Survey were multiplied by the National Census population projections for 2000 and 2010. The years lived with disability (YLD) of RA or OA in 2010 were adjusted for the projected changes in the summed measure of severity distribution (i.e., the sum products of the percentage distribution and the health-related quality of life score for three severity classes) using the corresponding regression equations. Between 2000 and 2010, the numbers of patients with RA and OA in Japan will increase by 14% (from 0.31 million to 0.36 million) and 27% (from 0.77million to 0.98 million), respectively, and accordingly, the YLD of RA and OA will increase by 3% (from 42.8 to 43.6 per 100 000) and 21% (from 65.8 to 79.1 per 100 000), respectively. Because of the decreasing proportion of severely affected patients, the increase in YLD may be smaller compared with the increase in the number of patients. As in other developed countries, the national burdens of RA and OA in Japan will increase between 2000 and 2010. However, any projection is likely to be an overestimate unless it considers future changes in the severity distribution associated with medical progress.


Determining the role of patterned cell proliferation in the shape and size of the Drosophila wing.
The present work is a detailed analysis of the numerical and positional parameters of cell proliferation in all of the derivatives of the wing disk. We have made use of twin clones resulting from mitotic recombination events at three different ages of development. The interfaces between twin clones indicate the relative position in the anlage of the mother cells. Interface types vary with age of clone initiation and with wing regions. They are indicative of the main allocation of postmitotic cells of the growing clones. Growth is exponential and intercalar, i.e., the progeny of ancestor cells becomes more and more separated. Clones are compact, indicating that daughter cells tend to remain side by side. The shape of the clones is wing region characteristic. Subpopulations of cells grow preferentially along veins and wing margins and show characteristic shapes in different pleural regions. The shape and size of the adult wing regions largely depend on the shape of clones and hence of the allocation of successive rounds of daughter cells. The role of mitogenic morphogens in wing size and shape is discussed.


Interchangeability of the Wii Balance Board for Bipedal Balance Assessment.
Since 2010, an increasing interest in more portable and flexible hardware for balance and posture assessment led to previously published studies determining whether or not the Wii Balance Board could be used to assess balance and posture, both scientifically and clinically. However, no previous studies aimed at comparing results from different Wii Balance Boards for clinical balance evaluation exist. The objective of this crossover study is to assess the interchangeability of the Wii Balance Board. A total of 6 subjects participated in the study and their balance was assessed using 4 different Wii Balance Boards. Trials were recorded simultaneously with Wii Balance Boards and with a laboratory force plate. Nine relevant clinical parameters were derived from center of pressure displacement data obtained from Wii Balance Board and force plate systems. Intraclass correlation coefficients (ICC), F tests, and Friedman tests were computed to assess the agreement between trials and to compare the Wii Balance Board and force plate results. Excellent correlations were found between the Wii Balance Board and force plate (mean ρ =.83). With the exception of 2 parameters, strong to excellent agreements were found for the 7 remaining parameters (ICC=.96). No significant differences were found between trials recorded with different Wii Balance Boards. Our results indicate that for most of the parameters analyzed, balance and posture assessed with one Wii Balance Board were statistically similar to results obtained from another. Furthermore, the good correlation between the Wii Balance Board and force plate results shows that Wii Balance Boards can be reliably used for scientific assessment using most of the parameters analyzed in this study. These results also suggest that the Wii Balance Board could be used in multicenter studies and therefore, would allow for the creation of larger populations for clinical studies. Ethical Committee of the Erasme Hospital (CCB B406201215142).


A study of hepatitis B vaccine efficacy 10 years after compulsory vaccination in Egypt.
This study aimed to determine the protective efficacy of hepatitis B vaccine against infection and chronic carriage in 720 children aged 10 years who were vaccinated in infancy. All children were tested for hepatitis B serologic markers including hepatitis B surface antigen (HBsAg), antibody to hepatitis B surface antigen (anti-HBs), and antibody to hepatitis B core antigen (anti-HBc) using 3rd generation ELISA technique. Only 37.9% of vaccinated children had protective anti-HBs indicating its decay with time. Hepatitis B infection occurred in 6.8% of the vaccinated children and it induced a boosting effect on anti-HBs level. HBsAg was detected in 0.6% only of the vaccinated children. Thus we could conclude that up to 10 years, booster doses are unnecessary possibly due to protective anamnestic response to antigenic challenge. Further follow-up studies for longer duration than 10 years are needed especially during adolescence with the onset of sexual activity to monitor the vaccine efficacy in preventing chronic carriage and the possible necessity for booster doses.


The value of conventional views and radiographic magnification in evaluating early rheumatoid arthritis.
Fifty-four patients with suspected early rheumatoid arthritis had radiographs taken of their hands and wrists in 4 views (posteroanterior [PA], oblique, reverse oblique, and Brewerton) using conventional techniques and, in the PA view, using radiographic magnification. The radiographs were "masked" and presented in random order to 2 radiologists specializing in bone and joint radiology who interpreted them for malalignment, erosions, joint space narrowing, and soft tissue swelling. The PA was the best conventional view for demonstrating malalignment, joint space narrowing, and soft tissue abnormalities; the Brewerton view was better for detecting erosive disease. Radiographic magnification was more sensitive than conventional films for evaluating erosive disease, but otherwise was no better than the conventional PA view. These results help the physician choose the radiologic technique or combination of techniques that is most likely to detect specific abnormalities.


Fatal outcome of spontaneous cerebral and intraventricular hemorrhage in a child with idiopathic thrombocytopenic purpura (ITP)--case report.
Idiopathic thrombocytopenic purpura (ITP) is the most prevalent acquired hemorrhagic diathesis in children characterised by antibody-mediated destruction of platelets. ITP is generally a self-limiting benign disorder but despite this good prognosis, ITP carries the risk of severe bleeding (mainly intracranial) that may threaten the child's life. We describe a case of a 5-year-old girl with idiopathic thrombocytopenic purpura in the course of EBV infection with massive cerebral and intraventricular hemorrhage and fatal outcome. This extremely rare case of intracranial haemorrhage in a child with ITP coexisting with EBV infection (a likely additional risk factor for hemorrhage) deserves attention considering the fatal outcome despite intensive treatment.


Cost-effectiveness of oral gemifloxacin versus intravenous ceftriaxone followed by oral cefuroxime with/without a macrolide for the treatment of hospitalized patients with community-acquired pneumonia.
We studied the cost-effectiveness of oral gemifloxacin with intravenous ceftriaxone followed by oral cefuroxime with or without a macrolide to treat patients hospitalized with community-acquired pneumonia. Data were prospectively collected as part of a randomized multicenter study. The costs evaluated included antimicrobial acquisition (1st level); plus preparation, dispensing, and administration costs, and treatment of antimicrobial-related adverse events and clinical failures (2nd level); plus per diem costs for hospital stay related to study drug administration (3rd level). At follow-up, clinical success was similar between gemifloxacin (76.9%)- and ceftriaxone (79.1%)-treated patients. The median 1st-level costs for gemifloxacin and ceftriaxone were $136 and $470 (P<0.001), respectively. For the 2nd level, these costs were $158 and $542 (P<0.001), and for the 3rd level, these were $5052 and $5789 (P=0.025), respectively. The median cost per expected success was $6568 for gemifloxacin and $7321 for ceftriaxone (P=0.29). Oral gemifloxacin is clinically effective and has an economic advantage over ceftriaxone, followed by oral cefuroxime with or without a macrolide.


Availability of living donor optimizes timing of liver transplant in high-risk waitlisted cirrhosis patients.
Liver transplant (LT) candidates have become older and frailer, with growing Non-alcoholic steatohepatitis (NASH) and comorbid disease burden in recent years, predisposing them for poor waitlist outcomes. We aimed to evaluate the impact of access to living donor liver transplantation (LDLT) in waitlisted patients at highest risk of dropout. We reviewed all adult patients with decompensated cirrhosis listed for LT from November 2012 to December 2018. Patients with a potential living donor (pLD) available were identified. Survival analyses with Cox Proportional Hazards models and time to LT with Competing risk models were performed followed by prediction model development. Out of 860 patients who met inclusion criteria, 360 (41.8%) had a pLD identified and 496 (57.6%) underwent LT, out of which 170 (34.2%) were LDLT. The benefit of pLD was evident for all, but patients with moderate to severe frailty at listing (interaction p = 0.03), height <160 cm (interaction p = 0.03), and Model for end stage liver disease (MELD)-Na score <20 (interaction p < 0.0001) especially benefited. Our prediction model identified patients at highest risk of dropout while waiting for deceased donor and most benefiting of pLD (time-dependent area under the receiver operating characteristic curve 0.82). Access to LDLT in a transplant program can optimize the timing of transplant for the increasingly older, frail patient population with comorbidities who are at highest risk of dropout.


Loss of spermatogonia and wide-spread DNA methylation defects in newborn male mice deficient in DNMT3L.
Formation of haploid spermatozoa capable of fertilization requires proper programming of epigenetic information. Exactly how DNMT3L (DNA methyltransferase 3-Like), a postulated regulator of DNA methyltransferase activity, contributes to DNA methylation pattern acquisition during gametogenesis remains unclear. Here we report on the role of DNMT3L in male germ cell development. A developmental study covering the first 12 days following birth was conducted on a Dnmt3L mutant mouse model; lower germ cell numbers and delayed entry into meiosis were observed in Dnmt3L-/- males, pointing to a mitotic defect. A temporal expression study showed that expression of Dnmt3L is highest in prenatal gonocytes but is also detected and developmentally regulated during spermatogenesis. Using a restriction enzyme qPCR assay (qAMP), DNA methylation analyses were conducted on postnatal primitive type A spermatogonia lacking DNMT3L. Methylation levels along 61 sites across chromosomes 4 and X decreased significantly by approximately 50% compared to the levels observed in Dnmt3L+/+ germ cells, suggesting that many loci throughout the genome are marked for methylation by DNMT3L. More so, hypomethylation was more pronounced in regions of lower GC content than in regions of higher GC content. Taken together, these data suggest that DNMT3L plays a more global role in genomic methylation patterning than previously believed.


Novel Pattern Recognition Receptor Protects Shrimp by Preventing Bacterial Colonization and Promoting Phagocytosis.
The recognition of pathogen-associated molecular patterns is accomplished by the recognition modules of pattern recognition receptors (PRRs). Leucine-rich repeats (LRRs) and C-type lectin-like domain (CTLD) represent the two most universal categories of recognition modules. In the current study, we identified a novel soluble and bacteria-inducible PRR comprising LRRs and a CTLD from the hepatopancreas of kuruma shrimp Marsupenaeus japonicus and named it Leulectin. The module arrangement of Leulectin is unique among all organisms. Both modules, together with the whole molecule, protected shrimp against Vibrio infection. By screening the pathogen-associated molecular patterns that shrimp might encounter, Leulectin was found to sense Vibrio flagellin through the LRRs and to recognize LPS through CTLD. The LRR-flagellin interaction was confirmed by pull-down and far-Western assays and was found to rely on the fourth LRR of Leulectin and the N terminus of flagellin. The recognition of LPS was determined by the long loop region of CTLD in a calcium-independent manner. By sensing the flagellin, LRRs could prevent its attachment to shrimp cells, thereby inhibiting Vibrio colonization. With the ability to recognize LPS, CTLD could agglutinate the bacteria and promote hemocytic phagocytosis. Our study clearly showed the division of labor and the synergy between different recognition modules and provided new insights into the concept of pattern recognition and the function of soluble PRRs in the antibacterial response.


[HIV infection--current possibilities in antiviral therapy].
Three drugs are currently available to treat HIV infection: zidovudine, didanosine, and zalcitabine. They resemble the natural nucleosides and inhibit retrotranscriptase, an enzyme which transforms HIV's genomic RNA into DNA. Indications for treatment are symptomatic HIV infection and, in asymptomatic patients, moderate immunodeficiency with a CD4-lymphocyte count below 350/mm3. In patients who have not yet received antiviral treatment, zidovudine remains the drug of choice, in spite of its toxicity for the bone marrow, which is particularly problematic in those with advanced immunodeficiency. Unfortunately, HIV develops resistance to zidovudine, and its efficacy wanes after a few months. When that happens, zidovudine may be replaced by didanosine, which is mainly toxic for the pancreas, or by zalcitabine, which causes peripheral neuropathy. A number of drugs are being developed. Among these, nonnucleoside retrotranscriptase inhibitors are well tolerated, but rapid development of resistance is problematic. Resistance seems less of a problem for inhibitors of the viral protease, but biodispensibility of these drugs is poor.


MicroRNAs in the prognosis of triple-negative breast cancer: A systematic review and meta-analysis.
Triple-negative breast cancer (TNBC) is a heterogeneous group of tumors characterized by their aggressive nature and poor associated survival. MicroRNAs (miRs) have been found to play an important role in the occurrence and development of human cancers, but their role in the prognosis of TNBC patients remains unclear. We performed a meta-analysis to explore the prognostic value of miRs in TNBC. We systematically searched the PubMed, Embase, and Web of Science databases to identify eligible studies. A meta-analysis was performed to estimate the pooled hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) for the associations between levels of miR expression (predictive factors) and overall survival (OS) and disease-free survival (DFS) (outcomes) in patients with TNBC. After performing the literature search and review, 21 relevant studies including 2510 subjects were identified. Six miRs (miR-155, miR-21, miR-27a/b, miR-374a/b, miR-210, and miR-454) were assessed in the meta-analysis. Decreased expression of miR-155 was associated with reduced OS (adjusted HR = 0.58, 95% CI: 0.34-0.99; crude HR = 0.67, 95% CI: 0.58-0.79). High miR-21 expression was also predictive of reduced OS (crude HR = 2.50, 95% CI: 1.56-4.01). We found that elevated levels of miR-27a/b, miR-210, and miR-454 expression were associated with shorter OS, while the levels of miR-454 and miR-374a/b expression were associated with DFS. Specific miRs could serve as potential prognostic biomarkers in TNBC. Due to the limited research available, the clinical application of these findings has yet to be verified.


Amyotrophic Lateral Sclerosis Survival Score (ALS-SS): A simple scoring system for early prediction of patient survival.
Our objectives were: (1) to identify independent prognostic factors to determine a survival score for amyotrophic lateral sclerosis (ALS) in a cohort of patients followed in the NEMO Centre (NEuroMuscular Omnicentre); (2) to replicate results in an independent cohort obtained from the Pooled Resource Open Access ALS Clinical Trial Consortium (PRO-ACT) database. Samples were collected from 428 ALS patients from the NEMO database and 2481 patients from the PRO-ACT database. Study design was a retrospective analysis with clinical and biochemical variables, using univariable and multivariable Cox models of analysis. Results showed that, in multivariable analysis, age at diagnosis, diagnostic delay, ALSFRS-R total score, Body Mass Index, aspartate aminotransferase and creatinine level were independently related to survival. These factors were recoded as categorical variables assigning a score from 5 to 15, and the sums of these scores were used to obtain the ALS-Survival Score (ALS-SS). This then allowed to identify three groups having different survival curves. The ALS-SS results were also replicated using data from the PRO-ACT database. In conclusion, considering independent prognostic factors, we were able to give an estimate of survival in our cohort of ALS patients. Whether this ALS-SS may be useful in clinical practice, and potentially in clinical trials, will have to be determined prospectively.


Statistical methods for cis-Mendelian randomization with two-sample summary-level data.
Mendelian randomization (MR) is the use of genetic variants to assess the existence of a causal relationship between a risk factor and an outcome of interest. Here, we focus on two-sample summary-data MR analyses with many correlated variants from a single gene region, particularly on cis-MR studies which use protein expression as a risk factor. Such studies must rely on a small, curated set of variants from the studied region; using all variants in the region requires inverting an ill-conditioned genetic correlation matrix and results in numerically unstable causal effect estimates. We review methods for variable selection and estimation in cis-MR with summary-level data, ranging from stepwise pruning and conditional analysis to principal components analysis, factor analysis, and Bayesian variable selection. In a simulation study, we show that the various methods have comparable performance in analyses with large sample sizes and strong genetic instruments. However, when weak instrument bias is suspected, factor analysis and Bayesian variable selection produce more reliable inferences than simple pruning approaches, which are often used in practice. We conclude by examining two case studies, assessing the effects of low-density lipoprotein-cholesterol and serum testosterone on coronary heart disease risk using variants in the HMGCR and SHBG gene regions, respectively.


cDNA cloning and characterization of a novel squid rhodopsin kinase encoding multiple modular domains.
Rhodopsin phosphorylation is one of the key mechanisms of inactivation in vertebrate and invertebrate visual signal transduction. Here we report the cDNA cloning and protein characterization of a 70-kDa squid rhodopsin kinase, SQRK. The cDNA encoding the 70-kDa protein demonstrates high sequence identity with octopus rhodopsin kinase (92%) and mammalian beta-adrenergic receptor kinases (63-65%), but only 33% similarity with bovine rhodopsin kinase, suggesting that invertebrate rhodopsin kinases may be structurally similar to beta-adrenergic receptor kinases. This cDNA encodes three distinct modular domains: RGS, S/TKc, and PH domains. The native SQRK is an eye-specific protein that is only expressed in photoreceptor cells and the optic ganglion as determined by immunoblotting. Purified SQRK is able to phosphorylate both squid and bovine rhodopsin. Squid rhodopsin phosphorylation by purified SQRK was sensitive to both Mg2+ and GTPgammaS but was insensitive to Ca2+/CaM regulation. The ability of SQRK to phosphorylate rhodopsin was totally lost in the presence of SQRK-specific antibodies. Our results suggest that SQRK plays an important role in squid visual signal termination.


A Turn-On Fluorescence Sensor Based on Nitrogen-Doped Carbon Dots and Cu2+ for Sensitively and Selectively Sensing Glyphosate.
Glyphosate has excellent herbicidal activity, and its extensive use may induce residue in the environment and enter into humans living through the food chain, causing negative impact. Here, water-soluble 1.55 nm size nitrogen-doped carbon quantum dots (NCDs) with strong blue fluorescence were synthesized using sodium citrate and adenine. The maximum excitation and emission wavelengths of NCDs were 380 nm and 440 nm, respectively. The above synthesized NCDs were first used for the construction of a fluorescence sensor for glyphosate detection. It was found that Cu2+ could quench the fluorescence of NCDs effectively through the photoinduced electron transfer (PET) process, which was confirmed using fluorescence lifetime measurements. Additionally, the fluorescence was restored with the addition of glyphosate. Hence, a sensitive turn-on fluorescence sensor based on NCDs/Cu2+ for glyphosate analysis was developed. The LODs of glyphosate for water and rice samples were recorded as 0.021 μg/mL and 0.049 μg/mL, respectively. The sensor was applied successfully for ultrasensitive and selective detection of glyphosate in environmental water and rice samples with satisfied recoveries from 82.1% to 113.0% using a simple sample pretreatment technique. The proposed strategy can provide a significant potential for monitoring glyphosate residue in water and agricultural product samples.


Cytochrome P450 in trypanosomatids.
Post-mitochondrial supernatant extracts prepared from bloodstream forms of Trypanosoma brucei brucei, T. cruzi epimastigotes, Leishmania donovani promastigotes and Crithidia fasciculata have been found to catalyse cytochrome P450-dependent reactions. Appreciable ethoxycoumarin deethylase and ethoxyresorufin deethylase activities were found in all of the above trypanosomatids, with T. cruzi epimastigotes having the highest activity (57.1 and 10.7 pmol/min/mg protein, respectively). In all four species these reactions were inhibited by the cytochrome P450 inhibitors carbon monoxide, proadifen and metyrapone. In contrast to rat liver microsomes, the trypanosomatid extracts showed no detectable pentoxyresorufin depentylase or pentamidine hydroxylase activity. Both C. fasciculata and T. b. brucei post-mitochondrial supernatants showed carbon monoxide difference spectra consistent with the presence of cytochrome P450 (9.6 and 6.3 pmol/mg protein, respectively). An additional hemoprotein which gave a carbon monoxide difference peak at 420 nm was also detected in C. fasciculata and T. b. brucei microsomes and C. fasciculata mitochondria. Subcellular fractionation of both early and late log C. fasciculata showed that the ethoxycoumarin deethylase activity was enriched in the microsomal fraction.


Fine needle aspiration diagnosis of renal oncocytoma. A mathematical morphologic approach.
Differentiation between renal oncocytomas and well-differentiated oxyphilic cell renal carcinomas from fine needle aspiration cytology smears may present considerable difficulties. To better define diagnostic criteria, we used high-resolution architectural characteristics of nucleus and cytoplasm based on mathematical morphologic concepts. Particulate structural elements were selected for their size and optical density by the so-called top-hat function. Spatial density, size distribution and a function of distance between particles were computed. We quantitated cellular samples from fine needle aspirates obtained from 10 renal oncocytomas and 5 well-differentiated oxyphilic cell renal carcinomas. In two of the former, cytologic diagnosis was doubtful. Subsequent removal of the tumor and its histologic examination established the final diagnosis in all cases. Stepwise discriminant analysis correctly classified all cases as oncocytomas or renal carcinomas, although the results need to be considered with caution due to the necessarily limited number of observations. Multivariate graphic representation by star glyphs clearly depicted the differences between oncocytoma and oxyphilic cell renal carcinomas and the abnormal characteristics of two oncocytoma cases misclassified initially.


Solution-Processable High-Quality Graphene for Organic Solar Cells.
The unique optical and electronic properties of graphene open up new opportunities for optoelectronics. This work reports the use of solution-processed high-quality graphene as transparent conductive electrode in an organic solar cell using an electrochemical approach. The fabricated thieno[3,4-b]thiophene/benzodithiophene:phenyl-C71-butyric acid methyl ester (PTB7:PCB71M) bulk heterojunction organic solar cell based on the exfoliated graphene (EG) anode exhibits a power conversion efficiency of 4.23%, making EG promising for next-generation flexible optoelectronic devices.


The Effect of Edible Mushroom on Health and Their Biochemistry.
Edible mushrooms are fungi that can be seen with the naked eye and are relatively easy to gather by hand. This review article highlights the health benefit and the biochemistry of several mushroom species. Agaricus bisporus, Pleurotus species. Lentinus edodes, and Volvariella species are the most acceptable varieties among the cultivated mushroom. Various biochemical methods such as methanol, ethanol, and water extract of different parts of the edible mushroom in the laboratory have been applied to determine and/or quantify the presence and effectiveness of their chemical compounds, food value, and medicinal properties. They contain varying amounts of carbohydrates, proteins, nucleic acids, lipids, minerals, terpenoids, phenolic compounds, steroids, and lectins and vitamins, as well as lowering cholesterol levels in the body. Due to the presence of those vital nutrients, mushrooms are the best food item with high nutritional value. These compounds have a wide range of therapeutic effects and can act as immunomodulatory, anticarcinogenic, antiviral, antioxidant, and anti-inflammatory agents. Routine consumption of edible mushrooms would give adequate protection due to the presence of all the necessary nutrients from them. Therefore, edible mushrooms are herbal antibiotics to many diseases as well as various cancers of humans.


A student's plea for global health studies in the medical school curriculum.
Public policy in Canada is sensitive to changes that have occurred in society as a consequence of immigration, globalization and a new understanding of aboriginal and ethnic cultures. The traditional medical school undergraduate curriculum does not accommodate these changes. The current emphasis on evidenced-based medicine may reinforce the traditional approach because there is a dearth of global healthcare research. This review of medical schools in Canada suggests that modifications of curricula are being attempted to meet the need for knowledge of global health. Integration of global health principles and information into the current curriculum promotes a better understanding of Canada's healthcare delivery system itself as well as its role globally.


Fecal alpha 1-antitrypsin concentration and gastrointestinal permeability to oligosaccharides in atopic dermatitis.
Severe allergic protein-losing enteropathy has been described in childhood atopic dermatitis (AD). Minor morphologic and functional abnormalities of the gastrointestinal mucosa, including altered permeability to oligosaccharides, are not uncommon in this condition, but the prevalence of occult enteric protein loss is unknown. We measured the random fecal alpha 1-antitrypsin (AAT) concentration, an indicator of enteric protein loss, in children with and without AD and found no significant difference between the groups. In half of the patients with AD, gastrointestinal permeability to oligosaccharides was also measured, and no relationship between this and fecal AAT was found.